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1.
Am J Audiol ; 30(2): 385-393, 2021 Jun 14.
Article in English | MEDLINE | ID: covidwho-1805677

ABSTRACT

Purpose The COVID-19 pandemic disrupted normal operations of health care services, broad sectors of the economy, and the ability to socialize freely. For those with tinnitus, such changes can be factors in exacerbating tinnitus. The purpose of this study was to determine tinnitus help-seeking behavior, which resources individuals utilized to cope during the pandemic, and what additional support is desired. Method An exploratory cross-sectional study design including 1,522 adults with tinnitus living in North America (Canada and the United States) was used. Data were collected through an online survey distributed by the American Tinnitus Association via e-mail. Free text from open-ended questions was analyzed using the automated content analysis. The responses to the structured questionnaire were analyzed using descriptive and nonparametric statistics. Results Significantly less tinnitus support was sought during the pandemic, and very few respondents utilized tinnitus support networks during the pandemic at the time the survey was conducted. Nonetheless, seeking support during the pandemic was significantly associated with significantly less tinnitus distress. The most frequently utilized resources for coping during the pandemic were contacting family and friends, spending time outdoors or in nature, relaxation, and exercise. Such tools for coping were associated with significantly less tinnitus distress. The support requested and advice provided by participants to health care services had overlap. The main support needs related to managing tinnitus included addressing hearing loss, providing peer support, finding cures, and accessing trained and understanding health care providers to help. The advice for professionals related to tinnitus management included the need for cures, personalized support, addressing hearing loss, targeting the tinnitus percept, and providing more information about the condition. Conclusions These findings provide suggestions on how to better support those with tinnitus at a time when health care is undergoing rapid changes. Findings can be used by stakeholders, clinical practitioners, and tinnitus support services to devise ways to work more effectively together to improve access to patient-driven, suitable, accessible, and evidence-based support. Supplemental Material https://doi.org/10.23641/asha.14558514.


Subject(s)
Adaptation, Psychological , COVID-19/epidemiology , Help-Seeking Behavior , Tinnitus/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Canada/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Psychological Distress , Surveys and Questionnaires , Tinnitus/therapy , United States/epidemiology , Young Adult
2.
Crit Care Explor ; 2(6): e0139, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1795099

ABSTRACT

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 pandemic has stretched ICU resources in an unprecedented fashion and outstripped personal protective equipment supplies. The combination of a novel disease, resource limitations, and risks to medical personnel health have created new barriers to implementing the ICU Liberation ("A" for Assessment, Prevention, and Manage pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; and "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, a proven ICU care approach that reduces delirium, shortens mechanical ventilation duration, prevents post-ICU syndrome, and reduces healthcare costs. This narrative review acknowledges barriers and offers strategies to optimize Bundle performance in coronavirus disease 2019 patients requiring mechanical ventilation. DATA SOURCES STUDY SELECTION AND DATA EXTRACTION: The most relevant literature, media reports, and author experiences were assessed for inclusion in this narrative review including PubMed, national newspapers, and critical care/pharmacology textbooks. DATA SYNTHESIS: Uncertainty regarding coronavirus disease 2019 clinical course, shifts in attitude, and changes in routine behavior have hindered Bundle use. A domino effect results from: 1) changes to critical care hierarchy, priorities, and ICU team composition; 2) significant personal protective equipment shortages cause; 3) reduced/restricted physical bedside presence favoring; 4) increased depth of sedation and use of neuromuscular blockade; 5) which exacerbate drug shortages; and 6) which require prolonged use of limited ventilator resources. Other identified barriers include manageable knowledge deficits among non-ICU clinicians unfamiliar with the Bundle or among PICU specialists deploying pediatric-based Bundle approaches who are unfamiliar with adult medicine. Both groups have been enlisted to augment the adult ICU work force to meet demand. Strategies were identified to facilitate Bundle performance to liberate patients from the ICU. CONCLUSIONS: We acknowledge current challenges that interfere with comprehensive management of critically ill patients during the coronavirus disease 2019 pandemic. Rapid response to new circumstances precisely requires established safety mechanisms and protocols like the ABCDEF Bundle to increase ICU and ventilator capacity and help survivors maximize recovery from coronavirus disease 2019 as early as possible.

3.
Crit Care Explor ; 2(9): e0202, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1795075

ABSTRACT

OBJECTIVES: Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the "baby lung" (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management. DESIGN: We adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings. SETTING: Interdisciplinary Collaboration in Systems Medicine Research Network. SUBJECTS: The simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model. CONCLUSIONS: Our model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.

4.
Crit Care Explor ; 2(9): e0207, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1795073

ABSTRACT

OBJECTIVES: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019. DESIGN: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020. SETTING: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey. PATIENTS: Eight critically ill patients on invasive mechanical ventilation, suffering from acute respiratory distress syndrome due to coronavirus disease 2019. INTERVENTIONS: Intramuscular injection of PLacental eXpanded (PLX)-PAD (300 × 106 cells) given as one to two treatments. MEASUREMENTS AND MAIN RESULTS: Mortality, time to discharge, and changes in blood and respiratory variables were monitored during hospitalization to day 17 posttreatment. Of the eight patients treated (median age 55 yr, seven males and one female), five were discharged, two remained hospitalized, and one died. By day 3 postinjection, mean C-reactive protein fell 45% (240.3-131.3 mg/L; p = 0.0019) and fell to 77% by day 5 (56.0 mg/L; p < 0.0001). Pao2/Fio2 improved in 5:8 patients after 24-hour posttreatment, with similar effects 48-hour posttreatment. A decrease in positive end-expiratory pressure and increase in pH were statistically significant between days 0 and 14 (p = 0.0032 and p = 0.00072, respectively). A decrease in hemoglobin was statistically significant for days 0-5 and 0-14 (p = 0.015 and p = 0.0028, respectively), whereas for creatinine, it was statistically significant between days 0 and 14 (p = 0.032). CONCLUSIONS: Improvement in several variables such as C-reactive protein, positive end-expiratory pressure, and Pao2/Fio2 was observed following PLacental eXpanded (PLX)-PAD treatment, suggesting possible therapeutic effect. However, interpretation of the data is limited due to the small sample size, use of concomitant investigational therapies, and the uncontrolled study design. The efficacy of PLacental eXpanded (PLX)-PAD in coronavirus disease 2019 should be further evaluated in a controlled clinical trial.

5.
Thromb J ; 18: 22, 2020.
Article in English | MEDLINE | ID: covidwho-1793931

ABSTRACT

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

6.
Clin Infect Dis ; 73(3): e524-e530, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1769204

ABSTRACT

BACKGROUND: Proadrenomedullin (proADM), a vasodilatory peptide with antimicrobial and anti-inflammatory properties, predicts severe outcomes in adults with community-acquired pneumonia (CAP) to a greater degree than C-reactive protein and procalcitonin. We evaluated the ability of proADM to predict disease severity across a range of clinical outcomes in children with suspected CAP. METHODS: We performed a prospective cohort study of children 3 months to 18 years with CAP in the emergency department. Disease severity was defined as mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen, broadening of antibiotics, complicated pneumonia), and severe (eg, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined using proportional odds logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS: Among 369 children, median proADM increased with disease severity (mild: median [IQR], 0.53 [0.43-0.73]; mild-moderate: 0.56 [0.45-0.71]; moderate-severe: 0.61 [0.47-0.77]; severe: 0.70 [0.55-1.04] nmol/L) (P = .002). ProADM was significantly associated with increased odds of developing severe outcomes (suspected CAP: OR, 1.68; 95% CI, 1.2-2.36; radiographic CAP: OR, 2.11; 95% CI, 1.36-3.38) adjusted for age, fever duration, antibiotic use, and pathogen. ProADM had an AUC of 0.64 (95% CI, .56-.72) in those with suspected CAP and an AUC of 0.77 (95% CI, .68-.87) in radiographic CAP. CONCLUSIONS: ProADM was associated with severe disease and discriminated moderately well children who developed severe disease from those who did not, particularly in radiographic CAP.


Subject(s)
Adrenomedullin , Community-Acquired Infections , Pneumonia , Biomarkers , Child , Community-Acquired Infections/diagnosis , Humans , Pneumonia/diagnosis , Prognosis , Prospective Studies , Protein Precursors , Severity of Illness Index
7.
Cancers (Basel) ; 12(5)2020 May 19.
Article in English | MEDLINE | ID: covidwho-1725511

ABSTRACT

The coronavirus disease 19 (COVID-19) pandemic is unprecedented as it reached all countries in the world within a record short period of time. Even though COVID-19 infection may be just severe in any adults, older adults (65-year-old or older) may experience a higher mortality rate. Among those affected, cancer patients may have a worse outcome compared to the general population because of their depressed immune status. As the health resources of most countries are limited, clinicians may face painful decisions about which patients to save if they require artificial ventilation. Cancer patients, especially the older ones, may be denied supportive care because of their shorter life expectancy. Thus, special considerations should be taken to prevent infection of older cancer patients and to provide them with adequate social support during their cancer treatment. The following proposal was reached: (1) Education of health care providers about the special needs of older cancer patients and their risks of infection. (2) Special consideration such as surgical masks and separate scheduling should be made to protect them from being infected. (3) Social services such as patient navigators should be provided to ensure adequate medical supply, food, and daily transportation to cancer centers. (4) Close monitoring through phone calls, telecommunication to ensure social distancing and psychological support from patient family to prevent anxiety and depression. (5) Shorter course of radiotherapy by use of hypofractionation where possible to decrease the needs for daily transportation and exposure to infection. (6) Enrollment of older cancer patients in clinical trials for potential antiviral medications if infection does occur. (7) Home health care telemedicine may be an effective strategy for older cancer patients with COVID-19 infection to avoid hospital admission when health care resources become restricted. (8) For selected patients, immunotherapy and targeted therapy may become the systemic therapy of choice for older cancer patients and need to be tested in clinical trials.

8.
PM R ; 14(2): 198-201, 2022 02.
Article in English | MEDLINE | ID: covidwho-1694679

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) survivors are at risk of functional decline. To address the current gap in knowledge about post-acute needs of those infected by COVID-19, we examined discharge function data to better prepare patients, providers, and health systems to return patients to optimal levels of functioning. OBJECTIVE: To examine the prevalence of functional decline and related rehabilitation needs at hospital discharge. DESIGN: Prospective chart review. SETTING: Academic tertiary care hospital. PARTICIPANTS: Hospitalized adults with a laboratory confirmed COVID-19 diagnosis, with admission dates between March 4, 2020 and May 1, 2020. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Discharge location; need for outpatient physical, occupational, or speech therapy; need for durable medical equipment at discharge; presence of dysphagia at discharge; functional decline. RESULTS: Three hundred eleven potential cases were reviewed. The final number of cases included in analysis was N = 288; patient ages ranged from 20 to 95 years old (mean 66.80 ± 15.31 years). Nearly 20 % of COVID-19 survivors were discharged to a location other than their home. Forty-five percent of survivors experienced functional decline impacting their discharge. Eighty-seven survivors (80.6%) who showed functional change during hospitalization were referred for additional therapy at discharge. At least 73 (67.6%) of these patients required durable medical equipment at discharge (in 12 cases this was not clearly documented). Twenty-nine (26.7%) of the survivors who showed functional changes had ongoing dysphagia at the time of hospital discharge. Ninety-seven of the survivors (40.6%) were never assessed by a PM&R physician, physical therapist, occupational therapist, or speech language pathologist during their hospitalization. CONCLUSIONS: COVID-19 mortality rates are frequently reported in the media, whereas the effects on function are not as well described. The information provided here highlights the need for rehabilitative services during and after hospitalization for COVID-19.


Subject(s)
COVID-19 , Adult , Aged , Aged, 80 and over , COVID-19 Testing , Humans , Middle Aged , Pandemics , Patient Discharge , Prospective Studies , SARS-CoV-2 , Young Adult
9.
Monatsschr Kinderheilkd ; 169(1): 52-56, 2021.
Article in German | MEDLINE | ID: covidwho-1694621

ABSTRACT

After initial reluctance masks have emerged as an important means of restricting the spread of SARS-CoV­2, the new coronavirus causing COVID-19. Other simple measures are keeping a distance of at least 1 ½â€¯m from other persons and observing hygiene recommendations, including washing or even disinfecting the hands, coughing into the crook of the arm and remaining at home when sick. Combining the initial letters of the German words for the three measures (Abstand-Hygiene-Alltagsmaske, distance-hygiene-face mask) the acronym AHA was formed, a colloquial German word meaning that the speaker understood the information presented. This acronym was later extended by the letter "L", initial letter of "Lüften" meaning air ventilation for indoor rooms and arriving at AHA­L, recommended by the federal German Health Institute the Robert Koch Institute. In fact, masks including surgical masks and face coverings can form an effective barrier against the spread of the virus: protecting other people from droplets expelled from the throat of the speaker wearing a mask and even in part protecting the wearer from inhaling droplets emanating from other peoples' throats. Studies to find out if wearing masks might impose risks did not find essential problems: alterations of respiratory parameters due to an increased airway resistance remained within normal limits in healthy adults and even in asthmatics whose disease was well controlled; however, many adults expressed their unease with masks describing them as cumbersome and inconvenient. Emotional resistance against masks made it increasingly more difficult for them to use a mask. Efficient application of masks requires, in addition to a logical explanation of its effect, the evocation of empathy for vulnerable people who can be protected from catching a possibly deadly disease. In children there are very few data on adverse effects of wearing a mask although there is ample experience in children with serious diseases compromising defense against infectious agents acquired via respiratory mucus membranes; however, when using masks appropriately in children relevant adverse effects have not been reported and are not to be expected. Masks should only be used in children when they are healthy and awake and can remove the masks themselves anytime they like. Children 10 years or older can use masks efficiently when they have been informed beforehand appropriate to their age. Under these conditions they can also be obliged to wear masks in certain situations, for example while walking through the school building to their desk in class. To limit the period of wearing a mask normally they will be allowed to remove the mask when sitting in class and keeping their distance. Children in primary schools may use masks, but they should not be obliged to wear them and children in kindergartens should not use masks. This exemption of younger children does not expose school and kindergarten teachers to additional risks since the infectivity with SARS-CoV­2 is age-dependent and increases with age reaching adult values only after 12 years of age.

10.
Mini Rev Med Chem ; 22(2): 273-311, 2022.
Article in English | MEDLINE | ID: covidwho-1666892

ABSTRACT

Due to the high mortality rate of the 2019 coronavirus disease (COVID-19) pandemic, there is an immediate need to discover drugs that can help before a vaccine becomes available. Given that the process of producing new drugs is so long, the strategy of repurposing existing drugs is one of the promising options for the urgent treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Although FDA has approved Remdesivir for the use in hospitalized adults and pediatric patients suffering from COVID-19, no fully effective and reliable drug has been yet identified worldwide to treat COVID-19 specifically. Thus, scientists are still trying to find antivirals specific to COVID-19. This work reviews the chemical structure, metabolic pathway, and mechanism of action of the existing drugs with potential therapeutic applications for COVID-19. Furthermore, we summarized the molecular docking stimulation of the medications related to key protein targets. These already established drugs could be further developed, and after their testing through clinical trials, they could be used as suitable therapeutic options for patients suffering from COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/virology , Metabolic Networks and Pathways/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Antiviral Agents/therapeutic use , Humans , Molecular Docking Simulation , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
11.
Trials ; 22(1): 172, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1622253

ABSTRACT

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/therapy , COVID-19/complications , Clinical Trials, Phase II as Topic , Disease Progression , Dose-Response Relationship, Drug , Equivalence Trials as Topic , Humans , Length of Stay , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/etiology , SARS-CoV-2
12.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522

ABSTRACT

The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.


Subject(s)
Benzylidene Compounds/pharmacology , COVID-19/drug therapy , Cholinergic Agents/pharmacology , Inflammation/drug therapy , Nicotine/metabolism , Pyridines/pharmacology , SARS-CoV-2/physiology , Tobacco Use Disorder/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cigarette Smoking/adverse effects , Dexamethasone/therapeutic use , HMGB1 Protein/blood , Humans , Pandemics , alpha7 Nicotinic Acetylcholine Receptor/agonists
13.
Clin Infect Dis ; 73(11): e3949-e3955, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561940

ABSTRACT

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Double-Blind Method , Humans , Immunogenicity, Vaccine
14.
Clin Infect Dis ; 73(11): e4073-e4081, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560481

ABSTRACT

BACKGROUND: No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. METHODS: Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (-1.41 vs -1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (-3.37 vs -3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. CONCLUSIONS: In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.


Subject(s)
COVID-19 , Hydroxychloroquine , Adult , COVID-19/drug therapy , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Treatment Outcome
15.
Clin Infect Dis ; 73(11): e4166-e4174, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560158

ABSTRACT

BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. CLINICAL TRIALS REGISTRATION: NCT04292899 and EUPAS34303.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Adult , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cohort Studies , Humans , Retrospective Studies , SARS-CoV-2 , Standard of Care , Treatment Outcome
16.
Front Pharmacol ; 12: 610745, 2021.
Article in English | MEDLINE | ID: covidwho-1554748

ABSTRACT

Background: Pneumonia is a prevalent and complicated disease among adults, elderly people in particular, and the debate on the optimal Chinese herbal injections (CHIs) is ongoing. Our objective is to investigate the comparative effectiveness of various CHIs strategies for elderly patients with pneumonia. Methods: A comprehensive search strategy was executed to identify relevant randomized controlled trials (RCTs) by browsing through several databases from their inception to first, Feb 2020; All of the direct and indirect evidence included was rated by Network meta-analysis under a Bayesian framework. Results: We ultimately identified 34 eligible randomized controlled trials that involved 3,111 elderly participants and investigated 4 CHIs combined with Western medicine (WM) (Xiyanping injection [XYP]+WM, Yanhuning injection [YHN]+WM, Tanreqing injection [TRQ]+WM, Reduning injection [RDN]+WM), contributing 34 direct comparisons between CHIs. Seen from the outcome of Clinical effective rate and time for defervescence, patients taking medicine added with CHIs [Clinical effective rate, XYP + WM(Odd ratio (OR): 0.74, 95%Credible intervals (CrIs):0.55-0.98), YHN + WM(OR: 0.66, 95%CrI: 0.45-0.95), TRQ + WM(OR: 0.65, 95%CrI: 0.50-0.83), RDN + WM(OR: 0.60, 95%CrI: 0.40-0.89); Time for defervescence, YHN + WM(Mean difference (MD): -2.11, 95%CrI: -3.26 to -0.98), XYP + WM(MD: -2.06, 95%CrI: -3.08 to -1.09), RDN + WM(MD: -1.97, 95%CrI: -3.61 to -0.35), TRQ + WM(MD: -1.69, 95%CrI: -2.27 to -1.04)] showed statistically better effect compared with participants in the Control group (CG) who only took WM. Meanwhile, based on the time for disappearance of cough, 3 out of 4 CHIs [TRQ + WM(MD: -2.56, 95%CrI: -3.38 to -1.54), YHN + WM(MD: -2.36, 95%CrI: -3.86 to -1.00) and XYP + WM(MD: -2.21, 95%CrI: -3.72 to -1.10)] strategies indicated improvement of clinical symptoms. Only XYP + WM(MD -1.78, 95%CrI: -3.29 to -0.27) and TRQ + WM (MD: -1.71, 95%CrI: -2.71 to -0.73) could significantly shorten the time for disappearance of pulmonary rales. Conclusion: According to the statistical effect size (The surface under the cumulative ranking), we found that XYP + WM was presumably to be the preferable treatment for treating elderly patients with pneumonia compared with WM alone in terms of clinical effective rate. Our findings were based on very limited evidence and thus should be interpreted with caution. The application of the findings requires further research.

19.
Front Neurol ; 12: 676095, 2021.
Article in English | MEDLINE | ID: covidwho-1526775

ABSTRACT

Treatment of pediatric-onset multiple sclerosis (POMS) has been tailored after observational studies and data obtained from clinical trials in adult-onset multiple sclerosis (AOMS) patients. There are an increasing number of new therapeutic agents for AOMS, and many will be formally studied for use also in POMS. However, there are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss the current state of the art of POMS therapy and will focus on the newer therapies (oral and infusion disease-modifying drugs) and on those still currently under investigation.

20.
Ann Thorac Surg ; 112(6): 1983-1989, 2021 12.
Article in English | MEDLINE | ID: covidwho-1520703

ABSTRACT

BACKGROUND: A life-threatening complication of coronavirus disease 2019 (COVID-19) is acute respiratory distress syndrome (ARDS) refractory to conventional management. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) (VV-ECMO) is used to support patients with ARDS in whom conventional management fails. Scoring systems to predict mortality in VV-ECMO remain unvalidated in COVID-19 ARDS. This report describes a large single-center experience with VV-ECMO in COVID-19 and assesses the utility of standard risk calculators. METHODS: A retrospective review of a prospective database of all patients with COVID-19 who underwent VV-ECMO cannulation between March 15 and June 27, 2020 at a single academic center was performed. Demographic, clinical, and ECMO characteristics were collected. The primary outcome was in-hospital mortality; survivor and nonsurvivor cohorts were compared by using univariate and bivariate analyses. RESULTS: Forty patients who had COVID-19 and underwent ECMO were identified. Of the 33 patients (82.5%) in whom ECMO had been discontinued at the time of analysis, 18 patients (54.5%) survived to hospital discharge, and 15 (45.5%) died during ECMO. Nonsurvivors presented with a statistically significant higher Prediction of Survival on ECMO Therapy (PRESET)-Score (mean ± SD, 8.33 ± 0.8 vs 6.17 ± 1.8; P = .001). The PRESET score demonstrated accurate mortality prediction. All patients with a PRESET-Score of 6 or lowers survived, and a score of 7 or higher was associated with a dramatic increase in mortality. CONCLUSIONS: These results suggest that favorable outcomes are possible in patients with COVID-19 who undergo ECMO at high-volume centers. This study demonstrated an association between the PRESET-Score and survival in patients with COVID-19 who underwent VV-ECMO. Standard risk calculators may aid in appropriate selection of patients with COVID-19 ARDS for ECMO.


Subject(s)
COVID-19/complications , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Adult , Humans , Respiratory Distress Syndrome/etiology , Retrospective Studies , Risk Assessment
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