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3.
J Med Internet Res ; 23(2): e23441, 2021 02 25.
Article in English | MEDLINE | ID: covidwho-1573892

ABSTRACT

BACKGROUND: In April 2020, two independent clinical trials to assess SARS-CoV-2 prophylaxis strategies among health care workers were initiated at our hospital: MeCOVID (melatonin vs placebo) and EPICOS (tenofovir disoproxil/emtricitabine vs hydroxychloroquine vs combination therapy vs placebo). OBJECTIVE: This study aimed to evaluate the reasons why health care workers chose to participate in the MeCOVID and EPICOS trials, as well as why they chose one over the other. METHODS: Both trials were offered to health care workers through an internal news bulletin. After an initial screening visit, all subjects were asked to respond to a web-based survey. RESULTS: In the first month, 206 health care workers were screened and 160 were randomized. The survey participation was high at 73.3%. Health care workers cited "to contribute to scientific knowledge" (n=80, 53.0%), followed by "to avoid SARS-CoV-2 infection" (n=33, 21.9%) and "the interest to be tested for SARS-CoV-2" (n=28, 18.5%), as their primary reasons to participate in the trials. We observed significant differences in the expected personal benefits across physicians and nurses (P=.01). The vast majority of volunteers (n=202, 98.0%) selected the MeCOVID trial, their primary reason being their concern regarding adverse reactions to treatments in the EPICOS trial (n=102, 69.4%). CONCLUSIONS: Health care workers' reasons to participate in prophylaxis trials in an acute pandemic context appear to be driven largely by their desire to contribute to science and to gain health benefits. Safety outweighed efficacy when choosing between the two clinical trials.


Subject(s)
Attitude of Health Personnel , COVID-19/drug therapy , COVID-19/psychology , Health Personnel/psychology , Randomized Controlled Trials as Topic/psychology , Adult , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Randomized Controlled Trials as Topic/methods , SARS-CoV-2/isolation & purification , Surveys and Questionnaires
7.
J Clin Epidemiol ; 139: 68-79, 2021 11.
Article in English | MEDLINE | ID: covidwho-1466592

ABSTRACT

OBJECTIVE: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. STUDY DESIGN: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. RESULTS: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled <50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect. CONCLUSIONS: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs. REGISTRATION: CRD42020192095.


Subject(s)
COVID-19/prevention & control , Randomized Controlled Trials as Topic/methods , Research Design/standards , COVID-19/epidemiology , Epidemiologic Studies , Humans
10.
Med Hypotheses ; 146: 110436, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1386311

ABSTRACT

Dental professionals work closely with patients and present an increased risk of person-to-person transmission of SARS-CoV-2. Moreover, the use of ultrasonic scalers, air-water syringes, and slow and high-speed handpieces, which are common in the dental office, generate spatter and aerosol. The use of preprocedural mouthrinses has been proposed to reduce the viral load in saliva and oropharyngeal tissues, thus decreasing viral load in dental aerosol. Although some mouthrinses demonstrates an antiviral effect, there is limited evidence about the clinical efficacy of any mouthrinse in the reduction of SARS-CoV-2 in the dental aerosol. We hypothesized that mouthrinses may reduce SARS-CoV-2 viral load in the oropharynx and its fluids reducing viral load in dental aerosol. The potential use of mouthrinses is discussed, along with proposal of in vitro and clinical studies, in order to evaluate this hypothesis. If this hypothesis holds true, dental professionals and patients may benefit from the routine use of preprocedural mouthrinses.


Subject(s)
COVID-19/transmission , COVID-19/virology , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Models, Biological , Mouthwashes/therapeutic use , SARS-CoV-2/isolation & purification , Viral Load , Aerosols , Antiviral Agents/therapeutic use , COVID-19/prevention & control , Dental Auxiliaries , Dentists , Disease Reservoirs/virology , Humans , In Vitro Techniques , Mouthwashes/chemistry , Oropharynx/virology , Pandemics/prevention & control , Randomized Controlled Trials as Topic/methods , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Saliva/virology
11.
Br J Anaesth ; 127(6): 834-844, 2021 12.
Article in English | MEDLINE | ID: covidwho-1377666

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression. METHODS: We performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality. Secondary outcomes included need for mechanical ventilation and ICU admission. Data sources were PubMed, Embase, MedRxiv, and the Cochrane library on July 2, 2021. RESULTS: We identified 17 RCTs that recruited 15 587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs 25.5%; odds ratio [OR]=0.94 [0.85-1.04]; P=0.23; I2=4%; TSA adjusted confidence interval [CI], 0.84-1.05), or reduction in need for mechanical ventilation (15.7% vs 15.4%; OR=1.01 [0.92-1.11]; P=0.82; I2=0%; TSA adjusted CI, 0.91-1.13), or ICU admission (22.4% vs 16.7%; OR=0.80 [0.21-3.09]; P=0.75; I2=63%; TSA adjusted CI, 0.0-196.05). Meta-regression did not reveal association with titre of convalescent plasma, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies. CONCLUSIONS: In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma treatment. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission. CLINICAL TRIAL REGISTRATION: CRD42021234201 (PROSPERO).


Subject(s)
COVID-19/therapy , Randomized Controlled Trials as Topic/methods , COVID-19/diagnosis , COVID-19/mortality , Humans , Immunization, Passive/mortality , Regression Analysis , Respiration, Artificial/mortality , Respiration, Artificial/trends , Treatment Outcome
12.
Pharmacol Res ; 173: 105848, 2021 11.
Article in English | MEDLINE | ID: covidwho-1373221

ABSTRACT

Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses. Age-associated decline in sex steroid hormone levels may mediate proinflammatory reactions in older adults, thereby increasing their risk of adverse outcomes, whereas sex hormones and/or sex hormone receptor modulators may attenuate the inflammatory response and provide benefit to COVID-19 patients. While multiple pharmacological options including anticoagulants, glucocorticoids, antivirals, anti-inflammatory agents and traditional Chinese medicine preparations have been tested to treat COVID-19 patients with varied levels of evidence in terms of efficacy and safety, information on sex-targeted treatment strategies is currently limited. Women may have more benefit from COVID-19 vaccines than men, despite the occurrence of more frequent adverse effects, and long-term safety data with newly developed vectors are eagerly awaited. The prevalent inclusion of men in randomized clinical trials (RCTs) with subsequent extrapolation of results to women needs to be addressed, as reinforcing sex-neutral claims into COVID-19 research may insidiously lead to increased inequities in health care. The huge worldwide effort with over 3000 ongoing RCTs of pharmacological agents should focus on improving knowledge on sex, gender and age as pillars of individual variation in drug responses and enforce appropriateness.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Health Equity/trends , Pharmacology, Clinical/trends , Randomized Controlled Trials as Topic/methods , Sex Characteristics , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/blood , COVID-19/drug therapy , COVID-19/immunology , Gonadal Steroid Hormones/antagonists & inhibitors , Gonadal Steroid Hormones/blood , Humans , Pharmacology, Clinical/methods , Precision Medicine/methods , Precision Medicine/trends
13.
J Postgrad Med ; 67(3): 134-138, 2021.
Article in English | MEDLINE | ID: covidwho-1367979

ABSTRACT

Objectives: We evaluated the extent of consent declines and consent withdrawals during the COVID-19 pandemic as seen in published randomized controlled trials (RCTs) and compared it with non-COVID-19 RCTs published at the same time and two historical controls. Methods: PubMed/Medline only was searched using key-word "COVID-19" and "RCTs" separately, and filtered for COVID-19 RCTs and non-COVID-19 RCTs respectively, published during a nine-month period (1 Feb - 1 Nov 2020). Exclusions were study protocols, observational studies, interim analysis of RCT data and RCTs with missing data. Primary outcome measures were the proportion of consent declines and consent withdrawals as percentage of total participants screened and randomized respectively in COVID-19 RCTs. We compared consent declines and consent withdrawals of COVID-19 RCTs with non-COVID-19 RCTs and two earlier studies on the same topic that served as historical controls (non-pandemic setting). Results: The search yielded a total of 111 COVID-19 RCTs and 49 non-COVID-19 RCTs. Of these, 39 (35.13%) COVID-19 RCTs and 11 (22.45%) non-COVID-19 RCTs were finally analysed. A total of 770/17759 (4.3%) consent declines and 100/7607 (1.31%) consent withdrawals were seen in 39 COVID-19 RCTs. A significant difference was observed in consent declines between COVID-19 vs non-COVID-19 RCTs [4.3% vs 11.9%, p < 0.0001] and between COVID-19 RCTs vs two historical controls [(4.3% vs 8.6%, p < 0.0001) and (4.3% vs 21.1%, p < 0.0001), respectively]. Conclusion: RCTs conducted during the COVID-19 pandemic appear to have significantly lower consent declines relative to non-COVID-19 RCTs during pandemic and RCTs conducted in non-pandemic settings.


Subject(s)
COVID-19 , Informed Consent , Patient Selection/ethics , Randomized Controlled Trials as Topic , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/therapy , Ethics, Research , Humans , Informed Consent/ethics , Informed Consent/legislation & jurisprudence , Informed Consent/standards , Randomized Controlled Trials as Topic/ethics , Randomized Controlled Trials as Topic/methods , SARS-CoV-2
17.
Expert Rev Vaccines ; 20(8): 1013-1025, 2021 08.
Article in English | MEDLINE | ID: covidwho-1284827

ABSTRACT

INTRODUCTION: Several vaccine candidates have been developed using different platforms, including nucleic acids (DNA and RNA), viral vectors (replicating and non-replicating), virus-like particles, peptide-based, recombinant proteins, live attenuated, and inactivated virus modalities. Although many of these vaccines are undergoing pre-clinical trials, several large clinical trials investigating the clinical efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines have produced promising findings. AREAS COVERED: In this review, we provide a status update on COVID-19 vaccines currently undergoing clinical trials and discuss issues of concern beyond vaccine efficacy and safety, including dosing regimens, the mixed vaccine strategy, prior severe acute respiratory syndrome coronavirus-2 infection, antibody levels, cellular immunity and protection, variants of concern, COVID-19 vaccine distribution, vaccination willingness, herd immunity, immunity passports, and vaccine indications. EXPERT OPINION: Four vaccines have obtained emergency use authorization, 87 are at the clinical development stage, and 186 are in pre-clinical development. While the knowledge and development of COVID-19 vaccines is rapidly expanding, the benefits of COVID-19 vaccines must outweigh the potential risks of adverse events. To combat the COVID-19 pandemic, clinicians should consistently update COVID-19-associated information, and healthcare authorities and manufacturers should work together to provide adequate and appropriate vaccinations for the prevention of COVID-19. PLAIN LANGUAGE SUMMARY: What is the context?Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic: the coronavirus disease 2019 (COVID-19) outbreak. The development and implementation of the COVID-19 vaccine could be an important measure to control the COVID-19 pandemic.What is new?Several phase 3 clinical trials have demonstrated the effectiveness and safety of COVID-19 vaccines for the prevention of SARS-CoV-2 infections. Several COVID-19 vaccines have obtained emergency use authorization and been implemented in many countries. Although concerns regarding unusual blood clots and low platelet counts have been raised, the benefits of COVID-19 vaccines outweigh the potential risks of adverse events.What is the impact?Except for children, the COVID-19 vaccine is recommended for all people, including those pregnant or immunocompromised. Healthcare authorities should advise people receiving the vaccine that they must seek medical attention if they have associated thromboembolism and thrombocytopenia symptoms. More studies are necessary to determine the appropriate vaccine dose and regimen strategy, as well as the effectiveness of COVID-19 vaccines against variants of concerns. A global effort must be made to achieve widespread vaccination and herd immunity.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Patient Safety , Animals , COVID-19/epidemiology , Clinical Trials, Phase III as Topic/methods , Fatigue/chemically induced , Female , Fever/chemically induced , Headache/chemically induced , Humans , Immunocompromised Host/drug effects , Immunocompromised Host/physiology , Male , Pregnancy , Randomized Controlled Trials as Topic/methods , Treatment Outcome
20.
Can J Cardiol ; 37(9): 1353-1364, 2021 09.
Article in English | MEDLINE | ID: covidwho-1252583

ABSTRACT

The COVID-19 crisis led to a flurry of clinical trials activity. The COVID-evidence database shows 2814 COVID-19 randomized trials registered as of February 16, 2021. Most were small (only 18% have a planned sample size > 500) and the rare completed ones have not provided published results promptly (only 283 trial publications as of February 2021). Small randomized trials and observational, nonrandomized analyses have not had a successful track record and have generated misleading expectations. Different large trials on the same intervention have generally been far more efficient in producing timely and consistent evidence. The rapid generation of evidence and accelerated dissemination of results have led to new challenges for systematic reviews and meta-analyses (eg, rapid, living, and scoping reviews). Pressure to regulatory agencies has also mounted with massive emergency authorizations, but some of them have had to be revoked. Pandemic circumstances have disrupted the way trials are conducted; therefore, new methods have been developed and adopted more widely to facilitate recruitment, consent, and overall trial conduct. On the basis of the COVID-19 experience and its challenges, planning of several large, efficient trials, and wider use of adaptive designs might change the future of clinical research. Pragmatism, integration in clinical care, efficient administration, promotion of collaborative structures, and enhanced integration of existing data and facilities might be several of the legacies of COVID-19 on future randomized trials.


Subject(s)
COVID-19 , Pandemics , Randomized Controlled Trials as Topic , COVID-19/therapy , Clinical Trials as Topic/methods , Clinical Trials as Topic/standards , Clinical Trials as Topic/statistics & numerical data , Drug Repositioning , Humans , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/standards , Randomized Controlled Trials as Topic/statistics & numerical data , Research Design/standards , SARS-CoV-2
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