Colchicine in COVID-19: an Old Drug, New Use.

Purpose of Review: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is a pandemic causing havoc globally. Currently, there are no Food and Drug Administration (FDA)-approved drugs to treat COVID-19. In the absence of effective treatment, off-label drug use, in lieu of evidence from published randomized, double-blind, placebo-controlled clinical trials, is common in COVID-19. Although it is vital to treat affected patients with antiviral drugs, there is a knowledge gap regarding the use of anti-inflammatory drugs in these patients. Recent Findings: Colchicine trials to combat inflammation in COVID-19 patients have not received much attention. We await the results of ongoing colchicine randomized controlled trials in COVID-19, evaluating colchicine's efficacy in treating COVID-19. Summary: This review gives a spotlight on colchicine's anti-inflammatory and antiviral properties and why colchicine may help fight COVID-19. This review summarizes colchicine's mechanism of action via the tubulin-colchicine complex. Furthermore, it discussed how colchicine interferes with several inflammatory pathways, including inhibition of neutrophil chemotaxis, adhesion, and mobilization; disruption of superoxide production, inflammasome inhibition, and tumor necrosis factor reduction; and its possible antiviral properties. In addition, colchicine dosing and pharmacokinetics, as well as drug interactions and how they relate to ongoing, colchicine in COVID-19 clinical trials, are examined.

A Neoadjuvant Chemotherapy Trial for Early Breast Cancer is Impacted by COVID-19: Addressing Vaccination and Cancer Trials Through Education, Equity, and Outcomes.

While COVID-19 vaccine distribution has addressed vulnerabilities related to age and comorbidities, there is a need to ensure vaccination of patients with cancer receiving experimental and routine treatment, where interruption of treatment by infection is likely to result in inferior outcomes. Among patients with cancer, those undergoing neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (Adj chemo) for early breast cancer (EBC) are at particularly high risk for inferior outcomes, in part, because optimal timing of chemotherapy is essential for promoting distant disease-free survival. COVID-19 data from the ongoing multicenter I-SPY 2 trial of NAC for EBC provides a window into the magnitude of the problem of treatment interruption, not only for the trial itself but also for routine Adj chemo. In the I-SPY 2 trial, 4.5% of patients had disruption of therapy by COVID-19, prior to wide vaccine availability, suggesting that nationally up to 5,700 patients with EBC were at risk for adverse outcomes from COVID-19 infection in 2020. To address this problem, vaccine education and public engagement are essential to overcome hesitancy, while equity of distribution is needed to address access. To accomplish these goals, healthcare organizations (HCO) need to not only call out disinformation but also engage the public with vaccine education and find common ground for vaccine acceptance, while partnering with state/local governments to improve efficiency of vaccine distribution. These approaches are important to improve trial access and to reduce susceptibility to COVID-19, as the pandemic could continue to impact access to clinical trials and routine cancer treatment.

Hormone replacement therapy after surgery for epithelial ovarian cancer.

BACKGROUND: Women who have undergone surgical treatment for epithelial ovarian cancer (EOC) may develop menopausal symptoms due to immediate loss of ovarian function following surgery and chemotherapy. Women may experience vasomotor symptoms, sleep disturbance, difficulty concentrating, sexual dysfunction, vaginal symptoms and accelerated osteoporosis. Although hormone replacement therapy (HRT) is the most effective treatment to relieve these symptoms, its safety has been questioned for women with EOC. OBJECTIVES: To assess the safety and efficacy of HRT for menopausal symptoms in women surgically treated for EOC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 6), MEDLINE via Ovid (1946 to 12 June 2019) and Embase via Ovid (1980 to 2019, week 23). We also handsearched conference reports and trial registries. There was no language restriction. SELECTION CRITERIA: We included randomized controlled trials (RCTs) with participants of any age and menopausal status who had undergone surgery for EOC and, after diagnosis and treatment, used any regimen and duration of HRT compared with placebo or no hormone therapy. We also included trials comparing different regimens or duration of administration of HRT. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies that met the inclusion criteria. They used Covidence to extract study characteristics, outcome data and to assess methodological quality of the included studies. MAIN RESULTS: Our search strategy identified 2617 titles, of which 2614 titles were excluded. Three studies, involving 350 women, met our inclusion criteria. Two of the studies included pre and postmenopausal women, and the third only included premenopausal women. The overall age range of those women included in the studies was 20 to 89.6 years old, with a median follow-up ranging from 31.4 months to 19.1 years. The geographical distribution of participants included Europe, South Africa and China. All stages and histological subtypes were included in two of the studies, but stage IV disease had been excluded in the third. The three included studies used a variety of HRT regimens (conjugated oestrogen with or without medroxyprogesterone and with or without nylestriol) and HRT administrations (oral, patch and implant), In all studies, the comparisons were made versus women who had not received HRT. The studies were at low or unclear risk of selection and reporting bias, and at high risk of performance, detection and attrition bias. The certainty of the evidence was low for overall survival and progression-free survival, and very low for quality-of-life assessment, incidence of breast cancer, transient ischaemic attack (TIA), cerebrovascular accident (CVA) and myocardial infarction (MI). Meta-analysis of these studies showed that HRT may improve overall survival (hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.54 to 0.93; 350 participants, 3 studies; low-certainty evidence). Quality-of-life assessment by use of the EORTC-C30 questionnaire was performed only in one study. We are uncertain whether HRT improves or reduces quality of life as the certainty of the evidence was assessed as very low (mean difference (MD) 13.67 points higher, 95% CI 9.26 higher to 18.08 higher; 1 study; 75 participants; very low-certainty evidence). Likewise, HRT may make little or no difference to progression-free survival (HR 0.76, 95% CI 0.57 to 1.01; 275 participants, 2 studies; low-certainty evidence). We are uncertain whether HRT improves or reduces the incidence of breast cancer (risk ratio (RR) 2.00, 95% CI 0.19 to 21.59; 225 participants, 2 studies; very low-certainty evidence); TIA (RR 5.00, 95% CI 0.24 to 102.42; 150 participants, 1 study; very low-certainty evidence); CVA (RR 0.67, 95% CI 0.11 to 3.88; 150 participants, 1 study; very low-certainty evidence); and MI (RR 0.20, 95% CI 0.01 to 4.10; 150 participants, 1 study; very low-certainty evidence). The incidence of gallstones was not reported in the included studies. AUTHORS' CONCLUSIONS: Hormone replacement therapy may slightly improve overall survival in women who have undergone surgical treatment for EOC, but the certainty of the evidence is low. HRT may make little or no difference to quality of life, incidence of breast cancer, TIA, CVA and MI as the certainty of the evidence has been assessed as very low. There may be little or no effect of HRT use on progression-free survival. The evidence in this review is limited by imprecision and incompleteness of reported relevant outcomes and therefore the results should be interpreted with caution. Future well-designed RCTs are required as this is an important area to women experiencing menopausal symptoms following surgical treatment for ovarian cancer, especially as doctors are often reluctant to prescribe HRT in this scenario. The evidence in this review is too limited to support or refute that HRT is very harmful in this population.

Pharmacotherapy in COVID-19; A narrative review for emergency providers.

INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords "COVID 19," "SARS-CoV-2," and "treatment." All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.

Droplet and Aerosol Generation With Mastoidectomy During the COVID-19 Pandemic: Assessment of Baseline Risk and Mitigation Measures With a High-performance Cascade Impactor.

HYPOTHESIS: Aerosols are generated during mastoidectomy and mitigation strategies may effectively reduce aerosol spread. BACKGROUND: An objective understanding of aerosol generation and the effectiveness of mitigation strategies can inform interventions to reduce aerosol risk from mastoidectomy and other open surgeries involving drilling. METHODS: Cadaveric and fluorescent three-dimensional printed temporal bone models were drilled under variable conditions and mitigation methods. Aerosol production was measured with a cascade impactor set to detect particle sizes under 14.1 µm. Field contamination was determined with examination under UV light. RESULTS: Drilling of cadaveric bones and three-dimensional models resulted in strongly positive aerosol production, measuring positive in all eight impactor stages for the cadaver trials. This occurred regardless of using coarse or cutting burs, irrigation, a handheld suction, or an additional parked suction. The only mitigation factor that led to a completely negative aerosol result in all eight stages was placing an additional microscope drape to surround the field. Bone dust was scattered in all directions from the drill, including on the microscope, the surgeon, and visually suspended in the air for all but the drape trial. CONCLUSIONS: Aerosols are generated with drilling the mastoid. Using an additional microscope drape to cover the surgical field was an effective mitigation strategy to prevent fine aerosol dispersion while drilling.

From Structural Studies to HCV Vaccine Design.

Hepatitis C virus (HCV) is a serious and growing public health problem despite recent developments of antiviral therapeutics. To achieve global elimination of HCV, an effective cross-genotype vaccine is needed. The failure of previous vaccination trials to elicit an effective cross-reactive immune response demands better vaccine antigens to induce a potent cross-neutralizing response to improve vaccine efficacy. HCV E1 and E2 envelope (Env) glycoproteins are the main targets for neutralizing antibodies (nAbs), which aid in HCV clearance and protection. Therefore, a molecular-level understanding of the nAb responses against HCV is imperative for the rational design of cross-genotype vaccine antigens. Here we summarize the recent advances in structural studies of HCV Env and Env-nAb complexes and how they improve our understanding of immune recognition of HCV. We review the structural data defining HCV neutralization epitopes and conformational plasticity of the Env proteins, and the knowledge applicable to rational vaccine design.

Myopericarditis in a previously healthy adolescent male following COVID-19 vaccination: A case report.

We report the case of a previously healthy 16-year-old male who developed myopericarditis following the second dose of his Pfizer-BioNTech COVID-19 vaccine, with no other identified triggers. Adolescents and young adults experiencing chest pain after COVD-19 vaccination should seek emergent medical care, and emergency providers should have a low threshold to consider and evaluate for myopericarditis. More data are needed to better understand the potential association between COVID-19 vaccines and myopericarditis. If a true causal link is identified, the risk must also be viewed in context with the millions of patients who have been safely vaccinated and the known morbidity and mortality from COVID-19 infection. As we see widespread vaccine rollout, it is important that all potential adverse reactions are reported as we continue to monitor for more rare but potentially serious side effects not identified in vaccination trials.

Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing coronavirus disease 2019 (COVID-19) pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, COVID-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine loading dose then 400 mg once or twice weekly for 12 weeks. The primary endpoint was confirmed or probable COVID-19-compatible illness. We measured hydroxychloroquine whole-blood concentrations. RESULTS: We enrolled 1483 healthcare workers, of whom 79% reported performing aerosol-generating procedures. The incidence of COVID-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events/person-year with once-weekly and 0.28 events/person-year with twice-weekly hydroxychloroquine compared with 0.38 events/person-year with placebo. For once-weekly hydroxychloroquine prophylaxis, the hazard ratio was .72 (95% CI, .44-1.16; P = .18) and for twice-weekly was .74 (95% CI, .46-1.19; P = .22) compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed COVID-19-compatible illness (154 ng/mL) versus participants without COVID-19 (133 ng/mL; P = .08). CONCLUSIONS: Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19-compatible illness among healthcare workers. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT04328467.

Chemoprophylaxis trial designs in epidemics: insights from a systematic review of COVID-19 study registrations.

BACKGROUND: Chemoprophylactics against emerging epidemic and pandemic infectious diseases offer potential for prevention but require efficacy and safety analysis before widespread use can be recommended. Chemoprophylaxis with repurposed drugs enables deployment ahead of development of novel vaccines. It may have particular utility as a stopgap ahead of vaccine deployment or when vaccines become less effective on virus variants, in countries where there may be structural inaccessibility to vaccines or in specific risk-groups. Rapid implementation of robust trial designs is a persistent challenge in epidemics. We systematically reviewed SARS-CoV-2 and COVID-19 chemoprophylaxis trial registrations from the first 21 weeks of the pandemic to critically appraise significant design features and alignment of study populations to clinical and public health uses, and describe candidate chemoprophylactic agents. METHODS: We searched online international trial databases from 31 Dec 2019 to 26 May 2020 using keywords "proph*" or "prevention". Trial protocols assessing efficacy of chemoprophylactic agents for COVID-19 were included. Trial components were screened for eligibility and relevant studies extracted. Key trial design features were assessed. RESULTS: We found 76 chemoprophylaxis study registrations, proposing enrolment of 208,367 people with median size of 490 (IQR 262-1710). A randomised design was specified for 63 trials, 61 included a control group and total proposed enrolment size was 197,010, median 600 (IQR 236-1834). Four protocols provided information on effect size sought. We estimate that for a control group attack rate of 10%, 66% of trials would be underpowered to detect a 50% effect size, and 97% of trials would be underpowered to detect a 30% effect size (at the 80% level). We found evidence of adaptive design in one trial registration only. Laboratory-confirmed infection with or without symptoms was the most common primary outcome. Polymerase chain reaction testing alone was used in 46% of trials, serological testing in 6.6% and 14.5% used both testing methods. Healthcare workers were the target population in 52/79 (65.8%) trials: 49 pre-exposure prophylaxis (PrEP) and 3 post-exposure prophylaxis (PEP). Sixteen trials (20.3%) planned PEP in close contacts. Five studies (6.3%) considered chemoprophylaxis in clinical-risk patients. Older adults were the focus of recruitment in only 3 (3.8%) studies (all long-term care facilities). Two (2.5%) studies of PrEP in the general population included older adults. Hydroxychloroquine was the most common candidate agent in 55/79 trials (69.6%), followed by chloroquine (4/79, 5.0%) and lopinavir/ritonavir (3/79, 3.8%). CONCLUSION: Many registered COVID-19 chemoprophylaxis efficacy trials were underpowered to detect clinically meaningful protection at epidemiologically informed attack rates. This, compounded with the time that has taken to organise these trials as compared to the rapid development of COVID-19 vaccines, has rendered these trials of marginal importance. International coordination mechanisms and collaboration is required. Supporting the design of feasible chemoprophylaxis trials, large enough to generate strong evidence, early on in an epidemic using adaptive platform trial designs will allow structured entry and exit of candidate agents and rapid stand-up of trial infrastructure. REVIEW PROTOCOL REGISTRATION: Our protocol is registered at https://www.osf.io/vp56f on May 20, 2020.

Videoconferenced Yoga Interventions for Cancer Patients and their Caregivers during the COVID-19 Pandemic: A Report from a Clinician's Perspective.

BACKGROUND: The acceptability of videoconferencing delivery of yoga interventions in the advanced cancer setting is relatively unexplored. The current report summarizes the challenges and solutions of the transition from an in-person (ie, face-to-face) to a videoconference intervention delivery approach in response to the Coronavirus Disease pandemic. METHOD: Participants included patient-family caregiver dyads who were enrolled in ongoing yoga trials and 2 certified yoga therapists who delivered the yoga sessions. We summarized their experiences using recordings of the yoga sessions and interventionists' progress notes. RESULTS: Out of 7 dyads participating in the parent trial, 1 declined the videoconferenced sessions. Participants were between the ages of 55 and 76 and mostly non-Hispanic White (83%). Patients were mainly male (83%), all had stage III or IV cancer and were undergoing radiotherapy. Caregivers were all female. Despite challenges in the areas of technology, location, and setting, instruction and personal connection, the overall acceptability was high among patients, caregivers, and instructors. Through this transition process, solutions to these challenges were found, which are described here. CONCLUSION: Although in-person interventions are favored by both the study participants and the interventionists, videoconference sessions were deemed acceptable. All participants had the benefit of a previous in-person experience, which was helpful and perhaps necessary for older and advanced cancer patients requiring practice modifications. In a remote setting, the assistance of caregivers seems particularly beneficial to ensure practice safety. CLINICALTRIALS.GOV: NCT03948100; NCT02481349.

Advances in mesenchymal stem cell therapy for immune and inflammatory diseases: Use of cell-free products and human pluripotent stem cell-derived mesenchymal stem cells.

Mesenchymal stem cell therapy (MSCT) for immune and inflammatory diseases continues to be popular based on progressive accumulation of preclinical mechanistic evidence. This has led to further expansion in clinical indications from graft rejection, autoimmune diseases, and osteoarthritis, to inflammatory liver and pulmonary diseases including COVID-19. A clear trend is the shift from using autologous to allogeneic MSCs, which can be immediately available as off-the-shelf products. In addition, new products such as cell-free exosomes and human pluripotent stem cell (hPSC)-derived MSCs are exciting developments to further prevalent use. Increasing numbers of trials have now published results in which safety of MSCT has been largely demonstrated. While reports of therapeutic endpoints are still emerging, efficacy can be seen for specific indications-including graft-vs-host-disease, strongly Th17-mediated autoimmune diseases, and osteoarthritis-which are more robustly supported by mechanistic preclinical evidence. In this review, we update and discuss outcomes in current MSCT clinical trials for immune and inflammatory disease, as well as new innovation and emerging trends in the field.

A simple, sensitive, and low-cost FACS assay for detecting antibodies against the native SARS-CoV-2 spike protein.

BACKGROUND: Hamburg is a city state of approximately 1.9 Mio inhabitants in Northern Germany. Currently, the COVID-19 epidemic that had largely subsided during last summer is resurging in Hamburg and in other parts of the world, underlining the need for additional tools to monitor SARS-CoV-2 antibody responses. AIM: We aimed to develop and validate a simple, low-cost assay for detecting antibodies against the native coronavirus 2 spike protein (CoV-2 S) that does not require recombinant protein or virus. METHOD: We transiently co-transfected HEK cells or CHO cells with expression vectors encoding CoV-2 S and nuclear GFP. Spike protein-specific antibodies in human serum samples bound to transfected cells were detected with fluorochrome conjugated secondary antibodies by flow cytometry orimmunofluorescence microscopy. We applied this assay to monitor antibody development in COVID-19 patients, household contacts, and hospital personnel during the ongoing epidemic in the city state of Hamburg. RESULTS: All recovered COVID-19 patients showed high levels of CoV-2 S-specific antibodies. With one exception, all household members that did not develop symptoms also did not develop detectable antibodies. Similarly, lab personnel that worked during the epidemic and followed social distancing guidelines remained antibody-negative. CONCLUSION: We conclude that high-titer CoV-2 S-specific antibodies are found in most recovered COVID-19 patients and in symptomatic contacts, but only rarely in asymptomatic contacts. The assay may help health care providers to monitor disease progression and antibody responses in vaccination trials, to identify health care personnel that likely are resistant to re-infection, and recovered individuals with high antibody titers that may be suitable asplasma and/or antibody donors.

A century of BCG: Impact on tuberculosis control and beyond.

BCG turns 100 this year and while it might not be the perfect vaccine, it has certainly contributed significantly towards eradication and prevention of spread of tuberculosis (TB). The search for newer and better vaccines for TB is an ongoing endeavor and latest results from trials of candidate TB vaccines such as M72AS01 look promising. However, recent encouraging data from BCG revaccination trials in adults combined with studies on mucosal and intravenous routes of BCG vaccination in non-human primate models have renewed interest in BCG for TB prevention. In addition, several well-demonstrated non-specific effects of BCG, for example, prevention of viral and respiratory infections, give BCG an added advantage. Also, BCG vaccination is currently being widely tested in human clinical trials to determine whether it protects against SARS-CoV-2 infection and/or death with detailed analyses and outcomes from several ongoing trials across the world awaited. Through this review, we attempt to bring together information on various aspects of the BCG-induced immune response, its efficacy in TB control, comparison with other candidate TB vaccines and strategies to improve its efficiency including revaccination and alternate routes of administration. Finally, we discuss the future relevance of BCG use especially in light of its several heterologous benefits.

The angiotensin II type 1 receptor blocker valsartan in the battle against COVID-19.

OBJECTIVE: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) uses the host's angiotensin-converting enzyme 2 (ACE2) as a cellular entry point. Therefore, modulating ACE2 might impact SARS-CoV-2 viral replication, shedding, and coronavirus disease 2019 (COVID-19) severity. Here, it was investigated whether the angiotensin II type 1 receptor blocker valsartan alters the expression of renin-angiotensin system (RAS) components, including ACE2, in human adipose tissue (AT) and skeletal muscle. METHODS: A randomized, double-blind, placebo-controlled clinical trial was performed, in which 36 participants (BMI 31.0 ± 0.8 kg/m2 ) with impaired glucose metabolism received either valsartan or placebo for 26 weeks. Before and after 26 weeks' treatment, abdominal subcutaneous AT and skeletal muscle biopsies were obtained, and gene expression of RAS components was measured by quantitative reverse transcription polymerase chain reaction. RESULTS: Valsartan treatment did not significantly impact the expression of RAS components, including ACE2, in AT and skeletal muscle. CONCLUSIONS: Given the pivotal role of ACE2 in SARS-CoV-2 spread and the clinical outcomes in COVID-19 patients, the data suggest that the putative beneficial effects of angiotensin II type 1 receptor blockers on the clinical outcomes of patients with COVID-19 may not be mediated through altered ACE2 expression in abdominal subcutaneous AT.

Factors associated with parents' willingness to enroll their children in trials for COVID-19 vaccination.

The coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented global toll and vaccination is needed to restore healthy living. Timely inclusion of children in vaccination trials is critical. We surveyed caregivers of children seeking care in 17 Emergency Departments (ED) across 6 countries during the peak of the pandemic to identify factors associated with intent to participate in COVID-19 vaccine trials. Questions about child and parent characteristics, COVID-19 expressed concerns and parental attitudes toward participation in a trial were asked.Of 2768 completed surveys, 18.4% parents stated they would enroll their child in a clinical trial for a COVID-19 vaccine and 14.4% would agree to a randomized placebo-controlled study. Factors associated with willingness to participate were parents agreeing to enroll in a COVID-19 vaccine trial themselves (Odds Ratio (OR) 32.9, 95% Confidence Interval (CI) (21.9-51.2)) having an older child (OR 1.0 (1.0-1.01)), having children who received all vaccinations based on their country schedule (OR 2.67 (1.35-5.71)) and parents with high school education or lower (OR 1.79 (1.18-2.74)). Mothers were less likely to enroll their child in a trial (OR 0.68 (0.47-0.97)). Only one fifth of families surveyed will consider enrolling their child in a vaccine trial. Parental interest in participation, history of vaccinating their child, and the child being older all are associated with parents allowing their child to participate in a COVID vaccine trial. This information may help decision-makers and researchers shape their strategies for trial design and participation engagement in upcoming COVID19 vaccination trials.

Slowing Down Myopia Progression with Contact Lenses - Everyday Cases from the Clinic.

BACKGROUND: An estimated 49.8% of the world population will be myopic by 2050. Multifocal contact lenses (MFCLs) and orthokeratology (OK) reduce peripheral retinal hyperopic defocus, which animal studies have shown to positively impact eye growth. MFCLs are expected to slow myopic progression by 20 - 50% and OK by 30 - 60%, making them valuable therapeutic tools. In view of the guidelines for myopia management published by the International Myopia Institute in 2019, the aim of this retrospective data analysis of a tertiary care center was to review past experience with OK and MFCLs for myopia control and gain information to update current practice. PATIENTS AND METHODS: The contact lens (CL) database of the Eye Clinic of the University Hospital of Basel was searched with the label "myopia progression" between January 2012 - 2020. Patients were included if they gave informed consent, were younger than 19 years old at baseline, and had no ocular comorbidities that could potentially compromise vision. Primary outcomes were progression of spherical equivalent refraction for MFCL patients and progression of axial length (AL) for the OK group, comparing with historical data from OK trials. Secondary outcomes were the presence of risk factors for myopia, age, refractive error at baseline, follow-up duration, and adverse effects during therapy. RESULTS: Twenty-one patients could be included, with a mean age of 12.80 ± 3.32 years (y) at baseline. The majority of patients were older than 12 years and already myopic (- 3.89 ± 2.30 diopters) when control treatment was started. Overall, follow-up ranged from 0.08 to 6.33 years (2.03 ± 1.66 y). In the patients treated with MFCLs, myopia control improved significantly when patients changed from spectacles to MFCLs. In the OK group, 14% dropped out during the first year and 2 patients had multiple AL measurements during therapy, which showed a slower growth of AL when compared to other OK trials and controls with spectacles. There were two cases of non-severe keratitis. Environmental risk factors had not been documented and only 48% of clinical records had a documented family risk assessment. CONCLUSION: Patients showed a slower myopia progression under MFCLs or OK, which supports their role as a treatment option in myopia management. In this regard, AL measurement is an important additional parameter to be included in the assessment of myopia progression in clinical practice. Identification of children at risk of developing high/pathologic myopia (family history, environmental risk factors) needs to improve so that the first stages of myopic shift can be recognized and targeted. Changes in lifestyle should be actively encouraged, especially when the impact of decreases in outdoor time secondary to COVID-19 is yet to become clear.