The impact of the first peak of the COVID-19 pandemic on childhood myopia control practice patterns among ophthalmologists-an international pediatric ophthalmology and strabismus council global perspective.

BACKGROUND: The prevalence of myopia keeps increasing during the COVID-19 pandemic. We aimed to map the worldwide treatment preferences of ophthalmologists managing myopia control during the first wave of the pandemic. METHODS: An online questionnaire inquiring about pharmacological and optical treatment patterns during the first half of 2020 was sent to pediatric ophthalmology as well as general ophthalmology memberships worldwide. The results among pediatric ophthalmologists were compared to a previous study we performed before the pandemic. RESULTS: A total of 2269 respondents from 94 countries were included. Most respondents were pediatric ophthalmologists (64.6%), followed by ophthalmologists from other subspecialties (32.3%). The preferred modality for all geographical regions was a combination therapy of pharmacological and optical treatments. When evaluated independently, the pharmacological treatment was more popular than the optical treatment in most regions other than East Asia (P < 0.001). Compared to a pre-pandemic questionnaire, the participation of pediatric ophthalmologists affiliated with non-university hospitals increased. Additionally, the prevalence of respondents utilizing either any type of pharmacological treatment and those that using only evidence-based treatments increased globally. Although a decline in the use of optical treatment was evident worldwide, the use of evidence-based optical treatments increased. CONCLUSION: Ophthalmologists around the world preferred a combination therapy of pharmacological and optical treatments. More pediatric ophthalmologists treated myopia progression and preferred a better evidence-based approach to control myopia. These trends reflect a positive response and more awareness of the rising prevalence of myopia due to the increased burden of myopia imposed by the COVID-19 pandemic.

Treatment for acute respiratory distress syndrome in adults: a narrative review of phase 2 and 3 trials.

INTRODUCTION: Ventilatory management and general supportive care of acute respiratory distress syndrome (ARDS) in the adult population have led to significant clinical improvements, but morbidity and mortality remain high. Pharmacologic strategies acting on the coagulation cascade, inflammation, oxidative stress, and endothelial cell injury have been targeted in the last decade for patients with ARDS, but only a few of these have shown potential benefits with a meaningful clinical response and improved patient outcomes. The lack of availability of specific pharmacologic treatments for ARDS can be attributed to its complex pathophysiology, different risk factors, huge heterogeneity, and difficult classification into specific biological phenotypes and genotypes. AREAS COVERED: In this narrative review, we briefly discuss the relevance and current advances in pharmacologic treatments for ARDS in adults and the need for the development of new pharmacological strategies. EXPERT OPINION: Identification of ARDS phenotypes, risk factors, heterogeneity, and pathophysiology may help to design clinical trials personalized according to ARDS-specific features, thus hopefully decreasing the rate of failed clinical pharmacologic trials. This concept is still under clinical investigation and needs further development.

Seven days treatment with the angiotensin II type 2 receptor agonist C21 in hospitalized COVID-19 patients; a placebo-controlled randomised multi-centre double-blind phase 2 trial.

BACKGROUND: COVID-19 morbidity and mortality remains high and the need for safe and effective drugs continues despite vaccines. METHODS: Double-blind, placebo-controlled, multi-centre, randomised, parallel group phase 2 trial to evaluate safety and efficacy of oral angiotensin II type 2 receptor agonist C21 in hospitalized patients with COVID-19 and CRP ≥ 50-150 mg/L conducted at eight sites in India (NCT04452435). Patients were randomly assigned 100 mg C21 bid or placebo for 7 days in addition to standard of care. Primary endpoint: reduction in CRP. The study period was 21 July to 13 October 2020. FINDINGS: 106 patients were randomised and included in the analysis (51 C21, 55 placebo). There was no significant group difference in reduction of CRP, 81% and 78% in the C21 and placebo groups, respectively, with a treatment effect ratio of 0.85 [90% CI 0.57, 1.26]. In a secondary analysis in patients requiring supplemental oxygen at randomisation, CRP was reduced in the C21 group compared to placebo. At the end of the 7-day treatment, 37 (72.5%) and 30 (54.5%) of the patients did not require supplemental oxygen in the C21 and placebo group, respectively (OR 2.20 [90% CI 1.12, 4.41]). A post hoc analysis showed that at day 14, the proportion of patients not requiring supplemental oxygen was 98% and 80% in the C21 group compared to placebo (OR 12.5 [90% CI 2.9, 126]). Fewer patients required mechanical ventilation (one C21 patient; four placebo patients), and C21 was associated with a numerical reduction in the mortality rate (one vs three in the C21 and placebo group, respectively). Treatment with C21 was safe and well tolerated. INTERPRETATION: Among hospitalised patients with COVID-19 receiving C21 for 7 days there was no reduction in CRP compared to placebo. However, a post-hoc analysis indicated a marked reduction of requirement for oxygen at day 14. The day 14 results from this study justify further evaluation in a Phase 3 study and such a trial is currently underway. FUNDING: Vicore Pharma AB and LifeArc, UK.

COVID-19: general overview, pharmacological options and ventilatory support strategies.

The novel coronavirus called "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2) caused an outbreak in December 2019, starting from the Chinese city of Wuhan, in the Hubei province, and rapidly spreading to the rest of the world. Consequently, the World Health Organization (WHO) declared that the coronavirus disease of 2019 (COVID-19) can be characterized as a pandemic. During COVID-19 several immunological alterations have been observed: in plasma of severe patients, inflammatory cytokines are at a much higher concentration ("cytokine storm"). These aspects are associated with pulmonary inflammation and parenchymal infiltrates with an extensive lung tissue damage in COVID-19 patients. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials (RCTs) for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments are currently being evaluated worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. As for ventilatory strategies, at the moment there are still no consistent data published about the different approaches and how they may influence disease progression. What will probably represent the real solution to this pandemic is the identification of a safe and effective vaccine, for which enormous efforts and investments are being put in place. This review will summarize the state-of-the-art of COVID-19 current treatment options and those potentially available in the future, as well as high flow oxygen therapy and non-invasive mechanical ventilation approaches.

Designing therapeutic strategies to combat severe acute respiratory syndrome coronavirus-2 disease: COVID-19.

A highly contagious coronavirus disease COVID-19 caused by a recently identified severe acute respiratory syndrome CoV-2 (SARS-CoV-2) initially detected in Wuhan, China has spread worldwide and become a major health crisis in the absence of specific vaccine or antiviral drugs. SARS-CoV-2 infection has resulted in overwhelming number of reported deaths. Unfortunately it is still spreading uncontrollably despite implementing stringent protective measures. Rapid development of effective therapeutic strategies for treatment and prevention of infection is crucially required. Although genomic characterization has assisted in unfolding various aspects of SARS-CoV-2 but development of specific antiviral drugs and vaccine against COVID-19 is still a worldwide challenge. Understanding the disease pathological course underlying the clinical manifestations of COVID-19 is imperative to identify the vital targets for drug development. SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) receptor to enter the host cell and primarily target type II alveolar cells. COVID-19 disease progression is associated with distressed immune functions and hyper active inflammatory system leading to development of cytokine storm which is a vital factor involved in disease advancement. The current review elucidates the disease pathology and summarizes the possible therapeutic options to battle against COVID-19 on the basis of current state of understanding about SARS-CoV-2 pathogenic pathways and knowledge gained from previous SARS and MERS-CoV epidemics. Therapeutic strategies to treat and prevent infection as well as to suppress the disease progression to reduce severity and mortality rate is discussed. Drug candidates currently under consideration and undergoing clinical trials for COVID-19 treatment are highlighted.