Conducting a phase III clinical trial in children during the COVID- 19 pandemic: Experience and lessons learnt from a clinical research facility of Nepal.

Clinical trials in humans are vital to test safety and efficacy of new interventions and are accompanied with the complexity of related regulatory guidelines, stringent time frame and financial burden particularly when participants are children. Conducting clinical trials in low and middle income countries, where 90% of global diseases occur, increases the complexity as resources, infrastructures, and experience related to clinical trials may be limited in some countries. During the COVID-19 pandemic, due to multiple infection control measures such as social distancing, lock-down of the societies, and increased work load of hospital workers, conducting clinical trials seemed very challenging. Related guidelines and recommendations on clinical trials required updates to adapt the situation for ongoing clinical trials to be continued and new clinical trials to be initiated. In this review report, we described the lessons learnt through our experiences, challenges we faced, and the mitigation measures implemented as a response while conducting a phase III clinical trial on a non-COVID-19 vaccine at a government children's hospital during the COVID-19 pandemic. We hope this report will contribute in lowering the obstacles to allow the successful completion of future studies, in countries where people live with the burden of vaccine-preventable diseases.

Coronary Artery Bypass Grafting Following COVID-19 Infection: Difficulties and Challenges.

The COVID-19 pandemic has raised challenges and dilemmas to perform cardiac surgery in the patients following COVID-19 infection due to lasting adverse impacts of the disease on the lungs. A 74-years-old patient, recently infected by COVID-19, with previous myocardial infarction and multiple percutaneous coronary interventions, in-stent thrombosis to the left anterior descending artery, and low resting saturation, presented with chest pain and underwent urgent coronary artery bypass grafting. His postoperative period remained challenging due to high oxygen requirements. He had otherwise an uneventful recovery and was discharged on domiciliary oxygen, which was weaned off over three months and he continues to do well at six months of follow-up. Keywords: Cardiac surgery; COVID-19; coronary artery bypass surgery; pandemic.

Kawasaki Disease like Multisystem Inflammatory Syndrome in a Toddler during SARS-CoV-2 Pandemic in Nepal.

Multisystem inflammatory syndrome in children is a new childhood inflammatory disorder associated with respiratory syndrome coronavirus 2 (SARS-CoV-2). This illness of elevated inflammatory markers and multiple organ involvement similar to Kawasaki disease is not commonly reported from Asia. A 17-month-old boy presented with acute onset fever, rash, non-exudative conjunctivitis and swellings of hands and legs. In x-ray chest there was infiltration on the right lower lobe and echocardiography showed evidence of coronary arteritis. The diagnosis of multisystem inflammatory syndrome in children was confirmed on the basis of characteristic clinical features and laboratory parameters fulfilling standard case definition for multisystem inflammatory syndrome in children. The child responded to treatment with intravenous immunoglobulin and high dose aspirin. Hence, amidst SARS-CoV-2 pandemic, multisystem inflammatory syndrome in children should be suspected and effectively treated even in a country like Nepal. Keywords: Kawasaki disease; multiple inflammatory syndrome in children; Nepal; respiratory syndrome coronavirus 2.

Facial Nerve Palsy in a Patient with Acute Pancreatitis: A Complication of Systemic Inflammation or a Mere Co-existence?

Acute pancreatitis can trigger a systemic inflammatory response leading to wide range of complications that could be local or systemic. Viruses have been implicated in most of the infective etiology of acute pancreatitis. Cranial nerve palsy in acute pancreatitis patient is a rare event. A 35-year-old male had mild pancreatitis which resolved with treatment. After a week of admission, he developed right sided facial palsy which gradually improved with oral steroids, acyclovir, and physiotherapy. Whether it was a complication of acute pancreatitis or a mere co-existence secondary to some infective cause could not be proven. Keywords: Acute pancreatitis; facial nerve palsy; viruses.

Preparedness for Coronavirus Disease in Hospitals of Nepal: A Nationwide Survey.

INTRODUCTION: Coronavirus disease pandemic has affected large number of people globally and has continued to spread. Preparedness of individual nations and the hospitals is important to effectively deal with the surge of cases. We aimed to obtain nation wide data from Nepal, about hospital preparedness for COVID-19. METHODS: Online questionnaire was prepared in accordance with the Center for Disease Control recommendations to assess preparedness of hospitals for COVID-19. The questionnaire was circulated to the over 800 doctors across the nation, who are the life members of six medical societies. RESULTS: We obtained 131 completed responses from all seven provinces. Majority of respondents had anaesthesiology as the primary specialty. Only 52 (39.7%) participants mentioned that their hospital had policy to receive suspected or proven cases with COVID-19. Presence of isolation ward was mentioned by 83 (63.4%) respondents, with only 9 (6.9%)mentioning the presence of airborne isolation. Supply of personal protective equipment (PPE) was inadequate as per 124 (94.7%) respondents. Critical care services for COVID-19 patients were possible only in hospitals of 42 (32.1%)respondents. RT-polymerase chain reaction could be performed only in the hospital of 6 (4.6%) respondents. CONCLUSIONS: It is apparent that most of the hospitals are not well prepared for management of patients with COVID-19. Resource allocation and policy making should be aimed to enhance national preparedness for the pandemic.

Comparison of fractional exhaled nitric oxide levels in chronic obstructive pulmonary disease, bronchial asthma and healthy subjects of Nepal.

INTRODUCTION: Fractional exhaled nitric oxide levels in exhaled breath can indicate ongoing eosinophilic airway inflammation, specifically in asthma. But its utility is being explored for central airway inflammations, including chronic obstructive pulmonary disease. Normal levels of fractional exhaled nitric oxide (FENO50) have been defined in different studies but not in Nepal. This study compares FENO50 levels in normal subjects, asthma and chronic obstructive pulmonary disease. METHODS: Single breath estimation of FENO50 was measured by a handheld electrochemical sensor-based device in normal non-smoking adults (n = 106), clinically controlled asthma (n = 106) and stable chronic obstructive pulmonary disease (n = 106). RESULTS: The geometric mean for FENO50 was 14 parts per billion (ppb) with a median of 16 ppb, first quartile at 11 ppb and third quartile at 20 ppb in normal non-smoking adults. The values were 31 ppb (geometric mean), 34 ppb (median), 17 ppb (first quartile) and 79 ppb (third quartile) in clinically controlled asthma. Similarly the values were 10 ppb (geometric mean), 11 ppb (median), 6 ppb (first quartile) and 17 ppb (third quartile) in stable chronic obstructive airway disease. The log-transformed data showed significantly higher FENO50 levels in the asthma group compared with the normal (p < 0.001) and chronic obstructive airway disease (p < 0.001). However, levels were similar between healthy and chronic obstructive airway disease groups (p = 0.08). CONCLUSIONS: FENO50 levels were higher in bronchial asthma (despite disease control) than in normal non-smoking adults and subjects with stable chronic obstructive pulmonary disease. Levels of FENO50 were similar between the chronic obstructive airway disease and normal groups.