Famotidine

In this trial, “integrated care” comprises two integrated care pathway interventions, cluster-randomised at Primary Care Network level: Coverscan™ (community based, multi-organ MRI with clinical decision support)(15) and Living with COVID Recovery™ (enhanced community based, digitally enabled rehabilitation)(16). The Coverscan will have a standardised report. For the first 100 scans across sites, there will be report by an independent radiologist, and a virtual, weekly multidisciplinary meeting to discuss any cases and potential implications of findings, management and/or referral to specialists. We did not have or develop an algorithmic management approach (i.e. clinical decision support) or a “manual” because the organ dysfunction in Long Covid is still being defined and a manual would involve approaches to any possible finding in lungs, heart, liver, pancreas and kidneys, which is not feasible, at present.
“Usual care” comprises usual investigations (e.g. routine blood tests, electrocardiogram, chest radiograph or exercise tolerance test); and self-managed rehabilitation with online resources (Your COVID Recovery™: https:\\www.yourcovidrecovery.nhs.uk) in the LC clinic pathway, which is standard of care.
In a nested, open label, adaptive platform trial, a 12-week course of one of three drug arms will be evaluated (individual level randomisation): famotidine+loratadine, colchicine and rivaroxaban, compared with no drugs.

Regular use of PPIs or H2RAs was firstly assessed by participants using a touchscreen questionnaire. The participants were asked “Do you regularly take any prescription medications?”. ‘Regularly’ was routinely defined as most days of the week for the last 4 weeks. If participant selected ‘Yes’ or ‘Unsure’, then they would be asked by a trained staff: “In the touch screen you said you are taking regular prescription medications. Can you now tell me what these are?” The recorded types of PPIs included omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. The kinds of H2RAs included ranitidine, cimetidine, famotidine and nizatidine.

We queried the MIMIC-IV database for all adult intensive care unit (ICU) stays from 2008 to 2019. Patients 18 years or older, were included if they met the sepsis-3 criteria [22 (link)]. We acquired the following information for each patient indexed by stay ID: age, gender, and risk scores including APS III [23 (link)], SAPS II [24 (link)], SOFA [25 (link)], OASIS [26 (link)], and the Charlson comorbidity index [27 (link)]. We also extracted data on time from ICU admission to H2RA administration (if applicable), and time from ICU admission to invasive mechanical ventilation (IMV). We extracted ICU length of stay, number of days until in-hospital mortality, and in-hospital 28-day mortality. We assessed the severity of respiratory dysfunction with daily means of PaO2/FiO2 (PF ratio) over a 7-day period after admission for each patient. We further categorized the severity of pulmonary dysfunction based on the Berlin definition of acute respiratory distress syndrome, ARDS (severe ARDS: P/F ratio < 100 mmHg; moderate ARDS: P/F ratio < 200 mmHg; mild ARDS: P/F ratio < 300 mmHg) [28 (link)]. Additionally, kidney function and liver function were followed for each patient over the same 7-day period using daily means of BUN, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Queries were performed in Google BigQuery [29 ]. Primary outcomes of interest included in-hospital mortality, ICU length of stay, and the use of IMV after day 1 of ICU stay. Secondary Outcomes included the mean P/F ratio, mean BUN/Cr ratio, AST, and ALT levels on days 1 through 7 of ICU stay. Patients were grouped by whether they had received H2RAs (ranitidine, famotidine, or cimetidine) from time of admission to 1 day of ICU stay (H2RA group) and those who did not (no H2RA group). We excluded patients who received H2RAs after day 1 of ICU admission as well as patients who were mechanically ventilated prior to receiving H2RAs. Patients with missing values in age, gender, comorbidities, or timestamps corresponding to H2RA use or mechanical ventilation (where these treatments were utilized) were also excluded.

Fifteen rats were randomly divided into three groups of five rats each: control, yoghurt, and food thickener groups. Famotidine powder (100 mg, equivalent to 10 mg famotidine) was mixed with 1 g of yoghurt and food thickener and immediately administered to rats via oral gavage. In the control group, famotidine mixed with water was similarly administered to the rats. Blood samples were collected from the subclavian vein into a heparinied syringe under no anasthesia at 0, 0.5, 1, 1.5, 2, 3, 4, and 6 h. Plasma samples were obtained via centrifugation with lithium heparin and stored at − 80 °C.