Adverse drug reactions, multimorbidity and polypharmacy: a prospective analysis of 1 month of medical admissions.

OBJECTIVE: To ascertain the burden and associated cost of adverse drug reactions (ADRs), polypharmacy and multimorbidity through a prospective analysis of all medical admissions to a large university teaching hospital over a 1-month period. DESIGN: Prospective observational study. SETTING: Liverpool University Hospital Foundation National Health Service (NHS) Trust, England. PARTICIPANTS: All medical admissions with greater than 24-hour stay over a 1-month period. MAIN OUTCOME MEASURES: Prevalence of admissions due to an ADR and associated mortality, prevalence and association of multimorbidity and polypharmacy with ADRs, and estimated local financial cost of admissions where an ADR was a contributing or main reason for admission with projected costs for NHS in England. RESULTS: There were 218 identified patient admissions with an ADR giving a prevalence of 18.4%. The majority of these (90.4%) were ADRs that directly resulted in or contributed to admission. ADRs thus accounted for 16.5% of total admissions. Those with an ADR were on average taking more medicines (10.5 vs 7.8, p<0.01) and had more comorbidities than those without an ADR (6.1 vs 5.2, p<0.01). Drugs most commonly implicated were diuretics, steroid inhalers, anticoagulants and antiplatelets, proton pump inhibitors, chemotherapeutic agents and antihypertensives. 40.4% of ADRs were classified avoidable or possibly avoidable. The mortality rate due to an ADR was 0.34%. The average length of stay for those with an ADR was 6 days. Direct 1-month cost to the Trust from ADR admissions was £490 716. Extrapolated nationally, the projected annual cost to the NHS in England is 2.21 billion. CONCLUSION: The local prevalence of admission and mortality from ADRs is higher than previously reported. Important factors that could be contributing to this include polypharmacy and multimorbidity. ADRs place a significant burden on patients and healthcare services with associated financial implications. Reducing inappropriate polypharmacy should be a major aim for preventing ADRs.

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.

OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 µg) or BNT (30 µg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 µg) versus BNT (30 µg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.