Changing from mandatory to optional genotyping results in higher acceptance of pharmacist-guided warfarin dosing

Aim: We evaluated the clinical acceptance and feasibility of a pharmacist-guided personalized consult service following its transition from a mandatory (mPGx) to optional (oPGx) CYP2C9/ VKORC1/ CYP4F2 genotyping for warfarin. Methods: A total of 1105 patients were included. Clinical acceptance and feasibility outcomes were analyzed using bivariate and multivariable analyses. Results: After transitioning to optional genotyping, genotype testing was still ordered in a large segment of the eligible population (52.1%). Physician acceptance of pharmacist-recommended doses improved from 83.9% (mPGx) to 86.6% (oPGx; OR: 1.3; 95% CI: 1.1–1.5; p = 0.01) with a shorter median genotype result turnaround time (oPGX: 23.6 hr vs mPGX: 25.1 hr ; p < 0.01). Conclusion: Ordering of genotype testing and provider acceptance of dosing recommendations remained high after transitioning to optional genotyping.

Racial and ethnic disparities in COVID-19 vaccinations in the United States during the booster rollout.

Background: We sought to quantify whether there were statistically significant disparities along race and ethnicity lines during the early rollout of Covid-19 vaccine booster doses in the United States. We also studied whether such disparities replicated or widened disparities that had already been observed during the initial series rollout as of 2 months earlier (Janssen) or 6 months earlier (Pfizer-BioNTech or Moderna), which comprised the booster-eligible population. Methods: This cross-sectional study of US adults (ages ≥18 years) used public data from US Centers for Disease Control and Prevention. The observed shares of vaccine doses for each race and ethnicity were compared to the expected shares, predicted based upon the compositions of the booster-eligible and initial series-eligible populations. Results: As of November 16, 2021, 123.5 million US adults were eligible for a booster dose of either the Pfizer-BioNTech, Moderna, or Janssen vaccines. Of these, 21.7 million had received a booster dose, among whom race and ethnicity information was available for 18.8 million booster recipients. A statistically significant higher share of Non-Hispanic White and Non-Hispanic Multiple/Other race individuals had received a booster vaccination than projected based on the composition of the booster-eligible population. A statistically significant lower share of Hispanic, Non-Hispanic American Indian/Alaskan Native, Non-Hispanic Asian, Non-Hispanic Black, and Non-Hispanic Native Hawaiian/Other Pacific Islander individuals had received a booster vaccination than expected based on the booster-eligible population. A secondary analysis of the booster-eligible population found that some of these disparities had already occurred at the time of the initial series. However, the booster campaign widened all of those disparities and added new disparities for Non-Hispanic American Indian/Alaskan Native and Non-Hispanic Native Hawaiian/Other Pacific Islander individuals. Conclusion: Disparities in Covid-19 vaccine administration on race and ethnicity lines occurred during the initial series rollout in the US. However, these disparities were not merely replicated but widened by the early booster rollout.

Likelihood of infecting or getting infected with COVID-19 as a function of vaccination status, as investigated with a stochastic model for New Zealand (Aotearoa)

Aim: The New Zealand government is transitioning from the Alert Level framework, which relies on government action and population level controls, to the COVID-19 Protection Framework, which relies on vaccination rates and allows for greater freedoms (for the vaccinated). As restrictions are eased, there is significant interest in understanding the relative risk of spreading COVID-19 posed by unvaccinated and vaccinated individuals. Methods: A stochastic branching process model is used to simulate the spread of COVID-19 for outbreaks seeded by unvaccinated or vaccinated individuals. The likelihood of infecting or getting infected with COVID-19 is calculated based on vaccination status. Results: A vaccinated traveler infected with COVID-19 is 9x less likely to seed an outbreak than an unvaccinated traveler infected with COVID-19. For a vaccination rate of 50%, unvaccinated individuals are responsible for 87% of all infections whereas 3% of infections are from vaccinated to vaccinated. When normalized by population, a vaccinated individual is 6.8x more likely to be infected by an unvaccinated individual than by a vaccinated individual. For a total population vaccination rate of 78.7%, which is equivalent to the 90% vaccination target for the eligible population (over 12 years old), this means that vaccinated individuals are 1.9x more likely to be infected by an unvaccinated individual than by a vaccinated, even though there are 3.7x more vaccinated individuals in the population. Conclusions: This work demonstrates that most new infections are caused by unvaccinated individuals. These simulations illustrate the importance of vaccination in stopping individuals from becoming infected with COVID-19 and in preventing onward transmission.

Updating estimates of the number of UK stroke patients eligible for endovascular thrombectomy: incorporating recent evidence to facilitate service planning

Introduction Endovascular thrombectomy (EVT) is a highly effective treatment for acute ischaemic stroke due to large arterial occlusion (LAO). To support decisions about service provision, we previously estimated the annual UK population eligible for EVT as ∼10% of stroke admissions. Since then, several trials have produced evidence that could alter these figures. We update our estimates considering information from studies and trials reporting 2018–2021 on incidence, presentation time and stroke severity and consider the possible impact of predicted demographic changes in the next 10–20 years. Patients and Methods We produce an updated decision tree describing the EVT eligible population for UK stroke admissions. One-way sensitivity analyses (using upper and lower confidence intervals for estimates at each branch of our decision tree) were used to identify where further research evidence is necessary to increase certainty around estimates for numbers of EVT eligible patients. Results The updated estimate for the number of UK stroke patients eligible for EVT annually was between 10,020 (no advanced imaging in early presenting patients) and 9,580 (advanced imaging in all early presenting patients), which compared with our estimates in 2017 is a minimal reduction. One-way sensitivity analyses established that enhanced evidence about eligibility for milder strokes, ASPECTS scores and pre-stroke disability are offset by evidence regarding a lower incidence of LAO. Importantly, predicted increases in life expectancy by 2040 may increase thrombectomy need by 40%. Discussion Information from additional randomised trials published during 2018–2020 with updated estimates of LAO prevalence had a minimal impact on overall estimates of stroke patients eligible for EVT in the UK. Ongoing research into the benefits of EVT for patients with mild stroke or European Stroke Journal For Peer Review lower ASPECTS scores has the potential to increase the estimates of the eligible population; future need for EVT will increase with the ageing population. Conclusion Our updated analyses show overall numbers eligible little changed, but evidence from ongoing trials and demographic changes have the potential to increase the need for EVT significantly.

Pfizer-BioNTech vaccine side effects among healthcare workers in Malta

Background COVID-19 vaccination is critical to protect healthcare workers (HCWs) from serious infection. The first vaccine approved for emergency use was the Pfizer-BioNtech vaccine. European countries received their first supplies at the end of December 2020. The European country of Malta started its vaccination roll-out immediately targeting HCWs. The aim of this study was to evaluate side effects. Methods An anonymous online Google Forms survey was disseminated to all HCWs via work e-mail addresses (29th March to 9th April 2021). This gathered demographic data and side-effects regarding pain, redness, and swelling at the injection site, fever, chills, fatigue, muscle/joint pains, headache, vomiting, and diarrhea severity following each dose (Likert scale). Descriptive, comparative, and multiple binary regression analyses were performed. Results There were 1480 responses (response rate 30.30%). The commonest side-effect (SE) was pain at the injection site (88.92% CI95%:87.21-90.42), with the majority reporting it as mild (51%) and moderate (43%). Fatigue reported by 72.97% (CI95%:70.65-75.17), with 42% reporting it as mild and 41% as moderate. Headaches reported by 44.28% (CI95%:41.74-46.80), with 51% claiming to be mild and 34% as moderate. Females had significantly (p = &lt;0.01 respectively) more pain (OR:1.90), redness (OR:2.49), swelling at the injection site (OR:1.33), fever (OR:1.74), chills (OR:2.32), fatigue (OR:2.43), muscle (OR:1.54) and joint pains (OR:2.01), headache (OR:2.07) and vomiting (OR:3.43) when adjusted for age and HCW role. Younger individuals (18-34 years) reported higher SE rates than older adults. Localised SE was reported following both vaccine doses, unlike systemic SE that was mostly reported following second doses. Conclusions Females and young adults appeared to be more susceptible to SE among this study's cohort, however the nature of these SE was mostly mild or moderate. This is encouraging and should allay vaccine apprehension/hesitancy. Key messages Vaccination benefits outweigh the minor side effects experienced. Caring physicians should be notified of the female higher susceptibility to side effects. Vaccination should be encouraged among all eligible population.

797Understanding bias in recruitment through population-based cancer registries

Focus of Presentation Participant recruitment through registries can provide population-based samples, but there are methodological challenges. We examine challenges and solutions in two studies recruiting participants through the Victorian Cancer Registry. Cross-sectional surveys of patients with colorectal, lung or ovarian cancer conducted in 2013-14 (study 1) and repeated in an ongoing study (study 2). The registry managed fast-track recruitment of eligible patients ( &gt; =40yrs, confirmed diagnosis, approached within 6-months of diagnosis) Findings In study 1, registry rules for confirmed diagnosis required surgical histopathology. For cancers primarily treated non-surgically (e.g. lung), selection bias was common. In study 2, confirmation rules were extended to include biopsies with subsequent hospital notification. The registry does not receive imaging notifications and pathology labs/hospital reports can be delayed (&gt;60days). Study eligibility criteria meant cases with advanced disease, common in lung cancer, or without a confirmed diagnosis within the study timeframe were excluded. However, colorectal and ovarian cases in study 1 were largely representative of the eligible population. In study 2, a different fast-track recruitment approach meant a longer time from diagnosis to response compared to study 1 (median 7 vs 5 months). Recruitment procedures are being improved through engagement between researchers and registry. Conclusions/Implications Local registry-based rules for recruitment and available data, study eligibility criteria and cancer type (particularly cancers without histopathological confirmation), may introduce bias. Researchers need to work closely with registry colleagues to understand and optimise recruitment. Key messages Registry-based recruitment can be biased. Early and ongoing communication between researchers and registry is strongly recommended.

Socio-Territorial Inequities in the French National Breast Cancer Screening Programme—A Cross-Sectional Multilevel Study

Background. France implemented in 2004 the French National Breast Cancer Screening Programme (FNBCSP). Despite national recommendations, this programme coexists with non-negligible opportunistic screening practices. Aim. Analyse socio-territorial inequities in the 2013–2014 FNBCSP campaign in a large sample of the eligible population. Method. Analyses were performed using three-level hierarchical generalized linear model. Level one was a 10% random sample of the eligible population in each département (n = 397,598). For each woman, age and travel time to the nearest accredited radiology centre were computed. These observations were nested within 22,250 residential areas called “Îlots Regroupés pour l’Information Statistique” (IRIS), for which the European Deprivation Index (EDI) is defined. IRIS were nested within 41 départements, for which opportunistic screening rates and gross domestic product based on purchasing power parity were available, deprivation and the number of radiology centres for 100,000 eligible women were computed. Results. Organized screening uptake increased with age (OR1SD = 1.05 [1.04–1.06]) and decreased with travel time (OR1SD = 0.94 [0.93–0.95]) and EDI (OR1SD = 0.84 [0.83–0.85]). Between départements, organized screening uptake decreased with opportunistic screening rate (OR1SD = 0.84 [0.79–0.87]) and départements deprivation (OR1SD = 0.91 [0.88–0.96]). Association between EDI and organized screening uptake was weaker as opportunistic screening rates and as département deprivation increased. Heterogeneity in FNBCSP participation decreased between IRIS by 36% and between départements by 82%. Conclusion. FNBCSP does not erase socio-territorial inequities. The population the most at risk of dying from breast cancer is thus the less participating. More efforts are needed to improve equity.

Defining type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis

Background Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status. Methods A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab). Results According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population). Conclusions There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions.