First SARS-CoV-2 vaccine booster and influenza vaccination: risk assessment of COVID-19 hospitalisation and death.

BACKGROUND: the influenza and SARS-CoV-2 viruses share a common respiratory symptomatology and transmission mode. COVID-19 and influenza R0 overlapped in the first epidemic wave. In autumn 2021-winter 2022, the influenza epidemic had a delayed onset compared to pre-COVID-19 years and lower incidence rates than in the pre-pandemic period. The SARS-CoV-2 and influenza vaccination campaign overlapped in 2021-2022. OBJECTIVES: to evaluate in the SARS-CoV-2 vaccinated cohort the effect of different timing of influenza vaccination on hospitalisations for COVID-19 and overall mortality. DESIGN: prospective cohort study. SETTING AND PARTICIPANTS: subjects aged 65 years or older who were administered the first booster dose of SARS-COV-2 vaccine between 01.10.2021 and 01.03.2022. Based on the date of influenza vaccination, subjects were divided into the following 4 different mutually exclusive groups: 1. two vaccinations in the same vaccination session; 2. influenza vaccination following SARS-CoV-2 vaccination; 3. influenza vaccination preceding SARS-CoV-2 vaccination; 4. no influenza vaccination. Using Cox regression models, hazard ratio (HR) and corresponding 95% confidence intervals (95% CI) of hospitalisation and death were estimated for the influenza-vaccinated subjects compared to influenza-unvaccinated subjects. MAIN OUTCOME MEASURES: ordinary hospital admissions for COVID-19 and general mortality. RESULTS: the cohort included 618,964 subjects: 16.3% received two vaccinations in the same vaccination session, 8.5% received the influenza vaccination after SARS-CoV-2 vaccination, 33.9% received it before and 41.1% did not receive an influenza vaccination. Those vaccinated against both SARS-CoV-2 and influenza had a combined HR of 0.73 (0.62-0.86) of hospitalisation for COVID-19 and 0.55 (0.49-0.62) of overall mortality compared to those vaccinated against SARS-CoV-2 only. CONCLUSIONS: influenza vaccination combined with SARS-CoV-2 vaccination increases the protective effect against hospitalisations and overall mortality compared to SARS-CoV-2 vaccination alone. Both organisational and communication actions aimed to promote and encourage vaccination are required.

Effectiveness and Safety of Non-Vitamin K Oral Anticoagulants in Non-Valvular Atrial Fibrillation Patients: Results of A Real-World Study in a Metropolitan Area of Northern Italy.

BACKGROUND: New oral anticoagulant agents (NOACs) are valid alternatives for vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (NVAF) for stroke prevention. In clinical practice, NOACs users may differ from patients enrolled in clinical trials in age or comorbidities, and thus it is a critical issue to evaluate the effectiveness and safety of NOACs in the real-world. Accordingly, we assessed two-year overall mortality and hospital admissions for myocardial infarction, stroke or bleeding in patients with NVAF users of NOACs compared to warfarin-treated patients. METHODS: This is a population-based retrospective new user active comparator study. All atrial fibrillation patients who were naïve and not switcher users of oral anticoagulants from January 2017 to December 2019 were included (n = 8543). Data were obtained from the electronic health records of the Milan Agency for Health Protection, Italy. Two-year risks for overall mortality, myocardial infarction, stroke and bleeding were computed using Cox models. Age, sex, number of comorbidities, use of platelet aggregation inhibitors and Proton pump inhibitors and area of residence were used as confounding factors. We also controlled by indication bias-weighting NOACs and warfarin users based on the weights computed by a Kernel propensity score. RESULTS: For all NOACs, we found a decrease in the risks compared with warfarin for mortality (from -25% to -49%), hospitalization for myocardial infarction (from -16% to -27%, statistically significant for apixaban, edoxaban and rivaroxaban) and ischemic stroke (from -23% to -41%, significant for dabigatran and apixaban). The risk of bleeding was decreased for rivaroxaban (-33%) and numerically but not significantly for the other NOACs. CONCLUSIONS: After two years of follow-up, in comparison with warfarin, NOACs users showed a significant reduction of overall mortality (all NOACs), hospital admission for myocardial infarction (apixaban and edoxaban), ischemic stroke (dabigatran) and bleeding (rivaroxaban).

[Evaluation of a public health programme: direct Clopidogrel administration by cardiology units in acute myocardial infarction]. / Valutazione di un intervento di sanità pubblica: somministrazione diretta del trattamento con Clopidogrel nell'infarto miocardico acuto.

OBJECTIVES: to compare the benefit of a personalised outpatient therapy prescribed upon discharge by the cardiology unit to the patients undergoing a percutaneous coronary intervention with drug-eluting stent or bare-metal stent vs. the usual practice. DESIGN: controlled, multicentre, non-randomized study that enrolled patients who underwent coronary stent implantation and treated in the year after stent implantation with two protocols: the treatment group received Clopidogrel directly from the cardiology unit at each monitoring visit; the control group received a prescription for outpatient treatment through the standard retail pharmacy channel. SETTING AND PARTICIPANTS: the recruited centres adopting the new treatment protocol are Magenta, Legnano, and Rho (ASL Milano1, Magenta - Lombardy Region, Northern Italy), with 477 patients included; the recruited centres following for the standard protocol are Niguarda and San Carlo (ASL Milano), with 307 patients included. We identified all patients aged ≥40 years, discharged after coronary stent implantation between January 1st, 2010 and March 31st, 2011, and followed for 1 year. MAIN OUTCOME MEASURES: all coronary events, second coronary interventions or deaths in the year after hospital discharge. RESULTS: we found differences between the two treatments in relation with coronary events: hazard ratio (HR) for the control group in patients with ST-elevation myocardial infarction (STEMI) is 3.32 (95%CI 1.67- 6.62), HR in patients with non-ST elevation myocardial infarction (NSTEMI) is 2.44 (95%CI 1.07-5.57). The compliance at 1 year is 80% in the treated group vs. 70% in the control group, respectively (p-value <0.01). CONCLUSIONS: the application of the therapeutic plan, governed by the interventional cardiology, increases treatment adherence and reduces the risk of cardiovascular events subsequent to the insertion of a stent. It is crucial, therefore, to improve the adherence to dual antiplatelet therapy by using high levels of integration between inpatient and outpatient care to reduce adverse health outcomes during post-surgery phase and to ensure the taking in charge of the patient.

Bell-shaped curves for prostaglandin-induced modulation of adenylate cyclase: two mutually opposing effects.

Each of the natural prostanoid is at least one order of magnitude more potent for its specific receptor (DP, EP, FP, IP and TP) than any of the other prostanoids. However, they are able to interact also with one or more of the other classes of prostanoid receptors. The concentration-response curves for modulation of adenylate cyclase activity in rabbit mesenteric artery smooth muscle cells by different prostaglandins are not always monotonic, i.e. simple sigmoidal curves in logarithmic scale, but they are often biphasic. Prostacyclin, iloprost and prostaglandin E(1) showed a convex bell-shaped curve, i.e. adenylate cyclase activity is stimulated at lower concentrations and inhibited at higher concentrations, while the curve of prostaglandin E(2) showed a concave bell-shaped curve, i.e. adenylate cyclase is inhibited at lower concentrations and stimulated at higher concentrations. By selectively inhibiting one of the transduction mechanisms present in mesenteric smooth muscle cells, we have demonstrated that the observed responses to these prostanoids are likely due to two mutually opposing effects. Thus, the data previously published by our laboratory on a prostacyclin analog, 5(Z)-carbacyclin, might be reinterpreted more correctly in the light of this new possibility.