Medicines' sales and shortages during the COVID-19 outbreak: A nationwide retrospective analysis

Background: The COVID-19 is a worldwide public health emergency. A possible direct result of this international outbreak is the disruption of medicine supply chains, which may also have consequences in the increase of drug shortages. Community pharmacies can contribute to early identification and report of medicines' supply and demand problems. Purpose(s): The aim of this study is to characterise the impact of COVID-19 on the outpatient medicines' sales and shortages during the initial outbreak Methods: A retrospective, time-trend analysis of medicine sales and shortages was performed from the 1st February to 30th April 2020 and its homologous period. Portuguese daily new laboratory confirmed COVID-19 cases and major national emergency measures were recorded. All data were subjected to rescaling using the min-max normalisation method to become comparable. Data analysis was performed using Microsoft Excel. Result(s): The COVID-19 outbreak resulted in an increased demand for medicines, with a peak reached just after the World Health Organization declaration of the state of pandemic. By the end of March, sales had already dropped to proportions similar to those of 2019. The maximum proportion of drug shortages was reached about one week after the sales peak and by the end of the study period its values were below those recorded in the pre-COVID-19 period. Conclusion(s): Data suggest medicines' sales and shortages were initially impacted by the COVID-19 outbreak in Portugal, although by the end of the study period, medicine markets had normalised. The long-term impacts of this pandemic on medicines' sales and shortages are unknown and should continue to be closely monitored.

T Cell mediate immune response: Real-Time PCR test for the rapid determination of SARS-CoV-2 specific CD4 and CD8 T Cells

Introduction Cellular immunity is pivotal for SARS-CoV-2 protection, but measurements of cellular-specific response are rarely performed due to costs and technical requirements. Hyris developed a direct Real-Time PCR (dRT-PCR) assay that measures CD4 and CD8 T cells immunoreactive to SARS-CoV-2 Spike protein by targeting CXCL10 mRNA (upregulated in response to IFN-gamma secreted by antigenspecific T Cell). This test uses a modular T cell activation method based on pool of synthetic peptides to stimulate Sspecific T cell, and those able to tolerate amino acid (AA) mutations that characterize new variants. The aim of this study was to evaluate the assay performances. Methods Whole blood (Li-He) of 13 SARS-CoV-2 naive and 116 vaccinated individuals were stimulated with a pool of Speptides (15 AA long) covering whole S protein (Wuhan) and left unstimulated (SCV2 T Activation kit). Whole blood of 78 healthy vaccinated individuals was stimulated with two sets of peptides covering the constant and mutated region of S protein of Omicron BA1.2 (SCV2 Omicron T Activation kit) and left unstimulated. After overnight incubation T cell activation was detected by bKIT dqTACT MS (CXCL10 and ACTIN mRNA) on the HYRIS bCUBE. Results The vaccinated subjects statistically shown level of relative mRNA expression of CXCL10 greater than unvaccinated subjects;109 vaccinated individuals were detected as reactive to stimulation (mean relative expression 0.043) with SARS-CoV-2 S peptides (Sensitivity 94%), while 10 naive were detected as not-reactive (mean expression -0.25) (Specificity 77%). Considering the 129 samples the AUC value of is 90% (CI 82%-98%). 78 samples activated with the constant and mutated region of S of Omicron peptides showed different quantities of T cells response. The 62% of sample assessed resulted reactive (with a ratio between the two stimulations above 15%) despite the AA mutations, showing that AA mutations can affect the magnitude of S T cell response. Conclusions Combining the modular utilization of synthetic peptide pools as activators and the direct measurement of CXCL10 mRNA in whole blood, dRT-PCR method was proven to be a reliable and efficient assay for the measurement of the individual antigen-specific T cells measurement of SARS-CoV-2 cellular immunity.

Digital Media and Pharmacovigilance: The SIMeF Pharmacovigilance Working Group Perspective: An International Journal of Medical Toxicology and Drug Experience

Introduction: Digital media are integrated in our daily routine, play a critical role in the dissemination of health information and disease prevention guidelines and are becoming more impacting in pharma-companies activities, with an increasing trend after the pandemic period. They pose pharmacovigilance challenges for application of PV rules. a structured approach is needed for pharmacovigilance departments in the new digital scenario. Objective: The SIMeF pharmacovigilance working group worked on digital topic since two years, addressing it in a structured way: from a a specific survey (1), to proposals for addressing the needs underlined, to seminars and events for capability building and discussions among experts. SIMEF group also worked on a proposal guideline for sup-porting PV departments (6), suggesting a framework for managing sponsored digital activities with potential collection of adverse events, to provide useful operative suggestions on PV requirements management. Methods: A research on the regulation in force and the current status of digital media was conducted, with a focus on pharmacovigilance, privacy and quality aspects. The guideline was written considering the expertise of the authors in the management of pharmacovigilance activities. Seminars were done to favour discussions among experts. Results: All healthcare sectors are impacted by digital media: scientific societies, academic institutions, patients' associations, hospitals and healthcare institutions are increasing their online presence 2,3. Social media are used by patients to compare health data, collect treatment information and discuss with physicians, with an increasing active role. Digital media should be considered as a potential source of AEs by pharmacompanies, when managing sponsored activities. PV aspects of digital activities are currently described, although not in details, in different regulations by EMA, FDA and MHRA. Management digital projects by pharmacompanies is complex and require a structured multifunctional process, to guarantee a holistic approach to regulatory and legal requirements. Many aspects should be considered for compliance and efficiency. SIMeF work pose considerations on the importance of crossfunctional work, early pharmacovigilance advice, tracking system, execution of risk-based assessment, escalation to quality, SOPs presence, personnel trainings (including vendors) and a Quality System covering PV. New skills and capability will be crucial for PV departments in future. Conclusion: Digital media are powerful instrument to increase patients and physicians involvement and to support disease knowledge. The rising amount of safety data generated through digital opens a challenge for pharmacompanies. This work is a starting point to trigger broader discussions around PV quality system for digital activities.

How to Stimulate Prosocial Behavior: an Experiment on the Effects of Frames and Incentives

While the study of cooperation has a long tradition in the social sciences, the current emergency caused by the SARS-COVID19 pandemics has made it even more important to understand cooperation, because the efficacy of the measures enacted to stop the diffusion of the virus rests on the ability to obtain large-scale cooperation (implementing behaviours which are costly for individuals, although they are necessary for collectivity). This study analyzes factors that influence prosocial behavior, focusing on the role of frames, meant as mental models that emerge in given circumstances leading individuals to define the situation in which they have to make their decisions (Kroneberg 2014) and how different incentives – monetary and non-monetary – affect the decision process. The results show that the exposure to elements that stimulate subjects to think about prosocial norms can influence individual behavior in the direction that is consistent with the norm elicited. Furthermore, the individual behavior does not differ significantly according to the incentive adopted, even though we register situations in which the incentive adopted could contribute to social norms salience, increasing cooperation levels. © 2021 Societa Editrice il Mulino. All rights reserved.

Metabolic dysfunction-associated fatty liver disease and liver fibrosis score in patients with COVID-19 as predictors of adverse clinical outcomes: an artificial intelligent application through machine learning

Introduction and aims. Patients with coronavirus disease-2019 (COVID-19) and metabolic-dysfunction associated fatty liver disease (MAFLD) appear to be at higher risk for severe manifestations like acute respiratory distress syndrome, especially in the youngest decades. Our aim was to examine whether patients with imaging-defined MAFLD and/or with increased non-invasive liver fibrosis scores (FIB-4) are at higher risk for severe illness from COVID-19, using a machine learning model. Methods. In this retrospective cohort study, we included 672 patients admitted for SARS-CoV-2 pneumonia between February the 28th 2020 and May the 1st 2021. Hepatic steatosis was detected by ultrasound or computed tomography (CT), whereas FIB-4 score was used to define the risk of advanced liver fibrosis. We used a machine learning (ML) model to evaluate the risks of both in-hospital death and prolonged hospitalizations (>28 days), considering MAFLD, a set of blood tests (hepatic profile;HP), and the FIB-4 score, either separately and together. Results. Three hundred-thirty-three (49.6% of total) had imaging-defined MAFLD. The accuracy in predicting in-hospital death in the whole sample was 0.709 for the HP alone, and 0.721 for HP+FIB-4 combined together;in the 55-to-75 age subgroup, the accuracies were respectively 0.842 and 0.855 for HP alone and HP+FIB-4 together. In the MAFLD subgroup, the accuracy in predicting death was 0.739 considering HP alone, and 0.772 when considering HP+FIB-4 together;whereas in the MAFLD 55-to-75 years cohort, the accuracies were respectively 0.825 for HP and 0.833 for HP+FIB-4. Similar results were obtained both in the entire cohort and in MAFLD patients when considering the accuracy in predicting prolonged hospitalization (>28 days). Conclusions. In our cohort of COVID-19 patients, the presence of a worse HP and a higher FIB-4 correlated with a higher risk of death and prolonged hospitalization, regardless of the presence of MAFLD. These findings could improve the clinical risk stratification of patients diagnosed with SARS-CoV-2 pneumonia.

POSA247 Impact of Transferring the Dispensing of Hospital-Only Medicines to Community Pharmacies during COVID-19 Pandemic: A Single-Arm, Before-and-After Study

Objectives: Ensuring the continuing of care is an imperative need, therefore throughout COVID-19 outbreak, the Portuguese Government released directives to guarantee hospital-only medicines' dispensing through the community pharmacy, reducing contacts between patients and Hospitals. This study aims to measure the value generated by the intervention of the community pharmacy in the dispensing of hospital medicines. Methods: A single-arm, before-and-after study with 3-month follow-up, was carried out in Portugal, enrolling a randomly selected sample of patients with at least one dispensation of a hospital-only medicine through the community pharmacy. Data was collected through a structured questionnaire applied by telephone interview from May 15th to October 10th, 2020. Main outcomes were access to medicines, therapeutic adherence (MAT-7), health-related quality-of-life (EQ-5D-3L), satisfaction with the service, travel and waiting time, and related costs to patients. Results: A total of 603 patients/caregivers accepted to participate in the study. The mean age was 55 years old (SD=16) and 50.6% were male. On average, the estimated time gained with the community pharmacy service was 115.1 minutes/visit compared to hospital. Annual savings derived from travel expenses (€237.6) and absenteeism (€67.4) reduction account for 271.6€/patient. There was an increase in the mean score of adherence to therapy (p<0.05) and no statistically significant changes in the mean EQ-5D-3L score. Overall, 91% of respondents would choose to continue to have access to their medication at the community pharmacy, in post-pandemic scenario. Participants reported an increase of satisfaction levels in all evaluated domains – pharmacist’s availability, opening hours, waiting time, privacy conditions and overall experience. Conclusions: Changing the dispense setting to the community pharmacies seems to promote better access, health outcomes and satisfaction for patients. Moreover, it ensures the persistence of treatments, promotes savings for patients and society, and reduces the burden of health care services, representing a crucial public health measure.

An early complication in patient with CoViD19 pneumonia

Background: In December 2019, many cases of atypical pneumonia with unknown etiology were reported in China. Later on, a new coronavirus was identified, named SARS-CoV-2. We present a case of SARS-CoV-2 pneumonia complicated by spontaneous pneumomediastinum (SPM), pneumothorax (PNX) and subcutaneous emphysema (SCE) without the use of an invasive or noninvasive positive pressure ventilator. Presentation of the case: A 42-year-old man with moderate dyspnea arrived at the DEA. He reported infection with SARS-CoV-2 from a week. He reported no medical history. At the entrance the patient was lucid, oriented and cooperative. The B.P. was 125/75 with sinus rhythm with pulse 75 bpm, apyretic, SpO2 88% on A.A. To DEA showed examinations: D-Dimer 549, fibrinogen 850, VES 75, PCR 8.33, LDH 295. The EGA (Reservoir 90%) detected: pO2 60.7 mmHg, pCO2 36.3, pH 7.47, SpO2 92% and P/F 67,4. The Rx thorax showed multiple hazy parenchymal opacities in the lower lobar seat bilaterally. He was submitted to therapy based on dexamethasone, fluid therapy, antibiotics, enoxaparin. After 36 hours, he presented progressive deterioration of respiratory function and chest CT showed: SPM, PNX, SCE. After two days he died. Conclusions: In many CoViD-19 studies the incidence of SPM, PNX, SCE is rare. The peculiarity of this case report is given by the serious SPM, PNX, SCE as an early complication in the absence of lung comorbidities, cough, consume alcohol, smoke tobacco or use recreational drugs. This suggests that others processes related to CoViD-19 might be the mechanism of air leak that progress to SPM, PNX, SCE.

COVID-DETECT: A Deep Learning Based Approach to Accelerate COVID-19 Detection

After two years of COVID-19 first infection and its speedy propagation, death and infection cases are till exponentially increasing. Unfortunately, during this a non-fully controlled situation, we noticed that the existing solutions for COVID-19 detection based on chest X-ray were not reliable enough in relation to the number of infected patients and the severity of the outbreak. To handle this issue by increasing the reliability and the efficiency of COVID-19 detection, we therefore deploy and compare the results of a set of reconfigurable classification approaches and deep learning techniques. Indeed, we have achieved a score of up to 99% accuracy with a dataset of 15,000 X-ray images, which makes the selected detection technique, deep learning, more reliable and effective. © 2021, Springer Nature Switzerland AG.

Dexamethasone in covid-19 patients with acute respiratory distress syndrome. experience from a cardiology department

Aims: We assessed the effectiveness of early administration of corticosteroids in patients affected by COVID-19 with moderate to severe acute respiratory distress syndrome requiring oxygen support. Methods: This is a single-center, retrospective, controlled cohort study including patients admitted to our hospital from March 13th to April 20th, 2020. Patients received an intravenous bolus of 8mg dexamethasone twice daily for 5 days or standard care only. Clinical and laboratory characteristics were abstracted by medical records. The primary endpoint was clinical improvement, defined as an increase in the arterial partial pressure of oxygen/fraction of inspired oxygen ratio ≥50%, respiratory rate <24 breaths/min, and decrease in C-reactive protein (CRP) ≥50% compared to the baseline. The secondary endpoint was weaning from any ventilatory support. Outcomes were assessed using Kaplan-Meier analysis with Log-rank test and multivariable Cox regression. Results: Thirty-seven patients (21.6% female;mean age, 63.3±11.4 years) were identified who needed non-invasive mechanical ventilation, 23 of whom received steroids and 14 standard care. Median follow-up was 20 days (range 7-52). Treatment with dexamethasone was associated with faster clinical improvement than standard care [median days, 2 vs. 6;hazard ratio (HR), 3.28;95% confidence interval (CI), 1.64-6.55;P <.0001) and earlier weaning from ventilatory support (median days, 4 vs. 7;HR, 2.24;95% CI, 1.13-4.43;P =.014). CRP decreased over time only in patients on corticosteroids (treatment effect P <.001). Conclusion: In COVID-19 patients with moderate-to-severe ARDS the early use of dexamethasone prevented disease progression, resulting from host inflammatory response, and improved clinical outcome.

Hospital outpatientactivity during the first lockdown for COVID-19: The experience of the outpatient clinic for urgent cardiological examinations at the hospital of Desio

Background: To face the health emergency due to the first spread in Italy of COVID- 19, a nationwide lockdown was instituted from 9 March to 3 May 2020. During this period all the hospital outpatient activities were suspended except for urgent cases. Objective: To evaluate the cardiological urgent outpatient examinations done in our hospital during the lockdown in view of the reduced hospitalizations and the increased cardiovascular deaths observed during the COVID-19 outbreak. Methods: The urgent cardiological examinations (requests with priority U and B, i.e., to be done within 3 and 10 days respectively) performed during the 8-week period of lockdown (38 working days) were compared with those performed during the same period in the previous year (37 working days). During the lockdown and the control period, the availability of urgent cardiological visits was the same (2 per day with priority U and 2 per day with priority B). The number of cardiological examinations performed and the main characteristics of the subjects attending the outpatient clinic in the two periods were evaluated, comparing them with the chi-square test and considering as significant p values <0.05. Results: The table shows the number of urgent cardiological outpatient examinations done on those available in the two periods under comparison. Cardiological urgent outpatient examinations LOCKDOWN CONTROL Chi-square p • with priority U (performed/available) 41/76 (53.9%) 71/74 (95.9%) 34.96 <0.01 • with priority B (performed/available) 28/76 (36.8%) 69/74 (93.2%) 52.20 <0.01 The reduction in the number of urgent cardiological outpatient examinations done during the lockdown was observed from the first week with a nadir at the third and a subsequent slow return to normality at the end of eight weeks. No significant differences in age, sex, history of heart diseases, reasons and outcomes of the examinations were observed in patients evaluated in the two periods. Conclusion: During the first lockdown introduced in Italy to face the COVID-19 pandemic, a statistically significant reduction of accesses to the outpatient clinic for urgent cardiological examinations of our hospital was observed with possible negative consequences in the diagnosis and treatment of cardiovascular diseases in the community.

YTTREX: Crowdsourced Analysis of YouTube’s Recommender System During COVID-19 Pandemic

Algorithmic personalization is difficult to approach because it entails studying many different user experiences, with a lot of variables outside of our control. Two common biases are frequent in experiments: relying on corporate service API and using synthetic profiles with small regards of regional and individualized profiling and personalization. In this work, we present the result of the first crowdsourced data collections of YouTube’s recommended videos via YouTube Tracking Exposed (YTTREX). Our tool collects evidence of algorithmic personalization via an HTML parser, anonymizing the users. In our experiment we used a BBC video about COVID-19, taking into account 5 regional BBC channels in 5 different languages and we saved the recommended videos that were shown during each session. Each user watched the first five second of the videos, while the extension captured the recommended videos. We took into account the top20 recommended videos for each completed session, looking for evidence of algorithmic personalization. Our results showed that the vast majority of videos were recommended only once in our experiment. Moreover, we collected evidence that there is a significant difference between the videos we could retrieve using the official API and what we collected with our extension. These findings show that filter bubbles exist and that they need to be investigated with a crowdsourced approach. © 2021, Springer Nature Switzerland AG.