Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review.

BACKGROUND: The use of composite outcome measures (COM) in clinical trials is increasing. Whilst their use is associated with benefits, several limitations have been highlighted and there is limited literature exploring their use within critical care. The primary aim of this study was to evaluate the use of COM in high-impact critical care trials, and compare study parameters (including sample size, statistical significance, and consistency of effect estimates) in trials using composite versus non-composite outcomes. METHODS: A systematic review of 16 high-impact journals was conducted. Randomised controlled trials published between 2012 and 2022 reporting a patient important outcome and involving critical care patients, were included. RESULTS: 8271 trials were screened, and 194 included. 39.1% of all trials used a COM and this increased over time. Of those using a COM, only 52.6% explicitly described the outcome as composite. The median number of components was 2 (IQR 2-3). Trials using a COM recruited fewer participants (409 (198.8-851.5) vs 584 (300-1566, p = 0.004), and their use was not associated with increased rates of statistical significance (19.7% vs 17.8%, p = 0.380). Predicted effect sizes were overestimated in all but 6 trials. For studies using a COM the effect estimates were consistent across all components in 43.4% of trials. 93% of COM included components that were not patient important. CONCLUSIONS: COM are increasingly used in critical care trials; however effect estimates are frequently inconsistent across COM components confounding outcome interpretations. The use of COM was associated with smaller sample sizes, and no increased likelihood of statistically significant results. Many of the limitations inherent to the use of COM are relevant to critical care research.

The path towards type V deep eutectic solvents: inductive effects and steric hindrance in the system tert-butanol + perfluoro tert-butanol.

The solid-liquid phase behaviour of two tertiary alcohols, perfluoro-tert-butanol and tert-butanol, was studied here using experimental (ITC, DSC and density measurements) and theoretical (MD simulations) approaches. The phase diagram of the binary mixture reveals highly negative deviations from ideality at low concentrations, as well as the formation of co-crystals and is characterized by two eutectic points, a congruent melting point and a peritectic reaction corresponding to TBH : TBF stoichiometries of 2 : 1 and 1 : 1 respectively. Excess molar enthalpies and volumes were calculated, showing negative and positive deviations from ideality, respectively. The effect of acidity, stereochemical hindrance and phobic effects and how they affect intermolecular interactions in these binary mixtures is discussed, with the aim of designing and fine-tuning type V deep eutectic solvents. The results showed that the fluorination of tertiary alcohols can be used for the tuning of the mixing properties and solid-liquid phase diagrams.

Motivation and Knowledge of Portuguese Community Pharmacists Towards the Reporting of Suspected Adverse Reactions to Medicines: A Cross-Sectional Survey.

The close contact between patients and community pharmacists, along with the extensive geographical distribution of pharmacies in Portugal, offer exceptional conditions to detect and report adverse drug reactions (ADR). This study aimed to evaluate the motivation and knowledge of spontaneous reporting of ADR by community pharmacists of Porto, Portugal. Secondly, we aimed to generate real-world evidence on the main factors determining ADR report and at raising potential alternatives to the current reporting procedure in community pharmacy. We performed a descriptive, cross-sectional, observational, anonymous web survey-based study. Between April and July 2021, a web survey was implemented, targeting community pharmacists in the Porto district, Portugal. We validated 217 surveys from pharmacists. Regular notifiers seem to be more familiarised than non-regular notifiers with the Portuguese Pharmacovigilance System (PPS), with the Portal RAM for reporting suspected ADR, and with the update of the concept of ADR. Moreover, regular notifiers seem to be more proactive with their care in questioning patients about ADR and have more self-knowledge to identify suspected ADR. Conversely, non-regular notifiers, seem to be more reluctant to be judged by their ADR reporting activities. Respondents suggested to simplify and optimise the reporting process (31% of the suggestions), or to integrate a reporting platform into the pharmacy's software (27%). This study identified opportunities to promote the ADR reporting process by community pharmacists, namely receiving feedback from the PPS on the reported case and its regulatory implications, implementing training programs in pharmacovigilance, and creating solutions to simplify the reporting process.

Detection and genome characterisation of SARS-CoV-2 P.6 lineage in dogs and cats living with Uruguayan COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in domestic animals have occurred from the beginning of the pandemic to the present time. Therefore, from the perspective of One Health, investigating this topic is of global scientific and public interest. OBJECTIVES: The present study aimed to determine the presence of SARS-CoV-2 in domestic animals whose owners had coronavirus disease 2019 (COVID-19). METHODS: Nasopharyngeal and faecal samples were collected in Uruguay. Using quantitative polymerase chain reaction (qPCR), we analysed the presence of the SARS-CoV-2 genome. Complete genomes were obtained using ARTIC enrichment and Illumina sequencing. Sera samples were used for virus neutralisation assays. FINDINGS: SARS-CoV-2 was detected in an asymptomatic dog and a cat. Viral genomes were identical and belonged to the P.6 Uruguayan SARS-CoV-2 lineage. Only antiserum from the infected cat contained neutralising antibodies against the ancestral SARS-CoV-2 strain and showed cross-reactivity against the Delta but not against the B.A.1 Omicron variant. MAIN CONCLUSIONS: Domestic animals and the human SARS-CoV-2 P.6 variant comparison evidence a close relationship and gene flow between them. Different SARS-CoV-2 lineages infect dogs and cats, and no specific variants are adapted to domestic animals. This first record of SARS-CoV-2 in domestic animals from Uruguay supports regular surveillance of animals close to human hosts.

A comprehensive review of adverse events to drugs used in COVID-19 patients: Recent clinical evidence.

BACKGROUND: Since the breakthrough of the pandemic, several drugs have been used to treat COVID-19 patients. This review aims to gather information on adverse events (AE) related to most drugs used in this context. METHODS: We performed a literature search to find articles that contained information about AE in COVID-19 patients. We analysed and reviewed the most relevant studies in the Medline (via PubMed), Scopus and Web of Science. The most frequent AE identified were grouped in our qualitative analysis by System Organ Class (SOC), the highest level of the MedDRA medical terminology for each of the drugs studied. RESULTS: The most frequent SOCs among the included drugs are investigations (n = 7 drugs); skin and subcutaneous tissue disorders (n = 5 drugs); and nervous system disorders, infections and infestations, gastrointestinal disorders, hepatobiliary disorders, and metabolism and nutrition disorders (n = 4 drugs). Other SOCs also emerged, such as general disorders and administration site conditions, renal and urinary disorders, vascular disorders and cardiac disorders (n = 3 drugs). Less frequent SOC were eye disorders, respiratory, thoracic and mediastinal disorders, musculoskeletal and connective tissue disorders, and immune system disorders (n = 2 drugs). Psychiatric disorders, and injury, poisoning and procedural complications were also reported (n = 1 drug). CONCLUSIONS: Some SOCs seem to be more frequent than others among the COVID-19 drugs included, although neither of the studies included reported causality analysis. For that purpose, further clinical studies with robust methodologies, as randomised controlled trials, should be designed and performed.

Burnout among Portuguese healthcare workers during the COVID-19 pandemic.

BACKGROUND: During COVID-19 pandemic, healthcare workers (HCWs) have had high workload and have been exposed to multiple psychosocial stressors. The aim of this study was to evaluate HCWs in terms of the relative contributions of socio-demographic and mental health variables on three burnout dimensions: personal, work-related, and client-related burnout. METHODS: A cross-sectional study was performed using an online questionnaire spread via social networks. A snowball technique supported by health care institutions and professional organizations was applied. RESULTS: A total of 2008 subjects completed the survey. Gender, parental status, marriage status, and salary reduction were found to be significant factors for personal burnout. Health problems and direct contact with infected people were significantly associated with more susceptibility to high personal and work-related burnout. Frontline working positions were associated with all three dimensions. Higher levels of stress and depression in HCWs were significantly associated with increased levels of all burnout dimensions. Higher levels of satisfaction with life and resilience were significantly associated with lower levels of all burnout dimensions. CONCLUSIONS: All three burnout dimensions were associated with a specific set of covariates. Consideration of these three dimensions is important when designing future burnout prevention programs for HCWs.

Marginal fit of zirconia copings fabricated after conventional impression making and digital scanning: An in vitro study.

STATEMENT OF PROBLEM: Although digital scanning has become popular, conventional impressions with polyvinyl siloxane (PVS) are still the gold standard for fabricating indirect restorations. Studies comparing the marginal fit obtained from both techniques are sparse. PURPOSE: The purpose of this in vitro study was to compare the marginal fit of zirconia copings fabricated by using a conventional impression and 2 digital scanning techniques. MATERIAL AND METHODS: A typodont mandibular left second premolar was prepared for a complete crown. Ten impressions were made in each experimental group: PVS group, conventional impression with PVS; TRIOS 3 group, impression with intraoral scanner TRIOS 3; and CS 3600 group, impression with intraoral scanner CS 3600. Thirty zirconia copings were fabricated with computer-aided design and computer-aided manufacturing (CAD-CAM) technology, and the marginal discrepancy was measured in 4 locations per specimen by using a stereo microscope. Additionally, the marginal discrepancy of each coping obtained in the PVS group was measured on the stone die produced, creating the PVS A group. The mean value of discrepancy was calculated for each location and each group. Statistically significant differences among the impression techniques were tested with 1-way ANOVA, repeated measures ANOVA, and the t test (α=.05). RESULTS: The mean ±standard deviation values of vertical marginal discrepancy were 106 ±87 µm for the PVS group, 34 ±49 µm for the PVS A group, 53 ±56 µm for the TRIOS 3 group, and 93 ±69 µm for the CS 3600 group. Statistically significant differences (P<.05) were found between the PVS group and TRIOS 3 group and between the CS 3600 group and TRIOS 3 group. CONCLUSIONS: Digital scanning with the TRIOS 3 showed lower values of marginal discrepancy than the digital scan with the CS 3600 and conventional impression making with an elastomer.

Reducing Potentially Inappropriate Prescriptions for Older Patients Using Computerized Decision Support Tools: Systematic Review.

BACKGROUND: Older adults are more vulnerable to polypharmacy and prescriptions of potentially inappropriate medications. There are several ways to address polypharmacy to prevent its occurrence. We focused on computerized decision support tools. OBJECTIVE: The available literature was reviewed to understand whether computerized decision support tools reduce potentially inappropriate prescriptions or potentially inappropriate medications in older adult patients and affect health outcomes. METHODS: Our systematic review was conducted by searching the literature in the MEDLINE, CENTRAL, EMBASE, and Web of Science databases for interventional studies published through February 2018 to assess the impact of computerized decision support tools on potentially inappropriate medications and potentially inappropriate prescriptions in people aged 65 years and older. RESULTS: A total of 3756 articles were identified, and 16 were included. More than half (n=10) of the studies were randomized controlled trials, one was a crossover study, and five were pre-post intervention studies. A total of 266,562 participants were included; of those, 233,144 participants were included and assessed in randomized controlled trials. Intervention designs had several different features. Computerized decision support tools consistently reduced the number of potentially inappropriate prescriptions started and mean number of potentially inappropriate prescriptions per patient. Computerized decision support tools also increased potentially inappropriate prescriptions discontinuation and drug appropriateness. However, in several studies, statistical significance was not achieved. A meta-analysis was not possible due to the significant heterogeneity among the systems used and the definitions of outcomes. CONCLUSIONS: Computerized decision support tools may reduce potentially inappropriate prescriptions and potentially inappropriate medications. More randomized controlled trials assessing the impact of computerized decision support tools that could be used both in primary and secondary health care are needed to evaluate the use of medication targets defined by the Beers or STOPP (Screening Tool of Older People's Prescriptions) criteria, adverse drug reactions, quality of life measurements, patient satisfaction, and professional satisfaction with a reasonable follow-up, which could clarify the clinical usefulness of these tools. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42017067021; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017067021.

Solvation of alcohols in ionic liquids - understanding the effect of the anion and cation.

In this work, we studied the effect of anion and cation properties on the interaction of alcohols with ionic liquids (ILs), using propan-1-ol as a molecular probe. The enthalpies of solution at infinite dilution of propan-1-ol in several ILs were measured by isothermal titration calorimetry (ITC). The calorimetric results were analysed together with molecular dynamics simulation and quantum chemical calculations of the interaction of the hydroxyl group of propan-1-ol with the anions. The results evidenced the role of the anion's basicity in the intermolecular interactions of alcohols and ionic liquids and further revealed a secondary effect of the cation nature on the solvation process. The effect of the anion basicity on the strength of the interaction of alcohols with ionic liquids was evaluated by comparing the results obtained for ILs with the same cation and different anions, [C4C1im][anion] (anions NTf2, PF6, FAP, DCA and TFA). The effect of the cation (size, aromaticity, charge distribution, and acidity) was explored using five different cations of the NTf2 series, [cation][NTf2] (cations C4C1im, C4C1pirr, C4py, C4C1pip, and C3C1C1im).

Vaporization of protic ionic liquids derived from organic superbases and short carboxylic acids.

This work presents a comprehensive evaluation of the phase behaviour and cohesive enthalpy of protic ionic liquids (PILs) composed of 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) organic superbases with short-chain length (acetic, propionic and butyric) carboxylic acids. Glass transition temperatures, Tg, and enthalpies of vaporization, ΔHvap, were measured for six [BH][A] (1 : 1) PILs (B = DBN, DBU; A = MeCOO, EtCOO, nPrCOO), revealing more significant changes upon increasing the number of -CH2- groups in the base than in the acid. The magnitude of ΔHvap evidences that liquid PILs have a high proportion of ions, although the results also indicate that in DBN PILs the concentration of neutral species is not negligible. In the gas phase, these PILs exist as a distribution of ion pairs and isolated neutral species, with speciation being dependent on the temperature and pressure conditions - at high temperatures and low pressures the separated neutral species dominate. The higher Tg and ΔHvap of the DBU PILs are explained by the stronger basicity of DBU (as supported by NMR and computational calculations), which increases the extent of proton exchange and the ionic character of the corresponding PILs, resulting in stronger intermolecular interactions in condensed phases.

Alcohols as molecular probes in ionic liquids: evidence for nanostructuration.

A comprehensive study of the solution and solvation of linear alcohols (propan-1-ol, butan-1-ol and pentan-1-ol) in ionic liquids (ILs) is presented. The effect of the alkyl chain size of both alcohols and ILs (1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [CnC1im][NTf2], ionic liquid series) on the thermodynamic properties of solution and solvation was used to obtain insight into the interactions between alcohols and ILs. Alcohols were used as molecular probes to ascertain whether their solvation in ILs would reflect IL nanostructuration. A trend shift was found in the values of enthalpy of solution and solvation for the [CnC1im][NTf2] series at a critical alkyl size (CAS) of C6. Further, the effect of the hydrogen bond basicity of the anion in the solvation of alcohols was explored based on the comparative study of the solvation of propan-1-ol in two different IL series, 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [CnC1im][NTf2] and hexafluorophosphate [CnC1im][PF6]. The results obtained provide experimental support for the strength of hydrogen bonds between the alcohols and the NTf2 and PF6 anions, providing insights into the IL intermolecular interactions, namely by indicating the ability of the alcohols to discriminate the IL anion hydrogen bond basicity.

How to promote adverse drug reaction reports using information systems - a systematic review and meta-analysis.

BACKGROUND: Adverse drug reactions (ADRs) are a well-recognized public health problem and a major cause of death and hospitalization in developed countries. The safety of a new drug cannot be established until it has been on the market for several years. Keeping drug reactions under surveillance through pharmacovigilance systems is indispensable. However, underreporting is a major issue that undermines the effectiveness of spontaneous reports. Our work presents a systematic review on the use of information systems for the promotion of ADR reporting. The aim of this work is to describe the state of the art information systems used to promote adverse drug reaction reporting. METHODS: A systematic review was performed with quantitative analysis of studies describing or evaluating the use of information systems to promote adverse drug reaction reporting. Studies with data related to the number of ADRs reported before and after each intervention and the follow-up period were included in the quantitative analysis. RESULTS: From a total of 3865 articles, 33 articles were included in the analysis; these articles described 29 different projects. Most of the projects were on a regional scale (62 %) and were performed in a hospital context (52 %). A total of 76 % performed passive promotion of ADR reporting and used web-based software (55 %). A total of 72 % targeted healthcare professionals and 24 % were oriented to patient ADR reporting. We performed a meta-analysis of 7 of the 29 projects to calculate the aggregated measure of the ADR reporting increase, which had an overall measure of 2.1 (indicating that the interventions doubled the number of ADRs reported). CONCLUSIONS: We found that most of the projects performed passive promotion of ADR reporting (i.e., facilitating the process). They were developed in hospitals and were tailored to healthcare professionals. These interventions doubled the number of ADR reports. We believe that it would be useful to develop systems to assist healthcare professionals with completing ADR reporting within electronic health records because this approach seems to be an efficient method to increase the ADR reporting rate. When this approach is not possible, it is essential to have a tool that is easily accessible on the web to report ADRs. This tool can be promoted by sending emails or through the inclusion of direct hyperlinks on healthcare professionals' desktops.

Hepatotoxicity related to agomelatine and other new antidepressants: a case/noncase approach with information from the Portuguese, French, Spanish, and Italian pharmacovigilance systems.

Antidepressants have been associated with a low incidence of idiosyncratic hepatic injury. Some of them, nefazodone or amineptine, were observed to induce severe hepatic injury and withdrawn from the market. Recently, some cases of this severe condition have been reported in association with agomelatine use. Therefore, the objective of this study is to learn the risk of hepatic damage with agomelatine as compared with other new antidepressants. We took data from the Spanish, French, Italian, and Portuguese pharmacovigilance system databases. A case/noncase approach to assess the strength of the association between whichever antidepressant and hepatotoxicity was performed; cases were defined as reports of hepatotoxicity; noncases were reports of all reactions other than hepatotoxicity. Exposure was the recording of a new antidepressant in a report, whether or not it was suspected of causing the reaction. During the period surveyed, 3300 cases of hepatotoxicity were collected for the antidepressants assessed. They represent 10.3% of all cases collected for these drugs; the corresponding figure for all drugs was 6.0%. Meanwhile, 63 cases of hepatotoxicity associated with agomelatine were collected since its introduction until the end of the period studied; they account for a percentage of 14.6. Agomelatine was statistically associated with hepatotoxicity in Spain [reporting odds ratio (ROR), 4.9 (95% confidence interval [CI], 2.4-9.7)], France (ROR, 2.4 [95% CI, 1.5-3.7]), and Italy (ROR, 5.1 [95% CI, 1.7-14.0]). Current results support the idea of agomelatine to be related to a higher hepatotoxicity risk. Physicians should consider early discontinuation if the condition is suspected; health authorities should promptly explore the best regulatory actions to be taken.

MedGAN: optimized generative adversarial network with graph convolutional networks for novel molecule design.

Generative Artificial Intelligence can be an important asset in the drug discovery process to meet the demand for novel medicines. This work outlines the optimization and fine-tuning steps of MedGAN, a deep learning model based on Wasserstein Generative Adversarial Networks and Graph Convolutional Networks, developed to generate new quinoline-scaffold molecules from complex molecular graphs, including hyperparameter adjustments and evaluations of drug-likeness attributes such as pharmacokinetics, toxicity, and synthetic accessibility. The best model was capable of generating 25% valid molecules, 62% fully connected, from which 92% were quinolines, 93% were novel, and 95% unique, preserving chirality, atom charge, and favorable drug-like properties while generating 4831 novel quinolines. These results provide valuable insights into how activation functions, optimizers, learning rates, neuron units, molecule size and constitution, and scaffold structure affect the performance of generative models and their potential to create new molecular structures, enhancing deep learning applications in computational drug design.

Unveiling the future: precision pharmacovigilance in the era of personalized medicine.

In the era of personalized medicine, pharmacovigilance faces new challenges and opportunities, demanding a shift from traditional approaches. This article delves into the evolving landscape of drug safety monitoring in the context of personalized treatments. We aim to provide a succinct reflection on the intersection of tailored therapeutic strategies and vigilant pharmacovigilance practices. We discuss the integration of pharmacogenetics in enhancing drug safety, illustrating how genetic profiling aids in predicting drug responses and adverse reactions. Emphasizing the importance of phase IV-post-marketing surveillance, we explore the limitations of pre-marketing trials and the necessity for a comprehensive approach to drug safety. The article discusses the pivotal role of pharmacogenetics in pre-exposure risk management and the redefinition of pharmacoepidemiological methods for post-exposure surveillance. We highlight the significance of integrating patient-specific genetic profiles in creating personalized medication leaflets and the use of advanced computational methods in data analysis. Additionally, we examine the ethical, privacy, and data security challenges inherent in precision medicine, emphasizing their implications for patient consent and data management.

A Comparison of Active Pharmacovigilance Strategies Used to Monitor Adverse Events to Antiviral Agents: A Systematic Review.

INTRODUCTION: The safety of antiviral agents in real-world clinical settings is crucial, as pre-marketing studies often do not capture all adverse events (AE). Active pharmacovigilance strategies are essential for detecting and characterising these AE comprehensively. OBJECTIVE: The aim of this study was to identify and characterise active pharmacovigilance strategies used in real-world clinical settings for patients under systemic antiviral agents, focusing on the frequency of AE and the clinical data sources used. METHODS: We conducted a systematic review by searching three electronic bibliographic databases targeting observational prospective active pharmacovigilance studies, phase IV clinical trials for post-marketing safety surveillance, and interventional studies assessing active pharmacovigilance strategies, focusing on individuals exposed to systemic antiviral agents. RESULTS: We included 36 primary studies, predominantly using Drug Event Monitoring (DEM), with a minority employing sentinel sites and registries. Human immunodeficiency virus (HIV) was the most common condition, with the majority using DEM. Within the DEM, there was a wide range of incidences of patients experiencing at least one AE, and most of these studies used one or two data sources. Sentinel site studies were less common, with two on hepatitis C virus (HCV) and one on HIV, each relying on one or two data sources. The single study using a registry focusing on HIV therapy reported using just one data source. Patient interviews were the most common data source, followed by medical records and laboratory tests. The quality of the studies was considered 'good' in 18/36, 'fair' in 1/36, and 'poor' in 17/36 studies. CONCLUSION: DEM was the predominant pharmacovigilance strategy, employing multiple data sources, and appears to increase the likelihood of detecting higher AE incidence. Establishing such a framework would facilitate a more detailed and consistent approach across different studies and settings.

Renal effects of selective cyclooxygenase-2 inhibitor anti-inflammatory drugs: A systematic review and meta-analysis.

Background: Selective cyclooxygenase-2 inhibitor anti-inflammatory drugs (coxibs) are associated with the development of adverse events, mainly gastrointestinal and cardiovascular, but renal effects are less known. Objective: To assess the renal risks of coxibs compared to placebo by means of a systematic review and meta-analysis. Methods: Randomized controlled trials that assessed renal effects of coxibs (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) were searched in PubMed, Embase, Scopus and other sources up to March 2024. Two independent reviewers performed study screening, data extraction, and risk of bias assessment. Random effect meta-analysis was employed to calculate the relative risks (RR) and 95% confidence intervals (CI) of renal effects of coxibs compared to placebo and inconsistency among studies (I 2 ). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Out of 5284 retrieved records, 49 studies (comprising 46 reports) were included. Coxibs increased the risk of edema (RR 1.46; 95% CI 1.15, 1.86; I 2  = 0%; 34 studies, 19,754 participants; moderate-certainty evidence), and celecoxib increased hypertensive or renal events (RR 1.24; 95% CI 1.08, 1.43; I 2  = 0%; 2 studies, 3589 participants; moderate-certainty evidence). Etoricoxib increased the risk of hypertension (RR 1.98; 95% CI 1.14, 3.46; I 2  = 34%; 13 studies, 6560 participants; moderate-certainty evidence); no difference was observed when pooling all coxibs (RR 1.26; 95% CI 0.91, 1.76; I 2  = 26%; 30 studies, 16,173 participants; moderate-certainty evidence). Conclusions: Coxibs likely increase the renal adverse effects, including hypertension and edema. Awareness about the renal risks of coxibs should be increased, mainly in high-risk patient.

Assessing medication use patterns by clinical outcomes severity among inpatients with COVID-19: A retrospective drug utilization study.

PURPOSE: This study assessed medication patterns for inpatients at a central hospital in Portugal and explored their relationships with clinical outcomes in COVID-19 cases. METHODS: A retrospective study analyzed inpatient medication data, coded using the Anatomical Therapeutic Chemical classification system, from electronic patient records. It investigated the association between medications and clinical severity outcomes such as ICU admissions, respiratory/circulatory support needs, and hospital discharge status, including mortality (identified by ICD-10-CM/PCS codes). Multivariate analyses incorporating demographic data and comorbidities were used to adjust for potential confounders and understand the impact of medication patterns on disease progression and outcomes. RESULTS: The analysis of 2688 hospitalized COVID-19 patients (55.3% male, average age 62.8 years) revealed a significant correlation between medication types and intensity and disease severity. Cases requiring ICU admission or ECMO support often involved blood and blood-forming organ drugs. Increased use of nervous system and genitourinary hormones was observed in nonsurvivors. Corticosteroids, like dexamethasone, were common in critically ill patients, while tocilizumab was used in ECMO cases. Medications for the alimentary tract, metabolism, and cardiovascular system, although widely prescribed, were linked to more severe cases. Invasive mechanical ventilation correlated with higher usage of systemic anti-infectives and musculoskeletal medications. Trends in co-prescribing blood-forming drugs with those for acid-related disorders, analgesics, and antibacterials were associated with intensive interventions and worse outcomes. CONCLUSIONS: The study highlights complex medication regimens in managing severe COVID-19, underscoring specific drug patterns associated with critical health outcomes. Further research is needed to explore these patterns.

Public's perspective on COVID-19 adenovirus vector vaccines after thrombosis with thrombocytopenia syndrome (TTS) reports and associated regulatory actions - A cross-sectional study in six EU member states.

OBJECTIVE: In 2021, thrombosis with thrombocytopenia syndrome (TTS) was confirmed by the European Medicines Agency (EMA) as a rare side effect of the COVID-19 adenovirus vector vaccines Vaxzevria® and Jcovden®. This study aimed to describe the public's knowledge of TTS and how it affected the willingness to be vaccinated with COVID-19 vaccines and other vaccines in six European countries. METHODS: From June to October of 2022, a multi-country cross-sectional online survey was conducted in Denmark, Greece, Latvia, Netherlands, Portugal, and Slovenia. The minimum target of participants to be recruited was based on the size of the country's population. The results were analysed descriptively. RESULTS: In total, 3794 respondents were included in the analysis; across the six countries, 33.3 %-68.3 % reported being familiar with signs and symptoms of TTS, although 3.1-61.4 % of those were able to identify the symptoms correctly. The reported changes in willingness to be vaccinated against COVID-19 and with other vaccines varied per country. The largest reported change in the willingness to be vaccinated with Vaxzevria® and Jcovden® was observed in Denmark (61.2 %), while the willingness to be vaccinated with other COVID-19 vaccines changed most in Slovenia (30.4 %). The smallest decrease in willingness towards future vaccination against COVID-19 was reported in the Netherlands (20.9 %) contrasting with the largest decrease observed in Latvia (69.1 %). CONCLUSION: Knowledge about TTS seemed to have influenced the public's opinion in Europe resulting in less willingness to be vaccinated with Vaxzevria® and Jcovden®. Willingness for vaccination against COVID-19 with other vaccines and widespread use of vaccines to prevent other diseases also differed and seemed to be determined by the approaches taken by national health authorities when reacting to and communicating about COVID-19 vaccination risks. Further investigation of optimal risk communication strategies is warranted.