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1.
J Clin Med ; 12(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38068499

RESUMO

Awareness related to the risk/benefit profile of therapies used in paediatric and elderly patients is limited. We carried out a study, called the MEAP 3.0 study, to collect and analyse evidence of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) that occurred in frail populations under polypharmacy in a real-world setting. Data were retrieved from reports of ADRs and pharmacological counselling from patients treated in hospitals and territorial health services. We collected 2977 ADRs reports and identified 'anti-infectives for systemic use' and 'cardiovascular system' as the most frequently implicated pharmacological classes in under-18 and over-65 patients, respectively. We detected 2179 DDIs, of which 10.7% were related to at least one ADR: 22 were classified as 'contraindicated' (7 in the paediatric group and 15 in the elderly one), and 61 as 'major' (6 in the paediatric patients and 55 in the geriatric ones), while 151 DDIs were classified as 'moderate' (10 referred to paediatric population, and 109 to elderly patient) and as 'minor' (1 in paediatric patients, and 31 in the elderly ones). The MEAP 3.0 project demonstrates that pharmacovigilance surveillance and therapeutic reconciliation are valid strategies to avoid potential DDIs and the occurrence of ADRs, allowing for personalised medicine.

2.
Pharmaceutics ; 15(12)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38139989

RESUMO

Exceptional advances have been made with systemic treatment for psoriasis (PSO). However, that disease still represents a heavy burden in terms of impact on healthcare systems worldwide. This study comprehensively assesses medication adherence in a real world setting in Italy across all phases-initiation, implementation, and persistence-of PSO therapies. By distinguishing between switches and swaps, it provides unique insights into the patient's own approach to prescribed therapy as well as clinical decision-making processes, enhancing our understanding of medication adherence and discontinuation in a real world daily setting. The study's refined methodology for assessing persistence, considering variations in refill gaps and complex dosing regimens, shows that anti-interleukin (IL) therapies are associated with longer periods of adherence compared with other available therapeutic strategies. Among the selected drugs, ixekizumab and secukinumab were the ones with higher rate of treatment adherence at the expense of anti-TNF-α and anti-PDE4 agents. Notably, patients who opt for swaps are approximately 2.8 times more likely to discontinue their PSO therapy within one year. These findings carry practical implications for optimizing medication adherence, including tailored patient counseling, monitoring, and therapeutic adjustments, highlighting the need for a comprehensive and patient-centered approach to managing these conditions.

3.
Front Pharmacol ; 14: 1245642, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027019

RESUMO

Background: The risk of falls and bone fractures with sodium-glucose co-transporter-2 (SGLT2) inhibitors has been characterized by conflicting evidence. Therefore, we decided to investigate the reporting probability of falls and fractures by comparing SGLT2 inhibitors with DPP4 inhibitors. Methods A retrospective, pharmacovigilance study of the European database of Individual Case Safety Reports (ICSRs) was conducted. Disproportionality analyses (Reporting Odds Ratio, ROR) were conducted to compare the reporting probability of falls or fracture between treatments. Results A total of 507 ICSRs reporting at least one fall or fracture with SGLT2 inhibitors were identified. The most reported SGLT2 inhibitor was canagliflozin (N = 188; 36.9%), followed by empagliflozin (N = 176; 34.5%), and dapagliflozin (N = 143; 28.0%). A total of 653 events related to fall or bone fracture were reported. Fall was the most reported event (N = 333; 51.0%). Among fractures (N = 320; 49.0%), the most reported were foot fractures (N = 40; 6.1%) and hip fractures (N = 32; 4.9%). SGLT2 inhibitors were associated with a lower reporting probability of fall than DPP4 inhibitors (ROR, 0.66; 95%CI, 0.57-0.78). The lower reporting probability of fall was also observed when the single SGLT2 inhibitor was compared to DPP4 inhibitors: dapagliflozin (ROR, 0.67; 95%CI, 0.53-0.83), canagliflozin (ROR, 0.56; 95%CI, 0.45-0.70), and empagliflozin (ROR, 0.77; 95%CI, 0.63-0.94). For fractures, canagliflozin showed a slightly significant increased reporting when compared with DPP4 inhibitors (not confirmed in the sensitivity analysis), whereas all other comparison showed no statistically significant difference. Conclusion SGLT2 inhibitors were associated with a lower reporting probability of fall than DPP4 inhibitors, in accordance with the reassuring evidence about the safety profile of these drugs. Future researches will help to confirm their long-term safety profile.

4.
Pharmaceuticals (Basel) ; 16(9)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37765039

RESUMO

Multisystem inflammatory syndrome in children (MIS-c) is an uncommon, but serious, inflammatory response that occurs after SARS-CoV-2 infection. As time went by, MIS-c was also reported as a potential adverse event following COVID-19 vaccination. A descriptive analysis was performed of Individual Case Safety Reports (ICSRs) associated with anti COVID-19 vaccines and related to the pediatric population from 2020 to 2022. The present pharmacovigilance study aimed to describe cases of MIS-c following COVID-19 vaccination, stratified by sex, reported in the Vaccine Adverse Events Reporting System (VAERS) and meeting the Brighton Collaboration criteria for case definition. We assessed all suspected cases through the case definition and classification of the Brighton Collaboration Group, and only definitive, probable, and possible cases were included in the analysis. The Reporting Odds Ratio (ROR) with 95% Confidence Interval (CI) was computed to assess if males have a lower/higher probability of reporting ICSRs with MIS-c compared with females. Overall, we found 79 cases of potentially reported MIS-c following vaccination. This study demonstrated that MIS-c following vaccination was more commonly reported for male subjects with a median age of 10 years (IQR 10.0-11.4), especially after the first dose of anti COVID-19 vaccines with a median time to onset of 27 days. Even so, the rate of occurrence of MIS-c following anti COVID-19 vaccines is lower (0.12/100,000 vaccinated subjects; 95% CI, 0.12-0.13). Overall, all ICSRs were serious and caused or prolonged hospitalization. Finally, disproportionality analysis showed that males had a higher reporting probability of MIS-c compared with females following immunization with mRNA COVID-19 vaccines. Since only a few years of marketing are available, further data from real-life contexts are needed.

5.
Biomedicines ; 11(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37626659

RESUMO

During pre-approval clinical trials, the safety of axi-cel, a second-generation CAR-T-cell therapy directed against CD19, which dramatically improved the prognosis of intractable B-cell lymphomas, has been investigated only in about 400 patients. Therefore, additional information on this issue is urgently needed. In the present paper, we evaluated the 2905 ICSRs with axi-cel as the suspected drug that had been uploaded in the EudraVigilance database from 1 January 2018 to 31 December 2022. About 80% of the reported adverse events were serious, and about 20% of them did not fully resolve or caused death. The adverse events most-frequently reported were Nervous system disorders (25.6%) and, among them, immune-effector-cell-associated neurotoxicity syndrome, followed by Immune system disorders (23.1%), General disorders and administration site conditions (12.0%), Blood and lymphatic system disorders (7.2%), and Infections and infestations (5.8%). Disproportionality analysis showed that the frequency of reported adverse events related to the nervous system was higher with axi-cel than with the other approved CAR-T-cells, except brexu-cel. In conclusion, real-world pharmacovigilance data showed that nervous system and immune system disorders are the adverse events most reported in axi-cel-related ICSRs and suggest that axi-cel could be more neurotoxic than other CAR-T-cells.

6.
Biomedicines ; 11(6)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37371680

RESUMO

Atrial fibrillation (AF) has been described in COVID-19 patients. Recently, some case reports and US pharmacovigilance analyses described AF onset as a rare adverse event following COVID-19 vaccination. The possible correlation is unclear. We systematically analyzed the reports of AF related to COVID-19 vaccines collected in the European pharmacovigilance database, EudraVigilance (EV), from 2020 to November 2022. We carried out descriptive and disproportionality analyses. Moreover, we performed a sensitivity analysis, excluding the reports describing other possible alternative AF causes (pericarditis, myocarditis, COVID-19, or other drugs that may cause/exacerbate AF). Overall, we retrieved 6226 reports, which represented only 0.3% of all those related to COVID-19 vaccines collected in EV during our study period. AF reports mainly referred to adults (in particular, >65 years old), with an equal distribution in sex. Reports were mainly related to tozinameran (54.04%), elasomeran (28.3%), and ChAdOx1-S (14.32%). The reported AF required patient hospitalization in 35% of cases and resulted in a life-threatening condition in 10% of cases. The AF duration (when reported) was highly variable, but the majority of the events had a short duration (moda = 24 h). Although an increased frequency of AF reporting with mRNA vaccines emerges from our study, other investigations are required to investigate the possible correlation between COVID-19 vaccination and the rare AF occurrence.

7.
J Cosmet Dermatol ; 22(9): 2420-2423, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37128806

RESUMO

The use of hyaluronic acid (HA)-based aesthetic therapies is growing steadily, and according to the International Society of Aesthetic Plastic Surgery, more than 4.3 million aesthetic procedures using HA were performed in 2019, an increase of 15.7% than 2018. More people are offering these types of services, often without proper training or qualifications. Therefore, there is an increasing number of reports in the literature relating to possible adverse events, with subsequent therapeutic problems and more or less serious consequences for patients. The aim of this research is to carry out a review of the literature in order to evaluate the impact of hyaluronic acid-based fillers in patients with autoimmune inflammatory diseases, in particular scleroderma and Systemic Lupus Erythematosus (SLE). Although HA plays a central role in the inflammatory process, the use of HA-based fillers in patients with autoimmune inflammatory diseases is still controversial. HA, in fact, in inflamed tissues helps to propagate the inflammatory response and, injected in the form of a dermal filler, could potentially promote reactivation of the underlying disease. For this reason, many specialists do not perform HA-based aesthetic treatments in patients with scleroderma or SLE. However, recent scientific evidence suggests that the use of HA-based fillers in patients with scleroderma can lead to improvement of skin lesions, with satisfactory results. In the literature, there are no clinical studies that contraindicate the administration of HA-based dermal fillers in patients with inflammatory disease.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos , Lúpus Eritematoso Sistêmico , Cirurgia Plástica , Humanos , Ácido Hialurônico/efeitos adversos , Técnicas Cosméticas/efeitos adversos , Rejuvenescimento , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/induzido quimicamente , Preenchedores Dérmicos/efeitos adversos
8.
Front Pediatr ; 11: 1149718, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168802

RESUMO

Background: Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin receptor agonist, provides a hematologic improvement in adults with severe aplastic anemia (SAA) refractory to immunosuppressive therapy (IST). The association of ELT and IST was approved by the US Food and Drug Administration (FDA) for adults and children ≥2 years of age as a first-line treatment for SAA. However, the effects of ELT on pediatric patients with SAA remain controversial and limited. Methods and findings: We conducted a systematic review of the most recent literature from Pubmed, Web of Science, and Embase, published up to 20th December 2022, in order to evaluate the available evidence on the efficacy and safety of ELT added to IST for the treatment of SAA in the pediatric population. Conclusion: Eltrombopag added to the IST has shown a good safety profile, without manifestations of excessive toxic effects, although not all the results obtained from our studies support the addition of ELT to the IST in the first-line treatment of children with SAA. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022325859.

9.
Biomed Pharmacother ; 164: 114912, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37210896

RESUMO

BACKGROUND: Despite the available evidence showing an association between cardiac arrhythmia and Immune Checkpoint Inhibitors (ICIs), few studies have compared this risk between ICIs. OBJECTIVES: We aim to evaluate Individual Case Safety Reports (ICSRs) of ICIs-induced cardiac arrhythmias and compare the reporting frequency of cardiac arrhythmias among ICIs. METHODS: ICSRs were retrieved from the European Pharmacovigilance database (Eudravigilance). ICSRs were classified based on the ICI reported (pembrolizumab, nivolumab, atezolizumab, ipilimumab, durvalumab, avelumab, cemiplimab, and dostarlimab). If more than one ICI was reported, the ICSR was classified as a combination of ICIs. ICSRs of ICI-related arrhythmias were described and the reporting frequency of cardiac arrhythmias was assessed by applying the reporting odds ratio (ROR) and its 95 % confidence interval (95 %CI). RESULTS: A total of 1262 ICSRs were retrieved, of which 147 (11.65 %) were related to combinations of ICIs. A total of 1426 events of cardiac arrhythmias were identified. The three most reported events were atrial fibrillation, tachycardia, and cardiac arrest. Ipilimumab was associated with a reduced reporting frequency of cardiac arrhythmias compared to all other ICIs (ROR 0.71, 95 %CI 0.55-0.92; p = 0.009). Anti-PD1 was associated with a higher reporting frequency of cardiac arrhythmias than anti-CTLA4 (ROR 1.47, 95 %CI 1.14-1.90; p = 0.003). CONCLUSION: This study is the first comparing ICIs for the risk of cardiac arrhythmias. We found that ipilimumab was the only ICI associated with a reduced reporting frequency. Further high-quality studies are needed to confirm our results.


Assuntos
Antineoplásicos Imunológicos , Fibrilação Atrial , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Ipilimumab , Farmacovigilância
10.
J Clin Med ; 12(8)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37109111

RESUMO

Atopy is an exaggerated IgE-mediated immune response to foreign antigens in which metabolic abnormalities of the leukotrienes (LTs) pathway play a crucial role. Recent studies have described sex as a key variable in LT biosynthesis, partly explaining why treatment with anti-LT drugs in atopic subjects leads to better control of symptoms in women. In addition, variability in LT production is often associated with single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase (ALOX5) gene, which encodes the leukotriene-synthesizing enzyme machinery, 5-lipoxygenase (5-LO). This study aimed to investigate whether two SNPs of ALOX5 are implicated in sex differences in allergic diseases in a prospective cohort of 150 age- and sex-matched atopic and healthy subjects. Rs2029253 and rs2115819 were genotyped using allele-specific RT-PCR, and serum levels of 5-LO and LTB4 were measured by ELISA. Both polymorphisms are significantly more common in women than in men, and their influences on LT production vary as a function of sex, leading to a decrease in men's and an increase in women's serum levels of 5-LO and LTB4. These data represent a new resource for understanding sex-related differences in lung inflammatory diseases, partly explaining why women are more likely to develop allergic disorders than men.

11.
Pharmacol Res ; 190: 106742, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36963592

RESUMO

Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.


Assuntos
Neoplasias Hematológicas , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Adulto , Linfócitos T , Neoplasias Hematológicas/terapia , Doença Crônica , Recidiva , Terapia Baseada em Transplante de Células e Tecidos
12.
Cardiovasc Diabetol ; 22(1): 24, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732760

RESUMO

BACKGROUND: Sodium-glucose co-transporters (SGLT) inhibitors (SGLT2i) showed many beneficial effects at the cardiovascular level. Several mechanisms of action have been identified. However, no data on their capability to act via epigenetic mechanisms were reported. Therefore, this study aimed to investigate the ability of SGLT2 inhibitors (SGLT2i) to induce protective effects at the cardiovascular level by acting on DNA methylation. METHODS: To better clarify this issue, the effects of empagliflozin (EMPA) on hyperglycemia-induced epigenetic modifications were evaluated in human ventricular cardiac myoblasts AC16 exposed to hyperglycemia for 7 days. Therefore, the effects of EMPA on DNA methylation of NF-κB, SOD2, and IL-6 genes in AC16 exposed to high glucose were analyzed by pyrosequencing-based methylation analysis. Modifications of gene expression and DNA methylation of NF-κB and SOD2 were confirmed in response to a transient SGLT2 gene silencing in the same cellular model. Moreover, chromatin immunoprecipitation followed by quantitative PCR was performed to evaluate the occupancy of TET2 across the investigated regions of NF-κB and SOD2 promoters. RESULTS: Seven days of high glucose treatment induced significant demethylation in the promoter regions of NF-kB and SOD2 with a consequent high level in mRNA expression of both genes. The observed DNA demethylation was mediated by increased TET2 expression and binding to the CpGs island in the promoter regions of analyzed genes. Indeed, EMPA prevented the HG-induced demethylation changes by reducing TET2 binding to the investigated promoter region and counteracted the altered gene expression. The transient SGLT2 gene silencing prevented the DNA demethylation observed in promoter regions, thus suggesting a role of SGLT2 as a potential target of the anti-inflammatory and antioxidant effect of EMPA in cardiomyocytes. CONCLUSIONS: In conclusion, our results demonstrated that EMPA, mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects.


Assuntos
Hiperglicemia , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , NF-kappa B/metabolismo , Transportador 2 de Glucose-Sódio/genética , Transportador 2 de Glucose-Sódio/metabolismo , Compostos Benzidrílicos/farmacologia , Glucose/toxicidade , Epigênese Genética
13.
Front Cardiovasc Med ; 10: 1093053, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36755799

RESUMO

Almost 20% of COVID-19 patients have a history of atrial fibrillation (AF), but also a new-onset AF represents a frequent complication in COVID-19. Clinical evidence demonstrates that COVID-19, by promoting the evolution of a prothrombotic state, increases the susceptibility to arrhythmic events during the infective stages and presumably during post-recovery. AF itself is the most frequent form of arrhythmia and is associated with substantial morbidity and mortality. One of the molecular factors involved in COVID-19-related AF episodes is the angiotensin-converting enzyme (ACE) 2 availability. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 to enter and infect multiple cells. Atrial ACE2 internalization after binding to SARS-CoV-2 results in a raise of angiotensin (Ang) II, and in a suppression of cardioprotective Ang(1-7) formation, and thereby promoting cardiac hypertrophy, fibrosis and oxidative stress. Furthermore, several pharmacological agents used in COVID-19 patients may have a higher risk of inducing electrophysiological changes and cardiac dysfunction. Azithromycin, lopinavir/ritonavir, ibrutinib, and remdesivir, used in the treatment of COVID-19, may predispose to an increased risk of cardiac arrhythmia. In this review, putative mechanisms involved in COVID-19-related AF episodes and the cardiovascular safety profile of drugs used for the treatment of COVID-19 are summarized.

14.
Vaccines (Basel) ; 11(2)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36851276

RESUMO

Although the safety profiles of mRNA COVID-19 vaccines (mRNA-1273 and BNT162b2) were evaluated in pre-authorization clinical trials, real-world data allow us to better define their benefit/risk ratio in the paediatric population. The current study aimed to evaluate the safety profiles of mRNA COVID-19 vaccines in children by analysing the pharmacovigilance data of the European spontaneous reporting system database EudraVigilance (EV) in the period from 1 January 2021, to 1 October 2022. During our study period, overall 4838 ICSRs related to mRNA COVID-19 vaccines referring to 5-11-year-old subjects were retrieved from EV, of which 96.9% were related to BNT162b2 and 49.3% were related to males. A total of 12,751 Adverse Events Following Immunization (AEFIs) were identified, of which 38.7% were serious. The most frequently reported AEFIs were pyrexia, headache, and vomiting. Only 20 Individual Case Safety Reports (ICSRs) reported Multisystem Inflammatory Syndrome (MIS) as an AEFI, all related to BNT162b2. The majority of MIS cases were females, and six cases were completely resolved at the time of reporting. Our results show a favourable risk-benefit profile for all mRNA COVID-19 vaccines in this paediatric sub-population, supporting their use in children. Considering the peculiarity and fragility of children, continuous safety monitoring of COVID-19 vaccines is required.

15.
Front Cardiovasc Med ; 9: 1010693, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211584

RESUMO

A new therapeutic class of oral agents firstly used for the treatment of type 2 diabetes mellitus is represented by gliflozines or sodium-glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors might be effective alone or in combination with any other drugs. This therapeutic class currently includes five agents: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin. SGLT2 inhibitors prevent the renal reabsorption of filtered glucose and sodium by blocking the SGLT2 co-transporters in the proximal convoluted renal tubule, facilitating glucose excretion in the urine (glycosuria) and lowering blood glucose levels. SGLT2 inhibitors have also shown to have pleiotropic effects and determine cardiovascular and renal prevention, thus leading to an extension of their therapeutic indication to include the heart failure. Despite their clinical benefits, warnings about adverse events have been implemented by Regulatory Agencies in the product's information since their introduction to the market. In particular, SGLT2 inhibitors have shown a strong impact on a high number of risk factors. They can cause hypoglycaemia, hypotension, lower limb amputation, fractures, genito-urinary infections, and diabetic ketoacidosis with different frequencies of onset. Despite some of these events are rare, they can lead to serious and dangerous complications, highlighting the importance of a strict monitoring of patients. Overall, SLGT-2 inhibitors are effective antidiabetic drugs with favorable advantages in renal and cardiovascular protection, and with a generally well-tolerated safety profile. This review aims to summarize the safety profile of SGLT2 inhibitors available in the market.

16.
Expert Rev Clin Pharmacol ; 15(10): 1225-1231, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36196903

RESUMO

INTRODUCTION: Drug repurposing represented an important contribution in the management of COVID-19, becoming the first line of defense to mitigate the effects of the new coronavirus. In a brief time, drug repurposing (DR) provided potentially effective and already available drugs for COVID-19, while specific therapies against SARS-CoV-2 and/or vaccines were developing. Identifying repurposed drugs requires a multidisciplinary approach, where clinical pharmacology represents the missing piece of the puzzle. AREAS COVERED: Nowadays, clinical pharmacology is recognized as a discipline at the core of translational science, whose activities lead to the identification of the right drug for the right patient. In the context of the COVID-19 pandemic, its role in drug development and therapy choice has been decisive and itself repositioned. In this review, we tried to highlight the important role of clinical pharmacology in the identification and evaluation of possible repurposed drugs for COVID-19. EXPERT OPINION: We believe that clinical pharmacology had an important role in identifying patient-oriented therapy during the COVID-19 pandemic. In this context, DR was just one of the challenges for clinical pharmacology, which proved that this discipline is ready to respond to future threats.


Assuntos
Tratamento Farmacológico da COVID-19 , Farmacologia Clínica , Humanos , Reposicionamento de Medicamentos , SARS-CoV-2 , Pandemias , Antivirais/farmacologia , Antivirais/uso terapêutico
17.
Front Immunol ; 13: 956825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36177033

RESUMO

Capillary leak syndrome (CLS) emerged as new adverse event after immunization (AEFI) associated to COVID-19 vaccination. CLS is a rare condition characterized by increased capillary permeability, resulting in hypoalbuminemia, hypotension, and edema mainly in the upper and lower limbs. Our pharmacovigilance study aims to evaluate the CLS onset following receipt of COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) compared to viral vector vaccines (Ad26.COV2-S and ChAdOx1-SARS-COV-2). We carried a cross-sectional study using all Individual Case Safety Reports (ICSRs) reporting a COVID-19 vaccine as suspected drug and CLS as AEFI, which were collected in the pharmacovigilance database EudraVigilance from January 1st, 2021, to January 14th, 2022. We applied the Reporting Odds Ratio (ROR) 95% CI for the disproportionality analysis. During our study period, CLS was described as AEFI in 84 out of 1,357,962 ICRs reporting a vaccine COVID-19 as suspected drug and collected in the EV database. Overall, the ICSR reported by CLS were mainly related to the viral vector COVID-19(ChAdOx1-SARS-COV-2 = 36; Ad26.COV2-S = 9). The mRNA COVID-19 vaccines were reported in 39 ICSRs (BNT162b2 =33; mRNA-1273 =6). Majority of ICSRs were reported by healthcare professionals (71.4%). Majority of the patients were adult (58.3%) and the female gender accounted in more than 65% of ICSRs referred both to classes vaccines. In particular, women were more represented in ICSRs referred to mRNA-1273 (83.3%) and to ChAdOx1-SARS-COV-2 (72.2%). The CLS outcome was more frequently favorable in mRNA ICSRs (33,3%) than the viral vector ones (13.3%). Among the ICSRs reporting CLS with unfavorable outcome, we found also 9 fatal cases (BNT162b2 = 1; ChAdOx1-SARS-COV-2 = 4; Ad26.COV2-S = 4). From disproportionality analysis emerged a lower CLS reporting probability after vaccination with mRNA vaccines compared to viral vector-based ones (ROR 0.5, 95% CI 0.3-0.7; p <0.001).Our findings, even if subject to the limitations of spontaneous reporting systems, suggest a small but statistically significant safety concern for CLS following receipt of COVID-19 viral vector vaccines, in particular with Ad26.COV2-S. Cytokine-release following T-cell activation could be involved in CLS occurrence, but a precise mechanism has been not yet identified. COVID-19 vaccines remain attentive as possible triggers of CLS.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Síndrome de Vazamento Capilar , Vacina de mRNA-1273 contra 2019-nCoV , Ad26COVS1 , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Síndrome de Vazamento Capilar/etiologia , Estudos Transversais , Citocinas , Feminino , Humanos , Farmacovigilância , RNA Mensageiro , SARS-CoV-2 , Vacinação/efeitos adversos , Vacinação/métodos
18.
J Clin Med ; 11(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36079034

RESUMO

Medical imaging is required for a complete clinical evaluation to identify lung involvement or pulmonary embolism during SARS-CoV-2 infection or pulmonary and cardiovascular sequelae. Contrast media (CM) have undoubtedly been useful in clinical practice due to their ability to improve medical imaging in COVID-19 patients. Considering their important use, especially in hospitalized COVID-19 patients, and that increased use of a medical tool could also be associated with its deeper knowledge, we chose to explore if new information emerged regarding CM safety profiles. We analyzed all Individual Case Safety Reports (ICSRs) validated by Campania Pharmacovigilance Regional Centre from 1 January 2018 to 31 December 2021 and reported a CM (ATC code V08) as a suspected drug. We compared CM-related reporting between 2 years before (period 1) and 2 years during (period 2) the COVID-19 pandemic. From our analysis, it emerged that, during the COVID-19 pandemic, CM-related ADR reporting decreased, but a significant increase in reporting of serious cases emerged. Serious ADRs were mainly related to iodinated CM (V08A ATC) compared to magnetic resonance imaging CM (V08C ATC). Cutaneous and respiratory disorders were the most frequently reported in both periods. No new or unknown ADRs were reported in the overall study period.

19.
Gels ; 8(7)2022 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-35877516

RESUMO

For many years, corneal transplantation has been the first-choice treatment for irreversible damage affecting the anterior part of the eye. However, the low number of cornea donors and cases of graft rejection highlighted the need to replace donor corneas with new biomaterials. Tissue engineering plays a fundamental role in achieving this goal through challenging research into a construct that must reflect all the properties of the cornea that are essential to ensure correct vision. In this review, the anatomy and physiology of the cornea are described to point out the main roles of the corneal layers to be compensated and all the requirements expected from the material to be manufactured. Then, a deep investigation of alginate as a suitable alternative to donor tissue was conducted. Thanks to its adaptability, transparency and low immunogenicity, alginate has emerged as a promising candidate for the realization of bioengineered materials for corneal regeneration. Chemical modifications and the blending of alginate with other functional compounds allow the control of its mechanical, degradation and cell-proliferation features, enabling it to go beyond its limits, improving its functionality in the field of corneal tissue engineering and regenerative medicine.

20.
Pharmacol Res ; 182: 106303, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35697289

RESUMO

OBJECTIVES: We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling. BACKGROUND: adverse cardiac remodeling characterized by left ventricle ejection fraction (LVEF) reduction, left ventricular end-systolic volume (LVESv) increase, and the 6-minute walking test (6MWT) reduction are relevant pathological mechanisms in CRTd non-responders and could be linked to changes in miRNAs (miRs), regulating cardiac fibrosis, apoptosis, and hypertrophy. METHODS: miRs levels and clinical outcomes (LVEF, cardiac deaths, and 6MWT) were evaluated at baseline and one year of follow-up in CRTd non-responders divided into ARNI-users and Non-ARNI users. RESULTS: At baseline, there were no differences in levels of inflammatory markers, miR-18, miR-145, and miR-181 (p > 0.05) between Non-ARNI users (n 106) and ARNI-users (n 312). At one year of follow-up, ARNI-users vs. Non-ARNI users showed lowest inflammatory markers (p < 0.01) and miR-181 levels (p < 0.01) and higher values of miR-18 (p < 0.01)and miR-145 (p < 0.01). At one year of follow-up, ARNI-users had a higher increase of LVEF (p < 0.01) and 6MWT (p < 0.01) along with a more significant reduction of LVESv (p < 0.01) compared to Non-ARNI users. Cox regression analysis evidenced that ARNI-based therapies increase the probability of anti-remodeling effects of CRTd. Based on symptomatic improvements, echocardiographic and functional classification improvements, 37 (34.9%) patients among ARNI-users became responders, while only twenty (6.4%) patients became responders among Non-ARNi-users. CONCLUSIONS: ARNI might influence epigenetic mechanisms modulating miRs implicated in the adverse cardiac remodeling responses to CRTd.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , MicroRNAs , Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Combinação de Medicamentos , Epigênese Genética , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Neprilisina/uso terapêutico , Receptores de Angiotensina/uso terapêutico , Volume Sistólico , Resultado do Tratamento , Remodelação Ventricular
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