Effectiveness of BNT162b2 vaccine against SARS-CoV-2 infection and severe COVID-19 in children aged 5-11 years in Italy: a retrospective analysis of January-April, 2022.

BACKGROUND: By April 13, 2022, more than 4 months after the approval of BNT162b2 (Pfizer-BioNTech) for children, less than 40% of 5-11-year-olds in Italy had been vaccinated against COVID-19. Estimating how effective vaccination is in 5-11-year-olds in the current epidemiological context dominated by the omicron variant (B.1.1.529) is important to inform public health bodies in defining vaccination policies and strategies. METHODS: In this retrospective population analysis, we assessed vaccine effectiveness against SARS-CoV-2 infection and severe COVID-19, defined as an infection leading to hospitalisation or death, by linking the national COVID-19 surveillance system and the national vaccination registry. All Italian children aged 5-11 years without a previous diagnosis of infection were eligible for inclusion and were followed up from Jan 17 to April 13, 2022. All children with inconsistent vaccination data, diagnosed with SARS-CoV-2 infection before the start date of the study or without information on the municipality of residence were excluded from the analysis. With unvaccinated children as the reference group, we estimated vaccine effectiveness in those who were partly vaccinated (one dose) and those who were fully vaccinated (two doses). FINDINGS: By April 13, 2022, 1 063 035 (35·8%) of the 2 965 918 children aged 5-11 years included in the study had received two doses of the vaccine, 134 386 (4·5%) children had received one dose only, and 1 768 497 (59·6%) were unvaccinated. During the study period, 766 756 cases of SARS-CoV-2 infection and 644 cases of severe COVID-19 (627 hospitalisations, 15 admissions to intensive care units, and two deaths) were notified. Overall, vaccine effectiveness in the fully vaccinated group was 29·4% (95% CI 28·5-30·2) against SARS-CoV-2 infection and 41·1% (22·2-55·4) against severe COVID-19, whereas vaccine effectiveness in the partly vaccinated group was 27·4% (26·4-28·4) against SARS-CoV-2 infection and 38·1% (20·9-51·5) against severe COVID-19. Vaccine effectiveness against infection peaked at 38·7% (37·7-39·7) at 0-14 days after full vaccination and decreased to 21·2% (19·7-22·7) at 43-84 days after full vaccination. INTERPRETATION: Vaccination against COVID-19 in children aged 5-11 years in Italy showed a lower effectiveness in preventing SARS-CoV-2 infection and severe COVID-19 than in individuals aged 12 years and older. Effectiveness against infection appears to decrease after completion of the current primary vaccination cycle. FUNDING: None. TRANSLATION: For the Italian translation of the summary see Supplementary Materials section.

Suspected adverse reactions to medications and food supplements containing Serenoa repens: A worldwide analysis of pharmacovigilance and phytovigilance spontaneous reports.

The safety of Serenoa repens (SR)-containing products was evaluated conducting a retrospective worldwide analysis of pharmaco- and phytovigilance report forms of suspected adverse reactions (SARs) collected up to 31 January 2022. Multivariate logistic regression was performed to estimate the odds ratios (ORs) of serious SAR. A total of 1810 report forms were analysed; 92% of subjects were males, with a median age of 69 years; 44% of cases were defined as serious. Subjects exposed to dietary supplements had a higher risk of developing serious SARs (OR: 1.60 [95% CI: 1.20-2.15]), as subjects exposed to 2-5 (OR: 1. 83 [95% CI: 1.30-2.58]) or more than 5 (OR: 3.45 [95% CI: 2.36-5.06]) suspect/interacting products. The probability of experiencing serious SAR was higher for subjects exposed to concomitant products (OR: 1.55 [95% CI: 1.15-2.08]), to more than four active compounds (OR: 4.38 [95% CI: 3.21-5.99]) and to SR for more than 14 days (OR: 1.89 [95% CI: 1.10-3, 22]), and lower for subjects exposed to higher doses of SR (OR: of 0.34 [95% CI: 0.20-0.58]). This evidence improves awareness on safety of SR containing products, suggesting the need of a further update of periodic reviews by national and international regulatory agencies.

Postmarketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12 to 39 years in Italy: A multi-database, self-controlled case series study.

BACKGROUND: Myocarditis and pericarditis following the Coronavirus Disease 2019 (COVID-19) mRNA vaccines administration have been reported, but their frequency is still uncertain in the younger population. This study investigated the association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccines, BNT162b2, and mRNA-1273 and myocarditis/pericarditis in the population of vaccinated persons aged 12 to 39 years in Italy. METHODS AND FINDINGS: We conducted a self-controlled case series study (SCCS) using national data on COVID-19 vaccination linked to emergency care/hospital discharge databases. The outcome was the first diagnosis of myocarditis/pericarditis between 27 December 2020 and 30 September 2021. Exposure risk period (0 to 21 days from the vaccination day, subdivided in 3 equal intervals) for first and second dose was compared with baseline period. The SCCS model, adapted to event-dependent exposures, was fitted using unbiased estimating equations to estimate relative incidences (RIs) and excess of cases (EC) per 100,000 vaccinated by dose, age, sex, and vaccine product. Calendar period was included as time-varying confounder in the model. During the study period 2,861,809 persons aged 12 to 39 years received mRNA vaccines (2,405,759 BNT162b2; 456,050 mRNA-1273); 441 participants developed myocarditis/pericarditis (346 BNT162b2; 95 mRNA-1273). Within the 21-day risk interval, 114 myocarditis/pericarditis events occurred, the RI was 1.99 (1.30 to 3.05) after second dose of BNT162b2 and 2.22 (1.00 to 4.91) and 2.63 (1.21 to 5.71) after first and second dose of mRNA-1273. During the [0 to 7) days risk period, an increased risk of myocarditis/pericarditis was observed after first dose of mRNA-1273, with RI of 6.55 (2.73 to 15.72), and after second dose of BNT162b2 and mRNA-1273, with RIs of 3.39 (2.02 to 5.68) and 7.59 (3.26 to 17.65). The number of EC for second dose of mRNA-1273 was 5.5 per 100,000 vaccinated (3.0 to 7.9). The highest risk was observed in males, at [0 to 7) days after first and second dose of mRNA-1273 with RI of 12.28 (4.09 to 36.83) and RI of 11.91 (3.88 to 36.53); the number of EC after the second dose of mRNA-1273 was 8.8 (4.9 to 12.9). Among those aged 12 to 17 years, the RI was of 5.74 (1.52 to 21.72) after second dose of BNT162b2; for this age group, the number of events was insufficient for estimating RIs after mRNA-1273. Among those aged 18 to 29 years, the RIs were 7.58 (2.62 to 21.94) after first dose of mRNA-1273 and 4.02 (1.81 to 8.91) and 9.58 (3.32 to 27.58) after second dose of BNT162b2 and mRNA-1273; the numbers of EC were 3.4 (1.1 to 6.0) and 8.6 (4.4 to 12.6) after first and second dose of mRNA-1273. The main study limitations were that the outcome was not validated through review of clinical records, and there was an absence of information on the length of hospitalization and, thus, the severity of the outcome. CONCLUSIONS: This population-based study of about 3 millions of residents in Italy suggested that mRNA vaccines were associated with myocarditis/pericarditis in the population younger than 40 years. According to our results, increased risk of myocarditis/pericarditis was associated with the second dose of BNT162b2 and both doses of mRNA-1273. The highest risks were observed in males of 12 to 39 years and in males and females 18 to 29 years vaccinated with mRNA-1273. The public health implication of these findings should be considered in the light of the proven mRNA vaccine effectiveness in preventing serious COVID-19 disease and death.

A descriptive study of commercial herbal dietary supplements used for dyslipidemia-Sales data and suspected adverse reactions.

Herbal dietary supplements (HDS) used for dyslipidemia represent a category of concern in Italy for suspected adverse reactions (ARs). However, we cannot estimate their safety, as we do not know their commercial profile. Sales data of HDS, and particularly, those used for dyslipidemia, were monitored for 2 years in two pharmacies of Rome. Meanwhile, spontaneous reports of suspected ARs potentially related to dyslipidemia supplements were collected by the Italian Phytovigilance System. The 50% of the total dietary supplements are herbal-derived; the 9% of HDS are recommended for dyslipidemia. From our data, 113 different brands have claims for improving lipids profile and 91% of them are multiingredient preparations. Fifteen spontaneous reports of suspected ARs concerned HDS used, for dyslipidemia. The most frequent ARs were joint, abdominal, and muscles pain; vomiting; erythema and hematological disorders; nausea; and rhabdomyolysis. Our findings point out the limited compliance of commercial dyslipidemia-HDS and scientific research about their intrinsic safety. A wide range of ingredients could not support the risk/benefit profile of the supplement. The variable compositions of HDS do not assure the safety, as they do not support the reproducibility of their pharmacological activities. This study could contribute to optimize consumer guidance about what they purchase and consume.

Anthraquinone laxatives use and colorectal cancer: A systematic review and meta-analysis of observational studies.

This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta-analysis using a random-effects model. Through the meta-analysis, we found that a history of AQ laxatives use compared with "other" and "no laxatives" use was associated with CRC development (OR: 1.41; 95% CI: 0.94-2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97-2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high-quality studies.

Acute liver injury following turmeric use in Tuscany: An analysis of the Italian Phytovigilance database and systematic review of case reports.

AIMS: Several cases of acute non-infectious cholestatic hepatitis recently appeared in Italy following consumption of Curcuma longa-containing dietary supplements. The aim of this research was to describe the Tuscan (Italy) cases of acute hepatitis and to compare them with similar cases of hepatotoxicity published in the literature by performing a systematic review. METHODS: Records of Tuscan cases of acute hepatitis were obtained from the Italian Phytovigilance system. Each spontaneous report was analysed in order to collect all relevant clinical information of patients and information concerning the Curcuma longa-containing dietary supplement. Moreover, both the RUCAM and WHO-UMC systems were used to evaluate the causal relationship between the use of dietary supplement and acute hepatitis. A systematic literature review was performed in MEDLINE and Embase and all case-reports and case-series published in English were included. RESULTS: Seven cases of acute hepatitis occurring in Tuscany up to September 2019 are described. In all cases, hepatotoxicity was associated with Curcuma longa formulations with high bioavailability and high dosage of curcumin/curcuminoids. The causal relationship was also supported by the positive dechallenge observed in most cases. In the 23 cases identified through the systematic review, the majority of patients were concomitantly exposed to at least one other medication and 16 of them experienced a positive dechallenge. CONCLUSIONS: Within the frame of poorly controlled and regulated products, such as dietary supplements, the evaluation of Italian cases of Curcuma longa-induced acute hepatitis and the systematic review of literature confirmed the association between Curcuma longa and liver injury.

Risk of SARS-CoV-2 infection and subsequent hospital admission and death at different time intervals since first dose of COVID-19 vaccine administration, Italy, 27 December 2020 to mid-April 2021.

To assess the real-world impact of vaccines on COVID-19 related outcomes, we analysed data from over 7 million recipients of at least one COVID-19 vaccine dose in Italy. Taking 0-14 days post-first dose as reference, the SARS-CoV-2 infection risk subsequently decreased, reaching a reduction by 78% (incidence rate ratios (IRR): 0.22; 95% CI: 0.21-0.24) 43-49 days post-first dose. Similarly, hospitalisation and death risks decreased, with 89% (IRR: 0.11; 95% CI: 0.09-0.15) and 93% (IRR: 0.07; 95% CI: 0.04-0.11) reductions 36-42 days post-first dose. Our results support ongoing vaccination campaigns.

Suspected adverse reactions to performance enhancing dietary supplements: Spontaneous reports from the Italian phytovigilance system.

Herbal tonic and adaptogens are often used to improve overall well-being. However, few clinical evidence supports their use and their safety is not known before marketing. In this context, the aim of our study was to analyze the spontaneous reports of suspected adverse reactions (ARs) to performance enhancing herbal dietary supplements collected by the Italian Phytovigilance System. Between March 2002 and September 2020, 110 spontaneous reports were collected, 58 of which related to products containing botanicals, alone or in association. Twenty-three serious reactions were reported, 21 of which required hospitalization, one was life-threatening and another caused disability. Dermatological and cardiovascular reactions were the most frequent. Hepatic ARs were the most serious (9 out of 10). A positive dechallenge was indicated in 69% of cases, while a positive rechallenge occurred in 15%. Concomitant use of other products was present in 18 reports (31%), while predisposing conditions were indicated in 17 (29%). Present data highlight safety concerns on herbal dietary supplements used as cognitive and physical performance enhancers, mainly due to their quality and use without expert supervision. Considering that postmarketing surveillance is not required for these products, spontaneous reports represent the only tool to point out risks related to food supplements.

Adverse events following cannabis for medical use in Tuscany: An analysis of the Italian Phytovigilance database.

AIMS: Despite a significant increase in using cannabis for medical purposes, current evidence on its safety in real-world clinical practice is still poorly characterised. By a case-by-case analysis of spontaneous reports of suspected adverse events (AEs) collected in Tuscany within the Italian Phytovigilance database, the aim of the present study was to describe AEs occurred in patients exposed to medical cannabis. METHODS: We evaluated all reports of cannabis-related suspected AEs collected within the Phytovigilance database up to December 2018. Information regarding cannabis therapy, patient's demographic and clinical characteristics, concomitant medications, AE description according to the Medical Dictionary for Regulatory Activities (MedDRA) classification, AE seriousness and AE outcome, were collected. The causality assessment was performed following World Health Organisation-Uppsala Monitoring Centre criteria. RESULTS: Fifty-three cannabis-related AE reports were analysed. The majority of patients were females (77.3%), with a mean age of 61.9 years. Thirty-nine (73.6%) cases were defined as nonserious and the majority of them (86.9%) showed a complete resolution or improvement. Forty-six (86.8%) cases were judged as probably related to cannabis consumption. The most frequently reported system organ class was psychiatric and nervous system disorders, and a potential drug-drug interaction was present in 16 cases. CONCLUSION: Cannabis was generally well tolerated and the majority of AEs were mild and transient. Our analysis highlighted important safety issues for clinical practice, in particular the need for an accurate prescription monitoring during the titration phase, particularly in the presence of concomitant medications.

Suspected adverse reactions associated with herbal products used for weight loss: spontaneous reports from the Italian Phytovigilance System.

PURPOSE: Overweight and obesity represent worldwide a rising health problem. In this context, dietary supplements and herbal preparations are often used as self-medication for weight loss. The aim of this study was to describe the safety profile of dietary supplements for weight control by analyzing spontaneous reports of suspected adverse reactions (ARs) received by the Italian Phytovigilance System, from July 2010 to October 2017. METHODS: The suspected ARs were collected using an ad hoc reporting form, registered in a database at the National Institute of Health and evaluated by a multidisciplinary group of experts. The causality assessment was performed using the WHO-UMC system or the CIOMS/RUCAM score. In case of serious adverse reactions, a feedback is provided to the reporter by e-mail. RESULTS: Sixty-six spontaneous reports were collected. ARs involved cardiovascular system (26%), liver (14%), central nervous system (12%), skin (9%), gastrointestinal system (17%), thyroid (8%), kidney (4%), and other organs/systems (10%). In 64% of cases, the reaction was serious. Dechallenge was positive in 46 cases; three cases of positive rechallenge were reported. After the causality assessment, the association between the product intake and the adverse reaction was judged as possible in the majority of the cases (n = 43; 65%). CONCLUSIONS: The data collected confirmed the existence of safety concerns on herbal dietary supplements used for body weight control, mainly related to quality of products and their use as self-medication. In this scenario, spontaneous reports represent the only tools available to monitor safety of these products.

Incidence and Risk Factors for Hepatitis C Virus Infection among Illicit Drug Users in Italy.

So far, only three small outdated studies have investigated hepatitis C virus (HCV) incidence and risk factors among illicit drug users (DUs) in Italy. Thus, during 2007-2010, we conducted a prospective cohort study among DUs attending 17 Italian rehabilitation centers serving urban areas. Two hundred eighty-four HCV-uninfected DUs were prospectively followed by interview and anti-HCV antibody and RNA testing every 6 months. Incidence was calculated using the person-years method. Infection predictors were assessed by time-dependent Cox analysis. Participants were mostly male (83.4%), under opioid substitution therapy (OST) (78.9%), non-injecting DUs (67.9%), and with a mean age of 30.8. Ninety-one of 224 DUs initially under OST interrupted treatment during the follow-up. Overall HCV incidence was 5.83/100 person-years at risk (PYAR) [95% confidence intervals (CI), 3.63-9.38]. The incidence did not significantly differ according the participants' sociodemographic characteristics or the degree of urbanization of the towns involved in the study. The incidence was higher for DUs under than for those not under OST (6.23 vs 4.50/100 PYAR; p = 0.681). Incidence was also higher for those with than for those without OST interruption (7.17 vs 5.04/100 PYAR; p = 0.55). However, all these differences were non-significant. At last follow-up visit, a significant decrease in frequency of sharing equipment for preparation/using drugs (by injection or not) was observed by analyzing either the whole cohort or DUs under OST only. Anti-HCV seroconversion resulted independently associated with sharing drug preparation/use equipment, backloading, having a HCV-positive sexual partner, or household and (marginally) intravenous injection. In this study, HCV incidence was non-negligible and OST seemed to lack effectiveness in reducing it. In Italy, implementation of combined harm reduction interventions and antiviral treatment of chronically infected DUs would be needed.

Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system.

AIMS: Red yeast rice (RYR) is contained in dietary supplements for patients with dyslipidemia. RYR supplements contain monacolin K, which is chemically identical to lovastatin, a licensed drug with a well-known risk profile. We aim to describe the safety profile of RYR by analysing spontaneous reports of suspected adverse reactions (ARs). METHODS: Within the Italian Surveillance System of Natural Health Products, suspected ARs were collected and evaluated by a multidisciplinary group of experts to assess causality using the WHO-UMC system or the CIOMS/RUCAM score, for hepatic reactions. The public version of the WHO-Vigibase was also queried. RESULTS: From April 2002 to September 2015, out of 1261 total reports, 52 reports concerning 55 ARs to RYR dietary supplements were collected. ARs consisted in myalgia and/or increase in creatine phosphokinase (19), rhabdomyolysis (1), liver injury (10), gastrointestinal reactions (12), cutaneous reactions (9) and other reactions (4). Women were involved in 70% of cases. In 13 cases, the reaction required hospitalization, and 28 patients were taking other medications. Dechallenge was positive in 40 reactions (73%), rechallenge was positive in 7. Causality resulted as certain (1), probable (31, 56%), possible (18, 34%), unlikely (3) or unassessable (2). Similar distribution emerged from the WHO-Vigibase. CONCLUSIONS: The potential safety signals of myopathies and liver injury raise the hypothesis that the safety profile of RYR is similar to that of statins. Continuous monitoring of dietary supplements should be promoted to finally characterize their risk profile, thus supporting regulatory bodies for appropriate actions.

Post-marketing active surveillance of Guillain Barré Syndrome following COVID-19 vaccination in persons aged ≥12 years in Italy: A multi-database self-controlled case series study.

BACKGROUND: Recently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy. METHODS: Study population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020-30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods. RESULTS: Increased risk of GBS was found after first (RI = 6.83; 95% CI 2.14-21.85) and second dose (RI = 7.41; 2.35-23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88-14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08-31.03) and second dose (RI = 7.71; 2.38-24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40-59 (RI = 4.50; 1.37-14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56-18.28). CONCLUSIONS: mRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events.

Postmarketing observational study on the safety of 2021/2022 and 2022/2023 influenza vaccination campaigns in Italy: TheShinISS-Vax|Flu study protocol.

INTRODUCTION: The purpose of TheShinISS-Vax|Flu study is to examine the association between influenza vaccines and adverse events requiring hospital admission or emergency care during the influenza vaccination campaigns 2021/2022 and 2022/2023 in Italy. METHODS AND ANALYSIS: This is a Self-Controlled Case Series multiregional study using linked routinely collected data from regional healthcare databases of the participating regions. Study participants will be persons aged ≥6 months, unvaccinated or who have received influenza vaccine during the influenza vaccination campaigns in the seasons 2021/2022 and 2022/2023 in Italy and who have experienced the outcome of interest for the first time during the study period (1 September 2021-30 June 2022 and 1 September 2022-30 June 2023 for the first and second vaccination campaigns, respectively). Risk periods will be specifically defined for each outcome and further subdivided into periods of 7 days. The exposures will be the first or second dose of the influenza vaccines administered during the two vaccination campaigns. Statistical analysis will be conducted separately for the data of the two campaigns. Exposure risk period will be compared with baseline risk period defined as any time of observation out of the risk periods. The modified SCCS method will be applied to handle event-dependent exposure and mortality and fitted using unbiased estimating equations to estimate relative incidences and excess of cases per 100 000 vaccinated by dose, age, sex and type of vaccine. Calendar period will be included as time-varying confounder in the model, where appropriate. ETHICS AND DISSEMINATION: The study received the approval from the National ethics committee for clinical trials of public research bodies and other national public institutions (PRE BIO CE n.0036723, 23/09/2022). Results will be published in peer-reviewed journals and reports in accordance with the publication policies of the Italian National Institute of Health and of the Italian Medicines Agency.

[Parole chiave. Appropriatezza prescrittiva, consumi farmaceutici, emofilia, fattori della coagulazione, malattia di von Willebrand, malattie emorragiche congenite.] / Strategie terapeutiche per il trattamento delle malattie emorragiche congenite.

Therapeutic strategies for the treatment of congenital bleeding disorders. Congenital hemorrhagic diseases (CHDs) are a group of rare disorders caused by quantitative or qualitative deficiency of one or more coagulation factors. Haemophilia A, Haemophilia B, and von Willebrand disease are the most common congenital bleeding disorders. Over the past decades, the evolution of CHDs treatments has resulted in an increase in the average life expectancy of patients and in an improvement in their quality of life; it has also enabled the prevention of bleeding complications much more effectively than in the past. This has been possible, especially for haemophilia, mainly because of earlier diagnosis, introduction of recombinant factors, especially long-acting factors, and availability of new non-substitutive therapies. In 2021, there was an increase in the overall expenditure and consumption of coagulation factors in Italy; the increase concerned especially the long-acting recombinant factors used in the treatment of Haemophilia A and B and the monoclonal antibody emicizumab. Waiting for innovative therapies that can enable individually tailored therapies, special attention must be paid to prescriptive appropriateness and to identify the best diagnostic and therapeutic care pathways for patients.

[Pharmacotherapy of Hemophilia A: expenditure and consumption for the year 2022 and future expenditure scenarios.] / Terapia dell'emofilia A: spesa e consumo per l'anno 2022 e scenari di spesa futura.

In 2021, the national expenditure for blood coagulation factors was 541.4 million, growing steadily over the past decade. Hemophilia A is the congenital hemorrhagic disease with the highest drug consumption and expenditure. It has also the highest annual increase. Data from the OsMed report showed an increased use of long-acting recombinant factors and a concomitant reduction in consumption of short-acting ones and also an increasing trend of emicizumab. Based on these findings, two possible expenditure scenarios were described: 1) assuming a 25% of reduction in consumption of short-acting recombinant factors with proportional redistribution to the consumption observed in 2022 for long-acting recombinant factors; 2) assuming that all new patients with a moderate and severe form of the disease will start prophylaxis with emicizumab and also calculating different switch percentages (20%, 30%, 50% or 70%). The first hypothesis showed a potential increase in expenditure of 3.3% (approximately 10 million euros) switching from short- to long-acting factors. In the second one, based on estimated number of patients with Hemophilia A on treatment, a total expenditure of about 457.6 million euros was estimated. Based on these findings, different expenditure outlooks were hypothesized and that there should be a switch from the recombinant factors to emicizumab. Specifically, an expenditure increase of 8% in the case of 20% switch and 28.1% in the case of 70% switch were estimated.

Interaction of Garcinia cambogia (Gaertn.) Desr. and Drugs as a Possible Mechanism of Liver Injury: The Case of Montelukast.

Overweight and obesity prevalence has increased worldwide. Apart from conventional approaches, people also resort to botanical supplements for reducing body weight, although several adverse events have been associated with these products. In this context, the present study aimed at evaluating the toxicity of Garcinia cambogia-based products and shedding light on the mechanisms involved. The suspected hepatotoxic reactions related to G. cambogia-containing products collected within the Italian Phytovigilance System (IPS) were examined. Then, an in vitro study was performed to evaluate the possible mechanisms responsible for the liver toxicity, focusing on the modulation of oxidative stress and Nrf2 expression. From March 2002 to March 2022, the IPS collected eight reports of hepatic adverse reactions related to G. cambogia, which exclusively involved women and were mostly severe. The causality assessment was probable in three cases, while it was possible in five. In the in vitro experiments, a low cytotoxicity of G. cambogia was observed. However, its combination with montelukast greatly reduced cell viability, increased the intracellular ROS levels, and affected the cytoplasmic Nrf2 expression, thus suggesting an impairment of the antioxidant and cytoprotective defenses. Overall, our results support the safety concerns about G. cambogia-containing supplements and shed light on the possible mechanisms underpinning its hepatotoxicity.

Safety Profile of Vitamin D in Italy: An Analysis of Spontaneous Reports of Adverse Reactions Related to Drugs and Food Supplements.

Vitamin D (VitD) is largely used in Italy, often inappropriately; thus, an evaluation of its safety is a crucial issue. This study analyses the adverse reactions (ARs) associated with the use of products containing VitD (VitDps) reported to the Italian National Pharmacovigilance and Phytovigilance networks. From March 2002 to August 2022, a total of 643 and 127 reports concerning 903 and 215 ARs were retrieved from Pharmacovigilance and Phytovigilance networks, respectively. Overall, 332 (29.6%) ARs were classified as serious, and the most described ones were hypercalcaemia, renal failure and tachycardia. Serious AR risk was significantly higher for subjects using more than four concomitant products (OR 2.44 [95% CI 1.30-4.60]) and VitD doses higher than 1000 IU/day (OR 2.70 [95% CI 1.30-5.64]). In Italy, there was a modest decrease in AR reporting, despite the slightly increased use of VitD during the COVID-19 pandemic. To the best of our knowledge, this is the first study describing all VitDps-related ARs observed in the Italian general population. Since underreporting is the main limitation of the safety reporting systems, the necessity to continue ARs monitoring, also using real-world data on VitDps prescription, use and outcome patterns is highlighted.

Safety and efficacy of COVID-19 vaccines in patients on dialysis: a multicentre cohort study in Italy.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of COVID-19 vaccines in patients undergoing haemodialysis in Italy compared to the general population. METHODS: In this cohort study, 118 dialysis centres from 18 Italian Regions participated. Individuals older than 16 years on dialysis treatment for at least 3 months, who provided informed consent were included. We collected demographic and clinical information, as well as data on vaccination status, hospitalisations, access to intensive care units and adverse events. We calculated the incidence, hospitalisation, mortality, and fatality rates in the vaccinated dialysis cohort, adjusted for several covariates. The incidence rates of infection in the dialysis cohort and the general population were compared through Standardised Incidence Rate Ratio. RESULTS: The study included 6555 patients vaccinated against SARS-CoV-2 infection according to the schedule recommended in Italy. Between March 2021 and May 2022, there were 1096 cases of SARS-CoV-2 infection, with an incidence rate after completion of the three-dose vaccination cycle of 37.7 cases per 100 person-years. Compared to the general population, we observed a 14% reduction in the risk of infection for patients who received three vaccine doses (Standardised Incidence Rate Ratio: 0.86; 95% Confidence Interval: 0.81-0.91), whereas no statistically significant differences were found for COVID-19-related hospitalisations, intensive care unit admissions or death. No safety signals emerged from the reported adverse events. CONCLUSIONS: The vaccination program against SARS-CoV-2 in the haemodialysis population showed an effectiveness and safety profile comparable to that seen in the general population.

Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy: A retrospective matched cohort study.

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged ≥ 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants. We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 - risk ratio)X100. Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14-118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2-20.2]. RVE decreased from 28.5 % (95 % CI: 24.7-32.1) in the time-interval 14-28 days to 7.6 % (95 % CI: -14.1 to 18.3) in the time-interval 56-118 days. However, RVE against severe COVID-19 was higher (34.0 %, 95 % CI: 23.4-42.7), decreasing from 43.2 % (95 % CI: 30.6-54.9) to 27.2 % (95 % CI: 8.3-42.9) over the same time span. Although RVE against SARS-CoV-2 infection was much reduced 2-4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated.