Surgical procedures as a major risk factor for chronic hepatitis C virus infection in Italy: Evidence from a case-control study

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Healthcare Database Networks for Drug Regulatory Policies: International Workshop on the Canadian, US and Spanish Experience and Future Steps for Italy

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Interactions between Natural Health Products and Oral Anticoagulants: Spontaneous Reports in the Italian Surveillance System of Natural Health Products

Introduction. The safety of vitamin K antagonists (VKA) use can be compromised by many popular herbal supplements taken by individuals. The literature reports that 30% of warfarin-treated patients self-medicates with herbs. Possible interactions represent an health risk. We aimed to identify all herbs-oral anticoagulants interactions collected in the Italian database of suspected adverse reactions to “natural health” products. Methods. The Italian database of spontaneous reports of suspected adverse reactions to natural products was analyzed to address herb-VKAs interactions. Results. From 2002 to 2009, we identified 12 reports with 7 cases of INR reduction in patients treated with warfarin (n = 3) and acenocoumarol (n = 4), and 5 cases of INR increase (all warfarin associated). It was reported 8 different herbal products as possibly interacting. Discussion. Our study confirms the risk of interactions, highlighting the difficulty to characterize them and their mechanisms and, finally, prevent their onset. The reported data underline the urgent need of healthcare providers being aware of the possible interaction between natural products and VKA, also because of the critical clinical conditions affecting patients. This is the first step to have the best approach to understand possible INR alterations linked to herb-VKA interaction and to rightly educate patients in treatment with VKA

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Death in Patients Hospitalised with COVID-19: A Retrospective Italian Cohort Study of 43,000 Patients

Introduction The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. Objective The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. Methods This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. Results Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89-1.06) or ARB (HR 0.98, 95% CI 0.89-1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. Conclusions ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis

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 COVID19 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

Rat models of acute inflammation: a randomized controlled study on the effects of homeopathic remedies

BACKGROUND: One of the cardinal principles of homeopathy is the "law of similarities", according to which patients can be treated by administering substances which, when tested in healthy subjects, cause symptoms that are similar to those presented by the patients themselves. Over the last few years, there has been an increase in the number of pre-clinical (in vitro and animal) studies aimed at evaluating the pharmacological activity or efficacy of some homeopathic remedies under potentially reproducible conditions. However, in addition to some contradictory results, these studies have also highlighted a series of methodological difficulties. The present study was designed to explore the possibility to test in a controlled way the effects of homeopathic remedies on two known experimental models of acute inflammation in the rat. To this aim, the study considered six different remedies indicated by homeopathic practice for this type of symptom in two experimental edema models (carrageenan- and autologous blood-induced edema), using two treatment administration routes (sub-plantar injection and oral administration). METHODS: In a first phase, the different remedies were tested in the four experimental conditions, following a single-blind (measurement) procedure. In a second phase, some of the remedies (in the same and in different dilutions) were tested by oral administration in the carrageenan-induced edema, under double-blind (treatment administration and measurement) and fully randomized conditions. Seven-hundred-twenty male Sprague Dawley rats weighing 170–180 g were used. Six homeopathic remedies (Arnica montana D4, Apis mellifica D4, D30, Atropa belladonna D4, Hamamelis virginiana D4, Lachesis D6, D30, Phosphorus D6, D30), saline and indomethacin were tested. Edema was measured using a water-based plethysmometer, before and at different times after edema induction. Data were analyzed by ANOVA and Student t test. RESULTS: In the first phase of experiments, some statistically significant effects of homeopathic remedies (Apis, Lachesis and Phosporus) were observed (the reduction in paw volume increase ranging from 10% to 28% at different times since edema induction). In the second phase of experiments, the effects of homeopathic remedies were not confirmed. On the contrary, the unblinded standard allopathic drug indomethacin exhibited its anti-inflammatory effect in both experimental phases (the reduction in paw volume increase ranging from 14% to 40% in the first phase, and from 18% to 38% in the second phase of experiments). CONCLUSION: The discrepancies between single-blind and double-blind methods in animal pharmacological research are noteworthy and should be better investigated, also in non-homeopathic research

Impatto della vaccinazione e della pregressa diagnosi sul rischio di infezione e di malattia severa associata a SARS-CoV-2. Un’analisi dei casi diagnosticati nel mese di ottobre 2022

In Italia, l’epidemia di infezioni da SARS-CoV-2 nel corso del 2022 è stata influenzata dalla predominanza della variante Omicron, caratterizzata da alta trasmissibilità, e dalla progressiva eliminazione di quasi tutte le misure non farmacologiche di prevenzione. La combinazione di questi due elementi ha determinato una notevole circolazione virale di SARS-CoV-2 con oltre 24,5 milioni di casi da inizio epidemia. Dato l’alto numero di persone che ha superato almeno una infezione da SARS-CoV-2 e l’alta copertura vaccinale nella popolazione è necessario stimare il ruolo protettivo dell’immunità associata sia al vaccino che all’infezione pregressa nel prevenire l’infezione e la malattia severa da COVID-19. Il presente rapporto fornisce una stima del rischio di infezione e di malattia grave, per il mese di ottobre 2022, sulla base della vaccinazione e della precedente infezione. La massima protezione contro la diagnosi di infezione da SARS-CoV-2 e la malattia severa si realizza attraverso una immunità ibrida (l’effetto combinato della vaccinazione e della pregressa infezione) mentre livelli di rischio più alto si riscontrano sempre tra le persone non vaccinate e senza una precedente diagnosi di infezione. A parità di fascia di età e di pregressa infezione, si osserva una tendenza alla riduzione del rischio di malattia severa associata alla vaccinazione, in particolare se recente

Oral ondansetron versus domperidone for symptomatic treatment of vomiting during acute gastroenteritis in children: multicentre randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Vomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking.</p> <p>Objectives</p> <p>To compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT.</p> <p>Methods/Design</p> <p>Multicentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled.</p> <p>Discussion</p> <p>The trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01257672">NCT01257672</a></p

Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

Huangqi Injection (a Traditional Chinese Patent Medicine) for Chronic Heart Failure: A Systematic Review

Chronic heart failure (CHF) is a global public health problem. Therefore, novel and effective drugs that show few side-effects are needed. Early literature studies indicated that Huangqi injection is one of the most commonly used traditional Chinese patent medicines for CHF in China. As a large number of clinical studies has been carried out and published, it is essential to evaluate the effectiveness and safety of Huangqi injection. Therefore, we carried out this systematic review under the support of the framework of the Joint Sino-Italian Laboratory (JoSIL).To evaluate the efficacy and safety of Huangqi injection for CHF according to the available scientific knowledge.An extensive search including PubMed, EMBASE, CBM, the Cochrane Library and Chinese literature databases was performed up to July 2008. Clinical trials regarding Huangqi injection for the treatment of CHF were searched for, irrespective of languages. The quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0, and RevMan 5.0 provided by the Cochrane Collaboration and STATA 9.2 were used for data analysis.After selection of 1,205 articles, 62 RCTs and quasi-RCTs conducted in China and published in Chinese journals were included in the review. The methodological quality of the trials was low. In most trials inclusion and exclusion criteria were not specified. Furthermore, only one study evaluated the outcomes for drug efficacy after an adequate period of time. For these reasons and because of the different baseline characteristics we did not conduct a meta-analysis.Although available studies are not adequate to draw a conclusion on the efficacy and safety of Huangqi injection (a traditional Chinese patent medicine), we hope that our work could provide useful experience on further studies on Huangqi injections. The overall level of TCM clinical research needs to be improved so that the efficacy of TCM can be evaluated by the international community and possibly some TCM can enter into the international market