Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review.

BACKGROUND: Genetic polymorphisms in genes involved in pain modulation have been reported to be associated to opioid efficacy and safety in different clinical settings. METHODS: The association between COMT Val158Met polymorphism (rs4680) and the inter-individual differences in the response to opioid analgesic therapy was investigated in a cohort of 87 Italian paediatric patients receiving opioids for cancer pain (STOP Pain study). Furthermore, a systematic review of the association between opioid response in cancer patients and the COMT polymorphism was performed in accordance with the Cochrane Handbook and the Prisma Statement. RESULTS: In the 87 paediatric patients, pain intensity (total time needed to reach the lowest possible level) was significantly higher for G/G than A/G and A/A carriers (p-value = 0.042). In the 60 patients treated only with morphine, the mean of total dose to reach the same pain intensity was significantly higher for G/G than A/G and A/A carriers (p-value = 0.010). Systematic review identified five studies on adults, reporting that opioid dose (mg after 24 h of treatment from the first pain measurement) was higher for G/G compared to A/G and A/A carriers. CONCLUSIONS: Present research suggests that the A allele in COMT polymorphism could be a marker of opioid sensitivity in paediatric cancer patients (STOP Pain), as well as in adults (Systematic Review), indicating that the polymorphism impact could be not age-dependent in the cancer pain context. TRIAL REGISTRATION: Registration number: CRD42017057831 .

Long-term efficacy of add-on stiripentol treatment in children, adolescents, and young adults with refractory epilepsies: A single center prospective observational study.

OBJECTIVE: To assess the long-term efficacy and tolerability of stiripentol (STP) as an adjunctive treatment in different forms of refractory epilepsies. METHODS: The medical records of all individuals consecutively treated with STP as add-on therapy for refractory epilepsies, irrespective of their being focal, generalized, or both, and followed at Meyer Children's Hospital between January 2007 and May 2018, were reviewed. The drug scheme administration consisted of a starting dose of STP of 10-15 mg/kg/d with increments every week, up to a maximum of 50 mg/kg/d, based on both age and weight. Etiology of epilepsy was codified as structural, genetic, infectious, immune, metabolic, and unknown. Responders were defined as patients who achieved a seizure frequency reduction of ≥50%. Retention rate was defined as the probability of continuing STP without additional therapy. Tolerability was assessed by reporting adverse events. RESULTS: A total of 132 individuals aged from 5 months to 43 years received add-on STP, including 30 patients with Dravet syndrome (DS). The median follow-up was 14.8 months (range = 4 months-18 years, interquartile range = 25.72). Twenty-nine individuals (22%) received more than two antiepileptic drugs. Benzodiazepines, mainly clobazam, were the most commonly used add-on drugs. Sixty-six patients (50%) were responders, and 13 of them (9.8%) were seizure-free. Responder rate was higher in the genetic etiology group (57%), especially in DS (18/30; 60%), and in patients with refractory focal onset epilepsy without bilateral tonic-clonic seizures (5/15; 33%). The median relapse-free survival was 27 months in the 66 responders. The median time to STP failure was 24.6 months in all 132 individuals. SIGNIFICANCE: This study confirms the long-term efficacy of add-on STP treatment in patients with different types of refractory epilepsies, including focal onset epilepsy without bilateral tonic-clonic seizures. Further confirmations based on prospectively designed studies are required to confirm STP efficacy in focal epilepsy.

A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study.

BACKGROUND: Inter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly, no studies have focused on children. The STOP Pain project aimed to evaluate the risk factors that contribute to clinical response and adverse drug reactions to opioids by means of a systematic review and a clinical investigation on paediatric oncological patients. METHODS: We conducted a systematic literature search in EMBASE and PubMed up to the 24th of November 2016 following Cochrane Handbook and PRISMA guidelines. Two independent reviewers screened titles and abstracts along with full-text papers; disagreements were resolved by discussion with two other independent reviewers. We used a data extraction form to provide details of the included studies, and conducted quality assessment using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Young age, lung or gastrointestinal cancer, neuropathic or breakthrough pain and anxiety or sleep disturbance were associated to a worse response to opioid analgesia. No clear association was identified in literature regarding gender, ethnicity, weight, presence of metastases, biochemical or hematological factors. Studies in children were lacking. Between June 2011 and April 2014, the Italian STOP Pain project enrolled 87 paediatric cancer patients under treatment with opioids (morphine, codeine, oxycodone, fentanyl and tramadol). CONCLUSIONS: Future studies on cancer pain should be designed with consideration for the highlighted factors to enhance our understanding of opioid non-response and safety. Studies in children are mandatory. TRIAL REGISTRATION: CRD42017057740 .

Long-term efficacy of add-on lacosamide treatment in children and adolescents with refractory epilepsies: A single-center observational study.

OBJECTIVE: To assess long-term efficacy and tolerability of lacosamide (LCM) as adjunctive treatment through a retrospective study in children and adolescents with refractory epilepsies. METHODS: All patients consecutively treated with LCM as add-on for refractory focal and generalized epilepsy and followed at the Neuroscience Center of Excellence of the Meyer Children's Hospital of Florence between January 2011 and September 2015 were included in the study. Responder rate, relapse-free survival, and retention rate were calculated. Tolerability was assessed by reporting adverse events. RESULTS: A total of 88 individuals (41 female) aged 4 months to 18 years (median 10.5 years; mean ± SD 10.6 ± 4.8 years) received add-on LCM treatment for refractory epilepsy. Thirty-four patients (38.6%) were responders with a median time to relapse of 48 months. Nine (26.4%) of the 34 responders were seizure-free. For all 88 patients, the probability of remaining on LCM without additional therapy was 74.4% at 6 months, 47.7% at 12 months, 27.9% at 24 months, 18.0% at 48 months, and 8.2% at 72 months of follow-up. No statistically significant differences in relapse and retention time were observed with regard to epilepsy and seizure types, duration and course of epilepsy, number and type of antiepileptic drugs (AEDs; sodium channel blockers vs others) used in add-on. The most frequent adverse events were dermatological (4/11) and behavioral (3/11). SIGNIFICANCE: This study documents a real-world progressive and significant loss of LCM efficacy over time in a pediatric population. Further prospective studies on larger populations are required to confirm the remarkable loss of LCM efficacy over time.

Comparative efficacy of antiepileptic drugs in children and adolescents: A network meta-analysis.

OBJECTIVE: To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years). METHODS: Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction. RESULTS: We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies. SIGNIFICANCE: This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria.

Propranolol 0.1% eye micro-drops in newborns with retinopathy of prematurity: a pilot clinical trial.

BACKGROUND: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. This study evaluated safety and efficacy of propranolol eye micro-drops in preterm newborns with ROP. METHODS: A multicenter open-label trial, planned according to the Simon optimal two-stage design, was performed to analyze safety and efficacy of propranolol micro-drops in newborns with stage 2 ROP. To this end, hemodynamic and respiratory parameters were monitored, and blood samples were collected weekly, for 3 wk. Propranolol plasma levels were also monitored. The progression of the disease was evaluated with serial ophthalmologic examinations. RESULTS: Twenty-three newborns were enrolled. Since the fourth of the first 19 newborns enrolled in the first stage of the study showed a progression to stage 2 or 3 with plus, the second stage was prematurely discontinued. Even though the objective to complete the second stage was not achieved, the percentage of ROP progression (26%) was similar to that obtained previously with oral propranolol administration. However, no adverse effects were observed and propranolol plasma levels were significantly lower than those measured after oral administration. CONCLUSION: Propranolol 0.1% eye micro-drops are well tolerated, but not sufficiently effective. Further studies are required to identify the optimal dose and administration schedule.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

BACKGROUND: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). METHODS: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. DISCUSSION: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

Pharmacovigilance of herb-drug interactions among preoperative patients.

The Pharmacovigilance Center of the University of Florence conducted a survey across 3 hospitals in Tuscany (Empoli, Florence, and Prato) on a sample population consisting of 478 patients admitted to the hospital for a preoperative assessment before surgical intervention. The aim of the study was to assess the concomitant use of herbal remedies (HRs) and prescribed medications and to evaluate the most important potential interactions. Almost 50% of the patients surveyed-238 of 478 (49.8 %)-used at least 1 HR. Among them, 55 (23.1%) were actually exposed to at least 1 potential interaction. In particular, 42 participants had an HR-drug interaction and 17 participants had a dietary supplement drug interaction. A large percentage of patients undergoing surgery take HRs that could potentially interact with drugs administered perioperatively. Antihypertensive, antiplatelet, anticoagulant, and central nervous system (CNS) agents were the main products involved. The use of HRs is not devoid of risks and adverse effects due to potential interactions that may be serious or even lifethreatening. HR-drug interactions should be deeply investigated, especially in high-risk patient populations. Health care professionals should pay close attention and always investigate the consumption of HRs among their patients.

[Eligibility for dabigatran therapy: the real-life experience of a Tuscany general hospital]. / Eleggibilità al trattamento con dabigatran: esperienza real-life di un policlinico toscano.

Introduction. Dabigatran has emerged as a promising alternative to vitamin K antagonists (VKAs) in non-valvular atrial fibrillation (NVAF). It has several clinical and practical advantages over VKAs that finally facilitate their use in clinical practice. The aim of this study is to describe patients taking dabigatran, to evaluate its use in the real world and the eligibility for therapy, according to the criteria established by the Italian Medicines Agency (AIFA). Methods. A retrospective review was conducted using dabigatran prescriptions in patients with NVAF. Data were retrieved from the prescriptions recorded in the hospital pharmacy of Careggi General Hospital from June to October 2013. Results. Data were related to 138 patients with NVAF who have at least one dabigatran prescription. Patients have a mean age of 79.0 ± 8.9 years, mean CHA2DS2-VASc 4.4 ± 3.0 and mean HAS-BLED 3.0 ± 1.0. 49.3% were male and 50% were older than 80 years; 18.8% were treated with high-dose dabigatran (150 mg). According to the AIFA criteria, 85.5% of patients were eligible for treatment: 34% were at high embolic and bleeding risk and 70.2% reported objective problems in routine coagulation monitoring. Conclusions. Our patients can be categorized in two groups: subjects with high risk of embolism and bleeding for whom the new oral anticoagulant dabigatran provides clinically important benefit, and subjects for whom the benefit derives from a simplified management of therapy. It should be interesting to evaluate the rate of therapeutic adherence in these patients in order to verify the expected clinical benefits.

Unforeseen cytomegalovirus retinopathy following high dose thiotepa and proton irradiation in a pediatric patient with high-risk medulloblastoma: A case report.

In immunocompetent individuals, cytomegalovirus (CMV) infection is usually mild but may cause severe complications such as retinitis, pneumonitis, and encephalitis in immunocompromised individuals. So far, cases of CMV retinitis in patients with medulloblastoma undergoing chemotherapy and radiotherapy, have not been reported. We herein report the case of a pediatric patient with high-risk medulloblastoma who experienced an unexpected CMV retinopathy and leukoencephalopathy following high dose thiotepa and proton irradiation. The patient underwent a four-course induction therapy (1st cycle: methotrexate and vinorelbine; 2nd cycle: etoposide and hematopoietic stem cells apheresis; 3rd cycle: cyclophosphamide and vinorelbine; 4th cycle: carboplatin and vinorelbine) and then a consolidation phase consisting in high dose thiotepa followed by autologous HSC transplant and proton cranio-spinal irradiation plus boost to the primary tumor site and pituitary site with concomitant vinorelbine. After two months of maintenance treatment with lomustine and vinorelbine, the patient showed complete blindness and leukoencephalopathy. A diagnosis of CMV retinopathy was made and oral valganciclovir was administered. CMV retinopathy was judged to be possibly related to the use of high dose thiotepa worsened by radiotherapy. This case report suggests that in pediatric patients undergoing immunosuppressive chemo-radiotherapy, CMV reactivation should be carefully monitored to prevent serious complications such as retinopathy and visual loss.

Complementary and Alternative Drugs Use among Preoperative Patients: A Cross-Sectional Study in Italy.

Complementary and alternative drugs (CADs) are widely used in preoperative patients and may lead to potential interactions and adverse reactions. The aim of our study is to evaluate the prevalence and the predictors of CADs use among preoperative patients using data from an Italian survey. This cross-sectional study, which enrolled 478 patients (response rate: 83.5%), was carried out in three Tuscany hospitals (Italy). The prevalence of CADs use was 49.8%: 233 out of 238 participants used herbal products and/or dietary supplements. Valeriana officinalis was the most reported product (19.4%). According to univariate analysis, users were commonly identified among middle-aged or older patients; unadjusted ORs were 2.1 (95% CI: 1.3-3.3) for patients aged 48-69 years, and 3.0 (95% CI: 1.9-4.7) for those of 70-95 years, when compared with individuals aged 18-47 years. Except for education and gender, adjusted estimates showed consistent results with univariate analyses: direct association was observed with higher education, and-although not significantly-with female gender. The high prevalence of CAD use in preoperative period could be suggestive of a certain risk of adverse effects due to CADs interactions. A careful medical history of CADs consumption should be ascertained before surgery.

Sensitivity of three commercial tests for SARS-CoV-2 serology in children: an Italian multicentre prospective study.

BACKGROUND: US Food and Drug Administration has issued Emergency Use Authorizations for hundreds of serological assays to support Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) diagnosis. The aim of this study is to evaluate, for the first time in children, the performance of three widely utilized SARS-CoV-2 serology commercial assays, Diesse Diagnostics (IgG, IgA, IgM) and Roche Diagnostics, both Roche Nucleocapsid (N) IgG and Roche Spike (S) IgG assays. METHODS: Sensitivity and 95% confidence intervals (CIs) were estimated for each of the three different serological tests and mixed and direct comparison were performed. Univariate and multivariate Poisson regression models were fitted to calculate incidence rate ratios and 95% CIs as estimate of the effects of age, gender, time on the serology title. A p-value < 0.05 indicated statistical significance. RESULTS: Overall, 149 children were enrolled in the study. A low sensitivity was found for Diesse IgA, IgM and IgG. Compare to Diesse, Roche S had a higher sensitivity at 15-28 days from infection (0.94, 95%CI: 0.73-1.0) and Roche N at 28-84 days (0.78, 95%CI: 0.58-0.91). When a direct comparison of IgG tests sensitivity was feasible for patients with pairwise information, Roche S and Roche N showed a statistically significant higher sensitivity compared to Diesse in all the study periods, whereas there was no difference between the two Roche tests. CONCLUSION: Roche S and Roche N serology tests seem to better perform in children. Large prospective studies are needed to better define the characteristics of those tests.

KETASER01 protocol: What went right and what went wrong.

OBJECTIVE: To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies. METHODS: KETASER01 is a multicenter, randomized, controlled, open-label, sequentially designed, non-profit Italian study that aimed to assess the efficacy of ketamine compared with conventional anesthetics in the treatment of refractory convulsive status epilepticus (RCSE) in children. RESULTS: During the 5-year recruitment phase, a total of 76 RCSEs treated with third-line therapy were observed in five of the 10 participating Centers; only 10 individuals (five for each study arm; five females, mean age 6.5 ± 6.3 years) were enrolled in the KETASER01 study. Two of the five patients (40%) in the experimental arm were successfully treated with ketamine and two of the five (40%) children in the control arm, where successfully treated with thiopental. In the remaining six (60%) enrolled patients, RCSE was not controlled by the randomized anesthetic(s). SIGNIFICANCE: The KETASER01 study was prematurely halted due to low eligibility of patients and no successful recruitment. No conclusions can be drawn regarding the objectives of the study. Here, we discuss the KETASER01 results and critically analyze the reasons for its failure in view of future trials.

Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297- 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a ß-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration  The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

Consensus conference on the appropriateness of palivizumab prophylaxis in respiratory syncytial virus disease.

Respiratory syncytial virus infection represents a clinical burden among young children under 24 months. Palivizumab is the only drug licensed in Italy for the prevention of serious lower respiratory tract disease requiring hospitalization caused by respiratory syncytial virus in children at high risk. However recommendations for palivizumab prophylaxis are heterogeneous. Not all the published documents agree about the clinical indications of palivizumab; this could lead to different clinical practices and concerns about the appropriateness of prophylaxis. These issues and the lack of evidence about palivizumab prophylaxis efficacy in specific medical conditions brought on the idea of a consensus conference on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications. The goal was to perform a review of the evidence regarding the efficacy and the safety of palivizumab and give recommendations in order to harmonize its use. A structured and validated method to conduct the consensus process was adopted. The consensus conference recommends palivizumab prophylaxis in infants born before 29 weeks and younger than 12 months at the start of the epidemic season. According to evidence from literature and experts' opinion, palivizumab prophylaxis is not recommended in preterm infants of gestational age ≥29 weeks, without co-morbidity (i.e., cardiac, bronchopulmonary diseases). The experts identified some clinical rare conditions for which the decision of prophylaxis should be entrusted to the specialists. The evaluation of the appropriateness of palivizumab prophylaxis in the single patient should be documented by the specialists. Pediatr Pulmonol. 2016;51:1088-1096. © 2016 Wiley Periodicals, Inc.

Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01).

INTRODUCTION: Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. METHODS AND ANALYSIS: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. ETHICS AND DISSEMINATION: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT02431663; Pre-results.

A case of pediatric Steven-Johnson Syndrome associated with albuterol consumption.

We describe a case of Steven-Johnson Syndrome (SJS) associated with albuterol exposure in a 6-year-old male. A possible contributing role of albuterol in SJS occurrence in the present case is strongly suggested by the temporal relationship between the event and the initiation of drug therapy as well as by the positive rechallenge. To the best of our knowledge, albuterol had not been previously associated with SJS in medical literature. It can be therefore possible that physicians, pediatricians in particular, probably not aware of the possible risk of albuterol-induced SJS, might underestimate skin reactions in children taking the drug, thus underreporting this kind of severe adverse drug reaction.

Herbalists' perception of risks involving commonly sold medicinal plants in Italy.

OBJECTIVE: Although there are several studies which have investigated pharmacists' knowledge of the safety of medicinal plants (MPs), no studies have examined herbalists' perception of risks associated with MPs. METHODS: We conducted a survey of 159 herbalists (participation rate 85.9%) in the region of Tuscany (Italy). Data were collected by means of a semi-structured questionnaire using a face-to-face interview. Risk perception was rated on a 10 cm Visual Analogic Scale (VAS). Herbalists' scores were then compared with those reported by a group of 10 experts in herbal medicine. RESULTS: When the overall risk was examined, herbalists had a low perception of the risks (VAS median ranged between 1.5 and 3.2) associated with the use of most MPs (Allium sativum, Aloe vera gel, Echinacea spp., Escholtzia californica, Harpagophytum procumbens, and propolis). They had an intermediate or high perception of risks associated with use of Cimicifuga racemosa, Citrus aurantium, and Panax ginseng (median ranged between 3.5 and 5.0), and for anthraquinone laxatives (median 7.2). Although the overall risk perceived by experts was generally higher than that reported by herbalists, differences were statistically significant only for Allium sativum and Escholtzia californica. CONCLUSION: The study shows that herbalists in Tuscany are knowledgeable about the relative risks of MPs when compared with experts in herbal medicine.