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Background Respectful care of bereaved parents after stillbirth plays a pivotal role in enabling the grieving process and reducing the traumatic impact of this life-changing event. Unfortunately, professionals and midwives, in particular, are often emotionally unprepared and frequently left alone when dealing with these stressful events. Aim The BLOSSoM (Burnout after perinatal LOSS in Midwifery) study aims to address the levels of professional burnout in Italian midwives and evaluate the psychological impact of bereavement care on professionals. Methods Web-based cross-sectional study, including socio-demographic questionnaire, survey on the knowledge of guidelines for stillbirth management and two psychometric tests: Maslach Burnout Inventory (MBI) and Impact of Event Scale - Revised (IES-R). Findings Of 445 female midwives, mean age 35.1 (SD 9.9), working years 11.2 (SD 10.2), 149 (33.4%) reported specific training on stillbirth and 420 (94.6%) highlighted the need for further training and support. Medium to high levels of burnout (Emotional Exhaustion) were present in 65 midwives (15.9%) with a high prevalence of Reduced Personal Accomplishment (292, 64.2%). ‘Communicating the diagnosis of death’ was considered the hardest task, followed by ‘assisting the meeting with the baby’; 109 midwives (24.5%) reported high IES-R scores (>30), suggesting symptoms of PTSD related to stillbirth events; a good level of knowledge of guidelines favoured Personal Accomplishment (OR 0.3 [0.1 – 0.6]). The number of stillbirths assisted by midwives was not associated with burnout levels. Conclusion Midwives are particularly at risk of developing professional burnout, as early as after five years of work, with a significant association with the psychological impact exerted by stressful events (stillbirth).

Data on cleaner and disinfectant exposure and misuse-related acute intoxications in Italy during SARS-CoV-2 pandemic are still lacking. The aim of the present study was to analyse and describe cleaner and disinfectant-related intoxications during SARS-CoV-2 pandemic in an Italian poison control centre. Data were obtained from the toxicological consultations requested to the Toxicology Unit and Poison Centre, Careggi University Hospital, Florence (Italy). We compared data from January 1st to April 30th of 2019 and 2020. Data concerning probable or acute intoxication from any causative agent in the general population (all age groups), from private individuals or from Regional and National health structures, were included in the analysis. A toxicological evaluation was also performed to calculate the Poisoning Severity Score.In 2019, 451 phone counselling sessions were performed and compared to a total of 410 calls received during the same period of 2020. In both periods, the majority of events occurred in paediatric (0–17 years) and adult (18–65 years) patients, who were mainly exposed to one toxic agent, and intoxications took place principally at home due to domestic accidents. The oral route of intoxication was the most frequently observed one, followed by inhalation of toxic agents, which increased by 4.7% in 2020. In 2020, sanitizers and cleaners were reported in 21.6% of cases compared to 12.5% in 2019. This is the first study describing cleaner and disinfectant-related intoxications in Italy. Our results suggested a possible misuse of these products during the SARS-CoV-2 pandemic, underling the effects of home isolation on mental health and unintentional toxic exposures.

Background The first 1000 days of life -including pregnancy and the first 2 years after birth- represent a critical window for health interventions. This systematic review aimed to summarize the evidence on the relationship between traffic-related air pollutants exposure in the first 1000 days of life and the development of wheezing and asthma, with a particular focus on windows of exposure. Methods Medline and Embase were searched from January 2000 to May 2020 to retrieve population-based birth-cohort studies, including registries, providing quantitative information on the association between exposure to traffic-related air pollutants during pregnancy or early life, and the risk of developing wheezing and asthma in childhood. Screening and selection of the articles were completed independently by three reviewers. The quality of studies was assessed using the Newcastle-Ottawa scale. Results Out of 9681 records retrieved, 26 studies from 21 cohorts were included. The most common traffic-related air pollutant markers were particulate matter (PM) and nitric oxides (NOx). The variability in terms of pollutants, exposure assessment methods, and exposure levels chosen to present the results did not allow a meta-analysis. Exposure to PM and NOx in pregnancy (10 cohorts) was consistently associated with an increased risk of asthma development, while the association with wheezing development was unclear. The second trimester of pregnancy seemed to be particularly critical for asthma risk. As for exposure during early life (15 cohorts), most studies found a positive association between PM (7/10 studies) and NOx (11/13 studies) and the risk of asthma development, while the risk of wheezing development was controversial. The period of postnatal exposure, however, was less precisely defined and a partial overlap between the period of exposure measurement and that of outcome development was present in a consistent number of studies (14 out of 15) raising doubts on the associations found. Conclusions Traffic-related air pollution during pregnancy is associated with an increased risk of asthma development among children and adolescents. The relationship between exposure in the first two years of life and the development of wheezing and asthma needs to be confirmed in studies with more precise exposure assessment.

Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population. Methods Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses. Results 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /μl vs CSI-: 3000 /μl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy. Conclusions CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.

Objectives The persistent positivity of aPLs, either isolated or associated with thrombotic and/or obstetric events (APS), has been associated with the increase of intima-media thickness (IMT) and carotid plaques. Despite the fact that aPLs can promote both thrombotic and obstetric complications, some pathogenic differences have been documented between the two entities. This study aimed to evaluate whether the atherosclerotic risk differs between subjects with obstetric and thrombotic APS. Methods A total of 167 APS women (36 obstetric and 131 thrombotic) were compared with 250 aPLs negative controls. IMT of the common carotid artery (CCA) and of the bulb and the prevalence of carotid plaques were assessed. Results CCA- and bulb-IMT were significantly higher in women with thrombotic APS, while being similar between the obstetric APS and the controls [CCA-IMT: mean (s.d.) 0.97 (0.49), 0.78 (0.22) and 0.81 (0.12) mm for the thrombotic, obstetric and control groups, respectively, P < 0.001 between thrombotic and controls, P = 0.002 between thrombotic and obstetric; bulb-IMT: mean (s.d.) 1.38 (0.79), 0.96 (0.27) and 0.96 (0.51) mm for the thrombotic, obstetric and control groups, P < 0.001]. Women with thrombotic APS had significantly increased risk of presenting carotid plaques. This risk was significantly lower in obstetric APS. Conclusion Unlike thrombotic APS, obstetric APS is not associated with an increase of markers of subclinical atherosclerosis. If confirmed on wider populations, these results could suggest different pathogenetic role of aPLs in promoting atherosclerosis in vascular and obstetric APS, and raise questions on the risk–benefit profile of thromboprophylaxis in obstetric APS outside pregnancy periods.

To compare the efficacy of Adalimumab (ADA) in noninfectious anterior uveitis (AU) and posterior segment (PS) involvement, associated with different conditions, with a focus on Behcet’s syndrome (BS). In this retrospective, multicenter post-hoc study, we evaluated the efficacy of ADA in terms of ocular control and relapses in 96 patients with AU and PS uveitis, either idiopathic (IU) or associated with BS or with other systemic disorders (OSD) (Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Vogt-Koyanagi-Harada, Inflammatory Bowel Disease), followed in three tertiary referral centers. Ninety-six patients (45 AU; 51 PS uveitis) were included. Eleven had IU, 58 BS, and 27 OSD. All patients with AU achieved complete long-term ocular control. In PS uveitis, 89%, 67% and 100% of patients with BS, IU and OSD achieved ocular control at the last follow-up (> 12 months), respectively. The lowest ocular relapse rate occurred in patients with AU with BS (1/13) or IU (0/2). ADA accounted for long-term disease control, and no predictors of ocular control and relapse were identified; particularly, ocular relapses seemed not related to systemic ones. Macular edema resolved in 75% and 67% of PS uveitis with BS and IU, respectively. ADA controls both anterior and posterior uveitis, with an efficacy similar in IU, BS and OSD patients. In BS, the efficacy of ADA seems to be independent of demographic and clinical characteristics, and ocular relapses mostly occurred independently from systemic ones. Based on our results, ADA may represent a valid alternative in anterior refractory uveitis.

Introduction Products containing anthraquinones (AQ) are mainly used as laxatives and have several biological effects. Long-term use of AQ laxatives is associated with an increased risk of serious adverse events (AEs), such as colorectal cancer (CRC). We will systematically synthesize the evidence on the potential association between the use of AQ laxatives and the risk of CRC. Methods and analysis We will search MEDLINE, Embase, Scopus, the Cochrane Library, Google Scholar, and Clinicaltrials.gov. To avoid missing any relevant studies, we will search the bibliographies of retrieved papers and recent reviews in the field. Interventions will include products containing oral AQ laxatives, in particular, those derived from rhubarb, senna, cascara, buckhorn, and aloe. Two review authors will independently screen title, abstract, and full texts and will independently extract data from included studies. The primary outcome is the number of participants diagnosed with CRC, while the secondary outcome will be cases of melanosis coli. We will also consider all other AEs reported in the included studies, in particular, intestinal bleeding, alterations of gastrointestinal motility, and potential for dependence. When possible and appropriate, for each outcome, a meta-analysis will be performed. Discussion This protocol is prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. The protocol gives an insight into the scope and parameters for the systematic review to be carried out. Systematic review registration PROSPERO CRD42019125414

Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features of this condition. The GCA pathogenesis remains largely unknown, but recent studies have suggested the involvement of oxidative stress, mainly sustained by an enhanced reactive oxygen species (ROS) production by immature neutrophils. On this basis, in the present study, we intended to evaluate, in GCA patients, the presence of systemic oxidative stress and possible alterations in the expression level of nuclear sirtuins, enzymes involved in the inhibition of inflammation and oxidative stress. Thirty GCA patients were included in the study and compared to 30 healthy controls in terms of leukocyte ROS production, oxidative stress and SIRT1 expression. Our results clearly indicated a significant increase (p < 0.05) both in the ROS levels in the leukocyte fractions and plasma oxidative stress markers (lipid peroxidation and total antioxidant capacity) in the GCA patients compared to the healthy controls. In PBMCs from the GCA patients, a significant decrease in SIRT1 expression (p < 0.05) but not in SIRT6 and SIRT7 expression was found. Taken together, our preliminary findings indicate that, in GCA patients, plasma oxidative stress is paralleled by a reduced SIRT1 expression in PBMC. Further studies are needed to highlight if and how these alterations contribute to GCA pathogenesis.

Behçet's syndrome (BS) is a chronic (auto)-inflammatory disorder characterized by different clusters of symptoms, including mucocutaneous and ocular involvements. Interleukin-1 inhibitors anakinra (ANA), canakinumab (CAN), and gevokizumab (GEV) represent a promising therapeutic alternative in BS. To date, evidence on the use of ANA, CAN, and GEV is mainly based on small isolated studies or case series, and the real place of anti-IL1 agents in the treatment of BS is still unclear. We performed a systematic review of current evidence on the efficacy and safety of anti-IL1 agents in BS. The PubMed search yielded a total of 398 references, from which we retrieved 24 studies for inclusion (4 clinical trials, 6 observational studies, 14 case reports, case series or letters to the editor). Four studies evaluated the overall efficacy of IL-1 inhibitors, 15 studies focused on the specific efficacy of ANA, whereas efficacy of CAN and GEV was evaluated in 8 and 3 studies, respectively. Both ANA and CAN were associated with good control of mucocutaneous and ocular manifestations. ANA resulted effective also for osteoarticular manifestations. GEV was studied only for ocular manifestations, but gave contrasting results. Discordant evidence supports the use of ANA and CAN in pediatric setting and for first-line treatment of general BS manifestations. Most frequent side effects were local or diffuse cutaneous reactions and injection site reactions, particularly for ANA treatment. Blocking the IL-1 pathway could be an effective therapeutic strategy in particular BS involvements.

Behcet's syndrome (BS) is a complex vasculitis, characterised by peculiar histological, pathogenetic and clinical features. Superficial venous thrombosis (SVT) and deep vein thrombosis (DVT) are the most frequent vascular involvements, affecting altogether 15-40% of BS patients. Atypical thrombosis is also an important clinical feature of BS, involving the vascular districts of the inferior and superior vena cava, suprahepatic veins with Budd-Chiari syndrome, portal vein, cerebral sinuses and right ventricle. On the other hand, arterial involvement, although affecting only 3-5% of patients, represents a unique feature of BS, with aneurysms potentially affecting peripheral, visceral and pulmonary arteries. Vascular events in BS are promoted by inflammation, with neutrophils playing a key role in the pathogenesis of thrombotic events; in turn, coagulative components such as fibrinogen, thrombin, factor Xa and factor VIIa amplify the inflammatory cascade. Understanding the contribution of inflammatory and coagulation components in the pathogenesis of BS vascular events is crucial to define the most effective therapeutic strategy. Control of vascular thrombosis is achieved with immunosuppressants drugs rather than anticoagulants. In particular, use of azathioprine and cyclosporine in association with low-dose corticosteroids should be considered in DVT and SVT cases, while treatment with cyclophosphamide together with anti-TNF-α agents can be effectively used in arterial involvement. More recently, the anti-TNF-α drugs have also been reported as a valid alternative for the treatment also of venous events, especially DVT. An exception to the use of anticoagulant in BS could be represented by cerebral veins thrombosis. In this review, we will depict the main characteristics of the vascular involvement in BS, briefly describing histological and pathogenetic features, while focusing on the clinical and therapeutical approaches of the vascular manifestations of BS.

According to American clinical guidelines, allopurinol and febuxostat may be prescribed as first-line therapy to treat hyperuricemia. However, the Italian Medicines Agency directive, called Nota 91, allows the reimbursement of second-line febuxostat in the case of failure and/or intolerance of a previous allopurinol therapy, so partially embracing European League Against Rheumatism recommendations and the British Society for Rheumatology Guideline. Such inconsistency might lead to heterogeneity among General Practitioners (GPs) in treatment of hyperuricemia. This study, therefore, aimed to evaluate the prescribing behavior of GPs in terms of compliance with Nota 91 and/or official guidelines.Using the Health Search Database, a retrospective cohort study was conducted to evaluate the patterns of use of allopurinol and febuxostat between 2011 and 2016.In total, 44,257 and 5837 patients were prescribed with allopurinol and febuxostat, respectively. Among febuxostat users, 4321 (74%) had a previous allopurinol treatment; 92% of switches to febuxostat were related to hyperuricemia, whereas 9% of switchers presented intolerance to allopurinol; 26% of patients were prescribed with febuxostat as first-line therapy. The presence of diabetes and/or moderate/severe renal disease were statistically significant determinants of febuxostat use as first-line therapy.Prescriptions of febuxostat were highly compliant to Nota 91. Only a sub-group of frontline prescriptions of febuxostat were mainly driven by the presence of renal dysfunction, which is able to increase the risk of allopurinol intolerance and/or inefficacy. These findings indicate that GPs' prescribing behavior for hyperuricemia is highly compliant with both regulatory directives and clinical guidelines.

Background and aims Cardiovascular disease (CVD), including coronary artery disease and stroke/peripheral artery disease, is less commonly reported than venous thromboembolism in subjects with antiphospholipid antibodies (aPLs) and little is known about the association of CVD with adjusted Global AntiphosPholipid Syndrome Score (aGAPSS). Methods Consecutive aPLs subjects were enrolled to assess the association of CVD with aGAPSS. Moreover, additional risk factors of CVD were identified by means of multivariate analysis to design an aGAPSS specific for CVD (aGAPSSCVD). Results A total of 192 aPLs subjects (34 males, 158 females, mean age 49.84 ± 12.0 years) were enrolled. CVD was reported in 52 subjects (27.1%), 26 episodes of coronary artery disease and 26 stroke/peripheral artery disease. The prevalence of CVD increased for increasing aGAPSS ranging from 20.5% in the lowest aGAPSS category, up to 37.9% in the highest category (p = 0.027). ROC analysis showed that aGAPSS detected 63.0% of CVD and was associated with OR for CVD of 2.52 (95%CI: 1.24–5.10, p = 0.010). When including obesity, diabetes and smoking habit in the score, we found that aGAPSSCVD detected 71.4% of CVD (72.4% for early-CVD and 69.0% for CVD after 50 years) with an OR for CVD of 4.68 (95%CI: 2.31–9.51, p Conclusions The aGAPSSCVD, obtained after adding obesity, smoking habit and diabetes to the standard aGAPSS, showed a higher detection rate of CVD in aPLs subjects, particularly of early-CVD. These results need to be validated in ad hoc designed prospective studies.

Women with criteria and non-criteria obstetric antiphospholipid syndrome (APS) carry an increased risk of pregnancy complications, including fetal growth restriction (FGR). The management of obstetric APS traditionally involves clinicians, obstetricians and gynaecologists; however, the most appropriate prophylactic treatment strategy for FGR prevention in APS is still debated. We performed a systematic review and network meta-analysis (NetMA) to summarize current evidence on pharmacological treatments for the prevention of FGR in APS. We searched PubMed and Embase from inception until July 2020, for randomized controlled trials and prospective studies on pregnant women with criteria or non-criteria obstetric APS. NetMA using a frequentist framework were conducted for the primary outcome (FGR) and for secondary outcomes (fetal or neonatal death and preterm birth). Adverse events were narratively summarised. Out of 1124 citations, we included eight studies on 395 pregnant patients with obstetric APS treated with low-dose aspirin (LDA) + unfractionated heparin (UFH) (n = 132 patients), LDA (n = 115), LDA + low molecular weight heparin (n = 100), LDA + corticosteroids (n = 29), LDA + UFH + intravenous immunoglobulin (n = 7), or untreated (n = 12). No difference among treatments emerged in terms of FGR prevention, but estimates were largely imprecise, and most studies were at high/unclear risk of bias. An increased risk of fetal or neonatal death was found for LDA monotherapy as compared to LDA + heparin, and for no treatment as compared to LDA + corticosteroids. The risk of preterm birth was higher for LDA + UFH + IVIg as compared to LDA or LDA + heparin, and for LDA + corticosteroids as compared to LDA or LDA + LMWH. No treatment was associated with an increased risk of bleeding, thrombocytopenia or osteopenia.

Objectives Psycholeptic drugs have been used in the older population for years, especially to control delirium and neuropsychiatric symptoms (NPS) of dementia. However, data from the literature confirm that the prolonged use of psycholeptics may be responsible for adverse reactions in older patients. The aim of this study was (1) to identify how many patients receive the first prescription of a psycholeptic drug during the hospital stay; (2) to evaluate the main sociodemographic and clinical characteristics of these patients; and (3) to verify if the prescribed psycholeptic drugs are continued after 3 months from the hospital discharge. Design Our retrospective study was based on data from the REPOSI (REgistro POliterapie SIMI) registry, a cohort of older patients hospitalized in internal medicine and geriatric wards throughout Italy from 2010 to 2018. Setting and Participants Patients aged 65 years or older who were not on home therapy with psycholeptic drugs were considered in the analyses. Methods We did both univariate and multivariate analyses in order to find the variables associated independently to an increased risk for first psycholeptic prescription at hospital discharge. Results At hospital discharge, 193 patients (5.8%) out of a total sample of 3322 patients were prescribed at least 1 psycholeptic drug. Cognitive impairment was the main risk factor for the introduction of psycholeptic drugs at discharge. Among them, 89.1% were still on therapy with a psycholeptic drug after 3 months from the hospital discharge. Conclusions and Implications Cognitive impairment represents the main risk factor for psycholeptic initiation in hospitalized older patients. The vast majority of these treatments are chronically continued after the discharge. Therefore, special attention is needed in prescribing psycholeptics at discharge, because their prolonged use may lead to cognitive decline. Moreover, their continued use should be questioned by physicians providing post-acute care, and deprescribing should be considered.

Background and objectives ANCA-associated vasculitis is extremely rare in children. We report the clinicopathologic features, long-term outcomes, and prognostic factors of a large pediatric cohort of patients with ANCA-associated kidney vasculitis. Design, setting, participants, & measurements This retrospective study included 85 consecutive patients with kidney biopsy specimen–proven ANCA-associated vasculitis from tertiary referral centers in Italy and Canada. Kidney biopsy specimens were categorized as focal, crescentic, sclerotic, or mixed, according to the Berden classification. The prognostic significance of baseline clinical, laboratory, and histologic findings was analyzed with respect to kidney failure or CKD stage 3–5/kidney failure. Results A total of 53 patients had microscopic polyangiitis (62%), and 32 had granulomatosis with polyangiitis (38%). Rapidly progressive GN was the most frequent presentation (39%); a third of the patients also had nephrotic-range proteinuria. Kidney biopsy specimens were classified as focal in 21% of the patients, crescentic in 51%, sclerotic in 15%, and mixed in 13%. Remission-induction therapies included cyclophosphamide in 78% of patients. A total of 25 patients (29%) reached kidney failure. The median (interquartile range) time to kidney failure or last follow-up was 35 (6–89) months in the whole cohort, and 73 (24–109) months among the patients who did not reach this outcome. Patients whose biopsy specimens showed sclerotic histology had significantly shorter kidney survival (hazard ratio, 11.80; 95% confidence interval, 2.49 to 55.99) and survival free of CKD stage 3–5 (hazard ratio, 8.88; 95% confidence interval, 2.43 to 32.48), as compared with those with focal/mixed histology. Baseline eGFR, low serum albumin, hypertension, central nervous system complications, and sclerotic histology, which reflected severe kidney involvement, were associated with both kidney failure and CKD stage 3–5/kidney failure at unadjusted analysis; no independent prognostic factors emerged at multivariable analysis. Conclusions Children with ANCA-associated kidney vasculitis often have aggressive presentation; a third of such children progress to kidney failure and this usually occurs early during follow-up. A severe clinical presentation is associated with the development of CKD or kidney failure.

Exposure of the embryo or fetus to ionizing radiations is a potential danger since it may induce clinically relevant fetal and/or neonatal damages. The aim of the present study was to examine fetal and neonatal outcomes after maternal exposure to radio-diagnostic procedures during first trimester of pregnancy, and to evaluate whether these effects might be related to the fetal absorbed dose of ionizing radiations. A 10-year prospective cohort study was performed on 1979 pregnant women who underwent a radio-diagnostic procedure within the first trimester of pregnancy. Women were divided into two groups: those exposed to abdominal or lumbar radio-diagnostic procedure (Cohort A, n = 130), and those exposed to radio-diagnostic procedures in any other body regions (Cohort B, n = 415). Health physicists performed tailored fetal radiation dose calculation. Multivariate logistic regression model was used to estimate the risk of adverse pregnancy outcomes. The tailored fetal radiation dose was calculated for a total of 97 women (range 0.05-92 mSv). Major congenital malformations were detected in four infants in Cohort A, six infants in Cohort B, and 24 infants in controls (p = 0.445). Multivariate analysis confirmed the negative association between age and adverse pregnancy outcomes (OR 1.08 [1.06���1.11]), and the protective role of folic acid. A higher rate of small for gestational age seems to be present in women who underwent radio-diagnostic procedures that involve maternal thyroid. Despite several limitations, our study confirms that exposure to radio-diagnostic procedures that may involve uterus at doses below 100 mSv does not increase the risk of embryo-fetal toxicity. The relationship between maternal thyroid irradiation and small for gestational age needs to be further investigated.

The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta-analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low-dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27-3.16 and OR 2.67, 95% CI 1.21-5.89 for controls vs. LMWH and LDA + LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/- LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.

Background: To know burden disease of a patient is a key point for clinical practice and research, especially in the elderly. Charlson’s Comorbidity Index (CCI) is the most widely used rating system, but when diagnoses are not available therapy-based comorbidity indices (TBCI) are an alternative. However, their performance is debated. This study compares the relations between Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), Chronic Disease Score (CDS), and severe multimorbidity, according to the CCI classification, in the elderly. Methods: Logistic regression and Receiver Operating Characteristic (ROC) analysis were conducted on two samples from Italy: 2579 nursing home residents (Korian sample) and 7505 older adults admitted acutely to geriatric or internal medicine wards (REPOSI sample). Results: The proportion of subjects with severe comorbidity rose with TBCI score increment, but the Area Under the Curve (AUC) for the CDS (Korian: 0.70, REPOSI: 0.79) and MCI (Korian: 0.69, REPOSI: 0.81) were definitely better than the DDCI (Korian: 0.66, REPOSI: 0.74). All TBCIs showed low Positive Predictive Values (maximum: 0.066 in REPOSI and 0.317 in Korian) for the detection of severe multimorbidity. Conclusion: CDS and MCI were better predictors of severe multimorbidity in older adults than DDCI, according to the CCI classification. A high CCI score was related to a high TBCI. However, the opposite is not necessarily true probably because of non-evidence-based prescriptions or physicians’ prescribing attitudes. TBCIs did not appear selective for detecting of severe multimorbidity, though they could be used as a measure of disease burden, in the absence of other solutions.

BACKGROUND The effect of direct-acting anti-virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies. AIM To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection. METHODS We performed a systematic review and meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects

Radiotherapy (RT) and transoral laser microsurgery (TLM) represent the main treatment modalities for early glottic carcinoma. Local failure is notoriously more frequent in T1b glottic cancer in comparison to T1a and T2 tumors. In this scenario, the role of anterior commissure (AC) involvement is still controversial. The aim of the present study was therefore to determine its potential prognostic power in worsening patients&rsquo, survival and outcomes. We categorized different tumor glottic fold locations with respect to the involvement of one (T1a) or both vocal cords, with or without AC involvement. We analyzed a retrospective cohort of 74 patients affected by Stage I glottic cancer, treated between 2011 and 2018 by TLM or RT at a single academic institution. There were 22 T1a (30%) and 52 T1b (70%) cases. The median follow-up period was 30 months (mean, 32.09 &plusmn, 18.738 months, range, 12&ndash, 79). Three-year overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and laryngectomy-free survival (LFS) were compared according to tumor location, extension, and cT category. According to both uni- and multivariate analyses, an increased risk for recurrence in T1b with AC involvement and T1a tumors was 7.31 and 9.45 times, respectively (p-values of 0.054 and 0.030, respectively). Among the 17 recurrences, T1b with AC involvement experienced 15 tumor relapses (88.2%), thus significantly affecting both the RFS and LFS in comparison to the other two tumor subcategories (T1a, p = 0.028 and T1b without AC involvement, p = 0.043). The deteriorating prognosis in the presence of AC involvement likely reflects the need to power the hazard consistency and discrimination of the T1b category when associated with such a risk factor, thus deserving an independent T category.

Objective To evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) in secondary prevention of pregnancy complications for patients with obstetric antiphospholipid syndrome (APS) and history of stillbirth. Methods We described three cases of obstetric APS patients with history of stillbirth treated with IVIg in four pregnancies. In addition, we conducted a systematic literature review on the use of IVIg in obstetric APS with history of stillbirth. Results Three patients with obstetric APS and history of stillbirth were treated with prophylactic IVIg, in addition to standard treatment (hydroxychloroquine, low-dose aspirin, low molecular weight heparin, and prednisone), in four pregnancies (three singleton and one twin). All pregnancies resulted in live healthy newborns. Long-term follow-up re-evaluations (24–53 months) did not shown any sign or symptom of active systemic disease, and the children were healthy. The systematic literature review retrieved only three cases of use of IVIg in obstetric APS patients with history of stillbirth. All three cases resulted in live healthy newborns. Only in one case, mild thrombocytopenia occurred during treatment, although this event was unlikely to be related to IVIg. Conclusion Our experience suggests that IVIg as secondary prevention of APS-related stillbirth is associated with good pregnancy and long-term outcomes, with no relevant safety concerns. However, the literature evidence on this topic is limited to few isolated cases, and further studies are needed to clarify which obstetric APS patients may benefit the most from IVIg.

All kinds of ear, nose, and throat and maxillofacial surgery (ENT/MFS) procedures are being increasingly performed in the elderly although old age is a major risk factor for increased postoperative complications. With only scarce evidence on the topic, surgeons are asked to critically evaluate their procedures’ indications and outcomes to balance the treatment risks and benefits. Our primary aim was to identify predictive factors for surgical outcomes in this setting and to create a predictive model for a tailored risk assessment. We analyzed a case series of 435 patients from an institutional clinical database at our academic tertiary care center. Multivariate logistic regression was used to identify all possible covariates and nomograms using stepwise backward method were generated. The performance was assessed by calibration curves and c-index. Overall complication rate was 18.3% within the first 30 days and the need for re-intervention was 5.9%. For those under general anesthesia, we identified specific risk factors and developed three risk-predicting models of overall, early, and late complications. All of the nomograms showed satisfactory accuracy with a c-index of 0.83, 0.75, 0.86, and 0.82, respectively. Using clinical preoperative variables, we constructed a model for predicting major adverse events in ENT/MFS patients. In our experience, patients over 65 showed a non-negligible risk for postoperative complications depending on several factors. Such tools might help in decision-making, by increasing the risk-awareness of clinicians, to better address peri-operative and post-operative care of these patients.

ObjectiveTo evaluate the effectiveness and safety of secukinumab in patients with a mucosal and articular Behçet’s phenotype resistant to conventional and biologic treatment.MethodsA multicentre retrospective study was performed on 15 patients with a mucosal and articular phenotype of Behçet’s syndrome fulfilling the International Criteria for Behçet’s Disease and refractory to treatment with colchicine, disease-modifying antirheumatic drugs and at least one antitumour necrosis factor-α agent. Minimum follow-up was set at 6 months. Six patients with a polyarticular involvement were treated with secukinumab 300 mg/month, while all other cases received secukinumab 150 mg/month. Dose increase from 150 to 300 mg per month and shortening of administration frequency were allowed for poor disease control. Response evaluation was based on the number of oral ulcers in the previous 28 days and Disease Activity Score-28 for articular manifestations.ResultsAt 3 months of follow-up, nine (66.7%) patients achieved a response (complete or partial), and this proportion further increased to 86.7% at 6 months, 76.9% at 12 months, 90.0% at 18 months and 100.0% after 24 months. Notably, all patients who started with secukinumab 300 mg/month achieved complete response by month 6. Seven (46.7%) patients could achieve a response only after switching to a higher dosage.ConclusionsOur study suggests that secukinumab at a dose of 150 and 300 mg per month is safe and effective for the long-term treatment of patients with Behçet’s syndrome with a mucosal and articular phenotype refractory to previous treatments. Notably, secukinumab 300 mg/month resulted in superior complete mucosal and articular responses with no serious or dose-related adverse effects.

Objectives A refractory chronic migraine (RCM) accompanied by medication-overuse headache (MOH) is an extremely disabling disease. Evidence suggests that in selected patients, chronic opioids may be a valuable therapeutic option for RCM. The aim of the present study was to evaluate the effectiveness and safety of prophylaxis with low-dose methadone (LDM) in patients affected by RCM with continuous headache and MOH. Methods A prospective cohort study was performed between May 2012 and November 2015 at the Headache Center and Toxicology Unit of the Careggi University Hospital. Eligible patients were treated with prophylactic LDM and followed up for 12 months. Headache exacerbations, pain intensity, use of rescue medications, and occurrence of adverse drug reactions (ADRs) were recorded. Results Thirty patients (24 females, median age 48 years) were enrolled. Nineteen (63%) patients dropped out, mainly because of early ADRs (n = 10), including nausea, vomiting, and constipation. At last available follow-up, LDM was associated with a significant decrease in the number of headache attacks/month (from a median of 45 (interquartile range 30–150) to 16 (5–30), p p p Conclusion LDM could represent a valuable and effective option in selected patients affected by RCM with continuous headache and MOH, although the frequency of early ADRs poses major safety concerns. Randomized controlled trials are needed to confirm the efficacy and safety of LDM prophylaxis.

Background Adverse drug event (ADEs) are a significant cause of emergency department (ED) visits and consequent hospitalization. Preventing ADEs and their related ED visits in outpatients remains a public health safety challenge. In this context, the aims of the present study were to describe the frequency, seriousness and preventability of outpatients' ADE-related ED visits and hospitalizations in the Italian general population, and to identify the presence of potential predictors of ADE-related hospitalization. Methods We performed a nationwide, multicentre, observational, retrospective study based on reports of suspected ADEs collected between January 1, 2007 and December 31, 2018 in 94 EDs involved in the MEREAFaPS project. Patients' demographic characteristics, their clinical status, suspected and concomitant drugs, ADE description, and its degree of seriousness, were collected. Causality and preventability were assessed using validated algorithms, and logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization, considering the following covariates: age, sex, ethnicity, number of implicated medications, parenteral administration, presence of interaction, therapeutic error, and/or complementary and alternative medicines (CAM). Results Within 12 years, 61,855 reports of suspected ADE were collected, of which 18,918 (30.6%) resulted in hospitalization (ADE defined as serious). Patients were mostly female (56.6%) and Caucasians (87.7%), with a mean age of 57.5 ± 25.0 years. 58% of patients were treated with more than two drugs, and 47% of ADEs leading to hospitalization were preventable. Anticoagulants, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently implicated agents for ED visits and/or hospitalization, which included clinically significant ADEs, such as haemorrhage for anticoagulants, moderate to severe allergic reactions for antibiotics, and dermatologic reactions and gastrointestinal disturbances for NSAIDs. Older age (1.54 [1.48-1.60]), higher number of concomitantly taken drugs (2.22 [2.14-2.31]), the presence of drug-drug interactions (1.52 [1.28-1.81]), and therapeutic error (1.54 [1.34-1.78]), were significantly associated with an increased risk of hospitalization. Conclusion Our long-term active pharmacovigilance study in ED provided a valid estimation of ADE-related hospitalization in a representative sample of the Italian general population and can suggest further focus on medication safety in outpatients, in order to early recognise and prevent ADEs.

Background Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome. Methods We screened patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction Results Of 856 patients, 41 (5%) had slowly progressive renal AAV. All had MPA and all but one was P-ANCA/myeloperoxidase (MPO) ANCA-positive. At diagnosis, the median age was 70 years [interquartile range (IQR) 64–78] and extra-renal manifestations were absent or subclinical (interstitial lung lesions in 10, 24%). The median (IQR) eGFR was 23 mL/min/1.73 m2 (15–35); six patients (15%) had started renal replacement therapy (RRT). All had proteinuria (median 1180 mg/24 h, IQR 670–2600) and micro-haematuria. Main histologic findings were extracapillary proliferation at chronic stages and glomerulosclerosis; following Berden’s classification, 6/28 biopsies (21%) were ‘focal’, 1/28 (4%) ‘crescentic’, 9/28 (32%) ‘mixed’ and 12/28 (43%) ‘sclerotic’. At last follow-up (median 32 months, IQR 12–52), 20/34 patients (59%) treated with immunosuppression had eGFR improvement >25% as compared with diagnosis, while 4/34 (12%) had started RRT. Conclusions AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression.

Behçet's syndrome (BS) is a systemic vasculitis considered as the prototype of a systemic inflammation-induced thrombotic condition whose pathogenesis cannot be explained just by coagulation abnormalities. Circulating hematopoietic progenitor cells (CPC), a population of rare, pre-differentiated adult stem cells originating in the bone marrow and capable of both self-renewal and multi-lineage differentiation, are mobilized in response to vascular injury and play a key role in tissue repair. In cardiovascular and thrombotic diseases, low circulating CPC number and reduced CPC function have been observed. Oxidative stress may be one of the relevant culprits that account for the dysfunctional and numerically reduced CPC in these conditions. However, the detailed mechanisms underlying CPC number reduction are unknown. On this background, the present study was designed to evaluate for the first time the possible relationship between CPC dysfunction and oxidative stress in BS patients. In BS patients, we found signs of plasma oxidative stress and significantly lower CD34+/CD45−/dim and CD34+/CD45−/dim/CD133+ CPC levels. Importantly, in all the considered CPC subsets, significantly higher ROS levels with respect to controls were observed. Higher levels of caspase-3 activity in all the considered CPC population and a strong reduction in GSH content in CPC subpopulation from BS patients with respect to controls were also observed. Interestingly, in BS patients, ROS significantly correlated with CPC number and CPC caspase-3 activity and CPC GSH content significantly correlated with CPC number, in all CPC subsets. Collectively, these data demonstrate for the first time that CPC from BS patients show signs of oxidative stress and apoptosis and that a reduced CPC number is present in BS patients with respect to controls. Interestingly, we observed an inverse correlation between circulating CPC number and CPC ROS production, suggesting a possible toxic ROS effect on CPC in BS patients. The significant correlations between ROS production/GSH content and caspase-3 activity point out that oxidative stress can represent a determinant in the onset of apoptosis in CPC. These data support the hypothesis that oxidative-stress-mediated CPC dysfunctioning may counteract their vascular repair actions, thereby contributing to the pathogenesis and the progression of vascular disease in BS.

Behcet's syndrome (BS) is a multisystemic vasculitis, characterized by different clinical involvements, including mucocutaneous, ocular, vascular, neurological, and gastrointestinal manifestations. Based on this heterogeneity, BS can be hardly considered as a single clinical entity. Growing evidence supports that, within BS, different phenotypes, characterized by clusters of co-existing involvements, can be distinguished. Namely, three major BS phenotypes have been reported: (a) the mucocutaneous and articular phenotype, (b) the extra-parenchymal neurological and peripheral vascular phenotype, and (c) the parenchymal neurological and ocular phenotype. To date, guidelines for the management of BS have been focused on the pharmacological treatment of each specific BS manifestation. However, tailoring the treatments on patient's specific phenotype, rather than on single disease manifestation, could represent a valid strategy for a personalized therapeutic approach to BS. In the present literature review, we summarize current evidence on the pharmacological treatments for the first-, second-, and third-line treatment of the major BS phenotypes.

Whereas some previous data on carriers with isolated antiphospholipid antibodies positivity (APP) suggested an increased risk of arterial events in this clinical setting, no data are available on subclinical atherosclerosis in this clinical setting. This article reports data on intima-media thickness of the common carotid artery (CCA-IMT) and of the Bulb (Bulb-IMT) and on the prevalence of carotid plaques in APP carriers and in subjects with antiphospholipid syndrome (APS) specifically stratifying for the presence of thrombotic manifestations, cardiovascular risk factors, antibody isotype and concomitant Systemic Lupus Erythematosus (SLE) or other autoimmune diseases.

First-line treatment of chronic phase (CP) chronic myeloid leukemia (CML) is based on the first-generation tyrosine kinase inhibitor (TKI) imatinib or the second-generation TKIs dasatinib or nilotinib. Thanks to the efficacy of TKIs, CML has switched from a fatal to a ‘chronic’ pathology, and data from clinical trials have become insufficient to drive physicians’ prescription choices and address long-term treatment outcomes. On the brink of commercialization of generic imatinib, this study aims to evaluate the therapeutic pattern of CP-CML and the occurrence of adverse events (AEs) over a decade of local real clinical practice. A retrospective cohort study was performed on CP-CML patients followed up in the Local Health Unit of Treviso (Veneto Region, Italy) during the period 2005–2015. Data were captured from both administrative databases and physicians’ patient diaries. Of 81 CP-CML patients, 73 were treated with first-line imatinib; among the second-generation TKIs, only nilotinib was used (n = 8). Overall, 38% of imatinib-treated subjects needed to switch, mainly due to intolerance, whereas no switches occurred in the nilotinib cohort. Osteoarticular pain was the most common AE and was significantly more frequent in the imatinib cohort (68.49 vs. 25.00%, p = 0.022). Other common AEs were dermatologic manifestations, asthenia, and diarrhea. Although based on a small population, this study represents an unbiased reference on the long-term management of CML in an Italian clinical setting. Our results indicate a better profile of first-line nilotinib, both in terms of persistency and tolerability. AEs remain a major concern, highlighting the importance of close monitoring.

OBJECTIVE Since Behcet's syndrome (BS) is the prototype of inflammation-induced thrombosis, immunosuppressants are recommended in place of anticoagulants. We undertook this study to assess the clinical efficacy and the corticosteroid-sparing effect of adalimumab (ADA)-based treatment versus disease-modifying antirheumatic drug (DMARD) therapy in a large retrospective cohort of patients with BS-related venous thrombosis. METHODS We retrospectively collected data on 70 BS patients treated with DMARDs or ADA-based regimens (ADA with or without DMARDs) because of venous complications. Clinical and imaging evaluations were performed to define vascular response. We explored differences in outcomes between ADA-based regimens and DMARDs with respect to efficacy, corticosteroid-sparing role, and time on treatment. We also evaluated the role of anticoagulants as concomitant treatment. RESULTS After a mean ± SD follow-up period of 25.7 ± 23.2 months, ADA-based regimens induced clinical and imaging improvement of venous thrombosis more frequently (P = 0.001) and rapidly (P < 0.0001) than did DMARDs. The mean dose of corticosteroids administered at the last follow-up visit was significantly lower with ADA-based regimens than with DMARDs (P < 0.0001). The time on treatment was significantly longer with ADA plus DMARDs than with DMARDs alone (P = 0.002). No differences were found in terms of efficacy and time on treatment between DMARDs or ADA-based regimens among patients who received anticoagulants and those who did not. CONCLUSION In this large retrospective study, we have shown that ADA-based regimens are more effective and rapid than DMARDs in inducing resolution of venous thrombosis in BS patients, allowing reduction of steroid exposure. Moreover, our findings suggest that anticoagulation does not modify the efficacy of either ADA-based regimens or DMARDs for venous complications.

Aims The use of complementary and alternative medicines (CAMs) during breastfeeding is increasing, mainly because of their presumed greater safety compared with conventional medications. However, CAMs can cause serious adverse effects, and there is limited high-quality evidence supporting their use during lactation. In Italy, specific investigations on the attitude of lactating women towards CAMs are lacking. The Herbal supplements in Breastfeeding InvesTigation (HaBIT) study aimed to explore attitudes to and knowledge on CAMs among lactating women. Methods A web-based survey was conducted over a 6-year period among lactating women resident in Tuscany, Italy. Data on lactating behaviour, CAMs use during pregnancy or breastfeeding, and women's knowledge about the efficacy and safety of CAMs were collected. Results A total of 388 lactating women answered the questionnaire. The majority of them were primiparae, with a high educational level. Of these, 204 women declared themselves to have used CAMs during breastfeeding. Moreover, 61% and 48% of subjects reported also using CAMs before and during pregnancy, respectively. A significant proportion of subjects were unable to identify correctly the types of CAMs they were using. Seventy-three per cent of women were convinced that CAMs were equally safe or safer than conventional medications; nevertheless, 65% of women admitted to have no scientific information about the potential risks of CAMs, and 14 CAMs users reported that they had experienced side effects. Conclusions These results demonstrate the need for healthcare providers to increase the awareness of breastfeeding women about CAMs. Further research is needed to support the evidence base for nonpharmaceutical approaches for symptom control during breastfeeding.

Herbal weight-loss supplements are sold as self-medication products, and are often used under the misconception that their natural origin guarantees their safety. Food supplements are not required to provide any benefit/risk profile evaluation before marketing; however, possible risks associated with use of herbal extracts in food supplements are becoming more and more documented in the literature. Some herbs are listed as the leading cause of herb-induced liver injury, with a severe or potentially lethal clinical course, and unpredictable herb-drug interactions. Garcinia cambogia (GC) extract and GC-containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we present four cases of acute liver failure in women taking GC extract for weight loss, and a literature review of clinical evidences about hepatic toxicity in patients taking dietary supplements containing GC extract.

Background:Evidence on the efficacy of Mepolizumab (MEPO) in Eosinophilic Granulomatosis with Polyangiitis (EGPA) is scarce [1].Objectives:To assess the efficacy and safety of MEPO in real-life clinical practice.Methods:We retrospectively included patients diagnosed with EGPA and treated with MEPO (100 or 300 mg/month). MEPO efficacy was evaluated in the first 12 months in terms of systemic disease and asthma control. The occurrence of any adverse event (AE) was recorded.Results:142 patients were included (38% males; median age 46.4 (IQR 36.7-54.4); 110 and 32 on MEPO 100 and 300 mg/month, respectively). General, ear-nose-throat, pulmonary, and neurological symptoms significantly decreased during treatment (table 1). MEPO accounted for a significant reduction in the BVAS (figure 1) and for a steroid sparing effect (figure 2). The proportion of patients with asthma attacks decreased by 90% at 12 months compared to t0, and asthma-related emergency accesses dropped from 17.4% to 2.3%. Overall, 21.1% of patients had a non-serious AE.Table 1.Control of clinical symptomsMEPO beginning (t0)3 monthsp-value(t3 vs t0)6 monthsp-value(t6 vs t0)12 monthsp-value(t12 vs t0)N obsN=142N=135N=123N=89General symptoms40 (28.2%)17 (12.6%)19 (15.5%)13 (14.6%)0.002Cutaneous manifestations13 (9.2%)6 (4.4%)0.0085 (4.1%)0.0254 (4.5%)0.180ENT manifestations106 (74.7%)52 (38.5%)44 (35.8%)29 (32.6%)Pulmonary manifestations130 (91.6%)59 (43.7%)39 (31.7%)28 (31.5%)Cardiac manifestations6 (4.2%)2 (1.5%)0.0832 (1.6%)0.08300.157Intestinal manifestations10 (7.0%)1 (0.7%)0.0054 (3.3%)0.0593 (3.4%)0.059Renal manifestations5 (3.5%)3 (2.2%)0.41400.0461 (1.1%)0.317Neurological manifestations36 (25.4%)22 (16.3%)0.01218 (14.6%)0.00310 (11.2%)0.035Figure 1.Changes in BVASFigure 2.Steroid treatmentConclusion:MEPO effectively controlled systemic and respiratory EGPA symptoms in a large European cohort, with no major safety concerns.References:[1]Wechsler et al. MEPO or Placebo for Eosinophilic Granulomatosis with Polyangiitis. NEJM. 2017Disclosure of Interests:Alessandra Bettiol: None declared, Maria Letizia Urban: None declared, Federico Alberici: None declared, Carlo Agostini: None declared, Chiara Baldini: None declared, Enrica Bozzolo: None declared, Paolo Cameli: None declared, Nunzio Crimi: None declared, Stefano Del Giacco: None declared, Allyson Egan: None declared, Georgina Espigol-Frigole Consultant of: Roche and Janssen, Mara Felicetti: None declared, Marco Folci: None declared, Paolo Fraticelli: None declared, Marcello Govoni: None declared, Anna Kernder Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Carlo Lombardi: None declared, Giuseppe Lopalco: None declared, Claudio Lunardi: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Frank Moosig: None declared, Simone Negrini: None declared, Thomas Neumann: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Giuseppe Paolazzi: None declared, paola parronchi: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Vito Racanelli: None declared, Carlo Salvarani: None declared, Maxime Samson: None declared, Jan Schroeder: None declared, Savino Sciascia: None declared, Renato A. Sinico: None declared, Benjamin Terrier: None declared, Paola Toniati: None declared, Domenico Prisco: None declared, Augusto Vaglio: None declared, Giacomo Emmi: None declared

Objectives To assess the association of the anticholinergic medication burden with hospitalization and mortality in nursing home elderly patients and to investigate the role of coronary artery disease (CAD). Design Longitudinal (5-year) retrospective observational study. Setting Nursing homes in Italy. Participants A total of 3761 nursing home older residents. Measurements A comprehensive clinical and functional assessment was carried out through the interRAI long-term care facility instrument. The anticholinergic burden was assessed through the anticholinergic cognitive burden (ACB) scale. Occurrence of hospitalization/all-cause mortality was the primary composite outcome. First hospitalization and all-cause mortality were the secondary outcomes of the study. Hazard ratios (HRs) and subdistribution HRs were obtained through Cox and competing risk (death as competing event for hospitalization) models. Results Within the sample (mean age 83 ± 7 years; 72% females) the incidence rate of the primary outcome was 10/100 person-year. After adjusting for potential confounders and compared with participants with an ACB of 0, those with an ACB of 1 [HR 1.46; 95% confidence interval (CI) 1.12–1.90] and ABC of 2+ (HR 1.41; 95% CI 1.11–1.79) presented an increased risk of developing the primary outcome. After stratification, the risk for the primary outcome increased along with the anticholinergic burden, only for participants affected by CAD (HR 1.53; 95% CI 0.94–2.50 and HR 1.71; 95% CI 1.09–2.68 for the ACB of 1 and ACB of 2+ groups). An ACB score of 2+ was marginally associated with first hospitalization, considering death as a competing risk, only for those with CAD (subdistribution HR 3.47; 95% CI 0.99–12.3). Conclusions Anticholinergic medication burden is associated to hospitalization and all-cause mortality in institutionalized older adults. CAD increases such risk. The effectiveness and safety profile of complex drug regimens should be reconsidered in this population.

Combination therapies are often needed to modify the concomitant risk factors for cardiovascular disease. Nonadherence to cardiovascular medications is a relevant concern, especially in polytherapy. We conducted a population-based, cohort study with the aim of quantifying the level of adherence and its related determinants in patients exposed to free 3-drug combination therapies, namely concurrent use of angiotensin-converting-enzyme inhibitor (ACEi), calcium channel blocker (CCB), and statin or of ACEi, statin, and low-dose aspirin. Within Health Search Database, we selected a cohort of adult patients concurrently prescribed with ACEi, CCB, and statin, as well as those prescribed with ACEi, statin and low-dose aspirin, from the January 1, 2002 to the December 31, 2014. Adherent patients were concurrent users of triple free pill regimen with a proportion of days covered ≥80% during 1-year follow-up; demographics and clinical determinants of 1-year adherence were identified by multivariate logistic regression. We found that more than half of patients prescribed with triple free drug combination therapy with ACEi plus CCB plus statin or ACEi plus statin plus low-dose aspirin, were found to be nonadherent to these treatments. Males and patients at high/very-high cardiovascular risk were more likely to be adherent, whereas depression and atrial fibrillation were associated with nonadherence. Our findings indicate that sex, cardiovascular risk, presence of atrial fibrillation, and depression can influence adherence to polytherapy. In conclusion, given that patients suffering from multiple cardiovascular risk factors are at higher risk of fatal events, strategies are needed to improve medication adherence to combination therapies.

Background: The concern for adverse events following immunization (AEFI) and anti-vaccination movements that lacked scientific evidence-based supports may reduce vaccine uptake in the general population. Thus, the aims of the present study were to characterize AEFI in general population (all age groups), in terms of frequency, preventability, and seriousness and to define predictors of their seriousness in children. Methods: A retrospective study was performed on suspected AEFI reports for children and adults who received any form of vaccinations, collected in Tuscany, Italy, between 1 January and 31 December 2017. Patients’ characteristics, suspected vaccines, and AEFI description were collected. Causality and preventability were assessed using WHO and Schumock and Thornton algorithms, respectively. Logistic regression was used to estimate the reporting odds ratios of potential predictors of AEFI seriousness in children. Results: A total of 223 suspected AEFI reports were collected, and the majority of them were defined as non-serious (76.7%). Reports were mostly related to one vaccine, and to a median of two to five strains/toxoids. The total number of simultaneously administered strains/toxoids and the presence of allergens did not correlate with AEFI seriousness. Considering vaccines with a high number of administered doses (≥60,000 doses), the rates estimated for serious AEFI reports were always very low, ranging between 0.01 and 0.2/1,000 doses. Twenty-four vaccines (8,993 doses) were not related to any AEFI. Conclusion: Results of present study showed that AEFI were very rare; the vast majority of them was non-serious and, despite the claims of anti-vaccination movements, the simultaneous administration of vaccines was safe and did not influence the risk of reporting a serious AEFI, particularly in children.

IntroductionFetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%–45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.Methods and analysisWe will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.Ethics and disseminationResults will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.PROSPERO registration numberCRD42019122831.

Aims The short version of the Perinatal Grief Scale (PGS) has 33 items of Likert type whose answers vary from 1 (strongly agree) to 5 (strongly disagree), and is used to assess the grief after perinatal loss and to identify women at major need of specific support. This is the first attempt to validate an Italian version of PGS. Materials and methods The English version of PGS by Potvin et al. was translated into Italian by a professional mother tongue English translator. The survey was administered at 3 different times (translated Italian version; original English version after 10 days; and same Italian version after other 10 days) to 16 Italian/English bilingual women who had experienced a perinatal loss. The reproducibility among the three administrations and concordance were assessed using Cronbach's alpha and Cohen's kappa, respectively. Results Considering the PGS, median score ranged from 74.5 (58.5-94.5) to 78 (64-95), with no significant difference among the three questionnaire administrations (p = 0.616). No significant difference emerged among the three administered questionnaires for subscales (p = 0.095, 0.410 and 0.410 for 'active grief' AG, 'difficulty in coping' DC and 'despair' D scores, respectively). Concordance varied from good to very good among all questionnaire administrations. Conclusions This Italian version of the PGS can be used by clinicians to assess Italian women's responses to stillbirth and perinatal loss, as well as by researchers for research purposes.

The aims of this study were to assess the prevalence of use and prescription appropriateness of drugs for peptic ulcer and gastrooesophageal reflux disease (GERD) at hospital admission and discharge. Patients aged 65 years or more hospitalized from 2010 to 2016 in 101 Italian internal medicine and geriatric wards in the context of the REPOSI register were scrutinized to assess if they were prescribed with drugs for peptic ulcer and GERD at hospital admission and discharge. Appropriateness of prescription was assessed considering the presence of specific conditions (i.e., history of peptic ulcer or gastrointestinal hemorrhages, advanced age, Helicobacter Pylori) or gastro-toxic drug combinations, according to the criteria provided by the reimbursement rules of the Agenzia Italiana del Farmaco (NOTA 1 and 48). Among 4715 enrolled patients, 3899 were discharged alive. At hospital discharge, 2412 (61.9%, 95%CI: 60.3–63.4%) patients were prescribed with drugs for peptic ulcer and GERD, a 12% of increase from hospital admission. Almost half of the patients (N = 1776, 45.6%, 95%CI: 44.0–47.1%) were inappropriately prescribed or not prescribed: among the drugs for peptic ulcer and GERD users, about 60% (1444/2412) were overprescribed, and among nonusers, 22% (332/1487) were underprescribed. Among patients newly prescribed at hospital discharge, 60% (392/668) were inappropriately prescribed. The appropriateness of drugs for peptic ulcer and GERD therapy decreased by 3% from hospital admission to discharge. Hospitalization missed the opportunity to improve the quality of prescription of this class of drug.

Malignant parotid tumours are rare and multiple prognostic factors exist.Through a retrospective study we aimed to identify nomograms predicting recurrence and mortality rates in 228 primary parotid cancers. Patients clinical, treatment and tumour characteristics were retrospectively collected between 1980 and 2005 at our Institution. Factors predictive of disease-free-specific-survival (DSS) and overall survival (OS) were calculated by univariate and multivariate analysis. Nomograms were then constructed.The 5- and 10-year DSS rates were 73% and 71.4%, and nomogram was drawn based on five parameters where perineural invasion showed the most significant predicting influence (p 0.001). The median follow-up was of 95 months and the 5- and 10-year OS rates were 68.7% and 53.1%; six predictive variables (age, histological grade, perineural invasion, pathological lymph node status, resection margins and distant metastasis) were used to create nomogram.Our nomograms provide a tailored outcome to a patient affected by malignant parotid tumour and give him/her a risk assessment for recurrence and mortality based on individual factors by a concordance index 0.8.

Introduction: Magistral preparations of therapeutic cannabis are extracted from standardized products imported from Holland or from the Florence Military Pharmaceutical Chemical Works, but extraction protocols differ among galenic laboratories. This study assessed the inter-laboratory variability in concentrations of cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabinol (THC), and tetrahydrocannabinolic acid (THCA) among different magistral oil preparations.Methods: 219 samples of Bediol, Bedrobinol, Bedrolite or FM-2 70 or 100 mg/ml in oil were collected from 3 laboratories. Concentrations of CBD, CBN, THC, and THCA were quantified by high-pressure liquid chromatography; inter-laboratories variability was assessed using the Kruskal–Wallis test.Results: A significant variability in CBD and THC concentrations was found for Bediol 70 mg/ml samples from 2 laboratories [for CBD: median 5.4 (range 4.8–6.6) vs. 6.1 (4.9–7.2) mg/ml, p = 0.033; for THC: 3.6 (3.1–3.9) vs. 4.0 (2.6–5.1) mg/ml, p = 0.020]. As for Bediol 100 mg/ml, a significant variability emerged in THC concentrations among the three considered laboratories [5.7 (-) vs. 4.2 (1.5–4.8) vs. 5.2 (4.2–6.9), p = 0.030]. No significant inter-laboratory variability emerged for Bedrocan and Bedrolite. Concentrations of CBD, CBN, and THC were

Benzodiazepines (BDZs) are widely prescribed in older people. The aims of the study are to assess the prevalence of inappropriate prescription of BZDs and the associated factors in acutely hospitalized older patients. Patients aged 65 years or more hospitalized from 2010 to 2017 in more than 100 Italian internal medicine and geriatric wards in the frame of the REPOSI register were included if prescribed with BDZs at hospital admission or discharge. Appropriateness of prescription was assessed according to the 2015 Beers criteria and their modified French and German versions. Among 4681 patients discharged from hospital, 15% (N = 710) were discharged with BDZs, and 62% of them (N = 441, 95% CI: 58.5%–65.6%) were inappropriately prescribed, being prescribed with BDZ to be always avoided in the elderly (45%), at higher doses than recommended (31%) or with no appropriate clinical conditions (19%). From admission to discharge the prevalence of inappropriate BDZ prescription decreased by 4%, but 62% of patients inappropriately prescribed at admission were still inappropriately prescribed at discharge. Among the 179 patients first prescribed at the time of discharge, half were inappropriately prescribed. Being female (OR 1.32, 95%CI 0.95–1.85), enrolled in REPOSI during the years 2016 and 2017 (OR 1.94, 95%CI 1.10–3.39; OR 1.57, 95%CI 0.95–2.58) and living in nursing homes (OR 2.04, 95%CI 0.95–4.37) were associated with an increased risk to be inappropriately prescribed. This study shows a high prevalence of inappropriate use of BDZ in acutely hospitalized older patients both at hospital admission and discharge.

In 2014, the Italian Medicines Agency (AIFA) amended the summary of product characteristics of codeine-containing medications limiting their use for maximum three days. This study attempted to clarify the impact of AIFA intervention on prescribing trends and appropriateness of use of codeine-containing medications and other opioids. Using the Health Search Database, a quasi-experimental interrupted time series analysis was conducted to evaluate changes in prescribing trends and appropriateness of use of codeine-containing medications and opioids between 2013 and 2015. Prescribing trends of codeine-containing medications significantly decreased (on average, − 352 days of treatment per month of observation), while long-acting opioids (LAOs) had an overall increase. Trends of inappropriate prescriptions significantly increased for two LAOs (i.e. tapentadol, naloxone-oxycodone), both before and after AIFA intervention. The use of paracetamol-codeine combination was effectively decreased in Italy because of AIFA intervention. Instead, prescriptions of tapentadol and oxycodone-naloxone stably increased over the study period irrespective of regulatory intervention. Given that the choice of the most appropriate opioid therapy is not straightforward, especially in elderly and/or comorbid patients, general practitioners should consider carefully alternative therapies on the bases of regulatory interventions.

Efficacy and safety profiles of different pharmacological interventions used to treat patent ductus arteriosus (PDA) are relatively unexplored. Integrating the findings of randomized clinical trials (RCTs) with those from observational studies may provide key evidence on this important issue. We aimed at estimating the relative likelihood of failure to close the PDA, need for surgical closure, and occurrence of adverse events among preterm and full-term infants treated with indomethacin, ibuprofen, or acetaminophen, placebo, or no treatment including both RCTs and observational studies. We searched PubMed, Embase, and the Register of Controlled Trials from inception to October 30, 2018. We first estimated proportions of subjects with failure to close the PDA, subjects in whom surgical closure was performed after pharmacological treatment, death, and subjects with selected adverse events (AEs). These estimates were obtained using frequentist random-effect meta-analysis of arm-specific proportions. We then compared active drugs with each other and with control (either placebo or no treatment) by summarizing results at the end of treatment reported in the papers, regardless of number of administration(s), dose, route and type of administration, and study design and quality. We also summarized primary outcome results separately at first, second and third cycles of treatment. These estimates were obtained using Bayesian random-effects network meta-analysis for mixed comparisons, and frequentist random-effect pairwise meta-analysis for direct comparisons. We included 64 RCTs and 24 observational studies including 14,568 subjects (5339 in RCTs and 9229 in observational studies, 8292 subjects received indomethacin, 4761 ibuprofen, 574 acetaminophen, and 941 control (including placebo or no intervention).The proportion of subjects with failure to close the PDA was 0.24 (95% Confidence Interval, CI: 0.20, 0.29) for indomethacin, 0.18 (0.14, 0.22) for ibuprofen, 0.19 (0.09, 0.30) for acetaminophen, and 0.59 (0.48, 0.69) for control. At end of treatment, compared to control, we found inverse associations between all active drugs and failure to close PDA (for indomethacin Odds Ratio, OR, was 0.17 [95% Credible Interval, CrI: 0.11-0.24], ibuprofen 0.19 [0.12-0.28], and acetaminophen 0.15 [0.09-0.26]), without differences among active drugs. We showed inverse associations between effective drugs and need for surgical closure, as compared to control (for indomethacin OR was 0.28 [0.15-0.50], ibuprofen 0.30 [0.16-0.54], and acetaminophen 0.19 [0.07-0.46]), without differences among drugs. Indomethacin was directly associated with intraventricular hemorrhage (IVH) (1.27; 1.00, 1.62) compared to ibuprofen, and to oliguria as compared to ibuprofen (3.92; 1.69, 9.82) or acetaminophen (10.8; 1.86, 93.1). In conclusion, active pharmacological treatment, with indomethacin, ibuprofen, or acetaminophen, is inversely associated with failure to close the PDA compared to non-treatment. Ibuprofen should be preferred to indomethacin to avoid occurrence of IVH or oliguria, acetaminophen should be preferred to indomethacin to avoid oliguria.

Background Dietary supplements and homeopathic medicines are largely used in children as complementary and alternative medicine (CAM) to treat different health conditions. Safety of CAM is unknown when they are marketed. This study analysed suspected CAM-related adverse reaction (AR) in pediatric population. Methods The Italian Phytovigilance system was searched for reports of suspected AR related to CAM use in children (0–18 years) from 2002 to 2018. AR reports were evaluated and information about patient's demographic characteristics, suspected CAM, conventional medications, and ARs were collected. In particular, we evaluated whether patient's and CAM characteristics, and concomitant drugs could be potential predictors of ARs seriousness. Results We evaluated 206 pediatric CAM-related AR reports, of which 69 were serious. Patients were mostly treated with only one CAM (n = 193), and 39% of AR reports were related to products containing 2–5 components. Most reported ARs were related to dietary supplements (57.18%), and skin and subcutaneous tissue disorders (40.29%) were the most involved System Organ Class. CAM-related AR reported as serious were higher in subjects exposed to homeopathic medicines (ROR 3.13 [1.88–5.22]), to CAM in presence of concomitant medications (ROR 1.77 [1.01–3.10]), to CAM containing 2–4 components (ROR 2.18 [1.13–4.22]), and to more than three concomitant CAM (ROR 7.81 [1.97–32.69]). Conclusion We provide new insights on factors that might increase the risk of serious AR associated with CAM use in children: products containing more than two components and simultaneously administered with conventional medications can represent a potential risk in children.

Objective. This study was aimed at assessing the long-term ocular control of adalimumab (ADA) in a large real-world population with noninfectious primary or secondary uveitis, focusing on the steroid-sparing effect and on disease-modifying antirheumatic drug (DMARD) cotreatment. Methods. In this retrospective, multicenter study, the efficacy of ADA was evaluated in terms of ocular control, changes in best-corrected visual acuity (BCVA), corticosteroid-sparing effect, and drug retention rate, overall and stratified according to DMARD cotreatment. Results. 106 patients were included. 88.7% had an associated systemic disease. After 6 and 12 months, proportions of patients with effective ocular control were 83.7% and 83.3%, respectively. At last the follow-up, 94.6% of patients had satisfactory ocular control. No difference in terms of ocular control at all time points emerged among patients starting ADA for ocular vs. systemic involvements. Patients with poor baseline BCVA remained stable or improved, while those with good BCVA hardly worsened. At 6 and 12 months, the median dose of prednisone significantly reduced to 5 mg/day (0-5) and 2.5 mg/day (0-5) (p<0.001). Over a median follow-up of 36 months, 38 subjects discontinued ADA treatment. Mild to moderate side effects were reported in 7 patients (6.6%). ADA ocular control, corticosteroid-sparing effect, and drug retention rate were not influenced by the concomitant use of DMARDs. Conclusion. The long-term ocular control of ADA in noninfectious primary or secondary uveitis is confirmed, also for BCVA preservation. Concomitant use of DMARDs does not provide additional benefits to ADA alone in terms of ocular control, steroid spare, and drug retention rate.

We read with interest the article by Chatzidionysiou et al ,1 which reported a post-hoc analysis of two trials on intravenous belimumab in systemic lupus erythematosus (SLE), showing a significant reduction of antiphospholipid antibodies (aPL) only in patients cotreated with antimalarials. However, this post-hoc analysis focused on anticardiolipin antibodies (aCL) only, with no data on anti-β2-glycoprotein I (antiβ2GPI) antibodies, which display the best diagnostic/prognostic value in antiphospholipid antibodies syndrome (APS). Moreover, although long-term use of antimalarials was reported to reduce aPL levels by itself,2 no information on the duration of antimalarials cotreatment was reported.1 Interestingly, treatment with belimumab was recently reported to induce aCL and antiβ2GPI disappearance in a small case series of patients with SLE-associated APS.3 We also reported a significant reduction in aCL and antiβ2GPI titres in 12 patients with SLE on belimumab, either alone or associated with antimalarials.4 This study aimed to assess the effect of subcutaneous belimumab (200 mg/week) versus placebo, in association with standard therapy +/- antimalarials, on aCL and antiβ2GPI titers in patients with SLE, …