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The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference (\"gold\") standard. The sensitivity and specificity of 5 serologic tests for S. stercoralis (in-house IFAT, NIE-ELISA and NIE-LIPS and the commercially available Bordier-ELISA and IVD-ELISA) were assessed on 399 cryopreserved serum samples. Accuracy was measured using fecal results as the primary reference standard, but also using a composite reference standard (based on a combination of tests). According to the latter standard, the most sensitive test was IFAT, with 94.6% sensitivity (91.2-96.9), followed by IVD-ELISA (92.3%, 87.7-96.9). The most specific test was NIE-LIPS, with specificity 99.6% (98.9-100), followed by IVD-ELISA (97.4%, 95.5-99.3). NIE-LIPS did not cross-react with any of the specimens from subjects with other parasitic infections. NIE-LIPS and the two commercial ELISAs approach 100% specificity at a cut off level that maintains ≥70% sensitivity. NIE-LIPS is the most accurate serologic test for the diagnosis of S. stercoralis infection. IFAT and each of the ELISA tests are sufficiently accurate, above a given cut off, for diagnosis, prevalence studies and inclusion in clinical trials.

Traditional faecal-based methods have poor sensitivity for the detection of S. stercoralis, therefore are inadequate for post-treatment evaluation of infected patients who should be carefully monitored to exclude the persistence of the infection. In a previous study, we demonstrated high accuracy of five serology tests for the screening and diagnosis of strongyloidiasis. Aim of this study is to evaluate the performance of the same five tests for the follow up of patients infected with S. stercoralis. Retrospective study on anonymized, cryo-preserved samples available at the Centre for Tropical Diseases (Negrar, Verona, Italy). Samples were collected before and from 3 to 12 months after treatment. The samples were tested with two commercially-available ELISA tests (IVD, Bordier), two techniques based on a recombinant antigen (NIE-ELISA and NIE-LIPS) and one in-house IFAT. The results of each test were evaluated both in relation to the results of fecal examination and to those of a composite reference standard (classifying as positive a sample with positive stools and/or at least three positive serology tests). The associations between the independent variables age and time and the dependent variable value of serological test (for all five tests), were analyzed by linear mixed-effects regression model. A high proportion of samples demonstrated for each test a seroreversion or a relevant decline (optical density/relative light units halved or decrease of at least two titers for IFAT) at follow up, results confirmed by the linear mixed effects model that showed a trend to seroreversion over time for all tests. In particular, IVD-ELISA (almost 90% samples demonstrated relevant decline) and IFAT (almost 87%) had the best performance. Considering only samples with a complete negativization, NIE-ELISA showed the best performance (72.5% seroreversion). Serology is useful for the follow up of patients infected with S. stercoralis and determining test of cure.

PurposeIntravenous trastuzumab, pertuzumab, and docetaxel are first-line standard of care for patients with HER2-positive metastatic breast cancer (mBC). MetaPHER is the first study assessing the safety and tolerability of subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy in a global patient population with HER2-positive mBC.MethodsIn this open-label, single-arm, multicenter, phase 3b study, eligible patients were ≥ 18 years old with histologically/cytologically confirmed previously untreated HER2-positive mBC. All received ≥ 1 subcutaneous trastuzumab 600 mg fixed dose plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance: 420 mg/kg) and docetaxel (≥ 6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy.ResultsAt clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia; the most common grade ≥ 3 events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%.ConclusionsSafety and efficacy with subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in mBC are consistent with historical evidence of intravenous trastuzumab with this combination. Findings further support subcutaneous administration not affecting safety/efficacy profiles of trastuzumab in HER2-positive BC with increased flexibility in patient care. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection has recently been approved for the treatment of HER2-positive early/mBC, further addressing the increasing relevance of and need for patient-centric treatment strategies.Trial registrationNCT02402712

Many hospitalizations for asthma could potentially be avoided with appropriate management. The aim of this study was to analyze data on disease management of a paediatric population with a hospitalization for asthma. The study population comprised 6-17 year old subjects belonging to three local health units of the Lombardy Region, northern Italy. Regional administrative databases were used to collect data on: the number of children with an incident hospitalization for asthma during the 2004-2006 period, anti-asthma therapy, specialist visit referrals, and claims for spirometry, released in the 12 months before and after hospitalization. Each patient's asthma management profile was compared with GINA guideline recommendations. Among the 183 hospitalized subjects, 101 (55%) received therapy before hospitalization and 82 (45%) did not. 10% did not receive any therapy either before or after hospital admission and in 13% the therapy was discontinued afterward. Based on GINA guidelines, asthma management adhered to recommendations only for 55% of subjects. Results may suggest that for half of hospitalized subjects, inaccurate diagnosis, under-treatment/scarce compliance with asthma guidelines by physicians, and/or scarce compliance to therapy by patients/their parents occurred. In all these cases, hospitalization would be a proxy indicator of preventable poor control of disease, rather than a proxy indicator of severity.

Background Treatment and prophylaxis of sepsis in very low birth weight neonates is a matter of concern and research is being undertaken with the aim to give rise to shared approaches based on solid evidence. As part of a European initiative, a survey was set up to describe the use of two drugs in this area. The Italian national practices concerning neonatal sepsis, as well as calls for related guidance, are described. Methods A standardized and previously tested questionnaire was submitted online to all Italian level III NICUs. A 5-point Likert scale was used to analyze attitudinal replies. Categorical variables were compared by χ2 analysis and 2-tailed P-values are reported. Results Data was provided by 38 Italian NICUs (36% of the country’s level III centers), 53% of which have 1–10 cases of bacterial sepsis monthly and 90% a prevalence of <1% fungal infections. Ciprofloxacin and fluconazole treatment for neonatal sepsis are scantly used in Italian NICUs (13% and 45%, respectively). Major concerns are related to the safety of ciprofloxacin and the efficacy of fluconazole. On the contrary, prophylaxis of fungal infections is a routine approach in many Italian NICUs. The use of both ciprofloxacin and fluconazole is characterized by a large inter-NICU variability in dose and scheme of use. The lack of adequate, shared evidence is a common consideration made by the survey participants. Conclusions Common approaches are needed to standardize and update a national drug strategy for the prevention and treatment of sepsis in very low birth weight newborns. This can be achieved through collaborative initiatives aimed at setting up guidelines, based on available data, and multicenter trials to produce new evidence that will address the knowledge gaps.

Background Although anti-asthma medications are amongst those most frequently under or over prescribed it is generally accepted that prescriptions for such agents can be used as a proxy for disease prevalence. The aims of this study were to estimate prevalence and incidence of childhood asthma in a representative Italian area by analysing three years of anti-asthmatic prescriptions and hospitalizations of subjects with chronic or first time treatment, and to underline appropriateness of therapeutic choices. Methods The analysis involved prescriptions given to 6-17 year olds between 2003 and 2005 in Italy's Lombardy Region. The youths were classified as potential asthmatics, based on the different degree of drug utilization: occasional, low or high users, and grouped as 'new onset' or 'chronic' cases based on the duration of therapy dispensed. The analysis of prescriptions and hospitalization rate of these groups provided an estimate of the 2005 asthma prevalence and incidence and allowed an estimation of the level of appropriateness of treatments. Results During 2005, the estimated incidence of potential asthmatics was 0.8% and the estimated prevalence was 3.5%. When viewed retrospectively for two years, records showed that 47% of potential asthmatics received prescriptions also during 2004 and 30% also during 2003. During the three years considered, 7.5%, 2.8%, and 1.5% of high, low, and occasional users, respectively, were hospitalized for asthma. The most important inappropriateness found was the prescription of long acting beta adrenergics as first time treatment. Conclusions This study allowed a proxy of asthma incidence, prevalence, and severity. The analyses highlighted a low compliance with the guidelines, suggesting that educational interventions are needed to obtain a more rational management of childhood asthma, especially in subjects starting therapy.

Objectives To delineate the safety and tolerability profile of methylphenidate and atomoxetine in children and adolescents with attention deficit hyperactivity disorder (ADHD) monitored for more than 1 year. Design A cohort study analyzing data from the national ADHD register on patients from the Lombardy Region treated with MPH or atomoxetine. Participants A total of 229 children (median age 11 years, range 6–17), enrolled in 15 regional centers between June 2007 and May 2010. Results The prevalence rate of pharmacological treatment for ADHD was 0.23%, whereas the estimated ADHD prevalence in the population was 0.95%. In total, 73.8% of patients had been treated with atomoxetine (10–90 mg daily) or MPH (10–75 mg daily); 22% of patients also received an additional psychotropic drug. Of the treated children, 26.9% discontinued the drug prior to 1 year of treatment, mostly because of adverse effects (28.6%). No new or unexpected adverse events (rate 39.2%) were encountered. Decreased appetite, headache, and unstable mood were the leading events. The most severe events occurred in two boys: one experienced absence seizures for the first time with MPH, the other experienced hallucinations with atomoxetine. Therapy was discontinued in ten male patients (7.7%) because of adverse events. All patients with adverse effects recovered well. Conclusions A very low rate of ADHD prevalence was estimated in Italian children compared to that reported in other countries. Although the medications for ADHD are generally well tolerated, with only mild or minor adverse effects in most cases, their rational use can only be guaranteed by disseminating and monitoring evidence-based practices and by monitoring the safety and efficacy of treatments in both the short and long terms with appropriate tools and approaches.

Purpose To compare family paediatricians’ and general practitioners’ habits on drug prescribing to children. Methods Prescriptions reimbursed by the Health Service and dispensed by the retail pharmacies of 15 local health units in the Lombardy Region of Italy during 2005 were analysed. Only family paediatricians and general practitioners who were in charge of children aged 6–13 years were included. Results During 2005, 239,296 children (43.6% of the selected population) received at least one drug prescription. The prevalence was higher in children treated by general practitioners (44.2 versus 43.4%), in particular in children 13 years old, with a prevalence of 38.7 versus 31.8% in children cared for by general practitioners and family paediatricians respectively. The prevalence of the most prescribed therapeutic classes was similar in the two groups. Some differences were found concerning the antibiotic classes, with family paediatricians prescribing penicillins more frequently and general practioners prescribing macrolides and cephalosporins more frequently. A total of 542 drugs were prescribed, 78% of which were prescribed by both the family paediatricians and the general practitioners. In all, only four drugs were prescribed by 75% or more physicians. The chance of receiving a drug prescription, adjusted for age, gender and local health unit of residence, was slightly higher in children cared for by general practitioners (OR 1.16; 95%CI 1.14–1.17). Conclusions Few differences were found between the prescribing patterns of family paediatricians and those of general practitioners. Differences exist in particular for older children and for some drug classes.

Purpose To evaluate the quality of data reporting and statistical methods performed in drug utilization studies in the pediatric population. Methods Drug utilization studies evaluating all drug prescriptions to children and adolescents published between January 1994 and December 2011 were retrieved and analyzed. For each study, information on measures of exposure/consumption, the covariates considered, descriptive and inferential analyses, statistical tests, and methods of data reporting was extracted. An overall quality score was created for each study using a 12-item checklist that took into account the presence of outcome measures, covariates of measures, descriptive measures, statistical tests, and graphical representation. Results A total of 22 studies were reviewed and analyzed. Of these, 20 studies reported at least one descriptive measure. The mean was the most commonly used measure (18 studies), but only five of these also reported the standard deviation. Statistical analyses were performed in 12 studies, with the chi-square test being the most commonly performed test. Graphs were presented in 14 papers. Sixteen papers reported the number of drug prescriptions and/or packages, and ten reported the prevalence of the drug prescription. The mean quality score was 8 (median 9). Only seven of the 22 studies received a score of ≥10, while four studies received a score of <6. Conclusions Our findings document that only a few of the studies reviewed applied statistical methods and reported data in a satisfactory manner. We therefore conclude that the methodology of drug utilization studies needs to be improved.