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Background The impact of educational strategies in the management of adverse treatment effects and drug interactions in adult patients with epilepsy with comorbidities remains undetermined. Objective The EDU-COM study is a randomised, pragmatic trial investigating the effect of a patient-tailored educational plan in patients with epilepsy with comorbidity. Methods 174 adult patients with epilepsy with chronic comorbidities, multiple-drug therapy and reporting at least one adverse treatment effect and/or drug interaction at study entry were randomly assigned to the educational plan or usual care. The primary endpoint was the number of patients becoming free from adverse treatment events and/or drug interactions after a 6-month follow-up. The number of adverse treatment events and drug interactions, health-related quality of life (HRQOL) summary score changes and the monetary costs of medical contacts and drugs were assessed as secondary outcomes. Results The primary endpoint was met by 44.0% of patients receiving the educational plan versus 28.9% of those on usual care (p=0.0399). The control group reported a significantly higher risk not to meet successfully the primary endpoint at the end of the study: OR (95% CI) of 2.29 (1.03 to 5.09). A separate analysis on drug adverse effects and drug interactions showed that the latter were more sensitive to the effect of educational treatment. Quality of life and costs were not significantly different in the two groups. Conclusions A patient-tailored educational strategy is effective in reducing drug-related problems (particularly drug interactions) in epilepsy patients with chronic comorbidities, without adding significant monetary costs. Registered at ClinicalTrials.gov, identifier NCT01804322, (http://www.clinicaltrials.gov).

Background Statins, due to their well-established pleiotropic effects, have noteworthy benefits in stroke prevention. Despite this, a significant proportion of high-risk patients still do not receive the recommended therapeutic regimens, and many others discontinue treatment after being started on them. The causes of non-adherence to current guidelines are multifactorial, and depend on both physicians and patients. The aim of this study is to identify the factors influencing statin prescription at Stroke Unit (SU) discharge. Methods This study included 12,750 patients enrolled on the web-based Lombardia Stroke Registry (LRS) from July 2009 to April 2012 and discharged alive, with a diagnosis of ischemic stroke or transient ischemic attack (TIA) and without contra-indication to statin therapy. By logistic regression analysis and classification trees, we evaluated the impact of demographic data, risk factors, tPA treatment, in-hospital procedures and complications on statin prescription rate at discharge. Results We observed a slight increase in statins prescription during the study period (from 39.1 to 43.9%). Lower age, lower stroke severity and prestroke disability, the presence of atherothrombotic/lacunar risk factors, a diagnosis of non-cardioembolic stroke, tPA treatment, the absence of in-hospital complications, with the sole exception of hypertensive fits and hyperglycemia, were the patient-related predictors of adherence to guidelines by physicians. Overall, dyslipidemia appears as the leading factor, while TOAST classification does not reach statistical significance. Conclusions In our region, Lombardia, adherence to guidelines in statin prescription at Stroke Unit discharge is very different from international goals. The presence of dyslipidemia remains the main factor influencing statin prescription, while the presence of well-defined atherosclerotic etiopathogenesis of stroke does not enhance statin prescription. Some uncertainties about the risk/benefit of statin therapy in stroke etiology subtypes (cardioembolism, other or undetermined causes) may partially justify the underuse of statin in ischemic stroke. The differences that exist between current international guidelines may prevent a more widespread use of statin and should be clarified in a consensus.

Activity of azadirachtin on phytoparasitic nematodes has been documented for some decades, but the relationship between its nematicidal efficacy and crop cycle length has not yet been clarified. This study aimed to assess the efficacy of an azadirachtin-based nematicide, for controlling the infestation of the root-knot nematode Meloidogyne incognita, on the short- and long-cycle crops, lettuce and tomato, respectively. Experiments on lettuce and tomato were carried out in a greenhouse infested by M. incognita, including non-treated soil, or treated with the nematicide fluopyram, as controls. In the experiment on the short-cycle lettuce crop, the azadirachtin product effectively suppressed M. incognita infestation and increased crop yield, without significant differences from fluopyram. In the tomato crop, both azadirachtin and fluopyram were not able to control nematode infestation, but resulted in significantly higher yields. Data from this study indicated that azadirachtin can be a valid alternative to fluopyram and other nematicides, for root-knot nematode control in short-cycle crops. Integration of azadirachtin with a synthetic nematicide or nematode-suppressive agronomical techniques, should be more suitable to long-cycle crops.

ObjectivesTo describe the long-term prognosis of epilepsy and prognostic patterns in a large cohort of newly diagnosed patients and identify prognostic factors.MethodsStudy participants were 13 Italian epilepsy centres with accessible records dating back to 2005 or earlier, complete data on seizure outcome and treatments, precise epilepsy diagnosis, and follow-up of at least 10 years. Records were examined by trained neurology residents for demographics, seizure characteristics, neurological signs, psychiatric comorbidity, first electroencephalogram (EEG) and MRI/CT, epilepsy type and aetiology, antiepileptic drugs (AEDs), and 1-year, 2-year, 5-year and 10-year seizure remissions. Five predefined prognostic patterns were identified: early remission, late remission, relapsing-remitting course, worsening course and no remission. Prognostic factors were assessed using multinomial logistic regression models.Results1006 children and adults were followed for 17 892 person-years (median 16 years; range 10–57). During follow-up, 923 patients (91.7%) experienced 1-year remission. 2-year, 5-year and 10-year remissions were present in 89.5%, 77.1% and 44.4% of cases. 5-year remission was associated with one to two seizures at diagnosis, generalised epilepsy, no psychiatric comorbidity, and treatment with one or two AEDs during follow-up. 10-year remission was associated with one or two AEDs. The most common prognostic pattern was relapsing-remitting (52.2%), followed by early remission (24.5%). 8.3% of cases experienced no remission. Predictors of a relapsing-remitting course were <6 seizures at diagnosis, (presumed) genetic aetiology and no psychiatric comorbidity.ConclusionsFew seizures at diagnosis, generalised epilepsy and no psychiatric comorbidity predict early or late seizure freedom in epilepsy. Achieving remission at any time after the diagnosis does not exclude further relapses.

Purpose The presence of a bulky tumour at staging on CT is an independent prognostic factor in malignant lymphomas. However, its prognostic value is limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on 18 F-FDG PET/CT could give a better evaluation of the total tumour burden and may help patient stratification. Different methods of TMTV measurement established in phantoms simulating lymphoma tumours were investigated and validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. Methods Data were processed by two nuclear medicine physicians in Reggio Emilia and Créteil. Nineteen phantoms filled with 18 F-saline were scanned; these comprised spherical or irregular volumes from 0.5 to 650 cm 3 with tumour-to-background ratios from 1.65 to 40. Volumes were measured with different SUVmax thresholds. In patients, TMTV was measured on PET at staging by two methods: volumes of individual lesions were measured using a fixed 41 % SUVmax threshold (TMTV 41 ) and a variable visually adjusted SUVmax threshold (TMTV var ). Results In phantoms, the 41 % threshold gave the best concordance between measured and actual volumes. Interobserver agreement was almost perfect. In patients, the agreement between the reviewers for TMTV 41 measurement was substantial ( ρ c  = 0.986, CI 0.97 – 0.99) and the difference between the means was not significant (212 ± 218 cm 3 for Créteil vs. 206 ± 219 cm 3 for Reggio Emilia, P  = 0.65). By contrast the agreement was poor for TMTV var . There was a significant direct correlation between TMTV 41 and normalized LDH ( r  = 0.652, CI 0.42 – 0.8, P <0.001). Higher disease stages and bulky tumour were associated with higher TMTV 41 , but high TMTV 41 could be found in patients with stage 1/2 or nonbulky tumour. Conclusion Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation. It should be evaluated in prospective studies.

Miltefosine (MIL)–allopurinol combination therapy administered at standard dosage is effective to treat canine leishmaniosis, nevertheless for some dogs the digestive tolerance of MIL is not acceptable. This study evaluates an alternative therapeutic protocol by using a modified dosage of MIL to increase its effectiveness and improve the digestive tolerance. Thirty-four Leishmania infantum owned naturally infected dogs were included and monitored for 180 days. The dogs were allocated in two randomized groups: Group X−18 dogs treated with MIL registered dose of 2 mg/kg, oral administration, once daily, for 28 days; Group Y−16 dogs treated with 1.2 mg/kg for 5 days followed by 2.5 mg/kg for 25 days. Both groups were also treated with allopurinol. Digestive tolerance was monitored by adverse events observation. Treatments effectiveness was evaluated by monitoring the reduction of clinical score, the improvement of clinicopathological abnormalities, the reduction of parasitological load by PCR and the number of relapses. 16.6% dogs of group X and 12.5% dogs of group Y showed treatment associated adverse events. The reduction of clinical score was 61.7% for group X and 71.6% for group Y. All dogs showed an improvement of laboratory parameters after treatment. Quantitative PCR showed better results in group Y compared to group X; relapses were only registered in four dogs of group X. The modified protocol demonstrates a better trend of results in term of tolerance, clinical effectiveness, parasitological load reduction and relapses control, suggesting it could be considered for new large-scale studies.

Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of heart failure. Cytoprotective gene therapy with vascular endothelial growth factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs. The aim of this work was to test the tolerability and feasibility of intracoronary administration, under fluoroscopic guidance, of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessments at 7- and 30-days post-procedure showed stable conditions compared to the pre-procedure phase. The results of this work indicate that intracoronary VEGF-B167 gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this therapy on disease progression.

Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of heart failure. Cytoprotective gene therapy with vascular endothelial growth factor-B (VEGF-B ) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs. The aim of this work was to test the tolerability and feasibility of intracoronary administration, under fluoroscopic guidance, of VEGF-B carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessments at 7- and 30-days post-procedure showed stable conditions compared to the pre-procedure phase. The results of this work indicate that intracoronary VEGF-B gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this therapy on disease progression.