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Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) requiring urgent treatment. Standardization of its diagnosis and optimal management is challenging. This study aimed to evaluate the role of centralized, rapid testing of ADAMTS13 in patients experiencing acute TMAs requiring plasma-exchange (PEX) and to estimate the incidence of TTP in a large Italian Region. We perfomed a cohort study in the frame of the project \"Set-up of a Lombardy network for the study and treatment of patients undergoing apheresis\", including 11 transfusion centers in the Region. Consecutive patients referred from 2014 to 2016 with acute TMAs requiring PEX were enrolled. Centralized ADAMTS13 activity testing was performed at the Milan Hemophilia and Thrombosis Center within 24 h. Forty-three TMA patients (44 events) were enrolled, of whom 35 (81%) had severe ADAMTS13 deficiency. Patients with severe ADAMTS13 deficiency were younger, mainly women, with a higher prevalence of autoimmune disorders and a lower prevalence of cancer. Clinical and laboratory characteristics of patients with and without severe ADAMTS13 deficiency largely overlapped, with a lower platelet count being the only baseline marker that significantly differed between the two patient groups (ADAMTS13 activity < 10% vs [greater than or equai to] 10%: median difference of -27 x 10.sup.9/l, 95% CI - 37 to - 3). PEX treatment was initiated in all patients, but soon discontinued in cases without severe ADAMTS13 deficiency. In this group, the mortality rate was higher and no episode exacerbations or relapses within 6 months occured. The estimated average annual incidence of acute acquired TTP events was 1.17 [0.78-1.55] per million people. Severe ADAMTS13 deficiency distinguished two groups of patients with largely overlapping clinical features but different treatment and disease course. This study provides a feasible model implemented in a large Italian region for the practical clinical approach to TMAs and underlines the importance of urgent ADAMTS13 activity testing for an accurate differential diagnosis and therapeutic approach.

Objective The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer’s biomarkers in a large sample of patients with mild cognitive impairment (MCI). Methods We measured Aβ42, t -tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose–positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO). Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were performed to assess and compar the biomarker prognostic performances in EO and LO groups. Linear Model was adopted for estimating the time-to-progression in relation with earlier/later onset MCI groups and biomarkers. Results In earlier onset patients, all the assessed biomarkers were able to predict cognitive decline ( p  < 0.05), with FDG-PET showing the best performance. In later onset patients, all biomarkers but t -tau predicted cognitive decline ( p  < 0.05). Moreover, FDG-PET alone in earlier onset patients showed a higher prognostic value than the one resulting from the combination of all the biomarkers in later onset patients (earlier onset AUC 0.935 vs later onset AUC 0.753, p  < 0.001). Finally, FDG-PET showed a different prognostic value between earlier and later onset patients ( p  = 0.040) in time-to-progression allowing an estimate of the time free from disease. Discussion FDG-PET may represent the most universal tool for the establishment of a prognosis in MCI patients and may be used for obtaining an onset-related estimate of the time free from disease.

Purpose To compare the efficacy, safety, Patient Global Impression of Improvement (PGI-I), and complications rates after 180-W GreenLight laser (180-W GL laser) standard and anatomical photoselective vaporization (sPVP and aPVP). Methods Within a multi-institutional database, we identified patients who underwent sPVP or aPVP to relief BPH symptoms. IPSS, Q max , and prostate-specific antigen (PSA) were measured at baseline and during the follow-up. PGI-I score as well as early and late complications were recorded at follow-up visits. Log-binomial and multivariable proportional odds regression models were fitted to estimate the effect of aPVP vs. sPVP on PGI-I as well as on early and late complication rates, before and after adjustment for propensity score. Results 813 patients were included. Of those, the 50.4% underwent aPVP. Patients who underwent aPVP had larger prostate (64 vs. 55 mL, p  < 0.001) and higher baseline PSA levels (3.1 vs. 2.5 ng/mL, p  < 0.001). PGI-I score was signaled as very improved, improved, slightly improved, unchanged, or worsened in 55.5, 32.8, 8.3, 2.3, and 1.2% of the cases, respectively, with no differences according the technique used ( p  = 0.420). Acute urinary retention occurred in 9.2 vs. 8.9% of patients after aPVP vs. sPVP ( p  = 0.872). All models failed to find differences in: patients’ satisfaction (OR 1.19, p  = 0.256), early complications (RR 0.93, p  = 0.387), early urge/incontinence symptoms (RR 0.97, p  = 0.814), and late complications rates (RR 0.70, p  = 0.053), after aPVP vs. sPVP. Conclusion Our results showed similar functional results and complication rates after aPVP and sPVP. However, aPVP was used in larger prostates. Both techniques guarantee high patient’s satisfaction.

More than half a century after their discovery, benzodiazepines (BDZs) still represent one of the largest and most widely prescribed groups of psychotropic compounds, not only in clinical psychiatry but also in the entire medical field. Over the last two decades, however, there has been an increased focus on the development of antidepressants and antipsychotics on the part of the pharmaceutical industry, clinicians, and researchers, with a reduced interest in BDZs, in spite of their widespread clinical use. As a consequence, many psychiatric residents, medical students, nurses, and other mental health professionals might receive poor academic teaching and training regarding these agents, and have the false impression that BDZs represent an outdated chapter in clinical psychopharmacology. However, recent advances in the field, including findings concerning epidemiology, addiction risk, and drug interactions, as well as the introduction of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition with related diagnostic changes, strongly encourage an updated appraisal of the use of BDZs in clinical practice. During a recent thematic event convened with the aim of approaching this topic in a critical manner, a group of young Italian psychiatrists attempted to highlight possible flaws in current teaching pathways, identify the main clinical pros and cons regarding current use of BDZs in clinical practice, and provide an updated overview of their use across specific clinical areas and patient populations. The main results are presented and discussed in this review.

Preliminary evidence suggests that palliative care may be useful for people with severe multiple sclerosis (MS). The aim of this study is to determine the effectiveness of a home-based palliative approach (HPA) for people with severe MS and their carers. This is a single-blind randomized controlled trial with a nested qualitative study. Seventy-five severe MS-carer dyads are being randomized (at three centers, one in each area of Italy) to HPA or usual care (UC) in a 2:1 ratio. Each center has a specially trained team consisting of four professionals (physician, nurse, psychologist, social worker). The team makes a comprehensive assessment of the needs of the dyads. HPA content is then agreed on, discussed with the patient's caring physician, and delivered over six months. The intervention is not intended to replace existing services. At later visits, the team checks the HPA delivery and reviews/modifies it as necessary. HPA and UC dyads are assessed at home by a blind examiner at baseline, and three and six months later; they also receive monthly telephone interviews. Dyads assigned to UC receive the examiner's visits and telephone interviews, but not the team visits. Primary outcome measures are changes in symptoms (Palliative care Outcome Scale-Symptoms-MS, POS-S-MS), and quality of life (the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), not assessed in patients with severe cognitive compromise) at three and six months. Other outcomes are changes in patient functional status and mood; changes in carer quality of life, mood and caregiving burden; costs; incorporation with standard care; unplanned hospital admissions; referrals to hospice; and deaths. The experience of participants will be evaluated qualitatively by individual semi-structured interviews (HPA patients and carers) and focus group meetings (HPA patients' caring physicians). The results of our study will show whether the HPA is feasible and beneficial to people with severe MS and their carers living in the three Italian geographic areas. The nested qualitative study will add to the understanding of the strengths and limitations of the intervention. The trial was registered with Current Controlled Trials (identifier: ISRCTN73082124) on 19 June 2014.

In normal awake infants, fidgety movements are seen from the age of 6 weeks to 20 weeks. The aim of the study was to test the predictive value of absent or abnormal spontaneous movements in young infants for the later development of neurological deficits. In a collaborative study involving five hospitals we collected data on the normal and abnormal quality of fidgety movements of 130 infants and compared it with assessments of neurological development done longitudinally until the age of 2 years. On the basis of ultrasound scans infants were classified as at low-risk or at high-risk of neurological deficits. Infants were videoed for 1 h every week from birth to discharge and then for 15 min every 3 to 4 weeks; quality of general movements was assessed. Repeated neurological assessments were also done until 24 months of corrected age. 67 (96%) of 70 infants with normal fidgety movements had a normal neurological outcome. Abnormal quality or total absence of fidgety movements was followed by neurological abnormalities in 57 (95%) of the 60 infants (49 had cerebral palsy and eight had developmental retardation or minor neurological signs). Specificity and sensitivity of fidgety movement assessment were higher (96% and 95%, respectively) than of ultrasound imaging of the infants' brain (83% and 80%, respectively). Our technique of assessing spontaneous motor activity can identify and distinguish between those infants who require early intervention for neurological abnormalities and those who do not. Our technique is simple, non-intrusive, reliable, quick, and can be done on very young infants.

Hen egg white avidin is increasingly used in the clinic as part of multifactor treatments such as pretargeted radionuclide therapy of cancer or as an antidote of biotinylated drugs. Taking into account that naturally occurring human antiavidin antibodies (HAVA) are common in humans, the present work investigates avidin immunogenicity as part of risk/benefit evaluations. Sera from 139 oncology patients naive to avidin were confirmed to exhibit HAVA with lognormally distributed titers. HAVA were boosted after avidin treatment, with no correlation with the avidin dose or with the basal titer. No antibody-related clinical symptoms were observed in 21 HAVA-positive patients treated with avidin. In mouse models, high mouse antiavidin antibody titers, induced to simulate the worst human condition, neither reduced the biotin uptake of intratissue-injected avidin nor affected the capacity of intravenously injected avidin to clear a biotinylated drug from circulation. In both models the avidin treatment was well tolerated. Results indicate that avidin immunogenicity does not affect its safety and efficacy, thus encouraging its further use in clinical applications.

Purpose To assess whether glycoprotein IIb/IIIa inhibition using tirofiban in low risk patients undergoing percutaneous coronary intervention (PCI) may reduce the risk of periprocedural myocardial infarction compared to standard care in poor responders to aspirin and/or clopidogrel. Methods We will enroll patients at ten European sites or more to participate in the Tailoring Treatment with Tirofiban in patients showing Resistance to aspirin and/or Resistance to clopidogrel (3T/2R) study with a pre-specified sample size of 240 patients out of 1,100 or more who will undergo screening. The primary outcome measure is troponin I or T elevation ratio at least three times the upper limit of normal within 48 h after completion of the PCI. Conclusion The results of 3T/2R study will evaluate whether tailored intensification of anti-platelet treatment based on poor individual response to oral anti-platelet agents may modulate the risk of periprocedural myocardial infarction during PCI. Our findings attempt at unraveling a new era of individualized anti-platelet treatment through the use of point-of-care assessment.

Primary bare metal stenting and abciximab infusion are currently considered the best available reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus eluting stents (SES), compared to bare metal stent (BMS), greatly reduce the incidence of binary restenosis and target vessel revascularisation (TVR), but their use on a routine basis results in a significant increase in medical costs. With current European list prices, the use of tirofiban instead of abciximab would save enough money to absorb the difference between SES and BMS. To assess whether in patients with STEMI the combination of SES with high dose bolus (HDB) tirofiban results in a similar incidence of major cardiovascular events (MACE) but in a lower binary restenosis rate after six months compared to BMS and abciximab. 160 patients are required to satisfy the primary composite end-point, including MACE and binary restenosis. The study is ongoing: the current paper focuses on the methodology and demography of the first 100 patients so far enrolled. Patients randomised to HDB tirofiban (n = 50, mean age: 62 +/- 12, 40 males) and abciximab (n = 50, mean age: 63 +/- 12, 38 males) do not differ for medical history, presentation profile, medications at discharge, angiographic profile and creatine-kinase MB-fraction at peak. The results of the trial will be available by the end of 2004: they will be crucial for the cardiologists to know whether the gold standard for AMI treatment should be reconsidered after the introduction of SES into the clinical practice.