G. Romano

OBJECTIVE: Rituximab, an anti-CD20 monoclonal antibody, has been used in lupus nephritis and membranous idiopathic nephropathy and has proved effective in non-renal manifestations of type II mixed cryoglobulinaemia (MC) syndrome. We investigated the possible efficacy and safety of rituximab in the treatment of cryoglobulinaemic nephritis. METHODS: Five patients with active, biopsy-proven, glomerulonephritis in hepatitis C virus (HCV)-related type II MC syndrome were treated with four weekly infusions of rituximab (375 mg/m2) in monotherapy, without steroids whenever possible. Rituximab was the first-line therapy in three cases. RESULTS: A rapid and sustained renal response was observed in all patients, in one of them without retreatment up to the last follow-up (month 21+). Renal biopsy was repeated after 6 months in one patient and histopathological improvement was documented. Three patients relapsed, at months +5, +7 and +12 of follow-up, respectively. Two of them were then retreated with rituximab and again presented a rapid improvement in renal function. Maintenance therapy with rituximab was performed in two patients: nephritis remission was maintained in both. Fc-gamma receptor 3a (FcgammaRIIIa) genotype characterization was consistent with the clinical response observed. Rituximab also proved effective against other active MC manifestations, when present. No major side-effects occurred and steroids were not required in the follow-up. CONCLUSIONS: Rituximab may provide effective and safe therapy in type II MC-related glomerulonephritis, possibly as first-line therapy, avoiding steroids and hazardous immunosuppressive treatment.

We propose a wearable wireless sensing system for monitoring human motion disorders. The system is designed to be used at home or outdoor, as a mobile healthcare device assisting the person during the daily activity. It provides in real time an early detection of specific motion disorders at their outset, with excellent performance in terms of sensitivity and precision. The system is composed of inertial measurement units, a station for the real-time processing (smartphone/tablet/PC), dedicated algorithms and, eventually, a headphone for auditory feedback. An auditory feedback can warn the patient about particularly dangerous situations as the freezing of gait in the case of Parkinsonian patients, and timely provide rhythmic auditory stimulations to release the gait block. Two different hard and soft implementations of the system are discussed in this paper. The first has just one sensor in a headset. This solution features a fine detection of body motion and in particular of trunk oscillations, easy wearability, through auditory feedback. It is particularly compact and energy efficient, since no wired/wireless connection is required to give the audio-feedback (which reflects on the battery life). However, the headset suffers of the presence of a joint (the neck), which can hide important features of very disordered gaits, as in the case of the Parkinson's disease or other neurodegenerative diseases. The second implementation has two sensors on the shins. It allows fine detection of gait features, and guarantees the best performance presented in the literature to date in terms of sensitivity, specificity, precision, and accuracy in detection of the gait freezing. As a drawback, it requires an additional device in the ear for the audio-feedback, which implies higher power consumption respect to the headset device, for the wireless communication to the microphone. Different recognition algorithms were implemented in the same board, using fusion of raw signals from accelerometers and gyroscopes. The two solutions, their implementations, and experimental results will be discussed in detail, outlining strengths and deficiencies of the twos.

Abstract Restless legs syndrome (RLS) is a possible consequence of end‐stage renal disease. However, conclusive data on the association between RLS and chronic renal failure (CRF) in nondialyzed patients are still lacking. The aims of this study were: (1) to look for an association between RLS and CRF in nondialyzed patients; (2) to analyze the characteristics of RLS and its consequences on nocturnal rest in nondialyzed patients with CRF; (3) to identify possible predictors of RLS occurrence in nondialyzed patients with CRF. We recruited 138 nondialyzed patients with CRF (mean age: 69.8 ± 11.7 years; male: 61.6%) and 151 controls (mean age: 60.2 ± 18.6 years; male: 42.4%). An expert in sleep medicine investigated the presence of RLS by means of a face‐to‐face interview. Fifteen nondialyzed CRF patients and five controls were diagnosed as RLS affected. A multivariate analysis confirmed that RLS was independently associated with CRF in nondialyzed patients ( P = 0.004). CRF patients RLS + were more commonly women and showed the presence of an iron deficiency compared with the RLS − ones. Independent predictors of RLS in nondialyzed CRF patients were: female sex (OR: 10.7, 95% CI: 2.2–31.3; P = 0.004) and percentage of transferrin saturation (OR: 0.6, 95% CI: 0.4–0.9; P = 0.04). This is the first case‐control study able to recognize an association between RLS and CRF in patients not yet on dialysis. Nephrologists should investigate and treat RLS in their nondialyzed patients with CRF. In particular, physicians should carefully investigate women and patients with iron deficiency in the presence of RLS symptoms. © 2010 Movement Disorder Society

Introduction: Orphan diseases are low-prevalence conditions with chronically debilitating or life-threatening consequences. Their treatments are generally called orphan drugs (OD). Health–technology assessment processes have traditionally considered cost-effectiveness analysis (CEA), when making reimbursement and pricing decisions for health-care plans. Valuing OD with standard CEA raises important issues due to uncertain evidence, inability to meet cost-effectiveness thresholds for reimbursement and high budget impact, among others. Multi-criteria decision analysis (MCDA) allows to overcome these issues and improve the technical and ethical quality of decisions regarding prioritization, coverage, and reimbursement of OD.Areas covered: A scoping review was conducted in order to characterize MCDA frameworks for assessing OD and implementation experiences. We reviewed electronic databases (Medline, Embase, Cochrane Library, EBSCO, CINAHL, EconLit, Web of Science, LILACS, Google Scholar) key journals (Orphanet Journal of Rare Diseases and Value in Health) and organization repositories.Expert opinion: The theoretical framework for MCDA considers areas related to characteristics of orphan diseases and their technologies’ clinical and economic impact. Participation processes are critical in incorporating societal values in weighting different dimensions and constructing decision rules. Local implementation pilots considering different stakeholders are necessary in order to pinpoint specific barriers and opportunities.

Romano G, Simonella R, Falleti E, Bortolotti N, Deiuri E, Antonutto G, De Vita S, Ferraccioli GF, Montanaro D. Physical training effects in renal transplant recipients. Clin Transplant 2010: 24: 510–514. © 2009 John Wiley & Sons A/S. Abstract: Introduction: Several studies demonstrated the benefits of rehabilitation in uraemic patients. This study evaluates physical and psychosocial effects of exercise on renal transplant recipients (RTRs). Patients and methods: Eight RTRs were evaluated before and after an exercise training consisting of thirty 40‐minute sessions, three times a week, performed with the interval training technique. Results: Hospital Anxiety and Depression Scale (HADS) significantly decreased (p < 0.04 and <0.008, respectively). Quality of life mean scores (SF‐36 test) significantly increased (p < 0.000). No differences were recorded for muscle and fat mass, maximal explosive power of the lower limbs, alkaline and acid phosphatase, parathormone (PTH), myoglobin, lipoprotein‐A, glomerular filtration rate (GFR), at rest heart rate, and cardiac troponin. IL‐6 decreased from 2.8 ± 0.6 to 1.7 ± 0.5 pg/mL (p < 0.01). Resting MAP fell from 112 ± 4 to 99 ± 3 mmHg (p < 0.02). The metabolic threshold rose from 33 ± 4 to 43 ± 5% (p < 0.033). The blood lactate level at peak exercise increased from 5.2 ± 0.9 to 6.2 ± 0.7 mmol/L (p < 0.012). The maximum oxygen uptake increased from 1200 ± 210 to 1359 ± 202 mL/min (p < 0.05), iso‐load oxygen uptake decreased from 1110 ± 190 to 1007 ± 187 mL/min (p < 0.034). The maximum working capacity increased from 90 ± 14 to 115 ± 15 watts (p < 0.000). Conclusion: This study suggests that an appropriate dose of physical training is a useful, safe and non‐pharmacologic contribution to RTR treatment.