A multi‐centre randomized trial of two different doses of nicotinamide in patients with recent‐onset Type 1 diabetes (the IMDIAB VI)

Background

Intensive insulin therapy is the gold standard by which Type 1 diabetes is treated. In addition to this therapy, administration of nicotinamide (NA) can be beneficial. This concept is reinforced by the results of a recent meta‐analysis of the use of NA in patients with recent‐onset Type 1 diabetes.

Methods

In this study we compared two different doses of NA in 74 patients with duration of Type 1 diabetes <4 weeks (mean age 13 years). Patients were randomly allocated in blind to two treatment groups: 38 patients received a dose of 25 mg/kg (b.w.) of NA and 36 patients received a dose of 50 mg/kg (b.w.) of NA. Intensive insulin therapy was carried out in order to optimize metabolic control as soon as possible after diagnosis and to maintain blood glucose level as near to normal as possible. Response to therapy was monitored throughout the study by investigating the occurrence of clinical (complete) remission defined, according to the recommendations of the International Diabetes Immunotherapy Group, as restoration of normal fasting and post‐prandial blood glucose without any insulin administration for more than 2 weeks. Moreover, the integrated measures of metabolic control (C‐peptide, HbA_1c and insulin dose) were analysed at 3‐ month intervals up to 1 year after diagnosis.

Results

There were no significant differences in the integrated measures of metabolic control between the two NA treated groups either at onset of the disease or at each 3‐month interval up to 1 year after diagnosis, although there was a tendency toward higher insulin dosages in the 50 mg NA group. No significant differences were observed in the rate of clinical remission between the two groups.

Conclusion

We conclude that patients with recent‐onset Type 1 diabetes treated with two different doses of NA, in addition to intensive insulin therapy, show similar residual beta‐cell function 1 year later. Since both doses of NA are likely to be effective in reducing beta‐cell dysfunction, the smaller dose of 25 mg/kg NA would be sufficient as a higher dose may induce insulin resistance. Copyright © 1999 John Wiley & Sons, Ltd.

     

Acute lymphoblastic leukaemia occurring as second malignancy: report of the GIMEMA Archive of Adult Acute Leukaemia

Between July 1992 and June 1996, 901 new cases of adult acute lymphoblastic leukaemia were recorded in the GIMEMA Archive of Adult Acute Leukaemia; 21 of them (2.3%) had a previous primary malignancy (PM). We found that secondary acute lymphoblastic leukaemia cases (sALL) presented with older age, a high incidence of pre-pre-B immunophenotype and a significantly higher prevalence of cancer among relatives compared to de novo ALL. The leukaemogenic activity of the cytotoxic drugs employed for the treatment of PM may have played a potential role in only a proportion of patients, opening the possibility that some sALL patients may have developed two or more malignancies due to individual predisposing factors.     

Adult-Onset Type 1 Diabetes: Current Understanding and Challenges

Recent epidemiological data have shown that more than half of all new cases of type 1 diabetes occur in adults. Key genetic, immune, and metabolic differences exist between adult- and childhood-onset type 1 diabetes, many of which are not well understood. A substantial risk of misclassification of diabetes type can result. Notably, some adults with type 1 diabetes may not require insulin at diagnosis, their clinical disease can masquerade as type 2 diabetes, and the consequent misclassification may result in inappropriate treatment. In response to this important issue, JDRF convened a workshop of international experts in November 2019. Here, we summarize the current understanding and unanswered questions in the field based on those discussions, highlighting epidemiology and immunogenetic and metabolic characteristics of adult-onset type 1 diabetes as well as disease-associated comorbidities and psychosocial challenges. In adult-onset, as compared with childhood-onset, type 1 diabetes, HLA-associated risk is lower, with more protective genotypes and lower genetic risk scores; multiple diabetes-associated autoantibodies are decreased, though GADA remains dominant. Before diagnosis, those with autoantibodies progress more slowly, and at diagnosis, serum C-peptide is higher in adults than children, with ketoacidosis being less frequent. Tools to distinguish types of diabetes are discussed, including body phenotype, clinical course, family history, autoantibodies, comorbidities, and C-peptide. By providing this perspective, we aim to improve the management of adults presenting with type 1 diabetes.     

EFFECTIVENESS OF ROBOTIC BALANCE TRAINING ON POSTURAL INSTABILITY IN PATIENTS WITH MILD PARKINSON’S DISEASE: A PILOT,SINGLE-BLIND,RANDOMIZED CONTROLLED TRIAL

ObjectiveTo examine whether tailored robotic platform training could improve postural stability compared with conventional balance treatment in patients with mild Parkinson’s disease.DesignRandomized single-blind pilot study.SubjectsTwenty-two patients with mild Parkinson’s disease (Hoehn & Yahr scale; H&Y 1–2).MethodsPatients were randomly assigned to an experimental group for robotic balance training and to a control group for conventional balance training. Each patient received 20 treatments (45 min/session, 5 times/week). Blinded evaluations were conducted before and after the treatment and 1 month post-treatment. Primary outcome measures were Mini BESTest, and Berg Balance Scale; secondary outcome measures were 10-Meter Walk Test, Five Times Sit to Stand Test, and Parkinson’s Disease Questionnaire 39.ResultsPrimary outcome measures in patients in both the experimental and control groups improved significantly after the balance treatment. Similar results were found for all the secondary outcome measures. The experimental group performed significantly better than the control group at both post-intervention and follow-up evaluation in the primary outcomes (p < 0.05). No significant differences between groups were found in secondary outcomes.ConclusionRobot-assisted balance training may be a promising tool to improve postural stability in patients with mild Parkinson’s disease.LAY ABSTRACTMore than 10 million people worldwide are living with Parkinson’s disease. Parkinson’s disease is a slowly progressive neurodegenerative disorder that leads to balance problems. Balance is a major concern in patients with Parkinson’s disease, and shows poor response to pharmacological treatment. It is known that exercise and physiotherapy can help. The best approach is to start exercising at the early stages of the disease with personalized rehabilitation treatment. This study explored the effectiveness of a new robotic platform treatment on balance compared with the conventional approach. Both trainings were found to improve balance, walking and quality of life. However, robotic balance training could have a major impact. The robotic device enables the training to be intense, fun, task-oriented, challenging and personalized, enhancing motor learning and neuroplasticity. This advance in rehabilitation technology could help to meet the challenges presented by Parkinson’s disease.Key words: robotic-assisted balance training, postural instability, neurorehabilitation, Parkinson’s disease

Postural instability (PI), or impaired balance, is one of the cardinal motor symptoms that characterizes Parkinson’s disease (PD). It is the inability to maintain equilibrium under both static and dynamic conditions, affecting balance control mainly in 4 domains: (i) balance during quiet stance, (ii) reactive postural adjustments to external perturbations, (iii) anticipatory postural adjustments, and (iv) dynamic balance (1).PI is prominent in the advanced stage of PD, as reflected by the Hoehn & Yahr scale, where this problem appeared clinically only in the third stage. Nevertheless, PI is also present in the early stages of PD, before any clinically visible balance disturbance has appeared (2).Early identification of instability and effective timely intervention is mandatory to limit the increasing burden of PI in the lives of patients with PD. In fact, PI leads to loss of mobility, falls, disability, and reduced quality of life (QoL). Among these, falls have a major economic burden, considerable morbidity, and high psychological impact. Limited responsiveness to dopaminergic therapy and deep brain stimulation implicates the need for alternative strategies to address balance disorder and prevent falls (3, 4). It is clear that exercise and physiotherapy play a beneficial role (5) and different studies have identified the beneficial effect on balance of a series of non-pharmacological approaches, such us treadmill training (6), robot-assisted gait training (7), tai chi (8), virtual reality (9), and movement strategy training (10). However, which rehabilitation strategies are useful in practice in reducing balance problems and falls is a matter of debate. Patients with PD may benefit from a personalized exercise programme and a multidisciplinary approach (11) designed to help avoid falls and maintain mobility.Recent technological advances in delivery of therapy (e.g. virtual reality and other gamification elements) have led to increasing interest in the field of neurorehabilitation in PD (12). A robotic device, hunova® (Movendo Technology, Genoa, Italy), has been developed recently to apply sensorimotor rehabilitation of the lower limbs and trunk in static and dynamic conditions. This robotic platform was introduced for post-stroke functional re-education, treatment of degenerative diseases of the central nervous system and lesions of the peripheral nervous system.The robotic program enables personalized treatment with a challenging progression from simple to difficult tasks, attentional strategies, augmented visual and audio feedbacks, in a stimulating environment. Therefore, this study hypothesized that the robotic platform training (experimental robotic training group) would be more effective in improving postural control and in decreasing falls risk than conventional training (conventional training group).To our knowledge, there are no published studies exploring the effects of this new technology in patients with PD. Therefore, the aim of this pilot study was to investigate the efficacy and feasibility of a 4-week hunova®-assisted training programme in patients with mild PD on postural control. The primary aim was to evaluate whether the robotic balance training is effective in improving postural stability. The secondary aim was to assess whether robotic balance training can also have a positive impact on risk of falls, walking ability, and QoL.     

Impact of environmental factors and physical activity on disability and quality of life in CIDP

Journal of Neurology - A few observational studies and randomized trials suggest that exercise and rehabilitation may improve activity limitation and quality of life (QoL) in patients with chronic...