OBJECTIVETo determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND METHODSA 24-week 2 3 2 factorial randomized controlled trial in adults with type 1 diabetes and IAH was conducted. All received comparable education, support, and congruent therapeutic targets aimed at rigorous avoidance of biochemical hypoglycemia without relaxing overall control. Primary end point was between-intervention difference in 24-week hypoglycemia awareness (Gold score). RESULTSA total of 96 participants (mean diabetes duration 29 years) were randomized. Overall, biochemical hypoglycemia (£3.0 mmol/L) decreased (53 6 63 to 24 6 56 min/24 h; P = 0.004 [t test]) without deterioration in HbA 1c . Hypoglycemia awareness improved (5.1 6 1.1 to 4.1 6 1.6; P = 0.0001 [t test]) with decreased SH (8.9 6 13.4 to 0.8 6 1.8 episodes/patient-year; P = 0.0001 [t test]). At 24 weeks, there was no significant difference in awareness comparing CSII with MDI (4.1 6 1.6 vs. 4.2 6 1.7; difference 0.1; 95% CI 20.6 to 0.8) and RT with SMBG (4.3 6 1.6 vs. 4.0 6 1.7; difference 20.3; 95% CI 21.0 to 0.4). Between-group analyses demonstrated comparable reductions in SH, fear of hypoglycemia, and insulin doses with equivalent HbA 1c . Treatment satisfaction was higher with CSII than MDI (32 6 3 vs. 29 6 6; P = 0.0003 [t test]), but comparable with SMBG and RT (30 6 5 vs. 30 6 5; P = 0.79 [t test]). CONCLUSIONSHypoglycemia awareness can be improved and recurrent SH prevented in longstanding type 1 diabetes without relaxing HbA 1c . Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII/RT, although satisfaction was higher with CSII.

ObjectivesTo assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities.MethodsAn unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×106, 3×106 or 10×106 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood.ResultsThere were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×106 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high.ConclusionIA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×106 tolDC but no systemic clinical or immunomodulatory effects were detectable.Trial registration numberNCT01352858.

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Background: Little research has directly evaluated the impact of increasing financial or material resources on health. One way of assessing this lies with assisting people to obtain full welfare benefit entitlements. In 2000-1, 2.3 million pensioners were living in poverty in the UK and estimates suggest that around one million do not claim the financial support to which they are entitled. The effectiveness of welfare rights advice services delivered via primary health care to promote health and reduce health inequalities is unknown.

This was the first placebo-controlled study in orthostatic training which has demonstrated that such a study is indeed feasible. An enhancement in overall autonomic tone is observed with HOT in tandem with a non-significant trend in symptom improvement. A larger, adequately powered, randomized controlled trial of tilt-training is now needed.