The Effectiveness of Pharmacological and Non-Pharmacological Interventions for Improving Glycaemic Control in Adults with Severe Mental Illness: A Systematic Review and Meta-Analysis

People with severe mental illness (SMI) have reduced life expectancy compared with the general population, which can be explained partly by their increased risk of diabetes. We conducted a meta-analysis to determine the clinical effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in people with SMI (PROSPERO registration: CRD42015015558). A systematic literature search was performed on 30/10/2015 to identify randomised controlled trials (RCTs) in adults with SMI, with or without a diagnosis of diabetes that measured fasting blood glucose or glycated haemoglobin (HbA1c). Screening and data extraction were carried out independently by two reviewers. We used random effects meta-analysis to estimate effectiveness, and subgroup analysis and univariate meta-regression to explore heterogeneity. The Cochrane Collaboration’s tool was used to assess risk of bias. We found 54 eligible RCTs in 4,392 adults (40 pharmacological, 13 behavioural, one mixed intervention). Data for meta-analysis were available from 48 RCTs (n = 4052). Both pharmacological (mean difference (MD), -0.11mmol/L; 95% confidence interval (CI), [-0.19, -0.02], p = 0.02, n = 2536) and behavioural interventions (MD, -0.28mmol//L; 95% CI, [-0.43, -0.12], p<0.001, n = 956) were effective in lowering fasting glucose, but not HbA1c (pharmacological MD, -0.03%; 95% CI, [-0.12, 0.06], p = 0.52, n = 1515; behavioural MD, 0.18%; 95% CI, [-0.07, 0.42], p = 0.16, n = 140) compared with usual care or placebo. In subgroup analysis of pharmacological interventions, metformin and antipsychotic switching strategies improved HbA1c. Behavioural interventions of longer duration and those including repeated physical activity had greater effects on fasting glucose than those without these characteristics. Baseline levels of fasting glucose explained some of the heterogeneity in behavioural interventions but not in pharmacological interventions. Although the strength of the evidence is limited by inadequate trial design and reporting and significant heterogeneity, there is some evidence that behavioural interventions, antipsychotic switching, and metformin can lead to clinically important improvements in glycaemic measurements in adults with SMI

Cross-sectional comparison of synovial fluid biochemical markers in equine osteoarthritis and the correlation of these markers with articular cartilage damage

AbstractObjective To investigate the relationship between biochemical markers in the synovial fluid of osteoarthritic and contralateral equine joints and gross articular cartilage pathology.Design Twenty-two horses underwent bilateral arthroscopy of their carpal or metacarpophalangeal joints following recent onset lameness. The degree of cartilage damage in each joint was scored and synovial fluid, from both the clinically affected and the contralateral joint, was collected. Bone specific alkaline phosphatase (BAP), 5D4 epitope of keratan sulphate (KS), total glycosaminoglycans (GAG) and hyaluronan (HA) were measured.Results The mean age of the horses was 4.1 years and the maximum duration of lameness was three months. Joints examined were midcarpal, antebrachiocarpal and metacarpophalangeal. The median concentration (semi-interquartile range) of BAP was significantly higher in the clinically active joint than in the contralateral joint, 21.75 (6.22) vs. 12.35 (4.07) units, while the other biomarkers measured were significantly lower in the clinically active joint than in the contralateral joint, i.e. KS 8.79 (1.96) μg/ml vs. 16.39 (5.65) μg/ml, KS:GAG ratio 0.19 (0.04) vs. 0.31 (0.10) and HA 741.6 (222) μg/ml vs. 1061.75 (325) μg/ml. BAP was positively (R=0.57), and KS (R=−0.57) and KS:GAG ratio (R=−0.49) were negatively correlated to the degree of cartilage damage within the joint.Conclusion The correlation between articular cartilage damage and synovial fluid BAP and KS imparts validity to their potential use as non-invasive diagnostic aids in equine osteoarthritis (OA). The positive correlation between BAP and cartilage damage suggests that there is a link between bone turnover and cartilage damage in OA