Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): A phase 3, randomised, open-label, treat-to-target non-inferiority trial
Garber A.J.,Baylor College of Medicine |
King A.B.,Diabetes Care Center |
Del Prato S.,University of Pisa |
Sreenan S.,Connolly Hospital |
And 6 more authors.
The Lancet | Year: 2012
Background Basal insulin therapy does not stop loss of ß-cell function, which is the hallmark of type 2 diabetes mellitus, and thus diabetes control inevitably deteriorates. Insulin degludec is a new, ultra-longacting basal insulin. We aimed to assess effi cacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus. Methods In this 52 week, phase 3, open-label, treat-to-target, non-inferiority trial, undertaken at 123 sites in 12 countries, we enrolled adults (aged =18 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA1c) of 7.0-10.0% after 3 months or more of any insulin regimen (with or without oral antidiabetic drugs). We randomly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine, stratifi ed by previous insulin regimen, via a central interactive response system. Basal insulin was titrated to a target plasma glucose concentration of 3.9-<5.0 mmol/L self-measured before breakfast. The primary outcome was non-inferiority of degludec to glargine measured by change in HbA1c from baseline to week 52 (non-inferiority limit of 0.4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00972283. Findings 744 (99%) of 755 participants randomly allocated degludec and 248 (99%) of 251 allocated glargine were included in the full analysis set (mean age 58.9 years [SD 9.3], diabetes duration 13.5 years [7.3], HbA1c 8.3% [0.8], and fasting plasma glucose 9.2 mmol/L [3.1]); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA1c decreased by 1.1% in the degludec group and 1.2% in the glargine group (estimated treatment diff erence [degludec-glargine] 0.08%, 95% CI-0.05 to 0.21), confi rming non-inferiority. Rates of overall confi rmed hypoglycaemia (plasma glucose <3.1 mmol/L or severe episodes requiring assistance) were lower with degludec than glargine (11.1 vs 13.6 episodes per patient-year of exposure; estimated rate ratio 0.82, 95% CI 0.69 to 0.99; p=0.0359), as were rates of nocturnal confi rmed hypoglycaemia (1.4 vs 1.8 episodes per patient-year of exposure; 0.75, 0.58 to 0.99; p=0.0399). Rates of severe hypoglycaemia seemed similar (0.06 vs 0.05 episodes per patient-year of exposure for degludec and glargine) but were too low for assessment of diff erences. Rates of other adverse events did not diff er between groups. Interpretation A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec, which are associated with lower risks of hypoglycaemia than insulin glargine.
Chotirmall S.H.,Nanyang Technological University |
Burke C.M.,Connolly Hospital
Expert Review of Respiratory Medicine | Year: 2015
In the elderly, asthma remains a clinical challenge. Recognition, diagnosis and treatment are all complex. Influenced by processes, such as aging, the identification of an 'asthma microbiome' presents a further challenge. This editorial discusses aging and the 'asthma microbiome' separately and then evaluates their potential relationship. Current evidence suggests that differences in the airway microbiome are associated with asthma, however, whether such associations are comparable or different for late-onset disease is yet to be established. Microbes are now linked to fundamental physiological processes, such as aging, based on data from invertebrate systems. This will likely confer implications for asthma in the elderly, and it is crucial that such emerging scientific data are considered in the context of aging, asthma and late-onset disease. © 2015 Informa UK Ltd.
Conway R.,Park University |
Conway R.,National University of Ireland |
Low C.,Connolly Hospital |
Coughlan R.J.,Park University |
And 2 more authors.
Seminars in Arthritis and Rheumatism | Year: 2015
Objective: Methotrexate is an effective treatment for a variety of inflammatory diseases. Robust evidence on the risk of serious liver injury is lacking. The aim of this study was to evaluate the relative risk and severity of liver disease among patients treated with methotrexate. Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials from 1 January 1990 to 24 April 2014 for double-blind randomised controlled trials of methotrexate versus comparator agents in adults with rheumatoid arthritis, psoriasis, psoriatic arthritis or inflammatory bowel disease. Studies with less than 100 subjects or of less than 24 weeks[U+05F3] duration were excluded. Two investigators independently searched both the databases. All authors reviewed the selected studies. We compared relative risk (RR) differences using the Mantel-Haenszel random effects method to assess total liver adverse events, minor liver enzyme abnormalities (≤3 ULN), major liver enzyme abnormalities (>3 ULN or treatment withdrawal) and a composite outcome of liver failure, fibrosis, cirrhosis or death. Results: A total of 32 studies with 13,177 participants met our inclusion criteria. Methotrexate was associated with an increased risk of total adverse liver events, RR = 2.19 (95% CI: 1.73-2.77, I2 = 68%), as well as minor and major liver enzyme abnormalities, RR = 2.16 (95% CI: 1.67-2.79, I2 = 68%) and RR = 2.63 (95% CI: 1.90-3.64, I2 = 10%), respectively. Patients treated with methotrexate were not at increased risk of liver failure, cirrhosis or death, RR = 0.12 (95% CI: 0.01-1.09, I2 = 0%). Conclusion: Our study found an increased risk of elevated transaminases but not liver failure, cirrhosis or death with methotrexate compared to other agents. We were unable to assess long-term liver toxicity due to the short duration of included clinical trials. © 2015 Elsevier Inc.
O'Neill B.J.,Connolly Hospital
BMJ case reports | Year: 2014
Bisphosphonate use has been identified as a contributory factor in atypical subtrochanteric fracture of the femur. These fractures are commonly treated with an intramedullary device. We present a case of implant failure of an intrameduallary device caused by non-union of an atypical subtrochanteric fracture.
Anyansi T.E.,Connolly Hospital |
Agyapong V.I.O.,St Jamess Hospital
International Journal of Psychiatry in Clinical Practice | Year: 2013
Background. Predictive factors are used to alert the clinician to the necessity of carrying out a suicide risk assessment in those patients whose demographic and clinical characteristics suggest the possibility of suicide. Aim. To identify demographic and clinical variables that could predict suicidal ideation in psychiatric outpatients. Methods. 150 consecutive return patients attending a psychiatric outpatient clinic were approached and requested to complete a clinician-administered semi-structured questionnaire designed to assess the aims of the study. The questionnaire comprised 18 questions most of which had either a checklist of possible answers or a yes/no answer. Data was analysed with descriptive statistics, univariate analysis and logistic regression using SPSS version 17. Results. Of the 150 patients approached with written information, 133 consented to take part in the study giving a response rate of 88.7%. The mean age was 40.6 years (s.d = 12.7). On univariate analysis, there was a statistically significant relationship (P < 0.05) between three of the predictor variables (age, marital status and history of self-harm) and the likelihood of experiencing suicidal ideation in the preceding 12 months. However, with all other factors controlled for, only two of the independent variables (history of self-harm and no history of psychiatric inpatient treatment) significantly predicted suicidal ideation in the previous 12 months with odds ratios of 5.409 and 2.836 respectively. Conclusion. Amongst variables studied, having a history of self-harm or no previous history of psychiatric inpatient treatment was the best predictor of suicidal ideation in the preceding year in a population of patients attending a psychiatric outpatient review clinic. © 2013 Informa Healthcare.