Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature.

AIM: The objective of this review was to assess the published evidence for an association between glycaemic variability and the development of chronic micro- and macrovascular complications in patients with diabetes mellitus (DM). METHODS: A systematic review of English-language literature published from January 1990 through November 2008 was performed. Interventional and observational studies in patients with type 1 or type 2 DM reporting a measure of glycaemic variability and its impact on the development or progression of micro- and macrovascular diabetic complications were assessed. RESULTS: A total of 18 studies -8 on type 1 DM and 10 on type 2 DM patients-meeting the inclusion criteria were identified. Studies in patients with type 1 DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two of the eight type 1 DM studies did glucose variability have a significant association with microvascular complications, but not with macrovascular complications. Among type 2 DM studies, a significant positive association between glucose variability and the development or progression of diabetic retinopathy, cardiovascular events and mortality was reported in 9 of 10 studies. Only one type 2 DM study reported no association between glucose variability and progression of retinopathy. CONCLUSIONS: Based on this overview of the available evidence, there appears to be a signal suggesting that glucose variability, characterized by extreme glucose excursions, could be a predictor of diabetic complications, independent of HbA1c levels, in patients with type 2 DM. Better daily control of blood glucose excursions, especially in the postprandial period, may reduce the risk of these complications. Future prospective trials evaluating and comparing the effect of the control of glycaemic variability on the development of diabetic micro- and macrovascular complications are needed to further strengthen the evidence base.

Intermediate and long-term outcomes of total ankle arthroplasty and ankle arthrodesis. A systematic review of the literature.

BACKGROUND: The efficacy of total ankle replacement compared with that of ankle fusion continues to be one of the most debated topics in foot and ankle surgery. The purpose of this study was to determine whether there are sufficient objective cumulative data in the literature to compare the two procedures. A systematic review of the literature addressing the intermediate and long-term outcomes of interest in total ankle arthroplasty and ankle arthrodesis was performed. METHODS: A comprehensive search of MEDLINE for all relevant articles published in English from January 1, 1990, to March 2005 was conducted. Additionally, relevant abstracts from the 2003 and 2004 annual proceedings of major orthopaedic meetings were eligible. Two reviewers evaluated each study to determine whether it was eligible for inclusion and collected the data of interest. Meta-analytic pooling of group results across studies was performed for the two procedures. The analysis of the outcomes focused on second-generation ankle implants. RESULTS: The systematic review identified forty-nine primary studies, ten of which evaluated total ankle arthroplasty in a total of 852 patients and thirty-nine of which evaluated ankle arthrodesis in a total of 1262 patients. The mean AOFAS (American Orthopaedic Foot and Ankle Society) Ankle-Hindfoot Scale score was 78.2 points (95% confidence interval, 71.9 to 84.5) for the patients treated with total ankle arthroplasty and 75.6 points (95% confidence interval, 71.6 to 79.6) for those treated with arthrodesis. Meta-analytic mean results showed 38% of the patients treated with total ankle arthroplasty had an excellent result, 30.5% had a good result, 5.5% had a fair result, and 24% had a poor result. In the arthrodesis group, the corresponding values were 31%, 37%, 13%, and 13%. The five-year implant survival rate was 78% (95% confidence interval, 69.0% to 87.6%) and the ten-year survival rate was 77% (95% confidence interval, 63.3% to 90.8%). The revision rate following total ankle arthroplasty was 7% (95% confidence interval, 3.5% to 10.9%) with the primary reason for the revisions being loosening and/or subsidence (28%). The revision rate following ankle arthrodesis was 9% (95% confidence interval, 5.5% to 11.6%), with the main reason for the revisions being nonunion (65%). One percent of the patients who had undergone total ankle arthroplasty required a below-the-knee amputation compared with 5% in the ankle arthrodesis group. CONCLUSIONS: On the basis of these findings, the intermediate outcome of total ankle arthroplasty appears to be similar to that of ankle arthrodesis; however, data were sparse. Comparative studies are needed to strengthen this conclusion.

Adverse events in coronary artery bypass graft (CABG) trials: a systematic review and analysis.

OBJECTIVES: To quantify the incidence of major adverse events (AEs) occurring in hospital or within 30 days after surgery in patients undergoing coronary artery bypass graft (CABG) surgery and to identify risk factors for these AEs. METHODS: Systematic review and analysis of studies published in English since 1990. Studies of isolated standard CABG reporting postoperative incidence of myocardial infarction (MI), stroke, gastrointestinal bleeding, renal failure, or death in hospital or within 30 days were eligible for inclusion. Incidence of these events was calculated overall and for selected patient groups defined by all elective CABG versus mixed (some non-elective); mean ejection fraction < or = 50% versus > 50%; mean age < or= 60 versus > 60 years; primary CABG versus some reoperations; randomised controlled trials versus cohort studies; and single centre versus multicentre studies. Odds ratios of selected AEs were computed according to group risk factors. RESULTS: 176 studies (205 717 patients) met all inclusion criteria. The average incidence of major AEs occurring in-hospital was death (1.7%); non-fatal MI (2.4%); non-fatal stroke (1.3%); gastrointestinal bleeding (1.5%); and renal failure (0.8%). Thirty day mortality was 2.1%. Meta-analyses show that age > 70, female sex, low ejection fraction, history of stroke, MI, or heart surgery, and presence of diabetes or hypertension are all associated with increased 30 day mortality after CABG. CONCLUSION: The incidence of major AEs in patients after CABG varies widely across studies and patient populations, and this heterogeneity must be controlled when using the literature to benchmark safety.

Discontinuation of antihypertensive drugs due to adverse events: a systematic review and meta-analysis.

We conducted a systematic review of randomized, controlled, monotherapy trials since 1990 of oral antihypertensive agents in patients with essential hypertension. Our objective was to quantify the frequency of discontinuation of antihypertensive agents due to adverse events from a meta-analysis of the studies. A total of 190 studies met inclusion criteria. The highest frequency of discontinuations due to adverse events (DAEs) occurred with calcium channel blockers (6.7%) and alpha-adrenergic blockers (6.0%); the lowest with diuretics and angiotensin receptor blockers (each 3.1%). Only in calcium channel blocker studies was the frequency of DAEs greater in treated patients than in patients receiving placebo, but the difference was not significant. This systematic review suggests that the frequency of DAEs in monotherapy antihypertensive trials varies across drug classes and should be considered when choosing drugs for patients with essential hypertension.