Objective: To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at nearnormal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy.Methods: Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome.Results: After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conven-tional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; PϽ.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (PϽ.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion:The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning.

ObjectivesSystematic review and meta-analysis of published observational cohort studies. To quantify the increased risk smokers have of experiencing a delayed and/or non-union in fractures, spinal fusion, osteotomy, arthrodesis or established non-unions.SettingMedical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Allied and Complementary Medicine Database (AMED) and Web of Science Core Collection from 1966 to 2015.Study eligibility criteria, participants and interventionsObservational cohort studies that reported adult smokers and non-smokers with delayed and/or non-union or time to union of the fracture, spinal fusion, osteotomy, arthrodesis or established non-union were eligible.Data extraction and outcome measures2 authors screen titles, abstracts and full papers. Data were extracted by 1 author and checked independently by a second. The relative risk ratios of smoking versus non-smoking and the mean difference in time to union patients developing a delayed and/or non-union were calculated.ResultsThe search identified 3013 articles; of which, 40 studies were included. The meta-analysis of 7516 procedures revealed that smoking is linked to an increased risk of delayed and/or non-union. When considered collectively, smokers have 2.2 (1.9 to 2.6) times the risk of experiencing delayed and/or non-union. In all the subgroups, the increased risk was always ≥1.6 times that of non-smokers. In the patients where union did occur, it was a longer process in the smokers. The data from 923 procedures were included and revealed an increase in time to union of 27.7 days (14.2 to 41.3).ConclusionsSmokers have twice the risk of experiencing a non-union after fracture, spinal fusion, osteotomy, arthrodesis or treatment of non-union. Time to union following fracture, osteotomy, arthrodesis or treatment of an established non-union is longer in smokers. Smokers should be encouraged to abstain from smoking to improve the outcome of these orthopaedic treatments.

Consideration of strategies such as the equine nasal strip for reducing negative extravascular pressures is warranted even for exercise at moderate intensities.

Aminocaproic acid (ACA) and Premarin w (PRE) are used to treat exercise-induced pulmonary haemorrhage (EIPH) at the racetrack based upon their putative coagulation effects. We hypothesized that neither ACA nor PRE would reduce EIPH because the literature does not substantiate coagulation deficits being manifested in EIPH. Six Thoroughbreds were run from 4 m s 21 until fatigue (1 m s 21 s £ 1 min increments; 68 inclined treadmill) after being treated with placebo, PRE (25 mg) or ACA (5 g) at 2-week intervals in a randomized crossover design. Coagulation and exercise-related variables were measured at rest and maximal effort. EIPH and inflammation were quantified via bronchoalveolar lavage fluid (BALF) 30-60 min post-exercise. EIPH was not altered by either treatment (3.8^1.7 (placebo), 4.6^3.2 (ACA) and 2.4^1.2 (PRE) £ 10 6 RBC ml 21 BALF; p ¼ 0.12), nor was coagulation. However, inflammation was decreased (5.9^0.9 (placebo), 4.4^0.9 (ACA) and 4.2^0.4 (PRE) £ 10 5 WBC ml 21 BALF; both p , 0.05). There was a trend for decreased time-to-fatigue (720^27 (placebo), 709^24 (ACA) and 726^28 (PRE) s; p ¼ 0.09 for placebo vs. ACA) and a reduction in plasma lactate (19.5^3.0 (placebo), 14.7^1.0 (ACA) and 17.6^2.5 (PRE) mmol l 21 ; p , 0.05 for placebo vs. ACA) following ACA administration. ACA and PRE were not effective in reducing EIPH, and ACA may be detrimental to performance. However, both may mitigate exercise-induced pulmonary inflammation.