Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy:Results of the EUROCONDOR Clinical Trial

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Effects of dynamic upper body exercise on lower limb isometric endurance.

Following preliminary indications that in some individuals arm exercise enhanced rather than reduced simultaneous leg endurance, ten young men and women performed three forms of intermittent work to volitional exhaustion, under duty cycles of 45 s work, 15 s rest. The protocols were as follows: (A) knee extensions at 30% maximum voluntary contraction (MVC); (B) 30% MVC knee extensions combined with arm cranking at 130% of their own lactate threshold; (C) combined 30% MVC knee extensions and arm cranking at 20% of their own lactate threshold. Heart rate, oxygen uptake ( _V O2), and blood lactate concentration were among the variables recorded throughout. All physiological indicators of demand were substantially higher in protocol B than in protocols A or C [heart rate: (A) 154 beats � min71, (B) 171 beats � min71, (C) 150 beats � min71; _V O2: (A) 11.9 ml � kg71 � min71, (B) 21.7 ml � kg71 � min71, (C) 14.2 ml � kg71 � min71; blood lactate concentration: (A) 3.3 mmol � l71, (B) 5.1 mmol � l71, (C) 2.8 mmol � l71], yet there were no significant differences (P40.05) in the endurance times between the three conditions [(A) 11.43 min, (B) 11.1 min, (C) 10.57 min] and seven participants endured longest in protocol B. Results from protocol (C) cast doubt on explanations in terms of psychological distraction. We suggest that lactic acid produced by the arms is shuttled to the legs and acts there either as a supplementary fuel source or as an antagonist to the depressing effects of increased potassium concentration

Indicators of maximal hiking performance in Laser sailors

Laser class sailors have to hike out, i.e. hook their feet under the toe straps near the centreline of the boat and hold their upper bodies over the edge of the boat, to counteract the heeling forces generated by the sails. To identify the parameters that are associated with maximal hiking performance, this cross-sectional observational study measures various knee extensor and hip flexor muscle performance characteristics in 55 Laser sailors and correlates each with the area-under-the-curve hiking moment over 3 min of hiking on a hiking dynamometer (HM180). Our results showed that higher body mass and HM180 were significantly associated with better race scores (Spearman’s rho = − 0.69 and − 0.62, respectively, both P &#60; 0.01) in male sailors who participated in the National Inter-School Laser competition. Body mass (Pearson’s correlation coefficient, r &#8805; 0.95, P &#60; 0.01 in both males and females), maximum voluntary isometric strength of the quadriceps (r &#8805; 0.80, P &#60; 0.01 in both males and females), and 3-RM knee extension strength (r &#8805; 0.80, P &#60; 0.01 in both males and females) were associated with a higher HM180. The correlations between height, abdominal muscle endurance (crunches), explosive lower body strength (vertical jumps), cycling time-to-exhaustion, quadriceps strength endurance, or isometric quadriceps endurance with incremental loads (bucket test), and HM180 were weaker (r &#60; 0.60). HM180 may be a useful performance indicator for Laser racing. Since strength measures correlated well with HM180, greater emphasis should be placed on developing maximum strength in the quadriceps to improve maximal hiking performance