SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS 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.FindingsBetween 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.InterpretationFluoxetine 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.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

No abstract

No abstract

Sm_nuary Yttrium-90 chelated by the tetraphosphonate EDTMP achieved a high uptake in bone and a rapid clearance from all soft tissues compared with 90Y nitrilotriacetate, citrate and acetate. The biological half-life of 90Y in the bone was greater than 72h. but the quantity, and therefore dose, could be reduced by 50% using repeated, non-toxic chelation therapy with the calcium salt of DTPA. This treatment should be able to supplement current treatments for leukaemia where the dose of external beam radiation is associated with considerable morbidity.Radiotherapy followed by allogeneic bone marrow transplantation is now a common procedure in the curative therapy of leukaemias. Specific deposition of yttrium into the skeleton demands its delivery in a chemical form with affinity for bone mineral alone. In the past, this has been difficult to achieve because even when chelated, liver uptake has been substantial, presumably because the stabilities of the complexes are insufficient to prevent transferrin binding or colloid formation in vivo. Ideally therefore, targeting agents are required with an intrinsically high affinity for bone, and also a high affinity for the yttrium ion. Compounds with these properties are the phosphonate analogues of polyaminocarboxylic acids, and one in particular (ethylene diamine tetra methylene phosphonate; EDTMP) has already been used to target 153Sm to bone mineral with considerable success (Goeckeler et al.. 1987). Because of chemical similarities between yttrium and the rare earths, EDTMP should form stable complexes with yttrium and carry it-specifically to the bone with comparable efficiency. Here, 90Y-EDTMP complexes have been prepared and compared with other chelating agents for targeting 90Y to the bone in vivo. Similar experiments are also described using the gamma-emitter yttrium-88 to determine the effects of carrier yttrium on tissue distnrbution.The adsorption of yttrium on hydroxyapatite is essentially irreversible under static conditions but elution in vivo is determined by rates of mineral resorption and new-bone formation. When considering its use in leukaemia therapy and bone marrow ablation, it would be advantageous to control the bone marrow dose by removing yttrium from the bone. Early studies aimed at lowering skeletal contamination by yttrium produced in nuclear accidents used repeated EDTA injections, and over a 14-day period, skeletal uptake was reduced to 70% of the control values (Cohn et al.. 1953). Conventionally, diethylene tnramine pentaacetic acid (DTPA) has been the agent of choice for the treatment of heavy metal overdose (Catsch, 1961), and yttnrum also has a high affinity for this chelator. A further aim of this work was to manipulate the biological half-life of 90Y and 88Y in bone by chelation therapy using DTPA, and determine the amount of isotope that could be removed from skeletal tissue. Materials and methods Production of carrier-free yttriwn-90A Dowex 50 W-X8 cation exchange column was loaded with ,20pCi 90Sr-mntrate and washed extensively ...

No abstract