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

HANDEDNESS IN EXTREMELY LOW-BIRTH-WEIGHT INFANTS - ETIOLOGY AND RELATIONSHIP TO INTELLECTUAL ABILITIES, MOTOR-PERFORMANCE AND BEHAVIOR AT 4 AND 6 YEARS

Hand preference was measured in a total group of 71 ELBW children to determine patterns of hand preference at 4 and 6 years, possible aetiological factors leading to handedness, and whether left or non right hand preference were markers for intellectual, motor, temperament or behavioural differences. At both 4 and 6 years the prevalence ot left handedness was increased, though this prevalence changed over the period of the study. Results supported brain injury as one mechanism leading to increased left hand preference, though this process did not adequately explain this increase. Possible reasons for this and the apparent change in prevalence with time are examined. Mixed handedness at 4 years was associated with lower intellectual abilities though otherwise children were similar in motor skills, temperament and behaviour independent of hand preference category

The Prevalence and Origins of Left Hand Preference in High-Risk Infants, and its Implications for Intellectual, Motor and Behavioral Performance At 4 and 6 Years

This study investigates the origins of hand preference at 4 years in a cohort of 115 high risk and premature infants: the relationship between patterns of hand preference and intellectual, motor. temperament and behavioural status at 4 and 6 years; and evidence for brain injury in mediating the relationship between hand preference and development disorder. Increased left hand preference was independently associated with extreme prematurity, high neonatal risk, increased numbers of minor physical anomalies, lowered itellectual and motor abilities, and more difficult temperament. These findings supported the presence of intrauterine and neonatal pathological mechanisms leading to left hand preference in a small number of children. Neither poor function of the non dominant hand nor absence of a family history of left handedness could further define this pathological subgroup. Support for pathological mechanisms producing left handedness was found predominately in the infants of high birth weight, whereas prevalence of left handedness was increased mainly among the extremely low birth weight infants. In this latter group the prevalence of left handedness was also increased among children of normal intelligence, suggesting that mechanisms other than brain damage lead to left hand preference in very premature infants

Characteristics at four months follow-up of infants born small for gestational age: a controlled study

In contrast to the effects of preterm birth, the extent to which shorter gestational age affects the cardiorespiratory fitness (CRF) levels of individuals who were born at term (ie, between 37 and 42\ua0weeks) is largely unknown. The aim of this study was to examine whether life-course CRF levels varied across different gestational ages within the at-term range