Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke

Background We collaboratively designed three large trials of fluoxetine for stroke recovery to facilitate an individual patient data meta-analysis (IPDM). MethodsWe performed fixed effects meta-analyses on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months) and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. FindingsWe recruited 5907 people (mean age 69∙5 years (SD 12∙3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, UK, Sweden and Vietnam; and randomized them to fluoxetine 20mg daily or matching placebo for 6 months. 5833 (98∙75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0∙96, 95% CI 0∙87 to 1∙05, p=0∙37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2∙64% vs 1∙8%, p=0∙03), falls with injury (6∙26% vs 4∙51%, p=0∙03), fractures (3∙15% vs 1∙39%, p&lt;0∙0001) and hyponatraemia (1∙22% vs 0∙61%, p=0∙01) but reduced new depression (10∙05% vs 13∙42%, p&lt;0∙0001). At 12 months, there was no difference in adjusted mRS (n=5760; COR 0∙98, 95% CI 0∙89 to 1∙07). Sensitivity analyses gave the same results.Interpretation Fluoxetine 20mg daily for six months did not improve functional recovery. It increased seizures, falls with injury, bone fractures but reduced depression frequency at 6 months. Trial Funding Stroke Association, National Institute of Health Research, Australian Government National Health and Medical Research Council, Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Brain Foundation, Swedish Society of Medicine, King Gustav V and Queen Victoria's Foundation of Freemasons and STROKE-Riksförbundet <br/

Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke

Background Three large randomised controlled trials of fluoxetine for stroke recovery have been performed. We perfomed an individual patient data meta-analysis (IPDM) on the combined data. Methods Fixed effects meta-analyses was performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. Findings The three trials recruited a combined total of 5907 people (mean age 69∙5 years (SD 12∙3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, UK, Sweden and Vietnam; and randomized them to fluoxetine 20mg daily or matching placebo for 6 months. Data on 5833 (98∙75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0∙96, 95% CI 0∙87 to 1∙05, p=0∙37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2∙64% vs 1∙8%, p=0∙03), falls with injury (6∙26% vs 4∙51%, p=0∙03), fractures (3∙15% vs 1∙39%, p<0∙0001) and hyponatraemia (1∙22% vs 0∙61%, p=0∙01) but reduced new depression (10∙05% vs 13∙42%, p<0∙0001). At 12 months, there was no difference in adjusted mRS (n=5760; COR 0∙98, 95% CI 0∙89 to 1∙07). Sensitivity analyses gave the same results. Interpretation Fluoxetine 20mg daily for six months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months

The organisation and delivery of health improvement in general practice and primary care: a scoping study

Background This project examines the organisation and delivery of health improvement activities by and within general practice and the primary health-care team. The project was designed to examine who delivers these interventions, where they are located, what approaches are developed in practices, how individual practices and the primary health-care team organise such public health activities, and how these contribute to health improvement. Our focus was on health promotion and ill-health prevention activities. Aims The aim of this scoping exercise was to identify the current extent of knowledge about the health improvement activities in general practice and the wider primary health-care team. The key objectives were to provide an overview of the range and type of health improvement activities, identify gaps in knowledge and areas for further empirical research. Our specific research objectives were to map the range and type of health improvement activity undertaken by general practice staff and the primary health-care team based within general practice; to scope the literature on health improvement in general practice or undertaken by health-care staff based in general practice and identify gaps in the evidence base; to synthesise the literature and identify effective approaches to the delivery and organisation of health improvement interventions in a general practice setting; and to identify the priority areas for research as defined by those working in general practice. Methods We undertook a comprehensive search of the literature. We followed a staged selection process involving reviews of titles and abstracts. This resulted in the identification of 1140 papers for data extraction, with 658 of these papers selected for inclusion in the review, of which 347 were included in the evidence synthesis. We also undertook 45 individual and two group interviews with primary health-care staff. Findings Many of the research studies reviewed had some details about the type, process or location, or who provided the intervention. Generally, however, little attention is paid in the literature to examining the impact of the organisational context on the way services are delivered or how this affects the effectiveness of health improvement interventions in general practice. We found that the focus of attention is mainly on individual prevention approaches, with practices engaging in both primary and secondary prevention. The range of activities suggests that general practitioners do not take a population approach but focus on individual patients. However, it is clear that many general practitioners see health promotion as an integral part of practice, whether as individual approaches to primary or secondary health improvement or as a practice-based approach to improving the health of their patients. Our key conclusion is that there is currently insufficient good evidence to support many of the health improvement interventions undertaken in general practice and primary care more widely. Future Research Future research on health improvement in general practice and by the primary health-care team needs to move beyond clinical research to include delivery systems and be conducted in a primary care setting. More research needs to examine areas where there are chronic disease burdens – cancer, dementia and other disabilities of old age. Reviews should be commissioned that examine the whole prevention pathway for health problems that are managed within primary care drawing together research from general practice, pharmacy, community engagement, etc

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit

Homocysteine, vitamin B12 and folate levels in premature coronary artery disease

BACKGROUND: Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD. METHODS: We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females) who were admitted for selective coronary angiography to two centers in Tehran. RESULTS: After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01). However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 ± 1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia. CONCLUSION: We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old) – especially in men -and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia

An exploration of lifestyle beliefs and lifestyle behaviour following stroke: findings from a focus group study of patients and family members

<p>Abstract</p> <p>Background</p> <p>Stroke is a major cause of disability and family disruption and carries a high risk of recurrence. Lifestyle factors that increase the risk of recurrence include smoking, unhealthy diet, excessive alcohol consumption and physical inactivity. Guidelines recommend that secondary prevention interventions, which include the active provision of lifestyle information, should be initiated in hospital, and continued by community-based healthcare professionals (HCPs) following discharge. However, stroke patients report receiving little/no lifestyle information.</p> <p>There is a limited evidence-base to guide the development and delivery of effective secondary prevention lifestyle interventions in the stroke field. This study, which was underpinned by the Theory of Planned Behaviour, sought to explore the beliefs and perceptions of patients and family members regarding the provision of lifestyle information following stroke. We also explored the influence of beliefs and attitudes on behaviour. We believe that an understanding of these issues is required to inform the content and delivery of effective secondary prevention lifestyle interventions.</p> <p>Methods</p> <p>We used purposive sampling to recruit participants through voluntary sector organizations (29 patients, including 7 with aphasia; 20 family members). Using focus group methods, data were collected in four regions of Scotland (8 group discussions) and were analysed thematically.</p> <p>Results</p> <p>Although many participants initially reported receiving no lifestyle information, further exploration revealed that most had received written information. However, it was often provided when people were not receptive, there was no verbal reinforcement, and family members were rarely involved, even when the patient had aphasia. Participants believed that information and advice regarding healthy lifestyle behaviour was often confusing and contradictory and that this influenced their behavioural intentions. Family members and peers exerted both positive and negative influences on behavioural patterns. The influence of HCPs was rarely mentioned. Participants' sense of control over lifestyle issues was influenced by the effects of stroke (e.g. depression, reduced mobility) and access to appropriate resources.</p> <p>Conclusions</p> <p>For secondary prevention interventions to be effective, HCPs must understand psychological processes and influences, and use appropriate behaviour change theories to inform their content and delivery. Primary care professionals have a key role to play in the delivery of lifestyle interventions.</p

New metrics for the Lancet Standing Commission on Liver Disease in the UK

Health Polic

Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial

SummaryBackgroundFew data are available from randomised trials about the effect of thrombolysis with alteplase on long-term functional outcome in patients who have had acute ischaemic stroke and no trial has reported effects on health-related quality of life. A secondary objective of the third International Stroke Trial (IST-3) was to assess the effect of thrombolysis on such outcomes at 18 months.MethodsIn this open-label, international, multicentre, randomised, controlled trial, 3035 patients with ischaemic stroke from 12 countries were randomly allocated within 6 h of onset via a secure central system to either intravenous alteplase (0·9 mg/kg; n=1515) plus standard care or standard care alone (control; n=1520). 2348 patients were scheduled for 18-month follow-up. For our main analysis, survivors were assessed at 18 months with the Oxford handicap scale (OHS; the primary outcome was the adjusted odds of OHS score 0–2). We also used the EuroQoL (EQ) instrument and asked questions about overall functioning and living circumstances. We analysed the OHS and the five EQ domains by ordinal logistic regression and calculated the mean difference between treatment groups in EQ utility index and visual analogue scale score. Analyses were adjusted for key baseline prognostic factors. This study is registered with controlled-trials.com, number ISRCTN25765518.FindingsAt 18 months, 408 (34·9%) of 1169 patients in the alteplase group versus 414 (35·1%) of 1179 in the control group had died (p=0·85). 391 (35·0%) of 1117 patients versus 352 (31·4%) of 1122 had an OHS score of 0–2 (adjusted odds ratio [OR] 1·28, 95% CI 1·03–1·57; p=0·024). Treatment was associated with a favourable shift in the distribution of OHS grades (adjusted common OR 1·30, 95% CI 1·10–1·55; p=0·002). Alteplase treatment was associated with significantly higher overall self-reported health (adjusted mean difference in EQ utility index 0·060; p=0·019). The differences between the groups in visual analogue scale score and the proportion living at home were not significant.InterpretationIST-3 provides evidence that thrombolysis with intravenous alteplase for acute ischaemic stroke does not affect survival, but does lead to statistically significant, clinically relevant improvements in functional outcome and health-related quality of life that are sustained for at least 18 months.FundingUK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, AFA Insurances Sweden, Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, the Australian Heart Foundation, Australian National Health and Medical Research Council, Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita (Regione dell'Umbria, Italy), and Danube University

Dark halo microphysics and massive black hole scaling relations in galaxies

We investigate the black hole (BH) scaling relation in galaxies using a model in which the galaxy halo and central BH are a self-gravitating sphere of dark matter (DM) with an isotropic, adiabatic equation of state. The equipotential where the escape velocity approaches the speed of light defines the horizon of the BH. We find that the BH mass (m•) depends on the DM entropy, when the effective thermal degrees of freedom (F) are specified. Relations between BH and galaxy properties arise naturally, with the BH mass and DM velocity dispersion following m• ∝ σF/2 (for global mean density set by external cosmogony). Imposing observationally derived constraints on F provides insight into the microphysics of DM. Given that DM velocities and stellar velocities are comparable, the empirical correlation between m• and stellar velocity dispersions σ⋆ implies that 7 6 the dense dark envelope surrounding the BH approaches the mean density of the BH itself, while the outer halo can show a nearly uniform kpc-scale core resembling those observed in galaxies