Background and Purpose-This prospective, multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications. Methods-We recruited 311 consecutive stroke patients admitted to hospital. Research nurses reviewed their progress on a weekly basis until hospital discharge and again at 6, 18, and 30 months after stroke. Results-Complications during hospital admission were recorded in 265 (85%) of stroke patients. Specific complications were as follows: neurological-recurrent stroke (9% of patients), epileptic seizure (3%); infections-urinary tract infection (24%), chest infection (22%), others (19%); mobility related-falls (25%), falls with serious injury (5%), pressure sores (21%); thromboembolism-deep venous thrombosis (2%), pulmonary embolism (1%); pain-shoulder pain (9%), other pain (34%); and psychological-depression (16%), anxiety (14%), emotionalism (12%), and confusion (56%). During follow-up, infections, falls, "blackouts," pain, and symptoms of depression and anxiety remained common. Complications were observed across all 3 hospital sites, and their frequency was related to patient dependency and duration after stroke. Conclusions-Our prospective cohort study has confirmed that poststroke complications, particularly infections and falls, are common. However, we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated.
Elevated glycogen synthase kinase-3 (GSK-3) activity is associated with Alzheimer disease. We have found that collapsin response mediator proteins (CRMP) 2 and 4 are physiological substrates of GSK-3. The amino acids targeted by GSK-3 comprise a hyperphosphorylated epitope first identified in plaques isolated from Alzheimer brain. Expression of wild type CRMP2 in primary hippocampal neurons or SH-SY5Y neuroblastoma cells promotes axon elongation. However, a GSK-3-insensitive CRMP2 mutant has dramatically reduced ability to promote axon elongation, a similar effect to pharmacological inhibition of GSK-3. Hence, we propose that phosphorylation of CRMP proteins by GSK-3 regulates axon elongation. This work provides a direct connection between hyperphosphorylation of these residues and elevated GSK-3 activity, both of which are observed in Alzheimer brain.
SummaryBackgroundCash-transfer programmes can improve the wellbeing of vulnerable children, but few studies have rigorously assessed their effectiveness in sub-Saharan Africa. We investigated the effects of unconditional cash transfers (UCTs) and conditional cash transfers (CCTs) on birth registration, vaccination uptake, and school attendance in children in Zimbabwe.MethodsWe did a matched, cluster-randomised controlled trial in ten sites in Manicaland, Zimbabwe. We divided each study site into three clusters. After a baseline survey between July, and September, 2009, clusters in each site were randomly assigned to UCT, CCT, or control, by drawing of lots from a hat. Eligible households contained children younger than 18 years and satisfied at least one other criteria: head of household was younger than 18 years; household cared for at least one orphan younger than 18 years, a disabled person, or an individual who was chronically ill; or household was in poorest wealth quintile. Between January, 2010, and January, 2011, households in UCT clusters collected payments every 2 months. Households in CCT clusters could receive the same amount but were monitored for compliance with several conditions related to child wellbeing. Eligible households in all clusters, including control clusters, had access to parenting skills classes and received maize seed and fertiliser in December, 2009, and August, 2010. Households and individuals delivering the intervention were not masked, but data analysts were. The primary endpoints were proportion of children younger than 5 years with a birth certificate, proportion younger than 5 years with up-to-date vaccinations, and proportion aged 6–12 years attending school at least 80% of the time. This trial is registered with ClinicalTrials.gov, number NCT00966849.Findings1199 eligible households were allocated to the control group, 1525 to the UCT group, and 1319 to the CCT group. Compared with control clusters, the proportion of children aged 0–4 years with birth certificates had increased by 1·5% (95% CI −7·1 to 10·1) in the UCT group and by 16·4% (7·8–25·0) in the CCT group by the end of the intervention period. The proportions of children aged 0–4 years with complete vaccination records was 3·1% (−3·8 to 9·9) greater in the UCT group and 1·8% (−5·0 to 8·7) greater in the CCT group than in the control group. The proportions of children aged 6–12 years who attended school at least 80% of the time was 7·2% (0·8–13·7) higher in the UCT group and 7·6% (1·2–14·1) in the CCT group than in the control group.InterpretationOur results support strategies to integrate cash transfers into social welfare programming in sub-Saharan Africa, but further evidence is needed for the comparative effectiveness of UCT and CCT programmes in this region.FundingWellcome Trust, the World Bank through the Partnership for Child Development, and the Programme of Support for the Zimbabwe National Action Plan for Orphans and Vulnerable Children.
SummaryBackgroundModel-based estimates of the global proportions of maternal deaths that are in HIV-infected women range from 7% to 21%, and the effects of HIV on the risk of maternal death is highly uncertain. We used longitudinal data from the Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA) network to estimate the excess mortality associated with HIV during pregnancy and the post-partum period in sub-Saharan Africa.MethodsThe ALPHA network pooled data gathered between June, 1989 and April, 2012 in six community-based studies in eastern and southern Africa with HIV serological surveillance and verbal-autopsy reporting. Deaths occurring during pregnancy and up to 42 days post partum were defined as pregnancy related. Pregnant or post-partum person-years were calculated for HIV-infected and HIV-uninfected women, and HIV-infected to HIV-uninfected mortality rate ratios and HIV-attributable rates were compared between pregnant or post-partum women and women who were not pregnant or post partum.Findings138 074 women aged 15–49 years contributed 636 213 person-years of observation. 49 568 women had 86 963 pregnancies. 6760 of these women died, 235 of them during pregnancy or the post-partum period. Mean prevalence of HIV infection across all person-years in the pooled data was 17·2% (95% CI 17·0–17·3), but 60 of 118 (50·8%) of the women of known HIV status who died during pregnancy or post partum were HIV infected. The mortality rate ratio of HIV-infected to HIV-uninfected women was 20·5 (18·9–22·4) in women who were not pregnant or post partum and 8·2 (5·7–11·8) in pregnant or post-partum women. Excess mortality attributable to HIV was 51·8 (47·8–53·8) per 1000 person-years in women who were not pregnant or post partum and 11·8 (8·4–15·3) per 1000 person-years in pregnant or post-partum women.InterpretationHIV-infected pregnant or post-partum women had around eight times higher mortality than did their HIV-uninfected counterparts. On the basis of this estimate, we predict that roughly 24% of deaths in pregnant or post-partum women are attributable to HIV in sub-Saharan Africa, suggesting that safe motherhood programmes should pay special attention to the needs of HIV-infected pregnant or post-partum women.FundingWellcome Trust, Health Metrics Network (WHO).
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