OBJECTIVES:To explore the barriers preventing pioglitazone use in stroke survivors and primary and secondary stroke care services. METHODS:A qualitative grounded theory approached design was used to assess post-stroke diabetes treatments and to assess clinical applicability of pioglitazone as a preventive treatment to minimize its side effects (SEs) associated. Three focus groups were established with 48 participants from Scotland and Wales health board centers during January 2019 to July 2022. RESULTS:A qualitative grounded theory approached design was used to assess post-stroke diabetes treatments and to assess clinical applicability of pioglitazone as a preventive treatment to minimize its SEs associated. Three focus groups were established with 48 participants from Scotland and Wales health board centers during January 2019 to July 2022. CONCLUSION:These strategies might allow greater treatment adherence by stroke survivors and increased confidence of the health care professionals in their practice. The findings suggest that further research will be needed to facilitate wider usage of pioglitazone in treating people with stroke and health education is necessitate when using diabetes drugs post-stroke.

IntroductionDiabetes is associated with an increased risk of stroke. In many cases, a diabetes diagnosis may predate a stroke; however, diabetes is often diagnosed during the hospital admission following a stroke. To explore the experiences of stroke survivors as they cope with a new diabetes diagnosis, particularly regarding developing an effective strategy for managing the disease.MethodsA qualitative grounded theory approach was used that employed focus group interviews with participants, including clinicians and stroke survivors, to develop a holistic understanding of primary and secondary stroke care services and the experiences of those accessing them.ResultsClinicians believed they were not optimally equipped to manage diabetes as a condition. They believed more emphasis should be placed on self-management, which would be better managed by lifestyle changes than medication alone. Conversely, stroke survivors with diabetes experienced an additional burden associated with the diagnoses but relied on clinicians to manage their diabetes and believed the clinicians were failing if they were unwilling or unable to achieve this.DiscussionThe research highlights the tensions between stroke survivors and healthcare professionals. Stroke survivors relied on the healthcare teams to provide the optimal treatment when they had recently undergone a significant health event where they had experienced a stroke and received a diabetes diagnosis. However, the healthcare teams, while recognizing the importance of a holistic and comprehensive treatment package, struggled to provide it due to resource limitations. To optimize post-stroke diabetes self-management education, a strategic framework that prioritizes patient empowerment and interdisciplinary collaboration is paramount. Tailoring educational interventions to align with individual patient profiles—considering their unique health status, personal preferences, and cultural context—is essential for fostering self-efficacy. Such a strategy not only empowers patients to take an active role in managing their diabetes post-stroke but also contributes to superior health outcomes and an elevated standard of living.

Background and Purpose Post-stroke morbidity is common, but little is known about the burden on patients’ lives from their own perspective. Understanding morbidity from the point of view of the patient may support targeted intervention in post-stroke recovery. This study used a stroke specific Patient Reported Outcome Measure (PROM) containing Mental health (MH) and Physical Health (PH) domains and 5 stroke specific questions. We aimed to consider trends over a 6-month period and further assess the association between the MH and PH measures and common clinical measures. Methods A multicenter prospective cohort study was conducted at 19 hospital sites across England and Wales. Patients were enrolled from August 2018 to September 2019. Clinical measures and PROMs were assessed at three timepoints: acutely following the index stroke, at 3 and 6-months post-stroke. Clinical measures and PROMs were assessed in each of these points. Results Physical health PROM domains show significant gradual improvement across the study period (χ2 42.6312, p<0.0001), whereas cognitive function domains (χ2 3.7849, p<0.875) did not echo this trend. All clinical measures (GAD-7, PHQ9, MoCA, MRS) were associated with poorer PROM MH outcomes, (aMD -4.4, CI -0.59, -0.29, p≤0.001, aMD -0.45, CI -0.59, -0.32, p= <0.001, aMD 0.75, CI 0.56, 0.95, aMD -1.91, CI -2.41, -1.47, p≤0.001). Clinical measures of disability, as per the MRS, are associated with poor PROM PH scores (aMD -0.57, 95% CI -0.94, -0.20, p=0.003). Conclusions This research indicates there is unmet cognitive burden in stroke survivors. PROMs may be able to measure unmet more discretely than common clinical tools that are used post-stroke. Further research and guidance on how to integrate PROMs into current clinical frameworks is essential.

The National Clinical Guideline for Stroke 2023 (Intercollegiate Stroke Working Party, 2023) marks a new ambition for stroke rehabilitation. Launched in April 2023, they propose a raft of recommendations that will transform occupational therapy provided to people with stroke and their families. It should be noted that the guidelines are a ‘partial’ update with some sections being out of scope for update, in which case the 2016 recommendations are carried forward. At the guidelines launch, two stroke survivors presented the plain language summary [https://www.stroke guideline.org/plainlanguagesummary/] and highlighted the importance of using this accessible educational tool with stroke survivors and their families to inform them of what they can expect along the pathway. Over the next two editions of The British Journal of Occupational Therapy, we will firstly present the new recommendations most pertinent to occupational therapists and secondly explore the opportunities and challenges these recommendations present for occupational therapy practice across the stroke pathway.

Abstract Background and Purpose The use of patient reported outcomes measures (PROMs) may offer utility that are important for stroke survivors. This study assessed the PROMIS-10, which contains Mental health (MH) and Physical Health (PH) domains, with an additional five stroke specific questions. The aim of this study was to evaluate the association between the MH and PH measures following a stroke and pre-existing health conditions. Methods A multicentre prospective cohort study at 19 hospital sites across England and Wales during 2019 was conducted. The association between each PROMIS-10 domain and demographic and health conditions were calculated using a multilevel multivariable linear and present the adjusted mean difference (aMD). Results The study enrolled 549 stroke survivors within 14 days of the index event, 232 were women (42.3%) and with a mean age of 72.7 years (SD = 12.9, range 25 to 97). The MH domain was scored as poor in 3.9% of participants, and very good or excellent in almost a half (48.4%). In contrast the PH domain was scored as poor in 39.9%, compared to very good or excellent in 8.5%. The MH domain was associated with pre-existing diabetes (aMD = − 2.01; 95%CI -3.91, − 0.12; p = 0.04), previous stroke (aMD = − 3.62; 95%CI -5.86, − 1.39; p = 0.001), age (aMD = 0.07; 95%CI: 0.01, 0.14; p = 0.037), and female sex (aMD = 1.91; 95%CI 0.28, 3.54; p = 0.022). The PH domain was found to be associated with sex (female) (aMD = 2.09; 95%CI 0.54, 3.65; p = 0.008) and previous stroke (aMD = − 3.05; 95%CI -5.17, − 0.93; p = 0.005). Conclusions Almost half of stroke survivors reported poor PH using a PROM with less reporting poor MH. age, and sex were associated with both MH and PH domains, and additionally pre-exising diabetes and stroke were associated with poorer MH. Clinical management offers an opportunity to investigate and intervene to prevent long term poorer health in stroke survivors.

Sexual reproduction is a complex process that contributes to differences between the sexes and divergence between species. From a male's perspective, sexual selection can optimize reproductive success by acting on the variance in mating success (pre-insemination selection) as well as the variance in fertilization success (post-insemination selection). The balance between pre- and post-insemination selection has not yet been investigated using a strong hypothesis-testing framework that directly quantifies the effects of post-insemination selection on the evolution of reproductive success. Here we use experimental evolution of a uniquely engineered genetic system that allows sperm production to be turned off and on in obligate male-female populations of Caenorhabditis elegans. We show that enhanced post-insemination competition increases the efficacy of selection and surpasses pre-insemination sexual selection in driving a polygenic response in male reproductive success. We find that after 10 selective events occurring over 30 generations post-insemination selection increased male reproductive success by an average of 5- to 7-fold. Contrary to expectation, enhanced pre-insemination competition hindered selection and slowed the rate of evolution. Furthermore, we found that post-insemination selection resulted in a strong polygenic response at the whole-genome level. Our results demonstrate that post-insemination sexual selection plays a critical role in the rapid optimization of male reproductive fitness. Therefore, explicit consideration should be given to post-insemination dynamics when considering the population effects of sexual selection.

Objective To determine psychometric properties of the PROMIS-10 and Standard Stroke Question Set (by International Consortium for Health Outcome Measures) presented as a new 15-item Patient Related Outcome (PRO), for patients with: acquired Brain Injury (ABI), Multiple sclerosis (MS) and Parkinson’s disease (PD). Methods In an eight centre, UK wide, cross-sectional study we approached patients during their routine follow-up to complete: a disease-specific instrument (European Brain Injury Questionnaire, Multiple Sclerosis Impact Scale, and Parkinson’s disease questionnaire); General Health questionnaire with a Quality of life measure (EQ-5D); and PRO. We validated the PRO using factor analysis to define the latent construct domains, then calculated the internal consistency (Cronbach’s-α), and construct validity (correlation). Results There were 340 patients with ABI (N = 91, median age = 55.1, 41% female), MS (N = 99, age = 58.9, 69%) and PD (N = 150, age = 74.5, 40%). Factor analysis suggested the PRO offered three domains of: physical health; functionality-capacity and mental health. All factors correlated strongly with the three disease-specific instruments, and the overall PRO had a large correlation with the EQ-5D (correlation>0.8) offering good construct validity and excellent internal consistency (∝>0.89). Interpretation The PRO offered promising psychometric properties and could be used in place of disease specific questionnaires for patients with ABI, MS, and PD. The PRO has three construct domains, describing patients’: mental health; physical health; and functional-capacity, and may be used in routine clinical practice. The PRO offered both relevance to each of the three separate neurological conditions and generalisability across all the conditions, increasing its utility.

Background and Purpose: The use of patient reported outcomes measures (PROMs) may offer utility and provide outcome measures that are important for stroke survivors. This study used a stroke specific PROM, which contains Mental health (MH) and Physical Health (PH). The primary aim of this study was to assess the association between the MH and PH measures following a stroke and preexisting health conditions. Methods: A multicenter prospective cohort study at 19 hospital sites across England and Wales during 2019 was conducted. Prevalence of morbidity within PROMs was estimated with 95% confidence intervals (95% CI). The association between each PROM domain and demographic and health conditions were calculated using a multilevel multivariable linear model fitting the adjusted mean difference (aMD). Results: PROM morbidity was high post stroke; 93.2% of the participants reported combined post stroke PROM morbidity. The MH domain was associated with pre-existing: diabetes, previous stroke, age, and sex. The PH domain was found to be associated with gender (female) and previous stroke, Conclusions: Stroke survivors ubiquitously suffer morbidity. Risk factors associated with worsening MH and PH morbidity have implications in clinical management as they offer an opportunity to intervene, particularly to prevent long term mental health. PROMs provide useful outcome measure that matter to stroke survivors.

Background: In myelodysplastic syndromes (MDS), thrombocytopenia is an adverse risk factor. Treatments in this setting are scarce. In a randomized international phase 2 trial (EQoL-MDS, EudraCT number 2010-022890-33), we reported effecacy and safety of eltrombopag for the treatment of thrombocytopenia in the first 90 patients with lower-risk MDS with a platelet (PLT) count < 30 Gi/L (Oliva et al. Lancet Hem 2017). However, there are concerns of regulatory agencies regarding the use of thrombopoetin rececptor agonists in MDS due to previous reports signalling disease progression in clinical trials with the use of romiplostim and of eltrombopag, the latter in high risk MDS. Objective: We are further evaluating safety by conducting a comprehensive analysis of mutations in a panel of major driver or candidate driver genes in cases enrolled in the EQoL-MDS trial using targeted-capture sequencing.

Approximately 10% to 15% of patients with essential thrombocythemia (ET) lack the common driver mutations, so-called "triple-negative" (TN) disease. We undertook a systematic approach to investigate for somatic mutations and delineate gene expression signatures in 46 TN patients and compared the results to those with known driver mutations and healthy volunteers. Deep, error-corrected, next-generation sequencing of peripheral blood mononuclear cells using the HaloPlexHS platform and whole-exome sequencing was performed. Using this platform, 10 (22%) of 46 patients had detectable mutations (MPL, n = 6; JAK2V617F, n = 4) with 3 of 10 cases harboring germline MPL mutations. RNA-sequencing and DNA methylation analysis were also performed by using peripheral blood mononuclear cells. Pathway analysis comparing healthy volunteers and ET patients (regardless of mutational status) identified significant enrichment for genes in the tumor necrosis factor, NFκB, and MAPK pathways and upregulation of platelet proliferative drivers such as ITGA2B and ITGB3. Correlation with DNA methylation showed a consistent pattern of hypomethylation at upregulated gene promoters. Interrogation of these promoter regions highlighted enrichment of transcriptional regulators, which were significantly upregulated in patients with ET regardless of mutation status, including CEBPβ and NFκB. For "true" TN ET, patterns of gene expression and DNA methylation were similar to those in ET patients with known driver mutations. These observations suggest that the resultant ET phenotype may, at least in part and regardless of mutation type, be driven by transcriptional misregulation and may propagate downstream via the MAPK, tumor necrosis factor, and NFκB pathways with resultant JAK-STAT activation. These findings identify potential novel mechanisms of disease initiation that require further evaluation.

Myelodysplastic syndrome (MDS) are clonal stem cell diseases characterized mainly by ineffective hematopoiesis. Here, we present an approach that enables robust long-term engraftment of primary MDS stem cells (MDS-SCs) in mice by implantation of human mesenchymal cell-seeded scaffolds. Critically for modelling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 104 CD34+ cells can be engrafted and expanded by this approach with the maintenance of the genetic make-up seen in the patients. Non-invasive high-resolution ultrasound imaging shows that these scaffolds are fully perfused. Our data shows that human microenvironment but not mouse is essential to MDS-SCs homing and engraftment. Notably, the alternative niche provided by healthy donor MSCs enhanced engraftment of MDS-SCs. This study characterizes a new tool to model MDS human disease with the level of engraftment previously unattainable in mice, and offers insights into human-specific determinants of MDS-SC microenvironment.

BackgroundKnowledge of the prevalence of morbidity secondary to stroke is important for health care professionals, health care commissioners, third sector organizations, and stroke survivors to understand the likely progress of poststroke sequelae and to aid in commissioning decisions, planning care, and adjusting to life after stroke. ObjectiveThe primary aim of the Morbidity PRevalence Estimate In StrokE (MORe PREcISE) study is to determine the prevalence of morbidity secondary to a stroke, predictors of morbidity, and trends in quality of life and functional status using patient-reported outcomes, cognitive and functional assessments. MethodsA total of 500 participants will be recruited across Wales and England within 14 days following an admission to a stroke unit for either an ischemic or hemorrhagic stroke as part of a multicenter cohort study. Participants are assessed at baseline ≤14 days poststroke and subsequently at 90 (± 14) days and 180 (± 14) days poststroke. At each time point, data will be collected relating to the following domains: participant demographics, routine clinical, patient reported, cognitive status, emotional well-being, and functional ability. ResultsRecruitment commenced in October 2018 with 20 sites opened as of September 2019 and was closed on October 31, 2019. ConclusionsThe primary outcome is the prevalence of morbidity at 6 months secondary to a stroke. Further analysis will consider temporal changes in the health-related domains to describe trends among baseline, 3-, and 6-month time points. Trial RegistrationClinicalTrials.gov NCT03605381; https://clinicaltrials.gov/ct2/show/NCT03605381 International Registered Report Identifier (IRRID)DERR1-10.2196/15851

Background: Standard immunosuppressive therapy (IST) for severe/very severe aplastic anemia (SAA/vSAA) patients not eligible for transplantation is horse antithymocyte globulin (hATG) plus ciclosporin (CsA).We report an open-label, phase III, randomized trial of hATG and CsA with or without EPAG in naive patients with SAA/vSAA (clinicaltrials.gov,NCT02009747).Methods: From July 2015 to April 2019, 197 treatmentnaive patients were enrolled (6 countries and 24 sites), stratified on disease severity, age and center.Patients were randomized to either standard IST (hATG 40 mg/kg x4d and CsA 5 mg/kg/d; arm A) or standard IST + EPAG (experimental arm B) at the dose of 150 mg/d from day +14 until 6 months (m) (or 3m, in case of early complete response (CR)).The primary endpoint was hematological CR at 3m. Secondary endpoints included overall survival (OS), hematological response at 6m, clonal evolution and number and allele burden of somatic myeloid mutations (central laboratory, King's College London, UK).The study was powered to detect an increase in CR from 7% in arm A to 21% in arm B at 3m, requiring at least 96 patients per arm.Results: One-hundred-one and 96 patients were randomized to arm A and arm B, respectively.Baseline characteristics were comparable between the 2 arms, including median age (52 and 55 years in arms A and B), age stratum (age < 40 was 35.6% in arm A and 30.2% in arm B), disease severity (vSAA was 33.7% in arm A and 35.4% in arm B), and presence of a PNH clone (59.2% in arm A and 45.2% in arm B).Median follow-up was 18 months.The primary endpoint was reached with 3m CR rates of 9.9% and 21.9% in arms A and B (pooled Odds Ratio 3.2, p = 0.012).Overall response (OR=CR +PR) rates were 31.7% and 59.4%, respectively.At time of analysis, OR at 6m for patients alive, not being transplanted and without clonal evolution was 50.0% in arm A vs 76.3% in arm B (Odds Ratio: 3.8).SAEs were comparable in both arms.Eight patients came off study prematurely in arm A and 7 in arm B requiring secondline transplantation.Clonal evolution occurred in 1 patient in arm A (karyotype abnormality 6.5m after randomization) and in 3 patients in arm B (2 karyotypic abnormalities and 1 MDS after 6.2, 6.3 and 12.0m after randomization).High sensitivity NGS analysis was performed using a 31 gene target molecular bar coded panel.At time of this analysis, samples were available from 163 patients at baseline, and 132 at 6m follow up with no difference in term of somatic myeloid mutations (baseline: VAF >1% 38.2% in arm A vs 36.6% in arm B).During the study, 22 patients died (14 in arm A, OS of 83.2% at 24m and 8 in arm B, OS 86.3% at 24m) (p = 0.142).Conclusions: This practice changing phase III trial support the combination of hATG, CsA and EPAG as the next first line standard-of-care for SAA/vSAA patients not eligible fortransplantation.RPDL, CD and AMR equally contributed Clinical Trial Registry: clinicaltrials.gov,

Background: Ischemic stroke is a devastating complication affecting children with sickle cell anemia. Genetic factors are likely to be important in determining the risk of stroke but are poorly defined. Methods: We have studied a cohort of 19 children who had an overt ischemic stroke before 4 years of age. We predicted genetic determinants of stroke would be more prominent in this group. We performed whole exome sequencing on this cohort and applied 2 hypotheses to our variant filtering. First, we looked for strong, potentially mono- or oligogenic variants for ischemic stroke, and second, we considered that more common polygenic variants will be enriched in our cohort. Candidate variants emerging from both strategies were validated in a cohort of 283 patients with sickle cell anemia and known pediatric cerebrovascular outcomes. We used principal component analysis in this cohort to control for relatedness and population substructure. Results: Our primary finding was that the Apoliprotein E genotypes epsilon 2/epsilon 4 and epsilon 4/ epsilon 4, defined by the interplay of rs7412 and rs429358, were associated with increased stroke risk, with an odds ratio of 4.35 ([95% CI, 1.85-10.0] P=0.0011) for ischemic stroke in the validation cohort. We also found that rs2297518 in NOS (NO synthase) 2 (odds ratio, 2.25 [95% CI, 1.21-4.19]; P=0.014) and rs2230123 in signal transducer and activator of transcription (odds ratio, 2.60 [95% CI, 1.30-5.20]; P=0.009) both had increased odds ratios for ischemic stroke, although these two variants were below the threshold for statistical significance after correction for multiple testing. Conclusions: These data identify new loci for future functional investigations into cerebrovascular disease in sickle cell anemia. Based on African population reference allele frequencies, the Apoliprotein E genotypes would be present in about 10% of children with sickle cell anemia and represent a genetic risk factor that is potentially modifiable by both dietary and pharmaceutical manipulation of its dyslipidemic effects.

BackgroundRecovery following a stroke is a long and ongoing process. Post-stroke follow-up after leaving the hospital is recommended. Methods for follow-up patients include face-to-face, via the telephone, post or online (internet). However, there is a debate which method is preferred by patients. This study aimed to determine whether telephone interview, online questionnaire and postal questionnaire were as acceptable as face-to-face follow-up.MethodsIn a blinded, UK-wide, multi-centre, Zelen's designed, 4-arm (postal, online, telephone, compared to face-to-face), pragmatic non-inferiority randomised controlled trial of the mode of administration, stroke survivors were randomised to postal, online, telephone and face-to-face assessment, in an equal ratio (1:1:1:1). The primary outcome was the proportion of participants that responded to the three allocation groups, compared to the face-to-face group. Subgroup analyses for age, aphasia and type and severity of stroke were carried out. A non-inferiority margin of 0.025 was used, and Holm-Bonferroni multiplicity adjustment was made.ResultsOf the 2074 eligible patients randomised, 55% were male (1142/2074), with an average age of 73.0years old (SD=13.2). Of those randomised, 22% (116/525), 9% (47/515) and 20% (101/513) responded in postal, online and telephone, respectively, compared to 17% (89/521) in the face-to-face group. The reduction in the online response rate compared to face-to-face was found to be both inferior and not non-inferior and estimated as an 8% reduction (95% CI 3.9 to 12.0%; p<0.001). The association with lower online completion was present regardless of age, stroke type (haemorrhage or infarct) and stroke severity. In haemorrhagic stroke, the reduction in response online, compared to face-to-face, was 21% (95% CI 10 to 32%; p value=0.002). A secondary analysis found non-aphasic stroke survivors preferred postal completion adjusted odds ratio of 1.43 (95% CI 1.04 to 1.95; p=0.026).ConclusionsThe study found that fewer stroke survivors completed follow-up assessment using an online method, compared to face-to-face. This finding was present in all age groups. Caution should be employed when considering online follow-up methods in stroke survivors, particularly in those who have experienced a cerebrovascular haemorrhage.Trials registrationClinicalTrials.gov, NCT03177161. Registered on 6 June 2017.

Ischemic stroke is a devastating complication of sickle cell anemia (SCA) and can affect children from a very young age. It is the commonest cause of stroke in the general pediatric population. The peak incidence is in the first decade of life and approaches 11% in the absence of stroke prevention programmes. The advent of transcranial doppler (TCD) screening as part of a primary stroke prevention programme has reduced the incidence of stroke by 90%. However, not all strokes are prevented by TCD, and TCD abnormalities are not specific, with up to 60% children receiving transfusions unnecessarily. Understanding the underlying pathophysiology of cerebrovasculopathy in SCA and recognition of important risk factors will lead to a more stringent identification of the at-risk population. Analysis of siblings with stroke and abnormal TCDs offers good evidence that a proportion of this variability is conferred by inherited genetic variation. Identifying those specific variants has proved elusive, with many conflicting findings reported in the literature, no doubt reflecting the limited power of many studies to address the complex overlay of environmental and genetic influences. To attempt to minimise the impact of non-genetic confounders, our study looked specifically at children who had an overt ischemic stroke or developed abnormal TCD measurements (TAMMV >200cm/s) prior to their 4th birthday, in the absence of potentially precipitating acute medical events. We recruited 22 patients, 19 of whom had an ischemic stroke, and 3 who developed abnormal TCD measurements, prior to 4 yrs of age. Additionally, we recruited the dizygotic twin of one stroke case, who had SCA, but, importantly, no cerebrovascular complications, as confirmed by MRI/A aged 15 yrs. We extracted DNA from peripheral blood samples. Exome library was prepared using Agilent SureSelect XT V7, sequencing was performed using Illumina NovaSeq. Alignment, assembly, variant calling and annotation were based on a GATK Best Practices workflow. For each sample, around 15000 non-synonymous variants were identified. Across the 22 case samples, 58 variants in 56 genes were predicted to be pathogenic or likely pathogenic, as determined with InterVar. These variants were interpreted with respect to dbSNP documentation and biological role of the gene they affected. Variant segregation within the twin pair was also considered. Two patients were homozygous for rs429358, a missense variant in the APOE gene that is pathogenic for familial hyperlipoproteinemia, type 3. Moreover, 3 further patients were compound heterozygous for this variant plus another APOE missense variant pathogenic for the same condition, rs7412. One of these 3 cases was the affected sibling of the twin pair and notably, the unaffected twin carried only heterozygous rs429358 and not rs7412. A further patient was heterozygous for rs121908043 in the LDL-R gene, which is pathogenic of Familial Hypercholesterolaemia, even in the heterozygous state. Finally, in an additional patient, we identified a potential compound heterozygote of a known pathogenic variant, rs118204068 with another missense variant rs11542065 in the LPL gene, to cause Hyperlipoproteinemia type 1. We have used whole exome sequencing to analyse patients with sickle cell anemia and stroke at a very young age, an extreme phenotype, in whom we predicted genetic factors would be a significant cause of stroke. We found 7 of the 22 patients (32%) had variants diagnostic of inherited dysplipidaemias, including 5 with familial hyperlipoproteinemia type 3, 1 with hyperlipoproteinemia type 1 and one with familial hypercholesterolemia. Our analysis included one twin set and it is noteworthy that the unaffected twin sibling did not carry the necessary variants defining the inherited dyslipidaemia. These conditions are characterised by improper breakdown and accumulation of LDL-C, triglycerides and cholesterol, which has been associated with vascular dysfunction and hemolysis in SCA and are strongly associated with stroke and cardiovascular disease in the general population. This is potentially an important finding that warrants further investigation into the role of lipids and hyperlipidemia in the development of stroke and cerebral vasculopathy in the sickle cell population. In the long term, we suggest that measurement, and potentially, control of lipids may form a component of the primary stroke prevention programme. Disclosures Brousse: Add medica: Consultancy; bluebird bio: Consultancy. Rees:Novartis: Other: Strategic advisory role,Principal investigator,sickle cell disease2.6 Investigator; Astra Zeneca (ticagrelor): Other: Data monitoring committees; TauRx (methylene blue): Other: Data monitoring committees; Alnylam: Other: Principal investigator; Global Blood Therapeutics: Other: Strategic advisory role; Celgene: Other: Strategic advisory role; Emmaus: Other: Strategic advisory role; Agios: Other: Grants.