ОПРЕДЕЛЕНИЕ ЭСТОЛИДОВ И ТРИАЦИЛГЛИЦЕРИНОВ МАСЛА СЕМЯН Sapium discolor: СОПОСТАВЛЕНИЕ РАЗДЕЛЕНИЯ ВЕЩЕСТВ В УСЛОВИЯХ ТРАДИЦИОННОЙ И МИКРОКОЛОНОЧНОЙ (МИЛИХРОМ А-02) ХРОМАТОГРАФИИ

Methods for the separation and UV detection of Sapium discolor seed oil estolides and triacylglycerols by traditional analytical as well as by microcolumn reversed-phase high-performance liquid chromatography approaches were developed. For the separation, the columns filled with Kromasil 100-5C18 sorbent were used together with the "propanol-2 – acteonitrile" mobile phase systems. The oil composition was calculated on the basis of the incremental approach. The propositions were confirmed by the mass-spectrometric and the electronic spectra data. The oil was shown to be composed of the traditional α-linolenic, linoleic, oleic, palmitic and stearic acids, and two unusual acids that match the literature data about their structure. Due to the presence of the acid radical with the chromophore O=COR1-CH=CH-CH=CHR2 composition in all estolides, the sensitive and the selective detection of the compounds was possible at the wavelength of 266 nm. This method of detection was a good alternative to the detection at 210 nm, allowing the detection of not only the estolides but also the triacylglycerols, although with approximately threefold reduced sensitivity. The experiment indicated the reduction of the total efficiency (as a number of theoretical plates) in the swap of traditional by microcolumn HPLC, and the subsequent method was proposed to separate the unseparated peaks that occur during this exchange by using the Magicplot student 2.7.2 software. This was achieved with good performance results of the qualitative and quantitative determination of the relative amounts of estolides in the oil.Key words: RP-HPLC, HPLC, microcolumn chromatography, triacylglycerols, estolides, UV detection, deconvolution of complex peaks, Magicplot student 2.7.2.(Russian)DOI: http://dx.doi.org/10.15826/analitika.2018.22.1.003Anh Van Nguyen1, V.I. Deineka1, Long Quoc Pham2, Phuong Lan Doan2,L.А. Deineka1 1Belgorod National Research University, Pobeda str., 85, Belgorod, Russian Federation, 308015.2 Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Viet Nam, 122300Разработаны условия разделения и УФ-детектирования эстолидов (триацилглицерины с одним олигомерным радикалом кислоты) и триацилглицеринов масла семян Sapium discolor в условиях традиционной аналитической и микроколоночной обращенно-фазовой высокоэффективной жидкостной хроматографии. Для разделения использовали колонки, заполненные сорбентом Kromasil 100-5C18, и подвижные фазы системы «пропанол-2 – ацетонитрил». С использованием инкрементного подхода рассчитан и в дальнейшем подтвержден анализом электронных и масс-спектров видовой состав компонентов масла. Показано, что масло содержит радикалы традиционных α-линоленовой, линолевой, олеиновой, пальмитиновой и стеариновой кислот и двух необычных, параметры которых удовлетворяют литературным данным об их строении. Благодаря присутствию во всех эстолидах радикала кислоты с хромофором состава O=COR1-CH=CH-CH=CHR2 возможно чувствительное селективное детектирование эстолидов при длине волны 266 нм. Этот способ детектирования является хорошим дополнением к детектированию при 210 нм, позволяющему обнаруживать не только эстолиды, но и триацилглицерины, хотя и примерно со втрое сниженной чувствительностью. Экспериментально оценено снижение суммарной эффективности (по числу теоретических тарелок) при переходе от колонок с диаметром 4-4.6 мм к микроколоночной ВЭЖХ и предложен способ разделения неразделенных пиков возникающих при этом за счет использования специальной программы Magicplot student 2.7.2, с хорошими характеристиками результатов определения относительных количеств эстолидных компонентов масла.Ключевые слова: обращенно-фазовая ВЭЖХ, микроколоночная ВЭЖХ, триацилглицерины, эстолиды, УФ-детектирование, разделение сложных пиков, Magicplot student 2.7.2.DOI: http://dx.doi.org/10.15826/analitika.2018.22.1.00

Adipose tissue-derived cytokines and their correlations with clinical characteristics in Vietnamese patients with type 2 diabetes mellitus

Adipokines are involved in the pathogenesis of metabolic disorders including obesity and type 2 diabetes mellitus (T2DM). This study investigates the levels of leptin, resistin, visfatin, secreted frizzled-related protein 5 (SFRP5), monocyte chemoattractant protein-1 (MCP-1) and retinol-binding protein 4 (RBP4) and their correlations with clinical parameters of overweight and T2DM. Methods: We recruited overweight 50 patients with T2DM, 88 non-overweight patients with T2DM, 29 overweight and 100 non-overweight individuals devoid of T2DM for this study. The levels of studied adipokines were measured by enzyme-linked immunosorbent assay and correlated with clinical parameters. Results: The levels of MCP-1 and SFRP5 were decreased while visfatin and RBP4 levels were increased in patients with T2DM compared to those in the control individuals (P<0.01). Among patients with T2DM, leptin and resistin levels were higher while RBP4 levels were lower in patients with overweight T2DM compared to those in patients with non overweight T2DM (P<0.0001, 0.019 and 0.05, respectively). Leptin and MCP-1 levels were correlated with HOMA-IR, QUICKI and HOMA-β. Leptin/MCP-1 ratio was correlated with insulin levels, HOMA-IR and HOMA-β indexes. Resistin/ RBP4, visfatin/MCP-1 and MCP-1/RBP4 ratios were strongly correlated with the levels of fasting glucose, HbA1c and HOMA-β. In addition, ROC curve analyses indicated a diagnostic potential of resistin/RBP4 and MCP-1/RBP4 indexes for T2DM (AUC=0.81 and 0.83, respectively) and β-cell function (AUC=0.76 and 0.74, respectively). Conclusions: Adipokines (leptin, resistin, visfatin, SFRP5, MCP-1, and RBP4) are associated with overweight and T2DM and may serve as a potential prognostic marker and therapeutic intervention for overweight-related T2DM

Determination of Sapium discolor seed oil estolides and triacylglycerines: comparison of the substances separation by conventional and microcolumn (Milichrome A-02) chromatography

Methods for the separation and UV detection of Sapium discolor seed oil estolides and triacylglycerols by traditional analytical as well as by microcolumn reversed-phase high-performance liquid chromatography approaches were developed. For the separation, the columns filled with Kromasil 100-5C18 sorbent were used together with the "propanol-2 - acteonitrile" mobile phase systems. The oil composition was calculated on the basis of the incremental approach. The propositions were confirmed by the mass-spectrometric and the electronic spectra data. The oil was shown to be composed of the traditional ?-linolenic, linoleic, oleic, palmitic and stearic acids, and two unusual acids that match the literature data about their structure. Due to the presence of the acid radical with the chromophore O=COR1-CH=CH-CH=CHR2 composition in all estolides, the sensitive and the selective detection of the compounds was possible at the wavelength of 266 nm. This method of detection was a good alternative to the detection at 210 nm, allowing the detection of not only the estolides but also the triacylglycerols, although with approximately threefold reduced sensitivity. The experiment indicated the reduction of the total efficiency (as a number of theoretical plates) in the swap of traditional by microcolumn HPLC, and the subsequent method was proposed to separate the unseparated peaks that occur during this exchange by using the Magicplot student 2.7.2 software. This was achieved with good performance results of the qualitative and quantitative determination of the relative amounts of estolides in the oil.Разработаны условия разделения и УФ-детектирования эстолидов (триацилглицерины с одним олигомерным радикалом кислоты) и триацилглицеринов масла семян Sapium discolor в условиях традиционной аналитической и микроколоночной обращенно-фазовой высокоэффективной жидкостной хроматографии. Для разделения использовали колонки, заполненные сорбентом Kromasil 100-5C18, и подвижные фазы системы «пропанол-2 - ацетонитрил». С использованием инкрементного подхода рассчитан и в дальнейшем подтвержден анализом электронных и масс-спектров видовой состав компонентов масла. Показано, что масло содержит радикалы традиционных ?-линоленовой, линолевой, олеиновой, пальмитиновой и стеариновой кислот и двух необычных, параметры которых удовлетворяют литературным данным об их строении. Благодаря присутствию во всех эстолидах радикала кислоты с хромофором состава O=COR1-CH=CH-CH=CHR2 возможно чувствительное селективное детектирование эстолидов при длине волны 266 нм. Этот способ детектирования является хорошим дополнением к детектированию при 210 нм, позволяющему обнаруживать не только эстолиды, но и триацилглицерины, хотя и примерно со втрое сниженной чувствительностью. Экспериментально оценено снижение суммарной эффективности (по числу теоретических тарелок) при переходе от колонок с диаметром 4-4.6 мм к микроколоночной ВЭЖХ и предложен способ разделения неразделенных пиков возникающих при этом за счет использования специальной программы Magicplot student 2.7.2, с хорошими характеристиками результатов определения относительных количеств эстолидных компонентов масла

The influence of human genetic variation on early transcriptional responses and protective immunity following immunization with Rotarix vaccine in infants in Ho Chi Minh City in Vietnam : a study protocol for an open single-arm interventional trial [awaiting peer review]

Background: Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design: We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion: This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389. Registered on 16 July 2018

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury. Funding: Bill & Melinda Gates Foundation

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. Methods We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. Findings Globally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1-7·8), from 65·6 years (65·3-65·8) in 1990 to 73·0 years (72·7-73·3) in 2017. The increase in years of life varied from 5·1 years (5·0-5·3) in high SDI countries to 12·0 years (11·3-12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1-33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8-15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9-6·7), from 57·0 years (54·6-59·1) in 1990 to 63·3 years (60·5-65·7) in 2017. The increase varied from 3·8 years (3·4-4·1) in high SDI countries to 10·5 years (9·8-11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4-1·7) in Saint Vincent and the Grenadines (62·4 years [59·9-64·7] in 1990 to 63·5 years [60·9-65·8] in 2017) to 23·7 years (21·9-25·6) in Eritrea (30·7 years [28·9-32·2] in 1990 to 54·4 years [51·5-57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6-2·3) in Algeria to 11·9 years (10·9-12·9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75·8 years [72·4-78·7]) and males (72·6 years [69·8-75·0]) and the lowest estimates were in Central African Republic (47·0 years [43·7-50·2] for females and 42·8 years [40·1-45·6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41·3% (38·8-43·5) for communicable diseases and by 49·8% (47·9-51·6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40·1% (36·8-43·0), although age-standardised DALY rates decreased by 18·1% (16·0-20·2)

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

The Global Burden of Diseases, Injuries and Risk Factors 2017 includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke