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1.
Aravinthan Varatharaj Maria Liljeroth Stig Cramer Charlotte Stuart Elina Zotova Angela Darekar Henrik Larsson Ian Galea 《Lancet》2017
Background
Systemic inflammation can affect disease expression in multiple sclerosis. The mechanism might involve blood–brain barrier disruption. We aimed to assess the effects of systemic inflammation on disease progression in multiple sclerosis and the role of blood–brain barrier disruption.Methods
We recruited adults with relapsing–remitting multiple sclerosis and healthy controls from the general population. Three-dimensional dynamic-contrast enhanced MRI was used to measure blood–brain barrier permeability in the normal-appearing white matter (NAWM). Urinary neopterin, a product of activated macrophages, was measured to provide a readout of systemic inflammation. All study activities were performed in University Hospital Southampton after ethics approval (REC 12/SC/0176).Findings
12 patients with mutliple sclerosis and 12 healthy controls were recruited. Blood–brain barrier permeability in NAWM, measured as the constant Ktrans, was significantly higher in patients than in controls (mean 0·024 ml/100g per min [SD·0·018] vs 0·006 [0·004], p=0·015). Systemic inflammatory activity, measured as the urinary neopterin:creatinine ratio (UNCR), was also significantly higher (3·35 [1·98] vs 1·36 [0·29], p=0·002). Across all participants, there was a weak positive correlation between Ktrans and UNCR (r=0·40, p=0·031).Interpretation
Our findings support the hypothesis that the effects of systemic inflammation on expression of multiple sclerosis disease are mediated by blood–brain barrier disruption. Targeting this disruption and systemic inflammation might provide novel avenues for disease-modifying therapy.Funding
University of Southampton, National Institute for Health Research, Multiple Sclerosis Society. 相似文献2.
Background
Trachoma is the most common infectious cause of blindness worldwide. In-vivo confocal microscopy (IVCM) provides high-resolution images of the ocular surface. We have previously reported a grading system for the quantitative assessment of these images in scarring trachoma. We found that the presence of trachomatous scarring was strongly associated with the presence of dendritiform cells (DFCs). The present study assessed whether there is an association between DFCs and clinical progression in scarring.Methods
Participants with trachomatous scarring in northern Tanzania were examined at baseline and 24 months (clinical assessment, photography, and IVCM of the upper tarsal conjunctiva). IVCM images were graded according to a validated grading system. Two independent observers identified scarring progression by comparing photographs taken at baseline and 24 months.Findings
800 participants were assessed clinically at baseline and 617 of them were re-examined at 24 months. There were 465 individuals who had photographs that could be confidently graded as having either progression or scarring, or not having progression. Progression was found to occur in 113 (24%) of the 465 individuals. IVCM images were obtained in 344 of these participants at baseline and 24 months, and 29 (8·4%) had DFCs present at baseline. The presence of DFCs at baseline was significantly associated with scarring progression (p=0·01), including adjustment for age and sex (p=0·03).Interpretation
The presence of DFCs on IVCM images is associated with progressive trachomatous conjunctival scarring. DFCs are thought to represent dendritic cells, which have a central role in mediating the immune response and potentially in the pathogenesis of trachomatous scarring. The nature of these cells warrants further investigation, potentially as a novel antifibrotic therapeutic target.Funding
Wellcome Trust senior research fellowship (to MB). National Institute for Health and Research academic clinical fellowship (to JH). 相似文献3.
Background
Infections can trigger acute vascular events but the differential effect of specific respiratory pathogens is unknown. We aimed to quantify the association between laboratory-confirmed respiratory bacterial or viral infections and first myocardial infarction or stroke to inform intervention development and targeting.Methods
Scottish Morbidity Record data on first myocardial infarction or stroke (International Classification of Diseases, 10th revision, codes) were linked to records of Streptococcus pneumoniae, influenza, rhinovirus, parainfluenza, respiratory syncytial virus, or human metapneumovirus from the Electronic Communication of Surveillance in Scotland (National Services Scotland) dataset on individuals aged 40 years or older from Jan 1, 2004, to Dec 31, 2014. We analysed incidence ratios for myocardial infarction or stroke in the 28 days after infection compared with baseline using self-controlled case series.Findings
There were 1227 individuals with myocardial infarction (751 men [61%]) and 762 with stroke (392 men [51%]). Median age was 68 years (IQR 59–77). The relative incidence of myocardial infarction was markedly raised in the first 1–3 days after both bacterial and viral infections (incidence ratio 5·98, 95% CI 2·47–14·4 [p<0·0001] and 5·59, 1·77–17·6 [p=0·003], respectively) and persisted for about 1 week. For stroke, the respective relative incidence after respiratory infection was even higher for days 1–3 (12·3, 5·48–27·7 [p<0·0001] and 6·79, 1·67–27·50 [p=0·007]). Elevated stroke risks after both bacterial and viral infections persisted to 28 days (p<0·0001).Interpretation
Our findings suggest that respiratory bacterial and viral infections act as vascular triggers. For stroke, the incidence ratio remained elevated a month after the date of respiratory sampling but for myocardial infarction the raised incidence ratio appeared to be more transient, suggesting potentially different mechanisms. This study highlights the need to ensure adequate uptake of influenza and pneumococcal vaccines as well as appropriate treatment during infections to reduce vascular risk.Funding
Academy of Medical Sciences. 相似文献4.
Sujit Mukherjee Oltin Pop Evangelos Triantafyllou Wafa Khamri Stuart Curbishley Mark Thursz David Adams Charalambos Antoniades 《Lancet》2017
Background
Tumour-associated macrophages are implicated in progression of hepatocellular carcinoma by dampening immune responses. Experimental models show that activation of the tumour-associated macrophage receptor, tyrosine-protein kinase mer (MERTK), in myeloid cells promotes tumour progression by suppressing innate and adaptive responses. We sought to investigate the role of MERTK and its sister molecule, AXL, in patients with hepatocellular carcinoma.Methods
Immunohistochemistry and multispectral imaging were performed for MERTK, AXL, and various macrophage activation markers on explanted hepatocellular carcinoma tissue (n=10), regenerative nodules (5), dysplastic nodules (5), and cirrhotic liver (controls, 5). Immunophenotyping of circulating monocytes was done. In-vitro co-culture systems were developed to modulate tumour-associated macrophage MERTK expression and determine the effects on CD14+, CD4+, and CD8+ leucocyte function.Findings
Peripheral leucocytes in hepatocellular carcinoma had higher MERTK expression (22·4% vs 10·7%, p=0·01) and a higher ratio of MERTK to AXL expression (39·1:1 vs 4·6:1, p=0·03) than cirrhotic controls. Immunohistochemical analysis confirmed increased macrophage MERTK expression in hepatocellular carcinoma compared with cirrhotic and healthy controls (p=0·01 and p=0·02, respectively). In vitro, induction of MERTK expression in CD14+ antigen-presenting cells reduced CD8+ (2·9% vs 10·7%, p=0·02) and CD4+ (3·6% vs 1·0%, p=0·04) T-cell proliferative responses to class I and II restricted antigens, respectively, with concomitant reduction (1·18% vs 5·59%, p=0·03) in the early activation marker CD69 in CD8+ T cells at 24 h. Antibody-mediated blockade of MERTK restored mean fluorescence intensity of the early activation marker CD28 in the same cells (p=0·037).Interpretation
We have identified an expanded population of MERTK-expressing immunosuppressive tumour macrophages in hepatocellular carcinoma. These cells can suppress innate and adaptive immune responses. We have shown that AXL is not similarly upregulated. Inhibition of MERTK signalling restores macrophage activation, thereby potentially identifying a novel immunotherapeutic target in hepatocellular carcinoma.Funding
National Institute for Health Research academic clinical fellowship. 相似文献5.
Background
Long-acting injectable (LAI) antipsychotics have been shown to reduce risk of relapse in people with psychosis. Second generation LAI antipsychotics such as paliperidone palmitate can have fewer side-effects and be better tolerated than first generation LAI antipsychotics. However, paliperidone palmitate is more expensive and there are few data comparing its effectiveness and tolerability with that of other LAI antipsychotics. We sought to address this issue by analysing a large electronic mental health case register.Methods
The South London and Maudsley NHS Foundation Trust Biomedical Research Centre Case Register was used to obtain data about people who had started treatment with an LAI antipsychotic between April 1, 2011, and Jan 31, 2015. The number of days spent as a psychiatric inpatient and the number of admissions to a psychiatric hospital were analysed using multivariable regression with age, sex, ethnicity, marital status, diagnosis, and London borough of residence as covariates.Findings
1281 people had started treatment with LAI antipsychotics. The most frequently prescribed LAI was paliperidone palmitate (n=430, 33·6%) followed by zuclopenthixol decanoate (226, 17·6%), flupentixol decanoate (203, 15·9%), risperidone (160, 12·5%), pipotiazine palmitate (114, 8·9%), haloperidol (71, 5·5%), fluphenazine decanoate (36, 2·8%), aripiprazole (27, 2·1%), and olanzapine embonate (14, 1·1%). There were no significant differences between paliperidone and other LAI antipsychotics in the number of days as an inpatient (β coefficient 5·4 days, 95% CI ?57·3 to 68·2) or number of hospital admissions after initiation of treatment (incidence rate ratio 1·07, 95% CI 0·62 to 1·83).Interpretation
The absence of differences in hospital admission after initiation of LAI antipsychotics indicates that the effectiveness of the second generation LAI paliperidone palmitate was similar to that of other LAI antipsychotics. However, the discontinuation rate in the first year of treatment is lower for paliperidone palmitate (35%) than for other LAI antipsychotics suggesting that it is better tolerated. These findings merit consideration in relation to the choice of LAI antipsychotic to prescribe in people with psychotic disorders.Funding
National Institute for Health Research, Medical Research Council. 相似文献6.
Jason J Ong Haochu Li Wu Dan Hongyun Fu Ewen Liu Wei Ma Demin Kang Meizhen Liao Gifty Marley Chongyi Wei Weiming Tang Stephen Pan Chuncheng Liu Bin Yang Ligang Yang Shujie Huang Joseph D Tucker 《Lancet》2017
Background
The wide range of interventions to promote HIV testing might inadvertently contribute to coerced testing. There has been concern about coerced HIV self-testing in non-research settings where there is minimal supervision. The aim of this study was to examine the prevalence and correlates of coerced HIV testing among men who have sex with men (MSM) in China.Methods
In July 2016, we recruited MSM from eight cities through BlueD, a gay social network mobile application. Data on sociodemographics, HIV self-testing, HIV facility testing, test coercion, condomless sex in the past 3 months, and transactional sex were collected. Coerced testing was defined as someone (partner, friend, employer, or others) forcing the participant to take an HIV test. Multivariable logistic regression was used to examine correlates of coerced testing among MSM who had ever received HIV testing.Findings
1312 men were included, most of whom were young (mean age 26·9 years [SD 6·3]). 1002 (76%) men were identified as gay, and 685 (52%) men had used HIV self-testing. 64 (15%) men reported coerced testing, and 39 of these men were forced to have a self-test. Adjusting for age, education, income, and residence, men who reported coerced testing were more likely to have ever self-tested for HIV (adjusted odds ratio 4·25; 95% CI 2·23–8·09). Coerced testing was more common among men who had sex with casual partners in exchange for gifts or money (3·34; 1·90–5·86) than among men who did not report transactional sex. Coerced testing was also more common among MSM who reported condomless anal sex in the preceding 3 months (2·38; 1·43–3·98) than among men who did not report condomless anal sex.Interpretation
HIV test coercion is uncommon among MSM in China, but is more likely in men who used HIV self-tests. As HIV self-testing is scaled up worldwide, research and enhanced post-test surveillance are needed.Funding
National Institute of Allergy and Infectious Diseases (1R01AI114310-01) and the Australian National Health Medical Research Council (APP1104781). The funders had no role in the design of the study, the collection, analysis, and interpretation of data, or in the writing of the Abstract. 相似文献7.
Background
Greater investment in primary care yields better population health outcomes. However, in the past decade general practice (GP) funding has reduced, while general practitioner workload has risen and secondary care funding has increased. To date, the impact of broader aspects of GP funding has not been examined. Using newly released GP financial data, we aimed to explore the association between greater investment in primary care and secondary care usage and costs applied at a national level in England.Methods
We constructed linear regression models to explore the association between practice funding for essential services and quality and outcomes framework (QOF) achievement, secondary care usage (accident and emergency [A&E] attendance, emergency admission, and outpatient attendance rates per 1000 registered patients), and patient satisfaction, adjusted for practice and demographic variables. We then conducted financial modelling to predict the impact of a hypothetical 10% funding increase on secondary care costs, for which we used standard cost estimates.Findings
We analysed 7767 practices in England. Mean funding per patient was £79·81 (95% CI 67·01–100·67). Funding was lower in General Medical Services (GMS) practices, which hold national contracts, than in Personal Medical Services practices, which have local contracts (£76·00 [66·52–89·20] vs 84·43 [66·68–107·09]). In GMS practices, greater funding was significantly associated with lower emergency admissions (regression coefficient β=–0·22), lower A&E attendances (?1·04), and higher patient satisfaction (overall satisfaction 0·4). We found no significant association with outpatient attendance or QOF performance. In our financial model, a 10% increase in primary care funding would create a return on investment of 78% in GMS practices overall and up to 110% in GMS practices receiving funding above the national capitation formula.Interpretation
GMS practices with higher levels of funding had lower secondary care usage and higher patient satisfaction. The lack of association between funding and QOF achievement might be attributable to the different funding stream and incentives for QOF. Our findings support the case for greater investment in primary care where the value of investment is over and above the national capitation formula.Funding
National Institute for Health Research. 相似文献8.
Background
Cancer cell plasticity, as seen in epithelial-to-mesenchymal transition, can lead to metastasis and therapeutic failure. Another cell type, the amoeboid, has now been isolated in oral cancer. Previously seen in, but not isolated from melanomas and sarcomas, it has been associated with poorer prognosis. The aim of the study was to investigate the role of the amoeboid cell in oral cancer, with the hypothesis that it is a plastic, but more invasive and chemoresistant, cell type.Methods
In this in-vitro study of oral cancer cell lines (n=6), fresh tumour specimens, and mice, we used high-throughput invasion assays, migration and drug response assays, protein and gene expression profiling, mechanistic and pathway analysis, fluorescence-activated cell sorting, gene knockdowns, and immunostaining. At least three cell lines were used for each laboratory technique, with a minimum of triplicate repeats and appropriate statistical analysis.Findings
In all cell lines, amoeboid cells were smaller than both epithelial and mesenchymal cells (median cell area 295 μm2 [IQR 218–399] vs 884 [573–1281] vs 598 [413–815]) but were significantly more migratory with a mean velocity of 1·1 μm/min (SD 0·2) versus 0·16 (0·08) for mesenchymal cells (p<0·0001). Amoeboid cells were four to 20 times more invasive than other cell types (p<0·0001). Greater chemoresistance was demonstrated against common agents including paclitaxel and etoposide. Gene analysis produced signatures associated with angiogenesis, anti-apoptosis, and invasion. Stemness genes were upregulated. Plasticity between phenotypes was clearly seen.Interpretation
We describe a new amoeboid cell phenotype, which is derived from epithelial cancer cells, that might confer upon carcinomas a greater ability to invade, disseminate, and resist therapy. A switch to an amoeboid phenotype could be a useful escape strategy for cancers, providing them with alternative modes for migration and invasion. However, this cell type essentially lacks keratin, which could complicate histopathological assessment of tumour spread. Pathway elucidation might yield new potential amoeboid targets. Targeting amoeboid cells, which may now become possible with their isolation and analysis, could be essential to improve patient outcomes.Funding
Royal College of Surgeons of England, British Association of Oral and Maxillofacial Surgeons, Facial Surgery Research Foundation, Faculty of Dental Surgeons (Royal College of Surgeons of England). 相似文献9.
Background
There is no standardised instrument for assessing social functioning in dementia, even though decline in social functioning is one of the diagnostic criteria for dementia and important to patients and their families. We aimed to develop a valid, reliable, acceptable instrument for assessing social function in people with dementia.Methods
We conducted qualitative interviews with 18 dyads of people with dementia and their family carers, a literature review, and focus groups with expert health-care professionals to develop the Social Functioning in Dementia (SF-DEM) instrument. SF-DEM measures the social functioning of a person with dementia using their own rating or a family carer's rating. We tested acceptability and psychometric properties of these measures in structured interviews at baseline and at 4 weeks' and 6–8 months' follow-up in a cohort of 30 dyads of people with mild dementia and their carers.Findings
SF-DEM had content validity. The instrument was acceptable to both patients and carers, who all rated it as acceptable or very acceptable. Inter-rater agreement was good or very good for all questions. Test–retest reliability was very strong for the carer-rated SF-DEM (intraclass correlation coefficient 0·89, 95% CI 0·73 to 0·96) and patient-rated version (0·80, 0·54 to 0·92), and both versions had internal consistency (Cronbach's α=0·71 for carer-rated SF-DEM and 0·64 for patient-rated). SF-DEM had concurrent validity, since it was moderately correlated with a question about overall social functioning (r=0·60, 95% CI 0·29 to 0·78 for carer-rated; 0·44, 0·07 to 0·68 for patient-rated). SF-DEM also had convergent validity, as evidenced by a moderate correlation between patient and carer ratings (r=0·59, 95% CI 0·07 to 0·81). At follow-up (mean duration 7·2 months, SD 0·5), patient-rated SF-DEM score increased by 1·3 points (95% CI ?0·3 to 2·9, p=0·10) and caregiver-rated SF-DEM score increased by 1·4 points (?0·1 to 2·9, p=0·06) for each point on a five point ordinal scale of social change.Interpretation
Patient-rated and carer-rated versions of the SF-DEM are reliable, valid, and acceptable measures of social function in people with mild dementia. Further research is required to test the generalisability to other populations.Funding
None. 相似文献10.
Background
Neuroblastoma is the commonest cancer in infants. Survival in high-risk groups is low (40–50%). Newer treatments are needed to improve survival and morbidity. Cytomegalovirus (CMV) is a common viral infection, which increases γδ T cells. We investigated the use of CMV-reactive γδ T cells as a potential new immunotherapy.Methods
Peripheral blood mononuclear cells from 30 paediatric haemato-oncology patients with or without CMV infection were analysed by flow cytometry. γδ T cells were expanded, and then co-cultured with CMV targets or neuroblastoma cells. T-cell activation, cytokine secretion, killing activity, and mechanisms were determined by ELISA, MTT colorimetric assay, and blocking assays. Novel γδ T cell receptors (TCR) were identified by sequencing.Findings
In paediatric haemato-oncology patients, acute CMV led to higher proportions of total γδ T cells (p=0·0002) with the dominant subtype Vδ1 (p=0·0035). CMV-reactive γδ T cells were of the effector memory phenotype and expanded to clinically significant numbers for adoptive transfer. When compared with γδ T cells from CMV-negative patients, CMV-reactive γδ T cells had statistically significantly higher interferon γ release (p<0·001) in co-cultures with CMV-infected fibroblasts and showed cytolytic activity against CMV-infected fibroblasts and neuroblastoma cells which was mediated by γδ TCR and the NKG2D receptor. Sequencing showed that the dominant γδ T-cell chains in CMV-infected patients were Vδ1 Vγ2. Within the TCRs, CDR3 sequences had minimal diversity, γ chains had wide variations, and we identified a novel subpopulation in some patients.Interpretation
We show that acute CMV infection in paediatric haemato-oncology patients leads to an increase in the Vδ1 Vγ2 subtype of γδ T cells. They can be expanded for adoptive transfer and are likely to retain killing ability post expansion. They recognise and kill CMV-infected targets and neuroblastoma cells via the γδ TCR and the NKG2D receptor. We have identified a novel TCR in a subpopulation of CMV-positive patients.Funding
Great Ormond Street Charity, National Institute for Health Research Biomedical Research Centre, Olivia Hodson Cancer Fund. 相似文献11.
Background
The burden of non-communicable diseases burden in China is enormous, with tobacco consumption a leading risk factor for the most prevalent NCDs. Therefore, understanding pattern of socioeconomic equalities of tobacco consumption will help to design targeted public health control measures. We aimed to investigate who tends to consume most tobacco in China.Methods
Nationally representative data from the 2013 China Health and Retirement Longitudinal Study (CHARLS) included smoking information on 17?663 respondents aged 45 years and older. Smoking prevalence and smoking quantities were defined to capture tobacco consumption. Using concentration index (defined as twice the area between the concentration curve and the line of equality), we estimated income-related inequality of tobacco consumption grouped by gender. The inequality of tobacco consumption was further decomposed into each determinant's specific contribution on using probit regression analysis and Ordinary Least Squares (OLS) regression models.Findings
About 16·03% of respondents consumed tobacco. By sex, 8449 men (29·65%) and 9213 women (3·54%) consumed tobacco. Furthermore, we found a significant pro-rich inequality of tobacco consumption. The concentration index of smoking incidence was 0·0438 (0·0412 for men; ?0·0393 for women). The concentration index of smoking quantities among people who smoke was 0·0385 (0·0333 for men; 0·0381 for women), whereas the concentration index of smoking quantities in the whole population was 0·0748 (0·0675 for men; ?0·0044 for women). Most of the inequality can be explained by education attainments, age, geographical areas, and economic status.Interpretation
Sex, education attainments, age, geographical areas, and economic status were strong predictors of tobacco consumption in China. Public health policies need to be targeted towards the less educated people and elderly people. Both the pattern and magnitude of inequality varied greatly between men and women, and public policies for tobacco control in men should be strengthened at southern-central and northern areas of China, whereas public policies for women should be strengthened in the eastern and northeastern areas of China.Funding
Research Program of Shaanxi Soft Science (2015KRM117), Shaanxi Provincial Youth Star of Science and Technology in 2016, Basic Scientific Research Funding of Xi'an Jiaotong University (SK2015007), and National Program for Support of Top-notch Young Professionals and China Medical Board (15-227). 相似文献12.
Felicity Fitzgerald Kevin Wing Asad Naveed Musa Gbessay J C G Ross Francesco Checchi Daniel Youkee Mohammed Boie Jalloh David Baion Ayeshatu Mustapha Hawanatu Jah Sandra Lako Shefali Oza Sabah Boufkhed Reynold Feury Julia Bielicki Elizabeth Williamson Diana M Gibb Shunmay Yeung 《Lancet》2017
Background
The case definition for suspected Ebola virus disease is broad, so many negative children are isolated for testing, risking nosocomial infection. We collected data on children admitted to Ebola holding units in Sierra Leone to refine the case definition and describe outcomes of admitted children.Methods
All children aged less than 13 years admitted to 11 Ebola holding units in Sierra Leone between Aug 1, 2014, and March 31, 2015, were eligible for inclusion. Data were collected from paper-based clinical records, district-wide laboratory results, burial records, staff interviews, and follow-up telephone calls. The cohort was split into training and validation datasets. A model was developed with multivariable logistic regression and compared with laboratory results to explore the sensitivity and specificity of the alternative case definition.Findings
Of 1054 children admitted, 309 (29%) tested positive for Ebola virus disease and 697 (66%) tested negative (48 [5%] missing). The model had an area under receiver operating characteristic curve of 0·80 (high performance). A case definition of Ebola virus disease contact alone, fever (in children >2 years), or fever and conjunctivitis (<2 years) was 94% sensitive and 35% specific. Contact, fever, and conjunctivitis, or contact, fever, anorexia, and two of abdominal pain, diarrhoea, or male sex (>2 years) improved specificity (97%), with sensitivity of 23%. Children testing negative had a case fatality rate of 8% versus 57% in those with Ebola virus disease (p<0·001).Interpretation
Contact history, fever, conjunctivitis, abdominal pain, and diarrhoea are key characteristics for diagnosis of paediatric Ebola virus disease. The case definitions developed can be used flexibly—for example, for triage into risk categories to reduce risk of nosocomial infection.Funding
Save the Children. 相似文献13.
Background
In 2013, the authors of the World Alzheimer Report estimated that 44·35 million people had dementia worldwide, causing a substantial economic cost for the society. Objective, systematic economic costs caused by dementia are needed to track disease burden and inform health policy. We aimed to estimate the global economic burden of dementia by country and regions.Methods
We searched PubMed, Google Scholar, Web of Science, the China National Knowledge Infrastructure Database, and Wanfang databases for studies of the economic costs of Alzheimer's disease and other forms of dementia that were published between Jan 1, 2000, and April 1, 2017. On the basis of the scienti?c literature and regressions, we used the latest dementia prevalence estimates from the 2013 World Alzheimer's Disease Report and several other data sources to estimate the economic costs of dementia by setting for different countries and regions.Findings
Our global estimates suggest that the total economic costs caused by dementia increased from US$279·6 billion in 2000 to $948 billion in 2016, with an annual growth rate of 15·94%. This included costs of informal care at $95·1 billion in 2000 and $401·9 billion in 2016, with the annual growth rate of 21·50%. Regional differences in the economic burden of dementia exist, and the highest economic burden was found in Europe and North America.Interpretation
Our ?ndings suggest that dementia is a substantial economic burden worldwide. A global and regional strategic action plan for dementia will be important to reduce the future burden of dementia.Funding
Tsinghua University Education Foundation (Global Health Program, 16-263). 相似文献14.
Yu-Lan Zhao Han-Huan Luo Xin-Tian Zhang Zashi Bianba Lin Li Qian Wang Lei Guo Dian Wang Yong-Ge Ze Shan Zheng 《Lancet》2017
Background
The rural and urban integration health-care system is a new and improved health-care system in Tibet, China. The aim of this study was to investigate whether these improvements might alter the clinical–pathologic characteristics of Tibetan female with breast cancer in Tibet.Methods
This was a single-centre cross-sectional study at Tibet Autonomous Region People's Hospital. We included Tibetan adult women who had been treated for breast cancer in this hospital between Jan 1, 1973, and Dec 31, 2015. The inclusion criteria were: (1) Tibetan adult woman living in Tibet; (2) histopathology or cytopathology, or both, confirming primary breast cancer; and (3) all the treatments were finished in this hospital. The Ethics Committee of TAR People's Hospital passed this project (ID Num: ME-TBHP-15-1). Patient consent was not required according to the routine. χ2 test and logistic regression were applied, using age group and census register as the two covariates.Findings
We included 273 patients with breast cancer in the final analysis. 14 patients were in the free health-care system, 183 patients had medical insurance combined with a rural cooperative health-care system, and 76 were in a rural and urban integration health-care system. We found a decrease in tumour size (>2 cm vs 2cm; odds ratio 0·117; 95% CI 0·036–0·383) and a decrease in the proportion patients who had invasion (0·460; 0·265–0·797) among women in the rural and urban integration health–care system. The proportion of patients in early stage cancer (5·737; 1·117–29·468) and advanced stage cancer (3·917; 1·406–10·914) increased in the rural and urban integration health–care system.Interpretation
This was the first report about Tibetan women with breast cancer in Tibet. Except for advanced stage breast cancer, the clinical–pathological characteristics of Tibetan women with breast cancer improved during different health-care systems. The overall management in patients with breast cancer in advanced stage might be one of the emphases in the rural and urban integration health-care system. Information and selection bias might be the limitations of this study.Funding
Natural Science Foundation of Tibet Autonomous Region (2015ZR-13-61). 相似文献15.
Carol Kan Jonathan Coleman Anubha Mahajan Mark McCarthy Gerome Breen Khalida Ismail Cathryn Lewis 《Lancet》2017
Background
A genetic overlap between type 2 diabetes and depression has been reported in twin studies, but the finding has not been replicated with data from genome-wide association studies. Visceral adiposity has been postulated as being on the causal pathway of the association between type 2 diabetes and depression. Since waist-to-hip ratio can be a proxy measure of intra-abdominal fat deposition, we examined its effect on the association using the polygenic scores approach in the UK Biobank.Methods
Type 2 diabetes polygenic scores were constructed from the association summary statistics of the Diabetes Genetic Replication And Meta-analysis Consortium, and depression polygenic scores from the Psychiatric Genetics Consortium Major Depressive Disorders Workgroup (29 studies at seven association p-value thresholds [p=0·001 to p=0·5). Logistic regression examined the association between type 2 diabetes polygenic scores and depression case-control status and the effect of body-mass index (BMI)-adjusted waist-to-hip ratio on the association, adjusting for ancestry, centres, and genotyping batches.Findings
The UK Biobank sample with genotyping data consisted of 152?551 participants. There were 10?005 cases and 19?314 controls for depression among individuals of European ancestry, with a mean age of 57·1 years (SD 7·8), BMI of 27·5 kg/m2 (4·7), and waist-to-hip ratio of 0·88 (0·09). Type 2 diabetes polygenic scores were not predictive of depression case-status at all p-value thresholds examined. The interaction between waist-to-hip ratio and type 2 diabetes polygenic scores had an effect on depression case-status (at p-value threshholds <0·2, β=0·37, p=0·02).Interpretation
Our exploratory study tentatively suggests that waist-to-hip ratio might have a role in the effect of type 2 diabetes polygenic scores on depression case-status. Higher adiposity is associated with greater level of inflammation, which is in turn associated with increased risk of type 2 diabetes and depression. Further research is needed to determine the direction of causation and to replicate our finding, given the cross-sectional design and the proxy use of waist-to-hip ratio for visceral adiposity.Funding
Novo Nordisk UK Research Foundation. 相似文献16.
Fanfan Chan Niannian Chen Jianrong He Jinhua Lu Fanghua Liu Weidong Li Wanqing Xiao Songying Shen Mingyang Yuan Kar Keung Cheng Huimin Xia Ben Willem Mol Xiu Qiu 《Lancet》2017
Background
Gestational hypertension and pre-eclampsia are major causes of perinatal mortality. Prediction of gestational hypertension and pre-eclampsia is of great interest because it enables early intervention, thus improving prognosis. Most existing prediction models consist of biomarkers, which might be unavailable in low-resourced countries. We aimed to establish a prediction model of gestational hypertension and pre-eclampsia using data at early pregnancy.Methods
We studied women with singleton delivery from Born in Guangzhou Cohort Study (BIGCS), China. Predictors included maternal age, educational level, income level, prepregnancy weight, height, passive smoking, and blood pressure collected at the first antenatal-care visit (around 16 weeks' gestation). Information on diagnosis of gestational hypertension or pre-eclampsia was extracted from medical records using international classification of disease code (ICD-10). We used logistic regression to develop prediction models. Discrimination and calibration were assessed with receiver operation characteristics (ROC) and calibration plot, respectively.Findings
Between Feb 1, 2012, and Jan 1, 2016, we recruited 12?915 women, of which 326 (2·52%) women were diagnosed with gestational hypertension and 82 (0·66%) had pre-eclampsia. The prediction model for gestational hypertension with maternal characteristics alone had an area under the ROC-curve of 0·67 (95% CI 0·62–0·72). Maternal mean arterial pressure (MAP) had an area under the curve (AUC) of 0·74 (95% CI 0·70–0·79), whereas the AUC of the model with MAP and maternal characteristic combined was 0·76 (0·72–0·81), which was slightly better than for MAP alone (p=0·03). Results for prediction of pre-eclampsia were very similar to those of gestational hypertension. Calibration plots showed that the prediction model with MAP had good fit.Interpretation
Our findings show that MAP has acceptable predictive ability of gestational hypertension and pre-eclampsia and can be used to triage further care. Our relatively large sample size ensured stronger statistical power. Model validation need to be performed in a separate population.Funding
National Natural Science Foundation of China (81673181), Guangzhou Science and Technology Bureau, Guangzhou, China (2011Y2-00025, 201508030037) 相似文献17.
Laura L Meijer Adam E Frampton Ingrid Garajová Chiara Caparello Tessa Y S Le Large Niccola Funel Enrico Vasile Justin Stebbing Jonathan Krell Geert Kazemier Elisa Giovannetti 《Lancet》2017
Background
Advanced pancreatic ductal adenocarcinoma remains a clinical challenge. Only a third of patients receiving FOLFIRINOX combination chemotherapy displays tumour downstaging. Because of their high stability in plasma, especially in extracellular vesicles, microRNAs (miRNAs) hold great promise as a new class of minimally invasive biomarkers. Our aim was to identify differently expressed, blood-based miRNAs to select and monitor patients with advanced pancreatic ductal adenocarcinoma who would benefit from FOLFIRINOX.Methods
In this prospective, multicentre study, we enrolled 50 patients with locally advanced or metastatic pancreatic ductal adenocarcinoma receiving FOLFIRINOX. The first cohort of 11 patients was selected according to their short versus long progression-free survival, and miRNA profiling was performed to identify differentially expressed circulating-free miRNAs. Emerging miRNAs, as well as various endogenous control miRNAs, were then validated in extracellular vesicles by RT-PCR in a second cohort of 16 non-progressive patients (ie, those with partial response or stable disease). No further analyses were performed in the other 23 patients, who included progressive patients or those without samples available for exosomes extraction.Findings
MiR-29a emerged as a potential biomarker both in the profiling and RT-PCR analyses, in the first and second cohorts, respectively. In particular, it was significantly upregulated (2·36-fold change, p=0·0024) in extracellular vesicles after five cycles of FOLFIRINOX therapy in non-progressive disease. Interestingly, the expression of miR-29a was significantly higher in extracellular vesicles than in circulating free miR-29a (p<0·0001). In addition, three miRNAs were considered to be normalising miRNAs; miR-93 showed the most stable expression and was chosen as an endogenous control.Interpretation
We show that altered levels of miR-29a in plasma extracellular vesicles can anticipate progression of pancreatic ductal adenocarcinoma and guide therapeutic options. Higher miR-29a expression in extracellular vesicles than in circulating free miR-29a suggests an active secretion and warrants further studies on its role in tumour–host interactions. These findings open new opportunities to explore blood-based miRNA profiles and specific miRNA candidates to select patients most likely to respond to FOLFIRINOX.Funding
Bennink Foundation, Netherlands; Cancer Center Amsterdam Foundation, Netherlands; AIRC Grant Start Up, Italy; FAS grant, Italy; Action Against Cancer, UK; No Surrender Cancer Trust (in memory of Jason Boas), UK. 相似文献18.
Background
Over 8·75 million people in the UK live with osteoarthritis, which has major social and economic costs. Although the current approach to managing this condition in primary care is suboptimal, any quality improvement must deliver value for money. Social return on investment (SROI) is a cost-benefit analysis that captures wider social benefits. Here, we describe a SROI analysis of a physiotherapy-led service (rather than the usual general practitioner [GP]-led model) delivering National Institute for Health and Care Excellence (NICE) guidance for managing osteoarthritis in six GP practices.Methods
SROI analysis was undertaken to determine the inputs, outputs, and outcomes associated with the intervention. These data were used to calculate a SROI ratio, which determined the level of social value created for every £1 of investment. To mitigate the risk of overclaiming any benefits created by the service, the calculation used conservative values and accounted for deadweight, displacement, drop-off, and attribution. A sensitivity analysis was performed and the SROI was externally validated.Findings
The SROI analysis showed that a physiotherapy-led service that delivers advice in line with NICE guidance created levels of social value that were greater than the cost of investment. Every £1 invested into the service resulted in a return of £2·43 to £4·03 in social value. The benefits (or outcomes) that patients gained from using the service were increased levels of physical activity, improved physical and mental health, reduced pain, and the saving in money and time spent travelling by accessing a local (GP-based) service. Outcomes for the National Health Service (NHS) were a reduction in health utilisation (eg, fewer GP consultations and secondary referrals) and the saving gained from the levels of weight loss seen in patients (ie, savings dispersed within the wider health system).Interpretation
SROI analysis shows that a physiotherapy-led service in primary care that delivers NICE guidance for managing osteoarthritis created an SROI for patients and the NHS. The service delivered benefits to patients, reduced health utilisation elsewhere in the system (eg, GP workload), and delivered value for money. SROI can provide a useful approach to support funding bodies to determine cost-effectiveness for commissioning services in health care.Funding
Health Innovation Network. 相似文献19.
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