WHO Risk Research Articles

Characteristics and Outcomes of Adult Patients with Malignancy-Associated Hemophagocytic Lymphohistiocytosis: A Single-Center, Prospective Analysis

Characteristics and Outcomes of Adult Patients with Malignancy-Associated Hemophagocytic Lymphohistiocytosis: A Single-Center, Prospective Analysis

Erythropoiesis Stimulating Agents (ESAS) in Supportive Care of Low-Risk Myelodysplastic Syndromes: Recamds Registry FINAL Results

Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It's matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs.Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion-dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed.183 patients, treated with standard-dose ESAs, have been retrospectively analyzed. Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1-118).ORR was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease(non-responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic-responders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic-responders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion-dependence, regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group 89% exhibit again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibits again macrocytosis, while 24% become normocytic.These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly stimulating erythroid production in MDS clones; in the minority of patients probably it happens recruiting residual polyclonal erythropoiesis.It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses. [Display omitted] DisclosuresMartinelli: Roche: Consultancy; Stemline Therapeutics: Consultancy; Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy; Daichii Sankyo: Consultancy; Astellas: Consultancy, Speakers Bureau.

Mental health and economic stressors associated with high-risk drinking and increased alcohol consumption early in the COVID-19 pandemic in the United States

Physical distancing measures to curb COVID-19 transmission introduced mental health and economic stressors, possibly impacting problematic drinking. This cross-sectional study examines mental health and economic stressors early in the COVID-19 pandemic which may be associated with heavy alcohol use and increased alcohol use. We administered an online survey of U.S. adults via social media April 5 to May 5, 2020. High-risk drinking was defined by WHO risk drinking levels, a daily average of ≥4 drinks for men and ≥3 drinks for women. Participants reported retrospective assessments of increased alcohol use if their past-week alcohol consumption exceeded their past-year average weekly alcohol consumption. We used logistic regression to assess possible covariates of high-risk drinking and increased alcohol use. Among 2175 participants, 10% (n = 222) reported high-risk drinking, and 36% (n = 775) reported increased alcohol consumption. In multivariable analysis, high-risk drinking was significantly associated with household job loss (OR = 1.41, 95%CI = (1.06, 1.88)) and depressive symptoms (OR = 1.05, 95% CI = (1.02, 1.07)), and women had higher odds of high-risk drinking than men (OR = 2.37, 95% CI = (1.32, 4.69)). Previous mental health diagnosis was not significantly associated with high-risk drinking during the pandemic (OR = 1.31, 95% CI = (0.98, 1.76)) in univariable analysis. High-risk drinkers were almost six times as likely to report retrospective assessments of increased alcohol consumption, controlling for mental health and economic stressors (OR = 5.97, 95% CI = (4.35, 8.32)). Findings suggest a need for targeted interventions to address the complex mental health and economic stressors that may increase alcohol consumption and high-risk drinking during and after the pandemic.

Outcomes of fertility treatment in patients with cardiac disease: a multi-centre experience

Abstract Introduction Risks of pregnancy in women with cardiac disease are well described, but data regarding the risks of assisted conception in this cohort is limited. As increasing numbers of older women seek fertility treatment, more women with congenital heart disease desire to have children of their own, and pre-implantation genetic testing (PGT) becomes more widely adopted, increasing numbers of women at risk of cardiac complications are likely to undergo fertility treatment. Aims To assess safety of fertility treatment in women with cardiac disease. Methods Multi-centre retrospective review of outcomes and complications in women with cardiac disease undergoing fertility treatment. Results 34 women with cardiac disease who underwent fertility treatment were identified, with 50 cycles undertaken. 24 patients (71%) received pre-pregnancy counselling. Four patients underwent assisted conception with PGT and two patients underwent IVF and egg collection for the purposes of surrogacy (both mWHO class III). The mean age at the start of an assisted conception cycle was 32 years. Cardiac disease was identified pre-pregnancy in 31 patients. Those diagnosed during pregnancy included a restrictive cardiomyopathy (presumed long standing), and pulmonary stenosis (PS) with an atrial septal defect (ASD). The Modified WHO (mWHO) risk category for the 34 women is seen in table 1. Those in mWHO class III include patients with mechanical valves, Fontan circulation, moderate LV systolic impairment, cyanotic heart disease due to previously undiagnosed PS and ASD, and a patient with Eisenmengers syndrome seeking surrogacy using her own eggs. Live births: 50 cycles resulted in 31 pregnancies; There were 31 live births, (including two sets of twins). One pregnancy lost a twin, and there were two first trimester miscarriages. Complications: Eight patients developed complications; four during fertility treatment and four during pregnancy (table 2). There was a correlation between higher mWHO class and higher rates of complications. No patients in mWHO class I experienced complications compared to 43% of mWHO class III. Of the 31 live births, five babies were delivered pre-term (<37/40). Conclusion The potential cardiac risks of assisted conception in patients with known cardiac disease, or older patients with risk factors for acquired cardiac disease should be considered by both reproductive medicine specialists and cardiologists before treatment commences. Formal pre-treatment / pre-pregnancy counselling is of paramount importance and should involve dialogue between both specialties and the patient to ensure all are aware of the potential risks, and action can be taken to minimise these. However, the presence of cardiac disease per se should not necessarily prevent patients accessing fertility treatment, as in many cases it can be used safely and successfully. Funding Acknowledgement Type of funding sources: None. Table 1. mWHO classificationsTable 2. Complications

Активность кишечной бактериальной гидролазы солей желчных кислот коррелирует с сердечно-сосудистым риском: исследование «случай — контроль»

Актуальность. Уровень сывороточного холестерина частично регулируется благодаря метаболизму желчных кислот в кишечнике, зависящему от активности бактериальной гидролазы солей желчных кислот (ГСЖК). Существующие данные относительно четкого влияния ГСЖК на липидный обмен и сердечно-сосудистый риск недостаточны и противоречивы. Целью исследования было оценить взаимо­связь между относительной активностью (ОА) кишечной бактериальной ГСЖК и уровнями сывороточного холестерина и сердечно-сосудистым риском (ССР). Материалы и методы. Исследование проводилось по дизайну «случай — контроль» и включало 26 относительно здоровых участников (контрольная группа) и 77 пациентов с дислипидемией, без анамнеза тяжелых сердечно-сосудистых событий (основная группа). У участников были определены общая ОА кишечной бактериальной ГСЖК, показатели липидного профиля и уровни ССР по 5 шкалам риска. Результаты. ОА кишечной бактериальной ГСЖК была выше у здоровых участников по сравнению с участниками с дислипидемией (р < 0,001). Была выявлена отрицательная корреляционная связь умеренной силы между ОА ГСЖК и общим холестерином (ОХ) (–0,38) и липопротеинами низкой плотности (ЛПНП) (–0,36) с линейным соотношением, которое определялось уравнением: ЛПНП = –5,33 • ОА ГСЖК + 4,479. Было обнаружено, что с увеличением ОА ГСЖК риск дислипидемии снижается (р < 0,001), ОШ = 1,06 • 10–10 (95% ДИ; 2,5 • 10–15 – 4,5 • 10–6). Выявлена умеренная отрицательная корреляционная взаимосвязь между ОА ГСЖК и ССР, оцененным по шкалам Globorisk (–0,34), Framingham (–0,34), алгоритму ACC/AHA 2013 (–0,32), PROCAM (–0,35) и шкале ВОЗ (–0,34). Выводы. Общая ОА кишечной бактериальной ГСЖК негативно коррелировала с ОХ, ЛПНП, ССР, оцененным по 5 шкалам, и негативно ассоциировалась с риском дислипидемии.

961Absolute cardiovascular disease risk scores and medication use in rural India

Abstract Background Low-to-middle-income countries (LMICs) have limited resources to tackle the burden of cardiovascular disease (CVD). Most screening guidelines recommend the use of absolute risk scoring to determine treatment, but there is uncertainty among policy makers and clinicians about which risk algorithm to choose. We aimed to compare laboratory-based absolute CVD risk algorithms in a LMIC setting. Methods The study was conducted in the Rishi Valley, Andhra Pradesh, India. Over 8,000 participants were surveyed between 2012-2015. The 10-year absolute risk was computed and compared using the Framingham, WHO, and Australian absolute risk CVD algorithms. Results In participants aged 35-74 years, 151 (3%) had prior CVD. In all algorithms, absolute CVD risk increased with age and was greater in men than women. Using the WHO algorithm 4% were characterized as high-risk while >29% were at high-risk using the Australian risk tool. Agreement of risk classification among men ranged from a high of 84% (Spearman’s rho (rs) =0.92) between Australian and Framingham algorithms to 43% (rs=0.6) between the Australian and WHO risk scores. Among the high-risk population, only 15% were on lipid-lowering or antihypertensive therapy. Conclusions The Framingham and Australian risk scores enable some discrimination between high- and low-risk groups. However, the WHO algorithm underestimates these high-risk groups. Even though one third of the participants were at high-risk, most of them were not receiving recommended treatment. Key messages Lab-based CVD risk assessment tools have the potential in identifying high-risk populations in LMICs but the WHO risk scoring tool should be used with caution.

970Comparison of lab-and non-lab based absolute cardiovascular disease risk scores in rural India

Abstract Background Over 75% of global cardiovascular (CVD) deaths occur in low-to-middle-income countries (LMICs). In limited resource settings non-lab-based CVD risk algorithms could be as effective as lab-based algorithms in identifying high-risk groups. We aimed to compare the concordance between lab-and non-lab-based absolute CVD risk algorithms in a LMIC setting. Methods The study was conducted in the Rishi Valley, Andhra Pradesh, India. Over 8,000 participants were surveyed between 2012-2015. The 10-year absolute CVD risk score was computed and compared using lab-and-non-lab based Framingham and WHO algorithms. Results In participants aged 35-74 years, absolute CVD risk score increased with age, and was greater in men than women, for all risk assessment tools. Using the Framingham lab-based algorithm, 15.6% were categorized as high-risk while 14.5% were at high-risk using the non-lab-based algorithm. The non-lab-based Framingham risk score had close agreement and strong correlation with the lab-based Framingham risk score in women (90%, Spearman’s rho (rs)=0.81) and men (83%, rs=0.89). Similarly, the non-lab-based WHO risk score had close agreement and strong correlation with the lab-based WHO risk score in women (95%, rs=0.83) and men (92% rs=0.84). In both cases, agreement was better in women than men (P < 0.05 for a two-sample test of proportions). Conclusions The effectiveness of non-lab-based Framingham and WHO algorithms are comparable to that of lab-based algorithms in discriminating high-and low-risk groups. However, the performance of non-lab-based risk score is better among women than men. Key messages Non-lab-based CVD risk algorithms could be effective and resource-efficient in LMIC settings, particularly among women.

Pregnancy in women with congenital heart diseases: Does the Carpreg II score significantly predict maternal outcomes in congenital heart diseases (PREG-GUCH study)?

Management of pregnancy and risk stratification in women with congenital heart diseases (CHD) are challenging especially due to physiological haemodynamic modifications that inevitably occur during pregnancy. To compare the accuracy of the main published scores including CARPREG II score in prediction of maternal complications during pregnancy in CHD patients. We included all pregnant women with CHD who delivered their babies after the 20th gestational week in our institution between 2007 and 2018 until 6 months postpartum. Pregnancy scores (CARPREG, CARPREG II, Harris, ZAHARA risk scores and modified WHO (mWHO) risk classification) were applied retrospectively. Of 121 pregnancies in 65 CHD patients, 30% had cardiovascular complications. The c-statistic was 0.577 (95% confidence interval (CI): 0.428, 0.727; P = 0.19) for CAPREG score, 0.593 (95% CI: 0.469, 0.717; P = 0.11) for the ZAHARA score, 0.601 (95% CI: 0.402, 0.799; P = 0.15) for Harris score, 0.646 (95% CI: 0.525, 0.767; P < 0.01) for the CARPREG II score and 0.751 (95% CI: 0.619, 0.884; P < 0.001) for the mWHO classification ( Fig. 1 ). Even if the new CARPREG II score seems to be better than most of the previously used scores as predictor of adverse maternal cardiovascular events mWHO appears to be more accurate in CHD patients.

Validating World Health Organization cardiovascular disease risk charts and optimizing risk assessment in China

BackgroundWorld Health Organization (WHO) released region-specific cardiovascular disease (CVD) risk prediction charts recently, but the extent to which the charts can apply to Chinese population is unknown. We aimed to validate the WHO CVD risk charts for East Asia, and evaluate their practicability combining with China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) equations among Chinese adults. MethodsThe China-PAR cohort with 93,234 participants aged 40–80 years was followed up during 1992–2015, including 29,337 participants from three sub-cohorts with follow-up period of over 10 years. We validated the WHO CVD risk charts using the China-PAR cohort by assessment of the predicted number of events, C index, calibration χ², and calibration plots, further elaborated the concordance between the China-PAR equations and the WHO risk charts. FindingsDuring an average follow-up of 13•64 years, 1849 incident CVD cases were identified from 29,337 participants. Both the laboratory-based and non-laboratory-based charts overestimated CVD events by 59% and 58% in men, and by 72% and 85% in women, respectively. However, 92% of participants identified as high risk by the China-PAR equations could be successfully detected by the laboratory-based charts at the cut-off point of 10%. We also observed that the non-laboratory-based charts demonstrated the poor performance for diabetic population, with high proportion of high-risk individuals (17% for men, 31% for women) would be missed. InterpretationAlthough the WHO CVD risk charts for East Asia apparently overestimated CVD risk among Chinese population, they could be pragmatic pre-selection tools, as potential supplement to the China-PAR equations. The widespread use of the WHO risk charts along with the China-PAR equations might facilitate the implementation of the risk-based CVD prevention in China. FundingFull funding sources are listed at the end of the paper (see Acknowledgments).

Facility-Based Surveillance Activities for COVID-19 Infection and Outcomes among Healthcare Workers in a Nigerian Tertiary Hospital.

ABSTRACTCOVID-19 in healthcare workers (HCWs) can result in nosocomial transmission, depletion in available workforce, and enhanced community transmission. This article describes surveillance for COVID-19 in HCWs at a tertiary healthcare facility, and documents the outcomes. A descriptive cross-sectional study of all HCWs identified from surveillance for COVID-19 from March 31 to August 31, 2020 was conducted. Healthcare workers were categorized as high risk and low risk using an adapted WHO Risk Assessment tool. Nasopharyngeal and oropharyngeal swab specimens obtained from high-risk subjects were tested by a reverse transcriptase PCR method. Data were analyzed with IBM SPSS version 25.0 software (IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY), and results were presented as frequencies and percentages. The level of significance was set at P < 0.05. During 5 months of surveillance, 1,466 HCWs with a mean age of 38.1 ± 9.7 years were identified as contacts. On risk assessment, 328 (22.4%) were adjudged high risk. High risk was associated with increasing age (P < 0.001), male gender (P = 0.001), and nonclinical staff (P = 0.002). Following testing, 78 (5.3%) in the high-risk category were confirmed to have COVID-19. There was no record of COVID-19 in HCWs adjudged low risk. Forty-four (56.4%) cases were epidemiologically linked to the community, 20 (25.7%) to patients, and 14 (17.9%) to another HCW. Surveillance and risk assessment are crucial to COVID-19 response in healthcare facilities and revealed HCW infections with predominantly nonoccupational epidemiological links in this study.

A Population Based Survey on the Association Between Tobacco Smoking and Cardiovascular Risk Using WHO Risk Prediction Algorithm Among a Rural Population in Mangalore, Karnataka

Background: Higher proportion of people die in India due to Cardiovascular diseases. Smoking causes about 10% of all CVD and 6 million people die from tobacco smoking every year through CVD, cancer and other causes. Aims &amp; Objectives: To determine the risk of developing cardiovascular events (fatal and non-fatal MI or Stroke) among the individuals above 40 years of age in next 10 years and to assess its magnitude of association with the smoking patterns among the study subjects. Methodology: A cross sectional study was conducted at Rural Mangalore among 230 residents above 40 years who were selected by simple random sampling. Pretested &amp; pre validated proforma for sociodemographic details, WHO/ISH cardiovascular risk prediction algorithm and GATS (Global Adult Tobacco Survey) Questionnaire was used. Statistics used: Chi square test and Multiple logistic regression was used. Data was analysed using SPSS version 22 software. Results: Out of 230 participants, 64% were males and 36% were females. WHO colour coding shows that 64.8% had low risk, 25.7% had moderate risk and 9.5% had high risk of getting CVD. 58.3% consumed chewable tobacco. Current smokeless tobacco users had moderate risk of CVD and Current smokers, current and past smokeless tobacco users had high risk of getting CVD independently. Conclusion: An increased risk of nonfatal myocardial infarctions among tobacco chewers was relatively lesser than for smokers and the highest increase in risk of acute myocardial infarction was in smokers who also chewed tobacco.

Body Mass Index Vs Fracture Risk Value Primary Osteoporosis (A Case Study on Women Ages 40-45 Years at Sub-Urban Area)

This study aims to determine the relationship between BMI and fracture risk value primary osteoporosis in women aged 40-45 years in sub-urban areas. And how to optimize social activities in the environment as an effort to reduce the risk of osteoporosis. Body mass index is one of the important risk factors for osteoporosis fractures because the protective effects of subcutaneous fat tissue on bone in elderly women are calculated using FRAX®tool. The WHO in collaboration with the Sheffield's University central of metabolic bone disease has created a calculating device, the WHO risk assessment fracture tool (FRAX®tool). FRAX®tool is an online-based device used to calculate the risk of osteoporosis fractures in major bones, namely proximal humerus, wrist, vertebrae, and femur bone in the next ten years. This research is an analytical study using a cross sectional design, the number of samples is 70 female respondents aged 40–45 years in Kelurahan Melong Asih, Cimahi. The relationship between body mass index and the risk of primary osteoporosis fracture, used the rank spearman correlation test. The results of this study indicate a strong negative correlation between body mass index and the risk value of osteoporosis major, while the relationship between body mass index and risk value for osteoporosis femur fracture was found to be a moderate negative correlation. From the results of the risk of major osteoporosis fracture the lower a person's body mass index, the greater the risk of major primary osteoporosis fracture, whereas the results of the risk of femur fracture are only in obese grade II that is low, while other criteria have the same value, so it cannot be concluded if the lower a person's body mass index, the greater the risk value of the femur fracture. Keywords : Body Mass Index; Fracture Risk Value; Osteoporosis.

In search for the hotspots of Disease X: A biogeographic approach to mapping the predictive risk of WHO's blueprint priority diseases

Background: Current trends of emerging infectious disease outbreaks (EIDs) forecast impending global epidemiological crises. Human-driven environmental changes, including climate change along with overpopulation and global travel, have been contributing to EIDs outbreaks in many developing countries. The subject has attracted increasing attention with the recent Ebola and Zika epidemics, which highlights the potential threats to human and animal health, social stability, and global trade and economy. The blueprint priority diseases (BPDs) is a list established by the World Health Organization of ten zoonotic diseases, which are in urgent need of research. We proposed mapping the predictive risk of the BPDs using spatial Bayesian models and species distribution modelling of the outbreaks following the year 2000. The aim is to provide a global perspective, measure predictive risks, and evaluate the use of biogeography on predicting diseases outbreaks. We also proposed disease biogeography as a tool for identifying the potential hotspots for Disease X listed in the BPDs. Methods and materials: Data of the observed outbreaks (2000–2018) were obtained from promed mail and WHO archives. Bioclimatic covariates and altitude data were extracted from ‘worldclim’ (R package dismo) and the 2017 land cover data (MODIS satellite imagery). We constructed species distribution models including bioclim, maxent and Bayesian models with absence data generated to map the predictive risk of future outbreaks. Results: Most of the predicted geographic risk extent estimated from the observed data of MERS, Marburg Virus Disease and Rift Valley fever were found to occur in arid and across the Middle East and Eastern regions of Africa. The predictive extent of Lassa fever and Ebola Virus Disease consisted of regions in the Western and Central Africa, predominated by humid rainforests. We found a significant correlation between the disease extent and the distribution of confirmed and suspected biological reservoirs and also with deforestation. The AUC of the generated models was maintained over 0.9 (average - 0.978). Conclusion: Biogeography is a robust tool in forecasting hotspots of EIDs outbreaks. We will also complete the analysis by aggregating the common risk factors of the predicted EIDs to characterize hotspots for an unknown Disease X.

Investigating Risk Factors for Falls among Community-Dwelling Older Adults According to WHO's Risk Factor Model for Falls.

The World Health Organization developed the Risk Factor Model for Falls to describe fall risks in a comprehensive manner. However, there was a lack of study adopting such framework in quantifying falls risk from different factors in a single model. Therefore, this study examined the risk factors from four domains in the Risk Factor Model for Falls among older adults. Secondary data analysis of 10-year assessment records of the Minimum Data Set-Home Care instrument. Hong Kong. 89,100 community-dwelling adults aged 65 and over who first applied for publicly funded long-term care services from 2005 to 2014. The Minimum Data Set-Home Care instrument was used to ascertain older adults' care needs and match them with appropriate services. Additionally, meteorological records from the same period were extracted from the Hong Kong Observatory. The logistic regression model was used to examine risk factors and their associations with falls. In total 70 factors were included in the analysis, of which 37 were significantly associated with falls. Behavioral risk factors generally had greater odds ratios of falling, as compared with biological, socioeconomic, and environmental factors. Out of all significant factors, functional status, alcohol drinking, and locomotion outdoors had the largest odds ratios of falling. Behavioral risk factors for falls are of remarkable influence yet are modifiable among older adults. Hence, falls prevention programs may need to prioritize addressing these factors.

The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND): A longitudinal public health research program targeting dementia risk reduction

AbstractBackgroundA substantial proportion of risk for age‐related dementia may be attributable to modifiable factors. The ISLAND Project responds to international calls (Lancet Commission, World Health Organisation) to investigate the effectiveness of public health strategies for reducing dementia risk. This large longitudinal and interventional cohort study will evaluate a sustained public health campaign to mitigate behaviours associated with dementia risk. The Tasmanian population comprises approximately 500,000 urban, rural and remote residents and has a prevalence of factors associated with dementia risk that is higher than Australian norms. This contained island population offers a unique opportunity for recruitment, cohort maintenance and tracking changes in participants’ dementia risk profile over time.MethodThe ISLAND Project aims to recruit 10% of Tasmanians aged 50 and over (target n=20,000). Participants will be offered a series of educational and community‐based interventions to build self‐efficacy in dementia risk management. Engagement with these interventions will be evaluated. Self‐report, online surveys administered annually will track changes in participants’ physical and mental health, social functioning, dementia risk literacy and risk‐related behaviours. Cognitive screening and biomarkers (e.g. blood) will be collected biennially. The Dementia Risk Profile (DRP) will support and track behaviour change. The DRP provides a traffic‐light indicator of personal risk and recommended actions, based on WHO risk reduction guidelines. The DRP can be updated every six months and printed to support health consultations.ResultThe ISLAND Project launched in June 2019. Preliminary data collected between October and December 2019 indicate the ambitious recruitment target is feasible, with 10,729 registering interest in the study, of whom 4,937 have provided research consent (73% female, median age 62 years). Participants’ postcodes signify reasonably representative geographical distribution (urban 77%, rural 22%; Figure 1) and current baseline data include: background and health (n=4270), knowledge (n=3781) and attitudes about dementia risk (n=3588), depression (n=3541) and the DRP (n=3269).ConclusionThe ISLAND Project aims to translate, into a public health setting, research evidence that reducing dementia risk can be achieved through modifying behaviours. Findings from this population‐based approach to dementia risk reduction will be used to inform future public health policy and practice.

Cardiovascular risk factors in China: a nationwide population-based cohort study

It is estimated that 4 million deaths are due to cardiovascular diseases each year in China. Comprehensive understanding about modifiable risk factors and how the risk differs across regions is needed to inform public health policies. We aimed to examine the geographical profile of cardiovascular disease risk across China. In this study, we analysed data from a nationwide, population-based screening project, which covered 152 rural counties and 100 urban districts from 31 provinces in China. Between Sept 1, 2015, and Nov 30, 2019, standardised measurements were taken from participants aged 35-75 years who had lived in the region for at least 6 of the preceding 12 months to collect information on blood pressure, blood lipids, blood glucose, physical activity, tobacco smoking, alcohol use, overweight or obesity, and intake frequencies of fruits, vegetables, whole grains, legumes, and red meat. Individuals with a high risk of cardiovascular disease were identified according to medical history and WHO risk prediction charts. 983 476 individuals were included in this study. Among the participants included, 10·3% (95% CI 10·2-10·3) had a high cardiovascular disease risk after standardising age and sex, with a range of 3·1-24·9% across counties or districts. Among the seven regions in mainland China, the prevalence of high risk of cardiovascular disease was relatively high in northeast China (12·6% [12·4-12·8]) and north China (11·4% [11·3-11·6]), whereas it was low in south China (8·0% [7·8-8·2]). The geographical profiles of the 12 major cardiovascular disease risk factors were different. We found that the regions with high cardiovascular disease risk were facing challenges such as obesity and high blood pressure (north China) and consumption of unhealthy non-staple food (low intake of fruits and vegetables or high intake of red meat; northeast China). By contrast, south China-the region with the lowest cardiovascular disease risk-had the highest prevalence of unhealthy staple food (low intake of whole grains and beans), abnormal metabolism (glucose and lipid), and low physical activity in the country. Risk for cardiovascular diseases varies geographically, and the major contributing risk factors are different across regions in China. Hence, geographically targeted interventions are needed to mitigate the risk and reduce the burden in such a vast country. Ministry of Science and Technology, Ministry of Finance, and National Health Commission of China.

Loss of SFRP1 expression is a key progression event in gastrointestinal stromal tumor pathogenesis

The mechanism of high-grade transformation in gastrointestinal stromal tumors (GISTs) remains to be clarified. We aim to discover the key progression events by studying biphasic GISTs. The study group included 101 GISTs. Nineteen of these had been screened from 263 GISTs to represent the early stage of GIST high-grade transformation, characterized by juxtaposed low-grade and high-grade regions in the same tumor (so-called biphasic GISTs). Mutational analyses, fluorescence in situ hybridization (FISH), NanoString analyses, telomere analysis, and gene expression profiling were carried out, followed by in silico analyses, cell line study, and immunohistochemical validation. Using gene expression analysis, downregulation of SFRP1 was revealed to be the main event in GIST high-grade transformation (p=0.013), accompanied by upregulation of EZH2. In silico analyses revealed that downregulation of SFRP1 was a common feature in GIST progression across several different series. Immunohistochemically, the expression of SFRP1 was validated to be significantly lower in high-grade GISTs (WHO risk group 3a or higher) than in low-grade GISTs (p<0.001), and attenuation/loss of SFRP1 was associated with GIST tumor progression (p<0.001). By NanoString and FISH analyses, chromosomal 9/9p loss was the only recurrent large-scale chromosome aberration in biphasic GISTs, with a correlation with SFRP1 downregulation. Subclones containing chromosome 9/9p loss could be appreciated in the low-grade parts of biphasic GISTs. TP53 mutation, RB1 loss, KIT/PDGFRA mutation, and alternative lengthening of telomeres did not play a significant role in GIST high-grade transformation. In conclusion, high-grade transformation of GISTs features SFRP1 downregulation and chromosome 9/9p loss.

Geographical profiles of cardiovascular risk and the risk factors in China: data from a nationwide population-based screening project

Abstract Background In China, an abundance of cardiovascular risk factors has contributed to the increasing prevalence of cardiovascular diseases (CVD), which caused almost 4 million deaths per year. However, comprehensive evidence on the geographical profiles of cardiovascular disease risk in China is lacking, as findings in prior studies have been limited to relatively small sample sizes, had incomplete regional coverage, or focused on a narrow risk factor spectrum. Purpose To compare the population CVD risk among different regions across China, and to describe the geographical distributions of CVD risk factors and their clusters throughout the nation. Methods In a nationwide population-based screening project covering 252 counties of China, standardized measurements were conducted to collect information on 12 major CVD risk factors. Individuals of high CVD risk were identified as those with previous CVD, or with a predicted 10-year risk of CVD greater than 10% according to the WHO risk prediction charts. We applied factor analysis to generate “clusters” that characterized the clustering of these risk factors, then explored their relationship with the local ambient temperature and per capital GDP. Results Among 983476 participants included, 9.2% were of high CVD risk, with a range of 1.6% to 23.6% across counties. Among the seven regions in China, the rate was relatively high in the Northeast (11.8%) and North China (10.4%), while low in the South China (7.2%) and Northwest (7.8%). We identified 6 clusters underlying CVD risk factors, including Obesity factor, Blood pressure factor, Staple food factor, Non-staple food factor, Smoking and alcohol factor, and Metabolic and physical activity factor (Figure). We found high risk regions were facing different leading challenges, like obesity and blood pressure for the North China, while unhealthy non-staple food for the Northeast. The South China, as the region with the lowest CVD risk, still had the highest prevalence of unhealthy staple food. Lower annual average ambient temperature was associated with higher risk in Blood pressure factor, Obesity factor and Non-staple food factor, but lower risk in Staple food factor and Metabolic and physical activity factor (p&amp;lt;0.001 for all), consistently between rural and urban. Higher per capital GDP was associated with lower risk in Non-staple food factor in urban and higher risk in Metabolic and physical activity factor in rural (p&amp;lt;0.05 for both). The correlation between per capital GDP and Smoking and alcohol factor differed significantly between in rural and urban regions (p=0.042). Conclusions The geographical profile of CVD risk in China is complex - population risk levels varied substantially across regions, which were contributed by different risk factors. China needs geographically targeted intervention strategies considering environmental and socio-economic factors to control CVD risk and reduce the burden related to CVD. Geographical disparity of risk clusters Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The National Key Research and Development Program from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science

In Search for the Hotspots of Disease X: A Biogeographic Approach to Mapping the Predictive Risk of WHO's Blueprint Priority Diseases

Background: Anthropization of natural habitats including climate change along with overpopulation and global travel have been contributing to EIDs outbreaks. The ongoing COVID-19 outbreak highlights the threats to human health, social stability and global trade and economy. The Blueprint Priority Diseases (BPDs) is a list established by the World Health Organization, which are in urgent need of research. We proposed mapping the predictive risk of the BPDs, identifying the environmental drivers and validating the use of disease biogeography as a tool for identifying the potential hotspots for Disease X.Methods: We used environmental predictor variables from satellite imagery such as landscape, deforestation, climatic covariates, and species distribution modelling by classical regression and Support Vector Machine (SVM) to model BPD occurrences from 2000 to 2019. The models were evaluated using AUC (>0.9) and a weighed mean was used to map the predictive risk of the BPDs and identify potential sites of Disease X.Results: We generated predictive risk maps for Ebola, Marburg, Nipah, Rift Valley Fever and coronavirus diseases using glm and SVM models. Elevation, tree cover loss and climatic covariates were found to significant triggers for disease emergence of BPD outbreaks. We identified regions in China and Uganda to be potential hotspots for Disease X.Conclusions: Using a biogeographic approach, existing disease databases and freely accessible environmental data, we were able to identify Wuhan as a potential hotspot of disease emergence in the absence of COVID-19 data. We confirm that distribution of disease emergence in humans is spatially dependent on environmental factors.Funding Statement: None to declare Declaration of Interests: None to declareEthical Approval: Not needed

MDS-391: Role of Erythropoiesis-Stimulating Agents (ESAs) in Supportive Care of Low-Risk Myelodysplastic Syndromes

Context: Erythropoiesis-stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients, and employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It is a matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs. Objective: Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS. An analysis of the erythropoietic response to ESA therapy in a cohort of anemic, non-transfusion-dependent MDS patient, enrolled in a retrospective registry, RECAMDS, a subgroup of Italian register, was performed. Design: Real-world analysis. Setting: Low-risk MDS. Patients: One hundred eighty-three patients treated with standard-dose ESAs have been retrospectively analyzed. Data analysis was performed according to IWG 2006 criteria at baseline and after 3 and 6 months of continuous treatment, with a sub-analysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl and mean serum EPO concentration of 51 mU/L after a mean time from diagnosis of 6 months (r.1–118). Interventions: ESAs to manage low-risk MDS. Main outcome measures: Results were evaluated according to IMWG 2006 criteria. Results: ORR was 83.6% (153/183); no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while the other 21/183 (11.2%) achieved response after 6 months. Nineteen patients with stable disease (non-responders, according to IWG criteria), in whom treatment was continued, achieved response after 9 months. In the macrocytic-responders group, 83.2% exhibited repeat macrocytosis after 3 months, while 16.8% became normocytic. In the normocytic-responders group, 89.8% exhibited repeat normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia with transfusion-dependence, which was regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group, 89% exhibit macrocytosis again after 3 months, while 11% became normocytic; in the normocytic group, 76% exhibited macrocytosis again, while 24% became normocytic. Conclusions: These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs, mainly stimulation of erythroid production in MDS clones. In the minority of patients, it likely happens due to recruiting residual polyclonal erythropoiesis. It is interesting to note that stimulating effects of ESAs last, even when the expression of dysplasia progresses.