Climate change has altered global hydrological cycles mainly due to changes in temperature and precipitation, which may exacerbate the global and regional water shortage issues, especially in the countries along the Belt and Road (B&R).In this paper, we assessed water supply, demand, and stress under three climate change scenarios in the major countries along the Belt and Road. We ensembled ten Global Climate Model (GCM) runoff data and downscaled it to a finer resolution of 0.1° × 0.1° by the random forest model.Our results showed that the GCM runoff was highly correlated with the FAO renewable water resources and thus could be used to estimate water supply. Climate change would increase water supply by 4.85%, 5.18%, 8.16% and water demand by 1.45%, 1.68%, 2.36% under RCP 2.6, 4.5, and 8.5 scenarios by 2050s, respectively. As a result, climate change will, in general, have little impact on water stress in the B&R countries as a whole. However, climate change will make future water resources more unevenly distributed among the B&R countries and regions, exacerbating water stress in some countries, especially in Central Asia and West Asia. Our results are informative for water resource managers and policymakers in the B&R countries to make sustainable water management strategies under future climate change. As of tHowever, there have been no studies reported in the literature to examine future water resources across the Belt and Road under the impacts of climate change. In this study, we assessed the supply and demand of water resources for 122 countries along the Belt and Road under different climate change scenarios for the mid-21st century. Our results will provide foundational information to policymakers to make adequate and sustainable water management strategies for the B&R in the face of climate change.Water resources can be quantified in multiple ways, such as stream flow, surface runoff, or total runoff . In the In this study, the total runoff data was obtained from the Coupled Model Intercomparison Project (CMIP5) of the IPCC fifth assessment . Those rHowever, the spatial resolution of most simulation results from CMIP5 GCM was too coarse to be used directly in climate change impacts studies. Downscaling techniques offer an alternative to develop finer resolution outputs . Of manyIn the current study, we used the runoff data of ten GCMs in the CMIP5 project . We firsPrevious studies have reported that due to lack of complete information about atmospheric phenomena, some assumptions were made during the development of GCMs, which caused systematic bias in GCM data . To corrCountry-based water demands were divided into three categories: agricultural, residential and industrial water demand as classified by the FAO. The current country-level water demands of these sectors were obtained from the FAO AQUASTAT, a global database of water resources developed by the FAO mainly based on countrywide statistics . We inte2 concentration will increase plant water use efficiency and thus reduce agricultural water demand  as in The residential water demand is affected by many factors, such as economic growth, technological evolution and global warming, which is indicated by residential water intensity  . We calc−1·capita−1), −1·capita−1·yr−1), and −1·capita−1·yr−1) of each country was computed by dividing the countries into high-income  and low-income  categories. In addition, global warming will also stimulate residential water demand. We calculated the global warming effect on residential water demand by assuming future residential water demand will increase by 1% as daily maximum air temperature increases 1 °C according to the previous studies , consisting of agricultural water demand (AWD), residential water demand (RWD) and industrial water demand (IWD) and RWR is renewable water resources (km3·yr−1). The classification standard of the WSI is as follows: WSI < 0.20: no water stress; 0.20 < WSI ≤ 0.60: low water stress; 0.60 < WSI ≤ 0.75: moderate water stress and WSI > 0.75: high water stress.3·yr−1, which was 16.64% lower than the FAO global water resources of 42,820.22 km3·yr−1 for the same period (2), we found that the regression models overestimated water resources in the dry areas and underestimated in the wet regions  renewable water resources in the B&R countries were 22997.05 km−1, while the poorest water resources region was North Africa with an average of 2.06 mm·yr−1. The areal based water resources in Southeast Asia were about 538 times that of North Africa. The highest water resources per capita among the B&R countries were found in South and Central America with an average of 39,901 m3·yr−1 compared with the lowest of 340 m3·yr−1 found in North Africa.Moreover, we found that water resources were unevenly distributed among the B&R countries . Southea3·yr−1 to 24,113.05 km3·yr−1, an increase of 4.85%, under RCP 2.6, a low climate change scenario. Under RCP4.5, a moderate climate change scenario, water resources in the B&R countries may increase by 5.18%, reaching 24,190.86 km3·yr−1. The renewable water resources in the B&R countries may see a slightly greater increase of 8.16%, with an amount of 24,874.33 km3·yr−1, under RCP8.5, the most aggressive climate change scenario in the IPCC fifth assessment.We found that climate change would slightly increase total renewable water resources amount of the Belt and Road by the mid-21st century. The renewable water resources of all the B&R countries may increase from the current 22,997.07 km−1 will slightly increase from 27.71% up to 28.19% and the proportion of areas with water resources greater than 800 mm·yr−1 will increase from the current 9.98% up to 10.72%. We found that different climate change scenarios had similar effects on water resources in terms of amount and spatial distribution though the impacts of RCP 8.5 was slightly more severe than those of RCP 2.6 and RCP 4.5.However, we found that climate change would exacerbate the uneven distribution of water resources among the B&R countries with exceptions in North Africa and the Mongolia Plateau . Future 3·yr−1, which were about 56% of the global water demands . Agricultural, residential and industrial water demand in the B&R countries accounted for 77.58%, 9.05% and 13.37%, respectively, of the total water demands of those countries. We found that future climate change would have a minor impact on water demands in the B&R with an increase of 1.45%, 1.68%, and 2.36% respectively under RCP 2.6, RCP 4.5, and RCP 8.5. However, the industrial and residential water demands would increase much faster than the total water demands due to the large share of agricultural water demand which was assumed unchanged with climate change in the current study. The industrial water demand will increase by 7.91%, 9.15%, and 10.58% respectively under RCP 2.6, RCP 4.5, and RCP 8.5. The residential water demand will increase by 4.33%, 5.04%, and 10.47% under RCP 2.6, RCP 4.5, and RCP 8.5, respectively.In addition to water supply, climate change may also increase water demands in various sectors. Our results showed that the current total water demands in the B&R countries were 2,010.05 kmSpatially, the high increase of water demands driven by future climate change was found in Central Africa and Papua New Guinean where the climate change induced more than 10% increase in water demands, while the growth rates of water demands induced by climate change may be less than 5% in most of the B&R countries in Asia, Europe, South America, and North and South Africa . MongoliWe found that climate change alone would have little impact on the overall status of water resources in the B&R countries with a slight increase in the total renewable water resources. Climate change will increase water supply by 4.85–8.16% and water demand by 1.45–2.36% without considering the climate change impacts on agricultural water demand. However, climate change will enhance the uneven distribution of water resources among the B&R countries and regions, exacerbating water stress in some countries, such as Iran, Tunisia, Afghanistan, Tajikistan, and Turkey, most of which have already suffered from water shortage . HoweverIn this paper, we developed a high-resolution global runoff dataset using the CMIP5 GCM outputs by downscaling the GCM runoff data with the random forest model. We found that the GCM runoff data was highly correlated with the FAO statistics of the renewable water resources. Previous studies compared the CMIP5 GCM runoff with observed runoff in 161 river basins across the globe and found that the GCM runoff data was generally comparable with the observations . However2 concentration. Many studies have shown that elevated CO2 concentration will increase plant and ecosystem water use efficiency (In the current study, we examined the impacts of climate change on the supply and demand of the renewable water resources in the B&R countries and found that future climate change might have a minor impact on water resources. This is because climate change will increase water supply more than water demands in most of the countries , 5. The ficiency . Our resficiency .2 concentration improving water use efficiency.In this study, we found that climate change may have little impact on the total demands of water resources in B&R countries. This is because agricultural water demand accounts for 77.58% of the total water demands in the B&R countries and we assumed that climate change had no impact on agricultural water demand. However, our results showed that climate change would considerably increase industrial and residential water demand . The ass2 effect alone will decrease water consumption by 4.1–12.2% through CO2-induced decrease of stomatal conductance (2 effects (2 interactions on plant growth and water use are complex and may vary in different climates and cropping systems. Further studies are needed to refine the estimates of agricultural water demand under future climate change.So far, experimental and model simulation studies have shown that warming alone may increase water demands by 3.6–15% through the boost of ET  and meanductance . These t effects . We acknAlthough climate change may have little impact on water stress for the B&R countries as a whole, some of the countries may still suffer more water stress due to climate change, especially countries in Central and West Asia, which are currently facing water shortage problems . Our resIn this paper, we developed a global runoff dataset by ensembling ten GCM outputs of total runoff and downscaled to a much finer resolution for analyzing climate change impacts on water resources and water stress in the B&R countries. We found that the GCM runoff was highly correlated with the FAO statistics of renewable water resources and thus could be reasonably used for further analyses. Our results showed that climate change would increase water supply by 4.85–8.16% and water demand by 1.45–2.36% in the B&R countries by 2050s. As a result, climate change will, in general, have little effect on water stress in the B&R countries as a whole, but it will exacerbate water shortage in some of the countries, especially in Central and West Asia. In addition, more countries are likely to suffer more severe water stress than countries benefiting from climate change. Different climate change scenarios had similar impacts on water stress in the B&R countries with a slightly greater number of countries suffering from more water stress under RCP 8.5 than RCP 4.5 and RCP 2.6.10.7717/peerj.12201/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.12201/supp-2Supplemental Information 2Click here for additional data file.10.7717/peerj.12201/supp-3Supplemental Information 3Click here for additional data file.


Birth was by elective caesarean in 12.1% (3.6–23.7%) or emergency caesarean in 9.5% (3.5–21.2%) . Preterm births (<37 weeks) ranged from 3.7% to 9.4% (p < 0.05), large for gestational age 10.3–26.7% (p < 0.001), admission to special care nursery 16.7–25.0% (p < 0.001), and neonatal hypoglycaemia (<2.6 mmol/L) 6.0–27.0% (p < 0.001). Many women with T1D and T2D had limited pregnancy planning including first trimester hyperglycaemia (HbA1c > 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p < 0.001). Conclusion: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy.Background: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. Methods: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. Results: The audit included 10,144 pregnancies  = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8–57.3%), metformin alone in 18.8% (0.4–43.7%), and metformin and insulin in 10.1% (1.5–23.4%); when compared between sites, all  Hyperglycaemia in pregnancy is a growing problem worldwide , posing Mapping variations in antenatal diabetes care is an important tool for improving the quality of care provided. A national audit and benchmarking program using standardised criteria was found to be useful for identifying aspects of pre-pregnancy and antenatal care needing improvement among women with diabetes , includiThis multicentre pilot audit was conducted under the governance of ADIPS. All diabetes in pregnancy services across Australia and New Zealand, including those from tertiary, rural, indigenous, public, and private settings were eligible to participate in the pilot program. All members of ADIPS were invited to participate by the ADIPS secretariat via email, website, and forums. Other health facilities were open for participation upon approaching the Secretariat. Our target for the pilot was to include 10 centres from diverse settings. The benchmarking centre was located in a metropolitan city with a large multiethnic population and had expertise from prior benchmarking analyses outside of pregnancy. The benchmarking centre also volunteered to be one of the pilot sites. Pregnancies in women with GDM, type 1 diabetes (T1D), or T2D resulting in live births between years 2014 and 2020 were eligible for inclusion in the audit. Data from women with multiple pregnancies or pregnancies ending in miscarriage, induced abortion, or stillbirth were excluded from the audit because of variations in sources. The audit tool was built upon the data set used previously , and theThe core data elements were complemented by demographic, treatment, and pregnancy outcome variables. Data items that were not specific to pregnancy were created based on nationally endorsed metadata standards accessible through a metadata online registry . The datThis pilot was undertaken in a “double blind” (site and participant) fashion. Data collection was coordinated by a trusted third party (TTP) process, where in this instance, a “trusted” agent acts as a channel for communication ensuring that participating sites remain anonymous to the benchmarking centre. Health services that volunteered to participate in the programme sent their existing locally approved data directly to the TTP after obtaining approval based on local policies. Data were deidentified before being sent to the benchmarking centre and were sent in a single Excel spreadsheet in standard format as an email attachment. Data were checked for completeness and formatting, and further queries were made to participating sites through the TTP for clarification as needed. All questioned data items that sites could not validate were deleted. All records containing births recorded as less than 28 weeks gestation were also deleted due to variations in data collection between sites. We accepted validated heights as low as 140 cm and as high as 185 cm and a validated weight maximum of 185 kg to avoid including data entry errors. The TTP created a unique identifier for each participating health service before disclosing the data for analysis to the benchmarking centre. Additionally, sites were re-coded at the central analysis site as an added security measure to preclude identification of any site from the analyses.Participating sites were provided with a feedback report describing clinical care in their centre. The benchmarking report enabled them to compare their performance against other participating sites and identify local service needs. Sites were able to identify only their own data reports. p < 0.05 taken as significant. The ethics approval for this project was granted by the Western Sydney University Human Research Ethics Committee .Comparisons were made between sites, but not between types of diabetes in pregnancy because of the selective nature of the audits. Outcome and other measures were reported based upon non-missing data. Sites having all data missing for a given variable were excluded from analyses relating to that variable. For categorical data, if the sites had reported only “Yes” values and the remaining cells were blank/missing, these were interpreted as “No”. Categorical variables were described using numbers and percentages and Pearson’s Chi-squared test, where appropriate, were used to compare groups. Continuous variables were described using mean ± standard deviation and compared using analysis of variance. Analyses were performed using IBM SPSS Version 24.0. Armonk, NY: IBM Corp. All tests are 2 tailed with n = 8696, T1D, n = 435, T2D, n = 1013) from 11 diabetes services , private urban clinic (n = 1), rural health service (n = 1)) after excluding multiple pregnancies (n = 103); pregnancies affected by new-onset diabetes after organ transplantation (n = 2) and maturity-onset diabetes of the young (n = 1); and pregnancies that ended in miscarriages, termination of pregnancy or perinatal death (n = 59)  . The maj(n = 59) . Eight s2, respectively. Within centres reporting these variables, 6.7% of the women documented having a history of hypertension and 9.1% reported smoking during pregnancy. Ethnicity was reported for 93% of women with significant variation in ethnic makeup across services. Most were European (33.1%), followed by South Asian (20.8%), East/South East Asian (13.8%), Māori/Pacific (12.5%), and Middle Eastern (8.1%). Aboriginal and Torres Strait Islander constituted 2.6% of women. p < 0.001). Elective and emergency caesarean delivery ranged from 3.6% to 23.7% and 3.5% to 21.2%, respectively (both p < 0.0001). Preterm birth (28 to <37 weeks) ranged from 3.7% to 9.4% (p < 0.05), large-for-gestational-age 10.3–26.7% (p < 0.0001), small-for-gestational-age 0–11.9% (p < 0.0001), admission to special care nursery 16.7–25.0% (p < 0.0001), neonatal hypoglycaemia (< 2.6 mmol/L) 6.0–27.0% (p < 0.0001), preeclampsia 2.0–5.2% (p < 0.0001), and shoulder dystocia 0–7.2% (p < 0.0001) all varied significantly across services. There was no significant difference in breastfeeding on discharge or jaundice requiring phototherapy. Major but not minor malformations varied across sites.The mean recorded gestational week at first visit to the participating diabetes service was beyond the recommended eight weeks of gestation  for womep < 0.05), while birthweight ≥4000 g ranged from 14.3% to 37.5% and 0–23.6% respectively. LGA reporting was limited due to missing variables for the centile calculator . T1D data were relatively complete and showed significant variation in neonatal hypoglycaemia (12.5–87.5%) and admission to special care nursery (12.5–100%) (both p < 0.001).Variable recording of birth outcomes occurred. While birth weight was available for 98.2% of infants, recording of several important neonatal outcomes was low. The reporting of malformations was limited, particularly among pregnancies complicated by T2D such that interpretation was difficult. Where recorded, rates of major pregnancy complications were high for women with both T1D and T2D. Elective caesarean rates ranged from 12.5–45.8% and emergency caesarean from 17.4% to 57.7% in T1D, and 0–73.7% and 0–48.3% in T2D. Gestational age at delivery was well recorded with marked variation in the prematurity rates (<37 weeks) of 7.5–52.1% in T1D and 13.6–31.6% in T2D , the majority of sites reported initial EDC based on last menstrual period with a few sites basing EDC on dating US scan, however the data many have been collected by the antenatal clinic- indicating work needed in aligning communication/documentation between stand-alone diabetes and associated antenatal services. Significantly, data on hypoglycaemia needing assistance were missing for all services except one centre, and none of the services reported data for the number of hypoglycaemic episodes: it is unclear whether this was due to missing or data or that these events are now very rare. The high rates of congenital anomalies in these live births  suggest major malformation rates would be higher reinforcing the need for preconception care for women with known diabetes. A recent meta-analysis showed a 70% reduction in congenital malformation in women who received preconception care . The larThe current audit tool may require refinement in the future to separate some ethnic groups explicitly  and metformin from other diabetes treatments at conception. Access to pre-pregnancy clinics  and the The major strength of this study is that it is the largest national benchmarking audit of diabetes in pregnancy services across Australia and New Zealand. Diabetes services with a range of characteristics in major metropolitan cities in Australia and New Zealand as well as in rural and private care settings were included. A major limitation of the audit is the lack of data on pregnancies ending before 28 weeks gestation including miscarriage, stillbirth or induced abortion and the audit will underestimate the proportion of pregnancies with some adverse outcomes  as a result. These data should be collected comprehensively in future audits. Another limitation was a difficulty defining a denominator in some analyses due to missing/uncoded data. There was some variation in GDM diagnosis: the study population included women with GDM diagnosed based on ADIPS 2014 , ADIPS 1Our national pilot audit provides information on how quality indicators in perinatal diabetes care have been followed and documented by diabetes services for women with pre-existing diabetes and GDM. Although the benchmarking report across sites is not shown in this paper, our findings indicate an under-recording of the diabetes care provided to these women and evidence that improvement in care is needed even among these volunteer sites with a major interest in optimising pregnancy outcomes. There is a particular need for targeted and improved pregnancy preparation for women with T2D. As quality perinatal care is integral for the survival and well-being of the fetus, an ongoing national audit is necessary to improve pregnancy care for women affected by hyperglycaemia according to the standards set by the ADIPS. This preliminary, and essentially exploratory audit, highlights that a national clinical audit with defined and regulated outcomes, is feasible and urgently needed with communication between both maternity and diabetes services.


Conclusion: Higher-risk groups are seen in male subjects with a history of smoking and diabetes and female smokers and arterial hypertension, becoming important subgroups for our primary healthcare centers and should be considered for ABI screening programs.Objective: To determine the prevalence and risk factors associated with peripheral arterial disease (PAD) in Northern Barcelona at 65 years of age. Methods: A single-center, cross-sectional study, including males and females 65 years of age, health care cardholders of Barcelona Nord. PAD was defined as an ankle–brachial index (ABI) < 0.9. Attending subjects were evaluated for a history of common cardiovascular risk factors. A REGICOR score was obtained, as well as a physical examination and anthropometric measurements. Results: From November 2017 to December 2018, 1174 subjects were included: 479 (40.8%) female and 695 (59.2%) male. Overall prevalence of PAD was 6.2% (95% CI: 4.8–7.6%), being 7.9% (95% CI: 5.9–9.9%) in males and 3.8% (95% CI: 2.1–5.5%) in females. An independent strong association was seen in male smokers and diabetes, with ORs pf 7.2 (95% CI: 2.8–18.6) and 1.8 (95% CI: 1.0–3.3), respectively, and in female smokers and hypertension, with ORs of 5.2 (95% CI: 1.6–17.3) and 3.3 (95% CI: 1.2–9.0). Male subjects presented with higher REGICOR scores ( Peripheral arterial disease (PAD) is the manifestation of atherosclerotic disease in the lower extremities, resulting in narrowing of the blood vessels and diminishing blood flow to the limbs. It is the third leading cause of cardiovascular pathology after coronary and cerebrovascular disease and an important indicator of cardiovascular risk . The merAssociated risk factors are common for cardiovascular diseases, such as smoking, diabetes, dyslipidemia and hypertension, among others. Active smoking has the strongest association, doubling the risk of PAD in these patients . TherefoThe ankle–brachial index (ABI) is an effective, easy and first-line noninvasive method in screening PAD ,5,6, witIn the United States, 8 to 12 million Americans suffer from PAD, with an overall prevalence of 3–10%, which increases to almost 50% in those greater than 85 years old . As for PAD is also influenced by gender and age, predominantly being associated with the male gender. Age is also an important factor, with a 20% increase observed in those older than 75 ,12. In aTo our knowledge, most studies focused on the prevalence of PAD performed in our region were inclusive of younger age groups, some including ages as young as 35 years old ,14. ThisThus, the aim of our study was to determine the prevalence of peripheral arterial disease through ABI in 65-year-old men and women in Northern Barcelona (Spain), as well as its associated risk factors.This is a single-center, populational-based, cross-sectional study, part of a larger pilot screening program evaluating abdominal aorta aneurysm . The proThe study was carried out in a health-integrated area AIS-Barcelona Nord, with a population base of 400,000 inhabitants, which corresponds to the area of treatment of our center. Inclusion criteria were all noninstitutionalized males and females of 65 years of age during the time of recruitment who were health care cardholders and resided for at least 6 months in the referred area.Contact information of the population was authorized and obtained through our public health census registry, and all eligible subjects received invitation letters informing them of the present study and tests to be performed. Those with incorrect postal data, terminal disease and deceased subjects were considered ineligible .Nonresponders to the first letter were invited again within 1 month. Those who agreed to participate were scheduled an appointment at our Vascular Lab Center with one of five trained vascular surgeon residents. Participants were contacted 48 h before the appointment to confirm attendance. Those who did not show up for the scheduled appointment after 3 occasions, those who did not wish to participate and subjects who did not respond to both invitation letters were excluded.After arrival, prior to questioning, a signed consent form was required from each participant. All subjects were questioned for a history of risk factors, such as: cigarette smoking: active, former (more than a year without smoking) or nonsmoker; hypertension, defined as systolic blood pressure ≥140/90 mmHg or subjects under antihypertensive treatment; dyslipidemia, defined as one or all of total blood cholesterol >200 mg/dL, low-density lipoprotein (LDL) cholesterol >100 mg/dL or triglycerides >150 mg/dL or subjects under treatment for dyslipidemia; diabetes, defined as those diagnosed and/or under antidiabetic treatment; history of cerebrovascular disease ; history of cardiac ischemia ; chronic renal disease (glomerular filtration <60 mL/min) and history of any aortic aneurismatic disease. Anthropometric measurements were also recorded: height (m), weight (kg), waist circumference (cm) and body mass index (BMI). A REGICOR score  was deteTo complete the assessment, a physical exam was performed, evaluating distal pulses through palpation. The presence of a pulse in one or both tibial arteries was considered adequate. Afterward, an ABI was performed in a standard manner : after aFor better analysis and interpretation of our results, we reviewed common risk factors among our study participants and those obtained from the official health department database, 2018 Catalan Health Survey “Enquesta Catalunya de Salut 2018” (ESCA) (ages 65–74 years old), and our primary care clinics (65 years old), with previous authorization from our health department.p < 0.05. Statistical analysis was performed through IBM SPSS Statistics for Windows, version 22.0 .Descriptive analysis was performed, and prevalence of PAD was obtained with the 95% confidence interval. Dichotomous variables were analyzed through Pearson’s chi-square test or Fisher’s exact test. Logistic regression models were used to obtain independent associated risk factors for PAD that were previously significant in the bivariate analysis. Interaction effect was also evaluated among these risk factors. Statistical significance results were considered for a value of From November 2017 to December 2018, a total of 2808 subjects were 65 years old during the time of recruitment. A total of 1174 subjects were finally included, 695 (59.2%) male and 479 (40.8%) female. Total participation rate was 43.1%, with higher participation from females (46.7%) than males (40.9%). A flow chart of initial screening with main results separated by sex is shown in n = 53, 72.6%), 20.5% IIA (n = 15), 5.5% IIB (n = 4) and 1.4% (n = 1). The difference in prevalence between male and female was statistically significant (p = 0.006). Male subjects presented at higher risk for PAD, with an OR of 2.2 (CI: 1.3–3.8).The overall prevalence of PAD was 6.2% (95% CI: 4.8–7.6%), male 7.9% (95% CI: 5.9–9.9%) and female 3.8% (95% CI: 2.1–5.5%), most of them corresponding to the Fontaine I classification , all subjects except for one had palpable distal pulses and none referred to intermittent claudication.p = 0.017) and female subjects hypertension (p = 0.026) and waist circumference (p = 0.018). No association was seen with a family history of abdominal aortic aneurysm, probably due to the small number of cases detected. Diabetes male subjects were more likely to have PAD  and in active smokers 7.2 (95% CI: 2.8–18.6) in comparison with nonsmokers. An association with diabetes and PAD was also seen in our male participants, with an OR of 1.8 (95% CI: 1.0–3.3)As for our female model, an association was also seen in relation to PAD and smoking, with an OR of 3.1 (95% CI: 1.0–9.6) in ex-smokers and 5.2 (95% CI: 1.6–17.3) in active smokers compared with nonsmokers. PAD was also higher in those female subjects with hypertension, with an OR of 3.3 (95% CI: 1.2–9.0) . No signn = 500) of our population were at low risk of developing a cardiovascular event in the following 10 years, 40.4% (n = 393) were at moderate risk and 8.1% (n = 79) were at a high-risk score. Four subjects were excluded from REGICOR analysis due to missing data. Male subjects presented with higher REGICOR scores (p < 0.001), putting them at a higher risk for developing a cardiovascular event in the following 10 years compared to our female subjects. Discarding 157 subjects who had already presented a previous cardiovascular event, 1013 subjects were classified according to their cardiovascular risk at 10 years with the REGICOR scale. In this regard, 51.4% (p < 0.001), and our male subjects had higher percentages of diabetes (p < 0.001), high blood pressure (p < 0.001), chronic renal insufficiency (p = 0.001) and cardiac ischemia (p < 0.001), presenting with more risk factors than our female participants. Regarding the history of aneurysmal disease, 3% (n = 35) had a family history of abdominal aneurismatic disease, with 26 of them being a first-degree family member.Characteristics of our 1174 studied men and women are best shown in Characteristics of our participants with those obtained from the 2018 Catalan Health Survey “Enquesta Catalunya de Salut 2018” (ESCA) and primary care centers located in our area of treatment of Barcelona Nord were reviewed in order to better assess the representation of our sample participants with our overall area of treatment population, as shown in In the present study, the prevalence of PAD in asymptomatic patients was 6.2% at age 65, which is in accordance with previous studies carried out in the Mediterranean area ,14,17. RThe worldwide prevalence of PAD is estimated to be 3–12% , affectiIn Spain, however, the prevalence of PAD is considerably lower. The ESTIME study  estimateTraditionally PAD is thought to be a male-predominant disease , but in The association of PAD with coronary artery disease is observed in 50% of patients and in 20% of patients with cerebrovascular disease ,26, becoThe strongest predictor of PAD in those 65 years and younger has been associated with diabetes and smoking , althougp < 0.001) with a high-risk score (considered > 10%) in those with PAD at 14.8% versus those with non-PAD at 12.7%. Therefore, screening with ABI in these subjects we believe to be important for the early implementation of secondary cardiovascular prevention.Stratification of cardiovascular risk was also attempted through the REGICOR score to identify those who had a higher risk of developing a cardiovascular event in the following 10 years. Altogether, we found higher scores in males (It should be noted that this study is part of a larger pilot screening program evaluating abdominal aorta aneurysms , thus exIn summary, the overall prevalence of PAD in North Barcelona at 65 years old is still significantly low compared to other regions of Europe , and malOur results concur with the literature on this topic for our region ,17 and o


Maternal adversity during pregnancy has been shown to be associated with some health outcomes in the offspring. This study investigated the association of maternal adversity during pregnancy and DNA methylation with offspring cardiovascular (CV) health.Longitudinal observational cohort studyAll pregnant residents in county Avon (∼0.9 million), UK, were eligible to participate if their estimated delivery date was between 1 April 1991 and 31 December 1992.Mother–offspring pairs enrolled in the Avon Longitudinal Study of Parents and Children cohort at seven (n=7431) and 17 years of age (n=3143).Offspring CV health primary measures were heart rate (HR), blood pressure (BP) and secondary measures were pulse-wave velocity and carotid intima–media thickness.Overall, there was no association between maternal adversity scores (number or perceived impact) and primary CV measures : 1.000-fold change 95% CI 0.999 to 1.001; diastolic BP: 1.000-fold change 95% CI 0.999 to 1.002). Some small offspring sex effects were observed and there was also a small association between methylation of some CpG sites and offspring BP measures.We found little evidence to support the overall association of maternal adversity during pregnancy and DNA methylation with offspring CV measures. Offspring sex-specific and age-specific associations require further investigation. A strength of this study is longitudinal collection of phenotypic data in both women and their child; detailed cardiovascular measures in the offspring have been collected at multiple time points.A limitation is attrition bias, with those of a higher socioeconomic status being more likely to remain in the study over time.In addition it is possible that some life stressors during pregnancy may have not have been captured given the list of potential stressors was not exhaustive.It is plausible that any effects during pregnancy may have been diluted by the inclusion of data about maternal stressors that was collected in the early postpartum phase (8 weeks post partum).et al in the early 20th century noted geographical differences in infant mortality rates, whereby regions of England with the highest infant mortality rates also had the highest rate of coronary heart disease (CHD) mortality.…adverse environmental influences in utero and during infancy, associated with poor living standards, directly increased susceptibility to the disease (CHD).’ Further extending this work, the Developmental Origins of Health and Disease hypothesisSeminal work conducted by Barker To date, much of the work in this area has focused on the impact of maternal nutrition during pregnancy, with comparatively fewer data on social adversity and trauma. However, there are some data to suggest that the ways in which women experience social adversity during pregnancy may induce similar changes to disease trajectory in the offspring as maternal malnourishment.4The time in utero represents a critical period of development, which may be particularly vulnerable to maternal stress. During this time, it is plausible the fetus is directly susceptible to the biological effects of maternal stress owing to its reliance on the maternal blood supply via the placenta. Epigenetics are mitotically heritable changes to gene expression that do not involve changes to the underlying genetic sequence. These changes in gene expression may provide some clues about the mechanisms through which maternal adversity embeds itself into an individual and her offspring. A recent review of maternal prenatal stress and infant DNA methylation identified several candidate genes implicated in the maternal central stress response that may be critical in driving phenotype changes for offspring.5The extent of cumulative damage to biological systems that occurs with increasing number, duration or severity of exposures, particularly with age, is likely to be a critical consideration in understanding associations between maternal adversity and the cardiovascular (CV) health of a child. This includes distinguishing the response  from the stimulus or stressor  itself. It is also notable that there appears to be a sexually dimorphic response with regards to several developmental exposures and CV conditions.This study therefore seeks to, (1) investigate the respective and cumulative impact of women’s exposure(s) to adversity during the perinatal period, and cord blood DNA methylation on CV health of her offspring, (2) establish whether associations are sex or age-dependent and (3) determine whether DNA methylation at birth is associated with CV outcomes. We hypothesise that greater maternal adversity will be associated with poorer CV health of offspring and DNA methylation will be associated with offspring CV measures.This study used longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC formerly ‘Children of the 90s’ study). ALSPAC is a prospective birth cohort study conducted in the UK. The full study protocol is available elsewhere with participation rates and reason for not participation.There were 13 617 mother–offspring pairs from singleton live births who survived to ≥1 year of age; only singleton pregnancies and those women with term deliveries were included in the analyses. When the oldest children were approximately 7 years of age, an attempt was made to bolster the initial sample with eligible cases who had failed to join the study originally, resulting in an additional 913 children being enrolled. The total sample size for analyses using any data collected after the age of 7 is therefore 15 454 pregnancies, resulting in 15 589 fetuses. Of these 14 901 were alive at 1 year of age. The number of children with CV measures at the subsequent 7-year and 17 year time points were 7431 and 5215 , respectData were those provided by women at (1) 0–18 weeks gestation, and (2) between 19 weeks gestation and 8 weeks post partum. Women retrospectively self-reported social adversities and rated its impact for the respective period. Adverse life events were assessed using a 41-item self-report questionnaire based on a Life Events Inventory,The primary outcomes were blood pressure (BP) and heart rate (HR) at 7 and 17 years of age. Duplicate measures of resting HR, systolic BP (SBP) and diastolic BP (DBP) were taken using a Dinamap 9301 Vital Signs Monitor while participants were seated, using the average of the two readings.Secondary outcomes were pulse-wave velocity (PWV) and carotid intima media thickness (cIMT) at 17 years of age, using the mean of three measures and the mean of three end-diastolic measurements of both the left and right side, respectively. A Vicorder device  was used to measure PWV and a Zonare Z.OneUltra system that had a a L10-5 linear transducer  was used to determine cIMT. Detailed protocols have been described elsewhere.11Embedded within the ALSPAC study is a human epigenetic resource; the Accessible Resource for Integrated Epigenomic Studies (ARIES).Raw intensity signals were processed and M-values were calculated using the minfi package.et al.15Directed acyclic graphs were constructed  from whi10.1136/bmjopen-2021-053652.supp1Supplementary data10.1136/bmjopen-2021-053652.supp2Supplementary dataOutcomes were log-transformed for anaylses. Linear mixed modelsP values were based on the likelihood ratio statistic except for the descriptive analyses, where p values for a sex difference were based on a t-test (for continuous variables) or Fisher’s exact test (for binary variables).18There was no direct involvement from participants in the study design. Select participants are part of a committee which meets to discuss and provide insights on acceptability, and study methodology and design. This committee was not involved in the formulation of the current research question and analyses.Characteristics and summary data of the sample are as shown in 10.1136/bmjopen-2021-053652.supp4Supplementary dataThere was no association between number of events and any of the primary offspring CV measures (CV time points combined) . ResultsIn contrast to our hypotheses, there was an association between perceived impact score and PWV in boys, whereby a four-unit increase in adversity score was associated with a 0.1% decrease in PWV  was associated with offspring SBP (1.013-fold change 95% CI 1.008 to 1.017 per SD). There was an association with methylation of cg07494499 (NXN) (1.012-fold change 95% CI: 1.008 to 1.017 per SD of the outcome) and cg02458152 (EFCAB1) (1.011-fold change 95% CI 1.007 to 1.015 per SD) and SBP. There was also an association between methylation of cg20222926 (FEZF1) (0.987-fold change 95% CI 0.982 to0.992 per SD) and DBP that appeared to be largely driven by rare, large DNA methylation changes . HoweverWe further explored how events clustered , and whe10.1136/bmjopen-2021-053652.supp3Supplementary dataIn contrast to the hypothesis, at the seven-year follow-up, female offspring of mothers who were admitted to hospital had a 2.5% lower HR (0.975 fold-change 95% CI: 0.956 to 0.994), 1.8% lower SBP (0.982 fold-change 95% CI: 0.967 to 0.996) and 2.6% lower DBP (0.974 fold-change 95% CI 0.957 to 0.992); argued with partner had a 2.4% lower HR (0.976 fold-change 95% CI 0.961 to 0.992) and a 1.5% lower DBP (0.985 fold-change 95% CI 0.971 to 0.0.999); argued with family and friends had a 1.8% lower SBP (0.982 fold-change 95% CI 0.965 to 0.999); took an exam had a 4.2% lower SBP (0.958 fold-change 95% CI 0.928 to 0.988); had a partner emotionally cruel to child had a 6.7% lower DBP (0.933 fold-change 95% CI 0.875 to 0.996) and had a partner emotionally cruel to her had a 2.9% lower HR (0.971 fold-change 95% CI 0.944 to 0.999). In agreeance with the hypothesis, at seven years female offspring of mothers who were in trouble with the law had a 9.0% higher SBP (1.090 fold-change 95% CI 1.003 to 1.185); were separated had a 3.1% higher SBP (1.031 fold-change 95% CI 1.005 to 1.058); and tried to have an abortion had a 10.4% higher DBP (1.104 fold-change 95% CI 1.012 to 1.205).In contrast to the hypotheses, at the seven-year follow-up, male offspring of mothers those who had an ill partner had a 2.9% lower SBP (0.971 fold-change 95% CI 0.951 to 0.992); became homeless had a 7.3% lower DBP (0.927 fold-change 95% CI: 0.88 to 0.978); were convicted of an offence had a 14.0% lower SBP (0.860 fold-change 95% CI: 0.743 to 0.996); were in trouble with the law had a 10.4% lower SBP (0.896 fold-change 95% CI 0.816 to 0.983); and had a partner who hurt them had a 6.1% lower DBP (0.939 fold-change 95% CI 0.999 to 0.993). In agreeance, at seven years male offspring who had mothers who attempted suicide had a 25.0% higher HR (1.250 fold-change 95% CI 1.018 to 1.535) and had income reduced had a 1.4% higher SBP (1.014 fold-change 95% CI 1.002 to 1.027).At 17 years of age, female offspring of mothers who were admitted to hospital had a 2.0% higher DBP (1.020 fold-change 95% CI 1.003 to 1.038); who attempted suicide had a 41.6% higher HR (1.416 fold-change 95% CI 1.081 to 1.854); had moved house had a 4.5% higher HR (1.045 fold-change 95% CI 1.012 to 1.079); whose partner was emotional cruel to them had a 2.1% (1.021 fold-change 95% CI 1.002 to 1.041) and 3.1% (1.031 fold-change 95% CI 1.006 to 1.056) higher SBP and DBP, respectively; whose partner rejected the pregnancy had a 7.2% higher HR (1.072 fold-change 95% CI 1.019 to 1.127) and was very ill has a 2.5% higher SBP (1.025 fold-change 95% CI 1.004 to 1.046).At 17 years of age, male offspring who had mothers that were admitted to hospital had a 2.2% higher DBP (1.022 fold-change 95% CI 1.001 to 1.043); were convicted of an offence had a 91.9% higher HR (1.919 fold-change 95% CI 1.209 to 3.045); had major financial problems had a 2.8% higher DBP (1.028 fold-change 95% CI 1.005 to 1.051); was told they were having twins had a 7.2% higher HR (1.072 fold-change 95% CI 1.006 to 1.144); took an exam had a 9.8% higher HR (1.098 fold-change 95% CI 1.027 to 1.174) and was very ill had a 3.2% (1.032 fold-change 95% CI 1.009 to 1.056) and 4.2% (1.042 fold-change 95% CI 1.013 to 1.072) higher SBP and DBP, respectively. Contrary to the hypothesis at 17 years of age, male offspring of mothers who argued with partner, had a partner who was emotionally cruel to them, had a partner who hurt their child, had a partner reject the pregnancy or possible harm to the baby had a 2.7% (0.973 fold-change 95% CI 0.948 to 0.999), 4.5% (0.955 fold-change 95% CI 0.915 to 0.998), 34.5% (0.655 fold-change 95% CI 0.492 to 0.873), 7.7% (0.923 fold-change 95% CI 0.0.865 to 0.984) and 5.0% (0.950 fold-change 95% CI 0.902 to 0.996) lower HR, respectively.There was no evidence of an overall association between our primary CV measures in offspring and maternal adversity. There was limited evidence to suggest that subtypes of adversity or specific may be associated with CV measures in an age-specific manner as well as an association between CV measures and some CpG probes.Associations between adversity and health outcomes previously reported in the literature are thought to be moderated by biological changes induced by the stress response. Global methylation is associated with CVD in adult populations.Few studies have looked at maternal adversity and CV risk factors in childhood and adolescence. Within this cohort, no association was observed between childhood adversity and BP at 7 and 11 years of age.Specific adversities were largely associated with favourable changes in offspring CV measures at age 7. At age 17, the direction of the association largely reversed, most pronounced in females. This is suggestive of a protective adaptive response to maternal adversity present in childhood that may reverse trajectory by age 17. Contrary to the original hypotheses, at age 7, specific maternal adversities largely appeared to have a protective effect on offspring CV measures. Similarly, in this same cohort, a different study observed that maternal prenatal anxiety and depressive symptomology was inversely associated with offspring BP at 10–11 years of age, although to a similar magnitude as paternal measures.A strength of the current study is its large sample size and its detailed collection of longitudinal phenotypic data in both mothers and their children followed into adolescence. However, as is the case with such long-term observational studies, over time, there is evidence of attrition, which may introduce bias, with those who were of a higher socioeconomic position being more likely to remain in the study over time thus potentially limiting the generalisabilty of the results. Moreover, the list of potentially life stressors was not exhaustive and may have resulted in measurement error influencing the results. In addition, the adversity scores calculated as part of this study have not been previously validated. Furthermore, to capture maternal adversity during pregnancy, we took the weighted average of the Life Events Inventory, which was inclusive from the beginning of pregnancy to 8 weeks post-partum). Thus, any effects may have been diluted by the inclusion of adversity in the 8 weeks post birth during the perinatal period. Lastly, future studies may benefit from the examination of specific key genes that have been identified in CVD pathways aside from global methylation measures.In summary, the results presented largely do not support an association between maternal prenatal adversity, and offspring methylation and CV measures during childhood and adolescence. There were, however some sex-specific and age-specific trends which would have to be confirmed in future studies. Identification and confirmation of these associations between maternal adversity and offspring CV function may assist with identifying high-risk populations for which additional monitoring may be appropriate.


To investigate the long-term clinical results of radiofrequency ablation (RFA) for bilateral papillary thyroid microcarcinoma (PTMC).3) treated by RFA were included in this retrospective study. Bilateral PTMC was defined as at least one tumor located in the contralateral lobe. Patients were followed up at 1, 3, 6, 12 months and every 6–12 months thereafter. Volume, volume reduction ratio (VRR) and local tumor recurrence were evaluated during the follow-up period.From October 2014 to February 2018, 47 patients  with 100 bilateral PTMC  developed lymph node metastasis and two patients (4.26%) had recurrent PTMC. All the recurrent lesions underwent additional RFA and two of them disappeared completely. No life-threatening or delayed complications occurred.After a mean follow-up period of 47.77 ± 11.54 months, the mean volume of bilateral PTMC decreased from 75.22 ± 73.87 mmWith sufficient preoperative evaluation, RFA might be a promising alternative for bilateral PTMC patients who were unsuitable for surgery or refused surgery. The incidence of thyroid cancer has increased worldwide, ranking in ninth among all cancers –4. ApproRFA is a commonly used thermal technique, has been reported as an effective and safe treatment for low-risk PTMC patients who refuse surgery or active surveillance –19. AfteTherefore, the purpose of this study was to evaluate the efficacy and safety of RFA for bilateral PTMC.The Institutional Review Board of our institution approved this retrospective study. All the patients were provided written information consent before RFA. The RFA informed consent emphasized that surgery was the routine treatment recommended by guidelines.Bilateral PTMC was defined as at least one tumor located in the contralateral lobe . The incFrom October 2014 to February 2018, 468 patients with bilateral PTMC underwent treatment in this institution. Among them, 76 patients who were unsuitable for surgery or rejected surgery underwent RFA. Among them, patients with follow-up period less than 24 months (N = 29) were excluded. At last, a total of 47 patients with 100 low-risk PTMC were evaluated.Before RFA, patients all underwent thorough examinations, including complete blood count, thyroid function tests, coagulation tests and imaging evaluation, including ultrasound and chest CT –14. The V is the volume, while a is the largest diameter, b and c are the other two perpendicular diameters.US were performed using a Siemens Acuson Sequoia 512 Ultrasound System (Siemens) or a Philips iU22 Ultrasound System  or a Mindray M9 Ultrasound System (Mindray). CNB and RFA were all performed using a Siemens Acuson Sequoia 512 Ultrasound System. Contrast-enhanced ultrasound (CEUS) was used to assess the tumor before and immediately after RFA procedure. The ultrasound contrast agent was sulfur hexafluoride (SonoVueR). After injection of 2.4 ml SonoVue followed by a 5 ml of normal saline flush, CEUS was applied to observe the real-time microbubble perfusions within the tumor and the surrounding thyroid tissues.All RFA procedures were performed by an experienced US physician. A bipolar RFA generator (CelonLabPOWER) and an 18-gauge bipolar RF applicator with 0.9 cm active tip (CelonProSurge micro 100-T09) were used.Patients lay on an operating table in the supine position with the neck hyperextended. The targeted tumor was evaluated by multi-angle scanning to determine a practical and proper approach. Doppler ultrasound was used to access the detailed vascular anatomy along the approach route to prevent bleeding. Local anesthetic (1% lidocaine) was injected at the subcutaneous puncture site and the thyroid anterior capsule. During the RFA procedure, the smaller lesion was ablated first.RFA procedure was performed using trans-isthmic approach and moving-shot technique. To prevent thermal injury, hydrodissection technique was performed by injection of normal saline to separate the target tumor from critical structures . Normal saline was injected using another needle (23 gauge) to form at least 1 cm distance between the tumor and the critical structure , 14.The initial RFA power was 3 W and was increased to 5 to 9 W if a transient hyperechoic zone did not form at the electrode tip in 10 s. To prevent marginal residue and recurrence, we enlarged the ablation area which exceeded the tumor edge (at least 3–5 mm) , 22. CEUPatients were followed up at 1, 3, 6 months and every 6–12 months thereafter by US, CEUS and chest CT. At 3 or 6 months after RFA, the ablated area was evaluated by CNB, which was performed to the central zone, the peripheral zone and surrounding thyroid parenchyma –24. The RFA was considered to successful when one of the criteria were met : (1) theP <0.05 was considered as statistically significant.Statistical analysis was performed using the SPSS statistical software (Version 25.0). Continuous data were presented as mean ± SD (range). Non-parametric Wilcoxon signed-rank tests were used to compare the pre-ablation with post-ablation volume as each follow-up period. A 3. The volume of dominant tumor was 108.77 ± 87.08 mm3.Clinical characteristics of patients before RFA are shown in For each tumor, the mean power was 3.92 ± 0.98 W. The mean RFA time was 224.09 ± 156.68 s and the mean energy was 853.64 ± 614.39 J.P <0.001) because of the enlarge ablation, which was gradually decreased from 6 months after RFA  and 4.26% (2/47), respectively. No distant metastasis was detected. No patient underwent delayed surgery during the follow-up. The clinical characteristics and outcomes of PTMC patients with local tumor recurrence are showed in All the 47 patients were tolerable to RFA. Four patients underwent local pain or discomfort and they all resolved spontaneously within 3 days. No patients had major or delayed complications.3 to 0.09 ± 0.43 mm3 with a mean VRR of 99.94 ± 0.28%. A total of 92 tumors disappeared completely. The incidences of LN metastasis and of recurrent PTMC were 2.13 and 4.26%, respectively. All recurrent lesions were successfully treated with an additional RFA. No major complications or sequelae were observed.To date, no study has been evaluated the clinical application of RFA for bilateral PTMC. In this study, after a mean follow-up period of 47.77 ± 11.54 months, the mean volume of bilateral PTMC decreased from 75.36 ± 73.86 mmvia intraglandular lymphatics  and the Research of Healthcare Big Data of Chinese PLA General Hospital (2019MBD-040).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA).We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences.p = 0.02) and cSAH  but not ischemic stroke  or mortality .We included 190 patients  from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9–17.4); recurrent cSAH 11.1% (95% CI 7.9–15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7–26.9), ischemic stroke 5.1% (95% CI 3.1–8) and death 8.3% (95% CI 5.6–11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH  CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.The online version contains supplementary material available at 10.1007/s00415-021-10706-3. Convexity subarachnoid haemorrhage (cSAH) describes non-traumatic subarachnoid bleeding limited to the subarachnoid space over the convexities of the brain that does not extend into the parenchyma, sylvian fissures, ventricles, or basal cisterns , 2. cSAHWe therefore performed an international collaborative individual patient data pooled analysis of cohort studies of patients with cSAH and known probable and possible CAA status to increase statistical power and improve the precision of event rate estimates for ICH, symptomatic ischemic stroke, recurrent cSAH and death. We investigated whether neuroimaging markers indicating probable CAA influences the risks of these events.A repeated systematic literature review (conducted by 2 authors ICH and DW) using PubMed, EMBASE and reference searches identified 21 potentially eligible publications for this individual patient-data pooled analysis, including our own cohort  . The seaAnonymized data was transferred from participating cohorts to the Stroke Research Centre, UCL Queen Square Institute of Neurology, using a pre-specified data collection sheet. Authors contributed individual patient-data, including patient characteristics, past medical history, medication history and, where available, baseline brain imaging markers and follow-up data. Data was checked for internal consistency with respect̄ to range, and consistency with published reports. Inconsistencies or missing data were reviewed, and attempts were made to resolve any inconsistencies by consensus. In case where missing values are present this is indicated in the tables.Symptomatic ICH was defined as acute or subacute onset of neurological symptoms  with radiological evidence of recent intracerebral haemorrhage . Recurrent cSAH was defined as acute haemorrhage limited to the subarachnoid space over the convexities of the brain, not extending into the parenchyma, sylvian fissures, ventricles, or basal cisterns . SymptomWe reported our study according to the STROBE guidelines and did the pooled analysis according to the PRISMA guidelines , 26. We Probable CAA (versus possible CAA) was diagnosed according to the modified Boston criteria by trained observers at each center. Convexity SAH was not included as a component of the modified Boston criteria , 23. WhiWe estimated the rates of each outcome event using Kaplan Meier survival curves. We investigated the association between the risk of cSAH and each outcome separately using the Cox proportional hazards model with a frailty term to account for differences between study cohorts. The frailty term allows the (absolute) risk to be different in the different studies, i.e., to adjust for unmeasured study-level covariates. We checked the proportional hazards assumption for all analyses by visual inspection of the log–log plot of survival (log cumulative hazard versus log time). If the lines were not parallel, we tested the proportional hazard assumption using Schoenfeld residuals.We performed a pooled multivariable regression analysis for each outcome using a frailty term to account for differences between study cohorts. The multivariable model included the prespecified variables probable CAA and age, as well as variables that had a p value below 0.2 in the univariable analysis for each outcome. As a sensitivity analysis we conducted a competing risk analysis for all of the outcome events. Due to a strong degree of overlap (collinearity), we did not include probable CAA and cortical superficial siderosis in the same model.Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC).Statistical analysis was performed using STATA 15 (StataCorp. 2017. We identified 190 eligible patients with cSAH in 13 cohorts published or recruited between 2001 and 2018 with 385 patient-years of follow-up (median follow-up time 1.4 years). The mean age was 74.5 (SD 8.8) and 86 (45.3%) were female. See Table Over the full period of follow-up, the frequency of events was as follows: 51 (26.8%) had an ICH, 39 (20.5%) a recurrent cSAH, and 19 (10%) an ischemic stroke; 31 (16.3%) died. Figure p = 0.023; Table p = 0.02; Table We observed 51 ICH over 385 patient-years, an absolute event rate of 13.2% (95% CI 9.9–17.4) per patient-year; the median time to ICH was 1.4 years (IQR 3.4), while 21.6% occurred in the first month . OAC use was not associated with the risk of recurrent cSAH .We observed 39 recurrent cSAH over 351 patient-years, an absolute event rate per patient-year of 11.1% (95% CI 7.9–15.2). The median time to recurrent cSAH was 1.3 years (IQR 3.3). The event rate was 11.9% (95% CI 8.3–16.5) for probable CAA and 7.1% (95% CI 1.9–18.3) for possible CAA  per patient-year was 21.4% (95% CI 16.7–26.9); 17 patients had both recurrent ICH and cSAH.p = 0.32; Table p = 0.33).We observed 19 symptomatic ischemic stroke events over 373 patients-years, an absolute event rate per patient-year of 5.1% (95% CI 3.1–8). The median time to ischemic stroke was 1.3 years (IQR 3.3). The event rate for patients with probable CAA was 4.7% 95% CI 2.6–7.7) and for patients with possible CAA 7.5% . In a sensitivity analysis, adding smoking status to the multivariable model did not change the findings (results not shown).We observed 31 deaths over 373 patient-years, an overall absolute event rate of 8.3% (95%CI 5.6–11.8) per patient-year. The median time to death was 1.2 years (IQR 3.3). There was no statistically significant difference in mortality between patients with probable CAA [7.3% for patients with probable CAA (95% CI 4.6–10.9)] and those without . The substantially higher ICH risk in probable compared to possible CAA (15.2% vs 1.8% per year)—with a similar ischemic stroke risk regardless of CAA status—might favor avoiding antithrombotics for patients with cSAH who meet the modified Boston criteria for probable CAA. There are no other observational data or randomized controlled trials addressing the risks of (re)starting antithrombotic drugs after cSAH. Data on whether antiplatelet drugs affect recurrent ICH risk after a symptomatic ICH are conflicting: while two small single center studies gave inconsistent data on whether the rate of recurrent ICH was increased by the use of aspirin , 35, theOur pooled analysis approach has several strengths. We have included the largest number of patients with cSAH associated with probable or possible CAA studied to date, with a long follow-up period, allowing us to provide more precise estimates of the rates of future ICH, cSAH, as well as ischemic stroke after a previous cSAH, including data on the longer-term time course of these events. The inclusion of detailed individual patient data additionally allowed us to evaluate multivariable models. Reassuringly, in our pooled analysis, the risk of bias was low, so any loss to follow-up is most likely due to random (non-informative) censoring.However, our study also has limitations. This was a retrospective study, although we only included studies where investigators had systematically and prospectively collected data on the follow-up events of interest as defined in the protocol. Additionally, imaging was not reviewed centrally. This is a potential source of bias as agreement between the different centers could not be tested. However, uniform definitions of CAA were applied by trained raters as per our predefined study protocol. Also, our rate of spreading symptoms was surprisingly low which we think to be due to the retrospective nature of the study and reflects an underestimation. This needs to be verified in an independent large cohort.We confirm that patients with cSAH are at high risk of future ICH and recurrent cSAH , with a high early risk. By contrast, the risk of ischemic stroke is much lower (5.1% per patient-year). Probable vs possible CAA is a predictor of higher ICH but not ischemic stroke risk. Our data provide precise risk estimates of key vascular outcomes after cSAH that can help inform prognosis and management decisions after cSAH.Supplementary file1 (DOCX 117 KB)Supplementary file2 (PDF 961 KB)Below is the link to the electronic supplementary material.


A shift toward the endovascular treatment of ophthalmic segment aneurysms is noticeable. However, it is not clear if the long-term treatment results improve with the development of endovascular methods. The aim of this study was to present the outcomes of the treatment of unruptured ophthalmic aneurysms using flow diverting devices (FDD) with or without coiling. This retrospective study included 52 patients with 65 UIAs treated in 2009–2016. The mean aneurysm size was 8.8 mm. Eight aneurysms were symptomatic. Therapeutic procedures included: 5 failed attempts, 55 first sessions with FDD deployment  and 3 retreatment procedures. To cover 55 ICAs, 25 Silk, 26 Pipeline, 9 Fred and 1 Surpass FDD were used. FDD with coiling was applied in 19(29.2%), mainly for symptomatic and larger aneurysms. Mean radiological and clinical follow-up was 12 and 61 months, respectively. Postprocedural deterioration was noted in 3(5.8%) patients, but in long-term the modified Rankin Scale grades 0–2 were achieved in 98.1% of patients. One patient died from the treated aneurysm rupture . Raymond–Roy occlusion classification class I or II was achieved in 98.5% in the long term, with similar results in both groups. Complications occurred in 40.4% of patients and the most frequent were: imperfect FDD deployment (15%), failed attempt of FDD deployment (9.6%) and late FDD stenosis (9.6%). Flow-diverting devices, with additional coiling in selected cases, may offer a very high proportion of satisfactory outcomes. However, in our experience the high risk of complications remains. Aneurysms of ICA-C6 occur with a frequency of approximately 5% of all intracranial aneurysms2. Besides the subarachnoid haemorrhage, the clinical presentations include visual deficits3. Surgical clipping and different endovascular techniques like coil embolisation, flow diverting device (FDD) deployment and combination of coiling with stenting are current options for the treatment of ICA-C6 aneurysms6. Permanent morbidity ranges from 0.8 to 38%11, and the new visual deficits occur more often after clipping than endovascular treatment14. Flow diverting stents are promising devices for a higher percentage of fully occluded aneurysms as compared to coil embolisation15.The ophthalmic segment of internal carotid artery (ICA-C6), starts at the distal dural ring and ends just before the posterior communicating artery originThe aim of this study was to present the clinical and radiological outcomes of endovascular treatment of unruptured ICA-C6 aneurysms using FDDs with or without coiling. Different factors were tested as potential predictors of the most favourable outcome.This retrospective study included 52 patients with 65 unruptured aneurysms (UIA) located on ICA-C6 treated in 2009–2016. The mean patient age was 52.5 years (range: 26–76 years old). Forty-five (86.5%) patients were female. Four (7.7%) patients had a history of subarachnoid haemorrhage (SAH) from another aneurysm. Twenty-seven (51.9%) patients were smokers, 26 (50%) patients had arterial hypertension and 7 (13.5%) had a positive family history of intracranial aneurysms.All study participants underwent regular, neurosurgical management and treatment. Afterwards, anonymized patient data was retrospectively analyzed by physicians who have access to patients’ medical records. The Bioethics Committee of the Medical University of Warsaw  approved this study and waived the need for informed consent. Moreover, the study has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.The mean radiological follow-up was 12 months (range: 1 to 24 months), and the mean clinical follow-up was 61 months (range: 3 to 111 months). The follow-up data were available for all patients.16, 26 (40%) aneurysm necks were small (≤ 4 mm) and 39 (60%) were large (> 4 mm); dome-to-neck ratio was ≤ 2 in 44 (67.7%) aneurysms and > 2 in 21 (32.3%) aneurysms  were ophthalmic, 24 (36.9%) superior hypophyseal artery and 2 3.1%) were dorsal ICA (blister-like) aneurysms. Eleven (21.2%) patients had more than one treated ICA-C6 aneurysm: unilaterally in 8 and bilaterally in 3 cases. The measurements of dome and neck in 2 blister-like aneurysms were feasible therefore they were analysed together with saccular aneurysms. According to the convention% were doo11; 21.2%), dizziness , SAH from another aneurysm  or non-specific complaints .Symptoms. Eight (12.3%) aneurysms were symptomatic, with multiple symptoms in 4. Visual field deficit was present in 6 patients, acuity decrease in 4, optic nerve atrophy in 1 and oculomotor nerve palsy in 1. The causes of neuroimaging in the remaining patients were headache  and 3 retreatment procedures. In total, there were 182 invasive procedures, including 119 DSAs.Twenty-five Silk, 26 Pipeline, 9 Fred and 1 Surpass FDD were used to cover 55 ICAs in 52 patients. FDD with additional coiling (FDD + C) was performed in 19 (29.2%) cases.Data on demographics, medical history, symptoms, aneurysms, treatment, complications and results were recorded from patient files. The follow up data were collected based on files from control hospital stays, ambulatory visits and telephone conversations. Indications for and its technique treatment were discussed by the whole team including neurosurgeons and interventional radiologists. All procedures were performed by 2 interventional radiologists . The clinical and radiological outcomes were assessed by neurosurgeons .18. The clinical status was established with the use of the modified Rankin Scale (mRS). Formal ophthalmologic evaluation was available for all patients with symptomatic UIAs. The clinical outcomes were calculated per patient, radiological outcomes per aneurysm, and complication risk per patient, per aneurysm and per procedure.Follow-up Dyna-CT was performed 3 months after the procedure in the last 28 patients of the series. Routinely, the patients underwent the follow-up DSA 6 and 12 months after the procedure. Further imaging was scheduled individually only for patients with incompletely occluded aneurysms. The Raymond–Roy (RROC) and O'Kelly-Marotta (OKM) grading scales were used for aneurysm occlusion assessmenthttps://www.R-project.org).Assessment of the differences between groups was done using t-test for numerical and chi-square or Fisher exact test for categorical data. Potential determinants of the outcome were assessed using one and multivariate logistical regression models, using R 3.5.1 statistical software . The Bioethics Committee of the Medical University of Warsaw  approved this study and waived the need for informed consent.On admission, 8 (15.5%) patients presented with vision symptoms (mRS grade 1) and 1 (1.9%) with cognitive impairment (mRS grade 2) after SAH in the past  patients including minor deficit in 2 and major in 1. One patient had prolonged cognitive impairment due to thromboembolic complications (mRS grade 4). At the discharge from hospital 51 (98.1%) patients were stable with their mRS scores as before the treatment.In follow-up, 49 patients were stable and 1 patient with postprocedural cognitive impairment significantly improved. One patient died from the treated aneurysm rupture. One patient deteriorated for a couple of months to mRS grade 3 because of thromboembolic complications at the 6-month follow-up DSA and she eventually improved to mRS grade 1. In the most recent follow-up, 98.1% of patients achieved satisfactory clinical outcome (mRS grades 0–2).The overall post-treatment risk of aneurysm rupture was 0.33% (1/304 aneurysm-years) during a mean follow-up of 61 months. The annual risk of aneurysm rupture after treatment reached 0.07%. The overall permanent morbidity (mRS > 2) and mortality rate was 1.9%. However, if all minor  and transient post-procedure deficits were included, then the combined morbidity and mortality was 17.3% (9/52).Visual symptoms were stable in follow-up in 4 (50%) patients. One (12.5%) patient had transient and two (25%) permanent deterioration after treatment. The vision improved only in one (12.5%) patient. Patients with asymptomatic UIAs had no visual complications immediately after treatment.p = 0.04).Immediate result of the first procedure. The complete occlusion was demonstrated in only 8 12.3%) aneurysms at the end of the procedure , symptomatic aneurysm, underwent FDD + C (Silk and 4 coils) procedure with immediate RROC class III. The last DSA was performed after SAH and revealed critical distal end stent stenosis and aneurysm remnant .p—not significant (NS)). At this stage 3 (5.6%) aneurysms with angiographic filling were qualified for retreatment. One stent thrombosis with moderate hemiparesis (mRS grade 3) occurred at the time of follow-up DSA procedure.The complete aneurysm occlusion was demonstrated in 73.4% Table . The resRetreatment was needed for 3 (4.6%) residual aneurysms initially treated with FDD in 1 (2.2%), and FDD + C in 2 . In long-term follow-up all these aneurysms were totally occluded and the patients maintained a good neurological condition .Recanalisation of 1 (1.5%) aneurysm from OKM D to OKM B2 was demonstrated in DynaCT at the 3-month follow-up after treatment of 8 mm aneurysm with FDD + C (Silk and HydroSoft coils). Discontinuation of Clopidogrel administration was recommended and the 6-month follow-up DSA revealed the total aneurysm occlusion without additional treatment.According to the OKM Scale, including the results of retreatment procedures, the most recent DSA showed no aneurysm filling (OKM D) in 62 (95.4%), entry remnant with no stasis (OKM C1) in 2 (3.1%) and subtotal filling with significant stasis (OKM B3) in 1 (1.5%) aneurysm which ruptured. Two aneurysms with entry remnant (OKM C1) were small, with a dome-to-neck ratio < 2, located close to the origin of the ophthalmic artery and were treated with FDD alone. The RROC class I or II was achieved in 98.5% of aneurysms, with insignificant difference between FDD + C and FDD groups  out of 55 targeted ICAs in follow-up and was symptomatic in 3 (60%) of them. The last accessible follow-up angiograms demonstrated stent occlusion in 2 (3.8%), stenosis in 2 (3.8%) and normalisation of blood flow in 1 patient. The new failures occurred in 4 (16%) of the Silk FDDs and in 1 (4.5%) of the Pipeline FDDs. None of Fred and Surpass FDDs occluded or narrowed.The follow-up DSA demonstrated the ophthalmic artery occlusion in 6 (10.9%) out of 55 ICAs covered with FDDs. There was no visual deterioration in these patients.During 182 invasive procedures, including all DSAs and treatment sessions, 18 34.6%) patients experienced 29 adverse events. The adverse events included: 3 complications following DSA, 5 failed treatment attempts, 19 procedural complications of completed treatment sessions and 2 access site complications .Nineteen procedural complications in 14 (26.9%) patients occurred during treatment procedures and included: imperfect FDD expansion (8), incorrect migration of FDD distal end (3), FDD thrombosis (3), ICA dissection (2) and vasospasm (3). The procedural complications occurred in 18.2% (6/33) of patients treated with FDD alone and in 42.1% (8/19) treated with FDD + C (The imperfect FDD expansion (Silk in 7 and Pipeline in 1) was treated with balloon angioplasty. The incorrect FDD (Silk in 1 and Pipeline in 2) migration demanded the device replacement in 1 and implantation of additional FDD in 1. The access site complications occurred in 2 cases and included femoral artery pseudoaneurysm (1) and thrombosis (1). Revision vascular surgery was needed in the latter case.Additionally, in follow-up a new FDD stenosis developed spontaneously in 4 cases (Silk in 3 and Surpass in 1), which led to SAH in one. To sum up, the early or late complications occurred in 21 (40.4%) patients. Neurological sequelae of all complications were detailed in the chapter “Success rates. Immediate technical success was defined as an accurate deployment of FDD, as it was planned, during the first procedure with no procedural complications. The immediate technical success rate was 70.7% (37/52) per patient and 70.8% (46/65) per aneurysm. The Immediate technical success rate was 76.1% (35/46) in FDD group and 57.9% (11/19) in FDD + C group .Six months technical success was defined as an aneurysm occlusion greater than 90% (RROC class I–II) and normal blood flow through the ICA (no stenosis/dissection/occlusion) at the 6-month follow-up DSA. The 6-month technical success rate was 63.6% (35/52) per patient, 70.8% (46/65) per aneurysm, 71.7% (33/46) in the FDD group and 68.4% (13/19) in the FDD + C group .Treatment success was defined as a conjunction of the following conditions: an aneurysm occlusion greater than 90% (RROC class I–II), no SAH from targeted aneurysm, mRS grade: 0–2 and no visual deterioration in the most recent follow-up. The treatment success rate was 94.2% (49/52) per patient, 95.4% (62/65) per aneurysm, 97.8% (45/46) in the FDD group and 89.5% (17/19) in the FDD + C group . However, the most desirable scenario  materialised in 47.7% (30/65) of cases only. Potential predictors of the most favourable outcome are presented in Table 11. Endovascular treatment shows some benefits over surgical clipping like a lower risk of visual and other neurologic complications14. However, more than one third of ICA-C6 UIAs are not completely occluded after traditional coiling with or without stenting8. That is why FDDs are now increasingly popular, but their effectiveness has to be proven in long-term evaluations. The risk of neurological deterioration immediately after treatment, beyond the visual symptoms, was 6% in our series. A satisfactory clinical outcome was achieved in 98.1% of patients. Permanent morbidity and mortality rates in similar series were: 0–4.5% and 0–1.4%, respectively20. The good general outcomes of our series are notably burdened by one catastrophic SAH from a treated aneurysm. Yet, our case of SAH reflects rather a problem of effectiveness of endovascular treatment in giant aneurysms. In this case the additional coiling was used, to promote the intra-aneurysmal thrombosis. However, only RROC class III was achieved. Probably, a denser coil packing should be attempted for such unstable aneurysms, for a more direct protection.A shift toward the endovascular treatment of ICA-C6 aneurysms is noticeable21. Optimistic literature data indicates that even two thirds of patients may improve their vision after embolisation and three quarters after surgical clipping13. However, many reports do not include objective ophthalmological evaluation. On the contrary, more critical observations demonstrate that vision improvement is rare and at least one third of patients have posttreatment visual dysfunction23. Our experience on 8 symptomatic UIAs also showed a 25% risk of permanent vision deterioration and a little chance for improvement. Not only our experience indicates that visual symptoms may also appear in delayed period24. Nevertheless, the permanent visual impairment after treatment of asymptomatic UIA is unlikely to occur, based on our and other series13.Visual improvement in symptomatic ICA-C6 aneurysms is also a goal of treatment. Indirect decompression with clinical improvement is possible after embolisation, because of a reduction in aneurysm pulsationThe immediate postprocedural complete obliteration rate was 4 times higher for aneurysms treated with FDD and coiling, but the mid- and long-term results were similar in the FDD and FDD + C groups. It indicates that FDDs alone are effective for most ICA-C6 UIAs and the additional coiling may be reasonable in selected cases.25. The use of additional coiling in 29% of aneurysms could be the reason for better results in our series. Selection of aneurysms for additional coiling depended mainly upon the size and symptoms. Symptomatic aneurysms (5/8) and those larger than 12 mm (10/11) were qualified mainly for FDD + C.The complete obliteration in 95.4% of aneurysms was finally achieved, as compared to 74.6–89.1% in other series25. The revision “stent-in-stent” procedures were safe and fully effective in our patients.The retreatment rate was 4.6% in our series and it ranges from 9 to 30% after coil embolisation and from 0.9 to 6.8% after flow-diversion in other seriesNowadays, we routinely use Dyna-CT imaging 3 months after FDD deployment. In our experience, the worst delayed complication is in-stent stenosis with persistent inflow to the aneurysm and the main purpose of doing Dyna-CT is to exclude this. The new FDD thrombosis or stenosis occurred in almost 10% of patients and all of them were diagnosed during the first half a year after treatment. Therefore, the close surveillance in this period is needed preferably with less invasive Dyna-CT, as one of adverse events was iatrogenic due to DSA procedure.28.Occlusion of the ophthalmic artery was demonstrated in 11%, with no clinical sequalae. In the other series this proportion ranged from 3.6 to 21.6% with questionable clinical significanceAbout 40% of patients experienced complications that, not rarely, were multiple. The most frequent technical complication was imperfect FDD deployment (15% of patients), followed by failed attempts of FDD deployment and late FDD stenosis. Therefore, patients should be informed about the cumulative risk of all invasive procedures and the potentially delayed adverse events.The procedural complications occurred in 42% of patients in the FDD + C group—more than twice as much as in the FDD group. Also, the immediate technical success rate was 18% lower in the FDD + C group than in the FDD group. Despite being insignificant, the differences should be pointed out for critical assessment whether the more complex treatment for more complex aneurysms is reasonable.The treatment success was as high as 95% per aneurysm within a mean follow-up of 5 years. However, the most desirable scenario succeeded in less than half of aneurysms. This indicates that aggressive treatment brings very good final results but is burdened by considerable complication risks.The multivariate analysis of demographic, clinical and morphometric factors demonstrated that younger age, higher dome-to-neck ratio and asymptomatic aneurysms favour the best outcomes.Limitations of the study. Four different kinds of FDD had been used according to the needs and local availability. Furthermore, the UIAs treated with FDD alone significantly differed from those treated with FDD and coiling. Therefore our retrospective analysis cannot serve as a comparison of the different devices and techniques. Whether FDD with coiling is more effective than FDDs alone in complex aneurysms has to be proven in prospective trials.Flow-diverting devices, with the use of additional coiling in selected cases, may offer a very high proportion of satisfactory radiological and clinical outcomes. However, in our experience the high risk of complications of different type and time impose the need for critical assessment and for further improvement of technical capabilities of implanted devices.


Eighty consecutive unsedated patients who underwent screening EGD with EB use were prospectively enrolled. To examine the aerosol ratio before, during, and after EGD, 0.3- and 0.5-μm aerosols were measured every 60 s using an optical counter. Moreover, the degree of contamination of the examiners’ goggles and vinyl gowns was assessed before and after EGD using a rapid adenosine triphosphate (ATP) test for simulated droplets. Data were available in 73 patients and showed that 0.3- and 0.5-μm particles did not increase in 95.8% (70/73) and 94.5% (69/73) of patients during EGD under EB. There were no significant differences in the total 0.3- or 0.5-μm particle counts before versus after EGD. The difference in the ATP levels before and after EGD was −0.6 ± 16.6 relative light units (RLU) on goggles and 1.59 ± 19.9 RLU on gowns . EB use during EGD may provide a certain preventive effect against aerosols and droplets, decreasing examiners’ exposure to viruses.Esophagogastroduodenoscopy (EGD) has a high risk of virus transmission during the current coronavirus disease 2019 era, and preventive measures are under investigation. We investigated the effectiveness of a newly developed patient-covering negative-pressure box system (Endo barrier Coronavirus disease 2019 (COVID-19) is a global pandemic. The COVID-19 pandemic has continued to cause dramatic shifts in the practice of endoscopy. In particular, the COVID-19 pandemic has had an extraordinary impact on the delivery of gastrointestinal endoscopy, with an initial reduction to 12% of the prepandemic level in the United Kingdom ,4,5,6.®; Okura Industrial Co. Ltd., Kagawa, Japan) (EB) [Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is highly contagious and spreads via respiratory droplets and direct contact . Recent an) (EB) . The newThe purpose of this study was to verify whether EB use during EGD effectively protects the examiner from exposure to aerosols and droplets using a particle counter and adenosine triphosphate (ATP) contamination tester.2, with a total supply of three air changes per hour, internal recirculation at 23 °C ± 1 °C, and humidity of <60%.This prospective, observational study was conducted at Kagawa Prefectural Shirotori Hospital from February 2021 to March 2021. Eighty consecutive unsedated patients who underwent screening EGD with EB use were prospectively enrolled. The inclusion criterion was an age of >18 years. The exclusion criteria were refusal to use the EB, a need for emergency endoscopic treatment, the presence of psychiatric disease or psychiatric symptoms, and the presence of severe respiratory disease. All EGD procedures were performed by a single endoscopist (S.F.) in the same room measuring 19.39 mThe EB, a newly developed patient-covering negative-pressure box with disposable vinyl films for preventing droplet transmission, was used during EGD . The patTo assess the examiner’s exposure to aerosols, 0.3and 0.5µm particles (simulated aerosols) were measured before and after EGD by a handheld optical particle counter  that suctioned air at 2.83 L/min a. First,® Pen and Lumitester PD-20® System  (® Pen is a kit that combines reagents with a swab used to pick up ATP from the test medium. The investigator (S.F.) took the swab from the kit, moistened it with sterilized water, uniformly wiped the object in every direction while avoiding the dry parts, returned the swab to the LuciPac® Pen, shook it well to ensure a reaction with the luminescent reagent, and inserted the LuciPac® Pen into the measurement chamber of the Lumitester PD-20® apparatus. According to the manufacturer, the benchmark for detecting contamination on non-critical instruments using these devices ranges from 200 to 500 RLU, and that for detecting contamination on the dominant hand is ≤1000 RLU. Therefore, we considered the anesthetists’ working environment in the operation room and their dominant hand to be clean at benchmarks of ≤500 and ≤1000 RLU, respectively.Surfaces with potential ATP (simulated droplets) contamination of goggles and disposal vinyl gowns were evaluated before and after EGD using the LuciPac, Japan) . ATP is Standard goggles and disposal vinyl gowns were used before the EGD procedure. Each pair of goggles was cleaned with alcohol before every EGD procedure. We acquired ATP samples to compare the ATP level before EGD with that after EGD. These samples were obtained in the same manner using the swab technique from the whole area of the goggles and from the top to the bottom of the front area of the gowns.The primary outcome was assessment of the changes in aerosols before and after EGD. The secondary outcome was analysis of the increase in the ratio of aerosols during EGD and examination of the changes in droplets using ATP before and after EGD. The cutoff value for the degree of contamination by the rapid ATP test was set at >150 RLU.p value of <0.05 was considered significant.Data are expressed as mean ± SD. All statistical analyses were performed using Prism 6 software . A Wilcoxon matched-pairs signed-rank test was used to evaluate statistical differences in the primary outcome measure. A nonparametric Wilcoxon/Mann–Whitney U-test was used to examine the statistical significance of differences between the two groups. A 2, and 68.8% (55/80) of patients had a medical history. Transnasal endoscopy was performed in 60% (48/80) of patients, and oral endoscopy was performed in 40% (32/80). No patients received intravenous sedation. The mean examination time was 236.6 ± 77.2 s, and biopsies were performed in 11 (13.8%) patients. During endoscopic examination, 29 (36.3%) patients developed burping, 23 (28.8%) developed reflux vomiting, 20 (25.0%) developed coughing, 2 (2.5%) developed sneezing, and 5 (6.3%) exhibited body motion. Because of faulty measurement equipment during the examination, 7 of the 80 patients underwent inadequate testing with the particle counter and ATP measurements.The baseline characteristics of all 80 patients are shown in p = 0.697) or 0.5-μm particles (p = 0.926)  and 94.5% (69/73) of patients, respectively. When we compared the total particle counts before and after EGD in each group, there was no significant difference in the production of either 0.3-μm particles (= 0.926) .Of 73 patients, 63 who successfully underwent continuous measurement of particles every 60 s during EGD were analyzed. The reasons for excluding 10 patients were a short examination time (<180 s) and technical errors. The 63 patients had an examination time of >240 s, which corresponded to the mean examination time of 236.6 s in all 80 enrolled patients. Accordingly, the particles were measured at the four time points of 60, 120, 180, and 240 s when the start of EGD was defined as 0 s. The increased ratio of 0.3- and 0.5-μm particles during EGD was calculated as the baseline control when the start of EGD was calibrated as 0% . The meaThe mean ATP level before EGD was 6.9 ± 6.8 RLU on goggles and 1.59 ± 19.9 RLU on gowns. The mean incremental difference in the ATP levels before and after EGD was −0.6 ± 16.6 RLU on goggles and 1.59 ± 19.9 RLU on gowns . These An = 73)  .n = 6) and those without increased aerosols (n = 67). The possible associated factors were examined. No significant factors were detected in the comparison between patients with and without increased aerosols. No complications involving perforations, bleeding, and respiratory suppression occurred in any patients during the current study.Seventy-three patients were divided into two groups: those with increased 0.3-μm and/or 0.5-μm aerosols  and without (n = 67) increased aerosols, no significant risk factors were detected as shown in Sagami et al.  reportedOnly a few studies have focused on droplet exposure among endoscopists using ATP Lumitesters. The World Health Organization adopts a 5-mm cutoff to distinguish between airborne transmission (<5 mm) and droplet transmission (>5 mm). Droplet transmission is defined as the transmission of diseases by expelled particles that have a propensity to settle quickly to the ground, usually within 1 m of the site of generation, because of their size. Thus, infection by droplet transmission occurs when the distance between infected patients and HCWs is small . TherefoThe EB consists of two main components: disposable vinyl film and specially designed frame. Okura Industries Corporation has recently announced that the price of single special frame amounted for approximately USD 545 in Japan. The cost for single disposable vinyl film is about USD 1.82 per case. Unfortunately, these products are not covered by Japanese medical insurance system, so in many cases the hospital must own the payment for them, or the patients themselves must pay for the disposable vinyl film.Our study has several limitations. First, this was an observational study with a single arm in a single institution. We were unable to establish a control group in which the EB was not used because the study begun during the pandemic and EB use was introduced as strict preventive measure in our hospital. Second, the total number of patients was relatively small, and the number of analyzed patients further decreased because of several technical and sampling errors. Third, this study involved a single endoscopist to minimize bias of the endoscopic technical procedure. Fourth, all included patients underwent EGD without sedation; thus, whether the presence or absence of sedation was associated with the increased aerosols remains uncertain. Fifth, small aerosols are easily dispersed because they are sensitive to ambient airflow, strong lateral currents, and ventilation . TherefoIn conclusion, EB use during EGD demonstrated an acceptable effect on aerosols and a sufficient outcome on droplets in terms of virus exposure among examiners.