Despite numerous efforts to improve the quality of maternal and child health medical services, over 20 million babies are born with low birth weights each year globally. However, factors related to low birth weight like physically demanding work during pregnancy, intimate partner violence, and food insecurity have not been explored well in Ethiopia. Thus, this study aimed to assess the prevalence of low birth weight and associated factors among neonates born in public Hospitals in North Shewa Zone, Central Ethiopia.p-value less than 0.05 was considered to declare the statistically significant association.A hospital-based cross-sectional study design was conducted from June 15 –to July 15, 2021, in North Shewa public hospitals. A total of 441 mothers and newborn pairs were selected by systematic random sampling. Data were collected using a pretested and structured interviewer-administered questionnaire with chart reviewing. Data entry and analysis were done using Epi Data version 3.1 and Statistical Package for the Social Sciences version 26 respectively. Binary logistic regression was done to identify factors associated with low birth weight. Adjusted odds ratio with its 95% confidence interval and a The prevalence of low-birth-weight was 17.7% . Pregnancy-related complication , grand-multiparty , physically demanding work during pregnancy , midd-upper arm circumference less than 23 cm , partner violence during pregnancy , and being member of household with food insecure  were factors significantly associated with low birth weight.This study showed that the magnitude of low birth weight was relatively high. Women with pregnancy-related complications, grand multiparty, physically demanding work during pregnancy, intimate partner violence, mid-upper arm circumference less than 23 cm, and food insecurity should be prioritized for mitigating LBW. Health care professionals should focus on Screening pregnant women for intimate partner violence, physically demanding activities, undernutrition and providing appropriate treatment during all maternal continuum of care might be helpful.The online version contains supplementary material available at 10.1186/s12887-022-03480-2. Low birth weight (LBW) is defined as “the weight at birth less than 2500 g (5.5lb) regardless of gestational age” According to World Health Organization . It is aDespite improvement in maternal and child health care, more than 4 million babies’ death occurs globally during their first 4 weeks of life with LBW being a major indirect cause of neonatal mortality. LBW newborns account for more than 80% of all neonatal deaths worldwide . In addiDuring the 65th World Health Assembly, member states of the United Nations set a national objective to reduce LBW by 30% in 2025 . BetweenEven though the Ethiopian government took significant steps to improve maternal and child health during the Millennium Development Goals (MDG)  through Various studies revealed that maternal nutrition, obstetric factors, chronic medical illnesses such as cardiovascular disease and HIV/AIDS, intimate partner violence, physically demanding work during pregnancy, maternal behavior and lifestyle factors, socioeconomic factors, and pregnancy-related complications are risk factors for LBW –18. WomeAlthough many studies have been conducted in developed and developing countries regarding the relationship between physically demanding work during pregnancy and LBW, there has been no study in Ethiopia linking physically demanding work during pregnancy with LBW. In addition, the existing LBW research failed to consider contributing variables like intimate partner violence and household food insecurity –23. TherThis study was conducted at public hospitals in North Shewa Zone. North Shewa zone is one of the 20 zones in Oromia Regional State and its administrative town is Fiche town, which is located 112 km away from Addis Ababa, the capital city of Ethiopia. The zone is administratively divided into 13 districts and two town administrations. As per the 2021 census, the zone has a total population of 1,786,067, of whom 876,252 were men and 909,815 were women . In termA public hospitals-based cross-sectional study was done among 448 mothers with their newborns who were selected by systematic random sampling technique. All alive newborns with their mothers who gave birth in selected Public Hospitals in North Shewa Zone from June 15, 20,201, to July 30, 2021, were the study population. Newborns of mothers in critical medical conditions and newborns with visible congenital anomalies were excluded from the study.n = 448). The sampling fraction or K-value was 2. The first study participant was selected by lottery method for each hospital independently and the next participants were selected every other.The sample size was determined for both objectives separately and a 10% non-response rate was added. The adequate sample size was obtained using a single population proportion formula with the assumptions of, a 21.6% prevalence of LBW , 95% conFour public hospitals from the North Shewa zone were included in the study. The number of study participants was proportionally allocated to each respective hospital based on estimations obtained from the previous delivery report as indicated in the figure below Fig. .Fig. 1ScA pretested and structured interviewer-administered questionnaire and medical record extraction were used. The questionnaire was adapted and modified from other peer-reviewed articles , 27–31. Intimate Partner Violence during Pregnancy (IPVP): was measured using a standardized tool developed by WHO [d by WHO . women wd by WHO , 33.Household food insecurity: was assessed using a Household Food Insecurity Access Scale (HFIAS) developed by Food and Nutritional Technical Assistance (FANTA) [ (FANTA) . The too (FANTA) . The too (FANTA) .Physically demanding work during pregnancy: was measured using the following eleven items related to domestic and other activities performed during the pregnancy period with Yes or No responses [esponses , 30, 35.esponses , 30. In Daily household chores: Whether the mother did her housework alone or with the assistance of a relative person throughout her pregnancy period.Undernutrition: Mothers with mid-upper arm circumference (MUAC) < 23 cm [ < 23 cm .Low birth weight: Newborns who weighed less than 2500 g [n 2500 g . It codeBirth-to-pregnancy interval is the period between the start of the index pregnancy and the preceding live birth. It has three categories, these are: <24monthes, between 24-47monthes, and ≥ 48 months are the three categories [tegories . It was Alcohol use: use of any amount unit of alcohol whether it is locally manufactured drinks , or beer, wine, and any alcoholic-liquors beverages [everages .The data were cleaned, checked, coded, and entered into Epi data statistical software version 3.1 and then exported to SPSS version 26 for analysis. Simple frequency, and summary statistics such as median, and interquartile range were generated as descriptive statistical analysis. The results were presented using frequencies, tables, and figures.P-value < 0.25 in the bivariable analysis were retained for the final model multivariable analysis. The multi co-linearity test was also done using VIF and tolerance tests to see the presence of correlation between independent variables. However, no variables with VIF > 10 and tolerance test < 0.1 were found. The Hosmer-Lemeshow and the Omnibus test were used to test the model’s goodness of fit. The model was deemed to be a good fit since the result was found to be insignificant for the Hosmer-Lemeshow test (p = 0.616), but significant for the Omnibus test (p = 0.000).Bivariable and multivariable binary logistic regression analyses were performed to see the association between independent variables and the outcome. To control all possible confounders, variables which have a P-value less than 0.05 was considered to declare a statistically significant association. The strength and direction of statistical association were reported using an adjusted odds ratio with it is 95% CI.In multivariable analysis, a The questionnaire was evaluated by experts in the related field. It was first developed in English language, then translated into Afaan Oromo and Amharic, with re-translation into English to ensure it is consistency. A pre-test was conducted in Chancho primary Hospital, on 5% of the total sample size to check for language clarity, estimate the time required for the interview, and necessary amendments were done accordingly. The training was given to data collectors and supervisors on the study’s objective, ethical principles, sample procedure, questionnaire content, confidentiality, and respondent rights. The principal investigator together with the supervisor checked the data for completeness on daily basis.In this study, of 448 participants, 441 delivered mothers-newborn pairs participated in the study with a 98.4% response rate. Seven respondents declined to take part in the study. The median and interquartile range (±IQR) of mothers’ age was 25 (±7) ranging from 18 to 41. Slightly more than two-thirds, 305 (69%) of the mothers were in the age group of 21–34 years. The majority of the participants (93.2%) were married and more than three-quarters, 370 (83.9%) were Orthodox Christians. Regarding maternal occupational status, more than half (59.9%) of the neonate’s mothers were housewives. The median and interquartile range of household incomes of the respondents were 3000 ETB ± 1500 per month  had attended ANC follow-up for their last pregnancies. In terms of pregnancy intentions, slightly more than three fourth (77.8%) of the neonate’s mothers desired to have the current pregnancy. Nearly a quarter of the mothers, 68 (22.8%), gave birth to the present newborns within less than 24 months after the previous childbirth. Concerning the mode of delivery, 338 (76.6%) of mothers had their babies via spontaneous vaginal delivery. In terms of gestational age at birth, 391 (88.7%) of mothers delivered their babies at full term  encountered pregnancy complications. The commonest complications were pregnancy-induced hypertension, severe nausea and vomiting, APH, and PROM as indicated below  of them were from household food secure and 79 (17.9%) had MUAC less than 23 cm (undernourished). The level of hemoglobin among neonates’ mothers ranged from 9.0 g/dl to 16.2 g/dl with a median and interquartile range (±IQR) of 13.2 g/dl (±2 g/dl). The proportion of mothers who had engaged in physically demanding work during the current pregnancy was 116 (26.3%). About three fourth, 332 (75.3%) of respondents took iron and folic acid supplements at least once and 114 (25. 9%) of them took less than 60 tablets during their recent pregnancies. 198 (44.9%) of mothers drank alcohol during their current pregnancy period  had a pre-existing medical disease. Of this four (36.3%) had chronic hypertension, four (36.3%) were reactive to HIV and two (18.1%) had DM respectively Table .Table 4MOf 441 study participants, 78 had low birth weight newborns. Therefore, the magnitude of low birth in the public hospital in the North Shewa zone was 17.7% . The median and interquartile range (±IQR) of the birth weight of the newborns was 3000 g (±800 g) ranging from1000 grams to 4500 g.p-value less than 0.25 in bivariable analysis. All variables with a p-value < 0.25 were retained for multivariable analysis. Accordingly, parity, pregnancy-related complications, MUAC, food insecurity, hard physical work during pregnancy, and intimate partner violence were statistically associated with LBW.Among all variables, age of the mothers, parity, gestational age at birth, pregnancy-related complication, additional meal intake, alcohol intake, ANC follow-up, hemoglobin level < 11, physically demanding work during the current pregnancy, food insecurity, MUAC less than 23 cm, and intimate partner violence were associated with LBW at In the present study, the odds of delivering LBW among mothers from households food-insecure were 2.3 times  higher as compared to mothers from households food-secure. Neonates who were born to grand multiparous mothers had 2.6 times  higher odds of being LBW compared to neonates delivered from multiparous. Neonates born to mothers who were engaged in physically demanding work during the current pregnancy period had a 2.2 times higher probability of being LBW than neonates born from mothers who didn’t engage in physically demanding work . Mothers who had MUAC less than 23 cm were 2.7 times more likely to have LBW as compared to mothers with MUAC greater than 22 cm . The likelihood of having LBW among mothers who had encountered pregnancy-related complications during index pregnancy was 2 times higher  as compared to mothers without pregnancy-related complications. Furthermore, Neonates born from mothers who were exposed to IPVP were 3.8 times  more likely to be LBW as compared to neonates born from mothers who did not expose to IPVP  to assess some variables like intimate partner violence and food insecurity, which may have a social desirability bias.This study revealed that newborns delivered to almost two out of every ten mothers were found to be low birth weight. Physically demanding work during pregnancy, food insecurity, intimate partner violence, grand multiparty, MUAC less than 23 cm, and pregnancy-related complications were significantly associated with LBW. Therefore, Healthcare professionals should focus on screening pregnant women for undernutrition, and exposure to partner violence and ensure that women have access to important health information about the causes of low birth weight. Public health education and awareness on the importance of limiting physically demanding activities during the pregnancy period might reduce the low birth weight.Additional file 1.


Individuals with SCD  have a higher prevalence of ICANs than the general population. We believe that MRA should be considered in the current American Society of Hematology guidelines, which already contain a recommendation for MRI at least once in adult SCD patients. However, the clinical significance of preventive treatment of unruptured aneurysms remains controversial.Magnetic resonance imaging (MRI) is used in patients with sickle cell disease (SCD) to detect silent cerebral infarcts. MR angiography (MRA) can identify arterial stenoses and intracranial aneurysms (ICANs) associated with SCD. In this study, we aimed to estimate the prevalence of ICANs in asymptomatic adult patients with SCD referred from the SCD clinic for routine screening by MRI/MRA using a 3T-MRI scanner. Findings were independently reviewed by two neuroradiologists. Between 2016 and 2020, 245 asymptomatic adults with SCD were stratified according to genotype . ICANs were found in 27 patients . ICANs were more frequent in SS/S-β0thalassemia patients  than in SC/βb+ patients (7/127 or 6%; 0.95 CI: 2–11%;  Sickle cell disease (SCD) is associated with vaso-occlusive phenomena which can result in a wide spectrum of clinical manifestations ,2,3,4. NMRI screening has been recommended by the American Society of Hematology (ASH) to detect silent cerebral infarctions (SCI) associated with neurocognitive impairment in a significant proportion of patients ,8,9 MR aIn this study, we aimed to estimate the prevalence of ICANs in all patients with SCD screened by MRA over a period of 5 years and the effect of genotype.This retrospective study was approved by the research ethics committee of the Centre Hospitalier de l’Université de Montréal and the requirement for informed consent was waived. Adult outpatients followed by the SCD clinic of the Department of Hematology were included if one or more 3T MRI/ MRA studies were performed as part of a screening program. Patients were categorized according to genotype: SS/S-β0thalassemia and SC/S-β+ Graham-Serjeant type 1. Inclusion criteria for this study were: age ≥ 18, genotypically confirmed SCD, and no prior history of neurovascular complications and at least one yearly follow-up.All MRIs were performed on a 3T scanner , and included three-dimensional fluid-attenuated inversion recovery (FLAIR) and time-of-flight intracranial angio-MRA without gadolinium injection. All studies were reviewed by a fellow in diagnostic neuroradiology and a certified neuroradiologist with more than 20 years of experience. Two independent readings were carried out and the discrepancies were resolved by consensus. The management and follow-up of patients with asymptomatic aneurysms were recorded.The prevalence of ICANs along with 95% confidence intervals  for each genotype was compared using Fisher’s exact test .Between 1 January 2016, and 31 December 2020, 271 patients with SCD were referred for brain MRI/MRA. This population was followed regularly and 84% were receiving a treatment . Twenty-two patients were excluded because of neurological symptoms and four other patients because of non-diagnostic imaging, leaving 245 neurologically asymptomatic adults with SCD studied over 5 years with a total of 369 brain MRI/MRAs .The median age (interquartile range) was 32 (25–42) years, and 125 (51%) were women. Unruptured saccular aneurysms were found in 27 patients . Nine patients (33%) had more than one aneurysm, for a total of 44 aneurysms: 40 were in the anterior circulation and four in the posterior circulation. All aneurysms were ≤10 mm (median 2.5 mm) .One patient with an asymptomatic 10 mm aneurysm was treated by coiling. Everyone else was observed, including 17 patients with asymptomatic aneurysms who underwent at least one follow-up MRA with a median time of 13.5 months between studies. One patient with a 3 mm internal carotid aneurysm also had a middle cerebral artery stenosis.p = 0.007; Fisher’s exact test) in SS/S-β0thalassemia patients (20/118 or 17% 0.95 CI: 11–25%) than in SC/Sβ+ patients . More specifically, in SC patients the prevalence was 3/110 or 3% 0.95 CI: 1–8%). Aneurysms were also more frequent  in patients over 30  as compared to younger patients . Median age of individuals with ICANs was 38 years and 43 years in SS/S-β0thalassemia and SC/Sβ+ respectively. Seventeen out of 27 ICAN+ patients underwent ≥ 2MRI/A. All ICANs remained stable in terms of size and morphology during consecutive scans.Aneurysms were more frequent  [Our results are in line with two previous publications on SCD reporting the prevalence of ICANs in 9% (5/55 patients)  and 6%  of adult < 0.05) . One sig < 0.05) ,16, alth < 0.05) .According to the American Heart/American Stroke Association, screening for ICAN is only recommended for patients at increased risk of aneurysm development, such as patients with a positive family history or those with predisposing disorders such as autosomal dominant polycystic kidney disease, coarctation of the aorta, or rare collagen diseases. Interestingly, all the above-mentioned groups show a frequency of ICANs comparable to our cohort of SCD patients . None ofMRA in the setting of unruptured ICAN screening is well recognized. A systematic review and meta-analysis reported a sensitivity of MRA in the diagnosis of ruptured and unruptured ICANs  of 95%   in compaThis is a monocentric study with a total number of patients that remains small, though much larger than previously published cohorts. Risk factors for ICANs, such as family history of an aneurysm, smoking or hypertension, were not systematically recorded as potential confounding factors as in causal research. Other factors associated with SCD specifically will be assessed in a future study addressing not only prevalence, but also incidence of ICANs, namely disease-modifying treatments such as hydroxyurea and transfusion program, ∝-globin deletions, SCD non-neurologic events and rate of SCD events.In summary, patients with SCD, and particularly SS/S-β0thalassemia patients, appear to have a higher prevalence of intracranial aneurysms than the general population. These results suggest that MRA could be added to the American Society of Hematology screening recommendations, which already include a routine MRI at least once in adults with SCD. However, the clinical significance and preventive treatment of unruptured aneurysms remain controversial and requires further inquiry. Future studies should aim to validate the results from our testing cohort. Additionally, longitudinal outcomes need to be assessed to better determine the long-term impact of these lesions. The natural history and real impact of specific treatments is not well known in literature. Future prospective and populational studies will help to define and evaluate specific surveillance and therapeutic strategies in this population.


Hemorrhagic cystitis (HC) is a frequent complication of allogeneic hematopoietic stem-cell transplantation (HSCT). HC worsens transplant outcomes and patient wellbeing in terms of pain, hospitalization, and need for supportive care. A deeper understanding of the risk factors of HC may lead to more intensive prevention in high-risk patients.In this report, we analyzed 237 consecutive patients who received HSCT with the aim of identifying possible risk factors for HC and their consequences, with a particular focus on transplant- and gender-related risk factors.p = 0.03). Risk factors identified for HC included age over 55 years, male recipient, HLA mismatch, reduced intensity conditioning, and cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Increased HC was seen in patients with grade II–IV acute GVHD and detectable BKV and JCV viruria. In a multivariate model, increased age remained significant (p = 0.013). Patients with HC had longer hospitalizations and increased non-relapse mortality (NRM). Among male recipients, independent risk factors for HC included age (p = 0.016) and prostate volume (p = 0.016). Prostatic hyperplasia (volume more than 40 cm3) occurred in 33% of male patients, of which 32% developed HC .HC occurred in 17% of patients, with a higher incidence in males (21% vs 11%, Age is the most important risk factor for HC. Additional potential risk factors include cyclophosphamide-based GVHD prophylaxis and HLA mismatch. Among male recipients, prostatic hyperplasia is an additional independent risk factor. As HC is common and associated with prolonged hospitalization, more intensive prophylactic strategies should be considered in high-risk patients. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative cell therapy for patients with hematologic malignancies. Conditioning chemotherapy may be myeloablative (MAC) or reduced-intensity (RIC), according to diagnosis, stem cell source, and the general condition of the patient. Different regimens are known to affect the duration and severity of cytopenias, and in some cases, the durability of disease control . After iThe incidence of HC varies between 12.2% and 36.9%, and the median occurrence is within the first 30 days. In the literature, the major risk factors for HC reported include age (in pediatrics), myeloablative conditioning regimen, and haploidentical or mismatched HLA donor . A compaCyclophosphamide has toxic effects on the bladder mucosa, and both cyclophosphamide-containing conditioning regimens and cyclophosphamide-based GvHD prophylactic regimens have been associated with increased HC , 7. ConsWhile there are some studies reporting a higher incidence of HC in males with benign prostatic hypertrophy , benign In the present study, we aimed to investigate the difference in incidence, severity, and duration of HC between males and females, and we aimed to evaluate the role of prostatic hypertrophy in the development of HC among other commonly tested risk factors. Our hypothesis was that prostatic hypertrophy might have put some male patients at higher risk of HC through augmented urinary retention and possible chemical/infectious damage.We retrospectively collected data on all 237 consecutive patients who underwent HSCT in our Institution from December 2017 to December 2020. Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) was calculated for all patients at the moment of hospitalization for HSCT . We collProphylaxis for GVHD consisted of a triple regimen including cyclosporine and mycophenolate mofetil and either post-transplant cyclophosphamide (PTCY) or methotrexate. Apart from patients with severe aplastic anemia, from April 2019 onward, a uniform PTCY-based GvHD prophylactic regimen was used for all patients, due to center choice and expertise. Acute and chronic GVHD (aGVHD and cGVHD) were evaluated according to current criteria on a scale of 0 to 4 and 0 to 3, respectively .Hemorrhagic cystitis was considered as any manifestation of macroscopic hematuria, from pinkish urine to massive clots, or acute anemia requiring urgent cauterization or intervention, corresponding to grade 2 to 4 hematuria according to current literature criteria , 12. BKV3, grade 1 if 20–40 cm3, grade 2 if 40–60 cm3, grade 3 if 60–80 cm3, and grade 4 if more than 80 cm3 in volume [Prostate volume and diameters were assessed in males by an expert urologist with pre-HSCT imaging reviewed when available. Manual segmentations and delineations of the prostate was outlined without seminal vesicles. The prostate volumes were measured by calculating prolate ellipse volume by means of the (height × length × width × π/6) formula. In order to minimize interobserver-dependent variations and selection and measurement biases, all the measurement were performed by the same urologist who was blinded to whether the patients did experience HC or not; the prostate volume quantification was performed by the same imaging technique, namely computed tomography (CT), as trans-rectal ultrasound (TRUS) was not available for all patients, and it could be expected to be more operator–dependent than CT. However, in a recent systematic review, prostate imaging with TRUS and CT was found to be sufficiently accurate when quantitative measurements of prostate gland volume are required . Prostatn volume .Hemorrhagic cystitis-free survival (HC-FS) was considered as time from transplantation to first episode of HC, death, or last follow-up.The effect of patient-related risk factors, including age, gender, HCT-CI and prostate volume in male patients, and procedure-specific risk factors, including HLA matching, GVHD prophylaxis, and conditioning regimen, on incidence and timing of HC was assessed in univariate and multivariate Cox regression analysis. The effect of parametric and non-parametric categorical variables and continuous variables on HC-FS was assessed using univariate and multivariate Cox regression analysis. Differences in median values were evaluated using Welch’s test for unequal variances and Student’s t test. Survival was compared using Kaplan Meier curves. Non-relapse mortality (NRM) was assessed by calculating cumulative incidence functions. Statistical analysis was performed with NCSS Statistical Software.Almost all patients underwent HSCT for hematologic malignancies. The stem cell source was predominantly matched unrelated and haploidentical donors. Patients and transplants characteristics are described in Table The majority of patients (76%) received a myeloablative conditioning regimen (MAC) consisting of thiotepa-busulfan-fludarabine (TT-Bu-Flu)  or fludap = 0.002). Using a cutoff of 55 years to define elderly patients (in accordance with the median age of our patient cohort), there was an increased risk of HC in elderly patients . An increased risk of HC was also seen in male patients vs. female patients . At day + 30, HC-FS was increased in females compared with males , with a plateau after the first month.The median onset of HC was day 8 after stem cell infusion. Patients who developed HC had a higher median age . There was also no difference in incidence of HC according to HCT-CI. Decreased HC-FS was seen in patients receiving RIC compared with MAC . Worthy of note, no patients treated with Flu-TBI (MAC regimen) experienced HC; in this subset, all patients were under 45 years old and had a diagnosis of ALL.HC occurred in a similar proportion of patients with acute malignancies and patients with chronic diseases, including myeloproliferative neoplasms and lymphomas . In detail, the incidence of HC was 6%, 15%, and 28% for sibling, matched unrelated, and haploidentical donors, respectively.To investigate the effect of HLA matching on incidence of HC, we compared HC in HLA identical (sibling and unrelated) vs. haploidentical transplants. Incidence of HC was higher in haploidentical transplants . Of note, HC occurred in two out of five patients (40%) with severe aplasia.Patients who received GVHD triple prophylaxis with PTCY had an increased incidence of HC compared with patients who received triple GVHD prophylaxis with MTX .p = 0.011).Overall, grade 0–1 or 2–4 acute GVHD occurred in 195 (82%) and 39 (18%) patients, respectively. The incidence of HC was decreased in patients with grade 0–1 aGVHD, compared with those with grade 2–4 aGVHD . Among the 29 patients with urine positive for both BKV and JCV, 12 (41%) developed HC. We found no correlation between prostatic hyperplasia and detection of BKV or JCV in urine.To investigate the effect of BKV and JCV infections on HC, we assessed patients for BKV and JCV viruria. BKV and JCV viruria was positive at some point in hospitalization, respectively, in 18% and 39% of patients. Patients with no viral reactivation had a lower incidence of HC compared with those with detectable BKV or JCV in urine (15% vs. 33% p = 0.001), both 6 months (8% vs. 25%) and 1 year (12% vs. 38%) after transplant .Median duration of HC was 7 days range 1–85 days). Treatment of HC consisted of adequate hydration and platelet transfusions for all patients; some patients required more intensive treatment, which included continuous bladder irrigation (55% of patients with HC), specific antiviral therapy with cidofovir (7%), endoscopic diathermocoagulation (10%), and intravesical instillation of Platelet-Rich Plasma (3%) or hyaluronic acid (3%). Non-relapse mortality was significantly higher for patients with HC . HC was increased in patients with prostatic hyperplasia of grade 2 and higher (volume more than 40 cm3), compared with patients with prostate volume less than 40 cm3 . As expected, age and prostate volume were strongly correlated (p < 0.001). Male patients with normal prostate volume (less than 40 cm3) had similar incidence of HC when compared to female population . In a multivariate model, increased HC was seen in patients with age greater than 55 years (p < 0.001). HLA mismatch (p = 0.008), and PTCY-based triple GVHD prophylaxis (p = 0.04); age greater than 55 years and prostate volume were independent risk factors for HC (p = 0.016).Within male patients, we also focused on the potential effect of prostate volume on HC. Median prostate volume was evaluable in all but 16 male patients and it was greater in patients who developed HC  [3 was able to discriminate two populations with significantly different risk of HC . While there is a seemingly obvious association between age and prostatic hyperplasia, the two variables remained independently associated with HC in multivariate analysis. Moreover, male patients with prostate volume less than 40 cm3 had similar incidence of HC compared to female population, enforcing the hypothesis that the prostate may play a part in influencing the higher incidence and severity of HC in male patients. We hypothesize that toxic metabolites  may have prolonged contact with bladder mucosa due to urinary retention in patients with prostatic hyperplasia. This exposure could reasonably contribute to chemical damage and bleeding in a thrombocytopenic and immunocompromised patient. Moreover, urinary retention may enhance viral damage from JCV and BKV on the urothelium. Prostate samples from patients with prostate cancer (PC) and prostatic hyperplasia have been found to be a reservoir of BKV and JCV in 22–32% of cases as well as a possible site of viral replication [Data on the role of gender in development of HC is sparse and conflicting. Gargiulo et al. found no difference in incidence of HC in a prospective population of 450 mixed pediatric and adult patients of both genders 13% vs. 11%), while Lunde et al. found in a retrospective study of 1321 consecutive patients that male gender was associated with higher incidence of HC  . In our lication , 18. As lication , 20.Overall, patients with HC experienced worse clinical outcomes. Not only was HC associated with more prolonged hospitalization, but it was also associated with higher probability of NRM. HC was most frequently the cause of a prolonged hospital stay, as the acute management requires invasive procedures and intensive transfusion support. Post-transplant multi-organ toxicity is associated with infections, severe cytopenias, and renal failure; thus, HC is only the tip of the iceberg.p = 0.1; 10 days vs. 18 days) [HC prophylaxis remains an area of debate. Some prophylactic approaches have been proposed based on prospective studies by the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and the European Conference on Infections in Leukemia (ECIL) guidelines on BKV-related HC, though the efficacy of these approaches has not been clearly demonstrated. In these reports, practices such as coadministration of Mesna with cyclophosphamide, urine alkalinization, intravenous hyper-hydration, and bladder continuous irrigation are addressed, while a role for antibiotic prophylaxis remains unclear , 21. In 18 days) . In our 18 days) , 21. A l18 days) , 24.Data on prostatic hyperplasia have never been reported in the setting of HSCT with PTCY. A prospective evaluation of post-void residual urine and measurement of acrolein and viruria may clarify the pathogenesis of HC and thereby inform prophylactic management.We recognize that our findings may present some limitations, especially concerning the retrospective nature of data collection, the missing data on prostate volume in some male patients and some variable transplant- and patient-related characteristics that may confound the analysis, as stem cell source and primary disease. We tried to overcome these limitations with multivariable risk analysis, while at the same time we remark the need for prospective trials in order to definitely explore risk factors and best prophylactic strategies for HC.In conclusion, age over 55 years is an independent risk factor for hemorrhagic cystitis in patients treated with allogeneic stem cell transplantation. Mismatched transplants and PTCY-based triple GVHD prophylaxis may influence risk but are not independent of age. For male patients, prostatic hypertrophy may be an additional risk factor. More intensive prophylactic strategies may represent a reasonable option to prevent HC in the setting of transplantation in high-risk adults.


Venous thromboembolism (VTE) is considered a common complication in lung cancer patients. Despite its widespread use, the Khorana score performed moderately in predicting VTE risk. This study aimed to determine the diagnostic utility of the Systemic Immunoinflammatory Index (SII) and to create a novel nomogram for predicting VTE in patients with pulmonary carcinoma.  The data, like clinical features and laboratory indicators, of inpatients diagnosed with lung cancer from March 2019 to March 2020 were collected and analyzed. Univariate and multivariate logistic analyses were performed to confirm the risk factors and then construct a nomogram model. The calibration curve and clinical decision curve analysis (DCA) were used to assess the model's fitting performance. The receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the diagnostic value of SII and the nomogram. P < 0.001). SII is the stronger correlator for VTE among inflammatory markers, of which the optimal cut-off value was 851.51. Univariate and multivariate analysis revealed that the age, metastasis, antitumor treatment, hemoglobin<100 g/L, SII>851.51 × 109/L, and D-dimer>2 folds were independent risk factors for lung cancer-related VTE, and a new prediction nomogram model was constructed based on them. ROC curve analysis showed the AUC of the new model and Khorana score were 0.708 (0.643-0.772) and 0.600 (0.531-0.699).  This study enrolled 369 lung patients with a VTE morbidity rate of 23.33%. The patients with VTE had higher SII levels than the non-VTE group (1441.47 ± 146.28 vs. 626.76 ± 26.04,  The SII was a simple and valuable biomarker for VTE, and the new nomogram model based on it can accurately forecast the occurrence of VTE. They can be utilized in clinical practice to identify those at high risk of VTE in lung cancer patients. Patient × 109/L . However × 109/L .Several studies have supported the tight relationship between immunity, inflammation, and thrombosis. The hyperinflammatory state in cancer patients' bodies generated enormous cytokines and inflammation mediators while stimulating the clotting response and ultimately promoting thrombosis . HematolRecently, some researchers have revealed that SII was a significant independent risk factor for PE , cerebraWe retrospectively reviewed the data of patients hospitalized at the First Hospital of Jilin University from March 2019 to March 2020 through the electronic medical record system. Inclusion criteria were as follows: (1) patients with a pathology-confirmed diagnosis of primary pulmonary carcinoma; (2) patients who underwent at least one vessel ultrasound examination or computed tomography pulmonary angiography (CTPA) within 6 months of their diagnosis; (3) patients with comprehensive laboratory data, of which the peripheral blood was drawn before antineoplastic therapy and within three weeks after diagnosis; and (4) patients without severe impairment of bone marrow hematopoietic function, hepatic or renal function. Exclusion criteria were as follows: (1) patients with second primary carcinoma; (2) patients with severe infection; (3) patients with diseases that may potentially affect the peripheral blood cells; (4) patients with incomplete clinical records. This study was approved by the medical ethics committee of the First Hospital of Jilin University (No 2017-362) and all research processes adhered to the Helsinki Declaration. Given the retrospective nature of the research, the patients' consent was waived by the ethics committee.Demographic data  and clinical information  were collected from medical records. The molecular subtypes were verified mostly in patients with lung adenocarcinoma, among which the epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), c-ROS oncogene 1 (ROS1), and anaplastic lymphoma kinase (ALK) were confirmed by next-generation sequencing (NGS) tests. Peripheral blood laboratory like WBC, neutrophil (N), lymphocyte (L), monocyte (M), platelet count (PLT), HB, C-reactive protein (CRP), albumin (ALB), and D-dimer was gathered. The calculation formulas of some hematological indicators were as follows: NLR = N/L; PLR = PLT/L; LMR = L/M; SII=PLT×N/L.This study defined VTE as DVT, superficial thrombophlebitis, and PE. The DVT was diagnosed primarily through ultrasound imaging of thrombus formation in the lumen, hypoechoic regions, and disruption of blood flow signals. Superficial phlebitis is diagnosed mostly based on clinical symptoms, like redness, swelling, and pain exhibiting in the skin along the vessel's path, given no thrombotic masses in the vessel. The diagnosis of pulmonary embolism is based on the characteristic clinical symptoms as well as the filling defect of the CTPA. The above diagnosis was independently identified and reviewed by two experienced radiologists.t-test. Continuous variables with nonnormal distribution were expressed as medians with interquartile range and compared by the Mann–Whitney test. Categorical variables were represented by cases and proportion, compared by chi-square or Fisher's exact test. Multivariate logistic regression analysis was performed for variables that had statistical significance in the univariate analysis. A nomogram model was constructed based on multivariate analysis through the “R” package. The receiver-operating characteristic (ROC) curve, calibration curve, and clinical decision curve analysis (DCA) were conducted using the “proc,” “resource selection,” and “rmda” packages. P-value<0.05 indicated that the difference was statistically significant.All statistical analysis was conducted using IBM SPSS Statistics (22.0) and R software (4.1.3). Continuous variables with normal distribution were presented as mean ± standard deviation, which was compared by an independent Student's A total of 369 patients with lung cancer were enrolled in this study with an average age of 60.05 (±9.24), including 181 males and 188 females. There were 86 cases diagnosed with VTE and 283 patients without VTE. The cumulative incidence of VTE within six months after lung cancer diagnosis was 23.33%. The clinical features of the two groups are shown in P < 0.005) in the VTE group, while HB was lower (P < 0.005) than those in the non-VTE group. The level of SII was higher in the VTE group than that of the non-VTE group . Furthermore, the analysis showed that the SII levels of patients with VTE at different phases varied in P < 0.005). As shown in As shown in Continuous data were converted into categorical variables for analysis in consideration of published papers and articles on risk factors and the model establishment of VTE. Blood counts were labeled according to the Khorana score, D-dimers were grouped according to the degree of elevation, and other hematological data were classed using cut-off values of the ROC curve. BMI was defined based on the crucial value of obesity in Chinese individuals.P-values less than 0.05 were included in the multifactorial analysis and the results are shown in P = 0.004), metastasis , antitumor treatment , HB <100 g/L , SII , and D-dimer  were independent prediction factors of VTE in patients with lung cancer. It highlighted that patients with SII >851.51 × 109/L had a 3.36-fold higher hazard of incurring VTE than those with SII ≤851.51 × 109/L.Firstly, the univariate logistic analysis showed that age, adenocarcinoma, gene mutation, metastasis, antitumor therapy, WBC, HB, PLT, CRP, NLR, PLR, LMR, SII, hypoproteinemia (Albumin <40 g/L), and D-dimer were correlated with VTE in lung cancer patients. These 15 variables with P = 0.427). The DCA curve in This study established a nomogram prediction model for VTE in lung cancer patients based on the results of the multivariate analysis as shown in Venous thromboembolism is an extremely widespread and possibly lethal illness. It is a common complication and the leading cause of non-neoplastic death in patients with malignant tumors, accounting for more than 3 million fatalities each year. Patients with lung cancer are exposed to a higher risk of VTE, of which the prevalence ranges from 12% to 16.4% [P < 0.001) [P = 0.001), of which the AUC was 0.795 and the cut-off point was 847.78 [Inflammatory indicators were considerably increased in VTE patients than in non-VTE patients in our study, both in terms of peripheral blood count and NLR, PLR, LMR, and SII, indicating a close bond between inflammatory status and thrombosis. The ROC curve and logistic regression analysis demonstrated that SII was the exclusive independent risk variable with the maximum AUC. The optimal cut-off value of SII was 851.51, which meant patients with SII >851.51 face a higher risk of developing VTE. Based on the finding that SII was the stronger correlator for VTE, we developed a nomogram model and internally validated its excellent diagnostic efficacy. Several recent studies have supported our conclusion that SII provided clinical diagnostic value for VTE. Gok et al. observed a total of 442 cases with acute pulmonary embolism (APE), of which SII was an independent predictor  . They fo< 0.001) . Another< 0.001) , while A< 0.001) . Peng ets 847.78 . Posteris 847.78 , which wβ and IL-6 but also enhanced the activation of nod-like receptor protein three inflammatory vesicles (NLRP3) inflammatory vesicles to promote thrombus formation [Multiple clinical studies demonstrated that SII did have a strong predictive value for VTE, while fundamental research provided theoretical support for the association of the inflammatory response with thrombosis . Alteredormation , 22. Morormation , 24. Ultormation . Recent ormation . SII wasormation –29.The Khorana score performed poorly in predicting VTE, particularly in lung cancer patients who may be at high risk of VTE . To tackHowever, there are some existing limitations in our current study that impede the interpretation of the findings. First and foremost, this was a single-center retrospective clinical study presented with a small sample volume of which merely 369 patients in total and only 86 cases with VTE. Secondly, there was a shortage of sufficient external validation targeting the new predictive model. In addition, we did not probe the prognosis value of the enrolled subjects on account of the low follow-up rate. Considering the above limitations, some prospective clinical trials with sufficient samples need to be designed in the future to evaluate the diagnostic and prognostic value of SII for lung cancer-related VTE.SII was a straightforward and valuable predictor for VTE events in lung cancer patients, especially for acute or subacute VTE. The new nomogram model, which consisted of the inflammatory marker, coagulation indicator, and tumor features, delivered an intuitive and accurate prediction of VTE. It could be used in clinical practice to identify lung cancer patients at high risk of VTE.


Exposure to air pollution is a well-known health risk. For instance, volatile and very volatile organic compounds (VOCs and VVOCs) are known to cause respiratory, haematologic or immune diseases, and even cancer. Based on the Luxembourgish indoor pollution surveillance program, we performed an exploratory analysis for the period 2014–2019, in order (1) to evaluate the prevalence of VOCs and VVOCs in households, and (2) to estimate the risks of lifelong exposure to selected VOCs on the health of the adult population. The database included 715 indoor air samples from 159 different households. Observed VOC and VVOC levels were similar to those in neighbouring countries. Our health impact assessment identified some health risks associated with the observed concentrations in Luxembourg. Furthermore, this study shows the major public health importance of having a national indoor pollution surveillance system in place. Highlights: (1) This study provides an overview of the domestic indoor pollution in Luxembourg. (2) (V)VOCs levels in Luxembourg were similar to those in neighbouring countries. (3) The results clearly show the importance of having a surveillance system in place. Exposure to air pollution is a well-known health risk. Depending on the compounds present, their concentration and their toxicity, different symptoms may arise after acute exposure, either topical  or systemic  . MoreoveAir pollution mainly includes particulate matter, inorganic gases and (V)VOCs, which are the focus of this study. (V)VOCs can be released into indoor air from furniture, carpets, housing products, dry-cleaning products, paints, organic-fuelled heating and cooking systems ,12. EnviIn recent years, household air pollution has been widely studied, analysing the concentration of different air pollutants in Europe ,14 and aLastly, within the Grand Duchy of Luxembourg, population and economical activities are distributed unevenly. The industrial sector (mainly mining and steel industry) dominates the south-west, where a higher population density can be found, whilst the remaining peripheral area focuses on agricultural activities and is less densely populated ,19. The In this context, we performed an exploratory analysis for the period 2014–2019 in order to evaluate the prevalence of the selected (V)VOCs in households, and to estimate the risks of lifelong exposure to selected (V)VOCs on the health of the adult population.A total of 715 indoor air samples  were collected from 159 different households in the Grand Duchy of Luxembourg from 2014 to 2019. They were collected as part of the national indoor pollution surveillance programme by the Unit Environmental Hygiene and Human Biological Monitoring, Laboratoire National de Santé . This programme foresees that physicians can request an investigation of the patient’s residence, in the case of health complaints for which they suspect a potential cause in the indoor environment. After keeping windows closed for 24 h and a normal use of the premises, air sampling pumps Gilair Plus  were placed in the most frequented rooms , at a central position and a medium height. For VVOCs, a cartridge impregnated with dinitrophenylhydrazine (DNPH) was used, Supelco LpDNPH S10 , and an air volume of 20 L was sampled. For VOCs, Tenax tubes were used and an air volume of 2 L was sampled. Sampling of VVOCs and VOCs was carried out following the ISO 16000-3:2011 and ISO 16000-6:2011 recommendations, respectively.VOC levels were analysed by thermal desorption (TD100 Markes) coupled to a gas chromatograph –mass spectrometer . VVOCs were analysed after elution with acetonitrile on a high-performance liquid chromatography system  with a diode-array detector (DAD VL+ Agilent). All the samples were analysed in the same laboratory for the entire period of the survey and quality controls were systematically performed following the ISO 16000-3:2011 and ISO 16000-6:2011 recommendations. GLIMS software  was used as a laboratory information system.The normal distribution of compound concentrations was studied first, both graphically (by boxplots) and statistically (by Shapiro–Wilk test). Due to high right-skewness, the Shapiro–Wilk test was used on log-transformed concentrations, but the normal hypothesis was rejected. Therefore, the results from chemical analyses were summarised using the geometrical mean (GM) and geometric standard deviation. Complementary quantile distribution measures were also calculated. All compounds were classified according to their compliance with guidance values provided by the German Association of Environmental Institutes (AGOEF) and the German Federal Environmental Agency (Umweltbundesamt) . Compounp-values (p ≤ 0.05) were subjected to a post hoc pairwise analysis via Mann–Whitney U test, and p-values were corrected using Holms method.Spatial analysis was based on three environmental regions: urban background influenced by traffic (UBT), urban background influenced by industries (UBI) and rural background (RB), corresponding to Luxembourg canton, Esch-sur-Alzette canton and the remaining cantons, respectively. Differences in concentrations among regions were studied using the non-parametrical Kruskal–Wallis test, due to a lack of normality. Compounds showing statistically significant Temporal analysis was performed using linear regression on concentrations and year of sampling.All statistical analyses were performed using R v4.0.3  and RStudio v1.4.1103 .iLCR is the estimated individual risk for lifelong (70 years) exposure to pollutant i (unitless), iEC the estimated exposure to pollutant i (μg m−3), and iIUR the inhalation unit risk for pollutant i (μg−1 m3). IUR is defined by the US EPA as the “upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent via inhalation per μg/m3 over a lifetime” [IUR values published by the California Office of Environmental Health Hazard Assessment (OEHHA) were used [Finally, a risk assessment on carcinogenic effects was performed for lifelong exposure to the selected pollutants. The methodology proposed by the United States Environmental Protection Agency (US EPA) was observed , using tifetime”  12-3). . (1)LCRiiHQ is the estimated non-carcinogenic risk for pollutant i (unitless) and iRfC the reference concentration for pollutant i (μg m−3). The US EPA defines the RfC as an “estimate of continuous inhalation exposure that is likely to be without an appreciable risk of deleterious effects during a lifetime” [RfC values were also obtained from the OEHHA [Additionally, non-carcinogenic risk was also estimated calculating the hazard quotient (HQ) for each compound and target-organ-specific hazard index (TOSHI), as proposed by the US EPA :(3)HQi=Eifetime”  (12-3). he OEHHA . CumulatAn overview of the concentrations found by compound is shown in s > 0.90, p < 0.001) and between them and ethyl-benzene . Otherwise, a low-to-moderate positive correlation was estimated generally, with the least correlated compounds being ethoxyethoxyethanol and trichloroethylene (mean rs = 0.01 for both).Co-exposure among selected compounds was assessed by Spearman’s correlation. A strong positive association was observed among the three xylenes (rp ≤0.05) for aromatic hydrocarbons (see p <0.001). The urban region influenced by industry presented a significantly higher level for benzene (p = 0.014).The Kruskal–Wallis test for comparing concentrations among environmental regions only showed statistically significant differences (bons see . Within p = 0.054). No significant difference was found for other compounds.Regarding other chemical categories, butoxypropanol presented higher values in the industrial region and lower values in the traffic-related region  and compound concentration (as the dependent variable). Log-transformed concentration was used due to right skewness. For compounds with a significant slope estimation (b estimate), relative variation was also calculated according to the geometric mean (GM) and guidance values, as shown in 3/year, −88.5% of its guidance value) and methylisothiazolinone . The remaining compounds with significant variation showed decreases that accounted for less than 10% of their guidance values.No compound showed a significant increase, according to the model fit. On the contrary, most of the selected compounds showed a decreasing trend. The strongest relative variations were found for perchloroethylene (−0.89 μg/mThe estimated risk derived from lifelong exposure to hazardous air pollutants is shown in IUR), followed by benzene and 1,4-dichorobenzene. Accordingly, naphthalene presented the highest estimated risk (148 expected cancer cases per 1 million people exposed to the GM concentration), followed by benzene (79 expected cancer cases), whilst the estimated risk for 1,4-dichlorobenzene is much lower (three expected cancer cases) due to its low measured concentration. On the other hand, formaldehyde has a lower IUR than the former, but an estimated risk similar to benzene (71 expected cancer cases), as exposure to this compound is generally higher. Globally, cancer risk after lifelong exposure to all compounds studied is estimated in 335-1162 expected cancer cases per 1 million people exposed to GM or the 90th percentile concentration, respectively.Regarding cancer risk, naphthalene has the highest estimated inhalation unit risk , but only the former is estimated to be a risk at the concentrations measured (hazard quotient of 1.3 at GM concentration and 6.2 at 90th percentile), the respiratory tract being its main target organ. When assessing the risk for target organs after exposure to all related compounds, only the respiratory tract is estimated to be at risk (hazard index of 1.4 at GM concentration and 6.4 at 90th percentile), majorly by exposure to formaldehyde. All remaining compounds assessed were estimated to be of very low risk (0 to 0.2 hazard quotient) for non-cancer chronic health effects.This study provides an overview of the current situation with regard to domestic indoor pollution in the Grand Duchy of Luxembourg. Measurements gathered over 5 years were included, allowing us to make more solid estimations and to reduce potential biases from short-term variations. Moreover, the inclusion of measurements from different environmental regions enabled a further characterisation of exposure from different backgrounds. The sample selection, being based on medical prescription, allowed a more conservative approach, studying the population that is expected to be at higher risk. However, this might lead to the overestimation of pollutant concentrations, and this must be kept in mind when interpreting the results.High levels were detected for several compounds, especially MIT, but also benzene, formaldehyde, limonene and β-pinene. To the best of our knowledge, there are no studies assessing MIT levels in household indoor air.3), as well as those for napthalene (GM 0.8 μg/m3), styrene (GM 1.4–3.9 μg/m3) and xylenes (GM 0.8–9.8 μg/m3) [3), Germany (GM 36.0 μg/m3) and Spain (GM 54.6 μg/m3) [3), but higher than the Netherlands’ (GM 4.1–6.4 μg/m3) and lower than Germany’s (GM 2.4–32.9 μg/m3) [Regarding the remaining compounds of study, their concentrations are mostly comparable to those found in other indoor air studies in European cities ,14,16. MSpain GM 4.6 μg/m39 μg/m3) .With respect to the geographical distribution of pollutants in the Grand Duchy of Luxembourg, in this study, households from urban settings influenced by traffic were found to have the lowest mean levels of aromatic hydrocarbons, whereas households from rural areas generally showed the highest values, followed by those from industrial areas. Cirillo et al.  describeRegarding the temporal analysis performed in this study, a global decreasing trend was found. MIT, which was the compound that most exceeded the guidance values, was also the one to show the greatest reduction during the period of study, along with perchloroethylene . A generalised improvement in air quality over the last few decades was also described by the European Environment Agency (EEA) , who assIUR and reference concentration values, different selections of pollutants and methodology variations. Payne-Sturges et al. [IUR values for benzene and ethylbenzene , estimating lower cancer risks for concentrations that were similar to or higher than ours . Huang et al. [Finally, risk assessment was also an important part of this study. The highest cancer risk was identified for exposure to naphthalene, benzene and formaldehyde, whereas non-cancer risk was only found for formaldehyde exposure, especially for the nervous system. Previous studies have also estimated the risk from exposure to indoor air pollution, but comparison among them is not straightforward due to the usage of older s et al.  used lowg et al.  and Dai g et al.  adapted g et al. . Howeverg et al. ,10. Estig et al. , LuxemboOur health impact assessment has identified some health risks associated with the observed concentrations. As observed (V)VOC levels in Luxembourg were similar to those in neighbouring countries, the identified health risk will also be comparable. The results clearly show the importance of having such a surveillance system in place to (i) support the prescribing physicians in patient management and care, (ii) define public health priorities for Luxembourg in the domain of indoor pollution and better targeted prevention, and to (iii) identify niches for focused science-policy research.


Both skeletal and visceral injuries are reported after cardiopulmonary resuscitation (CPR). This subgroup analysis of a randomized clinical study describes/compares autopsy documented injury patterns caused by two mechanical, piston-based chest compression devices: standard LUCAS® 2 (control) and LUCAS® 2 with active decompression  in non-survivors with out-of-hospital cardiac arrest (CA).We compared injuries documented by autopsies  after control and intervention CPR based on written relatives consent to use patients’ data. The pathologists were blinded for the device used. The cause of CA and injuries reported were based on a prespecified study autopsy template. We used Pearson's chi-squared test and logistic regression analysis with an alpha level of 0.05.N = 73) or forensic (N = 41) autopsy. The cause of CA was cardiac 53%, respiratory 17%, overdose/intoxication 14%, ruptured aorta 10%, neurological 1%, and other 5%. There were no differences between control and intervention in the incidence of rib fractures , or sternal fractures , respectively. The most frequent non-skeletal complication was bleeding  and intrathoracic was the most common location. Ten of the 114 patients had internal organ injuries, where lungs were most affected.221 patients were included in the main study (April 2015–April 2017) and 207 did not survive. Of these, 114  underwent medical (In non-survivors of OHCA patients, the most frequent cause of cardiac arrest was cardiogenic. Skeletal and non-skeletal fractures/injuries were found in both control and intervention groups. Bleeding was the most common non-skeletal complication. Internal organ injuries were rare. In the western world, 70% of all cardiac arrests (CA) occur due to ischemic cardiac disease, and 49/100 000 Europeans are treated for sudden out-of-hospital CA (OHCA) annually.5The active decompression (AD) technique of cardiopulmonary resuscitation (CPR) is performed manually by applying a suction cup on the chest and typically pulling it above the anatomic neutral level.The aim of this secondary study from a randomized clinical trial was to describe (autopsies) the cause of CA and compare injury patterns caused by two mechanical, piston-based chest compression devices LUCAS® 2 and LUCAS® 2 AD in patients with non-traumatic OHCA.The study was conducted in cooperation with the emergency medical service (EMS) of Oslo and Akershus . Adult patients with OHCA treated by ambulance crews and the rapid response car in Oslo were prospectively included in this cluster randomized, un-blinded clinical trial from April 2015 through April 2017.Eligible patients were non-survivors included in the randomized study by Berve et al. comparing hemodynamic measurements between LUCAS® 2 and LUCAS® 2 AD during OHCA CPR.−1, to a depth of approximately 5.3 cm. Both devices pull the patient’s sternum with the help of a suction cup.Both LUCAS® 2 and LUCAS® 2 AD are battery or mains powered, Conformite Européenne (CE) marked, piston-based chest compression devices with a suction cup. The devices compress the patient’s chest at a frequency of 102 compressions minAll patients who did not survive were eligible for a medical/or forensic autopsy. According to Norwegian legislation, any sudden unexpected death is considered unnatural. The police or a higher prosecution authority will generally request a forensic post-mortem examination. If the medical history may explain the sudden CA, or the police for any reason did not request a forensic examination, a medical autopsy is indicated with informed consent from the next of kin.Within 24 hours of death being established, the next of kin was contacted by the principal investigator (or someone representing he/she). The circumstances of death and medical considerations were presented and the possibility of a medical/or forensic autopsy to document cause of CA and CPR related injuries were discussed. If a forensic autopsy was not to be carried out, a medical autopsy was requested by the rapid response car doctor if next of kin consented. We were only allowed to use data from either medical/or forensic autopsy reports when permission from the patients’ next of kin was granted by written consent. Later, a follow-up conversation was performed to share and explain the autopsy findings to the next of kin.The primary outcome variables were injuries after LUCAS® 2 compared to LUCAS® 2 AD CPR and cause of OHCA based on autopsy reports. The secondary outcome measurements were association between CPR duration, age, sex and injuries.Duration of CPR was measured from start of mechanical chest compressions, verified electronically by reviewing LIFEPAK 15  defibrillator files in CODE-STAT 10 data review software . The LUCAS® devices electronically recorded force and depth data on each compression/decompression, chest height, and in addition duration of mechanical CPR. Manual CPR time prior to application of the mechanical chest compression device was calculated from patient report forms. CPR duration was registered continuously until (1) the patient was declared dead, or (2) the patient received sustained ROSC . In-depth information can be found in Berve et al.We provided a standardized autopsy protocol to the pathologist prior to study start. All cases were examined similarly, and the following assessments were included (1) skeletal injuries, (2) injuries on internal organs, (3) bleeding, and (4) cause of death. Cause of death was categorized into cardiac, respiratory, overdose/intoxication, bleedings, neurological, and other. Pathologists reported presence and localization of bleeding. Small soft tissue hemorrhage in the immediate vicinity of the fracture site were disregarded and not classified as bleeding. Hemorrhagic fluid (hematomas) in body cavities were estimated in liters (L). Truncal bleeding was classified into (1) mild/moderate soft tissue hemorrhage , (2) significant intra-abdominal hemorrhage (>0.3 L), or (3) significant intrathoracic hemorrhage (large soft tissue hemorrhages or hematomas in pleura (>0.2 L), pericardium, and/or mediastinum (>0.1 L). The forensic post-mortem examination included similar registry of data, but also included full body computed tomography (CT) scan of all cases. Data was extracted from the autopsy reports to the study database.p-values less than 0.05 as statistically significant. We did not perform any analysis on missing data. Multivariate logistic regression analysis was used to obtain odds ratio (OR) with 95% confidence intervals (CI) for the following outcomes: rib fractures, sternal fractures, non-skeletal injuries, and significant intrathoracic bleeding adjusted for sex, age (above or below 65 years), CPR duration (above or below median 38 minutes), and control vs intervention.We performed statistical analyses using SPSS 26 . Pearson's chi-squared test was used for categorical variables. We considered Power calculation for this study was performed on the primary outcome of the original study.ClinicalTrials.gov (NCT02479152).The Regional Ethical Committee  approved this study in 2015 and it was registered at In total, 221 patients with non-traumatic OHCA were accessed for eligibility (April 2015–April 2017), of whom 207 died (14survived). Of the 207 who died, we included 114 patients and excluded 93 patients (16 no consent and 77 no autopsy). Consent to use autopsy reports were obtained from next of kin.Medical autopsy was performed on 73 (64%) patients and forensic autopsies on 41 (36%) patients. The LUCAS® 2 group consisted of 64 patients and the LUCAS® 2 AD of 50 patients . The agen = 1 vs n = 1), myocardial infarction (n = 3 vs n = 2), and cardiac (n = 3 vs n = 1), respectively.The median age for the study population was 64 years (range: 19–91) and men represented 70% of all patients. The most common cause of CA based on autopsy reports was cardiac 53% , followed by respiratory 17%  and intoxications 14% , ruptured aorta 10%, neurological 1%, and other 5% . In the In general, there were no significant associations between any of the injury patterns and the independent variables tested in unadjusted or adjusted models with one or two exceptions . We founp = 0.37. For 9 patients the number of fractured ribs was not specified by the pathologists (At least one rib fracture occurred in 79 patients (70%) with no difference between the two groups. The median number of fractured ribs per patient were 5 (control) vs 7 (intervention), ologists . Overallologists .Ten patients (9%) had internal organ injuries. Lacerations on lungs and liver were most common. There was a higher number of internal organ injuries in the intervention group, but this was not statistically significant . The mosWe performed four logistic regression analyses to ascertain the association between some independent variables on the occurrence of any rib fracture, sternal fracture, visceral injuries or significant intrathoracic hemorrhage . In geneIn this study of non-survivors after OHCA we describe and compare injury patterns caused by two mechanical, piston-based chest compression devices, the LUCAS® 2 and the LUCAS® 2 AD. The most frequent cause of CA was cardiac (53%).Although this study documented the cause of cardiac arrest based on autopsies, it is comparable to the 60% of cardiac cause documented by the Norwegian Cardiac Arrest Registry 2021. Compared to the Registry data other causes like respiratory, intoxication, bleeding, and neurological were 17% vs 10%, 14% vs 8%, 10% vs 2%, 1% vs 8%, respectively. Differences in cause of arrest in our study and in the registry presumably have two main reasons. Firstly, selection bias in our study since it only includes patient that did not survive the cardiac arrest while the registry also includes surviving patients where a higher proportion will have reversible causes. Secondly, presumed cause of cardiac arrest in the Norwegian Cardiac Arrest Registry is not routinely adjudicated, and as such it is the best presumption of the treating personnel.Two factors usually contribute to injuries. One is the force applied to the patient’s chest and the other is CPR duration. Patient sex, age, muscle mass, and previous medical conditions may be associated factors. Tomlinson et al. investigated the relationship between forces (kilograms) applied to the chest of OHCA patients with compression depth.Non-skeletal injuries are relatively rare.In the study by Levy et al patients in both manual and mechanical CPR groups received manual compressions initially.Bystanders and/or EMS personnel performed manual chest compressions before the deployment of a mechanical chest compression device. Injuries may have taken place early in the CPR process.Few patients survived to hospital discharge due to the inclusion criteria. Patients with ROSC before rapid response car arrival were excluded. The overall survival rate in Oslo was 16% which is higher than the 6% we found in our study.CT scans are more sensitive at detecting complications such as pneumothorax/pneumoperitoneum. Only the forensic autopsy patients received CT scanning prior to autopsy, which can explain why such complications were less commonly found during medical autopsies. Yamaguchi et al. suggest that simultaneous CT investigation in addition to autopsy shows significantly higher incident of injuries.The sample size was planned for the primary endpoint of the original study. The post-hoc power calculations reveal a risk for type II errors due to limited number of cases. Still, this is one of the larger consecutive studies of injuries after mechanical CPR. The primary study was randomized (block-randomized with variable block size). For this secondary study we did not include surviving patients, and not every patient that died was subject to autopsy. This introduces a risk for selection bias. We have no reason to believe that group assignment influenced decision or consent process for autopsy, and it certainly could not affect the decisions about forensic autopsies. In the logistic regression analyses , the estIn non-surviving OHCA patients who received mechanical CPR most had a cardiac cause of arrest and skeletal injuries were common. Internal organ injuries were rare. Bleeding was the most common non-skeletal complication. Female gender and older age were associated with increased risk of intrathoracic bleeding. We conclude that mechanical chest compressions with active decompression do not cause more injuries than standard mechanical chest compressions.Norwegian National Advisory Unit on Prehospital Emergency Medicine (NAKOS), National association for Heart and Lung Patients (LHL), and Stryker (study coordinator).LW is a member of the Medical Advisory Board Stryker and hold patents through Oslo University Hospital Inven2 licensed to Stryker and Zoll. The other authors report no conflicts of interest.Polina Petrovich: Conceptualization, Methodology, Software, Formal analysis, Investigation, Data curation, Writing – original draft. Per Olav Berve: Conceptualization, Methodology, Investigation, Data curation, Writing – review & editing. Borghild Barth-Heyerdahl Roald: Conceptualization, Methodology, Investigation, Data curation, Writing – review & editing, Supervision. Håvard Wahl Kongsgård: Methodology, Investigation, Data curation, Writing – review & editing. Arne Stray-Pedersen: Conceptualization, Methodology, Investigation, Data curation, Writing – review & editing, Supervision. Jo Kramer-Johansen: Conceptualization, Methodology, Investigation, Data curation, Writing – original draft, Supervision. Lars Wik: Conceptualization, Methodology, Investigation, Data curation, Writing – original draft, Supervision, Project administration.


The GPCR database, GPCRdb supports >5000 interdisciplinary researchers every month with reference data, analysis, visualization, experiment design and dissemination. Here, we present our fifth major GPCRdb release setting out with an overview of the many resources for receptor sequences, structures, and ligands. This includes recently published additions of class D generic residue numbers, a comparative structure analysis tool to identify functional determinants, trees clustering GPCR structures by 3D conformation, and mutations stabilizing inactive/active states. We provide new state-specific structure models of all human non-olfactory GPCRs built using AlphaFold2-MultiState. We also provide a new resource of endogenous ligands along with a larger number of surrogate ligands with bioactivity, vendor, and physiochemical descriptor data. The one-stop-shop ligand resources integrate ligands/data from the ChEMBL, Guide to Pharmacology, PDSP Ki and PubChem database. The GPCRdb is available at  G protein-coupled receptors (GPCRs) account for 799  out of 2Nature . They are provided in the Guide to Pharmacology (GtP) database (i) and potency (pEC50) values. The largest source of tool compounds is ChEMBL  or functional ) data. Information about drugs approved by the US Food and Drug Administration is available from DrugCentral and DrugBank. Another source of consistently determined binding affinities – for psychoactive endogenous, tool and drug ligands—is the Ki database from the Psychoactive Drug Screening Program (https://pdsp.unc.edu/databases/kidb.php). Furthermore, commercial availability at vendors and physicochemical properties are provided for nearly all ligands in the PubChem database . These updates will increase GPCRdb's utility as a one-stop-shop for the GPCR community across basic research and drug discovery areas.Due to AlphaFold's limitation regarding lack of activation state specificity, we built 844 active or inactive state AlphaFold-MultiState models for 422 GPCRs in GPCRdb. We used structural templates published up until 4 July 2022 (published AlphaFold-MultiState models were based on templates until June 2021). The use of AlphaFold-MultiState removed the need for alternative backbone templates in our previously published GPCRdb's structure modelling pipeline ,19. All Refined structures revert mutations to wildtype. Missing regions are filled in from an AlphaFold model based solely only the given experimental structure and fitted by superposition at junction sites.i databases , as in (http://www.rdkit.org), CAS numbers via the Entrez E-utilities  , Guide t), as in . Ligand ), as in , as in , as in . Informatilities , UniProthttps://www.guidetopharmacology.org/download.jsp). These data contain a ‘principal’ and ‘secondary’ classification of many, but not all, endogenous ligands that is important in many scientific studies, for example when selecting a reference ligand for physiology-biased signaling   that arelication , the numStructure models page with or without loop and termini segments. In a model details page, users can view the 3D structure models color-coded by the AlphaFold confidence scores. All are full length models (include loops and termini) of wildtype sequence, except for AGRV1 which had to be reduced due to its extraordinary length of 6,306 amino acids. This includes 41 new and 71 longer receptors  compared to the AlphaFold-Multistate archive, and 5 receptors (10 models) that are not available from AlphaFold Protein Structure Database  databases. It currently contains 211 320 ligands and 466 278 binding affinity or potency values (6% (>20% if considering duplicates) and a 19% increase, respectively compared to GPCRdb's 2021 publication). The coverage of ligands across the receptors in the different human GPCR classes is A: 236 (75%), B1: 15 (100%), B2: 5 (15%), C: 12 (55%), F: 8 (73%) and T2: 25 (100%). Furthermore, the average number of ligands per receptor in each GPCR class is A: 612, B1: 400, C: 372, F: 90 and T2: 19.The GPCRdb ligand resource has been updated to incorporate the most recent version of ChEMBL  and add The receptor target selection page has added selection of receptors that are drug targets through two new columns ‘Target of an approved drug’, and ‘Target in clinical trials’, as defined in DrugBank, and DrugCentral. After selecting the receptor target, users can choose between two ligand bioactivity browsers. The ‘Compact (1 row/ligand)’ browser collates all binding or functional bioactivities of a given ligand and source database on one row by calculating minimum, average and maximum activity across studies. The ‘Extended (1 row/activity)’ browser instead lists the specific binding affinity or potency value of each study. This GPCRdb release has restructured potency and affinity data into separate tabs. It has also added fold selectivity values, along with the underlying number of experiments, allowing ligand selection based on their selectivity for the target of interest relative to all other stored GPCR targets. Both browsers also present information about vendors from which one can purchase the given ligand along with key physicochemical descriptors .This GPCRdb release contains a new page for individual ligands and its targets Figure . This cahttps://www.guidetopharmacology.org/nomenclature.jsp) and have an additional ranking by potency. For ligand-receptor pairs with multiple potency (pEC50) or affinity (pKi) values, the browser provides minimum, mean and maximum values, with grayscale background aiding comparison. Finally, the browser contains information about the ligand type, ligand name with a direct link to the ligand info page in GPCRdb, receptor information as family, species, IUPHAR and UniProt name and a popup showing the original references for bioactivities.The endogenous ligand-GPCR system spans different relationships ranging (ligand:receptor) 1:1, 1:many, many:1 and many:many relationships . To facihttps://gpcrdb.org and can also be accessed via a RESTful API, which complies with the OpenAPI specification using Swagger (code examples are available at https://docs.gpcrdb.org/web_services.html). The source code, the underlying data and a virtual machine configuration are all available in the repositories at https://github.com/protwis/.GPCRdb is available at


To assess stroke incidence over 44 years and association with risk factors. To study total stroke incidence at 60–82 years of age and risk factors.Prospective population study.Gothenburg, Sweden, with ∼450,000 inhabitants.A representative sample of a general population of women  in 5 age strata aged 38–60 years in 1968–1969  were followed up to the ages of 82–104 years in 2012. Further, analysis was also performed for the age interval 60–82 years.Incidence of total stroke (TS), ischaemic (IS), haemorrhagic (HS), non-specified (NS) and fatal (FS) strokes and association with baseline classic risk factors , low education, mental stress, pre-eclampsia and oral health as expressed by loss of teeth and bone score. Blood pressure in levels 1–3 according to modern guidelines. Associations with atrial fibrillation, diabetes and myocardial infarction shown in survival analyses. The five cohorts contributed to risk time data concerning associations with TS in the 60–82 age interval from the examination performed when they were 60.Three hundred and thirty-seven (23%) women had a first-ever stroke, 64 (19%) fatal. TS was associated with physical inactivity, high triglycerides and low education in multivariable analysis. The main sub-type IS was associated with systolic blood pressure, physical inactivity and low education. Pre-eclampsia showed association with IS only in the univariable analysis. FS was associated with systolic blood pressure and smoking. During 60–82 years of age, having <20 teeth , diabetes (HR 2.28 CI 1.09–4.76), WHR (HR 1.29 per 0.1 units CI 1.01–1.63), systolic blood pressure (HR 1.11 per 10 units CI 1.04–1.18) and smoking , were associated with TS in the combined five cohorts.Stroke is a common disease and the risk of stroke is a key issue demanding preventive strategies in primary health care. The present prospective population study of women showsOut of 1460 women, almost a quarter got a stroke. The stroke incidence 60–82 years of age was rather stable between the first four age cohorts but somewhat lower in the latest cohort, born 1930.Hypertension, low physical activity, low education and high triglyceride levels but not cholesterol were associated with stroke in women.Low education and loss of teeth are vulnerability factors that should need particular attention.Several classic risk factors showed independent associations with stroke. Vulnerability factors as low education and oral health, reflected by loss of teeth, also showed association with stroke. All these factors are possible to target in primary care preventive interventions. Stroke is a leading cause of death and disability worldwide . IncidenIncreased stroke risk associated with low education, particularly in women is largely explained by modifiable risk factors . NegativThe prospective Population Study of Women in Gothenburg (PSWG) offers unique possibilities to follow stroke incidence in a defined female population followed since 1968 . ChanginOur primary aim was to study women’s incidence of first-ever stroke, specified according to validated main type, and association with classic risk factors as well as with less well-known factors as SEP, working situation and oral health over a 44-year period. Further aim was to compare incidence and risk factors for stroke amongst the different birth cohorts from 60 to 82 years of age when stroke incidence is increasing.-survivors were 89%, 79% and 57%.Five population-based cohorts born 1930, 1922, 1918, 1914 and 1908 were invited 1968–1969 and 1462 (90.1%) women participated. The outcomes for the present study were first-ever stroke and stroke mortality after 44 years. A further aim concerned stroke incidence in separate sub-cohorts at ages 60–82 years, by use of information from the follow-up examinations 1974–1975, 1980–1981 and 1992–1993 to define baseline data from the examinations closest to age 60, with range 58–62, this included 1145 women after exclusion of two individuals with stroke before age 60 . The samICD-9 434, ICD-10 I63), haemorrhagic (HS)  and non-specified (NS). Subarachnoid haemorrhage was excluded. Medical records were scrutinised for all cases with unspecified or uncertain NPR stroke diagnoses , as well as those with ICD codes . Further, codes for transient ischaemic attacks (TIA)  were scrutinised to reveal possible stroke.Classification of stroke according to the International Classification of Diseases (ICD) was previously described . Hospitavia medical history interviews and fasting blood-glucose analyses. Smoking was dichotomised into current smokers and non-smokers. Self-reported intake of alcohol was assessed on a seven-level scale. As described in a recent study socioeconomic position (SEP) was defined from sociooccupational group classified as low, medium or high, based on reported occupation of spouse if available or own occupation and educational group [The PSWG included medical examinations, questionnaires, body mass index (BMI), waist-hip ratio (WHR), lipids with s-triglycerides, s-cholesterol total, , blood pressure (BP) measures and ECG examinations. Hypertension at baseline, 1968–1969, was defined as ≥160/≥95 mm Hg and/or treatment . For comal group . Self-rePre-eclampsia was based on a medical history questionnaire with eight questions concerning high blood pressure, albuminuria and general swelling. Oral health was based on dental examinations with number of teeth and level of periodontitis. The examination was carried out, per individual, by means of a clinical and radiographic examination (panoramic radiograph). The variable number of teeth was dichotomised with cut off at <20 teeth. Level of periodontitis was assessed from the radiographs by using a Schei ruler to measure bone loss adjacent to teeth by dividing the bone loss into five equal distances relative to the length of the roots of the teeth . Accordingly, the level of periodontitis was estimated as a mean score bone loss .n = 1459) during the whole follow-up 1968–2012, second stroke risk was analysed during the time period the different cohorts were aged 60–82 years. The primary analysis includes all available follow-up information on stroke incidence; in the secondary the comparison is restricted to the age interval when all five cohorts contribute data on stoke incidence  was also included. In addition, survival time 1968–2012 free from stroke was calculated for diabetes, myocardial infarction (MI), atrial fibrillation (AF) and hypertension at baseline. Interaction tests were performed to examine if the effect of some risk factors for stroke differed markedly between cohorts by adding an interaction term to the model defined as the product of two main effects in the model, e.g. low education × cohort.Out of 1460 women, 337 (23%), had a first-ever stroke during the 44-year follow-up distributed as follows: 262 (78%) IS, 39 (11%) HS, 38 (11%) NS. Fatal first-ever strokes constituted 64 cases (19%). NS were through validation minimised to 11% from 19%. Crude incidence was 7.0 per 1000 person years, and, standardised to the female population in Gothenburg the year 2000, it was 6.2. In multivariable Cox regression analyses significant associations were found between IS and systolic blood pressure, physical inactivity and low education . Triglycp < .001), atrial fibrillation (p < .001), myocardial infarction (p < .001) and hypertension at baseline (p < .001)  .n = 609) compared to those not working (n = 512), HR 0.92 (CI 0.51–0.999) (age-adjusted model). In cohort, 1930 no difference was observed, HR 1.12 (CI 0.55 − 2.26).In the cohorts 1908–1922, there was a lower risk of stroke for those with professional work (From a 44-year perspective, almost 25% of participants in the PSWG got a stroke and the main risk factors were hypertension, high triglycerides, low education and physical inactivity. Stroke fatality was associated with systolic blood pressure and smoking. Between 60 and 82 years in the five cohorts significant risk factors were systolic blood pressure, diabetes, WHR, smoking and oral health as reflected by number of teeth were associated with stroke.The population was well defined with a long follow-up time, high initial participation rate and a low drop-out rate. Endpoint validation through careful medical record examination, including CT examinations, decreased the number of incorrect diagnoses. CT has been performed in Gothenburg as routine in acute stroke from around 1980. Still the number of haemorrhagic strokes was too low to find significant risk factor associations. Stroke fatality reflects the most severe strokes.This long-term study includes comparison between five age cohorts reflecting different phases in women’s life. Further, the broad spectrum of parameters including oral health and social factors contributes important knowledge. Observations from ages 60 to 82 with risk data from examinations around 60 years of age show risk factors for stroke in a phase of life before the steep increase in stroke and severe comorbidities amongst elderly women.One limitation is that the number of participants is limited and conclusions regarding other ethnic groups or rural populations cannot be drawn. Further, the low total number of haemorrhagic strokes only revealed statistically significant results for systolic blood pressure. Another limitation is that socioeconomic factors important now are not always congruent with corresponding factors half a century ago. This may lead to underestimation of association between socioeconomic situation and stroke. We cannot rule out that socioeconomic factors might have influenced seeking hospital care pattern. Another limitation is that we have not studied risk factor load over time with different analyses such as in an earlier study on men . FurtherThe incidence figures were standardised using the Gothenburg female population in year 2000. Our rate of 7.0 per 1000 person years is higher than that in a recent report from southern Sweden , possiblA meta-analysis showed an association between SEP and stroke, partly explained by classic risk factors . Social It is interesting to note the strong association with stroke between 60 and 82 years of age that was shown for reduced number of teeth. This robust association may partly be caused by social factors, secondary effects of periodontal disease and inflammatory responses. The risk associated with poor oral health , showed Knowledge about the association between poor oral health and systemic disease including stroke has increased during the last decades ,28. PopuPre-eclampsia was associated with higher risk for stroke though not persisting in the multivariable analyses. Increased stroke risk in acute phases of pre-eclampsia is well known and is a risk factor for later stroke . The neeDiabetes before 60 years of age increased the risk for total stroke. Documented atrial fibrillation was recruited from electrocardiograms at defined time points and from registers, which probably underestimates this major risk factor since additional intermittent episodes can have occurred. In a meta-analysis 2016, atrial fibrillation was a significantly stronger stroke risk factor for women compared to men .As mentioned previously, risk factors for cardiovascular disease have been described in many male cohorts, some of which are similar to findings in women, whilst other can differ. In a male population born 1913 in Gothenburg followed for 48 years, a 20% stroke incidence amongst 854 men was observed i.e. similar to our study . Total aMental stress was not associated with stroke in the present study or in the male Gothenburg population study .Almost a quarter of the women suffered a first-ever stroke over 44 years, and 15% between 60 and 82 years of age. Lifestyle factors were associated with the risk for stroke as well as high triglyceride levels, but high cholesterol did not show any association with stroke in women. Poor dental health and low education can be indicators of low socioeconomic position and increased risk of later stroke. Collaboration between primary care and dental health care for risk cases might be a valuable issue. Long-term follow-up of borderline or high blood pressure and management of diabetes appears urgent. Primary health care has an important role in primary and secondary prevention of the common stroke disease.The Population Study of Women in Gothenburg was approved by the Ethics Committee of Gothenburg University, Dnr 179-92 S 208-01 2000, Ö 402-99, T331-14.