Effects Of Multiple Risk Factors Research Articles

How health risk factors affect inpatient costs among adults with stroke in China: the mediating role of length of stay.

As stroke has become the leading cause of death and disability in China, it has induced a heavy disease burden on society, families, and patients. Despite much attention within the literature, the effect of multiple risk factors on length of stay (LOS) and inpatient costs in China is still not fully understood. To analyse the association between the number of risk factors combined and inpatient costs among adults with stroke and explore the mediating effect of LOS on inpatient costs. A retrospective cross-sectional study was conducted among stroke patients in a tertiary hospital in Nantong City from January 2018 to December 2019. Lifestyle factors (smoking status, exercise), personal disease history (overweight, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation), family history of stroke, and demographic characteristics were interviewed by trained nurses. Inpatient costs and LOS were extracted from electronic medical records. Hierarchical multiple linear regression models and mediation analysis were used to examine the direct and indirect effects of the number of risk factors combined for stroke on inpatient costs. A total of 620 individuals were included, comprising 391 ischaemic stroke patients and 229 haemorrhagic stroke patients, and the mean age was 63.2 years, with 60.32% being male. The overall mean cost for stroke inpatients was 30730.78 CNY ($ 4444.91), and the average length of stay (LOS) was 12.50 days. Mediation analysis indicated that the greater number of risk factors was not only directly related to higher inpatient costs (direct effect = 0.16, 95%CI:[0.11,0.22]), but also indirectly associated with inpatient cost through longer LOS (indirect effect = 0.08, 95% CI: [0.04,0.11]). Furthermore, patients with high risk of stroke had longer LOS than those in low-risk patients, which in turn led to heavier hospitalization expenses. Both the greater number of risk factors and high-risk rating among stroke patients increased the length of stay and inpatient costs. Preventing and controlling risk behaviors of stroke should be strengthened.

Predicting perineal trauma during childbirth using data from a general obstetric population.

Perineal trauma is a common complication of childbirth and can have serious impacts on long-term health. Few studies have examined the combined effect of multiple risk factors. We developed and internally validated a risk prediction model to predict third and fourth degree perineal tears using data from a general obstetric population. Risk prediction model using data from all singleton vaginal deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019 and 2020. Third/fourth degree tears were diagnosed by an obstetrician or midwife at time of birth and defined as tears that extended into the anal sphincter complex or involved both the anal sphincter complex and anorectal mucosa. We used univariable and multivariable logistic regression with backward stepwise selection to develop the models. Candidate predictors included infant sex, maternal age, maternal body mass index, parity, mode of delivery, birthweight, post-term delivery, induction of labour and public/private antenatal care. We used the receiver operating characteristic (ROC) curve C-statistic to assess discrimination, and bootstrapping techniques were used to assess internal validation. Of 8,403 singleton vaginal deliveries, 8,367 (99.54%) had complete data on predictors for model development. A total of 128 women (1.53%) had a third/fourth degree tear. Three variables remained in the final model: nulliparity, mode of delivery (specifically forceps delivery or ventouse delivery) and increasing birthweight (per 100 gram increase) (C-statistic: 0.75, 95% CI: 0.71, 0.79). We developed a nomogram to calculate individualised risk of third/fourth degree tears using these predictors. Bootstrapping indicated good internal performance. Use of our nomogram can provide an individualised risk assessment of third/fourth degree tears and potentially aid counselling of women on their potential risk.

Unmasking the Hidden Danger: A Decade-Long Systematic Review of Case-Control Studies on Single Occupational Risks and Prostate Cancer.

The present systematic review addresses the influence of occupational exposures on prostate cancer risk. Eleven studies were analyzed for a range of occupational exposures, including but not limited to firefighting, physical activity, night shift work, chemical exposure, and solar ultraviolet radiation. The results of the review reveal that firefighters exposed to harmful substances, individuals engaged in physically strenuous work, and workers with chronic night shift routines showed an increased likelihood of developing prostate cancer. Moreover, the review identified an increased risk associated with exposure to certain chemicals, including alkylphenolic compounds and benzene-related substances. The evidence underscores the importance of considering the cumulative effect of multiple risk factors in a comprehensive risk assessment. However, the conclusions indicate the necessity for further research to deepen these relationships and develop more effective strategies for the prevention of prostate cancer.

Sleep duration as a mediator of the effects of risk factors for substance use

PurposePrior research reveals many risk factors related to adolescent substance use. In this study, we build an argument that insufficient sleep partially explains the effects of multiple risk factors (neighborhood disorder, unstructured socializing, bullying victimization, family conflict, and weak family social control) on substance use. MethodWe tested this argument with a large sample of middle and high school students. The causal pathway for each risk factor was estimated with a series of negative binomial models and generalized structural equational modeling. Indirect effects were also estimated. ResultsThe analysis revealed that each risk factor and shorter sleep duration significantly increased adolescent substance use. Moreover, it was found that sleep duration partially mediated each risk factor's effect on substance use. The degree of mediation varied by the risk factor that was examined. ConclusionsFindings from this study indicate that sleep duration is an important risk factor for adolescent substance use. Moreover, sleep duration appears to explain a portion of the effect of the other risk factors on substance use. In considering these issues, this study offers new insights into the predictors of insufficient sleep and its consequences on adolescent development.

Heterogeneity in Adolescents' Non-Suicidal Self-Injury Behaviour Trajectories Based on the Group-Based Trajectory Model and a Decision Tree Analysis of Family-Related Determinants.

Non-suicidal self-injury (NSSI) is a global public health problem. While some studies have noted the importance of behavioural development patterns in NSSI, most NSSI research is based on cross-sectional survey data. Few studies explore the time-series heterogeneity of trajectories of NSSI symptoms and family-related influencing factors of NSSI. The purpose of the study was to identify the heterogeneity in trajectories of adolescents' NSSI behaviour and their family-related influencing factors. The group-based trajectory model (GBTM) was used to identify the heterogeneity in the NSSI behaviour trajectories of 208 adolescents in China. Next, the decision tree model (DTM) was used to analyse which family related factors influence the trajectory type. The GBTM revealed two heterogeneous trajectories of NSSI behaviour: the high-risk and low-risk NSSI behaviour groups. Next, DTM's average accuracy was 83.2%. A total of seven independent variables were used for the DTM: gender, number of NSSIs in the past month, and family economic, family structure, family conflict, parental psychological control, parental behavior control and family intimacy risks. Family conflict risk was located at the root node and was the most important factor. Heterogeneity within the population should be considered in the management of adolescents' NSSI behaviours. Further, from the perspective of family system theory and cumulative risk, focusing on the adverse effect of multiple risk factors on adolescents' NSSI addiction is more meaningful rather than the impact of single risk factors. Studies that use time series data should focus on the trend of dynamic changes in NSSI addiction characteristics over time.

Eclampsia, in vitro fertilization and the risk of preterm birth: a retrospective cohort study based on 2,880,759 samples.

Eclampsia and in vitro fertilization (IVF) are independent risk factors for preterm birth. Understanding the combined effects of multiple risk factors for preterm birth is critical to making accurate and personalized risk predictions. This study aimed to explore the interaction between eclampsia and IVF on the risk of preterm birth. A total of 2,880,759 eligible participants from Birth Data Files in the National Vital Statistics System (NVSS) database 2019 were enrolled in this retrospective cohort study. Some characteristics were collected, such as maternal age, prepregnancy body mass index (BMI), history of preterm birth, paternal age, race, newborn sex. Preterm birth was defined as <37 weeks gestation. Univariate and multivariate logistic regression models were utilized to assess the associations between eclampsia, IVF and preterm birth. The odds ratio (OR) and 95% confidence interval (CI) were calculated in this study. Relative excess risk due to interaction (RERI), attributable proportion (AP) and synergy index (S) were adopted to evaluate the interaction between eclampsia and IVF on the risk of preterm birth. The age of mothers and fathers, the number of multiple births, the proportion of mothers with a history of preterm birth, pregnancy infections, eclampsia and IVF among the preterm birth group were all higher than those among the non-preterm birth group. The incidence of preterm birth in eclampsia and IVF population was approximately 37.31% and 22.96%, separately. After adjusting some covariates, subjects with both eclampsia and IVF had a higher risk of preterm birth (OR =9.197, 95% CI: 6.795-12.448, P<0.001). Furthermore, the results (RERI =3.426, 95% CI: 0.639-6.213, AP=0.374, 95% CI: 0.182-0.565, S =1.723, 95% CI: 1.222-2.428) suggested that the interaction between eclampsia and IVF on preterm birth was statistically significant, indicating a synergistic interaction. Eclampsia and IVF might interact in a synergistic manner to increase the risk of preterm birth. Awareness of the risk profile associated with preterm birth is crucial for pregnant woman with IVF to implement dietary and lifestyle modifications.

Association between circulating leukocytes and arrhythmias: Mendelian randomization analysis in immuno-cardiac electrophysiology.

Cardiac arrhythmia is a common disease associated with high mortality and morbidity. Circulating leukocyte counts, which serve as a biomarker for assessing systemic immune status, have been linked to arrhythmias in observational studies. However, observational studies are plagued by confounding factors and reverse causality, whether alterations in circulating leukocyte components are causally associated with arrhythmias remains uncertain. The present study explored this question based on genetic evidence. We performed Mendelian randomization (MR) analysis to evaluate whether alterations in leukocyte counts affect aggregated risk of all types of arrhythmia or risk of five specific types of arrhythmia. Single-nucleotide polymorphisms serving as proxies for leukocyte differential counts were retrieved from the Blood Cell Consortium, and statistical data on arrhythmias were obtained from the UK Biobank), FinnGenand a meta-analysis of genome-wide association studies for atrial fibrillation. We applied inverse variance-weighted method as the primary analysis, complemented by a series of sensitivity analyses. Bidirectional analyses were conducted to assess reverse causality. Finally, multivariable MR was performed to study the joint effects of multiple risk factors. We found that genetically predicted differential leukocyte counts were not significantly associated with aggregated occurrence of all types of arrhythmia. In contrast, each 1-standard deviation increase in lymphocyte count was associated with 46% higher risk of atrioventricular block (OR 1.46, 95% CI 1.11-1.93, p=0.0065). A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy. Reverse MR analysis suggested that atrioventricular block was unlikely to cause changes in lymphocyte count. Primary MR analysis based on the inverse-variance weighted method suggested that changes in neutrophil count alter risk of right bundle branch block, and changes in basophil count alter risk of atrial fibrillation. However, these causal relationships were not robust in sensitivity analyses. We found no compelling evidence that neutrophil or lymphocyte counts cause atrial fibrillation. Our data support higher lymphocyte count as a causal risk factor for atrioventricular block. These results highlight the importance of immune cells in the pathogenesis of specific cardiac conduction disorders.

2314. Hospitalizations and Antibiotic Use in the Year Prior to an Incident C. difficile Infection for Medicare Beneficiaries in Four States, 2016–2018

Abstract Background Studies describing risk factors for Clostridioides difficile infection (CDI) are often limited in their ability to identify potentially important exposures occurring long before diagnosis. We describe hospitalizations and antibiotic use (AU) occurring up to one year prior to CDI diagnosis among Medicare beneficiaries. Methods We studied incident CDI cases (positive C. difficile test in a person ≥65 years without a positive test in the prior 8 weeks) identified during 2016–2018 through population-based CDI surveillance from four states participating in the Centers for Disease Control and Prevention’s Emerging Infections Program. The analysis included specimens collected in all settings and was limited to case patients who were identified as having fee-for-service Medicare and Part D drug coverage for the year preceding specimen collection. Inpatient hospitalization data was extracted from Medicare Provider Analysis and Review (MEDPAR) files and outpatient AU (prescriptions filled) was determined using Part D drug event files. Timing of hospitalizations and antibiotic prescriptions were described as recent (0–3 months prior to specimen collection) or remote (4–12 months prior). Results Of 1,953 CDI cases, 1,594 (82%) filled ≥1 course of outpatient antibiotics in the prior year; 805 (41%) filled an antibiotic both recently and remotely, 497 (25%) only remotely, and 292 (15%) only recently. Cases with outpatient AU received a median of 23.5 (IQR 12–46) total days supplied, and a median of 2 different antibiotic classes (IQR 1 – 3). The most frequent antibiotic classes filled include fluoroquinolones (17% of all antibiotics filled), 1st generation cephalosporins (10%), and folate pathway inhibitors (10%). Overall, 1,314 (67%) cases were hospitalized in the prior year; 569 (29%) were hospitalized both recently and remotely, 446 (23%) only recently, and 299 (15%) only remotely. Median length of stay was 13 days (IQR 6–28). A total of 142 cases (7%) did not have hospitalization or outpatient AU in the prior year, and 1,097 (56%) had both. Conclusion Incident CDI cases have substantial exposure to recent and remote hospitalization and outpatient AU. Understanding cumulative effects of multiple risk factors can guide prevention strategies, including antibiotic stewardship efforts. Disclosures Scott Fridkin, MD, Pfizer: Grant/Research Support Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.

Predicting perineal trauma during childbirth using data from a general obstetric population

Background: Perineal trauma is a common complication of childbirth and can have serious impacts on long-term health. Few studies have examined the combined effect of multiple risk factors. We developed and internally validated a risk prediction model to predict third and fourth degree perineal tears using data from a general obstetric population. Methods: Risk prediction model using data from all singleton vaginal deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019 and 2020. Third/fourth degree tears were diagnosed by an obstetrician or midwife at time of birth and defined as tears that extended into the anal sphincter complex or involved both the anal sphincter complex and anorectal mucosa. We used univariable and multivariable logistic regression with backward stepwise selection to develop the models. Candidate predictors included infant sex, maternal age, maternal body mass index, parity, mode of delivery, birthweight, post-term delivery, induction of labour and public/private antenatal care. We used the receiver operating characteristic (ROC) curve C-statistic to assess discrimination, and bootstrapping techniques were used to assess internal validation. Results: Of 8,403 singleton vaginal deliveries, 8,367 (99.54%) had complete data on predictors for model development. A total of 128 women (1.53%) had a third/fourth degree tear. Three variables remained in the final model: nulliparity, mode of delivery (specifically forceps delivery or ventouse delivery) and increasing birthweight (per 100 gram increase) (C-statistic: 0.75, 95% CI: 0.71, 0.79). We developed a nomogram to calculate individualised risk of third/fourth degree tears using these predictors. Bootstrapping indicated good internal performance. Conclusions: Use of our nomogram can provide an individualised risk assessment of third/fourth degree tears and potentially aid counselling of women on their potential risk.

The Impact of 51 Risk Factors on Life Expectancy in Canada: Findings from a New Risk Prediction Model Based on Data from the Global Burden of Disease Study

The aims of this study were (1) to develop a comprehensive risk-of-death and life expectancy (LE) model and (2) to provide data on the effects of multiple risk factors on LE. We used data for Canada from the Global Burden of Disease (GBD) Study. To create period life tables for males and females, we obtained age/sex-specific deaths rates for 270 diseases, population distributions for 51 risk factors, and relative risk functions for all disease-exposure pairs. We computed LE gains from eliminating each factor, LE values for different levels of exposure to each factor, and LE gains from simultaneous reductions in multiple risk factors at various ages. If all risk factors were eliminated, LE in Canada would increase by 6.26 years for males and 5.05 for females. The greatest benefit would come from eliminating smoking in males (2.45 years) and high blood pressure in females (1.42 years). For most risk factors, their dose-response relationships with LE were non-linear and depended on the presence of other factors. In individuals with high levels of risk, eliminating or reducing exposure to multiple factors could improve LE by several years, even at a relatively advanced age.

Risky behavior analysis for cross-border drivers: A logit model and qualitative comparative analysis of odds of fault and injury vulnerability in Guangdong, Hong Kong and Macau

Introduction: Due to globalization and the acceleration of cross-border exchanges, cross-border risk behaviors have received widespread attention. Previous research has concluded that foreign cross-border drivers engage in relatively more risk-taking behavior patterns and are likely to experience a higher crash rate or be more inclined to cause severe crashes. However, there is little evidence on the comparison of drivers who belong to the same ethnic group driving across within-country borders. Method: Based on the cross-border motor-vehicle crash reports in 2006–2010 from the Road Traffic Accident Database of the China Ministry of Public Security, this paper examines the risk factors of being at fault and getting killed or seriously injured in cross-border traffic crashes and casual paths toward crash liability and injury severity for Hong Kong and Macao drivers driving in the Chinese mainland. Results: There are extremely complex factors behind drivers from Hong Kong and Macao causing at-fault crashes or sustaining fatal and serious injuries in the Chinese mainland. Factors such as gender, age, illumination, and weather conditions do not individually affect the risk of driver at-fault crashes or severe casualties in the crashes among Hong Kong and Macao drivers driving in the Chinese mainland. Nonetheless, collectively, these factors influence them along with different vehicle types, roads, and environmental factors. Conclusions: This paper provides more theoretical findings for understanding the compound effect of multiple risk factors involving cross-border at-fault crashes or serious casualties. The conclusions of this research are valuable as representative references for cross-border risk management policies. Practical applications: To reduce the effects of different factors on cross-border risky driving behaviors and/or injurious crashes, various measures should be focused on, including specialized driver training, enhancement of the roads/environment, development of effective road safety campaigns, and directives facilitating cross-border cooperation in the field of road safety.

Effects of multiple risk factors on upper limb musculoskeletal disorders among workers in inner Brazil.

The literature discussing musculoskeletal diseases of inner northeastern workers is scarce, although 67,559 cases were reported in Brazil between 2007 and 2016. This study aimed to evaluate the effect of multiple risk factors that influence the symptoms of work-related musculoskeletal disorders (WMSDs) in wrists, elbows, and shoulders in workers from four different economic sectors. A sample included 420 workers from the inner regions of the Brazilian states of Alagoas and Bahia. The Nordic Musculoskeletal Questionnaire was used to capture pain symptoms on both sides of the body (left and right). Sociodemographic variables, items from the biomechanical exposure and organizational conditional, in addition to other questionnaires (JCQ, COPSOQ II, ERI) were used to assess the characteristics and occupational risks of the respondents. Ordinal logistic regression model was using to identify the relationship between symptoms and factors. This study highlights the psychosocial, biomechanical, occupational, and sociodemographic variables contributed to development of WMSDs. Use of hand-vibrating tool increased the likelihood of symptoms manifesting on the body. On the other hand, high job control and high job insecurity reduced the likelihood of developing symptoms. On the other hand, high job control and job satisfaction reduced the likelihood of developing symptoms. Factors such as age, curved spine, high job insecurity and excessive commitment contributed to the development of WMSDs only on one side of the body. The development of WMSDs is multifactorial. Sociodemographic, occupational, biomechanical, and psychosocial factors may commonly contribute to WMSD manifesting only on one side of the body more than on both sides.

Estimation of Construction Activity Duration Under Uncertainty Using Discrete Fuzzy Weighted Average Algorithm

This paper presents a qualitative risk assessment tool based on fuzzy set theory to estimate the amount of activity duration overrun under the combinatory effect of multiple risk factors. Applying proposed methodology, a set of duration modifiers to calculate the optimistic, most-likely and pessimistic duration values under uncertainty are calculated. To elaborate the methodology, a simulated bridge project with ten risk factors affecting activities duration is presented. Proposed model contributes to knowledge that could help minimize the schedule overrun and improve risk mitigation strategies through providing risk-based duration estimates instead of discrete values. Advantages of the developed approach compared to existing models include (1) considering the combinatory effect of multiple risk factors on activity duration, (2) accounting for uncertainty in experts’ evaluations by employing the interval-valued fuzzy numbers, and (3) utilizing a discrete fuzzy weighted average algorithm which avoids creation of incorrect fuzzy membership functions.

Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population: a cross-sectional study.

BACKGROUNDEpidemiologic studies have explored the association between a single cardiovascular risk factor (CVRF) and resting heart rate (RHR), but the research on the relation of multiple risk factors with RHR remains scarce. This study aimed to explore the associations between CVRFs clustering and the risk of elevated RHR.METHODSIn this cross-sectional study, adults aged 35–75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August 2020. We focused on seven risk factors: hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, alcohol use, and low physical activity. Multivariate logistic regression was used to calculate odds ratios (OR) for elevated RHR (> 80 beats/min).RESULTSAmong 1,045,405 participants, the mean age was 55.67 ± 9.86 years, and 60.4% of participants were women. The OR (95% CI) for elevated RHR for the groups with 1, 2, 3, 4 and ≥ 5 risk factor were 1.11 (1.08–1.13), 1.36 (1.33–1.39), 1.68 (1.64–1.72), 2.01 (1.96–2.07) and 2.58 (2.50–2.67), respectively (Ptrend < 0.001). The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex subgroups. Clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk factors. CONCLUSIONSThere was a significant positive association between the CVRFs clustering number and the risk of elevated RHR, particularly in young males. Compared clusters comprising more behavioral risk factors, clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR. RHR may serve as an indicator of the cumulative effect of multiple risk factors.

Mental health in children of parents being treated by specialised psychiatric services.

One in ten children have a parent diagnosed with a mental illness by specialised psychiatric services. Severe parental mental illness is a well-established risk factor for children's mental health problems, making the identification and support of these children a public health concern. This study investigated the mental health and family context of children of parents diagnosed with depression, anxiety, or bipolar disorder in this clinical setting. Parental reports on 87 children aged 8-17 years were analysed. The children's mental health was compared with that of a Swedish population-based sample. Multiple linear regression was used to investigate associations between child mental health and child gender, child age, parent symptoms and social status, family functioning, and perceived parental control. Furthermore, a cumulative risk index explored the effect of multiple risk factors on child mental health. The children reportedly had significantly more mental health problems than did the population-based sample and about one-third had scores above the clinical cut-off. A significant multiple linear regression explained 49% of the variance in child mental health, with lower perceived parental control and younger child age being associated with more child mental health problems. With more reported risk factors, children reportedly had more mental health problems. The results underline the importance of identifying a patient's children and assessing multiple relevant risk factors in the child's life. Furthermore, the results indicate that the needs of younger children and of patients in their parenting role are important to address.

Characterizing and mapping the spatial variability of HIV risk among adolescent girls and young women: A cross-county analysis of population-based surveys in Eswatini, Haiti, and Mozambique.

BackgroundTo stem the HIV epidemic among adolescent girls and young women (AGYW), prevention programs must target services towards those most at risk for HIV. This paper investigates approaches to estimate HIV risk and map the spatial heterogeneity of at-risk populations in three countries: Eswatini, Haiti and Mozambique.MethodsWe analyzed HIV biomarker and risk factor data from recent population-based household surveys. We characterized risk using three approaches: complementary log-log regression, latent class analysis (LCA), and presence of at least one risk factor. We calculated the proportion and 95 percent confidence intervals of HIV-negative AGYW at risk across the three methods and employed Chi-square tests to investigate associations between risk classification and HIV status. Using geolocated survey data at enumeration clusters and high-resolution satellite imagery, we applied algorithms to predict the number and proportion of at-risk AGYW at hyperlocal levels.ResultsThe any-risk approach yielded the highest proportion of at-risk and HIV-negative AGYW across five-year age bands: 26%-49% in Eswatini, 52%-67% in Haiti, and 32%-84% in Mozambique. Using LCA, between 8%-16% of AGYW in Eswatini, 37%-62% in Haiti, and 56%-80% in Mozambique belonged to a high vulnerability profile. In Haiti and Mozambique, the regression-based profile yielded the lowest estimate of at-risk AGYW. In general, AGYW characterized as “at risk” across the three methods had significantly higher odds of HIV infection. Hyperlocal maps indicated high levels of spatial heterogeneity in HIV risk prevalence and population density of at-risk AGYW within countries.ConclusionCharacterizing risk among AGYW can help HIV prevention programs better understand the differential effect of multiple risk factors, facilitate early identification of high-risk AGYW, and design tailored interventions. Hyperlocal mapping of these at-risk populations can help program planners target prevention interventions to geographic areas with populations at greatest risk for HIV to achieve maximal impact on HIV incidence reduction.

Cardiovascular Risk Factors and MRI Markers of Cerebral Small Vessel Disease: A Mendelian Randomization Study.

Cardiovascular risk factors have been implicated in the etiology of cerebral small vessel disease (CSVD); however, whether the associations are causal remains unclear in part due to the susceptibility of observational studies to reverse causation and confounding. Here, we use mendelian randomization (MR) to determine which cardiovascular risk factors are likely to be involved in the etiology of CSVD. We used data from large-scale genome-wide association studies of European ancestry to identify genetic proxies for blood pressure, blood lipids, body mass index (BMI), type 2 diabetes, smoking initiation, cigarettes per day, and alcohol consumption. MR was performed to assess their association with 3 neuroimaging features that are altered in CSVD (white matter hyperintensities [WMH], fractional anisotropy [FA], and mean diffusivity [MD]) using genetic summary data from the UK Biobank (N = 31,855). Our primary analysis used inverse-weighted median MR, with validation using weighted median, MR-Egger, and a pleiotropy-minimizing approach. Finally, multivariable MR was performed to study the effects of multiple risk factors jointly. MR analysis showed consistent associations across all methods for higher genetically proxied systolic and diastolic blood pressures with WMH, FA, and MD and for higher genetically proxied BMI with WMH. There was weaker evidence for associations between total cholesterol, low-density lipoprotein, smoking initiation, pulse pressure, and type 2 diabetes liability and at least 1 CSVD imaging feature, but these associations were not reproducible across all validation methods used. Multivariable MR analysis for blood pressure traits found that the effect was primarily through genetically proxied diastolic blood pressure across all CSVD traits. Genetic predisposition to higher blood pressure, primarily diastolic blood pressure, and to higher BMI is associated with a higher burden of CSVD, suggesting a causal role. Improved management and treatment of these risk factors could reduce the burden of CSVD.

P14.65 Survival in a consecutive series of 467 glioblastoma patients: impact of prognostic factors and recurrent treatment at two independent institutions

Abstract BACKGROUND Glioblastoma (GBM) is an aggressive primary brain tumor with median overall survival (OS) of less than one year in unselected adult patients. There is no standard therapy at recurrence. We aimed to evaluate OS in a consecutive series of GBM patients from Norway’s two largest regional health authorities, compare the effect of physicians’ choice of antineoplastic treatment upon recurrence and identify prognostic and predictive factors. MATERIAL AND METHODS Clinicopathological data from n=467 patients with histologically confirmed GBM diagnosed and treated at Haukeland and Oslo university hospitals from January 2015 to December 2017 was retrospectively collected. Data included tumor location, methylation status of the methylguanine-DNA methyltransferase (MGMT) promoter and mutation of the isocitrate dehydrogenase (IDH) genes, patient age and sex, extent of tumor resection at primary diagnosis, and treatment at first, second and third tumor recurrences. Cox-proportional hazards regression with pairwise analyses adjusted for multiple testing with Scheffé’s post-hoc test were used to adjust effect of multiple risk factors on mortality. RESULTS Median OS was 12.1 months and 21.4 % and 6.8 % of patients were alive at 2 and 5 years, respectively. Treatment at recurrence varied between institutions but did not impact OS (p=0.201). Median time to progression was 8.2 months. Age, MGMT promoter methylation, tumor location and extent of tumor resection were all independent prognostic factors for OS. Patients receiving radiotherapy to 60 Gray with concomitant and adjuvant temozolomide at primary diagnosis had best outcome with median OS of 16.1 months and 9.3% were alive at 5 years. At first recurrence patients eligible for gammaknife/stereotactic radiosurgery (GK/SRS) or surgery, alone or combined with chemotherapy, had superior survival compared to chemotherapy alone (p&amp;lt;0.0001 and p=0.014, respectively). On Scheffé’s post-hoc analyses only GK/SRS was superior to chemotherapy (p=0.01). At second and third recurrence none of the antineoplastic strategies came across as superior or inferior to each other using Cox. On Scheffé’s post-hoc analyses chemotherapy alone and combined with bevacizumab were superior at second recurrence (p=0.008 and p=0.042, respectively) and chemotherapy combined with bevacizumab was superior at third recurrence (p=0.043), compared to no antineoplastic treatment. Our retrospective study is limited by small sample sizes and heterogeneous treatment groups, especially at second and third recurrences, as well as patient selection. CONCLUSION Recurrence treatment differed between the two institutions but there was no difference in OS. Our findings underline the lack of standard therapy upon GBM recurrence and the urgent need for novel therapeutic strategies.

Psychological Effects of Different Harmonic Progressions in Film Music on Audience's Inner Hearing

Reverse total shoulder arthroplasty (RTSA) is being used to treat a number of shoulder disorders. The purpose of the present study was to investigate the correlation between psychological disorders, drug and alcohol abuse, and postoperative complications and outcomes after RTSA.A total of 128 patients who underwent an RTSA between January 2010 and February 2017 were identified. American Shoulder and Elbow Surgeons, SST, ROM, complications, radiographic outcomes and patient satisfaction were collected. Follow-up occurred at a minimum of 2 years postoperatively (average of 3.68 years). Statistical analysis evaluated the effects of multiple risk factors: psychological disorders, substance abuse, and preoperative diagnoses.Psychological disorder diagnosis correlated with statistically significant lower American Shoulder and Elbow Surgeons function (P = .027) and Simple Shoulder Test (P = .029) scores compared with those without a psychological disorder. It also conferred poor functional outcomes based on external rotation (P = .012). Complications, especially major complications, were more prevalent in patients with psychological diagnoses than without. A history of substance abuse correlated with a lower external rotation (P = .025).Both a preoperative psychological diagnosis and a history of substance abuse conferred worse objective and functional outcomes scores after RTSA.

Psychological disorders confer poor functional outcomes after reverse total shoulder arthroplasty

Reverse total shoulder arthroplasty (RTSA) is being used to treat a number of shoulder disorders. The purpose of the present study was to investigate the correlation between psychological disorders, drug and alcohol abuse, and postoperative complications and outcomes after RTSA. A total of 128 patients who underwent an RTSA between January 2010 and February 2017 were identified. American Shoulder and Elbow Surgeons, SST, ROM, complications, radiographic outcomes and patient satisfaction were collected. Follow-up occurred at a minimum of 2 years postoperatively (average of 3.68 years). Statistical analysis evaluated the effects of multiple risk factors: psychological disorders, substance abuse, and preoperative diagnoses. Psychological disorder diagnosis correlated with statistically significant lower American Shoulder and Elbow Surgeons function (P= .027) and Simple Shoulder Test (P= .029) scores compared with those without a psychological disorder. It also conferred poor functional outcomes based on external rotation (P= .012). Complications, especially major complications, were more prevalent in patients with psychological diagnoses than without. A history of substance abuse correlated with a lower external rotation (P= .025). Both a preoperative psychological diagnosis and a history of substance abuse conferred worse objective and functional outcomes scores after RTSA.