Validation of external and internal exposome of the findings associated to cerebral small vessel disease: A Mendelian randomization study

The exposome characterizes all environmental exposures and their impact on a disease. To determine the causally-associated components of the exposome for cerebral small vessel disease (CSVD), we performed mendelian randomization analysis of 5365 exposures on six clinical and subclinical CSVD measures. We found statistically significant evidence (FDR-corrected P < 0.05) that hypertension, high cholesterol, longer television-watching time, lower educational qualifications, younger age of first sexual intercourse, smoking, reduced pulmonary function, higher subjective overall health rating, and frequent tiredness were associated with increased risk of intracerebral hemorrhage or small vessel stroke. Adiposity, diabetes, frequent alcoholic drinks, higher white blood cell count and neutrophil count were significantly associated with higher risk of non-lobar hemorrhage or small vessel stroke, but not lobar hemorrhage. Hypertension, higher arm or leg fat-free mass and higher sitting height were significantly associated with higher white matter hyperintensities. The results were robust to sensitivity analyses and showed no evidence of horizontal pleiotropy. We also identified 41 exposures suggestively associated (uncorrected P < 0.05) with multiple CSVD measures as the “the CSVD exposome”. This exposome-wide association study provides insight into CSVD development and prevention.

Characterizing the Phytotoxic Effects of Hydrogen Peroxide Root Dips on Hybrid Phalaenopsis Orchid Plants

Hydrogen peroxide (H2O2) is a well-known oxidizing agent often used as a remedy by consumers to treat algae and root decay from presumed root disease on interior plants, as well as to encourage root growth and health. To characterize the phytotoxic effects and define the safe concentration threshold for H2O2 use on ‘Vivaldi’ hybrid phalaenopsis orchid (hybrid Phalaenopsis), root systems were dipped for 3 minutes in 0%, 3%, 6%, or 12% H2O2 one time and observed in greenhouse conditions for the following 27 days. Root systems of each plant were assessed over time for percent visible root damage; ratings of root health on a scale of 1 to 5 points, with 5 points indicating “very healthy”; and final fresh and dry weights. To determine when symptoms manifested above the root zone, foliage and flower damage was evaluated over time by assessing percent visible foliage damage, ratings of foliage health, percent foliar wilt, flower/bud count, and final foliage and flower fresh and dry weights. Over the evaluation period, the root health rating of the ‘Vivaldi’ hybrid phalaenopsis orchids treated with 12% H2O2 decreased from 5 to 1.13, whereas those treated with 3% H2O2 only decreased from 5 to 4.13. H2O2 concentrations of 6% and 12% damaged root health permanently, whereas the 3% H2O2 concentration only caused minor damage to overall root health. However, algae were not killed at the 3% rate. Neither foliage nor flowers were seriously affected during the 3 weeks after application, but foliage wilt did result in the 6% and 12% treatments by week 4. As H2O2 concentration increased, fresh weights decreased in roots and leaves. Although a single 3% H2O2 root dip did not result in severe symptoms of phytotoxicity, the treatment’s long-term plant health effects are unknown. Because the 3% H2O2 root dip caused minor plant health setbacks and failed to subdue algae populations in the root zone, consumers should be wary of using H2O2 to improve orchid (Orchidaceae) root health and should instead focus on altering care and watering practices.

P128 Sleep Need is more Strongly Associated with Self-rated Health and Daytime Function than Sleep Duration

Introduction Most studies examining associations between sleep and health outcomes focus on sleep duration or efficiency, ignoring individual differences in sleep need. We investigated whether sleep need is a more influential correlate of self-rated daytime function and health than sleep duration. Methods This study is a secondary analysis of the 2019 Sleep Health Foundation online survey of adult Australians (N=2,044, aged 18–90 years). Hierarchical multiple linear regressions assessed variance explained by demographics (Model 1: age, sex, BMI), self-reported sleep duration (Model 2: Model 1 + weighted variable of weekday/weekend sleep duration), and individual sleep need (Model 3: Model 2+ how often they get enough sleep to feel their best the next day, on a 5-point scale) on daytime function items for fatigue, concentration, motivation, and overall self-rated health (EQ-5D, VAS 0–100). Results Sleep need explained an additional 17.5–18.7% of the variance in fatigue, concentration, motivation, and health rating (all p &lt; 0.001 for R² change) in Model 3. Model 2 showed that sleep duration alone only explained 2.0–4.1% of the variance in these outcomes. Findings were similar when stratified by sex. Sleep need also explained greater variance for older adults than for younger and middle-aged adults, especially on health rating (Model 3: R² change = 0.11 for ages 18-24y, 0.14 for 45-54y, 0.27 for 75y+). Conclusions Sleep need explains more variance in daytime function and self-rated health than sleep duration. The role of sleep need on other daytime consequences, and in clinical populations, needs further exploration.

Implementation of a novel patient-reported outcomes measure for patients with cancer and COVID-19 infection.

153 Background: The long-term symptoms from COVID-19 (C19) infection in pts with cancer is not fully known. To monitor the evolution of this symptom burden over time, we designed and implemented a C19-specific patient-reported outcome (PRO) measure that integrated with a known measure of cancer symptom burden. Methods: Within the institutional initiative on C19 and cancer named Data-Driven Determinants for C19 Oncology Discovery Effort (D3CODE), pts with cancer & PCR-pos C19 are invited to participate in this longitudinal study. Pts complete the EQ-5D-5L, the 13 symptom severity & 6 interference items of the core MD Anderson Symptom Inventory (MDASI)+14 COVID-specific items, all scored on a 0-10 scale, 0 = none, 10 = worst imaginable. Pts complete the survey daily x 14 days from positive test date, then weekly x 3months, then monthly x 2yrs. Demographic and disease information was collected. Psychometric procedures determined validity and reliability of the MDASI-COVID. Results: Between 5/15/20 – 02/14/21, 2154 pts w PCR-confirmed C19 were invited to participate in the longitudinal study. 1282 (60%) pts provided consent and began the longitudinal completion of PRO surveys. Pts were 54.5% Female and 45.5% Male, median age 59 years (range 15 – 92). 1021 (80%) are White/Caucasian, 206 (16%) Hispanic, 113 (9%) African American, and 39 (3%) Asian. The validation analysis of MDASI-COVID instrument included the 1st 600 pts where the mean overall health rating on EQ-5D-5L was 78.3 (SD 19.6), best being 100. Highest mean (M) severity symptoms on the MDASI-COVID were fatigue (M 3.45, SD 2.17), drowsiness (M 2.50, SD 2.89), sleep disturbance (M 2.44, SD 2.99), malaise (M 2.37, SD 3.05), and distress (M 2.27, SD 2.90). Most severe (≥ 7) symptoms) reported were fatigue (21.3% of pts), change in taste (14.8%), change in smell (14.4%), malaise (14.3%), sleep disturbance (14.3%), and drowsiness (14%). showed internal consistency (Cronbach α) of the 27 symptom items was 0.957, of the 6 interference items was 0.937. Mean severity of the 27 symptom items was significantly correlated with overall EQ-5D-5L health rating (correlation = -0.45, P < 0.0005), demonstrating concurrent validity. Mean symptom severity and interference showed known-group validity between pts who required hospitalization (symptom M 2.32, SD 2.09; interference M 3.29, SD 3.02) and those who did not (symptom M 1.69, SD 1.85; interference M 2.20, SD 2.64) (symptom P 0.007; interference P 0.004). Conclusions: We successfully deployed a PRO-based long-term symptom monitoring platform for pts with C19 and cancer. The validation analysis of this novel C19 specific PRO, the MDASI-COVID, aids in the quantification of the global symptom burden in pts with both cancer and COVID-19 infection. Deployment of this measure in the ongoing longitudinal observational cohort allows for in-depth understanding of the long-term symptoms related to C19 and cancer.

O009 The Good Sleeper Scale-13 Items: a standardised questionnaire for the assessment of good sleepers

Introduction Good sleep is not merely the absence of sleep disorder symptoms, yet this criterion is commonly applied in research studies. We developed the Good Sleeper Scale-13 (GSS-13) to standardise identification of good sleepers. Methods We conducted a secondary analysis of the 2019 Sleep Health Foundation online survey of adult Australians (N = 2,044, aged 18–90 years). Possible GSS-13 items were chosen collaboratively with co-authors. Exploratory factor analysis (EFA) was conducted on 10% of the dataset chosen at random (N = 191) for factor identification and item reduction. Confirmatory factor analysis (CFA) on the remaining 90% (N = 1,853) tested model fit. Associations with sleep concerns, health, and daytime functioning tested validity of the final version. Results From EFA, six factors were identified: Adequate Sleep; Insomnia; Regularity; Timing; Sleep Duration; Perceived Sleep Problem. On CFA, model fit was comparable to other sleep instruments, X² (67) = 387.34, p &lt; .001, CFI = .95, TLI = .92, RMSEA = .05. Cronbach’s alpha was largely acceptable (≥.7) across subscales. Consistent correlations were found between GSS-13 global scores and outcomes, including “a good night’s sleep” (r = .65, p &lt; .001), feeling un-refreshed (r = -.53, p &lt; .001), and general health rating (r = .44, p &lt; .001). Classification accuracy for insomnia symptoms was also high (AUC = .84). Conclusions The GSS-13 is psychometrically sound, correlated well with sleep, health, and daytime functioning, and can be used to identify good sleepers for research. Future work will test relationships with other sleep measures.

Development and validation of a novel patient-reported outcomes (PRO) measure for symptom burden in patients with cancer and COVID-19 infection.

12113 Background: The symptom burden experienced by patients with cancer who contract the COVID-19 (C19) infection remains to be fully understood. To accurately assess this symptom burden, we developed a valid, reliable patient-reported outcome (PRO) measure of C19 symptoms combined with a known measure of cancer symptom burden. Methods: Within the institutional initiative on COVID-19 and cancer named Data-Driven Determinants for COVID-19 Oncology Discovery Effort (D3CODE), patients with cancer and PCR-positive C19 tests were invited to participate in this longitudinal study after providing consent. Pts completed the EQ-5D-5L and the 13 symptom severity and 6 interference items of the core MD Anderson Symptom Inventory (MDASI) plus 14 COVID-specific symptom items generated from literature and expert review. Items were measured on a 0-10 scale, 0 = none to 10 = worst imaginable symptom or interference. Demographic and disease information was collected. Psychometric procedures determined validity and reliability of the MDASI-COVID. Results: 600 pts enrolled, mean age 56.5y (range 20 to 91y). 59% female, 80% white. 78% solid tumors, 19% heme cancers. 12.5% required hospitalization for C19. Median number of days between positive C19 test and PRO completion was 17 days. Mean overall health rating on EQ-5D-5L was 78.3 (SD 19.6), best being 100. Highest mean (M) severity symptoms on the MDASI-COVID were fatigue (M 3.45, SD 2.17), drowsiness (M 2.50, SD 2.89), sleep disturbance (M 2.44, SD 2.99), malaise (M 2.37, SD 3.05), and distress (M 2.27, SD 2.90). Most severe (≥ 7) symptoms) reported were fatigue (21.3% of pts), change in taste (14.8%), change in smell (14.4%), malaise (14.3%), sleep disturbance (14.3%), and drowsiness (14%). Internal consistency (Cronbach α) of the 27 symptom items was 0.957, of the 6 interference items was 0.937. Mean severity of the 27 symptom items was significantly correlated with overall EQ-5D-5L health rating (correlation = -0.45, P < 0.0005), demonstrating concurrent validity. Mean symptom severity and interference showed known-group validity between patients who required C19 hospitalization (symptom M 2.32, SD 2.09; interference M 3.29, SD 3.02) and those who did not (symptom M 1.69, SD 1.85; interference M 2.20, SD 2.64) (symptom P 0.007; interference P 0.004). Conclusions: We have validated a novel PRO, the MDASI-COVID, to quantify the combined symptom burden in patients with cancer and COVID-19. This measure allows longitudinal evaluation of COVID-19 on cancer symptom burden and provide clinicians with an accurate tool for ongoing symptom assessment and management. Longitudinal analysis on long-term symptoms related to COVID-19 and cancer are ongoing.

Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study

Background Childhood obesity is reported to be associated with the risk of many diseases in adulthood. However, observational studies cannot fully account for confounding factors. We aimed to systematically assess the causal associations between childhood body mass index (BMI) and various adult traits/diseases using two-sample Mendelian randomization (MR). Methods After data filtering, 263 adult traits genetically correlated with childhood BMI (P < 0.05) were subjected to MR analyses. Inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods were used to estimate the causal effects. Multivariable MR analysis was performed to test whether the effects of childhood BMI on adult traits are independent from adult BMI. Results We identified potential causal effects of childhood obesity on 60 adult traits (27 disease-related traits, 27 lifestyle factors, and 6 other traits). Higher childhood BMI was associated with a reduced overall health rating (β = − 0.10, 95% CI − 0.13 to − 0.07, P = 6.26 × 10−11). Specifically, higher childhood BMI was associated with increased odds of coronary artery disease (OR = 1.09, 95% CI 1.06 to 1.11, P = 4.28 × 10−11), essential hypertension (OR = 1.12, 95% CI 1.08 to 1.16, P = 1.27 × 10−11), type 2 diabetes (OR = 1.36, 95% CI 1.30 to 1.43, P = 1.57 × 10−34), and arthrosis (OR = 1.09, 95% CI 1.06 to 1.12, P = 8.80 × 10−9). However, after accounting for adult BMI, the detrimental effects of childhood BMI on disease-related traits were no longer present (P > 0.05). For dietary habits, different from conventional understanding, we found that higher childhood BMI was associated with low calorie density food intake. However, this association might be specific to the UK Biobank population. Conclusions In summary, we provided a phenome-wide view of the effects of childhood BMI on adult traits. Multivariable MR analysis suggested that the associations between childhood BMI and increased risks of diseases in adulthood are likely attributed to individuals remaining obese in later life. Therefore, ensuring that childhood obesity does not persist into later life might be useful for reducing the detrimental effects of childhood obesity on adult diseases.

Supporting a Healthier Takeaway Meal Choice: Creating a Universal Health Rating for Online Takeaway Fast-Food Outlets

Digital food ordering platforms are used by millions across the world and provide easy access to takeaway fast-food that is broadly, though not exclusively, characterised as energy dense and nutrient poor. Outlets are routinely rated for hygiene, but not for their healthiness. Nutritional information is mandatory in pre-packaged foods, with many companies voluntarily using traffic light labels to support making healthier choices. We wanted to identify a feasible universal method to objectively score takeaway fast-food outlets listed on Just Eat that could provide users with an accessible rating that can infer an outlet’s ‘healthiness’. Using a sample of takeaway outlets listed on Just Eat, we obtained four complete assessments by nutrition researchers of each outlet’s healthiness to create a cumulative score that ranged from 4 to 12. We then identified and manually extracted nutritional attributes from each outlet’s digital menu, e.g., number of vegetables that have the potential to be numerated. Using generalized linear modelling we identified which attributes were linear predictors of an outlet’s healthiness assessment from nutritional researchers. The availability of water, salad, and the diversity of vegetables were positively associated with academic researchers’ assessment of an outlet’s healthiness, whereas the availability of chips, desserts, and multiple meal sizes were negatively associated. This study shows promise for the feasibility of an objective measure of healthiness that could be applied to all outlet listings on Just Eat and other digital food outlet aggregation platforms. However, further research is required to assess the metric’s validity, its desirability and value to users, and ultimately its potential influence on food choice behaviour.

Analisis Tingkat Kesehatan Bank Mandiri Syariah Dengan Metode Risk Profile, Good Corporate Governace, Earnings and Capital

The purpose of this research is to see the soundness level of Bank Syariah Mandiri with the method of Risk Profile, Good Corporate Governance, Earnings and Capital. The research method uses quantitative methods. Production factors in the RGEC method are the risk profile using credit risk (NPF), liquidity risk (FDR), income (ROA, ROE and BOPO) and capital (CAR). On the results of Good Corporate Governance using data processed and obtained from PT. Bank Syariah Mandiri. The object of this research is PT. Bank Syariah Mandiri. The sampling technique in this study using purposive sampling. This research period is 2013-2017. The data analysis technique used in this research is quantitative descriptive and using the RGEC method (Risk Profile, Good Corporate Governance, Earnings and Car), as for the benchmarks to determine the soundness level of a bank after each examination, namely by determining the results of the study classified into the bank's health rating. The results showed that the health of PT. Bank Syariah Mandiri which uses the Risk Profile approach, Good Corporate Governance, Earnings, and Capital as a whole can be said that Bank Syariah Mandiri is a fairly healthy bank.