Significant Univariate Associations Research Articles

Biomarkers of interstitial lung disease associated with primary Sjögren's syndrome

ObjectivesThe aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD).Methods69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs).ResultsAmong consecutively enrolled patients with pSS, the presence of pSS–ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS–ILD group (ILA 2 + ILA 3) than in the pSS–no-ILD and pSS–indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS–ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS–ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001).ConclusionsPatient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS–ILD.Clinical trial registrationNone.

The personality and cognitive traits associated with adolescents’ sensitivity to social norms

Little is known about the personality and cognitive traits that shape adolescents’ sensitivity to social norms. Further, few studies have harnessed novel empirical tools to elicit sensitivity to social norms among adolescent populations. This paper examines the association between sensitivity to norms and various personality and cognitive traits using an incentivised rule-following task grounded in Game Theory. Cross-sectional data were obtained from 1274 adolescents. Self-administered questionnaires were used to measure personality traits as well as other psychosocial characteristics. Incentivised rule-following experiments gauged sensitivity to social norms. A series of multilevel mixed effects ordered logistic regression models were employed to assess the association between sensitivity to norms and the personality and cognitive traits. The results highlighted statistically significant univariate associations between the personality and cognitive traits and sensitivity to norms. However, in the multivariate adjusted model, the only factor associated with sensitivity to norms was gender. The gender-stratified analyses revealed differences in the personality and cognitive traits associated with sensitivity to norms across genders. For males need to belong was significantly negatively associated with sensitivity to norms in the multivariate model. By comparison, emotional stability was negatively associated with sensitivity to norms for females. This study reinforced the findings from an earlier study and suggested female adolescents had higher levels of sensitivity to norms. The results indicated no consistent pattern between sensitivity to norms and the personality and cognitive traits. Our findings provide a basis for further empirical research on a relatively nascent construct, and bring a fresh perspective to the question of norm-following preferences among this age group.

Severity of depressive but not anxiety symptoms impacts glucose metabolism among patients with type 2 diabetes in primary care.

BackgroundData from primary care regarding the prevalence of symptoms of depression and anxiety, and their effect on glycemic control among people with diabetes is lacking in Hungary. The recently introduced Patient Health Record (PHR) requires family doctors to screen for depressive symptoms.ObjectivesWe aimed to investigate the prevalence of depressive and anxiety symptoms among patients with type 2 diabetes in the general practice, and the relationship between these affective disorders and glycated hemoglobin (HbA1c) level.MethodsWe included 338 consecutive patients with type 2 diabetes from six primary care practices in this cross-sectional study. A self-administered questionnaire (patient history, anthropometric, socioeconomic, laboratory parameters), the Beck Depression Inventory (BDI) and the Hamilton Anxiety Scale (HAM-A) were used.ResultsThe mean age of the sample was 64.0 ± 11.5 (years ± SD), 61% of participants were female. The prevalence of depressive symptoms was 21%, mainly moderate/severe symptoms (13%). Anxiety symptoms were more common (35%). We found significant univariate association between the depressive symptoms and HbA1c (p = 0.001), suicide attempt (p < 0.001), anxiety (p < 0.001), micro- and macrovascular complication (p = 0.028 and p < 0.001), education (p = 0.001) and place of residence (p = 0.002). In multivariate analysis, however, only BDI score had significant (p = 0.03191) association with glycemic control.ConclusionAmong primary care patients with type 2 diabetes, the prevalence of depressive symptoms was less frequent than anxiety symptoms. More severe depressive symptoms were associated with worse glycemic control.

Psychological risk indicators for peri-implantitis: A cross-sectional study.

The aim of this analytical cross-sectional study was to evaluate the association between peri-implantitis and psychological distress, and potentially related/mediating factors such as general health, bruxism, and lifestyle factors. Patients who received dental implants at a private practice in the Netherlands between January 2011 and January 2014 were recalled on a 5-year clinical and radiographic follow-up examination. Presence of peri-implantitis was examined, and patients completed questionnaires measuring psychological distress (Symptom Checklist [SCL]-90), bruxism, general health, and lifestyle factors. Associations between the self-reported factors and peri-implantitis were analysed with univariate and multivariate logistic regression models. A total of 230 patients (with 347 implants) were included in the analysis. Prevalence of (mild to severe) peri-implantitis was 30% (69 patients). Variables that showed a significant univariable association with peri-implantitis (p< .10) were the SCL-90 subdomain depression, smoking, current medical treatment, and lung problems. In the multivariate regression analysis, depression was the only variable that was significantly associated with peri-implantitis (p< .05). The presence of depressive symptoms is a risk indicator for peri-implantitis. Recognizing the potential negative impact of depressive symptoms may allow for better identification of high-risk patients.

Factors associated with altmetric attention scores for randomized phase III cancer clinical trials.

11014 Background: The rise of the internet and social media has created new opportunities for the rapid sharing of scientific findings among professional and public communities. Altmetric Attention Scores (Altmetrics) are real-time measures of scientific impact and attention through various public outlets, including news, blogs, and social media. Distributions and patterns of Almetrics for high-impact clinical cancer research remain under-reported. Our goal was to describe the relationship between Altmetrics and other characteristics of published trials. Methods: We identified all two-arm superiority phase III cancer randomized controlled trials (RCTs) with a publication date between 2015-2020 from HemOnc.org. For included trials, we tabulated the followed the data: Altmetric score as of February 11, 2022; positive study (yes/no); FDA registration trial (yes/no); primary endpoint (categorized as overall survival (OS), progression-free survival (PFS), event-free/disease-free survival (EFS/DFS), or other); journal tier (defined as tier 1: NEJM, Lancet, JAMA; tier 2: JCO, Blood, Lancet Oncology, JAMA Oncology, Annals of Oncology or Tier 3: other). Univariable testing was performed with Pearson correlation, Wilcoxon rank sum, and Kruskal-Wallis testing to identify associations between predictor variables and Altmetrics. For factors with significant univariable associations, we generated a multiple linear regression model to identify clinical trial factors predictive of Altmetric attention scores, with alpha = 0.05 defining statistical significance. Results: Of 673 publications identified per inclusion/exclusion criteria, Altmetric scores were found for 638 (95%). The median score was 38.9 (IQR 12.4-126.7) – well above the 95th percentile for all Altmetric scores. On univariable testing, positive studies (P &lt; 0.001), registration trials (P &lt; 0.001), those published in tier 1 journals (P &lt; 0.001), and trials with primary endpoint of OS (P = 0.002) were associated with increased Altmetric scores. On multivariable testing, positive studies (P = 0.006), registration trials (P &lt; 0.001), studies published tier 1 journals (P &lt; 0.001), and those reporting on OS (P = 0.03) persisted as significantly associated with increased engagement as measured by Altmetric scores. Conclusions: Social media and other online platforms represent an increasingly important avenue for the sharing of scientific and medical research. In this cross-sectional observational study, we found that certain characteristics of cancer clinical trials and publications are predictive of impact as measured by Altmetric scores. Specifically, positive registration trials published in traditionally defined high-impact journals and those reporting on OS as a primary endpoint tend to have the greatest Altmetric attention scores. The significance and consequences of these relationships warrant further investigation.

Comorbidity Trends in Patients Requiring Sternectomy and Reconstruction: Updated Data Analysis From 2005 to 2020.

Comorbidity trends after median sternectomy were studied at our institution by Vasconze et al (Comorbidity trends in patients requiring sternectomy and reconstruction. Ann Plast Surg. 2005;54:5). Although techniques for sternal reconstruction have remained unchanged, the patient population has become more complex in recent years. This study offers insight into changing trends in this patient population. A retrospective review was performed of patients who underwent median sternectomy followed by flap reconstruction at out institution between 2005 and 2020. Comorbidities, reconstruction method, average laboratory values, and complications were analyzed. A total of 105 patients were identified. Comorbidities noted were diabetes (27%), immunosuppression (16%), hypertension (58%), renal insufficiency (23%), chronic obstructive pulmonary disease (16%), and tobacco utilization (24%). The most common reconstruction methods were omentum (45%) or pectoralis major flaps (34%). Thirty-day mortality rates were 10%, and presence of at least 1 complication was 34% (hematoma, seroma, osteomyelitis, dehiscence, wound infection, flap failure, and graft exposure). Univariate analysis demonstrated that sex (P = 0.048), renal insufficiency, surgical site complication, wound dehiscence, and flap failure (P < 0.05) had statistically significant associations with mortality. In addition, body mass index, creatinine, and albumin had a significant univariate association with mortality (P < 0.05). Similar to the original study, there is an association between renal insufficiency and mortality. However, the mortality rate is decreased to 10%, likely because of improved medical management of patients with increasing comorbidities (80% with greater than one comorbidity). This has led to the increased use of omentum as a first-line option. Subsequent wound dehiscence and flap failure demonstrate an association with mortality, suggesting that increasingly complex patients are requiring a method of reconstruction once used a last resort as a first-line option.

Spinal cord grey matter atrophy in Multiple Sclerosis clinical practice

PurposeSeveral studies have indicated the relevance of spinal cord grey matter atrophy for Multiple Sclerosis (MS) related disability. This work aimed at evaluating feasibility and clinical relevance of MRI-derived estimations of spinal cord grey matter atrophy in clinical practice. MethodsA convenience sample of MS patients (n=48) and healthy controls (HC, n=11) was scanned using brain sagittal 3D T1w (MPRAGE) and transverse T2w-FLAIR, and transverse single-slice spinal cord 2D heavily T1w (PSIR: phase-sensitive inversion recovery) sequences. An experienced technician with neuroradiological supervision used a semiautomated thresholding method implemented in JIM software on PSIR sequences to obtain cross-sectional area (CSA) of the spinal canal (CSAcanal), whole cord (CSAcord), grey (CSAgm) and white matter (CSAwm) at C2-C3. MPRAGE and T2w-FLAIR sequences were used to obtain brain parenchymal, grey and white matter fractions (BPF, GMF and WMF) using the Statistical Parametric Mapping software. Appropriate statistical tests were used before and after age and sex adjustment. ResultsCSAgm and CSAwm could be obtained in all HC, but only 18 patients (37.5%) due to presence of lesions at C2-C3. Significant univariate associations between EDSS and BPF (rho =−0.376, p=0.015), GMF (rho =−0.287, p=0.069), CSAcanal (rho =−0.310, p=0.049), CSAcord (rho =−0.533 p<0.001) and CSAgm (rho =−0.511, p=0.062) were detected. After age/sex adjustment trends were observed for CSAcanal and CSAcord. ConclusionIn a clinical practice setting, relevance of spinal cord grey matter is confirmed, but cervical cord lesions could greatly hamper its application. Clinical associations with disability have been observed and seem stronger for spinal cord than for brain atrophy measures.

Predictors of bleeding in patients receiving direct oral anticoagulants.

The predictors of clinically significant bleeding events (CSBE) associated with direct oral anticoagulants (DOAC) are poorly characterised in the literature. To determine the incidence and predictors of CSBE in patients receiving DOAC. Patients who received DOAC during admission to a general medical unit over a 2-year period were retrospectively studied. Following the index admission, patients were followed for 12 months or for the duration of treatment (if the latter was less than 12 months). The relevant data were obtained by review of medical records. A total of 203 patients was studied over a mean follow-up period of 293 (±81) days. The incidence of CSBE was 13.7 (95% confidence interval (CI): 9.5-21.1) per 100 person-years. Age ≥ 75 years (P = 0.01), concurrent use of antiplatelet medications (P = 0.02) and lower estimated creatinine clearance (CrCl) (P = 0.03) had a significant univariate association with CSBE. However, in the multivariate logistic regression, only concurrent use of antiplatelet medications remained significantly associated with CSBE (adjusted odds ratio (OR) 3.6; 95% CI: 1.4-9.6; P = 0.01). Concurrent use of antiplatelet medications was also independently associated with major bleeding events (MBE) (adjusted OR 4.9; 95% CI: 1.1-21.4; P = 0.04). Although 39 (19.2%) patients received antiplatelet medications, the indications for concurrent antiplatelet use complied with current guidelines in only 3 (7.7%) patients. Caution should be exercised when prescribing antiplatelet medications with DOAC as this combination is a potential risk factor for both major and non-major clinically significant bleeding events. In most patients, the concurrent use of antiplatelet medications was discordant with the current consensus guidelines.

A taxonomy of childhood pedal cyclist injuries from latent class analysis: associations with factors pertinent to prevention

BackgroundStudies of pedal cyclist injuries have largely focused on individual injury categories, but every region of the cyclist’s body is exposed to potential trauma. Real-world injury patterns can be complex, and isolated injuries to one body part are uncommon among casualties requiring hospitalization. Latent class analysis (LCA) may identify important patterns in heterogeneous samples of qualitative data.MethodsData were taken from the Trauma Quality Improvement Program of the American College of Surgeons for 2017. Inclusion criteria were age 18 years or less and an external cause of injury code for pedal cyclist. Injuries were characterized by Abbreviated Injury Scale codes. Injury categories and the total number of injuries served as covariates for LCA. A model was selected on the basis of the Akaike and Bayesian information criteria and the interpretability of the classes. Associations were analyzed between class membership and demographic factors, circumstantial factors, metrics of injury severity, and helmet wear. Within-class associations of helmet wear with injury severity were analyzed as well.ResultsThere were 6151 injured pediatric pedal cyclists in the study sample. The mortality rate was 0.5%. The rate of helmet wear was 18%. LCA yielded a model with 6 classes: ‘polytrauma’ (5.5%), ‘brain’ (9.0%), ‘abdomen’ (11.0%), ‘upper limb’ (20.9%), ‘lower limb’ (12.4%), and ‘head’ (41.2%). Class membership had highly significant univariate associations with all covariates except insurance payer. Helmet wear was most common in the ‘abdomen’ class and least common in the ‘polytrauma’ and ‘brain’ classes. Within classes, there was no association of helmet wear with severity of injury.ConclusionsLCA identified 6 clear and distinct patterns of injury with varying demographic and circumstantial associations that may be relevant for prevention. The rate of helmet wear was low, but it varied among classes in accordance with mechanistic expectations. LCA may be an underutilized tool in trauma epidemiology.

SP9.1.2 Sarcopenia and myosteatosis predict thirty-day emergency laparotomy mortality [The FrOGS study

Abstract Aims Sarcopenia (low muscle mass - SM) and myosteatosis (low muscle quality - SM-RA) are associated with poor outcomes after elective cancer surgery. Body composition parameters have not been explored in emergency surgery and may offer additive value to risk prediction scores. This multicentre study assessed the association of body composition and survival after emergency laparotomy. Methods A retrospective longitudinal cohort of 674 patients, across 10 hospitals in southern England were recruited (NCT03534765). All patients underwent emergency laparotomy, fulfilling NELA criteria, between August 2016 and November 2017. Pre-operative CTs were blindly analysed using L3 slices, assessing SM and SM-RA. Regression analysis was used to assess associations of body composition and 30-day mortality. Results Six hundred and ten patients were included [283(46%) men, median(IQR) age 71 years (57-79)]. P-POSSUM and NELA predicted mortality was 7% and 4.5% respectively, with a length of stay of 15 days (9-24), 30-day mortality of 7.8% and 1-year mortality of 18.9%. Significant univariate associations between 30-day mortality and age (OR1.04 (1.02-1.07);p=0.001), Charlson score (OR 6.84 (1.64-28.55);p=0.008), P-POSSUM (OR 1.03 (1.02-1.05);p&amp;lt;0.001, NELA mortality (OR 1.06 (1.04-1.08);p&amp;lt;0.001), SM (OR 0.98 (0.97-0.99);p=0.003 and SM-RA (OR 0.93 (0.9-0.96);p&amp;lt;0.001. Significant multivariate associations between 30-day mortality and NELA (OR 1.05 (1.03-1.07); p &amp;lt; 0.001, P-POSSUM (OR 1.03 (1.01-1.04); p &amp;lt; 0.001, SM-RA (OR 0.94 (0.9-0.97); p &amp;lt; 0.001. Conclusions Sarcopenia and myosteatosis are associated with increased mortality in patients undergoing emergency surgery. Body composition should be considered as an objective adjunct to traditional risk assessments, further informing the shared-decision making process around emergency surgery.

Independent predictors of major cardiovascular events as quantitatively assessed by coronary CT-angiography: a long-term follow-up analysis

Abstract Introduction Quantitative CT coronary angiography using semi-automated software provides detailed information about plaque volume and high-risk plaque characteristics, beyond traditional measures like diameter stenosis. We assessed the potential value of plaque quantity and morphology to independently predict MACE in a cohort with long-term follow up. Methods In this secondary analysis of 301 symptomatic patients undergoing coronary CTA at baseline, total plaque volume (TPV), non-calcified- (NCPV), calcified- (CPV) and vulnerable coronary plaque volume (in mm3), diameter stenosis (in %) and remodeling index were quantified using semi-automated software (Autoplaque version 2.5, Cedars-Sinai Medical Center, Los Angeles, CA). Patients were followed for major cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction and coronary revascularization. Optimal thresholds for each quantitative CTA measure were computed using CART-algorithm (Classification and Regression Trees). Results Complete follow-up was available for 234 (78%) patients. The mean age was 59±10 years. Over a median follow-up of 10.7 years, the composite outcome occurred in 34 (15%) patients (5 patients with cardiovascular death, 6 with myocardial infarction, 26 with revascularization). Patients experiencing MACE had more frequently hypertension (p=0.03) and a higher Framingham risk score (p=0.002). Survival anaylsis using cox proportional hazard ratios showed significant univariate associations between MACE and TPV (HR 5.16; 95% CI 1.58–16.89; p=0.007), NCPV (HR 4.83; 95% CI 1.45–15.81; p=0.009), CPV (HR 2.86; 95% CI 1.39–5.86; p=0.004), vulnerable plaque volume (HR 3.35; 95% CI 1.52–7.41; p=0.003), diameter stenosis (HR 5.19; 95% CI 2.64–10.22; p&amp;lt;0.001) and remodeling index (HR 4.24; 95% CI 2.03–8.86; p&amp;lt;0.001). In multivariable cox regression analysis diameter stenosis (HR 3.70; 95% CI 1.72–7.93; p=0.001) and remodeling index (HR 2.69; 95% CI 1.19–6.09; p=0.018) remained significant independent predictors of MACE, adjusted for Framingham risk score (HR 2.56; 95% CI 1.26–5.22; p=0.010), however plaque volume and plaque subcomponents did not. Conclusion On long term follow-up, remodeling index and coronary diameter stenosis obtained by quantitative coronary CT angiography independently predicted MACE on multivariable assessment. More comprehensive plaque assessment algorithms including plaque volume as well as plaque subcomponents were significantly associated with MACE in univariate, but not multivariate analysis after adjustment for diameter stenosis and remodeling index. Funding Acknowledgement Type of funding sources: None.

Mediation of the APOE associations with Alzheimer's and coronary heart diseases through body mass index and lipids.

The APOE ε2/ε3/ε4 polymorphism is associated with multiple non-Mendelian traits, including high- (HDL-C) and low- (LDL-C) density lipoprotein cholesterol, triglycerides, body mass index (BMI), coronary heart disease (CHD), and Alzheimer's disease (AD). Lipids and BMI are risk factors for AD and CHD. Causal connections between the ε2 and ε4 alleles and these traits remain, however, poorly understood. We leverage comprehensive analyses of longitudinal data from four studies to examine potentially causal heterogeneous connections between these alleles, lipids, BMI, and diseases. We emphasize mutual mediation roles of lipids and BMI in their associations with the ε2 and ε4 alleles and their mediation roles in the associations of these alleles with AD and CHD. We confirmed previously reported significant univariate associations of these alleles with each trait, except CHD. We found, however, that most of the univariate- and mediation-analysis associations were affected by antagonistic heterogeneity/mediation. The mutual mediation analysis identified the associations of the APOE alleles with LDL-C as the least heterogeneous. The ε2 and ε4 alleles were associated with CHD through lipids, led by beneficial (βIE = - 0.071, pIE = 2.28 × 10-10) and adverse (βIE = 0.019, pIE = 7.37 × 10-6) associations, respectively, through LDL-C. Both these alleles were adversely associated with CHD through triglycerides. For AD, only BMI partially mediated the adverse association of the ε4 allele with AD (βIE = 0.016, pIE = 2.09 × 10-2). Our results suggest different roles of BMI and lipids in the AD and CHD pathogeneses. More comprehensive studies of causal connections between genetic variants and non-Mendelian traits are required as they can be critically affected by heterogeneous antagonistic relationships.

Associations between suicidal ideation and health-related quality of life among community-dwelling stroke survivors: 2013-2017 Korea National Health and Nutrition Examination Survey.

The study aimed to identify differences between individuals with stroke and the general population regarding socioeconomic, mental health, and Health-related quality of life (HRQOL) factors, and associations among Suicidal ideation (SI), HRQOL, and mental health. Data of individuals with stroke (n = 592) and without stroke (n = 23,562) aged 20 or older from the 2013-2017 Korea National Health and Nutrition Examination Survey were analyzed. Chi-square tests examined differences in socioeconomic status, mental health, and HRQOL (EQ-5D) between groups. Independent associations between each EQ-5D dimension and SI were analyzed through multivariable logistic regression. Individuals with stroke were more likely to have problems on all EQ-5D dimensions. Significant univariate associations were identified between four EQ-5D dimensions and SI among individuals with stroke. Pain/discomfort (odds ratio [OR] = 1.32; 95% confidence interval [CI], 1.01-1.75, p = 0.048) and anxiety/depression (OR = 4.66; 95% CI, 3.69-5.89, p < .0001) of the EQ-5D were associated with SI when adjusting for all socioeconomic variables; anxiety/depression (OR = 2.80; 95% CI, 2.18-3.60, p < .0001) was the only risk factor for SI after controlling for socioeconomic and mental health variables. Individuals with stroke showed higher rates for problems on the EQ-5D, SI, and depression compared to the general population. They also demonstrated significant associations between SI and each EQ-5D dimension except physical activity, especially pain/discomfort and depression/anxiety. The study's findings can be referred to when predicting suicide risk in individuals with stroke by analyzing their EQ-5D scores.

Diagnostic Value of Various Morphological Features of Horizontal and Vertical Laminar Fractures for Posterior Ligamentous Complex Injury of the Thoracolumbar Spine as Defined by Magnetic Resonance Imaging

To determine diagnostic value of morphological features of horizontal laminar fracture (HLF) and vertical laminar fracture (VLF) for diagnosis of posterior ligamentous complex (PLC) injury. This retrospective review comprised 271 consecutive patients with acute thoracolumbar fractures presenting to a Level 1 trauma center between January 2014 and January 2021. Two reviewers evaluated computed tomography and magnetic resonance imaging. VLFs were subclassified based on length and depth of lamina involved, as follows: type 1, full-length complete; type 2, full-length incomplete; type 3, partial-length complete or incomplete. HLFs were subclassified as follows: bilateral versus unilateral, displaced >2 mm versus nondisplaced, and lamina-only versus laminar and pedicle. We examined the diagnostic accuracy and the univariate and multivariate associations of laminar fracture subtypes with PLC injury as defined by black stripe discontinuity. Bilateral HLFs, laminar and pedicle fractures, displaced HLFs, and type 1 VLFs yielded a high positive predictive value for PLC injury (95%, 91%, 100%, and 86%, respectively). Type 2 and 3 VLFs did not show significant univariate associations with PLC injury. Bilateral HLFs, laminar and pedicle fractures, and displaced HLFs showed independent associations with PLC injury (adjusted odds ratio= 13.6, 8.4, 6, and 10.3, respectively; P < 0.002). Type 1 VLFs did not show a significant association with PLC (adjusted odds ratio= 10.3; P= 0.06). Bilateral HLFs, laminar and pedicle fractures, and displaced HLFs, but not any VLF subtypes, were independently associated with PLC injury. These findings may improve the reliability of PLC assessment by computed tomography.

Further Evidence That OPG rs2073618 Is Associated With Increased Risk of Musculoskeletal Symptoms in Patients Receiving Aromatase Inhibitors for Early Breast Cancer.

BackgroundAromatase inhibitors (AI) reduce recurrence and death in patients with early-stage hormone receptor-positive (HR +) breast cancer. Treatment-related toxicities, including AI-induced musculoskeletal symptoms (AIMSS), are common and may lead to early AI discontinuation. The objective of this study was to replicate previously reported associations for candidate germline genetic polymorphisms with AIMSS.MethodsWomen with stage 0-III HR + breast cancer initiating adjuvant AI were enrolled in a prospective clinic-based observational cohort. AIMSS were assessed by patient-reported outcomes (PRO) including the PROMIS pain interference and physical function measures plus the FACT-ES joint pain question at baseline and after 3 and 6 months. For the primary analysis, AIMSS were defined as ≥ 4-point increase in the pain interference T-score from baseline. Secondary AIMSS endpoints were defined as ≥ 4-point decrease in the physical function T-score from baseline and as ≥ 1-point increase on the FACT-ES joint pain question from baseline. The primary hypothesis was that TCL1A rs11849538 would be associated with AIMSS. Twelve other germline variants in CYP19A1, VDR, PIRC66, OPG, ESR1, CYP27B1, CYP17A1, and RANKL were also analyzed assuming a dominant genetic effect and prespecified direction of effect on AIMSS using univariate logistic regression with an unadjusted α = 0.05. Significant univariate associations in the expected direction were adjusted for age, race, body mass index (BMI), prior taxane, and the type of AI using multivariable logistic regression.ResultsA total of 143 participants with PRO and genetic data were included in this analysis, most of whom were treated with anastrozole (78%) or letrozole (20%). On primary analysis, participants carrying TCL1A rs11849538 were not more likely to develop AIMSS (odds ratio = 1.29, 95% confidence interval: 0.55–3.07, p = 0.56). In the statistically uncorrected secondary analysis, OPG rs2073618 was associated with AIMSS defined by worsening on the FACT-ES joint pain question (OR = 3.33, p = 0.004), and this association maintained significance after covariate adjustment (OR = 3.98, p = 0.003).ConclusionCarriers of OPG rs2073618 may be at increased risk of AIMSS. If confirmed in other cohorts, OPG genotyping can be used to identify individuals with HR + early breast cancer in whom alternate endocrine therapy or interventions to enhance symptom detection and implement strategies to reduce musculoskeletal symptoms may be needed.

Food insecurity, diet quality and body composition: data from the Healthy Life Trajectories Initiative (HeLTI) pilot survey in urban Soweto, South Africa.

To determine whether food security, diet diversity and diet quality are associated with anthropometric measurements and body composition among women of reproductive age. The association between food security and anaemia prevalence was also tested. Secondary analysis of cross-sectional data from the Healthy Life Trajectories Initiative (HeLTI) study. Food security and dietary data were collected by an interviewer-administered questionnaire. Hb levels were measured using a HemoCue, and anaemia was classified as an altitude-adjusted haemoglobin level < 12·5 g/dl. Body size and composition were assessed using anthropometry and dual-energy x-ray absorptiometry. The urban township of Soweto, Johannesburg, South Africa. Non-pregnant women aged 18-25 years (n 1534). Almost half of the women were overweight or obese (44 %), and 9 % were underweight. Almost a third of women were anaemic (30 %). The prevalence rates of anaemia and food insecurity were similar across BMI categories. Food insecure women had the least diverse diets, and food security was negatively associated with diet quality (food security category v. diet quality score: B = -0·35, 95 % CI -0·70, -0·01, P = 0·049). Significant univariate associations were observed between food security and total lean mass. However, there were no associations between food security and body size or composition variables in multivariate models. Our data indicate that food security is an important determinant of diet quality in this urban-poor, highly transitioned setting. Interventions to improve maternal and child nutrition should recognise both food security and the food environment as critical elements within their developmental phases.

Correlates of Variation in Guinea Worm Burden among Infected Domestic Dogs.

ABSTRACTThe Guinea Worm Eradication Program has been extraordinarily successful—in 2019, there were 53 human cases reported, down from the estimated 3.5 million in 1986. Yet the occurrence of Guinea worm in dogs is a challenge to eradication efforts, and underlying questions about transmission dynamics remain. We used routine surveillance data to run negative binomial regressions predicting worm burden among infected dogs in Chad. Of 3,371 infected dogs reported during 2015–2018, 38.5% had multiple worms. A multivariable model showed that the number of dogs in the household was negatively associated with worm burden (adjusted incidence rate ratio [AIRR] = 0.95, 95% CI: 0.93–0.97, P < 0.0001) after adjusting for dog age (AIRR = 0.99, 95% CI: 0.96–1.01, P > 0.1). This could relate to the amount of infective inocula (e.g., contaminated food or water) shared by multiple dogs in a household. Other significant univariable associations with worm burden included dog history of Guinea worm infection (IRR = 1.30, 95% CI: 1.18–1.45) and dog owners who were hunters (IRR = 0.78, 95% CI: 0.62–0.99, P < 0.05) or farmers (IRR = 0.83, 95% CI: 0.77–0.90, P < 0.0001). Further analysis showed that the number of dogs in the household was significantly and positively correlated with nearly all other independent variables (e.g., owner occupation: farmer, fisherman, or hunter; dog age, sex, and history of Guinea worm). The associations we identified between worm burden and dogs per household, and dogs per household and owner characteristics should be further investigated with more targeted studies.

Abstract PS5-25: Association of OPG rs2073618 and aromatase inhibitor induced musculoskeletal symptoms

Abstract Background: Adjuvant aromatase inhibitors (AI) reduce recurrence and mortality after early stage hormone receptor-positive (HR+) breast cancer (BC). Treatment-related toxicities, including AI-induced musculoskeletal symptoms (AIMSS), are common during adjuvant AI therapy. Prior work suggests the risk of AIMSS is associated with inherited germline genetic polymorphisms in several genes, such as TCL1A, CYP19A1, OPG, and VDR. These pharmacogenetic associations require replication in independent cohorts prior to clinical translation to identify patients at risk for AIMSS. The objective of this retrospective pharmacogenetic analysis was to replicate previously reported associations for candidate germline genetic polymorphisms with AIMSS. Methods: Women with stage 0-III HR+ BC initiating adjuvant endocrine therapy (ET) with tamoxifen or an AI were enrolled in a prospective clinic-based observational cohort. The type of ET was selected by the provider. A baseline (BL) blood sample was collected for isolation of germline DNA for pharmacogenetic analysis. AIMSS were assessed by patient-reported outcomes (PRO). Participants completed PROMIS pain interference (PI), PROMIS physical function (PF) and Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) measures at BL and after 3, 6, 9, 12, 24, 48 and 60 months (mo). The FACT-ES includes one question about joint pain, rated on a 5-point scale (“not at all” to “very much”). This secondary retrospective pharmacogenetic analysis was conducted in participants receiving AI therapy for whom blood samples and PRO scores at BL and 3 and/or 6 mo were available. For the primary analysis, we defined AIMSS as a ≥4 point increase in PI T score from BL to 3 and/or 6 mo. For secondary analyses, we evaluated alternate definitions of AIMSS including a ≥4 point decrease in PF T score and a ≥1 category increase on the FACT-ES joint pain question from BL to 3 and/or 6 mo. The primary hypothesis was that TCL1A rs11849538 is associated with AIMSS. Twelve other germline variants in CYP19A1, VDR, PIRC66, OPG, ESR1, CYP27B1, CYP17A1, and RANKL previously reported to be associated with AIMSS were also analyzed. We assumed a dominant genetic effect and pre-specified the direction of effect on AIMSS for each variant. We conducted univariate logistic regression to evaluate associations between each definition of AIMSS and candidate polymorphism using an unadjusted α=0.05. Significant univariate associations in the expected direction were adjusted for age, race, body mass index (BMI), prior taxane and type of AI using multivariable logistic regression. Results: Of 182 participants on AI, 143 with PRO and genetic data available were included in this analysis. Median age was 67, 85% were white, median BMI was 27.8 and 27% had prior taxane. 78% received anastrozole, 20% letrozole and 2% exemestane. On primary analysis, participants carrying TCL1A rs11849538 were not more likely to develop AIMSS as defined by increase in PI T score by ≥4 (OR=1.29, 95% CI: 0.55-3.07, p=0.56). None of the other polymorphisms was associated with increase in PI T score by ≥4. On secondary analysis, OPG rs2073618 was associated with AIMSS, as defined by an increase on the FACT-ES joint pain question ≥1 (OR=3.33, 95% CI: 1.48-7.49, p=0.004) and this association maintained significance after covariate adjustment (OR=3.98, 95% CI: 1.61-9.84, p=0.003). Age, race, BMI, prior taxane and type of AI were not associated with AIMSS on multivariate analysis. No other polymorphisms were associated with AIMSS on secondary analyses. Conclusions: Carriers of OPG rs2073618 may be at increased risk of AIMSS. If confirmed in other cohorts, OPG genotyping may be able to identify individuals with HR+ early BC at increased risk for AIMSS during AI therapy. Alternate ET or interventions to reduce musculoskeletal symptoms may be needed for this population. Citation Format: Daniel L Hertz, Karen Lisa Smith, Yuhua Zong, Christina L Gersch, Andrea Pesch, Arti Patel, Jennifer Lehman, N. Lynn Henry, Kelley M Kidwell, James M Rae, Vered Stearns. Association of OPG rs2073618 and aromatase inhibitor induced musculoskeletal symptoms [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-25.

Characteristics and determinants of high volume dispensing in long-term oral nutritional supplement users in primary care: a secondary analysis.

BackgroundOral nutritional supplements (ONS) are recommended for patients who are malnourished or at risk of malnutrition. Appropriate ONS prescribing requires regular monitoring to assess its continued requirement. Previous research identified long-term ONS prescriptions (>6 months) without review, with 70% of these influenced by social factors.AimTo investigate the characteristics of long-term ONS users in Ireland and the determinants of larger volumes of ONS dispensing.Design & settingSecondary analysis of anonymous dispensed pharmacy claims data of patients dispensed standard ONS for 12 consecutive months in 2018 (n = 912).MethodFactors showing significant (P<0.05) univariate associations with above the median consumption of ONS units were entered into a multivariable model.ResultsMedian age was 76 (range 18 to 101) years, with 66.9% of the sample being ≥65 years. Almost 70% of the samples were on polypharmacy (45.6%; ≥5 medications) or excessive polypharmacy (21.5%; ≥10 medications). Younger age and being on polypharmacy for drugs having an effect on the central nervous system (CNS) were significantly associated with being dispensed more ONS units in univariate and multivariate analysis. Those patients in the age range 18 to 44 were 2.5 fold more likely to be prescribed more ONS units (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5 to 4.3; P<0.001). Patients using CNS drugs or on CNS polypharmacy were more likely to be prescribed more ONS units (ORs 1.2 and 2.4; 95% CI 0.9 to 1.4 and 1.3 to 4.4 respectively; P = 0.029). ConclusionOlder age and polypharmacy characterise long-term ONS users in this study. Younger age and CNS medication polypharmacy are predictors of more ONS units prescribed over a year.

Veno-arterial CO2 difference and cardiac index in children after cardiac surgery.

Veno-arterial CO2 difference has been considered as a marker of low cardiac output. This study aimed to evaluate the correlation between veno-arterial CO2 difference and cardiac index estimated by MostCareTM in children after cardiac surgery and its association with other indirect perfusion parameters and the complex clinical course (vasoactive inotropic score above 15 or length of stay above 5 days).Data from 40 patients and 127 arterial and venous CO2 measurements for gap calculation taken 0-5 days postoperatively were available. The median (range) veno-arterial CO2 difference value was 9 (1-25 mmHg). The correlation between veno-arterial CO2 difference and cardiac index was not significant (r: -0.16, p = 0.08). However, there was a significant correlation between veno-arterial CO2 difference and vasoactive inotropic score (r: 0.21, p = 0.02), systolic arterial pressure (r: -0.43, p = 0.0001), dP/dtMAX (r: 0.26, p = 0.004), and arterio-venous O2 difference (r: 0.63, p = 0.0001). Systolic arterial pressure (OR 0.95, 95% CI 0.90-0.99), dP/dtMAX (OR 0.00, 95% CI 0.00-0.06), lactates (OR 1.87, 95% CI 1.21-3.31), and veno-arterial CO2 difference (OR 1.13, 95% CI 1.01-1.35) showed a significant univariate association with the complex clinical course. In conclusion, veno-arterial CO2 difference did not correlate with cardiac index estimated by MostCareTM in our cohort of post-cardiosurgical children, but it identified patients with the complex clinical course, especially when combined with other direct and indirect variables of perfusion.