Mixed-effects Multivariable Regression Research Articles

Metabolomic signatures of the long-term exposure to air pollution and temperature

BackgroundLong-term exposures to air pollution has been reported to be associated with inflammation and oxidative stress. However, the underlying metabolic mechanisms remain poorly understood.ObjectivesWe aimed to determine the changes in the blood metabolome and thus the metabolic pathways associated with long-term exposure to outdoor air pollution and ambient temperature.MethodsWe quantified metabolites using mass-spectrometry based global untargeted metabolomic profiling of plasma samples among men from the Normative Aging Study (NAS). We estimated the association between long-term exposure to PM2.5, NO2, O3, and temperature (annual average of central site monitors) with metabolites and their associated metabolic pathways. We used multivariable linear mixed-effect regression models (LMEM) while simultaneously adjusting for the four exposures and potential confounding and correcting for multiple testing. As a reduction method for the intercorrelated metabolites (outcome), we further used an independent component analysis (ICA) and conducted LMEM with the same exposures.ResultsMen (N = 456) provided 648 blood samples between 2000 and 2016 in which 1158 metabolites were quantified. On average, men were 75.0 years and had an average body mass index of 27.7 kg/m2. Almost all men (97%) were not current smokers. The adjusted analysis showed statistically significant associations with several metabolites (58 metabolites with PM2.5, 15 metabolites with NO2, and 6 metabolites with temperature) while no metabolites were associated with O3. One out of five ICA factors (factor 2) was significantly associated with PM2.5. We identified eight perturbed metabolic pathways with long-term exposure to PM2.5 and temperature: glycerophospholipid, sphingolipid, glutathione, beta-alanine, propanoate, and purine metabolism, biosynthesis of unsaturated fatty acids, and taurine and hypotaurine metabolism. These pathways are related to inflammation, oxidative stress, immunity, and nucleic acid damage and repair.ConclusionsUsing a global untargeted metabolomic approach, we identified several significant metabolites and metabolic pathways associated with long-term exposure to PM2.5, NO2 and temperature. This study is the largest metabolomics study of long-term air pollution, to date, the first study to report a metabolomic signature of long-term temperature exposure, and the first to use ICA in the analysis of both.

Apathy and Anxiety in De Novo Parkinson's Disease Predict the Severity of Motor Complications.

Neuropsychiatric and affective symptoms are prevalent in prodromal and clinical Parkinson's disease (PD). Some evidence suggests that they may also signify risk for motor complications (motor fluctuations and dyskinesias) of dopamine replacement therapy (DRT). To determine whether neuropsychiatric symptoms present in de novo PD (ie, before DRT initiation) predict the severity of eventual motor complications of DRT. We used clinical, demographic, neurobehavioral, and neuroimaging data from the Parkinson's Progression Markers Initiative (PPMI), a multicenter observational PD study. Participants were unmedicated at enrollment and 361 initiated DRT during PPMI follow-up. We used Cox proportional hazard and multivariate ordinal mixed-effects regression models to evaluate the relationship between baseline neuropsychiatric symptoms and motor complications as measured by the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The cumulative incidences of dyskinesias and motor fluctuations during follow-up (6.0 ± 1.5 years) were 34.3% and 59.9%, respectively. Both apathy and high trait-anxiety (top quartile) conveyed over two-fold increases in hazard for dyskinesia onset and for adverse impact on activities of daily living caused by both dyskinesias and motor fluctuations. The longitudinal severity of motor fluctuations and dyskinesias was significantly predicted by baseline trait-anxiety and apathy, but not depression. Models were adjusted for dimensionally related symptoms (eg autonomic dysfunction) and potential confounding variables (eg DRT dose). Apathy and anxiety levels in de novo PD may be neuropsychiatric biomarkers of vulnerability to earlier and more disabling motor complications of DRT.

Novel tonometer device distinguishes brain stiffness in epilepsy surgery

Complete surgical resection of abnormal brain tissue is the most important predictor of seizure freedom following surgery for cortical dysplasia. While lesional tissue is often visually indiscernible from normal brain, anecdotally, it is subjectively stiffer. We report the first experience of the use of a digital tonometer to understand the biomechanical properties of epilepsy tissue and to guide the conduct of epilepsy surgery. Consecutive epilepsy surgery patients (n = 24) from UCLA Mattel Children’s Hospital were recruited to undergo intraoperative brain tonometry at the time of open craniotomy for epilepsy surgery. Brain stiffness measurements were corrected with abnormalities on neuroimaging and histopathology using mixed-effects multivariable linear regression. We collected 249 measurements across 30 operations involving 24 patients through the pediatric epilepsy surgery program at UCLA Mattel Children’s Hospital. On multivariable mixed-effects regression, brain stiffness was significantly associated with the presence of MRI lesion (β = 32.3, 95%CI 16.3–48.2; p < 0.001), severity of cortical disorganization (β = 19.8, 95%CI 9.4–30.2; p = 0.001), and recent subdural grid implantation (β = 42.8, 95%CI 11.8–73.8; p = 0.009). Brain tonometry offers the potential of real-time intraoperative feedback to identify abnormal brain tissue with millimeter spatial resolution. We present the first experience with this novel intraoperative tool for the conduct of epilepsy surgery. A carefully designed prospective study is required to elucidate whether the clinical application of brain tonometry during resective procedures could guide the area of resection and improve seizure outcomes.

Change in Viral Load Count and Its Predictors Among Unsuppressed Viral Load Patients Receiving an Enhanced Adherence Counseling Intervention at Three Hospitals in Northern Ethiopia: An Exploratory Retrospective Follow-Up Study.

BackgroundEnhanced adherence counseling (EAC) is an interventional program that provides targeted adherence counseling for unsuppressed viral load people living with HIV who are receiving antiretroviral therapy before diagnosing treatment failure. However, there is a lack of evidence on change in viral load count among patients receiving EAC intervention. Therefore, this study aimed to assess change in viral load count and its predictors among people living with HIV (PLHIV) in northeast Ethiopia.MethodsA hospital-based retrospective follow-up study was conducted on 235 randomly selected patients with unsuppressed viral load who started EAC sessions between 2016 and 2019 at three governmental hospitals in the northern part of Ethiopia. Viral load count and patient individual factors were assessed at EAC program enrollment and viral load counts repeated at the end of EAC session. The main outcome variable was a change in viral load count during the EAC session period. A paired sample t-test was used to determine the mean difference in viral load count before and after EAC intervention. Linear mixed-effects models were used to assess the effect of selected factors on viral load count change.ResultsBased on the paired sample t-test, there was a significant mean difference in viral load count before and after EAC intervention (mean difference=16,904, (95% CI: 9986–23,821; p-value<0.001). The multivariable linear mixed-effects regression analysis showed that young age (β= 0.03; 95% CI: 0.01, 0.14), urban residence (β= −0.55; 95% CI: −0.63, −0.34), CD4 count of 201–500 cells/mm3 (β= −0.67; 95% CI: −0.87, −0.43) and long duration on ART (β= −0.01; 95% CI: −0.01, −0.02) were associated with the decline in viral load count.ConclusionWe detected a substantial decline in viral load count among patients receiving an EAC intervention. Young age, urban residence, CD4 count of 201–500 cells/mm3 and long duration on ART were the positive predictors of viral load suppression.

Efficiency Metrics at an Academic Freestanding Ambulatory Surgery Center: Analysis of the Impact on Scheduled End-Times.

Understanding the impact of key metrics on operating room (OR) efficiency is important to optimize utilization and reduce costs, particularly in freestanding ambulatory surgery centers. The aim of this study was to assess the association between commonly used efficiency metrics and scheduled end-time accuracy. Data from patients who underwent surgery from May 2018 to June 2019 at an academic freestanding ambulatory surgery center was extracted from the medical record. Unique operating room days (ORDs) were analyzed to determine (1) duration of first case delays, (2) turnover times (TOT), and (3) scheduled case duration accuracies. Spearman's correlation coefficients and mixed-effects multivariable linear regression were used to assess the association of each metric with scheduled end-time accuracy. There were 1378 cases performed over 300 unique ORDs. There were 86 (28.7%) ORDs with a first case delay, mean (standard deviation [SD]) 11.2 minutes (15.1 minutes), range of 2-101 minutes; the overall mean (SD) TOT was 28.1 minutes (19.9 minutes), range of 6-83 minutes; there were 640 (46.4%) TOT >20 minutes; the overall mean (SD) case duration accuracy was -6.6 minutes (30.3 minutes), range of -114 to 176; and there were 389 (28.2%) case duration accuracies ≥30 minutes. The mean (SD) scheduled end-time accuracy was 6.9 minutes (68.3 minutes), range of -173 to 229 minutes; 48 (15.9%) ORDs ended ≥1 hour before scheduled end-time and 56 (18.6%) ORDs ended ≥1 hour after scheduled end-time. The total case duration accuracy was strongly correlated with the scheduled end-time accuracy (r = 0.87, 95% confidence interval [CI], 0.84-0.89, P < .0001), while the total first case delay minutes (r = 0.12, 95% CI, 0.01-0.21, P = .04) and total turnover time (r = -0.16, 95% CI, 0.21-0.05, P = .005) were less relevant. Case duration accuracy had the highest association with the dependent variable (0.95 minutes changed in the difference between actual and schedule end time per minute increase in case duration accuracy, 95% CI, 0.90-0.99, P < .0001), compared to turnover time (estimate = 0.87, 95% CI, 0.75-0.99, P < .0001) and first case delay time (estimate = 0.83, 95% CI, 0.56-1.11, P < .0001). Standard efficiency metrics are similarly associated with scheduled end-time accuracy, and addressing problems in each is requisite to having an efficient ambulatory surgery center. Pursuing methods to narrow the gap between scheduled and actual case duration may result in a more productive enterprise.

Disorganisation of retinal inner layers is associated with reduced contrast sensitivity in retinal vein occlusion

Background/AimsTo determine if disorganisation of retinal inner layers (DRIL) is associated with reduced contrast sensitivity (CS) in patients with retinal vein occlusion (RVO) with a history of macular oedema (ME).MethodsProspective,...

Day of Illness and Outcomes in Bronchiolitis Hospitalizations.

Bronchiolitis is often described to follow an expected clinical trajectory, with a peak in severity between days 3 and 5. This predicted trajectory may influence anticipatory guidance and clinical decision-making. We aimed to determine the association between day of illness at admission and outcomes, including hospital length of stay, receipt of positive-pressure ventilation, and total cough duration. We compiled data from 2 multicenter prospective studies involving bronchiolitis hospitalizations in patients <2 years. Patients were excluded for complex conditions. We assessed total cough duration via weekly postdischarge phone calls. We used mixed-effects multivariable regression models to test associations between day of illness and outcomes, with adjustment for age, sex, insurance (government versus nongovernment), race, and ethnicity. The median (interquartile range) day of illness at admission for 746 patients was 4 (2-5) days. Day of illness at admission was not associated with length of stay (coefficient 0.01 days, 95% confidence interval [CI]: -0.05 to 0.08 days), positive-pressure ventilation (adjusted odds ratio: 1.0, 95% CI: 0.9 to 1.1), or total cough duration (coefficient 0.33 days, 95% CI: -0.01 to 0.67 days). Additionally, there was no significant difference in day of illness at discharge in readmitted versus nonreadmitted patients (5.9 vs 6.4 days, P = .54). The median cough duration postdischarge was 6 days, with 65 (14.3%) patients experiencing cough for 14+ days. We found no associations between day of illness at admission and outcomes in bronchiolitis hospitalizations. Practitioners should exercise caution when making clinical decisions or providing anticipatory guidance based on symptom duration.

Metabolomics signatures of the short-term exposure to air pollution and temperature

Background/Aim:Short-term exposures to air pollution and temperature have been reported to be associated with inflammation and oxidative stress. However, mechanistic understanding of the affected metabolic pathways is still lacking and the existing literature on the short-term exposure of air-pollution on the metabolome is limited. We aimed to determine the changes in the blood metabolome and the associated pathways related to short-term exposure to outdoor air pollution and temperature. Methods:We performed mass-spectrometry based untargeted metabolomic profiling of plasma samples from a large and well-characterized cohort of men (the Normative Aging Study) to identify metabolic pathways associated with short-term exposure to PM2.5, NO2, O3, and temperature (one, seven-, and thirty-day average of central site monitors). We used multivariable linear mixed-effect regression and independent component analysis (ICA) while simultaneously adjusting for all exposures and correcting for multiple testing. Results:Overall, 456 white men provided 648 blood samples, in which 1,158 metabolites were quantified, between 2000 and 2016. Average age and body mass index were 75.0 years and 27.7 kg/m2, respectively. Only 3% were current smokers. In the adjusted models, PM2.5, NO2, and temperature showed multiple statistically significant associations with several metabolites (40 metabolites for PM2.5, 100 metabolites for NO2, 1 metabolite for O3, and 14 metabolites for temperature). We identified eight metabolic pathways (glycerophospholipid, sphingolipid, glutathione, beta-alanine, pyrimidine, butanoate, propanoate, and methionine, cysteine, SAM and taurine metabolisms) perturbed with short-term exposure to air pollution and temperature. These pathways were involved in inflammation and oxidative stress, immunity, and nucleic acid damage and repair. Conclusions:We identified several significant metabolites and metabolic pathways associated with short-term exposure to air pollution and temperature; using an untargeted approach. This is the first study to report an untargeted metabolomic signature of temperature exposure, the first to use ICA, and the largest study to derive a metabolomic signature of air pollution.

Students exposure assessment towards PM number concentration while commuting from different transport modes during school timings

Among the various daily activities, commuting to school is considered as an important activity for the students. While commute, students are exposed to elevated particle concentrations that make significant contributions to their daily personal exposures. Present study compares the student exposure towards particle number concentration (PNC) and inhaled doses while commuting from different transports during morning (MT) and afternoon (AT) trips. PNC was measured from four different transport modes: two-wheeler (2W), three-wheeler (3W), passenger car (PC) and school bus (SB) during summer and winter seasons. In summer season, average total PNC was highest for 3W and SB during MT (5.53E+07 # m−3) and AT (5.29E+07 # m−3) trips respectively. However, in winter season, 3W has the highest average total PNC during MT (1.04E+08 # m−3) and AT (7.92E+07 # m−3) trips. Ventilation settings greatly influence the in-cabin PNC and found to be highest under window open (WO) scenario for PC and least under WO and window closed scenarios for SB during MT and AT trips respectively. The PNC exposure varies significantly with student seating positions inside SB and followed different trends during MT (front > middle > rear) and AT (rear > front > middle) trips. The mixed-effect multivariate linear regression model was used to estimate the effects of multiple predictor variables that influence the PNC measured from different transport modes while commuting. Background concentration (PNC) and meteorological variables (wind speed, ambient temperature and relative humidity) were important predictors of PNC measured while commuting and explained the variability between 0.04–27.31%.

Association between Non-Restorative Sleep and Quality of Life in Chinese Adolescents.

To examine non-restorative sleep and its impact on quality of life (QOL) in Chinese adolescents, this cross-sectional study included 2827 students aged 12–20 who were selected from 15 secondary schools in Hong Kong, China. Non-restorative sleep was assessed by a single item, rated on a 0–10 scale: “To what extent did you feel refreshed upon awakening over the past month?”. QOL was evaluated by the World Health Organization Quality of Life Measure—Abbreviated Version Hong Kong Chinese Version. Univariable and multivariable linear mixed-effects regressions were conducted to examine the influence of non-restorative sleep (NRS) on QOL. In the present sample, the mean overall QOL was 13.83, and the extent of feeling refreshed upon awakening was 4.75 on average. In multivariable linear mixed-effects regression, one unit feeling less refreshed upon awakening was associated with 0.37 units of poorer overall QOL after adjusting for age, gender, medical conditions, parental education and occupation, weekly hours of aerobic exercises, smoking and drinking habits. Additionally, adolescents with a significantly poorer overall QOL were more likely to be older, have medical problems, have parents with an educational level of primary school or below, have an unemployed father, engage in less weekly aerobic exercise, and be current smokers or former drinkers. Adolescents who experienced non-restorative sleep had a poorer QOL. Future studies are needed to alleviate non-restorative sleep to improve health outcomes in adolescents.

Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-year outcome compared to persistent low-remission status and represent a heterogeneous group

BackgroundThe long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity.MethodsWe included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups.ResultsWe identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA.ConclusionsIn clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

The Impact of Concomitant LOW Back Pain (LBP) on Functional Outcomes in Total Ankle Arthroplasty (TAA)

Although numerous studies have demonstrated that concomitant low back pain (LBP) is associated with worse functional outcomes in patients undergoing total hip and knee arthroplasty, no study has analyzed its impact on patients undergoing total ankle arthroplasty (TAA). The aim of this study was to determine the prevalence of LBP in people undergoing TAA and analyze its impact on patient reported functional outcome measures (PROMs). A retrospective review was performed on data from the Vancouver End Stage Ankle Arthritis Database. In total, 87 patients undergoing TAA were studied, with patient demographics collected preoperatively, including the absence or presence of LBP. Postoperative follow-up was performed at 5 years, primarily analyzing disease-specific PROMs including the Ankle Osteoarthritis Score and Ankle Arthritis Score. The Short Form-36 was used as a secondary outcome measure to assess global function. Multivariable linear mixed-effects regression models were conducted to compare the PROM between patients with LBP with those without LBP. In total, 30 patients (35%) presented with concomitant LBP. There were no significant differences at baseline between the LBP group and no LBP group in terms of demographics or baseline primary disease-specific PROMs. At 5 years, the patients with LBP had significantly worse Ankle Arthritis Score (32 ± 23 vs 22 ± 17, p = .03), Ankle Osteoarthritis Score Total (34 ± 23 vs 22 ± 16, p = .01), and Short Form-36 physical (PCS) components summaries (33 ± 12 vs 44 ± 9, p = .001) compared to the no-LBP group. Both groups improved significantly from baseline across all outcome measures. Our study demonstrated that the prevalence of concomitant LBP in end stage ankle arthritis undergoing TAA is similar to that described in arthritic knees and hips. If present, it can be associated with worse functional outcomes in the intermediate term. However it is not a contraindication to surgery, with patients still experiencing significant improvements from baseline. Further studies are needed to evaluate if LBP influences complications, implant failure rates and survival.

Planned Versus On-Demand Relaparotomy Strategy in Initial Surgery for Non-occlusive Mesenteric Ischemia

BackgroundThere has been insufficient evidence regarding a treatment strategy for patients with non-occlusive mesenteric ischemia (NOMI) due to the lack of large-scale studies. We aimed to evaluate the clinical benefit of strategic planned relaparotomy in patients with NOMI using detailed perioperative information. MethodsWe conducted a multicenter retrospective cohort study that included NOMI patients who underwent laparotomy. In-hospital mortality, 28-day mortality, incidence of total adverse events, ventilator-free days, and intensive care unit (ICU)–free days were compared between groups experiencing the planned and on-demand relaparotomy strategies. Analyses were performed using a multivariate mixed effects model and a propensity score matching model after adjusting for pre-operative, intra-operative, and hospital-related confounders. ResultsA total of 181 patients from 17 hospitals were included, of whom 107 (59.1%) were treated using the planned relaparotomy strategy. The multivariate mixed effects regression model indicated no significant differences for in-hospital mortality (61 patients [57.0%] in the planned relaparotomy group vs. 28 patients [37.8%] in the on-demand relaparotomy group; adjusted odds ratio [95% confidence interval] = 1.94 [0.78–4.80]), as well as in 28-day mortality, adverse events, and ICU-free days. Significant reduction in ventilator-free days was observed in the planned relaparotomy group. Propensity score matching analysis of 61 matched pairs with comparable patient severity did not show superiority of the planned relaparotomy strategy. ConclusionsThe planned relaparotomy strategy, compared with on-demand relaparotomy strategy, did not show clinical benefits after the initial surgery of patients with NOMI. Further studies estimating potential subpopulations who may benefit from this strategy are required.

Parallel assessment of albuminuria and plasma sTNFR1 in people with type 2 diabetes and advanced chronic kidney disease provides accurate prognostication of the risks of renal decline and death

Identification of people with diabetes and chronic kidney disease at high-risk of early mortality is a priority to guide intensification of therapy. We aimed to investigate the complementary prognostic value of baseline urine albumin-to-creatinine ratio (uACR) and plasma soluble tumour necrosis factor receptor-1 (sTNFR1) with respect to early mortality and renal functional decline in a population with type 2 diabetes and advanced chronic kidney disease. We measured plasma sTNFR1 in people with type 2 diabetes (HbA1c ≥ 48 mmol/mol) at 2 hospital sites in Dublin between October 15th, 2014 and July 17th, 2015. In a subgroup of patients with advanced chronic kidney disease at baseline (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/BSA) (n = 118), we collected clinical and longitudinal laboratory data to investigate relationships between sTNFR1 and renal and mortality endpoints by multivariable linear mixed-effects models and Cox proportional hazards regression models. The cohort was 64% male and 97% Caucasian. Mean age was 74 years, with a median type 2 diabetes duration of 16 years. Mean CKD-EPI eGFR was 42 mL/min/BSA and median [IQR] uACR was 3 [11] mg/mmol. Twenty-three (39%) people in quartiles 3 and 4 for plasma sTNFR1 died over 4-year follow-up. After adjustment for clinical variables, annual CKD-EPI eGFR decreased by − 0.56 mL/min/BSA/year for each logarithm unit increase in baseline uACR, corresponding to an annual loss of renal function of 3% per year. Furthermore, elevated uACR, but not sTNFR1, increased the risk of ≥ 40% decline in CKD-EPI eGFR (HR 1.5, p = 0.001) and doubling of serum creatinine (HR 2.0, p < 0.001). Plasma sTNFR1 did not predict a more negative trajectory in eGFR slope. However, for those people in quartiles 3 and 4 for plasma sTNFR1, an increased risk of incident mortality was detected (HR 4.9, p = 0.02). No such association was detected for uACR. In this elderly cohort of patients with type 2 diabetes and chronic kidney disease, sTNFR1 predicted short-to-medium term mortality risk but not risk of progressive renal functional decline. In contrast, parallel assessment of uACR predicted renal functional decline but not mortality, highlighting the complementary prognostic information provided by both parameters.

Patient Willingness to Accept Antibiotic Side Effects to Reduce Surgical Site Infection After Colorectal Surgery

BackgroundMechanical bowel preparation with antibiotics is associated with decreased surgical site infections (SSI) after colorectal surgery. However, antibiotics have side effects, such as vomiting. It is unknown how patient willingness to take antibiotics is affected by side effect severity. Materials and methodsThis was a single-center study of 86 patients (37 undergoing colorectal surgery) using a modified standard gamble technique. We presented patients with four hypothetical scenarios, holding SSI reduction constant and varying antibiotic side effect severity. Patients reported willingness to take antibiotics using a scale from 0 to 100. Patients also reported the maximum level of side effects they would accept. We examined the association between side effect severity and willingness to take antibiotics with a multivariable mixed-effects regression model and investigated differences in surgical and nonsurgical patients. ResultsAfter adjusting for age, sex, and patient type, willingness scores decreased with increasing side effect severity. No side effects: 92 (CI 86,99), mild: 83 (CI 76,90), moderate: 76 (CI 69,83), and severe: 46 (CI 38,52), P < 0.001. Surgical patients were more willing to take antibiotics at all severity levels compared with nonsurgical patients, P < 0.001. Surgical (57%) and nonsurgical (58%) patients reported that they would accept moderate side effects. Patients with prior SSI (n = 5) would take antibiotics regardless of side effect severity. ConclusionsIncreasing antibiotic side effect severity is associated with decreased willingness to take antibiotics during bowel preparation, despite a reduction in SSI. Adherence may be improved with strategies that increase patient education and decrease side effects during bowel preparation.

Negative affect and emotion dysregulation among people who inject drugs: An ecological momentary assessment study.

This study used ecological momentary assessment (EMA) to measure positive affect (PA) and negative affect (NA) among people who inject drugs (PWID) and examined associations with borderline personality disorder (BPD) symptoms and difficulties with emotion regulation, in the context of injection drug use. We recruited PWID, ages 18-35 years, through syringe exchange program sites in Chicago, Illinois. After completing a baseline interview including a screener for BPD and the Difficulties in Emotion Regulation Scale (DERS), participants used a mobile phone app to report mood, substance use, and injection behavior for 2 weeks. Participants who completed at least 2 EMA assessments were included in the analysis (N = 161). The mean age was 30, about 1/3 were women, 63% were non-Hispanic White, and 23% were Hispanic. In multivariable mixed-effects regression models, positive BPD screen was associated with greater momentary NA intensity and greater instability of both NA and PA. Independent of BPD screening status, DERS score was associated positively with momentary NA intensity and instability and negatively with PA intensity. This finding suggests that emotion dysregulation is an appropriate target for assessment and intervention. Whereas concurrent withdrawal was associated with both greater NA and less PA, opioid intoxication was associated with only greater PA. We did not find support for our hypothesis that emotion dysregulation would moderate the effect of withdrawal on NA. Findings support the validity of the EMA mood measure and the utility of studying mood and behavior among PWID using EMA on mobile phones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Association between Patient-Reported Health Status and Physical Activity Six Months after Upper and Lower Limb Fractures in Working-Aged Adults.

Physical activity limitations are common following upper and lower limb fractures in adults of working age. There is a lack of research investigating the factors associated with these limitations, such as pain, mental health problems, and mobility impairments. To report health status (EQ-5D) 6 months after upper and lower limb fracture in adults of working age (ages 18-69 years), and to determine the association between sedentary behavior (sitting time) and physical activity (steps, moderate-intensity physical activity [MPA]) 2 weeks and 6 months post-fracture with health status 6 months post-fracture. Prospective cohort study. Major (level I) trauma center. Sixty-three adults 18-69 years of age with upper or lower limb fractures who were recruited consecutively. Participants wore ActiGraph and activPAL accelerometers for 10 days, 2 weeks and 6 months post-fracture. At 6 months, participants completed the EQ-5D. We used linear mixed-effects multivariable regression analyses to explore associations between EQ-5D domains and sitting time, steps, or physical activity. Participants with mobility problems (compared to participants without) were highly sedentary at 2 weeks (β = 0.86, P = .04), took fewer steps/d (Ratio of Geometric Means [RGM] = 0.62, P = .02) and engaged in less MPA (RGM = 0.32, P = .01). In addition, they engaged in less MPA at 6 months (RGM = 0.52, P = .02). Participants with self-care problems (compared with participants without) took fewer steps per day at 6 months (RGM = 0.78, P = .04), and engaged in less MPA at 2 weeks (RGM = 0.31, P = .01) and 6 months (RGM = 0.48, P = .02). Adults with mobility and self-care problems 6 months post-fracture engaged in high levels of sedentary behavior and low levels of physical activity. These findings can guide clinicians on health problems to target in order to maximize recovery of physical activity following fracture.

Abstract 715: Circulating tumor DNA as a potential biomarker of radiographic tumor burden in small cell lung cancer

Abstract Introduction Blood-based next generation sequencing assays of circulating tumor DNA (ctDNA) have the ability to detect canonical SCLC tumor-associated mutations1,2. In non-small cell lung cancer, mean variant allele frequency (VAF) of clonal mutations in ctDNA is associated with radiographic tumor volume (TV)3. We sought to characterize the relationship between ctDNA mean VAF and total-body tumor burden in patients with SCLC. Methods Patients with both limited- and extensive-stage SCLC were identified prospectively and underwent serial blood draws as part of an IRB-approved protocol (IRB #030763). Using our previously developed ctDNA assay, mean VAF was calculated from patient plasma by sequencing 14 genes (all coding exons of TP53, RB1, BRAF, KIT, NOTCH1-4, PIK3CA, PTEN, and copy number variations in FGFR1, MYC, MYCL1, and MYCN)1,4. Three-dimensional total-body tumor burden was determined from positron emission tomography and computed tomography scans obtained during routine care using a radiation oncology treatment-planning software (MIM), and tumor segmentations were verified by radiation oncologists. Univariate association and multivariable mixed effects regression analyses (including presence of bone metastases and treatment status) were performed to evaluate the association between mean VAF and overall TV. We performed separate analyses for mean VAF of all variants identified and of TP53 variants only. Results We analyzed 75 concordant scans and blood draws from 25 patients with SCLC. The median interval between imaging and blood collection was 1 day (mean 3.5, range 0-16). Univariate analysis showed a positive association between mean VAF of all variants and overall TV (Spearman's ρ=0.292, p&amp;lt;0.01). When considering only treatment-naïve and pre-treatment samples (n=11), the magnitude of association increased and remained significant (ρ=0.618, p=0.048). The relationship between mean VAF of all variants and overall TV remained significant when adjusting for treatment status and bone metastases (p=0.046). When considering only TP53 variants, an overall univariate correlation analysis did not show a significant association between mean VAF and overall TV (ρ=0.184, p=0.175). However, among treatment-naïve and pre-treatment samples (n=8) with TP53 variants, the association was significant (ρ=0.762, p=0.037). This association remained significant (p=0.021) after adjusting for treatment status and presence of bone metastasis, with VAF increasing 3.7% for each fold increase in TV (95% CI: 0.7-6.7%). Conclusion In our study mean VAF (both overall and TP53 variants only) was positively correlated with three-dimensional total-body tumor burden in patients with SCLC. These results suggest that mean VAF may provide a useful snapshot of overall tumor burden and represent a dynamic biomarker that could be followed to monitor for disease progression in patients with SCLC.

Age at first calving in UK Jersey cattle and its associations with first lactation 305-day milk yield, lifetime daily milk yield, calving interval and survival to second lactation

The association between age at fist calving (AFC) and production, fertility and survivability in Jersey heifers requires evaluation and comparison with published literature on Holstein heifers. Lactation records from 7256 pedigree Jersey heifers were grouped by AFC. Analysis comprised mixed effects multivariable regression modelling and binary logistic regression modelling. Increased lifetime daily yield (LDY) was significantly associated with a reduced AFC; calving UK Jersey heifers at 24 months or below is optimal. Heifers calving at 25-26 months had a significantly lower mean calving interval (391 days; 95 per cent CI 386 to 397) than those calving over 30 months (399; 95 per cent CI 394 to 405) (P=0.03). Heifers with an AFC over 30 months were less likely to survive to second lactation than those with an AFC 18-24 months. Spring calving heifers produced significantly less milk per day (9.87 kg; 95 per cent CI 9.64 to 10.1) than autumn (10.18; 95 per cent CI 9.94 to 10.41) or winter calvers (10.07; 95 per cent CI 9.84 to 10.3) (P≤0.01). Heifers that calved in the winter had a significantly shorter calving interval (389 days; 95 per cent CI 394 to 383) (P≤0.01) than heifers calved in other seasons. The impact of AFC on Jersey production, fertility and longevity traits shows a similar trend to that seen in the Holstein, potentially on a lesser scale.

Fewer postoperative opioids are associated with decreased duration of stay for children with perforated appendicitis

BackgroundThe impact of postoperative opioid use on outcomes for children with perforated appendicitis is unknown. MethodsA retrospective cohort study was performed using the Pediatric Health Information System database from 2005 to 2015. Children 2 to 18 years with perforated appendicitis who underwent an appendectomy were identified. Postoperative day analgesic use was categorized as nonopioid analgesia alone, opioids (with or without nonopioid analgesia), or no analgesics. The impact of postoperative opioid use on postoperative duration of stay and 30-day readmission was evaluated using multivariable mixed-effects regression analysis. ResultsOverall, 47,726 children with perforated appendicitis were identified. On postoperative day 1, 17.7% received nonopioid analgesia alone, 77.6% received opioids, and 4.7% received no analgesics. On adjusted analysis, postoperative day 1 opioid use was associated with a 0.75-day (95% confidence interval: 0.54–0.96) increased postoperative duration of stay. Starting opioids after postoperative day 1 was associated with 2.21 days (95% confidence interval: 1.90–2.51) longer postoperative duration of stay. Among children who received opioids on postoperative day 1, continued use of opioids after postoperative day 1 was associated with a 1.88 day (95% confidence interval: 1.77–1.98) longer postoperative duration of stay. Postoperative day 1 opioid use did not significantly affect 30-day readmission. ConclusionEarly and continued postoperative opioid use is associated with prolonged postoperative duration of stay in children undergoing appendectomy for perforated appendicitis. Minimizing opioid use, even on postoperative day 2, may result in a decreased postoperative duration of stay.