Differential Treatment Efficacy Research Articles

Differential Efficacy of Storage Temperature and Postharvest Treatment on Shelf Life and Quality of Avocado Fruit (Persea americana Mill.).

Avocado fruit is a rich source of phytonutrients such as vitamins, minerals, carotenoids, carbohydrates, polyphenols and unsaturated fatty acids. However, due to its climacteric nature, fruits are highly susceptible to storage temperature, resulting in poor shelf life and reduced quality. In the present study avocado fruits (Accession CHES-HA-I/I) were stored at different low temperatures (5, 9 and 12°C with 90-95% relative humidity, RH) to identify optimum low temperature for cold storage. In a further experiment, avocado fruits were treated with 1-methylcyclopropene (1-MCP, 500ppb) and chitosan (0.5%) to extend the shelf life with better fruit quality. The results showed that storage temperatures had significant effect on physiological, biochemical and antioxidant activities of fruits. Lower physiological loss in weight (PLW), reduced respiration and ethylene production, and higher carbohydrates, protein and fat content were recorded in fruits stored at 9°C as compared to 12°C. Similarly, maximum antioxidant properties in terms of free radical scavenging activity (FRSA) and ferric reducing ability of plasma (FRAP) was found in avocado fruits stored at 9°C. It was also noticed that chilling injury was developed in fruits stored under 5°C. In addition, exogenous application of 1-MCP significantly reduced respiration and ethylene production rate at 9°C and extended the shelf life up to 42days with better fruit quality and more antioxidant activities. However, chitosan treated and control fruits had shelf life up to 28 and 21days respectively, with minimum nutritional content. From this study it is concluded that a storage temperature of 9°C and 1-MCP treatment significantly enhanced the shelf life of avocado fruits with better fruit quality as compared to other storage temperatures (5 and 12°C) and postharvest treatment (chitosan).

Desensitizing efficacy of a universal dentin adhesive containing mesoporous bioactive glass on dentin hypersensitivity: a randomized clinical trial with a split-mouth model

This split-mouth blinded randomized controlled study compared the efficacy of a desensitizing agent with oxalate/resin polymer and a universal adhesive containing mesoporous bioactive glass (MBG) for dentin hypersensitivity (DH) relief, using Schiff sensitivity score (SSS) and visual analog scale (VAS). Split quadrants containing teeth with DH were treated with either MS Coat ONE or Hi-Bond Universal with MBG as the functional additive. Assessments at baseline, immediately post-application, and at 1- and 2-week follow-ups used standardized stimulus protocols (air, cold, and acid). The SSS difference was the primary outcome, while the VAS difference was the secondary outcome. A mixed linear effect model performed statistical analysis. Immediate DH reduction occurred in response to air stimuli, with a significant decrease in Group HB than in Group MS (p = 0.0178). Cold stimulus reduction exhibited a gradual cumulative effect, with consistently greater reductions in Group HB than in Group MS (p ≤ 0.0377). Both groups effectively managed acidic stimuli, with no significant differences (p > 0.05). The VAS scores decreased gradually over the follow-up period (p < 0.0001). This study highlights the differential efficacy of treatments for various DH triggers and recommends specific approaches based on different stimulus types. The universal adhesive containing MBG demonstrated DH relief potential, promising efficacy identical to or superior to that of a dedicated desensitizing agent. Further research exploring the long-term efficacy and underlying mechanisms is warranted. The universal adhesive containing MBG can be adopted as an in-office desensitizing agent for DH relief. The desensitizing efficacy of universal adhesive matches or surpasses dedicated agents for air and cold stimuli.

Non-IgG4-Related Fibrosing Mediastinitis Diagnosed on Core Needle Biopsy and Treated with Steroids: A Case Study and Review of the Differential Diagnoses.

This study aimed to investigate the histological characteristics and treatment efficacy of non-immunoglobulin G4-related fibrosing mediastinitis and discuss differential diagnoses for this rare entity. We present a case study of non-immunoglobulin G4-related fibrosing mediastinitis diagnosed on core biopsy and treated with steroids. A total of four 18-gauge core needle biopsy specimens were obtained for surgical pathology. Analysis of the patient's medical history, radiological characteristics of fibrosing mediastinitis, histological features, immunohistochemistry results, the differential diagnosis and treatment efficacy of different types of fibrosing mediastinitis was performed. This report describes a unique presentation of fibrosing mediastinitis (syncope and weight loss) that was concerning for malignancy. Histological, laboratory and radiographical studies confirmed the diagnosis of non-immunoglobulin G4-related fibrosing mediastinitis. The patient received corticosteroid treatment which showed marked improvement after 1 month of treatment. Fibrosing mediastinitis is an extremely uncommon entity with unknown pathogenesis, and it is more important to rule out malignancy and infection than to delineate between fibrosing mediastinitis and IgG4-related disease. In doing this, we may reasonably initiate a trial of corticosteroids which may prove beneficial, as in this patient. More studies on the pathogenesis of fibrosing mediastinitis are necessary to guide better directed treatments.

CD3-immunotoxin mediated depletion of T cells in lymphoid tissues of rhesus macaques

Selective T-cell depletion prior to cell or organ transplantation is considered a preconditioning regimen to induce tolerance and immunosuppression. An immunotoxin consisting of a recombinant anti-CD3 antibody conjugated with diphtheria toxin was used to eliminate T-cells. It showed significant T-cell depletion activity in the peripheral blood and lymph nodes in animal models used in previous studies. To date, a comprehensive evaluation of T-cell depletion and CD3 proliferation for all lymphoid tissues has not been conducted. Here, two rhesus macaques were administered A-dmDT390-SCFBdb (CD3-IT) intravenously at 25 μg/kg twice daily for four days. Samples were collected one day prior to and four days post administration. Flow cytometry and immunofluorescence staining were used to evaluate treatment efficiency accurately. Our preliminary results suggest that CD3-IT treatment may induce higher depletion of CD3 and CD4 T-cells in the lymph nodes and spleen, but is ineffective in the colon and thymus. The data showed a better elimination tendency of CD4 T-cells in the B-cell zone relative to the germinal center in the lymph nodes. Further, CD3-IT treatment may lead to a reduction in germinal center T follicular helper CD4 cells in the lymph nodes compared to healthy controls. The number of proliferating CD3 T-cell indicated that repopulation in different lymphoid tissues may occur four days post treatment. Our results provide insights into the differential efficacy of CD3-IT treatment and T-cell proliferation post treatment in different lymphoid tissues. Overall, CD3-IT treatment shows potential efficacy in depleting T-cells in the periphery, lymph nodes, and spleen, making it a viable preconditioning regimen for cell or organ transplantation. Our pilot study provides critical descriptive statistics and can contribute to the design of larger future studies.

Are psychological interventions for adult PTSD more efficacious and acceptable when treatment is delivered in higher frequency? A meta-analysis of randomized controlled trials.

Two systematic reviews indicated that higher treatment frequency of psychological interventions for adult PTSD may lead to higher efficacy and less dropout. Yet, a quantitative review is missing. We conducted a thorough systematic literature search and included trials meeting the following criteria: a) random allocation, 2) PTSD was primary treatment focus, 3) ≥70% interview-based PTSD rate 4) mean age ≥18 years, and 5) N≥20. Treatment session frequency was analyzed dichotomously (< 1.5 vs. ≥ 1.5 sessions/week) and continuously (sessions per week & minutes per week). A total of 160 RCTs with data from 10,556 patients were included. Analyses yielded similar treatment efficacy irrespective of treatment frequency definitions and whether differential efficacy was estimated directly via head-to-head trials or indirectly via comparisons to the same comparison group. Intense (≥ 1.5 sessions/week) vs. standard (< 1.5 sessions/week) delivery was, however, associated with significantly lower dropout rates (as a proxy for acceptability) for trauma-focused interventions (18.64% vs 11.54%, respectively, p=.024), but not for non-trauma-focused interventions. We found no evidence for differential treatment efficacy of intense vs. standard psychotherapies for adult PTSD. Evidence for increased acceptability was found for intense vs. standard trauma-focused interventions.

Efficacy and acceptability of next step treatment strategies in adults with treatment-resistant major depressive disorder: protocol for systematic review and network meta-analysis

IntroductionFor major depression, a one-size-fits-all treatment does not exist. Patients enter a ‘trial-and-change’ algorithm in which effective therapies are subsequently applied. Unfortunately, an empirically based order of treatments has not...

Identification and inference for subgroups with differential treatment efficacy from randomized controlled trials with survival outcomes through multiple testing.

With the uptake of targeted therapies, instead of the "one-fits-all" approach, modern randomized controlled trials (RCTs) often aim to develop treatments that target a subgroup of patients. Motivated by analyzing the Age-Related Eye Disease Study (AREDS) data, a large RCT to study the efficacy of nutritional supplements in delaying the progression of an eye disease, age-related macular degeneration (AMD), we develop a simultaneous inference procedure to identify and infer subgroups with differential treatment efficacy in RCTs with time-to-event outcomes. Specifically, we formulate the multiple testing problem through contrasts and construct their simultaneous confidence intervals, which appropriately control both within- and across-marker multiplicity. Realistic simulations are conducted using real genotype data to evaluate the method performance under various scenarios. The method is then applied to AREDS to assess the efficacy of antioxidants and zinc combination in delaying AMD progression. Multiple gene regions including ESRRB-VASH1 on chromosome 14 have been identified with subgroups showing differential efficacy. We further validate our findings in an independent subsequent RCT, AREDS2, by discovering consistent differential treatment responses in the targeted and non-targeted subgroups identified from AREDS. This multiple-testing-based simultaneous inference approach provides a step forward to confidently identify and infer subgroups in modern drug development.

Short-Term Psychodynamic Psychotherapy for Depression: For Whom Does It Work? A Research Perspective.

Short-term psychodynamic psychotherapy (STPP) is an empirically supported treatment for depression that is frequently applied in clinical practice. However, it remains largely unclear which patients can benefit specifically from STPP for depression, because studies often have small sample sizes and, therefore, lack statistical power to examine patient characteristics associated with differential treatment efficacy. Individual participant data (IPD) meta-analyses, which combine patient-level data from multiple studies, can help overcome this obstacle. Currently, the first IPD meta-analysis project regarding STPP for depression is being conducted. We describe this project, its progress, and first findings.

Resilience as a predictor of quality of life in participants with borderline personality disorder before and after treatment

BackgroundStudies have suggested that psychotherapy improves the Quality of Life (QoL) of participants with Borderline Personality Disorder (BPD). However, there are no studies on the differential efficacy of treatments on the QoL of participants with BPD. Moreover, the relationship between QoL and resilience has rarely been studied in participants with BPD. Objectives: a) to examine whether people with BPD have worse QoL than the non-clinical population; b) to examine whether there are statistically significant differences between Dialectical Behavioural Therapy (DBT), Systems Training for Emotional Predictability and Problem Solving (STEPPS), or Cognitive Behavioural Therapy-Treatment at Usual (CBT-TAU) in the improvement of QoL; c) to examine whether participants show clinically significant improvements in QoL after treatment; d) to analyse whether resilience is associated with QoL before and after the BPD treatment; e) to analyse whether resilience is a predictor of QoL at pre-treatment and posttreatment.MethodThe sample comprised 403 participants (n = 202 participants diagnosed with BPD and n = 201 non-clinical). Participants filled out the Quality of Life Index, Resilience Scale, and Beck Depression Inventory. The clinical participants received one of these possible treatments, DBT, STEPPS, or CBT-TAU. MANOVA and regression analyses were performed.Resultsa) participants diagnosed with BPD had statistically significant lower resilience than the non-clinical population; b) all three forms of psychotherapy statistically improved QoL, but there were no statistically significant differences between DBT, STEPPS, and CBT-TAU in the improvement of QoL; c) participants did not show clinically significant improvements in QoL after treatment; d) resilience was associated with QoL before and after treatment; and e) resilience was a predictor of QoL before and after treatment.ConclusionIt is necessary to assess QoL and Resilience in studies on psychotherapy with BPD patients.

A clinical significance analysis of manualised psychological interventions for obsessive-compulsive disorder

AimsTo conduct an individual patient data meta-analysis of randomised controlled trials (RCTs) of manualised psychological treatments for obsessive-compulsive disorder (OCD), and examine the differential efficacy of psychological treatments by treatment type and format.BackgroundPrevious meta-analyses conclude that efficacious psychological treatments for OCD exist. However, determining the efficacy of psychological treatments requires multiple forms of assessment across a range of indexes, yet most previous meta-analyses in OCD are based solely on effect sizes.MethodWe evaluated treatment efficacy across 24 RCTs (n = 1,667) by conducting clinical significance analyses (using standardised Jacobson methodology) and standardised mean difference within-group effect-size analyses. Outcomes were Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores, evaluated at post-treatment and follow-up (3-6 months post-treatment).ResultPost-treatment, there was a large significant within-group effect size for treated patients (g = 1.28) and a small significant effect size for controls (g = 0.30). At follow-up, large within-group effect sizes were found for both treated patients (g = 1.45) and controls (g = 0.90). Clinical significance analyses indicated that treated patients were significantly more likely than controls to recover following an intervention, but recovery rates were low; post-intervention, only 32% of treated patients and 3% of controls recovered; rising to 38% and 21% respectively at follow-up. Regardless of allocation, only approximately 20% of patients were asymptomatic at follow-up. Across the different analysis methods, individual cognitive therapy (CT) was the most effective intervention, followed by group CT plus exposure and response prevention. Self-help interventions were generally less effective.ConclusionReliance on aggregated within-group effect sizes may lead to overestimation of the efficacy of psychological treatments for OCD. More research is needed to determine the most effective treatment type and format for patients with OCD.

Confident identification of subgroups from SNP testing in RCTs with binary outcomes

In modern drug development, genotype information becomes more frequently collected in randomized controlled trials (RCTs) for individualized risk prediction and personalized medicine development. Finding single nucleotide polymorphisms (SNPs) that are predictive of differential treatment efficacy, measured by a clinical outcome, is fundamentally different and more challenging than the traditional association test for a quantitative trait. With the objective to confidently identify and infer genetic subgroups with enhanced treatment efficacy from a large RCT for an eye disease, age-related macular degeneration (AMD), where the clinical endpoint is binary (progressed or not), we propose a novel SNP-testing procedure for binary clinical outcomes. Specifically, we formulate four contrasts to simultaneously assess all possible genetic effects on a logic-respecting efficacy measure, the relative risk (between treatment and control). Our method controls both within- and across-SNP multiplicity rigorously. We then use real genotype data to perform chromosome-wide simulations to evaluate our method performance and to provide practical recommendations. Finally, we apply the proposed method to perform a genome-wide SNP testing for the AMD trial and successfully identify multiple gene regions with genetic subgroups exhibiting enhanced efficacy in terms of decreasing the AMD progressionrate.

Predictors and moderators of treatment efficacy in reducing custodial grandmothers’ psychological distress

It is increasingly recommended that hypothesis-generating studies be conducted after initial RCTs in order to identify moderators of differential treatment efficacy on individual outcomes. Such analyses are important because they help clarify the best inclusion and exclusion criteria or choice of stratification for maximizing power in subsequent RCTs, reduce the chances of discarding interventions that may appear to lack efficacy when only average treatment effects are taken into consideration, and facilitate the matching of individual clients to treatment alternatives. We identified predictors and moderators of treatment-related change in psychological distress among custodial grandmothers (n = 343) assigned within a prior RCT to behavior parent training (BPT), cognitive behavior therapy (CBT), or information only control (IOC) conditions. Latent change scores in psychological distress were estimated for each grandmother across pre-test to post-test and pre-test to six months, as indicated by self-reported and clinical ratings of depression and anxiety symptoms. These estimates served as outcomes in classification and regression tree analyses conducted separately within the CBT and BPT conditions to identify predictors of treatment efficacy. Matched groups based upon identified predictors were then formed across all RCT conditions, and Predictor × RCT Condition interactions were computed to test for moderation of differential treatment efficacy. Grandmother age was the only predictor and moderator of BPT efficacy at both measurement points, whereas multifaceted predictors and moderators emerged for CBT which varied by time since treatment.

Evaluating substance use treatment efficacy for younger and older adults

The purpose of this study was to examine the differential efficacy of aftercare substance use treatments for younger (below 40, n = 107) versus older (40+, n = 114) adults (N = 221), using data from a randomized controlled trial in a community-based substance abuse treatment center. The younger adult sample had a mean age of 28.9 while the older adult sample had a mean age of 48.1. Primary outcomes were rates of abstinence and percent use days at 1-year follow-up. Outcomes were compared between standard cognitive behavioral relapse prevention (RP), Mindfulness-Based Relapse Prevention (MBRP), and 12-step-based treatment as usual (TAU). Results showed significant differences by treatment in the older, but not in younger, subsample of participants. Specifically, the older participants in MBRP had significantly higher abstinence rates compared with those in TAU. Further, the older individuals in MBRP had a significantly lower percent of days on which they used compared with those in TAU and RP. Overall, findings suggest that age group may impact aftercare treatment substance use outcomes.

Rapid LA-REIMS and comprehensive UHPLC-HRMS for metabolic phenotyping of feces

Ambient ionization-based techniques hold great potential for rapid point-of-care applicable metabolic fingerprinting of tissue and fluids. Hereby, feces represents a unique biospecimen as it integrates the complex interactions between the diet, gut microbiome and host, and is therefore ideally suited to study the involvement of the diet-gut microbiome axis in metabolic diseases and their treatments at a molecular level. We present a new method for rapid (<10 s) metabolic fingerprinting of feces, i.e. laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS) with an Nd:YAG laser (2940 nm) and quadrupole Time-of-Flight mass spectrometer as main components. The LA-REIMS method was implemented on mimicked crude feces samples from individuals that were assigned a state of type 2 diabetes or euglycaemia. Based on the generated fingerprints, enclosing 4923 feature ions, significant segregation according to disease classification was achieved through orthogonal partial least squares discriminant analysis (Q2(Y) of 0.734 and p-value of 1.93e−17) and endorsed by a general classification accuracy of 90.5%. A comparison between the discriminative performance of the novel LA-REIMS and our established ultra-high performance liquid-chromatography high-resolution MS (UHPLC-HRMS) metabolomics and lipidomics methodologies for fingerprinting of stool was performed. Based on the supervised modelling results upon UHPLC-HRMS (Q2(Y) ≥ 0.655 and p-value ≤ 4.11 e−5), equivalent or better discriminative performance of LA-REIMS fingerprinting was concluded. Eventually, comprehensive UHPLC-HRMS was employed to assess metabolic alterations as observed for the defined classes, whereby metformin treatment of the type 2 diabetes patients was considered a relevant study factor to acquire new mechanistic insights. More specifically, ten metabolization products of metformin were identified, with (hydroxylated) triazepinone and metformin-cholesterol reported for the first time in vivo.In conclusion, LA-REIMS was established as an expedient strategy for rapid metabolic fingerprinting of feces, whereby potential implementations may relate, but are not limited to differential diagnosis and treatment efficacy evaluation of metabolic diseases. Yet, LC-HRMS remains essential for in-depth biological interpretation.

PSS42 - SECUKINUMAB SIGNIFICANTLY REDUCES PSORIASIS-RELATED WORK IMPAIRMENT AND INDIRECT COSTS COMPARED TO USTEKINUMAB AND ETANERCEPT IN MOROCCO

The severity of psoriasis can impact work productivity. Whether differential treatment efficacy translates into differential indirect cost-savings is unknown. We compared indirect costs associated with secukinumab, ustekinumab and etanercept in Morocco. Work Productivity and Activity Impairment (WPAI) data from employed patients in CLEAR study (secukinumab versus ustekinumab) were used to assess the impact of psoriasis on work, and were applied to FIXTURE study (secukinumab versus etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (1) overall work impairment derived from WPAI data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (2) weekly/annual work productivity loss by PASI response level; (3) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (4) weighted average indirect costs for each treatment. Employment data was based on Morocco Annual Statistics, 2012 data. In CLEAR, 452 patients (67%) were employed at baseline. At week 16, percentages of overall work impairment/weekly mean hours lost decreased with higher PASI response: PASI < 50: 22.8%/9.70 hours; PASI 50-74: 13.3%/5.68 hours; PASI 75-89: 6.4%/2.73 hours; and PASI ≥ 90: 4.9%/2.10 hours. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (2.51/130.87 versus 3.06/159.73; P = 0.0006). Similar results were obtained for secukinumab versus etanercept (2.93/152.78 versus 4.58/238.94; P < 0.0001). Average annual indirect cost-savings with secukinumab were 366.41 MAD versus ustekinumab (P = 0.0006) and 1093.97 MAD versus etanercept (P < 0.0001). Secondary analyses using week 52 data, different PASI distributions, or considering the full employed and non-employed patient population, supported these results. Secukinumab significantly reduces work impairment and associated indirect costs of psoriasis, when compared with ustekinumab and etanercept, at week 16 through week 52.

Studying the differential efficacy of postsymptom antitoxin treatment in type A versus type B botulism using a rabbit spirometry model.

ABSTRACTBotulinum neurotoxin (BoNT) serotypes A, B and E are responsible for most cases of human botulism. The only approved therapy for botulism is antitoxin treatment administered to patients after symptom onset. However, a recent meta-analysis of antitoxin efficacy in human botulism cases over the past century concluded that a statistically significant reduction in mortality is associated with the use of type E and type A antitoxin, but not with type B antitoxin. Animal models could be highly valuable in studying postsymptom antitoxin efficacy (PSAE). However, the few attempts to evaluate PSAE in animals relied on subjective observations and showed ∼50% protection. Recently, we developed a novel spirometry model for the quantitative evaluation of PSAE in rabbits and used it to demonstrate full protection against BoNT/E. In the current study, a comparative evaluation of PSAE in botulism types A and B was conducted using this quantitative respiratory model. A lethal dose of each toxin induced a comparable course of disease both in terms of time to symptoms (TTS, 41.9±1.3 and 40.6±1.1 h, respectively) and of time to death (TTD, 71.3±3.1 and 66.3±1.7 h, respectively). However, in accordance with the differential serotypic PSAE observed in humans, postsymptom antitoxin treatment was fully effective only in BoNT/A-intoxicated rabbits. This serotypic divergence was reflected by a positive and statistically significant correlation between TTS and TTD in BoNT/A-intoxicated rabbits (r=0.91, P=0.0006), but not in those intoxicated with BoNT/B (r=0.06, P=0.88). The rabbit spirometry system might be useful in the evaluation toolkit of botulism therapeutics, including those under development and intended to act when antitoxin is no longer effective.

Abstract PR11: Temporal patterns of breast cancer treatment initiation and completion among black and white women in the Carolina Breast Cancer Study

Abstract Black women suffer from a persistent disparity in breast cancer mortality after controlling for prognostic and sociodemographic factors, suggesting that differential receipt or efficacy of treatment may contribute to their poorer outcomes. Black women are more likely to experience delays in diagnostic workup and initiation of treatment, but it is not known whether i) timeliness of subsequent care is also impacted, and ii) racial disparities in time to treatment initiation and completion persist among black and white women with comparable clinical and sociodemographic characteristics. The Carolina Breast Cancer Study Phase III is a large population-based cohort of North Carolina women newly diagnosed with breast cancer. This study was restricted to black and white women undergoing surgery for the treatment of nonmetastatic disease. We investigated mean differences in the distribution of time from diagnosis to earliest surgery, chemotherapy, or radiation treatment (treatment initiation) and once started, time to treatment completion (treatment duration) by race. Only treatment-oriented surgeries excluding biopsies were included in this analysis, and last or definitive surgery was defined as the final treatment-oriented surgery occurring prior to recurrence and within 18 months of diagnosis. Cumulative incidence curves were used to graphically examine the distributions of time to treatment initiation and treatment duration, and general linear models were used to estimate crude and adjusted mean differences in time to treatment initiation and duration between black and white women. We also conducted stratified analyses to examine racial disparities by age and stage at diagnosis, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) positivity, treatment pathway (surgery only, surgery plus chemotherapy, surgery plus radiation, or all three modalities), marital status, education level, income, and insurance type. A total of 1,328 black and 1,331 white women met study inclusion criteria. Overall, black women had an average of 3.68 additional days to treatment initiation and 34.26 days longer treatment duration than white women, for 37.94 days longer total treatment time (95% confidence interval (CI): 34.21-41.67). Adjustment for clinical and sociodemographic factors resulted in a greater estimated mean difference in time to initiate treatment (4.04 days, 95% CI: 3.08-5.00), while it attenuated the mean difference in treatment duration towards the null (9.07 days, 95% CI: 6.82-11.32). Black women experienced significantly longer time to initiate treatment and treatment duration in nearly every stratum of clinical or sociodemographic factor examined. Black women with stage II or III tumors had significantly longer time to initiate treatment than white women (4.50 and 7.84 days, respectively), and after starting treatment, treatment duration was approximately 25 days longer for black women with stage I and II disease. Black women undergoing radiation and/or chemotherapy had longer time to initiate treatment and significantly longer treatment durations. Having a college education or higher or being insured through Medicaid were associated with the greatest mean differences in time to treatment initiation comparing black and white women. Younger age at diagnosis, HR+ or HER2- disease, being unmarried, having less than a high school education, and being uninsured were associated with the greatest mean differences in treatment duration by race. Overall, black women experienced longer intervals between diagnosis and treatment initiation and greater treatment durations after controlling for clinical and sociodemographic factors. Racial disparities were more pronounced in examination of treatment duration, suggesting that interventions to improve care coordination and timeliness should be targeted at high-risk groups. Citation Format: Sophie E. Mayer, Melissa Troester, Stephanie B. Wheeler, Andrew Olshan, Lisa A. Carey, Jessica Tse, Katherine E. Reeder-Hayes. Temporal patterns of breast cancer treatment initiation and completion among black and white women in the Carolina Breast Cancer Study [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr PR11.

Abstract P4-10-01: Race, place and delays in breast cancer treatment across the care continuum in the Carolina breast cancer study

Abstract Black women have a persistent disparity in breast cancer survival after controlling for clinical factors, suggesting that differential receipt or efficacy of treatment may contribute to poorer outcomes. Delays in initiating treatment and subsequent spillover effects into time to completion are one proposed mechanism by which these survival disparities may occur. The Carolina Breast Cancer Study Phase III is a large population-based study of North Carolina women with incident breast cancer. For this analysis, we included black (n=1328) and white (n=1331) women with stage I-III disease whose treatment included surgery with or without adjuvant therapies. Patients were grouped by treatment pathway (surgery only, surgery + chemotherapy, surgery + radiation, or all three modalities). We investigated the association of race with delays in treatment initiation, duration and completion. Delays in initiation of first treatment were modeled in two ways: i) time to initiation &amp;gt;30 days from diagnosis, and ii) time to initiation above the 75th percentile. Extended duration and delay in completion were defined as being &amp;gt; 75th percentile in days between initiation and end of treatment (duration) or days from diagnosis to end of treatment (completion) compared to others in the same pathway. Models controlled for treatment pathway, age, and tumor characteristics. Additional models controlled for demographic factors (marital status, income, education, insurance) and county-level factors related to care access (% urban and health professional shortage area status). In analyses adjusted only for age at diagnosis, black women had a significantly higher risk of treatment delays whether measured by delay&amp;gt;30 days (risk ratio (RR) 1.24, 95% CI 1.12-1.37) and or by highest quartile of time to initiation (RR 1.23, 95% CI 1.07-1.40) compared to whites. They were also at higher risk of extended treatment duration (RR 1.47, 95% CI 1.29-1.69) and time to completion (RR 1.58, 95% CI 1.37-1.81) compared to others in the same pathway. Interestingly, adjustment for tumor characteristics did not impact effect estimates. While adjustment for demographic factors had little impact on the association of race with delays in initiation, it attenuated the association of race with delays in treatment duration and completion. Further adjustment for care access factors slightly attenuated the association of race with treatment initiation and completion, but did not impact associations with treatment duration. Significant racial disparities remained in delay across all phases of care after adjustment for clinical, demographic and access factors. Overall, black women were at higher risk of delays in treatment initiation, extended duration and time to completion than white women receiving similar treatment, and these disparities appear to be compounded over the care continuum. These findings suggest that racial differences in income, education and insurance may partly explain observed disparities in treatment duration and time to completion, whereas care access factors may have more impact on disparities in treatment initiation, and interventions that target both patient-level and care access barriers may be needed to improve timely delivery across the care continuum. Citation Format: Reeder-Hayes KE, Mayer SE, Olshan A, Carey LA, Wheeler SB, Tse C-K, Troester M. Race, place and delays in breast cancer treatment across the care continuum in the Carolina breast cancer study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-10-01.

Abstract P3-08-01: Prognostic performance of EndoPredict in invasive lobular carcinoma

Abstract Background: Invasive lobular carcinomas (ILC) account for around 15% of all oestrogen receptor (ER) positive invasive breast cancers. The EndoPredict assay (EPclin) is a multigene classifier to predict the likelihood of distant recurrence in ER-positive, HER2-negative breast cancer patients treated with adjuvant endocrine therapy and has been validated in several retrospective translational studies. However, these validation studies did not include an analysis of the histological subtypes. Here, we investigate the role of EPclin for the prediction of distant recurrence in women with ILC and compare the prognostication to those with invasive ductal carcinoma (IDC) in TransATAC. Methods: Data on EPclin and histological type of tumour were available for 928 postmenopausal women with ER-positive, HER2-negative disease treated with 5 years of tamoxifen or anastrozole. The primary endpoint was distant recurrence and the primary objective was to assess the prognostic value of EPclin for the prediction of distant recurrence in women with invasive lobular carcinoma. Kaplan–Meier and Cox regression analyses were used to determine distant recurrence risk for 0-10 years of follow-up. Likelihood ratio tests were used to assess the prognostic information provided by EPclin. Hazard Ratios (HR) are for a change in 1 Standard Deviation. Results: 141 (15.2%) had ILC, 710 (76.5%) IDC, and the remaining 77 (8.3%) were of different histological type. EPclin provided highly significant prognostic value for distant recurrence in women with ILC (HR=3.33 (2.33-4.77), P&amp;lt;0.001; LR-χ2=38.4). For those with IDC, EPclin was highly prognostic for distant recurrence over 10 years of follow-up (HR=2.41 (2.04-2.84), P&amp;lt;0.001; LR-χ2=95.5). EPclin was more prognostic in IDC than ILC, and a significant interaction between EPclin and tumour type (ILC/IDC) was observed (P-interaction=0.038). 89 (63.1%) women with ILC were categorised into the low EPclin risk group and 52 (36.9%) into the high risk group. A highly significant separation between EPclin low and high risk groups was observed for ILC (10-year distant recurrence risk low: 6.2% (2.6-14.2) vs. high: 36.6% (24.2-52.1); HR=7.36 (2.71-20.01)). For women with IDC, 406 (57.2%) were categorised into the low risk group by EPclin and 304 (42.8%) were deemed high risk, with significant separation between risk groups (10-year distant recurrence risk low: 6.2% (4.1-9.3) vs. high: 28.5% (23.5-34.3); HR=5.59 (3.48-8.98)). We did not observe any differential efficacy of treatment between histological subtype and EPclin risk group. Conclusions: This is the first analysis to focus on the role of EPclin for the prognostic assessment of women with ILC. Although numbers of women with ILC in TransATAC were small, EPclin provided highly significant prognostic information and risk stratification for this subgroup of women. 10-year distant recurrence risk in the EPclin low risk groups were similar between ILC and IDC, suggesting that chemotherapy is not indicated, irrespective of tumour type. Our results show that EPclin is informative in women with ILC. Citation Format: Sestak I, Kronenwett R, Denkert C, Cuzick J, Dowsett M. Prognostic performance of EndoPredict in invasive lobular carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-08-01.

Supplemental Material for Exposure and CBT for Chronic Back Pain: An RCT on Differential Efficacy and Optimal Length of Treatment

Supplemental Material for Exposure and CBT for Chronic Back Pain: An RCT on Differential Efficacy and Optimal Length of Treatment