Group Trial Research Articles

Outcomes of a Career Development Program for Underrepresented Minority Investigators in the AIDS Clinical Trials Group.

We surveyed awardees of the Minority HIV Investigator Mentoring Program (MHIMP) of the AIDS Clinical Trials Group. Most reported clinical specialization in infectious diseases or HIV medicine (86%), and all but 1 (95%) are engaged in medical/health sciences research. The MHIMP helped retain early-career minority investigators in HIV/AIDS-related research.

A cluster randomized controlled trial of an online psychoeducational intervention for people with a family history of depression

BackgroundPeople with a family history of major depressive disorder (MDD) or bipolar disorder (BD) report specific psychoeducational needs that are unmet by existing online interventions. This trial aimed to test whether an interactive website for people at familial risk for depression (intervention) would improve intention to adopt, or actual adoption of, depression prevention strategies (primary outcome) and a range of secondary outcome measures.MethodsIn this cluster randomised trial, primary care practises were randomised to either provide the link to the intervention or the control website. Primary health care attendees were invited by letter to opt into this study if they had at least one first-degree relative with MDD or BD and were asked to complete online questionnaires at baseline and 2-week follow-up.ResultsTwenty general practices were a randomized, and 202 eligible patients completed both questionnaires. Thirty-nine (19.3%) of participants were male and 163 (80.7%) female. At follow-up, compared to controls, the intervention group: (i) were more likely to intend to undergo, or to have actually undergone, psychological therapies (OR = 5.83, 95% CI: 1.58–21.47, p = .008); (ii) had better knowledge of depression risk factors and prevention strategies (mean difference = 0.47, 95% CI: 0.05–0.88, p = .029); and (iii) were more likely to accurately estimate their lifetime risk of developing BD (mean difference = 11.2, 95% CI: -16.52– -5.73, p < .001). There were no statistically significant between-group differences in change from baseline to follow up for any of the remaining outcome measures (Patient Health Questionnaire, Perceived Devaluation-Discrimination Questionnaire and Perceived Risk of Developing MDD).ConclusionThe opt-in nature of the study may have led to participation bias, e.g. underrepresentation of males, and hence may limit generalisability to the broader population at familial risk for depression. This is the first website internationally focusing specifically on informational needs of those at familial risk of depression. Our interactive website can play an important role in improving the outcomes of individuals at familial risk for depression. Testing the intervention in other settings (e.g. psychology, psychiatry, genetic counselling) appears warranted.Trial registrationThe study was prospectively registered with the Australian and New Zealand Clinical Trials Group (Registration no: ACTRN12613000402741).

Persistence of Human Immunodeficiency Virus-1 Drug Resistance Mutations in Proviral Deoxyribonucleic Acid After Virologic Failure of Efavirenz-Containing Antiretroviral Regimens.

BackgroundEfavirenz (EFV)-based regimens select broad drug resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs), limiting the effectiveness of EFV and other NNRTIs. The duration, persistence, and decay of drug resistance mutations (DRMs) in the proviral reservoir is not well defined.MethodsParticipants with virologic failure of EFV-based regimens and drug-resistant viremia with the K103N mutation in plasma ribonucleic acid (RNA) were identified from AIDS Clinical Trials Group (ACTG) studies A364 and A5095. These individuals received a second-line, boosted protease inhibitor-based regimen with suppression of viremia for up to10 years during long-term follow-up (median = 3.6 years; interquartile range, 2.1–6.9 years). Proviral deoxyribonucleic acid (DNA) from cryopreserved peripheral blood mononuclear cells was sequenced to identify the persistence of DRM.ResultsTwenty-eight participants from ACTG 364 and ACTG 5095 were evaluated. Sanger sequencing of proviral DNA detected K103N as well as additional reverse-transcriptase inhibitor (RTI) mutations. Ultradeep sequencing confirmed persistence of K103N in 71% of participants with minimal decay over time. In an adjusted model including years since suppression, persistent proviral K103N was 2.6 times more likely (95% confidence interval, 1.0–6.4) per log10 higher human immunodeficiency virus RNA at EFV failure.ConclusionsPersistence of RTI mutations in proviral DNA after virologic failure has implications for the effectiveness of future drug regimens and the recycling of RTI drugs.

Effects of enzymatically modified isoquercitrin in supplementary protein powder on athlete body composition: a randomized, placebo-controlled, double-blind trial

BackgroundEnzymatically modified isoquercitrin (EMIQ), a water-soluble quercetin, has been shown to intensify muscle hypertrophy in mice. We investigated the effect of EMIQ in supplementary protein powder on athlete body composition.MethodsForty Japanese males who played American football (age: 19.8 ± 1.4 years; body height: 174.1 ± 6.0 cm; body mass: 75.5 ± 10.7 kg) were assigned to a randomized, placebo-controlled, double-blind trial of parallel group. Participants received either EMIQ in whey protein (EW, n = 19) or contrast whey protein (W, n = 20) 6 days per week over 4 months. Body composition was assessed using dual-energy X-ray absorptiometry. Markers of oxidative stress, derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP), were assessed using a free radical analytical system. Data were analyzed using a univariate and repeated measures general model statistics.ResultsAfter 4 months, changes in lower limb fat-free mass and muscle mass were significantly greater in the EW group than in the W group (mean change ±95% CI; W: 324.1 ± 284.3, EW: 950.3 ± 473.2, p = 0.031, W: 255.7 ± 288.6, EW: 930.9 ± 471.5, p = 0.021, respectively). Moreover, the EW group exhibited a significantly higher BAP/d-ROMs ratio, antioxidation index, than the W group after 4 months (mean change ± SD; W: 8.8 ± 1.1, EW: 10.3 ± 2.8; p = 0.028). No significant differences in body mass, lean body mass, fat mass, or lower limb fat mass were observed between the groups.ConclusionIngestion of EMIQ in supplementary protein powder for 4 months exerts antioxidant effects and increases muscle mass among American football players.Trial registrationUniversity Hospital Medical Information Network Clinical Trial Registry, UMIN000036036. Retrospectively registered in 2019.

Adherence to Medication and Physical Activity among People Living with HIV/AIDS.

Background:The aim of this study was to investigate the adherence to medication and Physical Activity (PA) among People Living with HIV (PLHIV).Materials and Methods:In the present cross-sectional study, 122 PLHIV were selected. The research tools included the Baecke questionnaire and the AIDS Clinical Trials Group questionnaire. Data were analyzed by independent t test and multiple logistic regression.Results:The results of 7- and 30-day recalls showed that 76.21 and 82.23% of patients had proper medication adherence. The mean score of PA in patients was less than the recommended average score in the questionnaire. Furthermore, there was no significant difference observed between the medication adherence and PA.Conclusions:Although the adherence to medication was appropriate, nurses and health care providers should increase the level of PA for PLHIV by dealing with the related barriers to live an active life.

The role of saudi critical care trials group in advancing delirium prevention and management

Delirium is common among intensive care unit (ICU) patients; studies showed that delirium is linked to poor outcomes. Few studies have discussed delirium in the Arabic-speaking patients' population. The Saudi Critical Care Trials Group (SCCTG) is a leading entity for research and quality at ICU in Saudi Arabia. The SCCTG has worked on advancing delirium prevention and management by establishing multiple quality improvement projects as well as conducting research. The aim of this review is to highlight the effort of the SCCTG to improve delirium care at the ICU in Saudi hospitals.

PENGEMBANGAN LEMBAR KEGIATAN SISWA BERBASIS METODE PEMECAHAN MASALAH PADA MATERI SEGITIGA

Penelitian ini bertujuan menghasilkan lembar kegiatan siswa (LKS) berbasis metode pemecahan masalah pada materi segitiga yang valid dan praktis. Metode penelitian yang digunakan adalah penelitian pengembangan. Penelitian pengembangan ini dilakukan melalui dua tahap, yaitu tahap preliminary (tahap persiapan) serta tahap formative evaluation. Berdasarkan hasil analisis produk, diperoleh lembar kegiatan siswa berbasis metode pemecahan masalah yang valid dan praktis. Valid terlihat dari hasil penilaian ahli (validator) terhadap LKS, sementara praktis dilihat dari hasil uji coba small group terhadap siswa dalam menyelesaikan LKS yang diberikan. Berdasarkan analisis data hasil belajar siswa diperoleh rata-rata nilai 75,70 yang berarti hasil belajar siswa pada materi segitiga tergolong kategori baik, maka disimpulkan LKS yang telah dikembangkan memiliki efek potensial.

Compared to Conventional Dressing Techniques, Tranexamic Acid Injection Provide Better Surgical Outcomes in Spinal Fusion Surgery

The use of mechanical and chemical hemostatic control techniques in spinal fusion surgery is common in Indonesia. However, there has been no study comparing the two in a single clinical trials. This study aims to find out which best of tranexamic acid injection, a bulky compression dressing and a standard dressing in providing surgical outcomes in spinal fusion surgery. Thirty patients were grouped into three, 10 patients each. To Group 1, tranexamic acid at a dose of 500 mg/ml was administered pre operation and 2 hours later. For Group 2, a bulky compression dressing was performed by covering the surgical wounds with a low-adherent dressing, overlaid with four layers of sterile gauze and then sealed with a conformable adhesive retention tape. Standard dressing was applied to the patients of Group-3 using the same type of bandage and adhesive tape given to the Group-2, but only overlaid with two layers of sterile gauze. There is no statistical difference among trials groups for preoperative (P &gt; 0.220) and postoperative (P &gt; 0.380) hemoglobin levels and the level of perioperative blood loss (P &gt; 0.110). With respect to number of transfusion required, the tranexamic acid group was significantly lower compared to the standard dressing group (P = 0.018). No abnormality of wound seen in all three trials groups and only 2 patients of bulky compression dressing group reported experience of headache. In conclusion, tranexamic acid is better to promote hemostasis compared to conventional dressing techniques.

Uppsala Clinical Research Center—development of a platform to promote national and international clinical science

Uppsala Clinical Research Center (UCR) is a non-profit organization that provides service for clinical research aiming for development and improvement of health care in Sweden and worldwide. UCR was started in 2001 with the ambition to shift the focus of clinical research from new medications or devices launched by the industry to problem-based research on issues identified in clinical reality, for example through the national quality registries. In order to accomplish these goals, UCR has established services in: 1) clinical trials of new and old methods in health care; 2) quality development of the health care system supported by internet-based national quality registries; 3) biostatistics, epidemiology, and data management; 4) biobanking of biological materials (Uppsala Biobank); 5) high-throughput biochemical analyses (UCR laboratory); and 6) academic leadership by the members of the UCR research faculty. The UCR clinical trials group provides services for investigator-driven projects in all areas of health care, for global mega-trials on new pharmaceutical treatments and devices, for biobanking including biomarker and genetics analyses, and for clinical events adjudication in national as well as global mega-trials. During the last few years, UCR has been a pioneer in establishing the registry-based randomized clinical trial (R-RCT), which today is an international model on how to perform cost-effective pragmatic randomized trials in the real-world environment. In 2002, UCR started the first national competence center for national quality registries, which pioneered the development of the current internet-based technologies for registering, reporting, and supporting continuous systematic improvement of health care. UCR is currently harboring around 20 national quality registries in all areas of health care. Today, UCR is the leading European center for registry-based quality development and evaluation of new medical treatments in cardiovascular care and has started to support other European countries in implementing the UCR registry platform in order to improve quality of care in the European Union.

Multiple robustness estimation in causal inference

Estimation of average treatment effect is crucial in causal inference for evaluation of treatments or interventions in biostatistics, epidemiology, econometrics, sociology. However, existing estimators require either a propensity score model, an outcome vector model, or both is correctly specified, which is difficult to verify in practice. In this paper, we allow multiple models for both the propensity score models and the outcome models, and then construct a weighting estimator based on observed data by using two-sample empirical likelihood. The resulting estimator is consistent if any one of those multiple models is correctly specified, and thus provides multiple protection on consistency. Moreover, the proposed estimator can attain the semiparametric efficiency bound when one propensity score model and one outcome vector model are correctly specified, without requiring knowledge of which models are correct. Simulations are performed to evaluate the finite sample performance of the proposed estimators. As an application, we analyze the data collected from the AIDS Clinical Trials Group Protocol 175.

Hypertension as a predictor of advanced colorectal cancer outcome and cetuximab treatment response.

Adrenergic receptor stimulation is involved in the development of hypertension (htn) and has been implicated in cancer progression and dissemination of metastases in various tumours, including colon cancer. Adrenergic antagonists such as beta-blockers (bbs) demonstrate inhibition of invasion and migration in colon cancer cell lines and have been associated with decreased mortality in colorectal cancer (crc). We examined the association of baseline htn and bb use with overall (os) and progression-free survival (pfs) in patients with pretreated, chemotherapy refractory, metastatic crc (mcrc). We also examined baseline htn as a predictor of cetuximab efficacy. Using data from the Canadian Cancer Trials Group co.17 study [cetuximab vs. best supportive care (bsc)], we coded baseline htn and use of anti-htn medications, including bbs, for 572 patients. The chi-square test was used to assess the associations between those variables and baseline characteristics. Cox regression models were used for univariate and multivariate analyses of os and pfs by htn diagnosis and bb use. Baseline htn, bb use, and anti-htn medication use were not found to be prognostic for improved os. Baseline htn and bb use were not significant predictors of cetuximab benefit. In chemorefractory mcrc, neither baseline htn nor bb use is a significant prognostic factor. Baseline htn and bb use are not predictive of cetuximab benefit. Further investigation to determine whether baseline htn or bb use have a similarly insignificant impact on prognosis in patients receiving earlier lines of treatment remains warranted.

MCRN¯003/MYX·1: A Single Arm Phase II Study of High-Dose Weekly Carfilzomib Plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma after 1-3 Prior Therapies

Background: Carfilzomib, a second generation proteosome inhibitor, is effective in the treatment of relapsed and refractory multiple myeloma (RRMM). Recent phase II and phase III trials have demonstrated the efficacy of weekly dosing strategies. The aim of this study was to examine high dose once weekly carfilzomib in combination with weekly dexamethasone and low dose weekly cyclophosphamide (wCCD) in RRMM. It was hypothesized that this may offer a potent yet convenient and more financially viable triplet-based treatment option than existing combinations.Methods: The MCRN-003/MYX.1 multi-centre single arm phase II clinical trial is run through the Myeloma Canada Research Network (MCRN) with support from the Canadian Cancer Trials Group (CCTG). Patients who had at least one but not more than three prior lines of therapy and who did not have proteosome inhibitor (PI) refractory disease were eligible. Treatment consists of carfilzomib (20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28-day cycle, plus weekly oral dexamethasone 40 mg and cyclophosphamide 300 mg/m2 capped at 500 mg on days 1, 8, 15 and 22. Treatment continues until progression or intolerance, except for cyclophosphamide which is discontinued after 12 cycles. The total sample size of 76 patients includes a 6 patient lead-in phase where safety at 70 mg/m2 was evaluated. The primary objective was to observe an overall response rate (ORR) ≥ 80% after 4 cycles of protocol therapy. Secondary endpoints include safety, toxicity, kinetics of and maximal response depth and overall survival. This analysis is based on the locked data base of 2018 July 13.Results: Of the 76 patients accrued 1 was subsequently determined to be ineligible on the basis of bortezomib refractory disease, and 1 did not receive any protocol therapy due to a cardiac event occurring post-study registration but prior to treatment commencement. All patients who received therapy were included in the analysis as per protocol inclusive of the bortezomib exposed patient. Among these 75 patients, median age was 66 years with 33% being > 70 years of age. Thirty-seven percent were female. Thirty-nine percent received 1 prior line, 44% received 2 prior lines and 17% received 3 prior lines of therapy. High risk cytogenetics [(t4;14), t(14;16) and del P53] were identified in 32%. Twenty percent had ISS stage III disease and 11% had R-ISS stage III disease. Prior PI and immunomodulatory drug exposure was noted in 87% and 81% respectively.Within the first 4 cycles of therapy 84% (95% CI, 76-92%) of patients achieved PR or better, with ≥ VGPR achieved in 52% and ≥ CR in 9% (table 1, p = 0.0006). There was a trend toward a better ORR after 4 cycles based on the presence or absence of high-risk cytogenetics (75% vs 94% respectively, p = 0.051) not meeting statistical significance. The median duration of follow-up at the time of data analysis was 13.9 months (range 0.2 to 22.8 months). 18 patients have died with an estimated 1-year OS of 80%. The cause of death as assessed by the investigator was myeloma in 13 patients with 3 dying from a cause possibly or probably related to the study intervention.During the first 4 cycles of treatment, non-hematologic toxicity ≥ grade 3 occurred in 33% of patients; most commonly infection (16%) and fatigue (7%). Grade 3/4 anemia was observed in 17%, thrombocytopenia in 33% and neutropenia in 20%. Grade 3 or greater hypertension was seen in 4%, dyspnea in 1%, pulmonary edema in 1% and thrombotic microangiopathy in 4%; all resolved with no long-term sequelae. To date 37 (49%) patients have discontinued carfilzomib, 11 due to toxicity and 16 due to disease progression.Conclusion: This prospective phase II study demonstrates that wCCD is a safe and effective regimen in the treatment of RRMM. The study met its primary endpoint demonstrating a ≥ 80% ORR after 4 cycles of therapy. These results compare favourably to published phase III data examining weekly carfilzomib and dexamethasone as well as the established twice-weekly dosing strategies. This regimen will be a useful triplet-based option for RRMM especially in patients refractory to immunomodulatory agents who would otherwise be ineligible for the carfilzomib-lenalidomide-dexamethasone combination. [Display omitted] DisclosuresVenner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria. Leblanc:Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Sandhu:Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Bioverativ: Honoraria. White:Amgen, Celgene, Janssen, Takeda: Honoraria. Chen:Amgen: Honoraria. Louzada:Celgene: Honoraria; Janssen: Honoraria; amgen: Honoraria; pfizer: Honoraria. Hay:Amgen: Research Funding; Novartis: Research Funding; Janssen: Research Funding; Roche: Research Funding; Seattle Genetics: Research Funding; Kite: Research Funding.

Prognostic Significance of Neutrophil to Lymphocyte Ratio (NLR) in Relapsed/Refractory Aggressive Lymphoma Salvage Chemotherapy — Analysis ofCanadian Cancer Trials Group (CCTG)ly.10 Trial

Background: The neutrophil to lymphocyte ratio (NLR) at the time of diagnosis has been shown as a prognostic marker to predict outcomes of treatment in patients with aggressive lymphoma in both non-Hodgkin (NHL) and Hodgkin lymphoma (HD). The growing evidence that tumor microenvironment, host immunity and inflammatory responses play an important role in progression of different malignancies supports this rationale. The prognostic significance of NLR has only been studied in the frontline setting in HD and NHL. Therefore the aim of this study is to evaluate correlation of NLR with response to salvage therapy in patients with relapsed or refractory aggressive lymphoma.Methods: This is a retrospective review of participants in the CCTG LY.10 trial, a phase 2 clinical trial evaluating treatment with Gemcitabine, Dexamethasone and Cisplatin (GDP) in patients with relapsed or refractory NHL and HD who are eligible for Autologous Stem Cell Transplantation (ASCT). Seventy-seven patients were treated with GDP, 23 with HD and 51 with NHL. The overall response rate (ORR) including complete and partial response to GDP salvage therapy was 69.5% in HD and 49% in NHL. NLR was calculated on all patients at the time of relapse. Biomarker Threshold Models (Chen et al, 2014, Computational Statistics and Data Analysis, V71, page 324-334) were applied to identify the optimal cut off point for NLR. Categorical variables were compared using Chi-square test and survival distributions were compared using KM curves and Log-rank test.Results:A NLR of 8.4 was determined to be the optimal cut-off for prognosis. Among the full cohort of 77 patients, ORR in those with a NLR of < 8.4 was 70.6%, as compared with 33.4% for those with a NLR of > 8.4 (p=0.005). In the HD cohort the RR was 86.7% vs 50% (P =0.059) and was 63.9% vs 26.7% in the NHL cohort (P =0.015). In NHL the ability to proceed to transplant was correlated with NLR of <8.4 with 52.7% vs 20% of patients proceeding to ASCT (P = 0.031). All patients with HD proceeded to transplant regardless of their NLR. Patients with NLR <8.4 had better progression free survival (PFS) at 12 months; 100% vs 71% in patients with HD (P = 0.028) and 27 % vs 11% in patients with NHL (P =0.05).Conclusion:NLR is a readily available marker correlated with outcomes (ORR, transplant rate and PFS) and can be used to identify high risk patients at the time of relapse of aggressive lymphoma. This easily measurable prognostic marker would be especially useful in the era of novel treatment options to identify higher risk patients. Further analysis on larger data sets are required to validate this finding. DisclosuresHay:Seattle Genetics: Research Funding; Roche: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Amgen: Research Funding; Kite: Research Funding. Baetz:Merck: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding.

Establishing a multidisciplinary AIDS-associated Kaposi's sarcoma clinic: Patient characteristics, management and outcomes.

Kaposi's sarcoma (KS) typically occurs in the setting of immunodeficiency and specifically in the presence of HIV infection, when it is called AIDS-associated KS (AIDS-KS). In spite of impressive gains in the South African (SA) antiretroviral therapy (ART) roll-out programme since 2004, AIDS-KS still causes significant morbidity and mortality, and the treatment of advanced disease can be challenging owing to the centralisation of oncology services and the high incidence of concurrent infections. In 2014, a multidisciplinary AIDS-KS clinic (MKSC) was established at Tygerberg Hospital, Cape Town, with the goal of optimising management of AIDS-KS patients. To report on the characteristics and outcomes of patients seen during the first 6 months after the inception of the MKSC. A retrospective observational study was performed of all new cases referred to the MKSC from February to August 2014. Forty-two patients were included in the study. The median age was 34 years (range 20 - 60). Forty-one patients were on ART at time of diagnosis or were initiated by a median of 3 months after diagnosis. The median CD4+ count before diagnosis was 147 cells/µL (range 4- 811). The HIV viral load was undetectable in 22 cases (52.4%). Thirty-eight patients (90.5%) were classified as AIDS Clinical Trials Group (ACTG) poor risk, 10 patients (23.8%) had visceral KS, 14 patients (33.3%) were on tuberculosis (TB) treatment at time of presentation, and 22 patients (52.4%) received oncological therapy in addition to ART. After median follow-up of 25.6 months, 2-year overall survival (OS) was 61.1%. On univariate analysis, factors significantly associated with poor 2-year OS included ACTG S1 stage (S = systemic illness), visceral KS, being on TB treatment, and Eastern Cooperative Oncology Group performance status score &gt;2. In the T1 (T = tumour extent) subgroup, receiving chemotherapy was significantly associated with improved 2-year OS. Advanced AIDS-KS significantly affects young people in the Western Cape Province of SA despite 10 years of ART roll-out. There is a high prevalence of concomitant TB infection that could adversely affect adherence and response to treatment. Despite advanced disease at presentation and palliative treatment intent, survival outcomes are encouraging and seem to be positively affected by the increased use of chemotherapy. A multidisciplinary approach to diagnosis, staging and treatment and the exploration of prognostic indices specific to the sub-Saharan setting would be valuable in designing appropriate treatment algorithms.

568. The Impact of Disclosure Stigma on Virologic Outcomes in People Living with HIV

BackgroundHIV-related stigma is a leading barrier to engagement in HIV care and successful treatment. Disclosure Stigma (DS), the fear of disclosing one’s serostatus, is associated with poor adherence and retention in care, but its association with clinical indicators of HIV treatment is not well established. The purpose of this study was to determine the influence of DS on virologic suppression, and our hypothesis was that DS would be associated with lack of virologic suppression.MethodsThis cross-sectional study was performed between May 2015 and February 2016, at the largest publicly funded HIV clinic in South Texas. A survey was administered to consecutively recruited participants at routine follow-up who were: ≥18-years-old, HIV+, and receiving antiretroviral therapy. Surveys included demographics, sexual/HIV history, AIDS Clinical Trials Group baseline adherence questionnaire, and a validated HIV-stigma scale. Clinical data were obtained from medical records. The primary predictor was DS: the sum of 10 items ranked 0–4, with maximum score of 30 indicating highest stigma. The primary outcome was lack of virologic suppression (LOVS): most recent HIV-1 RNA>20 copies/mL. Bivariate analyses were conducted to examine: (i) predictors of DS and (ii) predictors of LOVS. Multivariate logistic regression models examined the relationship between DS and LOVS.ResultsFor 275 participants, median DS score was 18.5 (IQR 13, 23). In bivariate analysis, depression (OR 1.10; CI 1.05, 1.15) and perceived stress (OR 1.04; CI 1.01, 1.08) were significantly associated with increased DS. However, dissatisfaction with help received by friends/family was associated with reduced odds of DS (OR 0.46; CI 0.27, 0.78). DS was significantly inversely associated with LOVS (OR 0.96; CI 0.92, 0.99) and age (OR 0.97; CI 0.95, 0.998), and positively associated with drug use (OR 3.96; CI 1.53, 10.23). The association between DS and LOVS was maintained after adjusting for age, gender/sexual orientation, race/ethnicity, and drug use.ConclusionDS was highly prevalent in this cohort. The unanticipated inverse association between DS and LOVS highlights the complexity of this relationship. Despite this association, the balance of data in this cohort demonstrates an overall negative impact of DS. Further study is needed to understand this surprising finding.Disclosures All authors: No reported disclosures.

583. Demographic Factors and Clinical Outcomes Associated with Mental Health Medication Use in People Living with HIV

BackgroundMental health (MH) conditions and pain are common among people living with HIV (PLWH). An understanding of factors associated with prescriptions for these conditions and clinical impact of the prescriptions may improve care of MH disorders in PLWH.MethodsThe use of mental health/pain-related medications was examined among PLWH within the AIDS Clinical Trials Group A5322 (HAILO) study. Use of medications (any use and class) was compared by sex. Multivariable logistic models estimated the association between MH medications (any/none) with (i) insurance status and race/ethnicity and (ii) baseline and incident slow gait (>1 second/m) and neurocognitive impairment (NCI) over 4 years.ResultsOf 1035 participants, the median age was 51. 81% were men, 30% black, and 20% Hispanic. Similar numbers of men (34%) and women (38%) were on MH medications (P = 0.19).Women were more likely to be prescribed opioids (12% vs. 5%; P < 0.001); other classes were similar. In multivariable models, MH-medicated PLWH were more likely to have Medicare (odds ratio [OR] 2.50, 95% CI 1.50–4.16, P < 0.001) or public insurance (1.85; 1.23–2.78, P = 0.003) vs. no/unknown insurance; and less likely to be Hispanic vs. white (0.48; 0.33–0.69; P < 0.001). MH-medicated PLWH had greater odds of baseline slow gait (1.80; 1.34–2.40; P < 0.001). The sex-specific ORs for NCI were qualitatively different (men: 1.70; 1.09–2.66; women: 0.96; 0.43–2.18); but this difference was not significant in the multivariable model (P interaction = 0.227). There was an increased risk of incident slow gait among MH-medicated men but not women (hazard ratio 1.74; 1.22–2.48 vs. 0.76; 0.38–1.52, P interaction = 0.038), and a trend toward increased risk of incident NCI (1.76; 0.91, 3.39, P = 0.09) for both sexes.ConclusionOur results highlight socioeconomic and ethnic differences in prescription of MH medications. The higher proportion of opiate prescriptions among women needs confirmation and should be a priority for intervention. The greater risk of baseline NCI and incident slow gait among men may be the result of differences in toxicity, drug interactions, or persistent mental health symptoms; further investigation is needed to optimize outcomes in PLWH and prescription of mental health medications.Disclosures All authors: No reported disclosures.

Pilot study of the ability to probabilistically link clinical trial patients to administrative data and determine long-term outcomes.

Clinical trials are important but extremely costly. Utilization of routinely collected administrative data may simplify and enhance clinical trial data collection. The aim of this study was to test the feasibility of use of administrative databases in Ontario, Canada, for long-term clinical trial follow-up, specifically (a) to determine whether limited patient identifiers held by the Canadian Cancer Trials Group can be used to probabilistically link with individuals in the Institute for Clinical Evaluative Sciences databases and if so, (b) the level of concordance between the two data sets. This retrospective study was conducted through collaboration of established health service (Institute for Clinical Evaluative Sciences) and clinical trial (Canadian Cancer Trials Group) research groups in the province of Ontario, Canada, where healthcare is predominantly funded by the government. Adults with pre-treated metastatic colorectal cancer previously enrolled in the Canadian Cancer Trials Group CO.17 and CO.20 randomized phase III trials were included, limited to those in Ontario. The main outcomes were rate of successful probabilistic linkage and concordance of survival data, stated a priori. Probabilistic linkage was successful in 266/293 (90.8%) participants. In those patients for whom linkage was successful, the Canadian Cancer Trials Group (trial) and the Institute for Clinical Evaluative Sciences (administrative) data sets were concordant with regard to the occurrence of death during the period of clinical trial follow-up in 206/209 (98.6%). Death was recorded in the Institute for Clinical Evaluative Sciences, but not the Canadian Cancer Trials Group, for 57 cases, where the event occurred after the clinical trial cut-off dates. The recorded date of death matched closely between both databases. During the period of clinical trial conduct, administrative databases contained details of hospitalizations and emergency room visits not captured in the clinical trial electronic database. Prospective use of administrative data could enhance clinical trial data collection, both for long-term follow-up and resource utilization for economic analyses and do so less expensively than current primary data collection. Recording a unique identifier (e.g. health insurance number) in trial databases would allow deterministic linkage for all participants.

Nitrogen response models for winter cereals grown for forage

AbstractForage double cropping can increase production, reduce erosion risk and improve soil health. Farmer experience in the north‐eastern USA shows that winter cereals can, in 3–4 weeks (Feekes 9 harvest), produce high quality forage given sufficient N at dormancy break. Here, we evaluate crop response models to determine the most economic rate of N (MERN) for forage winter cereals. Sixty‐three on‐farm N‐rate trials (0, 34, 67, 101, 135 kg N/ha) were conducted in New York from 2013 to 2016. Trials were divided into four categories: (a) no yield response to N (group 1; 20 trials); (b) yield plateau exceeded the highest N rate (group 2; one trial); (c) the MERN was below the lowest N rate (group 3; seven trials) and (d) all other N‐responsive trials (group 4; 35 trials). For group 4, three statistical models were compared (quadratic plateau, exponential and square root plateau). Statistical, environmental and economic criteria showed that the quadratic plateau fits the data best and had the most stable predictions across scenarios. The four‐category analysis is effective in determining MERNs of individual trials, and the quadratic plateau is best for determining forage winter cereal MERNs and yields at MERNs for individual trials in the north‐eastern USA.

Can administrative data improve the performance of clinical trial economic analyses?

2 Background: Economic analyses of trials often rely on trial-collected health resource utilization data, which is expensive and may be incompletely recorded. We investigated whether routinely collected health administrative data (RCD) can be utilized to improve trial economic analysis performance. Methods: Health administrative data was probabilistically linked to Ontario patient data from the Canadian Cancer Trials Group CO.17 trial (n = 572), evaluating cetuximab plus best supportive care (n = 75 linked Ontario patients) versus best supportive care alone (n = 73). Completeness of trial data was compared to RCD. Cost-effectiveness in 2007 Canadian dollars was determined using RCD up to trial date of last contact (DOLC), and up to RCD DOLC. Incremental cost effectiveness ratio (ICER) confidence intervals (CI) were determined using bootstrapping with 5000 iterations. Cost-effectiveness acceptability curves were determined. Sensitivity analyses were performed. Results: Among 148 Ontario patients, up to trial DOLC, RCD vital status was concordant in &gt; 96%. 29 deaths occurred after trial DOLC. Up to trial DOLC there were 34 net additional hospitalizations in RCD, and 28 net additional emergency room visits. Using RCD, total cetuximab group costs were $3,023,034, and $1,191,118 for best supportive care alone up to trial DOLC. Cost difference was driven by cetuximab drug costs ($1,531,370). Using RCD, the ICER was $211,128 per life-year gained (90% CI: $101,396, $694,950) when data was limited to trial DOLC, and $164,378 (90% CI: -$138,260, $644,555) using routinely collected data DOLC. ICER estimates were similar to the original economic analysis using trial-collected data ($199,742 (95% CI $125,973, $652,492)). Estimates were robust in sensitivity analysis. Conclusions: Administrative data were more complete than trial-collected utilization data, even under optimal conditions. There was also longer follow-up. We found that cost differences were robust to varying costing assumptions. Our findings demonstrate the potential of administrative data sources to relieve institutions, sponsors and patients from the burden of collecting key utilization information which requires considerable effort and cost.

Patterns of Inguinal Lymph Node Metastases in Anal Cancer: Recommendations for Elective Clinical Target Volume (CTV) Delineation

In the era of conformal radiotherapy for anal cancer, the optimal CTV for inguinal lymph node irradiation remains uncertain. The purpose of this study was to document the location of radiographically involved inguinal lymph nodes in patients with anal canal cancer and to propose guidelines for elective inguinal CTV delineation. Patients with squamous cell carcinoma of the anal canal with inguinal lymph node metastases presenting to our institution between 2003 and 2017 were identified from a departmental database. Inguinal lymph nodes were considered involved based on at least one of the following: >1.5 cm on computed tomography (CT) or magnetic resonance imaging (MRI), FDG avidity greater than background liver on positron emission tomography (PET), or positive histology from lymph node biopsy. Distances from the center of the involved lymph node to the closest adjacent femoral vessel and to the inferior extent of the primary tumor were measured on a pre-treatment diagnostic imaging study. Position of lymph nodes relative to the right femoral vessels was recorded on a clock face with 12:00 anterior, 3:00 medial, 6:00 posterior, and 9:00 lateral. The anatomic location of each lymph node was transferred onto a representative CT scan of a patient in treatment position and compared to the inguinal lymph node CTV in the Australasian Gastrointestinal Trials Group (AGITG) consensus guidelines for intensity-modulated radiotherapy for anal cancer. We identified 41 patients with 81 positive inguinal lymph nodes. Median lymph node size was 16.1 mm (range 7-59 mm) in short axis and 21.4 mm (range 10-65 mm) in long axis. Median distances from the nearest femoral artery and vein were 19.8 mm (range 8-40 mm) and 17.1 mm (range 8-46 mm), respectively. Median distance from the inferior aspect of the primary tumor was 47.9 mm (range 4-108 mm). Relative to the femoral vessels, lymph nodes were located at 12:00 (n=7); 1:00 (n=28); 2:00 (n=35), 3:00 (n=5); 4:00 (n=1); 10:00 (n=1); 11:00 (n=4). No lymph nodes were identified in the 5:00-9:00 positions (lateral or posterior to the vessels). Volumes contoured according to AGITG consensus guidelines covered 70% of lymph nodes anteriorly and 85% of lymph nodes medially. Margins from the nearest femoral vessel required to cover 90% and 95% of lymph nodes were 29 mm and 30 mm anteriorly and 25 mm and 26 mm medially, respectively. Inferior borders of the inguinal CTV required to cover 90% and 95% of lymph nodes were 18 mm and 12 mm, respectively, from the inferior aspect of the primary tumor. Published guidelines for CTV delineation of the inguinal lymph node region in anal cancer may result in inadequate coverage of high-risk areas. Updated contouring guidelines based on the present study would ensure coverage of areas at high risk for harboring metastatic disease and may reduce toxicity by sparing low-risk areas.