Citations

Abstract Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT–comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, <1-99 days]; RIC/NMA, 21 days [range, <1-100 days]; P < .001). Patients receiving MAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95% CI, 36-42]; P = .046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P < .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCT was greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P < .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.

Abstract Background Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). Methods FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. Results There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (−7.6 points, P = 0.02) and mobility (−4.2, P = 0.02), the number of reported symptoms was associated with worse depression (−2.7 per symptom, P = 0.009) and anxiety (−2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (−2.8 per visit, P < 0.001) and fatigue (−2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P = 0.03). Conclusions PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.

Abstract Background: Aromatase inhibitors are a mainstay hormone receptor-positive breast cancer treatment. AIA occur in up to 50% of patients (pts), adversely affecting quality of life and treatment compliance. A small phase II clinical trial of oral testosterone unedeconate appeared to improve AIA over placebo (P), with no significant androgenic side effects. The current study was performed to confirm these findings. Methods: This randomized P-controlled trial enrolled postmenopausal women on adjuvant anastrozole or letrozole and experiencing moderate-to-severe AIA (≥5 on 0-10 scale). Pts were initially randomized to receive a subcutaneous pellet containing T 120 mg + anastrozole 8 mg (T+AIpellet) or P at the end of the first week on study (after obtaining baseline hot flash data) and at 3 months (mo). Due to slow accrual, the protocol was amended to change the route of delivery to topical T or P applied to the skin once daily for 6 mo. Baseline and monthly questionnaires were administered, including: Modified Brief Pain Inventory for aromatase arthralgia (BPI-AIA), prolife of mood states (POMS), the menopause specific quality of life questionnaire (MENQOL), a hot flash diary, the hot flash related daily interference scale (HFRDIS) and a symptom experience questionnaire. The primary endpoint was intra-patient change in joint pain at 3 mo, compared using a two-sample t-test. Results: 227 pts were accrued between 9/1/2013-11/29/2017. 55 pts were randomized prior to the protocol amendment and received T+AIpellet or P. Baseline characteristics were balanced between arms, with the exceptions of median weight, BMI, hemoglobin (all higher in T arm), and breast tenderness, dissatisfaction with personal life/depression, and skin changes (all higher in P arm). Compared to baseline, there were no significant differences between T and P in average pain or joint stiffness at 3 (p=0.483) or 6 mo (p=0.573). Average pain was significantly lower each month compared to baseline, irrespective of treatment arm. There were no significant differences in any other items evaluated by BPI-AIA, POMS, MENQOL, hot flash diary or HFRDIS. Similarly, there were no substantial differences in toxicity. A subset analysis of the 55 pts randomized to receive T+AIpellet or P identified significant reductions in average pain scores with T+AIpellet during the first month (p=0.038), but not thereafter. T+AIpellet pts had significantly more reduction in reported % of baseline hot flash frequency (p=0.034) and score (p=0.031), nausea (p=0.019), fatigue (p=0.042), mood swings (p=0.026), hand/feet swelling (p=0.009), stress urinary incontinence (p=0.039) and changes in appearance, texture or tone of their skin (p=0.0083), than pts on P. Conclusions: Overall, T did not improve AIA or menopausal symptoms compared to P. While there was significant improvement in AIA over the study period, T did not facilitate this process. However, T+AIpellet was associated with improvement in short-term AIA and several menopausal symptoms compared to P, suggesting that subcutaneous T combined with anastrozole may be superior to transdermal T alone. Support: UG1CA189823, U10CA180820, U10CA189809; ClinicalTrials.gov Identifier: NCT01573442 Citation Format: Leon-Ferre RA, Le-Rademacher J, Terstriep S, Glaser R, Novotni P, Giuliano A, Copur MS, Jones C, Page S, Mitchell W, Birrell SN, Loprinzi CL. A randomized, double-blind, placebo-controlled trial of testosterone (T) for aromatase inhibitor-induced arthralgias (AIA) in postmenopausal women: Alliance A221102 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-01.

Abstract Background: Neoadjuvant chemotherapy is administered to patients with operable breast cancer to downstage the tumor to allow for less extensive surgery and to provide prognostic information about drug efficacy and risk of disease recurrence. Patients who achieve a pathological complete response (pCR) following neoadjuvant treatment have a more favorable outcome than patients with residual invasive disease. Single-agent poly(ADP-ribose) polymerase (PARP) inhibitors have clinical efficacy in BRCA-mutated breast cancer. Niraparib, a potent and selective PARP1/2 inhibitor, is approved for maintenance treatment of patients with recurrent ovarian cancer and has demonstrated strong antitumor activity in in vivo studies with BRCA1-mutant breast cancer. The objective of this study is to evaluate the antitumor activity of single-agent niraparib in the neoadjuvant treatment of patients with localized, human epidermal growth factor receptor 2 (HER2)-negative, BRCAmut breast cancer. Trial Design: This is an open-label, single-arm pilot study with a target enrollment of 20 evaluable patients. Eligible patients are those ≥18 years old with histologically-confirmed HER2-negative localized breast cancer and either a BRCA1 or BRCA2 mutation (germline or somatic) and no prior anti-cancer therapies for the current malignancy. Patients will receive 200 mg of oral niraparib once daily for 2 months, after which they may either proceed directly to surgery or receive chemotherapy at the discretion of the physician. The primary endpoint is tumor response rate based on the change in tumor volume as measured by breast MRI after 2 months of treatment with niraparib; a response is defined as ≥30% reduction of tumor volume from baseline. Secondary endpoints include pCR rate, tumor response rate based on the change in tumor volume as measured by breast ultrasound, and safety and tolerability. Data will be summarized in a descriptive nature by frequency distributions (number and percentage of patients) for categorical variables and by the mean, median, and standard deviation for continuous variables. Tumor response rate will be tabulated together with its 95% binomial exact confidence interval. Funding: TESARO, Inc., Waltham, MA, USA sponsored the study. Citation Format: Han H, Hamilton E, Irie H, Isakoff S, Jelovac D, Liem A, Liu MC, Milillo A, Nangia J, Page D, Reeves J, Santa-Maria C, Duncan M, Graham JR, Chen J, Dezube BJ, Spring L. Open-label, single-arm study evaluating the antitumor activity and safety of niraparib as neoadjuvant treatment in patients with localized, HER2-negative, BRCA-mutant breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-03-01.

Acute‐on‐chronic liver failure (ACLF) is characterized by multiple organ failure (OF) with high short‐term mortality. There is lack of population‐based data on trends on etiology specific ACLF related burden. National Inpatient Sample (2006‐2014) was queried using ICD‐09 codes for admissions with cirrhosis and ACLF (≥2 extrahepatic OF). Of 1,928,764 admissions for cirrhosis between 2006 and 2014, 112,174 (5.9%) had ACLF (4.5%, 1.2%, and 0.2% with ACLF 1, 2, and 3, respectively). The brain was the most common OF in 11.9%, followed by respiratory failure in 7.7%, cardiac failure in 6.3%, and renal failure in 5.6%. ACLF increased by 24% between 2006 and 2014 with a 63% increase in 179,104 patients with nonalcoholic steatohepatitis (NASH) cirrhosis (3.5% to 5.7%); a 28% increase in patients with 429,306 alcoholic cirrhosis (5.6% to 7.2%); a 25% increase in patients with 1,091,053 with other etiologies (5.2% to 6.5%); and no significant change in 229,301 patients with viral hepatitis (VH) (4.0% to 4.1%). In‐hospital mortality was higher among ACLF patients compared with patients without ACLF (44% versus 4.7%; P < 0.0001). Each NASH‐related ACLF patient compared with other etiologies had a longer mean length of stay (14 versus 12 days), was associated with higher median total charges (US $151,196 versus US $134,597), and had more frequent use of dialysis (45% versus 36%) and longterm care (32% versus 26%; P < 0.0001 for all). Results remained similar in a subgroup analysis after including half of admissions with cryptogenic cirrhosis as NASH. In conclusion, NASH cirrhosis is the most rapidly growing indication for ACLF‐related hospitalization and use of hospital resources. In the setting of improved treatment options for chronic hepatitis, the health care burden of chronic viral‐related liver disease remains stable. Population‐based strategies are needed to reduce the health care burden of cirrhosis, particularly related to NASH.

Background: Efforts to improve prescription of oral anticoagulation (OAC) drugs in patients with atrial fibrillation have had limited success in improving guideline adherence. Methods: We evaluated adherence to the American College of Cardiology/American Heart Association performance measures for OAC in eligible patients with a CHA 2 DS 2 -VASc score ≥2 and trends in prescription over time in the American Heart Association’s Get With The Guidelines–AFIB (atrial fibrillation) registry. Adjusted associations with in-hospital outcomes were also determined. The cohort included 33 235 patients with a CHA 2 DS 2 -VASc score ≥2 who were admitted for atrial fibrillation and were enrolled at 115 sites between January 1, 2013, and September 31, 2017. Results: The median (25th, 75th percentile) age was 73 years (65, 81 years); 51% were female; and the median (25th, 75th percentile) CHA 2 DS 2 -VASc score was 4 (3, 5). At admission, 16 206 (59.5%) of 27 221 patients with a previous diagnosis of atrial fibrillation were taking OAC agents, and OAC drug use at admission was associated with a lower adjusted odds of in-hospital ischemic stroke (odds ratio, 0.38; 95% CI, 0.24–0.59; P <0.0001). At discharge, prescription of OAC in eligible patients (no contraindications) was 93.5% (n=25 499 of 27 270). In a sensitivity analysis, when excluding only strict contraindications (4.6%, n=1497 of 32 806), OAC prescription at discharge was 80.3%. OAC prescription at discharge was higher in those aged ≤75 years, men, those with heart failure, those with previous atrial fibrillation ablation, and those with rhythm control ( P <0.0001 for all). OAC use was lowest in Hispanic patients (90.2%, P <0.0001). Prescription of OAC at discharge in eligible patients improved over time from 79.9% to 96.6% ( P <0.0001). Conclusions: Among hospitals participating in the GWTG-AFIB quality improvement program, OAC prescription at discharge in eligible guideline-indicated patients increased significantly and improved consistently over time. These data confirm that high-level adherence to guideline-recommended stroke prevention is achievable.

AbstractBackgroundThe study aims were to model acute pain intensity and opioid consumption trajectories up to 72 hr after open hepatic resection, identify predictors of trajectory membership and examine the association between trajectory memberships and 6‐month pain and psychological outcomes. This is a long‐term analysis of a published randomized controlled trial on the impact of medial open transversus abdominis plane catheters on post‐operative outcomes.MethodsA total of 152 patients (89 males; mean age 63.0 [range: 54–72]) completed questionnaires on pain and related characteristics pre‐operatively and 6 months post‐operatively. Total opioid use was recorded several times over a 72‐hr period while self‐reported pain intensity scores were collected multiple times until hospital discharge. Analyses were carried out using growth mixture modelling, logistic regression and general linear models.ResultsBoth pain intensity and opioid consumption showed that a four‐trajectory model best fits the data. Patients in the lowest opioid consumption trajectory were more likely to be classified in the constant mild pain intensity trajectory. Age and baseline levels of anxiety significantly predicted opioid trajectory membership while baseline depressive symptoms significantly predicted pain intensity trajectory membership. Patients in the two highest opioid consumption trajectories reported significantly higher levels of pain catastrophizing at 6 months compared to patients in the other 3 trajectories (all p < 0.05).ConclusionHigh consumption of opioids after surgery is associated with higher levels of pain catastrophizing 6 months later. Identification of patients within these trajectories may lead to the development of early interventions targeted to high risk individuals.SignificanceDifferences in initial levels of opioid consumption and rates of change in opioid consumption shortly after surgery can help predict long‐term psychological responses to pain. Identifying key characteristics associated with initial opioid consumption can lead to the development of cost‐effective early interventions targeted to high risk individuals.