Abstract Background Historically, the standard-of-care treatments for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC) have included targeted therapies, such as trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1), which have shown efficacy in clinical trials. Treatment choice and sequencing for patients with HER2+ mBC after first-line therapy have not been well delineated in the US real-world setting. Methods Patients who received at least two lines of therapy for HER2+ mBC diagnosed from January 2013 - April 2019 were selected from the Flatiron Health electronic health record-derived database. The Flatiron database is nationwide and comprises deidentified patient-level structured and unstructured data curated via technology-enabled abstraction in the US. The index date was the start date of the second line of therapy (2L). Treatment patterns from 2L onward were examined. Baseline information included disease stage at diagnosis and prior treatment for mBC. Duration of therapy was estimated using the Kaplan-Meier method. Results Among the 1390 patients with HER2+ mBC with a documented 2L therapy, the mean age at the initiation of 2L therapy was 60.4 years. Patients had one (n = 514; 37.0%), two (n = 390; 28.1%), or three or more (n = 461; 33.2%) metastatic sites by the start of 2L therapy. The most common metastatic sites were bone (n = 872; 62.7%), lung (n = 494; 35.5%), liver (n = 473; 34.0%), and brain (n = 223; 16.0%). The majority of patients (n = 1141; 82.1%) had positive hormone receptor status. Nearly half of patients (n = 601; 43.2%) had stage IV disease at their initial breast cancer diagnosis, 289 (20.8%) had stage III, and 277 (19.9%) had stage II. Before 2L therapy, 720 patients (51.8%) received a HER2-targeted combination therapy, 337 (24.2%) received hormone therapy alone, and 209 (15.0%) received HER2-targeted monotherapy. Among all included patients, 481 (34.6%) had two lines of systemic therapy for mBC, 359 (25.8%) had three, and 550 (39.6%) had four or more. Of these patients, 1290 (92.8%) had used a HER2-targeted agent (monotherapy or in combination) in at least one line of therapy, and 1108 (79.7%) had two or more lines of therapy containing a HER2-targeted agent. In 2L, the most frequently prescribed regimens were pertuzumab + trastuzumab + taxane (n = 246; 17.7%), T-DM1 monotherapy (n = 213; 15.3%), and trastuzumab monotherapy (n = 192; 13.8%). Overall, in 2L, 721 (51.9%) of all included patients received HER2-targeted combination therapy, 427 (30.7%) received HER2-targeted monotherapy, 82 (5.9%) received chemotherapy, and 118 (8.5%) received hormone therapy alone. Hormone therapy was combined with chemotherapy or targeted therapy in 622 patients (44.7%). Median (95% CI) duration of 2L therapy was 6 (6-6) months. Among the 909 patients who had third-line (3L) therapy, the most common regimens were T-DM1 (n = 170; 18.7%), pertuzumab + trastuzumab + taxane (n = 77; 8.5%), and hormone therapy alone (n = 59; 6.5%). Overall, in 3L, 446 patients (49.1%) had HER2-targeted combination therapy, 283 (31.1%) had HER2-targeted monotherapy, and 78 (8.6%) had chemotherapy, with hormone therapy added to chemotherapy or targeted therapy in 388 patients (42.7%). Median (95% CI) duration of 3L therapy was 5 (4-6) months. Conclusions The results of this real-world study of patients receiving care in community-based oncology clinics suggest that treatment patterns in later-line settings are variable, with no clear treatment approach for this patient population and patients often being re-treated with the same HER2-targeted therapies. As additional targeted therapies have recently been approved for HER2+ mBC with improvements in patient outcomes, future examination of the treatment landscape is warranted. Citation Format: Jenna Collins, Beth Nordstrom, Jackie Kwong, Brian Murphy, Melissa Pavilack. A real-world evidence study of treatment patterns among patients with HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-82.
The objective was to identify individuals with undiagnosed prediabetes from administrative data using adaptive techniques. The data source was a national Medicare Advantage Prescription Drug (MAPD) plan administrative data set. A retrospective, cross-sectional study developed and evaluated data adaptive logistic regression, decision tree, neural network, and ensemble predictive models for metabolic syndrome and prediabetes using 3 mutually exclusive cohorts (N = 279,903). The misclassification rate (MCR), average squared error (ASE), c-statistics, sensitivity (SN), and false positive (FP) rates were compared to select the final predictive models. MAPD individuals with continuous enrollment from 2013 to 2014 were included. Metabolic syndrome and prediabetes were defined using clinical guidelines, diagnosis, and laboratory data. A total of 512 variables identified through subject matter expertise in addition to utilizing all data available were evaluated for the modeling. The ensemble model demonstrated better discrimination (c-statistics, MCR, and ASE of 0.83, 0.24, and 0.16, respectively), high SN, and low FP rate in predicting metabolic syndrome than the individual data adaptive modeling techniques. Logistic regression demonstrated better discrimination (c-statistics, MCR, and ASE of 0.67, 0.13, and 0.11 respectively), high SN, and low FP rate in predicting prediabetes than the other adaptive modeling techniques or ensemble methods. The scored data predicted prediabetes in 44% of the MAPD population, which is comparable to 2005-2006 National Health and Nutrition Examination Survey prediabetes rates of 41%. The logistic regression model demonstrated good performance in predicting undiagnosed prediabetes in MAPD individuals.
Objective: To examine the association of obesity with healthcare resource utilization (HRU) and costs among commercially insured individuals. Methods: This retrospective observational cohort study used administrative claims from 1 January 2007 to 1 December 2013. The ICD-9-CM status codes (V85 hierarchy) from 2008 to 2012 classified body mass index (BMI) into the World Health Organizations’ BMI categories. The date of first observed BMI code was defined as the index date and continuous eligibility for one year pre- and post- index date was ensured. Post-index claims determined individuals’ HRU and costs. Sampling weights developed using the entropy balance method and National Health and Nutrition Examination Survey data ensured representation of the US adult commercially insured population. Baseline characteristics were described across BMI classes and associations between BMI categories, and outcomes were examined using multivariable regression. Results: The cohort included 9651 individuals with BMI V85 codes. After weighting, the BMI distribution was: normal (31.1%), overweight (33.4%), obese class I (22.0%), obese class II (8.1%) and obese class III (5.4%). Increasing BMI was associated with greater prevalence of cardiometabolic conditions, including hypertension, type 2 diabetes and metabolic syndrome. The use of antihypertensives, antihyperlipidemics, antidiabetics, analgesics and antidepressants rose with increasing BMI. Greater BMI level was associated with increased inpatient, emergency department and outpatient utilization, and higher total healthcare, medical and pharmacy costs. Conclusions: Increasing BMI was associated with higher prevalence of cardiometabolic conditions and higher HRU and costs. There is an urgent need to address the epidemic of obesity and its clinical and economic impacts.
Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer.Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor.Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group.The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.
Increasingly, helical CT is being used to screen trauma patients for aortic injury. Most aortic injuries visible at CT occur at or near the level of the ligamentum arteriosus; these injuries manifest as mediastinal hematoma, aortic contour deformity, intimal flaps, intraluminal debris, pseudoaneurysm, and pseudocoarctation. In the process of searching for aortic injury, however, the radiologist should not overlook other serious and more common thoracic injuries. Tracheobronchial tears appear at CT and radiography with persistent pneumothorax, subcutaneous emphysema, "fallen lung" sign, and malposition of endotracheal tube. The ruptured diaphragm, which tears more often on the left, appears asymmetric, irregular, or discontinuous, with herniation of bowel or viscera into the chest. In esophageal rupture, CT and radiography demonstrate left pneumothorax, pneumomediastinum, subcutaneous emphysema, and pleural effusion and atelectasis on the left. CT is better than trauma radiography for depicting fractures of the thoracic vertebral bodies and ribs, as well as for revealing pulmonary contusions and lacerations. CT is also useful for demonstrating unsuspected injuries caused by seat belts. Observation of these injuries should prompt a search for other serious internal organ injuries.
Introduction The current study surveyed collegiate student-athletes regarding their perceived level of importance surrounding 30 previously derived and empirically obtained athletic values to improve viability of sport psychological practices. Methods A total of 162 student-athletes enrolled in a private Midwestern NCAA Division 1 university within the United States of America completed tasks asking them to sort and rate utilized values based upon perceived importance surrounding athletic performance and sustained excellence. Results Results revealed a hierarchy of athletic values, favoring intrinsic values, useable when emphasizing the importance of value-driven behavior in applied sport psychological practices. Minimal differences were seen across gender, ethnicity, sport classification, and other comparative groups. Discussion Current results may help inform sport psychological practice while working within value-based frameworks.
Irritable bowel syndrome (IBS) patient care pathways are thought to vary, despite national clinical practice guidance in England. We present the findings of a multi-centre, observational, retrospective, cross-sectional, primary care research study to understand current patient pathways and quantify resource use.
Method
Primary care records were screened for potential study patients using FARSITE software at 8 participating practices in Salford and Greater Manchester.1Search criteria: patients aged 18–60; combination of READ code symptoms indicative of IBS and prescription of IBS medications 01/01/2009–31/12/2011. Inclusion criteria: medical diagnosis of IBS by GP or meeting ROME III criteria. Exclusion Criteria: diagnosis excluding IBS; IBS symptoms secondary to other condition; IBS medications only for non-GI symptoms. Data collected from date of study eligibility (above) to date of data collection. Ethical approval ref. 13/LO/0692.
Results
97/297 (33%) eligible patients provided consent for participation. Patient characteristics are shown in Table 1. There were a mean (SD) of 1.4 (1.4) visits to primary care per patient/year overall (range 0–9.4); with 2.9 (2.4) visits in 1styear (n = 24) and 0.8 (2.0) visits in 2ndyear (n = 33) after first presentation with abdominal symptoms. Overall 58 (60%) patients had an investigation; 45 (46%) had a blood test, 24 (25%) imaging, 25 (26%) endoscopic investigation. There were 53 sary/tertiary care referrals for IBS management in 32 (33%) patients; 18 (19%) patients were referred once, 14 (14%) patients >1 occasions, mean (SD) 0.15 (0.24) per patient/year overall. 8/53 (15%) referrals were with the presence of a red flag symptom (s). 26/32 (81%) patients were referred to Gastroenterology, 15/32 (47%) to Radiology. The mean (SD) number of drug treatments per patient/year overall was 0.74 (0.60). 72 (74%) patients received anti-spasmodics, 44 (45%) laxatives, 14 (14%) antidiarrhoeals and 6 (6%) antidepressants (specifically for IBS). 53 (55%) patients received a medication unlicensed for IBS management.
Conclusion
The ROME III criteria were inadequate for sub-typing 8% of patients, whose predominant presenting symptom was not constipation or diarrhoea. One in three patients was referred to secondary/tertiary care, the majority for non-red-flag symptoms; the appropriateness of these referrals warrants further investigation. Antispasmodics and laxatives were the most commonly prescribed medications, as expected. The use of antidepressants was less than anticipated although some may be receiving for depression. The high proportion of patients receiving unlicensed drugs suggests need for availability of licensed treatments specific for IBS.
Disclosure of interest
I. Caldwell: None Declared, J. Collins: None Declared, R. Dew Consultant for: Employee of pH Associates, commissioned by Almirall to provide research design, conduct analysis and provide scientific editorial services., M. Rance Employee of: Employee of Almirall UK Limited.
Reference
Caldwell I, et al. Abstract PWE-165, BSG Conference 2014. Gut 2014;63(Suppl 1):A1–A288
Purpose This viewpoint offers a perspective on the potential impact of an adapted yoga program for people with stroke-induced aphasia, with a call for additional work in this area. Conclusion Aphasia often results in decreased quality of life (QoL) from fewer social interactions, relationship strain between survivors and co-survivors, depression, and a multitude of other factors. We suggest a therapeutic yoga program for survivors and co-survivors could enhance several components of the dyad's lives that are frequently diminished as a result of aphasia, ultimately increasing QoL. In particular, we highlight the role of resilience and coping as essential tools on the rehabilitative journey in aphasia. After exploring yoga and other mind–body practices, we describe documented positive changes—including cognitive function, social integration, and QoL—following use of yoga in other chronic conditions. As people with communication deficits are typically excluded from these studies, further research is needed to establish whether these benefits generalize to people with aphasia.
Background Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are limited data regarding the prognostic significance of these mutations in a real-world setting. Methods This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). Results Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR [95% CI], 1.4 [0.9–2.3; p = 0.1]; second-line [subset of first-line cohort], HR, 1.6 [1.3–2.0; p = 0.0002]) or chemotherapy (first-line, HR, 1.4 [1.2–1.6; p < 0.0001]); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. Conclusions This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.
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