Real-world comparative effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer.

Aim: Provide real-world data on palbociclib as evidence of effectiveness in patient populations from routine clinical practice. Methods: This was a retrospective, observational cohort study of patients with HR+/HER2- metastatic breast cancer treated with palbociclib plus aromatase inhibitor (AI) or AI alone as first-line therapy within the US Oncology Network. Results: Patients treated with palbociclib plus AI (n = 838) versus AI alone (n = 450) had a numerically longer median overall survival (42.1 vs 35.7 months; hazard ratio [HR] = 0.90 [95% CI: 0.75-1.07]; p = 0.117) and a significantly extended real-world progression-free survival (21.0 vs 15.7 months; HR = 0.75 [95% CI: 0.64-0.88]; p = 0.0002) after normalized inverse probability treatment weighting. Conclusion: These real-world results support the use of palbociclib plus AI as first-line treatment in routine clinical practice for patients with HR+/HER2- metastatic breast cancer.

What is this summary about? This summary describes how well palbociclib works when used with an aromatase inhibitor in the real-world setting for people with a certain type of breast cancer that has spread to other areas of the body. Palbociclib stops cancer cells from growing and dividing. An aromatase inhibitor prevents the body from making the hormone estrogen, which is needed for certain types of breast cancer cells to grow. Palbociclib with an aromatase inhibitor is a standard first treatment used for people with this type of breast cancer that needs estrogen to grow and has spread to other areas of the body. In clinics, doctors may not always prescribe the two treatments together. The study wanted to find out if using the two treatments together worked better than using an aromatase inhibitor alone in the real-world setting. What were the results? The results suggest that in this population of patients treated in a real-world setting, people with breast cancer that needs estrogen to grow and has spread to other areas of the body who were treated with palbociclib plus an aromatase inhibitor lived longer without their cancer getting worse than those treated with an aromatase inhibitor alone. What do the results of the study mean? The results support the use of palbociclib with an aromatase inhibitor as a first treatment for breast cancer that has spread to other areas of the body, rather than an aromatase inhibitor only.

Real-World Tumor Response of Palbociclib in Combination With an Aromatase Inhibitor as First-Line Therapy in Pre/Perimenopausal Women With Metastatic Breast Cancer.

BACKGROUND: Limited real-world data exist regarding the efficacy of palbociclib in combination with endocrine therapy in pre/perimenopausal women with metastatic breast cancer. OBJECTIVE: We aimed to compare real-world tumor responses among pre/perimenopausal women who initiated palbociclib plus an aromatase inhibitor (AI) or AI monotherapy as first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. METHODS: This retrospective observational cohort study (NCT05012644) used electronic health record data from The US Oncology Network. Tumor responses were determined based on treating clinicians' assessments of radiologic evidence for changes in disease burden. Normalized inverse probability treatment weighting was used to balance baseline characteristics between treatment cohorts. RESULTS: Of 196 pre/perimenopausal women, 116 and 80 were in the palbociclib plus AI cohort and AI cohort, respectively. Real-world response rates (complete or partial response) were 52.1% and 46.2%, respectively (odds ratio, 1.27 [95% confidence interval 0.72‒2.24]). Among patients with one or more tumor assessments on treatment, real-world response rates were 60.0% in the palbociclib plus AI cohort (n = 103) and 49.9% in the AI cohort (n = 71; odds ratio, 1.51 [95% confidence interval 0.82‒2.77]). CONCLUSIONS: This real-world analysis suggests that pre/perimenopausal patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer appear more likely to respond to palbociclib plus AI versus AI alone as first-line therapy, which may support the combination as a standard-of-care treatment for this patient population.

Palbociclib (Ibrance^®) is a medicine for patients with metastatic breast cancer (MBC). Metastatic means that the cancer has spread to other places in the body. Patients take palbociclib with hormone therapy, such as an aromatase inhibitor (AI). Palbociclib plus an AI is a treatment for a type of MBC called HR+/HER2‒ MBC. HR+/HER2‒ stands for hormone receptor positive, human epidermal growth factor receptor 2 negative. Researchers wanted to observe responses to treatment in routine clinical practice among women with HR+/HER2­ MBC who had not reached menopause. A response is if a tumor shrinks or disappears after treatment. This study used healthcare information reported in electronic medical records of patients seen by doctors in The US Oncology Network. This study included 196 women with HR+/HER2­ MBC who had not reached menopause and had not received prior treatment for MBC. A total of 116 women received palbociclib plus an AI, and 80 women received an AI alone. Researchers used standard statistical approaches to balance baseline characteristics between the two treatment groups. These adjustments made the groups more similar so that researchers could compare treatment responses. Sixty percent of patients who took palbociclib plus an AI responded, compared with 50% of patients who took an AI alone. These results suggest that palbociclib plus an AI may benefit women with HR+/HER2‒ MBC who have not reached menopause.

Predictors of Neuropsychiatric Adverse Events with Smoking Cessation Medications in the Randomized Controlled EAGLES Trial.

BACKGROUND: Pre-treatment factors that increase smokers' risk of experiencing neuropsychiatric adverse events (NPSAEs) when quitting smoking are unknown. OBJECTIVE: To identify baseline smoker characteristics beyond the history of mental illness that predict which participants were more likely to experience moderate to severe NPSAEs in EAGLES. DESIGN: A prospective correlational cohort study in the context of a multinational, multicenter, double-blind, randomized trial. PARTICIPANTS: Smokers without (N = 3984; NPC)/with (N = 4050; PC) histories of, or current clinically stable, psychiatric disorders including mood (N = 2882; 71%), anxiety (N = 782; 19%), and psychotic (N = 386; 10%) disorders. INTERVENTIONS: Bupropion, 150 mg twice daily, or varenicline, 1 mg twice daily, versus active control (nicotine patch, 21 mg/day with taper) and placebo for 12 weeks with 12-week non-treatment follow-up. MAIN MEASURES: Primary safety outcome was the incidence of a composite measure of moderate/severe NPSAEs. Associations among baseline demographic/clinical characteristics and the primary safety endpoint were analyzed post hoc via generalized linear regression. KEY RESULTS: The incidence of moderate to severe NPSAEs was higher among smokers in the PC (238/4050; 5.9%) than in the NPC (84/3984; 2.1%). Three baseline characteristics predicted increased risk for experiencing clinically significant NPSAEs when quitting regardless of carrying a psychiatric diagnosis: current symptoms of anxiety (for every ~ 4-unit increase in HADS anxiety score, the absolute risk of occurrence of the NPSAE endpoint increased by 1% in both PC and NPC); prior history of suicidal ideation and/or behavior (PC, 4.4% increase; P = 0.001; NPC, 4.1% increase; P = 0.02), and being of White race (versus Black: PC, 2.9% ± 0.9 [SE] increase; P = 0.002; and NPC, 3.4% ± 0.8 [SE] increase; P = 0.001). Among smokers with psychiatric disorders, younger age, female sex, history of substance use disorders, and proxy measures of nicotine dependence or psychiatric illness severity also predicted greater risk. There were no significant interactions between these characteristics and treatment. Smokers with unstable psychiatric disorders or with current, active substance abuse were excluded from the study. CONCLUSIONS: Irrespective of cessation pharmacotherapy use, smokers attempting to quit were more likely to experience moderate to severe NPSAEs if they reported current anxiety or prior suicidal ideation at baseline and were White. In smokers with a psychiatric history, female sex, younger age, and greater severity of nicotine dependence were also predictive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01456936.

"Forgotten" Chapters in the History of Transcervical Sterilization: Carl Clauberg and Hans-Joachim Lindemann.

Transcervical sterilization is a non-surgical method of permanent female sterilization that is widely used and critically discussed. A review of the historiography of the method reveals that instances of its coercive use are not included in the historical account. This study offers a reexamination of the work of Carl Clauberg and Hans-Joachim Lindemann, to more deeply contextualize within the framework of current usage the coercive use of transcervical sterilization during the Third Reich and in postwar Germany. This inquiry is based on postwar criminal trial records on Clauberg, and on archival documents detailing Lindemann's activities in 1979. A comparative analysis examines arguments by medical historian Karl-Heinz Roth, and identifies shared characteristics and differences between Clauberg and Lindemann, their methods and scientific connections. The results demonstrate that the technique of transcervical sterilization has an abusive potential that may be explained as a function of the person of the physician, of the scientific method itself, and of societal and political influences. The analysis supports the argument that insights from the cases of Clauberg and Lindemann are transferrable geographically and over time, and have the potential to inform current medical practice, such as transcervical sterilization with the Essure device, whose historiographic exploration remains a desideratum.

Higher Antioxidant Activity, Total Flavonols, and Specific Quercetin Glucosides in Two Different Onion (Allium cepa L.) Varieties Grown under Organic Production: Results from a 6-Year Field Study.

We carried out a 6-year study to assess the effect of conventional, organic, and mixed cultivation practices on bioactive compounds (flavonoids, anthocyanins) and antioxidant capacity in onion. Total flavonoids, total anthocyanins, individual flavonols, individual anthocyanins, and antioxidant activity were measured in two varieties ('Hyskin' and 'Red Baron') grown in a long-term split-plot factorial systems comparison trial. This is the first report of repeated measurements of bioactive content over an extensive time period in a single crop type within the same trial. Antioxidant activity (DPPH and FRAP), total flavonol content, and levels of Q 3,4' D and Q 3 G were higher in both varieties under fully organic compared to fully conventional management. Total flavonoids were higher in 'Red Baron' and when onions were grown under organic soil treatment. Differences were primarily due to different soil management practices used in organic agriculture rather than pesticide/ herbicide application.

Evaluation of polyphenolic content and antioxidant activity in two onion varieties grown under organic and conventional production systems.

BACKGROUND: Onions contain a number of bioactive compounds, in particular polyphenols. They are rich sources of such compounds in the human diet and offer significant health benefits to the consumer. Demand for organic crops is steadily increasing partly based on the expected health benefits of organic food consumption. The current study examines the influence of organic and conventional crop management practices on bioactive polyphenolic content of onion. RESULTS: We examined the effect of conventional, organic, and mixed cultivation practices on the content of total phenolics, total flavonoids and antioxidant activity in two varieties of onion grown over 4 years in a split-plot factorial systems comparison trial. Levels of total phenolics and total flavonoids showed a significant year-on-year variation and were significantly different between organic and conventional production systems. The levels of total phenolics, total flavonoids and antioxidant activity in general were significantly higher (P < 0.05) under fully organic compared to fully conventional management. CONCLUSION: Organic cultivation practices resulted in significantly higher levels of potential bioactive compounds in onion. © 2016 Society of Chemical Industry.

Adverse Clinical Outcomes and Resource Utilization Associated with Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Infections after Elective Surgery.

BACKGROUND: Current studies of post-operative Staphylococcus aureus disease focus primarily on surgical site infections and are often limited to infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The objective of this retrospective cohort analysis was to describe the occurrence of and outcomes associated with post-operative MRSA and methicillin-sensitive S. aureus (MSSA) infections in patients undergoing elective surgical procedures. METHODS: Data were extracted from Health Facts for inpatients aged 18 years or older with pre-defined International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes, meeting additional criteria indicating that the procedure was elective. Post-operative S. aureus infection was identified by one or more qualifying culture positive for MRSA or MSSA. Multivariable regression models compared patients with MRSA, MSSA, and no S. aureus infection. RESULTS: Among 34,866 qualifying patients, the incidence of S. aureus infections was 0.9% during the index admission and 1.7% within 90 d after elective surgery, of which 36.6% and 38.4% were MRSA, respectively. The highest rates were observed among patients undergoing general surgery (2.2% during index admission, 3.2% within 90 d) and plastic surgery (1.8% during index admission, 3.1% within 90 d). Patients with MRSA and MSSA experienced poorer outcomes than uninfected patients, based on index admission length of stay (LOS; mean, 30.2, 22.7, and 5.7 d, respectively), hospital charges ($165,651, $134,313, and $52,077), and hospital mortality (odds ratios, 6.4 for MRSA, 4.8 for MSSA versus uninfected patients). Relative to MSSA infection, MRSA infection was associated with greater total hospital LOS and hospital charges but not with increased re-admission or mortality. CONCLUSIONS: The burden of post-operative S. aureus infection is shared among elective surgical procedures, however, rates and types of infections vary. Whereas MRSA infection results in substantially greater health care cost and LOS, mortality and re-admission rates are similar among patients with MRSA and MSSA. In elective surgery, infection control and surveillance for both MRSA and MSSA are warranted.

Variation in bioactive content in broccoli (Brassica oleracea var. italica) grown under conventional and organic production systems.

BACKGROUND: Broccoli and other cruciferous vegetables contain a number of bioactive compounds, in particular glucosinolates and polyphenols, which are proposed to confer health benefits to the consumer. Demand for organic crops is at least partly based on a perception that organic crops may contain higher levels of bioactive compounds; however, insufficient research has been carried out to either support or refute such claims. RESULTS: In this study we examined the effect of conventional, organic, and mixed cultivation practices on the content of total phenolics, total flavonoids, and total and individual glucosinolates in two varieties of broccoli grown over 2 years in a split-plot factorial systems comparison trial. Levels of total phenolics and total flavonoids showed a significant year-on-year variation but were not significantly different between organic and conventional production systems. In contrast, levels of the indolyl glucosinolates glucobrassicin and neoglucobrassicin were significantly higher (P < 0.05) under fully organic compared to fully conventional management. CONCLUSION: Organic cultivation practices resulted in significantly higher levels of glucobrassicin and neoglucobrassicin in broccoli florets; however, other investigated compounds were unaffected by production practices.

Cardiovascular safety of varenicline: patient-level meta-analysis of randomized, blinded, placebo-controlled trials.

Smoking is a major modifiable risk factor for cardiovascular (CV) disease. Varenicline is a pharmacological aid for smoking cessation. To explore the CV safety of varenicline, we investigated the incidence of CV events in varenicline-treated subjects across all phase 2-4 randomized placebo-controlled clinical trials of ≥12-week treatment duration conducted in smokers aged ≥18 years and sponsored by the drug manufacturer. This manuscript reports a subject-level meta-analysis of time to major adverse cardiovascular events (MACE; defined as CV-related death, nonfatal myocardial infarction, nonfatal stroke) and time to MACE+ (defined as MACE plus worsening or any procedure for peripheral vascular disease, hospitalization for angina, or performance of coronary revascularization). All events were adjudicated by an independent adjudication committee, blind to treatment assignment. Events were assessed during treatment and up to 30 days after the last treatment dose. The primary analytical method was a stratified logrank time-to-event analysis; secondary analyses were meta-analyses of incidence rate ratios and rate differences. Overall, 7002 subjects were included (varenicline: 4190; placebo: 2812) from 15 studies. MACE were reported by 13 varenicline subjects (0.31%) and 6 placebo subjects (0.21%) [hazard ratio, 1.95; 95% confidence interval (CI): 0.79-4.82; P = 0.15; risk difference, 0.006 events per subject-year; 95% CI: -0.003, 0.015, P = 0.19]. MACE+ were reported by 26 varenicline subjects (0.62%) and 12 placebo subjects (0.43%) (hazard ratio, 1.74; 95% CI: 0.91-3.34, P = 0.10; risk difference, 0.010; 95% CI: -0.002, 0.022, P = 0.11). This subject-level meta-analysis of MACE or MACE+ up to 30 days posttreatment in placebo-controlled clinical trials of varenicline found a trend toward increased incidence of these events in varenicline-treated patients that did not reach statistical significance. The overall number of events was low and the absolute risk of CV events with varenicline was small.

An inv(16) in Ph-negative cells of a chronic myelogenous leukemia patient after imatinib treatment.

Secondary chromosomal changes are known to develop in Philadelphia chromosome-negative (Ph-) cells of chronic myelogenous leukemia (CML) patients after treatment with imatinib mesylate, an ABL kinase inhibitor. We report here a novel case of a pericentric inversion of chromosome 16 as the sole cytogenetic abnormality in Ph- cells after treatment of Ph+ CML with imatinib.