Real-world treatment patterns for palbociclib plus an aromatase inhibitor, or an aromatase inhibitor alone, for patients with metastatic breast cancer in the Flatiron Database.

There are limited real-world comparative effectiveness data for palbociclib plus an aromatase inhibitor (AI) as a first-line (1L) treatment examining endpoints that require long term follow-up and post 1L progression. The Flatiron Health Analytic Database was used to characterize treatment and dosing patterns in patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) receiving palbociclib plus an AI vs an AI alone in routine US clinical practice. In addition, time to chemotherapy (TTC) and real-world progression-free survival (rwPFS) when combining 1L and second-line of therapy (rwPFS2) were assessed. Of 1324 patients who received palbociclib plus an AI between February 3, 2015 and March 31, 2020, 1110 (83.8%) started palbociclib at the recommended 125 mg/day dose. After stabilized inverse probability treatment-weighting (sIPTW), median TTC in patients treated with palbociclib plus an AI and AI alone was 37.4 months (95% confidence interval [CI], 33.7-40.7) and 29.2 months (95% CI, 26.8-33.5), respectively (hazard ratio [HR] = 0.77 [95% CI, 0.69-0.86], P < .0001); median rwPFS2 was 32.6 months (95% CI, 29.4-35.2) and 20.7 months (95% CI, 18.9-22.6), respectively (HR = 0.62 [95% CI, 0.54-0.70], P < .0001). Sensitivity analyses with propensity score matching showed similar results to sIPTW analyses. Results from this large real-world study examining additional effectiveness outcomes beyond 1L rwPFS and overall survival support the use of palbociclib plus an AI as a 1L treatment for patients with HR+/HER2- mBC.

Treatment outcomes in older patients with metastatic breast cancer receiving palbociclib plus an aromatase inhibitor: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary describes an article published in the medical journal Frontiers in Oncology in September 2023. The article reports results from a study that looked at breast cancer treatments for older patients aged 75 years or older. The study focused on a type of cancer called HR+/HER2- metastatic breast cancer. HR+/HER2- stands for hormone receptorpositive/human epidermal growth factor receptor 2-negative. This study evaluated whether older patients with this type of cancer benefited from the combination of two medicines - palbociclib and an aromatase inhibitor - compared with taking an aromatase inhibitor alone. HOW WAS THE STUDY IN THIS SUMMARY CARRIED OUT?: The Flatiron database contains medical records for people with cancer in the US. This study used deidentified health care information from this database. 'Deidentified' means that all information that could identify an individual was removed to protect individuals' privacy. People in this study received treatment in routine care and not in a clinical trial. WHAT DO THE RESULTS MEAN?: Older patients who took palbociclib plus an aromatase inhibitor lived longer than those who took an aromatase inhibitor alone. Older patients who took palbociclib plus an aromatase inhibitor also lived longer without their cancer getting worse and started chemotherapy later than those who took an aromatase inhibitor alone. These results support using palbociclib plus an aromatase inhibitor as the first treatment for patients aged 75 years or older with HR+/HER2- metastatic breast cancer.

This study evaluated outcomes in elderly patients with metastatic breast cancer treated in routine care. Overall, patients who took palbociclib plus an aromatase inhibitor (AI) lived longer, and lived longer without their cancer getting worse, than those who took an AI alone.

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.

Impact of COVID-19 on patients with metastatic breast cancer: REthink Access to Care and Treatment survey results.

Aim: Patients with metastatic breast cancer (MBC) may be vulnerable to changes in healthcare management, safety standards and protocols that occurred during the COVID-19 pandemic. Materials & methods: The REthink Access to Care & Treatment (REACT) survey assessed USA-based patient perspectives on COVID-19-related impacts to their MBC treatment experience between 27 April 2021 and 17 August 2021. Results: Participants (n = 341; 98.5% females, mean age 50.8 years) reported that overall oncology treatment quality was maintained during the pandemic. Delayed/canceled diagnostic imaging was reported by 44.9% of participants while telemedicine uptake was high among participants (80%). Conclusion: Overall, MBC care was minimally affected by the pandemic, possibly due to the expanded use of telemedicine, informing MBC management for future public health emergencies.

The COVID-19 pandemic has forced healthcare providers to change the way that healthcare is delivered. These changes could particularly affect people with metastatic breast cancer (MBC), an advanced stage of cancer that has spread to other parts of the body. The authors of this study used a web-based survey to ask 341 volunteers with MBC how the pandemic has affected their cancer treatment. The authors found that people with MBC thought that the quality of their care stayed the same during the pandemic. Most people (80%) surveyed were able to use telemedicine, the remote delivery of care by phone or computer, to replace in-person visits to their doctor. However, almost half of people surveyed reported delays or cancellation of their diagnostic imaging appointments. Overall, this study shows that the COVID-19 pandemic did not affect peoples' opinions of their MBC care. Increased use of telemedicine may have contributed to the lack of disruption in care. These findings will help guide MBC care during future public health emergencies.

Prolonging the lives of African-Americans with metastatic breast cancer by adding palbociclib to an aromatase inhibitor in routine clinical practice: a plain language summary of a real-world database study.

WHAT IS THIS SUMMARY ABOUT?: This summary is about a study that was published in the medical journal The Oncologist in July 2023. The combination of palbociclib with an aromatase inhibitor (AI) was approved by the FDA in 2015 as a treatment for people with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, the effectiveness of palbociclib in African-Americans with MBC is not well studied. The goal of this study was to find out whether adding palbociclib to an AI helped African-Americans with HR+/HER2- MBC live longer. WHAT ARE THE KEY TAKEAWAYS?: This study used de-identified medical information from the Flatiron Database. This database contains healthcare information on people with cancer treated by doctors in the United States but personal information is removed to maintain privacy. Medical information for people who received certain treatments in routine clinical practice or real-world setting was included in the study.This study showed that in the real-world setting, African-Americans with HR+/HER2- MBC lived longer when receiving palbociclib with an AI than with an AI alone. Also, the study showed that African-Americans treated with palbociclib plus an AI lived longer without their cancer getting worse than those treated with an AI alone. WHAT WAS THE MAIN CONCLUSION REPORTED BY THE RESEARCHERS?: These results support the use of palbociclib with an AI as a first treatment for African-Americans with HR+/HER2- MBC.Clinical Trial Registration: NCT05361655 (ClinicalTrials.gov).

Effectiveness of palbociclib plus an aromatase inhibitor in African Americans with metastatic breast cancer in routine clinical practice: a plain language summary.

OUHP: an optimized universal hairpin primer system for cost-effective and high-throughput RT-qPCR-based quantification of microRNA (miRNA) expression.

MicroRNAs (miRNAs or miRs) are single-stranded, ∼22-nucleotide noncoding RNAs that regulate many cellular processes. While numerous miRNA quantification technologies are available, a recent analysis of 12 commercial platforms revealed high variations in reproducibility, sensitivity, accuracy, specificity and concordance within and/or between platforms. Here, we developed a universal hairpin primer (UHP) system that negates the use of miRNA-specific hairpin primers (MsHPs) for quantitative reverse transcription PCR (RT-qPCR)-based miRNA quantification. Specifically, we analyzed four UHPs that share the same hairpin structure but are anchored with two, three, four and six degenerate nucleotides at 3'-ends (namely UHP2, UHP3, UHP4 and UHP6), and found that the four UHPs yielded robust RT products and quantified miRNAs with high efficiency. UHP-based RT-qPCR miRNA quantification was not affected by long transcripts. By analyzing 14 miRNAs, we demonstrated that UHP4 closely mimicked MsHPs in miRNA quantification. Fine-tuning experiments identified an optimized UHP (OUHP) mix with a molar composition of UHP2:UHP4:UHP6 = 8:1:1, which closely recapitulated MsHPs in miRNA quantification. Using synthetic LET7 isomiRs, we demonstrated that the OUHP-based qPCR system exhibited high specificity and sensitivity. Collectively, our results demonstrate that the OUHP system can serve as a reliable and cost-effective surrogate of MsHPs for RT-qPCR-based miRNA quantification for basic research and precision medicine.

Real-World Effectiveness of Palbociclib Plus Aromatase Inhibitors in African American Patients With Metastatic Breast Cancer.

BACKGROUND: Disparities in survival and clinical outcomes between African American and White patients with breast cancer (BC) are well documented, but African American patients have not been well represented in randomized clinical trials of CDK4/6 inhibitors. Real-world studies can provide evidence for effective treatment strategies for underreported patient populations. PATIENTS AND METHODS: This retrospective analysis of African American patients with HR+/HER2- metastatic breast cancer (mBC) from the Flatiron Health longitudinal database evaluated treatments for patients with BC in routine clinical practice in the US. Patients initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone between February 2015 and March 2020. Outcomes assessed included overall survival (OS) and real-world progression-free survival (rwPFS) until September 2020. RESULTS: Of 270 eligible patients, 127 (median age 64 years) were treated with palbociclib + AI, and 143 (median age 68 years) were treated with an AI. Median follow-up was 24.0 months for palbociclib + AI and 18.2 months for AI-treated patients. Median OS was not reached (NR; 95% CI, 38.2-NR) in the palbociclib + AI group versus 28.2 months (95% CI, 19.2-52.8) in the AI group (adjusted HR, 0.56; 95% CI, 0.36-0.89; P = .013). Median rwPFS was 18.0 months (95% CI, 12.4-26.7) in the palbociclib + AI group and 10.5 months (95% CI, 7.0-13.4) in the AI group (adjusted HR, 0.74; 95% CI, 0.47-1.17; P = .199). CONCLUSION: This comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2- mBC in real-world settings. TRIAL NUMBER: NCT05361655.

Prolonging the life of people with metastatic breast cancer in routine clinical practice by adding palbociclib to an aromatase inhibitor from a real-world database analysis: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article about a study called "P-REALITY X" that was published in the medical journal npj Breast Cancer in October 2022. "P-REALITY X" stands for Palbociclib REAl-world first-LIne comparaTive effectiveness studY eXtended. This study used information from a database to look at whether adding a second treatment (palbociclib) to an aromatase inhibitor (AI) helped people with a certain type of breast cancer to live longer. The type of breast cancer is metastatic hormone receptor-positive/human epidermal growth factor-negative breast cancer, also called HR-positive (or HR+)/HER2-negative (or HER2-) breast cancer. The study used information from the Flatiron Database. This database contains unidentified health care information collected from people seen by doctors in the USA. Only data from people who did not participate in a clinical trial were used. When people are treated outside of a clinical trial, this is called the real-world setting, or routine clinical practice. In clinical trials, people lived longer without their disease worsening if they were treated with palbociclib plus an AI versus being treated with an AI only. Based on the results of clinical trials, treatment with palbociclib plus an AI is already approved and recommended for people with HR+/HER2- breast cancer. This study looked at whether people lived longer if they were treated with palbociclib plus an AI versus being treated with an AI only in routine clinical practice as well. WHAT WERE THE RESULTS?: This study showed that, in routine clinical practice, people treated with the medicine palbociclib plus an AI lived longer than people treated with only an AI. WHAT DO THE RESULTS MEAN?: These results support the continued use of palbociclib plus an AI as the standard first medicine to be given to people with metastatic HR+/HER2- breast cancer. Clinical Trial Registration: NCT05361655 (ClinicalTrials.gov).

Vancomycin and Gentamicin Removal with the HA380 Cartridge during Experimental Hemoadsorption.

INTRODUCTION: Hemoadsorption has emerged as an adjunctive therapy for sepsis, but its impact on antibiotic levels remains poorly defined. We conducted an in vivo experimental study to investigate the removal of vancomycin and gentamicin during hemoadsorption using the HA380 cartridge, a novel styrene-divinylbenzene copolymer cartridge. METHODS: Six surgically prepared sheep were administered 2 g of vancomycin and 400 mg of gentamicin over 30 min, followed by a continuous infusion of vancomycin (20 mg/h). Hemoadsorption was implemented with a styrene-divinylbenzene copolymer HA380 cartridge at a blood flow of 120 mL/min. The removal ratio, sorbent-based clearance, and the mass removal rate were calculated for each time point. RESULTS: The mean 10-min vancomycin removal ratio exceeded 90% and declined to 68.0% at 30 min; 52.8% at 60 min, and 28.0% by 4 h. Due to constant plasma flow, clearance varied proportionally with the removal ratio. Over 4 hours, the total mass removal was 556 mg (SD 106.3). For gentamicin, the mean 10-min removal ratio was 96.9% and the final ratio at 4 h remained 53.0%, with clearances changing proportionately. The total mass removal of gentamicin was 138 mg (SD 26.6) over 4 h. The sorbent-based clearance of vancomycin was significantly lower than that of gentamicin (Pgroup < 0.0001). CONCLUSION: The novel HA380 sorbent cartridge appears safe and achieves significant vancomycin and gentamicin removal over a four-hour period. This information can be used by clinicians to guide their prescription and consider the additional dosing of at least an extra 25-35% amount in patients receiving HA380 hemoadsorption therapy during sepsis.

Telemental Health Collaborative Care Medication Management: Implementation and Outcomes.

Introduction: Access to quality mental health medication management (MM) in the United States is limited, even among those with employment-based health insurance. This implementation, feasibility, and outcome study sought to design and evaluate an evidence-based telemental health MM service using a collaborative care model (CoCM). Materials and Methods: CoCM MM was available to adult employees/dependents through their employer benefits, in addition to therapy. Outcomes included Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) collected at baseline and throughout participation. This analysis was not deemed to be human subjects research by the Western Institutional Review Board. Results: Over 17 months, 212 people enrolled and completed >2 assessments; the enrollees were 58.96% female with average age of 32.00 years (standard deviation [SD] = 7.38). In people with moderate to severe depression or anxiety, PHQ-9 and GAD-7 scores reduced by an average of 7.27 (SD = 4.80) and 6.71 (SD = 5.18) points after at least 12 ± 4 weeks in the program. At 24 ± 4 weeks, the PHQ-9 and GAD-7 reductions were on average 7.17 (SD = 5.00) and 6.03 (SD = 5.37), respectively. Approximately 65.88% of participants with either baseline depression or anxiety had a response on either the PHQ-9 or GAD-7 at 12 ± 4 weeks and 44.71% of participants experienced remission; at 24 ± 4 weeks, 56.41% had response and 41.03% experienced remission. Conclusions: An evidence-based CoCM telemedicine service within an employee behavioral health benefit is feasible and effective in reducing anxiety and depression symptoms when using measurement-based care. Widespread implementation of a benefit like this could expand access to evidence-based mental health MM.

Real-World Evaluation of a Large-Scale Blended Care-Cognitive Behavioral Therapy Program for Symptoms of Anxiety and Depression.

Introduction: Prior studies have supported the effectiveness of blended interventions for anxiety and depression; however, outcomes research of large-scale blended interventions for these conditions is limited. Objective: To investigate the outcomes of scaled-up blended care (BC) cognitive behavioral therapy (CBT), a program that combined video-based psychotherapy with internet CBT, for symptoms of anxiety and depression. Materials and Methods: Participants were 6,738 U.S.-based adults with elevated symptoms of anxiety (Generalized Anxiety Disorder-7 [GAD-7] ≥ 8) and/or depression (Patient Health Questionnaire-9 [PHQ-9] ≥ 10) at baseline who received BC-CBT as an employer-offered mental health benefit. The primary outcomes, anxiety (GAD-7) and depression (PHQ-9) symptoms, were routinely measured in the program. Recovery and reliable improvement in outcomes were calculated, and growth curve models evaluated change in outcomes during treatment and the effects of engaging in psychotherapy sessions on outcomes. Results: On average, participants received treatment for 7.6 (standard deviation = 6.2) weeks. By the end of care, 5,491 (81.5%) participants had reliable improvement in either anxiety or depression symptoms; in addition, 5,535 (82.1%) fell below the clinical threshold for either anxiety or depression symptoms (i.e., recovered). Declines in anxiety and depression symptoms were statistically significant over the course of BC-CBT (both p's < 0.01), with the rate of decline significantly decreasing for each outcome as treatment progressed (both p's < 0.01). Each psychotherapy session completed was significantly associated with lower anxiety and depression symptoms during the week of the session and the subsequent week (all p's < 0.01). Conclusions: This real-world study provides evidence that scaled-up BC-CBT can be effective in the treatment of symptoms of anxiety and depression.

Health-Related Quality of Life in Cancer Survivors with Chemotherapy-Induced Peripheral Neuropathy: A Randomized Clinical Trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating adverse effect of neurotoxic chemotherapy that significantly worsens the quality of life of cancer survivors. MATERIALS AND METHODS: Survivors of solid tumors with persistent moderate-to-severe CIPN defined as numbness, tingling, or pain rated ≥4 on an 11-point numeric rating scale (NRS) were randomized in a 1:1:1 ratio to 8 weeks of real acupuncture (RA) versus sham acupuncture (SA) versus usual care (UC). We previously reported the primary endpoint (NRS); here we report the following health-related quality of life endpoints: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), and Brief Fatigue Inventory (BFI). For each endpoint, the mean changes from baseline and 95% confidence intervals were estimated within each arm and compared between arms using linear mixed models. RESULTS: We enrolled 75 survivors of solid tumors with moderate-to-severe CIPN into the study. Compared with baseline, at week 8, FACT/GOG-Ntx, HADS anxiety, and ISI scores significantly improved in RA and SA, but not in UC. Compared with UC, at week 8, FACT/GOG-Ntx scores significantly increased in RA and SA arms indicating improved CIPN-related symptoms and quality of life (p = .001 and p = .01). There was no statistically significant difference between RA and SA. There was no difference in HADS depression or BFI among RA, SA, and UC at weeks 8 and 12. CONCLUSION: Acupuncture may improve CIPN-related symptoms and quality of life in cancer survivors with persistent CIPN. Further large sample size studies are needed to delineate placebo effects. IMPLICATIONS FOR PRACTICE: The authors conducted a randomized sham acupuncture- and usual care-controlled clinical trial to evaluate the impact of acupuncture on health-related quality of life outcomes in patients with solid tumors with chemotherapy-induced peripheral neuropathy (CIPN). Statistically significant improvements in quality of life, anxiety, insomnia, and fatigue were achieved with 8 weeks of real acupuncture when compared with baseline, without statistically significant differences between real and sham acupuncture. These findings suggest that acupuncture may be effective for improving CIPN-related symptoms and quality of life and reducing anxiety and insomnia in cancer survivors with persistent CIPN, with further study needed to delineate placebo effects.

Characterization of chemotherapy-induced peripheral neuropathy using patient-reported outcomes and quantitative sensory testing.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect in cancer survivors. This study aimed to assess the characteristics of quantitative sensory testing (QST) and its correlation with patient-reported outcomes (PROs) in cancer patients with and without CIPN. METHODS: We conducted a cross-sectional analysis using baseline data from two clinical trials in solid tumor cancer survivors with no CIPN symptoms rated < 2 on a 0-10 Numerical Rating Scale (NRS) or moderate-to-severe CIPN rated ≥ 4 on the NRS. We collected PROs (NRS, Neuropathic Pain Scale, and Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity subscale at baseline. QST [Tactile Threshold (TT), Vibration Threshold (VT), Thermal Threshold (THT)] measurements were used to assess sensory fiber function; they were compared between patients with and without CIPN using Wilcoxon rank-sum tests. We used Spearman correlation coefficients to estimate associations between PROs and QST in all patients. RESULTS: Among 116 participants with CIPN (median NRS 5.00) and 10 participants without CIPN (median NRS 0.00), the median (interquartile range) TT was 3.84 (3.47, 4.12) and 3.53 (3.00, 3.84) in feet, respectively (p = 0.043). The median VT was 17.90 (9.42, 26.95) and 7.73 (5.94, 11.11) in feet, respectively (p = 0.001). Thermal cool threshold was 30.00 °C (28.90, 30.57) and 30.67 °C (30.57, 30.93), respectively (p = 0.007). Correlation coefficients between PROs and QST measures ranged between 0.02 and 0.50 in absolute magnitude. CONCLUSION: Patients with moderate-to-severe CIPN had significantly impaired tactile, vibratory, and thermal thresholds compared to patients without CIPN. QST correlates with PROs, suggesting CIPN symptom severity may correspond to sensory fiber functionality. QST may be incorporated into future CIPN research.

Herbal Topical Analgesic for Pain Management: Perspectives from Cancer Patients.

OBJECTIVE: Herbs and natural products are increasingly used by cancer patients for pain management, but few studies have examined their integration within conventional cancer care. This study describes the characteristics, experiences, and perspectives of cancer patients who were prescribed an herbal topical analgesic for pain management. DESIGN AND SETTING: Program evaluation of a pilot herbal dispensary at a National Cancer Institute-designated comprehensive cancer center. SUBJECTS: Cancer patients who were prescribed the Tibetree Pain-Relieving Plaster (PRP) by an integrative medicine physician. METHODS: Sociodemographic and clinical characteristics of patients were abstracted from medical records. Semistructured phone interviews were conducted 1-2 weeks after PRP prescription to evaluate patient experiences with using PRP for pain. Interviews were analyzed through thematic content analysis. RESULTS: From February 2019 to February 2020, 50 patients were prescribed PRP. Median age (range) was 63 years (21-86), 37 patients (74%) were female, 14 (28%) were non-White, and 38 (76%) were using oral analgesics. During interviews, the majority of patients reported that the PRP improved pain and health-related outcomes, was convenient to use, and addressed pain management needs that were not fulfilled by oral analgesics. However, a few patients described adverse experiences with PRP, including skin irritation. CONCLUSIONS: Understanding patient experiences and perspectives is a critical step toward evidence-based integration of herbs and natural products into cancer pain management. Findings from this program evaluation will inform the design of a randomized clinical trial on the efficacy and safety of PRP for pain in patients with cancer.

Effectiveness of a Cognitive Behavioral Coaching Program Delivered via Video in Real World Settings.

Background: Many employees experience high levels of stress in the workplace, which negatively impact their productivity and well-being. Effective stress management interventions exist, but are inaccessible due to insufficient numbers of mental health providers, long waiting times to initiate care, high out-of-pocket cost of care, and stigma related to receiving psychotherapy. Introduction: The purpose of this study was to test the efficacy, in real-world circumstances, of a structured, cognitive behavioral coaching (CBC) program delivered through video or telephone. Materials and Methods: Retrospective data on 289 subjects who had sought support for emotional health through a behavioral health benefit offered through employers were examined. Changes in perceived stress and well-being over the course of the program were measured using the Perceived Stress Scale (PSS) and Warwick-Edinburgh Mental Well-being Scale (WEMWBS), respectively. Rates of reliable change and satisfaction with the coaching program were also assessed. Results: Scores on both the PSS and WEMWBS improved between baseline and follow-up. Approximately 61.9% (n = 289) of participants demonstrated reliable improvement on either measure. Discussion: CBC is a promising intervention that has the potential to significantly expand access to effective and more affordable interventions for emotional health care. Conclusions: Coaching, when delivered by accredited professionals trained in cognitive behavioral theory and interventions and working in real-world settings, can be efficacious in decreasing perceived stress and increasing well-being when delivered through video or telephone.

Ontogeny and Cross-species Comparison of Pathways Involved in Drug Absorption, Distribution, Metabolism, and Excretion in Neonates (Review): Kidney.

The kidneys play an important role in many processes, including urine formation, water conservation, acid-base equilibrium, and elimination of waste. The anatomic and functional development of the kidney has different maturation time points in humans versus animals, with critical differences between species in maturation before and after birth. Absorption, distribution, metabolism, and excretion (ADME) of drugs vary depending on age and maturation, which will lead to differences in toxicity and efficacy. When neonate/juvenile laboratory animal studies are designed, a thorough knowledge of the differences in kidney development between newborns/children and laboratory animals is essential. The human and laboratory animal data must be combined to obtain a more complete picture of the development in the kidneys around the neonatal period and the complexity of ADME in newborns and children. This review examines the ontogeny and cross-species differences in ADME processes in the developing kidney in preterm and term laboratory animals and children. It provides an overview of insights into ADME functionality in the kidney by identifying what is currently known and which gaps still exist. Currently important renal function properties such as glomerular filtration rate, renal blood flow, and ability to concentrate are generally well known, while detailed knowledge about transporter and metabolism maturation is growing but is still lacking. Preclinical data in those properties is limited to rodents and generally covers only the expression levels of transporter or enzyme-encoding genes. More knowledge on a functional level is needed to predict the kinetics and toxicity in neonate/juvenile toxicity and efficacy studies. SIGNIFICANCE STATEMENT: This review provides insight in cross-species developmental differences of absorption, distribution, metabolism, and excretion properties in the kidney, which should be considered in neonate/juvenile study interpretation, hypotheses generation, and experimental design.

Memory T Cell Proliferation before Hepatitis C Virus Therapy Predicts Antiviral Immune Responses and Treatment Success.

The contribution of the host immune system to the efficacy of new anti-hepatitis C virus (HCV) drugs is unclear. We undertook a longitudinal prospective study of 33 individuals with chronic HCV treated with combination pegylated IFN-α, ribavirin, and telaprevir/boceprevir. We characterized innate and adaptive immune cells to determine whether kinetics of the host response could predict sustained virologic response (SVR). We show that characteristics of the host immune system present before treatment were correlated with successful therapy. Augmentation of adaptive immune responses during therapy was more impressive among those achieving SVR. Most importantly, active memory T cell proliferation before therapy predicted SVR and was associated with the magnitude of the HCV-specific responses at week 12 after treatment start. After therapy initiation, the most important correlate of success was minimal monocyte activation, as predicted by previous in vitro work. In addition, subjects achieving SVR had increasing expression of the transcription factor T-bet, a driver of Th1 differentiation and cytotoxic effector cell maturation. These results show that host immune features present before treatment initiation predict SVR and eventual development of a higher frequency of functional virus-specific cells in blood. Such host characteristics may also be required for successful vaccine-mediated protection.

Blended Care-Cognitive Behavioral Therapy for Depression and Anxiety in Real-World Settings: Pragmatic Retrospective Study.

BACKGROUND: The past few decades saw considerable advances in research and dissemination of evidence-based psychotherapies, yet available treatment resources are not able to meet the high need for care for individuals suffering from depression or anxiety. Blended care psychotherapy, which combines the strengths of therapist-led and internet interventions, can narrow this gap and be clinically effective and efficient, but has rarely been evaluated outside of controlled research settings. OBJECTIVE: This study evaluated the effectiveness of a blended care intervention (video-based cognitive behavior therapy and internet intervention) under real-world conditions. METHODS: This is a pragmatic retrospective cohort analysis of 385 participants with clinical range depression and/or anxiety symptoms at baseline, measured using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), who enrolled in blended care psychotherapy treatment. Participants resided in the United States and had access to the blended care intervention as a mental health benefit offered through their employers. Levels of depression and anxiety were tracked throughout treatment. Hierarchical linear modeling was used to examine the change in symptoms over time. The effects of age, gender, and providers on participants' symptom change trajectories were also evaluated. Paired sample t-tests were also conducted, and rates of positive clinical change and clinically significant improvement were calculated. RESULTS: The average depression and anxiety symptoms at 6 weeks after the start of treatment were 5.94 and 6.57, respectively. There were significant linear effects of time on both symptoms of depression and anxiety (ß=-.49, P<.001 and ß=-.64, P<.001). The quadratic effect was also significant for both symptoms of depression and anxiety (ß=.04, P<.001 for both), suggesting a decelerated decrease in symptoms over time. Approximately 73% (n=283) of all 385 participants demonstrated reliable improvement, and 83% (n=319) recovered on either the PHQ-9 or GAD-7 measures. Large effect sizes were observed on both symptoms of depression (Cohen d=1.08) and of anxiety (d=1.33). CONCLUSIONS: Video blended care cognitive behavioral therapy interventions can be effective and efficient in treating symptoms of depression and anxiety in real-world conditions. Future research should investigate the differential and interactive contribution of the therapist-led and digital components of care to patient outcomes to optimize care.

Chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer survivors: a comparison of patient-reported outcomes and quantitative sensory testing.

PURPOSE: CIPN is a common, debilitating, and dose-limiting side effect of chemotherapy. Here, we describe characteristics of patients with CIPN using both patient-reported outcomes (PRO) and quantitative sensory testing (QST). METHODS: Breast cancer survivors with persistent moderate to severe CIPN defined by a rating of 4 or greater on a 0-10 Numeric Rating Scale (NRS) from two ongoing clinical trials were included. PROs included the Neuropathic Pain Scale (NPS) and Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity (FACT/GOG-Ntx). QST included tactile and vibration detection threshold measurements. Data were analyzed using descriptive statistics and Spearman correlation coefficients. RESULTS: 49 female patients with a mean age of 61 years were assessed; 63% were Caucasian. Mean NRS scores were 4.2, 5.7, and 4.3 on 0-10 scale for pain, numbness, and tingling, respectively. Mean NPS score was 41.0 on a 0-100 scale, and the mean FACT/GOG-Ntx score was 25.8 on a 0-44 scale. QST showed mild to moderate impairments in tactile and vibration perception. The FACT/GOG-Ntx subscale for numbness was negatively correlated with tactile and vibration thresholds in both hands and feet (both p < 0.05). NPS was positively correlated with tactile thresholds in the hands and feet (p < 0.05). CONCLUSION: Patients with moderate to severe CIPN report moderate pain, numbness, and tingling, and exhibit reduced tactile and vibration perception on QST. Weak to moderate correlations were observed between PRO and QST. These data suggest that QST outcomes are associated with CIPN symptoms and may be useful in helping monitor and manage CIPN treatment.

Modified- versus immediate-release tofacitinib in Japanese rheumatoid arthritis patients: a randomized, phase III, non-inferiority study.

Objective: Tofacitinib is an oral Janus kinase inhibitor for treatment of RA. We compared tofacitinib modified-release (MR) 11 mg once daily (QD) with tofacitinib immediate-release (IR) 5 mg twice daily (BID) in Japanese patients with RA and inadequate response to MTX. Methods: Phase III, randomized, double-blind, double-dummy, 12-week study. Patients were randomized to tofacitinib MR 11 mg QD (n = 104) or IR 5 mg BID (n = 105), with stable MTX. Compliance was based on returned pill counts. The primary objective was to demonstrate non-inferiority of MR 11 mg QD to IR 5 mg BID. Non-inferiority was declared if the upper bound of the two-sided 95% CI for the difference in change from baseline in DAS28-4(CRP) at week 12 was <0.6. Results: At week 12, with tofacitinib MR 11 mg QD and IR 5 mg BID, respectively, the change from baseline in least squares mean DAS28-4(CRP) was -2.43 and -2.85; the mean difference was 0.43 (95% CI 0.17, 0.69). Non-inferiority of MR 11 mg QD to IR 5 mg BID was not met. Improvement of DAS28-4(CRP) ⩾1.2 was observed in 89 and 85% of patients, respectively, corresponding to a clinically important, significant change in both groups. The frequency of adverse events (52.9 and 51.4%, respectively) and serious adverse events (4.8 and 3.8%, respectively) was generally similar between treatments. No deaths were reported. Conclusion: Non-inferiority of MR 11 mg QD to IR 5 mg BID was not met in this study. However, clinically meaningful improvements in RA were observed with both tofacitinib formulations in Japanese patients. The safety profile was similar with both formulations. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02281552.