Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes: The ORCA-V1 Randomized Clinical Trial.

Importance: The prevalence of e-cigarette use among US adults, especially young adults, is rising. Many would like to quit vaping nicotine but are unable to do so. Cytisinicline, a plant-based alkaloid, targets nicotinic acetylcholine receptors, reduces nicotine dependence, and helps adults to stop smoking cigarettes.

Cytisinicline for Smoking Cessation: A Randomized Clinical Trial.

Importance: Cytisinicline (cytisine) is a plant-based alkaloid that, like varenicline, binds selectively to α4β2 nicotinic acetylcholine receptors, which mediate nicotine dependence. Although not licensed in the US, cytisinicline is used in some European countries to aid smoking cessation, but its traditional dosing regimen and treatment duration may not be optimal.

Objective: To evaluate the efficacy and tolerability of cytisinicline for smoking cessation when administered in a novel pharmacokinetically based dosing regimen for 6 or 12 weeks vs placebo.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

Context: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy.

Objective: To evaluate safety and efficacy of intranasal carbetocin in PWS.

Preparatory routines for emotional regulation in performance enhancement.

Preparatory routines (PR) are a necessary tool for achieving optimal emotional states and effective performance, especially in self-paced motor skills. Numerous studies in the area of applied sport psychology have found a positive effect of PR on blocking out distractions and regulating performance thoughts, actions, and emotions. PR contain behavioral and mental components that can be applied in different time periods before and after the event itself: pre-competitive activity routines (PCA-R), pre-performance routines (PP-R), and post-performance activity routines (PPA-R).

Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.

Background: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum.

Strong vaccine responses during chemotherapy are associated with prolonged cancer survival.

Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)-induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high numbers of immunosuppressive myeloid cells in patients, allowing the development of much stronger therapeutic HPV16 vaccine (ISA101)-induced tumor immunity.

Androgen Receptor Modulation Optimized for Response-Splice Variant: A Phase 3, Randomized Trial of Galeterone Versus Enzalutamide in Androgen Receptor Splice Variant-7-expressing Metastatic Castration-resistant Prostate Cancer.

Background: Detection of androgen receptor (AR) splice variant-7 (AR-V7) messenger RNA (mRNA) in circulating tumor cells (CTCs) is associated with a suboptimal response to abiraterone and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). Galeterone inhibits CYP17 and AR, and induces AR protein degradation. We hypothesized that galeterone would be clinically superior to enzalutamide in AR-V7-positive (AR-V7+) mCRPC.

Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial.

Background: Docetaxel and cabazitaxel improve overall survival compared with mitoxantrone in patients with metastatic castration-resistant prostate cancer. Custirsen (OGX011) is a second generation highly specific antisense oligonucleotide that inhibits the production of clusterin, an antiapoptotic protein that is upregulated in response to chemotherapy and that confers treatment resistance. We aimed to assess whether custirsen in combination with cabazitaxel and prednisone increases overall survival in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel.

Borealis-1: a randomized, first-line, placebo-controlled, phase II study evaluating apatorsen and chemotherapy for patients with advanced urothelial cancer.

Background: Five-year survival of patients with inoperable, advanced urothelial carcinoma treated with the first-line chemotherapy is 5%-15%. We assessed whether the Hsp27 inhibitor apatorsen combined with gemcitabine plus cisplatin (GC) could improve overall survival (OS) in these patients.

Patients And Methods: This placebo-controlled, double-blind, phase II trial randomized 183 untreated urothelial carcinoma patients (North America and Europe) to receive GC plus either placebo (N = 62), 600 mg apatorsen (N = 60), or 1000 mg apatorsen (N = 61).

Custirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): a phase 3, multicentre, open-label, randomised trial.

Background: Clusterin is a chaperone protein associated with treatment resistance and upregulated by apoptotic stressors such as chemotherapy. Custirsen is a second-generation antisense oligonucleotide that inhibits clusterin production. The aim of the SYNERGY trial was to investigate the effect of custirsen in combination with docetaxel and prednisone on overall survival in patients with metastatic castration-resistant prostate cancer.

Psychological Preparation for Paralympic Athletes: A Preliminary Study.

Since the first Paralympics in 1960 there has been an increase in social and scientific interest in Paralympic athletes' personality, their preparation, and their sport results. During the last 20 yr, researchers and practitioners have been focused on psychological-skills programs for athletes with disabilities. The purpose of this article was to describe a psychological-preparation program for Israeli Paralympic athletes.

Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration-resistant prostate cancer treated with custirsen.

Elevated levels of clusterin (CLU), a stress-induced and secreted cytoprotective chaperone, are associated with advanced tumor stage, metastasis, treatment resistance, and adverse outcome in several cancers. Custirsen, a second-generation antisense oligonucleotide, inhibits CLU production in tumor cells and reduces serum CLU levels. A Phase 2 study evaluated custirsen in combination with second-line chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC) who had progressed while on or within 6 months of first-line docetaxel-based chemotherapy.

Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer.

Background: As screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in a screening setting.

Objective: We prospectively assessed the accuracy of circulating methylated SEPT9 DNA (mSEPT9) for detecting CRC in a screening population.

Economic assessment of the integrated generation of solid fuel and biogas from biomass (IFBB) in comparison to different energy recovery, animal-based and non-refining management systems.

The study aimed at the identification of favourable land use options for semi-natural grassland management and preservation. Economic assessments of energy recovery by the integrated generation of solid fuel and biogas from biomass (IFBB) in comparison with dry fermentation (DF) and hay combustion systems (HC), beef cattle production (BC) and non-refining landscape preservation measures, such as mulching (MU) and composting (CO), were carried out in this study. Energy recovery systems made profitable use of semi-natural grasslands with the highest economic returns attained by IFBB-AO (Return On Investment, ROI: 22.

Using a powered bone marrow biopsy system results in shorter procedures, causes less residual pain to adult patients, and yields larger specimens.

Background: In recent years, a battery-powered bone marrow biopsy system was developed and cleared by the U.S. Food and Drug Administration to allow health care providers to access the bone marrow space quickly and efficiently.

Enhancing patient-provider communication with the electronic self-report assessment for cancer: a randomized trial.

Purpose: Although patient-reported cancer symptoms and quality-of-life issues (SQLIs) have been promoted as essential to a comprehensive assessment, efficient and efficacious methods have not been widely tested in clinical settings. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment-Cancer (ESRA-C) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits. Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians.

Improved endpoints for cancer immunotherapy trials.

Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints.

Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.

Background: Hereditary angioedema due to C1 inhibitor deficiency is characterized by recurrent acute attacks of swelling that can be painful and sometimes life-threatening.

Methods: We conducted two randomized trials to evaluate nanofiltered C1 inhibitor concentrate in the management of hereditary angioedema. The first study compared nanofiltered C1 inhibitor concentrate with placebo for treatment of an acute attack of angioedema.

Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer.

Purpose: Therapeutic prostate-specific antigen (PSA) -targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study.

Patients And Methods: In total, 125 patients were randomly assigned in a multicenter trial of vaccination series.

Lessons from randomized phase III studies with active cancer immunotherapies--outcomes from the 2006 meeting of the Cancer Vaccine Consortium (CVC).

After years of effort to develop active cancer immunotherapies, seven candidate products achieved promising results in phase I/II studies that triggered phase III randomized studies. One candidate to date has received an approvable letter from the United States Food and Drug Administration (FDA), defining a clear path to licensure for sipuleucel-T (Provenge, Dendreon) within the next couple of years. The other phase III studies failed to achieve statistical criteria for some or all of the critical endpoints.

Factors that predict treatment choice and satisfaction with the decision in men with localized prostate cancer.

Purpose: Men diagnosed with localized prostate cancer (LPC) often have the opportunity to participate in the treatment choice. The purpose of this study was to evaluate relationships between influential factors on treatment choice and the decision-related outcomes of decisional conflict and satisfaction.

Patients And Methods: This report presents data from 260 men diagnosed with LPC who were identified by their clinicians as having a choice of treatments.

A clinical development paradigm for cancer vaccines and related biologics.

Therapeutic cancer vaccines are a heterogeneous group of complex biologics with distinctly different clinical characteristics than cytotoxic agents. The current clinical development paradigm used for oncology drug development is based on criteria developed for cytotoxic agents. More flexible and focused developmental guidelines are needed to address the unique characteristics of therapeutic cancer vaccines.

Sample size computation for two-sample noninferiority log-rank test.

When an experimental therapy is less extensive, less toxic, or less expensive than a standard therapy, we may want to prove that the former is not worse than the latter through a noninferiority trial. In this article, we discuss a modification of the log-rank test for noninferiority trials with survival endpoint and propose a sample size formula that can be used in designing such trials. Performance of our sample size formula is investigated through simulations.