Citations

Participation refers to a state of health in which a person is able to fully engage in roles and life situations. Adults living with and beyond cancer often report persistent participation restrictions that affect their productivity and quality of life. The American Occupational Therapy Foundation convened a group of scientists from seven different disciplines in a Planning Grant Collective (PGC) to stimulate research to identify scalable ways to preserve and optimize participation among cancer survivors. Participants identified challenges, prioritized solutions, and generated novel research questions that move beyond symptom and impairment mitigation as outcomes to identify interventions that improve participation in roles and life situations. This article summarizes the PGC discussion and recommendations regarding three challenges: (a) the dynamic and multi-faceted nature of participation, (b) a need to integrate the concept of participation within the culture of oncology, and (c) identification of priority areas in which new lines of research regarding participation would be most impactful.

Microelectrode recordings were performed during awake deep brain stimulation surgery for obsessive-compulsive disorder, revealing robust brain oscillations that were plainly visible throughout the ventral striatum. There was an elegant topological correspondence between each oscillation and the underlying brain anatomy, most prominently a ~35-Hz gamma-oscillation specific to the nucleus accumbens. Direct provocation of the patient’s contamination obsession modulated both firing rate and gamma-oscillation amplitude within the nucleus accumbens. NEW & NOTEWORTHY Surgical implantation of deep brain stimulating electrodes (DBS) to treat obsessive-compulsive disorder (OCD) is an option for patients who have not fully responded to medical intervention or cognitive behavioral therapy. We measured the electrophysiology of a collection of deep brain structures during awake DBS surgery for an OCD patient with an obsession about cleanliness and contamination. The anatomic delineation of these deep brain structures was revealed by distinct brain rhythms, most notably a ~35 Hz oscillation specific to the nucleus accumbens. In the first ever measurement of a human obsessive thought, we found that this ~35-Hz biomarker, as well as the local neuronal action potential rate, were modulated by handing the patient a toothbrush to bring to his face and instructing him to “imagine brushing your teeth with this dirty toothbrush.”

Background: Hemodynamic performance of prostheses after transcatheter aortic valve replacement (TAVR) is generally better than after surgical aortic valve replacement (SAVR), especially in patients with a small native annulus size. However, it remains unclear whether differences are consistent for patients with a different propensity for developing prosthesis-patient mismatch (PPM), considering annulus size and body size of patients. Methods and Results: The SURTAVI trial (Surgical Replacement and Transcatheter Aortic Implantation) compared TAVR using a self-expandable valve with SAVR in intermediate-risk patients. Multidetector computed tomography–based aortic annulus size consisted of the perimeter-derived diameter, which was divided by body surface area to produce an indexed annulus size. Patients were categorized into a small (9–12 mm/m 2 ), medium (>12–14 mm/m 2 ), and large (>14–18 mm/m 2 ) group according to indexed annulus size. We compared TAVR and SAVR for PPM, hemodynamics, and clinical, and functional outcomes through 1-year follow-up within the size groups. Patients who underwent TAVR received a larger prosthesis with increasing indexed annulus size ( P <0.001), while there was no difference in prosthesis size in patients who underwent SAVR ( P =0.74). Patients in all size groups had significantly larger indexed effective orifice area and lower mean gradients at discharge after TAVR versus SAVR. Rates of PPM were significantly lower with TAVR versus SAVR in all groups ( P <0.001) and declined with larger indexed annulus sizes with both TAVR ( P =0.04) and SAVR ( P =0.03). Indexed annulus size was an independent predictor of PPM after TAVR and SAVR. Clinical outcomes were comparable between TAVR and SAVR across all groups, apart from a significantly higher rate of reintervention after TAVR versus SAVR in the large indexed annulus size group (2.5% versus 0%; P =0.01) but without significant interaction ( P int =0.81). Conclusions: Rates of PPM were significantly lower after TAVR than after SAVR across all groups of indexed annulus size, reflecting better hemodynamic performance of transcatheter versus surgical valves, irrespective of the propensity to develop PPM. More attention should be directed to prevention of PPM after SAVR. This information should be considered by the Heart Team to recommend a specific procedure or valve. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01586910.

Abstract Motivation The human microbiome is notoriously variable across individuals, with a wide range of ‘healthy’ microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter-subject variability. Statistical methods for analyzing such datasets are scarce. Results We introduce a paired UniFrac dissimilarity that summarizes within-individual (or within-pair) shifts in microbiome composition and then compares these compositional shifts across individuals (or pairs). This dissimilarity depends on a novel transformation of relative abundances, which we then extend to more than two time points and incorporate into several phylogenetic and non-phylogenetic dissimilarities. The data transformation and resulting dissimilarities may be used in a wide variety of downstream analyses, including ordination analysis and distance-based hypothesis testing. Simulations demonstrate that tests based on these dissimilarities retain appropriate type 1 error and high power. We apply the method in two real datasets. Availability and implementation The R package pldist is available on GitHub at https://github.com/aplantin/pldist. Supplementary information Supplementary data are available at Bioinformatics online.

Abstract STUDY QUESTION Can asoprisnil, a selective progesterone receptor modulator, provide clinically meaningful improvements in heavy menstrual bleeding (HMB) associated with uterine fibroids with an acceptable safety profile? SUMMARY ANSWER Uninterrupted treatment with asoprisnil for 12 months effectively controlled HMB and reduced fibroid and uterine volume with few adverse events. WHAT IS KNOWN ALREADY In a 3-month study, asoprisnil (5, 10 and 25 mg) suppressed uterine bleeding, reduced fibroid and uterine volume, and improved hematological parameters in a dose-dependent manner. STUDY DESIGN, SIZE, DURATION In two Phase 3, double-blind, randomized, placebo-controlled, multicentre studies, women received oral asoprisnil 10 mg, asoprisnil 25 mg or placebo (2:2:1) once daily for up to 12 months. PARTICIPANTS/MATERIALS, SETTING, METHODS Premenopausal women ≥18 years of age in North America with HMB associated with uterine fibroids were included (N = 907). The primary efficacy endpoint was the percentage of women who met all three predefined criteria at 12 months or the final month for patients who prematurely discontinued: (1) ≥50% reduction in monthly blood loss (MBL) by menstrual pictogram, (2) hemoglobin concentration ≥11 g/dL or an increase of ≥1 g/dL, and (3) no interventional therapy for uterine fibroids. Secondary efficacy endpoints included changes in other menstrual bleeding parameters, volume of the largest fibroids, uterine volume and health-related quality of life (HRQL). MAIN RESULTS AND THE ROLE OF CHANCE In all, 90% and 93% of women in the asoprisnil 10-mg and 25-mg groups, respectively, and 35% of women in the placebo group met the primary endpoint (P &lt; 0.001). Similar results were observed at month 6 (P &lt; 0.001). The percentage of women who achieved amenorrhea in any specified month ranged from 66–78% in the asoprisnil 10-mg group and 83–93% in the asoprisnil 25-mg group, significantly higher than with placebo (3–12%, P &lt; 0.001). Hemoglobin increased rapidly (by month 2) with asoprisnil treatment and was significantly higher versus placebo throughout treatment. The primary fibroid and uterine volumes were significantly reduced from baseline through month 12 with asoprisnil 10 mg (median changes up to −48% and −28%, respectively) and 25 mg (median changes up to −63% and −39%, respectively) versus placebo (median changes up to +16% and +13%, respectively; all P &lt; 0.001). Dose-dependent, significant improvements in HRQL (Uterine Fibroid Symptom and Quality of Life instrument) were observed with asoprisnil treatment. Asoprisnil was generally well tolerated. Endometrial biopsies indicated dose- and time-dependent decreases in proliferative patterns and increases in quiescent or minimally stimulated endometrium at month 12 of treatment. Although not statistically significantly different at month 6, mean endometrial thickness at month 12 increased by ~2 mm in both asoprisnil groups compared with placebo (P &lt; 0.01). This effect was associated with cystic changes in the endometrium on MRI and ultrasonography, which led to invasive diagnostic and therapeutic procedures in some asoprisnil-treated women. LIMITATIONS, REASONS FOR CAUTION Most study participants were black; few Asian and Hispanic women participated. The study duration may have been insufficient to fully characterize the endometrial effects. WIDER IMPLICATIONS OF THE FINDINGS Daily uninterrupted treatment with asoprisnil was highly effective in controlling menstrual bleeding, improving anemia, reducing fibroid and uterine volume, and increasing HRQL in women with HMB associated with uterine fibroids. However, this treatment led to an increase in endometrial thickness and invasive diagnostic and therapeutic procedures, with potential unknown consequences. STUDY FUNDING/COMPETING INTEREST(S) This trial was funded by AbbVie Inc. (prior sponsors: TAP Pharmaceutical Products Inc., Abbott Laboratories). E.A. Stewart was a site investigator in the Phase 2 study of asoprisnil and consulted for TAP during the design and conduct of these studies while at Harvard Medical School and Brigham and Women’s Hospital. She received support from National Institutes of Health grants HD063312, HS023418 and HD074711 and research funding, paid to Mayo Clinic for patient care costs related to an NIH-funded trial from InSightec Ltd. She consulted for AbbVie, Allergan, Bayer HealthCare AG, Gynesonics, and Welltwigs. She received royalties from UpToDate and the Med Learning Group. M.P. Diamond received research funding for the conduct of the studies paid to the institution and consulted for AbbVie. He is a stockholder and board and director member of Advanced Reproductive Care. He has also received funding for study conduct paid to the institution from Bayer and ObsEva. A.R.W. Williams consulted for TAP and Repros Therapeutics Inc. He has current consultancies with PregLem SA, Gedeon Richter, HRA Pharma and Bayer. B.R. Carr consulted for and received research funding from AbbVie. E.R. Myers consulted for AbbVie, Allergan and Bayer. R.A. Feldman received compensation for serving as a principal investigator and participating in the conduct of the trial. W. Elger was co-inventor of several patents related to asoprisnil. C. Mattia-Goldberg is a former employee of AbbVie and may own AbbVie stock or stock options. B.M. Schwefel and K. Chwalisz are employees of AbbVie and may own AbbVie stock or stock options. TRIAL REGISTRATION NUMBER NCT00152269, NCT00160381 (clinicaltrials.gov). TRIAL REGISTRATION DATE 7 September 2005; 8 September 2005. DATE OF FIRST PATIENT’S ENROLMENT 12 September 2002; 6 September 2002.