Niraparib maintenance treatment improves time without symptoms or toxicity (TWiST) versus routine surveillance in recurrent ovarian cancer: a TWiST analysis of the ENGOT-OV16/NOVA trial

Purpose: this study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer. Patients and methods: mean progression-free survival (PFS) was estimated for niraparib and RS by fitting parametric survival distributions to Kaplan-Meier data for 553 patients with recurrent ovarian cancer who were enrolled in the phase III ENGOT-OV16/NOVA trial. Patients were categorized according to the presence or absence of a germline BRCA mutation-gBRCAmut and non-gBRCAmut cohorts. Mean time with toxicity was estimated based on the area under the Kaplan-Meier curve for symptomatic grade 2 or greater fatigue, nausea, and vomiting adverse events (AEs). Time with toxicity was the number of days a patient experienced an AE post-random assignment and before disease progression. TWiST was estimated as the difference between mean PFS and time with toxicity. Uncertainty was explored using alternative PFS estimates and considering all symptomatic grade 2 or greater AEs. Results: in the gBRCAmut and non-gBRCAmut cohorts, niraparib treatment resulted in a mean PFS benefit of 3.23 years and 1.44 years, respectively, and a mean time with toxicity of 0.28 years and 0.10 years, respectively, compared with RS. Hence, niraparib treatment resulted in a mean TWiST benefit of 2.95 years and 1.34 years, respectively, compared with RS, which is equivalent to more than four-fold and two-fold increases in mean TWiST between niraparib and RS in the gBRCAmut and non-gBRCAmut cohorts, respectively. This TWiST benefit was consistent across all sensitivity analyses, including modeling PFS over 5-, 10-, and 15-year time horizons. Conclusion: patients who were treated with niraparib compared with RS experienced increased mean TWiST. Thus, patients who were treated with niraparib in the ENGOT-OV16/NOVA trial experienced more time without symptoms or symptomatic toxicities compared with control

Prolonged conservative treatment or 'early' surgery in sciatica caused by a lumbar disc herniation: rationale and design of a randomized trial [ISRCT 26872154]

BACKGROUND: The design of a randomized multicenter trial is presented on the effectiveness of a prolonged conservative treatment strategy compared with surgery in patients with persisting intense sciatica (lumbosacral radicular syndrome). METHODS/DESIGN: Patients presenting themselves to their general practitioner with disabling sciatica lasting less than twelve weeks are referred to the neurology outpatient department of one of the participating hospitals. After confirmation of the diagnosis and surgical indication MRI scanning is performed. If a distinct disc herniation is discerned which in addition covers the clinically expected site the patient is eligible for randomization. Depending on the outcome of the randomization scheme the patient will either be submitted to prolonged conservative care or surgery. Surgery will be carried out according to the guidelines and between six and twelve weeks after onset of complaints. The experimental therapy consists of a prolonged conservative treatment under supervision of the general practitioner, which may be followed by surgical intervention in case of persisting or progressive disability. The main primary outcome measure is the disease specific disability of daily functioning. Other primary outcome measures are perceived recovery and intensity of legpain. Secondary outcome measures encompass severity of complaints, quality of life, medical consumption, absenteeism, costs and preference. The main research question will be answered at 12 months after randomization. The total follow-up period covers two years. DISCUSSION: Evidence is lacking concerning the optimal treatment of lumbar disc induced sciatica. This pragmatic randomized trial, focusses on the 'timing' of intervention, and will contribute to the decision of the general practictioner and neurologist, regarding referral of patients for surgery

Decision Support Framework for Developing Regional Energy Strategies

In an effort to reduce “carbon pollution” as well as prepare the U.S. for the impacts of climate change, President Obama’s 2013 Climate Action Plan calls for changes to be made to the nation’s energy system. In addition to focusing on alternative portfolios of different fuels and power-generation technologies, researchers and advisory panels have urged that changes to the nation’s energy system be based on a decision-making framework that incorporates stakeholders and accounts for real-world resource, supply, and demand constraints. To date, research and development on such a framework have proven elusive. The research reported here describes the development and test of a potential decision support framework that combines elements from structured decision-making (SDM) with portfolio analysis, methods that have been used independently to elicit preferences in complex decision contexts. This hybrid framework aimed to (1) provide necessary background information to users regarding the development of coupled climate-energy strategies; (2) account for users’ values and objectives; (3) allow for the construction of bespoke energy portfolios bounded by real-world supply and demand constraints; and (4) provide a more rigorous basis for addressing trade-offs. Results show that this framework was user-friendly, led to significant increases in users’ knowledge about energy systems and, importantly, led to more internally consistent decisions. For these reasons, this framework may serve as a suitable template for supporting decisions about energy transitions in the United States and abroad

Community Centered Solar Development (CCSD) Study Interviews

Large-scale solar (LSS, defined here as ground-mounted photovoltaic projects ≥1 MWDC) has grown rapidly in the U.S., accounting for nearly half of new electric generating capacity added to the U.S. grid in 2022. All sources of electricity bring positive and negative impacts to hosting communities and the rapid growth of LSS has increased the urgency to understand those impacts. Yet, information about the potential positive and negative impacts of LSS on host communities, and the factors or drivers leading to support or opposition to a project, is lacking. This information gap limits how project developers, municipalities, and local siting authorities can address community concerns and appropriately align proposed projects to best suit and benefit local communities. As part of Berkeley Lab’s Community-Centered Solar Development (CCSD) project, this research set out to explore deep insights and perceptions from LSS stakeholders that only qualitative data can provide to identify key factors driving project success or threatened failure. Case studies, such as those utilized in this research, are uniquely adept at capturing the subjective experience of individuals and at identifying variables, structures, and interactions between stakeholders. Our case studies included 54 semi-structured interviews across 7 different LSS sites, representing a diversity of geographies, project sizes (MW), site types (i.e., greenfield, agrivoltaic, and brownfield / contaminated sites), zoning jurisdiction types, and more (Table 1). In addition to local residents living in close proximity to these LSS sites, we interviewed other key stakeholders involved in the projects such as developers, decision-makers, utility representatives, landowners, and individuals from community-based organizations. The overarching aim of this case study research was two-fold: (1) to inform subsequent tasks in the CCSD research project (including an upcoming national survey of LSS neighbors), and (2) to provide insights into the following set of research questions: -What are the key positive and negative drivers leading to support and opposition to LSS projects? -To what extent do LSS projects exacerbate or mitigate perceived inequities and marginalization within hosting communities and how can those inequities be mitigated going forward? -What strategies can communities employ to align LSS development with local land-use plans and community needs and values? The research findings and next steps are described in this slide deck report

Perceptions of Large-Scale Solar Project Neighbors: Results From a National Survey

Driven by favorable economics, policy factors, and decarbonization goals, large-scale solar (LSS, defined here as ground-mounted photovoltaic projects ≥1 MWDC) has expanded rapidly in recent years, with more than 90 gigawatts (GW) now installed across the United States. Growth in LSS deployment is anticipated to accelerate in response to growing electricity demand and utility, state, and federal decarbonization goals. This continued expansion hinges, in part, on the continued support of local residents and decision-makers in communities hosting LSS projects. Understanding the perceptions and attitudes of existing LSS neighbors is critical to inform and enable future LSS deployment, and to improve outcomes for those host communities. As of 2022, there were more than 10 million U.S. homes within 3 miles of LSS plants. Yet, until recently, no comprehensive study had examined the experiences and perceptions of these LSS neighbors. In 2023, a Berkeley Lab team worked with the University of Michigan and Michigan State University to conduct the first-of-its-kind nationally representative survey of LSS neighbors as part of the Community-Centered Solar Development research project. The survey effort ultimately collected 984 responses from residents within 3 miles of existing LSS projects. The survey results are available for download via the full summary analysis slide deck report, as well as a shorter (~4 page) summary brief. The survey instrument (questionnaire) is also available for download for those interested in understanding the survey design or replicating questions in future research