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Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI).The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEVFrom Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEVIn individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.

Trial Protocol

Supplementary Methods

Association between pre-treatment CD4+ T-cell density from available baseline tumor tissue (n=14) and the duration of time on treatment in days.

Waterfall plots demonstrating the percent change in sum of RECIST v1.1 target lesions compared to baseline. Twenty-five out of 26 patients were included; 1 patient withdrew consent and no follow-up imaging was available for review. The waterfall plots are color-coded by (A) best overall response (PR, SD, PD), (B) cohort (1-6), and (C) tumor type (melanoma, RCC, NSCLC). The majority of patients who experienced disease progression on the study had progression in non-target lesions, as denoted by as asterisk (*), and therefore the percent change in tumor from baseline by RECIST is less than the 20% disease progression threshold for multiple patients who had PD.

Lung diseases can complicate pregnancy, but little is known about the experiences of pregnancy among women living with such diseases. This survey aimed to understand the experiences of women with a lung condition before and during pregnancy, in childbirth and post-partum. The survey was translated into nine languages and hosted online between March and May 2018. This paper reports on 327 women who had asthma, cystic fibrosis (CF), lymphangioleiomyomatosis (LAM) and sarcoidosis as a sole or primary lung condition. Women with CF and LAM were most likely to report that their condition influenced their decision to have children. Those with CF and LAM who did become pregnant reported greater satisfaction with their healthcare during pregnancy and gave more consideration to factors such as location and type of birth; they were also more concerned about the impact of the pregnancy on their health than women with other diseases. Women with sarcoidosis reported receiving conflicting advice as to both the impact of their condition on pregnancy and how becoming pregnant might impact their health. Women with asthma reported not always being able to access the information they needed from healthcare professionals. The results suggest that healthcare providers should be having dialogues with affected women early on, from before conception, throughout the pregnancy and after giving birth, and training should be provided to healthcare staff to equip them with the information they need to do this., This survey found that having a lung condition can play a significant role in women's decisions around family planning, pregnancy and birth. Women wanted more specialist support and better information before, during and after pregnancy. https://bit.ly/3CSpHt9

In December 2014, the National Academies of Sciences convened the first of 2 meetings to discuss the potential risks and benefits of so-called gain-of-function (GOF) research, which was defined by the National Scientific Advisory Board for Biosecurity as research toward increasing the transmissibility, pathogenicity, or ability to evade countermeasures of pathogens with pandemic potential. The symposium was part of a deliberative process undertaken by the United States (US) government to inform in developing guidelines for the safe conduct of GOF research. Participants discussed scientific, technical, and ethical aspects regarding the conduct of research, biosafety measures in the US, and, to a minimal degree, biosafety in other countries. The dearth of information available regarding codified international biosafety requirements and norms, as well as the stringency and verification of their implementation, is particularly troubling as many countries conduct or plan to conduct GOF research. This analysis was conducted to inform policy makers, scientists, and biosafety professionals on a global scale of strengths and potential safety weaknesses by comparing publicly available regulations, laws, guidelines, and published articles describing biosafety processes and measures in other developed countries that may conduct GOF research compared to measures in place in the US. As GOF research has the potential to cause pandemic illness, the findings in this review can be applied to address potential safety gaps by countries with established biosafety capabilities and can serve as a comprehensive guide for countries with nascent or developing biosafety capability working with high-consequence pathogens or contemplating conducting GOF research.

Introduction: Spill response procedures are an important aspect of laboratories where infectious materials are handled. The decades-old conventional method of spill cleanup uses paper towels to cover the spill. It requires 2 staff and involves a considerable amount of bending and squatting and being able to balance in those positions while wearing personal protective equipment (PPE). In this article, we describe a method that simplifies spill cleanup and compares it to the conventional method. The simplified method can be easily conducted by 1 person, takes about half the time, generates less waste, and reduces the amount of time spent in contaminated areas. Objective: The objective is to describe a modified, simple method of spill cleanup. Methods: A mock spill was created and a spill response initiated per the institution’s procedure. The simplified procedure uses a pail filled with decontaminant and a household mop dripping with the decontaminant. Mopping is done from the noncontaminated area toward the contaminated area so the spill does not spread. Mopping is done more than once, and all the materials used, including the mop(s), are disposed as biohazardous material. Results: The simplified spill cleanup process described here can be performed by just one person and does not require bending and squatting while wearing PPE. The kit is very simple, consisting of a pail and a mop, which are common household tools familiar to most people. Conclusion: The mop-and-pail methodology is simple, requires only one staff member, generates less biological waste, and requires less training and practice while effectively cleaning the spill.

Introduction To capture the patient’s attitude toward remote monitoring of motor neuron disease (MND) in care and clinical trials, and their concerns and preferences regarding the use of digital technology. Methods We performed an international multi-centre survey study in three MND clinics in The Netherlands, the United Kingdom, and Australia. The survey was co-developed by investigators and patients with MND, and sent to patients by e-mail or postal-mail. The main topics included: patients’ attitude towards remote care, participating in decentralized clinical trials, and preferences for and concerns with digital technology use. Results In total, 332 patients with MND participated. A majority of patients indicated they would be happy to self-monitor their health from home (69%), be remotely monitored by a multidisciplinary care team (75%), and would be willing to participate in clinical trials from home (65%). Patients considered respiratory function and muscle strength most valuable for home-monitoring. The majority of patients considered the use of at least three devices/apps (75%) once a week (61%) to be acceptable for home-monitoring. Fifteen percent of patients indicated they would not wish to perform home-measurements; reporting concerns about the burden and distress of home-monitoring, privacy and data security. Conclusion Most patients with MND exhibited a positive attitude toward the use of digital technology in both care and clinical trial settings. A subgroup of patients reported concerns with home-monitoring, which should be addressed in order to improve widespread adoption of remote digital technology in clinical MND care.

The food–energy–water (FEW) nexus describes interactions among domains that yield gains or trade-offs when analysed together rather than independently. In a project about renewable energy in rural Alaska communities, we applied this concept to examine the implications for sustainability and resilience. The FEW nexus provided a useful framework for identifying the cross-domain benefits of renewable energy, including gains in FEW security. However, other factors such as transportation and governance also play a major role in determining FEW security outcomes in rural Alaska. Here, we show the implications of our findings for theory and practice. The precise configurations of and relationships among FEW nexus components vary by place and time, and the range of factors involved further complicates the ability to develop a functional, systematic FEW model. Instead, we suggest how the FEW nexus may be applied conceptually to identify and understand cross-domain interactions that contribute to long-term sustainability and resilience. While the food–energy–water nexus has become a focal point for inter- and cross-disciplinary studies in recent years, this analysis of rural communities contextualizes how effective the nexus is for describing and studying interactions.

Social distancing due to COVID-19 may adversely impact treatment of adults with serious mental illness, especially those receiving intensive forms of community-based care, in part through weakening of the therapeutic alliance. Veterans and staff at a Veterans Affair (VA) medical center were surveyed 3 months after social distancing disrupted usual service delivery in intensive community-based treatment programs. Veterans (n = 105) and staff (n = 112) gave similar multi-item ratings of service delivery after social distancing, which involved far less face-to-face contact and more telephone contact than usual and rated their therapeutic alliances and clinical status similarly as "not as good" on average than before social distancing. Self-reported decline in therapeutic alliance was associated with parallel decline in clinical status indicators. Both veterans and staff indicated clear preference for return to face-to-face service delivery after the pandemic with some telehealth included.

Stimulating innate immunity can potentially enable us to overcome resistance to PD-(L)1 blockade. We previously conducted a phase 1 trial of cabiralizumab (anti-CSF1R) with sotigalimab (CD40 agonistic antibody) and nivolumab. Our purpose was to determine safety and the effects of this regimen on circulating and tumor-infiltrating immune cells and to determine the activity of this regimen in a phase 1b trial for melanoma patients whose disease had progressed on anti-PD-(L)1. CyTOF analysis on circulating immune cells taken before and during treatment revealed a reduction in non-classical monocytes and an increase in dendritic cells. Patients with prolonged stable disease had less T-regulatory cells and more circulating antigen presenting cells after treatment compared to patients that were treated for a shorter time. In the phase 1b component of the trial in 13 melanoma patients, objective response rates were: 1 confirmed partial response (7.7%), 1 unconfirmed partial response (7.7%), 5 stable disease (38.5%) and 6 disease progression (42.6%). Despite therapy-induced changes in circulating immune cells and previous preclinical studies supporting rationale for this combination, responses in humans were insufficient to proceed to the second stage of the phase 1b trial. Given the challenges with translating doses from mice to humans, we proceeded to study various doses of anti-CSF1R in combination with CD40 agonist and anti-PD-1 in a murine model. Higher dose anti-CSF1R in mice was associated with increased tumor growth, worse survival and by single-cell RNA-sequencing analyses, we identified a more suppressive monocyte/macrophage profile in murine tumors. Our study suggests that more anti-CSF1R might not be better. Further optimization of cabiralizumab dosing is necessary to evaluate the clinical potential in combination with anti-PD-1 and anti-CD40 in a difficult-to treat patient population whose therapeutic options are limited. Citation Format: Dijana Djureinovic, Sarah A. Weiss, Irina Krykbaeva, Rihao Qu, Ioannis Vathiotis, Myrto Moutafi, Lin Zhang, Ana L. Perdigoto, Wei Wei, Gail Anderson, William Damsky, Michael Hurwitz, Barbara Johnson, Amit Mahajan, Frank Hsu, Kathryn Miller-Jensen, Yuval Kluger, Mario Sznol, Susan M. Kaech, Marcus Bosenberg, Lucia Jilaveanu, Harriet M. Kluger. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3287.

Food, energy, and water (FEW) are basic needs for well-being and quality of life. Assessing FEW security allows residents, communities, and policy makers to make informed decisions about how to sustain and improve well-being. We have developed a FEW security assessment framework that examines four components of security: availability, access, quality, and preference. With the help of local community members, we interviewed 114 households in three rural Alaska communities to assess FEW security, drivers and outcomes of FEW security, and potential interactions among FEW components and with renewable energy (RE) developments. While FEW security was high overall, preference and quality, especially for food, was lower. Food harvested from the local environment (i.e. subsistence) was necessary to include in security assessments given that 24% of participants reported insecurity when asked about contemporary sources (i.e. purchased) versus 5% reporting insecurity for subsistence food sources (i.e., harvested). The major influences on FEW security tended to originate from outside the community, including factors such as transportation, income, fuel prices, and weather. One internal factor, health, was both a driver and an outcome of FEW security. Satisfaction with RE varied (42%-68%) with dissatisfaction due to unreliability, uncertainty of the economic benefit, desire for other types of RE, or wanting more RE (n = 6). Communication about RE projects was key to managing expectations, promoting knowledge, and identifying benefits for residents. Participants did not identify linkages between RE and FEW security. Our assessment tool can be used by communities and policy makers to contextualize FEW security into more insightful and specific components, allowing for identification of attainable actions to improve FEW security and thus individual and community well-being.

Background Veterans and their families seek care in all health care settings; therefore, it is imperative for nurses to understand the unique needs of this population to effectively provide care. Sample The research was conducted at a U.S. Midwestern University that uses Veteran-centric simulations throughout their baccalaureate nursing program with 41% of the simulations during the first semester being Veteran centric. A convenience sample of first semester nursing students participated in this study. Methods A descriptive-comparative research design was used to compare students' perception of confidence and comfort in caring for Veterans at the beginning and end of the first semester. Results Findings from this study indicate a significant improvement in students' perceptions from the beginning to the end of the first semester (p Conclusion This study adds to the body of literature using empirical research to evaluate the effectiveness of simulation in increasing students' awareness of Veteran's health care needs.