Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Novel non-helical antimicrobial peptides insert into and fuse lipid model membranes.

This research addresses the growing menace of antibiotic resistance by exploring antimicrobial peptides (AMPs) as alternatives to conventional antibiotics. Specifically, we investigate two linear amphipathic AMPs, LE-53 (12-mer) and LE-55 (16-mer), finding that the shorter LE-53 exhibits greater bactericidal activity against both Gram-negative (G(-)) and Gram-positive (G(+)) bacteria. Remarkably, both AMPs are non-toxic to eukaryotic cells. The heightened effectiveness of LE-53 is attributed to its increased hydrophobicity (H) compared to LE-55. Circular dichroism (CD) reveals that LE-53 and LE-55 both adopt ß-sheet and random coil structures in lipid model membranes (LMMs) mimicking G(-) and G(+) bacteria, so secondary structure is not the cause of the potency difference. X-ray diffuse scattering (XDS) reveals increased lipid chain order in LE-53, a potential key distinction. Additionally, XDS study uncovers a significant link between LE-53's upper hydrocarbon location in G(-) and G(+) LMMs and its efficacy. Neutron reflectometry (NR) confirms the AMP locations determined using XDS. Solution small angle X-ray scattering (SAXS) demonstrates LE-53's ability to induce vesicle fusion in bacterial LMMs without affecting eukaryotic LMMs, offering a promising strategy to combat antibiotic-resistant strains while preserving human cell integrity, whereas LE-55 has a smaller ability to induce fusion.

Home testing for SARS-CoV-2 and impact on surveillance in New York State.

PURPOSE: To determine the distribution of diagnosed SARS-CoV-2 infections by testing modality (at-home rapid antigen [home tests] versus laboratory-based tests in clinical settings [clinical tests]), assess factors associated with clinical testing, and estimate the true total number of diagnosed infections in New York State (NYS). METHODS: We conducted an online survey among NYS residents and analyzed data from 1012 adults and 246 children with diagnosed infection July 13-December 7, 2022. Weighted descriptive and logistic regression model analyses were conducted. Weighted percentages and prevalence ratios by testing modality were generated. The percent of infections diagnosed by clinical tests via survey data were synthesized with daily lab-reported results to estimate the total number of diagnosed SARS-CoV-2 infections in NYS July 1-December 31, 2022. RESULTS: Over 70% of SARS-CoV-2 infections in NYS during the study period were diagnosed exclusively with home tests. Diagnosis with a clinical test was associated with age, race/ethnicity, and region among adults, and sex, age, and education among children. We estimate 4.1 million NYS residents had diagnosed SARS-CoV-2 infection July 1-December 31, 2022, compared to 1.1 million infections reported over the same period. CONCLUSIONS: Most SARS-CoV-2 infections in NYS were diagnosed exclusively with home tests. Surveillance metrics using laboratory-based reporting data underestimate diagnosed infections.

Novel Helical Trp- and Arg-Rich Antimicrobial Peptides Locate Near Membrane Surfaces and Rigidify Lipid Model Membranes.

Antibiotics are losing effectiveness as bacteria become resistant to conventional drugs. To find new alternatives, antimicrobial peptides (AMPs) are rationally designed with different lengths, charges, hydrophobicities (H), and hydrophobic moments (µH), containing only three types of amino acids: arginine, tryptophan, and valine. Six AMPs with low minimum inhibitory concentrations (MICs) and <25% toxicity to mammalian cells are selected for biophysical studies. Their secondary structures are determined using circular dichroism (CD), which finds that the % α-helicity of AMPs depends on composition of the lipid model membranes (LMMs): gram-negative (G(-)) inner membrane (IM) >gram-positive (G(+)) > Euk33 (eukaryotic with 33 mol% cholesterol). The two most effective peptides, E2-35 (16 amino acid [AA] residues) and E2-05 (22 AAs), are predominantly helical in G(-) IM and G(+) LMMs. AMP/membrane interactions such as membrane elasticity, chain order parameter, and location of the peptides in the membrane are investigated by low-angle and wide-angle X-ray diffuse scattering (XDS). It is found that headgroup location correlates with efficacy and toxicity. The membrane bending modulus KC displays nonmonotonic changes due to increasing concentrations of E2-35 and E2-05 in G(-) and G(+) LMMs, suggesting a bacterial killing mechanism where domain formation causes ion and water leakage.

Analysis on the factors associated with COVID-19 infection among Chinese residents after the implementation of the 10 new rules to optimize COVID-19 response: a cross-sectional study.

Introduction: This study aimed to investigate the status of COVID-19 infection and the associated factors among Chinese residents after the implementation of the 10 New Rules to optimize COVID response. Methods: Participants were recruited using convenience sampling. The study used self-filled questionnaires to examine COVID-19 infection and associated factors among Chinese residents, from December 29, 2022, to January 2, 2023. For the statistical analysis, descriptive and quantitative analyses were used. The potential risk factors for COVID-19 infection were identified by multivariable logistic regression analysis. Results: After the adjustments in control strategies against COVID-19, the infection rate of COVID-19 was high among respondents, and 98.4% of individuals who tested positive showed symptoms including cough, fever, fatigue, headache, sore throat, nasal congestion, sputum production, muscle and joint pain, and runny nose. The main problems respondents reported were the shortage of drugs and medical supplies, the increased burden on families, and the unreliable information source of COVID-19 infection. Logistic regression showed that isolating patients with COVID-19 at home was associated with a lower risk of COVID-19 infection (OR = 0.58, 95%CI: 0.42-0.81). Conclusion: COVID-19 infection among residents is closely related to age, gender, and epidemic prevention measures. The government needs to strengthen education for individuals and centrally manage and properly address difficulties that may arise during COVID-19.

Efficacy and safety of first-line immune checkpoint inhibitors combined with chemotherapy for extensive-stage small cell lung cancer: A network meta-analysis.

The efficacy and safety of first-line immune checkpoint inhibitors plus chemotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) remains unevaluated, and there are no reports to directly compare the efficacy and safety among different immunotherapy (especially adebrelimab and surplulimab). Suitable phase III randomized controlled trials with two or more different arms were included. Independent reviewers screened and extracted relevant data and disagreements were resolved through consensus. Fixed-effect consistency models were used to calculate the overall survival (OS), progression-free survival (PFS), objective response rate, adverse events ≥ 3, and safety outcomes in the clinically relevant subgroups. In this network meta-analysis, six randomized controlled clinical trials (CAPSTONE-1, ASTRUM-005, CASPIAN, IMpower133, KEYNOTE-604, and an ipilimumab + chemotherapy trial) with totaling 3662 patients were involved. Compared to chemotherapy, immune checkpoint inhibitors plus chemotherapy present higher possibilities to bring about better OS and PFS. Serplulimab + chemotherapy significantly showed a better survival profit in comparison with ipilimumab + chemotherapy (0.67; 0.50-0.90). Compared with chemotherapy, adebrelimab + chemotherapy (0.72; 0,58-0.90), atezolizumab + chemotherapy (0.76; 0.60-0.96) durvalumab + chemotherapy (0.75; 0.62-0.91), and serplulimab + chemotherapy (0.63;0.49-0.82) all presented significantly better overall survival. In terms of progression-free survival, serplulimab + chemotherapy showed better efficacy in comparison with adebrelimab + chemotherapy (0.72; 0,53-0.97), atezolizumab + chemotherapy (0.62; 0.46-0.84), durvalumab + chemotherapy (0.60; 0.45-0.80). Compared with chemotherapy, adebrelimab + chemotherapy (0.67; 0.54-0.83) and serplulimab + chemotherapy (0.48; 0.48-0.86) all presented significantly better PFS. Immunotherapy plus chemotherapy had similar probabilities to cause adverse events of grade ≥ 3. In comparison with chemotherapy, immune checkpoint inhibitors plus chemotherapy were likely to be more suitable for the first-line treatment of ES-SCLC. According to our analysis, serplulimab plus chemotherapy and adebrelimab plus chemotherapy present higher possibilities to show better efficacy and safety, however, the level of evidence of this type of comparison is limited.

Changes in Prescribed Opioid Dosages Among Patients Receiving Medical Cannabis for Chronic Pain, New York State, 2017-2019.

Importance: Patients with chronic pain often receive long-term opioid therapy (LOT), which places them at risk of opioid use disorder and overdose. This presents the need for alternative or companion treatments; however, few studies on the association of medical cannabis (MC) with reducing opioid dosages exist. Objective: To assess changes in opioid dosages among patients receiving MC for longer duration compared with shorter duration. Design, Setting, and Participants: This cohort study of New York State Prescription Monitoring Program data from 2017 to 2019 included patients receiving MC for chronic pain while also receiving opioid treatment. Of these, patients receiving LOT prior to receiving MC were selected. Individuals were studied for 8 months after starting MC. Data were analyzed from November 2021 to February 2022. Exposures: Selected patients were divided into 2 groups based on the duration of receiving MC: the nonexposure group received MC for 30 days or fewer, and the exposure group received MC for more than 30 days. Main Outcomes and Measures: The main outcome was opioid dosage, measured by mean daily morphine milligram equivalent (MME). Analyses were conducted for 3 strata by opioid dosage prior to receiving MC: MME less than 50, MME of 50 to less than 90, and MME of 90 or greater. Results: A total of 8165 patients were included, with 4041 (median [IQR] age, 57 [47-65] years; 2376 [58.8%] female) in the exposure group and 4124 (median [IQR] age, 54 (44-62) years; 2370 [57.5%] female) in the nonexposure group. Median (IQR) baseline MMEs for the exposure vs nonexposure groups were 30.0 (20.0-40.0) vs 30.0 (20.0-40.0) in the lowest stratum, 60.0 (60.0-70.0) vs 60.0 (60.0-90.0) in the middle stratum, and 150.0 (100.0-216.2) vs 135.0 (100.0-218.0) in the highest stratum. During follow-up, significantly greater reductions in opioid dosage were observed among the exposure group. A dose-response association of patients' opioid dosage at baseline was observed with the differences in the monthly MME reductions between exposure and nonexposure groups, with a difference of -1.52 (95% CI, -1.67 to -1.37) MME for the lowest stratum, -3.24 (95% CI, -3.61 to -2.87) MME for the middle stratum, and -9.33 (95% CI, -9.89 to -8.77) MME for the highest stratum. The daily MME for the last month of the follow-up period among patients receiving longer MC was reduced by 48% in the lowest stratum, 47% in the middle stratum, and 51% in the highest stratum compared with the baseline dosages. Among individuals in the nonexposure group, daily MME was reduced by only 4% in the lowest stratum, 9% in the middle stratum, and 14% in the highest stratum. Conclusions and Relevance: In this cohort study of patients receiving LOT, receiving MC for a longer duration was associated with reductions in opioid dosages, which may lower their risk of opioid-related morbidity and mortality.

An all-Africa dataset of energy model "supply regions" for solar photovoltaic and wind power.

With solar and wind power generation reaching unprecedented growth rates globally, much research effort has recently gone into a comprehensive mapping of the worldwide potential of these variable renewable electricity (VRE) sources. From a perspective of energy systems analysis, the locations with the strongest resources may not necessarily be the best candidates for investment in new power plants, since the distance from existing grid and road infrastructures and the temporal variability of power generation also matter. To inform energy planning and policymaking, cost-optimisation models for energy systems must be fed with adequate data on potential sites for VRE plants, including costs reflective of resource strength, grid expansion needs and full hourly generation profiles. Such data, tailored to energy system models, has been lacking up to now. In this study, we present a new open-source and open-access all-Africa dataset of "supply regions" for solar photovoltaic and onshore wind power to feed energy models and inform capacity expansion planning.

Experiences of HIV/STD Providers in New York State During Hurricane Sandy: Strengths, Challenges, and Recommendations.

OBJECTIVES: The aim of this study was to assess strengths and challenges experienced by HIV/STD providers in providing care during the response to Hurricane Sandy (Sandy) in New York State, and their recommendations for future preparedness. METHODS: A mixed methods approach, including a focus group (n = 3), interviews (n = 3), and survey (n = 31) of HIV/STD providers, was used. Key words identified by means of open coding methodology from collected data were organized into strengths, challenges, and recommendations and then grouped into federal and study-associated preparedness capabilities. RESULTS: Key words were organized into 81 strengths (38.8%), 73 challenges (34.9%), and 55 recommendations (26.3%). Services most interrupted during Sandy were related to HIV/STD outreach and education. While providers reported challenges with external agency communication, the ability to still connect clients to needed resources was reported as a strength. Strengthening partnerships with federal, state, and local agencies was among the major recommendations made by these providers. CONCLUSIONS: This study presents unique information about challenges experienced by HIV/STD providers in providing services during a natural disaster and the use of national public health emergency preparedness capabilities to address and overcome those challenges. Lessons learned and recommendations regarding inter-agency communications emerged as an important priority during a natural disaster to minimize or reduce service interruption.

Generating Subcounty Health Data Products: Methods and Recommendations From a Multistate Pilot Initiative.

BACKGROUND: County Health Rankings & Roadmaps (CHR&R) makes data on health determinants and outcomes available at the county level, but health data at subcounty levels are needed. Three pilot projects in California, Missouri, and New York explored multiple approaches for defining measures and producing data at subcounty geographic and demographic levels based on the CHR&R model. This article summarizes the collective technical and implementation considerations from the projects, challenges inherent in analyzing subcounty health data, and lessons learned to inform future subcounty health data projects. METHODS: The research teams used 12 data sources to produce 40 subcounty measures that replicate or approximate county-level measures from the CHR&R model. Using varying technical methods, the pilot projects followed similar stages: (1) conceptual development of data sources and measures; (2) analysis and presentation of small-area and subpopulation measures for public health, health care, and lay audiences; and (3) positioning the subcounty data initiatives for growth and sustainability. Unique technical considerations, such as degree of data suppression or data stability, arose during the project implementation. A compendium of technical resources, including samples of automated programs for analyzing and reporting subcounty data, was also developed. RESULTS: The teams summarized the common themes shared by all projects as well as unique technical considerations arising during the project implementation. Furthermore, technical challenges and implementation challenges involved in subcounty data analyses are discussed. Lessons learned and proposed recommendations for prospective analysts of subcounty data are provided on the basis of project experiences, successes, and challenges. CONCLUSIONS: This multistate pilot project offers 3 successful approaches for creating and disseminating subcounty data products to communities. Subcounty data often are more difficult to obtain than county-level data and require additional considerations such as estimate stability, validating accuracy, and protecting individual confidentiality. We encourage future projects to further refine techniques for addressing these critical considerations.

Superstorm Sandy's impact on the provision of WIC (Special Supplemental Nutrition Program for Women, Infants, and Children) services in New York State.

OBJECTIVE: Services provided by the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) were interrupted in 2012 when Superstorm Sandy struck New York State (NYS). The present study evaluates the impact on WIC providers. DESIGN: A focus group, telephone interviews and anonymous online survey were conducted. Qualitative data were analysed by coding transcribed text into key words and identifying major and minor themes for strengths, challenges and recommendations using national public health preparedness capabilities. Survey responses were analysed quantitatively; reported challenges were classified by preparedness capability. SETTING: The focus group was held at a 2014 regional WIC meeting. Interviews and a survey were conducted via telephone in 2014 and online in 2015, respectively. SUBJECTS: WIC staff representing New York City and three NYS counties. RESULTS: In the focus group (n 12) and interviews (n 6), 'emergency operations coordination' was the most cited capability as a strength, 'environmental health protection' (against environmental hazards) as a challenge and 'flexibility' (on rules and procedures) as a recommendation. In the survey (n 24), the capability 'information sharing' was most often cited as a challenge. Most staff (66·6 %) reported their programmes were at least somewhat prepared for future weather-related disasters. Only 16·7 % indicated having practiced a work-related emergency response plan since Sandy. Staff who practiced an emergency response plan were more likely to indicate they were prepared (P < 0·05). CONCLUSIONS: The study identified WIC programme areas requiring preparedness improvements. The research methodology can be utilized to assess the continuity of other public health services during disasters.

New York State Public Health System Response to Hurricane Sandy: An Analysis of Survey Feedback.

OBJECTIVE: The objective was to provide a broad spectrum of New York State and local public health staff the opportunity to contribute anonymous feedback on their own and their agencies' preparedness and response to Hurricane Sandy, perceived challenges, and recommendations for preparedness improvement. METHODS: In 2015, 2 years after Hurricane Sandy, public health staff who worked on Hurricane Sandy response were identified and were provided a link to the anonymous survey. Quantitative analyses were used for survey ratings and qualitative content analyses were used for open-ended questions. RESULTS: Surveys were completed by 129 local health department (LHD) staff in 3 counties heavily impacted by Sandy (Nassau, Suffolk, and Westchester) and 69 staff in the New York State Department of Health who supported the LHDs. Staff agreed that their Hurricane Sandy responsibilities were clearly defined and that they had access to adequate information to perform their jobs. Challenges were reported in the operational, communication, service interruptions, and staff categories, with LHD staff also reporting challenges with shelters. CONCLUSIONS: New York local and state public health staff indicated that they were prepared for Hurricane Sandy. However, their feedback identified specific challenges and recommendations that can be addressed to implement improved preparedness and response strategies. (Disaster Med Public Health Preparedness. 2016;10:454-462).