Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens.

BACKGROUND: Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient's genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location. However, traditional value frameworks and approval pathways pose challenges which may limit patient access to PO therapies. OBJECTIVES: This study describes challenges in assessing PO and TA medicines, explores possible solutions, and provides actionable recommendations to facilitate an iterative life-cycle assessment of these medicines. METHODS: After reviewing the published literature, we obtained insights from key stakeholders and European experts across a range of disciplines, through individual interviews and an industry workshop. The research was guided and refined by an international expert committee through 2 sounding board meetings. RESULTS: The current challenges faced by PO and TA medicines are multiple and can be demonstrated through real-world examples of the current barriers and opportunities. A life-cycle approach to assessment should be taken, including key actions at the early stages of evidence generation, regulatory and reimbursement stage, as well as payment and adoption solutions that make use of the evolving evidence base. Working toward these solutions to maximize PO medicine value is a shared responsibility and stands to benefit all stakeholders. CONCLUSIONS: Our call to action is to expand access to comprehensive genomic testing, foster a learning health care system, enable fast and equitable access to cost-effective treatments, and ultimately improve health outcomes.

Effect of Chalcogenophenes on Chiroptical Activity of Twisted Tetracenes: Computational Analysis, Synthesis and Crystal Structure Thereof.

The synthesis of multiply substituted acenes is still a relevant research problem, considering their applications and future potential. Here we present an elegant synthetic protocol to afford tetra-peri-substituted naphthalene and tetracene from their tetrahalo derivatives by a Pd(0)-catalyzed C-C cross-coupling method in a single step. The newly synthesized tetracenes were characterized by NMR, HRMS, UV-vis spectrophotometry, and single-crystal X-ray diffraction (SCXRD). In addition, the first systematic computational study of the effect of chalcogenophenyl substitutions on the chiroptical properties of twistacenes was reported here. The gas phase computational studies using density functional theory (DFT) on a series of chalcogenophene-substituted tetracenes revealed that their chiroptical activity could be systematically increased via the atomistic tuning of peripheral substituents.

Mucormycosis diagnosis revisited: Current and emerging diagnostic methodologies for the invasive fungal infection (Review).

Mucormycosis, which is a life threatening condition, is one of the side effects experienced by post-COVID-19 patients. Early identification and timely treatment are essential to stop the dissemination of the disease, since invasive mucormycosis has a very high fatality rate and significant disease dispersion. Conventional diagnostic techniques, including clinical diagnosis, serology, histopathology and radiology, have limitations in diagnosing the disease at an early stage. This warrants the need for advanced diagnostic tools such as nucleic acid diagnostics, advanced serological tests (ELISpot), PCR (pan-Mucorale test) and multiplex PCR. These techniques have been introduced to identify this invasive fungal infection at an incipient stage, thereby helping clinicians to prevent adverse outcomes. The use of biosensors and micro-needle based diagnostic methodologies will pave the way for devising more point-of-care tests that can be employed for the detection of mucormycosis at an incipient stage. The present review discusses the current techniques available and their drawbacks, and the usefulness of advanced diagnostic tools. Furthermore, the possibility of using future diagnostic methods for the diagnosis of mucormycosis is highlighted.

Pregnancy Complications Among Resettled Refugees in Illinois.

Newly resettled refugee populations often have significant health care needs including pregnancy complications; yet research is lacking on pregnancy complications among refugees in Illinois. This was a retrospective analysis of the 2016-2017 hospital discharge data of refugee women of childbearing age (15-44 years) in Illinois. There were 3,355 hospital encounters by refugee women in our analysis, and 19.1% (n = 640) were associated with complications mainly related to pregnancy. The majority of hospital encounters associated with complications mainly related to pregnancy occurred after the first 8 months of US arrival (85.2%) and were among women who had Medicaid insurance (90.3%), ≥ 5 hospital encounters (60.2%), and who were most commonly from Iraq (23.3%) or Burma (19.4%). Refugee women may benefit from increased awareness and education about prenatal care, support in access, and prompt referrals.

Effect of Bicycle Ergometer Training and Nordic Walking Training on Improving Functional Exercise Capacity in Asthma Patients.

Introduction Asthma is a chronic respiratory condition characterized by inflammation of the airway leading to breathlessness. Exercise training has been recognized as a valuable component in the management of asthma, enhancing lung function and overall well-being. Bicycle ergometer training and Nordic walking are two distinct forms of exercise that have been shown to improve cardiovascular fitness and respiratory function. Despite the potential benefits of these exercises, limited research directly compares their efficacy in improving functional capacity specifically in asthma patients. The study thus aims to address this gap by providing personalized, tailored exercise programs for asthma patients. Methods A single-blinded experimental study using a simple random sampling method was conducted. A sample of 40 subjects was recruited for the study based on inclusion and exclusion criteria and were assigned into two groups. Group A subjects were trained with a bicycle ergometer and Group B subjects were trained with Nordic walking. The intervention was given to both groups for 12 weeks. The outcome measures used were the six-minute walk test, Modified Borg Scale, and Mini Asthma Quality of Life Questionnaire. Results A baseline analysis of outcome measures was done, which was followed up by a post-test analysis after 12 weeks. Pre-test and post-test data were compared using a paired t-test. Intergroup analysis was done by an independent t-test. Both groups showed significant improvement in post-test results. On comparing the two groups, Group A showed significant improvement as compared to Group B. Conclusion The study concludes that bicycle ergometer training is effective in improving functional capacity and enhancing the quality of life in asthma patients.

Coronavirus Disease 2019 (COVID-19) Vaccination Coverage, Intentions, Attitudes, and Barriers by Race/Ethnicity, Language of Interview, and Nativity-National Immunization Survey Adult COVID Module, 22 April 2021-29 January 2022.

The National Immunization Survey Adult COVID Module used a random-digit-dialed phone survey during 22 April 2021-29 January 2022 to quantify coronavirus disease 2019 (COVID-19) vaccination, intent, attitudes, and barriers by detailed race/ethnicity, interview language, and nativity. Foreign-born respondents overall and within racial/ethnic categories had higher vaccination coverage (80.9%), higher intent to be vaccinated (4.2%), and lower hesitancy toward COVID-19 vaccination (6.0%) than US-born respondents (72.6%, 2.9%, and 15.8%, respectively). Vaccination coverage was significantly lower for certain subcategories of national origin or heritage (eg, Jamaican [68.6%], Haitian [60.7%], Somali [49.0%] in weighted estimates). Respondents interviewed in Spanish had lower vaccination coverage than interviewees in English but higher intent to be vaccinated and lower reluctance. Collection and analysis of nativity, detailed race/ethnicity and language information allow identification of disparities among racial/ethnic subgroups. Vaccination programs could use such information to implement culturally and linguistically appropriate focused interventions among communities with lower vaccination coverage.

Lessons Learned From a Qualitative COVID-19 Investigation Among Essential Workers With Limited English Proficiency in Southwest Kansas.

In this commentary, we briefly describe our methodology in conducting a remote qualitative investigation with essential workers from southwest Kansas, and then describe some key considerations, challenges, and lessons learned in recruiting and conducting interviews remotely. From August 4, 2020 through August 26, 2020, Centers for Disease Control and Prevention (CDC) staff conducted five phone interviews with culturally and linguistically diverse employees in southwest Kansas to understand COVID-19 knowledge, attitudes, and practices and communication preferences. Our experience details the potential challenges of the federal government in recruiting individuals from these communities and highlights the possibilities for more effectively engaging health department and community partners to support investigation efforts. Optimizing recruitment strategies with additional participation from community partners, developing culturally and linguistically appropriate data collection tools, and providing supportive resources and services may augment participation from refugee, immigrant, and migrant (RIM) communities in similar remote investigations.

Exploring the discrimination and stigma faced by transgender in Chennai city-A community-based qualitative study.

Background: Transgender people experience widespread prejudice discrimination, violence and other harms of stigma and trans-phobia (dislike of or prejudice against trans-sexual or transgender people). To study various modes in which transgenders experience the stigma and discrimination and to understand situations and circumstances under which they are vulnerable toward stigma and discrimination. Materials and Methods: The present study was a mixed-method study which was conducted during the months of January to June 2019 among 43 study participants. Focus group discussion and in-depth interview was conducted with these participants with subsequent transcription. Interpretative phenomenological analysis (IPA) was used for analysis. Results: Transgenders face discrimination and stigma in various setting including education, employment, healthcare, and various public setting. Difficulties in getting government identity cards (ID), facing difficulties in changing ID cards after transition, discrimination in getting bank loan, homelessness, travelling rejections were considered as major obstacles and discrimination by the study participants. Conclusion: Multilevel interventions are needed for transgender populations, including legal protections, improvement of various settings. Inclusive measures should be taken to improve their status focusing on social stigma coupled with psychological pain and economic hardship.

Community Health Worker Initiatives: An Approach to Design and Measurement.

CONTEXT: The Centers for Disease Control and Prevention supports the engagement of community health workers (CHWs) to help vulnerable populations achieve optimum health through a variety of initiatives implemented in several organizational units. PROGRAM: This article provides a unified and comprehensive logic model for these initiatives that also serves as a common framework for monitoring and evaluation. IMPLEMENTATION: We developed a logic model to fully describe the levels of effort needed to effectively and sustainably engage CHWs. We mapped monitoring and evaluation metrics currently used by federally funded organizations to the logic model to assess the extent to which measurement and evaluation are aligned to programmatic efforts. EVALUATION: We found that the largest proportion of monitoring and evaluation metrics (61%) currently used maps to the "CHW intervention level" of the logic model, a smaller proportion (37%) maps to the "health system and community organizational level," and a minimal proportion (3%) to the "statewide infrastructure level." DISCUSSION: Organizations engaging CHWs can use the logic model to guide the design as well as performance measurement and evaluation of their CHW initiatives.

A Logic Model Framework for Planning an International Refugee Health Research, Evaluation, and Ethics Committee.

Collaborative approaches to supporting the health of refugees and other newcomer populations in their resettlement country are needed to address the complex medical and social challenges they may experience after arrival. Refugee health professionals within the Society of Refugee Healthcare Providers (SRHP)-the largest medical society dedicated to refugee health in North America-have expressed interest in greater research collaborations across SRHP membership and a need for guidance in conducting ethical research on refugee health. This article describes a logic model framework for planning the SRHP Research, Evaluation, and Ethics Committee. A logic model was developed to outline the priorities, inputs, outputs, outcomes, assumptions, external factors, and evaluation plan for the committee. The short-term outcomes include (1) establish professional standards in refugee health research, (2) support evaluation of existing refugee health structures and programs, and (3) establish and disseminate an ethical framework for refugee health research. The SRHP Research, Evaluation, and Ethics Committee found the logic model to be an effective planning tool. The model presented here could support the planning of other research committees aimed at helping to achieve health equity for resettled refugee populations.

Exposure to zinc oxide nanoparticles (ZnO-NPs) induces cardiovascular toxicity and exacerbates pathogenesis - Role of oxidative stress and MAPK signaling.

The precise toxico-pathogenic effects of zinc oxide nanoparticles (ZnO-NPs) on the cardiovascular system under normal and cardiovascular disease (CVD) risk factor milieu are unclear. In this study, we have investigated the dose-dependent effects of ZnO-NPs on developing chicken embryo and cell culture (H9c2 cardiomyoblast, HUVEC and aortic VSMC) models. In addition, the potentiation effect of ZnO-NPs on simulated risk factor conditions was evaluated using; 1. Reactive oxygen species (ROS) induced cardiac remodeling, 2. Angiotensin-II induced cardiac hypertrophy, 3. TNF-α induced HUVEC cell death and 4. Inorganic phosphate (Pi) induced aortic VSMC calcification models. The observed results illustrates that ZnO-NPs exposure down regulates vascular development and elevates oxidative stress in heart tissue. At the cellular level, ZnO-NPs exposure reduced the cell viability and increased the intracellular ROS generation, lipid peroxidation and caspase-3 activity in a dose-dependent manner in all three cell types. In addition, ZnO-NPs exposure significantly suppressed the endothelial nitric oxide (NO) generation, cardiac Ca2+ - ATPase activity and enhanced the cardiac mitochondrial swelling. Moreover, inhibition of p38 MAPK and JNK signaling pathways influence the cytotoxicity. Overall, ZnO-NPs exposure affects the cardiovascular system under normal conditions and it exacerbates the cardiovascular pathogenesis under selected risk factor milieu.

Movement-Based Therapies for Resettled Refugee Populations in the United States.

Persons who are refugees may experience mental health concerns, such as posttraumatic stress disorder and depression, due to multiple layers of trauma experienced before, during, and after fleeing their country of origin. Although several health system- and community-based mental health interventions have been found to be effective in improving mental health outcomes among persons who are refugees in the United States, these services are underutilized among refugees. Movement-based and mind body-focused practices, such as yoga, may play an important role as complementary mental health supports for refugees. Data on the effectiveness of these practices in these populations are limited, and further research is needed. However, these practices can still be introduced in a safe way by trained professionals and offered as adjunctive therapeutic approaches to traditional Western psychotherapy options. We offer recommendations for clinical providers working with persons who are refugees and for movement-based facilitators and therapists on how to introduce these practices to resettled refugee populations in the United States.

Health of Asylees Compared to Refugees in the United States Using Domestic Medical Examination Data, 2014-2016: A Cross-Sectional Analysis.

BACKGROUND: Between 2008 and 2018, persons granted asylum (asylees) increased by 168% in the United States. Asylees are eligible for many of the same domestic benefits as refugees under the US Refugee Admissions Program (USRAP), including health-related benefits such as the domestic medical examination. However, little is known about the health of asylees to guide clinical practice. METHODS: We conducted a retrospective cross-sectional analysis of domestic medical examination data from 9 US sites from 2014 to 2016. We describe and compare demographics and prevalence of several infectious diseases such as latent tuberculosis infection (LTBI), hepatitis B and C virus (HBV, HCV), and select sexually transmitted infections and parasites by refugee or asylee visa status. RESULTS: The leading nationalities for all asylees were China (24%) and Iraq (10%), while the leading nationalities for refugees were Burma (24%) and Iraq (19 %). Approximately 15% of asylees were diagnosed with LTBI, and 52% of asylee adults were susceptible to HBV infection. Prevalence of LTBI (prevalence ratio [PR] = 0.8), hepatitis B (0.7), hepatitis C (0.5), and Strongyloides (0.5) infections were significantly lower among asylees than refugees. Prevalence of other reported conditions did not differ by visa status. CONCLUSIONS: Compared to refugees, asylees included in our dataset were less likely to be infected with some infectious diseases but had similar prevalence of other reported conditions. The Centers for Disease Control and Prevention's Guidance for the US Domestic Medical Examination for Newly Arrived Refugees can also assist clinicians in the care of asylees during the routine domestic medical examination.

Wearable Activity Monitor Use Is Associated With the Aerobic Physical Activity Guidelines and Walking Among Older Adults.

PURPOSE: To examine wearable activity monitor (WAM) use and its association with meeting the 2008 aerobic Physical Activity Guidelines (PAG) and walking among older adults. DESIGN: Cross-sectional. SETTING: FallStyles 2015 national consumer panel survey. SAMPLE: 1,317 U.S. adults aged ≥ 60 years. MEASURES: Self-reported WAM use, meeting aerobic PAG, and walking. Covariates included age, sex, race/ethnicity, education level, marital status, annual household income, and geographic region of the country. ANALYSIS: Chi-square tests to examine associations between WAM use and respondent demographic characteristics. Logistic regressions to explore associations between WAM use and meeting aerobic PAG and walking adjusted for demographics (e.g., education, income). RESULTS: Among older adults, 8.0% were current WAM users and 11.3% were past WAM users. Current WAM use was most prevalent among those aged 65-74 (16.6%), females (9.4%), college graduates (13.8%), and those with incomes $75,000-$99,999 (14.8%). Current WAM users were more likely than never WAM users to report meeting aerobic PAG (OR: 3.98; 95% CI: 2.07, 7.66) and walking (OR: 3.90; 95% CI: 1.57, 9.69). Past and never WAM use were not associated with meeting aerobic PAG or walking. CONCLUSION: We found current WAM use is associated with meeting the aerobic PAG and walking among older adults. Further longitudinal research is needed to understand whether WAM could promote increased PA among older adults.

Long-Term Physical Health Outcomes of Resettled Refugee Populations in the United States: A Scoping Review.

Several studies describe the health of recently resettled refugee populations in the US beyond the first 8 months after arrival. This review summarizes the results of these studies. Scientific articles from five databases published from January 2008 to March 2019 were reviewed. Articles were included if study subjects included any of the top five US resettlement populations during 2008-2018 and if data described long-term physical health outcomes beyond the first 8 months after arrival in the US. Thirty-three studies met the inclusion criteria (1.5%). Refugee adults had higher odds of having a chronic disease compared with non-refugee immigrant adults, and an increased risk for diabetes compared with US-born controls. The most commonly reported chronic diseases among Iraqi, Somali, and Bhutanese refugee adults included diabetes and hypertension. Clinicians should consider screening and evaluating for chronic conditions in the early resettlement period. Further evaluations can build a more comprehensive, long-term health profile of resettled refugees to inform public health practice.

Potential Impact of COVID-19 on Recently Resettled Refugee Populations in the United States and Canada: Perspectives of Refugee Healthcare Providers.

Recently resettled refugee populations may be at greater risk for exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that causes coronavirus 2019 (COVID-19), and face unique challenges in following recommendations to protect their health. Several factors place resettled refugees at elevated risk for exposure to persons with COVID-19 or increased severity of COVID-19: being more likely to experience poverty and live in crowded housing, being employed in less protected, service-sector jobs, experiencing language and health care access barriers, and having higher rates of co-morbidities. In preparing for and managing COVID-19, resettled refugees encounter similar barriers to those of other racial or ethnic minority populations, which may then be exacerbated by unique barriers experienced from being a refugee. Key recommendations for resettlement and healthcare providers include analyzing sociodemographic data about refugee patients, documenting and resolving barriers faced by refugees, developing refugee-specific outreach plans, using culturally and linguistically appropriate resources, ensuring medical interpretation availability, and leveraging virtual platforms along with nontraditional community partners to disseminate COVID-19 messaging.

Evaluation of Endocan and Tumor Necrosis Factor-α as Inflammatory Biomarkers in Type 2 Diabetes and Periodontal Disease.

Purpose: Type 2 diabetes mellitus (type 2 DM) and periodontitis encompass vascular endothelial changes. Endocan, a marker of endothelial dysfunction, has not been previously evaluated in diabetic patients with periodontal disease. This study was designed to evaluate the levels of endocan and tumor necrosis factor-alpha (TNF-α) in chronic periodontitis (CP) subjects with type 2 DM before and after nonsurgical periodontal therapy (NSPT). Materials and Methods: This study included 75 subjects with varying degrees of CP. Group I-included 25 systemically healthy individuals with CP, and Groups II and III-included 25 CP patients each with type 2 DM under good control (hemoglobin A1c [HbA1c] <7%) and poor control (HbA1c >8%), respectively. Periodontal parameters were assessed, and gingival crevicular fluid collections were performed for all patients at baseline and again following three months of NSPT. Levels of endocan and TNF-α were assessed using enzyme-linked immunosorbent assay. Results: Endocan levels were elevated in CP subjects with type 2 DM at baseline. There was a significant reduction in the Endocan and HbA1c levels (p < 0.01) among all the groups after NSPT. Conclusion: Endocan may be used as a novel diagnostic marker for pateints with type 2 DM and CP and as a potential prognostic marker for monitoring improvement in periodontal and glycemic status during NSPT.

Evaluation of a Program to Improve Linkage to and Retention in Care Among Refugees with Hepatitis B Virus Infection - Three U.S. Cities, 2006-2018.

An estimated 257 million persons worldwide have chronic hepatitis B virus (HBV) infection (1). CDC recommends HBV testing for persons from countries with intermediate to high HBV prevalence (≥2%), including newly arriving refugees (2). Complications of chronic HBV infection include liver cirrhosis and hepatocellular carcinoma, which develop in 15%-25% of untreated adults infected in infancy or childhood (3). HBV-infected patients require regular monitoring for both infection and sequelae. Several studies have evaluated initial linkage to HBV care for both refugee and nonrefugee immigrant populations (4-9), but none contained standardized definitions for either linkage to or long-term retention in care for chronic HBV-infected refugees. To assess chronic HBV care, three urban sites that perform refugee domestic medical examinations and provide primary care collaborated in a quality improvement evaluation. Sites performed chart reviews and prospective outreach to refugees with positive test results for presumed HBV infection during domestic medical examinations. Linkage to care (29%-53%), retention in care (11%-21%), and outreach efforts (22%-71% could not be located) demonstrated poor access to initial and ongoing HBV care. Retrospective outreach was low-yield. Interventions that focus on prospective outreach and addressing issues related to access to care might improve linkage to and retention in care.