Public and Political Opinion on Medicaid

Medicaid has long been a political litmus test and a target for substantial programmatic changes. But what does the public feel about Medicaid, especially during a pandemic? In this study, the authors analyze more than one million Medicaid-related tweets from December 1, 2018 to September 30, 2020. They found a high volume of political posts on Twitter around Medicaid topics, peaking in January 2020 in the context of news about Medicaid expansion and the prior administration’s Medicaid block grant proposal. As the pandemic hit, the number of Twitter posts about Medicaid and the pandemic increased, and the volume of political tweets on other Medicaid topics dropped. The posts themselves also appeared to be less polarized. These patterns suggest that when the public sees Medicaid operate as a safety net, the program is far less polarizing than partisan politics might indicate. Highlighting Medicaid’s role during the pandemic could help strengthen public support for the program in non-crisis times and better position it to respond to future economic downturns

Complete mitochondrial genome sequence of an Australian little penguin (Eudyptula minor novaehollandia, J.R. Forster, 1781)

In this paper, we report the complete mitochondrial genome of an Australian little penguin (Eudyptula minor novaehollandia). The mitogenome sequence has been found to be circular, and 17,608 bp in length. Similar to other Spheniscidae species, the genome encoded a typically conserved structure consisting of 13 protein-coding genes (PCGs), two rRNA genes, and 22 tRNA genes, as well as all protein coding sequences started with methionine. The lengths of 12S ribosomal RNA and 16S ribosomal RNA were 977 bp and 1612 bp, respectively, and were located between tRNA-Phe and tRNA-Leu. The overall base composition of the mitogenome of E. minor novaehollandia had slightly higher AT (55.5%) content than GC (45.5%). The complete mitogenome sequence determined in this study would be useful to track the deeper evolutionary history and conservation of E. minor novaehollandia

Franklin County, North Carolina : an action-oriented community diagnosis ; findings and next steps of action

Between October 2006 and April 2007, a team of six students from the School of Public Health at the University of North Carolina at Chapel Hill, conducted an Action-Oriented Community Diagnosis (AOCD) of Franklin County, North Carolina. The purpose of this AOCD was to learn about the strengths, challenges, and needs of the community, to assist the community in identifying priorities, and to bring the community together to openly discuss and work towards action steps that address the identified issues. The AOCD was conducted with the help of preceptors Cynthia Gary and Becky Leonard at the Franklin County Health Department. The AOCD process began with the team becoming acquainted with Franklin County by reviewing available data on the area, attending events, and meeting residents and employees. The team proceeded to conduct 39 interviews with community members and service providers, as well as one focus group of six youth. The team analyzed this data and created a list of the 14 issues that were most often mentioned as priorities to the people of Franklin County. Each issue was summarized in a theme statement that represented the team’s understanding of popular sentiment. With the help of a Forum Planning Committee (FPC) that consisted of nine service providers and community members, the team planned a community forum. The FPC narrowed the greater list of 14 themes to 5, based on importance and changeability. The themes selected were: Youth Recreation and Entertainment: There is a desire for additional public facilities in Franklin County to provide recreation and/or entertainment activities for youth. Economic Development: There is a need to support new and current businesses in Franklin County to enhance local economy and create new job opportunities. Physical Activity: A lack of physical activity options is contributing to increasing rates of obesity in Franklin County. Mental Health: There is an impression that the needs of people with mental health concerns are not being met, either because of a lack of services, lack of awareness of services available, or stigma attached to seeking help for mental health. Transportation: There is a need for inexpensive transportation options to increase access to services and resources for some residents of Franklin County. The community forum took place on April 24, 2007. At the forum, small group discussions led to the creation of action steps for four of the five themes (the discussion on transportation was dissolved for lack of attendees). Forum attendees then volunteered to oversee the execution of each action step, listed below. Youth Recreation and Entertainment: Talk to the board of the Boys & Girls Club about hosting fundraising events for youth participation in recreation. Talk to county political leaders about funding/tax allocation for more recreation facilities and options for youth. Talk to the Franklin County Schools superintendent about a sports uniform recycling program. Contact church leaders about scholarships for youth participation in recreation activities. Communicate with 4-H, Parks and Recreation, and The Franklin Times about the need to increase recreation facilities and activity options in Franklin County. Ask for support from these organizations in creating new options and increasing county-wide communication about recreation and entertainment options for youth. Economic Development: Establish a study committee to look at educational opportunities that match current local job opportunities. Support the application for the 21st Century grant for Franklin County Schools. Encourage continued support for economic development by increasing awareness of activities and initiatives among community members and county commissioners. Build collaboration between agencies (such as the Health Department, Planning, etc.) to work on a one-stop permitting process. Physical Activity: Talk to The Franklin Times about publishing a regular health column written by representatives of community organizations. Encourage physical activity competitions among various places of employment, community groups, schools, and other organizations in the county. Mental Health: Plan a meeting to organize the formation of a mental health advocacy group that will work to increase the number of mental health providers in Franklin County through recruitment and education. The team hopes that the engagement and motivation displayed by the people of Franklin County at the forum will result in continuing momentum to meet and build upon these action steps. In addition, the team would like to make the following recommendations as actions that may help build upon the county’s strengths while addressing some of its needs: Expand inter-agency communication. Many service providers were not aware of other programs and resources in the county. One positive step in this direction is an inter-agency lunch that takes place the last Wednesday of each month. Provide additional activity options for youth other than sports. Involve youth in the planning of facilities or programs that affect youth. Continue to support economic growth and increased job opportunities while respecting the pace and tranquility that residents appreciate. Begin to recognize and address nutrition as a contributor to obesity. Improve communication between decision-makers and the community, to better inform leaders of the county’s needs and the public of the activities and decisions made by their government. Conduct greater in-depth analysis of the needs and implications of the growing Latino population. Work towards greater service provision in Spanish. The purpose of this document is to serve as a resource to Franklin County by describing the Franklin County AOCD process, discussing the findings, and presenting the next steps of action developed by the Franklin County community.Master of Public Healt

Effect of police enforcement and extreme social inequalities on violence and mental health among women who sell sex: findings from a cohort study in London, UK

OBJECTIVES: To examine legal and social determinants of violence, anxiety/depression among sex workers. METHODS: A participatory prospective cohort study among women (inclusive of transgender) ≥18 years, selling sex in the last 3 months in London between 2018 and 2019. We used logistic generalised estimating equation models to measure associations between structural factors on recent (6 months) violence from clients or others (local residents, strangers), depression/anxiety (Patient Health Questionnaire-4). RESULTS: 197 sex workers were recruited (96% cisgender-women; 46% street-based; 54% off-street) and 60% completed a follow-up questionnaire. Street-based sex workers experienced greater inequalities compared with off-street in relation to recent violence from clients (73% vs 36%); police (42% vs 7%); intimate partner violence (IPV) (56% vs 18%) and others (67% vs 17%), as well as homelessness (65% vs 7%) and recent law enforcement (87% vs 9%). Prevalence of any STI was 17.5% (17/97). For street-based sex workers, recent arrest was associated with violence from others (adjusted OR (aOR) 2.77; 95% CI 1.11 to 6.94) and displacement by police was associated with client violence (aOR 4.35; 95% CI 1.36 to 13.90). Financial difficulties were also associated with client violence (aOR 4.66; 95% CI 1.64 to 13.24). Disability (aOR 3.85; 95% CI 1.49 to 9.95) and client violence (aOR 2.55; 95% CI 1.10 to 5.91) were associated with anxiety/depression. For off-street sex workers, financial difficulties (aOR 3.66; 95% CI 1.64 to 8.18), unstable residency (aOR 3.19; 95% CI 1.36 to 7.49), IPV (aOR 3.77; 95% CI 1.30 to 11.00) and alcohol/drug use were associated with client violence (aOR 3.16; 95% CI 1.26 to 7.92), while always screening and refusing clients was protective (aOR 0.36; 95% CI 0.15 to 0.87). Disability (aOR 5.83; 95% CI 2.34 to 14.51), unmet mental health needs (aOR 3.08; 95% CI 1.15 to 8.23) and past eviction (aOR 3.99; 95% CI 1.23 to 12.92) were associated with anxiety/depression. CONCLUSIONS: Violence, anxiety/depression are linked to poverty, unstable housing and police enforcement. We need to modify laws to allow sex workers to work safely and increase availability of housing and mental health services

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC). METHODS: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial. Primary endpoint for Phase I was dose limiting toxicity (DLT); for Phase II best overall response. Samples were analysed for pharmacokinetics, EGFR dimers in circulating exosomes and Comet assay quantitating DNA damage. RESULTS: Eighteen patients received FOLFIRI and AZD8931. At 160 mg bd, 1 patient experienced G3 DLT; 160 mg bd was used for cohort expansion. No grade 5 adverse events (AE) reported. Seven (39%) and 1 (6%) patients experienced grade 3 and grade 4 AEs, respectively. Of 12 patients receiving 160 mg bd, best overall response rate was 25%, median PFS and OS were 8.7 and 21.2 months, respectively. A reduction in circulating HER2/3 dimer in the two responding patients after 12 weeks treatment was observed. CONCLUSIONS: The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT01862003

Phase II randomized preoperative window-of-opportunity study of the PI3K inhibitor pictilisib plus anastrozole compared with anastrozole alone in patients with estrogen receptor-positive breast cancer

Purpose: Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. Patients and Methods: In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. Results: There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination: anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P =.03);for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression. Conclusion: Adding pictilisib to anastrozole significantly increases suppression of tumor cell proliferation in luminal B primary breast cancer

Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries

Background: The burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course. Method/Design: This is a prospective multi-centre observational study aiming to enrol 7–8000 participants aged ≥ 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later. Discussion: Data from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for “Integrated Management of Childhood Illness” used in dengue-endemic countries. Trial registration: NCT01550016. Registration Date: March 7, 201

A Phase I/II trial of Oral SRA737 (a Chk1 Inhibitor) given in combination with low-dose gemcitabine in patients with advanced cancer

Purpose: This was a phase I/II trial of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 given in combination with gemcitabine. Its objectives were to establish the safety profile, recommended phase 2 dose (RP2D), pharmacokinetics profile, and clinical activity of SRA737. Patients and Methods: Patients with advanced solid tumors were enrolled into dose-escalation cohorts and treated in 28-day cycles with oral SRA737 on days 2, 3, 9, 10, 16 and 17, and intravenous gemcitabine on days 1, 8 and 15. Treatment was continued until progression. Each expansion cohort included up to 20 patients with specific genetically defined tumors. Results: The RP2D was determined to be 500 mg SRA737 combined with low-dose (250 mg/m2) gemcitabine. Of 143 enrolled patients, 77 were treated at doses of at least 500 mg SRA737 combined with 250 mg/m2 gemcitabine. Common toxicities of nausea, vomiting, fatigue and diarrhea were primarily mild to moderate, and rarely led to treatment discontinuation. Anemia, neutropenia and thrombocytopenia were grade ≥3 in 8.3% to 11.7% of patients treated at the RP2D. The objective response rate (ORR) was 10.8% overall and notably the ORR in anogenital cancer was 25%. Partial tumor responses were observed in anogenital cancer, cervical cancer, high-grade serous ovarian cancer, rectal cancer, and small cell lung cancer. Conclusions: SRA737 in combination with low-dose gemcitabine was well tolerated with lower myelotoxicity than has been seen at standard doses of gemcitabine or with other combinations of Chk1 inhibitors with gemcitabine. Tumor responses were observed in anogenital and other solid tumors

SnoN expression is differently regulated in microsatellite unstable compared with microsatellite stable colorectal cancers

BACKGROUND: SnoN is an important regulator of the transforming growth factor beta (TGFβ) signalling pathway and has been shown to exhibit both tumour promotion and suppression activity. METHODS: To further explore the role of this complex molecule in colorectal tumorigenesis, we examined 52 paired normal and tumour colorectal specimens stratified by level of microsatellite instability; 18 with high-level microsatellite instability (MSI-H) and 34 microsatellite stable (MSS). SnoN transcript expression was quantitated by real-time PCR and analysed with respect to clinical indicators of prognosis. RESULTS: Within the MSI-H subgroup, SnoN was commonly either up-regulated (6/18, 33%) or down-regulated (7/18, 39%). A significantly different distribution of SnoN expression was observed in MSS cancers compared with MSI-H (P ≤ 0.001). Whilst 17/34 (50%) of MSS tumours demonstrated up-regulation, none showed down-regulated expression. Within the MSI-H subgroup, up-regulation was significantly correlated with lack of repeat tract mutation in the TGFβRII gene (P ≤ 0.025), suggesting that SnoN is more frequently up-regulated in the presence of functional TGFβ signalling. CONCLUSION: Together these data support the notion that SnoN has both oncogenic and tumour suppressive properties depending on other genetic changes within the tumour, and that the MSI-H pathway of colorectal tumorigenesis presents an excellent model for the study of these opposing functions

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275.</p