Evaluating Patient Perceptions on PrEP Screening and Referral in the Acute Care Setting.

Pre-exposure prophylaxis (PrEP) for HIV is highly effective, yet uptake has been limited. We measured PrEP knowledge, eligibility, and referral willingness among patients receiving emergency or acute care in Washington, DC. We surveyed HIV-negative patients with STI-related complaints on HIV risk behaviors, PrEP knowledge, eligibility, and willingness for PrEP referral. Among 174 participants, 70% were PrEP unaware and 33% were PrEP eligible. Most participants (81%) supported learning more, 64% would consider taking PrEP, and 28% agreed to immediate referral. Willingness to learn more about PrEP suggests referral from non-traditional settings may increase uptake. Further evaluation of this approach is warranted.

Feminizing gender-affirming hormone therapy for the transgender and gender diverse population: An overview of treatment modality, monitoring, and risks.

AIMS: Feminizing gender-affirming hormone therapy (GAHT) can be utilized to help transfeminine transgender and gender diverse (TGD) individuals achieve the transformation of outward sex characteristics, thereby leading to improvements in psychological and social well-being. In this narrative review, we aim to summarize current guidelines for feminizing GAHT management as well as the available literature describing the associated health risks pertaining to cardiovascular disease, thromboembolic disease, bone health, and cancer risks. METHODS: Relevant literature from January 2019 through July 2022 pertaining to feminizing GAHT was identified using PubMed, Cochrane Library, EMBASE, and MEDLINE. A narrative summary was performed with the inclusion of more recently published guidance from the World Professional Association for Transgender Health, Standards of Care Version 8. RESULTS: Guidance regarding the prescribing of feminizing GAHT with estrogen, antiandrogen, and progesterone medications is summarized along with considerations of the cardiovascular, thromboembolic, bone health, and cancer risks associated with these therapies. CONCLUSIONS: Feminizing GAHT is a highly effective method for transfeminine TGD patients to achieve medically necessary changes in secondary sex characteristics. Knowledge of the health risks of feminizing GAHT is largely drawn from research in the cisgender population, with a growing body of literature in TGD-specific patient populations. Feminizing GAHT appears to carry a low risk profile for most patients; however, further research describing the risks of hormone management around the time of gender-affirming surgery and in the aging TGD population is needed to optimize GAHT in the context of the evolving health risks over a TGD patient's lifespan.

A definition of free sugars for the UK.

Public Health England has set a definition for free sugars in the UK in order to estimate intakes of free sugars in the National Diet and Nutrition Survey. This follows the recommendation from the Scientific Advisory Committee on Nutrition in its 2015 report on Carbohydrates and Health that a definition of free sugars should be adopted. The definition of free sugars includes: all added sugars in any form; all sugars naturally present in fruit and vegetable juices, purées and pastes and similar products in which the structure has been broken down; all sugars in drinks (except for dairy-based drinks); and lactose and galactose added as ingredients. The sugars naturally present in milk and dairy products, fresh and most types of processed fruit and vegetables and in cereal grains, nuts and seeds are excluded from the definition.

Dietary intake of carbohydrates and risk of type 2 diabetes: the European Prospective Investigation into Cancer-Norfolk study.

In the present study, we investigated the association between dietary intake of carbohydrates and the risk of type 2 diabetes. Incident cases of diabetes (n 749) were identified and compared with a randomly selected subcohort of 3496 participants aged 40-79 years. For dietary assessment, we used 7 d food diaries administered at baseline. We carried out modified Cox proportional hazards regression analyses and compared results obtained from the different methods of adjustment for total energy intake. Dietary intakes of total carbohydrates, starch, sucrose, lactose or maltose were not significantly related to diabetes risk after adjustment for confounders. However, in the residual method for energy adjustment, intakes of fructose and glucose were inversely related to diabetes risk. The multivariable-adjusted hazard ratios (HR) of diabetes comparing the extreme quintiles of intake were 0·79 (95 % CI 0·59, 1·07; P for trend = 0·03) for glucose and 0·62 (95 % CI 0·46, 0·83; P for trend = 0·01) for fructose. In the nutrient density method, only fructose was inversely related to diabetes risk (HR 0·65, 95 % CI 0·48, 0·88). The replacement of 5 % energy intake from SFA with an isoenergetic amount of fructose was associated with a 30 % lower diabetes risk (HR 0·69, 95 % CI 0·50, 0·96). Results of the standard and energy partition methods were similar to those of the residual method. These prospective findings suggest that the intakes of starch and sucrose are not associated, but that those of fructose and glucose are inversely associated with diabetes risk. Whether the inverse associations with fructose and glucose reflect the effect of substitution of these carbohydrate subtypes with other nutrients (i.e. SFA), their net higher intake or other nutrients associated with their intake remains to be established through further investigation.

Dietary intake measurement using 7 d diet diaries in British men and women in the European Prospective Investigation into Cancer-Norfolk study: a focus on methodological issues.

The aim of the present study was to describe the energy, nutrient and crude v. disaggregated food intake measured using 7 d diet diaries (7dDD) for the full baseline Norfolk cohort recruited for the European Prospective Investigation into Cancer (EPIC-Norfolk) study, with emphasis on methodological issues. The first data collection took place between 1993 and 1998 in Norfolk, East Anglia (UK). Of the 30,445 men and women, aged 40-79 years, registered with a general practitioner invited to participate in the study, 25,639 came for a health examination and were asked to complete a 7dDD. Data from diaries with data recorded for at least 1 d were obtained for 99% members of the cohort; 10,354 (89·8%) of the men and 12,779 (91·5%) of the women completed the diet diaries for all 7 d. Mean energy intake (EI) was 9·44 (SD 2·22) MJ/d and 7·15 (SD 1·66) MJ/d, respectively. EI remained approximately stable across the days, but there was apparent under-reporting among the participants, especially among those with BMI >25 kg/m². Micronutrient density was higher among women than among men. In conclusion, under-reporting is an issue, but not more so than that found in national surveys. How foods were grouped (crude or disaggregated) made a difference to the estimates obtained, and comparison of intakes showed wide limits of agreement. The choice of variables influences estimates obtained from the food group data; while this may not alter the ranking of individuals within studies, this issue may be relevant when comparing absolute food intakes between studies.

Introduction of a formative assessment tool in a post-graduate training program in India: a mixed methods evaluation.

BACKGROUND: Our institution has longstanding post-graduate education and training partnership programs in Emergency Medicine (EM) across India. A programmatic challenge has been the integration and uptake of evidence-based medicine and lifelong learning concepts. Formative assessment (FA) is intended to enable learners to monitor learning, identify strengths and weaknesses, and target areas of growth. As part of a program improvement initiative, we introduced an online FA tool to existing summative assessments. This study investigates how the FA tool was used and perceived by trainees. METHODS: 246 trainees across 19 sites were given access to the FA tool. Usage metrics were monitored over 12 months. Semi-structured interviews were conducted in person with trainees using a purposive sampling methodology. A hybrid thematic analysis approach was used to determine themes. Interviews were coded independently by two blinded researchers using NVivo software. The study was deemed exempt by our institutional review board. RESULTS: There was high variability in trainees' utilization of the FA tool. Trainees who used the FA tool more performed better on summative exams (r = 0.35, p < 0.001). Qualitative analysis revealed that trainees were motivated to learn for improved clinical knowledge and to be a good physician, not only passing exams. Benefits of the tool included the relationship to clinical practice and thorough explanation of answers, while disadvantages included topics unrelated to India. CONCLUSION: The integration of a FA tool has provided positive outcomes for trainees in EM education programs in India. Lessons learned may apply globally to other contexts and programs.

Intakes and sources of isoflavones, lignans, enterolignans, coumestrol and soya-containing foods in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk), from 7 d food diaries, using a newly updated database.

OBJECTIVE: A diet rich in phyto-oestrogens has been suggested to protect against a variety of common diseases but UK intake data on phyto-oestrogens or their food sources are sparse. The present study estimates the average intakes of isoflavones, lignans, enterolignans and coumestrol from 7 d food diaries and provides data on total isoflavone, lignan and phyto-oestrogen consumption by food group. DESIGN: Development of a food composition database for twelve phyto-oestrogens and analysis of soya food and phyto-oestrogen consumption in a populationbased study. SETTING: Men and women, aged 40­79 years, from the general population participating in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) between 1993 and 1997, with nutrient and food data from 7 d food diaries. SUBJECTS: A subset of 20 437 participants. RESULTS: The median daily phyto-oestrogen intake for all men was 1199 mg (interquartile range 934­1537mg; mean 1504mg, SD 1502mg) and 888mg for all women (interquartile range 710­1135 mg; mean 1205 mg, SD 1701mg). In soya consumers, median daily intakes were higher: 2861 mg in men (interquartile range 1304­7269mg; mean 5051mg, SD 5031mg) and 3142 mg in women (interquartile range 1089­7327mg; mean 5396 mg, SD 6092 mg). In both men and women, bread made the greatest contribution to phyto-oestrogen intake ­ 40?8% and 35?6%, respectively. In soya consumers, vegetable dishes and soya/goat's/sheep's milks were the main contributors ­ 45?7% and 21?3% in men and 38?4% and 33?7% in women, respectively. CONCLUSIONS: The ability to estimate phyto-oestrogen intake in Western populations more accurately will aid investigations into their suggested effects on health.

Structural basis for severe pain caused by mutations in the voltage sensors of sodium channel NaV1.7.

Voltage-gated sodium channels in peripheral nerves conduct nociceptive signals from nerve endings to the spinal cord. Mutations in voltage-gated sodium channel NaV1.7 are responsible for a number of severe inherited pain syndromes, including inherited erythromelalgia (IEM). Here, we describe the negative shifts in the voltage dependence of activation in the bacterial sodium channel NaVAb as a result of the incorporation of four different IEM mutations in the voltage sensor, which recapitulate the gain-of-function effects observed with these mutations in human NaV1.7. Crystal structures of NaVAb with these IEM mutations revealed that a mutation in the S1 segment of the voltage sensor facilitated the outward movement of S4 gating charges by widening the pathway for gating charge translocation. In contrast, mutations in the S4 segments modified hydrophobic interactions with surrounding amino acid side chains or membrane phospholipids that would enhance the outward movement of the gating charges. These results provide key structural insights into the mechanisms by which these IEM mutations in the voltage sensors can facilitate outward movements of the gating charges in the S4 segment and cause hyperexcitability and severe pain in IEM. Our work gives new insights into IEM pathogenesis at the near-atomic level and provides a molecular model for mutation-specific therapy of this debilitating disease.

The Relationship between Substance Use Stigma and COVID-19 Vaccine Hesitancy.

Two parallel public health epidemics affecting the United States include the COVID-19 pandemic and a rise in substance use disorders (SUDs). Limited research has examined the potential relationship between these two epidemics. Our objective was therefore to perform an exploratory study in order to examine the association between public stigma toward people with a past history of opioid, methamphetamine, cocaine, and alcohol use disorder and COVID-19 vaccine hesitancy. A national sample of U.S. adults (N = 6515) completed a survey which assessed the degree of negative perceptions toward individuals with a past history of substance use disorders (referred to as substance use stigma) and COVID-19 vaccine hesitancy, along with variables such as racial prejudice, source of health news, and other demographics. We evaluated four multivariable logistic regression models to predict COVID-19 vaccine hesitancy, utilizing substance use stigma toward opioids, methamphetamine, cocaine, and alcohol use as independent variables. We found that COVID-19 vaccine hesitancy was positively associated with substance use stigma toward opioid (AOR = 1.34, p < 0.05), methamphetamine (AOR = 1.40, p < 0.01), and cocaine (AOR = 1.28, p < 0.05) use, but not alcohol use (AOR = 1.06, n.s.). Predictive models that incorporate substance use stigma may therefore improve our ability to identify individuals that may benefit from vaccine hesitancy interventions. Future research to understand the underlying reasons behind the association between substance use stigma and COVID-19 vaccine hesitancy may help us to construct combined interventions which address belief systems that promote both substance use stigma and vaccine hesitancy.

Vitamins, minerals, essential fatty acids and colorectal cancer risk in the United Kingdom Dietary Cohort Consortium.

The risk for colorectal cancer may be influenced by the dietary intake of various vitamins, minerals and essential fatty acids. We conducted a pooled analysis of dietary data collected using food diaries in seven prospective studies in the United Kingdom Dietary Cohort Consortium. Five hundred sixty-five cases of colorectal cancer were matched with 1,951 controls on study centre, age, sex and recruitment date. Dietary intakes of retinol, vitamin A, thiamin, riboflavin, vitamin B6, folate, vitamin B12, vitamin D, calcium, iron, magnesium, potassium, n - 6 fatty acids, n - 3 fatty acids and the ratio of n - 6 to n - 3 fatty acids were estimated and their associations with colorectal cancer examined using conditional logistic regression models, adjusting for exact age, height, weight, energy intake, alcohol intake, fiber intake, smoking, education, social class and physical activity. There were no statistically significant associations between colorectal cancer risk and dietary intake of any of the vitamins, minerals or essential fatty acids examined.

Targeted Screening for HIV Pre-Exposure Prophylaxis Eligibility in Two Emergency Departments in Washington, DC.

Pre-exposure prophylaxis (PrEP) is an effective method to prevent HIV acquisition in high-risk individuals. This cross-sectional survey study estimated the proportion of patients who were PrEP eligible among a targeted sample of emergency department (ED) patients with chief complaints indicative of HIV risk. Research assistants screened a convenience sample of adult patients who presented to two hospital EDs in Washington, DC, during a 6-month period with genitourinary, substance use, or intentional injury-related complaints. Patients with these complaints who reported being sexually active within the past 6 months and HIV negative completed a computer-assisted survey that included questions on sexual practices and partners, substance use, and attitudes and knowledge about PrEP. We used the Centers for Disease Control and Prevention (CDC) clinical guidelines to determine whether PrEP use was indicated. We report differences in PrEP eligibility by demographic characteristics, knowledge, and attitudes. Of the 410 participants, the majority were black (85%), and heterosexual females (72%). PrEP use was indicated in 20% (N = 84), most commonly because of condomless sex with a person of unknown HIV status (82%) and/or a sexually transmitted infection (STI) diagnosis (41%). One-third (34%) of participants had heard of PrEP. Overall, 36% of the sample (N = 148) wanted to learn more about PrEP while in the ED. The percentage who wanted to learn more about PrEP was higher among PrEP-eligible patients (52%) compared with PrEP-ineligible patients (32%). Using CDC criteria, targeted screening identified that a substantial proportion of ED patients are PrEP eligible based on their self-reported behaviors.

Correction: Co-targeting the MAPK and PI3K/AKT/mTOR pathways in two genetically engineered mouse models of schwann cell tumors reduces tumor grade and multiplicity.

[This corrects the article DOI: 10.18632/oncotarget.1609.].

Development of a Global Health Milestones Tool for Learners in Emergency Medicine: A Pilot Project.

OBJECTIVES: In medical education and training, increasing numbers of institutions and learners are participating in global health experiences. Within the context of competency-based education and assessment methodologies, a standardized assessment tool may prove valuable to all of the aforementioned stakeholders. Milestones are now used as the standard for trainee assessment in graduate medical education. Thus, the development of a similar, milestone-based tool was undertaken, with learners in emergency medicine (EM) and global health in mind. METHODS: The Global Emergency Medicine Think Tank Education Working Group convened at the 2016 Society for Academic Medicine Annual Meeting in New Orleans, Louisiana. Using the Interprofessional Global Health Competencies published by the Consortium of Universities for Global Health's Education Committee as a foundation, the working group developed individual milestones based on the 11 stated domains. An iterative review process was implemented by teams focused on each domain to develop a final product. RESULTS: Milestones were developed in each of the 11 domains, with five competency levels for each domain. Specific learning resources were identified for each competency level and assessment methodologies were aligned with the milestones framework. The Global Health Milestones Tool for learners in EM is designed for continuous usage by learners and mentors across a career. CONCLUSIONS: This Global Health Milestones Tool for learners in EM may prove valuable to numerous stakeholders. The next steps include a formalized pilot program for testing the tool's validity and usability across training programs, as well as an assessment of perceived utility and applicability by collaborating colleagues working in training sites abroad.

Cancer. TERT promoter mutations and telomerase reactivation in urothelial cancer.

Reactivation of telomerase, the chromosome end-replicating enzyme, drives human cell immortality and cancer. Point mutations in the telomerase reverse transcriptase (TERT) gene promoter occur at high frequency in multiple cancers, including urothelial cancer (UC), but their effect on telomerase function has been unclear. In a study of 23 human UC cell lines, we show that these promoter mutations correlate with higher levels of TERT messenger RNA (mRNA), TERT protein, telomerase enzymatic activity, and telomere length. Although previous studies found no relation between TERT promoter mutations and UC patient outcome, we find that elevated TERT mRNA expression strongly correlates with reduced disease-specific survival in two independent UC patient cohorts (n = 35; n = 87). These results suggest that high telomerase activity may be a better marker of aggressive UC tumors than TERT promoter mutations alone.

Co-targeting the MAPK and PI3K/AKT/mTOR pathways in two genetically engineered mouse models of schwann cell tumors reduces tumor grade and multiplicity.

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that occur spontaneously, or from benign plexiform neurofibromas, in the context of the genetic disorder Neurofibromatosis Type 1 (NF1). The current standard treatment includes surgical resection, high-dose chemotherapy, and/or radiation. To date, most targeted therapies have failed to demonstrate effectiveness against plexiform neurofibromas and MPNSTs. Recently, several studies suggested that the mTOR and MAPK pathways are involved in the formation and progression of MPNSTs. Everolimus (RAD001) inhibits the mTOR and is currently FDA approved for several types of solid tumors. PD-0325901 (PD-901) inhibits MEK, a component of the MAPK pathway, and is currently in clinical trials. Here, we show in vitro than MPNST cell lines are more sensitive to inhibition of cellular growth by Everolimus and PD-901 than immortalized human Schwann cells. In combination, these drugs synergistically inhibit cell growth and induce apoptosis. In two genetically engineered mouse models of MPNST formation, modeling both sporadic and NF1-associated MPNSTs, Everolimus, or PD-901 treatment alone each transiently reduced tumor burden and size, and extended lifespan. However, prolonged treatment of each single agent resulted in the development of resistance and reactivation of target pathways. Combination therapy using Everolimus and PD-901 had synergistic effects on reducing tumor burden and size, and increased lifespan. Combination therapy allowed persistent and prolonged reduction in signaling through both pathways. These data suggest that co-targeting mTOR and MEK may be effective in patients with sporadic or NF1-associated MPNSTs.