Real-world clinical evaluation of natural and induced vasomotor symptoms in the USA and Europe.

OBJECTIVE: This study aimed to examine physicians' and patients' perceptions regarding symptom burden and impact in women experiencing natural vasomotor symptoms (nVMS) or vasomotor symptoms induced by endocrine therapy for breast cancer (iVMS). METHODS: The cross-sectional survey based on real-world clinical consultations was conducted in the USA and five European countries. Obstetrician-gynecologists, primary-care physicians and oncologists provided demographic and symptom data for patients experiencing VMS; patients optionally self-reported their experiences via questionnaires, including their symptom profile and work/activity burden through the Menopause Quality of Life (MENQOL) and Work Productivity and Activity Impairment (WPAI) tools. RESULTS: Physicians completed survey forms on 2451 consulting patients; patients completed 1029 questionnaires. nVMS and iVMS severity was significantly associated with the severity of mood symptoms and sleep disturbances (p < 0.0001). However, around half of the patients with mild nVMS/iVMS also experienced moderate-severe mood changes (55.4%/43.7%) or sleep disturbances (42.4%/40.4%). Presence of mood/sleep disturbances alongside nVMS increased MENQOL vasomotor scores (p = 0.004/p < 0.001). Presence of sleep disturbances increased WPAI activity impairment (p < 0.001) but mood changes did not. Similar findings were reported for iVMS patients. CONCLUSION: Significant burden from the triad of natural or induced menopausal symptoms, sleep disturbances and mood changes affected women's daily activities, work and quality of life more than vasomotor symptoms alone.

Considerations for paediatric student-led telepractice in speech-language therapy: A pilot observational study from South Africa.

BACKGROUND: COVID-19 necessitated emergency telepractice for student-led speech-language therapy clinical practicals in training institutions, with limited preparation and evidence-based guidelines. Beyond the pandemic, practitioners and university training sites are likely to continue to offer telepractice necessitating thorough preparation for telepractice services underpinned by a comprehensive understanding of the complexities involved in online therapy. AIMS: Adopting realist evaluation principles, our aim in this paper was to explore broadly what works and does not work in a set of student-led telepractice sessions in a diverse, resource-limited context. The broader goal of this project was to provide evidence-based support to enhance the efficiency and success of telepractice sessions in student clinical training contexts. METHODS & PROCEDURES: We used qualitative observational methods with reflexive thematic analysis to analyse 28 video recordings and 61 observation notes of student-led paediatric telepractice sessions from a South African university clinic as part of a pilot study. OUTCOMES & RESULTS: We identified four overarching considerations for student-led telepractice: (1) additional, specific preparation is required, (2) with greater management of technology and adaptation of tasks, especially during times of poor connectivity; (3) telepractice relies heavily on caregiver input and collaboration; and (4) promoting engagement online, holding a client's attention, building rapport and offering reinforcement are critical skills that are complicated by the lack of face-to-face contact. CONCLUSIONS & IMPLICATIONS: Our findings indicate that telepractice pedagogy needs to be explicitly taught and students require practical assistance as they learn how to use this service delivery approach effectively. There are some aspects peculiar to telepractice that require unique consideration and planning, especially in contexts where service providers and users may be unfamiliar with this form of service provision. The findings of this pilot study can be used by clinical educators and student clinicians to enhance clinical training opportunities involving telepractice. WHAT THIS PAPER ADDS: What is already known on this subject Many speech-language therapy (SLT) student clinicians had to transition quickly to telepractice service provision during COVID-19 with limited existing guidelines and support, especially in contexts where teletherapy is typically non-existent or difficult to access. Although there is some literature available on experiences of telepractice, there is very little evidence-based research which explores the mechanics of such sessions in real-time and which offers practical support to student clinicians and clinical educators engaging in this mode of service delivery. What this study adds This pilot study examined video-recorded, student-led, paediatric, speech-language teletherapy sessions to understand challenges and considerations involved in using telepractice as a clinical training tool. Findings show that additional preparation for telepractice sessions is required, particularly in contexts of poor digital literacy; students must learn to manage technology, especially when connectivity poses a challenge, and adapt therapy tasks for online work with clients; telepractice relies heavily on caregiver input and collaboration, more so than in in-person consultations, and this relationship requires careful management; and promoting engagement online, holding a client's attention, building rapport and offering reinforcement are critical yet challenging skills in telepractice. What are the potential or actual clinical implications of this work? Our findings highlight a need to teach telepractice pedagogy explicitly and support students practically in learning how to provide therapy effectively via this mode of service delivery. Observational methods for studying practices in recorded telepractice sessions can be used as part of a reflective approach to clinical training. Using already available data allowed us to unpack the 'messy reality' of clinical training using telepractice.

The discovery of multiple active mys-related LTR-retroelements within the Neotominae subfamily of cricetid rodents.

Retrotransposon families in the rodent family Cricetidae have been understudied in contrast to Muridae, both taxa classified within the superfamily Muroidea. Therefore, we carried out a study to advance our knowledge of the unique mys LTR-retroelement identified in Peromyscus leucopus, by incorporating intra-ORF PCR, quantitative dot blots, DNA and protein library screens, the generation of molecular phylogenies, and analyses of orthologous LTR-retroelement loci. These analyses led to the discovery of three additional related families of LTR-retroelements, which include a 2900 bp full-length element of mys-related sequences (mysRS), an 8000 bp element containing the mys ORF1 sequence (mORF1) with ERV-related sequences downstream in the reverse orientation, as well as an 1800 bp element primarily consisting of mys ORF2 (mORF2) related sequences flanked by LTRs. Our data revealed only a few full-length mys elements among genera of the Neotominae subfamily of cricetid rodents, most existing as partial copies. The mysRS and mORF1 elements are also limited to the genomes of the Neotominae subfamily, whereas mORF2 appears to be restricted to the Peromyscus genus. Molecular phylogenies demonstrating concerted evolution along with an assessment of orthologous loci in Peromyscus for the presence or absence of elements are consistent with activity of these novel LTR-retroelement families within this genus. Together with known activity of various families of non-LTR retroelements in Peromyscus species, we propose that retrotransposons have been continually contributing to the dynamics of Peromyscus genomes promoting genomic diversity and may be correlated with the evolution of more than 50 identified Peromyscus species.

A balancing act: Non-directive communication, risk perceptions, and meeting patient needs in genetic counseling: A South African case study.

Genetic counseling (GC) traditionally follows a non-directive counseling approach. Although a cornerstone of GC teaching and theory, there has been debate on whether GC is, can be, or should be a patient-led service due to challenges in practice, as well as the advancement and complexity of genetic testing. Personal risk perceptions and patient expectations within particular contexts may further affect how genetic counselors discuss risk information, even while attempting to remain neutral. Less is known about the process of GC communication in non-Western settings. This paper presents empirical evidence from a South African prenatal GC consultation where tensions become apparent due to differing risk perceptions and expectations between a genetic counselor and a patient, which ultimately impacts non-directive communication practice. The case study forms part of a larger qualitative study focusing on risk and uncertainty communication within GC consultations in Cape Town, South Africa. A blended sociolinguistic approach drawing on principles of conversation analysis (CA) and theme-orientated discourse analysis (TODA) provides evidence of the complexity of imparting risk information and challenging patients to reflect on their decision-making, whilst refraining from sharing personal risk perceptions during everyday practice. The case study demonstrates how a genetic counselor may become implicitly and explicitly directive in their communication approach within the same consult which may reveal their personal risk perceptions on the matter discussed. In addition, the case study reveals how a genetic counselor may grapple with the dilemma of honoring the non-directive guidelines of the profession, whilst simultaneously supporting a patient who requests advice. The ongoing debate on non-directive counseling, decision-making, and patient care in GC is important for the reflection and development of the profession to understand how to assist and support patients facing sensitive and difficult decisions, in a meaningful, and contextually-tailored manner.

Synergistic effects of an atmospheric pressure plasma jet and pulsed electric field on cells and skin.

Nonthermal atmospheric pressure plasmas produce reactive plasma species including charged particles and reactive oxygen nitrogen species, which are known to induce oxidative stress in living cells in liquid or tissue. In the meantime, pulsed electric fields have been widely used in reversible or irreversible electropermeabilization for either the delivery of plasmid DNA or inactivation of cancer cells. This work discusses the synergistic effects of nanosecond pulsed plasma jets and pulsed electric field on inactivation of pancreatic cancer cells in vitro and enhancement of plasmid DNA delivery to guinea pig skin in vivo. Higher inactivation rates of the cancer cells in suspension were obtained with combined treatment of 300-ns 50 kV/cm pulsed electric field and a 1-min exposure of a nanosecond pulsed, 250-µm plasma jet. Increased efficiency of gene electrotransfer to skin was also observed after a 3-min treatment of a nanosecond pulsed, 1-mm plasma jet. Application of the plasma alone at the same dosage did not have significant effect on gene delivery. These findings signify the dosage-dependent cell-response to both the electric fields and plasma. Importantly, the use of cold plasma to increase the sensitization of the biological cells in response to pulsed electric fields could be an effective approach to enhance the desired effects in electroporation-based applications.

Nurses' Perceptions of Rooming-in for Caregivers of Infants with CCHD.

Congenital heart disease (CHD) is the most common congenital defect. Infants with critical congenital heart disease (CCHD) require complex medical care, and their caregivers need extensive training before being discharged home to safely care for their child. The rooming-in process provides caregivers with an opportunity to learn, practice, and manage the skills required for discharge to home during hospitalization. Although the literature reflects positive implications for the use of the rooming-in process in other populations (e.g., neonatal abstinence syndrome), literature about the rooming-in process in a pediatric cardiac care setting is limited. There remains a gap in the literature pertaining to the viewpoints of nurses, specifically as it relates to implementing a rooming-in process. Therefore, a qualitative study design was chosen to explore the nurses' perceptions of the rooming-in process using focus groups. The purpose of this study was to gain insight from nurses as to strategies to enhance the rooming-in process for caregivers of infants with CCHD. Additionally, we explored potential education and interventions to improve outcomes for infants with CCHD preparing to be discharged home.

Video-recording complex health interactions in a diverse setting: Ethical dilemmas, reflections and recommendations.

Video-recording healthcare interactions provides important opportunities for research and service improvement. However, this method brings about tensions, especially when recording sensitive topics. Subsequent reflection may compel the researcher to engage in ethical and moral deliberations. This paper presents experiences from a South African genetic counselling study which made use of video-recordings to understand communicative processes in routine practice. Video-recording as a research method, as well as contextual and process considerations are discussed, such as researching one's own field, issues of trust and anonymity, the challenge of providing true informed consent and capturing details which may cause psychological harm. Several recommendations for research practice in diverse healthcare settings are made. This includes the value of reflective pieces, the importance of retrospective consent, disclosure of the limitations to anonymity, as well as the collective responsibility of those involved to produce ethical research. These recommendations have value for genetic counselling and other healthcare fields.

Perceived challenges in the informed consent process: Mismatches between enrollers and researchers at a South African clinical research site.

Enrollers play a critical yet often overlooked role in clinical research, particularly in informed consent processes. Study retention may depend in part on how complex information is conveyed to potential participants. This qualitative study aimed to assess communicative barriers during consent and enrolment in two South African TB/HIV clinical studies. In particular, we compared our own perceptions of potential challenges to consent with that of thirteen enrollers, gained via reflective journaling and focus group discussions. Some overlap of identified challenges was evident, including terminology, jargon and consent document format. However there were mismatches to identified challenges. Enrollers provided further insights into potential challenges to consent, in particular, blood withdrawal, discussion of sexual issues and misunderstanding of study participation. Enrollers also reported feeling ill-equipped to provide counselling when participants became distressed. We offer several recommendations for strengthening the inclusion of enrollers in the development of clinical research protocols and consent documents.

Observer variability identifying attention deficit/hyperactivity disorder in 10-year-old children born extremely preterm.

AIM: A DSM-5 diagnosis of attention deficit/hyperactive disorder (ADHD) requires that symptoms be present in two settings. We wanted to see how teachers and parents compare on their assessments. METHODS: We evaluated how well Child Symptom Inventory-4 (CSI-4) reports from 871 parents and 634 teachers of 10-year-old children born before the 28th week of gestation provided information about indicators of school dysfunction. RESULTS: Kappa values for parent and teacher agreement of any ADHD were at best fair to poor (<0.41). Nevertheless, ADHD identified by each alone provided a moderate amount of information about such indicators of school dysfunction as grade repetition. Only occasionally did agreement provide more information than provided by only one reporter. Mother's social class and intelligence level did not discriminate between parents who did and did not agree with the teacher. CONCLUSION: ADHD identified by a single observer can provide appreciable information about a range of the child's functions needed for success in school and, therefore, should not be discounted when another observer does not consider the child to have ADHD symptoms.

'Nurses don't deal with these issues': nurses' role in advance care planning for lesbian, gay, bisexual and transgender patients.

AIMS AND OBJECTIVES: We used a question from the Healthcare Equality Index to explore nurses' knowledge and understanding of medical advance directives, medical power of attorney and other legal documents for lesbian, gay, bisexual and transgender patients. BACKGROUND: Until the landmark ruling in Obergefell vs. Hodges, lesbian, gay, bisexual and transgender individuals and same-sex couples have had limited relationship rights as only a few states recognised marriages and provided legal protections for same-sex couples. Health care providers' knowledge of and attitudes towards advance care planning plays a significant role in determining whether or not individuals successfully complete advance directives, yet advance care planning for lesbian, gay, bisexual and transgender individuals is poorly understood among both health care providers and same-sex couples. DESIGN: These data were part of a larger research study that explored the current state of lesbian, gay, bisexual and transgender-sensitive nursing practice. METHOD: Undergraduate nursing students recruited and interviewed nurse key informants (n = 268) about medical advance directives, medical power of attorney and other legal documents for lesbian, gay, bisexual and transgender patients. RESULTS: Nearly 50% of key informants indicated a lack of knowledge of advance directives, over 26% reported the difficulties nurses face regarding advance directives are the same for both lesbian, gay, bisexual and transgender and heterosexual patients, and nearly 25% indicated difficulties including having to decide who has the legal right to make decisions for the patient. CONCLUSION: The study demonstrated the need for education and training for practising nurses in advance care planning for lesbian, gay, bisexual and transgender patients and same-sex couples. RELEVANCE TO CLINICAL PRACTICE: Nurses are in a position to act as educators, advocates and decision makers for their patients. Nurse's lack of understanding of advance care planning may negatively impact the type and quality of care lesbian, gay, bisexual and transgender patients receive.

Does your organization use gender inclusive forms? Nurses' confusion about trans* terminology.

AIMS AND OBJECTIVES: To describe nurses confusion around trans* terminology and to provide a lesson in Trans* 101 for readers. BACKGROUND: Of the estimated 9 million persons in the United States of America who are identified as lesbian, gay, bisexual and transgender, about 950,000 (0.2-0.5% of adult population) are identified as trans* (a term that encompasses the spectrum, including transgender, transsexual, trans man, trans woman and other terms). The Institute of Medicine (2011, The health of lesbian, gay, bisexual and transgender people: Building a foundation for better understanding. The National Academies Press, Washington, DC) identified transgender persons as an understudied population with significant need for health research, yet the nursing literature contains little guidance for educating nurses on trans* issues. DESIGN: This is a mixed methods structured interview design with nurse key informants. The scripted interview was based on the Health Care Equality Index, which evaluates patient-centred care to lesbian, gay, bisexual and transgender patients and families. These data were part of a larger research study that explored the current state of lesbian, gay, bisexual and transgender-sensitive nursing practice. METHOD: Undergraduate nursing students recruited and interviewed 268 nurse key informants about gender inclusive forms (capable of identifying trans* patients) at their agencies. RESULTS: Only 5% reported use of gender inclusive forms, 44% did not know about inclusive forms, 37% did not understand what a gender inclusive form was and 14% confused gender with sexual orientation. CONCLUSION: The study demonstrated a critical need for education in gender identity and sexual orientation terminology. RELEVANCE TO CLINICAL PRACTICE: The lack of understanding of concepts and terminology may affect basic care of lesbian, gay, bisexual and transgender patients especially those who identify as transgender.

"We are just not sure what that means or if it's relevant": Uncertainty when gathering family history information in South African prenatal genetic counseling consultations.

Uncertainty impacts the process of health communication. The management and tolerance of uncertainty during healthcare discussions have gained renewed focus due to the growing challenge of obtaining and delivering complex health information, and the offer of health services in diverse contexts. Prenatal genetic counseling (GC) provides education, support and testing options for patients and couples facing a genetic or congenital diagnosis or risk during pregnancy. Gathering detailed and accurate family history information is essential to determine a patient's genetic risk. In South Africa, contextual factors such as patient literacy, language diversity, limited written patient health records, and a lack of familiarity with GC services may increase the potential for misunderstandings during GC consultations. This study uses a qualitative sociolinguistic approach to analyse 9 video-recorded South African prenatal GC consultations to understand the impact of uncertainty on the process of gathering family history information. The findings reveal uncertainty is introduced in different ways during family history taking. This includes when patients have no knowledge about their family history; when they have some knowledge but the details are unclear; or when patients have knowledge but the details are confusing. Uncertainty can lead to interactional trouble in the form of knowledge asymmetries, interrogative questioning, reversals in epistemic authority, and the potential for mistrust. Suggestions are made for how genetic specialists can manage uncertainty in GC family history taking. These include recognizing contextual sources of uncertainty, understanding how patients may respond to uncertainty and being aware of personal responses to moments of discomfort. Specific communication training recommendations and video-based sociolinguistic methods to enhance reflection and communication practice are highlighted. These approaches may enhance the effectiveness of GC communication and strengthen patient-specialist relationships, especially in diverse settings.

Nano-Pulse Treatment Overcomes the Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer.

We previously reported that nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes, and tumors were harvested at 4-h, 8-h, 1-day, 3-day, 7-day, and 3-month post-treatment intervals for the analysis of frequencies, death, and functional markers of various immune cells in addition to the suppressor function of regulatory T cells (Tregs). NPT was verified to elicit strong in situ vaccination (ISV) against breast cancer and promote both acute and long-term T cell memory. NPT abolished immunosuppressive dominance systemically and in the TME by substantially reducing Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). NPT induced apoptosis in Tregs and TAMs. It also functionally diminished the Treg suppression capacity, explained by the downregulation of activation markers, particularly 4-1BB and TGFß, and a phenotypic shift from predominantly activated (CD44+CD62L-) to naïve (CD44-CD62L+) Tregs. Importantly, NPT selectively induced apoptosis in activated Tregs and spared effector CD4+ and CD8+ T cells. These changes were followed by a concomitant rise in CD8+CD103+ tissue-resident memory T cells and TAM M1 polarization. These findings indicate that NPT effectively switches the TME and secondary lymphatic systems from an immunosuppressive to an immunostimulatory state, allowing cytotoxic T cell function and immune memory formation to eliminate cancer cells and account for the NPT in situ vaccination.

Treatment utilization and non-drug interventions for vasomotor symptoms in breast cancer survivors taking endocrine therapy: Real-world findings from the United States and Europe.

OBJECTIVES: Vasomotor symptoms induced by endocrine therapy are common in breast cancer survivors and a risk factor for therapy discontinuation and lower quality of life. The REALISE study evaluated the real-world treatment landscape in breast cancer survivors with vasomotor symptoms taking endocrine therapy, including pharmaceuticals, lifestyle changes, and over-the-counter products. STUDY DESIGN: Secondary analysis of the Adelphi Vasomotor Disease Specific Programme™, a large cross-sectional point-in-time survey and chart review conducted in the US and five European countries (February-October 2020). Oncologists provided demographic, clinical, and treatment data for adult breast cancer survivors with induced vasomotor symptoms taking endocrine therapy (tamoxifen or aromatase inhibitors); patients voluntarily completed self-report surveys on their symptom severity, concomitant sleep and/or mood symptoms, lifestyle changes, and use of over-the-counter products. MAIN OUTCOME MEASURES: Patient characteristics; vasomotor symptom severity; use of pharmaceuticals, lifestyle changes, and over-the-counter products (from pre-defined lists); lines of treatment. RESULTS: Overall, 77 oncologists reported data for 618 breast cancer survivors, of whom 183 (29.6 %) completed self-report forms. Physicians classified 420 (68.0 %) women as experiencing moderate-severe vasomotor symptoms, of whom 66.9 % were receiving treatment. In total, 15.2 % of all breast cancer survivors were prescribed systemic hormone therapy. Venlafaxine (24.7 %), citalopram (16.5 %), and paroxetine (13.6 %) were the most commonly prescribed nonhormonal medications. Lifestyle changes (77.8 %) and over-the-counter products (61.6 %) were common, especially in patients with concomitant sleep and/or mood symptoms. CONCLUSIONS: Despite contraindications, a relatively large proportion of treatment-seeking breast cancer survivors with vasomotor symptoms were prescribed systemic hormone therapy. This, combined with high patient-reported use of lifestyle changes and over-the-counter products, suggests a need for symptomatic relief and demand for new nonhormonal alternatives with established safety profiles in this population.

Neuropsychological and ASD phenotypes in rare genetic syndromes: A critical review of the literature.

OBJECTIVE: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by core deficits in social communication and restricted and repetitive behaviors and interests. Recent advances in clinical genetics have improved our understanding of genetic syndromes associated with ASD, which has helped clarify distinct etiologies of ASD and document syndrome-specific profiles of neurocognitive strengths and weaknesses. Pediatric neuropsychologists have the potential to be impactful members of the care team for children with genetic syndromes and their families. METHOD: We provide a critical review of the current literature related to the neuropsychological profiles of children with four genetic syndromes associated with ASD, including Tuberous Sclerosis Complex (TSC), fragile X syndrome (FXS), 22q11.2 deletion syndrome, and Angelman syndrome. Recommendations for assessment, intervention, and future directions are provided. RESULTS: There is vast heterogeneity in terms of the cognitive, language, and developmental abilities of these populations. The within- and across-syndrome variability characteristic of genetic syndromes should be carefully considered during clinical evaluations, including possible measurement limitations, presence of intellectual disability, and important qualitative differences in the ASD-phenotypes across groups. CONCLUSIONS: Individuals with genetic disorders pose challenging diagnostic and assessment questions. Pediatric neuropsychologists with expertise in neurodevelopmental processes are well suited to address these questions and identify profiles of neurocognitive strengths and weaknesses, tailor individualized recommendations, and provide diagnostic clarification.

To trust or not to trust: an exploratory qualitative study of personal and community perceptions of vaccines amongst a group of young community healthcare workers in Soweto, South Africa.

As South Africa debates the implementation of mandatory vaccination policies to address coronavirus disease 2019 (COVID-19) vaccine hesitancy, many adults remain unpersuaded of the need and benefits of vaccination. Several surveys suggest that this is particularly true for younger adults and for those living in low-income communities. Therefore, we sought the views of youth training to become community health workers (CHWs) as a youth group at the intersection of the community and the health system. This research was conducted in a township of South Africa, a country with a long history of political mistrust. Using semi-structured interviews and an interview guide, we explored young CHWs' perceptions (n = 20) of vaccine hesitancy for themselves, their peers and the community. Audio-recorded interviews were transcribed, and thematic analysis was undertaken. Findings suggest widespread COVID-19 vaccine hesitancy in this community, especially amongst young people. Reported reasons for this hesitancy appear linked to a complex interrelated network of factors, including 'uncertainty' about the outcome and effectiveness of the vaccines; 'fear' of the vaccines, driven by a myriad of rumours and conspiracy theories within the community; a 'lack of control' over other people's behaviour and a desire not to be controlled especially by the government but at the same time a resignation towards impending mandatory vaccine policies and a 'lack of trust' particularly in the government's intentions with vaccine roll-out and their health messaging. While mandatory vaccination policies in several organizations have shown success, with South Africa's complex social history and recent civil unrest, the roll-out of any mandatory vaccination policy will require careful health messaging with a focus on trust-building between communities, health systems and authorities through more personalized approaches that consider contextual nuances.

Modification of the Tumor Microenvironment Enhances Anti-PD-1 Immunotherapy in Metastatic Melanoma.

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8+ and CD4+ T cells. Additionally, the combination therapy induced higher MHC-I surface expression on tumor cells to hamper tumor cells escaping from immune recognition. Furthermore, we found that activating T cells by exposure to IL-12 resulted in tumors sensitized to anti-PD-1 treatment, suggesting a therapeutic strategy to improve responses to checkpoint blockade.

The seroprevalence of COVID-19 in patients living with HIV in metropolitan Detroit.

BACKGROUND: COVID-19, a novel respiratory illness caused by SARS-CoV-2, has become a global pandemic. As of December 2020, 4.8% of the 941 people living with HIV in our Ryan White clinic have tested polymerase chain reaction positive for SARS-CoV-2. The aim of our study was to estimate the seroprevalence of COVID-19 in our Ryan White people living with HIV, irrespective of known past infection. METHODS: We conducted a cross-sectional study that recruited people living with HIV in the Ryan White program at Henry Ford Hospital in Detroit, Michigan, from September 2020 through May 2021. All Ryan White patients were offered participation during clinic visits. After informed consent, patients completed a survey, and had blood sampled for SARS-CoV-2 antibody testing. RESULTS: Of the 529 individuals who completed the written survey, 504 participants were tested for SARS-CoV-2 antibody and 52 people living with HIV were COVID-19 immunoglobulin (Ig) G positive resulting in a seroprevalence of 10.3%. Among 36 persons with PCR-confirmed COVID-19, 52.8% were IgG negative. Inclusion of PCR positive but IgG-negative people living with HIV yields a COVID-19 infection prevalence of 14.1%. CONCLUSIONS: These findings suggest that passive public health-based antibody surveillance in people living with HIV significantly underestimates past infection.

Evaluation of the impact, treatment patterns, and patient and physician perceptions of vasomotor symptoms associated with menopause in Europe and the United States.

OBJECTIVES: This study elicited the views of physicians and patients with vasomotor symptoms (VMS) associated with menopause on the impact of VMS and treatment patterns/perceptions. STUDY DESIGN: Data from the Adelphi VMS Disease Specific Programme, a point-in-time survey conducted in 5 European countries and the United States in 2020, were used. Primary care providers (PCPs) and gynecologists seeing ≥3 patients/week with VMS associated with menopause completed a survey and chart review; their patients were invited to complete a survey and questionnaires. MAIN OUTCOME MEASURES: Physicians reported treatment patterns and patient-specific symptoms and treatment preferences. Patients described symptoms, impact of VMS, and treatment satisfaction. RESULTS: Participants included 115 PCPs and 118 gynecologists. Physicians reviewed the charts of 1816 patients, 854 of whom completed surveys. Moderate/severe impact of VMS on sleep, mood, quality of life, and work/study was reported by 35.8 %, 31.6 %, 23.6 %, and 15.4 % of women, respectively. Based on chart review, 64.8 % of women were currently prescribed treatment for VMS, most commonly hormone therapy (HT; 73.1 %), followed by selective serotonin or serotonin-norepinephrine reuptake inhibitors (31.3 %). Most women (57.3 %) with VMS were eligible for HT but averse to using it. Despite 91.4 % of physicians finding HT to be effective, 62.7 % agreed (slightly-strongly) that their patients are generally reluctant to use it. One-third of women were dissatisfied with VMS control. CONCLUSIONS: VMS can considerably impact daily life. Effective treatment options that are better accepted could potentially improve management of VMS and lead to better quality of life for women with VMS associated with menopause. CLINICAL TRIAL REGISTRATION: None.

Acupuncture intervention for acute pain in the Emergency Department trial: a consensus process.

PURPOSE: This document describes the consensus process and intervention for a National Institutes of Health (NIH)-funded multi-site feasibility study utilizing acupuncture for ACUte paIn in The EmergencY Department (ACUITY). The acupuncture intervention is designed to be flexible and responsive to the most common Emergency Department (ED) scenarios, including trauma, acute pain of the low back, abdomen and/or musculoskeletal system, renal colic and headache. BACKGROUND: Opioids remain a primary treatment for acute ED pain with attendant risk of adverse effects, addiction liability, diversion and death. Effective/safer options for acute pain are needed. Although acupuncture therapy has shown promise for acute pain in the ED alone or in conjunction with usual care, pragmatic trials are needed to obtain definitive and generalizable evidence. METHODS: An Acupuncture Advisory Panel was convened that included nine acupuncture experts with 5-44 years of experience in practice and 2-16 years of experience in the acute pain care setting. A modified Delphi process was used with provision of a literature review, surveys of our panel members, three online discussions and email discussion as needed. The STandards for Reporting Interventions in Controlled Trials (STRICTA) checklist was used as a guide. RESULTS: A responsive acupuncture intervention was agreed on for ACUITY. Session forms were fashioned in REDCap (Research Electronic Data Capture program to capture essential treatment data, assess fidelity and inform our design for a future pragmatic multi-site randomized controlled trial (RCT) of acupuncture in the ED, and for use by other future researchers. CONCLUSION: Development of a responsive manualization intervention provides the appropriate framework for conducting a future, pragmatic, multi-site, definitive RCT of acupuncture in the ED. TRIAL REGISTRATION NUMBER: NCT04880733 (ClinicalTrials.gov).