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BACKGROUND: Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. METHODS: We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy. Patients who were frail or had a high burden of coexisting conditions were eligible. The primary outcome was a composite of death from cardiovascular causes (cardiovascular death) or nonfatal myocardial infarction assessed in a time-to-event analysis. RESULTS: A total of 1518 patients underwent randomization; 753 patients were assigned to the invasive-strategy group and 765 to the conservative-strategy group. The mean age of the patients was 82 years, 45% were women, and 32% were frail. A primary-outcome event occurred in 193 patients (25.6%) in the invasive-strategy group and 201 patients (26.3%) in the conservative-strategy group (hazard ratio, 0.94; 95% confidence interval [CI], 0.77 to 1.14; P = 0.53) over a median follow-up of 4.1 years. Cardiovascular death occurred in 15.8% of the patients in the invasive-strategy group and 14.2% of the patients in the conservative-strategy group (hazard ratio, 1.11; 95% CI, 0.86 to 1.44). Nonfatal myocardial infarction occurred in 11.7% in the invasive-strategy group and 15.0% in the conservative-strategy group (hazard ratio, 0.75; 95% CI, 0.57 to 0.99). Procedural complications occurred in less than 1% of the patients. CONCLUSIONS: In older adults with NSTEMI, an invasive strategy did not result in a significantly lower risk of cardiovascular death or nonfatal myocardial infarction (the composite primary outcome) than a conservative strategy over a median follow-up of 4.1 years. (Funded by the British Heart Foundation; BHF SENIOR-RITA ISRCTN Registry number, ISRCTN11343602.).
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A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research, prevention, and care of individuals and populations. Nevertheless, several challenges exist, and few artificial intelligence tools have been shown to improve cardiovascular and stroke care sufficiently to be widely adopted. This scientific statement outlines the current state of the art on the use of artificial intelligence algorithms and data science in the diagnosis, classification, and treatment of cardiovascular disease. It also sets out to advance this mission, focusing on how digital tools and, in particular, artificial intelligence may provide clinical and mechanistic insights, address bias in clinical studies, and facilitate education and implementation science to improve cardiovascular and stroke outcomes. Last, a key objective of this scientific statement is to further the field by identifying best practices, gaps, and challenges for interested stakeholders.
Subject(s)
Cardiovascular Diseases , Heart Diseases , Stroke , United States , Humans , Artificial Intelligence , American Heart Association , Cardiovascular Diseases/therapy , Cardiovascular Diseases/prevention & control , Stroke/diagnosis , Stroke/prevention & controlABSTRACT
BACKGROUND: Streptococcus pyogenes-related skin infections are increasingly implicated in the development of rheumatic heart disease (RHD) in lower-resourced settings, where they are often associated with scabies. The true prevalence of S. pyogenes-related pyoderma may be underestimated by bacterial culture. METHODS: A multiplex qPCR for S. pyogenes, Staphylococcus aureus and Sarcoptes scabiei was applied to 250 pyoderma swabs from a cross-sectional study of children <5 years in The Gambia. Direct PCR-based emm-typing was used to supplement previous whole genome sequencing (WGS) of cultured isolates. RESULTS: Pyoderma lesions with S. pyogenes increased from 51% (127/250) using culture to 80% (199/250) with qPCR. Compared to qPCR, the sensitivity of culture was 95.4% for S. pyogenes (95% CI 77.2-99.9) in samples with S. pyogenes alone (22/250, 9%), but 59.9% (95% CI 52.3-67.2) for samples with S. aureus co-infection (177/250, 71%). Direct PCR-based emm-typing was successful in 50% (46/92) of cases, identifying 27 emm-types, including six not identified by WGS (total 52 emm-types). CONCLUSIONS: Bacterial culture significantly underestimates the burden of S. pyogenes in pyoderma, particularly when co-infected with S. aureus. Molecular methods should be used to enhance the detection of S. pyogenes in surveillance studies and clinical trials of preventative measures in RHD-endemic settings.
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The evolution of the electronic health record, combined with advances in data curation and analytic technologies, increasingly enables data sharing and harmonization. Advances in the analysis of health-related and health-proxy information have already accelerated research discoveries and improved patient care. This American Heart Association policy statement discusses how broad data sharing can be an enabling driver of progress by providing data to develop, test, and benchmark innovative methods, scalable insights, and potential new paradigms for data storage and workflow. Along with these advances come concerns about the sensitive nature of some health data, equity considerations about the involvement of historically excluded communities, and the complex intersection of laws attempting to govern behavior. Data-sharing principles are therefore necessary across a wide swath of entities, including parties who collect health information, funders, researchers, patients, legislatures, commercial companies, and regulatory departments and agencies. This policy statement outlines some of the key equity and legal background relevant to health data sharing and responsible management. It then articulates principles that will guide the American Heart Association's engagement in public policy related to data collection, sharing, and use to continue to inform its work across the research enterprise, as well as specific examples of how these principles might be applied in the policy landscape. The goal of these principles is to improve policy to support the use or reuse of health information in ways that are respectful of patients and research participants, equitable in impact in terms of both risks and potential benefits, and beneficial across broad and demographically diverse communities in the United States.
Subject(s)
American Heart Association , Information Dissemination , Humans , United States , Data CollectionABSTRACT
BACKGROUND: Cardiovascular health literacy (CVHL) and social determinants of health (SDoH) play interconnected and critical roles in shaping cardiovascular health (CVH) outcomes. However, awareness of CVH risk has declined markedly, from 65% of women being aware that cardiovascular disease (CVD) is the leading cause of death for women in 2009 to just 44% being aware in 2019. The American Heart Association Research Goes Red (RGR) initiative seeks to develop an open-source, longitudinal, dynamic registry that will help women to be aware of and participate in research studies, and to learn about CVD prevention. We proposed to leverage this platform, particularly among Black and Hispanic women of reproductive age, to address CVHL gaps and advance health equity. METHODS: The primary objective of the study is to evaluate the cross-sectional association of CVHL, SDoH using a polysocial score, and CVH in women of reproductive age at increased risk of developing hypertension (HTN). To achieve this we will use a cross-sectional study design, that engages women already enrolled in the RGR registry (registry-enrolled). To enhance the racial and ethnic/social economic diversity of the cohort, we will additionally enroll 300 women from the Baltimore and Washington D.C. community into the Social Determinants of the Risk of Hypertension in Women of Reproductive Age (SAFE HEART) Study. Community-enrolled and registry-enrolled women will undergo baseline social phenotyping including detailed SDoH questionnaire, CVH metrics assessment, and CVHL assessment. The secondary objective is to assess whether a 4-month active health education intervention will result in a change in CVHL in the 300 community-enrolled women. DISCUSSION: The SAFE HEART study examines the association between CVHL, SDoH, and CVH, with a focus on racial and ethnic minority groups and socioeconomically disadvantaged women of reproductive age, and the ability to improve these parameters by an educational intervention. These findings will inform the future development of community-engaged strategies that address CVHL and SDoH among women of reproductive age.
Subject(s)
American Heart Association , Hypertension , Social Determinants of Health , Adult , Female , Humans , Middle Aged , Young Adult , Cross-Sectional Studies , Health Literacy , Hispanic or Latino/statistics & numerical data , Hypertension/epidemiology , Hypertension/ethnology , Registries , Risk Factors , United States/epidemiology , Black or African AmericanABSTRACT
Escape of genetically distinct farmed Atlantic salmon (Salmo salar) raises concerns about their potential interactions with wild populations and the disruption of local adaptation through genetic admixture. It is often unknown whether genetic origin or common domestication effects will have a greater influence on consequences posed by escaped farmed fish. Previous work showed that domestication could have prevalent effects on the behaviour and growth of farmed salmon, independent of their genetic origin. Yet, less is known whether this extends more broadly to gene expression, particularly at critical early life stages. Thus, we compared the expression of 24 transcripts related to the immune response, structural maintenance, stress response and iron metabolism among distinct farmed (North American [NA] and European [EO]), wild (Newfoundland) and F1 hybrid salmon at hatching under controlled conditions using qPCR analyses. A slightly higher number of transcripts were differentially expressed between the wild population relative to EO (i.e. atf3a, atf3b, bnip3, trim37a, ftm, hp and gapdh) than NA-farmed salmon (i.e. epdl2, hba1a, hba1b, hbb4 and ftm). The most differences existed between the two farmed strains themselves (11 of 24 transcripts), with the fewest differentially expressed transcripts found between the F1 hybrids and the domesticated/wild maternal strains (4 of 24 transcripts). Interestingly, despite similarities in the overall extent of gene expression differences among cross types, the expression patterns differed relative to a past study that compared fry from the same cross types at the end of yolk sac absorption. Overall, our findings suggest that interbreeding of escaped farmed salmon with wild Newfoundland populations would alter transcript expression levels and that developmental stage influences these changes.
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RATIONALE: Cardiovascular disease remains the leading cause of death in women. To address its determinants including persisting cardiovascular risk factors amplified by sex and race inequities, novel personalized approaches are needed grounded in the engagement of participants in research and prevention. OBJECTIVE: To report on a participant-centric and personalized dynamic registry designed to address persistent gaps in understanding and managing cardiovascular disease in women. METHODS AND RESULTS: The American Heart Association and Verily launched the Research Goes Red registry (RGR) in 2019, as an online research platform available to consenting individuals over the age of 18 years in the United States. RGR aims to bring participants and researchers together to expand knowledge by collecting data and providing an open-source longitudinal dynamic registry for conducting research studies. As of July 2021, 15 350 individuals have engaged with RGR. Mean age of participants was 48.0 48.0Ā±0.2 years with a majority identifying as female and either non-Hispanic White (75.7%) or Black (10.5%). In addition to 6 targeted health surveys, RGR has deployed 2 American Heart Association-sponsored prospective clinical studies based on participants' areas of interest. The first study focuses on perimenopausal weight gain, developed in response to a health concerns survey. The second study is designed to test the use of social media campaigns to increase awareness and participation in cardiovascular disease research among underrepresented millennial women. CONCLUSIONS: RGR is a novel online participant-centric platform that has successfully engaged women and provided critical data on women's heart health to guide research. Priorities for the growth of RGR are centered on increasing reach and diversity of participants, and engaging researchers to work within their communities to leverage the platform to address knowledge gaps and improve women's health.
Subject(s)
Cardiovascular Diseases/epidemiology , Patient Participation/methods , Registries , Adolescent , Adult , Aged , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/therapy , Female , Humans , Middle Aged , Patient-Centered Care/methods , Social MediaABSTRACT
BACKGROUND: Islamic leaders, staff, and Muslim parents in the UK are supportive of healthy lifestyle intervention delivery through Islamic Religious Settings. Such interventions are necessary given high obesity rates in British South Asian (40%) compared to White British (32%) children of equivalent age. Co-production can facilitate the development of culturally appropriate health interventions, however it can be theoretically and practically challenging, and evaluation of co-production within an Islamic Religious Setting context is lacking.Ā The aim of this study was to examine the feasibility and acceptability of taking a co-production approach to develop an obesity-prevention toolkit for Islamic Religious Settings. METHODS: An obesity-prevention toolkit for use in Islamic Religious Settings, incorporating physical activity, healthy diet, and organisational change, has been co-produced to be evidence-informed and contextually relevant. A qualitative process evaluation was employed to examine experiences of co-production. Semi-structured interviews (n = 15) and a focus group (n = 5) were conducted with toolkit co-production stakeholders, e.g., subject experts, an Islamic scholar, and Islamic Religious Setting staff. Transcripts were analysed inductively using reflexive thematic analysis. RESULTS: The analysis revealed four major themes regarding stakeholders' experiences of co-producing a childhood obesity-prevention toolkit for Islamic Religious Settings. These themes are: (1) attitudes towards obesity-prevention through Islamic Religious Settings, (2) benefits of co-production including capacity building and ownership (3) negotiating involvement, power, and perspectives within the co-production process, and (4) the complexities of effective communication in co-production. CONCLUSION: This study adds to the evidence-base in support of delivering health promotion through faith settings. Taking a co-production approach to develop an obesity-prevention toolkit for Islamic Religious Settings provided benefit to the toolkit product and local stakeholders. The toolkit is currently being implemented across Bradford, UK and there is potential to adapt the toolkit to other geographical contexts, and for evaluating effectiveness for preventing obesity in British Muslim families.
Subject(s)
Health Promotion , Islam , Qualitative Research , Humans , Health Promotion/methods , Female , Male , Focus Groups , Obesity/prevention & control , United Kingdom , Exercise , Pediatric Obesity/prevention & control , Adult , Child , Diet, Healthy/methodsABSTRACT
BACKGROUND: For health services to help people plan for or prevent pregnancy, health professionals need an acceptable way to identify individuals' preferences. OBJECTIVE: To assess women's views on the acceptability of specific questions about pregnancy preferences when asked by health professionals in a variety of primary care contexts. METHODS: One-to-one in-depth interviews with 13 women aged 18-48 from across the UK, involving role-play scenarios and ranking exercises. Interviews covered a range of settings and health professionals, different question wording, and ways of asking (in person or digitally). We conducted a thematic Framework Analysis, focussing on themes relating to feelings and preferences. RESULTS: Women were generally open to being asked about pregnancy preferences if they understood the rationale, it was asked in a relevant context, such as in women's health-related consultations, and there was follow-up. After signposting, an open question, such as 'How would you feel about having a baby in the next year?' was preferred in a face-to-face context as it enabled discussion. While some women valued a face-to-face discussion with a health professional, for others the privacy and convenience of a digital option was preferred; methods should be tailored to the target population. CONCLUSION: Discussion of pregnancy preferences via a range of formats is acceptable to, and valued by, women in the UK across a range of primary care settings. Acceptability to health professionals and feasibility of implementation needs further exploration and would benefit from greater public awareness of the benefits of pregnancy planning.
Subject(s)
Intention , Women's Health , Pregnancy , Female , Humans , Qualitative Research , Emotions , Primary Health CareABSTRACT
INTRODUCTION: There is growing scientific and policy recognition that optimising health before a potential pregnancy (preconception health) improves reproductive outcomes and the lifelong health of future children. However, public awareness on this topic is low. We conducted a public consultation to develop language recommendations and identify and prioritise approaches to inform research and improve public awareness of preconception health. METHODS: A public consultation was undertaken with people of any gender aged 18-50 years living in the United Kingdom who were not currently expecting a child. Public contributors were recruited through patient and public involvement, community and support groups, an existing cohort study, and an LGBTQ+ charity. An initial round of online group discussions (February/March 2021) explored public contributors' knowledge of preconception health, their recommendations for appropriate language, and ideas about public health approaches. In a subsequent discussion round (May 2021), language recommendations were refined and suggested approaches prioritised. Discussions were summarised based on notes taken by two researchers. RESULTS: Fifty-fourĀ people joined the initial discussion round (66% women, 21% men, 13% nonbinary or transgender; 55% aged 18-30 years, 30% 31-40 years, 15% 41-50 years). Of these, 36 people (67%) participated in the subsequent round. Very few had heard the term 'preconception health', understood what it means, or why and for whom it is important. They recommended avoiding unfamiliar terms without further explanation (e.g., preconception health, medical terms), using language that is positive, encouraging and gender-sensitive where possible, and using messages that are specific, nonjudgmental and realistic. The phrases 'health and well-being during the childbearing years', 'health and well-being before pregnancy and parenthood' and 'planning for parenthood' resonated with most public contributors. School-based education, social media campaigns and the National Health Service emerged as priority approaches/settings for raising awareness. CONCLUSION: This public consultation produced recommendations from a diverse group of people of reproductive age in the United Kingdom to improve language and prioritise approaches that increase public understanding of preconception health in ways that are relevant and appropriate to them. This should begin in schools and will require adaptation of curricula, alongside co-development of public awareness campaigns and guidance for healthcare professionals. PATIENT OR PUBLIC CONTRIBUTION: This public consultation included a diverse group of members of the public. They were not involved in the original design of the project, but following the initial round of online group discussions, they contributed to the interpretation and refinement of the emerging concepts in a subsequent round of group meetings. After the consultation activity, public contributors formed a Public Advisory Group and have subsequently been involved in other studies on the same topic. Two public contributors (E.R. and F.F.) provided critical input in the preparation and revision of this manuscript and are co-authors of the paper.
Subject(s)
Health Knowledge, Attitudes, Practice , Preconception Care , Humans , Female , Male , Adult , United Kingdom , Adolescent , Middle Aged , Young Adult , Language , Pregnancy , AwarenessABSTRACT
Black women in the USA experience some of the poorest health outcomes and this is especially true for those involved in the carceral system who are at elevated risks for HIV/STIs, reproductive health, and chronic diseases. This study aimed to investigate Black women's experience accessing healthcare services. We conducted semi-structured interviews with 43 women from Project EWORTH under community supervision in New York City. We analysed responses focusing on barriers to healthcare engagement. All interviews were recorded, and data analysis was conducted using NVivo. Themes influencing Black women's ability to engage with healthcare providers and systems included: 1) disclosed provider mistrust/judgement; 2) feeling disrespected by providers and the medical system; 3) mistrust of medical providers/system/hospital/government; 4) lack of health communication; 5) low health literacy; 6) provider gender preference. Findings highlight the need to improve trust and collaboration between healthcare providers and Black women. This study addresses the critical gap in understanding perceptions of discrimination, stigma, and barriers to attaining health care. Funders and accreditation agencies must hold providers and organisations accountable for acquiring and making available diversity, equity and inclusion training for providers, demonstrating increasingly equitable medical relationships through responsiveness to patient feedback, and increasing the number of Black providers.
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PURPOSE: While many women worldwide use contraception, there is a paucity of research on individual experiences of side effects. To address this gap, we investigated individual's contraception experiences. METHODS: Women aged 18 to 35, living in the UK were invited to participate in an online survey on contraception. Free text responses were collected. Through a directed content analysis approach, we developed a coding framework (based on existing literature and initial response review) including six themes; method(s) of contraception, side effect(s) experienced, impact of side effect(s), timing of side effect(s), interactions with healthcare practitioners, and trial-and-error. RESULTS: Overall, 337 participants provided free-text responses. Side effect experiences and impacts varied greatly between individuals and contraceptives. Most participants described negative effects, including mental health issues and bleeding problems. However, some shared positive experiences mainly related to bleeding management or the absence of side effects. Participants described how side effects often varied or appeared over time. Some participants felt unheard by healthcare practitioners. CONCLUSIONS: This study highlights how specific contraceptive experience is to the individual. We advocate for a patient-centred approach to contraceptive counselling. Practitioners should play an active role in improving contraception prescription, acknowledging the diverse experiences and preferences of patients.
This UK based study highlights the individual nature of contraceptive experiences and how side effects are often overlooked by healthcare practitioners emphasising the need for patient-centred contraceptive counselling that considers the impacts on physical and mental health.
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This study examined retention and its relationship to mental health, substance use, and social determinants of health in a randomized clinical trial of a behavioral HIV/sexually transmitted infection prevention intervention with drug-involved Black women (N = 348) under community supervision programs in New York City. Using secondary analysis, we used logistic models to test the association between factors related to mental health, substance use, and social determinants of health and follow-up assessment completion (three, six, and 12 months). Participants who were diagnosed with schizophrenia had lower odds of retention. Participants who misused prescription opiates during their lifetime or food insecure in the past 90 days had higher odds of retention throughout the intervention.
Subject(s)
HIV Infections , Sexually Transmitted Diseases , Substance-Related Disorders , Humans , Female , HIV Infections/diagnosis , Sexually Transmitted Diseases/prevention & control , Substance-Related Disorders/diagnosis , Mental Health , Delivery of Health CareABSTRACT
Addressing the pervasive gaps in knowledge and care delivery to reduce sex-based disparities and achieve equity is fundamental to the American Heart Association's commitment to advancing cardiovascular health for all by 2024. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders around the globe to identify and remove barriers to health care access and quality for women. A concise and current summary of existing data across the areas of risk and prevention, access and delivery of equitable care, and awareness and education provides a framework to consider knowledge gaps and research needs critical toward achieving significant progress for the health and well-being of all women.
Subject(s)
American Heart Association , Cardiovascular Diseases , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Female , Health Services Accessibility , Humans , United States/epidemiologyABSTRACT
BACKGROUND: Socioeconomic disadvantage is a strong determinant of adverse outcomes in patients with heart failure. However, the contribution of community-level economic distress to adverse outcomes in heart failure may differ across races and ethnicities. METHODS: Patients of self-reported Black, White, and Hispanic race and ethnicity hospitalized with heart failure between 2014 and 2019 were identified from the Medicare MedPAR Part A 100% Files. We used patient-level residential ZIP code to quantify community-level economic distress on the basis of the Distressed Community Index (quintile 5: economically distressed versus quintiles 1-4: nondistressed). The association of continuous and categorical measures (distressed versus nondistressed) of Distressed Community Index with 30-day, 6-month, and 1-year risk-adjusted mortality, readmission burden, and home time were assessed separately by race and ethnicity groups. RESULTS: The study included 1 611 586 White (13.2% economically distressed), 205 840 Black (50.6% economically distressed), and 89 199 Hispanic (27.3% economically distressed) patients. Among White patients, living in economically distressed (versus nondistressed) communities was significantly associated with a higher risk of adverse outcomes at 30-day and 1-year follow-up. Among Black and Hispanic patients, the risk of adverse outcomes associated with living in distressed versus nondistressed communities was not meaningfully different at 30 days and became more prominent by 1-year follow-up. Similarly, in the restricted cubic spline analysis, a stronger and more graded association was observed between Distressed Community Index score and risk of adverse outcomes in White patients (versus Black and Hispanic patients). Furthermore, the association between community-level economic distress and risk of adverse outcomes for Black patients differed in rural versus urban areas. Living in economically distressed communities was significantly associated with a higher risk of mortality and lower home time at 1-year follow-up in rural areas but not urban areas. CONCLUSIONS: The association between community-level economic distress and risk of adverse outcomes differs across race and ethnic groups, with a stronger association noted in White patients at short- and long-term follow-up. Among Black patients, the association of community-level economic distress with a higher risk of adverse outcomes is less evident in the short term and is more robust and significant in the long-term follow-up and rural areas.
Subject(s)
Heart Failure/complications , Heart Failure/epidemiology , Long Term Adverse Effects/pathology , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Male , Medicare , Race Factors , United StatesABSTRACT
A single SARS-CoV-2 vaccine dose reduces onward transmission from case-patients. We assessed the potential effects of receiving 2 doses on household transmission for case-patients in England and their household contacts. We used stratified Cox regression models to calculate hazard ratios (HRs) for contacts becoming secondary case-patients, comparing contacts of 2-dose vaccinated and unvaccinated index case-patients. We controlled for age, sex, and vaccination status of case-patients and contacts, as well as region, household composition, and relative socioeconomic condition based on household location. During the Alpha-dominant period, HRs were 0.19 (0.13-0.28) for contacts of 2-dose BNT162b2-vaccinated case-patients and 0.54 (0.41-0.69) for contacts of 2-dose Ch4dOx1-vaccinated case-patients; during the Delta-dominant period, HRs were higher, 0.74 (0.72-0.76) for BNT162b2 and 1.06 (1.04-1.08) for Ch4dOx1. Reduction of onward transmission was lower for index case-patients who tested positive ≥2 months after the second dose of either vaccine.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , BNT162 Vaccine , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination , England/epidemiologyABSTRACT
Although it is known that the whitefish, an ancient salmonid, expresses three distinct gonadotropin-releasing hormone (GnRH) forms in the brain, it has been thought that the later-evolving salmonids (salmon and trout) had only two types of GnRH: GnRH2 and GnRH3. We now provide evidence for the expression of GnRH1 in the gonads of Atlantic salmon by rapid amplification of cDNA ends, real-time quantitative PCR and immunohistochemistry. We examined six different salmonid genomes and found that each assembly has one gene that likely encodes a viable GnRH1 prepropeptide. In contrast to both functional GnRH2 and GnRH3 paralogs, the GnRH1 homeolog can no longer express the hormone. Furthermore, the viable salmonid GnRH1 mRNA is composed of only three exons, rather than the four exons that build the GnRH2 and GnRH3 mRNAs. Transcribed gnrh1 is broadly expressed (in 17/18 tissues examined), with relative abundance highest in the ovaries. Expression of the gnrh2 and gnrh3 mRNAs is more restricted, primarily to the brain, and not in the gonads. The GnRH1 proximal promoter presents composite binding elements that predict interactions with complexes that contain diverse cell fate and differentiation transcription factors. We provide immunological evidence for GnRH1 peptide in the nucleus of 1-year-old type A spermatogonia and cortical alveoli oocytes. GnRH1 peptide was not detected during other germ cell or reproductive stages. GnRH1 activity in the salmonid gonad may occur only during early stages of development and play a key role in a regulatory network that controls mitotic and/or meiotic processes within the germ cell.
Subject(s)
Salmo salar , Animals , Male , Salmo salar/metabolism , Trout/genetics , Trout/metabolism , Gonadotropin-Releasing Hormone/genetics , Gonadotropin-Releasing Hormone/metabolism , Brain/metabolism , Promoter Regions, Genetic/geneticsABSTRACT
STUDY QUESTION: What is the proportion of women who experience natural conception after a livebirth via assisted reproductive technology (ART)? SUMMARY ANSWER: Current evidence suggests that natural conception pregnancy may occur in at least one in five women after having a baby via IVF or ICSI. WHAT IS KNOWN ALREADY: It is widely known that some women having babies via ART go on to conceive naturally. This reproductive history is of media interest and often described as 'miracle' pregnancies. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was carried out. Ovid Medline, Embase, and PsycINFO were searched until 24 September 2021 for English language, human studies from 1980. Search terms were used for the concepts of natural conception pregnancy, assisted reproduction, and livebirth. PARTICIPANTS/MATERIALS, SETTING, METHODS: The inclusion criterion was studies with an outcome measure of the proportion of women experiencing natural conception pregnancy after an ART livebirth. Quality of studies was assessed using the Critical Appraisal Skills Programme cohort study checklist or AXIS Appraisal tool for cross-sectional studies, and a risk of bias assessment was carried out. No studies were excluded based on quality. Random-effects meta-analyses were adopted to produce a pooled effect estimate of the proportion of natural conception pregnancy after ART livebirth. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1108 distinct studies were identified, resulting in 54 studies after screening by title and abstract. Eleven studies including 5180 women were selected for this review. The included studies were mostly of moderate quality with a maximum follow-up period ranging from 2 to 15 years. Four studies reported natural conception livebirths which were used as known underestimates of natural conception pregnancies. The pooled estimate for the proportion of women having natural conception pregnancies after ART livebirth was 0.20 (95% CI, 0.17-0.22). LIMITATIONS, REASONS FOR CAUTION: The studies varied widely according to methodology, population, cause of subfertility, type and outcome of fertility treatment, and length of follow-up, leading to potential bias relating to confounding, selection bias, and missing data. WIDER IMPLICATIONS OF THE FINDINGS: Current evidence suggests that contrary to widely held views, natural conception pregnancy after ART livebirth is far from rare. National, data-linked studies are needed to provide more accurate estimates of this incidence and analysis of associated factors and trends over time to facilitate tailored counselling of couples considering further ART. STUDY FUNDING/COMPETING INTEREST(S): This work was conducted as part of an academic clinical fellowship awarded to AT by the National Institute for Health Research (NIHR). NIHR has had no input into the study design, data collection, and analysis, nor the writing of this study. No authors have any conflicts of interest. REGISTRATION NUMBER: PROSPERO (CRD42022322627).
Subject(s)
Fertilization , Reproductive Techniques, Assisted , Pregnancy , Humans , Female , Cohort Studies , Pregnancy Rate , Cross-Sectional Studies , Fertilization in Vitro/methodsABSTRACT
BACKGROUND: The coronavirus disease 2019 pandemic led to clinical practice changes, which affected cancer preventive care delivery. OBJECTIVES: To investigate the impact of the coronavirus disease 2019 pandemic on the delivery of colorectal cancer (CRC) and cervical cancer (CVC) screenings. RESEARCH DESIGN: Parallel mixed methods design using electronic health record data (extracted between January 2019 and July 2021). Study results focused on 3 pandemic-related periods: March-May 2020, June-October 2020, and November 2020-September 2021. SUBJECTS: Two hundred seventeen community health centers located in 13 states and 29 semistructured interviews from 13 community health centers. MEASURES: Monthly up-to-date CRC and CVC screening rates and monthly rates of completed colonoscopies, fecal immunochemical test (FIT)/fecal occult blood test (FOBT) procedures, Papanicolaou tests among age and sex-eligible patients. Analysis used generalized estimating equations Poisson modeling. Qualitative analysts developed case summaries and created a cross-case data display for comparison. RESULTS: The results showed a reduction of 75% for colonoscopy [rate ratio (RR) = 0.250, 95% CI: 0.224-0.279], 78% for FIT/FOBT (RR = 0.218, 95% CI: 0.208-0.230), and 87% for Papanicolaou (RR = 0.130, 95% CI: 0.125-0.136) rates after the start of the pandemic. During this early pandemic period, CRC screening was impacted by hospitals halting services. Clinic staff moved toward FIT/FOBT screenings. CVC screening was impacted by guidelines encouraging pausing CVC screening, patient reluctance, and concerns about exposure. During the recovery period, leadership-driven preventive care prioritization and quality improvement capacity influenced CRC and CVC screening maintenance and recovery. CONCLUSIONS: Efforts supporting quality improvement capacity could be key actionable elements for these health centers to endure major disruptions to their care delivery system and to drive rapid recovery.
Subject(s)
COVID-19 , Colorectal Neoplasms , Humans , Early Detection of Cancer/methods , Public Health , Pandemics/prevention & control , Mass Screening/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Occult Blood , ColonoscopyABSTRACT
BACKGROUND: Gastric cancer (GC), gastroesophageal junction cancer (GEJC), and esophageal adenocarcinoma (EAC), together, are leading causes of cancer deaths worldwide. Patient health-related quality of life (HRQoL) and well-being has become increasingly important alongside traditional oncologic outcomes for both patients and clinicians and may aid treatment decisions. We conducted a survey to examine the clinical characteristics, humanistic burden, and the effects of first-line (1L) treatment in patients with GC/GEJC/EAC, across different geographic regions, to address the paucity of real-world data. METHODS: Clinicians treating patients with unresectable advanced or metastatic GC/GEJC/EAC in China, France, Germany, Japan, the United Kingdom, and the United States, during April-October 2019, were invited to provide data on their patients' demographics, clinical characteristics, treatment, and HRQoL via medical chart reviews, clinician surveys, and patient questionnaires. Data were analyzed using descriptive statistics, regression analyses comparing active treatment and best supportive care. Patients were also stratified into subgroups that were identified either as human epidermal growth factor receptor 2 (HER2) positive, HER2 negative (which has a higher prevalence but for whom there are limited treatment options), or unknown HER2 status. RESULTS: Survey data were analyzed for 995 patients, 87% of whom were on active treatment, most commonly dual or triple chemotherapy. Demographics and clinical characteristics were similar across countries with most patients having GC and the lowest incidence of GEJC and EAC in China. Overall, most patients had de novo disease with good response to 1L treatment, while their HRQoL and well-being was significantly worse than the general population. In 682 patients on active treatment with HER2 negative or unknown status, HRQoL also appeared to be worse in those with recurrent disease. Regression analysis identified several drivers of treatment decisions and factors impacting patients' HRQoL, including stage of disease and comorbidities. CONCLUSIONS: In patients with advanced GC/GEJC/EAC, screening and assessment of HER2 status as well as patient-reported HRQoL outcomes are invaluable in aiding treatment decisions. The introduction of appropriate therapy soon after diagnosis has the prospect of achieving improved HRQoL and survival in these patients.