Pilot study of women's perspectives when abnormal uterine bleeding occurs during perimenopause.

OBJECTIVE: We gained insights into women's experiences and knowledge about the occurrence of vaginal bleeding during perimenopause requiring evaluation. METHODS: Qualitative inquiry was chosen to explore topics in greater depth to understand individuals' experiences. Interviews with individuals were chosen due to the sensitive nature of gynecologic symptoms and management. Interviews were completed following gynecologic care to explore individuals' experiences with the evaluation and management of vaginal bleeding during perimenopause. RESULTS: Twelve individuals were interviewed between December 2019 and March 2020. Patient uncertainty about the medical significance of developing vaginal bleeding during perimenopause was associated with self-appraisal and gathering information from multiple sources. This experience of seeking evaluation and treatment resulted in varying degrees of trust concerning information received within or outside the clinic. Regarding new technologies that could replace the current invasive tests performed for diagnosis (i.e. ultrasound, hysteroscopy and biopsy), most women preferred the smartphone app and tampon home collection option. CONCLUSIONS: The experience of irregular or heavy vaginal bleeding during perimenopause is fraught with ambiguity, feelings of uncertainty about how to make sense of symptoms and inevitably begins with a period of self-appraisal.

Morphological, Molecular, and Histopathological Data for Sebekia mississippiensis Overstreet, Self, and Vliet, 1985 (Pentastomida: Sebekidae) in the American Alligator, Alligator mississippiensis Daudin, and the Spotted Gar, Lepisosteus oculatus Winchell.

Novel molecular data from both mitochondrial ( cytochrome c oxidase subunit 1) and ribosomal regions ( 18S, ITS1-5.8S, ITS2, and 28S) are provided for Sebekia mississippiensis Overstreet, Self, & Vliet, 1985 , a pentastome infecting the American alligator, Alligator mississippiensis Daudin, 1801, and the spotted gar, Lepisosteus oculatus Winchell, 1864. Adult and nymphal pentastomes are described from the lungs and liver of the type host, A. mississippiensis, collected from Mississippi, while additional nymphs are described from the esophageal lining of L. oculatus specimens collected from Louisiana. This sequencing data will facilitate more accurate identification of various life cycle stages of S. mississippiensis, enabling future work to resolve many ambiguities in the literature regarding this species. Additionally, histopathological data are provided from both the definitive and intermediate hosts.

"I think we've got too many tests!": Prenatal providers' reflections on ethical and clinical challenges in the practice integration of cell-free DNA screening.

BACKGROUND: The recent introduction of cell-free DNA-based non-invasive prenatal screening (cfDNA screening) into clinical practice was expected to revolutionize prenatal testing. cfDNA screening for fetal aneuploidy has demonstrated higher test sensitivity and specificity for some conditions than conventional serum screening and can be conducted early in the pregnancy. However, it is not clear whether and how clinical practices are assimilating this new type of testing into their informed consent and counselling processes. Since the introduction of cfDNA screening into practice in 2011, the uptake and scope have increased dramatically. Prenatal care providers are under pressure to stay up to date with rapidly changing cfDNA screening panels, manage increasing patient demands, and keep up with changing test costs, all while attempting to use the technology responsibly and ethically. While clinical literature on cfDNA screening has shown benefits for specific patient populations, it has also identified significant misunderstandings among providers and patients alike about the power of the technology. The unique features of cfDNA screening, in comparison to established prenatal testing technologies, have implications for informed decision-making and genetic counselling that must be addressed to ensure ethical practice. OBJECTIVES: This study explored the experiences of prenatal care providers at the forefront of non-invasive genetic screening in the United States to understand how this testing changes the practice of prenatal medicine. We aimed to learn how the experience of providing and offering this testing differs from established prenatal testing methodologies. These differences may necessitate changes to patient education and consent procedures to maintain ethical practice. METHODS: We used the online American Congress of Obstetricians and Gynecologists Physician Directory to identify a systematic sample of five prenatal care providers in each U.S. state and the District of Columbia. Beginning with the lowest zip code in each state, we took every fifth name from the directory, excluding providers who were retired, did not currently practice in the state in which they were listed, or were not involved in a prenatal specialty. After repeating this step twice and sending a total of 461 invitations, 37 providers expressed interest in participating, and we completed telephone interviews with 21 providers (4.6%). We developed a semi-structured interview guide including questions about providers' use of and attitudes toward cfDNA screening. A single interviewer conducted and audio-recorded all interviews by telephone, and the interviews lasted approximately 30 minutes each. We collaboratively developed a codebook through an iterative process of transcript review and code application, and a primary coder coded all transcripts. RESULTS: Prenatal care providers have varying perspectives on the advantages of cfDNA screening and express a range of concerns regarding the implementation of cfDNA screening in practice. While providers agreed on several advantages of cfDNA, including increased accuracy, earlier return of results, and decreased risk of complications, many expressed concern that there is not enough time to adequately counsel and educate patients on their prenatal screening and testing options. Providers also agreed that demand for cfDNA screening has increased and expressed a desire for more information from professional societies, labs, and publications. Providers disagreed about the healthcare implications and future of cfDNA screening. Some providers anticipated that cfDNA screening would decrease healthcare costs when implemented widely and expressed optimism for expanded cfDNA screening panels. Others were concerned that cfDNA screening would increase costs over time and questioned whether the expansion to include microdeletions could be done ethically. CONCLUSIONS: The perspectives and experiences of the providers in this study allow insight into the clinical benefit, burden on prenatal practice, and potential future of cfDNA screening in clinical practice. Given the likelihood that the scope and uptake of cfDNA screening will continue to increase, it is essential to consider how these changes will affect frontline prenatal care providers and, in turn, patients. Providers' requests for additional guidance and data as well as their concerns with the lack of time available to explain screening and testing options indicate significant potential issues with patient care. It is important to ensure that the clinical integration of cfDNA screening is managed responsibly and ethically before it expands further, exacerbating pre-existing issues. As prenatal screening evolves, so should informed consent and the resources available to women making decisions. The field must take steps to maximize the advantages of cfDNA screening and responsibly manage its ethical issues.

CONTEXTE: L'introduction récente du dépistage prénatal non invasif (dépistage cfDNA) exempt de cellules à base d'ADN dans la pratique clinique devait révolutionner le dépistage prénatal. Le dépistage cfDNA de l'aneuploïdie fœtale a démontré une meilleure sensibilité et spécificité que le dépistage sérique classique et peut être effectué au début de la grossesse. Cependant, on ne sait pas si et comment les pratiques cliniques assimilent ce nouveau type de test dans leurs processus de consentement et de conseil éclairés. Depuis l'introduction du dépistage cfDNA dans la pratique en 2011, l'absorption et la portée ont augmenté de façon spectaculaire. Les professionnels sont sous pression pour rester à jour avec l'évolution rapide des échantillons cfDNA, gérer la demande croissante des patients, et suivre l'évolution des coûts de test, tout en essayant d'utiliser la technologie de manière responsable et éthique. Bien que la littérature clinique sur le dépistage cfDNA a montré des avantages pour les populations de patients spécifiques, elle a également identifié des malentendus importants entre les professionnels et les patients sur le pouvoir de la technologie. Les caractéristiques uniques du dépistage cfDNA, par rapport aux technologies de dépistage prénatal établies, ont des implications pour la prise de décisions éclairées et le conseil génétique qui rentrent en compte pour assurer une pratique éthique. OBJECTIFS: Cette étude a exploré les expériences des professionnels à la pointe du dépistage génétique non invasif aux États-Unis pour comprendre comment ce test modifie la pratique de la médecine prénatale. Nous avons cherché à savoir comment l'expérience de fournir et d'offrir ce test diffère des méthodes plus anciennes de dépistage prénatal. Ces différences peuvent nécessiter des changements dans l'éducation du patient et les procédures de consentement pour maintenir une pratique éthique. MÉTHODES: Nous avons utilisé l'annuaire en ligne du Congrès américain des médecins obstétriciens et gynécologues pour identifier un échantillon systématique de cinq fournisseurs de soins prénatals dans chaque État américain et le District de Columbia. En commençant par le code postal le plus bas dans chaque état, nous avons pris tous les cinquièmes noms de l'annuaire, à l'exclusion des prestataires qui étaient à la retraite, ne pratiquait pas actuellement dans l'état dans lequel ils ont été énumérés, ou ne sont pas impliqués dans une spécialité prénatale. Après avoir répété cette étape deux fois et l'envoi d'un total de 461 invitations, 37 professionnels ont exprimé leur intérêt à participer, et nous avons réalisé des entrevues téléphoniques avec 21 fournisseurs (4,6 %). Nous avons développé un entretien semi-dirigé comprenant des questions sur l'utilisation de fournisseurs de dépistage et les attitudes envers le cfDNA. Un seul intervieweur a mené et enregistré toutes les interviews par téléphone, les entretiens ont duré environ 30 minutes chacun. Nous avons développé en collaboration un dictionnaire par un processus itératif d'examen de la transcription et de l'application du code, et un codeur primaire a codé toutes les transcriptions. RÉSULTATS: Les professionnels de soins prénataux ont des points de vue variés sur les avantages du dépistage cfDNA et expriment une gamme de préoccupations concernant la mise en œuvre du dépistage cfDNA dans la pratique. S'ils ont convenu de plusieurs avantages de cfDNA, y compris une précision accrue, un retour plus rapide des résultats et une diminution de risque de complications, une préoccupation exprimée est qu'il n'y a pas suffisamment pour conseiller et éduquer les patients sur les options de dépistage et de dépistage prénatal. Les professionnels ont également convenu que la demande pour le dépistage cfDNA a augmenté et ont souhaité plus d'informations émanant des sociétés professionnelles, des laboratoires et des publications. Les fournisseurs étaient en désaccord au sujet des implications sur la santé et sur l'avenir du dépistage cfDNA. Certains fournisseurs prévoyaient que le dépistage cfDNA diminuerait les coûts des soins de santé lorsqu'ils seront appliqués largement et a exprimé son optimisme pour l'élargissement des échantillons de dépistage cfDNA. D'autres craignaient que le dépistage cfDNA augmenterait les coûts au fil du temps et se sont demandé si la possibilité d'y inclure les microdélétions pourrait être fait sur le plan éthique. CONCLUSIONS: Les perspectives et les expériences des fournisseurs dans cette étude permettent d'avoir un aperçu de l'avantage clinique, de la charge sur la pratique prénatale, et du futur potentiel du dépistage cfDNA dans la pratique clinique. Compte tenu de la probabilité que la portée et l'acceptation du dépistage cfDNA vont continuer à augmenter, il est essentiel d'examiner comment ces changements auront une incidence sur les fournisseurs de soins prénataux de première ligne et sur les patients. Les demandes de professionnels pour obtenir des conseils et des données supplémentaires ainsi que leurs préoccupations sur le manque de temps disponible pour expliquer aux patients les options de dépistage et de tests indiquent des problèmes potentiellement lourds. Il est important de veiller à ce que l'intégration clinique du dépistage cfDNA soit gérée de façon responsable et éthique avant qu'il ne se développe davantage, aggravant les problèmes préexistants. Comme le dépistage prénatal évolue, de même devrait évoluer le consentement éclairé et les ressources disponibles pour que les femmes puissent prendre leur décision. La discipline doit prendre des mesures pour maximiser les avantages du dépistage cfDNA et gérer de façon responsable les questions éthiques qui s'y rapportent.

Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age.

OBJECTIVE: To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake. STUDY DESIGN: A national sample of 1861 US-based adults was surveyed using a validated online survey instrument. The survey was administered by a commercial survey research company. Respondents were randomized to receive a survey about prenatal testing for trisomy 13 and 18 or trisomy 21. Participants were asked to select among testing modalities, including cffDNA testing, and rank the features of testing that they considered most important to decision making. RESULT: There was substantive interest in the use of cffDNA testing rather than traditional screening mechanisms, with a minority of respondents reporting that they would support the use of both methods in combination. The lower rates of false-negative and false-positive test results and the ability to use the test earlier in the pregnancy were the most highly rated benefits of cffDNA testing. Participants expressed strong support for diagnostic confirmation via invasive testing after a positive result from either screening or cffDNA testing. However, almost one-third of participants reported that they would not endorse the use of either invasive or non-invasive prenatal testing. CONCLUSION: There appears to be support for uptake of non-invasive prenatal tests. Clinical guidelines should therefore go forward in providing guidance on how to integrate non-invasive methods into the current standard of care. However, our findings indicate that even when accuracy, which is rated by patients as the most important aspect of prenatal testing, is significantly improved over existing screening methods and testing is offered non-invasively, the number of individuals who reported that they would decline any testing remained the same. Attention should therefore be directed at ensuring that the right of informed refusal of prenatal testing is not impacted by new, non-invasive methods.

Best ethical practices for clinicians and laboratories in the provision of noninvasive prenatal testing.

OBJECTIVE: The goal of this study is to provide an ethical framework for clinicians and companies providing noninvasive prenatal testing using cell-free fetal DNA or whole fetal cells. METHOD: In collaboration with a National Institutes of Health-supported research ethics consultation committee together with feedback from an interdisciplinary group of clinicians, members of industry, legal experts, and genetic counselors, we developed a set of best practices for the provision of noninvasive prenatal genetic testing. RESULTS: Principal recommendations include the amendment of current informed consent procedures to include attention to the noninvasive nature of new testing and the potential for a broader range of results earlier in the pregnancy. We strongly recommend that tests should only be provided through licensed medical providers and not directly to consumers. CONCLUSION: Prenatal tests, including new methods using cell-free fetal DNA, are not currently regulated by government agencies, and limited professional guidance is available. In the absence of regulation, companies and clinicians should cooperate to adopt responsible best ethical practices in the provision of these tests.

Chloride inhibition of nitrite uptake for non-teleost Actinopterygiian fishes.

Fish that transport environmental chloride with a gill uptake mechanism (gill epithelial Cl(-)/HCO(3)(-)cotransport exchange system), also transport nitrite into plasma through the same mechanism. Because of the relationship between nitrite uptake and the gill chloride uptake mechanism, nitrite uptake can provide insight regarding the method of chloride uptake for fish. This study was designed to determine if non-teleost fishes concentrate nitrite in their plasma, and to determine if chloride inhibits nitrite uptake in non-teleost fish. To determine if bowfin Amia calva, spotted gar Lepisosteus oculatus, alligator gar Atractosteus spatula, and paddlefish Polyodon spathula concentrate environmental nitrite in their plasma, individuals were exposed to concentrations of 0, 1, 10, or 100 mg/L nitrite-N. After exposure, all species had plasma nitrite-N concentrations greater than environmental levels. To determine if chloride inhibits nitrite uptake for spotted gar, alligator gar, and paddlefish, fish were exposed to 1 mg/L nitrite-N and 20 mg/L chloride as calcium chloride, or to 1 mg/L nitrite-N only. Chloride effectively prevented nitrite from being concentrated in the plasma of all species. It appears that non-teleost fish concentrate nitrite in their plasma via their chloride uptake mechanism and that this is an ancestral characteristic for teleost.