Search

Increasing concentrations of polybrominated flame retardants, including polybrominated diphenyl ethers (PBDEs), in breast milk cause concern about possible developmental effects in nursed babies. Because previous studies in rats have indicated effects on sex steroids and sexually dimorphic behavior after maternal exposure to polychlorinated biphenyls (PCBs), our goal in the present study was to determine if developmental exposure to 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE-99) induces similar endocrine-mediated effects. Pregnant rats were exposed to vehicle or PBDE-99 (1 or 10 mg/kg body weight, daily during gestational days 10-18). For comparison, we also included a group exposed to the technical PCB mixture Aroclor 1254 (30 mg/kg body weight, daily). PBDE exposure resulted in pronounced decreases in circulating sex steroids in male offspring at weaning and in adulthood. Female offspring were less affected. Anogenital distance was reduced in male offspring. Puberty onset was delayed in female offspring at the higher dose level, whereas a slight acceleration was detected in low-dose males. The number of primordial/primary ovarian follicles was reduced in females at the lower dose, whereas decline of secondary follicles was more pronounced at the higher dose. Sweet preference was dose-dependently increased in PBDE-exposed adult males, indicating a feminization of this sexually dimorphic behavior. Aroclor 1254 did not alter sweet preference and numbers of primordial/primary and secondary follicles but it did affect steroid concentrations in males and sexual development in both sexes. PBDE concentrations in tissues of dams and offspring were highest on gestational day 19. These results support the hypothesis that PBDEs are endocrine-active compounds and interfere with sexual development and sexually dimorphic behavior. [ABSTRACT FROM AUTHOR]

Background and Objectives: Older adults experiencing neurocognitive disease (NCD) contend with complex care often characterized by high emotional strain. Mitigating complex care with decision support tools can clarify options. When used in conjunction with the practice of shared decision making (SDM), these tools can improve satisfaction and confidence in treatment. The use of these tools for cognitive health has increased, but more is needed to understand how these tools incorporate social needs into treatment plans., Research Design and Methods: We conducted an environmental scan using a MEDLINE-informed search strategy and feedback from an expert steering committee to characterize current tools and approaches for engaging older adults experiencing NCD. We assessed their application and development, incorporation of social determinants, goals or preferences, and inclusion of caregivers in their design., Results: We identified 11 articles, 7 of which show that SDM helps guide tool development and that most center on clinical decision making. Types of tools varied by clinical site and those differences reflected patient need. A collective value across tools was their use to forge meaningful conversations. Most tools appeared designed without the explicit goal to elicit patient social needs or incorporate nonclinical strategies into treatment plans., Discussion and Implications: Several challenges and opportunities exist that center on strategies to engage patients in the design and testing of tools that support conversations with clinicians about cognitive health. Future work should focus on building and testing adaptable tools that support patient and family social care needs beyond clinical care settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Online health information seeking is changing the way people engage with health care and the health system. Recent changes in practices related to seeking, accessing, and disseminating scientific research, and in particular health information, have enabled a high level of user engagement., Objective: This study aims to examine an innovative model of research translation, The Huberman Lab Podcast (HLP), developed by Andrew Huberman, Professor of Neurobiology and Ophthalmology at the Stanford School of Medicine. The HLP leverages social media to deliver health information translated into specific, actionable practices and health strategies directly to the general public. This research characterizes the HLP as an Active Model of Research Translation and assesses its potential as a framework for replicability and wider adoption., Methods: We applied conventional content analysis of the YouTube transcript data and directed content analysis of viewers' YouTube comments to 23 HLP episodes released from January to October 2021, reflecting the time of data analysis. We selected 7 episodes and a welcome video, to describe and identify key characteristics of the HLP model. We analyzed viewer comments for 18 episodes to determine whether viewers found the HLP content valuable, accessible, and easy to implement., Results: The key HLP features are direct-to-the-consumer, zero-cost, bilingual, and actionable content. We identified 3 main organizing categories and 10 subcategories as the key elements of the HLP: (1) Why: Educate and Empower and Bring Zero Cost to Consumer Information to the General Public; (2) What: Tools and Protocols; Underlying Mechanisms; and Grounded in Science; (3) How: Linear and Iterative Knowledge Building Process; Lecture-Style Sessions; Interactive and Consumer Informed; Easily Accessible; and Building the Community. Analysis of viewers' comments found strong consumer support for the key HLP model elements., Conclusions: This Active Model of Research Translation offers a way to synthesize scientific evidence and deliver it directly to end users in the form of actionable tools and education. Timely evidence translation using effective consumer engagement and education techniques appears to improve access and confidence related to health information use and reduces challenges to understanding and applying health information received from health providers. Framing complex content in an approachable manner, engaging the target audience, encouraging participation, and ensuring open access to the content meet current recommendations on innovative practices for leveraging social media or other digital platforms for disseminating science and research findings to the general public, and are likely key contributors to HLP impact and potential for success. The model offers a replicable framework for translating and disseminating scientific evidence. Similar active models of research translation can have implications for accessing health information and implementing health strategies for improved outcomes. Areas for further investigation are specific and measurable impacts on health, usability, and relevance of the model for reaching marginalized and high-risk populations., (©Maka Tsulukidze, Stuart W Grande, John A Naslund. Originally published in JMIR Formative Research (https://formative.jmir.org), 05.12.2023.)

Objectives: Purposeful SDM posits four modes of shared decision making (SDM). The use of each mode depends on the type of problem of care that is being addressed. We sought to identify how current observer-based SDM measures apply to each mode of Purposeful SDM., Methods: Four coders, working independently, evaluated 192 items pertaining to 12 observer-based SDM process measures. They classified the items into 6 themes that vary across Purposeful SDM modes and then into one of the four modes (weighing, negotiating, problem-solving, developing insight). Disagreements were resolved by consensus., Results: The items were classified as pertaining to the following themes: problem (28), roles/participation (84), options (62), preferences (21), decision (15), and evaluation (6). They were then classified as pertaining particularly to the SDM modes of weighing (54), negotiating (5), problem-solving (0), and developing insight (0) modes, with 191 items applying broadly to all modes of Purposeful SDM., Conclusions: Observer-based SDM measures describe behaviors pertinent to all modes but lack items sensitive to behaviors particular to some modes of SDM., Practice Implications: New or revised observer-based measures of the SDM process could help estimate the extent to which the appropriate SDM mode is being used to address the patient's problem., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mobile Health (mHealth) interventions have received a mix of praise and excitement, as well as caution and even opposition over recent decades. While the rapid adoption of mHealth solutions due to the COVID-19 pandemic has weakened resistance to integrating these digital approaches into practice and generated renewed interest, the increased reliance on mHealth signals a need for optimizing development and implementation. Despite an historically innovation-resistant medical ethos, mHealth is becoming a normalized supplement to clinical practice, highlighting increased demand. Reaching the full potential of mHealth requires new thinking and investment. The current challenge to broaden mHealth adoption and to ensure equity in access may be overcoming a "design purgatory," where innovation fails to connect to practice. We recommend leveraging the opportunity presented by the COVID-19 pandemic to disrupt routine practice and with a new focus on theory-driven replicability of mHealth tools and strategies aimed at medical education and professional organizations.

Objectives: The incidence of surgical bailout during transcatheter aortic valve replacement (TAVR) is ∼1%, with an associated 50% in-hospital mortality. We performed an exploratory qualitative study of TAVR team perceptions regarding routine surgical bailout planning with patients., Methods: We developed a semistructed interview guide to explore clinician perspectives on the TAVR consent process, managing intraoperative emergencies, and involving patients in surgical contingency planning. We interviewed surgeons, cardiologists, and anesthesiologists involved with TAVR in 4 hospitals. We performed qualitative thematic analysis via independent coding of salient quotations from the transcribed texts. Codes were categorized based on shared meaning and the final themes were derived by identifying key content, and examining its relational nature., Results: Thirteen interviews were conducted, identifying 4 major themes. Participants agreed that eliciting patient preference for bailout is crucial, particularly when surgical outcome is ambiguous. In those cases, participants offered criteria for determining which patients should be engaged in a more nuanced discussion. The ethos of specialty clinicians impacted anticipation and response to procedural emergencies. Finally, physician attitudes reflected strong emotional responses to patient death/morbidity, particularly in iatrogenic injury. Participants expressed anxiety with performing TAVR without surgical backup, while also demonstrating willingness to respect patients' wishes., Conclusions: The TAVR team supports engaging patients regarding potential surgical bailout and honoring their preferences in the event of complication. However, clinical judgment about the expected outcome of bailout would frame that discussion. Participants described the emotional weight of not pursuing bailout if indicated and the importance of good coping mechanisms., (© 2022 The Author(s).)

Following COVID-19, the CDC asked individuals to social distance and state and local authorities nationwide began issuing curfews and recommendations to "shelter-in-place." Known to be more susceptible to the negative effects of COVID-19 and often coping with higher levels of social isolation, many worried that older adults' mental health would suffer. While computer-mediated communication (CMC) is on the rise among older adults, whether and how older adults leverage the social benefits of CMC remains underexplored. This study assesses older adults' CMC use after COVID and the impact of CMC engagement on access to connection, information, and resources. We follow 22 older adults over 6 weeks, using longitudinal qualitative surveys to study CMC use patterns and mental health outcomes. Results revealed that while older adults exhibited purpose-driven CMC engagement, limited integration into larger online communities restricted access to up-to-the-minute information, notably early in the pandemic. Longitudinal findings show progressively less engagement with online news and information, withdrawal from online social engagement, and a progressive relaxing of social distancing. This study sheds light on how best to reach older adults following disaster, and where older adults may be disadvantaged as social media becomes a modern "emergency broadcast system.", Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

In the wake of COVID-19 social distancing recommendations, social media assumed a central - if unofficial - role in ensuring that individuals remained informed and connected throughout the pandemic. Yet while research shows that social media can be an effective platform for connecting individuals socially and fostering social support exchanges, both the platforms and the support exchanged therein have been mired in considerable controversies regarding their use as a tool for positive social engagement. The goal of this study is to qualitatively evaluate longitudinal changes to social media engagement during social distancing recommendations and orders to shelter-in-place. To do this, we collected longitudinal, qualitative survey data from a group of adults over the eight weeks during which most states had issued orders to shelter-in-place. We analyze data for evidence of social connection, stress reduction, and support exchange, and evaluate the impact of online social ties on staying informed and on compliance with CDC recommendations and shelter-in-place orders. Results showed a clear longitudinal evolution of users' online social engagement. Early use was characterized by agentic purposeful engagement, information sharing, and community resource mobilization. However, over time these patterns gave way to more passive use characterized by listlessness, contentiousness and misinformation as the pandemic wore on in weeks. As social media comes to occupy an increasingly important role in the exchange of information (and misinformation) this study has important implications for the health of users and the role of social media in future disasters, including how social media impacts both stress and health related behaviors., (© 2021 The Authors.)

Transitions in breast cancer care are associated with significant increases in stress and anxiety, and this stress can negatively impact mental and physical health. Social support has been shown to alleviate such distress, but whether, how, and how often social support is accessed through existing support networks is unclear. Our study examines changes in social media use following breast cancer diagnosis and treatment, using hand-coded longitudinal data from 30 breast cancer survivors' Facebook pages for the 6 months surrounding cancer diagnosis and for the 6 months surrounding transition off cancer therapy. Results revealed that following diagnosis, there was a significant increase in posting behavior and self-disclosure. However, this increase in posts did not correspond to an increase in support requests. In addition, while participants' primary support requests were for resources, support provided tended to be lower-cost emotional support. Finally, temporal maps indicated that participants started off increasing their engagement but withdrew over time. Our findings suggest that Facebook offered participants a platform for continued social engagement and self-disclosure - but showed several indications that support was principally low-effort, limited quality, and ill-fitting.

Background: Eswatini (formerly Swaziland) has one of the highest rates of TB and HIV co-disease in the world. Despite national efforts to improve service delivery and prevent TB and HIV transmission, rates remain high. A recent prospective, observational study of integrated, patient-selected IPT delivery showed extraordinary improvements in IPT adherence, running counter to previous assumptions. This prompted the need to understand contextual and unseen study factors that contributed to high rates of adherence., Objective: To investigate high rates of IPT adherence rates among people living with HIV who participated in an observational study comparing modes of IPT delivery., Methods: Community-based participatory research guided the development of in-person administration of semi-structured questionnaires. Observational and field note data were analyzed. Qualitative data were analyzed using content analysis., Results: We interviewed 150 participants and analyzed responses from the 136 who remembered being given a choice of their IPT delivery method. Fifty-seven percent were female and the median age was 42. Nearly 67% of participants chose to receive facility-based IPT. High rates of self-reported IPT treatment adherence were linked to four key concepts: 1) adherence was positively impacted by community education; 2) disclosure of status served to empower participant completion; 3) mode of delivery perceptions positively impacted adherence; and 4) choice of treatment delivery seen as helpful but not essential for treatment completion., Discussion: Achieving higher rates of IPT adherence in Eswatini and similar rural areas requires community-engaged education and outreach in coordination with care delivery systems., Competing Interests: This work was undertaken within the resources available to the authors via their institutions. The authors declare no financial or other conflicts of interest. Support for this work was provided by the TB CARE II project, which is funded by the United States Agency for International Development (USAID) under Cooperative Agreement Number AID-OAA-A-10-00021. The project’s prime recipient is the University Research Co, LLC (URC), Chevy Chase, MD, USA, and the Geisel School of Medicine at the Dartmouth Section of Infectious Disease and International Health, Hanover, NH, USA, is a sub-recipient. Any affiliation with home institutions does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors declare no financial or other conflicts of interest.

Importance: Shared decision-making (SDM) is widely advocated for patients with valvular heart disease yet is not integrated into the heart team model for patients with symptomatic aortic stenosis. Decision aids (DAs) have been shown to improve patient-centered outcomes and may facilitate SDM., Objective: To determine whether the repeated use of a DA by heart teams is associated with greater SDM, along with improved patient-centered outcomes and clinician attitudes about DAs., Design, Setting, and Participants: This mixed-methods study included a nonrandomized pre-post intervention and clinician interviews. It was conducted between April 30, 2015, and December 7, 2017, with quantitative analysis performed between January 12, 2017, and May 26, 2017, within 2 academic medical centers in northern New England among 35 patients with symptomatic aortic stenosis who were at high to prohibitive risk for surgery. The qualitative analysis was performed between August 6, 2018, and May 7, 2019. The Severe Aortic Stenosis Decision Aid was delivered by 6 clinicians, with patients choosing between transcatheter aortic valve replacement and medical management., Main Outcomes and Measures: Clinician SDM performance was measured using the Observer OPTION5 scale with dual-independent coding of audiotaped clinic visits. Previsit and postvisit surveys measured the patient's knowledge, satisfaction, and decisional conflict. Audiotaped clinician interviews were coded, and qualitative thematic analysis was performed., Results: Six male clinicians and 35 patients (19 of 34 women [55.9%; 1 survey was missing]; mean [SD] age, 85.8 [7.8] years) participated in the study. Shared decision-making increased stepwise with repeated use of the DA (mean [SD] Observer OPTION5 scores: usual care, 17.9 [7.6]; first use of a DA, 60.5 [30.9]; fifth use of a DA, 79.0 [8.4]; P < .001 for comparison between usual care and fifth use of DA). Multiple uses of the DA were associated with increased patient knowledge (mean difference, 18.0%; 95% CI, 1.2%-34.8%; P = .04) and satisfaction (mean difference, 6.7%; 95% CI, 2.5%-10.8%; P = .01) but not decisional conflict (mean [SD]: usual care, 96.0% [9.4%]; first use of DA, 93.8% [12.5%]; fifth use of DA, 95.0% [11.2%]; P = .60). Qualitative analysis of clinicians' interviews revealed that clinicians perceived that they used an SDM approach without DAs and that the DA was not well understood by elderly patients. There was infrequent values clarification or discussion of stroke risk., Conclusion and Relevance: In a mixed-methods pilot study, use of a DA for severe aortic stenosis by heart team clinicians was associated with improved SDM and patient-centered outcomes. However, in qualitative interviews, heart team clinicians did not perceive a significant benefit of the DA, and therefore sustained implementation is unlikely. This pilot study of SDM clarifies new research directions for heart teams.

Setting: Five human immunodeficiency virus (HIV) care facilities in Eswatini., Objective: To identify critical factors that enabled persons living with HIV to successfully complete a 6-month course of isoniazid preventive therapy (IPT) provided through a choice of facility-based or community-based delivery, coordinated with antiretroviral therapy (ART) refills., Design: This was a mixed methods, retrospective cross-sectional study., Results: Between June and October 2017, we interviewed 150 participants who had completed IPT in the previous year. Fourteen participants did not recall being offered a choice, and were excluded from the analysis. Of the remaining 136, 56.6% were female and 64.7% chose facility-based care; the median age was 42.5 years. Most participants reported that having a choice was important to their treatment completion (87.7%) and that linking IPT and ART refills facilitated undergoing IPT (98.5%). Participants were knowledgeable about the benefits of IPT and valued the education received from their providers. Participants also reported a high rate of IPT disclosure (95%) to friends and family members., Conclusion: Offering patients a choice of IPT delivery, linking IPT with ART refills, emphasizing patient education and engagement with healthcare workers, and supporting disclosure of IPT are critical factors to enabling IPT completion. These interventions should be incorporated throughout Eswatini and in similar high tuberculosis and HIV burden settings., Competing Interests: Conflicts of interest: none declared., (© 2019 The Union.)

Background: Social media has emerged as the epicenter for exchanging health-related information, resources, and emotional support. However, despite recognized benefits of social media for advancing health-promoting support exchange, researchers have struggled to differentiate between the different ways social support occurs and is expressed through social media., Objective: The objective of this study was to develop a fuller understanding of social support exchange by examining the ways in which breast cancer patients discuss their health needs and reach out for support on Facebook and to develop a coding schema that can be useful to other social media researchers., Methods: We conducted a retrospective qualitative assessment of text-based social support exchanges through Facebook among 30 breast cancer survivors. Facebook wall data were systematically scraped, organized, coded, and characterized by whether and which types of support were exchanged. Research questions focused on how often participants posted related to cancer, how often cancer patients reached out for support, and the relative frequency of informational, instrumental, or socioemotional support requests broadcast by patients on the site., Results: A novel ground-up coding schema applied to unwieldy Facebook data successfully identified social support exchange in two critical transitions in cancer treatment: diagnosis and transition off cancer therapy. Explanatory coding, design, and analysis processes led to a novel coding schema informed by 100,000 lines of data, an a priori literature review, and observed online social support exchanges. A final coding schema permits a compelling analysis of support exchange as a type of peer community, where members act proactively to buffer stress effects associated with negative health experiences. The coding schema framed operational definitions of what support meant and the forms each type of support could take in social media spaces., Conclusions: Given the importance of social media in social interaction, support exchange, and health promotion, our findings provide insight and clarity for researchers into the different forms informational, resource, and emotional support may take in Web-based social environments. Findings support broader continuity for evaluating computer-mediated support exchange., (©Jude P W Mikal, Stuart W Grande, Michael J Beckstrand. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.10.2019.)

There is a rapid evolution of care delivery taking place across the globe in response to an explosion of novel health technologies. Growing in parallel to this expansion is the anticipation of mHealth technologies to drive patient-centered care into the future. Despite this hope, continuing reports of health inequities and lived experiences of substandard care fill national, state, and community health reports. The impact of these inequities is particularly pernicious on Black men and their long-term health status. As decades of robust evidence substantiates needed interventions, current progress is not seeing expected gains. In this commentary, we argue that at the heart of these inequities are issues of access, health literacy, institutional racism, and growing social distance between clinicians and Black men. To address these inequities, we suggest that digital interventions, designed to support decision-making, information exchange, and shared accountability have the best hope to overcome current inequities by promoting authentic relationships that ultimately drive better communication between Black men and their clinicians., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Atrial fibrillation (AF) is a common arrhythmia that increases patients' risk of stroke, and determining an optimal prevention therapy is a preference-sensitive decision appropriate for shared decision making (SDM). Utilizing community-based focus groups, we explored beliefs and values around options for stroke prevention. Interview transcripts from five independent focus groups were qualitatively assessed and organized into themes. Most participants were taking a blood thinner (93%) and more than half of participants (64%) reported having AF. Few participants were familiar with newer therapies. Qualitative analysis revealed three themes: (a) fearing loss of self-control through debilitating stroke, (b) recognizing uncertainty in how to weigh risks and benefits of new treatments, and (c) needing mutual respect between clinicians and patients to consider new/alternative treatment regimens. These findings help direct future research efforts examining optimal timing for SDM and decision aids to promote mutual respect.

Background: Young people living with juvenile idiopathic arthritis (JIA) face a number of communication barriers for achieving optimal health as they transition from pediatric care into adult care. Despite growing interest in mobile or wireless technologies to support health (mHealth), it is uncertain how these engagement tools might support young people, their families, and care teams to optimize preference-based treatment strategies., Objective: This study aims to examine how an mHealth patient support system (mPSS) might foster partnership between young people living with JIA, their families, and care teams., Methods: Semistructured interviews with young people (5-15 years old), their families, and JIA care teams were conducted using researcher-developed interviews guides. Transcribed data were qualitatively analyzed using conventional content analysis., Results: We conducted semistructured interviews with 15 young people, their parents, and 4 care team members. Content analysis revealed the potential of an mPSS to support productive dialogue between families and care teams. We identified four main themes: (1) young people with JIA face communication challenges, (2) normalizing illness through shared experience may improve adherence, (3) partnership opens windows into illness experiences, and (4) readiness to engage appears critical for clinic implementation., Conclusions: A human-centered mPSS design that offers JIA patients the ability to track personally relevant illness concerns and needs can enhance communication, generate consensus-based treatment decisions, and improve efficiency and personalization of care. Technology that supports continuous learning and promotes better understanding of disease management may reduce practice burden while increasing patient engagement and autonomy in fostering lasting treatment decisions and ultimately supporting personalized care and improving outcomes., (©Stuart W Grande, Meghan R Longacre, Karin Palmblad, Meera V Montan, Rikard P Berquist, Andreas Hager, Greg Kotzbauer. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 22.02.2019.)

Health disparities associated with chronic illness experiences of black men demonstrate widespread, systematic failures to meet an urgent need. Well-established social and behavioral determinants that have led to health disparities among black men include racism, discrimination, and stress. While advocacy work that includes community-engagement and tailoring health promotion strategies have shown local impact, evidence shows the gaps are increasing. We suspect that failure to reduce current disparities may be due to conventional public health interventions and programs; therefore, we submit that innovative interventions, ones that embrace digital technologies and their ability to harness naturally occurring social networks within groups, like black men, have particular importance and deserve attention. This commentary characterizes the current literature on chronic illness among black men as well as health interventions that use digital technology, to build a case for expanding research in this area to reduce the overwhelming burden of chronic illness among black men., (©Stuart W Grande, Ledric D Sherman. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.05.2018.)

Background: Atrial fibrillation is a common irregular heart rhythm that increases patients' risk of stroke. Aspirin, warfarin, direct oral anticoagulants, and an implantable device can reduce this risk. Given the availability of multiple comparable options, this decision depends on patient preferences and is appropriate for the use of decision aids and other efforts to promote shared decision making. The objective of this review was to examine the existence and accessibility of, as well as select outcomes associated with, published, formally evaluated patient decision aids for stroke prevention in atrial fibrillation., Methods: Six databases were searched from inception to March 2016 with a research librarian. Two authors independently reviewed potential articles, selected trials meeting inclusion criteria, and assessed outcome measures. Outcomes included patient knowledge, involvement, choice, and decisional conflict., Results: The search resulted in 666 articles; most were excluded for not examining stroke prevention in atrial fibrillation and 7 studies were eventually included. Six decision aids displayed combinations of aspirin, warfarin, or no therapy; 1 included a direct oral anticoagulant. Interventions were associated with increased patient knowledge, increased likelihood of making a choice, and low decisional conflict. Use of decision aids in this review was associated with less selection of warfarin. None of the tested decision aids are currently available., Discussion: Published patient decision aids for stroke prevention in atrial fibrillation are not accessible for clinical use. Given the availability of multiple comparable options, there is a need to develop and test new patient decision aids in this context., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Are the benefits of recording clinical encounters shared across different groups, or do they vary based on social position? Studies show that educated patients record their clinical visits to enhance their experience, but very little is known about recording benefits among "hard-to-reach" populations., Objective: To examine the reactions of homeless people to the idea of using a smartphone to record their own clinical encounter, either covertly or with permission from their physician., Method: We conducted semi-structured interviews with individuals at a temporary housing shelter in Northern New England. A thematic analysis identified themes that were iteratively refined into representative groups., Results: Eighteen (18) interviews were conducted, 12 with women and six with men. Initial reactions to clinical recordings were positive (11 of 18). A majority (17 of 18) were willing to use recordings in future visits. A thematic analysis characterized data in two ways: (i) by providing reliable evidence for review, they functioned as an advocacy measure for patients; (ii) by promoting transparency and levelling social distance, this technology modified clinical relationships., Discussion: Recordings permitted the sharing of data with others, providing tangible proof of behaviour and refuting misconceptions. Asking permission to record appeared to modify relationships and level perceived social distance with clinicians., Conclusions: We found that while many rural, disadvantaged individuals felt marginalized by the wide social distance between themselves and their clinicians, recording technology may serve as an advocate by holding both patients and doctors accountable and by permitting the burden of clinical proof to be shared., (© 2016 The Authors Health Expectations Published by John Wiley & Sons Ltd.)

Objective: Describe cardiovascular clinicians' perceptions of Shared Decision Making following use of a decision aid (DA) for stable coronary artery disease (CAD) "PCI Choice", in a randomized controlled trial., Methods: We conducted a semi-structured qualitative interview study with cardiologists and physician extenders (n=13) after using PCI Choice in practice. Interviews were transcribed then coded. Codes were organized into salient themes. Final themes were determined by consensus with all authors., Results: Most clinicians (70%) had no prior knowledge of SDM or DAs. Mixed views about the role of the DA in the visit were related to misconceptions of how patient education differed from SDM. Qualitative assessment of clinician perceptions generated three themes: 1) Gaps exist in clinician knowledge around SDM; 2) Clinicians are often uncomfortable with modifying baseline practice; and 3) Clinicians express interest in using DAs after initial exposure within a research setting., Conclusions: Use of DAs by clinicians during clinic visits may improve understanding of SDM. Initial use is marked by a reluctance to modify established practice patterns., Practice Implications: As clinicians explore new approaches to benefit their patients, there is an opportunity for DAs that provide clinician instruction on core elements of SDM to lead to enhanced SDM in clinical practice., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Setting: South African miners suffer the highest tuberculosis (TB) rates in the world. Current efforts to stem the epidemic are insufficient. Historical legacies and persistent disease burden demand innovative approaches to reshape health care delivery to better serve this population., Objective: To characterize social and behavioral health determinants for successful TB care delivery and treatment from the perspective of miners/ex-miners, health care workers and policy makers/managers., Design: We conducted applied ethnography with 30 miners/ex-miners, 13 family/community members, 14 health care providers, and 47 local policy makers/managers in South Africa., Results: Miners/ex-miners felt health care delivery systems failed to meet their needs. Many had experienced unnecessary physical and psychological harm due to limited health education about TB, minimal engagement in their own care, lack of trust in providers, and a system that did not value their experience. Stigma and fear associated with TB result in denial of symptoms and delays in care seeking. Health care providers and policy makers/managers felt discouraged by system constraints in providing optimal care., Conclusion: Our findings describe long-term effects of perpetual TB misinformation and stigma resulting from fear and disempowerment among miners and their families/communities. To reduce the TB burden, there is an urgent need to co-design a care delivery system with miners to better meet their needs.

Objectives: OPTION(12) is the most widely used tool to measure shared decision-making (SDM) in health care. A newer scale, OPTION(5), has been proposed as a more parsimonious measure that better addresses core concepts of SDM. This study compares OPTION(5) to OPTION(12) in prenatal genetic counselling., Methods: Two raters independently used OPTION(12) and OPTION(5) to score 27 clinical encounters between genetic counsellors (GC) and women with pregnancies at increased risk for genetic conditions. Global and item scores on the two instruments were compared to test concurrent validity and to identify usability in this context. Inter-rater reliability was also assessed for both instruments., Results: Mean scores for OPTION(12) were 43.8 (SD=9.7), and for OPTION(5) were=60.6 (SD=12.5). The correlation between OPTION(12) and OPTION(5) scores was r=0.70. Inter-rater reliability was 0.70 and 0.85 for OPTION(12) and OPTION(5) respectively, however mean inter-rater reliability for individual items was 0.31 and 0.63 for OPTION(12) and OPTION(5) respectively., Conclusions: GCs exhibit SDM as measured by both OPTION instruments. OPTION(5) exhibits improved psychometric performance relative to OPTION(12), and more specifically targets the core constructs of SDM. However, refinement of OPTION instruments or manuals is needed to improve reliability and validity in GC assessment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer., Design: Community-based participatory research (CBPR) using think-aloud protocols (phases 1 and 2) and semistructured interviews (phase 3)., Setting: Underserved community settings (eg, knitting groups, bingo halls, senior centres) and breast clinics., Participants: In phase 1, we recruited a convenience sample of clinicians and academics. In phase 2, we targeted women over 40 years of age, of low SES, regardless of breast cancer history, and in phase 3, women of low SES, recently diagnosed with breast cancer., Intervention: The pictorial encounter decision aid was derived from an evidence-based table comparing treatment options for breast cancer (http://www.optiongrid.org)., Outcome Measures: We assessed the usability, acceptability and accessibility of the pictorial decision aid prototypes using the think-aloud protocol and semistructured interviews., Results: After initial testing of the first prototype with 18 academics and health professionals, new versions were developed and tested with 53 lay individuals in community settings. Usability was high. In response to feedback indicating that the use of cartoon characters was considered insensitive, a picture-only version was developed and tested with 23 lay people in phase 2, and 10 target users in phase 3., Conclusions and Relevance: Using CBPR methods and iterative user testing cycles improved usability and accessibility, and led to the development of the Picture Option Grid, entirely guided by multiple stakeholder feedback. All women of low SES recently diagnosed with early stage breast cancer found the Picture Option Grid usable, acceptable and accessible., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: To assess the impact, acceptability and feasibility of a short encounter tool designed to enhance the process of shared decision-making and parental engagement., Methods: We analyzed video-recordings of clinical encounters, half undertaken before and half after a brief intervention that trained four clinicians how to use Option Grids, using an observer-based measure of shared decision-making. We also analyzed semi-structured interviews conducted with the clinicians four weeks after their exposure to the intervention., Results: Observer OPTION(5) scores were higher at post-intervention, with a mean of 33.9 (SD=23.5) compared to a mean of 16.1 (SD=7.1) for pre-intervention, a significant difference of 17.8 (95% CI: 2.4, 33.2). Prior to using the intervention, clinicians used a consent document to frame circumcision as a default practice. Encounters with the Option Grid conferred agency to both parents and clinicians, and facilitated shared decision-making. Clinician reported recognizing the tool's positive effect on their communication process., Conclusions: Tools such as Option Grids have the potential to make it easier for clinicians to achieve shared decision-making., Practice Implications: Encounter tools have the potential to change practice. More research is needed to test their feasibility in routine practice., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To examine the motivations of patients recording clinical encounters, covertly or otherwise, and why some do not wish to record encounters., Design: Mixed-methods analysis of survey data and nested semistructured interviews., Setting: Survey to UK audience, using social media and radio broadcast., Participants: 168 survey respondents, of whom 161 were 18 years of age or older (130 completions). Of the 56 participants who agreed to be contacted, we included data from 17 interviews., Results: 19 (15%) respondents indicated having secretly recorded a clinical encounter and 14 (11%) were aware of someone who had secretly recorded a clinical encounter. 45 (35%) said they would consider recording secretly and 44 (34%) said they would record after asking permission. Totally, 69% of respondents indicated their desire to record clinical encounters, split equally between wanting to do so covertly or with permission. Thematic analysis of the interviews showed that most patients are motivated by the wish to replay, relisten and share the recording with others. Some are also motivated by the idea of owning a personal record, and its potential use as verification of a poor healthcare experience. The rationale for permission seeking was based on the wish to prioritise a trusting relationship with a health professional. Those who preferred to record covertly described a pre-existing lack of trust, a fear that recording would be denied, and a concern that an affronted clinician would deny them access to future care. There was a general wish that recording should be facilitated., Conclusions: Patients' prime motivation for recording is to enhance their experience of care, and to share it with others. Patients know that recording challenges the 'ceremonial order of the clinic', and so some decide to act covertly. Patients wanted clearer, more permissive policies to be developed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To assess the feasibility of Option Grids(®)for facilitating shared decision making (SDM) in simulated clinical consultations and explore clinicians' views on their practicability., Methods: We used mixed methods approach to analyze clinical consultations using the Observer OPTION instrument and thematic analysis for follow-up interviews with clinicians., Results: Clinicians achieved high scores on information sharing and low scores on preference elicitation and integration. Four themes were identified: (1) Barriers affect practicability of Option Grids(®); (2) Option Grids(®) facilitate the SDM process; (3) Clinicians are aware of the gaps in their practice of SDM; (4) Training and ongoing feedback on the optimal use of Option Grids(®) are necessary., Conclusion: Use of Option Grids(®) by clinicians with background knowledge in SDM did not facilitate optimal levels of competency on the SDM core concepts of preference elicitation and integration. Future research must evaluate the impact of training on the use of Option Grids(®), and explore how best to help clinicians bridge the gap between knowledge and action., Practice Implications: Clinicians proficiently imparting information in simulations struggled to elicit and integrate patient preferences - understanding this gap and developing strategies to close it are the next steps for implementing SDM into clinical practice., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The phenomenon of patients covertly recording clinical encounters has generated controversial media reports. This study aims to examine the phenomenon and analyze the underlying issues., Methods and Findings: We conducted a qualitative analysis of online posts, articles, blogs, and forums (texts) discussing patients covertly recording clinical encounters. Using Google and Google Blog search engines, we identified and analyzed 62 eligible texts published in multiple countries between 2006 and 2013. Thematic analysis revealed four key themes: 1) a new behavior that elicits strong reactions, both positive and negative, 2) an erosion of trust, 3) shifting patient-clinician roles and relationships, and 4) the existence of confused and conflicting responses. When patients covertly record clinical encounters - a behavior made possible by various digital recording technologies - strong reactions are evoked among a range of stakeholders. The behavior represents one consequence of an erosion of trust between patients and clinicians, and when discovered, leads to further deterioration of trust. Confused and conflicting responses to the phenomenon by patients and clinicians highlight the need for policy guidance., Conclusions: This study describes strong reactions, both positive and negative, to the phenomenon of patients covertly recording clinical encounters. The availability of smartphones capable of digital recording, and shifting attitudes to patient-clinician relationships, seems to have led to this behavior, mostly viewed as a threat by clinicians but as a welcome and helpful innovation by some patients, possibly indicating a perception of subordination and a lack of empowerment. Further examination of this tension and its implications is needed.

Background: Efforts have been made to measure integration in health care delivery, but few existing instruments have adopted a patient perspective, and none is sufficiently generic and brief for administration at scale. We sought to develop a brief and generic patient-reported measure of integration in health care delivery., Methods: Drawing on both existing conceptualisations of integrated care and research on patients' perspectives, we chose to focus on four distinct domains of integration: information sharing, consistent advice, mutual respect and role clarity. We formulated candidate items and conducted cognitive interviews with end users to further develop and refine the items. We then pilot-tested the measure., Results: Four rounds of cognitive interviews were conducted (n = 14) and resulted in a four-item measure that was both relevant and understandable to end users. The pilot administration of the measure (n = 15) further confirmed the relevance and interpretability of items and demonstrated that the measure could be completed in less than one minute., Conclusions: This new measure, IntegRATE, represents a patient-reported measure of integration in health care delivery that is conducive to use in both routine performance monitoring and research. The psychometric properties of the measure will be assessed in the next stage of development.

Objective: Existing theoretical work in decision making and behavior change has focused on how individuals arrive at decisions or form intentions. Less attention has been given to theorizing the requirements that might be necessary for individuals to work collaboratively to address difficult decisions, consider new alternatives, or change behaviors. The goal of this work was to develop, as a forerunner to a middle range theory, a conceptual model that considers the process of supporting patients to consider alternative health care options, in collaboration with clinicians, and others., Methods: Theory building among researchers with experience and expertise in clinician-patient communication, using an iterative cycle of discussions., Results: We developed a model composed of five inter-related propositions that serve as a foundation for clinical communication processes that honor the ethical principles of respecting individual agency, autonomy, and an empathic approach to practice. We named the model 'collaborative deliberation.' The propositions describe: (1) constructive interpersonal engagement, (2) recognition of alternative actions, (3) comparative learning, (4) preference construction and elicitation, and (5) preference integration., Conclusions: We believe the model underpins multiple suggested approaches to clinical practice that take the form of patient centered care, motivational interviewing, goal setting, action planning, and shared decision making., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Increasingly, people with diverse health conditions turn to social media to share their illness experiences or seek advice from others with similar health concerns. This unstructured medium may represent a platform on which individuals with severe mental illness naturally provide and receive peer support. Peer support includes a system of mutual giving and receiving where individuals with severe mental illness can offer hope, companionship, and encouragement to others facing similar challenges. In this study we explore the phenomenon of individuals with severe mental illness uploading videos to YouTube, and posting and responding to comments as a form of naturally occurring peer support. We also consider the potential risks and benefits of self-disclosure and interacting with others on YouTube. To address these questions, we used qualitative inquiry informed by emerging techniques in online ethnography. We analyzed n = 3,044 comments posted to 19 videos uploaded by individuals who self-identified as having schizophrenia, schizoaffective disorder, or bipolar disorder. We found peer support across four themes: minimizing a sense of isolation and providing hope; finding support through peer exchange and reciprocity; sharing strategies for coping with day-to-day challenges of severe mental illness; and learning from shared experiences of medication use and seeking mental health care. These broad themes are consistent with accepted notions of peer support in severe mental illness as a voluntary process aimed at inclusion and mutual advancement through shared experience and developing a sense of community. Our data suggest that the lack of anonymity and associated risks of being identified as an individual with severe mental illness on YouTube seem to be overlooked by those who posted comments or uploaded videos. Whether or not this platform can provide benefits for a wider community of individuals with severe mental illness remains uncertain.

Objective: Examine existing reviews of patient engagement methods to propose a model where the focus is on engaging patients in clinical workflows, and to assess the feasibility of advocated patient engagement methods., Methods: A literature search of reviews of patient engagement methods was conducted. Included reviews were peer-reviewed, written in English, and focused on methods that targeted patients or patient-provider dyads. Methods were categorized to propose a conceptual model. The feasibility of methods was assessed using an adapted rating system., Results: We observed that we could categorize patient engagement methods based on information provision, patient activation, and patient-provider collaboration. Methods could be divided by high and low feasibility, predicated on the extent of extra work required by the patient or clinical system. Methods that have good fit with existing workflows and that require proportional amounts of work by patients are likely to be the most feasible., Conclusion: Implementation of patient engagement methods is likely to depend on finding a "sweet-spot" where demands required by patients generate improved knowledge and motivate active participation., Practice Implications: Attention should be given to those interventions and methods that advocate feasibility with patients, providers, and organizational workflows., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Patient-centered health care is a central component of current health policy agendas. Shared decision making (SDM) is considered to be the pinnacle of patient engagement and methods to promote this are becoming commonplace. However, the measurement of SDM continues to prove challenging. Reviews have highlighted the need for a patient-reported measure of SDM that is practical, valid, and reliable to assist implementation efforts. In consultation with patients, we developed CollaboRATE, a 3-item measure of the SDM process., Objective: There is a need for scalable patient-reported measure of the SDM process. In the current project, we assessed the psychometric properties of CollaboRATE., Methods: A representative sample of the US population were recruited online and were randomly allocated to view 1 of 6 simulated doctor-patient encounters in January 2013. Three dimensions of SDM were manipulated in the encounters: (1) explanation of the health issue, (2) elicitation of patient preferences, and (3) integration of patient preferences. Participants then completed CollaboRATE (possible scores 0-100) in addition to 2 other patient-reported measures of SDM: the 9-item Shared Decision Decision Making Questionnaire (SDM-Q-9) and the Doctor Facilitation subscale of the Patient's Perceived Involvement in Care Scale (PICS). A subsample of participants was resurveyed between 7 and 14 days after the initial survey. We assessed CollaboRATE's discriminative, concurrent, and divergent validity, intrarater reliability, and sensitivity to change., Results: The final sample consisted of 1341 participants. CollaboRATE demonstrated discriminative validity, with a significant increase in CollaboRATE score as the number of core dimensions of SDM increased from zero (mean score: 46.0, 95% CI 42.4-49.6) to 3 (mean score 85.8, 95% CI 83.2-88.4). CollaboRATE also demonstrated concurrent validity with other measures of SDM, excellent intrarater reliability, and sensitivity to change; however, divergent validity was not demonstrated., Conclusions: The fast and frugal nature of CollaboRATE lends itself to routine clinical use. Further assessment of CollaboRATE in real-world settings is required., Competing Interests: Glyn Elwyn has received funding from the Informed Medical Decisions Foundation, Boston, MA, USA, and provides ad hoc consulting to Emmi Solutions. No other authors have conflicts of interests to report.

Although support among policy makers and academics for the wide scale adoption of shared decision making (SDM) is growing, actual implementation is slow, and faces many challenges. Extensive systemic barriers exist that prevent physicians from being able to champion SDM and lead practice change. In other areas of public health where implementation has been a challenge, community-based participatory research (CBPR) has effectively engaged resistant stakeholders to improve practice and the delivery of care. Might CBPR, defined broadly as research that engages participants in the conception, design, and implementation of relevant health programs, be a more effective way to engage physicians, patients, and managers in the implementation process? Consequently, we argue that adopting a participatory approach may help to overcome recognized barriers to progress in this area.

The objective of this research was to explore interview data to understand and characterize the nature of brotherhood in a sample of African American men at two historically Black colleges and universities. The authors used thematic analysis on semistructured interview data, collected by an ethnically diverse research team. Recruitment and interviews were conducted at two historically Black colleges and universities in Texas. Twenty African American men, 18 to 35 years old, were randomly selected from 62 recruited participants. Five categories framed brotherhood and health care utilization: (a) trust lessens individual barriers to action, (b) identity unites men through a process of authentication, (c) generations lead by example, (d) approaching life as a shared learning experience, and (e) social pressure and ridicule uphold collective action. Findings suggest that participants trust a group view, identify with the collective, and respond to social pressure to conform; therefore, brotherhood acts as a support mechanism, and its validation influences individual-level engagement and nonengagement.

Objective: Measuring the process of shared decision making is a challenge, which constitutes a barrier to research and implementation. The aim of the study was to report the development of CollaboRATE, brief patient-reported measure of shared decision making., Methods: We used the following stages: (1) item formulation; (2) cognitive interviews; (3) item refinement; and (4) pilot testing of final items. Participants were over 18 years old, recruited from the public areas of the Dartmouth-Hitchcock Medical Center., Results: The key finding of this study is that developing a brief patient-reported measure of shared decision making requires a move away from terms such as 'decisions', 'options' and 'preferences'. Although technically correct, these terms act as barriers. They are often unfamiliar, and they also implicitly assume that patients are willing to take active roles in decision making; whereas patients are often unaware that decisions are required, or have taken place, never mind feel that they could or should have participated in them., Conclusion: These methods have allowed us to develop a brief, patient-reported measure of shared decision making that is highly accessible to intended users., Practice Implications: The potential strength of the CollaboRATE will be the ability for completion in less than 30s, and across a range of routine settings., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Triphenyltin (TPT) is an organotin compound (OTC) previously widely used as an antifouling agent in paints applied in the marine environment, a fungicide, and as an agricultural pesticide. In female aquatic invertebrates, certain OTCs induce the so-called imposex, an abnormal induction of male sex characteristics. OTC-induced environmental endocrine disruption also occurs in fish and mammals and a number of in vivo and in vitro studies have argued that OTCs may act through inhibition of the aromatase enzyme. In vivo studies supporting the aromatase inhibition hypothesis in mammals are lacking. Recently, the causal relationship between inhibition of aromatase and imposex was questioned, suggesting aromatase independent mechanisms of action for this phenomenon. We conducted a comprehensive investigation to identify the most sensitive window of exposure to TPTCl and to examine the effects of pre- and postnatal exposure on postnatal development in rats. The results on brain and gonadal aromatase activity obtained from offspring of dams exposed to 2 mg TPTCl/kg bw are reported here. Female and male offspring rats were exposed to 2 mg TPTCl/kg bw/d in utero from gestation day 6 through lactation until weaning on PND 21, or from gestation day 6 until termination at adulthood. Male offspring were sacrificed from PND 58 and female offspring at first estrus after PND 58. Pre- and postnatal TPT exposure clearly affected brain and gonadal aromatase activity in a sex-dependent fashion. While brain aromatase activity was significantly increased on PND 21 and at adulthood in female offspring, male offspring exhibited a significant decrease in brain aromatase activity only at adulthood. Ovarian aromatase activity was unaffected at both time points investigated. In contrast, testicular aromatase activity was significantly increased in males on PND 21 and significantly decreased at adulthood independent from the duration of treatment. The results of the present study confirm our previously reported observations regarding sex-dependent differences in sexual development after TPT exposure with the male rat being more susceptible to disturbances through this endocrine active compound than the female. We conclude that TPT administered during the particularly vulnerable period of development can affect aromatase activity in rats., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The reproductive effects of the coadministration of di-2-(ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) were studied in both foetal and adult male rat offspring exposed in utero. Pregnant Wistar rats were treated by oral gavage from gestation day 13 to 21 with vehicle control, 150 mg DEHP/kg body weight (bw)/day, 100 mg DBP/kg bw/ or a combination of the two compounds (DEHP 150 + DBP 100 mg/kg bw/day). An additional group of dams received 500 mg DBP/kg bw/day. A significant decrease in foetal testicular testosterone levels was observed in animals exposed to 500 mg DBP/kg/day or the phthalate mixture. Similarly, histological analysis of the foetal testis revealed that the coadministration of DEHP and DBP was able to increase the diameter of seminiferous cords and induce gonocyte multinucleation at doses that individually had no significant effects on these variables. However, in the phthalate mixture group, no significant changes were observed in anogenital distance and nipple retention, variables that are used to indicate possible anti-androgenic effects. Also, the adult endpoints investigated, that included reproductive organ weights and the number of spermatids per testis, were unaffected by any treatment regimen. Overall, coadministration of DEHP and DBP in utero significantly reduced testicular testosterone levels and resulted in misshapen seminiferous cords and gonocyte multinucleation in rat foetal testis. Our results also confirm that these foetal endpoints seem to be the most sensitive markers of prenatal phthalate exposure.

Consumers are exposed to organotin compounds (OTCs) via contaminated fish and seafood due to the accumulation of these compounds in marine organisms. Certain OTCs are immunotoxic and may also have endocrine disrupting properties resulting in adverse effects on the reproductive tract in mollusks and mammals. Since effects of in utero exposure to endocrine disrupting chemicals on the reproductive system are dependent on the critical window of exposure during its development, we conducted a comprehensive study with the aim to identify the most sensitive window of exposure to TPTCl and to investigate the effects of pre- and postnatal treatment on sexual development in rats. Male and female offspring rats were exposed to 2 or 6 mg TPTCl/kg b.w. and day either in utero and during lactation (gestation day 6 until weaning on PND 21) or from gestation day 6 until termination. As previously reported, offspring in the 6 mg TPTCl dose group exhibited high perinatal mortality and therefore no further evaluation was carried out at this dose level (Grote, K., Hobler, C, Andrade, A.J.M., Wichert Grande, S., Gericke, C., Talsness, C.E., Appel, K.E., Chahoud, I., 2007. Effects of in utero and lactational exposure to triphenyltin chloride on pregnancy outcome and postnatal development in rat offspring. Toxicology 238, 177-185). In the present paper, results on postnatal development obtained from surviving offspring of dams exposed to 2mg TPTCl/kg b.w. are reported. Male offspring were sacrificed on PND 64 or 65 and female offspring at first estrus after PND 58. A clear sex difference in response to treatment was observed. Male postnatal development was severely affected with decreases in body weight gain, reproductive organ weights and testosterone concentration as well as a significant delay in the age at preputial separation. In contrast, females exhibited a precocious completion of vaginal opening while all other endpoints were unaffected. Most of these effects were already present in animals that were only exposed until weaning indicating that these effects may be irreversible and continued treatment until termination had contributed less than expected to the severity of the observed effects. The results of the present study suggest that the sensitive window for the evaluated endpoints seems to be the period of prenatal development and that male offspring rats were more susceptible to treatment.

Background: Polybrominated diphenyl ethers (PBDEs) are capable of disrupting thyroid hormone homeostasis. PBDE-47 (2,2',4,4'-tetrabromodiphenyl ether) is one of the most abundant congeners found in human breast adipose tissue and maternal milk samples., Objectives: We evaluated the effects of developmental exposure to low doses of PBDE-47 on the female reproductive system., Methods: Pregnant Wistar rats were administered vehicle (peanut oil) or PBDE-47 [140 or 700 microg/kg body weight (bw)] on gestation day (GD) 6, or 5 mg 6-n-propyl-2-thiouracil (PTU)/L in the drinking water from GD7 through postnatal day (PND) 21., Results: In female offspring sacrificed on PND38, there was a significant decrease in ovarian weight after exposure to PTU or 140 microg/kg PBDE-47. Alterations in folliculogenesis were apparent: we observed a decrease in tertiary follicles and serum estradiol concentrations in the offspring exposed to either PTU or 700 microg/kg PBDE-47. PTU exposure also resulted in a decrease in primordial follicles. On PND100, persistent effects on the thyroid glands included histologic and morphometric changes after exposure to either PTU or PBDE-47. No relevant changes in reproductive indices were observed after mating the exposed F1 females with nontreated males., Conclusions: Administration of PBDE-47 at doses relevant to human exposure led to changes in the rat female reproductive system and thyroid gland.

The organotin compound (OTC) triphenyltin (TPT) is used extensively as a herbicide, pesticide and fungicide in agriculture as well as, together with tributyltin (TBT), in marine antifouling paints. We studied the effects of in utero exposure to 2 or 6 mg triphenyltinchloride (TPTCl)/kgb.w. on pregnancy outcome and postnatal development in rat offspring. Gravid Wistar rats were treated per gavage from gestational day 6 until the end of lactation. In the 6 mg TPTCl dose group gestational mortality in dams as well as an increased incidence of anticipated and delayed parturition was observed. Furthermore, treatment resulted in a significant increase in perinatal mortality, a decrease in lactational body weight gain as well as in delayed physical maturation of offspring. Similarily, exposure to 2mg TPTCl/kgb.w. resulted in a significant increase in perinatal mortality and in delayed eye opening. Lactational body weight gain and other landmarks of physical maturation were unaffected in the low dose group. We conclude, that in utero exposure to TPTCl at the described dose levels severely affected pregnancy outcome and perinatal survival of offspring. These results were unexpected, as in two earlier studies with pubertal rats TPTCl at the same dose levels no signs of general toxicity were observed.

Di(2-ethylhexyl) phthalate (DEHP) is used in numerous consumer products, mainly imparting flexibility and durability to polyvinyl chloride (PVC) based plastics. It is a known reproductive and developmental toxicant in male rodents. However, data regarding effects of DEHP on female reproductive health are particularly sparse. We performed an extensive dose-response study following developmental exposure to DEHP and evaluated the effects on adult female reproductive function. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low doses were: 0.015, 0.045, 0.135, 0.405 and 1.215mgDEHP/kg/bw/day and the high doses were: 5, 15, 45, 135 and 405mg DEHP/kg/bw/day. At the doses tested, no effects on organ (liver, kidney, spleen, thymus, thyroid, ovary and uterus) or body weights were detected. Female offspring presented a normal pattern of estrous cyclicity with no hormonal alterations (serum estradiol and progesterone). A statistically significant increase in tertiary atretic follicles was observed at the highest dose (405mgDEHP/kg/day). Morphometric analysis indicated that uterus and vagina luminal epithelial cell height were unaffected by treatment. An increase in the number of ovarian atretic tertiary follicles was the only effect observed in adult female offspring exposed in utero and during lactation to DEHP.

The reproductive effects of in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The selected endpoints included reproductive organ weights, testicular function, hormonal status, sexual behaviour and fertility. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low-doses were 0.015, 0.045, 0.135, 0.405 and 1.215 mg DEHP/kg body weight (bw)/day, and the high-doses were 5, 15, 45, 135 and 405 mg DEHP/kg bw/day. A reduction in daily sperm production of 19-25% in relation to control was observed in animals exposed to 15, 45, 135 and 405 mg/kg/day. Quantitation of specific cell types shows that the observed effects in daily sperm production are not related to changes in the number of Sertoli cells or their capability to support early stages spermatocytes. A low incidence of cryptorchidism was observed in DEHP exposed groups with a lowest observed adverse effect level of 5mg/kg/day. Serum testosterone concentration was similar to control at most doses but was significantly increased at 0.045, 0.405 and 405 mg DEHP/kg/day. In spite of this effect, the weight of seminal vesicle with coagulating glands was significantly reduced at 405 mg/kg/day. Testis, epididymis and prostate weights were similar among groups. Fertility and sexual behaviour were not affected by DEHP treatment at any dose. Overall, our results show that in utero and lactational DEHP exposure reduces daily sperm production and has the potential to induce reproductive tract abnormalities (of which cryptorchidism seems to be the most sensitive in our rat strain) in male offspring rats. The lowest observed adverse effect levels (LOAELs) for these effects were 15 and 5 mg/kg/day, respectively. Therefore, the no observed adverse effect level (NOAEL) for this study can be set at 1.215 mg/kg/day.

Di-(2-ethylhexyl)-phthalate (DEHP) is a commonly used plasticizer which can act as an endocrine disruptor. It has been suggested that in addition to its antiandrogenic effects, DEHP may interfere with estrogen metabolism through suppression of aromatase enzyme activity. This enzyme catalyzes the conversion of testosterone to estradiol and plays a critical role in brain sexual differentiation. We investigated the effects of two wide ranges of DEHP doses on brain aromatase activity of male and female rat offspring. Wistar rat dams were treated daily with DEHP and peanut oil (control) by gavage from gestation day 6 to lactation day 21 at doses of 0.015, 0.045, 0.135, 0.405 and 1.215mgDEHP/kgbodyweight(bw)/day (low doses) and at 5, 15, 45, 135 and 405mgDEHP/kgbw/day (high doses). Aromatase activity was determined in hypothalamic/preoptic area (HPOA) brain sections from male and female pups on postnatal days (PNDs) 1 and 22. In males on PND 1, aromatase activity was inhibited at low doses and increased at high doses resulting in a non-monotonic dose-response profile which resembled a J-shaped curve. Inhibition was statistically significant at 0.135 and 0.405mgDEHP/kg/day, while increased activity was observed at 15, 45 and 405mg/kg/day. In contrast to findings on PND 1, aromatase activity at weaning (PND 22) was more affected in females than in males. An increase in aromatase activity was observed at only one dose in males (0.405mg/kg/day) while an increase in activity was observed at all doses in the females except for 0.045 and 5mgDEHP/kg/day. Overall, these results indicate that males and females respond differently to DEHP not only in regard to the age at which effects are manifested, but also in the shape of the dose-response curve. To our knowledge, this is the first study to report biological effects of DEHP at doses that overlap with the estimated exposure of the general human population.

An extensive dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) was conducted. A wide range of low and high DEHP doses were tested. Reproductive effects were evaluated on male offspring rats. Female Wistar rats were treated daily with DEHP and peanut oil by gavage from gestation day 6 to lactation day 21 at doses of 0.015, 0.045, 0.135, 0.405 and 1.215 mg DEHP/kg body weight (bw)/day (low doses) and at 5, 15, 45, 135 and 405 mg DEHP/kg bw/day (high doses). Nipple retention and reduced anogenital distance, both sensitive markers of anti-androgenic effects during development, were only seen in males exposed to the highest dose (405 mg/kg/day). Delayed preputial separation was observed in animals exposed to 15 mg DEHP/kg/day and higher doses. Histopathological examination of the testis on postnatal days (PNDs) 1 and 22 revealed changes at 135 and 405 mg DEHP/kg/day. The most prominent finding on PND 1 was the presence of bi- and multinucleated gonocytes. On PND 22 signs of reduced germ cell differentiation in seminiferous tubules of exposed animals were observed. Testis weight on PND 22 was significantly increased at 5, 15, 45 and 135 mg/kg/day, an effect that qualitatively differs from exposure to higher doses. The current results show that DEHP acts as an anti-androgen at a high dose exposure (405 mg/kg/day). However, these results also indicate that other subtle developmental effects occur at lower DEHP doses.

Phthalates are chemicals used in many industrial products (plastic toys, shampoos, soaps), and are suspected of inducing adverse effects on the male reproductive system. In the present study, we evaluated the effects of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP) on the reproductive function and sexual behavior of male offspring rats, exposed in utero and during lactation (0, 20, 100 and 500 mg/kg per day by gavage). The effects produced clearly demonstrate the ability of DEHP to disrupt the androgen-regulated development of the male reproductive tract. Absolute and relative weights of androgen-dependent tissue organs (ventral prostate and seminal vesicle) were significantly reduced at the highest dose level tested (500 mg/kg per day). Impairment of male sexual behavior (500 mg/kg per day) was also observed. Moreover, the reduction in daily sperm production and epididymal sperm counts observed after administration of the highest dose suggests an impairment of the spermatogenic processes. Most of the adverse effects reported here were observed both during puberty and during adulthood, indicating permanent effects of in utero and lactational DEHP exposure.

Triphenyltin (TPT) belongs to the group of organotin compounds which have been shown to affect reproduction in mammals. It is used as a fungicide and antifouling agent and the main source of human exposure is via food. We studied the effects of 2 or 6 mg TPT/kg bw on female sexual development using a modification of the Rodent 20-Day Thyroid/Pubertal Female Assay. Moreover, the effect of TPT before the onset of puberty was investigated. Beginning at postnatal day (PND) 23 female Wistar rats were treated per gavage until either PND 33 or the first estrus after PND 53. A delay in the completion of vaginal opening (VO) was observed in the 6 mg TPT group, while the 2mg TPT group showed advanced VO. Significantly increased ovarian weights were observed in both treatment groups. Steroid hormone levels and ovarian aromatase activity were affected after exposure to 6 mg TPT/kg bw, while treatment with 2mg TPT/kg bw resulted in minor changes of these endpoints. We conclude that peripubertal exposure to 6 mg TPT/kg bw, and to a lesser extent to 2mg TPT/kg bw, affects female sexual development.

Phthalates, a class of chemicals used as plasticizers, are economically important due to several industrial applications. Di(2-ethylhexyl)phthalate (DEHP) is the most commonly used phthalate plasticizer, and it has been described as a potent antiandrogen in males. We performed an extensive dose-response study following developmental exposure to DEHP and evaluated the effects on female reproductive development. Two wide ranges of doses that included dose levels relevant for human exposure as well as high doses typically used in toxicological studies were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 22. The low doses were 0.015, 0.045, 0.135, 0.405, and 1.215 mg DEHP/kg body weight (bw)/day, and the high doses were 5, 15, 45, 135, and 405 mg DEHP/kg bw/day. At the dose levels tested, no signs of maternal toxicity were observed. A significant delay in the age at vaginal opening (approximately 2 days) at 15 mg DEHP/kg bw/day and above, as well as a trend for a delay in the age at first estrus at 135 and 405 mg DEHP/kg bw/day (approximately 2 days), was observed. Liver enlargement (characteristic of phthalate exposure in rats) was limited to the 135- and 405-mg DEHP/kg bw/day doses. Anogenital distance and nipple development were unaffected. Based on the results of delayed pubertal onset, the no observed adverse effect level for female reproductive development may be set at 5 mg DEHP/kg bw/day.

Increasing concentrations of polybrominated flame retardants, including polybrominated diphenyl ethers (PBDEs), in breast milk cause concern about possible developmental effects in nursed babies. Because previous studies in rats have indicated effects on sex steroids and sexually dimorphic behavior after maternal exposure to polychlorinated biphenyls (PCBs), our goal in the present study was to determine if developmental exposure to 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE-99) induces similar endocrine-mediated effects. Pregnant rats were exposed to vehicle or PBDE-99 (1 or 10 mg/kg body weight, daily during gestational days 10-18). For comparison, we also included a group exposed to the technical PCB mixture Aroclor 1254 (30 mg/kg body weight, daily). PBDE exposure resulted in pronounced decreases in circulating sex steroids in male offspring at weaning and in adulthood. Female offspring were less affected. Anogenital distance was reduced in male offspring. Puberty onset was delayed in female offspring at the higher dose level, whereas a slight acceleration was detected in low-dose males. The number of primordial/primary ovarian follicles was reduced in females at the lower dose, whereas decline of secondary follicles was more pronounced at the higher dose. Sweet preference was dose-dependently increased in PBDE-exposed adult males, indicating a feminization of this sexually dimorphic behavior. Aroclor 1254 did not alter sweet preference and numbers of primordial/primary and secondary follicles but it did affect steroid concentrations in males and sexual development in both sexes. PBDE concentrations in tissues of dams and offspring were highest on gestational day 19. These results support the hypothesis that PBDEs are endocrine-active compounds and interfere with sexual development and sexually dimorphic behavior.