Racism as a public health issue in environmental health disparities and environmental justice: working toward solutions.

BACKGROUND: Environmental health research in the US has shown that racial and ethnic minorities and members of low-socioeconomic groups, are disproportionately burdened by harmful environmental exposures, in their homes, workplace, and neighborhood environments that impact their overall health and well-being. Systemic racism is a fundamental cause of these disproportionate exposures and associated health effects. To invigorate and inform current efforts on environmental justice and to raise awareness of environmental racism, the National Institute of Environmental Health Sciences (NIEHS) hosted a workshop where community leaders, academic researchers, and NIEHS staff shared perspectives and discussed ways to inform future work to address health disparities. OBJECTIVES: To share best practices learned and experienced in partnerships between academic researchers and communities that are addressing environmental racism across the US; and to outline critical needs and future actions for NIEHS, other federal agencies, and anyone who is interested in conducting or funding research that addresses environmental racism and advances health equity for all communities. DISCUSSION: Through this workshop with community leaders and researchers funded by NIEHS, we learned that partnerships between academics and communities hold great promise for addressing environmental racism; however, there are still profound obstacles. To overcome these barriers, translation of research into plain language and health-protective interventions is needed. Structural changes are also needed in current funding mechanisms and training programs across federal agencies. We also learned the importance of leveraging advances in technology to develop creative solutions that can protect public health.

Assessing the quality and value of metabolic chart data for capturing core outcomes for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

BACKGROUND: Generating rigorous evidence to inform care for rare diseases requires reliable, sustainable, and longitudinal measurement of priority outcomes. Having developed a core outcome set for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we aimed to assess the feasibility of prospective measurement of these core outcomes during routine metabolic clinic visits. METHODS: We used existing cohort data abstracted from charts of 124 children diagnosed with MCAD deficiency who participated in a Canadian study which collected data from birth to a maximum of 11 years of age to investigate the frequency of clinic visits and quality of metabolic chart data for selected outcomes. We recorded all opportunities to collect outcomes from the medical chart as a function of visit rate to the metabolic clinic, by treatment centre and by child age. We applied a data quality framework to evaluate data based on completeness, conformance, and plausibility for four core MCAD outcomes: emergency department use, fasting time, metabolic decompensation, and death. RESULTS: The frequency of metabolic clinic visits decreased with increasing age, from a rate of 2.8 visits per child per year (95% confidence interval, 2.3-3.3) among infants 2 to 6 months, to 1.0 visit per child per year (95% confidence interval, 0.9-1.2) among those ≥ 5 years of age. Rates of emergency department visits followed anticipated trends by child age. Supplemental findings suggested that some emergency visits occur outside of the metabolic care treatment centre but are not captured. Recommended fasting times were updated relatively infrequently in patients' metabolic charts. Episodes of metabolic decompensation were identifiable but required an operational definition based on acute manifestations most commonly recorded in the metabolic chart. Deaths occurred rarely in these patients and quality of mortality data was not evaluated. CONCLUSIONS: Opportunities to record core outcomes at the metabolic clinic occur at least annually for children with MCAD deficiency. Methods to comprehensively capture emergency care received at outside institutions are needed. To reduce substantial heterogeneous recording of core outcome across treatment centres, improved documentation standards are required for recording of recommended fasting times and a consensus definition for metabolic decompensations needs to be developed and implemented.

Recommendations on screening for primary prevention of fragility fractures.

BACKGROUND: Fragility fractures are a major health concern for older adults and can result in disability, admission to hospital and long-term care, and reduced quality of life. This Canadian Task Force on Preventive Health Care (task force) guideline provides evidence-based recommendations on screening to prevent fragility fractures in community-dwelling individuals aged 40 years and older who are not currently on preventive pharmacotherapy. METHODS: We commissioned systematic reviews on benefits and harms of screening, predictive accuracy of risk assessment tools, patient acceptability and benefits of treatment. We analyzed treatment harms via a rapid overview of reviews. We further examined patient values and preferences via focus groups and engaged stakeholders at key points throughout the project. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence for each outcome and strength of recommendations, and adhered to Appraisal of Guidelines for Research and Evaluation (AGREE), Guidelines International Network and Guidance for Reporting Involvement of Patients and the Public (GRIPP-2) reporting guidance. RECOMMENDATIONS: We recommend "risk assessment-first" screening for prevention of fragility fractures in females aged 65 years and older, with initial application of the Canadian clinical Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD). The FRAX result should be used to facilitate shared decision-making about the possible benefits and harms of preventive pharmacotherapy. After this discussion, if preventive pharmacotherapy is being considered, clinicians should request BMD measurement using dual-energy x-ray absorptiometry (DXA) of the femoral neck, and re-estimate fracture risk by adding the BMD T-score into FRAX (conditional recommendation, low-certainty evidence). We recommend against screening females aged 40-64 years and males aged 40 years and older (strong recommendation, very low-certainty evidence). These recommendations apply to community-dwelling individuals who are not currently on pharmacotherapy to prevent fragility fractures. INTERPRETATION: Risk assessment-first screening for females aged 65 years and older facilitates shared decision-making and allows patients to consider preventive pharmacotherapy within their individual risk context (before BMD). Recommendations against screening males and younger females emphasize the importance of good clinical practice, where clinicians are alert to changes in health that may indicate the patient has experienced or is at higher risk of fragility fracture.

"When there is no money, that is when I vomit blood": the domino effect and the unfettered lethal exploitation of Black labor on Dominican sugar plantations.

BACKGROUND: In this article, I utilize the concept of the Plantationocene as an analytical framework to generate a holistic and historical understanding of the present-day struggles of a mostly Haitian migrant workforce on sugar plantations in the Dominican Republic. METHODS: Inspired by Paul Farmer's methodology, I combine political economy, history, and ethnography approaches to interpret the experiences of sugarcane cutters across historical and contemporary iterations of colonial, post-colonial, and neo-colonial practices over the course of five centuries. RESULTS: My findings elucidate the enduring power of capitalism, implicating corporate and state elites, as the structural scaffolding for acts of racialized violence that condition the life-and-death circumstances of Black laborers on Caribbean plantations to this day. Although today's sugarcane cutters may suffer differently than their enslaved or wage labor ancestors on the plantation, I argue that an unfettered racialized pattern of lethal exploitation is sustained through the structural violence of neoliberalism that links present conditions with the colonial past. CONCLUSIONS: Ultimately, this paper contributes understandings of the plantationocene's enduring effects in the global south by demonstrating how imperialist arrangements of capitalism are not a distant memory from the colonial past but instead are present yet hidden and obscured while relocated and reanimated overseas to countries like the Dominican Republic, where American capitalists still exploit Black bodies for profit and power.

Insertion-trigger residues differentially modulate endosomal escape by cytotoxic necrotizing factor toxins.

The cellular specificity, potency, and modular nature of bacterial protein toxins enable their application for targeted cytosolic delivery of therapeutic cargo. Efficient endosomal escape is a critical step in the design of bacterial toxin-inspired drug delivery (BTIDD) vehicles to avoid lysosomal degradation and promote optimal cargo delivery. The cytotoxic necrotizing factor (CNF) family of modular toxins represents a useful model for investigating cargo-delivery mechanisms due to the availability of many homologs with high sequence identity, their flexibility in swapping domains, and their differential activity profiles. Previously, we found that CNFy is more sensitive to endosomal acidification inhibitors than CNF1 and CNF2. Here, we report that CNF3 is even less sensitive than CNF1/2. We identified two amino acid residues within the putative translocation domain (E374 and E412 in CNFy, Q373 and S411 in CNF3) that differentiate between these two toxins. Swapping these corresponding residues in each toxin changed the sensitivity to endosomal acidification and efficiency of cargo-delivery to be more similar to the other toxin. Results suggested that trafficking to the more acidic late endosome is required for cargo delivery by CNFy but not CNF3. This model was supported by results from toxin treatment of cells in the presence of NH4Cl, which blocks endosomal acidification, and of small-molecule inhibitors EGA, which blocks trafficking to late endosomes, and ABMA, which blocks endosomal escape and trafficking to the lysosomal degradative pathway. These findings suggest that it is possible to fine-tune endosomal escape and cytosolic cargo delivery efficiency in designing BTIDD platforms.

When numbers eclipse narratives: a cultural-political critique of the 'ethical' impacts of short-term experiences in global health in Dominican Republic bateyes.

With the rising demand for short-term experiences in global health (STEGH) is an ever-increasing volume of literature that focuses attention on ethics and ethical concerns, such as the effects of STEGH on host populations. Such concerns have driven the development of ethical principles and guidelines, with discussions and debates largely centred around normative questions of positive/negative and benefit/harm for us/them. Using a critical medical humanities lens, this paper blurs these dichotomous framings and offers a more complex understanding of the effects and effectiveness of STEGH on hosts. I explore STEGH that send volunteers from North American universities to the Dominican Republic to participate in service-learning activities aimed at improving the lives of impoverished Haitian migrants living in bateyes I address the following questions: What perspectives about the impacts of interventions on host communities manifest through STEGH? What tensions emerge through interactions among diverse stakeholders related to those perspectives, and with what effects? Drawing together critical theory and ethnography, I examined the perspectives of three stakeholder groups: student and faculty volunteers, host organisation staff, and hosts in batey communities. Data collected from observations and interviews were counterposed; I analysed interactions and interplay between stakeholders. My findings revealed conflicts around an emergent theme: counting efforts, or volunteers' proclivity for numerical evidence of impactful STEGH for hosts. With attention on power relations, I argue that a preoccupation with quantifiable evidence eclipsed and erased the lived realities of hosts, thereby blocking a fully ethical engagement. These sociopolitical effects, often overlooked in conventional ethics assessments, are no less harmful and may reinforce rather than reduce inequalities that the global health movement seeks to eliminate. My study offers a compelling case for how the critical medical humanities lend critical insights in the name of improving global health.

Modular domain swapping among the bacterial cytotoxic necrotizing factor (CNF) family for efficient cargo delivery into mammalian cells.

Modular AB-type bacterial protein toxins target mammalian host cells with high specificity and deliver their toxic cargo into the cytosol. Hence, these toxins are being explored as agents for targeted cytosolic delivery in biomedical and research applications. The cytotoxic necrotizing factor (CNF) family is unique among these toxins in that their homologous sequences are found in a wide array of bacteria, and their activity domains are packaged in various delivery systems. Here, to study how CNF cargo and delivery modules can be assembled for efficient cytosolic delivery, we generated chimeric toxins by swapping functional domains among CNF1, CNF2, CNF3, and CNFy. Chimeras with a CNFy delivery vehicle were more stably expressed, but were less efficient at cargo delivery into HEK293-T cells. We also found that CNFy cargo is the most universally compatible and that CNF3 delivery vehicle is the most flexible and efficient at delivering cargo. These findings suggest that domains within proteins can be swapped and accommodate each other for efficient function and that an individual domain could be engineered for compatibility with multiple partner domains. We anticipate that our insights could help inform chemical biology approaches to develop toxin-based cargo-delivery platforms for cytosolic cargo delivery of therapeutics or molecular probes into mammalian cells.

Gut microbiome composition of wild western lowland gorillas is associated with individual age and sex factors.

OBJECTIVES: Environmental and ecological factors, such as geographic range, anthropogenic pressure, group identity, and feeding behavior are known to influence the gastrointestinal microbiomes of great apes. However, the influence of individual host traits such as age and sex, given specific dietary and social constraints, has been less studied. The objective of this investigation was to determine the associations between an individual's age and sex on the diversity and composition of the gut microbiome in wild western lowland gorillas. MATERIALS AND METHODS: Publicly available 16S rRNA data generated from fecal samples of different groups of Gorilla gorilla gorilla in the Central African Republic were downloaded and bioinformatically processed. The groups analyzed included habituated, partially habituated and unhabituated gorillas, sampled during low fruit (dry, n = 28) and high fruit (wet, n = 82) seasons. Microbial community analyses (alpha and beta diversity and analyses of discriminant taxa), in tandem with network-wide approaches, were used to (a) mine for specific age and sex based differences in gut bacterial community composition and to (b) asses for gut community modularity and bacterial taxa with potential functional roles, in the context of seasonal food variation, and social group affiliation. RESULTS: Both age and sex significantly influenced gut microbiome diversity and composition in wild western lowland gorillas. However, the largest differences were observed between infants and adults in habituated groups and between adults and immature gorillas within all groups, and across dry and wet seasons. Specifically, although adults always showed greater bacterial richness than infants and immature gorillas, network-wide analyses showed higher microbial community complexity and modularity in the infant gorilla gut. Sex-based microbiome differences were not evident among adults, being only detected among immature gorillas. CONCLUSIONS: The results presented point to a dynamic gut microbiome in Gorilla spp., associated with ontogeny and individual development. Of note, the gut microbiomes of breastfeeding infants seemed to reflect early exposure to complex, herbaceous vegetation. Whether increased compositional complexity of the infant gorilla gut microbiome is an adaptive response to an energy-limited diet and an underdeveloped gut needs to be further tested. Overall, age and sex based gut microbiome differences, as shown here, maybe mainly attributed to access to specific feeding sources, and social interactions between individuals within groups.

Implementation science as a leadership capability to improve patient outcomes and value in healthcare.

When evidence thresholds are met, adopting healthcare innovations should add value, and this is forgone when evidence is not translated into practice. Activities that are not supported by evidence lead to ineffective or unnecessary care, or harm, poor outcomes, and low-value healthcare. This article provides an overview of implementation science, which is the scientific study of why implementation succeeds or fails. We draw parallels between the LEADS in a Caring Environment leadership framework and implementation science process models and frameworks. Taken together, the principles and practices in LEADS and the aims of implementation science are effectively quite similar and can be useful for healthcare management looking to optimize resources when implementing evidence-based practice and innovation into routine clinical care.

Cytosolic Delivery of Multidomain Cargos by the N Terminus of Pasteurella multocida Toxin.

The zoonotic pathogen Pasteurella multocida produces a 146-kDa modular toxin (PMT) that enters host cells and manipulates intracellular signaling through action on its Gα protein targets. The N terminus of PMT (PMT-N) mediates cellular uptake through receptor-mediated endocytosis, followed by the delivery of the C-terminal catalytic domain from acidic endosomes into the cytosol. The putative native cargo of PMT consists of a 710-residue polypeptide with three distinct modular subdomains (C1-C2-C3), where C1 contains a membrane localization domain (MLD), C2 has an as-yet-undefined function, and C3 catalyzes the deamidation of a specific active-site glutamine residue in Gα protein targets. However, whether the three cargo subdomains are delivered intact or undergo further proteolytic processing during or after translocation from the late endosome is unclear. Here, we demonstrate that PMT-N mediates the delivery of its native C-terminal cargo as a single polypeptide, corresponding to C1-C2-C3, including the MLD, with no evidence of cleavage between subdomains. We show that PMT-N also delivers nonnative green fluorescent protein (GFP) cargo into the cytosol, further supporting that the receptor-binding and translocation functions reside within PMT-N. Our findings further show that PMT-N can deliver C1-C2 alone but that the presence of C1-C2 is important for the cytosolic delivery of the catalytic C3 subdomain by PMT-N. In addition, we further refine the minimum C3 domain required for intracellular activity as comprising residues 1105 to 1278. These findings reinforce that PMT-N serves as the cytosolic delivery vehicle for C-terminal cargo and demonstrate that its native cargo is delivered intact as C1-C2-C3.

Impact of stress on the gut microbiome of free-ranging western lowland gorillas.

Exposure to stressors can negatively impact the mammalian gastrointestinal microbiome (GIM). Here, we used 454 pyrosequencing of 16S rRNA bacterial gene amplicons to evaluate the impact of physiological stress, as evidenced by faecal glucocorticoid metabolites (FGCM; ng/g), on the GIM composition of free-ranging western lowland gorillas (Gorilla gorilla gorilla). Although we found no relationship between GIM alpha diversity (H) and FGCM levels, we observed a significant relationship between the relative abundances of particular bacterial taxa and FGCM levels. Specifically, members of the family Anaerolineaceae (ρ=0.4, FDR q=0.01), genus Clostridium cluster XIVb (ρ=0.35, FDR q=0.02) and genus Oscillibacter (ρ=0.35, FDR q=0.02) were positively correlated with FGCM levels. Thus, while exposure to stressors appears to be associated with minor changes in the gorilla GIM, the consequences of these changes are unknown. Our results may have implications for conservation biology as well as for our overall understanding of factors influencing the non-human primate GIM.

Recommandations sur le dépistage pour la prévention primaire des fractures de fragilisation.

CONTEXTE: Les fractures de fragilisation sont un important problème de santé chez les adultes âgés et peuvent entraîner des incapacités, des hospitalisations et le placement en établissement de soins de longue durée, en plus de nuire à la qualité de vie. La présente ligne directrice du Groupe d'étude canadien sur les soins de santé préventifs (le Groupe d'étude) formule des recommandations fondées sur des données probantes au sujet du dépistage pour la prévention des fractures de fragilisation chez les personnes âgées de 40 ans et plus vivant dans la collectivité qui ne sont pas sous traitement pharmacologique préventif. MÉTHODES: Nous avons commandé des revues systématiques sur les bénéfices et les préjudices du dépistage, l'exactitude prédictive des outils d'évaluation du risque, les bénéfices du traitement, ainsi que l'acceptabilité de celui-ci par les patients. Nous avons analysé les préjudices des traitements au moyen d'un examen rapide de revues systématiques. Nous avons en outre analysé les valeurs et les préférences des patients par l'entremise de groupes de discussion et auprès d'intervenants mobilisés à certains moments clés, tout au long du projet. Nous avons utilisé l'approche méthodologique GRADE (Grading of Recommendations, Assessment, Development and Evaluation) afin de déterminer la certitude des données probantes pour chacune des issues cliniques ainsi que la force des recommandations, et nous avons appliqué les lignes directrices de l'instrument AGREE (Appraisal of Guidelines for Research and Evaluation), du Guidelines International Network (GIN) et du guide de rédaction Guidance for Reporting Involvement of Patients and the Public (GRIPP 2). RECOMMANDATIONS: Nous recommandons un dépistage débutant par une estimation du risque pour la prévention des fractures de fragilisation chez les femmes de 65 ans et plus. Le dépistage se fait d'abord au moyen de l'outil canadien FRAX, qui mesure le risque de fracture, sans densité minérale osseuse (DMO). Le score FRAX devrait guider la prise de décision partagée entourant les bénéfices et les préjudices potentiels de la pharmacothérapie préventive. Après cette discussion, si une pharmacothérapie préventive est envisagée, les médecins devraient demander une mesure de la DMO par absorptiométrie à rayons X biphotonique (DEXA) du col du fémur, puis réévaluer le risque de fracture en intégrant le score T de la DMO au score FRAX (recommandation conditionnelle, données de faible certitude). Nous ne recommandons pas le dépistage chez les femmes de 40­64 ans et les hommes de 40 ans et plus (recommandation forte, données de très faible certitude). Ces recommandations s'appliquent aux personnes vivant dans la collectivité qui ne sont pas sous pharmacothérapie pour la prévention des fractures de fragilisation. INTERPRÉTATION: Le dépistage débutant par une estimation du risque chez les femmes de 65 ans et plus facilite la prise de décision partagée et permet aux patientes d'envisager la pharmacothérapie préventive en fonction de leur propre risque (avant DMO). Le fait de ne pas recommander le dépistage chez les hommes et les femmes plus jeunes rappelle l'importance des bonnes pratiques cliniques, en vertu desquelles les médecins doivent demeurer à l'affût de tout changement de l'état de santé des personnes qui pourrait indiquer qu'elles ont subi une fracture de fragilisation ou pourraient y être plus sujettes.

Pregnant women's views on how to promote the use of a decision aid for Down syndrome prenatal screening: a theory-informed qualitative study.

BACKGROUND: For pregnant women and their partners, the decision to undergo Down syndrome prenatal screening is difficult. Patient decision aids (PtDA) can help them make an informed decision. We aimed to identify behaviour change techniques (BCTs) that would be useful in an intervention to promote the use of a PtDA for Down syndrome prenatal screening, and to identify which of these BCTs pregnant women found relevant and acceptable. METHODS: Using the Behaviour Change Wheel and the Theoretical Domains Framework, we conducted a qualitative descriptive study. First, a group of experts from diverse professions, disciplines and backgrounds (eg. medicine, engineering, implementation science, community and public health, shared decision making) identified relevant BCTs. Then we recruited pregnant women consulting for prenatal care in three clinical sites: a family medicine group, a birthing centre (midwives) and a hospital obstetrics department in Quebec City, Canada. To be eligible, participants had to be at least 18 years old, having recently given birth or at least 16 weeks pregnant with a low-risk pregnancy, and have already decided about prenatal screening. We conducted three focus groups and asked questions about the relevance and acceptability of the BCTs. We analysed verbatim transcripts and reduced the BCTs to those the women found most relevant and acceptable. RESULTS: Our group of experts identified 25 relevant BCTs relating to information, support, consequences, others' approval, learning, reward, environmental change and mode of delivery. Fifteen women participated in the study with a mean age of 27 years. Of these, 67% (n = 10) were pregnant for the first time, 20% (n = 3) had difficulty making the decision to take the test, and 73% had made the decision with their partner. Of the 25 BCTs identified using the Behaviour Change Wheel, the women found the following 10 to be most acceptable and relevant: goal setting (behaviour), goal setting (results), problem solving, action plan, social support (general), social support (practical), restructuring the physical environment, prompts/cues, credible sources and modelling or demonstration of the behaviour. CONCLUSIONS: An intervention to promote PtDA use among pregnant women for Down syndrome prenatal screening should incorporate the 10 BCTs identified.

Psychosocial Factors of Health Professionals' Intention to Use a Decision Aid for Down Syndrome Screening: Cross-Sectional Quantitative Study.

BACKGROUND: Decisions about prenatal screening for Down syndrome are difficult for women, as they entail risk, potential loss, and regret. Shared decision making increases women's knowledge of their choices and better aligns decisions with their values. Patient decision aids foster shared decision making but are rarely used in this context. OBJECTIVE: One of the most promising strategies for implementing shared decision making is distribution of decision aids by health professionals. We aimed to identify factors influencing their intention to use a DA during prenatal visit for decisions about Down syndrome screening. METHODS: We conducted a cross-sectional quantitative study. Using a Web panel, we conducted a theory-based survey of health professionals in Quebec province (Canada). Eligibility criteria were as follows: (1) family physicians, midwives, obstetrician-gynecologists, or trainees in these professions; (2) involved in prenatal care; and (3) working in Quebec province. Participants watched a video depicting a health professional using a decision aid during a prenatal consultation with a woman and her partner, and then answered a questionnaire based on an extended version of the theory of planned behavior, including some of the constructs of the theoretical domains framework. The questionnaire assessed 8 psychosocial constructs (attitude, anticipated regret, subjective norm, self-identity, moral norm, descriptive norm, self-efficacy, and perceived control), 7 related sets of behavioral beliefs (advantages, disadvantages, emotions, sources of encouragement or discouragement, incentives, facilitators, and barriers), and sociodemographic data. We performed descriptive, bivariate, and multiple linear regression analyses to identify factors influencing health professionals' intention to use a decision aid. RESULTS: Among 330 health professionals who completed the survey, 310 met the inclusion criteria: family physicians, 55.2% (171/310); obstetrician-gynecologists, 33.8% (105/310); and midwives, 11.0% (34/310). Of these, 80.9% were female (251/310). Mean age was 39.6 (SD 11.5) years. Less than half were aware of any decision aids at all. In decreasing order of importance, factors influencing their intention to use a decision aid for Down syndrome prenatal screening were as follows: self-identity (beta=.325, P<.001), attitude (beta=.297, P<.001), moral norm (beta=.288, P<.001), descriptive norm (beta=.166, P<.001), and anticipated regret (beta=.099, P=.003). Underlying behavioral beliefs significantly related to intention were that the use of a decision aid would promote decision making (beta=.117, 95% CI 0.043-0.190), would reassure health professionals (beta=.100, 95% CI 0.024-0.175), and might require more time than planned for the consultation (beta=-.077, 95% CI -0.124 to -0.031). CONCLUSIONS: We identified psychosocial factors that could influence health professionals' intention to use a decision aid about Down syndrome screening. Strategies should remind them of the following: (1) using a decision aid for this purpose should be a common practice, (2) it would be expected of someone in their societal role, (3) the experience of using it will be satisfying and reassuring, and (4) it is likely to be compatible with their moral values.

Use of a patient decision aid for prenatal screening for Down syndrome: what do pregnant women say?

BACKGROUND: Patient decision aids (PtDAs) help people make difficult, values-sensitive decisions. Prenatal screening for assessing the risk of genetic conditions in the fetus is one such decision and patient decision aids are rarely used in this clinical context. We sought to identify factors influencing pregnant women's use of a patient decision aid for deciding about prenatal screening for Down syndrome (DS). METHODS: This qualitative study was embedded in a sequential mixed-methods research program whose main aim is to implement shared decision-making (SDM) in the context of prenatal screening for DS in the province of Quebec, Canada. We planned to recruit a purposive sample of 45 pregnant women with low-risk pregnancy consulting for prenatal care at three clinical sites. Participating women watched a video depicting a prenatal care follow-up during which a pregnant woman, her partner and a health professional used a PtDA to decide about prenatal screening for DS. The women were then interviewed about factors that would influence the use of this PtDA using questions based on the Theoretical Domains Framework (TDF). We performed content analysis of transcribed verbatim interviews. RESULTS: Out of 216 eligible women, 100 agreed to participate (46% response rate) and 46 were interviewed. Regarding the type of health professional responsible for their prenatal care, 19 participants (41%) reported having made a decision about prenatal screening for DS with an obstetrician-gynecologist, 13 (28%) with a midwife, 12 (26%) with a family physician, and two (4%) decided on their own. We identified 54 factors that were mapped onto nine of the 12 TDF domains. The three most frequently-mentioned were: opinion of the pregnant woman's partner (n = 33, 72%), presentation of the PtDA by health professional and a discussion (n = 27, 72%), and not having encountered a PtDA (n = 26, 57%). CONCLUSION: This study allowed us to identify factors influencing pregnant women's use of a PtDA for prenatal screening for DS. Use of a PtDA by health professionals and patients is one step in providing the needed decision support and our study results will allow us to design an effective implementation strategy for PtDAs for prenatal screening for DS.

Actual use of and adherence to ibuprofen 400 mg tablet dosing instructions in a simulated OTC environment
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OBJECTIVE: Evaluate adherence of US consumers to proposed label directions for a new 400 mg ibuprofen formulation. METHODS: In this single-arm, open-label, multicenter, 30-day study simulating an over-the-counter (OTC)-like environment, US analgesic consumers reviewed proposed product packaging for a new 400 mg ibuprofen formulation and made a purchase decision. Purchasers used the product as needed and recorded use over 30 days. Outcomes included the percentage of participants who exhibited correct or acceptable product use for the primary endpoint (not exceeding 1,200 mg/day > 2 times during the study) or secondary endpoint (not exceeding 400 mg/dose > 2 times during the study) and adherence to the labeled dosing interval of 6 - 8 hours. Primary endpoint success was met if the lower bound of the 95% confidence interval (CI) was ≥ 85%. RESULTS: Of 685 purchasers providing use data, correct or acceptable use behavior occurred in 95.2% (95% CI: 93.6%, 96.8%) regarding total daily dose and in 84.4% (95% CI: 81.7%, 87.1%) regarding the number of tablets taken per dosing occasion. Most participants (87.3%) never used > 1,200 mg/day or took > 1 tablet/dose (78.1%). Nearly 43% of subjects re-dosed within 6 hours of the previous dose; of these, ~ 82% re-dosed between the 4- and 6-hour time intervals. Adverse events were consistent with prior ibuprofen 200 mg experience. CONCLUSION: This study provides evidence that a majority of US consumers would be able to use OTC ibuprofen 400 mg tablets in a manner consistent with product labeling. Misuse rates were low and unlikely to generate an excess risk of clinically important adverse events.
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Multigene panels in prostate cancer risk assessment: a systematic review.

PURPOSE: Single-nucleotide polymorphism (SNP) panel tests have been proposed for use in the detection of, and prediction of risk for, prostate cancer and as prognostic indicator in affected men. A systematic review was undertaken to address three research questions to evaluate the analytic validity, clinical validity, clinical utility, and prognostic validity of SNP-based panels. METHODS: Data sources comprised MEDLINE, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and EMBASE; these were searched from inception to April 2013. The gray-literature searches included contact with manufacturers. Eligible studies included English-language studies evaluating commercially available SNP panels. Study selection and risk of bias assessment were undertaken by two independent reviewers. RESULTS: Twenty-one studies met eligibility criteria. All focused on clinical validity and evaluated 18 individual panels with 2 to 35 SNPs. All had poor discriminative ability (overall area under receiver-operator characteristic curves, 58-74%; incremental gain resulting from inclusion of SNP data, 2.5-11%) for predicting risk of prostate cancer and/or distinguishing between aggressive and asymptomatic/latent disease. The risk of bias of the studies, as assessed by the Newcastle Ottawa Scale (NOS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tools, was moderate. CONCLUSION: The evidence on currently available SNP panels is insufficient to assess analytic validity, and at best the panels assessed would add a small and clinically unimportant improvement to factors such as age and family history in risk stratification (clinical validity). No evidence on the clinical utility of current panels is available.Genet Med 18 6, 535-544.

Reflections on the cost of "low-cost" whole genome sequencing: framing the health policy debate.

The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy.

Child and family experiences with inborn errors of metabolism: a qualitative interview study with representatives of patient groups.

BACKGROUND: Patient-centered health care for children with inborn errors of metabolism (IEM) and their families is important and requires an understanding of patient experiences, needs, and priorities. IEM-specific patient groups have emerged as important voices within these rare disease communities and are uniquely positioned to contribute to this understanding. We conducted qualitative interviews with IEM patient group representatives to increase understanding of patient and family experiences, needs, and priorities and inform patient-centered research and care. METHODS: We developed a sampling frame of patient groups representing IEM disease communities from Canada, the United States, and United Kingdom. With consent, we interviewed participants to explore their views on experiences, needs, and outcomes that are most important to children with IEM and their families. We analyzed the data using a qualitative descriptive approach to identify key themes and sub-themes. RESULTS: We interviewed 18 organizational representatives between February 28 and September 17, 2014, representing 16 IEMs and/or disease categories. Twelve participants voluntarily self-identified as parents and/or were themselves patients. Three key themes emerged from the coded data: managing the uncertainty associated with raising and caring for a child with a rare disease; challenges associated with the affected child's life transitions, and; the collective struggle for improved outcomes and interventions that rare disease communities navigate. CONCLUSION: Health care providers can support children with IEM and their families by acknowledging and reducing uncertainty, supporting families through children's life transitions, and contributing to rare disease communities' progress toward improved interventions, experiences, and outcomes.