Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances.

OBJECTIVE: To assess the outcomes of pregnancies at high-risk for rare autosomal trisomies (RATs) and segmental imbalances (SIs) on cell-free DNA (cfDNA) screening. METHOD: A retrospective study of women who underwent cfDNA screening between September 2019 and July 2021 at three ultrasound services in Australia. Positive predictive values (PPVs) were calculated using fetal chromosomal analysis. RESULTS: Among 23,857 women screened, there were 93 high-risk results for RATs (0.39%) and 82 for SIs (0.34%). The PPVs were 3.8% (3/78, 95% CI 0.8%-10.8%) for RATs and 19.1% (13/68, 95% CI 10.6%-30.5%) for SIs. If fetuses with structural anomalies were also counted as true-positive cases, the PPV for RATS increased to 8.5% (7/82, 95% CI 3.5%-16.8%). Among 85 discordant cases with birth outcomes available (65.4%), discordant positive RATs had a significantly higher proportion of infants born below the 10th and 3rd birthweight percentiles than expected (19.6% (p = 0.022) and 9.8% (p = 0.004), respectively), which was not observed in the SI group (2.9% < 10th (p = 0.168) and 0.0% <3rd (p = 0.305)). CONCLUSION: The PPVs for SI and RAT results are low, except when a structural abnormality is also present. Discordant positive RATs are associated with growth restriction.

Selecting, refining and identifying priority Cochrane Reviews in health communication and participation in partnership with consumers and other stakeholders.

BACKGROUND: Priority-setting partnerships between researchers and stakeholders (meaning consumers, health professionals and health decision-makers) may improve research relevance and value. The Cochrane Consumers and Communication Group (CCCG) publishes systematic reviews in 'health communication and participation', which includes concepts such as shared decision-making, patient-centred care and health literacy. We aimed to select and refine priority topics for systematic reviews in health communication and participation, and use these to identify five priority CCCG Cochrane Reviews. METHODS: Twenty-eight participants (14 consumers, 14 health professionals/decision-makers) attended a 1-day workshop in Australia. Using large-group activities and voting, participants discussed, revised and then selected 12 priority topics from a list of 21 previously identified topics. In mixed small groups, participants refined these topics, exploring underlying problems, who they affect and potential solutions. Thematic analysis identified cross-cutting themes, in addition to key populations and potential interventions for future Cochrane Reviews. We mapped these against CCCG's existing review portfolio to identify five priority reviews. RESULTS: Priority topics included poor understanding and implementation of patient-centred care by health services, the fact that health information can be a low priority for health professionals, communication and coordination breakdowns in health services, and inadequate consumer involvement in health service design. The four themes underpinning the topics were culture and organisational structures, health professional attitudes and assumptions, inconsistent experiences of care, and lack of shared understanding in the sector. Key populations for future reviews were described in terms of social health characteristics (e.g. people from indigenous or culturally and linguistically diverse backgrounds, elderly people, and people experiencing socioeconomic disadvantage) more than individual health characteristics. Potential interventions included health professional education, interventions to change health service/health professional culture and attitudes, and health service policies and standards. The resulting five priority Cochrane Reviews identified were improving end-of-life care communication, patient/family involvement in patient safety, improving future doctors' communication skills, consumer engagement strategies, and promoting patient-centred care. CONCLUSIONS: Stakeholders identified priority topics for systematic reviews associated with structural and cultural challenges underlying health communication and participation, and were concerned that issues of equity be addressed. Priority-setting with stakeholders presents opportunities and challenges for review producers.

Research priorities in health communication and participation: international survey of consumers and other stakeholders.

OBJECTIVE: To identify research priorities of consumers and other stakeholders to inform Cochrane Reviews in 'health communication and participation' (including such concepts as patient experience, shared decision-making and health literacy). SETTING: International. PARTICIPANTS: We included anyone with an interest in health communication and participation. Up to 151 participants (18-80 years; 117 female) across 12 countries took part, including 48 consumers (patients, carers, consumer representatives) and 75 professionals (health professionals, policymakers, researchers) (plus 25 people who identified as both). DESIGN: Survey. METHODS: We invited people to submit their research ideas via an online survey open for 4 weeks. Using inductive thematic analysis, we generated priority research topics, then classified these into broader themes. RESULTS: Participants submitted 200 research ideas, which we grouped into 21 priority topics. Key research priorities included: insufficient consumer involvement in research (19 responses), 'official' health information is contradictory and hard to understand (18 responses), communication/coordination breakdowns in health services (15 responses), health information provision a low priority for health professionals (15 responses), insufficient eliciting of patient preferences (14 responses), health services poorly understand/implement patient-centred care (14 responses), lack of holistic care impacting healthcare quality and safety (13 responses) and inadequate consumer involvement in service design (11 responses). These priorities encompassed acute and community health settings, with implications for policy and research. Priority populations of interest included people from diverse cultural and linguistic backgrounds, carers, and people with low educational attainment, or mental illness. Most frequently suggested interventions focused on training and cultural change activities for health services and health professionals. CONCLUSIONS: Consumers and other stakeholders want research addressing structural and cultural challenges in health services (eg, lack of holistic, patient-centred, culturally safe care) and building health professionals' communication skills. Solutions should be devised in partnership with consumers, and focus on the needs of vulnerable groups.

Can consumers learn to ask three questions to improve shared decision making? A feasibility study of the ASK (AskShareKnow) Patient-Clinician Communication Model(®) intervention in a primary health-care setting.

OBJECTIVE: To test the feasibility and assess the uptake and acceptability of implementing a consumer questions programme, AskShareKnow, to encourage consumers to use the questions '1. What are my options; 2. What are the possible benefits and harms of those options; 3. How likely are each of those benefits and harms to happen to me?' These three questions have previously shown important effects in improving the quality of information provided during consultations and in facilitating patient involvement. METHODS: This single-arm intervention study invited participants attending a reproductive and sexual health-care clinic to view a 4-min video-clip in the waiting room. Participants completed three questionnaires: (T1) prior to viewing the intervention; (T2) immediately after their consultation; and (T3) two weeks later. RESULTS: A total of 121 (78%) participants viewed the video-clip before their consultation. Eighty-four (69%) participants asked one or more questions, and 35 (29%) participants asked all three questions. For those making a decision, 55 (87%) participants asked one or more questions, while 27 (43%) participants asked all three questions. Eighty-seven (72%) participants recommended the questions. After two weeks, 47 (49%) of the participants recalled the questions. CONCLUSIONS: Enabling patients to view a short video-clip before an appointment to improve information and involvement in health-care consultations is feasible and led to a high uptake of question asking in consultations. PRACTICE IMPLICATIONS: This AskShareKnow programme is a simple and feasible method of training patients to use a brief consumer-targeted intervention that has previously shown important effects in improving the quality of information provided during consultations and in facilitating patient involvement and use of evidence-based questions.

Localization of inhibitory antibodies to the biotin domain of human pyruvate carboxylase.

Pyruvate carboxylase [EC 6.4.1.1] plays an important anaplerotic role in many species by catalyzing the carboxylation of pyruvate to oxaloacetate. To extend our understanding about the structure and function of pyruvate carboxylase (PC), a series of monoclonal antibodies were raised against sheep liver PC and those displaying inhibitory activity were further characterized. The binding epitopes of two monoclonal antibodies that displayed strong inhibitory activity were mapped. Six overlapping fragments of the human enzyme were expressed as thioredoxin fusion proteins in Escherichia coli and subjected to Western blot analysis. Both monoclonal antibodies (MAbs) recognized fragments encompassing the enzyme's C-terminal region, known to contain the structured biotin domain. Through deletion analysis, this domain was determined to be a minimal size of 80 amino acids. Further deletions that disrupted the conformation of the domain abolished antibody binding, indicating these antibodies recognized discontinuous epitopes. To further define the critical residues required for antibody recognition, a model of the domain was produced and an alanine scan performed on selected surface-exposed residues. Our results show that residues encompassing the biotin attachment site, but not biotin itself, are critical for the binding of both antibodies. These data provide a mechanism to explain the inhibitory activity of the antibodies.

Three questions that patients can ask to improve the quality of information physicians give about treatment options: a cross-over trial.

OBJECTIVE: To test the effect of three questions (what are my options? what are the benefits and harms? and how likely are these?), on information provided by physicians about treatment options. METHODS: We used a cross-over trial using two unannounced standardized patients (SPs) simulating a presentation of mild-moderate depression. One SP was assigned the intervention role (asking the questions), the other the control role. An intervention and control SP visited each physician, order allocated randomly. The study was conducted in family practices in Sydney, Australia, during 2008-09. Data were obtained from consultation audio-recordings. Information about treatment options and patient involvement were analyzed using the Assessing Communication about Evidence and Patient Preferences (ACEPP) tool and the OPTION tool. RESULTS: Thirty-six SP visits were completed (18 intervention, 18 control). Scores were higher in intervention consultations than controls: ACEPP scores 21.4 vs. 16.6, p<0.001, difference 4.7 (95% CI 2.3-7.0) and OPTION scores 36 vs. 25, p=0.001, difference 11.5 (95% CI 5.1-17.8), indicating greater information provision and behavior supporting patient involvement. CONCLUSION: Asking these three questions improved information given by family physicians and increased physician facilitation of patient involvement. Practice implications. These questions can drive evidence-based practice, strengthen patient-physician communication, and improve safety and quality.

Shared decision making in Australia in 2011.

The paper describes the current position of shared decision making (SDM) within the Australian healthcare system. SDM POLICY IN AUSTRALIA: Support for SDM exists through guidelines and policy documents, and is strongly endorsed by consumer organisations; however, there is no clear overarching policy framework for SDM in Australia. TOOLS FOR SDM: There are limited tools available for SDM in clinical practice. Access to tools exists through some Australian health research and consumer organisation websites but the use of tools remains idiosyncratic. IMPLEMENTATION OF SDM: Comparatively little has been achieved in the implementation of SDM in Australia. Although there is wide recognition that consumer involvement in health decisions is important, provision of resources and infrastructure to achieve it is limited, and there is no clear strategy to support implementation within the healthcare system. SDM IN THE FUTURE: Current reforms to the healthcare system may enable a more centralised approach to implementation of SDM in the future. A new federally funded consumer health information organisation may assist by providing a central point through which SDM interventions may be made available to the Australian public and the Australian Charter of Rights has the potential to provide a national framework for consumer involvement. However, priority needs to be given to SDM by both federal and state governments with greater investment in SDM research and in activities to support implementation in clinical practice.