Joint ABS-UKCGG-CanGene-CanVar consensus regarding the use of CanRisk in clinical practice.

BACKGROUND: The CanRisk tool, which operationalises the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is used by Clinical Geneticists, Genetic Counsellors, Breast Oncologists, Surgeons and Family History Nurses for breast cancer risk assessments both nationally and internationally. There are currently no guidelines with respect to the day-to-day clinical application of CanRisk and differing inputs to the model can result in different recommendations for practice. METHODS: To address this gap, the UK Cancer Genetics Group in collaboration with the Association of Breast Surgery and the CanGene-CanVar programme held a workshop on 16th of May 2023, with the aim of establishing best practice guidelines. RESULTS: Using a pre-workshop survey followed by structured discussion and in-meeting polling, we achieved consensus for UK best practice in use of CanRisk in making recommendations for breast cancer surveillance, eligibility for genetic testing and the input of available information to undertake an individualised risk assessment. CONCLUSIONS: Whilst consensus recommendations were achieved, the meeting highlighted some of the barriers limiting the use of CanRisk in clinical practice and identified areas that require further work and collaboration with relevant national bodies and policy makers to incorporate wider use of CanRisk into routine breast cancer risk assessments.

Conserving ecosystem integrity: Ecological theory as a guide for marine protected area monitoring.

Global policies increasingly focus on the importance of maintaining or improving the integrity of ecosystems, but defining, assessing, and monitoring integrity in marine protected areas (MPAs) remains a challenge. In this paper, we conceptualized ecological integrity along dimensions of heterogeneity and stability containing seven components: physical structure, diversity, function, persistence, resistance, resilience, and natural variability. Through a structured literature search, we identified indicators and metrics used for quantifying ecosystem status components in the marine environment, then reviewed MPA management plans worldwide for inclusion of these components. We evaluated 202 papers applying 83 ecological indicators built from 72 metrics. Ecosystem components were most comprehensively addressed by metrics of taxa presence, organisms count, and area occupied by benthic organisms, and community structure, biomass, and percent cover indicators. Of the 557 MPA management plans we reviewed globally, 93% used at least one ecosystem status term or its synonym in an ecologically relevant context, but 39% did not address any components of stability. In particular, resistance was mentioned in only 1% of management plans, but in some cases it may be inferred from indicators and metrics used to track the best addressed component in management plans, diversity. Plans for MPAs with both an ecological/biological purpose and a research and education purpose contained ecosystem status terms more frequently than other plans, suggesting that engagement with the scientific community may have improved the application of these terms. An improved understanding of how to operationalize and measure ecological integrity can help MPA monitoring and management.

Effects of colour-coded compartmentalised syringe trays on anaesthetic drug error detection under cognitive load.

BACKGROUND: Anaesthetic drug administration is complex, and typical clinical environments can entail significant cognitive load. Colour-coded anaesthetic drug trays have shown promising results for error identification and reducing cognitive load. METHODS: We used experimental psychology methods to test the potential benefits of colour-coded compartmentalised trays compared with conventional trays in a simulated visual search task. Effects of cognitive load were also explored through an accompanying working memory-based task. We hypothesised that colour-coded compartmentalised trays would improve drug-detection error, reduce search time, and reduce cognitive load. This comprised a cognitive load memory task presented alongside a visual search task to detect drug errors. RESULTS: All 53 participants completed 36 trials, which were counterbalanced across the two tray types and 18 different vignettes. There were 16 error-present and 20 error-absent trials, with 18 trials presented for each preloaded tray type. Syringe errors were detected more often in the colour-coded trays than in the conventional trays (91% vs 83%, respectively; P=0.006). In signal detection analysis, colour-coded trays resulted in more sensitivity to the error signal (2.28 vs 1.50, respectively; P<0.001). Confidence in response accuracy correlated more strongly with task performance for the colour-coded tray condition, indicating improved metacognitive sensitivity to task performance (r=0.696 vs r=0.447). CONCLUSIONS: Colour coding and compartmentalisation enhanced visual search efficacy of drug trays. This is further evidence that introducing standardised colour-coded trays into operating theatres and procedural suites would add an additional layer of safety for anaesthetic procedures.

Proactive breast cancer risk assessment in primary care: a review based on the principles of screening.

In the UK, the National Institute for Health and Care Excellence (NICE) recommends that women at moderate or high risk of breast cancer be offered risk-reducing medication and enhanced breast screening/surveillance. In June 2022, NICE withdrew a statement recommending assessment of risk in primary care only when women present with concerns. This shift to the proactive assessment of risk substantially changes the role of primary care, in effect paving the way for a primary care-based screening programme to identify those at moderate or high risk of breast cancer. In this article, we review the literature surrounding proactive breast cancer risk assessment within primary care against the consolidated framework for screening. We find that risk assessment for women under 50 years currently satisfies many of the standard principles for screening. Most notably, there are large numbers of women at moderate or high risk currently unidentified, risk models exist that can identify those women with reasonable accuracy, and management options offer the opportunity to reduce breast cancer incidence and mortality in that group. However, there remain a number of uncertainties and research gaps, particularly around the programme/system requirements, that need to be addressed before these benefits can be realised.

Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1 updates to tumour pathology and cancer incidence.

BACKGROUND: BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk.org) provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors. METHODS: BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult height as continuous. RESULTS: BARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34%-44% of these carriers would be reclassified to the near-population and 15%-22% to the high-risk categories based on the UK National Institute for Health and Care Excellence guidelines. Under the EOC multifactorial model, 62%, 35% and 3% of PALB2 carriers have lifetime EOC risks of <5%, 5%-10% and >10%, respectively. Including height as continuous, increased the breast cancer relative risk variance from 0.002 to 0.010. CONCLUSIONS: These extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.

Comprehensive epithelial tubo-ovarian cancer risk prediction model incorporating genetic and epidemiological risk factors.

BACKGROUND: Epithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. A multifactorial risk model based on known genetic and epidemiological risk factors (RFs) for EOC can help identify women at higher risk who could benefit from targeted screening and prevention. METHODS: We developed a multifactorial EOC risk model for women of European ancestry incorporating the effects of pathogenic variants (PVs) in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1, a Polygenic Risk Score (PRS) of arbitrary size, the effects of RFs and explicit family history (FH) using a synthetic model approach. The PRS, PV and RFs were assumed to act multiplicatively. RESULTS: Based on a currently available PRS for EOC that explains 5% of the EOC polygenic variance, the estimated lifetime risks under the multifactorial model in the general population vary from 0.5% to 4.6% for the first to 99th percentiles of the EOC risk distribution. The corresponding range for women with an affected first-degree relative is 1.9%-10.3%. Based on the combined risk distribution, 33% of RAD51D PV carriers are expected to have a lifetime EOC risk of less than 10%. RFs provided the widest distribution, followed by the PRS. In an independent partial model validation, absolute and relative 5-year risks were well calibrated in quintiles of predicted risk. CONCLUSION: This multifactorial risk model can facilitate stratification, in particular among women with FH of cancer and/or moderate-risk and high-risk PVs. The model is available via the CanRisk Tool (www.canrisk.org).

Capturing the experiences of patients with inherited optic neuropathies: a systematic review of patient-reported outcome measures (PROMs) and qualitative studies.

PURPOSE: To identify and comprehensively evaluate studies capturing the experience of individuals affected by an inherited optic neuropathy (ION), focusing on patient-reported outcome measures (PROMs) and qualitative studies where the health status and quality of life (QoL) of these individuals have been explored. METHODS: Systematic review of five databases using a search strategy combining four concepts: (1) ION; (2) QoL and health status; (3) PROMs; and (4) qualitative research. Studies assessing the impact of ION on any QoL domain using a PROM or qualitative methodology were included and appraised, using criteria based on the COSMIN checklist (for PROM studies) and the CASP checklist (for qualitative studies). RESULTS: Of 1326 unique articles identified, six studies were included. Five PROMs were identified: Visual Function Index (VF-14); Hospital Anxiety and Depression Scale (HADS); a novel graphical online assessment tool (NGOAT) for reporting emotional response to vision loss; a new PROM informed by the DSM-V Criteria for Major Depressive Disorder; and an interpersonal and career 'impact rating' PROM. The psychometric performance of included PROMs were poorly described. Qualitative studies found that vision loss resulted in psychosocial losses including loss of social and communication skills and loss of independence and freedom. Factors that modified the response to vision loss were also identified. CONCLUSION: The current PROMs used by individuals with ION have poor content coverage, primarily measuring activity limitation and emotional well-being, and insufficient reporting of psychometric performance. There is a need to develop a PROM for individuals ION to report their experiences of living with their condition.

The impact of digital health interventions on the psychological outcomes of patients and families receiving paediatric palliative care: A systematic review and narrative synthesis.

BACKGROUND: Digital health interventions are becoming increasingly important and may be particularly relevant for paediatric palliative care. In line with the aims of palliative care, digital health interventions should aim to maintain, if not improve, psychological wellbeing. However, the extent to which the psychological outcomes of digital health interventions are assessed is currently unknown. AIM: To identify and synthesise the literature exploring the impact of all digital health interventions on the psychological outcomes of patients and families receiving paediatric palliative care. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: MEDLINE, EMBASE, Health Management Information Consortium, PsycINFO, Cumulative Index to Nursing and Allied Health Literature and the Midwives Information & Resource Service were searched on the 27th July 2020, in addition to the first five pages of Google Scholar. To be included in the review, papers must have contained: quantitative or qualitative data on psychosocial outcomes, data from patients aged 0-18 receiving palliative care or their families, a digital health intervention, and been written in English. RESULTS: Three studies were included in the review. All looked at the psychological impact of telehealth interventions. Papers demonstrated fair or good quality reporting but had small sample sizes and varied designs. CONCLUSIONS: Despite the design and development of digital health interventions that span the technological landscape, little research has assessed their psychosocial impact in the paediatric palliative care community. Whilst the evidence base around the role of these interventions continues to grow, their impact on children and their families must not be overlooked.

Boosting the input: 9-month-olds' sensitivity to low-frequency phonotactic patterns in novel wordforms.

To learn their first words, infants must attend to a variety of cues that signal word boundaries. One such cue infants might use is the language-specific phonotactics to track legal combinations and positions of segments within a word. Studies have demonstrated that, when tested across statistically high and low phonotactics, infants repeatedly reject the low-frequency wordforms. We explore whether the capacity to access low-frequency phonotactic combinations is available at 9 months when pre-exposed to wordforms containing statistically low combinations of segments. Using a modified head-turn procedure, one group of infants was presented with nonwords with low-frequency complex onsets (dr-), and another group was presented with zero-frequency onset nonwords (dl-). Following pre-exposure and familiarization, infants were then tested on their ability to segment nonwords that contained either the low- or the zero-frequency onsets. Only infants in the low-frequency condition were successful at the task, suggesting some experience with these onsets supports segmentation.

Surgery, Complications, and Quality of Life: A Longitudinal Cohort Study Exploring the Role of Psychosocial Factors.

OBJECTIVE: To determine whether psychosocial factors moderate the relationship between surgical complications and quality of life (QoL). BACKGROUND: Patients who experience surgical complications have significantly worse postoperative QoL than patients with an uncomplicated recovery. Psychosocial factors, such as coping style and level of social support influence how people deal with stressful events, but it is unclear whether they affect QoL following a surgical complication. These findings can inform the development of appropriate interventions that support patients postoperatively. METHODS: This is a longitudinal cohort study; data were collected pre-op, 1 month post-op, 4 months post-op, and 12 months post-op. A total of 785 patients undergoing major elective gastrointestinal, vascular, or cardiothoracic surgery who were recruited from 28 National Health Service sites in England and Scotland took part in the study. RESULTS: Patients who experience major surgical complications report significantly reduced levels of physical and mental QoL (P < 0.05) but they make a full recovery over time. Findings indicate that a range of psychosocial factors such as the use of humor as a coping style and the level of health care professional support may moderate the impact of surgical complications on QoL. CONCLUSIONS: Surgical complications alongside other sociodemographic and psychosocial factors contribute to changes in QoL; the results from this exploratory study suggest that interventions that increase the availability of healthcare professional support and promote more effective coping strategies before surgery may be useful, particularly in the earlier stages of recovery where QoL is most severely compromised. However, these relationships should be further explored in longitudinal studies that include other types of surgery and employ rigorous recruitment and follow-up procedures.

Conceptual framework for living with and beyond cancer: A systematic review and narrative synthesis.

OBJECTIVE: The concept of living with and beyond cancer is now emerging in policy and literature. Rather than viewing this notion simply as a linear timeline, developing an agreed understanding of the lived experience of people affected by cancer will aid the development of person-centred models of care. METHODS: A systematic review was conducted. The review question was "What does the term 'living with and beyond cancer' mean to people affected by cancer?" The protocol for the review was preregistered in the PROSPERO database (PROSPERO CRD42017059860). All included studies were qualitative, so narrative synthesis was used to integrate descriptions and definitions of living with and beyond cancer into an empirically based conceptual framework. RESULTS: Out of 2345 papers that were identified and 180 that were reviewed, a total of 73 papers were included. The synthesis yielded three interlinked themes: Adversity (realising cancer), Restoration (readjusting life with cancer), and Compatibility (reconciling cancer), resulting in the ARC framework. CONCLUSIONS: Three themes describe the experience of living with and beyond cancer: adversity, restoration, and compatibility. The ARC framework provides an empirically informed grounding for future research and practice in supportive cancer care for this population.

Informing the Consent Process for Surgeons: A Survey Study of Patient Preferences, Perceptions, and Risk Tolerance.

BACKGROUND: Despite the ethical and statutory requirement to obtain consent for surgical procedures, the actual process itself is less well defined. The degree of disclosure and detail expected may vary greatly. A recent shift toward a more patient-centered approach in both clinical and medico-legal practice has significant implications for ensuring appropriate and legal practice in obtaining informed consent before surgery. METHODS: Two hundred patients undergoing elective surgery across two hospitals returned a survey of attitudes toward consent, perceived important elements in the consent process, and risk tolerance, as well as demographic details. RESULTS: No significant associations between patient demographics and survey responses were found. Patients were least concerned with the environment in which consent was taken and the disclosure of uncommon complications. The most important factors related to communication and rapport between clinician and patients, as opposed to procedure- or complication-specific items. A majority of patients preferred risks to be described using proportional descriptors, rather than percentage or non-numeric descriptors. CONCLUSIONS: Risk tolerance and desired level of disclosure varies for each patient and should not be presumed to be covered by standardized proformas. We suggest an individualized approach, taking into account each patient's background, understanding, and needs, is crucial for consent. Communications skills must be prioritized to ensure patient satisfaction and reduced risk of litigation.

Fourteen-month-olds' sensitivity to acoustic salience in minimal pair word learning.

During the first two years of life, infants concurrently refine native-language speech categories and word learning skills. However, in the Switch Task, 14-month-olds do not detect minimal contrasts in a novel object-word pairing (Stager & Werker, 1997). We investigate whether presenting infants with acoustically salient contrasts (liquids) facilitates success in the Switch Task. The first two experiments demonstrate that acoustic differences boost infants' detection of contrasts. However, infants cannot detect the contrast when the segments are digitally shortened. Thus, not all minimal contrasts are equally difficult, and the acoustic properties of a contrast matter in word learning.

Nine-month-olds use frequency of onset clusters to segment novel words.

Before their first birthday, infants have started to identify and use information about their native language, such as frequent words, transitional probabilities, and co-occurrence of segments (phonotactics), to identify viable word boundaries. These cues can then be used to segment new words from running speech. We explored whether infants are capable of detecting a novel word form using the frequency of occurrence of the onset alone to further characterize the role of phonotactics in speech segmentation. Experiment 1 shows that English-learning 9-month-olds can successfully segment a word from natural speech if the onset is legal in English (i.e., pleet) but not if the onset is illegal (i.e., tleet). Experiment 2 shows that English-learning 9-month-olds are successful at word segmentation when presented with two onset clusters that vary in statistical frequency. Infants familiarized to a high-frequency onset (i.e., trom) were successful at segmenting the target word embedded in speech, but those familiarized to the low-frequency onset (i.e., drom) were unsuccessful. Together, these results show that infants use statistical information from the speech input and that low levels of exposure to onset phonotactics alone might not be sufficient in identifying word boundaries.

Treating insomnia in people who are incarcerated: a feasibility study of a multicomponent treatment pathway.

Around 60% of people who are incarcerated have insomnia; 6-10 times more prevalent than the general population. Yet, there is no standardized, evidence-based approach to insomnia treatment in prison. We assessed the feasibility of a treatment pathway for insomnia in a high-secure prison to inform a future randomized controlled trial (RCT) and initial efficacy data for sleep and mental health outcomes. We used a within-participants pre-post design. The stepped-care pathway included: self-management with peer support, environmental aids, and cognitive behavioral therapy for insomnia (CBTi). Assessment measures for insomnia, well-being, mood, anxiety, suicidality, overall health, sleepiness, fatigue, and cognitive functioning were administered at baseline and pathway exit. Feasibility criteria included eligibility to participate, CBTi uptake, and assessment completion. Forty-two adult males who are incarcerated were approached of which 95.2% were eligible. Of those deemed eligible, most participated (36/40, 90.0%). Most who completed baseline completed post-assessments (28/36, 77.8%) and of these, most showed improvements in their subjective sleep (27/28, 96.4%). Large reductions were found from pre- to posttreatment in insomnia severity (d = -1.81, 95% CI: 8.3 to 12.9) and 57.0% reported no clinically significant insomnia symptoms at post-assessment. There was no overall change in actigraphy-measured sleep. Large treatment benefits were found for depression, anxiety, well-being, and cognitive functioning, with a medium benefit on suicidal ideation. The treatment pathway for insomnia in prison was feasible and may be an effective treatment for insomnia in people who are incarcerated, with additional promising benefits for mental health. A pragmatic RCT across different prison populations is warranted. This paper is part of the Sleep and Circadian Health in the Justice System Collection.

Factors influencing patient decision-making to undergo shoulder arthroplasty.

Aims: Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients' decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research. Methods: Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached. Results: Two overall categories emerged: the motivations to consider surgery, and the information participants used to inform their decision-making. Motivations were, broadly, the relief of pain and the opportunity to get on with life and regain independence. When participants' symptoms and restrictions prevented them enjoying life to a sufficient extent, this provided the motivation to proceed with surgery. Younger participants tended to focus on maintaining employment and recreational activities, and older patients were eager to make the most of their remaining lifetime. Participants gathered information from a range of sources and were keen to optimize their recovery where possible. An important factor for participants was whether they trusted their surgeon and were prepared to delegate responsibility for elements of their care. Conclusion: Relief of pain and the opportunity to get on with life were the primary reasons to undergo shoulder arthroplasty. Participants highlighted the importance of the patient-surgeon relationship and the need for accurate information in an accessible format which is relevant to people of different ages and functional demands.

Acceptability of magnetic resonance imaging for prostate cancer diagnosis with patients and GPs: a qualitative interview study.

BACKGROUND: Magnetic resonance imaging (MRI) of the prostate is a new, more accurate, non-invasive test for prostate cancer diagnosis. AIM: To understand the acceptability of MRI for patients and GPs for prostate cancer diagnosis. DESIGN AND SETTING: Qualitative study of men who had undergone a prostate MRI for possible prostate cancer, and GPs who had referred at least one man for possible prostate cancer in the previous 12 months in West London and Devon. METHOD: Semi-structured interviews, conducted in person or via telephone, were audio-recorded and transcribed verbatim. Deductive thematic analysis was undertaken using Sekhon's Theoretical Framework of Acceptability, retrospectively for patients and prospectively for GPs. RESULTS: Twenty-two men (12 from Devon, age range 47-80 years), two patients' partners, and 10 GPs (6 female, age range 36-55 years) were interviewed. Prostate MRI was broadly acceptable for most patient participants, and they reported that it was not a significant undertaking to complete the scan. GPs were more varied in their views on prostate MRI, with a broad spectrum of knowledge and understanding of prostate MRI. Some GPs expressed concerns about additional clinical responsibility and local availability of MRI if direct access to prostate MRI in primary care were to be introduced. CONCLUSION: Prostate MRI appears to be acceptable to patients. Some differences were found between patients in London and Devon, mainly around burden of testing and opportunity costs. Further exploration of GPs' knowledge and understanding of prostate MRI could inform future initiatives to widen access to diagnostic testing in primary care.