Variation in UK fracture liaison service consultation conduct and content before and during the COVID pandemic: results from the iFraP-D UK survey.

We conducted a survey of FLSs' consultation conduct and content which identified marked variation in whether FLS HCPs discussed osteoporosis medicine with patients. A review of service pro formas showed more content related to 'investigating' and 'intervening' than to 'informing'. We propose an expanded FLS typology and model FLS pro forma. PURPOSE: To investigate the nature of direct patient contact in fracture liaison service (FLS) delivery, examine the use and content of pro formas to guide information eliciting and sharing in FLS consultations, and determine service changes which were implemented as a result of the COVID-19 pandemic. METHODS: An electronic survey of UK FLS healthcare practitioners (HCPs) was distributed through clinical networks, social media, and other professional networks. Participants were asked to upload service pro formas used to guide consultation content. Documentary analysis findings were mapped to UK FLS clinical standards. RESULTS: Forty-seven HCPs responded, providing data on 39 UK FLSs, over half of all 74 FLSs reporting to FLS-database. Results showed variation in which HCP made clinical decisions, whether medicines were discussed with patients or not, and in prescribing practice. Services were variably affected by COVID, with most reporting a move to more remote consulting. The documentary analysis of eight service pro formas showed that these contained more content related to 'investigating' and 'intervening', with fewer pro formas prompting the clinician to offer information and support (e.g., about coping with pain). Based on our findings we propose an expanded FLS typology and have developed a model FLS pro forma. CONCLUSION: There is marked variation in the delivery of services and content of consultations in UK FLSs including discussion about osteoporosis medications. Clinical standards for FLSs should clarify the roles of primary and secondary HCPs and the importance of holistic approaches to patient care.

"We are not a typical family anymore": Exploring the experiences and support needs of fathers of children with Fragile X syndrome in Australia.

A diagnosis of the X-linked condition Fragile X syndrome (FXS) in a child commonly reveals the mother's carrier status. Previous research focused on the genetic counseling process for the child and maternal family, despite calls for more research on the support needs of fathers. This study explored experiences and support needs of fathers at least 1 year after their child's FXS diagnosis to understand barriers and enablers and optimize health outcomes for the family. In-depth interviews were conducted with 11 fathers recruited through the Australian Genetics of Learning Disability Service and the Fragile X Association. Deidentified transcripts were analyzed using thematic analysis guided by an inductive approach. Four themes emerged: (1) making life easier through understanding-yesterday and today, (2) the path to a new normal-today and tomorrow, (3) seeking information and support, and (4) what men want. Fathers reported diagnostic odysseys, postdiagnostic grief, and challenges adjusting. They highlighted difficulties in understanding their child's unique behaviors and needs, responding to their partner's psychological support needs, planning for their child's future, and navigating complex health and disability systems. Participants suggested health professionals facilitate father-to-father support and psychological counseling. These findings highlight the unmet needs of fathers and suggest that a strengths-based approach is critically important given the recognized mental health impact.

Current and Emerging Imaging Techniques for Neurofibromatosis Type 1-Associated Cutaneous Neurofibromas.

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.

Clinical and imaging modality factors impacting radiological interpretation of breast screening in young women with neurofibromatosis type 1.

Young women with Neurofibromatosis type 1 (NF1) have a high risk of developing breast cancer and poorer survival following breast cancer diagnosis. International guidelines recommend commencing breast screening between 30 and 35 years; however, the optimal screening modality is unestablished, and previous reports suggest that breast imaging may be complicated by the presence of intramammary and cutaneous neurofibromas (cNFs). The aim of this study was to explore potential barriers to implementation of breast screening for young women with NF1.Twenty-seven women (30-47 years) with NF1 completed breast screening with breast MRI, mammogram and breast ultrasound. Nineteen probably benign/suspicious lesions were detected across 14 women. Despite the presence of breast cNFs, initial biopsy rate for participants with NF1 (37%), were comparable to a BRCA pathogenic variant (PV) cohort (25%) (P = 0.311). No cancers or intramammary neurofibromas were identified. Most participants (89%) returned for second round screening.The presence of cNF did not affect clinician confidence in 3D mammogram interpretation, although increasing breast density, frequently seen in young women, impeded confidence for 2D and 3D mammogram. Moderate or marked background parenchymal enhancement on MRI was higher in the NF1 cohort (70.4%) than BRCA PV carriers (47.3%), which is an independent risk factor for breast cancer.Breast MRI was the preferred mode of screening over mammogram, as the majority (85%) with NF1 demonstrated breast density (BI-RADS 3C/4D), which hinders mammogram interpretation. For those with high breast density and high cNF breast coverage, 3D rather than 2D mammogram is preferred, if MRI is unavailable.

Exploring the impact of the reclassification of a hereditary cancer syndrome gene variant: emerging themes from a qualitative study.

The complexity of genetic variant interpretation means that a proportion of individuals who undergo genetic testing for a hereditary cancer syndrome will have their test result reclassified over time. Such a reclassification may involve a clinically significant upgrade or downgrade in pathogenicity, which may have significant implications for medical management. To date, few studies have examined the psychosocial impact of a reclassification in a hereditary cancer syndrome context. To address this gap, semi-structured telephone interviews were performed with eighteen individuals who had a BRCA1, BRCA2 or Lynch syndrome-related (MLH1, MSH2, MSH6 or PMS2) gene variant reclassified. The interviews were analysed utilising an inductive, qualitative approach and emergent themes were identified by thematic analysis. Variable levels of recall amongst participants were found. Common motivations for initial testing included a significant personal and/or family history of cancer and a desire to "find an answer". No individual whose uncertain result was upgraded reported negative psychosocial outcomes; most reported adapting to their reclassified result and appraised their genetic testing experience positively. However, individuals whose likely pathogenic/pathogenic results were downgraded reported feelings of anger, shock and sadness post reclassification, highlighting that additional psychosocial support may be required for some. Genetic counselling issues and recommendations for clinical practice are outlined.

Expanding the Australian Newborn Blood Spot Screening Program using genomic sequencing: do we want it and are we ready?

Since the introduction of genome sequencing in medicine, the factors involved in deciding how to integrate this technology into population screening programs such as Newborn Screening (NBS) have been widely debated. In Australia, participation in NBS is not mandatory, but over 99.9% of parents elect to uptake this screening. Gauging stakeholder attitudes towards potential changes to NBS is vital in maintaining this high participation rate. The current study aimed to determine the knowledge and attitudes of Australian parents and health professionals to the incorporation of genomic sequencing into NBS programs. Participants were surveyed online in 2016 using surveys adapted from previous studies. The majority of parents (90%) self-reported some knowledge of NBS, with 77% expressing an interest in NBS using the new technology. This was significantly lower than those who would utilise NBS using current technologies (99%). Although, many health professionals (62%) felt that new technologies should currently not be used as an adjunct to NBS, 79% foresaw the use of genomic sequencing in NBS by 2026. However, for genomic sequencing to be considered, practical and technical challenges as well as parent information needs were identified including the need for accurate interpretation of data; pre-and post-test counselling; and appropriate parental consent and opt-out process. Therefore, although some support for implementing genomic sequencing into Australian NBS does exist, there is a need for further investigation into the ethical, social, legal and practical implications of introducing this new technology as a replacement to current NBS methods.

Characterization of health concerns in people with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis 1 (NF1) is a common cancer predisposition syndrome. Affected individuals require lifelong surveillance and often suffer progressive disfigurement due to cutaneous neurofibromas. The aim of this research was to characterize health concerns and quality of life (QOL) in a population cohort. METHODS: An online survey was completed by 68 adults and 32 parents of children with NF1, and 60 controls. The survey included the Skindex-29 QOL scale, 5D-itch scale, and additional health questions. RESULTS: Frequency of itch was high in children (50%) and adults (69%), with most expressing interest in treatment for itch. The presence of itch and increased visibility of NF1 were predictors of poorer QoL. Many adults (53%) and parents (44%) desired access to treatment to improve cosmetic appearance. Muscle weakness/tiredness was also prevalent amongst (60-70%) adults and children with NF1. Two-thirds of adults with NF1 reported limited awareness of NF1 services and poor knowledge of surveillance, particularly breast screening in young women. CONCLUSION: This study highlights the impact of NF1-related itch and visibility in adults and children with a need for cosmetic and itch treatment. The findings emphasize a need for strategies to promote awareness, and access to management and treatment of NF1 in adults.

Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese-American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia-broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with "frequent" neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aß phase = 0 (lacking detectable Aß plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer's disease neuropathology.

PHOENIX (Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays): protocol for a randomised, multicentre feasibility study.

INTRODUCTION: Two million out of the UK's 5 million routine diagnostic CT scans performed each year incorporate the thoracolumbar spine or pelvic region. Up to one-third reveal undiagnosed osteoporosis or vertebral fractures. We developed an intervention, Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays ('PHOENIX'), to facilitate early detection and management of osteoporosis in people attending hospitals for CT scans. METHODS AND ANALYSIS: A multicentre, randomised, pragmatic feasibility study. From the general CT-attending population, women aged ≥65 years and men aged ≥75 years attending for CT scans are invited to participate, via a novel consent form incorporating Fracture Risk Assessment (FRAX) questions. Those at increased 10-year risk (within the amber or red zones of the UK FRAX graphical outputs for further action) are block randomised (1:1:1) to (1) PHOENIX intervention, (2) active control or (3) usual care. The PHOENIX intervention comprises (i) retrieving the CT scans using the NHS Image Exchange Portal, (ii) Mindways QCT Pro software analysis of CT hip and spine none density with CT vertebral fracture assessment, (iii) sending the participants' general practitioner (GP) a clinical report including diagnosis, necessary investigations and recommended treatment. Baseline CT scans from groups 2 and 3 are assessed with the PHOENIX intervention only at study end. Assuming 25% attrition, the study is powered to find a predicted superior osteoporosis treatment rate with PHOENIX (20%) vs 16% among patients whose GPs were sent the FRAX questionnaire only (active control) and 5% in the usual care group. Five hospitals are participating to determine feasibility. The co-primary feasibility outcome measures are (a) ability to randomise 375 patients within 10 months and (b) retention of 75% of survivors, completing their 1-year bone health outcome questionnaire. Secondary 1-year outcomes include osteoporosis/vertebral fracture identification rates and osteoporosis treatment rates. Stakeholder acceptability and economic aspects are evaluated. ETHICS AND DISSEMINATION: Approved by committee (National Research Ethics Service) East of England (EE) as REF/19/EE/0176. Dissemination will be through the Royal Osteoporosis Society (to patients and public) as well as to clinician peers via national and international bone/rheumatology scientific and clinical meetings. TRIAL REGISTRATION NUMBER: ISRCTN14722819.

Evaluating the model of offering expanded genetic carrier screening to high school students within the Sydney Jewish community.

Programs offering reproductive genetic carrier screening (RGCS) to high school students within the Ashkenazi Jewish community in several countries including Canada and Australia have demonstrated high uptake and retention of educational messages over time. This study was undertaken to evaluate whether testing for an expanded number of conditions in a high school setting would impact the effectiveness of education. In this questionnaire-based study, genetic carrier testing for nine conditions was offered to 322 year 11 students from five high schools, with students attending a compulsory 1-h education session prior to voluntary testing. Comparison of pre- and post-education measures demonstrated a significant increase in knowledge, positive attitudes, and reduced concern immediately after the education session. Retention of knowledge, measures of positive attitude, and low concern over a 12-month period were significantly higher than baseline, although there was some reduction over time. In total, 77% of students exhibited informed choice regarding their intention to test. A significant increase in baseline knowledge scores and positive attitude was also demonstrated between our original 1995 evaluation (with testing for only one condition) and 2014 (testing for nine conditions) suggesting community awareness and attitudes to RGCS have increased. These findings validate the implementation of effective education programs as a key component of RGCS and are relevant as gene panels expand with the introduction of genomic technologies.

The psychological impact and experience of breast cancer screening in young women with an increased risk of breast cancer due to neurofibromatosis type 1.

Women with neurofibromatosis type 1 (NF1) have an increased risk of developing early breast cancer with a poorer prognosis compared to the general population. Therefore, international management guidelines recommend regular screening in women with NF1 starting from 30 to 35 years. As the psychological impacts of breast cancer screening in other high-risk populations cannot be extended to women with NF1, due to increased incidence of cognitive and mental health issues, the psychological harms of breast screening in women with NF1 are unknown. Consequently, the aim of this study was to assess the psychological impact of breast cancer screening in women with NF1 attending an established risk management clinic. Twenty-eight women with NF1 (30-50 years) completed psychological well-being and patient experience questionnaires, administered across five time points, before and after their initial and second round annual breast screening visits. Preliminary findings demonstrated the screening regimen was well-tolerated, with most participants reporting high satisfaction with the screening process. Overall, no significant increase in psychological distress related to the breast screening process was identified, with mean cancer worry and anxiety scores decreasing over time. However, some women did experience negative aspects of screening and barriers to re-attendance at annual breast screening appointments. As some women with NF1 exhibited clinical levels of psychological distress prior to screening, efforts to identify those at risk and additional support to address concerns and expectations throughout the breast screening process may be beneficial.

Improving uptake of Fracture Prevention drug treatments: a protocol for Development of a consultation intervention (iFraP-D).

INTRODUCTION: Prevention of fragility fractures, a source of significant economic and personal burden, is hindered by poor uptake of fracture prevention medicines. Enhancing communication of scientific evidence and elicitation of patient medication-related beliefs has the potential to increase patient commitment to treatment. The Improving uptake of Fracture Prevention drug treatments (iFraP) programme aims to develop and evaluate a theoretically informed, complex intervention consisting of a computerised web-based decision support tool, training package and information resources, to facilitate informed decision-making about fracture prevention treatment, with a long-term aim of improving informed treatment adherence. This protocol focuses on the iFraP Development (iFraP-D) work. METHODS AND ANALYSIS: The approach to iFraP-D is informed by the Medical Research Council complex intervention development and evaluation framework and the three-step implementation of change model. The context for the study is UK fracture liaison services (FLS), which enact secondary fracture prevention. An evidence synthesis of clinical guidelines and Delphi exercise will be conducted to identify content for the intervention. Focus groups with patients, FLS clinicians and general practitioners and a usual care survey will facilitate understanding of current practice, and investigate barriers and facilitators to change. Design of the iFraP intervention will be informed by decision aid development standards and theories of implementation, behaviour change, acceptability and medicines adherence. The principles of co-design will underpin all elements of the study through a dedicated iFraP community of practice including key stakeholders and patient advisory groups. In-practice testing of the prototype intervention will inform revisions ready for further testing in a subsequent pilot and feasibility randomised trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from North West-Greater Manchester West Research Ethics Committee (19/NW/0559). Dissemination and knowledge mobilisation will be facilitated through national bodies and networks, publications and presentations. TRIAL REGISTRATION NUMBER: researchregistry5041.

Genetic counselors, patients', and carers' views on an Australian clinical genetics service information system.

The Genetic Information System (GIS) is an Australian database of family genetic information. This health information technology system has been used by all 31 publicly operated clinical genetics services across New South Wales (NSW) and the Australian Capital Territory (ACT) for over a decade. As these services are separated geographically, the linkage engendered by the GIS facilitates the services to operate as a virtual state-wide service. This study aimed to explore the views of genetic counselors, patients, and carers on the use and storage of family genetic information in the GIS. Data were collected using audio-recorded semi-structured telephone interviews with genetic counselors experienced with using the GIS and focus groups with past patients/carers of the services. Using thematic analysis, four themes were identified from genetic counselor participant interviews (n = 12): (a) Shared information is valuable; (b) inconsistent data entry provides a challenge; (c) perceived need for the GIS to be current and integrated with other health systems; and (d) future challenges and strategies for the GIS. Three themes were identified following three focus groups with consumer participants (n = 14): (a) access to family genetic information provides a 'clearer picture'; (b) support, but caution, concerning use of information for relatives' health care; and (c) stewardship of family information. Genetic counselors and consumers identified similar advantages and privacy concerns regarding the sharing of family genetic information and all participants wanted patients/carers to be better informed about the GIS early in the genetic counseling process. Consumers were reassured by genetics health professionals' stewardship of their information, but surprised the GIS was not available nationally or for private geneticists or certain non-genetic specialists. These findings may inform further development of the GIS and other clinical genetic databases and lead to increased patient/carer knowledge through education and resource development.

Helping young children understand inherited cancer predisposition syndromes using bibliotherapy.

Communication with children about hereditary conditions in the family can be difficult for parents. Yet, good communication strategies are leading determinants of adaptation and resilience. With inherited cancer predisposition syndromes that can affect young children such as Li-Fraumeni syndrome (LFS) and hereditary pheochromocytoma and paraganglioma syndrome (HPPS), genetic testing and subsequent surveillance in at-risk children is the optimal intervention. Given testing often commences early, providing children and their parents with appropriate genetic counseling and communication strategies is important for informed decision making. To inform such communication strategies, we used a bibliotherapeutic framework, where stories are delivered prescriptively (i.e., 'bibliotherapy'), to develop a psycho-educational resource for children aged 5-10 years old at risk of either LFS or HPPS. Illustrated storybooks for children were created based on models of developmental comprehension. To ascertain their experience, parents were invited to read a storybook to their child/ren and participate in semi-structured qualitative interviews. Transcripts were analyzed thematically using a general inductive approach. The bibliotherapeutic resource reportedly supported parents with communication about these issues without raising emotional distress in either themselves or their children. The key stages of a bibliotherapeutic interaction were facilitated by the use of this resource, and all parents reported that it would have been useful when their children were first tested and/or diagnosed. This study lays the foundation for the application of bibliotherapy as a psycho-educational intervention in genetic counseling and demonstrates that bibliotherapy may improve the process of communication between parents and children regarding pediatric-inherited cancer syndromes.

Developing a model Fracture Liaison Service consultation with patients, carers and clinicians: a Delphi survey to inform content of the iFraP complex consultation intervention.

Fracture Liaison Services are recommended to deliver best practice in secondary fracture prevention. This modified Delphi survey, as part of the iFraP (Improving uptake of Fracture Prevention drug Treatments) study, provides consensus regarding tasks for clinicians in a model Fracture Liaison Service consultation. PURPOSE: The clinical consultation is of pivotal importance in addressing barriers to treatment adherence. The aim of this study was to agree to the content of the 'model Fracture Liaison Service (FLS) consultation' within the iFraP (Improving uptake of Fracture Prevention drug Treatments) study. METHODS: A Delphi survey was co-designed with patients and clinical stakeholders using an evidence synthesis of current guidelines and content from frameworks and theories of shared decision-making, communication and medicine adherence. Patients with osteoporosis and/or fragility fractures, their carers, FLS clinicians and osteoporosis specialists were sent three rounds of the Delphi survey. Participants were presented with potential consultation content and asked to rate their perception of the importance of each statement on a 5-point Likert scale and to suggest new statements (Round 1). Lowest rated statements were removed or amended after Rounds 1 and 2. In Round 3, participants were asked whether each statement was 'essential' and percentage agreement calculated; the study team subsequently determined the threshold for essential content. RESULTS: Seventy-two, 49 and 52 patients, carers and clinicians responded to Rounds 1, 2 and 3 respectively. One hundred twenty-two statements were considered. By Round 3, consensus was reached, with 81 statements deemed essential within FLS consultations, relating to greeting/introductions; gathering information; considering therapeutic options; eliciting patient perceptions; establishing shared decision-making preferences; sharing information about osteoporosis and treatments; checking understanding/summarising; and signposting next steps. CONCLUSIONS: This Delphi consensus exercise has summarised for the first time patient/carer and clinician consensus regarding clearly defined tasks for clinicians in a model FLS consultation.

Frailty and neuropathology in relation to dementia status: the Cambridge City over-75s Cohort study.

OBJECTIVE: To examine the relative contributions of frailty and neuropathology to dementia expression in a population-based cohort study. DESIGN: Cross-sectional analysis of observational data. SETTING: Population-representative clinicopathological cohort study. PARTICIPANTS: Adults aged 75+ recruited from general practice registries in Cambridge, UK, in 1985. MEASUREMENTS: A 39-item frailty index and 15-item neuropathological index were used to operationalize frailty and neuropathology, respectively. Dementia status was ascertained by clinical consensus at time of death. Relationships were evaluated using logistic regression models in participants with autopsy records (n = 183). Model fit was assessed using change in deviance. Population attributable fraction for frailty was evaluated in relation to dementia incidence in a representative sample of the survey participants (n = 542). RESULTS: Participants with autopsy were 92.3 ± 4.6 years at time of death, and mostly women (70%). Average frailty index value at last survey before death was 0.34 ± 0.16. People with dementia (63% of the sample) were frailer, had lower MMSE scores, and a higher burden of neuropathology. Frailty and neuropathological burden were significantly and independently associated with dementia status, without interaction; frailty explained an additional 3% of the variance in the model. Assuming a causal relationship and based on population-attributable fraction analyses, preventing severe frailty (Frailty Index ≥ 0.40) could have avoided 14.2% of dementia cases in this population-based cohort. CONCLUSIONS: In the very old, frailty contributes to the risk for dementia beyond its relationship with the burden of traditional dementia neuropathologies. Reducing frailty could have important implications for controlling the burden of dementia. Future research on frailty interventions should include dementia risk as a key outcome, public health interventions and policy decisions should consider frailty as a key risk factor for dementia, and biomedical research should focus on elucidating shared mechanisms of frailty and dementia development.

Waiting for a diagnosis in Rubinstein-Taybi: The journey from "ignorance is bliss" to the value of "a label".

The journey to receiving a diagnosis for rare genetic disease can be long and emotionally impactful. This study describes parental experiences of receiving their child's diagnosis of Rubinstein-Taybi syndrome (RTS), a rare genetic condition characterized by growth and developmental delay together with dysmorphic features. Parents from the RTS Australia support group participated in qualitative, semi-structured phone interviews, which were transcribed verbatim and thematically analyzed. Questions focused on psychosocial challenges and benefits pre and post-diagnosis. Ten mothers and three fathers participated, with the mean age of diagnosis being 8 months. Parents reported positive psychological effects from a slight delay in diagnosis, and negative effects from an extended diagnostic delay, suggesting the ideal time for a parent to receive a diagnosis lies in the post attachment stage, prior to the development of significant parental concerns. This stage would vary depending on condition severity. Parents desired a diagnosis to reduce uncertainty; however, uncertainty remained post diagnosis, and shifted its focus from broadly encompassing etiology and prognosis, to specifically focusing on concerns regarding severity within the spectrum. Perceived benefits of a diagnosis mainly centered on the provision of a label. Parents articulated that a label increased social acceptance, enhanced coping, promoted communication, and improved access to medical, financial, and support services. This study provides insights into the experience of families prior to and following receipt of a diagnosis. It also highlights the possibility of an optimal time window to receive a diagnosis; in which bonding is maximized and parental distress is minimized.

Determining medical decision-making capacity in brain tumor patients: why and how?

BACKGROUND: Brain tumor patients are at high risk of impaired medical decision-making capacity (MDC), which can be ethically challenging because it limits their ability to give informed consent to medical treatments or participation in research. The European Association of Neuro-Oncology Palliative Care Multidisciplinary Task Force performed a systematic review to identify relevant evidence with respect to MDC that could be used to give recommendations on how to cope with reduced MDC in brain tumor patients. METHODS: A literature search in several electronic databases was conducted up to September 2019, including studies with brain tumor and other neurological patients. Information related to the following topics was extracted: tools to measure MDC, consent to treatment or research, predictive patient- and treatment-related factors, surrogate decision making, and interventions to improve MDC. RESULTS: A total of 138 articles were deemed eligible. Several structured capacity-assessment instruments are available to aid clinical decision making. These instruments revealed a high incidence of impaired MDC both in brain tumors and other neurological diseases for treatment- and research-related decisions. Incapacity appeared to be mostly determined by the level of cognitive impairment. Surrogate decision making should be considered in case a patient lacks capacity, ensuring that the patient's "best interests" and wishes are guaranteed. Several methods are available that may help to enhance patients' consent capacity. CONCLUSIONS: Clinical recommendations on how to detect and manage reduced MDC in brain tumor patients were formulated, reflecting among others the timing of MDC assessments, methods to enhance patients' consent capacity, and alternative procedures, including surrogate consent.

TDP-43 Related Neuropathologies and Phosphorylation State: Associations with Age and Clinical Dementia in the Cambridge City over-75s Cohort.

Pathologies associated with the Tar-DNA binding protein 43 KDa (TDP-43) are associated with neurodegenerative diseases and aging. Phosphorylation of cellular proteins is a well-accepted mechanism of biological control and can be associated with disease pathways. Phosphorylation state associated with TDP-43 associated pathology has not been investigated with respect to dementia status in a population representative sample. TDP-43 immunohistochemistry directed toward phosphorylated (TDP-43P) and unphosphorylated (TDP-43U) was assessed in sections of hippocampus and temporal cortex from 222 brains donated to the population representative Cambridge City over-75s Cohort. Relationships between dementia status and age at death for TDP-43 immunoreactive pathologies by phosphorylation state were investigated. TDP-43 pathologies are common in the oldest old in the population and often do not conform to MacKenzie classification. Increasing age is associated with glial (TDP-43P) and neuronal inclusions (TDP-43P and TDP-43U), neurites, and granulovacuolar degeneration (GVD). Dementia status is associated with GVD and glial (TDP-43 P) and neural inclusions (TDP-43 P and U). Dementia severity was associated with glial (TDP-43P) and neuronal inclusions (TDP-43U and TDP-43P), GVD, and neurites. The associations between dementia severity and both glial cytoplasmic inclusions and GVD were independent from other pathologies and TDP-43 neuronal cytoplasmic inclusions. TDP-43 pathology contributes to dementia status and progression in a variety of ways in different phosphorylation states involving both neurons and glia, independently from age and from classic Alzheimer-related pathologies. TDP-43 pathologies as cytoplasmic inclusions in neurons or glia or as GVD contribute independently to dementia.

Pre-genetics clinic resource evaluation for adults with intellectual disability: The pre-genetics clinic aid.

People with intellectual disability (PWID) consistently identify the importance of health service information that is accessible and relevant. Resources tailored to the information and support needs of PWID can facilitate inclusivity in their health care (including access to genomic medicine) and improve healthcare outcomes. Despite the fact that PWID are commonly referred to genetics services, there is a lack of appropriate resources to help them prepare for their appointments. We therefore aimed to evaluate the feasibility and acceptability of a booklet for PWID to read with their carers prior to their genetics appointment, to help them prepare for what they may experience. With input from Easy to Read experts and PWID who were members of the New South Wales (NSW) Council for Intellectual Disability, the information booklet 'Getting ready for your visit to the genetics clinic' was produced. Australian healthcare professionals (HCP) familiar with clinical genetics services were invited to complete an anonymous online survey designed to assess perceived relevance, readability, and utility of the resource. Recruitment of HCPs was pursued via affiliated clinical services and email distribution through clinical genetics organizations. Sixty-six HCPs completed and submitted the survey. The results demonstrated that HCPs believed the booklet represented a typical clinical genetics service appointment and that the majority would provide a copy of the resource to clients and their carers. They reported that the booklet was easy to understand and entailed appropriate content and images which were presented clearly and simply. Some minor modifications were recommended and incorporated into the resource. A model of customizable booklets such as this could be transferrable across clinical genetics services and guide development of other resources for PWID. This may help to reduce healthcare disparities, improve client satisfaction, and facilitate involvement of PWID in their own healthcare decisions.