Quality of life and family functioning 12 months after diagnosis of childhood brain tumour: A longitudinal cohort study.

BACKGROUND: The wellbeing of a child with brain tumour is affected by several factors. We present the first investigation of quality of life and family functioning in a parent and child across the first 12 months after diagnosis, examining potential factors to guide the provision of psychosocial resources to families who most need them. PROCEDURE: Data were collected from parents/carers in Queensland, Australia, from 2020 to 2023. Child (parent/carer-proxy reported) and carer quality of life was assessed across three timepoints (repeated measures analysis of variance [ANOVA]) and by five potential co-variates (mixed between-within ANOVA). Family functioning was assessed across two timepoints (repeated-measures t-test), and by potential co-variates (repeated measures ANOVA). Univariate relationships were explored with Pearson's correlation coefficient; significant relationships were entered into multiple regression models. RESULTS: Ninety-six diverse families were represented. Quality of life (child, carer) and family functioning did not change across time. Children from households with lower income reported worse cognitive difficulties (p = .023) and pain and hurt (p = .013) than those from a higher income. Caregiver quality of life was poorer for those whose child had received chemotherapy and/or radiation, was aged less than 4 years at diagnosis, and had a lower household income. At 12 months, caregiver quality of life was correlated with family functioning (r = -.45, p < .001), with positive adaptation being a significant key predictor (beta = -.66, p < .005). CONCLUSIONS: The following factors indicate a need for increased early psychosocial support: cognitive difficulties, aged <4 years at diagnosis, receiving chemotherapy and/or radiation, and low household income.

"Make it better for the women and babies who come after me": Findings from women in Australia completing the international Babies Born Better survey.

BACKGROUND: Woman-centered maternity service delivery is endorsed by Australian federal health policy. Despite this, little evaluation of maternity care is conducted through the lens of women. We examined the responses of women birthing in Australia to the international Babies Born Better 2018 (Version 2) open-response survey. METHODS: An online international survey was distributed primarily by means of social media for women who had given birth in the last 5 years. In addition to closed-ended questions to describe the sample, a series of open-ended questions recorded women's experiences and satisfaction with their maternity care and place of birth. RESULTS: Of 1249 women who reported birthing their most recent baby in Australia and speaking English, 84% responded to at least one open-ended evaluation question. We thematically analyzed the data to identify three related themes of safety, choice, and respect for women. Women's experiences of these were closely tied to their model of care; those birthing at home with a private midwife more so reported positive experiences than those discussing obstetric care or, to a lesser extent, midwifery-led care in a hospital. There was a strong preference and need for (1) access to affordable care with a known practitioner from early pregnancy to postpartum, and (2) individualized care with the removal of restrictive hospital policies not aligned with woman-centered practice. DISCUSSION: This is the first Australian national study of women's maternity experiences and evaluations. Consistent with previous state-based research, women birthing in Australia continue to report maternity "care" that is physically and emotionally harmful. They also stated a need to address the psychosocial aspects of becoming a mother, in addition to the biological ones. Women and other birthing people must be at the center of defining quality maternity health service delivery, and services must be accountable for preventing and addressing harm, as defined by all birthing people.

Hyperglycaemia following immune checkpoint inhibitor therapy-Incidence, aetiology and assessment.

AIMS: We systematically studied the presence of hyperglycaemia during treatment with Immune Checkpoint Inhibitors (ICPI) for cancer, in those with and without diabetes at baseline, and determined the cause of new-onset hyperglycaemia, METHODS: Retrospective review of electronic records of those receiving an ICPI for melanoma, lung or renal cancer. RESULTS: Overall, 959 participants were included. In this study, 103 had diabetes at baseline (10.7%). Those with lung cancer had the highest frequency of diabetes; 131 people had hyperglycaemia (defined as at least one glucose ≥11.1 mmol/L) in the year after starting an ICPI. The incidence was 55% in those with diabetes at baseline, and 8.6% in those without baseline diabetes. Among 74 with new-onset hyperglycaemia (without pre-existing diabetes) 76% was attributable to steroid induced diabetes, with 9.5% due to ICPI Induced diabetes resembling type 1 diabetes. CONCLUSIONS: Hyperglycaemia is common in persons receiving an ICPI for cancer, including 8.6% of those without known diabetes. While much of this is due to glucocorticoid use, care is needed to avoid missing those with ICPI-induced diabetes who are at risk of diabetic ketoacidosis, which is a medical emergency.

Supporting families through paediatric brain tumour: Unmet needs and suggestions for change.

OBJECTIVE: From diagnosis and beyond, a paediatric brain tumour and its treatment impact the child and their family in a myriad of ways. While it is considered best practice to offer ongoing psychosocial support for all family members, there is little scholarly investigation of both families' experiences and the practical implications of offering such care. We aimed to explore families' experiences of paediatric brain tumour and their associated psychosocial health service needs. METHODS: Families receiving care at the Queensland Children's Hospital in Brisbane, Australia, for a child (0-18 years) who had been diagnosed with a brain tumour between 2019 and 2022 were invited to be interviewed about their experiences. Using qualitative description, we analysed these interviews to identify families' unmet psychosocial health service needs and their suggestions for improvement. RESULTS: Twenty-three clinically and socially diverse families were represented. While parents/carers expressed gratitude for the care their child had received, most also described unmet needs for the broader family. We identified three primary needs to be addressed: (1) parents want accessible psychological/emotional support for themselves; (2) parents/carers want additional guidance to navigate the hospital setting to reduce uncertainty and loss of control; and (3) parents want support to minimise treatment-associated trauma for their child. CONCLUSIONS: Our findings evidence the need for improved family-centred psychosocial care within paediatric brain tumour care in Queensland, Australia. We propose a counselling and care coordination intervention to support parents/carers to care for themselves, their child, and their family through an extremely challenging experience.

What are the predictors of TOMM failure in clinical TBI populations? A retrospective analysis.

OBJECTIVES: To determine base rates of invalid performance on the Test of Memory Malingering (TOMM) in patients with traumatic brain injury (TBI) undertaking rehabilitation who were referred for clinical assessment, and the factors contributing to TOMM failure. METHODS: Retrospective file review of consecutive TBI referrals for neuropsychological assessment over seven years. TOMM failure was conventionally defined as performance <45/50 on Trial 2 or Retention Trial. Demographic, injury, financial compensation, occupational, and medical variables were collected. RESULTS: Four hundred and ninety one TBI cases (Median age = 40 years [IQR = 26-52], 79% male, 82% severe TBI) were identified. Overall, 48 cases (9.78%) failed the TOMM. Logistic regression analyses revealed that use of an interpreter during the assessment (adjusted odds ratio [aOR] = 8.25, 95%CI = 3.96-17.18), outpatient setting (aOR = 4.80, 95%CI = 1.87-12.31) and post-injury psychological distress (aOR = 2.77, 95%CI = 1.35-5.70) were significant multivariate predictors of TOMM failure. The TOMM failure rate for interpreter cases was 49% (21/43) in the outpatient setting vs. 7% (2/30) in the inpatient setting. By comparison, 9% (21/230) of non-interpreter outpatient cases failed the TOMM vs. 2% (4/188) of inpatient cases. CONCLUSIONS: TOMM failure very rarely occurs in clinical assessment of TBI patients in the inpatient rehabilitation setting. It is more common in the outpatient setting, particularly in non-English-speaking people requiring an interpreter. The findings reinforce the importance of routinely administering stand-alone performance validity tests in assessments of clinical TBI populations, particularly in outpatient settings, to ensure that neuropsychological test results can be interpreted with a high degree of confidence.

Implementing a home-based virtual hypertension programme-a pilot feasibility study.

INTRODUCTION: Implementing a health system-based hypertension programme may lower blood pressure (BP). METHODS: We performed a randomized, controlled pilot study to assess feasibility, acceptability, and safety of a home-based virtual hypertension programme integrating evidence-based strategies to overcome current barriers to BP control. Trained clinical pharmacists staffed the virtual collaborative care clinic (vCCC) to remotely manage hypertension using a BP dashboard and phone "visits" to monitor BP, adherence, side effects of medications, and prescribe anti-hypertensives. Patients with uncontrolled hypertension were identified via electronic health records. Enrolled patients were randomized to either vCCC or usual care for 3 months. We assessed patients' home BP monitoring behaviour, and patients', physicians', and pharmacists' perspectives on feasibility and acceptability of individual programme components. RESULTS: Thirty-one patients (vCCC = 17, usual care = 14) from six physician clinics completed the pilot study. After 3 months, average BP decreased in the vCCC arm (P = 0.01), but not in the control arm (P = 0.45). The vCCC participants measured BP more (9.9 vs. 1.2 per week, P < 0.001). There were no intervention-related adverse events. Participating physicians (n = 6), pharmacists (n = 5), and patients (n = 31) rated all programme components with average scores of >4.0, a pre-specified benchmark. Nine adaptations in vCCC design and delivery were made based on potential barriers to implementing the programme and suggestions. CONCLUSION: A home-based virtual hypertension programme using team-based care, technology, and a logical integration of evidence-based strategies is safe, acceptable, and feasible to intended users. These pilot data support studies to assess the effectiveness of this programme at a larger scale.

Pre-transplant cognitive screening is a poor predictor of post-transplant cognitive status.

INTRODUCTION: Transplant centers hesitate to transplant patients with cognitive impairment. It is unclear if pre-kidney transplant (KT) cognitive screening can predict post-KT cognitive function. METHODS: We evaluated pre- to post-KT cognitive function with the Montreal Cognitive Assessment (MoCA) in a cohort of 108 patients. We used an adjusted logistic regression model to assess pre- to post-KT changes in cognitive status (continuous variable) and a linear mixed model to assess changes in MoCA scores (categorical variable) pre- to post- KT. RESULTS: The average pre- and post-KT MoCA scores were 25.3 ± 3.0 and 26.4 ± 2.8, respectively. Final pre-KT score did not predict post-KT cognitive status (OR = 1.08; 95% CI: .92-1.26; P = .35). 32% of the patients with a final pre-KT score ≥26 had at least one post-KT score < 26. Conversely, 61% of the patients with a final pre-KT score < 26 had at least one post KT score ≥26. In the linear mixed model analysis, the final pre-KT score was associated with a small, clinically insignificant (ß = .34; 95% CI: .19-.49; P < .001) effect on the post-KT score. CONCLUSION: A low pre-KT MoCA score is not a strong independent predictor of post-KT cognitive function and should not preclude patients from receiving a KT.

Incidental posterior rib hyperostosis on chest CT: incidence and etiology.

OBJECTIVE: Incidental rib hyperostosis is defined as asymmetric cortical thickening and sclerosis of the medial posterior ribs and is important because it may lead to unnecessary laboratory testing, additional imaging and occasionally biopsy. The purpose of this study is to identify the incidence of rib hyperostosis within different patient groups known to have an increased propensity towards osteophyte formation and ankylosis. METHODS: This study was a retrospective cohort study reviewing chest CT examinations in a control group of patients over 50 years old and three different patient populations: psoriatic arthritis, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis (DISH). Each CT was evaluated by an attending musculoskeletal and cardiothoracic radiologist to identify rib hyperostosis, osteophyte formation, ankylosis, and spinal curvature. Two senior radiology residents also performed consensus reads and inter-reader reliability was calculated between the two groups. RESULTS: Two hundred eighty-two individuals were included in the study of which 38 (13.5%) had at least one hyperostotic rib. The ankylosing spondylitis population and the DISH population had the highest incidence of rib hyperostosis with a relative risk of 5.6 (p = 0.012) and 5.3 (p = < 0.001) when compared to the control group. There was good inter-reader reliability for the presence of rib hyperostosis with a kappa estimate of 0.739. CONCLUSION: Incidentally detected rib hyperostosis is most likely the sequela of abnormal stress on the ribs secondary to rib hypomobility from fusion at the costovertebral joint. The incidence of rib hyperostosis is markedly increased in the DISH and ankylosis spondylitis study populations.

Immune landscape, evolution, hypoxia-mediated viral mimicry pathways and therapeutic potential in molecular subtypes of pancreatic neuroendocrine tumours.

OBJECTIVE: A comprehensive analysis of the immune landscape of pancreatic neuroendocrine tumours (PanNETs) was performed according to clinicopathological parameters and previously defined molecular subtypes to identify potential therapeutic vulnerabilities in this disease. DESIGN: Differential expression analysis of 600 immune-related genes was performed on 207 PanNET samples, comprising a training cohort (n=72) and two validation cohorts (n=135) from multiple transcriptome profiling platforms. Different immune-related and subtype-related phenotypes, cell types and pathways were investigated using different in silico methods and were further validated using spatial multiplex immunofluorescence. RESULTS: The study identified an immune signature of 132 genes segregating PanNETs (n=207) according to four previously defined molecular subtypes: metastasis-like primary (MLP)-1 and MLP-2, insulinoma-like and intermediate. The MLP-1 subtype (26%-31% samples across three cohorts) was strongly associated with elevated levels of immune-related genes, poor prognosis and a cascade of tumour evolutionary events: larger hypoxic and necroptotic tumours leading to increased damage-associated molecular patterns (viral mimicry), stimulator of interferon gene pathway, T cell-inflamed genes, immune checkpoint targets, and T cell-mediated and M1 macrophage-mediated immune escape mechanisms. Multiplex spatial profiling validated significantly increased macrophages in the MLP-1 subtype. CONCLUSION: This study provides novel data on the immune microenvironment of PanNETs and identifies MLP-1 subtype as an immune-high phenotype featuring a broad and robust activation of immune-related genes. This study, with further refinement, paves the way for future precision immunotherapy studies in PanNETs to potentially select a subset of MLP-1 patients who may be more likely to respond.

The molecular biology of pancreatic neuroendocrine neoplasms: Challenges and translational opportunities.

Pancreatic neuroendocrine neoplasms (PanNENs) are rare, highly heterogeneous tumours. There have been significant recent advances in our knowledge of genomic events underlying their pathogenesis. However, treatment decisions remain largely based on tumour stage and grade which is inadequate, the current classification paradigm failing to capture the significant heterogeneity in tumour biology. There is a well-acknowledged unmet clinical need for novel biomarkers to enable individualised risk-adapted therapeutic strategies for PanNEN patients. Improvements in our understanding of the molecular biology of multiple solid tumours have led to the development of new biomarker assays and gene expression signatures to guide treatment decisions in other cancer types. A similar index for PanNENs, to improve patient prognostication and classification, would be highly clinically relevant and with advances in the field now seems potentially possible. This article will seek to review the molecular biology of PanNENs, the subtypes developed to date and the potential clinical opportunities these advances may afford.

Families' experiences of child and adolescent brain tumor: A systematic review and synthesis of qualitative research.

OBJECTIVES: Brain tumors are the most common and fatal of all solid tumors for children and adolescents; those who survive live with long-term physical and emotional consequences, as do their families. We aimed to synthesize relevant qualitative evidence on families' experiences and psychosocial service needs across the lifespan to identify gaps in care delivery and research. METHODS: Searches were conducted in Medline, CINAHL, PsycInfo, Embase, and Web of Science. Identified papers were assessed with the Joanna Briggs Institute Critical Appraisal Tool. Data were extracted into NVivo12 and analyzed by qualitative description and, where appropriate, thematic analysis. RESULTS: The search yielded 628 papers, of which 40 (33 studies) were eligible (6%). Although the methodological quality of the papers was low, we identified concerns that were consistently reported over time and from different perspectives. Individual family members had varying psychosocial needs to be addressed within healthcare, schooling, and public policy. These include for survivor's mental health (particularly for body image), and to the disproportionate biopsychosocial burden faced by mother-caregivers. CONCLUSIONS: Addressing the biological aspects of brain tumor cannot be our only focus. We have an obligation to provide services that meet the needs of families across diagnosis, treatment, survivorship, palliative care, and bereavement.

Fertility experiences in women reporting endometriosis: findings from the Understanding Fertility Management in Contemporary Australia survey.

PURPOSE: To examine the fertility experiences of women reporting and not reporting endometriosis in a population-based survey. MATERIALS AND METHODS: A cross-sectional survey among a community sample of 1543 women in Australia. Data were analysed to compare fertility management between women who did and did not report endometriosis. Factors associated with unintended pregnancy, infertility diagnosis, time to conception and live birth were identified through multivariable analyses. RESULTS: While individual contraceptive use did not differ by endometriosis status, avoiding pregnancy was less important to women reporting endometriosis (50.5%) than to others (68.7%; p < .001). Women reporting endometriosis were approximately three times more likely to report an infertility diagnosis-the majority (39.7%) of which were 'unexplained female or male infertility'-(p < .001) and six times more likely to report taking longer than 12 months to conceive than those who did not report endometriosis (p < .001). Although more women reporting a diagnosis of endometriosis also reported never having been pregnant (11.9%) than those who did not report a diagnosis (6.0%), this difference was not statistically significant (p = .060). There were also no endometriosis-associated differences in women's reports of unintended pregnancy, abortion, having been pregnant, or having had a live birth. CONCLUSIONS: Our findings counter the common assertion that women with endometriosis are unlikely to conceive, and support the need for health care and information that addresses all aspects of fertility management (not just infertility) for women with endometriosis.

Men's perceptions of prostate cancer diagnosis and care: insights from qualitative interviews in Victoria, Australia.

BACKGROUND: The Victorian Prostate Cancer Registry (Australia) revealed poorer rates of survival for men diagnosed with prostate cancer in one Victorian regional area than for men in metropolitan Melbourne. We sought to explore the perceptions and experiences of prostate cancer diagnosis, treatment, and care of men diagnosed with prostate cancer who lived in regional or metropolitan areas and of men who had not been so diagnosed. Our goal was to contribute to the evidence from which can be built continuing improvements in prostate health care. METHODS: Using the qualitative method of in-depth interviews to gain access to explanation and meaning, we interviewed 21 men: 10 recruited through the Prostate Cancer Outcome Registry-Victoria and 11 from the community. Transcripts were analysed thematically. RESULTS: We identified four main themes within which men discussed prostate cancer: Case-finding, Diagnosis, Treatment and Care, and Spreading the Word. Contrasts revealed between regional and metropolitan areas related mostly to the more limited supportive care in regional areas. CONCLUSIONS: It is evident from the perspectives of these men that every aspect of prostate cancer care would benefit from attention: publicising the need to check prostate health, treatment, and supporting men in the years after treatment. Continuing to work on systemic improvements is an important goal for all those committed to men's health.

Vascular, inflammatory, and metabolic factors associated with cognition in aging persons with chronic epilepsy.

We examined cognition in aging persons with chronic epilepsy; characterized targeted vascular, inflammatory, and metabolic risk factors associated with abnormal cognitive aging in the general population; and examined associations between cognition and vascular, inflammatory, and metabolic health. Participants included 40 persons with chronic localization-related epilepsy and 152 controls, aged 54.6 and 55.3, respectively. Participants underwent neuropsychological assessment, clinical examination, and fasting blood evaluation for quantification of vascular status (systolic and diastolic blood pressure, obesity/body mass index [BMI], total and high-density lipoprotein [HDL] cholesterol level, and homocysteine), inflammatory markers (high sensitivity C-reactive protein [hs-CRP], and interleukin-6 [IL-6]), and metabolic status (insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], glucose). Epilepsy participants exhibited impairment across all cognitive factor scores (all p's < 0.0001); abnormalities in BMI (p = 0.049), hs-CRP (p = 0.046), HOMA-IR (p = 0.0040), and fasting glucose (p = 0.03), with significant relationships between higher HOMA-IR with poorer Immediate Memory (p = 0.03) and Visuospatial Ability (0.03); elevated hs-CRP with poorer Visuospatial (p = 0.035) and Verbal Ability (p = 0.06); elevated BMI with poorer Speed/Flexibility (p = 0.04), Visuospatial (p = 0.001) and Verbal Ability (p = 0.02); and lower HDL with poorer Verbal Learning/Delayed Memory (p = 0.01), Speed/Flexibility (p = 0.043), and Working Memory (p = 0.008). Aging persons with chronic epilepsy exhibit multiple abnormalities in metabolic, inflammatory, and vascular health that are associated with poorer cognitive function.

Mortality and morbidity trends after the first year in survivors of acute myocardial infarction: a systematic review.

BACKGROUND: Most studies of outcomes after myocardial infarction (MI) focus on the acute phase after the index event. We assessed mortality and morbidity trends after the first year in survivors of acute MI, by conducting a systematic literature review. METHODS: Literature searches were conducted in Embase, MEDLINE, and the Cochrane Database of Systematic Reviews to identify epidemiological studies of long-term (>10 years) mortality and morbidity trends in individuals who had experienced an acute MI more than 1 year previously. RESULTS: Thirteen articles met the inclusion criteria. Secular trends showed a consistent decrease in mortality and morbidity after acute MI from early to more recent study periods. The relative risk for all-cause death and cardiovascular outcomes (recurrent MI, cardiovascular death) was at least 30% higher than that in a general reference population at both 1-3 years and 3-5 years after MI. Risk factors leading to worse outcomes after MI included comorbid diabetes, hypertension and peripheral artery disease, older age, reduced renal function, and history of stroke. CONCLUSIONS: There have been consistent improvements in secular trends for long-term survival and cardiovascular outcomes after MI. However, MI survivors remain at higher risk than the general population, particularly when additional risk factors such as diabetes, hypertension, or older age are present.

Clinicians' perceptions of women's experiences of endometriosis and of psychosocial care for endometriosis.

BACKGROUND: Endometriosis is a complex, chronic condition with known psychological and social implications for women. Little is known about clinicians' perceptions of the psychosocial aspects of endometriosis and associated care. AIM: To describe clinicians' perceptions of women's experiences of living with endometriosis and of the provision of psychosocial care for endometriosis. MATERIALS AND METHODS: A qualitative approach was taken using semi-structured interviews with eight gynaecologists and four general practitioners who provide care to women with endometriosis in Victoria, conducted by telephone and in person from June to December 2014. RESULTS: Clinicians' perceptions of women's experiences of endometriosis were consistent with those reported by women, particularly when discussing potential infertility. However, less comprehensive descriptions of the effects of endometriosis on women's work and social life and intimate relationships were observed. Some clinicians asserted that endometriosis is caused by poor mental health. General practitioners positioned themselves as best placed to provide psychosocial care to women with endometriosis; gynaecologists suggested various potential providers but rarely themselves. Most clinicians assessed themselves as not being adequately trained to understand and provide care for the psychosocial aspects of endometriosis; half of the gynaecologists did not believe it was necessary for them to do so. CONCLUSIONS: The findings of this research demonstrate clinicians' need for further support in the provision of psychosocial care for women with endometriosis, potentially through expanded clinical guidelines and professional development opportunities.

Identification of biological pathways regulated by PGRN and GRN peptide treatments using transcriptome analysis.

Mutations in progranulin (PGRN) have been linked to two neurodegenerative disorders, heterozygote mutations with frontotemporal lobar degeneration (FTLD) and homozygote mutations with neuronal ceroid lipofuscinosis (NCL). Human PGRN is 593aa secreted growth factor, made up of seven and a half repeats of a highly conserved granulin motif that is cleaved to produce the granulin peptides A-G and paragranulin. While it is thought that PGRN protects against neurodegeneration through its role in inflammation and tissue repair, the role of PGRN and granulins in the nervous system is currently unclear. To better understand this, we prepared recombinant PGRN, granulin A-F and paragranulin, and used these to treat differentiated neuronal SH-SY5Y cells. Using RNA sequencing and bioinformatics techniques we investigated the functional effects of PGRN and the individual granulins upon the transcriptome. For PGRN treatment we show that the main effect of short-duration treatments is the down-regulation of transcripts, supporting that signalling pathway induction appears to be dominant effect. Gene ontology analysis, however, also supports the regulation of biological processes such as the spliceosome and proteasome in response to PGRN treatment, as well as the lysosomal pathway constituents such as CHMP1A, further supporting the role of PGRN in lysosomal function. We also show that the response to granulin treatments involves the regulation of numerous non-coding RNA's, and the granulins cluster into groups of similar activity on the basis of expression profile with paragranulin and PGRN having similar expression profiles, while granulins B, D, E and G appear more similar.