Public health qualifications, motivation, and experience of pharmacy professionals: exploratory cross-sectional surveys of pharmacy and public health professionals.

BACKGROUND: Pharmacy professionals (pharmacists and pharmacy technicians; PPs) are recognised for delivering public health interventions (micro level). There is increased policy focus on population health management, but limited knowledge regarding the role of PPs within UK's public health meso and macro levels. This study aimed to explore UK PPs' public health qualifications, specialisations, and motivations and barriers to pursuing advanced public health practice. METHODS: In this cross-sectional study, we developed and piloted two surveys, and we disseminated them separately via email to UK pharmacy and public health networks and social media, between June 19, and Oct 26, 2021. PPs with an interest or experience in public or population health were invited to participate in the study. We asked PPs questions about public health qualifications, specialisations, motivations, and barriers, and we also asked PHPs for opinions regarding the value of specialist public health skills for PPs. Numerical data were summarised, and responses collated into themes. NHS Health Research Authority tool identified ethics approval not required; and the questionnaire included consent request. FINDINGS: 128 PPs (85% pharmacists) and 54 PHPs responded. Of the PPs who responded, 90 (70%) were female and 35 (27%) were male; 62 (48%) were White British, 19 (14%) were Asian or Asian British, 14 (12%) were Black or Black British. They worked in primary care (34%, n=43), secondary care (26%, n=33), Community Pharmacy (13%, n=16), and public health bodies (13%, n=16). Overall, 34 (27%) of 128 PPs (32 pharmacists; 2 pharmacy technicians) possessed public health qualifications (MPH, PhD). Motivations for these qualifications were ambition to work as PP in public health PP (31%; 17/55 respondents), public health as alternative career (29%; 16/55), general interest (27%; 15/55) recommended or required for current role (11%; 6/55). Themes of barriers included limited training opportunities and poor career pathways. For the PHP survey, 36 (67%) of 54 were female and 16 (30%) were male. They worked as Consultants or Directors (28%, n=15), Registrars (24%, n=13), Practitioners (15%, n=8). 45 (87%) of 52 PHP respondents agreed that specialist PPs in public health would be beneficial to public health; 13 (45%) of 29 respondents recommended a public health Master's degree, eight (27%) recommended experience or postgraduate modules in health economics and health inequalities, three (10%) recommended credentialing for PPs to specialise. INTERPRETATION: Findings suggest responding PPs are motivated to advance in public health practice, despite barriers. Collaboration with PHPs and development of communities of practice might address barriers identified and contribute to advanced public health practice for PPs, supporting the increased focus on population health management in the UK. Limitations include the exploratory nature of the study, and the fact that PPs responding to public health surveys might be more motivated to advance in public health practice than those not responding. FUNDING: NHS England and UK Health Security Agency.

A pharmacy-led sore throat test and treat (STTT) service: antigen testing and antibiotic supply rates during the period of heightened public awareness of Group A Streptococcus infections.

BACKGROUND: Community pharmacies in Wales delivered an NHS-funded sore throat test and treat (STTT) service during the period of increased invasive Group A Streptococcus (iGAS) incidents in winter 2022-23. Service users were screened using FeverPAIN/CENTOR scores, offered GAS rapid antigen detection tests (RADT) if appropriate, and antibiotics if indicated. OBJECTIVES: To evaluate the service's response to a substantial rise in sore throat presentations during a period of heightened public anxiety. METHODS: Cross-sectional study with anonymized individual-level data from electronic pharmacy records of all eligible STTT service users, between January 2022 and March 2023. RESULTS: Antibiotics were supplied to 24% (95% CI: 23-24) of people who used the STTT service and 31% (95% CI: 31-32) of those who met the threshold for an RADT. Of 27 441 STTT consultations, 9308 (33.9%) occurred during December 2022. In the week commencing 2 December 2022, following the announcements of increased iGAS incidents, we observed a statistically significant increase of 1700 consultations (95% CI: 924-2476) and a statistically significant decrease in supply rate of 13.9 antibiotics per 100 RADT (95% CI: -18.40 to -9.40). Antibiotic supply rates increased thereafter to those observed before the announcements of iGAS incidents. Referral rates to other primary care or emergency settings remained below 10% throughout the study period. CONCLUSIONS: Our findings suggest that, despite a dramatic increase in sore throat consultation rates in response to media reports, the pre-specified pathway followed by pharmacists ensured appropriate use of antibiotics, and absorbed a substantial workload that would otherwise end up in other healthcare settings.

Impact of high-fat diet on cognitive behavior and central and systemic inflammation with aging and sex differences in mice.

Aging and age-related diseases are associated with cellular stress, metabolic imbalance, oxidative stress, and neuroinflammation, accompanied by cognitive impairment. Lifestyle factors such as diet, sleep fragmentation, and stress can potentiate damaging cellular cascades and lead to an acceleration of brain aging and cognitive impairment. High-fat diet (HFD) has been associated with obesity, metabolic disorders like diabetes, and cardiovascular disease. HFD also induces neuroinflammation, impairs learning and memory, and may increase anxiety-like behavior. Effects of a HFD may also vary between sexes. The interaction between Age- and Sex- and Diet-related changes in neuroinflammation and cognitive function is an important and poorly understood area of research. This study was designed to examine the effects of HFD on neuroinflammation, behavior, and neurodegeneration in mice in the context of aging or sex differences. In a series of studies, young (2-3 months) or old (12-13 months) C57BL/6J male mice or young male and female C57Bl/6J mice were fed either a standard diet (SD) or a HFD for 5-6 months. Behavior was assessed in Activity Chamber, Y-maze, Novel Place Recognition, Novel Object Recognition, Elevated Plus Maze, Open Field, Morris Water Maze, and Fear Conditioning. Post-mortem analyses assessed a panel of inflammatory markers in the plasma and hippocampus. Additionally, proteomic analysis of the hypothalamus, neurodegeneration, neuroinflammation in the locus coeruleus, and neuroinflammation in the hippocampus were assessed in a subset of young and aged male mice. We show that HFD increased body weight and decreased locomotor activity across groups compared to control mice fed a SD. HFD altered anxiety-related exploratory behavior. HFD impaired spatial learning and recall in young male mice and impaired recall in cued fear conditioning in young and aged male mice, with no effects on spatial learning or fear conditioning in young female mice. Effects of Age and Sex were observed on neuroinflammatory cytokines, with only limited effects of HFD. HFD had a more significant impact on systemic inflammation in plasma across age and sex. Aged male mice had induction of microglial immunoreactivity in both the locus coeruleus (LC) and hippocampus an effect that HFD exacerbated in the hippocampal CA1 region. Proteomic analysis of the hypothalamus revealed changes in pathways related to metabolism and neurodegeneration with both aging and HFD in male mice. Our findings suggest that HFD induces widespread systemic inflammation and limited neuroinflammation. In addition, HFD alters exploratory behavior in male and female mice, and impairs learning and memory in male mice. These results provide valuable insight into the impact of diet on cognition and aging pathophysiology.

Effects of residential acaricide treatments on patterns of pathogen coinfection in blacklegged ticks.

Medically important ixodid ticks often carry multiple pathogens, with individual ticks frequently coinfected and capable of transmitting multiple infections to hosts, including humans. Acquisition of multiple zoonotic pathogens by immature blacklegged ticks (Ixodes scapularis) is facilitated when they feed on small mammals, which are the most competent reservoir hosts for Anaplasma phagocytophilum (which causes anaplasmosis in humans), Babesia microti (babesiosis) and Borrelia burgdorferi (Lyme disease). Here, we used data from a large-scale, long-term experiment to ask whether patterns of single and multiple infections in questing nymphal I. scapularis ticks from residential neighbourhoods differed from those predicted by independent assortment of pathogens, and whether patterns of coinfection were affected by residential application of commercial acaricidal products. Quantitative polymerase chain reaction was used for pathogen detection in multiplex reactions. In control neighbourhoods and those treated with a fungus-based biopesticide deployed against host-seeking ticks (Met52), ticks having only single infections of either B. microti or B. burgdorferi were significantly less common than expected, whereas coinfections with these 2 pathogens were significantly more common. However, use of tick control system bait boxes, which kill ticks attempting to feed on small mammals, eliminated the bias towards coinfection. Although aimed at reducing the abundance of host-seeking ticks, control methods directed at ticks attached to small mammals may influence human exposure to coinfected ticks and the probability of exposure to multiple tick-borne infections.

Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders.

OBJECTIVE: People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. METHODS: We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other. RESULTS: Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. CONCLUSIONS: CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.

Survival in Huntington's disease and other young-onset dementias.

OBJECTIVES: To compare survival and risk factors associated with mortality in common young-onset dementias (YOD) including Huntington's disease. METHODS: This retrospective cohort study included inpatients from an Australian specialist neuropsychiatry service, over 20 years. Dementia diagnoses were based on consensus criteria and Huntington's disease (HD) was confirmed genetically. Mortality and cause of death were determined using linkage to the Australian Institute of Health and Welfare National Death Index. RESULTS: There were 386 individuals with YOD included. The dementia types included frontotemporal dementia (FTD) (24.5%), HD (21.2%) and Alzheimer's disease (AD) (20.5%). 63% (n = 243) individuals had died. The longest median survival was for those who had HD, 18.8 years from symptom onset and with a reduced mortality risk compared to AD and FTD (hazard ratio 0.5). Overall, people with YOD had significantly increased mortality, of 5-8 times, compared to the general population. Females with a YOD had higher standardised mortality ratio compared to males (9.3 vs. 4.9) overall. The most frequent cause of death in those with HD was reported as HD, with other causes of death in the other YOD-subtypes related to dementia and mental/behavioural disorders. DISCUSSION: This is the first Australian study to investigate survival and risk factors of mortality in people with YOD. YOD has a significant risk of death compared to the general population. Our findings provide useful clinical information for people affected by YOD as well as future planning and service provision.

Carer burden and behavioral disturbance is similar between younger-onset Alzheimer's disease and behavioral variant frontotemporal dementia.

OBJECTIVES: Carer burden is common in younger-onset dementia (YOD), often due to the difficulty of navigating services often designed for older people with dementia. Compared to Alzheimer's disease (AD), the burden is reported to be higher in behavioral variant frontotemporal dementia (bvFTD). However, there is little literature comparing carer burden specifically in YOD. This study hypothesized that carer burden in bvFTD would be higher than in AD. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary neuropsychiatry service in Victoria, Australia. PARTICIPANTS: Patient-carer dyads with YOD. MEASUREMENTS: We collected patient data, including behaviors using the Cambridge Behavioral Inventory-Revised (CBI-R). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI-12). Descriptive statistics and Mann-Whitney U tests were used to analyze the data. RESULTS: Carers reported high burden (ZBI-12 mean score = 17.2, SD = 10.5), with no significant difference in burden between younger-onset AD and bvFTD. CBI-R stereotypic and motor behaviors, CBI-R everyday skills, and total NUCOG scores differed between the two groups. There was no significant difference in the rest of the CBI-R subcategories, including the behavior-related domains. CONCLUSION: Carers of YOD face high burden and are managing significant challenging behaviors. We found no difference in carer burden between younger-onset AD and bvFTD. This could be due to similarities in the two subtypes in terms of abnormal behavior, motivation, and self-care as measured on CBI-R, contrary to previous literature. Clinicians should screen for carer burden and associated factors including behavioral symptoms in YOD syndromes, as they may contribute to carer burden regardless of the type.

Comparing survival and mortality in patients with late-onset and young-onset vascular dementia.

OBJECTIVES: Vascular dementia (VD) is one of the more common types of dementia. Much is known about VD in older adults in terms of survival and associated risk factors, but comparatively less is known about VD in a younger population. This study aimed to investigate survival in people with young-onset VD (YO-VD) compared to those with late-onset VD (LO-VD) and to investigate predictors of mortality. DESIGN: Retrospective file review from 1992 to 2014. SETTING: The inpatient unit of a tertiary neuropsychiatry service in Victoria, Australia. PARTICIPANTS: Inpatients with a diagnosis of VD. MEASUREMENTS AND METHODS: Mortality information was obtained from the Australian Institute of Health and Welfare. Clinical variables included age of onset, sex, vascular risk factors, structural neuroimaging, and Hachinksi scores. Statistical analyses used were Kaplan-Meier curves for median survival and Cox regression for predictors of mortality. RESULTS: Eighty-four participants were included with few clinical differences between the LO-VD and YO-VD groups. Sixty-eight (81%) had died. Median survival was 9.9 years (95% confidence interval 7.9, 11.7), with those with LO-VD having significantly shorter survival compared to those with YO-VD (6.1 years and 12.8 years, respectively) and proportionally more with LO-VD had died (94.6%) compared to those with YO-VD (67.5%), χ2(1) = 9.16, p = 0.002. The only significant predictor of mortality was increasing age (p = 0.001). CONCLUSION: While there were few clinical differences, and older age was the only factor associated with survival, further research into the effects of managing cardiovascular risk factors and their impact on survival are recommended.

Cerebrospinal fluid neurofilament light and cerebral atrophy in younger-onset dementia and primary psychiatric disorders.

BACKGROUND AND AIMS: Neurodegeneration underpins the pathological processes of younger-onset dementia (YOD) and has been implicated in primary psychiatric disorders (PSYs). Cerebrospinal fluid (CSF) neurofilament light (NfL) has been used to investigate neurodegeneration severity through correlation with structural brain changes in various conditions, but has seldom been evaluated in YOD and PSYs. METHODS: This retrospective study included patients with YOD or PSYs with magnetic resonance imaging (MRI) of the brain and CSF NfL analysis. Findings from brain MRI were analysed using automated volumetry (volBrain) to measure white matter (WM), grey matter (GM) and whole brain (WB) volumes expressed as percentages of total intracranial volume. Correlations between NfL and brain volume measurements were computed whilst adjusting for age. RESULTS: Seventy patients (47 with YOD and 23 with PSY) were identified. YOD types included Alzheimer disease and behavioural variant frontotemporal dementia. PSY included schizophrenia and major depressive disorder. MRI brain sequences were either fast spoiler gradient-echo (FSPGR) or magnetization-prepared rapid acquisition gradient-echo (MPRAGE). In the total cohort, higher NfL was associated with reduced WB in the FSPGR and MPRAGE sequences (r = -0.402 [95% confidence interval (CI), -0.593 to -0.147], P = 0.008 and r = -0.625 [95% CI, -0.828 to -0.395], P < 0.001, respectively). Higher NfL was related to reduced GM in FSPGR (r = 0.385 [95% CI, -0.649 to -0.014], P = 0.017) and reduced WM in MPRAGE (r = -0.650 [95% CI, -0.777 to -0.307], P < 0.001). Similar relationships were seen in YOD, but not in PSY. CONCLUSION: Higher CSF NfL is related to brain atrophy in YOD, further supporting its use as a nonspecific marker of neurodegeneration severity.

Location, location, location: does providing public health services from community pharmacies contribute to tackling health inequalities?

BACKGROUND: Community pharmacies have long been advocated as an accessible source of advice on health improvement in communities. This cross-sectional study explored the association between provision of pharmacy public health services and factors that might influence the extent to which pharmacies contribute to tackling inequalities. METHODS: Publically available data were used to explore the association between pharmacy public health service provision and pharmacy characteristics (socioeconomic deprivation, urbanity, opening hours and workload). Regression models were fitted to the number of service consultations. The association between the number of services provided and the mean number of consultations across each service was investigated using regression models. RESULTS: Pharmacies showed a propensity for being situated in areas of higher socioeconomic deprivation. There was no association between socioeconomic deprivation and number of service consultations a pharmacy provided. Clustering of pharmacies in less affluent areas led to over half of all public health service consultations being in the two most deprived quintiles. CONCLUSIONS: Providing healthcare services from pharmacies in more deprived areas does not mean the public use them or that pharmacies will prioritize their delivery. The higher prevalence of pharmacies in disadvantaged communities is an important factor in ensuring pharmacy services support reducing inequalities.

Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease.

Adrenoceptors (ARs) throughout the brain are stimulated by noradrenaline originating mostly from neurons of the locus coeruleus, a brainstem nucleus that is ostensibly the earliest to show detectable pathology in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The α1-AR, α2-AR, and ß-AR subtypes expressed in target brain regions and on a range of cell populations define the physiological responses to noradrenaline, which includes activation of cognitive function in addition to modulation of neurometabolism, cerebral blood flow, and neuroinflammation. As these heterocellular functions are critical for maintaining brain homeostasis and neuronal health, combating the loss of noradrenergic tone from locus coeruleus degeneration may therefore be an effective treatment for both cognitive symptoms and disease modification in neurodegenerative indications. Two pharmacologic approaches are receiving attention in recent clinical studies: preserving noradrenaline levels (e.g., via reuptake inhibition) and direct activation of target adrenoceptors. Here, we review the expression and role of adrenoceptors in the brain, the preclinical studies which demonstrate that adrenergic stimulation can support cognitive function and cerebral health by reversing the effects of noradrenaline depletion, and the human data provided by pharmacoepidemiologic analyses and clinical trials which together identify adrenoceptors as promising targets for the treatment of neurodegenerative disease.

Effects of Tick-Control Interventions on Tick Abundance, Human Encounters with Ticks, and Incidence of Tickborne Diseases in Residential Neighborhoods, New York, USA.

Tickborne diseases (TBDs) such as Lyme disease result in ≈500,000 diagnoses annually in the United States. Various methods can reduce the abundance of ticks at small spatial scales, but whether these methods lower incidence of TBDs is poorly understood. We conducted a randomized, replicated, fully crossed, placebo-controlled, masked experiment to test whether 2 environmentally safe interventions, the Tick Control System (TCS) and Met52 fungal spray, used separately or together, affected risk for and incidence of TBDs in humans and pets in 24 residential neighborhoods. All participating properties in a neighborhood received the same treatment. TCS was associated with fewer questing ticks and fewer ticks feeding on rodents. The interventions did not result in a significant difference in incidence of human TBDs but did significantly reduce incidence in pets. Our study is consistent with previous evidence suggesting that reducing tick abundance in residential areas might not reduce incidence of TBDs in humans.

To swab or not to swab? Using point-of-care tests to detect Group A Streptococcus infections as part of a Sore Throat Test and Treat service in community pharmacy.

BACKGROUND: The community pharmacy-led Sore Throat Test and Treat (STTT) service in Wales allowed pharmacists to undertake a structured clinical assessment with FeverPAIN/Centor scores and a point-of-care test (POCT) for Group A Streptococcus (GAS) infection. A new service model was temporarily agreed as a result of COVID-19, without routine use of POCT. OBJECTIVES: To explore the impact of removing the requirement for GAS POCT from a community pharmacy STTT service on antibiotic supply. METHODS: Analysis of STTT consultation data, obtained for two periods: November 2018 (date the service went live) to September 2019 (pre-pandemic); and November 2020 (date the new service model was introduced) to May 2021. RESULTS: For consultations eligible for POCT, the antibiotic supply rate increased from 27% (922/3369) (95% CI: 26%-29%) with the pre-pandemic service model (FeverPAIN/Centor + POCT) to 63% (93/147) (95% CI: 55%-71%) with the new model (FeverPAIN/Centor only); the percentage of patients who were not issued an antibiotic, despite their high clinical score, decreased from 56% (646/1154) to 9.3% (8/86). CONCLUSIONS: Preliminary data suggest that for every 100 STTT consultations with patients with a Centor score of ≥3 or a FeverPAIN score of ≥2, the use of POCT may spare up to 36 courses of antibiotics, increasing to 47 for patients with higher clinical scores, suggesting that the pre-COVID delivery model (FeverPAIN/Centor + POCT) is the optimal pathway and POCT in addition to clinical scores may result in fewer antibiotic prescriptions for sore throat symptoms. These findings have implications for STTT service delivery during and beyond the COVID-19 pandemic.

Characteristics of the sore throat test and treat service in community pharmacies (STREP) in Wales: cross-sectional analysis of 11 304 consultations using anonymized electronic pharmacy records.

BACKGROUND: An NHS-funded sore throat test and treat (STTT) service was introduced in selected community pharmacies in Wales. Service users were screened using FeverPAIN/Centor scores, offered rapid antigen detection testing (RADT) to detect group A Streptococcus if appropriate, and supplied with antibiotics (by the pharmacist) if indicated. Following an initial evaluation, the service was rolled out nationally. OBJECTIVES: This study forms part of the long-term STTT evaluation. The aim was to describe characteristics of the service and service users, the delivery, service outcomes, patient safety and antibiotic prescribing. METHODS: Cross-sectional descriptive study using anonymized individual-level data from electronic pharmacy records of all eligible STTT service users between November 2018 and February 2020. RESULTS: We identified 11 304 pharmacy STTT consultations in service users aged 6 years and over, with a median age of 25 years (IQR: 12 to 44). RADT was undertaken in 8666 (76.7%) consultations with 2503 (28.9% of RADT) positive tests. In total, 2406 (21.3%) service users were supplied with antibiotics. Pharmacists managed 91% of consultations in the pharmacy and referred only 937 (9.3%) service users to a GP and 27 (0.2%) to the Emergency Department. Higher rates of antibiotic supply were observed in out-of-hours consultations when compared with in-hours (24.9% versus 20.9%). CONCLUSIONS: This is the largest description of a pharmacy-led STTT service to date and suggests it can be delivered at scale to align with a pre-specified pathway that promotes appropriate use of RADT and antibiotics. The service could substantially reduce workload from a common illness in other heavily pressurized areas of primary and emergency care.

The Diagnostic Challenge of Young-Onset Dementia Syndromes and Primary Psychiatric Diseases: Results From a Retrospective 20-Year Cross-Sectional Study.

OBJECTIVE: Distinguishing a dementia syndrome from a primary psychiatric disease in younger patients can be challenging and may lead to diagnostic change over time. The investigators aimed to examine diagnostic stability in a cohort of patients with younger-onset neurocognitive disorders. METHODS: A retrospective review of records was conducted for patients who were admitted to an inpatient neuropsychiatry service unit between 2000 and 2019, who were followed up for at least 12 months, and who received a diagnosis of young-onset dementia at any time point. Initial diagnosis included Alzheimer's disease-type dementia (N=30), frontotemporal dementia (FTD) syndromes (N=44), vascular dementia (N=7), mild cognitive impairment (N=10), primary psychiatric diseases (N=6), and other conditions, such as Lewy body dementia (N=30). RESULTS: Among 127 patients, 49 (39%) had a change in their initial diagnoses during the follow-up period. Behavioral variant FTD (bvFTD) was the least stable diagnosis, followed by dementia not otherwise specified and mild cognitive impairment. Compared with patients with a stable diagnosis, those who changed exhibited a higher cognitive score at baseline, a longer follow-up period, greater delay to final diagnosis, and no family history of dementia. Patients whose diagnosis changed from a neurodegenerative to a psychiatric diagnosis were more likely to have a long psychiatric history, while those whose diagnosis changed from a psychiatric to a neurodegenerative one had a recent manifestation of psychiatric symptoms. CONCLUSIONS: Misdiagnosis of younger patients with neurocognitive disorders is not uncommon, especially in cases of bvFTD. Late-onset psychiatric symptoms may be the harbinger to a neurodegenerative disease. Close follow-up and monitoring of these patients are necessary.

Carer burden and psychological distress in young-onset dementia: An Australian perspective.

OBJECTIVES: Carer burden in dementia is associated with poor outcomes, including early nursing home placement for people with dementia and psychological distress for their carers. Carers of people with young-onset dementia (YOD) are particularly vulnerable to carer burden. Yet they are often overlooked by clinicians as dementia services are generally designed for older people. We sought to estimate the rate of burden and psychological distress in carers of YOD at a state-wide tertiary service based in Australia. METHODS: We conducted a cross-sectional study examining 71 dyads from a Neuropsychiatry service. We collected patient demographic and clinical data including the Neuropsychiatry Unit Cognitive Assessment tool (NUCOG) and Mini-Mental State Examination (MMSE). Carer data, such as demographics and psychological distress, were obtained using Depression Anxiety Stress Scale 21 (DASS-21). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI). RESULTS: Higher carer burden, measured using ZBI, was associated with longer duration of dementia and greater severity of overall cognitive impairment. Carers who felt burdened reported higher levels of stress, depression, and anxiety measured using DASS-21. Multiple linear regression analysis found carer burden was independently predicted by duration of dementia, total cognition score and carers experiencing psychological stress. DISCUSSION: We found that patient variables of dementia duration and cognitive impairment and carer variable of carer stress to be associated with carer burden. Poor executive function was associated with carer stress. Early identification and management of carer burden and psychological distress is important for outcomes. Ideally, this should be provided by a specialist YOD service.

Allogeneic Bone Marrow Transplant as a Cure for Refractory T-Cell Large Granular Lymphocytic Leukemia in an Adolescent.

T-cell large granular lymphocytic (T-LGL) leukemia is a rare, typically indolent neoplasm with a median age of onset above 60 years. Pathogenesis involves clonal T-cell expansion, and nearly all reported pediatric cases have been associated with concurrent autoimmune disease. Immunosuppressive therapy often mitigates sequelae, but definitive cure is not routinely achieved. Here we present an otherwise healthy 13-year-old with T-LGL leukemia refractory to all standard treatments. Our patient ultimately underwent allogeneic bone marrow transplant (BMT) and is now stable in remission 3 years post-BMT. BMT may offer a viable definitive cure for refractory T-LGL leukemia in very young patients.

Clinical correlates of movement disorders in adult Niemann-Pick type C patients measured via a Personal KinetiGraph.

BACKGROUND: Niemann-Pick type C (NPC) is an autosomal recessive progressive neurodegenerative disorder caused by mutations in the NPC1 or NPC2 genes. Patients with this disorder have variable phenotypic presentations that often include neuropsychiatric manifestations, cognitive decline, and movement disorders. There is considerable interpatient variation in movement disorders, with limited quantitative measurements describing the movements observed. Objective measurements using wearable sensors provide clinically applicable monitoring of patients with Parkinson's disease, and hence may be utilized in patients with NPC. OBJECTIVE: To explore the relationship between objective measurements of movement obtained via the use of the Personal KinetiGraph (PKG) with the clinical information obtained via questionnaires and clinical rating tools of patients with Niemann-Pick type C. METHODS: Twelve patients with Niemann-Pick type C were recruited who wore the PKG for 6 days during regular activities. A 6-day output was provided by the manufacturer, which provided bradykinesia (BK) and dyskinesia (DK) scores. BK and DK scores were further divided into their interquartile ranges. A fluctuation score (FDS), percentage time immobile (PTI), and percent time with tremors (PTT) were also provided. Clinical assessments included Abnormal Involuntary Movement Scale (AIMS), Epworth Sleepiness Score (ESS), Falls, Neuropsychiatric Unit Assessment Tool (NUCOG), Parkinson's disease questionnaire (PDQ), and modified Unified Parkinson's Disease Rating Scale (UPDRS) which were performed over telehealth within 2 weeks of PKG use. Pearson's correlation analyses were utilized to explore the relationship between DK and BK quartiles and clinical measures. RESULTS: We found bradykinesia to be a feature among this cohort of patients, with a median BKS of 22.0 (7.4). Additionally, PTI scores were elevated at 4.9 (8.2) indicating elevated daytime sleepiness. Significant correlations were demonstrated between BK25 and Falls (r = - 0.74, 95% CI = [- 0.95, - 0.08]), BK50 and Falls (r = - 0.79, 95% CI = [- 0.96, - 0.19]), and BK75 and Falls (r = - 0.76, 95% CI = [- 0.95, - 0.11]). FDS correlated with PDQ (r = - 0.7, 95% CI = [- 0.92, - 0.18]), UPDRS IV (r = - 0.65, 95% CI = [- 0.90, - 0.09]), UPDRS (r = - 0.64, 95% CI = [- 0.9, - 0.06]), and AIMS (r = - 0.96, 95% CI = [- 0.99, - 0.49]). DK25 in comparison with NUCOG-A (r = 0.72, 95% CI = [0.17, 0.93]) and DK75 in comparison with NUCOG (r = 0.64, 95% CI = [0.02, 0.91]) and NUCOG-A (r = 0.63, 95% CI = [0.01, 0.90]) demonstrated significant correlations. Additionally, duration of illness in comparison with PTI (r = 0.72, 95% CI = [0.22, 0.92]) demonstrated significance. CONCLUSIONS: Utilization of PKG measures demonstrated that bradykinesia is under recognized among NPC patients, and the bradykinetic patients were less likely to report concerns regarding falls. Additionally, the FDS rather than the DKS is sensitive to the abnormal involuntary movements of NPC-reflecting a differing neurobiology of this chorea compared to levodopa-induced dyskinesias. Furthermore, dyskinetic individuals performed better in cognitive assessments of attention which may indicate an earlier timepoint within disease progression.

Time to diagnosis in younger-onset dementia and the impact of a specialist diagnostic service.

OBJECTIVES: While early diagnosis of younger-onset dementia (YOD) is crucial in terms of accessing appropriate services and future planning, diagnostic delays are common. This study aims to identify predictors of delay to diagnosis in a large sample of people with YOD and to investigate the impact of a specialist YOD service on this time to diagnosis. DESIGN: A retrospective cross-sectional study. SETTING: The inpatient unit of a tertiary neuropsychiatry service in metropolitan Victoria, Australia. PARTICIPANTS: People diagnosed with a YOD. MEASUREMENTS AND METHODS: We investigated the following predictors using general linear modeling: demographics including sex and location, age at onset, dementia type, cognition, psychiatric diagnosis, and number of services consulted with prior to diagnosis. RESULTS: A total of 242 inpatients were included. The mean time to diagnosis was 3.4 years. Significant predictors of delay included younger age at onset, dementia type other than Alzheimer's disease (AD) and behavioral-variant frontotemporal dementia (bvFTD), and increased number of services consulted. These predictors individually led to an increased diagnostic delay of approximately 19 days, 5 months, and 6 months, respectively. A specialized YOD service reduced time to diagnosis by 12 months. CONCLUSION: We found that younger age at onset, having a dementia which was not the most commonly occurring AD or bvFTD, and increasing number of services were significant predictors of diagnostic delay. A novel result was that a specialist YOD service may decrease diagnostic delay, highlighting the importance of such as service in reducing time to diagnosis as well as providing post-diagnostic support.

Mortality in dementia is predicted by older age of onset and cognitive presentation.

OBJECTIVES: Survival information in dementia is important for future planning and service provision. There have been limited Australian data investigating survival duration and risk factors associated with mortality in younger-onset dementia. METHODS: This was a cross-sectional retrospective study investigating survival in inpatients with a diagnosis of dementia admitted to a tertiary neuropsychiatry service from 1991 to 2014. The Australian Institute of Health and Welfare National Death Index was used to obtain mortality information. RESULTS: A total of 468 inpatients were identified, of which 75% had symptom onset at ⩽65 years of age (defined as younger-onset dementia). Dementia was categorised into four subtypes, Alzheimer's dementia, frontotemporal dementia, vascular dementia and other dementias; 72% of the patients had died. Overall median survival duration was 10.6 years with no significant differences in duration within the dementia subtypes (p = 0.174). Survival in older-onset dementia (symptom onset at >65 years of age) was about half of that in younger-onset dementia (median survival 6.3 years compared to 12.7 years, respectively). Independent predictors of mortality were having older-onset dementia (hazard ratio: 3.2) and having initial presenting symptoms being cognitive in nature (hazard ratio: 1.5). Females with an older-onset dementia had longer survival compared to males with an older-onset dementia, and this was reversed for younger-onset dementia. Older-onset dementia and younger-onset dementia conferred 3 and 6 times, respectively, increased risk of death compared to the general population. CONCLUSION: This is the largest Australian study to date investigating survival and risk factors to mortality in dementia. We report important clinical information to patients with dementia and their families about prognosis which will assist with future planning. Our findings suggest that for both older-onset dementia and younger-onset dementia, 'new onset' psychiatric symptoms precede the cognitive symptoms of a neurodegenerative process. This, and sex differences in survival depending on the age of onset of the dementia warrant further investigation.