An intra-tumoral niche maintains and differentiates stem-like CD8 T cells.

Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy1-8. However, the reason some tumours have high CD8 T cell infiltration while others do not remains unclear. Here we investigate the requirements for maintaining a CD8 T cell response against human cancer. We find that CD8 T cells within tumours consist of distinct populations of terminally differentiated and stem-like cells. On proliferation, stem-like CD8 T cells give rise to more terminally differentiated, effector-molecule-expressing daughter cells. For many T cells to infiltrate the tumour, it is critical that this effector differentiation process occur. In addition, we show that these stem-like T cells reside in dense antigen-presenting-cell niches within the tumour, and that tumours that fail to form these structures are not extensively infiltrated by T cells. Patients with progressive disease lack these immune niches, suggesting that niche breakdown may be a key mechanism of immune escape.

Effect of Coffee and Chocolate Ingestion on Clozapine Dose and on Plasma Clozapine and Norclozapine Concentrations in Clinical Practice.

BACKGROUND: Some reports point to dietary caffeine intake as a cause of increased plasma clozapine concentrations in certain patients. METHODS: We compared clozapine dose and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in male and female smokers and nonsmokers in relation to reported (i) coffee (caffeine) and (ii) chocolate (caffeine and theobromine) intake in samples submitted for clozapine therapeutic drug monitoring, 1993-2017. RESULTS: There was information on coffee ingestion for 16,558 samples (8833 patients) from males and 5886 samples (3433 patients) from females and on chocolate ingestion for 12,616 samples (7568 patients) from males and 4677 samples (2939 patients) from females. When smoking was considered, there was no discernible effect of either coffee or chocolate ingestion either on the median dose of clozapine or on the median plasma clozapine and norclozapine concentrations in men and in women. However, cigarette smoking was associated with higher coffee and chocolate consumption. Although male nonsmokers who reported drinking 3 or more cups of coffee daily had significantly higher median plasma clozapine and norclozapine concentrations than those who drank less coffee, they were also prescribed a significantly higher clozapine dose. There was no clear effect of coffee ingestion on plasma clozapine and norclozapine in female nonsmokers. IMPLICATIONS: Inhibition of clozapine metabolism by caffeine at the doses of caffeine normally encountered in those treated with clozapine is unlikely even in male nonsmokers. Measurement of plasma caffeine in an appropriate sample should be considered in any future investigation into a presumed clozapine-caffeine interaction.

Assessment of frailty and quality of life and their correlation in the haemodialysis population at Palmerston North Hospital, New Zealand.

AIM: End-stage kidney disease (ESKD) is increasingly becoming a healthcare concern in New Zealand and haemodialysis remains the most common modality of treatment. Frailty and health-related quality of life (HRQOL) are established predictors of prognosis and have already been shown to be poor in the dialyzing population. Existing data show correlation between these measures in the ESKD population, however there is little evidence for those on haemodialysis specifically. Our study aimed to assess for a correlation between frailty and HRQOL in the haemodialysis population at Palmerston North Hospital, and to assess for any differences in frailty and HRQOL scores between indigenous Maori and non-Maori subgroups. METHODS: A cross-sectional study was conducted involving 93 in-centre haemodialysis patients from Palmerston North Hospital, New Zealand. Baseline demographic data was measured alongside frailty and HRQOL scores, which were measured using the Kidney Disease Quality of Life tool (KDQOL-36) and the Edmonton Frail Scale. RESULTS: A statistically significant negative correlation was observed between frailty and all aspects of HRQOL (p < .05), with the strongest correlation observed between frailty and the physical component (r = -.64, p = <.001). Independent samples t-test showed no statistically significant difference between scores for Maori and non-Maori in frailty (M = 7.4, SD = 3.3 vs. M = 6.8, SD = 3.2; t (91) = -0.92, p = .80), or HRQOL (p values > .05 in all components). CONCLUSION: A negative correlation was observed between frailty and HRQOL. This information can be beneficial in guiding discussions around treatment modality and for future patients and useful in enabling better predictions of prognosis. No statistically significant differences in frailty and HRQOL scores were observed between Maori and non-Maori groups, however the generalizability of this finding is limited due to the insufficient size of the study population.

Prenatal testosterone synchrony in first-time parents predicts fathers' postpartum relationship quality.

There is evidence that men's testosterone levels decline across the transition to fatherhood and that this decline may reflect fathers' investment in the new family. There is also emerging evidence that cohabiting couples show synchrony or within-couple associations in testosterone levels during the perinatal period. Hormonal synchrony may act as a mechanism that supports fathers' biological preparation for parenthood, perhaps by facilitating perinatal declines in paternal testosterone. However, few studies have examined testosterone synchrony and change within couples. A sample of 97 U.S. couples expecting their first child provided testosterone samples during pregnancy, and of those couples, 78 couples also provided testosterone at seven months postpartum. Couples reported on relationship satisfaction both at prenatal and postpartum visits. Bayesian multilevel modeling revealed within-couple testosterone synchrony both during pregnancy and postpartum. Testosterone synchrony during pregnancy predicted a greater drop in fathers' testosterone levels from prenatal to postpartum and higher paternal postpartum relationship quality. Fathers' lower prenatal testosterone levels also subsequently predicted higher self-reported postpartum relationship quality for both parents. In sum, this study finds that couples' testosterone levels show synchrony across the transition to parenthood in ways that are associated with couple relationship quality and men's neuroendocrine preparation for fatherhood.

Police, ambulance and psychiatric co-response versus usual care for mental health and suicide emergency callouts: A quasi-experimental study.

OBJECTIVE: Mental health-related calls to emergency services made via 111 (New Zealand) or 000 (Australia) often represent critical junctures for the person in crisis. Traditionally, police, ambulance and mental health services work separately to manage such emergencies. Sequential agency responses may be protracted and cause escalation. This study tests multi-agency co-response aiming for more integrated, faster, safer and less coercive management of mental health crises. METHODS: Immediate and 1-month outcomes of mental health emergency calls made to police and ambulance were compared according to whether they occurred on days with co-response availability. Outcomes measured included emergency department admission and waiting times, psychiatric admissions, compulsory treatment, use of force, detention in police cells and the time to resolution of the event. Relative risk estimates were constructed. RESULTS: A total 1273 eligible mental health emergency callouts occurred between March 2020 and March 2021 (38% coded 'mental health' emergencies, 48% suicide risk and 14% as 'other'), 881 on days with co-response availability and 392 on days without. Co-response interventions were resolved faster and were more likely to be community-based. Fewer than one-third (32%) led to emergency department admissions, compared with close to half (45%) on days without co-response (risk ratio: 0.7 [0.6, 0.8]). In the following month, the number of emergency department and mental health admissions reduced (p < 0.01 and 0.05, respectively). There were no statistically significant differences in use of force and few people were detained in police custody. CONCLUSION: Co-response intervention increased the likelihood of mental health crises being resolved in the community and reduced hospitalisations. Benefits were sustained at 1 month.

Pathways of care: a qualitative study of barriers and facilitators to engaging dementia care among underserved and minority populations in the US and Germany.

OBJECTIVE: To identify barriers and facilitators to the use of formal dementia services among underserved and minority groups (UMG) in the United States and Germany. METHOD: Semi-structured qualitative interviews with caregivers (N = 18) of persons with dementia in the United States and Germany. Data were analyzed using thematic analysis. RESULTS: Caregivers described their experiences in three stages of seeking, initiating, and utilizing care, and different factors served to hinder or enable the use of care services in each stage. The most important factors included limited knowledge about dementia, challenges interacting with healthcare systems, and how closely formal services met the expectations and needs of caregivers, particularly with regard to accommodating cultural or ethnic/racial identity. Caregivers preferred interacting with service care providers who shared a similar identity to receive information or services. CONCLUSION: Barriers and facilitators to using dementia care services vary by stage of engaging services and may be shared across different healthcare contexts. Targeting specific barriers and strengthening facilitators could help reduce disparities in dementia care among UMG.

A plant-specific syntaxin-6 protein contributes to the intracytoplasmic route for the begomovirus CabLCV.

Because of limited free diffusion in the cytoplasm, viruses must use active transport mechanisms to move intracellularly. Nevertheless, how the plant single-stranded DNA begomoviruses hijack the host intracytoplasmic transport machinery to move from the nucleus to the plasmodesmata remains enigmatic. Here, we identified nuclear shuttle protein (NSP)-interacting proteins from Arabidopsis (Arabidopsis thaliana) by probing a protein microarray and demonstrated that the cabbage leaf curl virus NSP, a facilitator of the nucleocytoplasmic trafficking of viral (v)DNA, interacts in planta with an endosomal vesicle-localized, plant-specific syntaxin-6 protein, designated NSP-interacting syntaxin domain-containing protein (NISP). NISP displays a proviral function, unlike the syntaxin-6 paralog AT2G18860 that failed to interact with NSP. Consistent with these findings, nisp-1 mutant plants were less susceptible to begomovirus infection, a phenotype reversed by NISP complementation. NISP-overexpressing lines accumulated higher levels of vDNA than wild-type. Furthermore, NISP interacted with an NSP-interacting GTPase (NIG) involved in NSP-vDNA nucleocytoplasmic translocation. The NISP-NIG interaction was enhanced by NSP. We also showed that endosomal NISP associates with vDNA. NISP may function as a docking site for recruiting NIG and NSP into endosomes, providing a mechanism for the intracytoplasmic translocation of the NSP-vDNA complex toward and from the cell periphery.

Use of Real-World Evidence for Regulatory Approval and Coverage of Medical Devices: A Landscape Assessment.

OBJECTIVES: To enhance the generalizability of the evidence it reviews, the US Food and Drug Administration (FDA) has encouraged manufacturers to expand the submission of real-world evidence (RWE). The extent to which this evidence, which is generated outside of research settings, can support decision making remains unclear. We described the current use of RWE for medical devices, assessed manufacturers' challenges in generating and using it for regulatory and coverage decisions, and identified opportunities to expand its use. METHODS: We conducted 27 solo and group interviews with FDA officials and representatives of device manufacturers, payers, and health technology assessment organizations. All interviews used a semistructured protocol and were transcribed to allow thematic analysis. RESULTS: Accessing and linking real-world data sources, identifying unique devices, capturing longitudinal data, limited staff expertise, and uncertain return on investment have hampered efforts to use real-world data. Many companies in our sample were conducting research using real-world data, but none had submitted RWE as the primary evidence supporting a premarket approval. FDA guidance was helpful, but regulatory requirements remained ambiguous and examples of successful regulatory decisions based on RWE were limited. Payers mainly used RWE to supplement experimental evidence in coverage decisions, evaluated both types of evidence in similar ways, and had concerns about the rigor of RWE. CONCLUSIONS: Technical challenges may slow efforts to generate and use RWE in the near term. Additional regulatory guidance and examples, greater use of rigorous study designs and analytic methods, and continued stakeholder engagement could accelerate the use of RWE.

The acceptability and feasibility of a pilot study examining the impact of a mobile technology-based intervention informed by behavioral economics to improve HIV knowledge and testing frequency among Latinx sexual minority men and transgender women.

BACKGROUND: We developed a novel intervention that uses behavioral economics incentives and mobile-health text messages to increase HIV knowledge and testing frequency among Latinx sexual minority men and Latinx transgender women. Here we provide a theoretically-grounded assessment regarding the intervention's acceptability and feasibility. METHODS: We conducted 30-min exit interviews with a stratified sample of participants (n = 26 Latinx sexual minority men, 15 Latinx transgender women), supplemented with insights from study staff (n = 6). All interviews were recorded, transcribed, and translated for a content analysis using Dedoose. Cohen's Kappa was 89.4% across coded excerpts. We evaluated acceptability based on how participants cognitively and emotionally reacted to the intervention and whether they considered it to be appropriate. We measured feasibility based on resource, scientific and process assessments (e.g., functionality of text messaging service, feedback on study recruitment procedures and surveys). RESULTS: Regarding acceptability, most participants clearly understood the intervention as a program to receive information about HIV prevention methods through text messages. Participants who did not complete the intervention shared they did not fully understand what it entailed at their initial enrollment, and thought it was a one-time engagement and not an ongoing program. Though some participants with a higher level of education felt the information was simplistic, most appreciated moving beyond a narrow focus on HIV to include general information on sexually transmitted infections; drug use and impaired sexual decision-making; and differential risks associated with sexual positions and practices. Latinx transgender women in particular appreciated receiving information about Pre-Exposure Prophylaxis. While participants didn't fully understand the exact chances of winning a prize in the quiz component, most enjoyed the quizzes and chance of winning a prize. Participants appreciated that the intervention required a minimal time investment. Participants shared that the intervention was generally culturally appropriate. Regarding feasibility, most participants reported the text message platform worked well though inactive participants consistently said technical difficulties led to their disengagement. Staff shared that clients had varying reactions to being approached while being tested for HIV, with some unwilling to enroll and others being very open and curious about the program. Both staff and participants relayed concerns regarding the length of the recruitment process and study surveys. CONCLUSIONS: Our theoretically-grounded assessment shows the intervention is both acceptable and feasible. TRIAL REGISTRATION: The trial was registered on May 5, 2017 with the ClinicalTrials.gov registry [ NCT03144336 ].

Health Factors as Potential Mediators of the Longitudinal Effect of Loneliness on General Cognitive Ability.

OBJECTIVE: Higher levels of loneliness in older adulthood predict cognitive decline, but research on mediating mechanisms is sparse. We examine multisystemic physiological risk, functional ability, self-rated health, depressive symptoms, and social participation as mediating processes for the association between loneliness and general cognitive ability over a 10-year follow-up in an older adult sample. METHODS: Three waves of data from 3,005 individuals (mean intake age: 69.30 (SD: 7.85) years; female = 51.61%) recruited during Wave 1 of the National Social Life, Health, and Aging Project were used to test whether hypothesized mediators collected at the 5-year follow-up explained effects of baseline loneliness on 10-year general cognitive ability. RESULTS: The relationship between baseline loneliness and 10-year general cognitive ability was not mediated by multisystemic physiological risk. Functional ability (b = -0.24, SE = 0.05, p <0.001), self-rated health (b = -0.08, SE = 0.02, p <0.001), depressive symptoms (b= -0.20, SE = 0.05, p <0.001), and social participation (b = -0.03, SE = 0.01, p = 0.016) significantly mediated effects. Indirect effects remained significant after adjusting for demographic covariates and 5-year general cognitive ability, except social participation. DISCUSSION: Loneliness may influence cognitive ability indirectly, signaling waning physical and psychiatric health more proximally correlated with cognitive ability. These mechanisms may serve as targets of intervention for cognitive maintenance in lonely older adults.

Mapping transcription factor interactome networks using HaloTag protein arrays.

Protein microarrays enable investigation of diverse biochemical properties for thousands of proteins in a single experiment, an unparalleled capacity. Using a high-density system called HaloTag nucleic acid programmable protein array (HaloTag-NAPPA), we created high-density protein arrays comprising 12,000 Arabidopsis ORFs. We used these arrays to query protein-protein interactions for a set of 38 transcription factors and transcriptional regulators (TFs) that function in diverse plant hormone regulatory pathways. The resulting transcription factor interactome network, TF-NAPPA, contains thousands of novel interactions. Validation in a benchmarked in vitro pull-down assay revealed that a random subset of TF-NAPPA validated at the same rate of 64% as a positive reference set of literature-curated interactions. Moreover, using a bimolecular fluorescence complementation (BiFC) assay, we confirmed in planta several interactions of biological interest and determined the interaction localizations for seven pairs. The application of HaloTag-NAPPA technology to plant hormone signaling pathways allowed the identification of many novel transcription factor-protein interactions and led to the development of a proteome-wide plant hormone TF interactome network.

Ameliorating Episodic Memory Deficits in a Young Adult With Developmental (Congenital) Amnesia.

OBJECTIVES: Although the spacing effect has been investigated extensively in a variety of populations, few studies have focused on individuals with hippocampal amnesia and none, to our knowledge, have investigated differences in performance as a function of spacing schedule in these cases. In the current study, we investigated the benefit of expanding and equal-interval, compared to massed, spacing schedules in a developmental amnesic person, H.C., who shows congenitally based abnormal development of the hippocampal memory system. METHODS: Given the possibility of plasticity and reorganization in the developing brain, we investigated whether H.C. would benefit more from an expanding versus equal-interval schedule using a continuous recognition paradigm, even though this task has been shown to recruit structures within the medial temporal lobe, including the hippocampus. RESULTS: H.C. and matched controls both showed a clear spacing effect, although neither group benefited more from an equal-interval or expanding spacing schedule. CONCLUSIONS: The results of the current study show that the spacing effect is an effective and clinically meaningful memory intervention technique that may be applied to clinical conditions known to affect hippocampal function and episodic memory early in life. (JINS, 2018, 24, 1003-1012).

Normative Retinal Thicknesses in Common Animal Models of Eye Disease Using Spectral Domain Optical Coherence Tomography.

Purpose This study demonstrates a standardized approach to measuring retinal thickness (RT) using spectral domain optical coherence tomography (SD-OCT) in commonly used animal models of disease and reports a normative data set for future use. Materials and Methods Twenty normal eyes of 4 adult animal models (5 rats, 5 rabbits, 5 canines, and 5 mini-pigs) were used. Manual measurements were made on the commercially available Heidelberg Spectralis™ SD-OCT to determine the total, inner, and outer retinal thickness (RT) at fixed distances from the optic nerve head (ONH) (1, 2, 3, 4, 5, and 6 mm away) in order to control for normal variation in retinal thickness. Analysis of variance (ANOVA) with P value <0.05 indicated statistical significance. Results Total RT significantly decreased with increasing distance from the ONH for the canine, mini-pig, and rabbit vascular models. Inner RT significantly decreased for the canine, mini-pig, rabbit vascular, and rabbit avascular models; and outer RT significantly decreased for only the canine model. Among the animal models, RT at similar distances from the ONH were significantly different for total, inner, and outer RT. Conclusion There are significant differences in the total, inner, and outer RT of normal canine, mini-pig, rabbit, and rat retinas with SD-OCT using a standardized approach. These measurements provide a normative reference for future studies and illustrate a standardized method of assessing RT.

Evidence for Retromutagenesis as a Mechanism for Adaptive Mutation in Escherichia coli.

Adaptive mutation refers to the continuous outgrowth of new mutants from a non-dividing cell population during selection, in apparent violation of the neo-Darwinian principle that mutation precedes selection. One explanation is that of retromutagenesis, in which a DNA lesion causes a transcriptional mutation that yields a mutant protein, allowing escape from selection. This enables a round of DNA replication that establishes heritability. Because the model requires that gene expression precedes DNA replication, it predicts that during selection, new mutants will arise from damage only to the transcribed DNA strand. As a test, we used a lacZ amber mutant of Escherichia coli that can revert by nitrous acid-induced deamination of adenine residues on either strand of the TAG stop codon, each causing different DNA mutations. When stationary-phase, mutagenized cells were grown in rich broth before being plated on lactose-selective media, only non-transcribed strand mutations appeared in the revertants. This result was consistent with the known high sensitivity to deamination of the single-stranded DNA in a transcription bubble, and it provided an important control because it demonstrated that the genetic system we would use to detect transcribed-strand mutations could also detect a bias toward the non-transcribed strand. When residual lacZ transcription was blocked beforehand by catabolite repression, both strands were mutated about equally, but if revertants were selected immediately after nitrous acid exposure, transcribed-strand mutations predominated among the revertants, implicating retromutagenesis as the mechanism. This result was not affected by gene orientation. Retromutagenesis is apt to be a universal method of evolutionary adaptation, which enables the emergence of new mutants from mutations acquired during counterselection rather than beforehand, and it may have roles in processes as diverse as the development of antibiotic resistance and neoplasia.

National Trends in Indicators of a Medical Home for Children.

OBJECTIVES: The patient centered medical home is now widely supported as a strategy for delivering high quality primary care. The objective of this study was to examine whether children's primary care experiences nationally have become more aligned with the medical home model over time, and how this may have varied for vulnerable children. METHODS: This study analyzed data on 289,672 children, aged 0-17 years, of families responding to one of three iterations of National Survey of Children's Health from 2003, 2007 and 2011-2012. Each year, we assessed indicators of four medical home features (access, continuity, comprehensiveness, and family-centeredness) and a total medical home score for children nationally and for those with a set of social and demographic risk factors. RESULTS: Indicators of access and continuity, and total medical home scores fluctuated but improved overall from 2003 to 2012 (7.1, 6.7 and 1.4 % point increases, respectively), while indicators of comprehensiveness and family-centered care measures declined (2.4 and 1.8 % point decreases, respectively). Children with the highest levels of social and demographic risk experienced larger fluctuations in these measures over time. CONCLUSIONS FOR PRACTICE: There were improvements in the extent to which children's primary care experiences aligned with a medical home model, though not linearly or for all component features. Children with more risk factors experienced more volatile changes, suggesting a particular need to attend to the primary care experiences of the most vulnerable children.

Implementation of a Continuous Patient Monitoring System in the Hospital Setting: A Qualitative Study.

BACKGROUND: Technology can improve care delivery, patient outcomes, and staff satisfaction, but integration into the clinical workflow remains challenging. To contribute to this knowledge area, this study examined the implementation continuum of a contact-free, continuous monitoring system (CFCM) in an inpatient setting. CFCM monitors vital signs and uses the information to alert clinicians of important changes, enabling early detection of patient deterioration. METHODS: Data were collected throughout the entire implementation continuum at a community teaching hospital. Throughout the study, 3 group and 24 individual interviews and five process observations were conducted. Postimplementation alarm response data were collected. Analysis was conducted using triangulation of information sources and two-coder consensus. RESULTS: Preimplementation perceived barriers were alarm fatigue, questions about accuracy and trust, impact on patient experience, and challenges to the status quo. Stakeholders identified the value of CFCM as preventing deterioration and benefitting patients who are not good candidates for telemetry. Educational materials addressed each barrier and emphasized the shared CFCM values. Mean alarm response times were below the desired target of two minutes. Postimplementation interview analysis themes revealed lessened concerns of alarm fatigue and improved trust in CFCM than anticipated. Postimplementation challenges included insufficient training for secondary users and impact on patient experience. CONCLUSION: In addition to understanding the preimplementation anticipated barriers to implementation and establishing shared value before implementation, future recommendations include studying strategies for optimal tailoring of education to each user group, identifying and reinforcing positive process changes after implementation, and including patient experience as the overarching element in frameworks for digital tool implementation.

Bone mineral density in osseointegration implant surgery: A review of current studies (Review).

Osseointegration implant (OI) surgery is the latest rehabilitation technology for amputees, where a bone-anchored implant obviates the limitations of traditional socket prostheses. The bone mineral density (BMD) in the periprosthetic and other anatomical regions can be used to assess bone remodelling following OI surgery. Currently, limited studies have used BMD measurements in reporting post-operative OI outcomes and the association between the maintenance of BMD and implant efficacy has remained elusive. This review captured and analysed all studies that have reported the BMD as an objective outcome measure in patients with trans-femoral or trans-tibial OI. The PubMed, Medline, Scopus and Web of Science databases were searched using the terms 'amputation', 'osseointegration' and 'bone mineral density'. A total of 6 studies involving human participants were included for analysis. All studies used dual X-ray absorptiometry and/or X-rays for measuring BMD. Rehabilitation of trans-femoral or trans-tibial amputation using OI may help restore healthy BMD by enabling physiological bone loading. However, there is a low correlation between the BMD around the OI and the success of OI surgery or the risk of periprosthetic fractures. This review summarises the current evidence on BMD assessment in OI for lower limb amputee rehabilitation. Despite the great variability in the results, the available evidence suggests that OI may help restore BMD following surgery. The limited evidence calls for further investigation, as well as the development of a standard BMD measurement protocol.

Consciousness of subjective time in the brain.

"Mental time travel" refers to conscious experience of remembering the personal past and imagining the personal future. Little is known about its neural correlates. Here, using functional magnetic resonance imaging, we explored the hypothesis that mental time travel into "nonpresent" times (past and future) is enabled by a special conscious state (chronesthesia). Well-trained subjects repeatedly imagined taking one and the same short walk in a familiar environment, doing so either in the imagined past, present, or future. In an additional condition, they recollected an instance in which they actually performed the same short walk in the same familiar setting. This design allowed us to measure brain activity correlated with "pure" conscious states of different moments of subjective time. The results showed that the left lateral parietal cortex was differentially activated by nonpresent subjective times compared with the present (past and future > present). A similar pattern was observed in the left frontal cortex, cerebellum, and thalamus. There was no evidence that the hippocampal region is involved in subjective time travel. These findings provide support for theoretical ideas concerning chronesthesia and mental time travel.

'An accident waiting to happen' - experiences of police officers, paramedics, and mental health clinicians involved in 911-mental health crises: a cross-sectional survey.

WHAT IS KNOWN ON THE SUBJECT: Police and ambulance staff are increasingly asked to help people experiencing mental health crises, but they often feel under-prepared. The single frontline service approach is time-intensive and risks a coercive pathway to care. The emergency department is the default location for transfers by police or ambulance involving a person involved in a mental health crisis, despite being viewed as suboptimal. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: Police and ambulance staff struggled keeping up with the mental health demand, reporting inadequate mental health training, little enjoyment and negative experiences when trying to access help from other services. Most mental health staff had adequate mental health training and enjoyed their work, but many experienced difficulties getting help from other services. Police and ambulance staff found it hard to work with mental health services. WHAT ARE THE IMPLICATIONS FOR PRACTICE: The combination of limited training, poor interagency referral processes, and difficulties accessing support from mental health services means that when police and ambulance services attend mental health crises alone, distress may be heightened and prolonged. Enhanced mental health training for first responders and more streamlined referral processes may improve process and outcomes. Mental health nurses have key skills that could be utilized in assisting police and ambulance staff who attend 911 emergency mental health calls. New models such as co-response teams, whereby police, mental health clinicians and ambulance staff respond conjointly should be trialled and evaluated. ABSTRACT: INTRODUCTION: First responders are increasingly called to assist people experiencing mental health crises but little research exists canvassing multi-agency perspectives of such work. AIM/QUESTION: To understand the views of police officers, ambulance and mental health staff attending mental health or suicide-related crises in Aotearoa New Zealand and to discover how they experience current models of cross-agency collaboration. METHODS: A descriptive cross-sectional survey involving mixed methods. Quantitative data were analysed using descriptive statistics and free text by content analysis. RESULTS: Participants included 57 police officers, 29 paramedics and 33 mental health professionals. Mental health staff felt adequately trained, but only 36% described good processes for accessing inter-agency support. Police and ambulance staff felt undertrained and unprepared. Accessing mental health expertise was considered difficult by 89% of police and 62% of ambulance staff. DISCUSSION: Frontline services struggle managing mental health-related 911 emergencies. Current models are not working well. Miscommunication, dissatisfaction and distrust exist between police, ambulance and mental health services. CONCLUSION: The single-agency frontline response may be detrimental to service users in crisis and under-utilizes the skills of mental health staff. New ways of inter-agency cooperation are required, such as co-located police, ambulance and mental health nurses responding in partnership.

Development of a latent dementia index in the aging, demographics, and memory study: Validation and measurement invariance by sex.

Latent variable models can create a latent dementia index (LDI) using cognitive and functional ability to approximate dementia likelihood. The LDI approach has been applied across diverse cohorts. It is unclear whether sex affects its measurement properties. We use Wave A (2001-2003) of the Aging, Demographics, and Memory Study (n = 856). Multiple group confirmatory factor analysis (CFA) was used to test measurement invariance (MI) using informant-reported functional ability and cognitive performance tasks, which we group into verbal, nonverbal, and memory. Partial scalar invariance was found, allowing for testing sex differences in LDI means (MDiff = 0.38). The LDI correlated with consensus panel dementia diagnosis, Mini-Mental State Examination (MMSE), and dementia risk factors (low education, advanced age, and apolipoprotein ε4 [APOE-ε4] status) for men and women. The LDI validly captures dementia likelihood to permit estimation of sex differences. LDI sex differences indicate higher dementia likelihood in women, potentially due to social, environmental, and biological factors.