Mild behavioral impairment domains are longitudinally associated with pTAU and metabolic biomarkers in dementia-free older adults.

BACKGROUND: The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers. METHODS: Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tested using adjusted linear mixed-effects models. RESULTS: The sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, the MBI domain of abnormal perception was associated with steeper increases in plasma pTau181. Abnormal perception, decreased motivation, and impulse dyscontrol were associated with homocysteine or insulin dysregulation. DISCUSSION: Apart from the association with plasma pTau181, our results suggest that MBI might also represent metabolic dysregulation, probably contributing to dementia transition among older adults with subjective cognitive decline or mild cognitive impairment. HIGHLIGHTS: Mild behavioral impairment (MBI) psychosis was associated with steeper increases in plasma p. pTau could be a pharmacological target to treat agitation and psychosis symptoms. MBI domains were linked to metabolic dysregulation involving insulin and homocysteine.

Challenges and proposed solutions to conducting Alzheimer's disease psychosis trials.

Alzheimer's disease psychosis (ADP) produces a significant burden for patients and their care partners, but at present there are no approved treatments for ADP. The lack of approved treatments may be due to the challenges of conducting clinical trials for this disease. This perspective article discusses distinct challenges and proposed solutions of conducting ADP trials involving seven key areas: (1) methods to reduce the variable and sometimes high rates of placebo response that occur for treatments of neuropsychiatric symptoms; (2) the use of combined or updated criteria that provide a precise, consensus definition of ADP; (3) the use of eligibility criteria to help recruit individuals representative of the larger ADP population and overcome the difficulty of recruiting patients with moderate-to-severe ADP; (4) consideration of multiple perspectives and implementation of technology to reduce the variability in the administration and scoring of neuropsychiatric symptom assessments; (5) the use of clinically appropriate, a priori-defined severity thresholds and responder cutoffs; (6) the use of statistical approaches that address absolute effect sizes and a three-tier approach to address the fluctuation of neuropsychiatric symptoms; and (7) the implementation of feasible diagnostic and target-engagement biomarkers as they become available. The goal of these proposed solutions is to improve the evaluation of potential ADP therapies, within the context of randomized, placebo-controlled trials with clinically meaningful endpoints and sustained treatment responses.

A nematode-specific ribonucleoprotein complex mediates interactions between the major nematode spliced leader snRNP and its target pre-mRNAs.

Spliced leader trans-splicing of pre-mRNAs is a critical step in the gene expression of many eukaryotes. How the spliced leader RNA and its target transcripts are brought together to form the trans-spliceosome remains an important unanswered question. Using immunoprecipitation followed by protein analysis via mass spectrometry and RIP-Seq, we show that the nematode-specific proteins, SNA-3 and SUT-1, form a complex with a set of enigmatic non-coding RNAs, the SmY RNAs. Our work redefines the SmY snRNP and shows for the first time that it is essential for nematode viability and is involved in spliced leader trans-splicing. SNA-3 and SUT-1 are associated with the 5' ends of most, if not all, nascent capped RNA polymerase II transcripts, and they also interact with components of the major nematode spliced leader (SL1) snRNP. We show that depletion of SNA-3 impairs the co-immunoprecipitation between one of the SL1 snRNP components, SNA-2, and several core spliceosomal proteins. We thus propose that the SmY snRNP recruits the SL1 snRNP to the 5' ends of nascent pre-mRNAs, an instrumental step in the assembly of the trans-spliceosome.

Gorse (Ulex europeaus) wastes with 5,6-dimethyl benzimidazole supplementation can support growth of vitamin B12 producing commensal gut microbes.

Many commensal gut microbes are recognized for their potential to synthesize vitamin B12, offering a promising avenue to address deficiencies through probiotic supplementation. While bioinformatics tools aid in predicting B12 biosynthetic potential, empirical validation remains crucial to confirm production, identify cobalamin vitamers, and establish biosynthetic yields. This study investigates vitamin B12 production in three human colonic bacterial species: Anaerobutyricum hallii DSM 3353, Roseburia faecis DSM 16840, and Anaerostipes caccae DSM 14662, along with Propionibacterium freudenreichii DSM 4902 as a positive control. These strains were selected for their potential use as probiotics, based on speculated B12 production from prior bioinformatic analyses. Cultures were grown in M2GSC, chemically defined media (CDM), and Gorse extract medium (GEM). The composition of GEM was similar to CDM, except that the carbon and nitrogen sources were replaced with the protein-depleted liquid waste obtained after subjecting Gorse to a leaf protein extraction process. B12 yields were quantified using liquid chromatography with tandem mass spectrometry. The results suggested that the three butyrate-producing strains could indeed produce B12, although the yields were notably low and were detected only in the cell lysates. Furthermore, B12 production was higher in GEM compared to M2GSC medium. The positive control, P. freudenreichii DSM 4902 produced B12 at concentrations ranging from 7 ng mL-1 to 12 ng mL-1. Univariate-scaled Principal Component Analysis (PCA) of data from previous publications investigating B12 production in P. freudenreichii revealed that B12 yields diminished when the carbon source concentration was ≤30 g L-1. In conclusion, the protein-depleted wastes from the leaf protein extraction process from Gorse can be valorised as a viable substrate for culturing B12-producing colonic gut microbes. Furthermore, this is the first report attesting to the ability of A. hallii, R. faecis, and A. caccae to produce B12. However, these microbes seem unsuitable for industrial applications owing to low B12 yields.

[Driving: What is the relevance and usability of the Reisberg scale in 2023?] / Conduite automobile : Quelle est la pertinence et l'utilité de l'échelle de Reisberg en 2023 ?

The publication of the decree on the care of people with neurocognitive disorders brought to the fore the Reisberg's Global Deterioration Scale, a scale that only few clinicians use in memory centers or in geriatric. This scale has a number of limitations, not least of which is that it is obsolete, since it does not take into account disease advances in scientific knowledge with biomarkers. Consequently, the stages evoked no longer correspond to current descriptions. Moreover, it only concerns Alzheimer's disease, whereas in our practice we encounter other neurodegenerative pathologies. Even if we decide to use another global assessment scale, such as the Clinical Dementia Rating or the Functional Assessment Staging, they cannot replace a personalized assessment. Indeed, it is important to stress that this decree does not take into account the relevance of personalized assessments using, for example, neuropsychological tests to estimate driving ability. A personalized assessment accompanied by a real-life driving test would be preferable than a score on a global scale. This article therefore presents the Global Deterioration Scale, highlighting its unsuitability for assessing whether or not to continue driving.

Impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic prescribing for people with dementia in nursing home settings.

OBJECTIVES: This study aimed to determine the impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic use in people with dementia living in nursing homes. METHODS: This was a comparative analysis of baseline data from two large nursing home studies, one conducted during (COVID-iWHELD study) and one prior (WHELD study) to the pandemic. It involves data from 69 and 149 nursing homes, and 1006 and 666 participants respectively. Participants were people with established dementia (score >1 on Clinical Dementia Rating Scale). Resident data included demographics, antipsychotic prescriptions and neuropsychiatric symptoms using the Neuropsychiatric Inventory Nursing Home version. Nursing home data collected were nursing home size and staffing information. RESULTS: Overall prevalence of neuropsychiatric symptoms was unchanged from pre-pandemic prevalence. Mean antipsychotic use across the sample was 32.0%, increased from 18% pre-pandemic (Fisher's exact test p < 0.0001). At a nursing home level, the medians for the low, medium and high tertiles for antipsychotic use were 7%, 20% and 59% respectively, showing a disproportionate rise in tertile three. Residents in these homes also showed a small but significant increase in agitation. CONCLUSION: There has been a significant increase in antipsychotic prescribing in nursing homes since the COVID-19 pandemic, with a disproportionate rise in one third of homes, where median prescription rates for antipsychotics were almost 60%. Strategies are urgently needed to identify these nursing homes and introduce pro-active support to bring antipsychotic prescription rates back to pre-pandemic levels.

Formulation of water-soluble Buddleja globosa Hope extracts and characterization of their antimicrobial properties against Pseudomonas aeruginosa.

Buddleja globosa Hope (BG) extracts are traditionally used to treat skin and gastric ulcers due to their healing properties. Non-aqueous solvents such as ethanol and DMSO are usually used to extract naturally occurring compounds. However, the cytotoxicity of these solvents and the low water solubility of the extracted compounds can hinder their biomedical applications. To overcome the limited solubility of the BG extracts, we aimed to enhance the solubility by processing a standardized hydroalcoholic extract (BG-126) through spray drying (SD), with and without two solubility enhancers. Spray-dried BG (BG-SD) extracts and spray-dried BG extracts plus polyvinylpyrrolidone (BG-SD PVP) and Soluplus® (BG-SD SP) were developed starting from BG-126 (containing 53% ethanol). These four formulations were characterized by total phenolic content, water solubility at 25°C and 37°C, and antimicrobial properties against Pseudomonas aeruginosa. All the SD formulations presented a solubility that allowed them to reach maximum concentrations of 1,024 µg/ml catechin for BG-SD and 2,048 µg/ml catechin for BG-SD PVP and BG-SD SP for antimicrobial testing. BG-SD showed the highest antimicrobial potency with a minimum inhibitory concentration (MIC) of 512 µg/ml catechin, followed by BG-126 with a MIC of 1,024 µg/ml catechin and SP. BG-126 was also shown to inhibit biofilm formation, as well as the excipients PVP and SP. The spray-dried BG (BG-SD) extract represents a promising natural active component with enhanced antimicrobial properties against P. aeruginosa for further research and the development of novel phytopharmaceuticals.

Implementation of the WHO integrated care for older people (ICOPE) programme in clinical practice: a prospective study.

BACKGROUND: The INSPIRE integrated care for older people (ICOPE)-CARE programme is a public health programme implementing the ICOPE health-care pathway in clinical practice. The primary objective of this study was to describe the large-scale implementation and feasibility of the INSPIRE ICOPE-CARE guidelines in clinical practice. The secondary aims were to describe the characteristics of patients who were identified as positive for abnormalities in intrinsic capacity (ie, locomotion, cognition, psychology, vitality, hearing, and vision) during step 1, and to describe the prevalence of these positive screenings. METHODS: In this prospective study, we evaluated a real-life population of users of primary care services in the Occitania region (France). Participants who were aged 60 years and older and lived in a community were eligible for inclusion in our study. Individuals aged ≥60 years were screened (step 1) by health-care providers or through self-assessments using digital tools (the ICOPE MONITOR app and the ICOPEBOT conversational robot). Our implementation strategy involved raising awareness among health-care professionals about the WHO ICOPE programme, training professionals in the ICOPE-CARE guidelines, and developing a digital infrastructure (ie, digital tools, a database, and a remote ICOPE monitoring platform). The feasibility of implementing the INSPIRE ICOPE-CARE guidelines was determined by the anticipated inclusion of ≥10 000 participants, and having a follow-up rate of over 50%. FINDINGS: Between Jan 1, 2020, and November 18, 2021, 10 903 older people (mean age 76·0, SD 10·5 years; 6627 [60·8%] of whom were women) had a baseline step 1 screening done, and 5185 (70·4%) of 7367 eligible participants had a 6-month follow-up of step 1 screening. 10 285 (94·3%) participants had a positive intrinsic capacity result during screening at baseline. 958 (9·3%) participants were evaluated with step 2 (in-depth assessments). Positive intrinsic capacity was confirmed in 865 (90·3%) participants. Most recommendations in step 3 (care plan) were related to locomotion, vitality, and cognition. INTERPRETATION: The high number of participants included in our study, as well as the high rates of follow-up, provides evidence to suggest that the large-scale implementation of ICOPE in clinical practice is feasible. The very high prevalence of positive screening for impaired intrinsic capacity during step 1, as well as the high rates of confirmed deficits in intrinsic capacity during step 2, suggest that the INSPIRE ICOPE-CARE programme is able to target individuals who are at increased risk for functional loss and disability. FUNDING: Occitania Regional Health Agency, Region Occitanie and Pyrénées-Méditerranée, European Regional Development Fund, and The Interreg Program V-A Spain-France-Andorra.

A novel, essential trans-splicing protein connects the nematode SL1 snRNP to the CBC-ARS2 complex.

Spliced leader trans-splicing is essential for gene expression in many eukaryotes. To elucidate the molecular mechanism of this process, we characterise the molecules associated with the Caenorhabditis elegans major spliced leader snRNP (SL1 snRNP), which donates the spliced leader that replaces the 5' untranslated region of most pre-mRNAs. Using a GFP-tagged version of the SL1 snRNP protein SNA-1 created by CRISPR-mediated genome engineering, we immunoprecipitate and identify RNAs and protein components by RIP-Seq and mass spectrometry. This reveals the composition of the SL1 snRNP and identifies associations with spliceosome components PRP-8 and PRP-19. Significantly, we identify a novel, nematode-specific protein required for SL1 trans-splicing, which we designate SNA-3. SNA-3 is an essential, nuclear protein with three NADAR domains whose function is unknown. Mutation of key residues in NADAR domains inactivates the protein, indicating that domain function is required for activity. SNA-3 interacts with the CBC-ARS2 complex and other factors involved in RNA metabolism, including SUT-1 protein, through RNA or protein-mediated contacts revealed by yeast two-hybrid assays, localisation studies and immunoprecipitations. Our data are compatible with a role for SNA-3 in coordinating trans-splicing with target pre-mRNA transcription or in the processing of the Y-branch product of the trans-splicing reaction.

Predictors of nursing home placement at 2 years in Alzheimer's disease: A follow-up survey from the THERAD study.

OBJECTIVES: Nursing Home Placement (NHP) can prove to be the only solution to some dead-end situations in Alzheimer's disease (AD). The predictors of NHP are known and can be related to either the person with dementia or his/her caregiver. We aimed to identify predictors of NHP among people with AD over a 2-year follow-up period, with a particular interest in the modifiable predictors, notably those involving caregivers. METHODS: We studied data from the THERAD study, a French monocentric randomized controlled trial, involving 196 community-dwelling dyads, primarily assessing an educational intervention in AD. We performed a bivariate analysis followed by a multivariate Cox model, with a backward stepwise procedure. RESULTS: The mean age of the patients was 82 years old, 67.7% were women and 56.9% were living with a partner. The mean age of the caregivers was 65.8 years old, 64.6% were women and half were spouses of the patients with a moderate burden. During the follow-up, 23 patients died and 49 were institutionalized. The majority of NHPs occurred during the first year (35 NHP). The mean time to NHP was 27.77 months after the diagnosis. Five independent predictors of NHP were found: a higher patient education level (aHR 6.31; CI95% = 1.88-21.22), a high caregiver Burden (aHR 3.97; CI95% = 1.33-11.85), the caregiver being the offspring of the patient (aHR 2.92; CI95% = 1.43-5.95), loss of autonomy (aHR 2.75; CI95% = 1.13-6.65) and disinhibition as a behavioural and psychological symptoms of dementia (BPSD) (aHR 2.38; CI95% = 1.26-4.47). CONCLUSIONS: Our data are in accordance with the literature in identifying loss of autonomy, burden and BPSD (disinhibition) as risk factors of NHP. We also found high patient education level and status of offspring caregiver as additional factors. It is essential to take into account the caregiver status when designing psychoeducational trials aiming to delay NHP. Further studies need to take into account both the modifiable risk factors related to the patient (productive BPSD) and the needs of offspring caregivers (work-life balance, mental load).

Relapse in Dementia-related Psychosis and Clinical Decisions.

Patients with dementia can experience hallucinations and delusions because of their underlying neurodegenerative condition, a syndrome known as dementia-related psychosis. Dementia-related psychosis contributes to morbidity and mortality among patients with dementia and increases the burden on caregivers and the health care system. With no pharmacological treatment currently approved in the United States for this condition, patients are often treated off-label with antipsychotics. Though typical and atypical antipsychotics have demonstrated variable to modest efficacy in dementia-related psychosis, serious safety concerns arise with their use. Accordingly, clinical and Centers for Medicare & Medicaid Services guidelines recommend trying antipsychotics only when other therapies have failed and encourage treatment discontinuation of antipsychotics after 4 months to assess whether ongoing therapy is needed. Discontinuation of effective antipsychotic treatment, however, may increase the risk for relapse of symptoms and the associated morbidities that accompany relapse. A randomized medication withdrawal clinical trial design allows assessment of relapse risk after discontinuation and can provide initial information on longer-term safety of therapy for dementia-related psychosis. Given the substantial unmet need in this condition, new, well-tolerated therapies that offer acute and sustained reduction of symptoms while also preventing recurrence of symptoms of psychosis are critically needed.

Impact of an educational programme on Alzheimer's disease patients' quality of life: results of the randomized controlled trial THERAD.

BACKGROUND: Although educational interventions are recommended in Alzheimer's disease (AD), studies assessing the impact of interventions such as "therapeutic patient education" are scarce. Indeed, the intrinsic nature of the disease is considered a barrier to patients' involvement in such approaches. We aimed to evaluate an intervention by using a "dyadic" approach (patient and caregiver) in both intervention and assessment. METHODS: THERAD is a monocentric, randomized, controlled trial assessing the effects of a 2-month educational programme in mild to moderately severe AD patients among 98 dyads (caregiver/patient) on caregiver-reported patient quality of life (QOL) at 2 months. Community-dwelling patients and their caregivers were recruited in ambulatory units of the French Toulouse University Hospital. Self-reported patient QOL, autonomy, behavioural and psychological symptoms and caregiver QOL and burden were collected at 2, 6 and 12 months. Linear mixed models were used in modified intention-to-treat populations. We also performed sensitivity analysis. RESULTS: A total of 196 dyads were included, 98 in each group. The mean age of the patients was 82 years, 67.7% were women, diagnosed with AD (+/- cerebrovascular component) (mean MMSE =17.6), and 56.9% lived with a partner. The mean age of the caregivers was 65.7 years, and 64.6% were women (52.3% offspring/42.6% spouses), with a moderate burden (mean Zarit score = 30.9). The mean caregiver-reported patient QOL was lower than the self-reported QOL (28.61 vs. 33.96). We did not identify any significant difference in caregiver-reported patients' QOL (p = 0.297) at 2 months, but there was a significant difference in self-reported patients' QOL at 2 months (p = 0.0483) or 6 months (p = 0.0154). No significant difference was found for the secondary outcomes. The results were stable in the sensitivity analyses. CONCLUSIONS: This randomized controlled trial assessing an educational intervention in 196 dyads (Alzheimer's disease affected patient/caregiver) highlights the need to better consider the patient's point of view, since only the self-reported QOL was improved. Additional studies using this dyadic approach are necessary in targeted subpopulations of caregivers (spouse vs. child, gender) and of patients (severity of cognitive impairment or behavioural disturbances) TRIAL REGISTRATION: THERAD study NCT01796314 . Registered on February 19, 2013.

Trial of Pimavanserin in Dementia-Related Psychosis.

BACKGROUND: Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HT2A inverse agonist and antagonist pimavanserin on psychosis related to various causes of dementia are not clear. METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) at weeks 8 and 12 were randomly assigned in a 1:1 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end point, assessed in a time-to-event analysis, was a relapse of psychosis as defined by any of the following: an increase of at least 30% in the SAPS-H+D score and a CGI-I score of 6 (much worse) or 7 (very much worse), hospitalization for dementia-related psychosis, stopping of the trial regimen or withdrawal from the trial for lack of efficacy, or use of antipsychotic agents for dementia-related psychosis. RESULTS: Of the 392 patients in the open-label phase, 41 were withdrawn for administrative reasons because the trial was stopped for efficacy; of the remaining 351 patients, 217 (61.8%) had a sustained response, of whom 105 were assigned to receive pimavanserin and 112 to receive placebo. A relapse occurred in 12 of 95 patients (13%) in the pimavanserin group and in 28 of 99 (28%) in the placebo group (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.73; P = 0.005). During the double-blind phase, adverse events occurred in 43 of 105 patients (41.0%) in the pimavanserin group and in 41 of 112 (36.6%) in the placebo group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin. CONCLUSIONS: In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).

Erratum to: HARMONY Study: Pimavanserin Significantly Prolongs Time to Relapse of Dementia-Related Psychosis.

[This corrects the article DOI: 10.1093/geroni/igaa057.530.].

Longitudinal Course of Agitation and Aggression in Patients with Alzheimer's Disease in a Cohort Study: Methods, Baseline and Longitudinal Results of the A3C Study.

BACKGROUND: To present methodology, baseline results and longitudinal course of the Agitation and Aggression in patients with Alzheimer's Disease Cohort (A3C) study. OBJECTIVES: The central objective of A3C was to study the course, over 12 months of clinically significant Agitation and Aggression symptoms based on validated measures, and to assess relationships between symptoms and clinical significance based on global ratings. DESIGN: A3C is a longitudinal, prospective, multicenter observational cohort study performed at eight memory clinics in France, and their associated long-term care facilities. SETTING: Clinical visits were scheduled at baseline, monthly during the first 3 months, at 6 months, at 9 months and at 12 months. The first three months intended to simulate a classic randomized control trial 12-week treatment design. PARTICIPANTS: Alzheimer's Disease patients with clinically significant Agitation and Aggression symptoms lived at home or in long-term care facilities. MEASUREMENTS: Clinically significant Agitation and Aggression symptoms were rated on Neuropsychiatric Inventory (NPI), NPI-Clinician rating (NPI-C) Agitation and Aggression domains, and Cohen Mansfield Agitation Inventory. Global rating of agitation over time was based on the modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. International Psychogeriatric Association "Provisional Diagnostic Criteria for Agitation", socio-demographics, non-pharmacological approaches, psychotropic medication use, resource utilization, quality of life, cognitive and physical status were assessed. RESULTS: A3C enrolled 262 AD patients with a mean age of 82.4 years (SD ±7.2 years), 58.4% women, 69.9% at home. At baseline, mean MMSE score was 10.0 (SD±8.0), Cohen Mansfield Agitation Inventory score was 62.0 (SD±15.8) and NPI-C Agitation and Aggression clinician severity score was 15.8 (SD±10.8). According to the International Psychogeriatric Association agitation definition, more than 70% of participants showed excessive motor activity (n=199, 76.3%) and/or a verbal aggression (n=199, 76.3%) while 115 (44.1%) displayed physical aggression. The change of the CMAI score and the NPI-C Agitation and Aggression at 1-year follow-up period was respectively -11.36 (Standard Error (SE)=1.32; p<0.001) and -6.72 (SE=0.77; p<0.001). CONCLUSION: Little is known about the longitudinal course of clinically significant agitation symptoms in Alzheimer's Disease about the variability in different outcome measures over time, or the definition of a clinically meaningful improvement. A3C may provide useful data to optimize future clinical trials and guide treatment development for Agitation and Aggression in Alzheimer's Disease.

Molecular detection of Mycobacterium tuberculosis from buccal swabs among adult in Peru.

Tuberculosis (TB) diagnosis relies on a sputum sample, which cannot be easily obtained from all symptomatic patients. Mycobacterium tuberculosis DNA can be detected from oral swabs, a noninvasive, safe alternative sample type; however, reported sensitivities have been variable and likely depend on sample collection, processing procedures and host characteristics. We analyzed three buccal swab samples from 123 adults with culture-confirmed TB in Lima, Peru. We compared the sensitivity and specificity of two sample collection devices (OmniSwab and EasiCollect FTA cards) and examined factors associated with detection. DNA was extracted with a commercially available kit and detected via real-time PCR IS6110 amplification. Overall sensitivity for buccal samples was 51% (95% Confidence Interval [CI] 42-60%). Specificity from a single sample among healthy controls was 96.7% (95% CI 83-99.9%). Positive sputum smear and cavitary disease, correlates of disease burden, were associated with detection via buccal swab. Although we observed higher sensitivities with the Omniswab samples, this appeared to be due primarily to differences in patient characteristics (e.g., cavitary disease). Overall, our findings support the potential for a buccal sample-based TB assay. Future work should focus on assay optimization and streamlining the assay workflow.

Emergency department and hospital admissions among people with dementia living at home or in nursing homes: results of the European RightTimePlaceCare project on their frequency, associated factors and costs.

BACKGROUND: Evidence is lacking on the differences between hospitalisation of people with dementia living in nursing homes and those living in the community. The objectives of this study were: 1) to describe the frequency of hospital admission among people with dementia in eight European countries living in nursing homes or in the community, 2) to examine the factors associated with hospitalisation in each setting, and 3) to evaluate the costs associated with it. METHODS: The present study is a secondary data analysis of the RightTimePlaceCare European project. A cross-sectional survey was conducted with data collected from people with dementia living at home or who had been admitted to a nursing home in the last 3 months, as well as from their caregivers. Data on hospital admissions at 3 months, cognitive and functional status, neuropsychiatric symptoms, comorbidity, polypharmacy, caregiver burden, nutritional status, and falls were assessed using validated instruments. Multivariate regression models were used to investigate the factors associated with hospital admission for each setting. Costs were estimated by multiplying quantities of resources used with the unit cost of each resource and inflated to the year 2019. RESULTS: The study sample comprised 1700 people with dementia living in the community and nursing homes. Within 3 months, 13.8 and 18.5% of people living in nursing homes and home care, respectively, experienced ≥1 hospital admission. In the nursing home setting, only polypharmacy was associated with a higher chance of hospital admission, while in the home care setting, unintentional weight loss, polypharmacy, falls, and more severe caregiver burden were associated with hospital admission. Overall, the estimated average costs per person with dementia/year among participants living in a nursing home were lower than those receiving home care. CONCLUSION: Admission to hospital is frequent among people with dementia, especially among those living in the community, and seems to impose a remarkable economic burden. The identification and establishment of an individualised care plan for those people with dementia with polypharmacy in nursing homes, and those with involuntary weight loss, accidental falls, polypharmacy and higher caregiver burden in the home care setting, might help preventing unnecessary hospital admissions.

Health workers perception on telemedicine in management of neuropsychiatric symptoms in long-term care facilities: Two years follow-up.

The management of neuropsychiatric symptoms is a challenge in long-term care facilities. Our objective was to assess the perception of telemedicine, as a useful tool to connect staff to specialized units. In this multicenter prospective study, 90 patients from ten facilities benefited from 180 sessions over two years. The primary outcome was the perception of telemedicine evaluated through semi-structured interviews at baseline and two years later. Our results revealed positive perceptions of telemedicine, confirmed after two years of real-life experience with its use. Not only do staff members believe that telemedicine is not a downgraded version of medicine, but they also believe that it could improve the quality of care. They expressed a very positive sense of recognition of their professional qualifications and indicated their need to be involved in change processes to ensure successful implementation and better adherence to telemedicine as a service.

Oxidative Stress, Telomere Shortening, and Apoptosis Associated to Sarcopenia and Frailty in Patients with Multimorbidity.

BACKGROUND: The presence of oxidative stress, telomere shortening, and apoptosis in polypathological patients (PP) with sarcopenia and frailty remains unknown. METHODS: Multicentric prospective observational study in order to assess oxidative stress markers (catalase, glutathione reductase (GR), total antioxidant capacity to reactive oxygen species (TAC-ROS), and superoxide dismutase (SOD)), absolute telomere length (aTL), and apoptosis (DNA fragmentation) in peripheral blood samples of a hospital-based population of PP. Associations of these biomarkers to sarcopenia, frailty, functional status, and 12-month mortality were analyzed. RESULTS: Of the 444 recruited patients, 97 (21.8%), 278 (62.6%), and 80 (18%) were sarcopenic, frail, or both, respectively. Oxidative stress markers (lower TAC-ROS and higher SOD) were significantly enhanced and aTL significantly shortened in patients with sarcopenia, frailty or both syndromes. No evidence of apoptosis was detected in blood leukocytes of any of the patients. Both oxidative stress markers (GR, p = 0.04) and telomere shortening (p = 0.001) were associated to death risk and to less survival days. CONCLUSIONS: Oxidative stress markers and telomere length were enhanced and shortened, respectively, in blood samples of polypathological patients with sarcopenia and/or frailty. Both were associated to decreased survival. They could be useful in the clinical practice to assess vulnerable populations with multimorbidity and of potential interest as therapeutic targets.