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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.
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Precursores de RNA , RNA Líder para Processamento , Ribonucleoproteínas Nucleares Pequenas , Spliceossomos , Animais , RNA Líder para Processamento/metabolismo , RNA Líder para Processamento/genética , Precursores de RNA/metabolismo , Precursores de RNA/genética , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Ribonucleoproteínas Nucleares Pequenas/genética , Spliceossomos/metabolismo , Spliceossomos/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Trans-Splicing , Ligação ProteicaRESUMO
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.).
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Antipsicóticos/uso terapêutico , Demência/psicologia , Alucinações/tratamento farmacológico , Piperidinas/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Ureia/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Demência/tratamento farmacológico , Método Duplo-Cego , Feminino , Alucinações/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Modelos de Riscos Proporcionais , Transtornos Psicóticos/etiologia , Recidiva , Ureia/uso terapêuticoRESUMO
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.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Proteínas Nucleares , RNA de Helmintos , RNA Líder para Processamento , Trans-Splicing , Animais , Regiões 5' não Traduzidas , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas Nucleares/metabolismo , Ribonucleoproteínas Nucleares Pequenas/genética , Splicing de RNA , RNA de Helmintos/genética , RNA Líder para Processamento/genéticaRESUMO
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.
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Biomarcadores , Disfunção Cognitiva , Proteínas tau , Humanos , Feminino , Masculino , Proteínas tau/sangue , Idoso , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Estudos Longitudinais , Homocisteína/sangue , Transtornos Psicóticos/sangue , Doença de Alzheimer/sangue , Idoso de 80 Anos ou maisRESUMO
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.
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Antipsicóticos , COVID-19 , Demência , Humanos , Antipsicóticos/uso terapêutico , Pandemias , Demência/tratamento farmacológico , Demência/epidemiologia , Demência/psicologia , COVID-19/epidemiologia , Casas de SaúdeRESUMO
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.
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Antipsicóticos , Demência , Transtornos Psicóticos , Idoso , Antipsicóticos/uso terapêutico , Demência/tratamento farmacológico , Humanos , Medicare , Transtornos Psicóticos/tratamento farmacológico , Recidiva , Estados UnidosRESUMO
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).
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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.
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Demência , Estudos Transversais , Demência/diagnóstico , Demência/epidemiologia , Demência/terapia , Serviço Hospitalar de Emergência , Europa (Continente)/epidemiologia , Hospitalização , Hospitais , Humanos , Casas de SaúdeRESUMO
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.
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Assistência de Longa Duração , Telemedicina , Seguimentos , Humanos , Casas de Saúde , Percepção , Estudos ProspectivosRESUMO
In this work, the first example of a radical stereodivergent reaction directed towards the stereoselective synthesis of both (R*,R*)- and (R*,S*)-2,2'-biflavanones promoted by samarium diiodide is reported. Control experiments showed that the selectivity of this reaction was exclusively controlled by the temperature. It was possible to generate a variety of 2,2'-biflavanones bearing different substitution patterns at the aromatic ring in good-to-quantitative yields, being both stereoisomers of the desired compounds obtained with total or high control of selectivity. A mechanism that explains both the generation of the corresponding 2,2'-biflavanones and the selectivity is also discussed. The structure and stereochemistry determination of each isomer was unequivocally elucidated by single-crystal X-ray diffraction experiments.
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BACKGROUND: Rapid and accurate diagnosis of childhood tuberculosis (TB) is challenging because children are often unable to produce the sputum sample required for conventional tests. Stool is an alternative sample type that is easy to collect from children, and studies investigating the use of stool for molecular detection of Mycobacterium tuberculosis (Mtb) have led to promising results. Our objective was to evaluate stool as an alternative specimen to sputum for Mtb detection in children. We did so using the TruTip workstation (Akonni Biosystems), a novel automated lysis and extraction platform. METHODS: We tested stool samples from 259 children aged 0-14 years old, in Lima, Peru who presented with TB symptoms. Following extraction with TruTip, we detected the presence of Mtb DNA by IS6110 real-time PCR. We calculated assay sensitivity in two groups: (1) children with culture confirmed TB (N = 22); and (2) children with clinically-diagnosed unconfirmed TB (N = 84). We calculated specificity among children in whom TB was ruled out (N = 153). Among children who were diagnosed with TB, we examined factors associated with a positive stool test. RESULTS: Assay sensitivity was 59% (95% confidence interval [CI]: 39-80%) and 1.2% (95% CI: 0.0-6.5%) in children with culture-confirmed and clinically-diagnosed unconfirmed TB, respectively, and specificity was 97% (95% CI: 93-99%). The assay detected Mtb in stool of 7/7 children with smear-positive TB (100% sensitivity; 95% CI: 59-100%), and in 6/15 of children with smear-negative, culture-confirmed TB (40% sensitivity; 95% CI: 16-68%). Older age, smear positivity, culture positivity, ability to produce sputum and cavitary disease were associated with a positive stool result. CONCLUSION: Testing of stool samples with the TruTip workstation and IS6110 amplification yielded sensitivity and specificity estimates comparable to other tests such as Xpert. Future work should include detection of resistance using the TruTip closed amplification system and assay optimization to improve sensitivity in children with low bacillary loads.
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Fezes/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Tuberculose/diagnóstico , Adolescente , Criança , Pré-Escolar , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Peru , Sensibilidade e Especificidade , Tuberculose/microbiologiaRESUMO
Following publication of the original article [1]. The authors reported that there is a mistake in Fig. 1: the number of patients in the control group its 449 patients, instead of 455.
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BACKGROUND: Dementia is a syndrome, with a wide range of symptoms. It is important to have a timely diagnosis during the disease course to reduce the risk of medication errors, enable future care planning for the patient and their relatives thereby optimizing quality of life (QoL). For this reason, it is important to avoid a diagnosis of dementia not otherwise specified (DNOS) and instead obtain a diagnosis that reflects the underlying pathology. The aim of this study was to investigate the prevalence and associated factors of DNOS in persons with dementia living at home or in a nursing home. METHODS: This is a cross-sectional cohort study performed in eight European countries. Persons with dementia aged ≥65 years living at home (n = 1223) or in a nursing home (n = 790) were included. Data were collected through personal interviews with questionnaires based on standardised instruments. Specific factors investigated were sociodemographic factors, cognitive function, and mental health, physical health, QoL, resource utilization and medication. Bivariate and backward stepwise multivariate regression analyses were performed. RESULTS: The prevalence of DNOS in the eight participating European countries was 16% (range 1-30%) in persons living at home and 21% (range 1-43%) in persons living in a nursing home. These people are more often older compared to those with a specific dementia diagnosis. In both persons living at home and persons living in a nursing home, DNOS was associated with more severe neuropsychiatric symptoms and less use of anti-dementia medication. In addition, persons with DNOS living at home had more symptoms of depression and less use of antidepressant medication. CONCLUSIONS: The prevalence of DNOS diagnosis is common and seems to vary between European countries. People with DNOS are more often older with more severe neuropsychiatric symptoms and receive fewer anti-dementia medication, anxiolytics and antidepressants. This would support the suggestion that a proper and specific diagnosis of dementia could help the management of their disease.
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Demência/diagnóstico , Demência/epidemiologia , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Cognição/fisiologia , Estudos de Coortes , Estudos Transversais , Demência/psicologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Vida Independente/psicologia , Vida Independente/tendências , Masculino , Casas de Saúde/tendências , Prevalência , Qualidade de Vida/psicologiaRESUMO
BACKGROUND: To assess the quality of life of people with dementia, measures are required for self-rating by the person with dementia, and for proxy rating by others. The Quality of Life in Alzheimer's Disease scale (QoL-AD) is available in two versions, QoL-AD-SR (self-rating) and QoL-AD-PR (proxy rating). The aim of our study was to analyse the inter-rater agreement between self- and proxy ratings, in terms of both the total score and the items, including an analysis specific to care setting, and to identify factors associated with this agreement. METHODS: Cross-sectional QoL-AD data from the 7th Framework European RightTimePlaceCare study were analysed. A total of 1330 cases were included: n = 854 receiving home care and n = 476 receiving institutional long-term nursing care. The proxy raters were informal carers (home care) and best-informed professional carers (institutional long-term nursing care). Inter-rater agreement was investigated using Bland-Altman plots for the QoL-AD total score and by weighted kappa statistics for single items. Associations were investigated by regression analysis. RESULTS: The overall QoL-AD assessment of those with dementia revealed a mean value of 33.2 points, and the proxy ratings revealed a mean value of 29.8 points. The Bland-Altman plots revealed a poor agreement between self- and proxy ratings for the overall sample and for both care settings. With one exception (item 'Marriage' weighted kappa 0.26), the weighted kappa values for the single QoL-AD items were below 0.20, indicating poor agreement. Home care setting, dementia-related behavioural and psychological symptoms, and the functional status of the person with dementia, along with the caregiver burden, were associated with the level of agreement. Only the home care setting was associated with an increase larger than the predefined acceptable difference between self- and proxy ratings. CONCLUSIONS: Proxy quality of life ratings from professional and informal carers appear to be lower than the self-ratings of those with dementia. QoL-AD-SR and QoL-AD-PR are therefore not interchangeable, as the inter-rater agreement differs distinctly. Thus, a proxy rating should be judged as a complementary perspective for a self-assessment of quality of life by those with dementia, rather than as a valid substitute.
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Doença de Alzheimer/psicologia , Procurador/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários/normas , Idoso , Idoso de 80 Anos ou mais , Cuidadores/psicologia , Estudos Transversais , Feminino , Serviços de Assistência Domiciliar , Humanos , Masculino , AutorrelatoRESUMO
Objectives: to evaluate the frequency of potentially inappropriate medication (PIM) prescription among older people with dementia (PwD) from eight countries participating in the European study 'RightTimePlaceCare', and to evaluate factors and adverse outcomes associated with PIM prescription. Methods: survey of 2,004 PwD including a baseline assessment and follow-up after 3 months. Interviewers gathered data on age, sex, prescription of medication, cognitive status, functional status, comorbidity, setting and admission to hospital, fall-related injuries and mortality in the time between baseline and follow-up. The European Union(7)-PIM list was used to evaluate PIM prescription. Multivariate regression analysis was used to investigate factors and adverse outcomes associated with PIM prescription. Results: overall, 60% of the participants had at least one PIM prescription and 26.4% at least two. The PIM therapeutic subgroups most frequently prescribed were psycholeptics (26% of all PIM prescriptions) and 'drugs for acid-related disorders' (21%). PwD who were 80 years and older, lived in institutional long-term care settings, had higher comorbidity and were more functionally impaired were at higher risk of being prescribed two PIM or more. The prescription of two or more PIM was associated with higher chance of suffering from at least one fall-related injury and at least one episode of hospitalisation in the time between baseline and follow-up. Conclusions: PIM use among PwD is frequent and is associated with institutional long-term care, age, advanced morbidity and functional impairment. It also appears to be associated with adverse outcomes. Special attention should be paid to psycholeptics and drugs for acid-related disorders.
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Demência/tratamento farmacológico , Prescrição Inadequada , Lista de Medicamentos Potencialmente Inapropriados , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/efeitos adversos , Demência/diagnóstico , Demência/psicologia , Interações Medicamentosas , Prescrições de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Avaliação Geriátrica , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Polimedicação , Padrões de Prática Médica , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVES: To investigate informal caregivers' psychological well-being and predicted increase in psychological well-being, when caring for persons with dementia (PwDs) living at home, related to caregiver, PwD and formal care (FC) factors. METHOD: A cohort study at baseline and 3 months' follow-up in eight European countries. Caregivers included (n = 1223) were caring for PwDs aged ≥ 65 years at home. Data on caregivers, PwDs and FC were collected using standardized instruments. Regression analysis of factors associated with caregiver psychological well-being at baseline and 3 months later was performed. RESULTS: Factors associated with caregiver psychological well-being at baseline were positive experience of caregiving, low caregiver burden, high quality of life (QoL) for caregivers, male gender of PwD, high QoL of PwD, few neuropsychiatric symptoms and depressive symptoms for the PwD. At follow-up, caregivers with increased psychological well-being experienced of quality of care (QoC) higher and were more often using dementia specific service. Predicting factors for caregivers' increased psychological well-being were less caregiver burden, positive experience of caregiving, less supervision of the PwD and higher caregiver QoL, if PwD were male, had higher QoL and less neuropsychiatric symptoms. Furthermore, higher QoC predicted increased caregivers' psychological well-being. CONCLUSION: Informal caregiving for PwDs living at home is a complex task. Our study shows that caregivers' psychological well-being was associated with, among other things, less caregiver burden and higher QoL. Professionals should be aware of PwD neuropsychiatric symptoms that might affect caregivers' psychological well-being, and provide proper care and treatment for caregivers and PwDs.
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Cuidadores/psicologia , Efeitos Psicossociais da Doença , Demência/enfermagem , Satisfação Pessoal , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Feminino , Seguimentos , Serviços de Assistência Domiciliar , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
COVID-19 , Demência/complicações , Administração dos Cuidados ao Paciente , Guias de Prática Clínica como Assunto , Comportamento Problema/psicologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/prevenção & controle , Demência/psicologia , Demência/terapia , Surtos de Doenças/prevenção & controle , França , Humanos , Pandemias , SARS-CoV-2RESUMO
PURPOSE: To describe available and utilized formal care and service at home for persons with dementia, from diagnosis to end-of-life stage, in eight European countries. DESIGN: A descriptive cross-country design concerning eight European countries as a part of the European research project RightTimePlaceCare. METHODS: The research team in each country used a mapping system to collect country-specific information concerning dementia care and service system. The mapping system consists of 50 types of care and service activities. Sixteen of the 50 predefined activities concerning care and service at home were selected for this study and subdivided into three categories, following the stages of dementia. FINDINGS: Availability was reported to be higher than utilization, and the findings indicated more similarities than differences among the eight countries involved. Even though there were several available activities of "basic care and services" and "healthcare interventions," they were utilized by few in most countries. Furthermore, "specialized dementia care and services" were sparsely available and even more sparsely utilized in the participating countries. CONCLUSIONS: The findings indicated that persons with dementia in Europe received formal care and service on a general, basic level but seldom adjusted to their specific needs. CLINICAL RELEVANCE: This study describes the gap between service provision and utilization enabling nurses to develop individually adjusted care plans for persons with dementia during the progress of the disease. The findings do not include matters of quality of care or how to best organize effective care and services. However, the activities of care and services presented here should shed light on what room there is for improvement when it comes to enabling persons with dementia to go on living at home.
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Atenção à Saúde/normas , Demência/enfermagem , Serviços de Assistência Domiciliar , Serviços Comunitários de Saúde Mental/normas , Demência/reabilitação , Europa (Continente) , Acessibilidade aos Serviços de Saúde/normas , Serviços de Assistência Domiciliar/normas , Serviços de Assistência Domiciliar/estatística & dados numéricos , Humanos , Apoio SocialRESUMO
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.
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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.