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INTRODUCTION: Guidelines are important tools for supporting quality management in the care of patients with cancer. However, in clinical practice barriers exist to their implementation. Consequently, Quincie aims at: (1) gaining a comprehensive picture of the implementation of quality indicators from the national guideline on palliative care for patients with incurable cancer in palliative care units and (2) describing the factors that facilitate and hinder their implementation to develop recommendations. METHODS AND ANALYSIS: The Quincie study follows a mixed-methods approach across two study phases. In phase 1, routinely collected data of 845 patients with incurable cancer from eight palliative care units in the commuting area of the Comprehensive Cancer Centre Lower Saxony will be analysed, regarding the implementation of 10 quality indicators from the national guideline on palliative care. Structural characteristics of the palliative care units will also be collected. In phase 2, recommendations for the practical implementation of the quality indicators, focusing on the achievement of the quality objectives identified in phase 1, will be developed in an implementation workshop. These recommendations will be subsequently agreed on via a Delphi survey. ETHICS AND DISSEMINATION: Ethical approval has been given by the ethics committee of the Hannover Medical School (first vote, No. 10567_BO_K_2022) and other relevant institutions. The results will provide urgently needed insights on the implementation of the national guideline on palliative care in clinical care and on the factors that facilitate and hinder this implementation. The results are expected to promote better care for patients with incurable cancer. The results will be directly reported to the participating palliative care units and will be published in relevant peer-reviewed journals. They will also be presented at national conferences. TRIAL REGISTRATION NUMBER: German Clinical Trials Register (DRKS00029965).
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Neoplasias , Cuidados Paliativos , Indicadores de Qualidade em Assistência à Saúde , Humanos , Cuidados Paliativos/normas , Cuidados Paliativos/organização & administração , Neoplasias/terapia , Alemanha , Projetos de Pesquisa , Técnica DelphiRESUMO
BACKGROUND: Needs-based, patient-oriented palliative care includes palliative day care clinics as a specialized semi-inpatient care offer. However, the establishment and development of these facilities has been unsystematic. Research is needed to strengthen their transparency and ensure their accessibility, quality, and structural adequacy. A national Delphi study was conducted to generate appropriate recommendations for the establishment and development of palliative day care clinics in Germany. METHODS: Recommendations were formulated from focus group data on the development and expansion of palliative day care clinics in Germany. Experts on in- and outpatient palliative care rated 28 recommendations for relevance and feasibility, respectively, using a 4-point Likert-type scale. Suggestions for improvement were captured via free text comments. Items were considered consented when more than 80% of the experts scored them 4 (strongly agree) or 3 (somewhat agree), regarding both relevance and feasibility. RESULTS: A total of 23 experts (32% response rate) completed three Delphi rounds. Following the first round, 10 of 28 recommendations were revised according to participants' comments; 1 recommendation was rejected. After the second round, 3 of these 10 recommendations were revised, while 3 were rejected. Consensus was achieved after the third round for 22 of the initial recommendations. CONCLUSIONS: The Delphi-consented recommendations provide a basis for the targeted evidence- and needs-based development of palliative day care clinics. The findings show a need for standards setting and the meaningful integration of these clinics into existing structures. TRIAL REGISTRATION: The present study was prospectively registered on April 20, 2020, with the German Clinical Trials Register (DRKS00021446).
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Consenso , Técnica Delphi , Grupos Focais , Cuidados Paliativos , Humanos , Alemanha , Cuidados Paliativos/normas , Cuidados Paliativos/métodos , Grupos Focais/métodos , Hospital Dia/normas , Hospital Dia/métodos , Feminino , Pessoa de Meia-Idade , Masculino , AdultoRESUMO
INTRODUCTION: A needs-based and patient-oriented hospice and palliative care also includes day hospices as a specialised semi-inpatient care offer. The establishment and development of these facilities in Germany has been rather unsystematic. In order to ensure quality and adequacy of these structures, research is needed. METHODS: A Delphi consensus study was conducted online from November 2022 to February 2023 aiming at generating recommendations for the development and expansion of day hospices in Germany. For each recommendation, the participants indicated on a four-point verbal rating scale how much they agreed upon a) the relevance and b) the feasibility of the recommendation. Items were considered consented when 80% of the participants (strongly) agreed with the recommendation regarding both criteria. If no consensus was reached, the recommendations were revised according to the participants' free text comments and presented in the next Delphi round. Descriptive analyses were applied. RESULTS: A total of 64 experts participated in the first Delphi round and 44 in the second. In round 1, 34 recommendations and in round 2 six recommendations were consented. The final set contains a total of 40 recommendations: 18 on the tasks of day hospices, 13 on cooperation, 7 on funding, and 2 on public relations. DISCUSSION: Recommendations for the development and expansion of day hospices in Germany were developed. Due to their highly rated feasibility, the recommendations should be directly transferable into care practice. It remains to be seen to what extent they will be taken into account in the renegotiation of the framework agreement for day hospices. CONCLUSION: The Delphi-consented recommendations provide a basis to guide action in the currently very dynamic development of hospice work and palliative care in Germany.
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Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Humanos , Alemanha , Cuidados Paliativos , Consenso , Técnica DelphiRESUMO
We compared characteristics of HIV diagnosis and recent HIV infection (ie, likely acquired within the last year) in Cambodia. We included individuals ≥ 15 years old accessing HIV testing. From August 2020 to August 2022, 53 031 people were tested for HIV, 6868 were newly diagnosed, and 192 were recently infected. We found differences in geographical burden and risk behaviors with diagnosis and recency (eg, men who have sex with men, transgender women, and entertainment workers had a nearly 2-fold increased odds of testing positive for recent infection compared to being diagnosed with HIV). Recent infection surveillance may provide unique insights into ongoing HIV acquisition to inform programs.
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Infecções por HIV , Minorias Sexuais e de Gênero , Pessoas Transgênero , Masculino , Humanos , Feminino , Adolescente , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Camboja/epidemiologia , Programas de RastreamentoRESUMO
BACKGROUND: The Malawi Ministry of Health implemented a new surveillance activity in April 2019 to detect recent HIV infections using a rapid test for recent infection (RTRI) to identify areas of ongoing transmission and guide response activities. SETTING: At 23 health facilities in Blantyre District, healthcare workers (HCWs) were trained to conduct recent infection testing. In September 2019, we conducted a cross-sectional survey at these sites to explore the acceptability and feasibility of integrating this activity into routine HIV testing services (HTS). METHODS: Research assistants interviewed HCWs using a semi-structured survey. Descriptive statistics were used to summarize quantitative responses and thematic analysis was used to group open-ended text. RESULTS: We interviewed 119 HCWs. Eighty-two percent of participants reported the RTRI was easy-to-use. HCWs perceived high client acceptability; 100% reported clients as 'somewhat' or 'very accepting'. Challenges included 68% of HCWs estimating they spend ≥20 min beyond routine HTS per client for this activity and 51% performing at least two additional finger pricks to complete the testing algorithm. HCWs differed in their perceptions of whether results should be returned to clients. CONCLUSION: This study assessed HCW experiences using point-of-care RTRIs for HIV recent infection surveillance. Overall, HCWs perceived RTRIs to be acceptable, easy-to-use, and valuable. Though only clients with new HIV diagnoses are tested for recent infection, additional time may be substantial at high-volume health service delivery points. Providing response plans or aggregated recent infection results to HCWs and/or clients may support motivation and sustainability of this novel surveillance activity.
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Infecções por HIV , Estudos Transversais , Estudos de Viabilidade , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV , Pessoal de Saúde , Humanos , MalauiRESUMO
Persons infected with HIV are more likely to transmit the virus during the early stages (acute and recent) of infection, when viral load is elevated and opportunities to implement risk reduction are limited because persons are typically unaware of their status (1,2). Identifying recent HIV infections (acquired within the preceding 12 months)* is critical to understanding the factors and geographic areas associated with transmission to strengthen program intervention, including treatment and prevention (2). During June 2019, a novel recent infection surveillance initiative was integrated into routine HIV testing services in Malawi, a landlocked country in southeastern Africa with one of the world's highest prevalences of HIV infection. The objectives of this initiative were to collect data on new HIV diagnoses, characterize the epidemic, and guide public health response (2). New HIV diagnoses were classified as recent infections based on a testing algorithm that included results from the rapid test for recent infection (RTRI)§ and HIV viral load testing (3,4). Among 9,168 persons aged ≥15 years with a new HIV diagnosis who received testing across 103 facilities during October 2019-March 2020, a total of 304 (3.3%) were classified as having a recent infection. Higher proportions of recent infections were detected among females, persons aged <30 years, and clients at maternal and child health and youth clinics. Using a software application that analyzes clustering in spatially referenced data, transmission hotspots were identified with rates of recent infection that were significantly higher than expected. These near real-time HIV surveillance data highlighted locations across Malawi, allowing HIV program stakeholders to assess program gaps and improve access to HIV testing, prevention, and treatment services. Hotspot investigation information could be used to tailor HIV testing, prevention, and treatment to ultimately interrupt transmission.
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Hotspot de Doença , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Teste de HIV/métodos , Vigilância de Evento Sentinela , Análise Espacial , Adulto , Feminino , Humanos , Malaui/epidemiologia , Masculino , Saúde Pública , Software , Adulto JovemRESUMO
We evaluated the impact of language concordance-clinician or public health worker fluency in a patient's primary language-on coronavirus disease 2019 (COVID-19) contact tracing outcomes among 2668 Spanish-speaking adults in San Francisco. Language concordance was associated with 20% greater odds of COVID-19 testing and 53% greater odds of support service referrals.
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BACKGROUND: The extent to which vaccinated persons diagnosed with coronavirus disease 2019 (COVID-19) can transmit to other vaccinated and unvaccinated persons is unclear. METHODS: Using data from the San Francisco Department of Public Health, this report describes outcomes of household contact tracing during 29 January-2 July 2021, where fully vaccinated patients with COVID-19 were the index case in the household. RESULTS: Among 248 fully vaccinated patients with breakthrough infections, 203 (82%) were symptomatic and 105 were identified as the index patient within their household. Among 179 named household contacts, 71 (40%) contacts tested, over half (56%) were fully vaccinated and the secondary attack rate was 28%. Overall transmission from a symptomatic fully vaccinated patient with breakthrough infection to household contacts was suspected in 14 of 105 (13%) of households. Viral genomic sequencing of samples from 44% of fully vaccinated patients showed that 82% of those sequenced were infected by a variant of concern or interest and 77% by a variant carrying mutation(s) associated with resistance to neutralizing antibodies. CONCLUSIONS: Transmission from fully vaccinated symptomatic index patients to vaccinated and unvaccinated household contacts can occur. Indoor face masking and timely testing of all household contacts should be considered when a household member receives a positive test result in order to identify and interrupt transmission chains.
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COVID-19 , Busca de Comunicante , COVID-19/prevenção & controle , Características da Família , Humanos , SARS-CoV-2 , São Francisco/epidemiologiaRESUMO
To effectively control the spread of COVID-19, it is essential that all jurisdictions have the capacity to rapidly contact trace all close contacts of each and every case. We describe the early experience in the City and County of San Francisco, where contact tracing capability was rapidly expanded to respond to COVID-19. Important prerequisites to scale up included rapid expansion of the COVID-19 contact tracing workforce, a comprehensive training and onboarding program, and the institution of effective performance management metrics. The San Francisco model for contact tracing, including focusing on rigorous training, recruiting, and partnering with community-based organizations from diverse, affected communities, is an inclusive approach relevant to other jurisdictions and settings.
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COVID-19/prevenção & controle , Busca de Comunicante , Mão de Obra em Saúde , SARS-CoV-2 , Humanos , Resiliência PsicológicaRESUMO
While occasional déjà vu is benign in the general population, rare neuropsychological cases with persistent déjà vu have been described in the literature. We report the case of MN, a 25-year-old woman, who suffered a cerebral haemorrhage in the right thalamo-callosal region and experienced recurrent déjà vu episodes. Through clinical interviews and memory tasks related to déjà vu, we assumed that source memory errors and an inappropriate feeling of familiarity (measured by the number of false recognitions) were critically involved in MN's déjà vu. Based on this, we developed the first neuropsychological intervention dedicated to déjà vu. The rationale was to train MN to detect elements that could produce an inappropriate feeling of familiarity and to promote metacognitive awareness about déjà vu. This intervention was effective at reducing the frequency of déjà vu episodes in MN's daily life, as well as the number of false recognitions in memory tasks. In addition to its clinical contribution, this single-case study contributes to the limited literature on patients whose déjà vu is not related to epileptic abnormalities and medial temporal brain damage, and provide supportive evidence of the role of an erroneous feeling of familiarity and of metacognitive processes in déjà vu.
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Ilusões , Adulto , Cognição , Emoções , Feminino , Humanos , Reconhecimento PsicológicoRESUMO
Our senses are constantly stimulated in our daily lives but we have only a limited understanding of how they affect our cognitive processes and, especially, our autobiographical memory. Capitalizing on a public science event, we conducted the first empirical study that aimed to compare the relative influence of the five senses on the access, temporal distribution, and phenomenological characteristics of autobiographical memories in a sample of about 400 participants. We found that the access and the phenomenological features of memories varied as a function of the type of sensory cues, but not their temporal distribution. With regard to their influence on autobiographical memory, an overlap between some senses was found, with on one hand, olfaction and taste and, on the other, vision, audition, and touch. We discuss these findings in the light of theories of perception, memory, and the self, and consider methodological implications of the sensory cuing technique in memory research, as well as clinical implications for research in psychopathological and neuropsychological populations.
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OBJECTIVE: To review the current literature on the use of viscoelastic hemolytic assays, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), during the perioperative period of patients and determine the ability of TEG and ROTEM to detect hypercoagulability and identify increased risk of the development of venous thromboembolism (VTE). DATA SOURCES: PubMed, EMBASE, and Cochrane online databases were queried through February 11, 2018, by pairing the terms "thromboelastography," "viscoelastic hemostatic assays," and "rotational thromboelastometry" with "venous thromboembolism," "deep vein thrombosis," "pulmonary embolism," and "hypercoagulability." STUDY SELECTION: Inclusion and exclusion criteria were established to determine relevance and quality of data, of which 2.54% of initially identified studies met. DATA EXTRACTION AND SYNTHESIS: Articles and citations were reviewed for relevance by 2 independent individuals following PRISMA guidelines as well as a quality assessment of data as established by Zaza et al. In studies that separated patients postoperatively by VTE development or no VTE development, data were pooled utilizing a modified DerSimmion and Laird random effects model. RESULTS: One thousand eight hundred ninety-three articles were assessed for eligibility, yielding 370 abstracts. Of the 370 abstracts, 35 studies were included, and of these, only 5 were included in the meta-analysis. Studies included postsurgical patients in a variety of surgical fields, encompassing a total of 8939 patients, with 717 thrombotic events reported. Elevated maximum amplitude (MA) was a statistically significant indicator of hypercoagulability across at least 1 perioperative time point in 17 (50%) of the articles reviewed, consisting of 6348 (72%) patients. The pooled mean MA value for defining hypercoagulability was greater than 66.70 mm. Using a prepublished value for hypercoagulability of 65 mm, the combined effect of MA on the development of VTE in postsurgical patients was determined to be 1.31 (95% confidence, 0.74-2.34, P = 0.175) and was 46% sensitive and 62% specific in predicting a postoperative VTE. CONCLUSIONS: Only 1 parameter, MA, was consistently used to both define hypercoagulability and be predictive of VTE after traumatic injury and surgical intervention; however, there remains a broad variability in the definition of hypercoagulability as determined by MA and thus limits its predictive ability. In addition, when hypercoagulability was measured throughout the perioperative period, TEG consistently demonstrated hypercoagulability starting on post-op day 1 (POD1). LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Embolia Pulmonar , Trombofilia , Tromboembolia Venosa , Humanos , Tromboelastografia , Trombofilia/diagnóstico , Tromboembolia Venosa/diagnósticoRESUMO
Learning and memory impairments are common in individuals with multiple sclerosis (MS) and have pervasive effects on everyday life functioning. Hence, memory and learning have received particular attention in the cognitive rehabilitation literature in MS. The effectiveness of memory rehabilitation on memory performance is supported by several studies, but the generalisability of the benefits to daily life and memory for real-life events has rarely been examined. Recently, a new line of research focusing on memory for personal life events (i.e., autobiographical memory) has emerged in the MS literature. This approach is complementary to classical learning and memory paradigms and also allows for approaching memory in a broader context, one that considers memory as the ability to remember past episodes and imagine events that may occur in one's personal future (i.e. future thinking). This review provides an overview of the findings in this line of work. The first part summarises current evidence regarding the cognitive and neural mechanisms underlying autobiographical memory and future thinking impairments in MS. It points out that these domains are frequently and early impaired in individuals with MS because of an executive/frontal-related deficit. Individuals with MS are generally aware of these deficits and their negative impact on everyday life, so the development of strategies to alleviate such deficits seems of paramount importance. Thus, in the second part, I present the main outcomes of a cognitive intervention developed by our research group, which has been specifically designed to alleviate autobiographical memory and future thinking impairments in individuals with MS. The implications of these findings for neuropsychological care and well-being of individuals with MS are discussed in the final section, with an emphasis on the functional role of autobiographical memory and future thinking in various domains, including personal identity.
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Transtornos da Memória/etiologia , Memória Episódica , Esclerose Múltipla/psicologia , Córtex Cerebral/fisiopatologia , Função Executiva , Feminino , Previsões , Humanos , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/fisiopatologia , Deficiências da Aprendizagem/reabilitação , Masculino , Transtornos da Memória/fisiopatologia , Transtornos da Memória/reabilitação , Esclerose Múltipla/complicações , Neuroimagem , Testes Neuropsicológicos , Pesquisa Qualitativa , Índice de Gravidade de Doença , PensamentoRESUMO
The impact of memory loss on the self in Alzheimer's disease (AD) is poorly understood. Previous research is mixed on whether episodic or semantic memories are most important for supporting identity. The present study examined autobiographical memories cued by self-images (e.g., I am a father) and non-self-related cues in 16 AD patients and 29 healthy older adults. The AD group generated fewer self-images and memories compared to controls, but demonstrated similar temporal organization of self-cued memories. In both groups, self-images were supported by semantic memories that were temporally clustered around times of identity-formation. These self-supporting memories are proposed to form a scaffold to support the self and may persist the longest in AD, as opposed to memories from early adulthood per se. In both AD and control groups, self-images cued more semantic memories than non-self-relevant cues, further suggesting that semantic autobiographical memories play a fundamental role in supporting the self. These findings demonstrate that the self remains largely intact in AD, in spite of severe episodic memory deficits and global cognitive decline. In later stages of the disease, these self-supporting memories could provide effective tools for reminiscence therapy.
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Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Rememoração Mental/fisiologia , Autoimagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Atenção/fisiologia , Feminino , Humanos , Masculino , Transtornos da Memória/fisiopatologia , Memória Episódica , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Recent studies suggest that different forms of episodic simulation-mental representations of past, future, or atemporal events-recruit many of the same underlying cognitive and neural processes. This leads to the question whether there are distinctive hallmark characteristics of episodic future thinking: the subjective sense that imagined events belong to and will occur in the personal future. In this study, we aimed at shedding light on the cognitive ingredients that contribute to this sense of future occurrence by asking participants to imagine personal and experimenter-provided future events associated with high or low degrees of belief in future occurrence and then to reflect on the bases for their beliefs. Results showed that contextualising autobiographical knowledge (i.e., articulating links between items of information associated with imagined future events, goals, and personal characteristics) is a critical aspect of belief in future occurrence, and autobiographical knowledge can be flexibly used to either support or suppress belief in future occurrence. These findings indicate that episodic future thought not only depends on simulation processes (i.e., the construction of detailed mental representations for future events) but also requires that imagined events are meaningfully integrated within an autobiographical context.
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Imaginação , Memória Episódica , Processos Mentais , Metacognição , Pensamento , Adulto , Cultura , Feminino , Previsões , Humanos , Masculino , Rememoração MentalRESUMO
While it is established that goal processing is a central component of episodic future thinking, how personal goals shape future event representations is not fully understood. Here, we explored the influence of the source of motivation underlying goal pursuit. Personal goals differ in their degree of self-concordance, which depends on the primary motives underlying goal pursuit. We distinguished between self-concordant (what one wants to achieve) and non-self-concordant (what one has to achieve) goals. Participants were asked to imagine specific future events associated with each type of goals. We found that self-concordant future events have a privileged phenomenological status: they are associated with a stronger sense of "realness" and of pre-experiencing the future, are more integrated with autobiographical knowledge, and are characterized by more positive and intense emotions. Furthermore, psychological need satisfaction was a characteristic component of self-concordant future thoughts. Implications of these findings for motivation and goal pursuit are discussed.
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Objetivos , Imaginação/fisiologia , Satisfação Pessoal , Pensamento/fisiologia , Adulto , Feminino , Humanos , Masculino , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: To evaluate the available literature for associations between nutrition and outcomes after operative treatment of long bone and long bone periarticular fractures. DATA SOURCES: Systematic review of English-language articles in the MEDLINE, Embase, PubMed, and Cochrane computerized literature databases (through December 2015) using PRISMA guidelines. STUDY SELECTION: Randomized controlled trials, quasi-randomized controlled trials, case-control studies, and cohort studies (retrospective and prospective) involving long bone and long bone periarticular fractures that included the effect of nutritional status on fracture union, time to union, and any related soft-tissue complication were eligible for review. DATA EXTRACTION: Two authors independently extracted data from the selected studies using a standardized data collection form with predefined data fields for demographics, interventions, study methods, complications, and management outcomes. DATA SYNTHESIS: Although one of the original aims of the study was to conduct a meta-analysis, the available literature did not offer sufficient data for meta-analysis. CONCLUSIONS: Although our systematic review demonstrates a possible role for oral nutritional supplementation and vitamin supplementation in the orthopaedic trauma patient, there remains a need for well-designed trials to clarify this role. There is likely benefit to multidisciplinary approaches to nutritional optimization in the orthopaedic trauma patient, and this should be explored further in forthcoming work. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Fixação de Fratura/métodos , Consolidação da Fratura/fisiologia , Fraturas Ósseas/cirurgia , Desnutrição/epidemiologia , Apoio Nutricional/métodos , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Seguimentos , Fixação de Fratura/efeitos adversos , Fraturas Ósseas/diagnóstico por imagem , Humanos , Masculino , Desnutrição/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
While the efficacy of mental visual imagery (MVI) to alleviate autobiographical memory (AM) impairment in multiple sclerosis (MS) patients has been documented, nothing is known about the brain changes sustaining that improvement. To explore this issue, 20 relapsing-remitting MS patients showing AM impairment were randomly assigned to two groups, experimental (n = 10), who underwent the MVI programme, and control (n = 10), who followed a sham verbal programme. Besides the stringent AM assessment, the patients underwent structural and functional MRI sessions, consisting in retrieving personal memories, within a pre-/post-facilitation study design. Only the experimental group showed a significant AM improvement in post-facilitation, accompanied by changes in brain activation (medial and lateral frontal regions), functional connectivity (posterior brain regions), and grey matter volume (parahippocampal gyrus). Minor activations and functional connectivity changes were observed in the control group. The MVI programme improved AM in MS patients leading to functional and structural changes reflecting (1) an increase reliance on brain regions sustaining a self-referential process; (2) a decrease of those reflecting an effortful research process; and (3) better use of neural resources in brain regions sustaining MVI. Functional changes reported in the control group likely reflected ineffective attempts to use the sham strategy in AM.