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1.
Science ; 367(6483): 1195-1196, 2020 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-32165571
2.
Leuk Lymphoma ; : 1-9, 2020 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-32148161

RESUMEN

Cancer-related cognitive impairment (CRCI) has not been objectively assessed in chronic lymphocytic leukemia (CLL). It is currently unclear how much of CRCI is attributable to disease, treatment, or both. We used CLL as a novel model to study the differential roles of disease and treatment in CRCI. One hundred and fifty CLL patients (100 treatment-naïve and 50 chemotherapy-treated) including 84 patients with higher-risk of CLL progression completed objective neuropsychological tests. Sociodemographic-adjusted linear regression models examined cognitive outcomes in relation to risk and treatment. Higher-risk patients recalled two fewer words on a memory task (ß = -1.8, 95%CI -3.3,-0.3) and took 15 s longer on an executive function task (ß = 15.4, 95%CI 3.1, 27.6) than lower-risk patients, independent of treatment. Treated patients reported greater cognitive difficulties than treatment-naive patients (ß = -6.1, 95%CI -10.1, -2.2) but did not perform worse on objective measures. Higher-risk patients experienced impairments in executive function and memory suggesting that disease biology contributes to CRCI independent of treatment.

3.
Leuk Lymphoma ; : 1-9, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32175786

RESUMEN

Family and migration studies suggest a genetic risk of developing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). We hypothesized that CLL patients have an increased risk of additional clonally unrelated B-cell malignancies. To test this, we studied 467 CLL patients (2743 person-years (PYs)) at a single institution over 17 years. The incidence rate (IR) of any additional B-cell lymphoid malignancy was 10.9 per 1000 PYs (n = 30, 6.4%). Eighteen (4%) patients had a clonally unrelated B-cell malignancy (IR = 6.6 per 1000 PYs). Standardized incidence ratios (SIRs) were used to compare the incidence of additional clonally unrelated B-cell malignancies in CLL patients to the age- and sex-matched expected rates in the USA generated from the Surveillance, Epidemiology, and End Results (SEER) database. For the subset of 13 patients having data for comparison in the SEER database, the SIR was 5.41 (95% CI = 2.9, 9.3) which is supportive of our hypothesis.

6.
Stem Cell Reports ; 13(6): 1053-1067, 2019 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-31708478

RESUMEN

Cell lineage reprogramming via transgene overexpression of key master regulatory transcription factors has been well documented. However, the poor efficiency and lack of fidelity of this approach is problematic. Synthetic transcription factors (sTFs)-built from the repurposed CRISPR/Cas9 system-can activate endogenous target genes to direct differentiation or trigger lineage reprogramming. Here we explored whether sTFs could be used to steer mouse neural stem cells and mouse embryonic fibroblasts toward the oligodendrocyte lineage. We developed a non-viral modular expression system to enable stable multiplex delivery of pools of sTFs capable of transcriptional activation of three key oligodendrocyte lineage master regulatory genes (Sox10, Olig2, and Nkx6-2). Delivery of these sTFs could enhance neural stem cell differentiation and initiated mouse embryonic fibroblast direct reprograming toward oligodendrocyte progenitor-like cells. Our findings demonstrate the value of sTFs as tools for activating endogenous genes and directing mammalian cell-type identity.

7.
Clin J Oncol Nurs ; 23(6): 592-598, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31730601

RESUMEN

BACKGROUND: Understanding the experiences of patients with solid tumors who are in phase 1 clinical trials can help nurses to provide optimal care. OBJECTIVES: The purpose of this article is to describe patient perspectives of participating in a phase 1 trial and understanding their disease status and treatment options. In addition, the authors describe the impact of the disease and clinical trial participation on quality of life. METHODS: 30 patients were interviewed and audio recorded; the interviews were transcribed and content analysis methods were used to identify common themes. FINDINGS: Patients reported participating in the phase 1 clinical trial because their doctors informed and encouraged them, they had no other treatment options if they wanted to live longer, or they wanted to help future patients with cancer. Most believed that participation would improve or stabilize their illness and quality of life. They believed that, when the clinical trial ended, there would be new treatments. Participants reported that healthcare providers and family members provided support, and that compassion, cultural awareness, spiritual support, and the need for individual attention were important.

8.
Front Neurol ; 10: 1029, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31608006

RESUMEN

Increasing evidence suggests a role for endothelial cell (EC) dysfunction in pathogenesis of cerebral small vessel disease. Commonly used medications including certain antihypertensives and statins have EC-stabilizing effects. We used individual patient data from completed acute stroke trials to assess whether prior exposure to EC-stabilizing medications was associated with lacunar stroke, using lacunar stroke as a clinical proxy for cerebral small vessel disease. Across 12,002 patients with relevant data, 2,855 (24%) had a lacunar stroke presentation. Univariable analyses suggested potential confounding from vascular diseases treated with EC-stabilizing medications. Initial multivariable logistic regression gave conflicting results when describing the independent association of exposure to EC-stabilizing medication and lacunar stroke in the complete population (O.R. 0.87, 95% C.I.: 0.77- 0.98) and limited to those taking any antihypertensive (O.R. 1.51, 95% C.I.: 1.21-1.88). Re-running the analyses including statins in the EC-stabilizing category suggested a beneficial effect of EC-stabilizing medication exposure on lacunar stroke incidence (O.R. 0.83, 95% C.I.: 0.73-0.93). These results align with recent pre-clinical data and would support interventional trials of EC-stabilizing medication for preventing cerebral small vessel disease. Our results also suggest that analyses of EC-stabilizing interventions need to adjust for potential endothelial effects of other co-prescribed medication.

9.
Glob Health Sci Pract ; 7(3): 457-468, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31527058

RESUMEN

INTRODUCTION: Eclampsia-related conditions are the second leading direct cause of obstetric deaths in Bangladesh. Efforts to prevent such deaths in low- and middle-income countries are increasingly focused on task shifting at the primary care level to enable frontline providers to screen and initiate treatment for women with preeclampsia, severe preeclampsia, and eclampsia (PE/SPE/E). The MaMoni Health Systems Strengthening project (funded by the United States Agency for International Development) implemented a magnesium sulfate intervention at primary care facilities in 4 Bangladesh districts in 2016 and 2017. METHODS: The project trained frontline providers through a cascade approach from the national to the union level. A PE/SPE/E patient algorithm, digital blood pressure machines, and eclampsia kits with magnesium sulfate were supplied to service providers at each facility. We conducted a retrospective record review of facility-level data to assess the degree to which newly trained frontline providers adhered to a protocol that incorporated the use of magnesium sulfate for SPE/E in primary care settings. RESULTS: In total, 283 women were found to have PE/SPE/E. Fifty-four percent were managed according to the protocol. The required supplies were present at each facility, but some issues existed with regard to availability and functionality of blood pressure apparatuses. DISCUSSION: Challenges related to recordkeeping and service quality limited the analysis. Frontline providers need refresher trainings, ongoing supervision, properly calibrated blood pressure devices, and performance monitoring support in order to improve screening and management of PE/SPE/E in primary care facilities.

10.
Acta Biomater ; 97: 216-229, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31425890

RESUMEN

The pathology of multiple sclerosis (MS) is typified by focal demyelinated areas of the brain and spinal cord, which results in axonal degeneration and atrophy. Although the field has made much progress in developing immunomodulatory therapies to reduce the occurrence of these focal lesions, there is a conspicuous lack of licensed effective therapies to reduce axonal degeneration or promote repair. Remyelination, carried out by oligodendrocytes, does occur in MS, and is protective against axonal degeneration. Unfortunately, remyelination is not very efficient, and ultimately fails and so there is a research focus to generate new therapeutics to enhance remyelination leading to neuroprotection. To develop these therapies, we need preclinical models that well reflect remyelination in MS. We have previously characterized an ex vivo model that uses lysophosphatidylcholine (LPC) to cause acute and global demyelination of tissue slices, followed by spontaneous remyelination, which has been widely used as a surrogate for in vivo rodent models of demyelination. However, this ex vivo model lacks the focal demyelinated lesions seen in MS, surrounded by normal tissue from which the repairing oligodendrocytes are derived. Therefore, to improve the model, we have developed and characterized small macroporous cryogel scaffolds for controlled/regional delivery of LPC with diameters of either 0.5, 1 or 2 mm. Placement of LPC loaded scaffolds adjacent to ex vivo cultured mouse brain and spinal cord slices induced focal areas of demyelination in proximity to the scaffold. To the best of our knowledge, this is the first such report of spatial mimicry of the in vivo condition in ex vivo tissue culture. This will allow not only the investigation into focal lesions, but also provides a better platform technology with which to test remyelination-promoting therapeutics. STATEMENT OF SIGNIFICANCE: This manuscript is the first report of using macroporous hydrogels (cryogels) as a research tool for lysophosphatidylcholine (LPC) delivery, in order to create an ex vivo model of focal demyelination in the brain and spinal cord, which is of great relevance to multiple sclerosis research. Here, we transform an existing ex vivo model of demyelination by delivering LPC to focal regions of brain and spinal cord slice cultures. We have developed an easy-to-handle cylindrical and macroporous PEG-based sponge-like scaffold material (cryogel) that can deliver LPC only to a small area of the slice. Such cryogels are ideal as a delivery system in this culture model as they exhibit a soft but robust nature, with high mechanical deformability in their dry and swollen state, with no need to stay permanently hydrated. In addition, the synthesis of these cryogels is simple and easy to reproduce via photochemical cryopolymerisation using a PEG-diacrylate monomer and a photoinitiator, which are both commercially available. This more accurate model of demyelination will not only allow researchers to gain a better understanding of the CNS remyelination process in diseases such as MS, but also provides a platform technology, which could be utilized to screen and test pro-remyelination compounds which may help to find new therapeutics for progressive MS.

11.
Biomacromolecules ; 20(10): 4008-4014, 2019 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-31408325

RESUMEN

Polymeric nanoparticles (NPs) are attractive candidates for the controlled and targeted delivery of therapeutics in vitro and in vivo. However, detailed understanding of the uptake, location, and ultimate cellular fate of the NPs is necessary to satisfy safety concerns, which is difficult because of the nanoscale size of these carriers. In this work, we show how small chemical labels can be appended to poly(lactic acid-co-glycolic acid) (PLGA) to synthesize NPs that can then be imaged by stimulated Raman scattering microscopy, a vibrational imaging technique that can elucidate bond-specific information in biological environments, such as the identification of alkyne signatures in modified PLGA terpolymers. We show that both deuterium and alkyne labeled NPs can be imaged within primary rat microglia, and the alkyne NPs can also be imaged in ex vivo cortical mouse brain tissue. Immunohistochemical analysis confirms that the NPs localize in microglia in the mouse brain tissue, demonstrating that these NPs have the potential to deliver therapeutics selectively to microglia.

12.
Nat Neurosci ; 22(7): 1046-1052, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31182869

RESUMEN

Failed regeneration of CNS myelin contributes to clinical decline in neuroinflammatory and neurodegenerative diseases, for which there is an unmet therapeutic need. Here we reveal that efficient remyelination requires death of proinflammatory microglia followed by repopulation to a pro-regenerative state. We propose that impaired microglia death and/or repopulation may underpin dysregulated microglia activation in neurological diseases, and we reveal therapeutic targets to promote white matter regeneration.


Asunto(s)
Enfermedades Desmielinizantes/fisiopatología , Microglía/fisiología , Regeneración Nerviosa/fisiología , Animales , Cuerpo Calloso/efectos de los fármacos , Cuerpo Calloso/patología , Enfermedades Desmielinizantes/inducido químicamente , Femenino , Perfilación de la Expresión Génica , Humanos , Inflamación , Lisofosfatidilcolinas/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/clasificación , Esclerosis Múltiple/patología , Necrosis , Nestina/análisis , Fagocitosis , Ratas , Ratas Sprague-Dawley , Análisis de Secuencia de ARN , Sustancia Blanca/fisiología
13.
Blood Adv ; 3(10): 1568-1573, 2019 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-31101647

RESUMEN

Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings.

14.
Proc Natl Acad Sci U S A ; 116(19): 9622-9627, 2019 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-31015293

RESUMEN

White matter abnormalities are a nearly universal pathological feature of neurodegenerative disorders including Huntington disease (HD). A long-held assumption is that this white matter pathology is simply a secondary outcome of the progressive neuronal loss that manifests with advancing disease. Using a mouse model of HD, here we show that white matter and myelination abnormalities are an early disease feature appearing before the manifestation of any behavioral abnormalities or neuronal loss. We further show that selective inactivation of mutant huntingtin (mHTT) in the NG2+ oligodendrocyte progenitor cell population prevented myelin abnormalities and certain behavioral deficits in HD mice. Strikingly, the improvements in behavioral outcomes were seen despite the continued expression of mHTT in nonoligodendroglial cells including neurons, astrocytes, and microglia. Using RNA-seq and ChIP-seq analyses, we implicate a pathogenic mechanism that involves enhancement of polycomb repressive complex 2 (PRC2) activity by mHTT in the intrinsic oligodendroglial dysfunction and myelination deficits observed in HD. Our findings challenge the long-held dogma regarding the etiology of white matter pathology in HD and highlight the contribution of epigenetic mechanisms to the observed intrinsic oligodendroglial dysfunction. Our results further suggest that ameliorating white matter pathology and oligodendroglial dysfunction may be beneficial for HD.

15.
Mhealth ; 5: 7, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30976599

RESUMEN

Background: Mobile technology is a novel approach for delivering continuing medical education (CME), with numerous advantages including lower costs and the ability to reach larger numbers than traditional in-person CME workshops. Methods: From May 2015 to May 2017, we conducted two randomized controlled trials in a phased approach to evaluate the effectiveness of a mobile CME (mCME) approach for two cadres of health professionals in Vietnam. The first randomized controlled trial (RCT) tested the use of an SMS-based educational intervention among Community-Based Physician's Assistants; while feasible and acceptable, this intervention failed to improve medical knowledge among participants. Given the failure of the first RCT, and drawing on qualitative work conducted with participants at the conclusion of the trial, various modifications were employed in the second RCT conducted among HIV specialist physicians in Vietnam. Version 2.0 of the mCME intervention did lead to significant improvement in medical knowledge among intervention participants. Here, we discuss in detail the development of an mCME platform and the experiential "lessons learned" during two phases of implementation. Results: Numerous lessons were learned during implementation, including the importance of: (I) mixed methods approaches; (II) an underlying theoretical framework for behavior change projects; (III) expertise in software programming; (IV) aligning educational content to a well-defined participant population; and (V) engaging and motivating adult learners. We also discuss the critical importance of projects with local ownership and investment that are relevant to local problems. Conclusions: mHealth approaches for continued healthcare training and education is increasingly relevant in many low-resource settings, the lessons learned here will be valuable to other organizations looking to scale-up similar mHealth-type educational programmes.

16.
JMIR Med Educ ; 5(1): e12058, 2019 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-30998220

RESUMEN

BACKGROUND: The Mobile Continuing Medical Education Project (mCME V.2.0) was a randomized controlled trial designed to test the efficacy of a text messaging (short message service [SMS])-based distance learning program in Vietnam that included daily quiz questions, links to readings and online courses, and performance feedback. The trial resulted in significant increases in self-study behaviors and higher examination scores for intervention versus control participants. OBJECTIVE: The objective of this mixed-methods study was to conduct qualitative and quantitative investigations to understand participants' views of the intervention. We also developed an explanatory framework for future trial replication. METHODS: At the endline examination, all intervention participants completed a survey on their perspectives of mCME and self-study behaviors. We convened focus group discussions to assess their experiences with the intervention and attitudes toward continuing medical education. RESULTS: A total of 48 HIV specialists in the intervention group completed the endline survey, and 30 participated in the focus group discussions. Survey and focus group data suggested that most clinicians liked the daily quizzes, citing them as convenient mechanisms to convey information in a relevant manner. A total of 43 of the 48 (90%) participants reported that the daily quizzes provided motivation to study for continuing medical education purposes. Additionally, 83% (40/48) of intervention participants expressed that they were better prepared to care for patients with HIV in their communities, compared with 67% (32/48) at baseline. Participation in the online coursework component was low (only 32/48, 67% of intervention participants ever accessed the courses), but most of those who did participate thought the lectures were engaging (26/32, 81%) and relevant (29/32, 91%). Focus group discussions revealed that various factors influenced the clinicians' decision to engage in higher learning, or "lateral learning," including the participant's availability to study, professional relevance of the topic area, and feedback. These variables serve as modifying factors that fit within an adapted version of the health belief model, which can explain behavior change in this context. CONCLUSIONS: Qualitative and quantitative endline data suggested that mCME V.2.0 was highly acceptable. Participant behaviors during the trial fit within the health belief model and can explain the intervention's impact on improving self-study behaviors. The mCME platform is an evidence-based approach with the potential for adoption at a national scale as a method for promoting continuing medical education. TRIAL REGISTRATION: ClinicalTrials.gov NCT02381743; https://clinicaltrials.gov/ct2/show/NCT02381743.

17.
Methods Mol Biol ; 1936: 169-183, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30820899

RESUMEN

In vitro culture systems have been invaluable in understanding the cell biology of oligodendrocytes; the monoculture of primary oligodendroglia has helped characterize different stages of oligodendrocyte maturation in the absence of neurons. However, oligodendrocyte monocultures do not model the interaction of oligodendrocytes with neurons where they form myelin wraps. To circumvent this problem, coculture systems were developed; oligodendrocytes and neurons are cultured together, facilitating the study of myelin wraps and the interaction between the two cell types. However, this coculture system also has limitations, as other cells are not present and it does not represent the three-dimensional multicellular structure seen in vivo. Some of these limitations are resolved by using ex vivo slice cultures to serve as a three-dimensional culture system that is more similar to in vivo and can be used to study myelination, demyelination, and remyelination, over extended periods of time. Slice cultures are economical compared to in vivo studies and live imaging using them is less challenging. The focus of this chapter is to describe how to culture brain and spinal cord slices of mice and use them to study myelination, demyelination, and remyelination.


Asunto(s)
Encéfalo/citología , Técnicas de Cultivo de Célula/métodos , Vaina de Mielina/metabolismo , Médula Espinal/citología , Animales , Diferenciación Celular , Células Cultivadas , Técnicas de Cocultivo , Enfermedades Desmielinizantes , Ratones , Neuronas/citología , Oligodendroglía/citología , Remielinización
18.
Nanomaterials (Basel) ; 9(3)2019 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-30832394

RESUMEN

The efficacy of pharmaceutical agents can be greatly improved through nanocarrier delivery. Encapsulation of pharmaceutical agents into a nanocarrier can enhance their bioavailability and biocompatibility, whilst also facilitating targeted drug delivery to specific locations within the body. However, detailed understanding of the in vivo activity of the nanocarrier-drug conjugate is required prior to regulatory approval as a safe and effective treatment strategy. A comprehensive understanding of how nanocarriers travel to, and interact with, the intended target is required in order to optimize the dosing strategy, reduce potential off-target effects, and unwanted toxic effects. Raman spectroscopy has received much interest as a mechanism for label-free, non-invasive imaging of nanocarrier modes of action in vivo. Advanced Raman imaging techniques, including coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS), are paving the way for rigorous evaluation of nanocarrier activity at the single-cell level. This review focuses on the development of Raman imaging techniques to study organic nanocarrier delivery in cells and tissues.

19.
Proc Natl Acad Sci U S A ; 116(18): 9030-9039, 2019 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-30910981

RESUMEN

Cellular senescence is a form of adaptive cellular physiology associated with aging. Cellular senescence causes a proinflammatory cellular phenotype that impairs tissue regeneration, has been linked to stress, and is implicated in several human neurodegenerative diseases. We had previously determined that neural progenitor cells (NPCs) derived from induced pluripotent stem cell (iPSC) lines from patients with primary progressive multiple sclerosis (PPMS) failed to promote oligodendrocyte progenitor cell (OPC) maturation, whereas NPCs from age-matched control cell lines did so efficiently. Herein, we report that expression of hallmarks of cellular senescence were identified in SOX2+ progenitor cells within white matter lesions of human progressive MS (PMS) autopsy brain tissues and iPS-derived NPCs from patients with PPMS. Expression of cellular senescence genes in PPMS NPCs was found to be reversible by treatment with rapamycin, which then enhanced PPMS NPC support for oligodendrocyte (OL) differentiation. A proteomic analysis of the PPMS NPC secretome identified high-mobility group box-1 (HMGB1), which was found to be a senescence-associated inhibitor of OL differentiation. Transcriptome analysis of OPCs revealed that senescent NPCs induced expression of epigenetic regulators mediated by extracellular HMGB1. Lastly, we determined that progenitor cells are a source of elevated HMGB1 in human white matter lesions. Based on these data, we conclude that cellular senescence contributes to altered progenitor cell functions in demyelinated lesions in MS. Moreover, these data implicate cellular aging and senescence as a process that contributes to remyelination failure in PMS, which may impact how this disease is modeled and inform development of future myelin regeneration strategies.

20.
PLoS One ; 14(2): e0212686, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30794651

RESUMEN

The aim of the systematic review was to determine the effectiveness of organizational-level person-centered care for people living with dementia in relation to their quality of life, mood, neuropsychiatric symptoms and function. ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialised Register databases, were searched up to June 2018 using the terms dementia OR cognitive impairment OR Alzheimer AND non-pharmacological AND personhood OR person-centered care. Reviewed studies included randomized controlled trials (RCTs), cluster-randomized trials (CRTs) and quasi-experimental studies that compared outcomes of person-centered care and usual (non-person-centered) care, for people with a diagnosis of dementia. The search yielded 12 eligible studies with a total of 2599 people living with dementia in long-term care homes, 600 receiving hospital care and 293 living in extra-care community housing. Random-effects models were used to pool adjusted risk ratios and standard mean differences from all studies; the findings were assessed followed the PRISMA guidelines and GRADE criteria. Statistical heterogeneity was assessed using the I2 method and Chi2 P value; studies with low statistical heterogeneity were analyzed using a random-effects model with restricted maximum likelihood estimation in R. Analyses of pre/post data within 12 months identified: a significant effect for quality of life (standardized mean difference (SMD) 0.16 and 95% CI 0.03 to 0.28; studies = 6; I2 = 22%); non-significant effects for neuropsychiatric symptoms (SMD 0.06, 95% CI -0.08 to 0.19; studies = 4; I2 = 0%) and well-being (SMD 0.15, 95% CI -0.15 to 0.45; studies = 4; I2 = 77%); and no effects for agitation (SMD -0.05 (95% CI -0.17 to -0.07; studies 5; I2 = 0%) and depression (SMD -0.06 and 95% CI -0.27 to 0.15, studies = 5; I2 = 53%). The evidence from this review recommends implementation of person-centered care at the organizational-level to support the quality of life of people with living with dementia.


Asunto(s)
Disfunción Cognitiva/terapia , Demencia/terapia , Depresión/terapia , Medicina de Precisión , Calidad de Vida , Humanos , Cuidados a Largo Plazo
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