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1.
Am J Speech Lang Pathol ; 32(3): 1360-1375, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37120860

RESUMO

PURPOSE: There are increasing demands for aphasia assessment and intervention services to be delivered remotely. The purpose of this scoping review was to address what is known about the delivery of assessments and interventions using telehealth for people with poststroke aphasia. Specifically, the review sought to (a) identify which telehealth assessment protocols have been used, (b) identify which telehealth intervention protocols have been used, and (c) describe evidence on the effectiveness and feasibility of telehealth for people with poststroke aphasia. METHOD: A scoping review of the literature published in English since 2013 was conducted by searching MEDLINE, Embase, PsycINFO, CINAHL, and Scopus databases to identify relevant studies. A total of 869 articles were identified. Two reviewers screened records independently, finding 25 articles eligible for inclusion. Data extraction was conducted once and validated by the second reviewer. RESULTS: Two of the included studies examined telehealth assessment protocols, whereas the remaining studies focused on the delivery of telehealth interventions. The results of the included studies illustrated both effectiveness and feasibility regarding telehealth for people with poststroke aphasia. However, a lack of procedural variation among the studies was found. CONCLUSIONS: Overall, this scoping review yielded continued support for the use of telehealth practices as an alternate mode of delivering both assessment and intervention services to people with poststroke aphasia. However, further research is needed to investigate the range of aphasia assessment and intervention protocols that can be offered via telehealth, such as assessments or interventions that use patient-reported measures or address extralinguistic cognitive abilities.


Assuntos
Afasia , Telemedicina , Humanos , Afasia/diagnóstico , Afasia/etiologia , Afasia/terapia , Telemedicina/métodos
2.
J Neonatal Perinatal Med ; 16(1): 179-182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36744349

RESUMO

BACKGROUND: Varicella vaccination of non-immune post-partum women is recommended to reduce the risk of chickenpox in mothers and their infants. Though rare, transmission of the varicella vaccine strain vOka can occur from recent vaccinees to non-immune contacts who usually develop mild chickenpox. METHODS/RESULTS: Here we describe an infant hospitalized in the neonatal ICU with vaccine-strain varicella due to transmission from their mother who received the varicella vaccine post-partum. We describe the infection prevention and control strategies implemented to prevent further transmission. CONCLUSION: Vaccine-strain varicella transmission from mother to infant is a rare event and its occurrence in the neonatal ICU setting can be challenging. Anticipatory guidance for mothers vaccinated in the postpartum period and support of parents of an infected infant are recommended.


Assuntos
Vacina contra Varicela , Varicela , Lactente , Recém-Nascido , Feminino , Humanos , Varicela/prevenção & controle , Varicela/epidemiologia , Unidades de Terapia Intensiva Neonatal , Vacinação
3.
Inquiry ; 60: 469580221148880, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36680364

RESUMO

The COVID-19 pandemic increased social isolation for many older adults, causing concern for their health and well-being. To enhance understanding of how community-dwelling older adults were impacted by prolonged social isolation during COVID-19, a qualitative descriptive study was conducted to: (1) explore the self-reported factors supporting their resilience during COVID-19 related social isolation, and (2) to help understand the intentional and unintentional outcomes of the government mandated health measures. A total of 19 community dwelling older adults were sampled. Factors that supported older adults' resilience during COVID-19 included maintaining positivity, drawing on historical experiences of resilience and finding opportunities to connect with their community. However, collective safety came with losses: such as time, freedom, opportunity, engagement, and initiative. The findings provide insight on contributing factors to resilience against social isolation in older adults and suggest the value of collective, community-based approaches to build resilience across variable contexts in this population.


Assuntos
COVID-19 , Humanos , Idoso , Vida Independente , Pandemias , Isolamento Social , Governo
4.
J Appl Gerontol ; 42(4): 639-650, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464843

RESUMO

Language-based strategies are recommended to improve coherence, clarity, reciprocity, and continuity of interactions with persons living with dementia. Person-centered care is the gold standard for caring for persons with dementia. Person-centered communication (PCC) strategies include facilitation, recognition, validation, and negotiation. Little is known about which language-based strategies support PCC in home care. Accordingly, this study investigated the overlap between language-based strategies and PCC in home care interactions. Analysis of conversation of 30 audio-recorded interactions between personal support workers (PSWs) and persons living with dementia was conducted. The overlap between PCC and language-based strategies was analyzed. Of 11,347 communication units, 2578 overlapped with PCC. For facilitation, 21% were yes/no questions. For recognition, 25% were yes/no questions and 22% were affirmations. For validation, 81% were affirmations and positive feedback. Finally, 60% were yes/no questions for negotiation. The findings highlight the person-centeredness of language-based strategies. PSWs should use diverse language-based strategies that are person-centered.


Assuntos
Demência , Serviços de Assistência Domiciliar , Humanos , Comunicação , Idioma , Assistência Centrada no Paciente
5.
Int J Nurs Stud ; 136: 104365, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36327681

RESUMO

BACKGROUND: Many people living with dementia experience challenges comprehending language and benefit from nonverbal communication supports. Little published empirical evidence exists for care partners regarding supportive strategies for nonverbal communication with people living with dementia. This study aimed to conduct a scoping review of nonverbal strategies for care partners which have been observed to support communication with people living with dementia. METHODS: Current best practices for scoping research guided this review. CINAHL, PsycInfo, Scopus, and Pubmed databases were searched December 8, 2020. Empirical studies that examined the supportiveness of nonverbal communication strategies used by care partners of people living with dementia were eligible. All publication dates were included. Eligible studies were published in English in peer-reviewed journals. Studies were screened first by title and abstract, and subsequently by full-text review. Data charting was conducted using an evidence summary table, which was subsequently used for analysis. Results were presented in the form of a written summary. RESULTS: Sixteen studies were included in the final review. Six categories of supportive nonverbal communication strategies were identified: eye contact, gestures, facial expression, touch, close proximity, and frontal orientation. Studies observed six outcomes which indicated that these nonverbal strategies were supportive for communication with people living with dementia; however, person-centered outcomes were limited. CONCLUSIONS: The review identified supportive nonverbal communication strategies used by care partners with people living with dementia in the current literature. Disagreement exists in the literature regarding which outcomes define supportive nonverbal communication with people living with dementia. This in combination with the benefits of person-centered approaches to care with people living with dementia presents a critical need to delineate which nonverbal communication strategies are person-centered in future research. TWEETABLE ABSTRACT: Six supportive nonverbal communication strategies identified by scoping literature review, but there is disagreement in how the literature defines "supportive" @marie_y_s @EmmaBender19.


Assuntos
Demência , Humanos , Comunicação não Verbal , Atenção à Saúde , Pesquisa Empírica
6.
Int J Biomed Imaging ; 2022: 5860364, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313789

RESUMO

Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T1-weighted, proton density-weighted, T2-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.

7.
J Alzheimers Dis ; 84(2): 883-893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34602467

RESUMO

BACKGROUND: People with advanced dementia often exhibit responsive behaviors such as apathy, depression, agitation, aggression, and psychosis. Non-pharmacological approaches (e.g., listening to music, watching television, doing arts and crafts) are now considered as a first-line strategy to manage responsive behaviors in clinical practice due to the potential risks associated with the antipsychotic medications. To date, no evaluations of immersive non-head mounted virtual reality (VR) experience as a non-pharmacologic approach for people with advanced dementia living in nursing homes have been reported. OBJECTIVE: To evaluate the feasibility (acceptance and safety) of VR experience. METHODS: A single site case series (nonrandomized and unblinded) with a convenience sample (N = 24; age = 85.8±8.6 years; Cognitive Performance Scale score = 3.4±0.6) measuring depression and agitation before and after the intervention. The intervention was a 30-min long research coordinator- facilitated VR experience for two weeks (10 sessions). RESULTS: The intervention was feasible (attrition rate = 0% ; adverse events = 0). A reduction in depression and in agitation was observed after the intervention. However, we suggest extreme caution in interpreting this result considering the study design and small sample size. CONCLUSION: This study provides the basis for conducting a randomized controlled trial to evaluate the effect of VR experience on responsive behaviors in nursing homes. Since our intervention uses a smart remote-controlled projector without a headset, infectious exposure can be avoided following the COVID-19 pandemic-induced physical distancing policy in care homes.


Assuntos
COVID-19/virologia , Casas de Saúde , SARS-CoV-2/patogenicidade , Realidade Virtual , Idoso , Idoso de 80 Anos ou mais , Agressão/psicologia , Demência/psicologia , Feminino , Humanos , Masculino , Qualidade de Vida/psicologia
8.
Int J Older People Nurs ; 16(6): e12401, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34337872

RESUMO

BACKGROUND: Little is known about formal caregivers' lived experiences communicating with persons living with dementia (PLWD) who live in their own homes. Most information comes from research conducted in long-term care settings or home care settings involving family care partners. Yet, there are expected needs and rising demands for formal caregivers to provide support within clients' homes. OBJECTIVES: Accordingly, this study aimed to understand the lived experiences of personal support workers (PSWs) regarding their communication with PLWD who live in their own homes. METHODS: The study was grounded in a hermeneutic phenomenological research approach. Data were collected as part of the Be EPIC project, an evidence-informed, person-centred communication intervention for PSWs caring for PLWD. One, in-depth semi-structured interview was conducted with each of the PSWs (N = 15). Thematic analysis was completed on the interviews. RESULTS: Three major themes emerged: (1) Challenged by dementia-related impairments; (2) Valuing communication in care; and (3) Home is a personal space. Findings revealed that PSWs experience difficulties communicating with PLWD because of dementia-related impairments, despite PSWs recognizing the importance of communication when they provide optimal care in the homes of PLWD. This suggests that PSWs view communication as a crucial component of quality care but do not possess the skills necessary to ensure effective interactions. Findings also demonstrated the importance, uniqueness and impact of the personal home space on PSWs' experiences with communication. CONCLUSION: Overall, findings indicate that PSWs acknowledge the importance of communication as an integral element of providing optimal care, but dementia-related impairments and the intimate, personal home-based care context can hinder successful communication between PSWs and PLWD. The implications of the findings are that additional and targeted education and training are required for PSWs, especially on how dementia-related impairments impact communication within the context of home care based services for PLWD.


Assuntos
Demência , Serviços de Assistência Domiciliar , Cuidadores , Comunicação , Humanos
9.
J Clin Exp Neuropsychol ; 43(2): 199-212, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33827353

RESUMO

Some studies have found that bilingualism promotes cognitive reserve. OBJECTIVE: We aimed to determine whether bilingualism, defined as regularly (i.e. daily) using at least two languages at least since early adulthood, is associated with cognitive advantages in Parkinson's disease (PD) or whether the possible benefits of bilingualism are lost in the context of PD, possibly affecting quality of life (QoL) and independence. METHOD: Participants with idiopathic PD (n = 140, mean age = 67.9 [SD = 6.4], 78% men) completed standard neuropsychological tasks evaluating attention/working memory, language, executive function, memory, and visuospatial ability, as well as measures of wellbeing and functional independence. RESULTS: Bilinguals with PD (n = 21) performed worse than monolinguals with PD (n = 92) on attention/working memory and language measures. The between-group differences in attention/working memory were restricted to verbally-based measures. When measured along a continuum, a higher degree of bilingualism was correlated with lower scores on measures of attention/working memory and language. There were no group differences in self- or informant-reported cognitive decline, PD health-related QoL, or functional independence. CONCLUSIONS: Bilingualism in PD was not associated with better cognitive performance. Lower scores on language-based measures may reflect a distributed fund of linguistic information across more than one language, lower language proficiency in English, and/or other cultural artifacts. Furthermore, using normative data specific to the dominant language spoken or conducting neuropsychological testing in participants' self-reported most proficient language may enhance additional studies addressing this topic. Future research may also examine the roles of bilingualism over time and across other neurodegenerative diseases with and without EF impairment to illuminate further the impact of bilingualism on cognition and QoL, and shape culturally and linguistically diverse research and clinical care.


Assuntos
Multilinguismo , Doença de Parkinson , Adulto , Idoso , Cognição , Função Executiva , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Doença de Parkinson/complicações , Qualidade de Vida
10.
Aging Brain ; 1: 100018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-36911511

RESUMO

Using data from the COMPASS-ND study we investigated associations between hearing loss and hippocampal volume as well as cortical thickness in older adults with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's dementia (AD). SCD participants with greater pure-tone hearing loss exhibited lower hippocampal volume, but more cortical thickness in the left superior temporal gyrus and right pars opercularis. Greater speech-in-noise reception thresholds were associated with lower cortical thickness bilaterally across much of the cortex in AD. The AD group also showed a trend towards worse speech-in-noise thresholds compared to the SCD group.

11.
Dementia (London) ; 20(1): 5-27, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31335168

RESUMO

INTRODUCTION: The current qualitative systematic review identified and examined critically the literature on how persons with dementia experience transitions to long-term care. Results are intended to help develop guidelines for future care and research. METHOD: A search was conducted of OvidSP, SCOPUS, Web of Science, ProQuest, PsycINFO, CINAHL, AgeLine and Informit databases. In total, 4705 articles were reviewed (published 1954-2018). A textual narrative approach was used to synthesise the findings of the included articles. RESULTS: Seven articles met inclusion criteria (five using data collected from interviews with persons with dementia and two using reports from a proxy). Overall, the findings showed that transition to long-term care possesses varied meanings for persons with dementia, is often not the decision of the persons with dementia, and is a process throughout which social connections remain important. DISCUSSION: Accounts of the experiences of persons with dementia regarding transitions from community to long-term care show that they and their families should be supported: with respect to their individual contexts, to share the positives and negatives of the transition experiences, to make decisions together, and to maintain old and establish new social connections.


Assuntos
Demência , Assistência de Longa Duração , Humanos
12.
J Alzheimers Dis ; 75(3): 817-826, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32310168

RESUMO

BACKGROUND: Exercise is beneficial to maintain balance. Wii Fit©, a video game-based exercise, offers an enjoyable way to exercise and is feasible for older adults with neurocognitive disorders (NCD). OBJECTIVE: To evaluate the effects of Wii Fit© exercise training on the balance of older adults with NCD. METHODS: Systematic review and meta-analysis of randomized control trials using Cochrane collaboration tools. The participants were older adults (60 years and over) with NCD. Balance was measured with Berg Balance Scale (BBS) and Timed Up and Go (TUG). Two reviewers independently searched, selected, extracted data, assessed risk of biases, and determined the quality of evidence. Outcomes were evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A meta-analysis was performed. RESULTS: The literature search identified 522 source documents of which titles and abstracts were reviewed for 428 after removing 94 duplicates. The reviewers selected five studies out of 50 after a full text review. The overall effect of Wii Fit© exercise training on BBS was moderate, significant, and clinically meaningful (standardized mean difference [SMD] = 0.5 standard deviation [SD] [95% confidence interval CI] 0.08, 0.84]). No effect was observed with TUG scores (SMD = 0.00 SD [95% CI -0.44, 0.44]). The GRADE quality of evidence was very low. CONCLUSION: Wii Fit© exercise training has a positive effect on balance in older adults with NCD. However, further research with sufficient power is needed to evaluate its effectiveness.


Assuntos
Terapia por Exercício/métodos , Transtornos Neurocognitivos/terapia , Equilíbrio Postural , Idoso , Idoso de 80 Anos ou mais , Terapia por Exercício/instrumentação , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Aging Ment Health ; 24(5): 765-773, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-30521370

RESUMO

Objectives: The study used data from the Canadian Longitudinal Study on Aging to investigate the relationships among social support (measured as affectionate support, emotional/informational support, positive social interaction, tangible support), social participation and depression in caregivers and non-caregivers.Method: Hierarchical multiple regression was used to investigate relationships among social support, social participation, and depression. Analyses of variance were used to examine differences in the means of social support, social participation, and depression between the two participant groups.Results: Higher levels of affectionate support, positive social interaction, and social participation were associated with lower depression scores. Social participation was a significant mediator of the relationship between caregiver status and depression. Caregivers reported significantly higher levels of affectionate support, emotional/informational support, positive social interaction, and social participation than non-caregivers. There were no between-group difference in depression scores.Discussion: The study provides support for the beneficial role of social participation in preserving caregiver mental health. Results are discussed in the context of policy and practice implications for caregivers in Canada.


Assuntos
Cuidadores , Saúde da População , Canadá , Depressão/epidemiologia , Humanos , Estudos Longitudinais , Participação Social , Apoio Social
14.
J Aging Stud ; 48: 76-84, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30832933

RESUMO

The current paper addresses the nature of epistemic injustice as it may be experienced by persons with dementia. We describe how theoretical models of stigma align with the current model of epistemic injustice through a consideration of the concepts of 'stereotype', 'prejudice' and 'discrimination', shared by the two models. We draw on current understandings of dementia-related stigma to expand understandings of the epistemic injustice faced by persons with dementia. We discuss how these insights may inform the development of mechanisms to uphold the basic human right to speak, to be heard, and to be believed for persons with dementia.


Assuntos
Demência , Estigma Social , Estereotipagem , Idoso , Feminino , Humanos , Conhecimento , Masculino , Teoria Psicológica
15.
Mol Immunol ; 115: 39-55, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30482463

RESUMO

Interactions between germline-encoded natural killer (NK) cell receptors and their respective ligands on tumorigenic or virus-infected cells determine NK cell cytotoxic activity and/or cytokine secretion. NK cell cytokine responses can be augmented in and can potentially contribute to multiple sclerosis (MS), an inflammatory disease of the central nervous system focused upon the oligodendrocytes (OLs). To investigate mechanisms by which NK cells may contribute to MS pathogenesis, we developed an in vitro human model of OL-NK cell interaction. We found that activated, but not resting human NK cells form conjugates with, and mediate cytotoxicity against, human oligodendrocytes. NK cells, when in conjugate with OLs, rapidly synthesize and polarize IFN-γ toward the OLs. IFN-γ is capable of reducing myelin oligodendrocyte and myelin associated glycoproteins (MOG and MAG) content. This activity is independent of MHC class-I mediated inhibition via KIR2DL1, but dependent upon the interaction between NK cell-expressed KIR2DL4 and its oligodendrocyte-expressed ligand, HLA-G. NK cells from patients with MS express higher levels of IFN-γ following conjugation to OLs, more actively promote in vitro reduction of MOG and MAG and have higher frequencies of the KIR2DL4 positive population. These data collectively suggest a mechanism by which NK cells can promote pathogenic effects upon OLs.


Assuntos
Interferon gama/imunologia , Células Matadoras Naturais/imunologia , Oligodendroglia/imunologia , Receptores KIR2DL4/imunologia , Linhagem Celular , Citotoxicidade Imunológica/imunologia , Antígenos HLA-G/imunologia , Humanos , Esclerose Múltipla/imunologia , Glicoproteína Associada a Mielina/imunologia , Receptores de Células Matadoras Naturais/imunologia
16.
Clin Exp Immunol ; 194(3): 327-338, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30168848

RESUMO

Patients with common variable immunodeficiency (CVID) have increased fatigue compared with the general population. Fatigue is associated with lower quality of life (QoL), which is associated with higher mortality in CVID. This study aimed to determine the prevalence of self-reported fatigue for patients with CVID and to identify its possible drivers and burden on QoL. We analysed data from the 2013 Immune Deficiency Foundation (IDF) treatment survey. Answers were included from 873 CVID patients who responded (respondents). Of the 873 respondents included in the analysis, 671 (76·9%) reported fatigue, of whom 400 (83·7%) were receiving intravenous (i.v.) immunoglobulins (IVIG) and 271 (68·6%) were receiving subcutaneous (s.c.) immunoglobulins. This difference in fatigue between patients receiving IVIG and SCIG was statistically significant (P < 0·001). Dose and frequency of immunoglobulin replacement therapy (IgGRT) did not affect fatigue prevalence. Fatigued patients on IVIG reported greater infection rates and required more anti-microbials during the wear-off period. Fatigued patients reported worse health status than non-fatigued patients, and had lower rates of employment, education, household income and school attendance than their non-fatigued counterparts. Fatigue is increased in CVID, especially among patients receiving IVIG, compared to SCIG. Fatigue has a significant impact on QoL and productivity in patients with CVID. Further studies to identify the mechanisms of fatigue are warranted to help advance therapeutic measures to treat this disease and improve patients' QoL and wellbeing.


Assuntos
Imunodeficiência de Variável Comum/patologia , Imunodeficiência de Variável Comum/terapia , Fadiga/epidemiologia , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Qualidade de Vida , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/mortalidade , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
17.
Vox Sang ; 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29675923

RESUMO

BACKGROUND AND OBJECTIVES: Our research aim is to model latent therapeutic demand (LTD) for the immunoglobulin replacement therapy (IgGRT) of primary immune deficiency disorders (PIDDs) in the USA. Given the high level of variability of IgGRT use and major differences among American and European practices in the management of patients with PIDDs, we develop a USA-specific LTD model for common variable immune deficiency (CVID), hyper IGM syndrome, severe combined immune deficiency, Wiskott-Aldrich syndrome and X-linked agammaglobulinemia (XLA). METHODS AND MATERIALS: We use decision analysis methods to model the underlying IgGRT demand for PIDDs by assessing USA-specific epidemiology and treatment. Data for the epidemiology and treatment variables were obtained from the medical literature, USIDNET and Immune Deficiency Foundation. The uncertainty surrounding the variables was modelled using probability distributions and evaluated using Monte Carlo simulation. RESULTS: The mean treatment dose from USIDNET and European Society for Immunodeficiencies (ESID) was significantly different for treating CVID, and the number of annual infusions from USIDNET and ESID was significantly different for treating CVID and XLA. The mean and standard deviation of LTD for all PIDDs is 105·1 ± 88·5 g per 1000 population, with CVID contributing the most to LTD. CONCLUSION: Estimating country-specific LTD is important to ensure an adequate supply of IgGRT and an optimal treatment for patients with PIDDs and for improving national healthcare policymaking and production planning.

18.
Leukemia ; 32(2): 520-531, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28725044

RESUMO

Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies.


Assuntos
Antígenos CD19/imunologia , Sangue Fetal/imunologia , Interleucina-15/imunologia , Células Matadoras Naturais/imunologia , Receptores de Antígenos Quiméricos/imunologia , Idoso , Caspase 9/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica/imunologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imunoterapia Adotiva/métodos , Células K562 , Leucemia/imunologia , Leucemia/terapia , Linfoma/imunologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia
19.
N Engl J Med ; 374(11): 1032-1043, 2016 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-26981933

RESUMO

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells. METHODS: We used whole-exome sequencing and array-based comparative genomic hybridization to evaluate a subset of patients with CVID and low B-cell numbers. Mutant proteins were analyzed for DNA binding with the use of an electrophoretic mobility-shift assay (EMSA) and confocal microscopy. Flow cytometry was used to analyze peripheral-blood lymphocytes and bone marrow aspirates. RESULTS: Six different heterozygous mutations in IKZF1, the gene encoding the transcription factor IKAROS, were identified in 29 persons from six families. In two families, the mutation was a de novo event in the proband. All the mutations, four amino acid substitutions, an intragenic deletion, and a 4.7-Mb multigene deletion involved the DNA-binding domain of IKAROS. The proteins bearing missense mutations failed to bind target DNA sequences on EMSA and confocal microscopy; however, they did not inhibit the binding of wild-type IKAROS. Studies in family members showed progressive loss of B cells and serum immunoglobulins. Bone marrow aspirates in two patients had markedly decreased early B-cell precursors, but plasma cells were present. Acute lymphoblastic leukemia developed in 2 of the 29 patients. CONCLUSIONS: Heterozygous mutations in the transcription factor IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-cell numbers. (Funded by the National Institutes of Health and others.).


Assuntos
Linfócitos B , Imunodeficiência de Variável Comum/genética , Fator de Transcrição Ikaros/genética , Mutação , Adolescente , Adulto , Antígenos CD/análise , Medula Óssea/imunologia , Exame de Medula Óssea , Criança , Pré-Escolar , Cromossomos Humanos Par 7 , Imunodeficiência de Variável Comum/imunologia , Exoma , Feminino , Heterozigoto , Humanos , Imunoglobulina G/sangue , Contagem de Linfócitos , Masculino , Linhagem , Análise de Sequência de DNA/métodos
20.
Clin Exp Immunol ; 179(2): 146-60, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25384609

RESUMO

Primary antibody deficiencies require lifelong replacement therapy with immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both subcutaneous and intravenous routes of administering IgG can be effective and well tolerated. Treatment regimens can be individualized to provide optimal medical and quality-of-life outcomes in infants, children, adults and elderly people. Frequency, dose, route of administration, home or infusion-centre administration, and the use of self- or health-professional-administered infusion can be tailored to suit individual patient needs and circumstances. Patient education is needed to understand the disease and the importance of continuous therapy. Both the subcutaneous and intravenous routes have advantages and disadvantages, which should be considered in selecting each patient's treatment regimen. The subcutaneous route is attractive to many patients because of a reduced incidence of systemic adverse events, flexibility in scheduling and its comparative ease of administration, at home or in a clinic. Self-infusion regimens, however, require independence and self-reliance, good compliance on the part of the patient/parent and the confidence of the physician and the nurse. Intravenous administration in a clinic setting may be more appropriate in patients with reduced manual dexterity, reluctance to self-administer or a lack of self-reliance, and intravenous administration at home for those with good venous access who prefer less frequent treatments. Both therapy approaches have been demonstrated to provide protection from infections and improve health-related quality of life. Data supporting current options in IgG replacement are presented, and considerations in choosing between the two routes of therapy are discussed.


Assuntos
Imunoglobulina G/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Medicina de Precisão/métodos , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/patologia
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