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1.
BMC Geriatr ; 23(1): 439, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464306

RESUMO

BACKGROUND AND OBJECTIVES: Although the positive influence of social activity on health is now well-established, a complex relationship exists among social participation, personal, social and the environment. Social participation of older adults was examined in rural and urban settings to identify features of the built-environment and perception of neighborhood specific to the locale. RESEARCH DESIGN AND METHODS: Using cross-sectional data from the Canadian Longitudinal Study on Aging (CLSA), we examined social participation and health of older people (65 + yrs) in relation to the built environment and sociocultural contexts for urban and rural areas. A social participation index was derived from responses on the frequency of participating in 8 social activities over the past 12 months. Personal, household and neighborhood indicators were examined to develop multivariable regression models for social participation in urban and rural cohorts. RESULTS: No meaningful differences were seen with the frequency of social participation between rural and urban settings; however, the type of community-related activities differed in that a greater proportion of urban participants reported sports and educational/cultural events than rural participants. Service club activities were greater for rural than urban participants. Different neighborhood features were statistically significant factors in explaining social participation in rural than in urban locales, although transportation was a significant factor regardless of locale. Trustworthiness, belonging and safety were perceived factors of the neighborhood associated with higher social participation for rural participants. DISCUSSION AND IMPLICATIONS: The relationship between home and health becomes stronger as one ages. Social and physical features of built environment specific to urban and rural settings need to be considered when implementing appropriate social activities for older people.


Assuntos
Envelhecimento , Participação Social , Humanos , Idoso , Estudos Longitudinais , Canadá/epidemiologia , Estudos Transversais , População Urbana , População Rural
2.
BMC Health Serv Res ; 21(1): 401, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926430

RESUMO

BACKGROUND: Health Technology Reassessment (HTR) is a process that systematically assesses technologies that are currently used in the health care system. The process results in four outputs: increase use or decrease use, no change, or de-adoption of a technology. Implementation of these outputs remains a challenge. The Knowledge Translation (KT) field enables to transfer/translate knowledge into practice. KT could help with implementation of HTR outputs. This study sought to identify which characteristics of KT theories, models, and frameworks could be useful, specifically for decreased use or de-adoption of a technology. METHODS: A qualitative descriptive approach was used to ascertain the perspectives of international KT and HTR experts on the characteristics of KT theories, models, and frameworks for decreased use or de-adoption of a technology. One-to-one semi-structured interviews were conducted from September to December 2019. Interviews were audio recorded and transcribed verbatim. Themes and sub-themes were deduced from the data through framework analysis using five distinctive steps: familiarization, identifying an analytic framework, indexing, charting, mapping and interpretation. Themes and sub-themes were also mapped to existing KT theories, models, and frameworks. RESULTS: Thirteen experts from Canada, United States, United Kingdom, Australia, Germany, Spain, and Sweden participated in the study. Three themes emerged that illustrated the ideal traits: principles that were foundational for HTR, levers of change, and steps for knowledge to action. Principles included evidence-based, high usability, patient-centered, and ability to apply to the micro, meso, macro levels. Levers of change were characterized as positive, neutral, or negative influences for changing behaviour for HTR. Steps for knowledge to action included: build the case for HTR, adapt research knowledge, assess context, select interventions, and assess impact. Of the KT theories, models, and frameworks that were mapped, the Consolidated Framework for Implementation Research had most of the characteristics, except ability to apply to micro, meso, macro levels. CONCLUSIONS: Characteristics that need to be considered within a KT theory, model, and framework for implementing HTR outputs have been identified. Consideration of these characteristics may guide users to select relevant KT theories, models, and frameworks to apply to HTR projects.


Assuntos
Tecnologia Biomédica , Pesquisa Translacional Biomédica , Austrália , Canadá , Humanos , Espanha , Suécia , Reino Unido
3.
J Ment Health Policy Econ ; 23(3): 101-109, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853159

RESUMO

BACKGROUND: Since June 2017, the Primary Health Care Integrated Geriatric Services Initiative (PHC IGSI) has been implemented in Alberta, Canada to, among other aims, reduce costs of unplanned health service utilization while maximizing the utilization of available community resources to support people living with dementia living in communities. AIM OF THE STUDY: We performed an economic evaluation of this initiative to inform policy regarding sustainability, scale up and spread. METHODS: We used a cohort design together with a difference-in-difference approach and a propensity score matching technique to calculate impacts of the intervention on patient's health service utilization, including inpatient, outpatient and physician services, as well as prescription drugs. We then used a decision tree to compare between benefits and costs of the intervention and reported net benefits (NB) and return on investment ratios (ROI). We used a health system perspective and a time horizon of 1 year. Both deterministic and probabilistic sensitivity analyses were performed for the uncertainty of parameters. We analyzed real-world data extracted from the Alberta Health Administrative Databases. All costs/savings were inflated to 2019 CAD (CAD 1 \sim = USD 0.75) using the Canadian Consumer Price Index. RESULTS: The intervention reduced the use of hospital (inpatient, emergency, and outpatient) services by increasing the use of community services (physician and prescription drug). As hospital services are expensive, the PHC IGSI community intervention resulted in a NB from CAD 554 to 4,046 per patient-year for the health system, and a ROI from 1.3 to 3.1 meaning that every CAD invested in PHC IGSI would bring CAD 1.3 to 3.1 in return. The probability of PHC IGSI to be cost-saving was 56.4% to 69.3%. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The PHC IGSI is cost-effective in Alberta. IMPLICATIONS FOR HEALTH POLICY: The savings would be larger if the initiative is sustained, scaled up and spread because of not only a reduced cost of intervention in the sustainability phase, but also because of the increased number of patients that would be impacted. IMPLICATIONS FOR FURTHER RESEARCH: Future studies taking a societal perspective to also include costs for families and health and social sectors at the community level, would be desirable. Additionally, future works to determine how wellbeing is impacted by the PHC IGSI as vertical and horizontal integration interventions are implemented at the community level, are essential to undertake. Finally, in addition to people living with dementia, the PHC IGSI also supports people living in the community with frailty and other geriatric syndromes, therefore, the cost-savings estimated in this study are likely underestimated.


Assuntos
Prestação Integrada de Cuidados de Saúde/economia , Serviços de Saúde para Idosos/economia , Atenção Primária à Saúde/economia , Idoso , Alberta , Redução de Custos , Análise Custo-Benefício , Serviços de Saúde , Humanos
4.
J Biol Chem ; 293(42): 16261-16276, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30217825

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus that has conclusively been shown to cause human diseases. In HIV-1, specific interactions between the nucleocapsid (NC) domain of the Gag protein and genomic RNA (gRNA) mediate gRNA dimerization and selective packaging; however, the mechanism for gRNA packaging in HTLV-1, a deltaretrovirus, is unclear. In other deltaretroviruses, the matrix (MA) and NC domains of Gag are both involved in gRNA packaging, but MA binds nucleic acids with higher affinity and has more robust chaperone activity, suggesting that this domain may play a primary role. Here, we show that the MA domain of HTLV-1, but not the NC domain, binds short hairpin RNAs derived from the putative gRNA packaging signal. RNA probing of the HTLV-1 5' leader and cross-linking studies revealed that the primer-binding site and a region within the putative packaging signal form stable hairpins that interact with MA. In addition to a previously identified palindromic dimerization initiation site (DIS), we identified a new DIS in HTLV-1 gRNA and found that both palindromic sequences bind specifically the NC domain. Surprisingly, a mutant partially defective in dimer formation in vitro exhibited a significant increase in RNA packaging into HTLV-1-like particles, suggesting that efficient RNA dimerization may not be strictly required for RNA packaging in HTLV-1. Moreover, the lifecycle of HTLV-1 and other deltaretroviruses may be characterized by NC and MA functions that are distinct from those of the corresponding HIV-1 proteins, but together provide the functions required for viral replication.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano/química , RNA Viral/metabolismo , Proteínas de Ligação a RNA/química , Montagem de Vírus , Produtos do Gene gag do Vírus da Imunodeficiência Humana/química , Dimerização , Proteínas do Vírus da Imunodeficiência Humana/química , Proteínas do Vírus da Imunodeficiência Humana/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Nucleocapsídeo/genética , Proteínas de Ligação a RNA/fisiologia , Replicação Viral
6.
BMC Neurol ; 19(1): 101, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126259

RESUMO

BACKGROUND: Apathy is a prominent non-motor symptom in Parkinson's disease (PD). People with apathy show a lack of emotion, passion, and motivation. Between 17 and 70% of persons with PD have apathy; the extreme heterogeneity in these estimates is due to limited heterogeneous knowledge concerning how to diagnose PD. The lack of a widely utilized diagnostic process limits understandings on how to treat and manage apathy in PD. A scoping review of apathy in PD identified only one qualitative study investigating this symptom. It was our objective to assess perceived barriers and facilitators to diagnosing, treating, and managing apathy in PD, as described by key stakeholders. METHODS: This research applied qualitative methodology, utilizing focus groups and interviews with health care practitioners (HCPs), persons with PD, and caregivers. Evidence gathered from a scoping review on apathy in PD informed discussions that took place with participants. Data collection and analysis was conducted using framework analysis, applying the Theoretical Domains Framework and Behaviour Change Wheel. RESULTS: Eleven HCPs and five persons with PD/caregivers participated. Themes included interdisciplinary teams and communication with family to facilitate diagnosis and treatment, and the use of education and increased awareness of apathy to facilitate management. Themes surrounding barriers included lack of initiative and motivation to maintain treatment plans, and a lack of evidence for apathy specific interventions. While a key barrier identified was the lack of information HCPs have access to, persons with PD and caregivers would prefer to receive a diagnosis of apathy even with limited management methods. Thus, education and awareness were noted as two of the most important facilitators, overall. CONCLUSION: These findings suggest that diagnosing, treating, and managing apathy in PD requires interdisciplinary teams, that include family and caregivers. We identified that where HCPs perceive lack of knowledge as a barrier to diagnosis, persons with PD and caregivers find being given a diagnosis facilitates understanding. These findings highlight the importance of qualitative research involving persons with PD and apathy, caregivers, and HCPs who aid in management of this symptom. Barriers reported suggest future research must aim to identify apathy specific treatments, both pharmacologic and non-pharmacologic.


Assuntos
Apatia , Doença de Parkinson/psicologia , Cuidadores , Feminino , Grupos Focais , Humanos , Masculino , Pesquisa Qualitativa
7.
J Manipulative Physiol Ther ; 42(3): 167-176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31029467

RESUMO

OBJECTIVE: The purpose of this study was to investigate the report by mothers of their infants' condition before and after a trial of care provided by registered chiropractic clinicians in addition to ratings of satisfaction, cost of care, and reports of any adverse events or side effects. A second purpose was to report the demographic profile of infants who presented for care to 16 chiropractic clinics in the United Kingdom. METHODS: This observational study prospectively collected reports by mothers of their infants' demographic profiles and outcomes across several domains of infant behavior and their own mental state using the United Kingdom Infant Questionnaire. Participating registered chiropractors were recruited through the Royal College of Chiropractors annual meeting in January 2016, and 15 clinics and the Anglo-European College of Chiropractic University College teaching clinic volunteered to participate. RESULTS: In all, 2001 mothers completed intake questionnaires and 1092 completed follow-up forms. Statistically significant (P < .05) improvements were reported across all aspects of infant behavior studied, including feeding problems, sleep issues, excessive crying, problems with supine sleep position, infant pain, restricted cervical range of motion, and time performing prone positioning. Maternal ratings of depression, anxiety, and satisfaction with motherhood also demonstrated statistically significant improvement (P < .05). In total, 82% (n = 797) reported definite improvement of their infants on a global impression of change scale. As well, 95% (n = 475) reported feeling that the care was cost-effective, and 90.9% (n = 712) rated their satisfaction 8 or higher on an 11-point scale. Minor self-limiting side effects were reported (5.8%, n = 42/727) but no adverse events. CONCLUSION: In this study, mothers reported that chiropractic care for their infants was effective, safe, and cost-effective. Although the observational design makes it impossible to determine efficacy, the study's findings indicate that, on average, the changes observed by mothers were positive and may be clinically relevant.


Assuntos
Quiroprática/estatística & dados numéricos , Manipulação Quiroprática/estatística & dados numéricos , Mães/estatística & dados numéricos , Adulto , Feminino , Humanos , Lactente , Cuidado do Lactente/estatística & dados numéricos , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Estudos Prospectivos , Inquéritos e Questionários , Reino Unido
8.
J Clin Densitom ; 21(2): 179-184, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28438404

RESUMO

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated with unilateral anterolateral bowing with subsequent fracture and nonunion. In infancy, physiologic bowing of the lower leg can be confused with pathologic tibial dysplasia in NF1. Little is known about the bone physiology of the tibiae prior to fracture or predictors of fracture. The aim of this study was to characterize bone quality of bowed tibiae prior to fracture in NF1 using quantitative ultrasound (QUS). Bone quality was assessed on both tibiae (the non-bowed and bowed tibiae) using QUS to measure speed of sound (SOS) at the mid-shaft in 23 individuals with NF1. SOS (m/s) was determined and Z-scores generated using cross-sectional reference data of the same sex and age. The mean difference in SOS Z-scores when comparing the bowed tibia vs the individual's contralateral unaffected tibia was statistically significant with lower mean Z-scores in the bowed tibia (p = 0.001). Radiographs of all individuals with a clinical diagnosis of anterolateral bowing were reviewed, and in 2 individuals the radiographs showed minimal bowing with absence of characteristic cortical thickening and medullary canal narrowing in NF1-related tibial dysplasia, suggesting physiologic bowing. In both individuals, the Z-scores of the bowed leg were not lower than the unaffected leg supporting the suggestion of physiologic bowing rather than pathologic tibial dysplasia. These data show that dysplastic tibiae in NF1 prior to fracture and nonunion have abnormal bone quality with significant decreases in SOS even though radiographically the tibiae show a thickened cortex. These data also suggest that QUS can help distinguish dysplastic bowing vs physiologic bowing in infancy in NF1. QUS is an effective quantitative outcome measure for trials aimed at improving tibial bowing to prevent fracture, and it is a potential aid in diagnosis and clinical management in NF1.


Assuntos
Neurofibromatose 1/diagnóstico por imagem , Neurofibromatose 1/patologia , Tíbia/diagnóstico por imagem , Tíbia/patologia , Adolescente , Criança , Pré-Escolar , Osso Cortical/diagnóstico por imagem , Osso Cortical/patologia , Osso Cortical/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Neurofibromatose 1/fisiopatologia , Radiografia , Fatores de Risco , Tíbia/fisiopatologia , Fraturas da Tíbia/etiologia , Ultrassonografia , Adulto Jovem
9.
BMC Health Serv Res ; 18(1): 674, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30165846

RESUMO

BACKGROUND: Health Technology Reassessment (HTR) is an emerging field that shifts the focus from traditional methods of technology adoption to managing technology throughout its lifecycle. HTR is a mechanism to improve patient care and system efficiency through a reallocation of resources away from low-value care towards interventions and technologies that are high value. To achieve this, the outputs of HTR and its recommendations must be translated into practice. The evolving field of knowledge translation (KT) can provide guidance to improve the uptake of evidence-informed policies and recommendations resulting from the process of HTR. This paper argues how the theories, models and frameworks from KT could advance the HTR process. DISCUSSION: First, common KT theories, models and frameworks are presented. Second, facilitators and barriers to KT within the context of HTR are summarized from the literature. Facilitators and barriers to KT include ensuring a solid research evidence-base for the technology under reassessment, assessing the climate and context, understanding the social an political context, initiating linkage and exchange, having a structured HTR Process, adequate resources, and understanding the roles of researchers, knowledge users, and stakeholders can enhance knowledge translation of HTR outputs. Third, three case examples at the individual (micro), organizational (meso), and policy (macro) levels are used to illustrate to describe how a KT theory, model or framework could be applied to a HTR project. These case studies show how selecting and applying KT theories, models and frameworks can facilitate the implementation of HTR recommendations. CONCLUSION: HTR and KT are synergistic processes that can be used to optimize technology use throughout its lifecycle. We argue that the application of KT theories, models and frameworks, and the assessment of barriers and facilitators to KT can facilitate translation of HTR recommendations into practice.


Assuntos
Tecnologia Biomédica/métodos , Avaliação da Tecnologia Biomédica/métodos , Pesquisa Translacional Biomédica/métodos , Conhecimentos, Atitudes e Prática em Saúde , Política de Saúde , Recursos em Saúde/estatística & dados numéricos , Humanos , Pesquisadores/estatística & dados numéricos
10.
BMC Med Res Methodol ; 17(1): 161, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29207955

RESUMO

BACKGROUND: As implementation science advances, the number of interventions to promote the translation of evidence into healthcare, health systems, or health policy is growing. Accordingly, classification schemes for these knowledge translation (KT) interventions have emerged. A recent scoping review identified 51 classification schemes of KT interventions to integrate evidence into healthcare practice; however, the review did not evaluate the quality of the classification schemes or provide detailed information to assist researchers in selecting a scheme for their context and purpose. This study aimed to further examine and assess the quality of these classification schemes of KT interventions, and provide information to aid researchers when selecting a classification scheme. METHODS: We abstracted the following information from each of the original 51 classification scheme articles: authors' objectives; purpose of the scheme and field of application; socioecologic level (individual, organizational, community, system); adaptability (broad versus specific); target group (patients, providers, policy-makers), intent (policy, education, practice), and purpose (dissemination versus implementation). Two reviewers independently evaluated the methodological quality of the development of each classification scheme using an adapted version of the AGREE II tool. Based on these assessments, two independent reviewers reached consensus about whether to recommend each scheme for researcher use, or not. RESULTS: Of the 51 original classification schemes, we excluded seven that were not specific classification schemes, not accessible or duplicates. Of the remaining 44 classification schemes, nine were not recommended. Of the 35 recommended classification schemes, ten focused on behaviour change and six focused on population health. Many schemes (n = 29) addressed practice considerations. Fewer schemes addressed educational or policy objectives. Twenty-five classification schemes had broad applicability, six were specific, and four had elements of both. Twenty-three schemes targeted health providers, nine targeted both patients and providers and one targeted policy-makers. Most classification schemes were intended for implementation rather than dissemination. CONCLUSIONS: Thirty-five classification schemes of KT interventions were developed and reported with sufficient rigour to be recommended for use by researchers interested in KT in healthcare. Our additional categorization and quality analysis will aid in selecting suitable classification schemes for research initiatives in the field of implementation science.


Assuntos
Pesquisa Translacional Biomédica/classificação , Atenção à Saúde , Humanos , Pesquisadores
11.
BMC Health Serv Res ; 17(1): 596, 2017 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-28836979

RESUMO

BACKGROUND: Current acute care surgical practices do not focus on the unique needs of older adults. Adverse outcomes in older patients result from a complex interrelationship between baseline vulnerability and insults experienced during hospitalization. The purpose of this study is to assess the organizational readiness and the barriers and facilitators for the implementation of elder-friendly interventions in the acute care of unplanned abdominal surgery patients. METHODS: This cross-sectional mixed methods study included a convenience sample of clinician stakeholder groups. Eight focus groups were conducted with 33 surgical team members including: 10 health care aides, 6 licensed practical nurses, 6 registered nurses, 4 nurse managers and 7 surgeons, to identify barriers and facilitators to the implementation of an elder-friendly surgical unit. Audio recordings of the focus groups were transcribed verbatim and analysed using interpretive description techniques. Transcripts were coded along with explanatory memos to generate a detailed description of participant experiences. Themes were identified followed by refining the codes. Participants also completed the Organizational Readiness for Implementing Change questionnaire. Differences in organizational readiness scores across clinician stakeholder groups were assessed using Kruskal-Wallice tests. Mann-Whitney tests (Bonferroni's corrections for multiple comparisons) were conducted to assess pair-wise relationships. RESULTS: The focus group data were conceptualized to represent facilitators and barriers to change at two levels of care delivery. Readiness to change at the organizational level was evident in five categories that reflected the barriers and facilitators to implementing an elder-friendly surgical unit. These included education, environment, staffing, policies and other research projects. At the individual level barriers and facilitators were apparent in staff members' acceptance of new roles and duties with other staff, family and patients. Examples of these included communication, teamwork and leadership. The mean change commitment and change efficacy scores on the Organizational Readiness for Implementing Change Questionnaire were 3.7 (0.8) and 3.5 (0.9) respectively. No statistically significant differences were detected between the stakeholder groups. CONCLUSIONS: Staff are interested in contributing to improved care for elderly surgical patients; however, opportunities were identified to enhance facilitators and reduce barriers in advance of implementing the elder-friendly surgical unit intervention.


Assuntos
Atitude do Pessoal de Saúde , Serviços de Saúde para Idosos/organização & administração , Recursos Humanos em Hospital , Centro Cirúrgico Hospitalar/organização & administração , Abdome/cirurgia , Idoso , Canadá , Estudos Transversais , Feminino , Arquitetura Hospitalar , Hospitalização , Humanos , Masculino , Relações Profissional-Família , Inquéritos e Questionários
12.
BMC Neurol ; 16(1): 244, 2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27887589

RESUMO

BACKGROUND: Depression and anxiety remain under-diagnosed and under-treated in those with neurologic diseases such as dementia or Parkinson's Disease (PD). Our objectives were to first, to provide a synthesis of high quality guidelines available for the identification and management of depression or anxiety in those with dementia or PD. Second, to identify areas for improvement for future guidelines. METHODS: We searched MEDLINE, PsycINFO, and EMBASE (2009 to July 24, 2015), grey literature (83 sources; July 24-Sept 6, 2015), and bibliographies of included studies. Included studies were evaluated for quality by four independent reviewers the AGREE II tool. Guideline characteristics, statements and recommendations relevant to depression or anxiety for dementia and PD were then extracted. (PROSPERO CRD: 42016014584) RESULTS: 8121 citations were reviewed with 31 full text articles included for assessment with the AGREE II tool. 17 were of sufficient quality for inclusion. Mean overall quality scores were between 4.25 to 6.5. Domain scores were lowest in the areas of stakeholder involvement, applicability, and editorial independence. Recommendations for the screening and diagnosis of depression were found for PD and dementia. There was little evidence to guide diagnosis or management of anxiety. Non-pharmacologic therapies were recommended for dementia patients. Most advocated pharmacologic treatment for depression, for both PD and dementia, but did not specify an agent due to lack of evidence. CONCLUSIONS: The available recent high quality guidelines outline several recommendations for the management of comorbid depression or anxiety in PD or dementia. However there remain significant gaps in the evidence.


Assuntos
Demência/terapia , Doença de Parkinson/terapia , Guias de Prática Clínica como Assunto , Ansiedade/etiologia , Ansiedade/terapia , Depressão/etiologia , Depressão/terapia , Humanos
13.
J Med Genet ; 52(4): 256-61, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25612910

RESUMO

BACKGROUND: Tibial pseudarthrosis is associated with neurofibromatosis type 1 (NF1) and there is wide clinical variability of the tibial dysplasia in NF1, suggesting the possibility of genetic modifiers. Double inactivation of NF1 is postulated to be necessary for the development of tibial pseudarthrosis, but tissue or cell of origin of the 'second hit' mutation remains unclear. METHODS: Exome sequencing of different sections of surgically resected NF1 tibial pseudarthrosis tissue was performed and compared to germline (peripheral blood). RESULTS: A germline NF1 splice site mutation (c.61-2A>T, p.L21 M68del) was identified from DNA extracted from peripheral blood. Exome sequencing of DNA extracted from tissue removed during surgery of the tibial pseudarthrosis showed a somatic mutation of NF1 (c.3574G>T, p.E1192*) in the normal germline allele. Further analysis of different regions of the tibial pseudarthrosis sample showed enrichment of the somatic mutation in the soft tissue within the pseudarthrosis site and absence of the somatic mutation in cortical bone. In addition, a germline variant in PTPN11 (c.1658C>T, p.T553M), a gene involved in the RAS signal transduction pathway was identified, although the clinical significance is unknown. CONCLUSIONS: Given that the NF1 somatic mutation was primarily detected in the proliferative soft tissue at the pseudarthrosis site, it is likely that the second hit occurred in mesenchymal progenitors from the periosteum. These results are consistent with a defect of differentiation, which may explain why the mutation is found in proliferative cells and not within cortical bone tissue, as the latter by definition contains mostly mature differentiated osteoblasts and osteocytes.


Assuntos
Genes da Neurofibromatose 1 , Mutação , Neurofibromatose 1/genética , Pseudoartrose/genética , Tíbia/patologia , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Radiografia , Tíbia/diagnóstico por imagem
14.
Am J Med Genet A ; 167A(9): 2085-97, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25914166

RESUMO

Heterozygous germline mutations in the proto-oncogene HRAS cause Costello syndrome (CS), an intellectual disability condition with severe failure to thrive, cardiac abnormalities, predisposition to tumors, and neurologic abnormalities. More than 80% of patients share the HRAS mutation c.34G>A (p.Gly12Ser) associated with the typical, relatively homogeneous phenotype. Rarer mutations occurred in individuals with an attenuated phenotype and less characteristic facial features. Most pathogenic HRAS alterations affect hydrolytic HRAS activity resulting in constitutive activation. "Gain-of-function" and "hyperactivation" concerning downstream pathways are widely used to explain the molecular basis and dysregulation of the RAS-MAPK pathway is the biologic mechanism shared amongst rasopathies. Panel testing for rasopathies identified a novel HRAS mutation (c.179G>A; p.Gly60Asp) in three individuals with attenuated features of Costello syndrome. De novo paternal origin occurred in two, transmission from a heterozygous mother in the third. Individuals showed subtle facial features; curly hair and relative macrocephaly were seen in three; atrial tachycardia and learning difficulties in two, and pulmonic valve dysplasia and mildly thickened left ventricle in one. None had severe failure to thrive, intellectual disability or cancer, underscoring the need to consider HRAS mutations in individuals with an unspecific rasopathy phenotype. Functional studies revealed strongly increased HRAS(Gly60Asp) binding to RAF1, but not to other signaling effectors. Hyperactivation of the MAPK downstream signaling pathways was absent. Our results indicate that an increase in the proportion of activated RAS downstream signaling components does not entirely explain the molecular basis of CS. We conclude that the phenotypic variability in CS recapitulates variable qualities of molecular dysfunction.


Assuntos
Anormalidades Múltiplas/genética , Síndrome de Costello/genética , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adolescente , Adulto , Criança , Feminino , Genes ras/genética , Humanos , Masculino , Proteínas Quinases Ativadas por Mitógeno/genética , Fenótipo , Proto-Oncogene Mas , Transdução de Sinais/genética
15.
N Engl J Med ; 364(10): 918-27, 2011 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-21345092

RESUMO

BACKGROUND: Raw produce is an increasingly recognized vehicle for salmonellosis. We investigated a nationwide outbreak that occurred in the United States in 2008. METHODS: We defined a case as diarrhea in a person with laboratory-confirmed infection with the outbreak strain of Salmonella enterica serotype Saintpaul. Epidemiologic, traceback, and environmental studies were conducted. RESULTS: Among the 1500 case subjects, 21% were hospitalized, and 2 died. In three case-control studies of cases not linked to restaurant clusters, illness was significantly associated with eating raw tomatoes (matched odds ratio, 5.6; 95% confidence interval [CI], 1.6 to 30.3); eating at a Mexican-style restaurant (matched odds ratio, 4.6; 95% CI, 2.1 to ∞) and eating pico de gallo salsa (matched odds ratio, 4.0; 95% CI, 1.5 to 17.8), corn tortillas (matched odds ratio, 2.3; 95% CI, 1.2 to 5.0), or salsa (matched odds ratio, 2.1; 95% CI, 1.1 to 3.9); and having a raw jalapeño pepper in the household (matched odds ratio, 2.9; 95% CI, 1.2 to 7.6). In nine analyses of clusters associated with restaurants or events, jalapeño peppers were implicated in all three clusters with implicated ingredients, and jalapeño or serrano peppers were an ingredient in an implicated item in the other three clusters. Raw tomatoes were an ingredient in an implicated item in three clusters. The outbreak strain was identified in jalapeño peppers collected in Texas and in agricultural water and serrano peppers on a Mexican farm. Tomato tracebacks did not converge on a source. CONCLUSIONS: Although an epidemiologic association with raw tomatoes was identified early in this investigation, subsequent epidemiologic and microbiologic evidence implicated jalapeño and serrano peppers. This outbreak highlights the importance of preventing raw-produce contamination.


Assuntos
Capsicum/microbiologia , Surtos de Doenças , Intoxicação Alimentar por Salmonella/epidemiologia , Salmonella enterica , Solanum lycopersicum/microbiologia , Estudos de Casos e Controles , Análise por Conglomerados , Coriandrum/microbiologia , Surtos de Doenças/prevenção & controle , Contaminação de Alimentos/prevenção & controle , Microbiologia de Alimentos , Humanos , Razão de Chances , Restaurantes , Intoxicação Alimentar por Salmonella/microbiologia , Salmonella enterica/classificação , Salmonella enterica/isolamento & purificação , Sorotipagem , Estados Unidos/epidemiologia
16.
Am J Med Genet A ; 164A(6): 1555-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24668863

RESUMO

L1 syndrome is a group of overlapping, X-linked disorders caused by mutations in L1CAM. Clinical phenotypes within L1 syndrome include X-linked hydrocephalus with stenosis of the aqueduct of sylvius (HSAS); mental retardation, adducted thumbs, shuffling gait, and aphasia (MASA) syndrome; spastic paraplegia type 1; and agenesis of the corpus callosum. Over 200 mutations in L1CAM have been reported; however, only a few large gene deletions have been observed. We report on a 4-month-old male with a de novo whole gene deletion of L1CAM presenting with congenital hydrocephalus, aqueductal stenosis, and adducted thumbs. Initial failure of L1CAM gene sequencing suggested the possibility of a whole gene deletion of L1CAM. Further investigation through chromosome microarray analysis showed a 62Kb deletion encompassing the first exon of the PDZD4 gene and the entire L1CAM gene. Investigations into genotype-phenotype correlations have suggested that mutations leading to truncated or absent L1 protein cause more severe forms of L1 syndrome. Based on the presentation of the proband and other reported patients with whole gene deletions, we provide further evidence that L1CAM whole gene deletions result in L1 syndrome with a severe phenotype, deletions of PDZD4 do not cause additional manifestations, and that X-linked nephrogenic diabetes insipidus reported in a subset of patients with large L1CAM deletions results from the loss of AVPR2.


Assuntos
Deleção de Genes , Doenças Genéticas Ligadas ao Cromossomo X/genética , Deficiência Intelectual/genética , Molécula L1 de Adesão de Célula Nervosa/genética , Paraplegia Espástica Hereditária/genética , Anormalidades Múltiplas/genética , Diabetes Insípido Nefrogênico/genética , Estudos de Associação Genética , Humanos , Hidrocefalia/genética , Lactente , Masculino , Proteínas de Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Vasopressinas/genética , Análise de Sequência de DNA , Polegar/anormalidades
17.
MMWR Morb Mortal Wkly Rep ; 63(20): 441-5, 2014 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-24848215

RESUMO

While investigating an outbreak of gastrointestinal disease associated with a restaurant, the New York City Department of Health and Mental Hygiene (DOHMH) noted that patrons had reported illnesses on the business review website Yelp (http://www.yelp.com) that had not been reported to DOHMH. To explore the potential of using Yelp to identify unreported outbreaks, DOHMH worked with Columbia University and Yelp on a pilot project to prospectively identify restaurant reviews on Yelp that referred to foodborne illness. During July 1, 2012-March 31, 2013, approximately 294,000 Yelp restaurant reviews were analyzed by a software program developed for the project. The program identified 893 reviews that required further evaluation by a foodborne disease epidemiologist. Of the 893 reviews, 499 (56%) described an event consistent with foodborne illness (e.g., patrons reported diarrhea or vomiting after their meal), and 468 of those described an illness within 4 weeks of the review or did not provide a period. Only 3% of the illnesses referred to in the 468 reviews had also been reported directly to DOHMH via telephone and online systems during the same period. Closer examination determined that 129 of the 468 reviews required further investigation, resulting in telephone interviews with 27 reviewers. From those 27 interviews, three previously unreported restaurant-related outbreaks linked to 16 illnesses met DOHMH outbreak investigation criteria; environmental investigation of the three restaurants identified multiple food-handling violations. The results suggest that online restaurant reviews might help to identify unreported outbreaks of foodborne illness and restaurants with deficiencies in food handling. However, investigating reports of illness in this manner might require considerable time and resources.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Doenças Transmitidas por Alimentos/epidemiologia , Internet , Vigilância da População/métodos , Restaurantes/normas , Manipulação de Alimentos/normas , Humanos , Cidade de Nova Iorque/epidemiologia , Projetos Piloto
19.
J Public Health Manag Pract ; 20(2): 240-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24458313

RESUMO

CONTEXT: In 2000, the Centers for Disease Control and Prevention began funding health departments to implement integrated electronic systems for disease surveillance. OBJECTIVE: Determine the impact of discontinuing provider reporting for chronic hepatitis B and C, hepatitis A, and select enteric diseases. DESIGN: Laboratory and provider surveillance reports of chronic hepatitis B and C and enteric infections (Shiga toxin-producing Escherichia coli, Campylobacter, Listeria, noncholera Vibrio [eg, Vibrio parahaemolyticus], Salmonella, Shigella, and hepatitis A) diagnosed on January 1, 2007 to December 31, 2010 were compared for completeness and timeliness. Number of cases submitted by laboratories, providers, or both were assessed. RESULTS: From 2007 to 2010, the proportion of cases reported only by providers for enteric disease infections differed by disease, ranging from 4% (Shiga toxin-producing E coli) to 20% (noncholera Vibrio). For chronic hepatitis C, less than 1% of cases were reported by providers only. The number of complete laboratory reports increased over the time period from 80% to 95% for chronic hepatitis and 92% to 94% for enteric infections. Laboratory reports had higher completion for date of birth, sex, and zip codes. Provider reports had less than 60% completion for race/ethnicity versus 20% for laboratories. Laboratories were faster than providers at reporting chronic hepatitis B (median 4 vs 21 days), chronic hepatitis C (4 vs 18 days), Campylobacter (6 vs 10 days), noncholera Vibrio (11 vs 12 days), Salmonella (6 vs 7 days), Shigella (6 vs 13 days), and hepatitis A (3 vs 8 days); providers were faster than laboratories at reporting Shiga toxin-producing E coli (4 vs 7 days) and Listeria (5 vs 6 days). CONCLUSIONS: Laboratories reported more cases and their reports were timelier and more complete for all categories except race/ethnicity for chronic hepatitis, Campylobacter, noncholera Vibrio, Salmonella, Shigella, and hepatitis A. For chronic hepatitis, provider reporting could be eliminated in New York City with no adverse effects on disease surveillance. For enteric infections, more work is needed before discontinuing provider reporting.


Assuntos
Sistemas de Informação em Laboratório Clínico/estatística & dados numéricos , Doenças Transmissíveis/diagnóstico , Notificação de Doenças/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos , Vigilância da População/métodos , Centers for Disease Control and Prevention, U.S./normas , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/microbiologia , Notificação de Doenças/métodos , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/epidemiologia , Humanos , Cidade de Nova Iorque/epidemiologia , Fatores de Tempo , Estados Unidos/epidemiologia
20.
Healthcare (Basel) ; 12(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38610229

RESUMO

This study aimed to identify the individual, organizational, and environmental factors which contributed to COVID-19-related outcomes in long-term care facilities (LTCFs). A systematic review was conducted to summarize and synthesize empirical studies using a multi-level analysis approach to address the identified influential factors. Five databases were searched on 23 May 2023. To be included in the review, studies had to be published in peer-reviewed journals or as grey literature containing relevant statistical data. The Joanna Briggs Institute critical appraisal tool was employed to assess the methodological quality of each article included in this study. Of 2137 citations identified after exclusions, 99 records met the inclusion criteria. The predominant individual, organizational, and environmental factors that were most frequently found associated with the COVID-19 outbreak comprised older age, higher dependency level; lower staffing levels and lower star and subset domain ratings for the facility; and occupancy metrics and co-occurrences of outbreaks in counties and communities where the LTCFs were located, respectively. The primary individual, organizational, and environmental factors frequently linked to COVID-19-related deaths comprised age, and male sex; higher percentages of racial and ethnic minorities in LTCFs, as well as ownership types (including private, for-profit, and chain membership); and higher occupancy metrics and LTCF's size and bed capacity, respectively. Unfolding the risk factors collectively may mitigate the risk of outbreaks and pandemic-related mortality in LTCFs during future endemic and pandemics through developing and improving interventions that address those significant factors.

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