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INTRODUCTION: Stiff person syndrome (SPS) is a neurological disorder characterized by muscle rigidity primarily in the truncal muscles, commonly associated with autoantibodies to the glutamic acid-decarboxylase 65 kD receptor (GAD65). There is limited epidemiological information on patients with SPS. METHODS: We performed a retrospective case review using the National United States Veterans Affairs Health Administration electronic medical record system. We analyzed prevalence, demographics, disease characteristics, and treatment outcomes in SPS patients who were anti-GAD65 antibody positive. RESULTS: Fifteen patients met our criteria. Point prevalence was 2.06 per million, and period prevalence was 2.71 per million. Men to women ratio was 14:1. All patients benefitted from treatment with symptomatic antispasmodic agents. Ten of 15 patients received intravenous immunoglobulin, with a majority demonstrating stable or improved modified Rankin scores. DISCUSSION: This investigation was a large North American epidemiological study of SPS with predominantly male patients. Symptomatic therapy was beneficial for most patients, with less clear sustained benefit of immunotherapy. Muscle Nerve 58:801-804, 2018.
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Autoanticorpos/sangue , Glutamato Descarboxilase/imunologia , Rigidez Muscular Espasmódica/sangue , Rigidez Muscular Espasmódica/epidemiologia , Veteranos/estatística & dados numéricos , Adulto , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Rigidez Muscular Espasmódica/diagnóstico , Estados Unidos/epidemiologia , United States Department of Veterans Affairs/estatística & dados numéricosRESUMO
The needs of Urban American Indian/Alaska Native (AI/AN) populations are often not well understood. In order to inform programs and services, the Urban Indian Center of Salt Lake (UIC-SL), in cooperation with researchers from the University of Utah, undertook a community needs assessment of AI/AN living along Utah's Wasatch Front. A 60-item questionnaire was developed to capture information about health status, services used, unmet needs, and common sources of information about AI/AN community events and activities. Study participants (n = 336) were a convenience sample. Descriptive statistics, including mean, standard deviation, percentage, and 95% confidence intervals, were calculated. The most common health provider diagnosed medical conditions included hypertension, obesity, and diabetes. The prevalence of violence, substance abuse, and mental health conditions were also high among study participants and their families. Compared to the general Utah population, study participants experienced disparities relative to diabetes prevalence, cognitive and visual disabilities, and access to health care. In addition to health care services, respondents indicated a need for cultural, social, and educational programs. They also reported high levels of technology use, suggesting a possible avenue for communicating with this population. This community-based participatory research project provided rich information about the unmet needs of this urban AI/AN population. The results will be used to guide UIC-SL strategic planning, and a database created for this project will be available for future data collection, allowing for comparison of results between sites and over time.
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/estatística & dados numéricos , Nível de Saúde , Indígenas Norte-Americanos/estatística & dados numéricos , Avaliação das Necessidades/estatística & dados numéricos , Adulto , Pesquisa Participativa Baseada na Comunidade , Feminino , Humanos , Indígenas Norte-Americanos/psicologia , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Utah , Adulto JovemRESUMO
INTRODUCTION: One nationwide study (The Netherlands) of Lambert-Eaton myasthenic syndrome (LEMS) has been published. We report LEMS epidemiology and its therapeutic response in the United States Veterans Affairs (VA) population. METHODS: Medical records for all active patients (12.5 million) in the VA health system were queried for relevant ICD-9 codes for the period October 1, 1999 to September 30, 2013. Clinical, electrophysiologic, and serologic features were evaluated to confirm diagnosis; epidemiologic and treatment data were collected. RESULTS: Point prevalence was estimated at 2.6 per 1,000,000 (confirmed cases) and 3.3 per 1,000,000 (combined confirmed and probable cases). Crude prevalence was similarly estimated at 9.2 and 10.9 per 1,000,000 respectively. A total of 18 of 48 (38%) patients received 3,4-diaminopyridine (3,4-DAP); 14 of 18 (78%) improved. CONCLUSIONS: This investigation was a large North American epidemiologic study of LEMS. LEMS prevalence in the national VA population was found to be similar to previously published rates in other large international populations. Most patients experienced improvement with therapy, including a majority with 3,4-DAP. Muscle Nerve 56: 421-426, 2017.
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Síndrome Miastênica de Lambert-Eaton/epidemiologia , Síndrome Miastênica de Lambert-Eaton/terapia , Vigilância da População , United States Department of Veterans Affairs , Veteranos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Plasmaferese/tendências , Vigilância da População/métodos , Bloqueadores dos Canais de Potássio/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , United States Department of Veterans Affairs/tendênciasRESUMO
Accelerating cancer research is expected to require new types of clinical trials. This report describes the Intensive Trial of OMics in Cancer (ITOMIC) and a participant with triple-negative breast cancer metastatic to bone, who had markedly elevated circulating tumor cells (CTCs) that were monitored 48 times over 9 months. A total of 32 researchers from 14 institutions were engaged in the patient's evaluation; 20 researchers had no prior involvement in patient care and 18 were recruited specifically for this patient. Whole-exome sequencing of 3 bone marrow samples demonstrated a novel ROS1 variant that was estimated to be present in most or all tumor cells. After an initial response to cisplatin, a hypothesis of crizotinib sensitivity was disproven. Leukapheresis followed by partial CTC enrichment allowed for the development of a differential high-throughput drug screen and demonstrated sensitivity to investigational BH3-mimetic inhibitors of BCL-2 that could not be tested in the patient because requests to the pharmaceutical sponsors were denied. The number and size of CTC clusters correlated with clinical status and eventually death. Focusing the expertise of a distributed network of investigators on an intensively monitored patient with cancer can generate high-resolution views of the natural history of cancer and suggest new opportunities for therapy. Optimization requires access to investigational drugs.
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Redes Comunitárias , Pesquisadores , Neoplasias de Mama Triplo Negativas/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Prova Pericial , Feminino , Seguimentos , Humanos , Leucaférese , Estudos Longitudinais , Pessoa de Meia-Idade , Metástase Neoplásica , Células Neoplásicas Circulantes , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Background: Few studies have examined the menopausal transition in American Indian and Alaska Native (AI/AN) women; these reports indicate they are the most likely group to report bothersome vasomotor symptoms (VMS). Evidence demonstrates VMS may be a biomarker for chronic diseases. Thus, evidence-based interventions to improve VMS and other symptoms and health-screening rates for urban midlife AI/AN women are needed. Objective: The objectives of this community-based project were to form a Community Advisory Board (CAB) with whom to: 1) conduct CAB meetings (similar to a focus group) with midlife AI/AN women to understand their lived health care experiences and needs during the menopausal transition; and 2) obtain guidance in creating a tailored intervention. Methods: Eligible participants indicated they were registered members of American Indian Tribes, self-identified as a woman, aged 35 or older, and were recruited through the Urban Indian Center of Salt Lake and community outreach. Three CAB meetings were conducted via Zoom. A qualitative-descriptive approach was used for analysis, with the aim of staying close to the data to understand AI/AN women's experiences and needs. Transcripts were iteratively coded using content/thematic analysis. Results: Four themes emerged: 1) lack of and desire for information about the menopause transition; 2) barriers to accessing care; 3) matriarchal priorities impacting personal health outcomes; and 4) preferences for Indigenous and integrative medicine as first-line interventions, followed by conventional medicine. Conclusions: Among this sample of urban AI/AN women, there was a great need for and interest in information about menopause, both for themselves and for their daughters and family. Integrative and Indigenous approaches were preferred. Proposed next steps include developing and pilot-testing a nurse-delivered health-education intervention with Indigenous, integrative, and conventional medical content.
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BACKGROUND: Tobacco use remains the leading cause of death and disability in the USA and is disproportionately concentrated among low socioeconomic status (SES) populations. Community Health Centers (CHCs) are a key venue for reaching low SES populations with evidence-based tobacco cessation treatment such as Quitlines. Electronic health record (EHR)-based interventions at the point-of-care, text messaging (TM), and phone counseling have the potential to increase Quitline reach and are feasible to implement within CHCs. However, there is a lack of data to inform how, when, and in what combination these strategies should be implemented. The aims of this cluster-randomized trial are to evaluate multi-level implementation strategies to increase the Reach (i.e., proportion of tobacco-using patients who enroll in the Quitline) and Impact (i.e., Reach × Efficacy [efficacy is defined as the proportion of tobacco-using patients who enroll in Quitline treatment that successfully quit]) and to evaluate characteristics of healthcare system, providers, and patients that may influence tobacco-use outcomes. METHODS: This study is a multilevel, three-phase, Sequential Multiple Assignment Randomized Trial (SMART), conducted in CHCs (N = 33 clinics; N = 6000 patients). In the first phase, clinics will be randomized to two different EHR conditions. The second and third phases are patient-level randomizations based on prior treatment response. Patients who enroll in the Quitline receive no further interventions. In phase two, patients who are non-responders (i.e., patients who do not enroll in Quitline) will be randomized to receive either TM or continued-EHR. In phase three, patients in the TM condition who are non-responders will be randomized to receive either continued-TM or TM + phone coaching. DISCUSSION: This project will evaluate scalable, multi-level interventions to directly address strategic national priorities for reducing tobacco use and related disparities by increasing the Reach and Impact of evidence-based tobacco cessation interventions in low SES populations. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03900767) on April 4th, 2019.
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Centros Comunitários de Saúde/organização & administração , Registros Eletrônicos de Saúde/organização & administração , Linhas Diretas/organização & administração , Atenção Primária à Saúde/organização & administração , Abandono do Uso de Tabaco/métodos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Proteínas de Drosophila , Comportamentos Relacionados com a Saúde , Humanos , Ciência da Implementação , Capacitação em Serviço/organização & administração , Desenvolvimento de Programas , Fatores Socioeconômicos , Envio de Mensagens de Texto , Dispositivos para o Abandono do Uso de Tabaco , UtahRESUMO
OBJECTIVES: The aim was to estimate the impact of TNF inhibitor (TNFi) exposure on radiographic disease progression in US Veterans with RA during the first year after initiating therapy. METHODS: This historical longitudinal cohort design used clinical and claims data to evaluate radiographic progression after initiation of TNFi. US Veterans with RA initiating TNFi treatment (index date), ≥ 6 months pre-index and ≥ 12 months post-index VA enrolment/activity, and initial (6 months pre-index to 30 days post-index) and follow-up (10-18 months post-index) bilateral hand radiographs were eligible. The cumulative TNFi exposure and change in modified Sharp score (MSS) between initial and follow-up radiographs were calculated. The percentage of patients with clinically meaningful change in MSS (≥ 5) for each month of exposure was assessed using a longitudinal marginal structural model with inverse probability of treatment weights. Mean values and CIs were generated using 1000 bootstrapped samples. RESULTS: For 246 eligible patients, the mean (s.d.) age was 58 (11) years; 81% were male. The mean (s.d.) initial MSS was 19.6 (33.4) (range 0-214). The mean change (s.d.) in MSS was 0.3 (3.6) (median 0, range -19 to 22). Patients with the greatest exposure had the least radiographic progression for both crude and adjusted model analyses. Adjusted rates of MSS change ≥ 5 points (95% CI) were 10.6% (9.8%, 11.4%) for patients with 3 months of exposure compared with 5.4% (5.1%, 5.7%) for patients with 12 months of exposure. CONCLUSION: One-year changes in radiographic progression were small. Patients with the greatest cumulative TNFi exposure experienced the least progression.
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Genomic hypomethylation and chromosomal instability are frequent characteristics of human cancer cells. Targeted deletion of Lsh leads to a global defect in genomic methylation, and Lsh-deficient mice die at birth with a reduced body weight. Here, we examine the growth pattern of embryonal fibroblasts derived from Lsh-/- mice. The absence of Lsh leads to a severe proliferative defect of fibroblasts with lower saturation density, early signs of senescence, and a lower frequency of immortalization. The impaired growth rate in vitro may be in part responsible for the small size of Lsh-deficient mice. In addition, Lsh-/- fibroblasts accumulated high centrosome numbers, formed multipolar spindles, displayed micronuclei formation, and elevated nuclear DNA content. A similar increase in centrosome abnormalities was observed when wild-type fibroblasts were treated with a DNA-demethylating agent, suggesting that genomic hypomethylation plays an important role in mitotic defects of Lsh-/- murine embryonal fibroblasts, possibly by altering chromatin structure. Because supernumerary centrosomes are a common feature in cancer cells, this Lsh-dependent pathway has the potential to contribute to genetic instability and chromosomal aberrations during tumor progression.
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Azacitidina/análogos & derivados , DNA Helicases/deficiência , Fibroblastos/citologia , Fibroblastos/enzimologia , Animais , Azacitidina/farmacologia , Ciclo Celular/genética , Divisão Celular/genética , Células Cultivadas , Centrossomo/efeitos dos fármacos , Centrossomo/fisiologia , DNA Helicases/genética , Decitabina , Embrião de Mamíferos , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Camundongos , Mitose/genética , Fuso Acromático/metabolismoRESUMO
BACKGROUND: The KRAS gene is mutated in about 40 % of colorectal cancer (CRC) cases, which has been clinically validated as a predictive mutational marker of intrinsic resistance to anti-EGFR inhibitor (EGFRi) therapy. Since nearly 60 % of patients with a wild type KRAS fail to respond to EGFRi combination therapies, there is a need to develop more reliable molecular signatures to better predict response. Here we address the challenge of adapting a gene expression signature predictive of RAS pathway activation, created using fresh frozen (FF) tissues, for use with more widely available formalin fixed paraffin-embedded (FFPE) tissues. METHODS: In this study, we evaluated the translation of an 18-gene RAS pathway signature score from FF to FFPE in 54 CRC cases, using a head-to-head comparison of five technology platforms. FFPE-based technologies included the Affymetrix GeneChip (Affy), NanoString nCounter™ (NanoS), Illumina whole genome RNASeq (RNA-Acc), Illumina targeted RNASeq (t-RNA), and Illumina stranded Total RNA-rRNA-depletion (rRNA). RESULTS: Using Affy_FF as the "gold" standard, initial analysis of the 18-gene RAS scores on all 54 samples shows varying pairwise Spearman correlations, with (1) Affy_FFPE (r = 0.233, p = 0.090); (2) NanoS_FFPE (r = 0.608, p < 0.0001); (3) RNA-Acc_FFPE (r = 0.175, p = 0.21); (4) t-RNA_FFPE (r = -0.237, p = 0.085); (5) and t-RNA (r = -0.012, p = 0.93). These results suggest that only NanoString has successful FF to FFPE translation. The subsequent removal of identified "problematic" samples (n = 15) and genes (n = 2) further improves the correlations of Affy_FF with three of the five technologies: Affy_FFPE (r = 0.672, p < 0.0001); NanoS_FFPE (r = 0.738, p < 0.0001); and RNA-Acc_FFPE (r = 0.483, p = 0.002). CONCLUSIONS: Of the five technology platforms tested, NanoString technology provides a more faithful translation of the RAS pathway gene expression signature from FF to FFPE than the Affymetrix GeneChip and multiple RNASeq technologies. Moreover, NanoString was the most forgiving technology in the analysis of samples with presumably poor RNA quality. Using this approach, the RAS signature score may now be reasonably applied to FFPE clinical samples.
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Neoplasias Colorretais/patologia , Formaldeído , Inclusão em Parafina , Transdução de Sinais , Fixação de Tecidos , Proteínas ras/metabolismo , Neoplasias Colorretais/genética , Humanos , Mutação , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
The need to use resources efficiently and reduce environmental impacts of industrial products and processes is becoming increasingly important in engineering design; therefore, green engineering principles are gaining prominence within engineering education. This paper describes a general framework for incorporating green engineering design principles into engineering curricula, with specific examples for chemical engineering. The framework for teaching green engineering discussed in this paper mirrors the 12 Principles of Green Engineering proposed by Anastas and Zimmerman (Environ. Sci. Technol. 2003, 37, 94A-101A), especially in methods for estimating the hazardous nature of chemicals, strategies for pollution prevention, and approaches leading to efficient energy and material utilization. The key elements in green engineering education, which enlarge the "box" for engineering design, are environmental literacy, environmentally conscious design, and beyond-the-plant boundary considerations.