Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 67
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-39330914

RESUMO

OBJECTIVE: To examine, among persons discharged from inpatient rehabilitation for traumatic brain injury (TBI), the degree to which pre-TBI factors were associated with post-TBI hospitalization for psychiatric reasons. The authors hypothesized that pre-TBI psychiatric hospitalization and other pre-TBI mental health treatment would predict post-TBI psychiatric hospitalization following rehabilitation discharge, up to 5 years post-TBI. SETTING: Five Veterans Affairs Polytrauma Rehabilitation Centers. PARTICIPANTS: Participants with nonmissing rehospitalization status and reason, who were followed at 1 year (N = 1006), 2 years (N = 985), and 5 years (N = 772) post-TBI. DESIGN: A secondary analysis of the Veterans Affairs TBI Model Systems, a multicenter, longitudinal study of veterans and active-duty service members with a history of mild, moderate, or severe TBI previously admitted to comprehensive inpatient medical rehabilitation. This study examined participants cross-sectionally at 3 follow-up timepoints. MAIN MEASURES: Psychiatric Rehospitalization was classified according to Healthcare Cost and Utilization Project multilevel Clinical Classifications diagnosis terminology (Category 5). RESULTS: Rates of post-TBI psychiatric hospitalization at years 1, 2, and 5 were 4.3%, 4.7%, and 4.1%, respectively. While bivariate comparisons identified pre-TBI psychiatric hospitalization and pre-TBI mental health treatment as factors associated with psychiatric rehospitalization after TBI across all postinjury timepoints, these factors were statistically nonsignificant when examined in a multivariate model across all timepoints. In the multivariable analysis, pre-TBI psychiatric hospitalization was significantly associated with increased odds of post-TBI psychiatric hospitalization only at 1-year post-TBI (adjusted odds ratio = 2.65; 95% confidence interval, 1.07-6.55, P = .04). Posttraumatic amnesia duration was unrelated to psychiatric rehospitalization. CONCLUSIONS: Study findings suggest the limited utility of age, education, and pre-TBI substance use and mental health utilization in predicting post-TBI psychiatric hospitalization. Temporally closer social and behavior factors, particularly those that are potentially modifiable, should be considered in future research.

2.
J Int Neuropsychol Soc ; 27(1): 1-11, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32641194

RESUMO

OBJECTIVES: Survivors of childhood brain tumors experience neurological sequelae that disrupt everyday adaptive functioning (AF) skills. The Neurological Predictor Scale (NPS), a cumulative measure of tumor treatments and sequelae, predicts cognitive outcomes, but findings on its relation to informant-reported executive dysfunction (ED) and AF are mixed. Given known effects of frontal-subcortical system disruptions on AF, this study assessed the NPS' relationship with AF as mediated by frontal systems dysfunction, measured by the Frontal Systems Behavior Scale (FrSBe). METHODS: 75 participants (Mage = 23.5, SDage = 4.5) were young adult survivors of childhood brain tumors at least 5 years past diagnosis. FrSBe and Scales of Independent Behavior-Revised (SIB-R), a measure of AF, were administered to informants. Parallel multiple mediator models included Apathy and ED as mediators, and age at diagnosis and time between diagnosis and assessment as covariates. RESULTS: More complex treatment and sequelae were correlated with poorer functioning. Mediation models were significant for all subscales: Motor Skills (MS), p = .0001; Social Communication (SC), p = .002; Personal Living (PL), p = .004; Community Living (CL), p = .007. The indirect effect of ED on SC and CL was significant; the indirect effect of Apathy was not significant for any subscales. CONCLUSIONS: More complex tumor treatment and sequelae were associated with poorer long-term AF via increased ED. Cognitive rehabilitation programs may focus on the role of executive function and initiation that contribute to AF, particularly SC and CL skills, to help survivors achieve comparable levels of independence in everyday function as their peers.


Assuntos
Neoplasias Encefálicas , Disfunção Cognitiva , Neoplasias Encefálicas/complicações , Cognição , Função Executiva , Humanos , Testes Neuropsicológicos , Sobreviventes , Adulto Jovem
3.
Neuropsychol Rev ; 29(4): 465-483, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31748842

RESUMO

Rett syndrome is the second most common cause of intellectual disability in females worldwide. The severity of many individuals' impairment limits the effectiveness of traditional assessment. However, clinician and parent reports of adaptive functioning may provide insight into these patients' abilities. This review aims to synthesize the current literature assessing adaptive functioning in Rett syndrome and evaluate existing measurement tools in this population. A search was conducted on PubMed using the search term "Rett syndrome." Studies that quantitatively assessed adaptive functioning outcomes in Rett syndrome with published and normed questionnaire measures were included. Twenty-three studies met inclusion criteria. Overall results indicate that the population of people with Rett syndrome is highly impaired, both in overall adaptive functioning as well as in specific subdomains (e.g., mobility, activities of daily living). Atypical Rett syndrome groups performed better on measures of adaptive functioning relative to patients with classic Rett syndrome. Our findings identified measurement weaknesses, as many of the studies found floor effects and therefore were unable to capture meaningful variability in outcomes. Individuals with Rett syndrome are highly reliant on caregivers due to disrupted adaptive functioning abilities. Optimizing measurement of adaptive skills in Rett syndrome will facilitate the quantification of meaningful change in skills and the identification of efficacious interventions aimed at improving outcomes and quality of life.


Assuntos
Adaptação Psicológica , Testes Psicológicos , Síndrome de Rett/psicologia , Atividades Cotidianas , Cuidadores , Comunicação , Pessoal de Saúde , Humanos , Socialização
4.
J Int Neuropsychol Soc ; 25(7): 729-739, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31084659

RESUMO

OBJECTIVE: Radiation therapy (RT) improves rates of survival of patients with childhood brain tumors but increases deficits in cognition and independent living skills. Previous literature has studied difficulties in basic cognitive processes, but few explore impairment in higher-order skills such as adaptive functioning. Some studies identify females as at risk for cognitive deficits due to RT, but few investigate sex differences in adaptive functioning. It was hypothesized that females would exhibit poorer long-term independent living skills and core cognitive skills relative to males following RT. METHODS: Forty-five adult survivors of posterior fossa childhood brain tumors (24 females) completed the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Memory Scale, Third Edition (WMS-III) Digit Span Forward (DSF) and Backward (DSB), and Oral Symbol Digit Modalities Test (OSDMT). Informants completed the Scales of Independent Behavior-Revised (SIB-R). RESULTS: DSF and OSDMT were positively correlated with all five SIB-R domains, full-scale IQ (FSIQ) was positively correlated with four SIB-R domains, and DSB was positively correlated with three SIB-R domains. There was an interaction between sex and RT for OSDMT and community living skills with trend level interactions for personal living skills and broad independent living skills, where females without RT had higher scores than females with RT. CONCLUSIONS: Female survivors were more affected by RT than males across the community living skills domain of adaptive functioning as well as processing speed. Processing speed deficits may have a cascading impact on daily living skills. Future studies should investigate how clinical and biological factors may contribute to personalized treatment plans between sexes. (JINS, 2019, 25, 729-739).


Assuntos
Atividades Cotidianas , Adaptação Psicológica/fisiologia , Sobreviventes de Câncer , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Neoplasias Infratentoriais/radioterapia , Radioterapia/efeitos adversos , Adulto , Feminino , Humanos , Vida Independente , Masculino , Fatores Sexuais
5.
J Int Neuropsychol Soc ; 22(5): 501-11, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26954713

RESUMO

OBJECTIVES: The cerebellum (CB) is known for its role in supporting processing speed (PS) and cognitive efficiencies. The CB often sustains damage from treatment and resection in pediatric patients with posterior fossa tumors. Limited research suggests that CB atrophy may be associated with the radiation treatment experienced during childhood. The purpose of the study was to measure cerebellar atrophy to determine its neurobehavioral correlates. METHODS: Brain magnetic resonance images were collected from 25 adult survivors of CB tumors and age- and gender-matched controls (M age= 24 years (SD=5), 52% female). Average age at diagnosis was 9 years (SD=5) and average time since diagnosis was 15 years (SD=5). PS was measured by the Symbol Digit Modality Test. To quantify atrophy, an objective formula was developed based on prior literature, in which Atrophy=[(CB White+CB Gray Volume)/Intracranial Vault (ICV)]controls-[(CB White+CB Gray+Lesion Size Volume)/ICV]survivors. RESULTS: Regression analyses found that the interaction term (age at diagnosis*radiation) predicts CB atrophy; regression equations included the Neurological Predictor Scale, lesion size, atrophy, and the interaction term and accounted for 33% of the variance in oral PS and 48% of the variance in written PS. Both interactions suggest that individuals with smaller CB lesion size but a greater degree of CB atrophy had slower PS, whereas individuals with a larger CB lesion size and less CB atrophy were less affected. CONCLUSION: The results of the current study suggest that young age at diagnosis and radiation is associated with CB atrophy, which interacts with lesion size to impact both written and oral PS.


Assuntos
Neoplasias Cerebelares/complicações , Cerebelo/patologia , Deficiências do Desenvolvimento/complicações , Sobrevida , Adolescente , Adulto , Atrofia/diagnóstico por imagem , Atrofia/etiologia , Estudos de Casos e Controles , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/mortalidade , Cerebelo/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Análise Fatorial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Exame Neurológico , Testes Neuropsicológicos , Análise de Regressão , Índice de Gravidade de Doença , Adulto Jovem
6.
Pediatr Blood Cancer ; 63(11): 2019-25, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27463526

RESUMO

BACKGROUND: The relationship between apathy and endocrine dysfunction, both frequent outcomes of neurological insult, has not yet been investigated in brain tumor survivors. The present study aimed to assess the relationship between pituitary disorders and apathy and other facets of executive function in long-term adult survivors of childhood brain tumors and to differentiate between apathy and depression in this population. PROCEDURE: Seventy-six adult survivors of childhood brain tumors at least 5 years past diagnosis participated. An informant completed the Frontal Systems Behavior Scale (FrSBe), and 75 of the 76 participants completed a Structured Clinical Interview for the DSM-IV-TR (SCID). Information on neuroendocrine dysfunction was obtained through medical chart review. RESULTS: Clinically significant levels of apathy on the FrSBe were identified in 41% of survivors. Pituitary dysfunction significantly explained 9% of the variance in apathy scores and affected whether an individual presented with clinical levels of apathy. Pituitary dysfunction predicted higher levels of executive dysfunction but did not impact whether a participant reached clinical levels of executive dysfunction. A past major depressive episode (MDE) significantly predicted current apathy but showed no relationship with pituitary disorders. Radiation treatment predicted pituitary dysfunction but not the differences in apathy or executive functions. CONCLUSIONS: Apathy and executive dysfunction in survivors of childhood brain tumors are strongly predicted by pituitary dysfunction, and individuals with pituitary dysfunction are more likely to present with clinical levels of apathy as adults. Clinical levels of apathy may present absent of current depression, and pituitary dysfunction impacts apathy uniquely.


Assuntos
Apatia , Neoplasias Encefálicas/complicações , Função Executiva , Doenças da Hipófise/etiologia , Adulto , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/psicologia , Criança , Feminino , Humanos , Masculino , Sobreviventes
7.
Genet Med ; 16(4): 347-55, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24651602

RESUMO

Hearing loss is a common and complex condition that can occur at any age, can be inherited or acquired, and is associated with a remarkably wide array of etiologies. The diverse causes of hearing loss, combined with the highly variable and often overlapping presentations of different forms of hearing loss, challenge the ability of traditional clinical evaluations to arrive at an etiologic diagnosis for many deaf and hard-of-hearing individuals. However, identifying the etiology of a hearing loss may affect clinical management, improve prognostic accuracy, and refine genetic counseling and assessment of the likelihood of recurrence for relatives of deaf and hard-of-hearing individuals. Linguistic and cultural identities associated with being deaf or hard of hearing can complicate access to and the effectiveness of clinical care. These concerns can be minimized when genetic and other health-care services are provided in a linguistically and culturally sensitive manner. This guideline offers information about the frequency, causes, and presentations of hearing loss and suggests approaches to the clinical evaluation of deaf and hard-of-hearing individuals aimed at identifying an etiologic diagnosis and providing informative and effective patient education and genetic counseling.


Assuntos
Perda Auditiva/diagnóstico , Perda Auditiva/etiologia , Atenção à Saúde , Aconselhamento Genético , Testes Genéticos , Perda Auditiva/genética , Perda Auditiva/patologia , Humanos , Relações Médico-Paciente , Guias de Prática Clínica como Assunto , Estados Unidos
8.
J Genet Couns ; 23(1): 16-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23881473

RESUMO

Newborn screening (NBS) is a minimally invasive lifesaving test. There is currently no federal mandate for NBS, thus states determine their own screening panel based on the recommendations of the Secretary's Advisory Committee on Heritable Disorders in Newborn and Children (SACHDNC), which was recently re-chartered as the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children (DACHDNC). After NBS is completed, a couple of residual blood spots remain. While some states allow these spots to be used for public health and scientific research purposes, parents are not always informed about these additional uses. This paper addresses the National Society of Genetic Counselors' (NSGC's) position about NBS and blood spot storage/use and the rationale for these positions. The National Society of Genetic Counselors strongly supports newborn screening for the uniform screening panel of conditions recommended by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. NSGC also supports storage and use of blood spot samples by newborn screening laboratories and transparent policies that govern these activities.


Assuntos
Aconselhamento Genético , Consentimento Livre e Esclarecido , Triagem Neonatal , Sociedades Médicas , Humanos , Recém-Nascido , Recursos Humanos
9.
JAMA ; 312(18): 1880-7, 2014 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-25326637

RESUMO

IMPORTANCE: Clinical exome sequencing (CES) is rapidly becoming a common molecular diagnostic test for individuals with rare genetic disorders. OBJECTIVE: To report on initial clinical indications for CES referrals and molecular diagnostic rates for different indications and for different test types. DESIGN, SETTING, AND PARTICIPANTS: Clinical exome sequencing was performed on 814 consecutive patients with undiagnosed, suspected genetic conditions at the University of California, Los Angeles, Clinical Genomics Center between January 2012 and August 2014. Clinical exome sequencing was conducted as trio-CES (both parents and their affected child sequenced simultaneously) to effectively detect de novo and compound heterozygous variants or as proband-CES (only the affected individual sequenced) when parental samples were not available. MAIN OUTCOMES AND MEASURES: Clinical indications for CES requests, molecular diagnostic rates of CES overall and for phenotypic subgroups, and differences in molecular diagnostic rates between trio-CES and proband-CES. RESULTS: Of the 814 cases, the overall molecular diagnosis rate was 26% (213 of 814; 95% CI, 23%-29%). The molecular diagnosis rate for trio-CES was 31% (127 of 410 cases; 95% CI, 27%-36%) and 22% (74 of 338 cases; 95% CI, 18%-27%) for proband-CES. In cases of developmental delay in children (<5 years, n = 138), the molecular diagnosis rate was 41% (45 of 109; 95% CI, 32%-51%) for trio-CES cases and 9% (2 of 23, 95% CI, 1%-28%) for proband-CES cases. The significantly higher diagnostic yield (P value = .002; odds ratio, 7.4 [95% CI, 1.6-33.1]) of trio-CES was due to the identification of de novo and compound heterozygous variants. CONCLUSIONS AND RELEVANCE: In this sample of patients with undiagnosed, suspected genetic conditions, trio-CES was associated with higher molecular diagnostic yield than proband-CES or traditional molecular diagnostic methods. Additional studies designed to validate these findings and to explore the effect of this approach on clinical and economic outcomes are warranted.


Assuntos
Exoma , Doenças Genéticas Inatas/diagnóstico , Técnicas de Diagnóstico Molecular , Doenças Raras/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Doenças Raras/genética , Análise de Sequência de DNA/métodos
10.
Lancet HIV ; 11(6): e369-e379, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734015

RESUMO

BACKGROUND: Doravirine and islatravir is an investigational, once-daily, single-tablet regimen with high antiviral potency, favourable safety and tolerability, and low propensity for resistance. We report week 48 results from a phase 3 trial evaluating switch from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (0·75 mg). METHODS: This phase 3, multicentre, randomised, active-controlled, open-label, non-inferiority trial was conducted at 77 research, community, and hospital-based clinics in 15 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation schedule to switch to doravirine (100 mg) and islatravir (0·75 mg) or to continue their baseline ART regimen. Block randomisation was based on a block size of four, and randomisation was stratified by baseline regimen (ie, protease inhibitor, integrase inhibitor, or other). Participants in the doravirine and islatravir group were instructed to take one tablet at approximately the same time each day, and participants in the baseline ART group continued to take the medication according to the locally approved label. HIV-1 RNA and safety evaluations were done at baseline and weeks 4, 12, 24, 36, and 48. CD4 cell counts were measured at baseline, week 24, and week 48. The primary endpoint was proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug) using the US Food and Drug Administration snapshot approach and prespecified non-inferiority margin of 4%. This study is registered with ClinicalTrials.gov (NCT04223778) and is completed. FINDINGS: Between Feb 18 and Oct 2, 2020, 740 individuals were screened for eligibility, of whom 672 (90·8%) participants (249 [37·1%] women and 423 [62·9%] men; median CD4 count of 678 cells per µL [IQR 496-868]) were randomly assigned to doravirine (100 mg) and islatravir (0·75 mg; n=336) or to continue baseline ART (n=336). The last follow-up visit occurred on Sept 8, 2021. At week 48, zero of 336 participants in the doravirine and islatravir group versus five (1·5%) of 336 participants in the baseline ART group had greater than or equal to 50 HIV-1 RNA copies per mL (difference -1·5, 95% CI -3·4 to -0·3). The per-protocol analysis showed consistent results. Headache was the most common adverse event in both groups (35 [10·4%] of 336 participants in the doravirine and islatravir group, 16 [4·8%] of 336 in the baseline ART group), infection rates were similar (113 [33·6%] in both groups), and discontinuations due to adverse events were low (seven [2·1%] vs one [0·3%]). 66 (19·6%) of 336 participants had treatment-related adverse events in the doravirine and islatravir group compared with 30 (8·9%) of 336 in the baseline ART group. In the islatravir and doravirine group, CD4 cell counts (mean change -30·3 cells per µL) and total lymphocyte counts (mean change -0·26 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral combinations used in clinical practice for adults with HIV-1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Piridonas , Triazóis , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Feminino , Adulto , Masculino , HIV-1/efeitos dos fármacos , HIV-1/genética , Pessoa de Meia-Idade , Piridonas/administração & dosagem , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Carga Viral/efeitos dos fármacos , Contagem de Linfócito CD4 , Esquema de Medicação , Resultado do Tratamento , Terapia Antirretroviral de Alta Atividade , RNA Viral/sangue , Combinação de Medicamentos , Desoxiadenosinas
11.
Lancet HIV ; 11(6): e357-e368, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734016

RESUMO

BACKGROUND: Doravirine and islatravir is an investigational, once-daily regimen with high antiviral potency, favourable safety and tolerability, and a low propensity for resistance. We investigated a switch from bictegravir, emtricitabine, and tenofovir alafenamide to doravirine (100 mg) and islatravir (0·75 mg) in virologically suppressed adults with HIV-1. METHODS: We conducted a phase 3, multicentre, randomised, active-controlled, double-blind, double-dummy, non-inferiority trial at 89 research, community, and hospital-based clinics in 11 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL for at least 3 months on bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation allocation schedule, with block randomisation based on a block size of four, to switch to doravirine (100 mg) and islatravir (0·75 mg) or continue bictegravir, emtricitabine, and tenofovir alafenamide orally once daily, with matching placebos taken by all participants. Participants, investigators, study staff, and sponsor personnel involved in study drug administration or clinical evaluation of participants were masked to treatment assignment until week 48. Participants were instructed at each visit to take one tablet from each of the two bottles received, one of study drug and one of placebo, once daily, and participants were assessed at baseline and weeks 4, 12, 24, 36, and 48. The primary endpoint was the proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug; US Food and Drug Administration snapshot; prespecified non-inferiority margin 4%). The study is ongoing, with all remaining participants in post-treatment follow-up, and is registered with ClinicalTrials.gov, NCT04223791. FINDINGS: We screened 726 individuals for eligibility between Feb 18 and Sept 3, 2020, of whom 643 (88·6%) participants were randomly assigned to a treatment group (183 [28·5%] women and 460 [71·5%] men). 322 participants were switched to doravirine (100 mg) and islatravir (0·75 mg) and 321 continued bictegravir, emtricitabine, and tenofovir alafenamide (two participants [one with a protocol deviation and one who withdrew] assigned to bictegravir, emtricitabine, and tenofovir alafenamide did not receive treatment). The last follow-up visit for the week 48 analysis occurred on Aug 26, 2021. At week 48, two (0·6%) of 322 participants in the doravirine and islatravir group compared with one (0·3%) of 319 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group had greater than or equal to 50 HIV-1 RNA copies per mL (difference 0·3%, 95% CI -1·2 to 2·0). The per-protocol analysis showed consistent results. 25 (7·8%) participants in the doravirine and islatravir group had headache compared with 23 [7·2%] participants in the bictegravir, emtricitabine, and tenofovir alafenamide group; 101 (31·4%) compared with 98 (30·7%) had infections; and eight (2·5%) participants in each group discontinued therapy due to adverse events. 32 (9·9%) participants had treatment-related adverse events in the islatravir and doravirine group comapred with 38 (11·9%) in the bictegravir, emtricitabine, and tenofovir alafenamide group. In the islatravir and doravirine group, CD4 cell counts (mean change -19·7 cells per µL) and total lymphocyte counts (mean change -0·20 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to daily doravirine (100 mg) and islatravir (0·75 mg) was non-inferior to bictegravir, emtricitabine, and tenofovir alafenamide at week 48. However, decreases in CD4 cell and total lymphocyte counts do not support the further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.


Assuntos
Adenina , Alanina , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , HIV-1 , Compostos Heterocíclicos de 4 ou mais Anéis , Piridonas , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Feminino , Masculino , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Adulto , Emtricitabina/administração & dosagem , Emtricitabina/uso terapêutico , HIV-1/efeitos dos fármacos , HIV-1/genética , Método Duplo-Cego , Piridonas/administração & dosagem , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Pessoa de Meia-Idade , Alanina/administração & dosagem , Adenina/análogos & derivados , Adenina/administração & dosagem , Adenina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Piperazinas/administração & dosagem , Amidas/administração & dosagem , Carga Viral/efeitos dos fármacos , Resultado do Tratamento , Esquema de Medicação , Desoxiadenosinas , Triazóis
12.
J Genet Couns ; 22(4): 492-507, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23430402

RESUMO

Limited data suggest that enhanced self-knowledge from genetic information related to non-medical traits can have a positive impact on psychological well-being. Deaf individuals undertake genetic testing for deaf genes to increase self-knowledge. Because deafness is considered a non-medical trait by many individuals, we hypothesized that deaf individuals receiving a genetic explanation for why they are deaf will experience increased psychological well-being. We report results from a prospective, longitudinal study to determine the impact of genetic testing (GJB2, Cx26; GJB6, Cx30) on perceived personal control (PPC), anxiety, and depression in deaf adults (N = 209) assessed following pre-test genetic counseling as well as 1-month and 6-months following test result disclosure. Participants were classified as Cx positive (n = 82) or Cx negative/inconclusive (n = 127). There was significant evidence for Cx group differences in PPC and anxiety over time (PPC: Cx group*time interaction p = 0.0007; anxiety: Cx group*time interaction p = 0.002), where PPC scores were significantly higher, and anxiety scores were significantly lower for the Cx positive group relative to the negative/inconclusive group following test result disclosure. Compared to pre-test, PPC scores increased at 1-month (p = 0.07) and anxiety scores decreased at 6-months (p = 0.03) for the Cx positive group. In contrast, PPC scores decreased (p = 0.009, p < 0.0001) and anxiety scores increased (p = 0.09, p = 0.02) for the Cx negative/inconclusive group at 1- and 6-months post test result disclosure. Genetic testing for deaf genes affects the psychological well-being of deaf individuals. Increasing deaf adults' access to genetic testing may potentially enhance self-knowledge and increase psychological well-being for those who receive a genetic explanation, which could offer downstream health benefits.


Assuntos
Surdez/diagnóstico , Testes Genéticos , Conexina 26 , Conexinas , Surdez/psicologia , Feminino , Humanos , Estudos Longitudinais , Estudos Prospectivos
13.
Proc Natl Acad Sci U S A ; 107(32): 14229-34, 2010 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-20616003

RESUMO

MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo and a specific microRNA, miR-125a, controls the size of the stem cell population by regulating hematopoietic stem/progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell-autonomous manner, with increased HSPC apoptosis in mutant animals. An evolutionarily conserved microRNA cluster containing miR-99b, let-7e, and miR-125a was preferentially expressed in long-term hematopoietic stem cells. MicroRNA miR-125a alone was capable of increasing the number of hematopoietic stem cells in vivo by more than 8-fold. This result was accomplished through a differentiation stage-specific reduction of apoptosis in immature hematopoietic progenitors, possibly through targeting multiple proapoptotic genes. Bak1 was directly down-regulated by miR-125a and expression of a 3'UTR-less Bak1 blocked miR-125a-induced hematopoietic expansion in vivo. These data demonstrate cell-state-specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size.


Assuntos
RNA Helicases DEAD-box/fisiologia , Endorribonucleases/fisiologia , Células-Tronco Hematopoéticas/citologia , MicroRNAs/fisiologia , Animais , Apoptose/genética , Contagem de Células , Diferenciação Celular , Regulação para Baixo , Homeostase , Camundongos , Dados de Sequência Molecular , Ribonuclease III , Proteína Killer-Antagonista Homóloga a bcl-2/genética
15.
J Genet Couns ; 21(2): 256-72, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21818696

RESUMO

Empirical data on genetic counseling outcomes in the deaf population are needed to better serve this population. This study was an examination of genetics knowledge before and after culturally and linguistically appropriate pre-test genetic counseling in a diverse deaf adult sample. Individuals ≥18 years old with early-onset sensorineural deafness were offered connexin-26/30 testing and genetic counseling. Participants completed questionnaires containing 10 genetics knowledge items at baseline and following pre-test genetic counseling. The effects of genetic counseling, prior beliefs about etiology, and participant's preferred language on genetics knowledge scores were assessed (n = 244). Pre-test genetic counseling (p = .0007), language (p < .0001), prior beliefs (p < .0001), and the interaction between counseling and beliefs (p = .035) were predictors of genetics knowledge. American Sign Language (ASL)-users and participants with "non-genetic/unknown" prior beliefs had lower knowledge scores than English-users and participants with "genetic" prior beliefs, respectively. Genetics knowledge improved after genetic counseling regardless of participants' language; knowledge change was greater for the "non-genetic/unknown" beliefs group than the "genetic" beliefs group. ASL-users' lower knowledge scores are consistent with evidence that ethnic and cultural minority groups have less genetics knowledge, perhaps from exposure and access disparities. Culturally and linguistically appropriate pre-test genetic counseling significantly improved deaf individuals' genetics knowledge. Assessing deaf individuals' prior beliefs is important for enhancing genetics knowledge.


Assuntos
Surdez/genética , Testes Genéticos , Adulto , Conexina 26 , Conexina 30 , Conexinas/genética , Surdez/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Pediatr Dermatol ; 29(3): 333-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21575046

RESUMO

Livedo reticularis is a lacy mottling of the skin that can have many etiologies. We report a case of an 8-year-old boy with a diagnosis of melanoma who developed persistent livedo reticularis during treatment with interferon alpha-2B. To our knowledge, this is the first case report of livedo reticularis occurring as a side effect of interferon treatment for pediatric melanoma. Given the increasing incidence of pediatric melanoma, it is important that dermatologists be aware of potential side effects of interferon therapy to optimize care and education for these patients.


Assuntos
Antineoplásicos/efeitos adversos , Interferon-alfa/efeitos adversos , Livedo Reticular/etiologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Criança , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Livedo Reticular/patologia , Masculino , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
17.
Appl Neuropsychol Adult ; 29(4): 469-477, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32503366

RESUMO

The Reliable Digit Span (RDS) is a performance validity test (PVT) used widely within non-clinical samples, but its utility is in question in clinical groups with cognitive impairment. To investigate, RDS scores were calculated and correlated with the Neurological Predictor Scale, an informant-reported Activities of Daily Living score, and a proxy measure of intelligence (Vocabulary) for 83 adult survivors of childhood brain tumors and 105 healthy controls. Analyses were covaried for age at examination. Participants were divided into passing and failing groups at each RDS cutoff, and ANCOVAs for each of the three variables of interest covaried for age at the examination were run. RDS was correlated with all three variables of interest in survivors but only Vocabulary in controls. At the ≤7 cutoff, passing and failing survivors demonstrated significant differences across all variables of interest, while passing and failing controls differed only on Vocabulary. Differences were also found between passing and failing survivors at lower cutoffs. RDS is related to and likely impacted by various neurological and cognitive challenges faced by brain tumor survivors. Using the standard RDS cutoff of ≤7 may result in inaccurate interpretation of valid performance in this population; therefore, the use of other PVTs is recommended.


Assuntos
Atividades Cotidianas , Neoplasias Encefálicas , Sobreviventes de Câncer , Adulto , Neoplasias Encefálicas/complicações , Humanos , Testes Neuropsicológicos , Reprodutibilidade dos Testes , Sobreviventes
18.
J Clin Endocrinol Metab ; 107(7): 2036-2046, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35275602

RESUMO

CONTEXT: Adolescent males with hypogonadotropic hypogonadism (HH) have traditionally been treated with exogenous testosterone (T) or human chorionic gonadotropin (hCG) to produce virilization; however, those modalities do not result in growth of the testes and may promote premature maturation and terminal differentiation of Sertoli cells prior to their proliferation, which may impact future fertility. Another option is to use gonadotropins in those individuals to induce testicular growth, proliferation and maturation of Sertoli cells, and production of endogenous T with consequent virilization. OBJECTIVE: We examined the efficacy and safety of corifollitropin alfa (CFA) combined with hCG for the induction of testicular growth and pubertal development in adolescent boys with HH. METHODS: This was a 64-week, multicenter, open-label, single-group study of CFA in adolescent boys, aged 14 to younger than 18 years, with HH. Seventeen participants initiated a 12-week priming period with CFA (100 µg if weight ≤ 60 kg, or 150 µg if weight > 60 kg) given subcutaneously once every 2 weeks, after which they entered a 52-week combined treatment period with CFA, once every 2 weeks, and subcutaneous hCG, twice-weekly (hCG dose adjusted between 500 IU and 5000 IU to keep total T and estradiol levels within protocol-specified ranges). The primary efficacy end point was change from baseline in testicular volume (TV), measured as the sum of volumes of left and right testes by ultrasound. RESULTS: After 64 weeks of therapy with CFA/CFA combined with hCG, geometric mean fold increase from baseline in TV was 9.43 (95% CI, 7.44-11.97) (arithmetic mean of change from baseline at week 64, 13.0 mL). Hormonal, Tanner stage, and growth velocity changes were consistent with initiation and progression of puberty. Treatment was generally well tolerated. No participant developed anti-CFA antibodies. CONCLUSION: Treatment of adolescent boys with HH with CFA alone for 12 weeks followed by CFA combined with hCG for 52 weeks induced testicular growth accompanied by pubertal progression, increased T, and a pubertal growth spurt (EudraCT: 2015-001878-18).


Assuntos
Gonadotropina Coriônica , Hormônio Foliculoestimulante Humano , Hipogonadismo , Adolescente , Gonadotropina Coriônica/uso terapêutico , Hormônio Foliculoestimulante Humano/uso terapêutico , Humanos , Hipogonadismo/induzido quimicamente , Hipogonadismo/tratamento farmacológico , Masculino , Testículo , Testosterona/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA