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Positive effects of new anti-amyloid-ß (Aß) monoclonal antibodies in Alzheimer's disease (AD) have been attributed to brain amyloid reduction. However, most anti-Aß antibodies also increase the CSF levels of the 42-amino acid isoform (Aß42). We evaluated the associations of changes in CSF Aß42 and brain Aß-PET with cognitive and clinical end points in randomized trials of anti-Aß drugs that lowered (ß- and γ-secretase inhibitors) or increased CSF Aß42 levels (anti-Aß monoclonal antibodies) to test the hypothesis that post-treatment increases in CSF Aß42 levels are independently associated with cognitive and clinical outcomes. From long-term (≥12â months) randomized placebo-controlled clinical trials of anti-Aß drugs published until November 2023, we calculated the post-treatment versus baseline difference in ADAS-Cog (cognitive subscale of the Alzheimer's Disease Assessment Scale) and CDR-SB (Clinical Dementia Rate-Sum of Boxes) and z-standardized changes in CSF Aß42 and Aß-PET Centiloids (CL). We estimated the effect size [regression coefficients (RCs) and confidence intervals (CIs)] and the heterogeneity (I2) of the associations between AD biomarkers and cognitive and clinical end points using random-effects meta-regression models. We included 25 966 subjects with AD from 24 trials. In random-effects analysis, increases in CSF Aß42 were associated with slower decline in ADAS-Cog (RC: -0.55; 95% CI: -0.89, -0.21, P = 0.003, I2 = 61.4%) and CDR-SB (RC: -0.16; 95% CI: -0.26, -0.06, P = 0.002, I2 = 34.5%). Similarly, decreases in Aß-PET were associated with slower decline in ADAS-Cog (RC: 0.69; 95% CI: 0.48, 0.89, P < 0.001, I2 = 0%) and CDR-SB (RC: 0.26; 95% CI: 0.18, 0.33, P < 0.001, I2 = 0%). Sensitivity analyses yielded similar results. Higher CSF Aß42 levels after exposure to anti-Aß drugs are independently associated with slowing cognitive impairment and clinical decline. Increases in Aß42 may represent a mechanism of potential benefit of anti-Aß monoclonal antibodies in AD.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Fragmentos de Peptídeos , Humanos , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/tratamento farmacológico , Fragmentos de Peptídeos/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Tomografia por Emissão de Pósitrons , Masculino , FemininoRESUMO
OBJECTIVE: Neuropsychiatric symptoms (NPSs) have been linked to cognitive decline. This study explored ethnic differences and the effects of baseline NPSs on incident mild cognitive impairment (MCI) among 386 Hispanic and non-Hispanic participants from the Texas Harris Alzheimer's Research Study. METHODS: Data on NPSs from the Neuropsychiatric Inventory Questionnaire were available for all participants. Cox proportional hazards regression models were used to estimate the effect of ≥1 NPS at baseline and Hispanic ethnicity on incident MCI over a 7-year follow-up period. RESULTS: NPSs at baseline were associated with incident MCI for Hispanic participants but not non-Hispanic participants. Being Hispanic with at least one NPS at baseline had an 11-times higher risk of incident MCI. CONCLUSIONS: The Hispanic participants converted to MCI to a greater extent than the non-Hispanic participants. Only depressive symptoms increased the risk of MCI among non-Hispanics. Being of Hispanic ethnicity and having NPSs appeared to jointly increase the risk of progressing to MCI. To better understand the Alzheimer's disease continuum, further studies should explore other cultural, genetic, and medical risk factors influencing disease progression. Our findings strongly suggest the need to incorporate NPSs as outcomes of disease progression in future clinical trials involving Hispanic participants.
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Essential tremor (ET) may present with head tremor (HT), of presumed cerebellar nature. Deep brain stimulation (DBS) targeting the ventral intermediate (Vim) nucleus of the thalamus is a highly effective therapy for medication-refractory ET. However, stimulation-related side effects may include cerebellar abnormalities, such as postural instability. This retrospective cohort study evaluated the risk of post-Vim DBS postural instability (primary outcome measure) in patients with versus without head tremor (HT vs. nHT). The primary outcome measure, namely post-DBS postural instability, was assessed in both groups using a Wilcoxon rank sum t-test. The time to postural instability was determined using Cox proportional hazards regression analysis adjusted for age and sex. Out of 30 patients analyzed during the follow up period, there was similar postural instability detected in HT (9/14, 64%) and nHT patients (11/16, 69%) at 24 months post-Vim DBS (p=0.82), adjusted hazard ratio[aHR]=0.82, p=0.69). These data suggest that the presence or absence of HT does not have an impact on postural instability after bilateral Vim DBS in patients with ET.
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Estimulação Encefálica Profunda , Tremor Essencial , Humanos , Tremor/etiologia , Tremor Essencial/terapia , Estudos Retrospectivos , Estimulação Encefálica Profunda/efeitos adversos , Tálamo , Núcleos Ventrais do Tálamo , Resultado do TratamentoRESUMO
BACKGROUND: Breast attenuation artifacts occurring with upright cadmium-zinc-telluride (CZT) cardiac imaging systems have not been well characterized. METHODS: 216 consecutive patients with Single Photon Emission Computerized Tomography myocardial perfusion imaging and no angiographically significant obstructive coronary artery disease were identified. All upright and supine SPECT images as well as coronary angiograms were reviewed and analyzed in blinded fashion. RESULTS: In women imaged upright, more visual false positive defects were noted in the inferior wall compared to the anterior wall (26 vs. 10 at rest, p = 0.006, and 33 vs. 13 at stress, p < 0.001). Visual inferior wall defects were more common in the upright than supine position at stress (33 vs. 23, p = 0.018) and rest (26 vs. 14, p = 0.011), and most apparent in non-obese women (13 vs. 8, at stress, p = 0.059 and 11 vs. 5, at rest, p = 0.014). CONCLUSIONS: With upright CZT myocardial perfusion imaging, women often have visible inferior wall attenuation artifact defects, likely from pendant breast tissue. These inferior wall attenuation artifacts may be seen in non-obese female patients.
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Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Artefatos , Cádmio , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Imagem de Perfusão do Miocárdio/métodos , Telúrio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , ZincoRESUMO
BACKGROUND: The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population-based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. METHODS: Data from the Texas Cancer Registry (1995-2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non-Hispanic) and geographic location (border vs non-border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel-Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. RESULTS: Hispanic patients were diagnosed at a younger age than non-Hispanic patients and presented with increased comorbidities. Whereas non-Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79-2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) compared with Hispanics living elsewhere in Texas. CONCLUSIONS: Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.
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Doenças Hematológicas/etnologia , Hispânico ou Latino , Área Carente de Assistência Médica , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Acessibilidade aos Serviços de Saúde , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/mortalidade , Humanos , Incidência , Cobertura do Seguro , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/etnologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etnologia , Leucemia Mieloide Aguda/mortalidade , Leucemia Promielocítica Aguda/epidemiologia , Leucemia Promielocítica Aguda/etnologia , Leucemia Promielocítica Aguda/mortalidade , Masculino , México/etnologia , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/etnologia , Síndromes Mielodisplásicas/mortalidade , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/etnologia , Transtornos Mieloproliferativos/mortalidade , Pobreza , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Sistema de Registros , Análise de Regressão , População Rural , Fatores Sexuais , Texas , Adulto JovemRESUMO
The objective of this study is to examine the role of the cerebellum in the tremor-dominant subtype of cervical dystonia (CD). CD patients with head tremor at onset (Tr-CD) were age- and sex-matched to CD patients without head tremor at onset (nTr-CD). All patients were evaluated for cerebellar disability using the Scale for the Assessment and Rating of Ataxia (SARA), gait variability using ProtoKinetics Zeno Walkway, and cerebellar volume analysis extracted from brain magnetic resonance imaging (MRI) using a semiquantitative scale. Compared to nTr-CD (n = 10, median age, 70.5 years), Tr-CD patients (n = 10, 71.5 years) exhibited higher median SARA scores (9 vs 7.5, p = 0.03) and greater median gait variability index (131 vs 124, p = 0.03). SARA scores inversely correlated with cerebellar volume in all patients (- 0.4, p = 0.04). Tr-CD patients exhibited greater superior vermian atrophy than nTr-CD patients (p = 0.01). Head tremor at onset heralds a CD subtype with prominent axial cerebellar disability and atrophy of the superior vermis of the cerebellum.
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Cerebelo/patologia , Torcicolo/complicações , Torcicolo/patologia , Tremor/etiologia , Tremor/patologia , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , SíndromeRESUMO
BACKGROUND: Limited data address the roles of gender, perfusion defect reversibility, and imaging position in interpretation of images acquired on an upright/supine cadmium-zinc-telluride (CZT) cardiac imaging system. METHODS AND RESULTS: From a consecutive cohort of patients imaged on an upright/supine CZT camera, 260 patients with coronary angiograms were studied. Multivariable models identified gender as a significant effect modifier for imaging variables of CAD. For males, a supine summed stress score (SSS) ≥ 3 provided high accuracy (sensitivity 70.7%, specificity 72.2%), and highest contribution to multivariable models. In females, supine SSS ≥ 2 provided the best cut-off for defect size and severity (sensitivity 90%, specificity 35.9%), but specificity was improved substantially to 53.3% with decrease in sensitivity to 80% by also requiring quantitative identification of perfusion defect reversibility in the supine position. Eight variables, accurate for predicting coronary disease, were more accurate with supine than upright imaging. CONCLUSIONS: Perfusion defect reversibility improved specificity in female patients for detection of coronary disease compared to perfusion defect size and extent alone. Supine images provided superior accuracy for detection of coronary disease compared to upright images.
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Cádmio , Doença da Artéria Coronariana/diagnóstico por imagem , Câmaras gama , Imagem de Perfusão do Miocárdio , Posicionamento do Paciente , Telúrio , Tomografia Computadorizada de Emissão de Fóton Único , Zinco , Idoso , Estudos de Coortes , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores Sexuais , Postura Sentada , Decúbito DorsalRESUMO
BACKGROUND: In 2017, the CDC listed heart disease as the leading cause of death, with pneumonia and influenza being the eighth cause of death. Several studies have suggested the protective effects of influenza vaccination on myocardial infarction (MI). Available evidence supports the use of influenza vaccination in decreasing cardiovascular events, and the Joint Commission considers influenza vaccination a metric of quality care for hospitalized patients. Our specific aim was to evaluate the combined use of pneumococcal pneumonia vaccine (PPV) and influenza vaccine on cardiovascular outcomes and mortality. METHODS: A retrospective observational study was conducted using the 2012-2015 US National Inpatient Sample (NIS) database, to compare cardiovascular events in adult patients who did and did not receive vaccination during their hospitalization. ICD-9 codes were used to extract data for specific variables. The outcomes included MI, transient ischemic attacks, cardiac arrest, stroke, heart failure, and death. Adjusted relative risks (RR) were calculated using survey-weighted generalized linear models after adjusting for gender, race, socioeconomic status, diabetes, hypertension, hyperlipidemia, smoking status, prior coronary artery disease, and cerebrovascular disease. The effect of vaccination on in-hospital mortality was assessed in each subgroup of cardiovascular events using RR regressions. RESULTS: This study included 22,634,643 hospitalizations, of which 21,929,592 did not receive immunization. Vaccination solely against influenza was associated with lower MI (RR = 0.84, 95% CI: 0.82-0.87, p < 0.001), TIA (RR = 0.93, 95% CI: 0.9-0.96, p < 0.001), cardiac arrest (RR = 0.36, 95% CI: 0.33-0.39, p < 0.001), stroke (RR = 0.94, 95% CI: 0.91-0.97, p < 0.001), and mortality (RR = 0.38, 95% CI: 0.36-0.4, p < 0.001). Vaccination with PPV alone was associated with MI (RR = 1.13, 95% CI: 1.11-1.16, p < 0.001), TIA (RR = 1.28, 95% CI: 1.26-1.31, p < 0.001), stroke (RR = 1.21, 95% CI: 1.18-1.24, p < 0.001), and lower mortality (RR = 0.47, 95% CI: 0.45-0.49, p < 0.001). Combined PPV and influenza vaccine was associated with lower mortality (2.21% vs. 1.03%, p < 0.001) and lower cardiac arrest (0.61% vs. 0.51%, p < 0.001). In the adjusted analysis, the RR was 0.46 (95% CI: 0.43, 0.49) for mortality in the combined vaccinated cohort. The combined vaccination group also had a significantly reduced risk of mortality among those admitted with MI (RR = 0.46), transient ischemic attacks (RR = 0.58), and stroke (RR = 0.42) compared to the nonvaccinated group. CONCLUSIONS: Our study shows a significantly reduced risk of mortality with influenza vaccine and PPV and with combined pneumococcal and influenza vaccination. These data suggest that in-hospital administration of pneumonia and influenza vaccines appears safe and supports the use of combined vaccination during hospitalization due to their cardiovascular benefits.
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Vacinas contra Influenza , Influenza Humana , Infarto do Miocárdio , Pneumonia Pneumocócica , Adulto , Humanos , Influenza Humana/prevenção & controle , Infarto do Miocárdio/epidemiologia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , VacinaçãoRESUMO
BACKGROUND: Coronavirus disease (COVID-19) has been associated with adverse pregnancy outcomes. Due to the lack of effective treatments for COVID-19, it becomes imperative to assess the geographical differences and trends in the current clinical care and outcomes of COVID-19 in pregnant women. METHODS: A PubMed search was performed to screen articles reporting therapeutics and outcomes of confirmed COVID-19 in pregnant women prior to August 27, 2020. We performed searches, quality assessments of eligible studies, extracted and reported data according to PRISMA guidelines. Meta-analyses and cumulative meta-analyses of proportions were performed for estimating each outcome and their pattern over time respectively. RESULTS: One thousand two hundred thirty nine pregnant women with COVID-19 from 66 studies were analyzed. In case series analysis reflecting average-risk patients, the proportion of oxygen support, antibiotics, antivirals, and plasma therapy administration except for hydroxychloroquine was substantially higher in Asian studies (55, 78, 80, 6, and 0%) compared to the US (7, 1, 12, 0, and 7%) or European (33, 12, 14, 1, and 26%) studies, respectively. The highest preterm birth and the average length of hospital stay (35%, 11.9 days) were estimated in Asian studies compared to the US studies (13%, 9.4 days) and European studies (29%, 7.3 days), respectively. Even in case reports reflecting severe cases, the use of antivirals and antibiotics was higher in Asian studies compared to the US, Latin American, and European studies. A significant decline in the use of most therapeutics along with adverse outcomes of COVID-19 in pregnant women was observed. CONCLUSIONS: Geographical differences in therapeutic practice of COVID-19 were observed with differential rates of maternal and clinical outcomes. Minimizing the use of some therapeutics particularly antibiotics, antivirals, oxygen therapy, immunosuppressants, and hydroxychloroquine by risk stratification and careful consideration may further improve maternal and clinical outcomes.
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Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/terapia , Hidroxicloroquina/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Respiração Artificial , SARS-CoV-2 , Adulto , Ásia/epidemiologia , COVID-19/epidemiologia , Cesárea , Europa (Continente)/epidemiologia , Feminino , Humanos , Imunização Passiva , Recém-Nascido , América Latina/epidemiologia , Tempo de Internação , Gravidez , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Nascimento Prematuro , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem , Soroterapia para COVID-19RESUMO
OBJECTIVE: The purpose of this study was to determine whether patients with functional movement disorders (FMDs) differ in their internal versus external locus of control (LOC) and whether LOC in these patients affected disease severity, quality of life, and functional impairment compared with control subjects with degenerative (Parkinson's disease) and nondegenerative (focal dystonia) neurological conditions. METHODS: A total of 156 patients with FMD (N=45), Parkinson's disease (N=64), and focal dystonia (N=47) were recruited between June 2015 and August 2017. The authors administered the general Levenson Multidimensional LOC (LOC-G) and health-specific Multidimensional Health LOC (LOC-H) scales. An internal LOC was represented similarly in both scales: the external LOC included "chance" and "powerful others" in the LOC-G measure and chance, "other people," and "doctors" in the LOC-H measure. Quality of life, functional impairment, and FMD severity were assessed. One-way analysis of variance and adjusted logistic regressions were used, as well as ordinary least-squares between and within groups, respectively. RESULTS: Patients with FMD had lower external chance LOC-G scores compared with patients in the Parkinson's disease group (odds ratio=0.90, p=0.03) and higher internal (odds ratio=1.22, p=0.01) and lower external (odds ratio=0.77, p=0.02) doctors LOC-H scores compared with patients in the focal dystonia group. External powerful others LOC-G score was associated with functional impairment (regression coefficient=-0.04, p=0.02). There were no effects of LOC on quality of life or disease severity. CONCLUSIONS: Patients with FMD exhibited high "within our control" internal general and health-specific frame of reference. LOC had no influence on quality of life or disease severity in this patient population.
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Transtorno Conversivo/psicologia , Distúrbios Distônicos/psicologia , Controle Interno-Externo , Transtornos dos Movimentos/psicologia , Doença de Parkinson/psicologia , Transtornos Psicofisiológicos/psicologia , Adulto , Idoso , Transtorno Conversivo/fisiopatologia , Estudos Transversais , Distúrbios Distônicos/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/fisiopatologia , Doença de Parkinson/fisiopatologia , Transtornos Psicofisiológicos/fisiopatologia , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: The aim of this study was to compare a standard versus segmental withdrawal during screening colonoscopy and its effect on the adenoma detection rate (ADR). METHODS: We performed a single-center clinical trial of average-risk patients 50 years of age and older undergoing screening colonoscopy. Patients were randomized into four groups: a standard withdrawal of at least 6 or 8 minutes and a segmental withdrawal, in which ≥3 or ≥4 minutes were dedicated to the right side of the colon, with a minimum withdrawal time of at least 6 or 8 minutes, respectively. RESULTS: There were 311 patients in the study. There was no difference in ADR between the standard and segmental groups (relative ratio [RR] 0.91, P = 0.50), even after stratifying for right-sided adenomas. During standard withdrawal, an increased continuous withdrawal time was associated with a higher ADR (RR 1.08, P <0.001) and total adenomas per patient (RR 1.12, P < 0.001). A binary analysis of ≥8 minutes or <8 minutes withdrawal was associated with an increased adenomas per colonoscopy (RR 1.86, P = 0.04). These differences were not observed in the segmental group. CONCLUSIONS: Overall, there was no benefit from a segmental withdrawal protocol on ADR, but this may have been the result of the inherent limitations in the study design. After sensitivity analysis, a segmental withdrawal protocol led to an improvement in the detection of adenomas per colonoscopy and polyps per colonoscopy. A larger sample size is needed to confirm these findings.
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Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Colonoscopia/métodos , Adenoma/patologia , Colo/patologia , Neoplasias do Colo/patologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BackgroundThe higher level of background parenchymal enhancement (BPE) at breast MRI has the potential for early detection and prediction of the risk of breast cancer. However, conflicting findings have been reported about the association between the level of BPE at breast MRI and the presence of breast cancer.PurposeTo evaluate the association between qualitative and quantitative BPE at dynamic contrast material-enhanced MRI and breast cancer among populations with average risk and high risk separately.Materials and MethodsA retrospective meta-analysis of observational studies comparing either qualitative or quantitative assessments of BPE in women with and women without breast cancer was performed for studies published through July 2018. Pooled odds ratios (ORs) or standardized mean differences and 95% confidence intervals (CIs) were estimated by using DerSimonian-Laird random-effects models. The heterogeneity across the studies was measured by using the statistic Iâ2. Sensitivity analyses were conducted to test this association according to different study characteristics. P values less than or equal to 5% were considered to indicate statistically significant results.ResultsEighteen studies comprising 1910 women with breast cancer and 2541 control participants were included in the analysis. Among women with high risk, at least moderate BPE (OR, 1.6; 95% CI: 1.0, 2.6; P = .04) or at least mild BPE (OR, 2.1; 95% CI: 1.5, 3.0; P < .001) was associated with higher odds of breast cancer. Furthermore, women with breast cancer showed a higher average BPE percentage compared with control participants with high risk (standardized mean difference, 0.5; 95% CI: 0.2, 0.9; P = .001). No association was observed between at least mild BPE level (P = .15) or at least moderate BPE level (P = .38) and the presence of breast cancer among the population with average risk.ConclusionA higher level of background parenchymal enhancement measured at breast MRI is associated with the presence of breast cancer in women with high risk, but not in women with average risk.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Mann and Pinker in this issue.
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Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Mama/diagnóstico por imagem , Feminino , Humanos , Estudos Observacionais como Assunto , Reprodutibilidade dos TestesRESUMO
Idiopathic normal pressure hydrocephalus (NPH) remains both oversuspected on clinical grounds and underconfirmed when based on immediate and sustained response to cerebrospinal fluid diversion. Poor long-term postshunt benefits and findings of neurodegenerative pathology in most patients with adequate follow-up suggest that hydrocephalic disorders appearing in late adulthood may often result from initially unapparent parenchymal abnormalities. We critically review the NPH literature, highlighting the near universal lack of blinding and controls, absence of specific clinical, imaging, or pathological features, and ongoing dependence for diagnostic confirmation on variable cutoffs of gait response to bedside fluid-drainage testing. We also summarize our long-term institutional experience, in which postshunt benefits in patients with initial diagnosis of idiopathic NPH persist in only 32% of patients at 36 months, with known revised diagnosis in over 25% (Alzheimer's disease, dementia with Lewy bodies, and progressive supranuclear palsy). We postulate that previously reported NPH cases with "dual" pathology (ie, developing a "second" disorder) more likely represent ventriculomegalic presentations of selected neurodegenerative disorders in which benefits from shunting may be short-lived, with a consequently unfavorable risk-benefit ratio. Ann Neurol 2017;82:503-513.
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Hidrocefalia de Pressão Normal/complicações , Hidrocefalia de Pressão Normal/cirurgia , Doenças Neurodegenerativas/etiologia , Progressão da Doença , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/etiologia , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Doenças Neurodegenerativas/diagnóstico por imagem , PubMed/estatística & dados numéricosRESUMO
OBJECTIVE: To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. METHODS: A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. RESULTS: Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). CONCLUSIONS: A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients.
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Doenças do Sistema Nervoso/epidemiologia , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Idoso , Antiparkinsonianos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Doença de Parkinson/tratamento farmacológico , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Exercise is the AHA/ACC guideline-recommended stress modality for myocardial perfusion imaging, but many patients are unable to exercise to target heart rate on a conventional treadmill. We examined the feasibility and safety of stress imaging using an anti-gravity treadmill in patients with perceived poor exercise capacity. METHODS AND RESULTS: 49 patients were recruited for stress testing by anti-gravity treadmill (n = 29) or to a regadenoson control group (n = 20). Seventeen anti-gravity test patients (59%) reached target heart rate obviating the need for a pharmacologic stress agent. Adverse effects of the anti-gravity treadmill were limited to minor muscle aches in 5 subjects. Stress myocardial perfusion image quality judged by 3 blinded readers on a 5-point scale was comparable for the anti-gravity treadmill (4.30 ± SD 0.87) vs pharmacologic stress (4.28 ± SD 0.66). CONCLUSION: Stress testing using an anti-gravity treadmill is feasible and may help some patients safely achieve target heart rate.
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Teste de Esforço/métodos , Imagem de Perfusão do Miocárdio/métodos , Compostos Organofosforados , Compostos de Organotecnécio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Estudos de Viabilidade , Feminino , Gravitação , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
BACKGROUND: Diagnostic performance of stress-only imaging using a Cadmium-Zinc-Telluride (CZT) camera has not been directly compared in the same patients to stress-only attenuation-corrected conventional Anger camera images. METHODS: 112 subjects with correlative coronary angiographic data and 40 subjects with <5% pre-test likelihood of coronary disease completed attenuation-corrected stress-only images on a conventional Anger camera and uncorrected upright and supine stress images on a CZT camera. Two readers provided independent, blinded interpretations of stress-only images. RESULTS: Upright and supine stress-only CZT images and attenuation-corrected Anger camera images provided similar positive (reader 1/reader 2, 50.0%/44.1% vs 46.4%/51.9%) and negative (66.7%/64.0% vs 67.9%/67.7%) predictive values (all P = NS) for obstructive coronary artery disease; however, the sensitivity was higher (81.3% vs 58.3%, P = .05), specificity lower (29.7% vs 50.0%, P = .005), and normalcy rate lower (87.5% vs 100%, P = .025) with attenuation-corrected Anger camera images for the first reader with no significant differences between cameras for the second reader. CONCLUSIONS: Stress-only upright and supine CZT imaging was non-inferior statistically to attenuation-corrected stress-only Anger camera imaging. Nevertheless, stress-only CZT imaging may be associated with reduced diagnostic sensitivity for some readers compared to attenuation-corrected Anger camera images, which may be less acceptable clinically compared to stress plus rest images.
Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Teste de Esforço , Câmaras gama , Processamento de Imagem Assistida por Computador/métodos , Imagem de Perfusão do Miocárdio/instrumentação , Idoso , Cádmio , Doença da Artéria Coronariana/fisiopatologia , Diagnóstico por Computador/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Telúrio , Tomografia Computadorizada de Emissão de Fóton Único , ZincoRESUMO
OBJECTIVES: Helicobacter pylori is prevalent worldwide, especially in Latin America. Triple and quadruple antibiotic therapies have been relatively effective; however, resistance has emerged in recent years. The treatment success rate of these regimens on the border of the United States and Mexico is unknown. Our study attempted to determine eradication rates of two major regimens based on urea breath test (UBT) results in patients previously diagnosed as having H. pylori in a single center in El Paso, Texas, a city on the geographic border with Mexico. METHODS: This was a retrospective cohort study of adult patients with H. pylori who underwent UBT after being treated with triple therapy (amoxicillin/clarithromycin/proton pump inhibitor for 14 days), quadruple therapy (tetracycline/metronidazole/bismuth/proton pump inhibitor, usually for 10 days), or both for H. pylori from 2010 to 2015 in a county hospital. Patients were excluded if they did not complete therapy or if their treatment regimen was unknown. The Student t test and the χ2 test were used to analyze the data. The cumulative incidence and 95% confidence interval (CI) for treatment success were estimated. RESULTS: A total of 104 patients completed the treatment for H. pylori and had UBT. Mean age was 53 years, 76% were women, 85% were Hispanic, and mean body mass index was 30.5 kg/m2. Of the 104 patients diagnosed as having H. pylori, 88 received triple therapy (84.6%) and 16 received quadruple therapy: 12 (11.5%) standard quadruple therapy, 4 (3.9%) triple therapy plus metronidazole. There were no differences between groups regarding age, sex, body mass index, or ethnicity. Overall, 90 (86.5%, 95% CI 78-92) patients had negative UBT after initial treatment. Based on posttreatment UBT, the triple therapy group had a similar eradication rate compared with the quadruple therapy group (78/88, 88.6% vs 12/16, 75.0%, P = 0.22). Of the 14 patients with positive posttreatment UBT, 12 (85.7%) received retreatment (2 were lost to follow-up), 11 (91.7%) received quadruple therapy, and 1 (8.3%) received triple therapy. Eradication was successful in 9 of 12 (75%, 95% CI 43-95) patients at retreatment. As such, of the initial 104 patients, 99/104 (95.2%) achieved H. pylori eradication posttreatment (either initial or retreatment). CONCLUSIONS: In a predominantly Hispanic population on the US-Mexico border, H. pylori eradication rates based on UBT results were relatively high and were similar for triple therapy and quadruple therapy. Quadruple therapy was effective for those who failed the initial H. pylori treatment. This may have implications for cost-effective therapy in our region.
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Antiácidos/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Inibidores da Bomba de Prótons/uso terapêutico , Ureia/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Testes Respiratórios , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/metabolismo , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Texas , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Low level of vitamin D (VD) has been linked with a higher risk of cancers. The aim of this study was to assess the prevalence of low VD in patients with breast cancer in a predominantly Mexican Hispanic/Latino patient population, a fast growing and relatively understudied population. MATERIALS/METHODS: We sought to evaluate the serum VD levels in breast cancer patients diagnosed at the Texas Tech University Breast Cancer Center in El Paso, TX, between May 2013 and May2014 via a retrospective chart review of the Electronic Medical Records. RESULTS: We identified a total of 83 consecutive breast cancer patients with available VD levels. Mean age 57 yr, 94% were Hispanics. VD was insufficient (<30 ng/ml) in 86% of patients (95% CI: 0.76-0.92) and it was deficient (<20 ng/ml) in 39% (95% CI: 0.28-0.50). CONCLUSION: VD deficiency is widely prevalent in Hispanic/Latino patients with breast cancer. This is quite alarming in view of possible increased risk of cancer with low VD and potentially worse cancer outcomes. This calls for increased efforts to screen for, diagnose, and treat VD deficiency in this patient population. Further pharmacogenomics studies are warranted to explore the underlying etiology of VD deficiency in this paradoxically sunny region.
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Neoplasias da Mama/sangue , Americanos Mexicanos , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etnologia , Adulto , Idoso , Neoplasias da Mama/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Texas/epidemiologia , Deficiência de Vitamina D/complicaçõesRESUMO
BACKGROUND: Phosphatidylethanol (PEth) is a metabolite of ethanol (EtOH), and its concentration in whole blood samples is a direct biomarker of alcohol consumption. Because PEth is also present in the brain and incorporated in lipid membranes, it can be used to classify deceased individuals on alcohol consumption status at the time of death. The purpose of this study was to detect PEth homologs in postmortem brains of individuals known to have had alcohol use disorder (AUD) and to determine the relationship between serum alcohol at the time of death and PEth in the cerebellum (CE) and orbital frontal cortex (OFC). METHODS: Postmortem brain was collected and stored according to standard protocol. Psychiatric symptoms experienced prior to death were obtained by next of kin psychological autopsy to categorize subjects. Thirty male subjects were chosen for analyses: 10 with AUD with positive serum EtOH levels present at time of autopsy (AUD-W), 10 with AUD without positive serum EtOH levels (AUD-WO), and 10 controls. PEth 16:0/18:1 and 16:0/18:2 were quantified in 50 mg of CE and OFC of human postmortem brain using HPLC and mass spectrometric detection (triple quadrupole). RESULTS: Results of this study were as follows: (i) PEth 16:0/18:1 and 16:0/18:2 were detected in the CE and OFC of all subjects diagnosed with AUD, (ii) PEth 16:0/18:1 levels were about 10-fold higher than PEth 16:0/18:2 in all subjects and both areas of brain, (iii) AUD-W subjects had higher PEth homolog levels in CE and OFC than controls and AUD-WO subjects, (iv) PEth 16:0/18:1, but not PEth 16:0/18:2, levels in CE and OFC of AUD-W subjects correlated significantly with serum EtOH levels at the time of death. CONCLUSIONS: Quantification of combined PEth homolog levels in postmortem human brain is a good candidate as a diagnostic factor to classify drinking status, especially for those with AUD at the time of death. For alcohol research studies with postmortem brain, verification of drinking status is essential.
Assuntos
Transtornos Relacionados ao Uso de Álcool/metabolismo , Cerebelo/metabolismo , Morte , Etanol/sangue , Lobo Frontal/metabolismo , Glicerofosfolipídeos/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Homologia de Sequência de Aminoácidos , Adulto JovemRESUMO
OBJECTIVE: We sought to examine the clinical and electrographic differences between patients with combined epileptic (ES) and psychogenic nonepileptic seizures (PNES) and age- and gender-matched patients with ES-only and PNES-only. METHODS: Data from 138 patients (105 women [77%]), including 46 with PNES/ES (39±12years), 46 with PNES-only (39±11years), and 46 with ES-only (39±11years), were compared using logistic regression analysis after adjusting for clustering effect. RESULTS: In the cohort with PNES/ES, ES antedated PNES in 28 patients (70%) and occurred simultaneously in 11 (27.5%), while PNES were the initial presentation in only 1 case (2.5%); disease duration was undetermined in 6. Compared with those with ES-only, patients with PNES/ES had higher depression and anxiety scores, shorter-duration electrographic seizures, less ES absence/staring semiology (all p≤0.01), and more ES arising in the right hemisphere, both in isolation and in combination with contralateral brain regions (61% vs. 41%; p=0.024, adjusted for anxiety and depression) and tended to have less ES arising in the left temporal lobe (13% vs. 28%; p=0.054). Compared with those with PNES-only, patients with PNES/ES tended to show fewer right-hemibody PNES events (7% vs. 23%; p=0.054) and more myoclonic semiology (10% vs. 2%; p=0.073). CONCLUSIONS: Right-hemispheric electrographic seizures may be more common among patients with ES who develop comorbid PNES, in agreement with prior neurobiological studies on functional neurological disorders.