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Discrepancies between HIV-1 RNA results assayed by different FDA-approved platforms have been reported. Plasma samples collected from 332 randomly selected clinical trial participants during the second year of antiretroviral treatment were assayed with three FDA-approved platforms: UltraSensitive Roche Amplicor Monitor, v1.5 (Monitor), the Abbott RealTime HIV-1 test on the m2000 system (Abbott), and the Roche TaqMan HIV-1 test, v2.0 (TaqMan). Samples from 61 additional participants with confirmed HIV-1 RNA levels of >50 copies/ml during trial follow-up were also included. Endpoints were HIV-1 RNA quantification of ≤50 copies/ml versus >50 copies/ml at an individual-sample level (primary) and determination of confirmed virologic failure (VF) from longitudinal samples. A total of 389 participants had results obtained from all assays on at least one sample (median = 6). Proportions of results of >50 copies/ml were 19% (Monitor), 22% (TaqMan), and 25% (Abbott). Despite indication of strong agreement (Cohen's kappa, 0.76 to 0.82), Abbott was more likely to detect HIV-1 RNA levels of >50 copies/ml than Monitor (matched-pair odds ratio [mOR] = 4.2; modified Obuchowski P < 0.001) and TaqMan (mOR = 2.1; P < 0.001); TaqMan was more likely than Monitor (mOR = 2.6; P < 0.001). Despite strong agreement in classifying VF across assay comparisons (kappa, 0.75 to 0.92), at a 50-copies/ml threshold, differences in the probability of VF classification (in the same direction as primary) were apparent (all McNemar's P < 0.007). At a 200-copies/ml VF threshold, no differences between assays were apparent (all P > 0.13). Despite strong agreement among assays, significant differences were observed with respect to detecting HIV-1 RNA levels of >50 copies/ml and identifying VF at the 50-copies/ml threshold. This has important implications for the definition of VF in clinical trials and clinical practice.
Assuntos
Infecções por HIV/virologia , HIV-1/isolamento & purificação , Plasma/virologia , RNA Viral/sangue , Carga Viral/métodos , Adolescente , Adulto , Idoso , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Falha de Tratamento , Adulto JovemRESUMO
Background: During the COVID-19 pandemic, use of telemedicine (TM) increased dramatically, but it is unclear how use varies by characteristics of people with Alzheimer's disease (AD), multiple sclerosis (MS), or Parkinson's disease (PD). Methods: This cross-sectional study used US PharMetrics Plus commercial claims data from January 1, 2019, to December 31, 2021. TM use (≥1 Current Procedural Terminology code) was assessed in each study year (2019, 2020, and 2021) among people with ≥1 inpatient or ≥2 outpatient diagnosis codes ≥30 days apart for AD, MS, or PD. Any TM use and disease-related visits (AD, MS, or PD diagnosis code within TM claim) were summarized, and characteristics of TM users versus nonusers during the pandemic (2020 and 2021) were described. Results: Among people with AD, MS, or PD, 0.9% used TM in 2019 versus 58.0% in 2020 and 42.5% in 2021. Among TM users in 2020 and 2021, the majority had TM visits related to their neurological disorder (73.2% and 64.6%, respectively). During the pandemic, approximately 25% of total TM visits (n = 296,434) were provided by a neurologist. Mean (SD) age of TM users was similar to nonusers (60.5 [15.1] and 61.5 [15.3] years), but TM users were more likely to be female (62% vs 60%), enrolled in Medicare (33% vs 30%), and reside in western (64.2% vs 35.8%) or eastern (61.0% vs 39.0%) regions versus nonusers. Conclusions: Although results indicate expanded use of and access to TM among people with AD, MS, or PD, differences in patient and health care provider characteristics for TM use were notable.
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Mitochondrial respiratory chain disorders are clinically and genetically heterogeneous. There are several mitochondrial DNA (mtDNA) point mutations responsible for common mitochondrial diseases such as mitochondrial encephalopathy, lactic acidosis, stroke-like events, myoclonic epilepsy and ragged red fibers, neuropathy, ataxia, retinitis pigmentosa, and Leber's hereditary optic neuropathy. As a result of the clinical overlap, it is usually necessary to analyze more than one mutation for a patient suspected of a mitochondrial disorder. Molecular diagnosis is often performed using polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) analysis of the most likely point mutations. However, this method is time-consuming and often produces problems associated with incomplete restriction enzyme digestion. In addition, PCR/RFLP analysis may not be able to detect a low percentage of heteroplasmy. For a more effective method of diagnosing mtDNA disorders, we have developed a multiplex PCR/ allele-specific oligonucleotide (ASO) dot blot hybridization method to simultaneously analyze 11 point mutations. The PCR products from a DNA sample containing a homoplasmic wild-type or mutant mtDNA sequence will hybridize to either the wild-type or the mutant ASO probe. The PCR products of a heteroplasmic DNA sample will hybridize to both wild-type and mutant ASO probes. This PCR/ASO method allows the detection of low percentage mutant heteroplasmy.
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DNA Mitocondrial/genética , Biologia Molecular/métodos , Mutação Puntual , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Alelos , Autorradiografia , Primers do DNA/química , Humanos , Hibridização de Ácido Nucleico , Sondas de Oligonucleotídeos/metabolismo , Oxigênio/metabolismo , FosforilaçãoRESUMO
Chronic hepatitis B, C, and D virus infections contribute significantly to the morbidity and mortality of immunocompromised individuals. To contextualize discussion of these infections in immunocompromised patients, this paper provides an overview of aspects of infection in normal hosts. It then describes differences in disease, diagnostic testing, and therapeutic management observed in immunocompromised patients.
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Hepatite B Crônica/diagnóstico , Hepatite B Crônica/terapia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/terapia , Hepatite D Crônica/diagnóstico , Hepatite D Crônica/terapia , Hospedeiro Imunocomprometido , Hepatite B Crônica/patologia , Hepatite C Crônica/patologia , Hepatite D Crônica/patologia , HumanosRESUMO
BACKGROUND: The COBAS(®) AmpliPrep(®)/COBAS(®) TaqMan(®) HCV Test, v2.0 (CAP/CTM2) is used for HCV RNA viral load monitoring. OBJECTIVES: The performance of the CAP/CTM2 was compared to other widely used tests, including a manual version of the assay (the COBAS(®) TaqMan(®) HCV Test, v2.0 for use with the High Pure System, HPS/CTM2) predominantly used during phase III clinical trials for the new direct acting antiviral therapies. STUDY DESIGN: Low HCV RNA level comparisons were performed across tests (Abbott Realtime HCV Test, ART; COBAS(®) AmpliPrep(®)/COBAS(®) TaqMan(®) HCV Test, v1.0, CAP/CTM1; CAP/CTM2; and HPS/CTM2) using dilutions of the 2nd HCV WHO International Standard. Additionally, the clinical performance of the CAP/CTM2 was evaluated with 421 leftover HCV RNA-positive routine clinical samples. RESULTS: All quantifiable WHO dilutions were within ±0.3log10IU/mL of the expected results across tests and the analytical sensitivity resulted in a limit of detection of 12IU/mL (95% confidence interval, 10, 15). When clinical samples were tested the results for 87% (367 of 421) of all sample comparisons were within ±0.5log10IU/mL. When low viral load results (25-3500IU/mL) were compared, values obtained by the ART assay were significantly lower (p<0.0001) than those obtained with the CAP/CTM2. CONCLUSIONS: The new CAP/CTM2 showed good accuracy with comparable sensitivity to comparator assays. The new kit is well-suited for use in the routine diagnostic laboratory, especially for accurate monitoring of patients receiving triple therapy or interferone-free regimens.
Assuntos
Monitoramento de Medicamentos/métodos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , RNA Viral/isolamento & purificação , Carga Viral/métodos , Ensaios Clínicos como Assunto , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , RNA Viral/genética , Kit de Reagentes para Diagnóstico , Sensibilidade e EspecificidadeRESUMO
While more than two-thirds of football players are under the age of 14, little biomechanics research has been conducted to quantify head impact exposure for players in this age range. The objective of this study was to quantify head impact exposure and the influence of age for 9-13 year old football players. Kinematic data from over 4400 head impacts were collected from 25 youth football players on two teams for one season using in-helmet accelerometers. The 50th and 95th percentile magnitudes for linear and rotational head acceleration and the number of impacts sustained were determined for each player. Comparisons were made for each metric by team and by player age. Players on the 9-11 year old team sustained an average of 154 ± 126 impacts with a 95th percentile linear acceleration magnitude of 40 g. On the 10 to 13 year old team, players sustained an average of 193 ± 158 impacts with a 95th percentile linear acceleration magnitude of 47 g. Players on the older team sustained slightly more and higher magnitude impacts than those on the younger team. These differences in head impact exposure were not significant due to large variation between players within each team.
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Head impact exposure in youth football has not been well-documented, despite children under the age of 14 accounting for 70% of all football players in the United States. The objective of this study was to quantify the head impact exposure of youth football players, age 9-12, for all practices and games over the course of single season. A total of 50 players (age = 11.0 ± 1.1 years) on three teams were equipped with helmet mounted accelerometer arrays, which monitored each impact players sustained during practices and games. During the season, 11,978 impacts were recorded for this age group. Players averaged 240 ± 147 impacts for the season with linear and rotational 95th percentile magnitudes of 43 ± 7 g and 2034 ± 361 rad/s(2). Overall, practice and game sessions involved similar impact frequencies and magnitudes. One of the three teams however, had substantially fewer impacts per practice and lower 95th percentile magnitudes in practices due to a concerted effort to limit contact in practices. The same team also participated in fewer practices, further reducing the number of impacts each player experienced in practice. Head impact exposures in games showed no statistical difference. While the acceleration magnitudes among 9-12 year old players tended to be lower than those reported for older players, some recorded high magnitude impacts were similar to those seen at the high school and college level. Head impact exposure in youth football may be appreciably reduced by limiting contact in practices. Further research is required to assess whether such a reduction in head impact exposure will result in a reduction in concussion incidence.
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Traumatismos Craniocerebrais/prevenção & controle , Futebol Americano/lesões , Aceleração , Fenômenos Biomecânicos , Criança , Traumatismos Craniocerebrais/fisiopatologia , Movimentos da Cabeça/fisiologia , Dispositivos de Proteção da Cabeça , Humanos , Rotação , TelemetriaRESUMO
Significant advancements in molecular diagnostics have been made since the inception and application of PCR-based technologies in clinical diagnostic laboratories and the management of HIV-1 infected patients. More recently, real-time PCR has improved the overall performance of assays used for detecting and quantifying HIV-1 RNA viral load in patients undergoing antiretroviral treatment. The effects of these changes and the interpretations of the HIV-1 viral load results are discussed in this review in the context of the different assays used, the viral dynamics of the HIV-1 virus, and the recent changes to HIV-1 treatment guidelines.
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Infecções por HIV/diagnóstico , RNA Viral/análise , Carga Viral/imunologia , Guias como Assunto/normas , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Reação em Cadeia da Polimerase em Tempo Real/normas , Sensibilidade e Especificidade , Carga Viral/métodosRESUMO
We investigated cystic fibrosis transmembrane conductance regulator (CFTR) activation by clinically used phosphodiesterase inhibitors (PDEis) in Calu-3 cell monolayers alone and in combination with A2B adenosine receptor stimulation. This receptor pathway has previously been shown to activate wild-type and mutant CFTR molecules. Several PDEis, including milrinone, cilostazol (Pletal), papaverine, rolipram, and sildenafil (Viagra), produced a short circuit current (Isc) that was glibenclamide-sensitive, achieving 20-85% of forskolin-stimulated Isc. Papaverine, cilostazol, and rolipram also augmented both the magnitude and the duration of Isc following low dose stimulation of adenosine receptors with Ado (0.1-1.0 microM, P < 0.01). Subsequent studies demonstrated that very low concentrations of cilostazol or papaverine (approximately 1/2 peak serum concentrations) were sufficient to activate Isc, and both agents markedly augmented Ado-stimulated Isc (1 microM, P < 0.01). Our results provide evidence that select PDEis, at concentrations achieved as part of systemic therapies, can activate CFTR-dependent Isc in Calu-3 cell monolayers. These studies also indicate that PDEis have the capacity to augment an endogenous CFTR-activating pathway in an "in vivo"-like model system, and supports future investigations of these agents relevant to cystic fibrosis.