Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress

Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS. We included a consecutive sample of 14 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations and 56 healthy control subjects of equal sex and age distribution. Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of –20 mmHg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04–0.15 Hz) and the high–frequency (HF) band (0.15–0.50 Hz), using an autoregressive algorithm. Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP, compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control. CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents

Manovacuometria realizada por meio de traqueias de diferentes comprimentos

Manovacuometry is a simple, fast, and non-invasive test, with maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) obtained to assist respiratory muscle assessment. Currently, there is a wide variety of models and brands of manovacuometers with different trachea diameters and lengths. However, the interference of these models in the measurements obtained by these equipments needs to be investigated. Thus, this study mainly aimed to verify the influence of tracheal length on maximal respiratory pressures (MRP), obtained by an analog manovacuometer, in healthy individuals. Our secondary objective was to verify the correlation between measurements. Fifty individuals, aged 18 to 30, of both sexes, were evaluated by spirometry and manovacuometry. MIP and MEP were performed using tracheas with same internal diameter (0.5 cm) and 30 cm, 60 cm, and 90 cm length. Significantly lower MIP values were observed when comparing a 90 cm trachea to 30 and 60 cm tracheas (Friedman’s ANOVA test and Wilcoxon test with Bonferroni adjustment). Tracheas with 30, 60, and 90 cm length and same diameter did not affect MIP and MEP values, except the 90 cm trachea for MIP values, which may interfere in the physical therapy clinical practice. Further studies are required to analyze the need for standardizing the trachea length used in manovacuometers.La manovacuometría es una prueba sencilla, rápida y no invasiva por la cual se obtienen la presión inspiratoria máxima (PImax) y la presión espiratoria máxima (PEmax), con el objetivo de ayudar en el examen muscular respiratorio. Hoy día se encuentran una gran variedad de modelos y marcas de manovacuometros, con diferentes diámetros y longitudes de las tráqueas, pero hacen falta estudios sobre la interferencia de estos modelos en las mediciones por este instrumento. En este texto se propone examinar en sujetos sanos, en primer lugar, la influencia en la longitud de las tráqueas en las presiones respiratorias máximas, obtenidas por manovacuometros analógicos, y en segundo lugar comprobar la existencia de correlación entre las mediciones. Se evaluaron a cincuenta sujetos entre 18 y 30 años de edad, tanto varones como mujeres, empleando la espirometría y la manovacuometría. Se midió la PImax y la PEmax empleando tráqueas de mismo diámetro interno (0,5 cm) y con longitudes de 30, 60 e 90 cm. Se observaron valores significativamente menores de PImax con la tráquea de longitud de 90 cm en comparación con las PImax con las tráqueas de 30 y 60 cm (prueba de Friedman’s ANOVA, la de Wilcoxon con ajustes de Bonferroni). Las tráqueas de 30, 60 y 90 cm de longitud y mismo diámetro no influyeron en los valores de la PEmax y de la PImax, con excepción de la tráquea de 90 cm en los valores de la PImax, lo que puede interferir la práctica clínica fisioterapéutica. Se necesitan más estudios para evaluar la necesidad de estándares de la longitud de tráqueas empleadas en manovacuometros.A manovacuometria é um teste simples, rápido e não invasivo por meio do qual a pressão inspiratória máxima (PImáx) e a pressão expiratória máxima (PEmáx) são obtidas, a fim de auxiliar na avaliação muscular respiratória. Atualmente, há grande variedade de modelos e marcas de manovacuômetros, com diferentes diâmetros e comprimentos de traqueias, no entanto, a interferência desses modelos nas medidas obtidas por esses equipamentos necessita de investigação. Desta forma, o objetivo primário deste estudo foi verificar a influência do comprimento de traqueias nas pressões respiratórias máximas, obtidas por meio de manovacuômetro analógico, em indivíduos saudáveis e, secundariamente, se há correlação entre as medidas. Foram avaliados 50 indivíduos, de 18 a 30 anos, de ambos os sexos, por meio da espirometria e manovacuometria. As PImáx e PEmáx foram realizadas com uso de traqueias de mesmo diâmetro interno (0,5 cm) e comprimentos de 30, 60 e 90 cm. Foram observados valores significativamente menores de PImáx obtidos com a traqueia de comprimento de 90 cm comparados às PImáx obtidas com as traqueias de 30 e 60 cm (teste de Friedman’s ANOVA com teste de Wilcoxon com ajuste de Bonferroni). As traqueias de 30, 60 e 90 cm de comprimento e mesmo diâmetro não influenciaram os valores de PEmáx e PImáx, exceto a traqueia de 90 cm para os valores de PImáx, o que pode interferir na prática clínica fisioterapêutica. Novos estudos são necessários para analisar a necessidade de padronização do comprimento da traqueia utilizada em manovacuômetros

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin