RESUMO
INTRODUCTION: AAC-8 and AAC-24 are two widely used scales to evaluate abdominal aortic calcification (AAC) on X-ray images. Levels of ≥3 (AAC-8) and ≥5 points (AAC-24) are of high relevance since they are associated with greater risk of cardiovascular events. Given that it is unknown, our aim was to determine the reliability of both scales at those levels of atherosclerotic burden. METHODS: The sample (93 subjects, 67.3 ± 9.7 years, BMI 28.8 ± 3.8, 57.6% smokers, 64.1% with hypertension) was classified according to quartiles of calcification. Six clinicians evaluated AAC independently with both scales on lateral lumbar spine X-ray images. We analyzed inter-rater agreement with the intraclass correlation coefficient (ICC) and the Bland-Altman scatterplots. RESULTS: We assessed 15 pairs of raters. Scores in both scales were significantly correlated with cardiovascular risk (r = 0.31 and r = 0.32; p < 0.005). Agreement was very high in the first quartile and moderate in the rest (p < 0.05). At cut-off points, ICC = 0.70 (95%CI, 0.54-0.86) and ICC = 0.68 (95%CI, 0.60-0.85) with AAC-8 and AAC-24. With the Bland-Altman method, mean of the differences ranged between 0 and 0.4 (AAC-8), and between 0.2 and 1 (AAC-24), while 95% limits of agreement showed values between 2.9 and 4.4 (AAC-8), and between 6 and 11.2 (AAC-24). Analyzing entire scales, ICC = 0.97 (95%CI, 0.97-0.98) and ICC = 0.98 (95%CI, 0.97-0.98) for AAC-8 and AAC-24, respectively. CONCLUSION: Both scales presented only moderate reliability at levels of atherosclerotic burden. Analyzing quartiles with ICC and the Bland-Altman plot showed concordant results. High global ICC values traditionally reported with both scales are likely biased. IMPLICATIONS FOR PRACTICE: AAC predicts subsequent vascular morbidity and mortality and should implicate evaluation of cardiovascular risk. Optimal visualisation of AAC and its correct assessment are mandatory in order to maximize patient care.
Assuntos
Aorta Abdominal , Vértebras Lombares , Aorta Abdominal/diagnóstico por imagem , Viés , Humanos , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.
Assuntos
Aconselhamento Genético , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/genética , Guias de Prática Clínica como Assunto/normas , Transtornos de Deglutição , Seguimentos , Humanos , Distrofia Miotônica/complicaçõesRESUMO
OBJECTIVES: The aim of the study was to assess changes in and factors associated with anatomical [carotid artery intima-media thickness (CIMT)] and functional (arterial stiffness) markers of subclinical cardiovascular disease progression in antiretroviral-naïve patients starting triple combination antiretroviral therapy containing contemporary protease inhibitors. METHODS: This was a planned substudy of the ATADAR (Metabolic Effects of Atazanavir/Ritonavir Versus Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine in naïve HIV-1 Infected Patients) clinical trial (ClinicalTrials.gov identifier NCT01274780). ATADAR is a multicentre, randomized, open-label clinical trial comparing the effects of ritonavir-boosted atazanavir and darunavir, both with tenofovir/emtricitabine, in antiretroviral-naïve HIV-infected patients. Common CIMT and aortic augmentation index (AIx@75) were measured at baseline and after 12 months of follow-up. Antiretroviral treatment, traditional cardiovascular risk factors and HIV-related factors were assessed as potential predictors of CIMT and Aix@75 changes using linear regression analysis. RESULTS: Thirty-three patients were included in this pilot study. While CIMT significantly increased in the pooled population [median (interquartile range (IQR)) 68 (-13, 128) µm; P = 0.0511], AIx@75 did not [median (IQR) 1 (-6, 5)%; P = 0.8964]. Patients on darunavir showed a trend to faster CIMT progression than those on atazanavir [median change (IQR) 117 (-2, 143) vs. -6 (-58, 89) µm, respectively; P = 0.0917]. However, after adjustment in the multivariate analysis, a higher baseline Framingham score was the only factor associated with CIMT progression (coefficient 16.02; 95% confidence interval -1.04, 33.08; P = 0.064). AIx@75 change was not associated with any baseline factor. CONCLUSIONS: CIMT was a more sensitive marker of subclinical vascular disease progression than arterial stiffness in antiretroviral-naïve patients starting antiretroviral therapy with contemporary protease inhibitors. Classical risk factors but not antiretroviral therapy were associated with faster CIMT progression.
RESUMO
OBJECTIVE: To provide data on incidence of early diagnosis of HIV infections and define prevalence and incidence of asymptomatic sexually transmitted infections (STI) in men who have sex with men (MSM). METHODS: We assessed a prospective cohort study of HIV-uninfected MSM at high risk for HIV infection. Participants were selected through a risk-assessment questionnaire, and they were screened for HIV infection (quarterly) and for other STI (yearly): syphilis, and hepatitis A, B and C (serology); Chlamydia trachomatis and Neisseria gonorrhoeae in penis and rectum; and human papillomavirus in anus and mouth (PCR). RESULTS: Between November 2009 and October 2012, a total of 258 HIV-uninfected MSM at high risk for HIV infection were included and followed up for a median of 2 years (interquartile range 1.4, 2.5). Nineteen acute HIV infections were diagnosed (incidence, 3.9 per 100 person-years). Prevalence of STI at baseline was follows: syphilis 8.4% (95% confidence interval (CI) 5.4-12.7); hepatitis C virus (HCV) 2.0% (95% CI 0.7-4.8); C. trachomatis in penis 3.2% (95% CI 1.5-6.5) and in rectum 6.5% (95% CI 3.9-10.5); N. gonorrhoeae in penis 2.0% (95% CI 0.8-5.0) and in rectum 6.1% (95% CI 3.6-10.1); human papillomavirus in anal canal 75.7% (95% CI 68.8-81.5) and in mouth 3.8% (95% CI 1.8-7.7). CONCLUSIONS: The implementation of the Check-Ear Project in a MSM community centre allowed for the identification of early HIV infections and asymptomatic STI among MSM. The high incidence of HIV infections and the high prevalence of STI strongly support the recommendation of periodic screenings among sexually active MSM.
Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Adulto , Diagnóstico Precoce , Infecções por HIV/virologia , Humanos , Incidência , Masculino , Prevalência , Vigilância em Saúde Pública , Fatores de Risco , Infecções Sexualmente Transmissíveis/etiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: The most recent guidelines suggest using integrase strand-transfer inhibitors (InSTIs) as the preferred antiretroviral regimens for naive HIV-infected individuals. However, resistance to InSTIs is not monitored in many centres at baseline. This study aimed to evaluate the prevalence of InSTI resistance substitutions in newly diagnosed patients with acute/recent HIV infection. METHODS: Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of <6 months, from 12 May 2015 to 12 May 2016. Sequences were obtained by high-throughput sequencing. RESULTS: Five out of 36 consecutive patients (13.89%, 95% CIâ=â4.67-29.5) with acute/recent HIV infection were detected to have strains carrying InSTI polymorphisms or substitutions conferring low-level resistance to raltegravir and elvitegravir. Four patients had the 157Q polymorphism and one patient had the Q95K substitution. All cases were MSM patients infected with subtype B strains. Viral loads ranged from 2.92 to 6.95 log10 copies/mL. In all cases, the mutational viral load was high. Three patients initiated dolutegravir-based regimens and became undetectable at first viral load control. There were no major viral or epidemiological differences when compared with patients without InSTI substitutions. CONCLUSIONS: Although signature InSTI substitutions (such as Y143R/C, N155H or Q148K/R/H) were not detected, polymorphisms and substitutions conferring low-level resistance to raltegravir and elvitegravir were frequently found in a baseline genotypic test. All cases were infected with subtype B, the most frequent in Europe. In the context of primary HIV infection, virological response should be carefully monitored to evaluate the impact of these InSTI polymorphisms and substitutions.
Assuntos
Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/genética , Mutação de Sentido Incorreto , Adulto , Substituição de Aminoácidos , Europa (Continente) , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Taxa de Mutação , Estudos Prospectivos , Análise de Sequência de DNARESUMO
The convergent preparation of Janus molecular nanoparticles by thiourea-"clicking" of α,α'-trehalose halves has been implemented; the strategy allows access to macrocyclic derivatives with seggregated cationic and lipophilic domains that in the presence of DNA undergo pH-dependent self-assembly into lamellar superstructures, as established by electrochemical, structural (SAXS), microscopical (TEM) and computational techniques, that mediate transfection in vitro and in vivo.
Assuntos
Química Click/métodos , DNA/química , Nanopartículas/química , Oligossacarídeos/química , Trealose/química , Animais , Células COS , Chlorocebus aethiops , DNA/metabolismo , Concentração de Íons de Hidrogênio , Nanopartículas/metabolismo , Oligossacarídeos/metabolismo , Espalhamento a Baixo Ângulo , Trealose/metabolismo , Difração de Raios XRESUMO
BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Hepatite C/epidemiologia , Hepatite C/imunologia , Adolescente , Adulto , Estudos de Coortes , Coinfecção/epidemiologia , Coinfecção/imunologia , Coinfecção/virologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1 , Hepacivirus , Hepatite C/complicações , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto JovemRESUMO
OBJECTIVES: To longitudinally assess the shedding of antimicrobial resistant Clostridium difficile strains by clinically healthy dogs raised at breeding facilities. METHODS: 18 puppies from three different litters (#1, 2 and 3) were sampled weekly from parturition to day 20-55 postpartum. Faecal samples from the mothers of litters #2 and 3 were also available for analysis. Bacterial isolates were ribotyped, tested for in vitro antimicrobial susceptibility and further characterised. RESULTS: C. difficile was recovered from all sampled animals of litters #1 and 2, and a third of puppies from litter #3, but marked differences in C. difficile recovery were detected in different age groups (0-100%). Recovered PCR ribotypes included 056 (22 isolates), 010 (6 isolates), 078 and 213 (2 isolates each), and 009 and 020 (1 isolate each). Different ribotypes were shed by four individual animals. Regardless of their origin and ribotype, all isolates demonstrated full resistance to levofloxacin. Additionally, all but one isolate (belonging to ribotype 078) were resistant to ertapenem, and all ribotype 010 isolates displayed high-level resistance to clindamycin, clarithromycin and erythromycin. A single ribotype 078 isolate showed metronidazole heteroresistance. CLINICAL SIGNIFICANCE: Healthy dogs can shed antimicrobial-resistant C. difficile strains.
Assuntos
Derrame de Bactérias , Doenças do Cão/microbiologia , Enterocolite Pseudomembranosa/veterinária , Fezes/microbiologia , Animais , Antibacterianos/farmacologia , Doenças Assintomáticas , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Cães , Farmacorresistência Bacteriana/genética , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/microbiologia , Feminino , Masculino , Testes de Sensibilidade Microbiana , Ribotipagem/veterináriaRESUMO
BACKGROUND: Several potential immunological benefits have been observed during treatment with the CC chemokine receptor 5 (CCR5) antagonist maraviroc, in addition to its antiviral effect. Our objective was to analyse the in vitro effects of CCR5 blockade on T lymphocyte function and homeostasis. METHODS: Peripheral blood mononuclear cells (PBMCs) from both HIV-negative (n=28) and treated HIV-positive (n=27) individuals were exposed in vitro to different concentrations of maraviroc (0.1-100 µM). Effects on T cell activation were analysed by measuring the expression of the CD69, CD38, HLA-DR and CD25 receptors as well as CCR5 density using flow cytometry. Spontaneous and chemokine-induced chemotaxis were measured by transwell migration assays, and polyclonal-induced proliferation was assessed by a lymphoproliferation assay and carboxyfluorescein succinimidyl ester staining. RESULTS: Maraviroc increases CCR5 surface expression on activated T cells, even at low doses (0.1 µM). Slight differences were detected in the frequency and mean fluorescence intensity of activation markers at high concentrations of maraviroc. Expression of CD25, CD38 and HLA-DR tended to decrease in both CD4+ and CD8+ T lymphocytes, whereas expression of CD69 tended to increase. Maraviroc clearly inhibits T cell migration induced by chemokines in a dose-dependent manner. Moreover, at 100 µM, maraviroc tends to inhibit T cell proliferation. CONCLUSIONS: These data showed that in vitro exposure to maraviroc decreases some activation expression markers on T lymphocytes and also migration towards chemoattractants. These results support the additional immunological effects of CCR5 blockade and suggest that maraviroc might have potential capacity to inhibit HIV-associated chronic inflammation and activation, both by directly affecting T cell activation and by reducing entrapment of lymphocytes in lymph nodes.
Assuntos
Fármacos Anti-HIV/farmacologia , Cicloexanos/farmacologia , Imunossupressores/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Triazóis/farmacologia , Antígenos CD/análise , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Antígenos HLA-DR/análise , Humanos , Leucócitos Mononucleares/química , Ativação Linfocitária/efeitos dos fármacos , Maraviroc , Receptores CCR5/análiseRESUMO
OBJECTIVES: The aim of the study was to assess the separate contributions of smoking, diabetes and hypertension to acute coronary syndrome (ACS) in HIV-infected adults relative to uninfected adults. METHODS: Two parallel case-control studies were carried out. In the first study, HIV-positive adults diagnosed with ACS between 1997 and 2009 (HIV+/ACS) were matched for age, gender and known duration of HIV infection with HIV-positive adults without ACS (HIV+/noACS), each individual in the HIV+/ACS group being matched with three individuals in the HIV+/noACS group. In the second study, each individual in the HIV+/ACS group in the first study was matched for age, gender and calendar date of ACS diagnosis with three HIV-negative individuals diagnosed with ACS between 1997 and 2009 (HIV-/ACS). Each individual in the HIV-/ACS group was then matched for age and gender with an HIV-negative adult without ACS (HIV-/noACS). After matching, the ratio of numbers of individuals in the HIV+/ACS, HIV+/noACS, HIV-/ACS and HIV-/noACS groups was therefore 1 : 3 : 3 : 3, respectively. We performed logistic regression analyses to identify risk factors for ACS in each case-control study and calculated population attributable risks (PARs) for smoking, diabetes and hypertension in HIV-positive and HIV-negative individuals. RESULTS: There were 57 subjects in the HIV+/ACS group, 173 in the HIV+/noACS group, 168 in the HIV-/ACS group, and 171 in the HIV-/noACS group. Independent risk factors for ACS were smoking [odds ratio (OR) 4.091; 95% confidence interval (CI) 2.086-8.438; P < 0.0001] and a family history of cardiovascular disease (OR 7.676; 95% CI 1.976-32.168; P = 0.0003) in HIV-positive subjects, and smoking (OR 4.310; 95% CI 2.425-7.853; P < 0.0001), diabetes (OR 5.778; 95% CI 2.393-15.422; P = 0.0002) and hypertension (OR 6.589; 95% CI 3.554-12.700; P < 0.0001) in HIV-negative subjects. PARs for smoking, diabetes and hypertension were 54.35 and 30.58, 6.57 and 17.24, and 9.07 and 38.81% in HIV-positive and HIV-negative individuals, respectively. CONCLUSIONS: The contribution of smoking to ACS in HIV-positive adults was generally greater than the contributions of diabetes and hypertension, and was almost twice as high as that in HIV-negative adults. Development of effective smoking cessation strategies should be prioritized to prevent cardiovascular disease in HIV-positive adults.
Assuntos
Síndrome Coronariana Aguda/etiologia , Diabetes Mellitus/epidemiologia , Infecções por HIV/complicações , Hipertensão/epidemiologia , Fumar/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipercolesterolemia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Espanha/epidemiologiaRESUMO
OBJECTIVE: Rituximab has emerged as an efficacious option for drug-resistant myasthenia gravis (MG). However, reports published only describe the short-term follow-up of patients treated and little is known about their long-term clinical and immunologic evolution. Our objective was to report the clinical and immunologic long-term follow-up of 17 patients (6 MuSK+MG and 11 AChR+MG) and compare the response between AChR+MG and MuSK+MG patients. METHODS: Myasthenia Gravis Foundation America postintervention status and changes in treatment and antibody titers were periodically determined. Lymphocyte subpopulations, total immunoglobulin, immunoglobulin G (IgG) anti-MuSK subclasses, and anti-tetanus toxoid IgG before and after treatment were also studied. RESULTS: After a mean post-treatment period of 31 months, 10 of the AChR+MG patients improved but 6 of them needed reinfusions. In contrast, all MuSK+MG patients achieved a remission (4/6) or minimal manifestations (2/6) status and no reinfusions were needed. Consequently, in the MuSK+MG group, prednisone doses were significantly reduced and concomitant immunosuppressants could be withdrawn. Clinical improvement was associated with a significant decrease in the antibody titers only in the 6 MuSK+MG patients. At last follow-up MuSK antibodies were negative in 3 of these patients and showed a decrease of over 80% in the other 3. CONCLUSION: In view of the long-lasting benefit observed in MuSK+MG patients, we recommend to use rituximab as an early therapeutic option in this group of patients with MG if they do not respond to prednisone. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that IV rituximab improves the clinical and immunologic status of patients with MuSK+MG.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Autoanticorpos/sangue , Miastenia Gravis/sangue , Miastenia Gravis/tratamento farmacológico , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Adulto , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Estudos Longitudinais , Masculino , Miastenia Gravis/diagnóstico , Rituximab , Resultado do TratamentoRESUMO
INTRODUCTION: The lack of accepted homogeneous criteria for the definition of some demyelinating diseases makes diagnostic characterization difficult and limits data interpretation and therapeutic recommendations. Recurrent encephalomyelitis (ADE-R) along with borderline cases of neuromyelitis optica (NMO) are especially controversial. OBJECTIVE: To describe the clinical and radiological evolution of an adult-onset ADE-R versus NMO case throughout 9 years of follow-up. PATIENT AND METHODS: Our patient presented with severe symptoms of rhombencephalomyelitis and the cranial and spinal magnetic resonance imaging (MRI) showed large lesions, with gadolinium enhancement in brainstem and spinal cord, correlating with the clinical picture. Infectious aetiology was excluded, IgG index was normal and NMO antibodies were negative. After treatment with intravenous corticosteroids and plasmapheresis, there was excellent recovery in the acute phase. During follow-up, seven relapses have occurred, mainly in the spinal cord, with good recovery and the same symptomatology, albeit with different severity. Immunosuppressive treatment was introduced since the beginning. CONCLUSIONS: Our case shares common features of both ADE-R and NMO, illustrating that diagnostic characterization is not easy in spite of current criteria.
Assuntos
Encefalite/diagnóstico , Neuromielite Óptica/diagnóstico , Azatioprina/uso terapêutico , Tronco Encefálico/patologia , Corticosterona/uso terapêutico , Encefalite/patologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Metilprednisolona/uso terapêutico , Neuromielite Óptica/patologia , Plasmaferese , Recidiva , Medula Espinal/patologia , Adulto JovemAssuntos
Micoses/veterinária , Zoonoses , Animais , Humanos , Micoses/transmissão , Medicina VeterináriaRESUMO
Numerous studies have observed cardiac biomarker release with prolonged exercise. Despite this, we are unsure as to the constituent aspects of any given exercise bout that may be important in promoting cardiac biomarker release. This study examined the influence of exercise duration and intensity on the appearance of cardiac biomarkers. Twenty-one subjects ran for 45, 90 and 180 min at 85% and 95% of their individual anaerobic threshold on six different days randomized. Cardiac troponin I (cTnI) and N-terminal pro-brain natiuretic peptide (NT-proBNP) were assayed from blood samples collected before, 30 min and 3 h post-exercise. NT-proBNP was elevated after all exercise trials (range before: 21-32; range post: 38-67 ng/L). Peak post-exercise concentrations of NT-proBNP were associated with exercise duration (P=0.049), but not exercise intensity (P=0.451). cTnI was elevated after all exercise trials (range before: 0.007-0.011; range post: 0.008-0.021 µg/L). Peak post-exercise concentrations of cTnI were associated with exercise duration (P=0.003) and intensity (P=0.037). Data suggest that while both cTnI and NT-proBNP increased after all exercise trials, the mediating effect of duration influenced both NT-proBNP and cTnI while intensity influenced only cTnI.
Assuntos
Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Esforço Físico/fisiologia , Corrida/fisiologia , Troponina I/sangue , Adulto , Análise de Variância , Biomarcadores/sangue , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Neurologists should anticipate and recognize the onset of respiratory failure in patients with neuromuscular diseases. Symptoms vary according to the speed of onset of respiratory muscle weakness. Catastrophic situations usually occur in three clinical scenarios: 1) incorrect management of acute respiratory failure of neuromuscular origin, autonomic dysfunction or during general anaesthesia of patients with neuromuscular diseases ; 2) incorrect prognosis and treatment due to the lack of a correct diagnosis. This situation is more common in ventilated patients with associated muscular weakness, acute neuropathies or motor neuron disease, and 3) inappropriate medical intervention in patients with neuromuscular disease with a definitive diagnosis but longstanding disease (amyotrophic lateral sclerosis, spinal muscular atrophy, myotonic dystrophy and other muscular dystrophies).
Assuntos
Doença Aguda , Doenças Neuromusculares/complicações , Doenças Neuromusculares/fisiopatologia , Insuficiência Respiratória/etiologia , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/fisiopatologia , Síndrome de Guillain-Barré/terapia , Humanos , Doenças Musculares/complicações , Doenças Musculares/diagnóstico , Doenças Musculares/fisiopatologia , Doenças Musculares/terapia , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Miastenia Gravis/fisiopatologia , Miastenia Gravis/terapia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/terapia , Polineuropatias/complicações , Polineuropatias/diagnóstico , Polineuropatias/fisiopatologia , Polineuropatias/terapia , Prognóstico , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Espirometria/instrumentação , Espirometria/métodosRESUMO
BACKGROUND: The use of HAART combining 2 nucleoside analogues reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor (PI) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) has shown comparable efficacy. The study was designed to compare long term (2 years) effectiveness of two antiretroviral (ARV) treatment strategies in patients not previously treated: starting with a nelfinavir based HAART switching to nevirapine in case of failure or side effects or the reverse sequence. METHODS: This multicenter, randomized, open label clinical trial enrolled ARV-naïve HIV patients with CD4 counts below 500 cells/mm3. They were randomly assigned to start ddI + d4T + nelfinavir (switching to ZDV + 3TC + NEV in case of failure or toxicity) (PI-NEV arm) or ddI + d4T + nevirapine, switching to ZDV + 3TC + NFV in case of failure or toxicity (NEV-PI arm). The primary study endpoint was the Kaplan-Meier estimates of the time to failure after switching to second regimen if necessary (considering failure as two consecutive plasma HIV-1 RNA determinations above 200 copies/mL, death, a new category C event or toxicity leading to treatment discontinuation of the second regimen) after a minimum follow-up of two years. RESULTS: A total of 137 patients were evaluable (67 and 70 in the PI-NEV and NEV-PI arms respectively). Baseline characteristics did not differ among groups. Kaplan-Meier estimates of time to failure did not show differences between the two arms neither in the on-treatment (OT) analysis (log rank test, p = 0.81) nor in the intent-to-treat (ITT) analysis (p = 0.58). At 24 months, the estimated proportion of patients free of failure were 72% and 66% respectively in the PI-NEV and NEV-PI arms OT analysis (p = 0.54) and 73% and 64% in the PI-NEV and NEV-PI arms in the ITT analysis (p = 0.49). The difference in the median in CD4+ lymphocyte count at 24 months was not significantly different in the two groups: 393 and 307 CD4 cells/mm3 in the PI-NEV and NEV-PI arms respectively (p = 0.167). The incidence of adverse events (AEs) in the two arms was very similar: 50 (75%) in the PI-NEV and 54 (70%) in the NEV-PI group, as it was for grade 3-4 AEs leading to drug switching. CONCLUSION: At two years both treatments strategies (PI-NEV vs NEV-PI) had a high and comparable efficacy and were generally well tolerated.
Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
OBJECTIVES: To study the impact of lopinavir/ritonavir-containing therapy on plasma lipids and body fat of HIV-infected adults and to assess whether lopinavir plasma levels at steady state are correlated with plasma lipids and body fat after 24 weeks. METHODS: Patients had their antiretroviral therapy switched to an antiretroviral regimen containing lopinavir/ritonavir plus one or two non-thymidine analogues. Body composition was assessed by dual energy X-ray absorptiometry at baseline and at week 24 and an intensive pharmacokinetic (PK) 12 h profile was performed at week 2. RESULTS: Twenty-six patients were included. Plasma triglycerides (from 206 mg/dL to 261 mg/dL, P = 0.09) and total cholesterol (from 201 to 206 mg/dL, P = 0.03) increased from baseline to week 24. There was a significant rise in total fat (from 10.9 to 11.9 kg, P = 0.02) and limb fat (from 3.8 to 4.4 kg, P = 0.02) from baseline to week 24. We did not find any correlation between PK lopinavir levels and changes over time for triglycerides, cholesterol or body fat composition. CONCLUSIONS: There was an increase in plasma triglycerides and total cholesterol levels and a gain in both total and limb fat at 24 weeks, but these changes were not correlated with lopinavir plasma levels.