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INTRODUCTION: Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live-attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients. METHODS: Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included. RESULTS: We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p ≤ .0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft-versus-host disease (GVHD) did not affect the compliance with measles (p = .08) or YF vaccination (p = .7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p < .0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination. CONCLUSION: A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem.
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Trasplante de Células Madre Hematopoyéticas , Sarampión , Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Adulto , Niño , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunización Secundaria , Sarampión/prevención & control , Vacuna Antisarampión/administración & dosificación , Vacunación , Vacunas Virales , Fiebre Amarilla/prevención & control , Vacuna contra la Fiebre Amarilla/administración & dosificaciónAsunto(s)
Anticonvulsivantes/efectos adversos , Levetiracetam/efectos adversos , Rabdomiólisis/inducido químicamente , Anticonvulsivantes/uso terapéutico , Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Epilepsia Generalizada/tratamiento farmacológico , Epilepsia Generalizada/etiología , Femenino , Humanos , Italia , Levetiracetam/uso terapéutico , Persona de Mediana EdadRESUMEN
Background: Handwriting is an acquired complex cognitive and motor skill resulting from the activation of a widespread brain network. Handwriting therefore may provide biologically relevant information on health status. Also, handwriting can be collected easily in an ecological scenario, through safe, cheap, and largely available tools. Hence, objective handwriting analysis through artificial intelligence would represent an innovative strategy for telemedicine purposes in healthy subjects and people affected by neurological disorders. Materials and Methods: One-hundred and fifty-six healthy subjects (61 males; 49.6 ± 20.4 years) were enrolled and divided according to age into three subgroups: Younger adults (YA), middle-aged adults (MA), and older adults (OA). Participants performed an ecological handwriting task that was digitalized through smartphones. Data underwent the DBNet algorithm for measuring and comparing the average stroke sizes in the three groups. A convolutional neural network (CNN) was also used to classify handwriting samples. Lastly, receiver operating characteristic (ROC) curves and sensitivity, specificity, positive, negative predictive values (PPV, NPV), accuracy and area under the curve (AUC) were calculated to report the performance of the algorithm. Results: Stroke sizes were significantly smaller in OA than in MA and YA. The CNN classifier objectively discriminated YA vs. OA (sensitivity = 82%, specificity = 80%, PPV = 78%, NPV = 79%, accuracy = 77%, and AUC = 0.84), MA vs. OA (sensitivity = 84%, specificity = 56%, PPV = 78%, NPV = 73%, accuracy = 74%, and AUC = 0.7), and YA vs. MA (sensitivity = 75%, specificity = 82%, PPV = 79%, NPV = 83%, accuracy = 79%, and AUC = 0.83). Discussion: Handwriting progressively declines with human aging. The effect of physiological aging on handwriting abilities can be detected remotely and objectively by using machine learning algorithms.
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Tuberculosis (TB) is a major infectious complication in hematopoietic stem cell transplant (HSCT) recipients in countries with high TB prevalence. Identifying and treating latent tuberculosis infection (LTBI) helps to prevent TB reactivation after transplantation. Few studies have compared the tuberculin skin test (TST) with interferon Gamma release assays (IGRA) to diagnose LTBI in HSCT candidates. We compared TST and QuantiFeron TB gold in tube (QTF-GIT) and prospectively evaluated the incidence of active tuberculosis in 126 HSCT candidates and 58 HSCT recipients with chronic GVHD followed at the outpatient clinic. TB was diagnosed by culture in Mycobacteria media and by commercial real-time PCR kit. Considering the positivity of any test, the prevalence of LTBI was 8.7% in HSCT candidates (11 out of 126) and 12.5% in HSCT recipients with chronic GVHD (6 out of 48). QTF-GIT indeterminate results were detected in 2.4% of the HSCT candidates. Fair to good agreement (K > 0.50) between tests was observed in both cohorts. Cumulative incidence of TB was 3% in the GVHD cohort. TB was diagnosed in 2 chronic GVHD recipients, both cases confirmed by positive culture and PCR. None of the 11 patients with LTBI diagnosed pre-HSCT who received INH prophylaxis developed TB.
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Trasplante de Células Madre Hematopoyéticas , Tuberculosis , Estudios de Cohortes , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Prospectivos , Prueba de Tuberculina , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis/etiologíaRESUMEN
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease lacking effective therapies. Cell replacement therapy has been suggested as a promising therapeutic approach for multiple neurodegenerative diseases, including motor neuron disease. We analyzed expanded mesenchymal stem cells (MSCs) isolated from sporadic ALS patients and compared them with MSCs isolated from healthy donors. MSCs were isolated from bone marrow by Percoll gradient and maintained in culture in MSC Medium until the third passage. Growth kinetics, immunophenotype, telomere length, and karyotype were evaluated during in vitro expansion. Osteogenic, adipogenic, chondrogenic, and neurogenic differentiation potential were also evaluated. No morphological differences were observed in the MSCs isolated from donors or patients. The cellular expansion potential of MSCs from donors and patients was slightly different. After three passages, the MSCs isolated from donors reached a cumulative population doubling higher than from patients but the difference was not statistically significant. No significant differences between donors or patients were observed in the immunophenotype analysis. No chromosomal alteration or evidence of cellular senescence was observed in any samples. Both donor and patient MSCs, after exposure to specific conditioning media, differentiated into adipocytes, osteoblasts, chondrocytes, and neuron-like cells. These results suggest that extensive in vitro expansion of patient MSCs does not involve any functional modification of the cells, including chromosomal alterations or cellular senescence. Hence, there is a good chance that MSCs might be used as a cell-based therapy for ALS patients.
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Esclerosis Amiotrófica Lateral/patología , Células de la Médula Ósea/citología , Células Madre Mesenquimatosas/citología , Adulto , Anciano , Esclerosis Amiotrófica Lateral/sangre , Células de la Médula Ósea/metabolismo , Diferenciación Celular , Proliferación Celular , Femenino , Citometría de Flujo , Humanos , Cariotipificación , Masculino , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Telómero/genéticaRESUMEN
Triptans mediate vasoconstriction of meningeal vessels via stimulation of vascular 5-hydroxytryptamine (5-HT)(1B) receptors. These drugs are recommended for acute treatment in patients with moderate-to-severe migraine attacks and in those patients with mild-to-moderate headache that are not controlled adequately by other agents. Yet, approximately 25% of all migraine users and 40% of all attacks do not respond to triptan treatment. Among the hypothesis to explain this is the possibility that genetic single nucleotide polymorphisms that alter the receptor, for example changing the transcriptional rate and therefore the amount of target protein might change the clinical response to these drugs. In the present contribution, we therefore decided to evaluate whether single nucleotide polymorphisms on the 5-HT(1B) gene might contribute to inter-individual variability in clinical responses to triptans. Two polymorphisms in the promoter region of the 5-HT(1B) receptor (T-261G and A-161T) and the synonymous variation G861C in the coding region were genotyped by restriction fragment length polymorphism in 105 migraine patients. In our sample population, 71% of patients responded to triptans. Allelic and diplotype frequencies were not significantly different between responders and non-responders. On the other hand, extrapolation of in vitro data on promoter activity would suggest that patients with higher copy number of receptors respond slightly better. Our data therefore do not support the involvement of 5-HT(1B) single nucleotide polymorphisms in mediating the inter-individual variability to triptans.
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Migraña con Aura/tratamiento farmacológico , Migraña sin Aura/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Receptor de Serotonina 5-HT1B/efectos de los fármacos , Agonistas de Receptores de Serotonina/farmacología , Triptaminas/farmacología , Adulto , Anciano , Alelos , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Migraña con Aura/genética , Migraña sin Aura/genética , Sistemas de Lectura Abierta , Polimorfismo de Longitud del Fragmento de Restricción , Regiones Promotoras Genéticas , Receptor de Serotonina 5-HT1B/genética , Receptor de Serotonina 5-HT1B/metabolismoRESUMEN
Amyotrophic Lateral Sclerosis is a progressive fatal neurodegenerative disease that targets motor neurons. Its origin is unknown but a main role of reactive astrogliosis and microglia activation in the pathogenesis has been recently demonstrated. Surrounding neurons with healthy adjoining cells completely stops motor neuron death in some cases. Hence stem cell transplantation might represent a promising therapeutic strategy. In this study MSCs were isolated from bone marrow of 9 patients with definite ALS. Growth kinetics, immunophenotype, telomere length and karyotype were evaluated during in vitro expansion. No significant differences between donors or patients were observed. The patients received intraspinal injections of autologous MSCs at the thoracic level and monitored for 4 years. No significant acute or late side effects were evidenced. No modification of the spinal cord volume or other signs of abnormal cell proliferation were observed. Four patients show a significant slowing down of the linear decline of the forced vital capacity and of the ALS-FRS score. Our results seem to demonstrate that MSCs represent a good chance for stem cell cell-based therapy in ALS and that intraspinal injection of MSCs is safe also in the long term. A new phase 1 study is carried out to verify these data in a larger number of patients.
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Esclerosis Amiotrófica Lateral/cirugía , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/fisiología , Neuronas/fisiología , Adulto , Anciano , Células de la Médula Ósea/fisiología , Diferenciación Celular/fisiología , Proliferación Celular , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neuronas Motoras , Factores de Tiempo , Trasplante Autólogo/métodosRESUMEN
OBJECTIVES: To divide amyotrophic lateral sclerosis (ALS) patients in two clusters according to their illness representation, and to identify, between the two clusters, the differences in functional state, mood, and quality of life. METHODS: Seventy-four patients with ALS were recruited at our ALS Centre from different Italian regions, having been for multidisciplinary consultations. The patients' functional impairment was evaluated by the ALS Functional Rating Scale as well as the Bulbar Score and Forced Vital Capacity. Psychological Characteristics and quality of life of ALS patients were evaluated by Profile of Mood State, Illness Perception Questionnaire, and 36-item Short Form Health Survey. RESULTS: Only few of the ALS patients studied showed critical mood ratings. On the whole, the perceived quality of life, mood state, and the dimensions relating to their illness representation seem to be correlated to the functional state and respiratory capacity. The clustering of patients according to their illness representations allowed to highlight that ALS patients can be divided into two groups: adaptors and nonadaptors. The patients of the two groups, adaptors and nonadaptors, differed in respiratory capacity as well as in their mood and health-related quality of life. CONCLUSIONS: This study supports the Common Sense Model (CSM) of illness representation when considering ALS patients. Their psychological reactions to illness and quality of life depend not only on the severity of the illness but also on the way the illness is represented. Therefore, CSM could become the theoretical framework for psychological interventions in ALS patients.
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Afecto , Esclerosis Amiotrófica Lateral/psicología , Estado de Salud , Calidad de Vida , Esclerosis Amiotrófica Lateral/fisiopatología , Actitud Frente a la Salud , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Capacidad VitalRESUMEN
Hematopoietic stem cell transplantation (HSCT) is an important therapeutic option for some hematological diseases. However, patients who undergo HSCT acquire a state of immunodeficiency that causes significant mortality. Reconstitution of thymic function is needed to support the immune system. One way to measure thymic function is through T-cell receptor excision circle (TREC) quantification. TRECs are generated by T-cell receptor gene rearrangements during T-cell maturation in the thymus and represent a reliable marker for thymic output. In this study, we aimed to assess aging and malignant hematological diseases as two important factors that may influence thymic output before HSCT. We observed that patients before HSCT presented signal joint TREC (sjTREC) numbers lower than 606.55 copies/µg DNA (low values) compared with healthy individuals, with an odds ratio (OR) of 12.88 [95% confidence interval (CI): 5.26-31.53; p < 0.001]. Our results showed that a group of older individuals (≥50 years old), comprising both healthy individuals and patients, had an OR of 10.07 (95% CI: 2.80-36.20) for low sjTREC values compared with younger individuals (≤24 years old; p < 0.001). Multiple logistic regression analysis confirmed that both older age (≥50 years old) and malignant hematological diseases and their treatments were important and independent risk factors related to thymic function impairment (p < 0.001). The median sjTREC value for patients of all ages was significantly lower than the sjTREC median for the subgroup of older healthy individuals (≥50 years old; p < 0.001). These data suggested that patients before HSCT and healthy individuals exhibited age-dependent thymic impairment, and that prior treatment for hematological diseases may exacerbate aging-related deterioration of natural thymic function. Furthermore, we analyzed these patients 9 months post-HSCT and compared patients who underwent autologous HSCT with those who underwent allogeneic HSCT. Both groups of patients achieved sjTREC copy numbers similar to those of healthy individuals. We did not find a close relationship between impaired thymic function prior to HSCT and worse thymic recovery after HSCT.
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Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Linfopoyesis , Timo/citología , Timo/metabolismo , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/citología , Subgrupos de Linfocitos T/metabolismo , Adulto JovenRESUMEN
Potentially causative missense variations in the ANG gene and a positive association with the synonymous rs11701-G substitution was detected mainly in Irish and Scottish ALS patients. We screened 262 Italian SOD1 negative ALS patients (250 sporadic) and 415 matched controls for sequence variations in the coding, 3'/5' UTR and 5' flanking (642 bp) regions of the ANG gene. We identified 53 sequence variations of which 46 new, 20 with a minor allele frequency (MAF) >or=0.01 and only three localised in the coding sequence, namely the missense I46V, identified in one patient and two controls, and the synonymous G86G and T97T corresponding to rs11701 and rs2228653. None of the detected SNPs or of their haplotypic combinations was significantly associated with ALS susceptibility or clinical features. In conclusion, we did not detect the association with rs11701-G or with any other newly detected variation in the ANG regulatory region. Furthermore we did not identify potentially causal mutations in the coding region.
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Esclerosis Amiotrófica Lateral/genética , Susceptibilidad a Enfermedades , Variación Genética , Regiones Promotoras Genéticas/fisiología , Ribonucleasa Pancreática/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/epidemiología , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Humanos , Italia/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Our study was aimed to evaluate the feasibility and safety of intraspinal cord implantation of autologous mesenchymal stem cells (MSCs) in a few well-monitored amyotrophic lateral sclerosis (ALS) patients. METHODS: Seven patients affected by definite ALS were enrolled in the study and two patients were treated for compassionate use and monitored for at least 3 years. Bone marrow was collected from the posterior iliac crest according to the standard procedure and MSCs were expanded ex vivo according to Pittenger's protocol. The cells were suspended in 2 ml autologous cerebrospinal fluid and transplanted into the spinal cord by a micrometric pump injector. RESULTS: The in vitro expanded MSCs did not show any bacterial o fungal contamination, hemopoietic cell contamination, chromosomic alterations and early cellular senescence. No patient manifested major adverse events such as respiratory failure or death. Minor adverse events were intercostal pain irradiation and leg sensory dysesthesia, both reversible after a mean period of 6 weeks. No modification of the spinal cord volume or other signs of abnormal cell proliferation were observed. A significant slowing down of the linear decline of the forced vital capacity was evident in four patients 36 months after MSCs transplantation. CONCLUSIONS: Our results demonstrate that direct injection of autologous expanded MSCs into the spinal cord of ALS patients is safe, with no significant acute or late toxicity, and well tolerated. The clinical results seem to be encouraging.
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Esclerosis Amiotrófica Lateral/cirugía , Trasplante de Células Madre Mesenquimatosas , Médula Espinal/cirugía , Adulto , Anciano , Trasplante de Médula Ósea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante AutólogoRESUMEN
Motor neurons in amyotrophic lateral sclerosis (ALS) are characterized by the presence of inclusion bodies composed of intermediate filament (IF) proteins. Peripherin protein is as components of these inclusions and rare mutations in peripherin gene (PRPH) were identified in sporadic ALS cases. The aim of this study was to further define the spectrum of PRPH mutations in a cohort of 122 Italian ALS patients. We screened the coding sequence, the exon/intron boundaries, and the 5'-3' un-translated regions (UTRs) in 122 ALS patients. Eighteen sequence variations were detected. Seven variants were not identified in a panel of at least 245 matched controls, including 2 missense variations, namely p.R133P and p.D141Y, each identified in one heterozygous patient. p.R133P was newly identified whereas p.D141Y was previously described in one homozygous sporadic ALS patient. These 2 variants were predicted to have a deleterious effect on protein structure or function. This work contributes to determine the role of PRPH gene variants in ALS. Further studies are necessary to define the mechanisms through which the mutant peripherin could cause ALS phenotype.
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Esclerosis Amiotrófica Lateral/genética , Predisposición Genética a la Enfermedad/genética , Proteínas de Filamentos Intermediarios/genética , Glicoproteínas de Membrana/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Adulto , Anciano , Distribución de Chi-Cuadrado , Estudios de Cohortes , Biología Computacional/métodos , Evaluación de la Discapacidad , Femenino , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Periferinas , Adulto JovenRESUMEN
Amyotrophic lateral sclerosis (ALS) is a devastating incurable neurodegenerative disease that targets motor neurons, manifesting as a linear decline in muscular function and leading to death within 2 - 5 years of diagnosis. The vast majority of ALS cases are sporadic, the aetiopathology of which is incompletely understood. Recent data have implicated the microenvironment of the motor neuron as a primary target of the pathophysiology. Any experimental therapeutic approach to ALS is very difficult because of some peculiarities of the disease, such as the unknown origin, the spatial diffusion of motor neuron loss and the paucity of animal models. Despite such daunting challenges, in experimental models a number of potential benefits of stem cells in ALS therapy have been demonstrated: by providing non-compromised supporting cells such as astrocytes, microglia or growth factor-excreting cells, onset can be delayed and survival increased. Moreover, in animal models of acute or chronic motor neuron injury, neural stem cells implanted into the spinal cord have been shown to differentiate into motor neurons, with some evidence of axonal sprouting and formation of nerumuscular junctions with host muscle. Here we summarise and discuss current preclinical and clinical evidence regarding stem cells application in ALS, particularly focusing on methodological issues.
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Esclerosis Amiotrófica Lateral/cirugía , Trasplante de Células Madre , Animales , Modelos Animales de Enfermedad , Humanos , Neuronas Motoras/citologíaRESUMEN
Virakinetics II was designed as an observational, multicenter cohort study conducted in HIV-positive patients treated with NFV-based combinations. Trough (pre-dose) concentrations of NFV+M8 in plasma were determined using a novel ELISA test (NFV TDM-ELISA) and analyzed using clinical and laboratory parameters. Drug levels were sorted as below, within or above a given interval (<0.8 microg/mL, 0.8-3.5 microg/mL and >3.5 microg/mL, respectively). Longitudinal analysis was performed in a subset of patients who underwent two or more determinations. Ninety patients on NFV-containing HAART were enrolled and 43 were coinfected with HCV and/or HBV. Among coinfected patients, 10 subjects had a clinical or histological diagnosis of cirrhosis. Compared to the HIV-monoinfected, the coinfected patients were significantly older, more treatment-experienced, with higher frequency of lipodystrophy and altered liver function test values (all p values: <0.05). Coinfected patients were also more likely to be on a reduced dose of NFV than monoinfected (p=0.03). No significant difference was observed between the two groups with regard to NFV+M8 trough values and concentration range distribution. Median NFV+M8 C(trough) concentrations were higher in coinfected patients, but without reaching statistical significance (p=0.2). This new ELISA test proved to be a rapid, convenient and reliable tool for assessing NFV+M8 plasma levels in HIV-positive patients. It could be suitable for use within the framework of routine clinical practice even in peripheral centers without specialized laboratories.
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Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Nelfinavir/análogos & derivados , Adulto , Terapia Antirretroviral Altamente Activa , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Nelfinavir/farmacocinética , Nelfinavir/uso terapéutico , Plasma/químicaRESUMEN
Cluster headache (CH) is a well-defined primary headache syndrome, but cases of symptomatic headache with clinical features of CH have been previously reported. Idiopathic Intracranial Hypertension (IIH) is a secondary headache disorder characterized by headache and visual symptoms, without clinical, radiological or laboratory evidence of intracranial pathology. Both papilloedema and IIH-related headache are typically bilateral, however asymmetrical or even unilateral localizations are described in literature. We report the case of a previously headache-free woman who presented cluster-like headache and asymmetrical papilloedema related to IIH. In our opinion the asymmetrical presentation supports, in this case, the hypothesis of cavernous sinus involvement in the IIH-related cluster-like headache pathogenesis.
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Cefalalgia Histamínica/complicaciones , Seudotumor Cerebral/etiología , Adulto , Femenino , Humanos , Papiledema/etiología , Seudotumor Cerebral/complicacionesRESUMEN
Chronic tension type headache (CTTH) has a strong impact on the Quality Of Life (QOL). We carried out an open-label randomized clinical trial on 18 patients with CTTH in order to compare two different regimens of pharmacological prophylaxis: the first provided for the use of amitriptyline 20 mg/d during 3 months, while in the second we combined amitriptyline with tizanidine (4 mg/d) in the first 3 weeks of treatment. Our hypothesis is that the combination therapy may guarantee an improvement of QOL even in the early stages of treatment. In fact, it's as well-known, there is a delay of 2-3 weeks in the prophylactic effect of amitriptyline, with a consequent persistence, in the first phases of therapy, of the headache and its negative impact. We assessed the following outcome measures: frequency, pain intensity, duration of headache and the Headache Impact Test (HIT) score, used as headache-related QOL measure. The combination therapy was effective since the first month of treatment, with a significant reduction of the headache, greater than one obtained with amitriptyline alone, in terms of frequency (-52.3% vs. -40.7%), intensity (-59.51% vs. -20.39%) and duration (-53.17% vs. -36.16%). This trend was confirmed by the HIT. Our data suggest that the combination of tizanidine with amitriptyline is faster than the amitriptyline alone in providing an improvement in the headache pattern and correlated QOL.
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Amitriptilina/administración & dosificación , Analgésicos/administración & dosificación , Clonidina/análogos & derivados , Cefalea/prevención & control , Cefalea/psicología , Calidad de Vida , Adulto , Amitriptilina/efectos adversos , Analgésicos/efectos adversos , Enfermedad Crónica , Clonidina/administración & dosificación , Clonidina/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Dimensión del DolorRESUMEN
In order to evaluate the potential risk of nelfinavir (NFV) accumulation in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients with liver disease, we investigated the concentrations of NFV and M8, the active metabolite of NFV, in plasma HIV-positive (HIV+) patients coinfected with HCV. A total of 119 HIV+ subjects were included in our study: 67 HIV+ patients, 32 HIV+ and HCV-positive (HCV+) patients without cirrhosis, and 20 HIV+ and HCV+ patients with cirrhosis. Most of the enrolled patients (chronically treated) were taking NFV at the standard dosage of 1,250 mg twice a day. To assay plasma NFV and M8 concentrations, patients underwent serial plasma samplings during the dosing interval at steady state. Plasma NFV and M8 concentrations were measured simultaneously by a high-performance liquid chromatography method with UV detection. The HIV+ and HCV+ patients with and without cirrhosis had significantly lower NFV oral clearances than the HIV+ and HCV-negative individuals (28 and 58% lower, respectively; P < 0.05), which translated into higher areas under the concentration-time curves for cirrhotic and noncirrhotic patients. The NFV absorption rate was significantly lower in cirrhotic patients, resulting in a longer time to the maximum concentration in serum. The mean ratios of the M8 concentration/NFV concentration were significantly lower (P < 0.05) in HIV+ and HCV+ subjects with cirrhosis (0.06 +/- 0.074) than in the subjects in the other two groups. The mean ratios for M8 and NFV were not statistically different between HIV+ and HCV-negative patients (0.16 +/- 0.13) and HIV+ and HCV+ patients without cirrhosis (0.24 +/- 0.17), but the interpatient variability was high. Our results indicate that the pharmacokinetics of NFV and M8 are altered in HIV+ and HCV+ patients, especially those with liver cirrhosis. Therefore, there may be a role for therapeutic drug monitoring in individualizing the NFV dosage in HIV-HCV-coinfected patients.