PubMed Health⌕ Search

Biomedical subjects

A Villar

Publications and source records attributed to A Villar.

At least 19 recordsLinked to original sources
PubMed2007

Screening for amnestic mild cognitive impairment and early Alzheimer's disease with M@T (Memory Alteration Test) in the primary care population.

OBJECTIVES: To design and validate a new screening test for amnestic Mild Cognitive Impairment (A-MCI) and early stage Alzheimer's disease (AD). METHODS: We develop a verbal episodic and semantic memory test: the Memory Alteration Test (M@T). Discriminative validity was assessed in a population sample of 400 aged individuals from primary care population centres in Barcelona, Spain, 50 patients with A-MCI according to Petersen et al. criteria, and 66 with early AD (Global Deterioration Scale-4 stage) according to the NINCDS-ADRDA criteria. RESULTS: The M@T is quick, 5-min, and easy to administer and to score. M@T mean scores were significantly different between all groups: 41.4 (SD = 4.9) in the primary care population, 31.5 (SD = 3.9) in the A-MCI group and 21.8 (SD = 4.9) in early AD. A cut-off score of 37 points had a sensitivity of 96% and a specificity of 79% for A-MCI diagnosis (AUC = 0.932). A cut-off score of 28 points had a sensitivity of 92% and a specificity of 98% for early AD diagnosis (AUC = 0.99) and a sensitivity of 87 % and specificity of 82% to differentiate between A-MCI and AD patients. CONCLUSION: The M@T provides efficient and valid screening for A-MCI and early stage AD, and discriminates between A-MCI and early AD patients.

Aged↗
PubMed2007

Current use of by-passing agents in Europe in the management of acute bleeds in patients with haemophilia and inhibitors.

The ultimate goal of treatment for patients with inhibitory antibodies should be to permanently eradicate the inhibitor by immune tolerance induction therapy (ITI). However, ITI procedures fail in a substantial number of patients and in many countries ITI is not even offered owing to its high cost. How patients with inhibitors are managed in different European countries is evaluated with a special focus on the use of by-passing agents, i.e. recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC), as well as the type of monitoring performed. Investigators from 22 large haemophilia centres participating within the network of the European Haemophilia Therapy Standardisation Board (EHTSB) were asked to complete a questionnaire. rFVIIa was routinely used in all centres for both children and adults at dosages ranging from 90 to 250 mug kg(-1) at an interval of 2-4 h. aPCC was used in 85% of the centres in adults and in 25% of the centres in children with haemophilia A at dosages of 50-100 IU kg(-1) every 6-12 h. The corresponding figures for children and adults with haemophilia B were 40% and 15% of the centres, respectively. Higher dosages of both agents were considered in the case of life-threatening bleeds. General recommendations were developed, based on the information provided by the survey. The results clearly indicate the need for well-designed comparative studies to optimize the use of by-passing agents.

Acute Disease↗
PubMed2006

Current European practice in immune tolerance induction therapy in patients with haemophilia and inhibitors.

The management of patients with inhibitors is an important challenge in haemophilia care. The lack of randomized controlled trials means that clinical decisions are generally based on subjective opinions, and purchasers' attention is likely to focus on the costs of treatment. In order to assess the current management of inhibitor patients and use of immune tolerance induction therapy (ITI) in Europe, we performed a survey within a European network of 21 comprehensive care centres from 14 countries (the European Haemophilia Therapy Standardisation Board). The survey identified a total of 381 patients with inhibitors attending the centres, 211 (55.4%) of whom had never been exposed to ITI. Between 1998 and 2003, the centres performed 233 procedures and 114 (48.9%) were successful. The survey demonstrated that dosing, which is the time to start and stop the ITI, the type of concentrate to use and the definition of success varied among the centres. Well-designed trials are warranted to guide decision-making, but in the absence of these studies we have developed consensus guidance for the management of inhibitor patients based on current clinical practice, as identified by the survey, and review of the literature.

Adult↗
PubMed2005

Prophylactic treatment effects on inhibitor risk: experience in one centre.

Nowadays, the elective treatment for children with haemophilia is prophylaxis. There is a common consensus that this modality of therapeutic approach is not associated with a higher risk of inhibitor development. We analysed the inhibitor incidence in 50 haemophiliac children and its relationship with mutations, type of clotting factor used and treatment modality. There was a significant correlation between receiving on-demand treatment and an increased incidence of inhibitors, independently of mutations or factor used. We advise putting haemophiliac children under prophylactic treatment as soon as possible, especially if they have mutations associated with high risk of inhibitor development, as prophylaxis is negatively associated with the development of inhibitors.

Blood Coagulation Factors↗
PubMed2005

Psychometric field study of the new haemophilia quality of life questionnaire for adults: the 'Hemofilia-QoL'.

Although there is a worldwide interest in the assessment of health-related quality-of-life (HRQoL) in haemophilia patients, no non-disease specific instruments (for adults) are readily available. In this paper, a haemophilia-specific quality-of-life assessment measure for adults (the Hemofilia-QoL questionnaire) has been developed and tested for psychometric properties in 121 adults with haemophilia living in Spain. The Hemofilia-QoL questionnaire is a self-report modular instrument that assesses nine relevant HRQoL domains for patients with haemophilia (e.g. physical health, daily activities, joint damage, pain, treatment satisfaction, treatment difficulties, emotional functioning, mental health, relationships and social activity). Psychometric examination involved the assessment of data quality, scaling assumptions, reliability (internal consistency and test-retest) and validity (concurrent; external clinical criterion and sensitivity). The Hemofilia-QoL 36-item version questionnaire had acceptable internal consistency and retest reliability values. The questionnaire shows excellent concurrent validity (with the SF-36 Health Survey) and external clinical criterion validity (haemophilia clinical status) and sensitivity (health status changes) as well. The Hemofilia-QoL is now available for adult assessment and is ready for use in clinical research in Spain.

Adolescent↗
PubMed2004

Health status and health-related quality of life of children with haemophilia from six West European countries.

A multicentre, international, cross-sectional study was carried out in the frame of field testing of the first haemophilia-specific quality-of-life (QoL) questionnaire (Haemo-QoL). The aim of this paper is to describe health status and health care and their impact on QoL in haemophilic children in Western Europe. Children aged 4-16 years with severe haemophilia without inhibitors were enrolled by 20 centres in France, Germany, Italy, the Netherlands, Spain and the United Kingdom. Clinical information was collected by the physicians with a medical documentation form. Health-related QoL (HRQoL) of children was assessed with Haemo-QoL, available for three age groups. Clinical data were available in 318 patients, 85.5% with haemophilia A. The mean age at first bleeding was 11 months, at first joint bleed 25 months. Functional joint impairments were found in 11.3%. Prophylaxis treatment was given to 66.7% of children in whom breakthrough bleeds occurred 0.4 times a month compared to 1.1 bleeds in children receiving on-demand treatment. A significantly higher factor consumption was found only in the two younger age groups of prophylaxis patients compared to on-demand patients. HRQoL was satisfactory in this cohort: young children were impaired mainly in the dimension 'family' and 'treatment', whereas older children had higher impairments in the so-called 'social' dimensions, such as 'perceived support' and 'friends'. Health care of children in Western Europe is progressively improving with a large diffusion of home treatment and prophylaxis. This provides a high level of health status and HRQoL, being better in haemophilic adolescents on prophylaxis.

Adolescent↗
PubMed2004

Development of a new disease-specific quality-of-life questionnaire to adults living with haemophilia.

A haemophilia-specific health-related quality-of-life questionnaire (named 'Hemofilia-QoL') was developed to assess quality-of-life in adults with haemophilia, and was psychometrically tested. Seventy-three interviews with haemophilia patients and health care professionals were used to generate the items included in the questionnaire, and expert ratings on the items formulated were used to screen them for potential omission. This was followed by psychometric testing in a sample of 35 patients. Preliminary psychometric testing of the revised questionnaire version, which contains 10 domains (physical health, physical role, joint damage, pain, treatment satisfaction, emotional role, mental health, social support), showed acceptable reliability (alpha = 0.94 for the Hemofilia-QoL total score) and validity, and this will be examined in a subsequent study with a larger patient sample.

Adolescent↗
PubMed2004

Pharmacokinetics of activated recombinant coagulation factor VII (NovoSeven) in children vs. adults with haemophilia A.

To establish the pharmacokinetic profile of activated recombinant coagulation factor VII (rFVIIa; NovoSeven in children with haemophilia A, and to compare it with the pharmacokinetic profile in adults with haemophilia A. Twelve children (2-12 years) received one single dose of rFVIIa 90 and 180 micrograms kg(-1) in randomized order separated by a washout period of 48 h to 1 month. Six adults (18-55 years) received a single dose of rFVIIa 90 micrograms kg(-1). The pharmacokinetic analyses were based on a non-compartmental method. In children, the plasma level of FVII increased proportionally with the dose. The total body clearance normalized for body weight was significantly faster in children than in adults (FVII:C, 58 vs. 39 mL kg(-1) h(-1) and FVIIa, 78 vs. 53 mL kg(-1) h(-1), P < 0.05). A trend towards a larger volume of distribution at steady-state in children than in adults was observed (P > 0.05). Dose proportionality was established for plasma concentrations of FVII in children with haemophilia A at the dose levels investigated (90 and 180 micrograms kg(-1) rFVIIa). Following administration of rFVIIa 90 micrograms kg(-1), significantly faster clearance was observed in children compared with adults, suggesting that higher doses of rFVIIa may be needed to achieve the same plasma levels as in adults.

Child↗
PubMed2004

Continuous infusion of B-domain deleted recombinant factor VIII (ReFacto) in patients with haemophilia A undergoing surgery: clinical experience.

This retrospective, open-label, non-comparative study evaluated continuous infusion of recombinant factor VIII (ReFacto), B-domain deleted recombinant FVIII (BDDrFVIII), in patients with haemophilia A undergoing surgery and requiring >5 consecutive days of treatment. Sixteen patients from eight centres underwent a total of 20 procedures. Haemostatic outcome was assessed as 'excellent' or 'good' in 75% of procedures, and target FVIII:C levels were maintained throughout the continuous infusion period. The reported volume of blood loss during surgery was also within the normal range for non-haemophilic patients for the type of surgery performed. Red blood cell transfusions were required to balance excessive blood loss during BDDrFVIII continuous infusion in eight (40%) procedures (seven patients), five with bleeding or requiring volume replacement and three to treat anaemia secondary to blood loss. Non-serious adverse events considered by investigators as possibly or probably related to BDDrFVIII continuous infusion were infrequent (n = 5) considering the duration of treatment (n =239 cumulative days of continuous infusion), and all of these were mild-to-moderate in severity. No thromboembolic complications were reported except for one case of thrombophlebitis occurring at the infusion site. Only two patients (four events) experienced serious adverse bleeding; BDDrFVIII was otherwise well-tolerated. These data show that continuous infusion of BDDrFVIII provides reliable haemostasis and is an effective and well-tolerated regimen for patients with haemophilia A undergoing surgery.

Adolescent↗
PubMed2003

Development and validation of a method for the polymorphic analysis of pharmaceutical preparations using near infrared spectroscopy.

A new method for the characterization and determination of crystalline miokamycin in a pharmaceutical preparation using near infrared spectroscopy is proposed. The procedure involves the identification against a spectral library of samples with contents above the legal limit (viz. 5% of the crystalline form in amorphous miokamycin) using the Mahalanobis distance as the discriminating criterion, and the determination of the total and crystalline contents using partial least squares models that provide errors <1%. The proposed method was validated following the ICH guidelines. Its simplicity and expeditiousness make it highly suitable for quality control analyses of solid dosage forms.

Chemistry, Pharmaceutical↗
PubMed2003

Progression of HIV infection and mortality by hepatitis C infection in patients with haemophilia over 20 years.

Hepatitis C virus (HCV) infection is an important cause of mortality in human immune deficiency virus (HIV)-positive haemophiliacs. This study describes progression to AIDS, death from HCV end-stage liver disease (ESLD) and all-cause mortality over 20 years. All HIV-positive haemophiliacs in La Paz University Hospital were included in this cohort. HIV seroconversion was estimated using mathematical techniques for interval-censored data from 1979 to 1985. Poisson regression was used to estimate rates of AIDS, death from ESLD and all causes in different periods: before 1988, 1988-89, 1990-91, 1992-93, 1994-95, 1996-97 and 1998-2001 using competing risk models. Among 383 cohort members, global AIDS incidence was 9.7 per 100 person-years, peaking in 1992-93 and dropping by 87% in 1998-2001 compared with before 1988 [incidence rate ratio (IRR) 0.13; 95% CI: 0.03-0.53]. Overall mortality was 7.5 per 100 person-years, was highest from 1992 to 1997, and fell by 66% in 1998-2001 compared with before 1988 (IRR 0.34; 95% CI: 0.14-0.81). Eighteen (5%) persons died of ESLD which represented 19% of deaths before 1988, 4% during 1988-89, 1990-91 and 1992-93, 2% in 1994-95, 10% in 1996-97 and 33% in 1998-2001. Overall death rate from ESLD was 0.5 cases per 100 person-years with no statistically significant trend observed over time. Important reductions in HIV disease progression to AIDS and death have been observed from 1998 to 2001, and can be attributed to highly active antiretroviral therapy. Although no increase in the rate of HCV-related deaths can be demonstrated, HCV accounts for an increasing proportion of deaths in the recent years.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group.

BACKGROUND: The purpose of this study was to determine the relative efficacy of doxorubicin versus methotrexate in combination with intravenous cyclophosphamide and 5-fluorouracil (FAC versus CMF) as adjuvant chemotherapy for operable breast cancer. PATIENTS AND METHODS: Over a 4-year period, 985 women undergoing curative surgery for breast cancer (T1-3 N0-2 M0, stage I-IIIA, UICC) from nine hospitals were stratified with respect to axillary node involvement (node positive versus node negative) and randomized to receive either FAC (500/50/500/m(2)) every 3 weeks for six cycles or CMF (600/60/600/m(2)) every 3 weeks for six cycles. RESULTS: The relative dose intensities of FAC and CMF were 87% and 85% of planned doses, respectively. Unadjusted data indicated a non-significant trend towards better results with FAC. In the prospectively formed subset of node-negative patients, disease-free survival and overall survival were statistically superior in the FAC treatment arm (P = 0.041 and 0.034, respectively), but this advantage was not seen in the subset of node-positive patients, probably because of a difference in the percentage of patients with four or more positive nodes. Adjusting data for size of treatment effect and potential interactions (number of positive nodes, tumor size, treatment center), the overall relative risk (RR) of disease recurrence and death were significantly lower with FAC treatment (RR 1.2, P = 0.03, and RR 1.3, P = 0.05, respectively). This result was mainly due to the difference observed in the node-negative patient population. Toxicity was mild: FAC induced more alopecia, emesis, mucositis and cardiotoxicity; this last was of clinical concern, but was infrequent and manageable. CMF induced more conjunctivitis and weight gain. There were no toxic deaths. CONCLUSIONS: Doxorubicin in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil is superior to methotrexate in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil as adjuvant chemotherapy for operable breast cancer. A treatment effect is particularly evident in the node-negative patients. Although the clinical toxicity of FAC is greater than that of CMF, the levels were manageable and clinically acceptable.

Adolescent↗
PubMed2002

The use of haemostatic drugs in haemophilia: desmopressin and antifibrinolytic agents.

Over the last 4 decades, there have been very significant advances in the treatment of haemophilia. Plasma products first became available in the 1960s, beginning with cryoprecipitate and then intermediate-purity plasma concentrates, for the treatment of haemophilia A and B. The disasters of viral infections amongst people with haemophilia in the 1980s served to stimulate both the development of techniques of viral inactivation of concentrates and the manufacture of purer products. We therefore now have safe plasma products that are also pure in that they are concentrates of only the deficient protein responsible for the congenital coagulopathy. Preparations of specific coagulation proteins obtained using recombinant biotechnology techniques have been available since 1995. By contrast, pharmacological options for the treatment of the haemophilia remain very limited. The only therapeutic alternatives of real practical value which have been available in the last 30 years for the treatment of haemophilic patients are desmopressin, antifibrinolytic agents, aprotinin, concentrated oestrogens, and local haemostatic agents such as topical thrombin or fibrin glue. This article aims to assess the pharmacological basis and accumulated experience relating to these drugs when used for the prevention and treatment of bleeding in patients with haemorrhagic disorders.

Antifibrinolytic Agents↗
PubMed2002

Successful thyroidectomy in a patient with Hermansky-Pudlak syndrome treated with recombinant activated factor VII and platelet concentrates.

Hermansky-Pudlak syndrome is a rare autosomal recessive disorder characterized by the absence of platelet dense bodies in association with albinism. We present the use of recombinant activated factor VII (rFVIIa) in a patient with Hermansky-Pudlak syndrome who underwent total thyroidectomy because of a large richly vascularized nodule (10 cm) compressing the trachea. The patient had a prolonged bleeding time (> 20 min) that remained unchanged after platelet transfusions. However, after infusion of platelets plus rFVIIa, it diminished to 5 min. The platelet aggregation response to adenosine diphosphate and collagen was diminished. Since an early age, the patient had repeated nose bleeding and an episode of melena requiring several tampons, cauterization and transfusions of packed red cells. In this case, we used rFVIIa in bolus for 1 day (four doses of 120 microg/kg every 2 h and six doses of 100 microg/kg every 3 h) and transfusion of platelet concentrates beginning just prior to surgery. No evidence of local bleeding complication could be detected during the entire post-operative period. The hemoglobin level remained normal and no transfusions of packed red cells were necessary. No adverse events occurred.

Blood Coagulation Tests↗
PubMed2002

[Acromegaly, multinodular toxic goiter and papillary carcinoma of the thyroid, potential role of G proteins].

It is well known that non-toxic goiter is not uncommon in acromegaly, but hyperthyroidism only occasionally occurs. In addition, the risk for the development of a malignant process is increased, the most often seen is carcinoma of the colon. Thyroid carcinoma is not frequent, nevertheless the rate in these patients is higher than general population. In this article, a case of hyperthyroidism, papillar carcinoma and acromegaly is presented. We reviewed the literature an discussed the possible pathogenesis.

Acromegaly↗
PubMed2001

Delayed inner ear maturation and neuronal loss in postnatal Igf-1-deficient mice.

Insulin-like growth factor-1 (IGF-1) has been shown to play a key role during embryonic and postnatal development of the CNS, but its effect on a sensory organ has not been studied in vivo. Therefore, we examined cochlear growth, differentiation, and maturation in Igf-1 gene knock-out mice at postnatal days 5 (P5), P8, and P20 by using stereological methods and immunohistochemistry. Mutant mice showed reduction in size of the cochlea and cochlear ganglion. An immature tectorial membrane and a significant decrease in the number and size of auditory neurons were also evident at P20. IGF-1-deficient cochlear neurons showed increased caspase-3-mediated apoptosis, along with aberrant expression of the early neural markers nestin and Islet 1/2. Cochlear ganglion and fibers innervating the sensory cells of the organ of Corti presented decreased levels of neurofilament and myelin P(0) in P20 mouse mutants. In addition, an abnormal synaptophysin expression in the somata of cochlear ganglion neurons and sensory hair cells suggested the persistence of an immature pattern of synapses distribution in the organ of Corti of these animals. These results demonstrate that lack of IGF-1 in mice severely affects postnatal survival, differentiation, and maturation of the cochlear ganglion cells and causes abnormal innervation of the sensory cells in the organ of Corti.

Aging↗
PubMed2001

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: a stepwise developed treatment schedule for advanced head-and-neck cancer.

PURPOSE: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. METHODS AND MATERIALS: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m(2) of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. RESULTS: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. CONCLUSIONS: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions.

Administration, Inhalation↗