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M Miravitlles

Publications and source records attributed to M Miravitlles.

At least 19 recordsLinked to original sources
PubMed2006

Alpha-1-antitrypsin deficiency: optimal therapeutic regimen based on population pharmacokinetics.

BACKGROUND: Exogenous doses of 60 mg/kg alpha(1)-antitrypsin (AAT) every 7 days are recommended in patients with severe AAT deficiency. However, long term administration of weekly doses is not well accepted by patients. Using pharmacokinetic simulations, we evaluated whether steady state minimum concentrations of total AAT can be maintained above the threshold of 0.5 g/l with longer intervals between doses. METHODS: Several sets of exogenous AAT versus time simulations were studied using a non-linear mixed effect approach with dosage regimens every 7, 14, 21, and 28 days. For each regimen the mean exogenous AAT trough concentrations and 5/95th percentiles were determined. The results obtained were applied to estimate the individual optimal dose at 7, 14, and 21 days in six patients using Bayesian analysis. RESULTS: The simulations showed that a dose of 50 mg/kg AAT every 7 days was sufficient to obtain nadir concentrations. Doses of 120 and 100 mg/kg every 14 days were also adequate, but 180 mg/kg given every 21 days required total AAT monitoring to avoid underdosage. Longer intervals were inappropriate. Dosage individualisation confirmed that AAT infusions given every 14 days maintained the nadir level of 0.5 g/l without a significant dose increase compared with current practice. When the time span between doses was fixed at 21 days, a mean relative AAT dose enhancement of 91% and 13%, respectively, was required to achieve sustained total AAT concentrations above the target level for 100% and 85% of the interval between doses. CONCLUSIONS: It is feasible to extend the interval between doses of AAT to 14 or 21 days to achieve adequate trough total AAT concentrations. This study might be used as a starting point for clinical evaluation of the regimens described.

Aged↗
PubMed2006

[Attitudes toward the diagnosis of chronic obstructive pulmonary disease in primary care].

OBJECTIVE: Although the prevalence of chronic obstructive pulmonary disease (COPD) has increased among women, it is still considered a disease that mainly affects men. This study aimed to identify the diagnostic attitudes of primary care physicians toward patients with COPD according to gender and spirometric results. METHODS: A representative sample of 839 primary care physicians participated in the study. Each physician dealt with 1 of 8 hypothetical cases based on a patient diagnosed with COPD. In half the cases, the physician was told the patient was a man. The other half of the physicians were told the same patient was a woman. After presentation of the medical history and results of physical examination, the physicians were asked to state a probable diagnosis and indicate the diagnostic tests that were necessary. They were then told the results of spirometry, which indicated obstruction ranging from moderate to severe. Negative results of bronchodilator tests and oral corticosteroid tests were then communicated. RESULTS: COPD was more likely to be the preliminary diagnosis for male patients than for females (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.15-2.1). This gender bias disappeared once the physicians were shown the abnormal results of spirometry. Patients with severe obstruction were more likely to be diagnosed with COPD than those with moderate obstruction (OR, 1.5; 95% CI, 1.08-2.09). CONCLUSIONS: There is gender bias in the diagnosis of COPD. Patients with moderate obstruction are often believed not to have COPD. These biases may compromise the early diagnosis of the disease in a group of patients with ever increasing risk.

Attitude of Health Personnel↗
PubMed2006

[Risk factors for increased cost of exacerbations of chronic bronchitis and chronic obstructive pulmonary disease].

OBJECTIVE: To identify what variables characterizing the patients, exacerbations, and treatment of chronic bronchitis and chronic obstructive pulmonary disease (COPD) are associated with a higher direct health cost. METHOD: Observational pharmacoeconomic study of exacerbations of chronic bronchitis and COPD (of probable bacterial etiology, defined as Anthonisen types I or II). Direct health costs were assessed during 30 days of follow-up. Logistic regression was employed for statistical analysis, with calculation of the adjusted odds ratios (OR). An exacerbation cost greater than 150 euros was defined as the dependent variable. RESULTS: Data on 1164 patients were collected by 252 physicians. Pharmacoeconomic data were complete in 947 patients (82.6%). In the first 30 days, 206 sought medical attention because of unsatisfactory response to treatment (21.8%), 69 (7.3%) attended the emergency room, and 22 (2.3%) were admitted to hospital. Overall, 101 exacerbations (10.7%) were classified as high cost (> 150 euros). Continuous oxygen therapy (OR = 7.58) and previous hospitalization (OR = 2.6) were associated with high-cost exacerbations, whereas diagnosis of chronic bronchitis (OR = 0.41) and treatment of the exacerbation with moxifloxacin or amoxicillin-clavulanic acid as opposed to clarithromycin (OR = 0.38) were associated with low-cost exacerbations. CONCLUSION: Treatment failure was reported for 21.8% of the patients with exacerbations of chronic bronchitis and COPD. Repeated medical visits and requests for complementary tests were the main factors responsible for increased cost. Variables associated with high-cost exacerbations were continuous oxygen therapy, previous hospitalization, and treatment with clarithromycin as opposed to moxifloxacin or amoxicillin-clavulanic acid.

Aged↗
PubMed2006

Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha1-antitrypsin deficiency in European countries.

The current study focuses on developing estimates of the numbers of individuals carrying the two most common deficiency alleles, PI*S and PI*Z, for alpha1-antitrypsin deficiency (AT-D) in Europe. Criteria for selection of epidemiological studies were: 1) AT phenotyping performed by isoelectrofocusing or antigen-antibody crossed electrophoresis; 2) rejection of "screening studies"; 3) statistical precision factor score of > or = 5 for Southwest, Western and Northern Europe, > or = 4 for Central Europe, > or = 3 for Eastern Europe; and 4) samples representative of the general population. A total of 75,390 individuals were selected from 21 European countries (one each from Austria, Belgium, Latvia, Hungary, Serbia-Montenegro, Sweden and Switzerland; two each from Denmark, Estonia and Lithuania; three each from Portugal and the UK; four each from Finland, The Netherlands, Norway and Spain; five each from Russia and Germany; six from Poland; eight from Italy; and nine from France). The total AT-D populations of a particular phenotype in the countries selected were: 124,594 ZZ; 560,515 SZ; 16,323,226 MZ; 630,401 SS; and 36,716,819 MS. The largest number of ZZ (5,000-15,000) were in Italy, Spain, Germany, France, the UK, Latvia, Sweden and Denmark, followed by Belgium, Portugal, Serbia-Montenegro, Russia, The Netherlands, Norway and Austria (1,000-2,000), with < 1,000 in each of the remaining countries. A remarkable lack in number of reliable epidemiological studies and marked differences among these European countries and regions within a given country was also found.

Alleles↗
PubMed2005

[Quality of life in patients with COPD: quantification criteria and therapeutic repercussions].

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronica diseases in developed countries. Prognosis of the disease is mainly determined by the degree of air flow obstruction. However, other factors, such as degree of deterioration of the quality of life related with health have been demonstrated to be significantly correlated with morbidity and mortality in COPD. Thus, one of the main objectives of the treatment of COPD is to improve the health condition of the patients, beyond the possible improvement of the lung function. New drugs developed for the treatment of COPD have shown a different impact on the health condition of those affected by COPD.

Humans↗
PubMed2005

Results of a case-detection programme for alpha1-antitrypsin deficiency in COPD patients.

Alpha1-antitrypsin (alpha1-AT) deficiency is an underdiagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The present authors have conducted a nationwide case detection programme of alpha1-AT deficiency in unselected patients with COPD using dried blood spots. The first phase analysed samples from 971 patients by determining alpha1-AT concentrations and identifying the deficient Z allele by genotyping using rapid real-time PCR. The second phase analysed 1,166 samples with alpha1-AT concentrations and identified both the S and the Z allele, but only in samples with low alpha1-AT concentrations. A total of eight (0.37%) individuals with the severe deficiency PiZZ were detected. In addition, three patients were identified with the PiSZ genotype in the second phase (0.3%). The global cost of the programme was 41,512, which represents 19.42 per sample and 5,189 per PiZZ detected. A sensitivity analysis demonstrated that performing Z genotype to all samples would have resulted in increased costs of 28 per sample and 7,479.5 per PiZZ case identified. In conclusion, a case detection programme of alpha1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood spots is feasible and at a reasonable cost per case detected. Diagnostic yield and costs depend largely on inclusion criteria and the protocol for processing of samples.

Adult↗
PubMed2004

[Costs of chronic obstructive pulmonary disease in Spain. Estimation from a population-based study].

OBJECTIVE: In the studies carried out to date, the cost of chronic obstructive pulmonary disease (COPD) may have been overestimated due to the inclusion of previously diagnosed patients seeking medical attention for their symptoms. As a result, the severity of the cases included in these studies may have been greater than in an unselected sample of the general population. The aim of the present study was to estimate the direct cost of COPD on the basis of a representative sample of the overall Spanish population between 40 and 69 years of age (from the IBERPOC study). METHOD: The cost was evaluated retrospectively by means of a questionnaire completed by the 363 patients with COPD from the IBERPOC study with questions referring to the previous year. Standardized spirometry was performed on all the patients by a pneumologist in each of the 7 geographical areas in which the study was carried out. RESULTS: Hospitalization accounted for the greatest expenditure (41% of total), followed by drug therapy (37%). The cost was euro;98.39 per patient, and euro;909.50 per previously diagnosed patient. The cost per person of severe COPD was more than 3 times that of moderate COPD and more than 7 times that of mild COPD. The estimated annual cost of COPD in Spain was euro;238.82 million (for 1997). CONCLUSION: The present study, which was the first to estimate the cost of COPD in a representative sample of the general population, found the cost to be lower than in studies analyzing samples of patients with previous diagnoses of COPD. The cost distribution is not in line with recommended health care practices, underlining the need to optimize resources used to monitor and treat the disease, with an emphasis on early diagnosis.

Adult↗
PubMed2004

Economic evaluation of the antibiotic treatment of exacerbations of chronic bronchitis and COPD in primary care.

This was an observational and economic survey performed in primary care practices throughout Spain to assess the effectiveness and direct medical costs derived from antibiotic treatment of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) in primary care. A total of 252 physicians included 1456 valid patients, 80% were male and the mean age was 68.2 years (SD = 9.8). The antibiotic treatment administered was moxifloxacin in 575 (39.5%), amoxicillin/clavulanate in 460 (31.6%) and clarithromycin in 421 (28.9%). No significant differences were found in clinical and demographic characteristics between treatment arms. The 30-days follow-up visit was completed by 1097 (75%) patients, who were therefore valid for economic evaluation. During follow-up, 440 new medical visits were generated, 69 patients required attendance in emergency wards (6.3%) and 22 were hospitalised (2%). The overall mean cost of exacerbation was Euro 118.58 [95% confidence interval (CI) = Euro 92.2-144.9] and Euro 52.44 (44.2%) were due to therapeutical failure. The mean cost of exacerbation was Euro 111.46 (95% CI = Euro 73.4-149.5) for patients treated with moxifloxacin, Euro 109.45 (95% CI = Euro 68.2-150.7) for those treated with amoxicillin/clavulanic acid and Euro 138.95 (95% CI = Euro 89.4-188.5) for patients receiving clarithromycin. In conclusion, a significant number of patients require new medical interventions after ambulatory treatment of exacerbations of CB or COPD. The mean cost of an exacerbation was Euro 118.58 and failure was responsible for 44.2% of the total cost of exacerbation.

Aged↗
PubMed2004

Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 year follow up study.

BACKGROUND: A study was undertaken to evaluate exacerbations and their impact on the health related quality of life (HRQL) of patients with chronic obstructive pulmonary disease (COPD). METHODS: A 2 year follow up study was performed in 336 patients with COPD of mean (SD) age 66 (8.2) years and mean (SD) forced expiratory volume in 1 second (FEV(1)) 33 (8)% predicted. Spirometric tests, questions regarding exacerbations of COPD, and HRQL measurements (St George's Respiratory Questionnaire (SGRQ) and SF-12 Health Survey) were conducted at 6 month intervals. RESULTS: A total of 1015 exacerbations were recorded, and 103 (30.7%) patients required at least one hospital admission during the study. After adjustment for baseline characteristics and season of assessment, frequent exacerbations had a negative effect on HRQL in patients with moderate COPD (FEV(1) 35-50% predicted); the change in SGRQ total score of moderate patients with > or =3 exacerbations was almost two points per year greater (worse) than those with <3 exacerbations during the follow up (p = 0.042). For patients with severe COPD (FEV(1) <35% predicted) exacerbations had no effect on HRQL. The change in SGRQ total score of patients admitted to hospital was almost 2 points per year greater (worse) than patients not admitted, but this effect failed to show statistical significance in any severity group. There was a significant and independent seasonal effect on HRQL since SGRQ total scores were, on average, 3 points better in measurements performed in spring/summer than in those measured in the winter (p<0.001). CONCLUSIONS: Frequent exacerbations significantly impair HRQL of patients with moderate COPD. A significant and independent effect of seasonality was also observed.

Adult↗
PubMed2003

[Screening program for alpha-1 antitrypsin deficiency in patients with chronic obstructive pulmonary disease, using dried blood spots on filter paper].

Alpha-1 antitrypsin (AAT) deficiency is an under-diagnosed disease and screening programs have therefore been recommended for patients with chronic obstructive pulmonary disease (COPD). We present the results of the pilot phase of a screening program for AAT deficiency in order to evaluate the technique used, the procedures for transporting samples and the results obtained. Over a period of one month, five centers collected samples from all COPD patients for whom plasma concentrations of AAT or Pi phenotype had not yet been determined. Capillary blood spots were dried on filter paper and then sent by surface mail to a central laboratory for study. An immunonephelometric assay was used to determine AAT and DNA phenotyping was done by use of a Light Cycler. Samples were analyzed from 86 COPD patients (76 men, 10 women) with a mean age of 68.2 years. AAT deficiency was ruled out for 74 patients (86%) who had concentrations above the cutoff established, although one of them was MZ heterozygote by genotype. Among the 12 remaining patients (13.9%), only two also had a Z allele. The rest were individuals with concentrations below the established threshold and no evidence of a Z allele (10 patients, 11.6%). The Z allele frequency observed (3/172; 1.74%) was very similar to that found in the general population. The results of this pilot study allowed us to confirm that the method used to collect samples worked well. The sampling method is applicable, easy and well-accepted by participating physicians. It allowed AAT concentrations and Z allele deficiency to be determined. The method correlates well with standard techniques used for samples in whole blood.

Aged↗
PubMed2003

[A comparison of moxifloxacin and amoxicillin in the treatment of community-acquired pneumonia in Latin America: results of a multicenter clinical trial].

Since community-acquired pneumonia (CAP) is a common disease with a high morbidity rate, it is important to obtain information concerning its etiology and susceptibility to antibiotics across different geographic areas. This study presents data obtained in 5 Latin American counties in the course of an international clinical trial that evaluated the efficacy and safety of treatment with either moxifloxacin or amoxicillin administered for 10 days to patients suspected of having CAP caused by a pneumococcal infection. Details are given of the pathogens identified, the patterns of sensitivity to antibiotics observed, and the clinical and microbiological results obtained.A total of 84 patients were studied, of whom 70 (83.3%) were evaluated at the end of the trial to determine the efficacy and safety of the treatment received. Gram-positive bacteria were found in samples from 29 patients (80.5%). The pathogen was Streptococcus pneumoniae in 28 of those cases (77.7%). Gram-negative bacteria were found in 7 patients (19.4%), the most common being Haemophilus influenzae in 3 patients (8.3%). The presence of atypical microorganisms was detected in 18 of the 70 patients (25%), mainly Mycobacterium pneumoniae (n=11), and in 6 cases (8.5%) the infection was mixed. Ten strains of S. pneumoniae (35.7%) were shown to be susceptible to penicillin, 2 (7.1%) were highly resistant, and 16 (57.1%) showed moderate resistance. The clinical success rate at the final visit after treatment was 94.1% for moxifloxacin and 91.7% for amoxicillin. The results of this trial demonstrate a high prevalence of S. pneumoniae with reduced susceptibility to penicillin in patients with CAP in Latin America. It also revealed a high incidence of atypical pathogens and mixed infection in 8.6% of patients. This information should be taken into account when establishing protocols for empirical treatment of CAP in Latin America.

Amoxicillin↗