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M J Otero

Publications and source records attributed to M J Otero.

At least 19 recordsLinked to original sources
PubMed2006

[Adverse drug events in out-patients as the cause of an initial consultation to neurology].

INTRODUCTION: The aim of this study was to determine the incidence and type of neurological adverse drug events as the cause of an initial consultation to neurology, identify the medications involved and evaluate the possibilities of prevention. METHODS: Prospective observational study lasting 1 year (February 10, 2004 to February 9, 2005) that included all new adult outpatients at a neurology ward. Suspected adverse drug events were evaluated by two investigators in order to establish causality relationships, severity, preventability and types of medication errors associated with the preventable cases. RESULTS: In a total of 685 patients who attended the neurology consult, 60 neurological adverse drug events were detected (8.7%), of which 70% were moderate and 30% mild. The most frequent adverse events detected were medication overuse headache (51.6%), mainly due to acetaminophen and ergot derivatives, and drug-induced Parkinsonism (33.3%), especially related to trimetazidine or sulpiride. Fifty-five adverse events (91.6%) were considered potentially preventable. Medication errors associated were overuse and self-medication (33.7 %), failure to follow treatment adequately (25.6%), excessive duration of treatment (16.3%) and prescribing an unnecessary medication (14.0%) or an inappropriate one (10.5%). CONCLUSIONS: The incidence of adverse drug events motivating an initial visit to a neurologist is high and the majority of these cases are preventable. Greater knowledge on the part of physicians concerning medication overuse headache and drugs that induce Parkinsonism, as well as public health education on the risks involved with the use of analgesics, could contribute to prevention.

Adolescent↗
PubMed2001

Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis.

We report the case of an 18-year-old patient who received an allogeneic bone marrow transplant from an HLA-identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft-versus-host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.

Adolescent↗
PubMed1999

Population estimation of valproic acid clearance in adult patients using routine clinical pharmacokinetic data.

The aim of the present study was to estimate valproic acid (VPA) clearance values for adult patients with epilepsy, using serum concentrations gathered during their routine clinical care. Retrospective steady state serum concentrations data (n=534) collected from 208 adult patients receiving VPA were studied. Data were analysed according to a one-compartment model using the NONMEM program. The influence of VPA daily dose (Dose), gender, age, total body weight (TBW), and comedication with carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PB) were investigated. The results of the population pharmacokinetics analysis were validated in a group of 30 epileptic patients. The final regression model for VPA clearance (Cl) was: $¿rm Cl¿left (¿rm L/h ¿right )=0¿rm. 004¿times TBW¿times Dose ¿0.304¿¿rm ¿times 1.363¿,¿rm CBZ¿times 1. 541¿,¿rm PHT¿times 1.397¿,¿rm PB.$ The inter-individual variability in VPA clearance, described by a proportional error model, had a variation coefficient (CV) of 23.4% and the residual variability, described using an additive model, was 11.4 mg/L. These results show that VPA clearance increased linearly with TBW, but increases nonlinearly with increasing VPA daily dose. Concomitant administration of CBZ, PHT and PB led to a significant increase in VPA clearance. The model predictions in the validation group were found to have satisfactory precision and bias. In conclusion, inter-individual variability in VPA clearance can be partly explained by TBW, daily dose and bitherapy with CBZ, DPH or PB. Inclusion of these factors allows this variability to be reduced by 37.23% which may be very useful for clinicians when establishing the initial VPA dosage regimen. However, the magnitude of inter-individual plus residual variabilities, remaining in the final model, render these dosage predictions imprecise and justify the need for VPA serum level monitoring in order to individualize dosage regimens more accurately.

Adolescent↗
PubMed1999

Valproate population pharmacokinetics in children.

OBJECTIVE: A population analysis of the kinetics of valproic acid (VPA) in children with epilepsy was performed in order to characterize the covariates which influence VPA clearance (CL). METHODS: A total of 770 steady-state serum concentration samples was analysed. These were collected during VPA therapy from 255 children, aged 0.1-14 years and weighting 4-74 kg. Age, total body weight (TBW), VPA daily dose, sex and comedication with carbamazepine (CBZ) were considered as covariates. Population analysis was made with NONMEM program, assuming a one-compartment model, fixing the VPA absorption rate, bioavailability and distribution volume at values found in the literature. The results of the population pharmacokinetics analysis were validated in a group of 45 epileptic patients. RESULTS: The final regression model for VPA clearance, that included TBW (kg), daily dose (mg/kg) and CBZ comedication as covariates with a significant influence on this parameter, was as follows: CL (L/h) = 0.012 TBW0.715 DOSE0.306(1.359 CBZ). The coefficient of variation for interpatient variability in CL was 21.4% and the residual variability estimated was 23.9% for a concentration of 65 mg/l. In order to estimate the predictive performance of the selected final model, predictions of the VPA serum concentrations were calculated and compared with VPA measured concentrations in the validation group. This assessment revealed an important improvement in the predictive performance of VPA concentrations in comparison with the basic model that did not include any covariates (root squared mean error: 19.50 vs. 39.73 mg/l). CONCLUSION: A population pharmacokinetic model is proposed to estimate the individual CL for paediatric patients receiving VPA in terms of patient's dose, weight and concomitant CBZ, in order to establish a priori dosage regimens.

Adolescent↗
PubMed1998

Normal and clonal B lineage cells can be distinguished by their differential expression of B cell antigens and adhesion molecules in peripheral blood from multiple myeloma (MM) patients--diagnostic and clinical implications.

Human MM is a haematologic disorder characterized by the accumulation of malignant plasma cells (PC), primarily in the bone marrow (BM). Although these cells characteristically home to the BM, in recent years several groups have detected the presence of related malignant B cells in the peripheral blood (PB) which could be implicated in the progression and spread of the disease. However, the proportion and origin of these clonotypic circulating B cells is still controversial. In this study, using a triple-staining flow cytometric procedure and a whole blood lysis method, PB B lineage cells could be divided into two populations according to their distinct repertoires of cell adhesion molecules and B cell antigens in untreated MM patients. The results show that: (i) the percentage and the absolute number of PB CD19+ B cells were decreased in MM patients compared with controls; (ii) the quantity and percentage of B cell antigens (CD20, CD22, CD24, DR, CD138) and adhesion molecules (beta1- and beta2-integrins, CD44, CD54, CD56, CD61 and CD62L) expressed by these PB CD19+ cells of MM patients and healthy subjects were similar and all of them were virtually polyclonal cells; (iii) a very minor circulating CD19-CD38++CD45-/dim subset was also detected which expressed CD138 (B-B4) (high intensity), monoclonal cytoplasmic immunoglobulin (cIg), and was negative for pan-B antigens (CD19, CD20, CD24, DR), surface immunoglobulin (sIg) and several adhesion molecules such as CD62L, CD18 and CD11a; this CD19-CD38++CD45-/dim CD138++ subset was not found in normal blood and exhibited a phenotypic profile which was closely related to that of malignant BM plasma cells, with the exception of the CD56 antigen. Polymerase chain reaction (PCR) analysis of IgH clonotypic rearrangements confirmed these results. We postulate that, in MM patients, circulating B lineage cells may be divided into two different categories: polyclonal CD19+ B cells and a very minor proportion of clonal CD138++ PC that escape from the BM.

Antigens, CD↗
PubMed1997

Carbamazepine population pharmacokinetics in children: mixed-effect models.

The aim of the authors' study was to investigate the factors affecting carbamazepine (CBZ) clearance (CL) in children with epilepsy. The factors evaluated were total body weight (TBW), age, dose, sex, and phenobarbital (PB) and valproic acid (VA) comedication. A total of 387 steady-state serum concentration samples was analyzed. These were collected during CBZ therapy from 201 children, aged 1-14 years and weighting 9-78 kg. Population CL was calculated by using NONMEM, with a one-compartment model with first-order absorption and elimination. The absorption rate, bioavailability, and volume of distribution were set at values found in the literature. The model found best to describe the data was CL = (0.0122 TBW + 0.0467 Dose) Age0.331 (1.289 PB). The interindividual variability in CL had a variation coefficient (CV) of 11.8%, and the residual error, described by using an additive model, was 1.5 mg/l. The results show that CL increases linearly with TBW and nonlinearly with age; thus older children have a lower CL with respect to TBW than do younger ones. Likewise CL was seen to increase with the increase in the CBZ dose, suggesting a dose-dependent autoinduction of CBZ metabolism. Concomitant PB administration affected CL: however, sex and VA comedication did not affect it significantly. The final regression model for CL, was validated in a different group of 74 children. The standarized prediction error (SPE) was not significantly different from zero (SPE = 0.028), indicating that the model proposed for CL can be used to make accurate dosage recommendations. With these population estimates, CBZ doses that would be suitable for pediatric patients of different ages are proposed.

Adolescent↗
PubMed1996

Scedosporium apiospermum pneumonia after autologous bone marrow transplantation.

Although opportunistic infections after bone marrow transplantation (BMT) are very common, only five cases of Pseudallescheria boydii infection have been reported in the literature, two of which were autopsy findings. A case of Scedosporium apiospermum infection after BMT, treated initially with amphotericin B (total dose of 2.5 g) and then with itraconazole (for 25 days), is reported here. When the patient failed to improve, Scedosporium apiospermum pneumonia was diagnosed and therapy was changed. The patient was treated successfully with miconazole (600 mg/8h for 32 days) and ketoconazole (200 mg/8h for 7 days) plus surgery.

Adult↗
PubMed1996

Application of population pharmacokinetics to the optimization of theophylline therapy.

The aim of this study was to determine theophylline clearance (Cl) values in adult patients using serum concentrations gathered from routine clinical care. This information was used to estimate an a priori dosing regimen that would permit steady-state concentrations of 5-15 mg/litre, now recommended for the treatment of chronic asthma, and to evaluate the need to establish monitoring strategies when theophylline is given at these lower doses and when it can be expected that almost no adverse effects are likely. Retrospective data from 204 asthmatic and COPD patients, with a total of 517 serum concentrations, were studied. Population pharmacokinetic analysis was performed with the MULTI(ELS) computer program according to a one-compartment model. The influence of the following factors on theophylline Cl were investigated: body weight (TBW, IBW and LBM) and age as continuous variables, and gender, smoking habit and the presence of congestive heart failure (CHF) as indicator variables. To validate the results of the population pharmacokinetic analysis, a second independent group of 63 patients was studied prospectively. Hypothesis testing to evaluate potentially significant factors produced a final model in which Cl was based on IBW (kg) and age (years), and was reduced by 25% in patients with moderate CHF and increased by 28% in patients who smoked (Cl (litres/h) = (0.037 IBW-0.006 age) x 1.284 smoke x 0.751 CHF). The variability in Cl, expressed as the coefficient of variation, was 36%. In adult non-smoker and non-CHF patients, application of a maintenance dosing regimen calculated from IBW and age using the final model for Cl would theoretically afford only 1.5% of patients with potentially toxic concentrations. Thus, measurement of serum theophylline concentrations (STC) would only be required when other conditions known to alter theophylline metabolism exist, such as smoking or disease factors. These appreciations could have important clinical implications at a time when the potential immunomodulatory activity of theophylline is being emphasized and health resources should be allocated properly.

Adolescent↗
PubMed1994

Erythropoietin in the treatment of delayed immune hemolysis of a major ABO-incompatible bone marrow transplant.

Delayed immune hemolysis can be observed after major ABO-incompatible bone marrow transplants (BMT). The management of these hemolytic episodes includes transfusion of group O red blood cells and increases of immunosuppression. Here we report the case of a 25-year-old patient who developed overt immune hemolysis on day +50 after a HLA-identical ABO-incompatible BMT. To avoid added immunosuppression, erythropoietin was started: an increase in reticulocytes sufficient to maintain hemoglobin despite persistent hemolysis was observed. We conclude that erythropoietin may have a role in the management of delayed-onset hemolysis of major ABO-incompatible BMT, especially when added immunosuppression is undesirable.

ABO Blood-Group System↗