Role of health-related quality of life measurements in the design of drug clinical trials.

OBJECTIVE: Health-related quality of life (HRQL) measurements enable us to take patient perception into account when evaluating treatment outcomes from clinical trials (CTs). The purpose of this study was to evaluate the use of HRQL questionnaires as a measurement of efficacy in CT design. METHODS: A duplicate systematic review of the CTs examined by a Clinical Research Ethics Committee between 1995 and 2006 was performed to check for use of HRQL. We gathered data concerning general aspects including medical specialty, drugs evaluated, methodological quality and inclusion of economic variables. For CTs including HRQL measurements, we analysed the type of questionnaire in use. Where there were no HRQL measurements, we analysed the methodological possibilities for including them, and the relevance of their absence. RESULTS: A total of 242 CTs were analysed; 69 (28.5%) included HRQL measurements, and 10 CTs (4.1%) used them as a primary endpoint. Only 22 CTs used more than one questionnaire. Data analysis by therapeutic area showed that HRQL was most commonly studied in the fields of rheumatology, urology, psychiatry and oncology. Only 33 CTs included economic variables. CONCLUSIONS: Measurements based on clinical parameters are the most commonly used means of measuring efficacy. Only a small percentage of CTs take the patient's perception of his/her health into account, despite the increasing importance given to this parameter. Including HRQL questionnaires in CTs design is still far from common.

Role of “health-related quality of life” measurements in the design of drug clinical trials

Objective Health-related quality of life (HRQL) measurements enable us to take patient perception into account when evaluating treatment outcomes from clinical trials (CTs). The purpose of this study was to evaluate the use of HRQL questionnaires as a measurement of efficacy in CT design. Methods A duplicate systematic review of the CTs examined by a Clinical Research Ethics Committee between 1995 and 2006 was performed to check for use of HRQL. We gathered data concerning general aspects including medical specialty, drugs evaluated, methodological quality and inclusion of economic variables. For CTs including HRQL measurements, we analysed the type of questionnaire in use. Where there were no HRQL measurements, we analysed the methodological possibilities for including them, and the relevance of their absence. Results A total of 242 CTs were analysed; 69 (28.5%) included HRQL measurements, and 10 CTs (4.1%) used them as a primary endpoint. Only 22 CTs used more than one questionnaire. Data analysis by therapeutic area showed that HRQL was most commonly studied in the fields of rheumatology, urology, psychiatry and oncology. Only 33 CTs included economic variables. Conclusions Measurements based on clinical parameters are the most commonly used means of measuring efficacy. Only a small percentage of CTs take the patient's perception of his/her health into account, despite the increasing importance given to this parameter. Including HRQL questionnaires in CTs design is still far from common (AU)

Objetivo Las medidas de “calidad de vida relacionada con la salud” (CVRS) permiten incorporar la percepción del paciente en la evaluación de los resultados obtenidos en los ensayos clínicos (EC). El objetivo de este estudio fue evaluar el uso de cuestionarios de CVRS como medida de eficacia en el diseño de ECs. Métodos Se lleva a cabo una revisión sistemática por duplicado de los ECs analizados por un Comité Ético de Investigación Clínica, entre los años 1995 y 2006. Se recogieron datos relativos a aspectos generales como la especialidad médica, fármacos evaluados, calidad metodológica o inclusión de variables económicas. Para aquellos ECs que incluían medidas de CVRS, se analizó el tipo de cuestionario utilizado. Para aquellos que no analizaban CVRS, se analizó la posibilidad metodológica de su análisis, así como la relevancia de su ausencia. Resultados Se analizaron un total de 242 ECs, 69 (28,5%) de los cuales incluyeron medidas de CVRS, 10 (4,1%) como variable primaria. Únicamente 22 ECs emplearon más de un cuestionario. El análisis de datos por áreas terapéuticas puso de manifiesto que reumatología, urología, psiquiatría y oncología, fueron las áreas donde la CVRS fue analizada en una mayor proporción. Únicamente 33 ECs incluyeron variables económicas. Conclusiones Las medidas basadas en parámetros clínicos son las más usadas como medidas de eficacia. Una pequeña proporción de ECs considera la percepción del estado de salud del paciente, en contraste a la creciente importancia asignada a estos aspectos. La inclusión de cuestionarios de CVRS en el diseño de ECs, está lejos de ser una medida habitual (AU)

[Modifications of the leukocytes in professional cyclists throughout the competition]. / Modificaciones de los leucocitos en ciclistas profesionales a lo largo de la competición.

In this work we plan to analyze and establish the leukocyte variations due to the effort of the competition, throughout 4 short-term turns (5 days and an average of 750 km each one), in 16 professional cyclists (24.8 2.3 year-old, 71.0 4.5 kg and 179.3 5.0 cm). The hematological parameters analyzed were leukocytes (WBC), neurtrophils (NEUT), lymphocytes (LYM), monocytes (MON), eosinophils (EOS) and basophils (BAS), and the results are presented as the percentage on the total number of leukocytes. The serum level of cortisol was also measured along study time (before and after each one of the 4 turns). The results show that the total number of leukocytes increase significantly in the turns, both in basal conditions (B) and after finishing the turn (F). The NEUT show an ongoing increase in their basal values from the first to the fourth round, but its values at the conclusion of this are significantly lower with respect to the situation of reference of the beginning of the cyclist turn. The LYM in rest upon beginning the turns are kept in similar values during the study period, increasing significantly after the 5 days of competition of each turn. The cortisol, as they are happening the turns, they decline its rates both in rest and after the competition (5 days turns). In conclusion the physical exercise throughout several cyclists turns give rise an increases in the leukocytes that is associated to a progressive decline of the cortisol levels probably because of the conditioning that the cyclist shows throughout the competition.

Early introduction of cereals into children's diets as a risk-factor for grass pollen asthma.

BACKGROUND: The prevalence of asthma has increased from the 1950s to the 1990s. The relationship between diet and asthma is an area of controversy that has never been fully evaluated. Attempts at dietary prevention of asthma have produced conflicting results. We have recently identified allergens from cereals that show cross-reactivity with proteins in grass pollen. An early intake of cereals in the diet during early life might cause IgE sensitization to cereals. It is not known whether such sensitization predisposes the development of allergy to pollen. METHODS: To test this hypothesis, a cross-sectional study and an observational case-control analysis of reviewed data were carried out on 16381 patients who had been admitted to our Allergy Unit between 1989 and 1999. All the patients underwent allergy tests to identify asthma risk-factors. All information in our data base was analysed using the SPSS computer system. RESULTS: There has been an increase of 7.8% in incidences of allergic asthma and a 7.3% increase in asthma due to grass pollen in the last decade. Grass-pollen asthma was associated with sensitization to cereals. The early introduction of cereals in the diet of children was found to be a risk factor for grass-pollen asthma (OR = 5.95; 95% CI 3.89-9.10). CONCLUSIONS: These findings document the progression of allergic asthma during a decade in a large sample of people who were influenced by similar environmental conditions and studied with the same diagnostic methods. This study represents the largest database of patients in which a common food is shown to be a risk factor for asthma.

Prevalence of abnormal levels of serum tumour markers in elderly people.

The study was conducted to evaluate the prevalence of abnormal levels of several serum tumour markers in an institutionalized elderly population. Serum tumour markers assay of carcinoembryonic antigen (CEA), the carbohydrate antigens CA 19-9, CA 72-4 and CA 15-3 (Enzymun-test, Boehringer Mannheim GmbH Diagnostic), alpha-fetoprotein (AFP) and prostate specific antigen (PSA) (Abbot Diagnostic Division) were performed in 228 unselected, institutionalized elderly subjects, whose mean age (SD) was 82.4 (5. 79) range (66-99 years). Patients with acute or neoplastic diseases were excluded from the study. The serum markers were also measured in 52 healthy young adults (controls). Using the established threshold values, 92 subjects (40%) were found to have at least one elevated marker. PSA was elevated in 33%, CA 19-9 in 16%, CEA in 11. 5%, CA 15-3 in 11%, CA 72-4 in 8% and AFP in 3%. We found a significant difference in the serum levels between the two groups for CEA, CA 19-9. CA 15-3, and PSA (p < 0.0001). Healthy aged people appear to have an elevated prevalence of elevated levels of serum tumour markers. The results suggest that apart from PSA, elevated antigen levels in elderly subjects are related to the ageing process itself rather than to occult pathology.

[Sexually transmitted diseases in a high risk subpopulation from the province of Soria]. / Enfermedades de transmisión sexual en una subpoblación de alto riesgo de la provincia de Soria.

BACKGROUND: Women who practise prostitution constitute a high risk group for acquiring sexually transmitted diseases (STD). The aim of this study was to know the frequency of these processes among prostitutes in the province of Soria. METHODS: A descriptive transversal study including 86 women who voluntarily went to a Family Planning Center (FPC) in Soria was carried out in the period between October 1986 to December 1991. Patients were submitted to: investigation of T. vaginalis, N. gonorrhoeae, G. vaginalis, C. trachomatis, S. agalactiae and yeast infections. Complete clinical history was obtained from all including sociodemographic variables and those of risk of infection. RESULTS: Of the 86 women studied 12 (14%) had positive syphilis tests (treponemic and reaginic). In 12 (14%) N. gonorrhoeae was isolated. The search for C. trachomatis was positive in 16 (18.60%). In 19 (22.10%) T. vaginalis was directly observed. Twenty-three (26.74%) presented some type of positive serology to B virus. Five (5.81%) were HIV-1 seropositive. Candida spp. was isolated in 27 (31.39%) as was G. vaginalis and S. agalactiae in 21 (24.41%). Clinical examination did not show any macroscopic lesion suggesting venereal disease. CONCLUSIONS: Infection by Candida spp. and G. vaginalis were found to be the most frequent. The seroprevalence of HIV-1 in this series was the lowest in the country having a clear relation with the use of intravenous drugs (IVDA). Sexually transmitted diseases maintain a high prevalence in high risk groups such as prostitutes thus requiring energic prevention plans, overall in the group of young IVDA prostitutes.

[Intestinal inflammatory disease in the province of Soria. Retrospective clinical and epidemiologic study from 1981 to 1990]. / Enfermedad inflamatoria intestinal en la provincia de Soria. Estudio clínico y epidemiológico retrospectivo del período 1981-1990.

The inflammatory bowel disease cases in Soria have been reviewed from 1981 to 1990. Thirty-two cases of ulcerative colitis (UC) and thirteen cases of Crohn's disease (CD) have been found. The mean incidence was 3.2/100.000 inhabitants/year in UC and 1.3/100.000/inhabitants/year in CD. The prevalence was 32 and 13/100.000 inhabitants respectively. We have found a progressive increase in incidence in both UC and CD during the period analyzed. Epidemiologic data (considering the majority come from rural areas), clinical course, endoscopic and radiologic findings, are similar to the results published in the literature. We have found a minor percentage that other authors in extraintestinal signs, complications and need of surgical intervention.

[The effect of thyroparathyroidectomy, parathyroid hormone and calcitonin on plasma strontium in rats]. / Efecto de la tiroparatiroidectomía, la parathormona y la calcitonina sobre el estroncio plasmático en rata.

The effect of thyroparathyroidectomy (TPTX) on the plasmatic Sr concentrations in rats previously supplemented with this element, has been studied, as well as its effect on the treatment of TPTX rats with hormonal combinations and, finally, the one presenting hormonal excess or defect of the phosphocalcium metabolism regulating hormones: parathormone (PTH) and calcitonin (CT). Twenty four hours after TPTX, the plasmatic Sr concentrations show a pattern similar to those of Ca and Mg and contrary to Pi. The subsequent evolution is different, as the plasmatic concentrations increase, probably due to the maintenance of Sr supplementation. The administration of this element to TPTX rats and the treatment with a hormonal combination with two of the following hormones: PTH, CT and T4 antagonize the hormonal effect on the restoration of the plasmatic concentrations of the elements analyzed. The PTH excess and defect (TPTX treated with CT + T4) show plasmatic increases in Sr; the CT excess provokes decreases while the defect (administration of PTH + T4) causes increases. The T4 administration reproduces the CT effects, but inconsistently. These results suggest that CT may be the hormone that plays a regulating role in the plasmatic Sr concentrations.

[Familial Parkinson disease]. / Enfermedad de Parkinson familiar.

We report the clinical findings and the pedigree of 10 patients of a family from Blacos, a small village in the Soria province, who had Parkinson's disease and in whom secondary causes and other diseases such as essential tremor or OPCA, to be considered in the differential diagnosis, had been ruled out. There were 6 males and 4 females with a mean age of 72.1 years; the mean age at the onset of symptoms was 67 years. All had the akinetic-rigid type of disease, and associated tremor was present in two cases. 90% were in functional classes I-II of the UPRS (United Parkinson's disease Rating Scale). 50% are presently receiving levodopa therapy, and only one has complications due to it. Emphasis is made on the etiological and pathogenetical heterogeneity of Parkinson's disease, where exogenous factors are probably superimposed to a genetic susceptibility.

[Skin and ungual pigmentation caused by ftorafur]. / Pigmentación cutánea y ungueal por ftorafur.

We report the case of a sixty-seven-years-old male diagnosed of a gastric adenocarcinoma that presented brown pigmentation in the dorsal of his both hands and fingernails while being on treatment with ftorafur, an analogous of 5-fluorouracil. To our knowledge this side effect has not been previously reported for ftorafur.