Adherence and effectiveness of highly active antiretroviral therapy.
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Biomedical subjects
Publications and source records attributed to A Díez.
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Previous studies show that fast exploration of a T-shaped maze by mature mice may predict an above average longevity. Since the nervous and the immune systems work in a coordinated fashion, and it seems that these two homeostatic systems both influence organismic aging and suffer a senescent decline, we have performed a comparative study of the above behavioral parameter and different functions of three representative immune cells: lymphocytes, macrophages and natural killer (NK) cells obtained from old (76 +/- 1 weeks of age) female OF1-Swiss mice. At 70 weeks of age the mice were divided into a 'fast' and a 'slow' group, containing 100 and 0%, respectively, of animals able to explore the 50 cm-long first arm of the maze in 20 s or less. At 76 +/- 1 weeks of age the animals were sacrificed, the peritoneal cell suspensions were obtained and the immune organs (axillary nodes, spleen and thymus) were isolated. The following leukocyte functions were studied in peritoneal macrophages: adherence to substrate, mobility (spontaneous and chemotaxis), ingestion of particles and superoxide anion production whereas mobility, lymphoproliferative response to the mitogen Con A and NK activity were studied in the immune-organ leukocyte suspensions. The results show that the aged fast mice have better immune functions than the aged slow mice.
BACKGROUND: The use of calcitonin is very common in patients diagnosed with osteoporosis. The objective of this study was to determine the percentage of adequate prescriptions of calcitonin for patients with osteoporosis and to estimate the costs due to inadequate prescription. PATIENTS AND METHODS: Observational study. Four pharmacies in Osona County (Barcelona) were randomly selected. During two time periods, July-September and November-December of 1994, all women filling prescriptions for calcitonin in any of the eight pharmacies were invited to participate in the study. Adequate and inadequate prescription of calcitonin was determined based on the patient's clinical record. Justifiable and non-justifiable prescriptions were then determined after implementing a protocol and reviewing X-rays of the spine. RESULTS: Forty-eight women agreed to participate (participation rate: 68%). In the first analysis, 58.3% (95% CI: 43-72) of prescriptions were determined to be inadequate whereas in the second analysis 29.2% (95% CI: 17-44) were considered non-justifiable. Chronic back pain was associated with non-justifiable prescription of calcitonin (odds ratio: 5.2; 95% CI: 1.3-33.4). In the best of situations, the excess in annual spending due to inadequate prescription was estimated at 13 million pesetas for Osona County, 1,300 million for Catalonia, and 4,300 million for Spain. CONCLUSIONS: Between one-third and one-half of patients prescribed calcitonin in the study area apparently do not need it. Many cases of chronic back pain are being treated as osteoporosis without being properly studied. The costs derived from this incorrect practice are important. This study highlights the need for better practices in the diagnosis of osteoporosis.
BACKGROUND: Densitometric screening for osteoporosis in postmenopausal women has not been demonstrated cost-effective. We have tried to identify clinical factors for screening previous to densitometry avoiding unnecessary explorations. PATIENTS AND METHODS SETTING: outpatient clinics of a menopausal unit in a 450-bed general hospital. Cross-sectional study, in two steps, of two groups of 140 and 284 women attending for physiological menopause. A clinical questionnaire, physical data and lumbar densitometry (Hologic QDR 1000) were obtained classifying the cases as "normal" or "low bone mass" (osteopenia or osteoporosis) according with the WHO criteria. In the first group a logistic regression analysis was done to identify predictive factors for abnormal densitometry, then validated in the second group. Sensitivity, specificity, predictive values (PV) and classification ability of clinical factors were analyzed. RESULTS: Four factors were independent predictors of abnormal densitometry: age > 51 (odds ratio [OR] = 6.64; 95% CI, 2.36-18.7); body weight < 70 kg (OR = 4.32; 95% CI, 1.71-10.09); years of fertility < 32 (OR = 3.77; 95% CI, 1.36-10.04), and number of live births > 2 (OR = 3.47; 95% CI, 1.27-9.53). Presence of one factor offers: sensitivity 91.9%; specificity 15%; positive PV 66.6%, and negative PV 50%, whereas the presence of two factors offers: sensitivity 62.7%; specificity 70%; positive PV 79.9%, and negative PV 50.3%. Clinical screening allows, when two factors are present, to avoid a 35.5% of densitometries and the false-negative cases represent 18%. CONCLUSIONS: Detection of bone-risk clinical factors (abnormal densitometry) yields a screening, previous to densitometry, that avoids at least one third of explorations in women with physiological menopause, improving the efficiency of the test.
There is considerable support for the concept that oxygen free radicals and related lipid peroxides play a key role in the pathogenesis of normal senescence and of age-related chronic degenerative diseases, including atherosclerosis. This has led to a great deal of interest regarding peroxidized LDL, which seems to be more atherogenic than LDL. In contrast, the relationship of total serum or plasma lipid peroxides (which also have a marked atherogenic action) with both aging and atherogenesis are not well understood. In view of the above, we have determined the level of serum lipid peroxide (expressed as thiobarbituric acid reactive substances) in a sample of 100 healthy men and women ranging in age from 20 to 70 years. Our data show that there is an age related increase in the concentration of lipid peroxide, with men showing higher or about equal values than women until about 60 years, after which age women show the higher values. Our data also suggest that in certain men and women, aging is linked to a decline in the competence of the oxyradical-detoxifying mechanisms, which results in increased serum lipid peroxidation. Further research is needed to find out if lowering the serum peroxide levels of aging subjects by diet supplementation with antioxidants will decrease that risk. An adequate intake of antioxidants seems especially indicated in post-menopausal women because of their apparent greater sensitivity to age related oxygen stress.
Alendronate is an aminobisphosphonate with a potent anti-reabsorptive action that does not appear to interfere with bone mineralization, and is even able to increase bone mineral density in osteoporotic postmenopausal women through a still not fully understood mechanism. This study was conducted to assess the direct effect of alendronate on diverse aspects of normal human osteoblast physiology. For that purpose, the in vitro effect of a wide range of concentrations [from 10(-1) to 10(-12) mol/L] of alendronate on cell viability, proliferation, collagen synthesis, and the mineral-depositing capacity of normal human osteoblasts was tested. Alendronate effects were examined at 48 and 96 h of culture in the presence or absence of fetal calf serum. In vitro alendronate affected osteoblast viability at concentrations equal to or higher than 10(-4) mol/L. At concentrations equal to or higher than 10(-3) mol/L, no viable cells were observed in cultures. In vitro alendronate at concentrations between 10(-5) and 10(-12) mol/L did not have any effect on the proliferative capacity of normal human osteoblasts determined by two different techniques: (1) tritiated thymidine incorporation to DNA and (2) cell counting. Collagen synthesis by normal human osteoblasts showed a tendency to decrease following incubation with alendronate supplemented with fetal calf serum. This decrease was only statistically significant after 96 h of culture; however, a dose-response effect could not be documented. Finally, no effect of alendronate was observed on calcium deposition in vitro by normal human osteoblasts at concentrations equal to or lower than 10(-5) mol/L. In conclusion, the present study shows that alendronate in vitro does not affect viability, proliferation, and mineral deposit capacity of normal human osteoblasts at the concentration at which it inhibits by 50% the resorptive capacity of osteoclasts that for this drug has been reported as 2 x 10(-9) mol/L.
Myelodysplastic syndromes (MDS) are a group of clonal disturbances with defective cellular differentiation. Vitamin D3 (VD) analogues can act on the differentiation and maturity of different cell lines. We studied the effects of VD on a series of patients with MDS in an open-design trial. Nineteen patients, 12 men and seven women, with MDS were included. Patients were 74.8 +/- 5.6 years (mean +/- SD), seven had refractory anaemia with ringed sideroblasts, five had refractory anaemia, one had refractory anaemia with excess of blasts and six had chronic myelomonocytic leukaemia. All the patients were in a low to intermediate risk group. Mean follow-up period was 26.21 months, range 9-75. Responders were defined as follows: granulocyte or platelet count increase by 50%, or haemoglobin increase of 1.5 g/dl or transfusion needs decrease by 50%. The first five patients received 266 microg of calcifediol three times a week and the other 14 received calcitriol (0.25-0.75 microg/d). Response was observed in 11 patients. In the calcifediol-treated group, one case responded, three were nonresponders, and one showed progression. In the calcitriol group, 10 were responders (two with major response), and four were non-responders. No correlation was observed between baseline levels of vitamin D metabolites and the presence of response. No hypercalcaemia was observed. Treatment with vitamin D3 metabolites could induce a long-standing response of the haematological disturbance in some low-intermediate risk MDS patients without inducing hypercalcaemia.
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BACKGROUND: The objective of the study is to assess the acceptance, compliance and side effects of antiretroviral therapy in relation to age, gender, risk group, HIV infection stage and type of treatment. METHODS: This is a cohort-observational study. Inclusion criteria were: consecutive non-selected IIV patients in which antiretroviral treatment was indicated on medical grounds. The study was carried out from February 1990 to February 1996. We measured: a) poor compliance, when suspicion (by medical history, analytical data and administered drug control by the hospital pharmacy) more than a 25% of prescribed treatment was not taken; b) adverse events that obliged to discontinued the drug; and c) long-term therapy, when treatment acceptance and compliance and regular follow-up was stated. Statistics methods: Ji-square and Student's t- test. RESULTS: 567 patients were included, with a median follow up of 609 days. Male 413, female 154. Mean age: 32.9 years. Average CD4+ cells: 0.260 x 10(9)/L. There was a history of intravenous drug use (IDU) in 60.4% of cases and CDC classification group C (1993) 34.2%. Antiretroviral treatment was refused by 16.6% of patients, more frequently IDU patients (21.3%, p < 0.0001). There was a drop-out rate of 17.3%, with no differences among different groups. Poor compliance was found in 23% of cases, more frequently in IDU and group-C patients. Adverse events were observed in 22.6% of cases, more frequently in female (33.8%, p < 0.0004) and group C patients (28.6%, p < 0.04). The treatments used (AZT monotherapy, DDI monotherapy, AZT DDI and AZT + DDC) had no influence on compliance or follow-up. Long-term follow-up and compliance was achieved in 47.6% of patients, with a lesser degree in IDU (42.4%, p < 0.002) and group C patients (39.7%, p < 0.006). CONCLUSIONS: HIV-infected patients treated with antiretroviral agents, not enrolled in clinical trials, had similar rates of compliance that patients with other chronic diseases. Treatment refusal and poor compliance were more frequent in IDU patients, while adverse events were more frequent in patients with more advanced HIV infection stage.
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BACKGROUND: To analyze the case-mix and efficiency in a group of Services of Internal Medicine (IM) from 52 Spanish hospitals with routinary clinical information system. METHODS: From a total amount of 566,726 discharges during 1992, we studied the 71,430 corresponding to IM, analyzing the Minimum Basic Data Set and the Diagnosis-Related Groups (DRG). The hospitals were classified as level A (< 250 beds), B (251-599) and C (600 or over). We analyzed: Major Diagnostic Category (MDC); DRG, raw average length of stay (ALOS); outliers, trimmed ALOS; mortality; case-mix index; performance index; ajusted ALOS (by standard performance and case-mix); associated complications; number of diagnoses per discharge. A Chi-square test was used for qualitative variables and a mean-comparison test (independent data) for the quantitative ones. RESULTS: Among the Internal Medicine Departments, IM was the Service that cared most patients, even more in the small-size hospitals. The most frequent DRG were: chronic obstructive pulmonary disease (COPD) 6.5% (DRG 088); simple pneumonia & pleuresy 6.1% (DRGs 089-090); heart failure 5.9% (DRG 127); stroke 4.5% (DRG 014); and angor pectoris 2.4% (DRG 140). The ALOS was shorter in the A-level hospitals (10.1 days) vs. B-level (11.6) and C-level (14.4). However, the trimmed ALOS was more homogeneous (A 8.8; B 9.9; C 11.7). The complexity indexes increased with the hospital level although the performance index also increased. CONCLUSIONS: The IM services provide care for a high percentage of hospital patients, especially in the small-size centers. In these, less complex patients are seen, with decreased comorbidity, complications and mortality and they solve their patients with shorter ALOS than the IM services in the large-size hospitals.
A semiparametric approach to match probability calculations using single locus probes has been developed and compared graphically with other standard methods by a one-sample simulation. The density functions obtained using this method are closer to the real distributions than those obtained by conventional approaches. Our method does not need to establish an arbitrary match threshold, which has been a source of problems in practical applications of standard methods. Moreover, it can be adjusted to any particular conditions by setting the experimental error and correlation of each laboratory. To assess the practical performance of this method we carried out a comparison experiment using a sample of 229 individuals analysed in duplicate.
The influence of sleep and meal schedules on performance in short distance running was assessed in a group of 8 national-class competition male sprinters. They were tested on Saturdays for five consecutive weeks. On each testing day, the performance time for an 80 m sprint was registered on eight different occasions during days 1 and 4, on 9 occasions on days 2 and 5, and on 7 occasions on day 3. On control days (days 1 and 4) performance gradually improved during the morning up to 13:00 h, decreased at 15:00 h, and again improved thereafter, with a maximum peak performance at 19:00 h. On day 2, in which sleep/wake cycles and meal-times were advanced for two hours, and on day 3, in which timetables were delayed for two hours, maximum peak performance was observed at 17:00 h and 21:00 h, respectively. At the time of maximum peak performance on both days a statistically significant improvement was observed as compared with the control day (day 2, p < 0.01; day 3, p = 0.001). On day 5, in which only the sleep/wake cycle was advanced for two hours, performance in the afternoon and evening was similar to that recorded on days 1 and 4. We observed that easy manipulation of sleep and meal schedules would allow competitive sprinters to synchronize peak power output with the time of the athletic event, increasing the chances for improvement in performance.
BACKGROUND: Fever of unknown origin (FUO) has been insufficiently studied in patients infected with HIV. The aim of this study was to determine the incidence, mean hospital stay, etiology, diagnostic methods and clinical course in patients infected with HIV and FUO. METHODS: Descriptive prospective study of patients infected with HIV and with FUO for a period of 24 months (February 1993-February 1995). Out of a total of 1,202 admissions, 100 were prompted by FUO in 95 patients (61 males, 34 women). Sixty-six per cent were parenteral drug abusers or had been so and the mean T CD4+ lymphocyte count was 0.061 x 10(9)/1 +/- 0.075 x 10(9)/1. RESULTS: The incidence of FUO was 8.3 every 100 patients/year. The mean hospital stay was 31.3 +/- 17.8 days, compared with an overall mean stay for HIV-positive patients of 14.6 +/- 8 days (p < 0.001). An etiologic diagnosis was achieved in 90% of cases. Pulmonary or extrapulmonary tuberculosis accounted for approximately 50% of cases, whereas non tuberculous mycobacteria (MAI and M. kansasii) for 20%. The other etiologies (CMV, visceral leishmaniasis, PCP, toxoplasmosis, cryptococcosis, lymphoma) accounted each for less than 5% of diagnoses. In 14 occasions there were two concomitant diagnoses. Mortality rate was 22%, which was higher when two simultaneous diagnosis were present [RR: 3.17 (1.5-6.6)]. In 45% of fatal cases one of the diagnoses went undiagnosed premortem. The highest diagnostic yield was obtained with sputum culture (34.2% of diagnosis) and blood culture (21.5%). CONCLUSIONS: FUO in common in patients infected with HIV, with important health resources consumption associated. The obtention of diagnosis was possible in a high percentage of patients. It is associated with a high hospital mortality rate. The most common diagnoses were tuberculosis and infections by other mycobacteria. It is possible to obtain the diagnosis with non-invasive procedures in 75% of cases.
AIDS is the first cause of opportunistic infections. The objective of the present study was the evaluation of the efficiency of bone marrow aspirate (BMA) for diagnosis of opportunistic infections in HIV infected patients with prolonged fever. Charts from 92 patients with BMA from 1992 to 1994 were reviewed. Diagnosis was achieved in 14.1% of cases. Diagnosis cannot be made by other methods in six leishmaniasis and in two disseminated tuberculosis. The sensibility was of 33.3% for mycobacterial infections, the sensibility of hemoculture was of 50%. The hemoglobin level was lower for patients with diagnostic BMA than for patients with not diagnostic BMA (77 g/l vs 97 g/l, p < 0.0004). The WBC counts was not different in both groups of patients, and platelets counts was greater in patients with BMA diagnostic (165 x 10(9)/l vs 102 x 10(9)/l, p < 0.001). In the patients with hemoglobin lower than 100 g/l the diagnostic efficiency was 18.6% (11 of 59 cases). The BMA was unprofitable in HIV infected patients with prolonged fever without hemocytopenias. Profitability increase in patients with hemoglobin lower than 100 g/l. The BMA in useful for leishmania identification. The hemoculture has greater sensitivity than BMA for the diagnosis of mycobacterial disseminated infection.
The effect of glutathione depletion on the viability of freshly isolated synaptosomes from whole brain was investigated in young and aged mice. Aging did not influence the GSH and ATP levels and the viability of these synaptosomes. However depletion of glutathione caused by the cytosolic glutathione inhibitor diethyl maleate (1 mM) resulted in a significant decline, after 60 min of incubation, in ATP levels and viability in the synaptosomes from aged mice but not in those from young mice. When synaptosomes were incubated in the presence of the mitochondrial glutathione inhibitor ethacrynic acid (0.2 mM) there was a similar decline in glutathione, ATP levels and synaptosomal viability, both in young and aged mice. These results emphasize the relative importance of the cytosolic glutathione pool for the maintenance of the plasma membrane integrity in synaptosomes from aged mice.
The allele frequency distributions of four VNTR loci amplified by PCR have been studied in a population of 205 individuals from Spain. The loci analysed are D1S80 and three STRs: HUMTH01, HUMFES/FPS and HUMACTBF2 (SE33). The former was visualized in Metaphor agarose gels, and the STRs in sequencing polyacrylamide gels under denaturing conditions which could separate alleles with differences of a single base. This is of particular importance in the HUMTH01 locus, a tetrameric STR in which two alleles (9.3 and 10) were detected differing in a single base. Furthermore, HUMACTBP2 has at least 30 alleles, some of which may vary by as little as one base. At this locus a variation in the allele mobility was observed, depending on the electrophoretic conditions. For this reason, there should be careful consideration before this marker is accepted and validated as a common interlaboratory system. This paper does not include any comparison of the frequencies obtained for this locus with other recent studies. For the rest of the loci, the frequencies found have been compared with other published population studies; they show a degree of difference, particularly in the D1S80 locus. Finally, the systems were tested for Hardy-Weinberg equilibrium, and some statistical parameters of forensic interest were calculated.