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Biomedical subjects

J M Peña

Publications and source records attributed to J M Peña.

At least 19 recordsLinked to original sources
PubMed2006

Bayesian analysis using continuous likelihood ratios for identifying pleural exudates.

STUDY OBJECTIVES: To ascertain if equations that calculate continuous likelihood ratios (CLRs) for pleural exudates improve pleural fluid categorization, especially when false positive or false negative test results are obtained by using Light's criteria. DESIGN AND SETTING: Retrospective review of the clinical and pleural fluid data from a consecutive series of patients with pleural effusion who underwent thoracentesis at the University Hospital Arnau de Vilanova (Lleida, Spain) over an 11-year period. PATIENTS AND METHODS: A total of 1490 patients with pleural effusion (298 transudates and 1192 exudates) were recruited into the study. The presence of a transudate or exudate was established by clinical judgment. We examined the comparative diagnostic accuracy of 4 tests (i.e. pleural fluid protein and lactate dehydrogenase (LDH), and pleural fluid to serum protein and LDH ratios) for discriminating between transudates and exudates. Decision thresholds were determined by receiver operating characteristics (ROC) analysis. Equations for calculating CLRs derived from a logistic regression analysis based on a previously described method. RESULTS: Individual pleural fluid tests did not differ in their diagnostic accuracies according to ROC analysis. We calculated CLRs for the elements of Light's criteria and pleural fluid protein, and also illustrated the sequential use of CLRs for determining posttest probabilities. Overall, CLR formulas had marginal performance for the correct categorization of pleural fluid. CONCLUSIONS: CLRs provide a probabilistic statement as to the likelihood an effusion is a transudate or exudate. However, clinical judgment is little changed by the application of CLRs, and in doubtful cases a great amount of uncertainty remains. This Bayesian approach is likely to have no major impact on the clinical practice.

Bayes Theorem↗
PubMed2006

[Immunophenotype of progression to AIDS: deficiency, activation and dysfunction of CD4 and CD8 T-cells].

INTRODUCTION: One key piece of information required when deciding whether to initiate antiretroviral therapy is the risk of AIDS. The aim of this study was to better characterize the baseline immunophenotypic profile of patients with progression to AIDS. MATERIAL AND METHODS: A cross-sectional analysis of the distribution of functional subpopulations of CD4+ and CD8+ T-lymphocytes in 85 intravenous drug addicts with HIV infection. The values observed on patient enrolment in a prospective study were analyzed. Those patients who progressed and did not progress were compared to the HIV-negative controls. Lymphocyte subpopulations were studied by flow cytometry, including the markers: CD3, CD4, CD7, CD8, CD45RO, CD38, HLA-DR and CD25. RESULTS: The immunophenotypic profile that precedes progression to AIDS was mainly characterized by an increase in memory (CD45RO) activated cells and total activated CD4+ and CD8+ cells, and by an increase of T CD4+ cells that have loss expression of markers as receptor or the differentiation marker CD7 (CD7-). Patients not meeting laboratory criteria to initiate antiretroviral therapy (> 350 CD4+ T-cells and < 30,000 HIV-ARN-copies/ml) also showed increased levels of CD4+ and CD8+ activation subsets (CD4+CD38+DR+, CD8+CD38+). DISCUSSION: The fact that immunological activation may contribute to immunological and clinical deterioration of HIV-positive patients might be an additional factor which should be taken into account when deciding whether to initiate antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Multidrug-resistant tuberculosis without HIV infection: success with individualised therapy.

OBJECTIVE: To evaluate the results of the treatment of non-HIV-infected multidrug-resistant tuberculosis (MDR-TB) patients admitted to a tuberculosis unit in a reference centre between June 1998 and December 2000. RESULTS: Twenty-five patients were studied (23 men). Empirical treatment was selected according to drugs previously used and adjusted according to in vitro test results. Patients had previously received an average of 5.5 drugs and were resistant to an average of 4.7 drugs. They were treated with a median number of four drugs (an injectable drug plus three oral drugs) for a median of 18 months. Ofloxacin and cycloserine was used in 17 cases (68%), ethionamide/prothionamide in 18 (72%) and para-aminosalicylic acid in 12 patients (48%). Psychological support and counselling was provided. Two patients required surgery. Globally, 21 patients (84%) met cure criteria. After a 24-month follow-up, none of the 21 patients who successfully completed treatment presented relapse or death. CONCLUSION: MDR-TB is a curable disease in non-HIV-infected patients. Individualised treatment regimens should be based on treatment history and the study of in vitro susceptibility and by promoting a relationship with the patient that makes adherence to treatment easier and minimises side effects.

Adult↗
PubMed2006

[Late nephrology referral influences on morbidity and mortality of hemodialysis patients. A provincial study].

OBJECTIVE: To evaluate the influence of late referral to nephrology of the patients with chronic renal failure in the morbimortality of the patients who start hemodialysis. SUBJETS AND METHODS: There were included in the study the patients who started hemodialysis (HD) as first form of treatment, and that survived at least three months in both hospitals of reference of the province of Huesca from january 1990 to december 2001. Patients who started HD after acute renal failure were excluded. Clinical and analytical data were determined for each patient at the start of HD and during the follow-up. Early (ER) and late referral (LR) were defined by the time of first nephrology encounter greather than or less than 4 months respectively, before HD initiation. Morbidity analysis (using multiple linear regression with rate of days of hospitalization as dependent variable) and global and anual during the first three years of follow-up survival analysis (using Cox proportional hazards regression) were carried out. RESULTS: A total of 139 patients (78%) started HD in the ER group and 39 (22%) in LR group. Mean follow-up was similar in both (ER = 34.43 +/- 25.5 months; LR = 34.42 +/- 28.37 months). At the start of dialysis LR was associated to higher proportion of temporary catheters, lower level of hematocrit and albumin, higher comorbidity and higher levels of urea and creatinine. Risk factors selected by the model in the morbidity analysis were index of comorbidity (CI), late referral, serum albumin, urea reduction ratio (URR) and hematocrit (R2 = 0.334, F = 16.97, p < 0.005). The final equation of regression was: Rate of hospitalization's days = 101.12 + (2.45 x CI) - (12. 11 x LR) - (11.57 x Alb.) - (0.43 x PRU) - (0.83 x Hto). Variables selected by Cox's regression model that were associated with survival throughout complete follow-up were hematocrit (RR = -0,207, CI 95% 0.726-0.910, p < 0.0005), index of comorbidity (RR = 0,265, CI 95% 1.066-1.594, p = 0.007), PRU (RR = - 0,059, CI 95% 0.893-0.996, p = 0.038) and type of dialysis membrane (RR = 0,771, Cl 95% 0.260-0.822, p = 0.007). Nevertheless, in successive models fitting after 12, 24 and 36 months of follow-up the variable LR influenced in an independent way survival first two years, losing his significance later. CONCLUSION: In our study patients of the group LR presented a worse clinical and metabolic situation at the beginning of the HD. Later there was demonstrated in this group a higher long-term morbidity and a lower survival the first two years.

Adult↗
PubMed2005

Abnormalities in the bone mineral metabolism in HIV-infected patients.

OBJECTIVE: To evaluate bone mineral metabolism in HIV infected and asymptomatic patients receiving highly active antiretroviral therapy (HAART) containing protease inhibitors (PI) and naïve patients. METHODS: We studied 30 asymptomatic HIV infected male patients, 13 in the naive group and 17 in the IP group, both without differences in demographics characteristics. We excluded women and patients with any known factor associated to osteopenia. We did a nutritional questionnaire, a DEXA scan in lumbar spine and femur, a study of CD4 lymphocytes, viral load and an analysis of bone formation and resorption markers in all patients. We compared vitamin D and PTH levels with a control group of healthy male volunteers age-pareated. For the statistical analysis we used the SPSS program. RESULTS: Osteopenia was present in 17/30 (57%), 8/13 (61.5%) in the naïve group and 9/17 (53%) in the PI group (not significant differences). We found a vitamin D deficiency in 86% of patients, with mean serum levels that was found to be significantly lower than those from a healthy control group (p=0.04). Testosterone level was significantly related to bone mineral density in lumbar spine (p</=0.05). CONCLUSIONS: HIV may be an individual risk factor in bone disorders, requiring calcium and vitamin D supplementation.

Adult↗
PubMed2005

Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain.

INTRODUCTION: There are very limited data about the prevalence of multiple hepatitis virus infections in HIV infected individuals. In HIV uninfected individuals with triple BCD hepatitis, hepatitis D virus (HDV) appears to be the dominant virus. However, in HIV infected patients with triple hepatitis it is not known if HDV replication inhibits hepatitis B virus (HBV) and/or hepatitis C virus (HCV) replication. METHODS: We calculated the prevalence of single (B or C), dual (BC) and triple (BCD) hepatitis in 423 HIV-infected patients with positive HCV serum antibodies and/or positive serum HBsAg. In patients with multiple infections we performed an evaluation of serum markers of HBV, HCV and HDV replication. RESULTS: The prevalence of multiple hepatitis was 4.7% (95% confidence interval, 2.7-6.7%). Multiple hepatitis occurred only among patients who acquired HIV through injection drug use. The most common multiple hepatitis was triple BCD. Patients with hepatitis BC and past or chronic hepatitis D were significantly more likely to have cirrhosis and a negative serum HBeAg and HCV PCR than patients with single hepatitis B or hepatitis C. Patients with chronic hepatitis D showed uniform suppression of HBV and HCV replication markers. CONCLUSIONS: In our geographic area approximately 5% of HIV infected patients with hepatitis suffer multiple hepatitis virus infection. In patients with triple hepatitis BCD virus infection, HDV appears to be the dominant virus causing inhibition of both HBV and HCV replication.

Adult↗
PubMed2005

Growing Bayesian network models of gene networks from seed genes.

MOTIVATION: For the last few years, Bayesian networks (BNs) have received increasing attention from the computational biology community as models of gene networks, though learning them from gene-expression data is problematic. Most gene-expression databases contain measurements for thousands of genes, but the existing algorithms for learning BNs from data do not scale to such high-dimensional databases. This means that the user has to decide in advance which genes are included in the learning process, typically no more than a few hundreds, and which genes are excluded from it. This is not a trivial decision. We propose an alternative approach to overcome this problem. RESULTS: We propose a new algorithm for learning BN models of gene networks from gene-expression data. Our algorithm receives a seed gene S and a positive integer R from the user, and returns a BN for the genes that depend on S such that less than R other genes mediate the dependency. Our algorithm grows the BN, which initially only contains S, by repeating the following step R + 1 times and, then, pruning some genes; find the parents and children of all the genes in the BN and add them to it. Intuitively, our algorithm provides the user with a window of radius R around S to look at the BN model of a gene network without having to exclude any gene in advance. We prove that our algorithm is correct under the faithfulness assumption. We evaluate our algorithm on simulated and biological data (Rosetta compendium) with satisfactory results.

Algorithms↗
PubMed2005

Globally multimodal problem optimization via an estimation of distribution algorithm based on unsupervised learning of Bayesian networks.

Many optimization problems are what can be called globally multimodal, i.e., they present several global optima. Unfortunately, this is a major source of difficulties for most estimation of distribution algorithms, making their effectiveness and efficiency degrade, due to genetic drift. With the aim of overcoming these drawbacks for discrete globally multimodal problem optimization, this paper introduces and evaluates a new estimation of distribution algorithm based on unsupervised learning of Bayesian networks. We report the satisfactory results of our experiments with symmetrical binary optimization problems.

Algorithms↗
PubMed2004

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naïve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control.

AIDS Vaccines↗
PubMed2004

Quantitation of human immunodeficiency virus type 1 RNA loads in cervicovaginal secretions in pregnant women and relationship between viral loads in the genital tract and blood.

The purpose of this study was to analyze the quantitation of the human immunodeficiency virus type 1 RNA (HIV-1 RNA) in the genital tract of HIV-1-infected pregnant women and to evaluate a possible correlation with the viral load in blood plasma (Spearman's rank correlation coefficient). A total of 38 each of cervical, vaginal, and blood samples from 38 women were obtained during the third trimester of pregnancy for quantitation of the HIV-1 RNA load. Viral loads were determined by reverse transcription-polymerase chain reaction. The HIV-1 RNA viral load was detectable in 29 of the 38 (76.3%) blood samples, in 6 of the 38 (15.7%) cervical secretion samples, and in 8 of the 38 (21%) vaginal secretion samples. Overall, the correlation between the HIV-1 RNA viral load in the blood plasma and in cervical secretion samples was 0.51 ( P<0.001). However, the correlation disappeared ( r=0.27) when three patients with high blood plasma viral loads were eliminated from the statistical study. The viral load in the vaginal secretions did not correlate with that in the blood samples ( r=0.26). There were two cases in which HIV-1 RNA was undetectable in the blood and cervix but was detectable in vaginal secretions: one woman had 220 copies/ml and the other 68 copies/ml. These results suggest that pregnant women with undetectable viral loads in blood plasma are still at risk of transmitting the virus vertically during vaginal delivery. Because of this, antiretroviral prophylaxis during vaginal delivery must be administered to HIV-1-infected women and their newborns, regardless of the mother's viral load in plasma. In conclusion, quantification of cervicovaginal levels of HIV-1 may represent a useful tool for assessing the individual risk associated with a vaginal delivery and for guiding decisions about whether a scheduled caesarean should be recommended.

Adult↗
PubMed2004

Impact of tuberculosis on the course of HIV-infected patients with a high initial CD4 lymphocyte count.

OBJECTIVE: To assess the influence of tuberculosis (TB) on the progression of human immunodeficiency virus (HIV) infection in patients without immunological impairment. MATERIAL AND METHODS: In an observational study of retrospective cohorts, the evolution of 28 HIV-infected patients with TB and a CD4 lymphocyte count >500 x 10(6) cells/l was compared with 56 HIV-infected patients without TB. Each case was paired with two controls by CD4 lymphocyte count (+/-50 x 10(6)/l) and date of starting follow-up (+/-6 months). The progression of HIV infection was evaluated as: 1) immunological progression: time to CD4 lymphocyte count <200 x 10(6)/l; 2) clinical progression: time to development of acquired immune-deficiency syndrome (AIDS), excluding TB; 3) survival; and 4) global disease progression: time to the first defined event in 1, 2 and/or 3. The times to these events were estimated using Kaplan Meier curves. RESULTS: There were no significant differences between the cohorts for age, sex and risk group. Faster immunological impairment (RR 2.94; 95%CI 1.46-8.6; P < 0.01), greater progression to AIDS (RR 4.01; 95%CI 1.66-9.69; P < 0.01), lower survival (RR 3.89; 95%CI 1.53-9.87; P < 0.05) and higher global disease progression (RR 2.82; 95%CI 1.57-5.09; P < 0.01) were found in the cohort of TB patients. These associations were still significant after adjustment for CD4 lymphocyte counts. CONCLUSION: The diagnosis of TB in HIV-infected patients with a high initial CD4 lymphocyte count (>500 x 10(6)/l) was related to greater progression to AIDS and shorter survival.

Adult↗
PubMed2001

A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98.

BACKGROUND: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. METHODS: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. RESULTS: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years). CONCLUSIONS: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

AIDS-Related Opportunistic Infections↗
PubMed2001

Fever of unknown origin: classic and associated with human immunodeficiency virus infection. a comparative study.

Fever of unknown origin (FUO) associated with HIV infection is different from classic FUO. Relevant etiologies, procedures and time to diagnosis were analyzed. Patients admitted with FUO from 1991 to 1996 were prospectively followed. Thirty with classic FUO (group I) and 46 with FUO and HIV (group II) were included. Data on diagnosis, time to achieve it, and procedures were registered. Diagnosis was obtained in 87% and 93% of cases in groups I and II. Infections were the most frequent cause in group II. Collagen diseases were found in group I and absent in group II. Prevalence of neoplasia was similar. Mean time to diagnosis was near 5 weeks. In HIV the predominant diagnostic method was the Lowenstein culture. Invasive methods were similarly employed. It is concluded that predominance of Mycobacteria and absence of collagen diseases make FUO associated with HIV a different form of FUO. No differences were found in approach and time to diagnosis.

Adult↗
PubMed2000

Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women.

OBJECTIVES: To assess the impact of HIV-related immunodeficiency and antiretroviral treatment on the occurrence and evolution of abnormal Papanicolaou tests. STUDY DESIGN: Cohort of 485 HIV-infected women with a known date of infection, enrolled during May 1993-April 1998 in 23 centres (gynaecology, infectious disease or STD clinics, or drug treatment centres) in 12 European countries; in 21 centres, follow-up was performed every 6 months (median follow-up: 2 years). METHODS: Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. The prevalence of squamous intraepithelial lesions (SIL), the incidence of SIL and regression from low-grade SIL were studied according to CD4 count after controlling for HPV detection results. RESULTS: Compared with women with CD4 cell counts > 500 x 10(6)/l, women with CD4 cell counts < 200 x 10(6)/l had a twofold increase in both prevalence and incidence of SIL and in non-regression from untreated low-grade SIL; in addition, these women had a lower response rate to treatment of high-grade cervical intraepithelial neoplasia. The increase in SIL incidence associated with a low CD4 cell count was significant in women not receiving antiretroviral treatment (relative risk, CD4 cell count 200-499 x 10(6)/l, 1.9; CD4 cell count < 200 x 10(6)/l, 2.9; CD4 cell count > 500 x 10(6)/l, reference), whereas it was less marked and not statistically significant in treated women. CONCLUSIONS: Severe HIV-related immunodeficiency strongly increases the risk of occurrence of SIL; antiretroviral treatment may reduce this risk, probably by restoring or at least preserving immune function.

Adolescent↗