Alfonso Muriel - Academia.edu (original) (raw)

Papers by Alfonso Muriel

Research paper thumbnail of Fear avoidance beliefs and low back pain:“practical reviews” from expert panel discussions versus comprehensive systematic reviews

Research paper thumbnail of Phacoemulsification in previously vitrectomized patients: An analysis of the surgical results in 100 eyes as well as the factors contributing to the cataract formation

European journal of ophthalmology

Purpose: To compare the incidence of complications and the outcome of phacoemulsification surgery... more Purpose: To compare the incidence of complications and the outcome of phacoemulsification surgery in patients with and without previous vitrectomy. Methods: We retrospectively investigated 60 patients in a study group that received phacoemulsification with posterior chamber IOL implantation (PC-IOL) in the vitrectomized eye and 60 patients in a control group that received only phacoemulsification with PC-IOL implantation from January 2003 to December 2007. The interval from PPV to cataract extraction, sex, age, type of cataract, intraoperative and postoperative complications, pre-and postoperative refraction were reviewed. Results: The most common indication of pars plana vitrectomy was diabetic retinopathy. Nucleosclerosis was the most common type of cataract. The most common intraoperative complication was posterior capsular rupture, but there was no statistical significance when compared with the control group (p=0.116). In addition, the most common postoperative complication was posterior capsular opacity. After phacoemulsification, the rate at which a BCVA of 0.5 or better was obtained was lower in the study group than the control group. The spread between actual and expected refraction showed no statistically significant difference when compared with the control group (p=0.309). Conclusions: Experienced surgeons can safely perform phacoemulsification and PC-IOL implantation in previously vitrectomized eyes. However, the outcome of visual acuity is limited by vitreoretinal pathology that requires vitrectomy.

Research paper thumbnail of High rate of didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving ribavirin

Antiviral therapy

Background: Nucleoside analogues may induce mitochondrial toxicity, particularly didanosine. Riba... more Background: Nucleoside analogues may induce mitochondrial toxicity, particularly didanosine. Ribavirin increases didanosine exposure, which might be clinically relevant when coadministered in HIV/HCV-coinfected patients. Objective: To evaluate, among 89 patients receiving highly active antiretroviral therapy (HAART) and therapy for chronic hepatitis C, clinically relevant mitochondrial toxicity in those treated with concomitant ribavirin and didanosine (n=35, 39%). Methods: From January 2000 to July 2002 longitudinal analysis of the incidence and clinical course of didanosine-related hyperamylasaemia, pancreatitis, hyperlactataemia/lactic acidosis or neuropathy. Risk factors were evaluated using univariate and multivariate Cox's proportional hazards model. Results: Among 35 patients who received concomitant didanosine (400 mg/day in 86%) and ribavirin (≥10 mg/kg/day in 91%), 20 (57%) developed one or more adverse events after a mean of 87 days. Most frequent laboratory abnormalities were hyperamylasaemia (18 patients, 51%) and hyperlactataemia (eight patients, 23%). Acute pancreatitis and symptomatic hyperlactataemia developed in 10 (28%) and six (17%) patients, respectively. Two patients (6%) with pancreatitis and severe lactic acidosis died; the other patients recovered uneventfully despite continuation of anti-HCV therapy in 83% after didanosine withdrawal in 40%. In the Cox's model higher baseline amylase levels (HR: 1.04, 95% CI: 1.02-1.06, P=0.001) and three nucleoside reverse transcriptase inhibitor-based HAART (HR: 5.3, 95% CI: 1.73-16.24, P=0.003) were significantly associated to toxicity. Conclusions: The coadministration of didanosine and ribavirin should be avoided in HIV/HCV-coinfected patients, due to a high rate of clinically significant toxicity, particularly in triple nucleoside-based HAART.

Research paper thumbnail of The magnitude of week 4 HCV RNA decay on pegylated interferon/ribavirin accurately predicts virological failure in patients with genotype 1

Antiviral therapy

Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on we... more Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on week 12 HCV RNA response, but earlier identification of non-responders offers clinical and economic advantages. To evaluate, among 129 HCV-genotype-1-infected, treatment-naive patients receiving peg-IFN/RBV, the feasibility of predicting treatment failure using receiver operating characteristics (ROC) curves after measuring week 4 HCV RNA decreases, and to assess baseline predictors of not achieving sustained virological response (SVR). Peg-IFN-alpha2b was used in 84.5% of patients. Fifty-three (41%) reached SVR. The best cutoff value of HCV RNA decrease at week 4 to predict non-SVR corresponded to 1 log10 IU/ml: sensitivity and negative predictive value: 100%; specificity: 64%; positive predictive value: 66%; ROC curve area: 0.91 (95% confidence interval [CI]: 0.86-0.96). By applying this threshold, treatment could have been discontinued at week 4 in 64% of virological non-responders (49/...

Research paper thumbnail of Comparison of routine versus targeted HIV testing strategies: coverage and estimated missed infections in emergency room and primary care centre

Journal of the International AIDS Society, 2014

Different HIV Testing Strategies (TS) and clinical care settings had not been face to face evalua... more Different HIV Testing Strategies (TS) and clinical care settings had not been face to face evaluated (1). We compared coverage, Newly Diagnosed HIV Infection (NDHI) and Estimated Missing HIV Infections (MHI) in Hospital Emergency Room (HER) and Primary Care Center (PCC), in DRIVE study (Spanish acronym of HIV infection Rapid Diagnosis) and in clinical practice the year before DRIVE. In DRIVE study, 18-60 years old, non-HIV-infected population visiting an HER or a PCC were proposed both a structured risk practices and clinical conditions questionnaire (RP&CC-Q) and a rapid HIV test. This arm is the HIV Routine TS. We analyze a hypothetical arm, where risk practices were universally assessed with an…

Research paper thumbnail of Incremental cost per newly diagnosed HIV infection (NDHI): routine (RTS), targeted (TTS), and current clinical practice testing strategies (CPTS)

Journal of the International AIDS Society, 2014

Although RTS as HIV Diagnosis was considered cost effectiveness [1], overall budget may be unaffo... more Although RTS as HIV Diagnosis was considered cost effectiveness [1], overall budget may be unaffordable for some countries. We explore Incremental cost per NDHI associated with different TS. From a health care perspective, using direct costs and Euros currency, we calculated budget and cost per NDHI of RTS (all patients were tested), TTS (Universal risk practices and clinical conditions-RP&CC - only positive were tested), and CPTS (Only patients physicians considered were tested). We considered DRIVE (Spanish acronym of HIV infection Rapid Diagnosis) study and clinical Practice outcomes. Population between 18-60 years, attending to a Hospital Emergency Room or to a Primary Care Center performed an HIV…

Research paper thumbnail of Do chronic myeloid leukemia patients with late “warning” responses benefit from “watch and wait” or switching therapy to a second generation tyrosine kinase inhibitor?

American Journal of Hematology, 2014

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia subopt... more In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late…

Research paper thumbnail of Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus ribavirin in HCV genotypes 1/4 according to HIV serostatus*

Journal of Viral Hepatitis, 2006

To evaluate, among 70 hepatitis C virus (HCV)monoinfected and 36 human immunodeficiency virus (HI... more To evaluate, among 70 hepatitis C virus (HCV)monoinfected and 36 human immunodeficiency virus (HIV)coinfected naïve patients with genotypes 1/4 receiving weight-adjusted pegylated interferon-a-2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV-RNA decreases. HCV-RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut-off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV-RNA (5AE75 vs 5AE72 log 10 IU/ml, P ¼ 0AE6), HCV monoinfection led to significantly lower HCV-RNA values at weeks 4 (3AE7 vs 4AE3 log 10 IU/ml, P ¼ 0AE01), 12 (2AE3 vs 3AE5 log 10 IU/ml, P ¼ 0AE01) and 24 (1AE4 vs 3AE3 log 10 IU/ml, P ¼ 0AE001) and a higher rates of viral clearance at weeks 24 (60% vs 36%, P ¼ 0AE02), 48 (46% vs 25%, P ¼ 0.03) and 72 (37% vs 17%). The lack of achieving an HCV-RNA decrease of at least 1 log 10 at week 4 was highly predictive of treatment failure for HCV-monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0AE86 [95% confidence interval (CI) 0AE77-0AE95], but not for HCV/ HIV-coinfected patients (cut-off, 0 log 10 , Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0AE71 (95% CI 0AE49-0AE93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1AE08-8.04, P ¼ 0AE01). Thus the magnitude of HCV-RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut-off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.

Research paper thumbnail of The effect on survival of a multidimensional intervention project (SEAD) in HIV/AIDS patients with follow-up and adherence (FUP/ADH) barriers

Journal of the International AIDS Society, 2012

ABSTRACT Purpose of the study: Irregular FUP/ADH were associated with higher mortality and resour... more ABSTRACT Purpose of the study: Irregular FUP/ADH were associated with higher mortality and resource use [1]. SEAD was a multidimensional intervention project, designed from the patient's perspective, to specifically attend patients with poor FUP/ADH in an HIV/AIDS outpatient clinic. Methods: From Jan 2006 to May 2010, patients with poor FUP/ADH were offered SEAD inclusion, all were evaluated by a nurse or a psychologist (adherence collaborators) who assessed all the reasons and barriers precluding a correct FUP/ADH. For each identified problem, different interventions were planned, using our own resources or coordinating others. Follow-up was censored in Nov 2011. Time to death after being admitted to SEAD and the effect of SEAD program intervention were assessed with Kaplan-Meier curves, log-Rank test and a Cox regression model. Summary of results: Overall, 215 patients were assessed: mean age 45 years, 24% women, IDU 75%, with baseline ADH >90% in only 23%; median HIV-RNA and CD4 cell count were 377 copies/ml and 326 cell/mcL. Patients entered in SEAD due to poor ADH in 17%, FUP problems in 23%, and both 60%. Main reasons driving poor FUP/ADH were severe bio-psycho-social problems 28%, severe drug and/or alcohol abuse 26%, logistic problems 18%, other psychiatric disorders 13%, oversights 9%, unknown 4% and antiretroviral intolerance 2%. Only 54% of patients received;>50% of planned interventions, due to population complexity. Cocaine/heroin and alcohol abuse were reported by 34% and 17% respectively. Afer a median follow-up of 3.7 [3.31-4.4] years 193 patients received a mean of 8 (2.5-12) interventions/year, achieving virological control in 64%. Probability of survival was 92%, 89% and 86% after 1, 2 and 3 years respectively. In Cox regression model an intervention of SEAD project higher than 50% of planned was an independent predictor of survival HR 0.336 (95% CI 0.156-0.725); p=0.005, after adjusting for age, alcohol or cocaine abuse, psychological attention, degree of adherence and follow-up, intravenous acquisition of HIV, and family support. Alcohol and cocaine abuse were associated with higher mortality HR 2.964 (95% CI 1.378-6.374); p=0.005 and HR 2.444 (95% CI 1.161-5.145); p=0.019. Conclusions: Being admitted to SEAD intervention project and receiving more than 50% of planned interventions increased survival expectancy.

Research paper thumbnail of 484 Impact of Hiv-Coinfection on the Outcome of Viral Cirrhosis Liver Transplant Candidates at a Reference Center from 2001–2008 and Predictors of Post-Transplant Survival

Journal of Hepatology, 2009

Research paper thumbnail of 1319 Prevalence and Effect of Graft vs Recipient IL28B SNP on Early HCV-Rna Kinetics in Patients on Peg-Ifn/RBV After Liver Transplantation

Journal of Hepatology, 2011

Research paper thumbnail of HCV clearance and treatment outcome in genotype 1 HCV-monoinfected, HIV-coinfected and liver transplanted patients on peg-IFN-α-2b/ribavirin

Journal of Hepatology, 2005

Background/Aims: Differences in HCV-RNA clearance during therapy might explain the lower efficacy... more Background/Aims: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients.

Research paper thumbnail of Risk Factors for Candidemia in Pediatric Patients With Congenital Heart Disease •

Infection Control and Hospital Epidemiology, 2006

To identify the main risk factors for the acquisition of candidemia in children with congenital h... more To identify the main risk factors for the acquisition of candidemia in children with congenital heart disease (CHD) in order to improve the clinical management of these patients. A case-control study. A large tertiary-care referral center in Spain with a pediatric intensive care unit (PICU) to which more than 500 children with CHD are admitted annually. All patients had CHD and were admitted to the PICU during 1995-2000. Case patients were defined as patients with candidemia, and control patients were defined as patients without candidemia. Twenty-eight case patients and 47 control subjects were included in the study. Case patients were younger (mean age [+/-SD], 12.5+/-32.0 vs 38.0+/-48.0 months; P<.01) and had a longer median PICU stay (19 vs 4 days; P<.01), and a greater percentage of case patients previously had Candida species isolated from specimens other than blood (eg, bronchial aspirates, urine, or skin specimens) (39% vs 4%; P<.01). Severity of clinical condition, as measured by the Therapeutic Intervention Scoring System (TISS) 1 week after PICU admission (odds ratio, 1.15; 95% confidence interval, 1.05-1.26; P<.01), and receipt of antibiotic treatment for more than 5 days (odds ratio, 13.42; 95% confidence interval, 1.31-137.13; P=.03) were independently associated with the development of candidemia. Patients with CHD who have a high TISS score 1 week after PICU admission and patients who have received prolonged antibiotic therapy should be considered at high risk for candidemia. Our results suggest that shorter courses of antibiotic therapy, routine surveillance culture for Candida species, and initiation of preemptive or empirical antifungal treatment could help in the clinical management of these patients.

Research paper thumbnail of Missing Scheduled Visits in the Outpatient Clinic as a Marker of Short-Term Admissions and Death

HIV Clinical Trials, 2012

Research paper thumbnail of Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance

Histopathology, 2011

Aims: Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are o... more Aims: Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are overexpressed in many tumours. We analysed the expression of relevant HSPs and heat shock factor 1 (HSF1) in classical Hodgkin lymphoma (cHL) and their relationship with caspase signalling pathways and patient outcome. Methods and results: Using tissue microarrays (TMAs), most cases showed strong immunohistochemical expression of HSPs 40, 60, 70, 90, 110, HO1, cell division cycle 37 homolog (CDC37) and HSF1, which points to cHL as a potential candidate to stressresponse inhibitors. Active caspases 3, 8 and 9 were detected in 55.1%, 55.4% and 96.2% of cases although cleaved poly (ADP-ribose) polymerase (PARP) was observed in only 16.1%, suggesting an improper functioning of apoptosis. Statistical analysis showed associations of HSP70 with active caspase 3 (P = 0.000); HSP40 with active caspase 9 (P = 0.031) and p53 (P = 0.003); HO1 with p53 (P = 0.006) and p21 (P = 0.005); and p53 with p21 (P = 0.015). Conclusions: Correlations between the expression of apoptotic markers and HSPs may suggest a role for the latter in modulating apoptosis in cHL, mainly through the HSP70-HSP40 system, and in the stabilization of p53. Survival analyses showed that absence of active caspase 8 and HO1 had a negative impact in patient outcome.

Research paper thumbnail of Candidemia in pediatric patients with congenital heart disease

Diagnostic Microbiology and Infectious Disease, 2006

Candidemia is an important problem in pediatrics. In our hospital, highest candidemia rates were ... more Candidemia is an important problem in pediatrics. In our hospital, highest candidemia rates were documented among children with congenital heart disease (CHD). A series was conducted to describe the clinical and mortality features of candidemia in these patients. Fifty-two cases (1988-2000) included very young infants (median age, 2 months) who received long-term antibiotic treatment (median, 20.5 days). Candida parapsilosis predominated (54%). Endovascular infections occurred in 11.5%. In-hospital mortality was 39% and related mortality 14%. Maintenance of catheter (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.0-37.2; P = .05) and severity of patients as measured with the Pediatric Risk Score of Mortality I (OR, 1.1, 95% CI, 1.0-1.3; P = .05) were independently associated with mortality. In summary, candidemia in children with CHD is diagnosed to very young infants with prolonged antibiotic therapy. Mortality is high but, in most cases, is not related to candidemia. Optimal management may include exclusion of endocarditis, early antifungal treatment, and catheter removal.

Research paper thumbnail of Tuberculosis Complicating Hepatitis C Treatment in HIV‐Infected Patients

Clinical Infectious Diseases, 2009

Tuberculosis characteristics and incidence were assessed among patients with concurrent human imm... more Tuberculosis characteristics and incidence were assessed among patients with concurrent human immunodeficiency virus infection and chronic hepatitis C virus infection who were receiving interferon-based therapy at 3 hospitals in Spain. Four of 570 patients (0.7 cases per 100 person-years; 95% confidence interval, 0.19-1.78 cases per 100 person-years) received a diagnosis of tuberculosis; all of them presented with a decrease in CD4+ cell count before diagnosis, and 3 of them received a delayed diagnosis. After tuberculosis treatment, all patients were cured.

Research paper thumbnail of Relevant gender differences in epidemiological profile, exposure to first antiretroviral regimen and survival in the Spanish AIDS Research Network

Antiviral Therapy, 2013

The possible differences in the disease spectrum and prognosis of HIV infection in women and men ... more The possible differences in the disease spectrum and prognosis of HIV infection in women and men is a major point of concern. Women are under-represented in randomized clinical trials and in some cohorts. Discordant results have often been obtained depending on the setting. We assessed gender differences in clinical and epidemiological features, antiretroviral treatment (ART) exposure and survival in two multicentre cohorts of HIV-positive subjects in Spain: CoRIS-MD and CoRIS. Competing risk regression models were used to assess gender effect on time to start ART and time to first ART change, and a Cox regression model to estimate gender effect on time to death. Between January 1996 and December 2008, 1,953 women and 6,072 men naive to ART at study entry were included. The trend analysis over time showed the percentage of women in the younger (<20 years) and older…

Research paper thumbnail of A cohort study of accidents occurring in mentally handicapped patients living in institutions

Annals of General Psychiatry, 2010

Background: Mentally handicapped patients who require extensive and generalised care and are resi... more Background: Mentally handicapped patients who require extensive and generalised care and are resident in mental health institutions have certain characteristics that could mean that they suffer certain types of accidents. The aim of this study was to determine the number and type of accident-related injuries in this population in order to design appropriate preventative strategies.

Research paper thumbnail of CD4 cell recovery during successful antiretroviral therapy in naive HIV-infected patients

AIDS, 2004

We evaluated the impact of HIV risk practice on immune reconstitution in a prospective cohort of ... more We evaluated the impact of HIV risk practice on immune reconstitution in a prospective cohort of 288 patients (176 former injecting drug users) who maintained complete virus suppression for more than 24 months. Significant differences in CD4 cell counts at 6 and 24 months were detected. Multivariate analysis showed that drug use was an independent predictor of poor immunological recovery. Injection drug abuse impairs short and long-term CD4 cell recovery in HIV-positive patients initiating successful highly active antiretroviral therapy.

Research paper thumbnail of Fear avoidance beliefs and low back pain:“practical reviews” from expert panel discussions versus comprehensive systematic reviews

Research paper thumbnail of Phacoemulsification in previously vitrectomized patients: An analysis of the surgical results in 100 eyes as well as the factors contributing to the cataract formation

European journal of ophthalmology

Purpose: To compare the incidence of complications and the outcome of phacoemulsification surgery... more Purpose: To compare the incidence of complications and the outcome of phacoemulsification surgery in patients with and without previous vitrectomy. Methods: We retrospectively investigated 60 patients in a study group that received phacoemulsification with posterior chamber IOL implantation (PC-IOL) in the vitrectomized eye and 60 patients in a control group that received only phacoemulsification with PC-IOL implantation from January 2003 to December 2007. The interval from PPV to cataract extraction, sex, age, type of cataract, intraoperative and postoperative complications, pre-and postoperative refraction were reviewed. Results: The most common indication of pars plana vitrectomy was diabetic retinopathy. Nucleosclerosis was the most common type of cataract. The most common intraoperative complication was posterior capsular rupture, but there was no statistical significance when compared with the control group (p=0.116). In addition, the most common postoperative complication was posterior capsular opacity. After phacoemulsification, the rate at which a BCVA of 0.5 or better was obtained was lower in the study group than the control group. The spread between actual and expected refraction showed no statistically significant difference when compared with the control group (p=0.309). Conclusions: Experienced surgeons can safely perform phacoemulsification and PC-IOL implantation in previously vitrectomized eyes. However, the outcome of visual acuity is limited by vitreoretinal pathology that requires vitrectomy.

Research paper thumbnail of High rate of didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving ribavirin

Antiviral therapy

Background: Nucleoside analogues may induce mitochondrial toxicity, particularly didanosine. Riba... more Background: Nucleoside analogues may induce mitochondrial toxicity, particularly didanosine. Ribavirin increases didanosine exposure, which might be clinically relevant when coadministered in HIV/HCV-coinfected patients. Objective: To evaluate, among 89 patients receiving highly active antiretroviral therapy (HAART) and therapy for chronic hepatitis C, clinically relevant mitochondrial toxicity in those treated with concomitant ribavirin and didanosine (n=35, 39%). Methods: From January 2000 to July 2002 longitudinal analysis of the incidence and clinical course of didanosine-related hyperamylasaemia, pancreatitis, hyperlactataemia/lactic acidosis or neuropathy. Risk factors were evaluated using univariate and multivariate Cox's proportional hazards model. Results: Among 35 patients who received concomitant didanosine (400 mg/day in 86%) and ribavirin (≥10 mg/kg/day in 91%), 20 (57%) developed one or more adverse events after a mean of 87 days. Most frequent laboratory abnormalities were hyperamylasaemia (18 patients, 51%) and hyperlactataemia (eight patients, 23%). Acute pancreatitis and symptomatic hyperlactataemia developed in 10 (28%) and six (17%) patients, respectively. Two patients (6%) with pancreatitis and severe lactic acidosis died; the other patients recovered uneventfully despite continuation of anti-HCV therapy in 83% after didanosine withdrawal in 40%. In the Cox's model higher baseline amylase levels (HR: 1.04, 95% CI: 1.02-1.06, P=0.001) and three nucleoside reverse transcriptase inhibitor-based HAART (HR: 5.3, 95% CI: 1.73-16.24, P=0.003) were significantly associated to toxicity. Conclusions: The coadministration of didanosine and ribavirin should be avoided in HIV/HCV-coinfected patients, due to a high rate of clinically significant toxicity, particularly in triple nucleoside-based HAART.

Research paper thumbnail of The magnitude of week 4 HCV RNA decay on pegylated interferon/ribavirin accurately predicts virological failure in patients with genotype 1

Antiviral therapy

Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on we... more Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on week 12 HCV RNA response, but earlier identification of non-responders offers clinical and economic advantages. To evaluate, among 129 HCV-genotype-1-infected, treatment-naive patients receiving peg-IFN/RBV, the feasibility of predicting treatment failure using receiver operating characteristics (ROC) curves after measuring week 4 HCV RNA decreases, and to assess baseline predictors of not achieving sustained virological response (SVR). Peg-IFN-alpha2b was used in 84.5% of patients. Fifty-three (41%) reached SVR. The best cutoff value of HCV RNA decrease at week 4 to predict non-SVR corresponded to 1 log10 IU/ml: sensitivity and negative predictive value: 100%; specificity: 64%; positive predictive value: 66%; ROC curve area: 0.91 (95% confidence interval [CI]: 0.86-0.96). By applying this threshold, treatment could have been discontinued at week 4 in 64% of virological non-responders (49/...

Research paper thumbnail of Comparison of routine versus targeted HIV testing strategies: coverage and estimated missed infections in emergency room and primary care centre

Journal of the International AIDS Society, 2014

Different HIV Testing Strategies (TS) and clinical care settings had not been face to face evalua... more Different HIV Testing Strategies (TS) and clinical care settings had not been face to face evaluated (1). We compared coverage, Newly Diagnosed HIV Infection (NDHI) and Estimated Missing HIV Infections (MHI) in Hospital Emergency Room (HER) and Primary Care Center (PCC), in DRIVE study (Spanish acronym of HIV infection Rapid Diagnosis) and in clinical practice the year before DRIVE. In DRIVE study, 18-60 years old, non-HIV-infected population visiting an HER or a PCC were proposed both a structured risk practices and clinical conditions questionnaire (RP&CC-Q) and a rapid HIV test. This arm is the HIV Routine TS. We analyze a hypothetical arm, where risk practices were universally assessed with an…

Research paper thumbnail of Incremental cost per newly diagnosed HIV infection (NDHI): routine (RTS), targeted (TTS), and current clinical practice testing strategies (CPTS)

Journal of the International AIDS Society, 2014

Although RTS as HIV Diagnosis was considered cost effectiveness [1], overall budget may be unaffo... more Although RTS as HIV Diagnosis was considered cost effectiveness [1], overall budget may be unaffordable for some countries. We explore Incremental cost per NDHI associated with different TS. From a health care perspective, using direct costs and Euros currency, we calculated budget and cost per NDHI of RTS (all patients were tested), TTS (Universal risk practices and clinical conditions-RP&CC - only positive were tested), and CPTS (Only patients physicians considered were tested). We considered DRIVE (Spanish acronym of HIV infection Rapid Diagnosis) study and clinical Practice outcomes. Population between 18-60 years, attending to a Hospital Emergency Room or to a Primary Care Center performed an HIV…

Research paper thumbnail of Do chronic myeloid leukemia patients with late “warning” responses benefit from “watch and wait” or switching therapy to a second generation tyrosine kinase inhibitor?

American Journal of Hematology, 2014

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia subopt... more In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late…

Research paper thumbnail of Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus ribavirin in HCV genotypes 1/4 according to HIV serostatus*

Journal of Viral Hepatitis, 2006

To evaluate, among 70 hepatitis C virus (HCV)monoinfected and 36 human immunodeficiency virus (HI... more To evaluate, among 70 hepatitis C virus (HCV)monoinfected and 36 human immunodeficiency virus (HIV)coinfected naïve patients with genotypes 1/4 receiving weight-adjusted pegylated interferon-a-2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV-RNA decreases. HCV-RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut-off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV-RNA (5AE75 vs 5AE72 log 10 IU/ml, P ¼ 0AE6), HCV monoinfection led to significantly lower HCV-RNA values at weeks 4 (3AE7 vs 4AE3 log 10 IU/ml, P ¼ 0AE01), 12 (2AE3 vs 3AE5 log 10 IU/ml, P ¼ 0AE01) and 24 (1AE4 vs 3AE3 log 10 IU/ml, P ¼ 0AE001) and a higher rates of viral clearance at weeks 24 (60% vs 36%, P ¼ 0AE02), 48 (46% vs 25%, P ¼ 0.03) and 72 (37% vs 17%). The lack of achieving an HCV-RNA decrease of at least 1 log 10 at week 4 was highly predictive of treatment failure for HCV-monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0AE86 [95% confidence interval (CI) 0AE77-0AE95], but not for HCV/ HIV-coinfected patients (cut-off, 0 log 10 , Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0AE71 (95% CI 0AE49-0AE93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1AE08-8.04, P ¼ 0AE01). Thus the magnitude of HCV-RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut-off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.

Research paper thumbnail of The effect on survival of a multidimensional intervention project (SEAD) in HIV/AIDS patients with follow-up and adherence (FUP/ADH) barriers

Journal of the International AIDS Society, 2012

ABSTRACT Purpose of the study: Irregular FUP/ADH were associated with higher mortality and resour... more ABSTRACT Purpose of the study: Irregular FUP/ADH were associated with higher mortality and resource use [1]. SEAD was a multidimensional intervention project, designed from the patient's perspective, to specifically attend patients with poor FUP/ADH in an HIV/AIDS outpatient clinic. Methods: From Jan 2006 to May 2010, patients with poor FUP/ADH were offered SEAD inclusion, all were evaluated by a nurse or a psychologist (adherence collaborators) who assessed all the reasons and barriers precluding a correct FUP/ADH. For each identified problem, different interventions were planned, using our own resources or coordinating others. Follow-up was censored in Nov 2011. Time to death after being admitted to SEAD and the effect of SEAD program intervention were assessed with Kaplan-Meier curves, log-Rank test and a Cox regression model. Summary of results: Overall, 215 patients were assessed: mean age 45 years, 24% women, IDU 75%, with baseline ADH >90% in only 23%; median HIV-RNA and CD4 cell count were 377 copies/ml and 326 cell/mcL. Patients entered in SEAD due to poor ADH in 17%, FUP problems in 23%, and both 60%. Main reasons driving poor FUP/ADH were severe bio-psycho-social problems 28%, severe drug and/or alcohol abuse 26%, logistic problems 18%, other psychiatric disorders 13%, oversights 9%, unknown 4% and antiretroviral intolerance 2%. Only 54% of patients received;>50% of planned interventions, due to population complexity. Cocaine/heroin and alcohol abuse were reported by 34% and 17% respectively. Afer a median follow-up of 3.7 [3.31-4.4] years 193 patients received a mean of 8 (2.5-12) interventions/year, achieving virological control in 64%. Probability of survival was 92%, 89% and 86% after 1, 2 and 3 years respectively. In Cox regression model an intervention of SEAD project higher than 50% of planned was an independent predictor of survival HR 0.336 (95% CI 0.156-0.725); p=0.005, after adjusting for age, alcohol or cocaine abuse, psychological attention, degree of adherence and follow-up, intravenous acquisition of HIV, and family support. Alcohol and cocaine abuse were associated with higher mortality HR 2.964 (95% CI 1.378-6.374); p=0.005 and HR 2.444 (95% CI 1.161-5.145); p=0.019. Conclusions: Being admitted to SEAD intervention project and receiving more than 50% of planned interventions increased survival expectancy.

Research paper thumbnail of 484 Impact of Hiv-Coinfection on the Outcome of Viral Cirrhosis Liver Transplant Candidates at a Reference Center from 2001–2008 and Predictors of Post-Transplant Survival

Journal of Hepatology, 2009

Research paper thumbnail of 1319 Prevalence and Effect of Graft vs Recipient IL28B SNP on Early HCV-Rna Kinetics in Patients on Peg-Ifn/RBV After Liver Transplantation

Journal of Hepatology, 2011

Research paper thumbnail of HCV clearance and treatment outcome in genotype 1 HCV-monoinfected, HIV-coinfected and liver transplanted patients on peg-IFN-α-2b/ribavirin

Journal of Hepatology, 2005

Background/Aims: Differences in HCV-RNA clearance during therapy might explain the lower efficacy... more Background/Aims: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients.

Research paper thumbnail of Risk Factors for Candidemia in Pediatric Patients With Congenital Heart Disease •

Infection Control and Hospital Epidemiology, 2006

To identify the main risk factors for the acquisition of candidemia in children with congenital h... more To identify the main risk factors for the acquisition of candidemia in children with congenital heart disease (CHD) in order to improve the clinical management of these patients. A case-control study. A large tertiary-care referral center in Spain with a pediatric intensive care unit (PICU) to which more than 500 children with CHD are admitted annually. All patients had CHD and were admitted to the PICU during 1995-2000. Case patients were defined as patients with candidemia, and control patients were defined as patients without candidemia. Twenty-eight case patients and 47 control subjects were included in the study. Case patients were younger (mean age [+/-SD], 12.5+/-32.0 vs 38.0+/-48.0 months; P<.01) and had a longer median PICU stay (19 vs 4 days; P<.01), and a greater percentage of case patients previously had Candida species isolated from specimens other than blood (eg, bronchial aspirates, urine, or skin specimens) (39% vs 4%; P<.01). Severity of clinical condition, as measured by the Therapeutic Intervention Scoring System (TISS) 1 week after PICU admission (odds ratio, 1.15; 95% confidence interval, 1.05-1.26; P<.01), and receipt of antibiotic treatment for more than 5 days (odds ratio, 13.42; 95% confidence interval, 1.31-137.13; P=.03) were independently associated with the development of candidemia. Patients with CHD who have a high TISS score 1 week after PICU admission and patients who have received prolonged antibiotic therapy should be considered at high risk for candidemia. Our results suggest that shorter courses of antibiotic therapy, routine surveillance culture for Candida species, and initiation of preemptive or empirical antifungal treatment could help in the clinical management of these patients.

Research paper thumbnail of Missing Scheduled Visits in the Outpatient Clinic as a Marker of Short-Term Admissions and Death

HIV Clinical Trials, 2012

Research paper thumbnail of Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance

Histopathology, 2011

Aims: Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are o... more Aims: Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are overexpressed in many tumours. We analysed the expression of relevant HSPs and heat shock factor 1 (HSF1) in classical Hodgkin lymphoma (cHL) and their relationship with caspase signalling pathways and patient outcome. Methods and results: Using tissue microarrays (TMAs), most cases showed strong immunohistochemical expression of HSPs 40, 60, 70, 90, 110, HO1, cell division cycle 37 homolog (CDC37) and HSF1, which points to cHL as a potential candidate to stressresponse inhibitors. Active caspases 3, 8 and 9 were detected in 55.1%, 55.4% and 96.2% of cases although cleaved poly (ADP-ribose) polymerase (PARP) was observed in only 16.1%, suggesting an improper functioning of apoptosis. Statistical analysis showed associations of HSP70 with active caspase 3 (P = 0.000); HSP40 with active caspase 9 (P = 0.031) and p53 (P = 0.003); HO1 with p53 (P = 0.006) and p21 (P = 0.005); and p53 with p21 (P = 0.015). Conclusions: Correlations between the expression of apoptotic markers and HSPs may suggest a role for the latter in modulating apoptosis in cHL, mainly through the HSP70-HSP40 system, and in the stabilization of p53. Survival analyses showed that absence of active caspase 8 and HO1 had a negative impact in patient outcome.

Research paper thumbnail of Candidemia in pediatric patients with congenital heart disease

Diagnostic Microbiology and Infectious Disease, 2006

Candidemia is an important problem in pediatrics. In our hospital, highest candidemia rates were ... more Candidemia is an important problem in pediatrics. In our hospital, highest candidemia rates were documented among children with congenital heart disease (CHD). A series was conducted to describe the clinical and mortality features of candidemia in these patients. Fifty-two cases (1988-2000) included very young infants (median age, 2 months) who received long-term antibiotic treatment (median, 20.5 days). Candida parapsilosis predominated (54%). Endovascular infections occurred in 11.5%. In-hospital mortality was 39% and related mortality 14%. Maintenance of catheter (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.0-37.2; P = .05) and severity of patients as measured with the Pediatric Risk Score of Mortality I (OR, 1.1, 95% CI, 1.0-1.3; P = .05) were independently associated with mortality. In summary, candidemia in children with CHD is diagnosed to very young infants with prolonged antibiotic therapy. Mortality is high but, in most cases, is not related to candidemia. Optimal management may include exclusion of endocarditis, early antifungal treatment, and catheter removal.

Research paper thumbnail of Tuberculosis Complicating Hepatitis C Treatment in HIV‐Infected Patients

Clinical Infectious Diseases, 2009

Tuberculosis characteristics and incidence were assessed among patients with concurrent human imm... more Tuberculosis characteristics and incidence were assessed among patients with concurrent human immunodeficiency virus infection and chronic hepatitis C virus infection who were receiving interferon-based therapy at 3 hospitals in Spain. Four of 570 patients (0.7 cases per 100 person-years; 95% confidence interval, 0.19-1.78 cases per 100 person-years) received a diagnosis of tuberculosis; all of them presented with a decrease in CD4+ cell count before diagnosis, and 3 of them received a delayed diagnosis. After tuberculosis treatment, all patients were cured.

Research paper thumbnail of Relevant gender differences in epidemiological profile, exposure to first antiretroviral regimen and survival in the Spanish AIDS Research Network

Antiviral Therapy, 2013

The possible differences in the disease spectrum and prognosis of HIV infection in women and men ... more The possible differences in the disease spectrum and prognosis of HIV infection in women and men is a major point of concern. Women are under-represented in randomized clinical trials and in some cohorts. Discordant results have often been obtained depending on the setting. We assessed gender differences in clinical and epidemiological features, antiretroviral treatment (ART) exposure and survival in two multicentre cohorts of HIV-positive subjects in Spain: CoRIS-MD and CoRIS. Competing risk regression models were used to assess gender effect on time to start ART and time to first ART change, and a Cox regression model to estimate gender effect on time to death. Between January 1996 and December 2008, 1,953 women and 6,072 men naive to ART at study entry were included. The trend analysis over time showed the percentage of women in the younger (<20 years) and older…

Research paper thumbnail of A cohort study of accidents occurring in mentally handicapped patients living in institutions

Annals of General Psychiatry, 2010

Background: Mentally handicapped patients who require extensive and generalised care and are resi... more Background: Mentally handicapped patients who require extensive and generalised care and are resident in mental health institutions have certain characteristics that could mean that they suffer certain types of accidents. The aim of this study was to determine the number and type of accident-related injuries in this population in order to design appropriate preventative strategies.

Research paper thumbnail of CD4 cell recovery during successful antiretroviral therapy in naive HIV-infected patients

AIDS, 2004

We evaluated the impact of HIV risk practice on immune reconstitution in a prospective cohort of ... more We evaluated the impact of HIV risk practice on immune reconstitution in a prospective cohort of 288 patients (176 former injecting drug users) who maintained complete virus suppression for more than 24 months. Significant differences in CD4 cell counts at 6 and 24 months were detected. Multivariate analysis showed that drug use was an independent predictor of poor immunological recovery. Injection drug abuse impairs short and long-term CD4 cell recovery in HIV-positive patients initiating successful highly active antiretroviral therapy.