Serological response to COVID-19 pneumonia and increasing severity over 18 months in a prospective cohort of hospitalized patients.

In this study, we present an 18-month serological follow-up of 294 patients with COVID-19 pneumonia. The aim was to assess the dynamics of serological response and its correlation with clinical worsening, as well as to describe clinical worsening determinants. Results of the study showed an early immunoglobulin M response, which clearly diminished starting at 4 months, but nonetheless, a small group of patients remained positive. As for immunoglobulin G, levels were higher up to 6 months in patients who presented clinical worsening during hospitalization. High titers of the immunoglobulin were maintained in all patients during follow-up, which would indicate that humoral immunity due to infection is long-lasting. Male sex, presence of myalgias and extensive radiological affectation were significantly correlated with clinical worsening.

Physical training program for people at risk of cardiovascular disorders in the primary care setting: A randomized clinical trial

Background and Objective: The impact of a physical training program on moderate–vigorous physical activity is still poorly known in primary cardiovascular prevention. Our objective was to determine the efficacy of a physical training program to promote moderate–vigorous physical activity and exercise in individuals at risk of suffering a cardiovascular event.Patients and methodsRandomized, parallel group controlled trial performed from October 2014 to July 2016. Sedentary patients at risk of suffering a cardiovascular event were randomized to the control group (CG) (72) or the intervention group (IG) (75). Intervention consisted of a 2-month physical training program. The main outcome was the proportion of patients achieving a “relevant response to Physical Activity” (increase≥240METs-min/week in moderate–vigorous Physical Activity using the International Physical Activity Questionnaire (IPAQ)). Secondary outcomes included the proportion of patients performing an “adequate amount of exercise” (≥360METs-min/week in moderate–vigorous exercise using the IPAQ).ResultsOf the 147 patients randomized, 132 (90%) completed the follow-up. Adherence to exercise performance was 91% and no adverse effects were recorded. The proportion of patients in the IG versus CG achieving the main outcome was 34.9% vs 11.6%; OR [95%CI]: 4.2 [1.7–10.4]. Furthermore, more patients in the IG performed an adequate amount of exercise (33.3% vs. 11.6%; OR: 4.1 [1.6–10.5]).ConclusionA short-duration physical training program performed in the primary care setting is efficacious and safe in promoting moderate–vigorous physical activity and exercise in the short-term, in a population at risk of suffering a cardiovascular event. (AU)

Antecedentes y objetivo: El impacto de programas de entrenamiento en actividad física moderada-vigorosa es poco conocido en prevención primaria cardiovascular. Nuestro objetivo fue analizar la eficacia de un programa de entrenamiento en promover la actividad física moderada-vigorosa y la práctica de ejercicio, en pacientes con riesgo de eventos cardiovasculares.Pacientes y métodoEnsayo clínico aleatorizado, paralelo, con grupo control (octubre 2014 a julio 2016). Pacientes sedentarios con riesgo de eventos cardiovasculares se aleatorizaron a un grupo control (GC) (72) o un grupo intervención (GI) (75). La intervención consistió en un programa de entrenamiento de 2meses. La variable pronóstica principal fue la proporción de pacientes que alcanzaron una «respuesta relevante en actividad física» (aumento≥240MET-min/sem actividad física moderada-vigorosa en el Cuestionario Internacional de Actividad Física [International Physical Activity Questionnaire, IPAQ]). Las variables pronósticas secundarias incluyeron la proporción de pacientes que realizaban una «adecuada cantidad de ejercicio»(≥360MET-min/sem ejercicio moderado-vigoroso en el IPAQ).ResultadosDe los 147 pacientes aleatorizados, 132 (90%) completaron el seguimiento. La adherencia a las sesiones fue del 91% y no se registraron efectos adversos. La proporción de pacientes en GI versus GC que alcanzaron el objetivo principal fue del 34,9% vs el 11,6%; OR: 4,2; IC 95%: 1,7-10,4. Significativamente más pacientes en el GI realizaron una adecuada cantidad de ejercicio (33,3% vs 11,6%; OR: 4,1; IC 95%: 1,6-10,5).ConclusiónUn programa de entrenamiento de corta duración realizado en atención primaria es eficaz y seguro a corto plazo en la promoción de la actividad física moderada-vigorosa y del ejercicio en una población con riesgo de eventos cardiovasculares. (AU)

Short versus long course therapy in the treatment of febrile urinary tract infections in men based on serum PSA values.

BACKGROUND: Febrile urinary tract infections (fUTI) in men are frequently complicated with subclinical prostatic involvement, measured by a transient increase in serum prostate-specific-antigen (sPSA). The aim of this study was to evaluate recurrence rates in a 6-month follow-up period of 2-week versus 4-week antibiotic treatment in men with fUTI, based on prostatic involvement. Clinical and microbiological cure rates at the end-of-therapy (EoT) were also assessed. METHODS: Open label, not-controlled, prospective study. Consecutive men diagnosed of fUTI were included. Duration of therapy was 2 weeks for patients with a sPSA level <5mg/L (short duration therapy, SDT) or 4 weeks for PSA >5 mg/L (long duration therapy, LDT). RESULTS: Ninety-one patients were included; 19 (20%) received SDT. Median age was 56.9 years (range 23-88). Bacteremia was present in 9.8% of patients (Escherichia coli was isolated in 91%). Both groups had similar demographic, clinical characteristics and laboratory findings. Median PSA levels were 2.3 mg/L in the SDT group vs 23.4 mg/L in the LDT group. In the 6-month visit, 26% of patients had achieved complete follow-up. Nonsignificant differences between groups were found neither in recurrence rates after 6 months (9% in SDT vs 10% in LDT) nor in clinical or microbiological cure rates at EoT (100% in SDT vs 95% in LDT and 95% in SDT vs 93% in LDT respectively). CONCLUSIONS: One fifth of men with fUTI did not present apparent prostatic involvement. A 2-week regimen seems adequate in terms of clinical, microbiological cure and recurrence rates for those patients without PSA elevation.

Physical training program for people at risk of cardiovascular disorders in the primary care setting: A randomized clinical trial.

BACKGROUND AND OBJECTIVE: The impact of a physical training program on moderate-vigorous physical activity is still poorly known in primary cardiovascular prevention. Our objective was to determine the efficacy of a physical training program to promote moderate-vigorous physical activity and exercise in individuals at risk of suffering a cardiovascular event. PATIENTS AND METHODS: Randomized, parallel group controlled trial performed from October 2014 to July 2016. Sedentary patients at risk of suffering a cardiovascular event were randomized to the control group (CG) (72) or the intervention group (IG) (75). Intervention consisted of a 2-month physical training program. The main outcome was the proportion of patients achieving a "relevant response to Physical Activity" (increase≥240METs-min/week in moderate-vigorous Physical Activity using the International Physical Activity Questionnaire (IPAQ)). Secondary outcomes included the proportion of patients performing an "adequate amount of exercise" (≥360METs-min/week in moderate-vigorous exercise using the IPAQ). RESULTS: Of the 147 patients randomized, 132 (90%) completed the follow-up. Adherence to exercise performance was 91% and no adverse effects were recorded. The proportion of patients in the IG versus CG achieving the main outcome was 34.9% vs 11.6%; OR [95%CI]: 4.2 [1.7-10.4]. Furthermore, more patients in the IG performed an adequate amount of exercise (33.3% vs. 11.6%; OR: 4.1 [1.6-10.5]). CONCLUSION: A short-duration physical training program performed in the primary care setting is efficacious and safe in promoting moderate-vigorous physical activity and exercise in the short-term, in a population at risk of suffering a cardiovascular event. TRIAL REGISTRATION: "Training Programme in Physical Activity". NCT03717363. TRIAL REGISTRATION: Clinicaltrials.gov.

Radicality of lymphadenectomy in lung cancer resections by thoracotomy and video-assisted thoracoscopic approach: A prospective, multicentre and propensity-score adjusted study.

OBJECTIVE: To analyse differences in intraoperative nodal assessment in patients undergoing lung cancer resection by thoracotomy and video-assisted thoracoscopy (VATS) in the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). METHODS: Prospective multicentre cohort study of anatomic pulmonary resections (n = 3533) performed from December 2016 to March 2018. Main surgical, clinical and oncological variables related with lymphadenectomy were compared according to surgical approach. Corresponding tests for homogeneity were performed. Multiple logistic regression analyses were used to determine the odds ratio (OR) and 95% confidence interval (95%CI). Covariate adjustment using the propensity score (PS) was performed to reduce confounding effects. RESULTS: After exclusions, 2532 patients were analysed. Systematic nodal dissection (SND) was performed in 65%, with a median of resected/sampled lymph nodes (LN) of 7 (IQR 4-12) and pathologic (p) N2 and uncertain (u) pNu rates of 9.4% and 28.9%, respectively. At multivariate analysis, the following were associated with thoracotomy (OR; 95%CI): SND (1.4; 1.08-1.96; p = 0.014), staging mediastinoscopy (2.6; 1.59-4.25; p < 0.001), tumor > 3 cm (2.1; 1.66-2.78; p < 0.001), central tumor (2.5; 1.90-3.24; p < 0.001); pN1 (1.8; 1.25-2.67; p < 0.002), pN2 (1.8; 1.18-2.76; p = 0.006), lower FEV1 (0.9; 0.98-0.99; p < 0.001), squamous cell carcinoma (1.5; 1.16-1.98; p = 0.002) and inexperienced surgeons in VATS (compared with > 100 VATS experience) (37.6; 13.55-104.6; p < 0.001). After PS adjustment, SND maintained the OR, but in the limit of signification (1.4; 1-1.98; p = 0.05). Nodal upstaging was significantly higher in the thoracotomy group. Complication rates of SND and no SND were similar. CONCLUSIONS: Thoracotomy was associated with a more thorough lymphadenectomy in GEVATS. Therefore, intraoperative lymph node evaluation performed at VATS should be improved to have better prognostic information and more solid grounds to indicate adjuvant therapy.

Prevalence, beliefs and impact of drug-drug interactions between antiretroviral therapy and illicit drugs among people living with HIV in Spain.

Drug use implies important challenges related to HIV management, particularly due to an increased risk of potential interactions between antiretroviral therapy (ART) and illicit drugs (pDDIs). This study analyses the prevalence and severity of pDDIs among people living with HIV (PLHIV). It also explores their awareness of pDDIs and their beliefs about the toxicity that they may cause, as well as the impact of pDDIs on selected health variables. We conducted an on-line cross-sectional survey across 33 Spanish hospitals and NGOs to collect demographics and clinical data. pDDIs were checked against the Interaction Checker developed by Liverpool University. The sample of the present study was composed of 694 PLHIV who used illicit drugs. They represented 49.5% of the 1,401 PLHIV that participated in the survey. After excluding 38 participants due to lack of information on their ART or illicit drug use, 335 (51.1%) participants consuming drugs presented with some potentially significant pDDIs between their ART and illicit drugs, with a mean of 2.1±1.7 (1-10) pDDIs per patient. The drugs most frequently involved in pDDIs were cocaine, cannabis, MDMA and nitrates ("poppers"). The prevalence of pDDIs across ART regimens was: protease inhibitors (41.7%); integrase inhibitor-boosted regimens (32.1%), and non-nucleoside reverse transcriptase inhibitors (26.3%). An awareness of pDDIs and beliefs about their potential toxicity correlated positively with intentional non-adherence (p<0.0001). Participants with pDDIs exhibited a higher prevalence of intentional non-adherence (2.19±1.04 vs. 1.93±0.94; p = 0.001). The presence of pDDIs was not associated with poorer results in the clinical variables analysed. A significant proportion of PLHIV who use drugs experience pDDIs, thereby requiring close monitoring. pDDIs should be considered in the clinical management of HIV patients. Adequate information about pDDIs and indicators about how to manage ART when PLHIV use drugs could improve ART non-adherence.

Recreational Drug Use in People Living with HIV in Spain: Factors Associated with Drug Use and the Impact on Clinical Outcomes.

We analysed the impact of recreational drug use (RDU) on different outcomes in people living with HIV (PLHIV). A multicentre retrospective cohort study was performed with two cohorts of PLHIV included: people using recreational drugs (PURD) vs. people not using recreational drugs (PNURD). Overall, 275 PLHIV were included. RDU was associated with men having sex with men (OR 4.14, 95% CI [1.14, 5.19]), previous sexually transmitted infections (OR 4.00, 95% CI [1.97, 8.13]), and current smoking (OR 2.74, 95% CI [1.44, 5.19]). While the CD4/CD8 ratio increased amongst PNURD during the follow-up year, it decreased amongst PURD (p = 0.050). PURD presented lower scores of self-reported and multi-interval antiretroviral adherence (p = 0.017, and p = 0.006, respectively), emotional well-being (p < 0.0001), and regular follow-up (p = 0.059), but paid more visits to the emergency unit (p = 0.046). RDU worsens clinical, immunological, and mental health outcomes amongst PLHIV.

RESUMEN: Analizamos el impacto del consumo de drogas recreativas sobre variables relacionadas con la salud en personas con VIH (PVIH). Estudio multicéntrico retrospectivo con dos cohortes de PVIH: consumidores de drogas recreativas (CDR) y no consumidores (NCDR). Se incluyeron 275 PVIH. El consumo de drogas recreativas se asoció al colectivo de hombres que mantienen sexo con hombres (OR 4.14, IC95% [1.14, 5.19]), a infecciones de transmisión sexual previas (OR = 4.00, IC95% [1.97, 8.13]) y a ser fumador (OR = 2.74, IC95% [1.44, 5.19]). El ratio CD4/CD8 aumentó entre los NCDR durante el año de seguimiento y disminuyó en los CDR (p = 0.050). Los CDR presentaron peor adherencia al tratamiento antiretroviral medida con dos métodos indirectos (p = 0.017 y p = 0.006, respectivamente), y bienestar emocional (p < 0.0001). Además, visitaron menos al especialista en enfermedades infecciosas (p = 0.059), y más a urgencias (p = 0.046). El consumo de drogas recreativas empeora los resultados clínicos y de salud mental entre las PVIH.

Fixed Ratio versus Lower Limit of Normality for Diagnosing COPD in Primary Care: Long-Term Follow-Up of EGARPOC Study.

Purpose: The best criterion for diagnosing airway obstruction in COPD, fixed ratio (FR: FEV1/FVC<0.7) or lower limit of normality (LLN), remains controversial. We compared the long-term evolution of COPD patients according to the initial obstruction criteria. Patients and Methods: Between 2005 and 2008, we evaluated 1728 subjects over 45 years of age with smoking history, pertaining to a primary care center. A total of 424 patients were obstructive by FR, after a bronchodilator test. Of those, 289 patients met obstruction criteria for both FR and LLN and were considered concordant patients (FR+LLN+), while 135 patients were obstructive by FR but non-obstructive by LLN and were defined as discordant patients (FR+LLN-). Results: Forty-eight patients (11.3%) were lost in follow-up, and 158 died (37.3%). After a median time of 120.4 months (IQR 25-75%: 110.2-128.8), 215 patients were spirometrically reevaluated. The annualized loss of FEV1/FVC was greater in discordant (FR+LLN-) patients [0.54 (0.8) vs 0.82 (0.7); p = 0.008], while 81% became concordant (FR+LLN+) during the follow-up. Hospitalization for COPD exacerbations was more frequent in concordant (FR+LLN+) patients (1.57±3.51 vs 0.77±2.29; p = 0.002). Adjusting for age, concordant (FR+LLN+) patients had greater COPD mortality (HR: 2.97; CI 95%: 1.27-7.3; p = 0.02). Conclusion: LLN seems to be less useful for COPD diagnosis in primary care. Discordant (FR+LLN-) patients lost more FEV1/FVC during their evolution and tended to become concordant. LLN predicted COPD hospitalizations and mortality more poorly.

Drug use and antiretroviral therapy (ART) interactions: a qualitative study to explore the knowledge, beliefs, adherence, and quality of life of people living with HIV taking ART and illicit drugs.

BACKGROUND: To explore the use of illicit drugs by people living with HIV (PLHIV) taking antiretroviral therapy (ART) and their relationship with variables relevant to the management of HIV infection, such as knowledge and beliefs about drug-drug interactions (DDIs), ART adherence, quality of life (QoL), and use of health-care resources. METHODS: 21 PLHIV in Spain who concomitantly took illicit drugs and ART participated in this qualitative study. Eight experts collaborated in the design of the semi-structured interview guide which explored the following topics: illicit drug use, knowledge and beliefs about DDIs and their impact on ART adherence, the effects of using illicit drugs on health, QoL, and use of health-care resources. Four of those experts, who were PLHIV and members of the executive boards of non-government organizations (NGOs) from four Spanish regions, recruited the participants through their NGOs and carried out the face-to-face interviews. Content analysis of the qualitative data was conducted with the support of the MAXQDA 12 program. RESULTS: Participants were mainly men (85.7%) and only 14.3% of them were heterosexual. Content analysis showed that the most frequently consumed illicit drugs were poppers, cocaine, and cannabis. Participants were polydrug users and this was, in many cases, prior to HIV diagnosis. Most participants presented theoretical potential moderate DDIs that would require monitoring. More than three quarters of them were not aware of these DDIs. Participants reported interactive toxicity beliefs that lead to intentional nonadherence behaviors. In most cases (n = 17), the participant's doctor knew about their drug use, however only six of them had had an open dialogue with their physician about it. Illicit drug use led to some health-related problems, mainly sexually transmitted infections. A positive QoL's self-perception was found among several participants that used recreational illicit drugs. CONCLUSIONS: Adequate information about DDIs and clues about how to manage ART when PLHIV are using illicit drugs could reduce the negative effects of such interactions and improve ART adherence and QoL.

Prevalence and patterns of illicit drug use in people living with HIV in Spain: A cross-sectional study.

This study assessed the prevalence and patterns of drug use among people living with HIV (PLHIV) in Spain. We conducted an observational cross-sectional study including 1401 PLHIV. Data were collected through 33 sites across Spain using an online computer-assisted self-administered interview. The survey measured use of illicit drugs and other substances, treatment adherence and health-related variables. To analyse patterns of drug use we performed cluster analysis in two stages. The most frequently consumed substances were: alcohol (86.7%), tobacco (55.0%), illicit drugs (49.5%), other substances (27.1%). The most prevalent illicit drugs used were cannabis (73.8%), cocaine powder (53.9%), and poppers (45.4%). Results found four clusters of PLHIV who used drugs. Two of them were composed mainly of heterosexuals (HTX): Cluster 1 (n = 172) presented the lowest polydrug use and they were mainly users of cannabis, and Cluster 2 (n = 84) grouped mostly men who used mainly heroin and cocaine; which had the highest percentage of people who inject drugs and presented the lowest level of treatment adherence (79.8±14.2; p < .0001). The other two clusters were composed mainly of men who have sex with men (MSM), who were mostly users of recreational drugs. Cluster 3 (n = 285) reported moderate consumption, both regarding frequency and diversity of drugs used, while Cluster 4 (n = 153) was characterized by the highest drug polyconsumption (7.4±2.2; p < .0001), and 4 grouped MSM who injected recreational drugs, and who reported the highest frequency of use of drugs in a sexual context (2.6±0.8; p < .0001) and rates of sexually transmitted infections (1.8±1.1; p < .01). This is the largest multi-centre cross-sectional study assessing the current prevalence and patterns of drug use among PLHIV in Spain. The highest prevalence of drug use was found among MSM, although HTX who used heroin and cocaine (Cluster 2) had the most problems with adherence to HIV treatment and the worst health status.

Psychosocial determinants of HIV testing across stages of change in Spanish population: a cross-sectional national survey.

BACKGROUND: The goal of this research is to study the psychosocial determinants of HIV-testing as a function of the decision or change stage concerning this health behavior. The determinants considered in the major ongoing health models and the stages contemplated in the Precaution Adoption Process Model are analysed. METHODS: A cross-sectional survey was administered to 1,554 people over 16 years of age living in Spain by a computer-assisted telephone interview (CATI). The sample design was randomised, with quotas of sex and age. The survey measured various psychosocial determinants of health behaviors considered in the main cognitive theories, the interviewees' stage of change concerning HIV-testing (lack of awareness, decision not to act, decision to act, action, maintenance, and abandonment), and the signal for the action of getting tested or the perceived barriers to being tested. RESULTS: Approximately two thirds of the population had not ever had the HIV test. The predominant stage was lack of awareness. The most frequently perceived barriers to testing were related to the health system and to the stigma. We also found that the psychosocial determinants studied differed depending on the respondents' stage of change. Perception of risk, perceived self-efficacy, proximity to people who had been tested, perceived benefits of knowing the diagnosis, and a positive instrumental and emotional attitude were positively associated with the decision and maintenance of testing behavior. However, unrealistic underestimation of the risk of HIV infection, stereotypes about the infection, and the perceived severity of HIV were associated with the decision not to be tested. CONCLUSIONS: There are various sociocognitive and motivational profiles depending on people's decision stage concerning HIV-testing. Knowing this profile may allow us to design interventions to influence the psychosocial determinants that characterise each stage of change.

Which is the Best Screening Strategy for COPD among Smokers in Primary Care?

We developed a questionnaire to detect cases of chronic obstructive pulmonary disease (COPD) and compared its reliability with other strategies. In order to develop the new questionnaire (COPD screening questionnaire from Terrassa [EGARPOC]) we used data from an epidemiological study on the prevalence of COPD in smokers and calculated the odds ratio for each variable showing significance for the diagnosis of COPD on regression analysis. For comparison among questionnaires and the portable spirometer COPD-6, a cross-sectional multicenter study was performed. The study included 407 smokers or ex-smokers over the age of 40 years with no known diagnosis of COPD, who completed the different questionnaires (EGARPOC, Respiratory Health Screening Questionnaire, COPD-population screener and 2 questions) and underwent spirometry with the COPD-6. We determined the sensitivity, specificity, positive and negative predictive values (S, Sp, PPV and NPV, respectively) and the area under the receiver operating characteristic ROC curve (AUC ROC) of all the questionnaires and the different COPD-6 cut-offs. The prevalence of COPD was 26.3%. The EGARPOC questionnaire showed an S of 81.8%, an Sp of 70.6%, and an NPV of 91.8%; 73.3% of individuals were correctly classified, and the AUC ROC was 0.841. On comparing the questionnaires by the Chi-square test, the 2-question questionnaire showed the worst discrimination; while with an optimal cut-off of forced expiratory volume in one 1 second (FEV1)/FEV6 of 0.78, the COPD-6 was significantly better than the questionnaires in the detection of COPD. Using a cut-off of FEV1/FEV6 of 0.78 the COPD-6 was found to be the best screening tool for COPD in primary care compared to the questionnaires tested, which did not show differences among them.

Sex differences in N-palmitoylethanolamide effectiveness in neuropathic pain associated with lumbosciatalgia.

BACKGROUND: Response to N-palmitoylethanolamide (PEA) appear to be influenced by hormonal changes. OBJECTIVE: To evaluate sex differences in the effectiveness of PEA. METHOD: Patients with neuropathic pain resulting from lumbosciatalgia were assigned to conventional treatment plus PEA or conventional treatment. The pain variables were measured using a visual analog scale and quality of life was assessed. RESULTS: One hundred and twelve patients were included. Significant differences were seen in men for all the variables. In women the differences were only significant for pain. A multivariate linear regression analysis showed a positive interaction between men and PEA treatment for the SF-12 mental component. CONCLUSION: Men treated with PEA are more likely to improve their quality of life regarding mental health, compared with women.

Prevalence, Risk Factors and Diagnostic Accuracy of COPD Among Smokers in Primary Care.

The prevalence of COPD is high, and most cases remain undiagnosed. In contrast, some patients labeled and treated as COPD do not have spirometric confirmation. Our objective was to determine the prevalence of COPD among smokers aged 45 years or older and investigate the accuracy of diagnosis of COPD in primary care. A population-based, epidemiological study was conducted in a primary care centre among subjects older than 45 years with a history of smoking. The participants underwent a clinical questionnaire and spirometry with bronchodilator test. Additionally, participants with newly diagnosed COPD, defined as postbronchodilator FEV1/FVC<0.7, underwent 4-week treatment with formoterol and budesonide to rule out reversible airflow obstruction. A total of 1,738 individuals (84.4% male) with a mean age of 59.9 years were included. The prevalence of COPD was 24.3% (95%, CI 22.3-26.4), with an overall underdiagnosis of 56.7%. Patients with COPD were older, more frequently male, with a lower body mass index, a longer history of smoking, lower educational level, previous occupational exposure, and more cardiovascular co-morbidity (all p < 0.001). After 4 weeks of treatment, 16% of initially obstructed patients had normal spirometry; in addition, 15.6% of individuals with a diagnosis of COPD did not have airflow obstruction. One out of four smokers 45 years or older presenting in primary care have airflow obstruction, mostly undiagnosed. However, among those with an initial diagnosis of COPD up to 16% will normalise spirometry after 4 weeks of treatment. There is also a significant number of individuals misdiagnosed with COPD.

HIV-infection, atherosclerosis and the inflammatory pathway: candidate gene study in a Spanish HIV-infected population.

BACKGROUND: Higher prevalence of atherosclerosis and higher cardiovascular risk is observed in HIV-infected individuals. The biological mechanisms underlying these processes are unclear. Several studies have implicated genetic variants in the inflammatory genes in cardiovascular disease and in HIV natural course infection. METHODS & FINDINGS: In this study we have tested the possible association between genetic variants in several inflammatory genes and asymptomatic cardiovascular disease measured by carotid intima media thickness (cIMT) and atherosclerotic plaque presence as dependent variables in 213 HIV-infected individuals. A total of 101 genetic variants in 25 candidate genes have been genotyped. Results were analyzed using Plink and SPSS statistical packages. We have found several polymorphisms in the genes ALOX5 (rs2115819 p = 0.009), ALOX5AP (rs9578196 p = 0.007; rs4769873 p = 0.004 and rs9315051 p = 0.0004), CX3CL1 (rs4151117 p = 0.040 and rs614230 p = 0.015) and CCL5 (rs3817655 p = 0.018 and rs2107538 p = 0.018) associated with atherosclerotic plaque. cIMT mean has been associated with CRP (1130864 p = 0.0003 and rs1800947 p = 0.008), IL1RN (rs380092 p = 0.002) and ALOX5AP (rs3885907 p = 0.02) genetic variants. CONCLUSIONS: In this study we have found modest associations between genetic variants in several inflammatory genes and atherosclerotic plaque or cIMT. Nevertheless, our study adds evidence to the association between inflammatory pathway genetic variants and the atherosclerotic disease in HIV-infected individuals.

HIV-associated neurocognitive disorders.

Currently, neuropsychological impairment among HIV+ patients on antiretroviral therapy leads to a reduction in the quality of life and it is an important challenge due to the high prevalence of HIV-associated neurocognitive disorders and its concomitant consequences in relation to morbidity and mortality- including those HIV+ patients with adequate immunological and virological status. The fact that the virus is established in CNS in the early stages and its persistence within the CNS can help us to understand HIV-related brain injury even when highly active antiretroviral therapy is effective. The rising interest in HIV associated neurocognitive disorders has let to development new diagnostic tools, improvement of the neuropsychological tests, and the use of new biomarkers and new neuroimaging techniques that can help the diagnosis. Standardization and homogenization of neurocognitive tests as well as normalizing and simplification of easily accessible tools that can identify patients with increased risk of cognitive impairment represent an urgent requirement. Future efforts should also focus on diagnostic keys and searching for useful strategies in order to decrease HIV neurotoxicity within the CNS.

Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain).

OBJECTIVE: We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. METHODS: We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. RESULTS: Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. CONCLUSIONS: Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.