Supervision of essential patient safety actions in medical units in a health institution.

OBJECTIVE: To determine the importance of the supervision of the essential patient safety actions (AESP) in the different Medical Units of the different levels of care in Mexico City. METHOD: The concern for quality in health care, understood as the safety of patients, is a fundamental aspect that involves the authorities and operational personnel. Supervisions were carried out in the different medical units of Mexico City. RESULTS: Positive correlations were observed between the implementation of the AESP and the number of damages, incidents, events and errors existing in the medical units. CONCLUSIONS: The supervision of the AESP program should be aimed at the prevention and management of risks in health care, recognizing the occurrence of adverse events as a reality resulting from a gradual work of a whole process of continuous improvement.

OBJETIVO: Determinar la importancia de la supervisión de las acciones esenciales de seguridad del paciente (AESP) en las diferentes unidades médicas de los distintos niveles de atención en la Ciudad de México. MÉTODO: La preocupación por la calidad en la atención de salud, entendida como la seguridad de los pacientes, es un aspecto fundamental que involucra a las autoridades y al personal operativo. Se realizaron supervisiones en las diferentes unidades médicas de la Ciudad de México. RESULTADOS: Se observaron correlaciones positivas entre la supervisión de las AESP y el número de daños, incidentes, eventos y errores existentes en las unidades médicas. CONCLUSIONES: La supervisión del programa de AESP debe estar destinado a la prevención y gestión de los riesgos en la atención de salud, reconociendo la ocurrencia de eventos adversos como una realidad producto de un trabajo paulatino de todo un proceso de mejora continua.

Cancer screening in people with HIV: Implementation in clinical practice and barriers perceived by medical specialists in Spain.

OBJECTIVE: To assess the degree of implementation of cancer screening recommendations in people living with HIV (PLHIV) in Spain. METHODS: A self-administered questionnaire was designed on the strategies used for early detection of the main types of cancer in PLHIV. The survey was distributed electronically to HIV physicians participating in the Spanish CoRIS cohort. RESULTS: 106 questionnaires were received from 12 different Spanish Autonomous Communities, with an overall response rate among those who accessed the questionnaire of 60.2%. The majority responded that they followed the CPGs recommendations for the early detection of liver (94.3%), cervical (93.2%) and breast (85.8%) cancers. In colorectal and anal cancer, the proportion was 68.9% and 63.2%, and in prostate and lung cancer of 46.2% and 19.8%, respectively. In hospitals with a greater number of beds, a tendency to perform more cancer screening and greater participation of the Infectious Diseases/HIV Services in the screening programmes was observed. Significant differences were observed in the frequency of colorectal and anal cancer screening among the different Autonomous Communities. The most frequent reasons for not performing screening were the scarcity of material and/or human resources and not being aware of what is recommended in the CPGs. CONCLUSIONS: There are barriers and opportunities to expand cancer screening programmes in PLHIV, especially in colorectal, anal and lung cancers. It is necessary to allocate resources for the early detection of cancer in PLHIV, but also to disseminate CPGs screening recommendations among medical specialists.

Immunologic phenotype of patients with long-COVID syndrome of 1-year duration.

Background: The pathophysiology of long-COVID remains unknown, and information is particularly limited for symptoms of very long duration. We aimed to assess the serological, T-cell immune responses and ANA titers of patients with long-COVID-19 syndrome of 1-year duration. Methods: Prospective, longitudinal study of hospitalized COVID-19 patients followed-up for 12 months. Sequential blood samples and COVID-19 symptom questionnaires (CSQ) were obtained, and humoral and cellular immune responses, antinuclear antibodies (ANA) and inflammation biomarkers were analyzed. Results: Of 154 patients discharged from hospital, 72 non-vaccinated with available CSQ in all visits were included. Of them, 14 (19.4%) reported persistent symptoms both at 6-months and 12-months, mainly asthenia (15.3%), myalgia (13.9%), and difficulty concentrating/memory loss (13.9%). Symptomatic patients were more frequently women, smokers, showed higher WHO severity score, and a trend to higher ICU admission. In the adjusted analysis, long-COVID syndrome was associated with lower frequency of detectable neutralizing antibodies (adjusted hazard ratio [aHR] 0.98; 95% confidence interval [CI], 0.97-0.99) and lower SARS-CoV-2-S1/S2 titers (aHR [95%CI] 0.14 [0.03-0.65]). T-cell immune response measured with a SARS-CoV-2-interferon-γ release assay was not different between groups. There was a higher frequency of positive ANA titers (≥160) in symptomatic patients (57.1% vs 29.3%, p=0.04), that was attenuated after adjustment aHR [95% CI] 3.37 [0.84-13.57], p=0.087. Levels of C-reactive protein and D-dimer were higher during follow-up in symptomatic patients, but with no differences at 12 months. Conclusion: Patients with 1-year duration long-COVID-19 syndrome exhibit a distinct immunologic phenotype that includes a poorer SARS-CoV-2 antibody response, low-degree chronic inflammation that tends to mitigate, and autoimmunity.

Robust long-term immunity to SARS-CoV-2 in patients recovered from severe COVID-19 after interleukin-6 blockade.

BACKGROUND: Whether interleukin-6 (IL-6) blockade in patients with COVID-19 will affect the protective immunity against SARS-CoV-2 has become an important concern for anti-IL-6 therapy. We aimed to investigate the effects of IL-6 blockade on long-term immunity to SARS-CoV-2. METHODS: Prospective, longitudinal cohort study conducted in patients hospitalized for severe or critical COVID-19 with laboratory confirmed SARS-CoV-2 infection. We assessed humoral (anti-S1 domain of the spike [S], anti-nucleocapsid [N], anti-trimeric spike [TrimericS] IgG, and neutralizing antibodies [Nab]) and T-cell (interferon-γ release assay [IGRA]) responses and evaluated the incidence of reinfections over one year after infection in patients undergoing IL-6 blockade with tocilizumab and compared them with untreated subjects. FINDINGS: From 150 adults admitted with confirmed SARS-CoV-2 infection, 78 were 1:1 propensity score-matched. Patients receiving anti-IL6 therapy showed a shorter time to S-IgG seropositivity and stronger S-IgG and N-IgG antibody responses. Among unvaccinated subjects one year after infection, median (Q1-Q3) levels of TrimericS-IgG (295 vs 121 BAU/mL; p = 0.011) and Nab (74.7 vs 41.0 %IH; p = 0.012) were higher in those undergoing anti-IL6 therapy, and a greater proportion of them had Nab (80.6% vs 57.7%; p = 0.028). T-cell immunity was also better in those treated with anti-IL6, with higher median (Q1-Q3) interferon-γ responses (1760 [702-3992] vs 542 [35-1716] mIU/mL; p = 0.013) and more patients showing positive T-cell responses in the IGRA one year after infection. Patients treated with anti-IL6 had fewer reinfections during follow-up and responded to vaccination with robust increase in both antibody and T-cell immunity. INTERPRETATION: IL-6 blockade in patients with severe COVID-19 does not have deleterious effects on long-term immunity to SARS-CoV-2. The magnitude of both antibody and T-cell responses was stronger than the observed in non-anti-cytokine-treated patients with no increase in the risk of reinfections. FUNDING: Instituto de Salud Carlos-III (Spain).

Survival benefit of remdesivir in hospitalized COVID-19 patients with high SARS-CoV-2 viral loads and low-grade systemic inflammation.

OBJECTIVES: To assess the benefits of remdesivir in hospitalized COVID-19 patients receiving combined immunomodulatory therapy (CIT) with dexamethasone and tocilizumab. METHODS: This was a cohort study of microbiologically confirmed COVID-19 hospitalized patients. The primary outcome was all-cause 28 day mortality. Secondary outcomes were need for invasive mechanical ventilation (IMV) and IMV/death. Subgroup analyses according to SARS-CoV-2 cycle threshold (Ct) values and inflammation biomarkers were performed. Multivariable marginal structural Cox proportional hazards regression models were used to analyse the association between remdesivir therapy and the risk of outcomes of interest. RESULTS: Of 1368 hospitalized patients treated with corticosteroids, 1014 (74%) also received tocilizumab, 866 (63%) remdesivir and 767 (56%) tocilizumab + remdesivir. The 28 day mortality was 9% in the overall cohort, with an adjusted HR (aHR) of 0.32 (95% CI = 0.17-0.59) for patients receiving CIT. In the latter group, the 28 day mortality was 6.5%, with an aHR of 1.11 (95% CI = 0.57-2.16) for remdesivir use and there were no differences in secondary outcomes. The risk of primary and secondary outcomes with remdesivir differed by Ct and C-reactive protein (CRP) levels in patients receiving CIT: for 28 day mortality, the aHR was 0.48 (95% CI = 0.21-1.11) for Ct <25, 0.12 (95% CI = 0.02-0.66) for Ct <25 and <5 day symptom duration and 0.13 (95% CI = 0.03-0.50) for CRP <38 mg/L; for IMV and IMV/death, the aHR was 0.32 (95% CI = 0.13-0.77) and 0.33 (95% CI = 0.17-0.63), respectively, in patients with Ct <25. CONCLUSIONS: The benefits of remdesivir administered with dexamethasone and tocilizumab in hospitalized COVID-19 patients differ depending on Ct and CRP. Remdesivir decreases the risk of mortality and need for IMV in patients with high viral loads and low-grade systemic inflammation.

Preemptive interleukin-6 blockade in patients with COVID-19.

Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes.

Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study.

BACKGROUND: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. METHODS: Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. FINDINGS: 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0•016) and SARS-CoV-2 viral load (p<0•001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0•35 [95%CI] [0•15-0•81], log-rank p = 0•014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1•63 [0•35-7•7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0•35 [0•11-0•89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3•1 [1•9-5] for S-IgG; and HR 3•0 [1•9-4•9] for N-IgG; log-rank p<0•001 for both). However, no significant differences between groups were found in either S-IgG (HR 1•56 [0•41-6•0]) nor N-IgG (HR 0•96 [0•26-3•5]) responses in an adjusted propensity score analysis. INTERPRETATION: Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. FUNDING: Instituto de salud Carlos III (Spain).

Infection With Chlamydia trachomatis Increases the Risk of High-grade Anal Intraepithelial Neoplasia in People Living With Human Immunodeficiency Virus.

BACKGROUND: We aimed to assess the relationship between sexually transmitted infections (STIs)-including a large panel of human papillomavirus (HPV) genotypes-and high-grade anal intraepithelial neoplasia (HGAIN) in men who have sex with men (MSM) who were living with human immunodeficiency virus (HIV). METHODS: In a prospective study in an HIV cohort, participants underwent high-resolution anoscopy (HRA) for anorectal swabs collection to investigate STIs and for anal biopsy. Multiplex real-time polymerase chain reactions were performed, detecting several STIs and 28 HPV genotypes. Univariate and multivariate generalized linear models were used to analyze the relationships of variables of interest with HGAIN. RESULTS: There were 145 participants included; in 49, 2 HRAs were performed. Ureaplasma urealyticum (UU) was detected in 25 (17.2%) participants, Chlamydia trachomatis (CT) in 13 (9.0%), Mycoplasma genitalium (MG) in 4 (2.8%), HPV16 in 38 (26.2%), HPV52 in 29 (20%), and HPV53 and HPV42 in 28 (19.3%) participants each. There were 35 (24.1%) subjects diagnosed with HGAIN. In the univariate analysis, HGAIN was associated with CT, UU, MG, HPV16, HPV53, HPV68, and HPV70, and significant interactions were found between CT and HPV16 (odds ratio [OR] 31.0 95% confidence interval [CI] 4.3-221.7) and between UU and HPV16 (OR 8.8, 95% CI 2.1-37.5). In the adjusted model, CT, HPV16, HPV53, HPV70, the CD4+/CD8+ ratio, and the interaction between CT and HPV16 remained independent predictors of HGAIN. HPV16, HPV53, and HPV70 persisted in the second HRA in all the participants with recurrent HGAIN. CONCLUSIONS: Coinfection with CT may potentiate the oncogenic capability of HPV16 and increase the risk of HGAIN in people with HIV. HPV53 and HPV70 should be considered among the genotypes associated with HGAIN.

Risk of cancer in HIV-infected patients in Spain, 2004-2015. The CoRIS cohort study. / Riesgo de cáncer en personas con VIH en España, 2004-2015. Estudio de la cohorte CoRIS.

INTRODUCTION: Cancer is a leading cause of death in individuals with HIV. METHODS: The incidence of cancer in HIV patients of the CoRIS cohort in the 2004-2009 and 2010-2015 periods has been analysed and compared to the incidence in the Spanish general population, estimated from data of the Spanish Cancer Registry Network. RESULTS: Between January 2004 and November 2015, 12,239 patients were included in CoRIS and 338 incident cancer cases were diagnosed. The overall incidence of cancer per 100,000 persons-year (95% CI) was 702.39 (629.51-781.42) with no significant differences between the 2periods. A 38% of the incident cancer cases were AIDS defining cancers (ADC) and 62% non-AIDS defining cancers (NADC). In the period 2010-2015, there was a significant decrease in the incidence of ADC (standardised incidence ratio [SIR]); 95% CI: 0.38; 0.21-0.66) and NADC predominated. Compared to the general population, the incidence of cancer was double in men with HIV. Higher relative risks were documented (SIR; 95% CI) for Hodgkin's lymphoma in both sexes (males: 8.37, 5.13-14.17; females: 21.83, 2.66-47.79), non-Hodgkin's lymphoma in males (5.30, 2.86-8.45) and cervical cancer (7.43, 3.15-13.87) and head and neck cancer (3.28, 1.21-5.82) in women. CONCLUSIONS: The overall incidence of cancer in individuals with HIV is higher than in the Spanish general population, and it has remained stable since 2004 with a current predominance of NADC. These data suggest that additional efforts should be made in the prevention and the early detection of cancer in these patients.

Estudio sobre la asociación de hipertrigliceridemia con los estados hipertensivos del embarazo / Study on the association of hypertriglyceridemia with hypertensive states of pregnancy

Resumen Antecedentes: La preeclampsia se presenta en el 8% de los embarazos y genera el 25% de las muertes perinatales. Aunque su etiología es multifactorial, algunas alteraciones metabólicas se asocian a la disfunción endotelial presente en la enfermedad, y su estudio podría identificar marcadores tempranos de daño. Objetivo: Determinar la relación existente entre concentración plasmática de triglicéridos en las pacientes embarazadas con enfermedad hipertensiva inducida por el embarazo. Método: Estudio prospectivo que incluyó 147 pacientes gestantes sanas y 120 mujeres con enfermedad hipertensiva inducida por el embarazo y se determinaron colesterol total, lipoproteínas de baja densidad (LDL), lipoproteínas de alta densidad (HDL), hemoglobina glucosilada (HbA1c), biometría hemática (BH), química sanguínea (QS), electrolitos séricos, nitritos séricos y pruebas de función hepática. Resultados: Se encontró una diferencia significativa en la concentración de triglicéridos entre las pacientes normotensas y con preeclampsia (261.22 ± 80.27 vs. 361.46 ± 135.17 mg/dl; p < 0.0008). Además, se observó una menor concentración sérica de nitritos en las pacientes con preeclampsia, que contribuye a explicar la vasoconstricción. Conclusiones: Se encontró una asociación entre la hipertrigliceridemia y la presencia de DM II con el desarrollo de la enfermedad hipertensiva inducida por el embarazo.

Abstract Background: Preeclampsia occurs in 8% of pregnancies and generates 25% of perinatal deaths. Although its etiology is multifactorial, some metabolic alterations are associated with the endothelial dysfunction present in the disease, and its study could identify early markers of damage. Objective: To determine the relationship between plasma concentration of triglycerides in pregnant patients with hypertensive disease induced by pregnancy. Methods: Prospective study that included 147 healthy pregnant women and 120 women with hypertensive disease induced by pregnancy. Total cholesterol, low-density lipoprotein, high-density lipoprotein, Hemoglobin A1c, triglycerides, BH, QS, serum electrolytes, serum nitrites and liver function tests were determined. Results: A significant difference was found in the concentration of triglycerides between normotensive and patients with preeclampsia (261.22 ± 80.27 vs. 361.46 ± 135.17 mg/dl, p < 0.0008). In addition, a lower serum concentration of nitrites was observed in patients with preeclampsia, which helps explain vasoconstriction. Conclusions: We found an association between hypertriglyceridemia and the presence of diabetes mellitus II with the development of hypertensive disease induced by pregnancy.

Is Latin America Ready to Identify Anaplastic Large Cell Lymphoma in Breast Implants Patients? Regional Encounter During the National Plastic Surgery Meeting in Cancun, Mexico.

INTRODUCTION: Anaplastic large cell lymphoma associated with breast implants is receiving increased attention. Most cases have been reported in Europe, North America (USA and Canada), Australia and New Zealand. Fewer cases have been reported in Latin America (including Mexico), Africa and Asia. METHODS: This report was delivered during our national plastic surgery meeting in Cancun in May 2017. Before the meeting, two participants reviewed the literature. The review was performed using the following information sources: PubMed, Embase, Cochrane, Fisterra, Google Scholar and LILACS, with entries from 1980 to August 2015 in several languages (English, Spanish, French and Portuguese). The results were revealed during the meeting to the other participants. The consensus was divided into two parts. The first part included an open-ended question regarding the incidence and prevalence of the problem. The second part included clinical scenarios with different items that were rated by the participants. After this activity, accordance among the responses was evaluated. RESULTS: Seven cases were reported during the meeting (3 from Mexico, 3 from Chile and 1 from Argentina). Fifty percent of the participants reported consulting with guidelines and clinical centers to help with potential cases. Most agreed that further studies must be done in cases of chronic seroma where the capsule plays an important role. DISCUSSION: A current debate exists about the incidence of this problem in Latin America because we did not report the same number of cases as Europe, Australia or North America. More studies are required to determine the differences among reports in Latin America. CONCLUSION: Most representatives agreed that further studies must be done. Concern is increasing, and the problem is known. Other factors involved may be considered, and the problem must not be ignored. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

High-grade anal intraepithelial neoplasia is associated with HIV-1 RNA rectal shedding in virologically suppressed MSM.

OBJECTIVE: The protective effect of ART has not yet been definitively established in MSM. We aimed to characterize the factors associated with persistent HIV-1 RNA rectal shedding. METHODS: Prospective study including virologically suppressed MSM from an HIV cohort. High-resolution anoscopy (HRA) was performed for screening of anal dysplasia, and rectal sampling for HIV-1 RNA quantification and sexually transmitted infections (STIs) investigation through multiplex PCR. Both generalized linear mixed (GLM) and zero-altered negative binomial (ZANB) models were performed. RESULTS: One hundred and fifty-five rectal swab samples from 132 virologically suppressed MSM were included. HIV-1 RNA was detectable in 61 (39.3%) samples, with median (IQR) rectal viral load (rVL) of 295.8 (158.8-522) copies/swab. Multivariable GLM showed that the presence of high-grade anal intraepithelial neoplasia (HG-AIN; OR 2.85 [95% CI 1.10-7.38]) and a protease inhibitor-based regimen (OR 2.49 [0.98-6.34]) resulted in increased risk for rectal HIV-1 shedding, whereas higher nadir CD4+/CD8+ T-cell ratio (OR 0.18 [0.04-0.93]) was negatively associated with rectal shedding. ZANB analyses showed that the best predictors of having detectable rVL were lower nadir CD4+/CD8+ T-cell ratio (OR 0.98 [0.96-0.99]) and PI-based regimens (OR 4.85 [1.29-18.24]); the presence of HG-AIN (RR 2.50 [1.41-4.45]), and a higher burden of STIs (RR 1.39 [1.03-1.85]) were predictors of rectal HIV-1 shedding intensity. CONCLUSION: The prevalence of HIV-1 RNA rectal shedding is high in virologically suppressed MSM. In addition to ART and the immune system integrity, local factors, including the co-existence of HG-AIN and the burden of STIs, may account for the persistence of HIV-1 RNA shedding in rectal mucosa.

Detection of a synthetic sex steroid in the American crocodile (Crocodylus acutus): Evidence for a novel environmental androgen.

Endocrine-disrupting contaminants (EDC's) are well known to alter sexual differentiation among vertebrates via estrogenic effects during development, particularly in organisms characterized by temperature-dependent sex determination. However, substances producing androgenic effects typically lack potency when tested in laboratory settings and are virtually unstudied in field settings. Here, we assay levels of a synthetic androgen, 17α-methyltestosterone (MT), in a heavily male-biased population of American crocodiles in the Tempisque River Basin of Costa Rica based on the recent hypothesis that this chemical is an EDC in developing crocodilian embryos. The presence of MT was documented in all field-collected samples of egg yolk and in plasma of all age classes in among population of crocodiles. Hatchlings exhibited higher plasma MT concentrations (102.1 ± 82.8 ng/mL) than juveniles (33.8 ± 51.5) and adults (25.9 ± 20.8 ng/mL). Among populations, crocodiles captured in the Tempisque River (62.9 ± 73.7 ng/mL) were higher in MT concentration than those from Tarcoles (13.3 ± 11.4 ng/mL) and negative controls (0.001 ± 0.0002 ng/mL). A mechanism for the bio-transport of MT and its subsequent effects is proposed.

Contribution of Oxidative Stress to Non-AIDS Events in HIV-Infected Patients.

OBJECTIVE: Recognition of potentially modifiable mechanisms implicated in the pathogenesis of non-AIDS events (NAEs) might help improve outcomes of HIV-infected individuals. HIV infection has been associated with increased oxidative stress. We assessed the association between F2-isoprostanes and serious NAEs, and whether they improve the predictive performance of inflammation and coagulation biomarkers. METHODS: Prospective multicenter cohort. Individuals who had an incident serious NAE and 2 sex- and age-matched participants with no events were selected. Measurement of F2-isoprostanes, highly sensitive C-reactive protein, interleukin-6, D-dimer, sCD14, sCD40, sCD163, and neopterin levels was performed in successive plasma samples collected from cohort inclusion. RESULTS: Biomarkers were measured in 78 participants developing serious NAEs or death, and 151 subjects with no events. Adjusted levels of F2-isoprostanes, and also of highly sensitive C-reactive protein, sCD14, and D-dimer were higher in individuals who developed serious NAEs, including or not non-AIDS deaths. The same results were observed when only samples collected since the time of achieving virological suppression were analyzed. The additive incorporation of each biomarker, ending with F2-isoprostanes, in an adjusted model was associated with a graded and significant increase in the quality of model fitting, and 94% sensitivity, 33% specificity, and 0.77 accuracy to predict serious NAEs including non-AIDS-related death. CONCLUSION: Oxidative stress is associated with a higher risk of serious NAEs, including non-AIDS deaths. This effect is independent and additive to biomarkers of inflammation, monocyte activation, and coagulation. Our results suggest that oxidative stress should be included among mechanisms to deal with to improve prognosis of HIV-infected individuals.

[Experience of the Mexican National Health System in the development of clinical practice guidelines]. / Experiencia del Sistema Nacional de Salud Mexicano en el desarrollo de guías de práctica clínica.

BACKGROUND: Clinical practice guidelines are tools that have been able to streamline decisions made in health issues and to decrease the gap between clinical action and scientific evidence. OBJECTIVE: The objective of the study is to share the experience in the development and to update the guidelines by the National Health System of Mexico. MATERIAL AND METHODS: The methodology in the development of the guidelines consists of 5 phases: prioritisation, establishment of work groups, development by adoption of international guidelines of de novo, validation and integration in the Master catalogue of clinical practice guidelines for its dissemination. RESULTS: The Master catalogue of clinical practice guidelines contains 664 guidelines, distributed in 42% Internal Medicine, 22% Surgery, 24% Pediatrics and 12% Gynecology. From the total of guidelines coverage is granted at an 85% of the Universal catalogue of health services, an 84% of the Catastrophic expenses protection fund and a 61% of the XXI Century Medical Insurance of the National Commission of Social Protection in Health. DISCUSSION: The result is the sum of a great effort of coordination and cooperation between the institutions of the National Health System, political wills and a commitment of 3,477 health professionals that participate in guidelines' development and update. CONCLUSION: Master catalogue guidelines' integration, diffusion and implantation improve quality of attention and security of the users of the National Health System.

[Deaths due to non-AIDS diseases among HIV infected patients: A 14-year study (1998-2011)]. / Muertes por enfermedades no asociadas directamente con el sida en pacientes con infección por el VIH: un estudio de 14 años (1998-2011).

BACKGROUND AND OBJECTIVE: The objective of this study was to analyze the deaths caused by non-AIDS diseases in a cohort of HIV-infected patients treated between 1998 and 2011. PATIENTS AND METHODS: Information on the causes of death was collected retrospectively, and then classified according to the deaths code (CoDe) algorithm. Patient characteristics and causes of death were compared for two periods: 1998-2004 and 2005-2011. RESULTS: A total of 159 out of the 1070 patients cared for in study period died, 56 (35%) due to AIDS events and 86 (54%) due to non-AIDS events (NAEs); in 17 (11%) the cause of death could not be determined. Overall, the main causes of death were infections (32%), cancer (17%), and unnatural deaths (17%). There was lower mortality from AIDS-related conditions during the second period (18.5% vs 47%; P<.001) and higher mortality from NAEs (68% vs 45%; P=.006). There was a very sharp increase in non-AIDS-defining cancers (18.5% vs 2.1%, p=001), and increased deaths from cardiovascular disease (9.2% vs 2.1%, P=.06). Patients who died in the second period were older, and had a better immunological and virological status at cohort entry and before death. They received antiretroviral therapy (ART) more often and were more often virologically suppressed before death (61.5% vs 24%; P=.001). CONCLUSIONS: Non-AIDS-defining cancers, unnatural deaths, and cardiovascular diseases are now major causes of death in patients with HIV. In recent years the majority of deceased patients are on ART and with virological suppression.

Membranoproliferative glomerulonephritis due to visceral leishmaniasis in an HIV patient.

BACKGROUND: Visceral leishmaniasis is an important opportunistic disease in HIV-positive patients. The information available on the effects of such co-infection in the kidney is limited. We describe a patient with HIV/leishmania coinfection who developed nephrotic syndrome and membranoproliferative glomerulonephritis. As far as we know, only 2 cases of this nephropathy in HIV/leishmania coinfection have been reported. CASE REPORT: A 47-year-old man developed nephrotic syndrome. He had been diagnosed with HIV infection and visceral leishmaniasis and was treated with antiretroviral therapy, antimonial compounds, liposomal amphotericin B and miltefosine, but the leishmania followed a relapsing course. Renal biopsy disclosed membranoproliferative glomerulonephritis and leishmania amastigotes were seen within glomerular capillary lumens. He was given miltefosine and liposomal amphotericin B but the leishmaniasis persisted. Stage 3B chronic renal disease and nephrotic range proteinuria tend to become stable by 15-month follow-up. CONCLUSIONS: Our case illustrated some aspects of leishmaniasis in HIV patients: its relapsing course, the difficulties in therapy, and the renal involvement.

Long-term effects of an intensive intervention in HIV-infected patients with moderate-high atherosclerotic cardiovascular risk.

OBJECTIVES: To evaluate the 5 year effects of an intensive intervention versus the standard-of-care intervention on cardiovascular risk factors in HIV-infected patients on antiretroviral therapy (ART). METHODS: This was a longitudinal study including virologically suppressed patients with at least two cardiovascular risk factors or a Framingham risk score ≥10%. Intensive and standard-of-care interventions aimed for low-density lipoprotein cholesterol (LDL-C) <100 and <130 mg/dL, respectively, by using lipid-lowering drugs. In the intensive group, switching ART when needed to achieve the LDL-C target and low-dose aspirin were used. Achievement of LDL-C targets and changes in carotid intima-media thickness (cIMT) and cardiovascular biomarkers were compared between groups at different timepoints through a 5 year period. RESULTS: Twenty-two and 25 patients in the intensive and standard intervention groups, respectively, were followed up. At 5 years, pre-specified LDL-C targets were achieved in 82% (intensive) and 81% (standard of care) of patients. The median (IQR) change in LDL-C in the intensive and standard intervention groups was -78 (-96/-39.7) and -49 (-72/-3) mg/dL, respectively (P = 0.04), and in the Framingham score was -4% (-8%/-1%) and 0% (-4%/6.5%), respectively (P = 0.01). There were no significant intra- or between-group changes in cIMT measurements. A significant decrease was observed in the intensive and standard groups in interleukin 6 (P = 0.001 and P = 0.002, respectively) and in tumour necrosis factor α (P = 0.023 and P = 0.052, respectively). Asymptomatic creatine phosphokinase elevations were observed in two patients assigned to the standard intervention group. CONCLUSIONS: An intensive intervention on cardiovascular risk factors in HIV-infected patients on ART was feasible, safe and capable of achieving LDL-C targets in the long term. Both intensive and standard interventions were accompanied by antiatherosclerotic changes in inflammatory cytokines and lack of cIMT progression.

Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain.

BACKGROUND: To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. METHODS: All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. RESULTS: Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. CONCLUSIONS: HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.