Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Pediatric pituitary adenoma and medulloblastoma in the setting of p53 mutation: case report and review of the literature.

Li-Fraumeni syndrome is a cancer predisposition condition associated with various tumor types. We present the case of a 6-year-old boy who initially presented with a pituitary adenoma that was successfully treated with surgery. It ultimately recurred, requiring further surgical intervention followed by proton beam therapy. He later developed a medulloblastoma, and genetic testing revealed TP53 germline mutation. The patient underwent gross total resection of this medulloblastoma, followed by proton-based craniospinal irradiation and adjuvant chemotherapy. He remained disease-free 12 months after radiation and 7 months after chemotherapy. Current literature does not report pituitary adenoma as the initial central nervous manifestation in Li-Fraumeni syndrome. Early genetic testing should be considered in pediatric patients who present with such rare tumor types to help identify cancer predisposing conditions. Furthermore, as evidenced by our case, the management of multiple brain tumors in the pediatric population poses challenges. A multidisciplinary approach involving neurosurgery, pediatric oncology, pathology, and radiation oncology remains crucial to optimize patient outcomes.

Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping.

BACKGROUND: Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted. OBJECTIVES: We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016. METHODS: Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%-19% of the virus population were considered to be low-frequency variants. RESULTS: From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants. CONCLUSIONS: Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.

Lipid changes and tolerability in a cohort of adult HIV-infected patients who switched to rilpivirine/emtricitabine/tenofovir due to intolerance to previous combination ART: the PRO-STR study.

Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ±âŸ38.4 mg/dL; week 48: 171.0 ±âŸ35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ±âŸ1.2; week 48: 4.0 ±âŸ1.2), HDL (baseline: 49.1 ±âŸ12.0 mg/dL; week 48: 49.2 ±âŸ45.8 mg/dL), LDL (baseline: 119.2 ±âŸ30.2 mg/dL; week 48: 114.2 ±âŸ110.7 mg/dL), and triglycerides (baseline: 136.6 ±âŸ86.8 mg/dL; week 48: 113.4 ±âŸ67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ±âŸ48.8 mg/dL; week 48: 173.4 ±âŸ36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ±âŸ1.6; week 48: 4.0 ±âŸ1.2), HDL (baseline: 46.4 ±âŸ12.5 mg/dL; week 48: 52.1 ±âŸ54.4 mg/dL), LDL (baseline: 127.0 ±âŸ36.3 mg/dL; week 48: 111.4 ±âŸ35.8 mg/dL), and triglycerides (baseline: 167.6 ±âŸ107.7 mg/dL; week 48: 122.7 ±âŸ72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients.

Bullying magnitud impacto en la calidad de vida relacionada a la salud y factibilidad de implementar una intervención sustentada en la evidencia / Bullying among study magnitude impact on HRQOLAND and feasibility of implementing an intervention supported in the evidence

Las situaciones de intimidación entre escolares emergen como un fenómenosocial complejo, culturalmente determinado, que ha ganado interés por supotencial impacto en la salud física, mental y social, particularmente en lainfancia. Un estudio previo en Bahía Blanca encontró que 36% de una muestrade escolares manifestaron participar en situaciones de intimidación.ObjetivosDescribir la magnitud de la intimidación entre pares, su relación con la Calidadde Vida Relacionada a la Salud (CVRS) y el clima escolar en cuatro escuelasmunicipales de Córdoba (CBA). Evaluar la factibilidad de implementar unaintervención en escuelas públicas de Bahía Blanca (BBCA).MétodosEn Córdoba se realizó un estudio cuantitativo y cualitativo (observación,entrevistas individuales y grupales). En Bahía Blanca se llevó a acabo un estudiode factibilidad y diseño antes-después. Se aplicaron cuestionarios a niños,padres y docentes sobre intimidación (PRECONCIMEI) y CVRS (KIDSCREEN).ResultadosCBA: De 560 alumnos, 39% refirió participar en situaciones de intimidación:17%agresores, 12% víctimas y 10% víctima-agresor. Estos últimos dos grupos presentaronmenores puntuaciones en CVRS. De 345 padres encuestados, 49% afirma que en laescuela que concurre su hijo/a ocurren situaciones de intimidación. En las escuelascon un clima escolar más desfavorable, se observó mayor frecuencia de niños/as conrol agresor y una percepción más negativa de las docentes. BBCA: se implementóuna intervención preventiva, universal, para fortalecer el clima escolar, con 8componentes centrales sustentados en un marco teórico y 14 periféricos.ConclusionesSi bien la frecuencia de intimidación y niveles de CVRS de los niños/as evidenciaron unempeoramiento al finalizar el año, los docentes y directivos valoraron positivamentelos contenidos, estrategias y la adaptabilidad de la intervención. Manifestaron estardispuestos a implementarla en su práctica el próximo año.

Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48-week analysis of results from the PROTEST study.

OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.

Cambios en resonancia magnética funcional en estudiantes de medicina con y sin restricción moderada de sueño / Changes in functional magnetic resonance imaging in medical students with and without moderate sleep deprivation

OBJETIVO: Describir los efectos de la restricción moderada del sueño en las regiones cerebrales involucradas en los procesos de inhibición cognitiva, función motora y fluidez fonológica, utilizando imágenes por resonancia magnética funcional (RMf). Materiales y métodos: Se estableció una condición de sueño habitual y otra de restricción moderada en 12 estudiantes diestros de pre y posgrado de Medicina, de entre 20 y 40 años. En ambos estados se utilizó la prueba psicológica de atención d2 e imágenes de RMf con paradigmas de función motora, fluencia fonológica y atención del tipo inhibición de la función ejecutiva Stroop. La restricción moderada de sueño fue de al menos el 63% con respecto al sueño habitual. Resultados: Se encontraron diferencias significativas en la activación cerebral con RMf para la función motora (p<0,05) entre el ciclo de sueño regular y el de restricción moderada. La actividad cerebral en RMf con los paradigmas de atención Stroop y fluidez fonológica no mostró diferencias significativas, así como tampoco la prueba psicológica de atención d2. Discusión: Se encontró interferencia en las activaciones cerebrales de representación motora con la restricción moderada de sueño, pero no se hallaron diferencias significativas en las activaciones de atención tipo Stroop, ni en la tarea de fluencia fonológica o las pruebas de atención d2. Esto podría deberse a una insuficiente restricción del sueño o a eficientes mecanismos de compensación en los sujetos de este estudio. Conclusión: Existen diferencias en las activaciones cerebrales de representación motora en la restricción moderada del sueño medidas con RMf

OBJECTIVE: To describe the effects of moderate sleep deprivation in brain regions involved in cognitive inhibition processes, motor function, and phonological fluency using functional Magnetic Resonance Imaging (fMRI). Materials and methods: A sample of 12 under-graduate and post-graduate medical students, between 20 and 40 years, were subjected to a follow-up of the number of hours of regular sleep in order compare to a moderate sleep deprivation after a nightshift. The d2 attention test and fMRI studies were used in both groups in order to evaluate motor function, verbal fluency and cognitive inhibition, or Stroop paradigms. The moderate sleep deprivation was at least 63% with respect to the regular sleep pattern during the previous week. Results: Significant differences in brain activity were found in fMRI to measure motor function (P<0.05) comparing regular sleep cycle and moderate sleep deprivation. The brain activity with fMRI Stroop paradigms and phonological fluency showed no significant differences between the two conditions, likewise with the psychological attention test d2. Discussion: The fMRI showed interference on motor representation activations in moderate sleep deprivation. No significant differences in fMRI were found in the processes of cognitive inhibition or Stroop paradigms, in phonological fluency, or in the psychological attention test d2. These could be attributed to inadequate sleep deprivation or efficient compensation mechanisms in the subjects of this study. Conclusión: There is a difference showed in fMRI on motor representation activations in moderate sleep deprivation

Linear Versus Non-Linear Dose-Response Relationship Between Prenatal Alcohol Exposure and Meconium Concentration of Nine Different Fatty Acid Ethyl Esters.

Presence of individual fatty acid ethyl esters (FAEEs) in meconium is considered to be a reliable biomarker of prenatal alcohol exposure, and their concentration has been found to be linearly associated with poor postnatal development, supporting the widely extended idea that ethanol is a non-threshold teratogen. However, a growing number of epidemiological studies have consistently found a lack of adverse short- and long-term fetal outcomes at low exposure levels. We therefore aimed to investigate the relationship between the concentration of individual FAEEs and prenatal alcohol exposure in meconium samples collected within the first 6 to 12?h after birth from 182 babies born to abstainer mothers and from 54 babies born to women who self-reported either light or moderate alcohol ingestion in the second or third trimester of pregnancy. In most cases, the individual FAEE concentrations were negligible and not significantly different (P >0.05) between exposed and control babies. The concentrations appeared to increase linearly with the dose only in the few babies born to mothers who reported >3 drinks/week. These results provide evidence that the correlation between prenatal alcohol exposure and individual FAEE concentrations in meconium is non-linear shape, with a threshold probably at 3 drinks/week.

A case series of 15 women inadvertently exposed to magnetic resonance imaging in the first trimester of pregnancy.

Information on the safety of first-trimester exposure to diagnostic magnetic resonance imaging (MRI) remains scarce. We are reporting a case series of 15 consecutive pregnant women who underwent an MRI scan with a 1.5-Tesla scanner of either the head (n = 5), cervical spine (n = 4), lumbar spine (n = 4), pelvis (n = 1) or knee (n = 1) in their first trimester of pregnancy (mean gestational age at exposure: 3.8 weeks). Patients were prospectively followed up until the completion of their pregnancy. Two cases received gadolinium as a contrast agent. There were 15 babies born alive. Of them, one baby was born with the left kidney not visualised by ultrasound examination, and another one with an overlapping toe in the right foot. None of these abnormalities were considered by the authors related to the MRI exposure. In conclusion, our study provides support to published preliminary evidence regarding the safety of MRI in the first-trimester pregnant women.

Assessment of fetal and neonatal outcomes in the offspring of women who had been treated with dried ginger (Zingiberis rhizoma siccus) for a variety of illnesses during pregnancy.

The present study was designed to investigate if exposure to dried ginger during pregnancy would increase the risk of adverse fetal and neonatal outcomes. Participants consisted of 159 singleton pregnant women who received dried ginger as a herbal medication. We also included a control group of 306 pregnant women who had not been exposed to any herbal medication or any known teratogen. No increased risk of major malformations was detected in exposed women (OR = 4.9; 95% CI 0.9-25.5; p = 0.051). The incidence of stillbirths in the exposed group was marginally higher than in the controls (OR = 7.8; 95% CI 0.9-70.3; p = 0.05). The risk was more evident when the exposed group was compared with the general population in the Republic of Korea (OR = 7.9; 95% CI 2.9-21.4; p < 0.0001). Other fetal and neonatal study outcomes investigated in the exposed group were similar (p > 0.05) to the controls. In conclusion, dried ginger does not appear to be a major teratogen. However, due to the limitations of the study, e.g. the large variability in the dose of dried ginger in the exposed group, as well as the concomitant exposure to other herbal medications, the increased incidence of stillbirths requires confirmation in larger cohort studies.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients.

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Consensus statement: recommendations for the management of metabolic bone disease in human immunodeficiency virus patients / Documento de consenso: Recomendaciones para el manejo de la enfermedad ósea metabólica en pacientes con virus de la inmunodeficiencia humana

"OBJECTIVE: To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients. PARTICIPANTS: Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS). METHODS: A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content. CONCLUSIONS: The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients"

"Objetivo Proporcionar unas recomendaciones prácticas para el manejo de la enfermedad metabólica ósea en pacientes con virus de la inmunodeficiencia humana (VIH). Participantes Miembros de diferentes sociedades científicas relacionadas con el metabolismo óseo y con la enfermedad VIH: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM) y Sociedad Española de Fractura Osteoporótica (SEFRAOS). Métodos Se realizó una búsqueda sistemática en PubMed de la evidencia disponible para cada aspecto, y se revisaron artículos escritos en inglés y en castellano con fecha de inclusión hasta 28 de mayo de 2013. Las recomendaciones se formularon según el sistema GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Los autores trabajaron por grupos en la formulación de cada apartado de las recomendaciones y posteriormente el documento global se discutió en una reunión conjunta. Todos los autores revisaron el documento escrito final y lo consensuaron. Conclusiones El documento establece unas recomendaciones prácticas basadas en la evidencia acerca de la evaluación y el tratamiento de la enfermedad metabólica ósea en pacientes con VIH"

Immune activation in amyloid-ß-related angiitis correlates with decreased parenchymal amyloid-ß plaque load.

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare but serious condition. A fraction of patients suffering from PACNS concurrently exhibit pronounced cerebral amyloid angiopathy (CAA) which is characterized by deposits of amyloid-ß (Aß) in and around the walls of small and medium-sized arteries of the brain. PACNS with CAA has been identified as a distinct disease entity, termed Aß-related angiitis (ABRA). Evidence points to an immune reaction to vessel wall Aß as the trigger of vasculitis. OBJECTIVE: To investigate whether the inflammatory response to Aß has (1) any effect on the status of immune activation in the brain parenchyma and (2) leads to clearance of Aß from brain parenchyma. METHODS: We studied immune activation and Aß load by quantitative immunohistochemical analysis in brain parenchyma adjacent to affected vessels in 11 ABRA patients and 10 matched CAA controls. RESULTS: ABRA patients showed significantly increased immune activation and decreased Aß loads in the brain parenchyma adjacent to affected vessels. CONCLUSION: Our results are in line with the hypothesis of ABRA being the result of an excessive immune response to Aß and show that this can lead to enhanced clearance of Aß from the brain parenchyma by immune-mediated mechanisms.

HCV clearance from saliva of HIV-HCV-coinfected patients on treatment with interferon plus ribavirin.

OBJECTIVE: To determine hepatitis C virus (HCV) RNA clearance from blood and saliva of HIV-HCV-coinfected patients undergoing combined therapy with pegylated interferon plus ribavirin (PEG-IFN-RIB). SUBJECTS AND METHODS: Study group was formed of 60 HIV-infected patients with chronic hepatitis C who were starting treatment with PEG-IFN-RIB. Blood and saliva samples were taken at baseline, at the end of treatment and 24 and 48 weeks later. A nested RT-PCR technique was used to detect HCV-RNA in saliva. RESULTS: HCV-RNA was detected in saliva at baseline in 64.7% of patients. Thirty-four patients completed follow-up. The response rate (undetectable HCV-RNA) in blood was 79.4% at the end of treatment; 55.8% at 24 weeks after the end of treatment and 50% at 48 weeks. HCV was detected in saliva of 13 (38.2%) patients at the end of treatment and in 18 (52.9%) patients at 24 and 48 weeks later. Concordance of HCV clearance from blood and saliva reached its maximum value at 48 weeks after the end of treatment (odds ratio, 112.51). CONCLUSION: In HIV-HCV-coinfected patients responders to PEG-IFN-RIB, the salivary glands do not appear to be a sanctuary site for HCV, although viral clearance from saliva may be slower than from blood.

Lymphoproliferative response to the 30-kDa protein and a crude lysate from Salmonella typhimurium in patients with ankylosing spondylitis.

OBJECTIVES: To determine the lymphoproliferative response to the 30-kDa protein (p30) of Salmonella typhimurium in patients with ankylosing spondylitis (AS). METHOD: Lymphoproliferative response was determined in peripheral blood mononuclear cells (PBMCs) from 30 patients with AS and 40 healthy subjects. Cells were cultured with concanavalin A (Con A), a crude lysate of S. typhimurium (StCL), or p30. Lymphoproliferation was measured by the MTT assay. RESULTS: Our data show that the mitogenic response to Con A was similar in both groups studied; however, the lymphoproliferative response to StCL and p30 was statistically higher in AS patients than in healthy subjects. CONCLUSIONS: Our data strongly suggest that S. typhimurium, and particularly p30, are associated with AS.

Fetal and neonatal outcomes in women taking domperidone during pregnancy.

The safety of domperidone in pregnancy remains unknown. Therefore, the study aimed to prospectively evaluate the fetal outcomes of women who were taking domperidone during pregnancy. In a prospective cohort study design, 120 1st- trimester pregnant women who were taking domperidone for controlling gastrointestinal tract symptoms and 212 age-matched pregnant women not exposed to any potential teratogenic agent, were followed-up until delivery. In the case group, domperidone was indicated for control of functional gastrointestinal disorders in 59.2%, the maximum dose was 30 mg/day and exposure occurred between 2(+4) and 20 weeks' gestation. Fetal outcomes including gestational age at birth, birth weight and length, head circumference at birth, and 1- and 5-min Apgar score were similar in the two study groups. There were three babies born with malformations in each group (OR = 0.6; 95% CI 0.1, 2.8). In conclusion, domperidone does not appear to be a major human teratogen. However, our findings require further confirmation in larger studies.

Eficacia de la premedicación anestésica en el paciente pediátrico con midazolam oral y acetaminofén. Estudio observacional / Efficacy of anesthetic premedication in pediatric patients using oral midazolam and acetaminophen. Observational study

La premedicación anestésica con midazolam, permite disminuir la ansiedad de los niños y los padres así como los requerimientos analgésicos, la aparición de eventos psicológicos negativos en el postoperatorio, y acorta los tiempos de inducción inhalatoria de la intubación orotraqueal. Se han desarrollado preparaciones magistrales utilizando ampollas de administración parenteral mezcladas con sustancias que modifican su sabor para mejorar la aceptación. Para determinar la eficacia de la premedicación con midazolam mezclado con acetaminofén se realizó un estudio observacional descriptivo prospectivo en 216 niños ASAI o II sometidos a procedimientos quirúrgicos o diagnósticos que requerían anestesia general; se aplicaron escalas de ansiedad-sedación (Yale modificada y RASS) y se valoró la tolerancia a la separación de los padres. Resultados: La escala de RASS aplicada al momento de la inducción evidenció que el 92% de los pacientes se encontraban en un grado adecuado de sedación para tolerar la máscara facial y la inducción inhalatoria, y además el 86% de los pacientes toleró de manera adecuada la separación de sus padres. El 61,6% de los pacientes se encontraban con un grado adecuado de sedación ansiólisis con la escala de Yale, previo al momento de la separación de los padres. Edad, género, escolaridad, estrato socioeconómico, tipo de valoración preanestésica o antecedente de anestesia no se correlacionaron con el grado de ansiedad-sedación. Conclusiones: La premedicación con la mezcla magistral utilizada disminuye la ansiedad en el momento en que el niño se separa de sus padres y permite una buena aceptación de la inducción anestésica inhalada.

Anesthetic premedication with midazolam helps reduce anxiety in the children and the parents, the need for analgesic use, and the development of negative psychological events during the postoperative period; it also results in shorter inhalation induction and orotracheal intubation. Compounded preparations have been developed using ampoules for parenteral administration mixed with flavor modifiers in order to improve acceptance. To determine the efficacy of premedication using a mix of midazolam plus acetaminophen, a prospective descriptive observational study was conducted in 216 children ASAI or II, scheduled for surgical or diagnostic procedures requiring general anesthesia. Anxiety-sedation scales were given (Modified Yale scale and RASS), and tolerance to separation from the parents was assessed. Results: The RASS scale applied at the time of induction showed that 92% of the patients were at an appropriate level of sedation to tolerate facemask inhalation induction, and 86% of patients tolerated well their separation from their parents. It was found that age, gender, education, socioeconomic status, pre-anesthetic check type (telephonic or in person), or a history of previous anesthesia, did not have a statistically significant correlation with the degree of anxiety-sedation. Conclusions: Premedication with a compounded preparation does reduce anxiety at the time of separating the child from its parents, and allows a good acceptance of the inhaled anesthetic induction.

Switching to lopinavir/ritonavir with or without abacavir/lamivudine in lipoatrophic patients treated with zidovudine/abacavir/lamivudine.

BACKGROUND: Discontinuation of thymidine nucleoside reverse transcriptase inhibitors (tNRTIs) is the only proven strategy for improving lipoatrophy. It is unclear whether switching to NRTI-sparing or to non-thymidine NRTI-containing therapy has differential effects on body fat recovery. METHODS: This was a 96 week, open-label, randomized study in suppressed patients with moderate/severe lipoatrophy and no prior virological failure while receiving a protease inhibitor and who had their triple NRTI regimen (zidovudine/lamivudine/abacavir) switched to lopinavir/ritonavir plus abacavir/lamivudine for a 1 month run-in period and then randomized to lopinavir/ritonavir plus abacavir/lamivudine versus lopinavir/ritonavir monotherapy. The KRETA trial is registered with ClinicalTrials.gov (number NCT00865007). RESULTS: Of 95 patients included, 88 were randomized to lopinavir/ritonavir plus abacavir/lamivudine (n = 44) or lopinavir/ritonavir monotherapy (n = 44). Median (IQR) baseline limb fat was 2.5 (1.6-3.7) kg in the lopinavir/ritonavir plus abacavir/lamivudine group and 2.5 (2.0-5.4) kg in the lopinavir/ritonavir monotherapy group. Six patients in the triple therapy group and 13 in the monotherapy group had discontinued study drugs by week 96. Although there were limb fat gains in each group at weeks 48/96 (+324/+358 g in lopinavir/ritonavir plus abacavir/lamivudine, P = 0.09/0.07, versus +215/+416 g in the lopinavir/ritonavir monotherapy group, P = 0.28/0.16), differences between groups were not significant [difference +109 g (95% CI -442, +660)/-57 g (95% CI -740, +625)]. CONCLUSIONS: In lipoatrophic patients treated with zidovudine/lamivudine/abacavir, switching to lopinavir/ritonavir monotherapy had no additional benefit in limb fat recovery relative to switching to lopinavir/ritonavir with abacavir/lamivudine. These data suggest that non-thymidine nucleosides such as abacavir/lamivudine are not an obstacle to limb fat recovery.