Impact of switching to raltegravir and/or adding losartan in lymphoid tissue fibrosis and inflammation in people living with HIV. A randomized clinical trial.

BACKGROUND: Persistent inflammation and immune activation are associated with lymph node fibrosis and end-organ diseases in treatment-suppressed people living with HIV (PLWH). We investigated the effect of switching to raltegravir and/or adding losartan on lymphoid tissue fibrosis and on the inflammatory/immune-activation mediators in treated HIV patients. METHODS: Chronic HIV-infected patients treated with two nucleoside reverse transcriptase inhibitors (2NRTI) and one non-NRTI (NNRTI) or protease inhibitor (PI) during at least 48 weeks were randomized to four groups (n = 48): 2NRTI + efavirenz (EFV), 2NRTI + EFV + losartan, 2NRTI + raltegravir and 2NRTI + raltegravir + losartan for 48 weeks. Tonsillar biopsy and peripheral blood markers of CD4 and CD8 T-lymphocyte activation and senescence, monocyte activation and soluble markers of inflammation were determined at baseline and at week 48 and compared between groups. RESULTS: No changes in lymphoid tissue architecture were observed. Adding losartan had no impact on lymphocyte subsets. Conversely, patients who switched to raltegravir showed a higher decrease in all activated [CD4+CD38+HLA-DR+, -0.3 vs. 0.48 (P = 0.033); CD8+CD38+ HLA-DR+, -1.6 vs. 1.3 (P = 0.02)] and senescent [CD4+CD28-CD57+, -0.3 vs. 0.26 (P = 0.04); CD8+CD28-CD57+, -6.1 vs. 3.8 (P = 0.002)] T lymphocytes. In addition, the median CD4/CD8 ratio increased by 0.35 in patients in the raltegravir group vs. 0.03 in the other arms (P = 0.002). Differences between groups in monocyte subpopulations or soluble inflammation markers were not observed. CONCLUSIONS: Losartan had no effect on lymphoid fibrosis or immune activation/inflammation. Conversely, switching to a regimen with raltegravir significantly decreased activated and senescent T-lymphocyte subpopulations and increased CD4/CD8 ratio in successfully treated PLWH.

Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of The Fetal Medicine Foundation results and meta-analysis.

OBJECTIVES: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancy and to define the performance of the test by combining our results with those identified in a systematic review of the literature. METHODS: The data for the prospective study were derived from screening for trisomies 21, 18 and 13 in twin pregnancies at 10 + 0 to 14 + 1 weeks' gestation. Two populations were included; first, self-referred women to the Fetal Medicine Centre in London or Brugmann University Hospital in Brussels and, second, women selected for the cfDNA test after routine first-trimester combined testing at one of two National Health Service hospitals in England. This dataset was used to determine the performance of screening for the three trisomies. Search of MEDLINE, EMBASE, CENTRAL (The Cochrane Library), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) was carried out to identify all peer-reviewed publications on clinical validation or implementation of maternal cfDNA testing for trisomies 21, 18 and 13 in twin pregnancy. A meta-analysis was then performed using our data and those in the studies identified by the literature search. RESULTS: In our dataset of 997 twin pregnancies with a cfDNA result and known outcome, the test classified correctly 16 (94.1%) of the 17 cases of trisomy 21, nine (90.0%) of the 10 cases of trisomy 18, one (50.0%) of the two cases of trisomy 13 and 962 (99.4%) of the 968 cases without any of the three trisomies. The literature search identified seven relevant studies, excluding our previous papers because their data are included in the current study. In the combined populations of our study and the seven studies identified by the literature search, there were 56 trisomy-21 and 3718 non-trisomy-21 twin pregnancies; the pooled weighted detection rate (DR) and false-positive rate (FPR) were 98.2% (95% CI, 83.2-99.8%) and 0.05% (95% CI, 0.01-0.26%), respectively. In the combined total of 18 cases of trisomy 18 and 3143 non-trisomy-18 pregnancies, the pooled weighted DR and FPR were 88.9% (95% CI, 64.8-97.2%) and 0.03% (95% CI, 0.00-0.33%), respectively. For trisomy 13, there were only three affected cases and two (66.7%) of these were detected by the cfDNA test at a FPR of 0.19% (5/2569). CONCLUSIONS: The performance of cfDNA testing for trisomy 21 in twin pregnancy is similar to that reported in singleton pregnancy and is superior to that of the first-trimester combined test or second-trimester biochemical testing. The number of cases of trisomies 18 and 13 is too small for accurate assessment of the predictive performance of the cfDNA test. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Detección de trisomías mediante la prueba del ADN fetal de la sangre materna en el embarazo de gemelos: actualización de los resultados de The Fetal Medicine Foundation y metaanálisis OBJETIVOS: Informar sobre la implementación clínica rutinaria del análisis de ADN fetal (cfDNA, por sus siglas en inglés) de la sangre materna para las trisomías 21, 18 y 13 en embarazos de gemelos y definir el rendimiento de la prueba mediante la combinación de los resultados de este estudio con los identificados en una revisión sistemática de la literatura. MÉTODOS: Los datos para el estudio prospectivo se derivaron del cribado de las trisomías 21, 18 y 13 en embarazos de gemelos entre 10+0 a 14+1 semanas de gestación. Se incluyeron dos poblaciones: la primera, las mujeres que acudieron sin recomendación de especialista al Centro de Medicina Fetal de Londres o al Hospital Universitario Brugmann de Bruselas y, la segunda, las mujeres seleccionadas para la prueba de cfDNA después de la prueba combinada rutinaria del primer trimestre en uno de los dos hospitales del Servicio Nacional de Salud de Inglaterra. Este conjunto de datos se utilizó para determinar el rendimiento de la detección de las tres trisomías. Se realizó una búsqueda en MEDLINE, EMBASE, CENTRAL (The Cochrane Library), ClinicalTrials.gov y en la Plataforma Internacional del Registro de Ensayos Clínicos (ICTRP, por sus siglas en inglés) de la Organización Mundial de la Salud para identificar todas las publicaciones revisadas por pares sobre la validación clínica o la implementación de pruebas de cfDNA materno para las trisomías 21, 18 y 13 en el embarazo de gemelos. A continuación, se realizó un metaanálisis de los datos propios y de los de los estudios identificados por la búsqueda bibliográfica. RESULTADOS: En el conjunto de datos propios de 997 embarazos de gemelos con un resultado de cfDNA conocido, la prueba clasificó correctamente 16 (94,1%) de los 17 casos de trisomía 21, nueve (90,0%) de los 10 casos de trisomía 18, uno (50,0%) de los dos casos de trisomía 13 y 962 (99,4%) de los 968 casos sin ninguna de las tres trisomías. La búsqueda bibliográfica identificó siete estudios relevantes, que excluyeron los artículos de los autores de este estudio ya que sus datos están incluidos en este estudio. En las poblaciones combinadas de este estudio y los siete estudios identificados por la búsqueda bibliográfica, hubo 56 embarazos gemelares con trisomía-21 y 3718 sin trisomía-21; la tasa de detección (TD) combinada ponderada y la tasa de falsos positivos (TFP) fueron del 98,2% (IC 95%: 83,2-99,8%) y del 0,05% (IC 95%: 0,01-0,26%), respectivamente. En el total combinado de los 18 casos de trisomía-18 y los 3143 embarazos sin trisomía-18, la TD combinada ponderada y la TFP fueron del 88,9% (IC 95%, 64,8-97,2%) y del 0,03% (IC 95%, 0,00-0,33%), respectivamente. Para la trisomía 13, sólo hubo tres casos afectados y dos (66,7%) de ellos fueron detectados por la prueba de cfDNA con una TFP del 0,19% (5/2569). CONCLUSIONES: La bondad del desempeño de la prueba de cfDNA para la trisomía 21 en el embarazo de gemelos es similar a la reportada en embarazos con feto único y es superior a la de la prueba combinada del primer trimestre o a la de la prueba bioquímica del segundo trimestre. El número de casos de trisomías 18 y 13 es demasiado pequeño para una evaluación precisa de la bondad de predicción de la prueba de cfDNA.

Outcome reporting across randomised controlled trials evaluating therapeutic interventions for pre-eclampsia.

BACKGROUND: Standardising outcome collection and reporting in pre-eclampsia trials requires an appraisal of current outcome reporting. OBJECTIVES: To map maternal and offspring outcome reporting across randomised trials evaluating therapeutic interventions for pre-eclampsia. SEARCH STRATEGY: Randomised trials were identified by searching bibliographical databases from inception to January 2016. SELECTION CRITERIA: Randomised controlled trials. DATA COLLECTION AND ANALYSIS: We systematically extracted and categorised outcome reporting. MAIN RESULTS: Seventy-nine randomised trials, reporting data from 31 615 maternal participants and 28 172 of their offspring, were included. Fifty-five different interventions were evaluated. Included trials reported 119 different outcomes, including 72 maternal outcomes and 47 offspring outcomes. Maternal outcomes were inconsistently reported across included trials; for example, 11 trials (14%) reported maternal mortality, reporting data from 12 422 participants, and 16 trials (20%) reported cardiovascular morbidity, reporting data from 14 963 maternal participants. Forty-three trials (54%) reported fetal outcomes and 23 trials (29%) reported neonatal outcomes. Twenty-eight trials (35%) reported offspring mortality. There was poor reporting of childhood outcomes: six trials (8%) reported neurodevelopmental outcomes. Less than half of included trials reported any relevant information regarding harms for maternal participants and their offspring. CONCLUSIONS: Most randomised trials evaluating interventions for pre-eclampsia are missing information on clinically important outcomes, and in particular have neglected to evaluate efficacy and safety in the offspring of participants. Developing and implementing a minimum data set, known as a core outcome set, in future pre-eclampsia trials could help to address these issues. TWEETABLE ABSTRACT: Future #preeclampsia research requires a core outcome set to reduce #research waste. @coreoutcomes @jamesmnduffy International Prospective Register of Systematic Reviews: CRD42015015529; www.crd.york.ac.uk/PROSPERO/display_record.aspID=CRD42015015529.

Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis.

OBJECTIVES: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies (SCA). METHODS: Searches of PubMed, EMBASE and The Cochrane Library were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between January 2011, when the first such study was published, and 31 December 2016. The inclusion criteria were peer-reviewed study reporting on clinical validation or implementation of maternal cfDNA testing in screening for aneuploidies, in which data on pregnancy outcome were provided for more than 85% of the study population. We excluded case-control studies, proof-of-principle articles and studies in which the laboratory scientists carrying out the tests were aware of fetal karyotype or pregnancy outcome. Pooled detection rates (DRs) and false-positive rates (FPRs) were calculated using bivariate random-effects regression models. RESULTS: In total, 35 relevant studies were identified and these were used for the meta-analysis on the performance of cfDNA testing in screening for aneuploidies. These studies reported cfDNA results in relation to fetal karyotype from invasive testing or clinical outcome. In the combined total of 1963 cases of trisomy 21 and 223 932 non-trisomy 21 singleton pregnancies, the weighted pooled DR and FPR were 99.7% (95% CI, 99.1-99.9%) and 0.04% (95% CI, 0.02-0.07%), respectively. In a total of 563 cases of trisomy 18 and 222 013 non-trisomy 18 singleton pregnancies, the weighted pooled DR and FPR were 97.9% (95% CI, 94.9-99.1%) and 0.04% (95% CI, 0.03-0.07%), respectively. In a total of 119 cases of trisomy 13 and 212 883 non-trisomy 13 singleton pregnancies, the weighted pooled DR and FPR were 99.0% (95% CI, 65.8-100%) and 0.04% (95% CI, 0.02-0.07%), respectively. In a total of 36 cases of monosomy X and 7676 unaffected singleton pregnancies, the weighted pooled DR and FPR were 95.8% (95% CI, 70.3-99.5%) and 0.14% (95% CI, 0.05-0.38%), respectively. In a combined total of 17 cases of SCA other than monosomy X and 5400 unaffected singleton pregnancies, the weighted pooled DR and FPR were 100% (95% CI, 83.6-100%) and 0.004% (95% CI, 0.0-0.08%), respectively. For twin pregnancies, in a total of 24 cases of trisomy 21 and 1111 non-trisomy 21 cases, the DR was 100% (95% CI, 95.2-100%) and FPR was 0.0% (95% CI, 0.0-0.003%), respectively. CONCLUSIONS: Screening by analysis of cfDNA in maternal blood in singleton pregnancies could detect > 99% of fetuses with trisomy 21, 98% of trisomy 18 and 99% of trisomy 13 at a combined FPR of 0.13%. The number of reported cases of SCA is too small for accurate assessment of performance of screening. In twin pregnancies, performance of screening for trisomy 21 is encouraging but the number of cases reported is small. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Optimising non-invasive mechanical ventilation: Which unit should care for these patients? A cohort study.

BACKGROUND: Use of noninvasive ventilation (NIV) has extended beyond intensive care units (ICUs), becoming usual practice in emergency departments (EDs) and general wards. OBJECTIVE: To analyse the relationship between nursing care and NIV outcome in different hospital units. DESIGN AND SETTINGS: Three university hospitals and one community hospital participated in a prospective observational cohort study. PARTICIPANTS: Ten units participated: 4 ICUs (1 surgical, 3 medical-surgical), 3 recovery (1 postsurgical, 2 EDs, 3 general wards). METHOD: Treatment success/failure, interface intolerance and complications were evaluated according to patient characteristics, nursing care provided, and procedures used. Complications analysed included bronchoaspiration, pneumothorax, skin lesions, inability to manage secretions, eye irritations, deteriorating level of consciousness, gastric distension, and excessive air losses around the mask. RESULTS: Of 387 patients, 194 (50.1%) were treated in ICU, 121 (31.3%) in ED, 38 (9.8%) postsurgery, and 34 (8.8%) in general wards. Regression analysis, adjusted for APACHE score and NIV indication, showed 3.3 times greater risk of NIV failure (95% CI [1.2-9.2]) in a university-hospital ICU with <50 NIV cases/year, compared to a community hospital ICU. In ICUs and general wards, NIV was suspended in 12% of patients due to interface intolerance. Acute-on-chronic lung diseases (ACLD) had lower risk of NIV failure (OR 0.2 [95% CI 0.06-0.69]) and lack of humidification was not associated with treatment failure (OR 0.2 [95% CI 0.1-0.4]). Poor secretion management was linked to pneumonia (OR 2.5 [95% CI 1.1-5.9]) and early weaning/extubation (OR 3.3 [95% CI 1.2-8.9]). Interface intolerance was associated with conventional ICU ventilators (OR 4.4 [95% CI 2.1-9.2]) and nasal skin lesions with excessive air losses (OR 2.4 [95% CI 1.1-5.3]), especially with oronasal masks (OR 3.5 [95% CI 1.1-11.3]). CONCLUSIONS: Acute respiratory failure patients with pneumonia admitted to general wards had increased interface intolerance and NIV failure. Rotating mask types could improve NIV success in any unit administering this therapy.

Diagnostic accuracy of cancer antigen 125 for endometriosis: a systematic review and meta-analysis.

BACKGROUND: The development of a non-invasive and accurate diagnostic biomarker for endometriosis is urgently needed. OBJECTIVE: Evaluate the diagnostic accuracy of serum cancer antigen 125 (CA 125) for endometriosis. SEARCH STRATEGY: We searched EMBASE, MEDLINE, and Web of Science from inception to January 2016. SELECTION CRITERIA: Diagnostic accuracy studies of serum CA 125 (index test) for histologically confirmed endometriosis (reference standard) were included. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted study characteristics and data. Methodological quality was assessed using Quality Assessment of Comparative Diagnostic Accuracy Studies (QUADAS-2) checklist. MAIN RESULTS: Twenty-two studies (16 cohort, six case-control), 3626 participants, were identified. Bivariate hierarchical models were used to pool accuracy data of 14 studies (2920 participants) using CA 125 ≥ 30 units/ml. Pooled specificity was 93% (95% CI 89-95%) and sensitivity 52% (95% CI 38-66%). CA 125 was significantly more sensitive for the diagnosis of moderate or severe endometriosis compared with minimal disease (63%, 95% CI 47-77% versus 24%, 95%CI 19-32%, P-value = 0.001). CONCLUSIONS: CA 125 performs well as a rule-in test facilitating expedited diagnosis and ensuring investigation and treatment can be confidently tailored for the management of endometriosis. Unfortunately, a negative test, CA 125 < 30 units/ml, is unable to rule out endometriosis. TWEETABLE ABSTRACT: Blood test CA 125: a rule-in test for the diagnosis of women presenting with symptoms of endometriosis.

Clinical significance of psychiatric comorbidity in children and adolescents with obsessive-compulsive disorder: subtyping a complex disorder.

A promising approach in relation to reducing phenotypic heterogeneity involves the identification of homogeneous subtypes of OCD based on age of onset, gender, clinical course and comorbidity. This study aims to assess the sociodemographic characteristics and clinical features of OCD patients in relation to gender and the presence or absence of another comorbid disorder. The sample comprised 112 children and adolescents of both sexes and aged 8-18 years, all of whom had a diagnosis of OCD. Overall, 67 % of OCD patients had one comorbid diagnosis, 20.5 % had two such diagnoses and 2.6 % had three comorbid diagnoses. The group of OCD patients with a comorbid neurodevelopmental disorder had significantly more family history of OCD in parents (p = .049), as compared with the no comorbidity group and the group with a comorbid internalizing disorder, and they also showed a greater predominance of males (p = .013) than did the group with a comorbid internalizing disorder. The group of OCD patients with internalizing comorbidity had a later age of onset of OCD (p = .001) compared with both the other groups. Although the initial severity was similar in all three groups, the need for pharmacological treatment and for hospitalization due to OCD symptomatology was greater in the groups with a comorbid neurodevelopmental disorder (p = .038 and p = .009, respectively) and a comorbid internalizing disorder (p = .008 and p = .004, respectively) than in the group without comorbidity. Our findings suggest that two subtypes of OCD can be defined on the basis of the comorbid pathology presented. The identification of different subtypes according to comorbidity is potentially useful in terms of understanding clinical variations, as well as in relation to treatment management and the use of therapeutic resources.

One-Year Follow-up of Children and Adolescents with Major Depressive Disorder: Relationship between Clinical Variables and Abcb1 Gene Polymorphisms.

Introduction: Differences in response to fluoxetine (FLX) may be influenced by certain genes that are involved in FLX transportation (ABCB1). We examined remission and recovery from the index episode in a cohort of patients treated with FLX, and also investigated associations between genetic variants in ABCB1 and remission, recovery, and suicide risk. Methods: This was a naturalistic 1-year follow-up study of 46 adolescents diagnosed with major depressive disorder (MDD). At 12 months they underwent a diagnostic interview with the K-SADS-PL. Results: It was found that remission was around 69.5% and recovery 56.5%. Remission and recovery were associated with lower scores on the CDI at baseline, with fewer readmissions and suicide attempts, and with lower scores on the CGI and higher scores on the GAF scale. No relationship was found between ABCB1 and remission or recovery. However, a significant association was observed between the G2677T ABCB1 polymorphism and suicide attempts. Conclusion: Other factors such as stressful events, family support, and other genetic factors are likely to be involved in MDD outcome.

On the origin of Robertsonian fusions in nature: evidence of telomere shortening in wild house mice.

The role of telomere shortening to explain the occurrence of Robertsonian (Rb) fusions, as well as the importance of the average telomere length vs. the proportion of short telomeres, especially in nature populations, is largely unexplored. In this study, we have analysed telomere shortening in nine wild house mice from the Barcelona Rb system with diploid numbers ranging from 29 to 40 chromosomes. We also included two standard (2n=40) laboratory mice for comparison. Our data showed that the average telomere length (considering all chromosomal arms) is influenced by both the diploid number and the origin of the mice (wild vs. laboratory). In detail, we detected that wild mice from the Rb Barcelona system (fused and standard) present shorter telomeres than standard laboratory mice. However, only wild mice with Rb fusions showed a high proportion of short telomeres (only in p-arms), thus revealing the importance of telomere shortening in the origin of the Rb fusions in the Barcelona system. Overall, our study confirms that the number of critically short telomeres, and not a simple reduction in the average telomere length, is more likely to lead to the origin of Rb fusions in the Barcelona system and ultimately in nature.

[Intensive care unit profesionals's knowledge about non invasive ventilation comparative analysis]. / Análisis comparativo de los conocimientos en ventilación mecánica no invasiva de profesionales de cuidados intensivos.

AIMS: The literature highlights the lack of noninvasive ventilation (NIV) protocols and the variability of the knowledge of NIV between intensive care units (ICU) and hospitals, so we want to compare NIV nurses's Knowledge from 4 multipurpose ICU and one surgical ICU. METHODS: Multicenter, crosscutting, descriptive study in three university hospitals. The survey instrument was validated in a pilot test, and the calculated Kappa index was 0.9. Returning a completed survey is an indication of informed consent. Analysis by Chi square test. RESULTS: 117 responded (65%) nurses, 11±9.7 years of experience in ICU and 9.2±7.2 in use of NIV. One of the multipurpose ICU, was initiated NIV an average of 6 years later than the others (95% CI [3.3 to 8.6], P<.001). Only 23.1% of nurses would place a non-vented mask (with no exhalation port) by conventional ventilator, the rest any kind of face mask. 12.7% believed that the mask must be adjusted to the "2-finger" fit while 29% would seal the mask to the patient's face and cover the mask opening where air escapes to facilitate patient/ventilator synchronization. In the surgical ICU agitation identifies mostly as a complication of NIV compared with multipurpose UCIs (31.6% vs 1.8%, P<.001). 56.4% of nurses do not consider respiratory physiotherapy as nursing care, with no difference between units. CONCLUSIONS: Knowledge about types of interface is very dependent on the material of the unit. More training for complications of NIV as agitation and handling secretions it is necessary.

[Critical reading of systematic reviews and meta-analyses about diagnostic imaging]. / Lectura crítica de revisiones sistemáticas y metanálisis en el diagnóstico por imagen.

Systematic reviews of diagnostic validity have been proposed as the best methodological tool to integrate all the available evidence and to help physicians decide whether to use a given diagnostic test. These studies aim to synthesize the results obtained in different primary studies into a couple of indices, generally sensitivity and specificity, or into a summary receiver operating characteristic (ROC) curve. Although there is a certain parallelism with reviews about the efficacy of therapeutic interventions, reviews of diagnostic validity have certain peculiarities that add complexity to the analysis and interpretation of the results. This article emphasizes the methodological aspects that make it possible to critically assess the extent to which the results of a review of the validity of diagnostic tests are valid and provides rudimentary knowledge of the statistics necessary to understand the results.

Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients.

There is little known about pharmacogenetic of fluoxetine in children and adolescents. In this study, we evaluate, for the first time, the influence of CYP2D6, CYP2C9 and ABCB1 genotypes on the steady-state plasma concentrations of fluoxetine and its active metabolite (S)-norfluoxetine, and on the clinical improvement in children and adolescent patients receiving fluoxetine treatment. The assessment was performed in 83 patients after 8 and 12 weeks of treatment. Fluoxetine/(S)-norfluoxetine ratio was negatively correlated with the number of active CYP2D6 alleles (r: -0.450; P<0.001). Regarding the G2677T ABCB1 polymorphism, T allele carriers showed significantly higher improvements on the majority of scales including the Clinical Global Impression-Improvement scale (P<0.001). Our results confirm the influence of CYP2D6 genetic variants in fluoxetine pharmacokinetics and provide evidence for the potential effect of the ABCB1 genotype on the clinical improvement in children and adolescent patients treated with fluoxetine.

First-trimester uterine artery Doppler and adverse pregnancy outcome: a meta-analysis involving 55,974 women.

OBJECTIVES: To determine the accuracy with which uterine artery Doppler in the first trimester of pregnancy predicts pre-eclampsia and fetal growth restriction, particularly early-onset disease. METHODS: We searched MEDLINE (1951-2012), EMBASE (1980-2012) and the Cochrane Library (2012) for relevant citations without language restrictions. Two reviewers independently selected studies that evaluated the accuracy of first-trimester uterine artery Doppler to predict adverse pregnancy outcome and performed data extraction to construct 2 × 2 tables. We synthesized sensitivity and specificity for various Doppler indices using a bivariate random-effects model. RESULTS: From 1866 citations, we identified 18 studies (55,974 women). The sensitivity and specificity of abnormal uterine artery flow velocity waveform (FVW) in the prediction of early-onset pre-eclampsia were 47.8% (95% CI: 39.0-56.8) and 92.1% (95% CI: 88.6-94.6), and in the prediction of early-onset fetal growth restriction were 39.2% (95% CI: 26.3-53.8) and 93.1% (95% CI: 90.6-95.0), respectively. The sensitivities for predicting any pre-eclampsia and fetal growth restriction were 26.4% (95% CI: 22.5-30.8) and 15.4% (95% CI: 12.4-18.9), respectively, and the specificities were 93.4% (95% CI: 90.4-95.5%) and 93.3% (95% CI: 90.9-95.1), respectively. The number needed to treat (NNT) with aspirin to prevent one case of early-onset pre-eclampsia fell from 1000 to 173 and from 2500 to 421 for background risks varying between 1% and 0.4%, respectively. CONCLUSIONS: First-trimester uterine artery Doppler is a useful tool for predicting early-onset pre-eclampsia, as well as other adverse pregnancy outcomes. Based on the NNT, abnormal uterine artery Doppler in low-risk women achieves a sufficiently high performance to justify aspirin prophylaxis in those who test positive.

In vitro effects of the CCR5 inhibitor maraviroc on human T cell function.

BACKGROUND: Several potential immunological benefits have been observed during treatment with the CC chemokine receptor 5 (CCR5) antagonist maraviroc, in addition to its antiviral effect. Our objective was to analyse the in vitro effects of CCR5 blockade on T lymphocyte function and homeostasis. METHODS: Peripheral blood mononuclear cells (PBMCs) from both HIV-negative (n=28) and treated HIV-positive (n=27) individuals were exposed in vitro to different concentrations of maraviroc (0.1-100 µM). Effects on T cell activation were analysed by measuring the expression of the CD69, CD38, HLA-DR and CD25 receptors as well as CCR5 density using flow cytometry. Spontaneous and chemokine-induced chemotaxis were measured by transwell migration assays, and polyclonal-induced proliferation was assessed by a lymphoproliferation assay and carboxyfluorescein succinimidyl ester staining. RESULTS: Maraviroc increases CCR5 surface expression on activated T cells, even at low doses (0.1 µM). Slight differences were detected in the frequency and mean fluorescence intensity of activation markers at high concentrations of maraviroc. Expression of CD25, CD38 and HLA-DR tended to decrease in both CD4+ and CD8+ T lymphocytes, whereas expression of CD69 tended to increase. Maraviroc clearly inhibits T cell migration induced by chemokines in a dose-dependent manner. Moreover, at 100 µM, maraviroc tends to inhibit T cell proliferation. CONCLUSIONS: These data showed that in vitro exposure to maraviroc decreases some activation expression markers on T lymphocytes and also migration towards chemoattractants. These results support the additional immunological effects of CCR5 blockade and suggest that maraviroc might have potential capacity to inhibit HIV-associated chronic inflammation and activation, both by directly affecting T cell activation and by reducing entrapment of lymphocytes in lymph nodes.

Accuracy of CT angiography in the diagnosis of acute gastrointestinal bleeding: systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of computed tomography (CT) angiography in the evaluation of patients with an episode of acute gastrointestinal haemorrhage. METHODS: Systematic review and meta-analysis to estimate pooled accuracy indices. A bivariate random effects model was adjusted to obtain a summary receiver-operating characteristic (sROC) curve and the corresponding area under the curve (AUC). RESULTS: Twenty-two studies were included and provided data on 672 patients (range of age 5-74) with a mean age of 65 years. The overall sensitivity of CT angiography for detecting active acute GI haemorrhage was 85.2 % (95 % CI 75.5 % to 91.5 %). The overall specificity of CT angiography was 92.1 % (95 % CI 76.7 % to 97.7 %). The likelihood ratios for positive and negative test results were 10.8 (95 % CI 3.4 to 34.4) and 0.16 (95 % CI 0.1 to 0.27) respectively, with an AUC of 0.935 (95 % CI 0.693 to 0.989). The sources of heterogeneity explored had no significant impact on diagnostic performance. CONCLUSIONS: CT shows high diagnostic accuracy and is an excellent diagnostic tool for detection and localising of intestinal bleeding sites. It is highly available, provides fast detection and localisation of the bleeding site, and is minimally invasive. KEY POINTS: • CT angiography is increasingly used for investigating severe gastrointestinal bleeding. • This systematic review and meta-analysis updates previous ones. • In patients with massive gastrointestinal bleeding, CT angiography/MDCT detects bleeding accurately. • CT angiography is useful in locating the bleeding site and determining appropriate treatment.

Normal gray and white matter volume after weight restoration in adolescents with anorexia nervosa.

OBJECTIVE: The aim of this study was to determine whether treated, weight-stabilized adolescents with anorexia nervosa (AN) present brain volume differences in comparison with healthy controls. METHOD: Thirty-five adolescents with weight-recovered AN and 17 healthy controls were assessed by means of psychopathology scales and magnetic resonance imaging. Axial three-dimensional T1-weighted images were obtained in a 1.5 Tesla scanner and analyzed using optimized voxel-based morphometry (VBM). RESULTS: There were no significant differences between controls and weight-stabilized AN patients with regard to global volumes of either gray or white brain matter, or in the regional VBM study. Differences were not significant between patients with psychopharmacological treatment and without, between those with amenorrhea and without, as well as between patients with restrictive versus purgative AN. DISCUSSION: The present findings reveal no global or regional gray or white matter abnormalities in this sample of adolescents following weight restoration.

Effect of working conditions on non-work-related sickness absence.

BACKGROUND: There is limited evidence of the role of working conditions as prognostic factors for non-work-related sickness absence (i.e. absence due to injuries or diseases of non-occupational origin). AIMS: To analyse the association between working conditions and time to return to work (RTW) in workers with long-term (>15 days) non-work-related sickness absence. METHODS: We followed up a total of 655 workers, who completed a baseline questionnaire including physical and psychosocial work factors, until their non-work-related long-term sickness absence ended. Time to RTW was determined based on the health insurance company register. Cox proportional hazard models were constructed to evaluate the associations between working conditions and time to RTW. RESULTS: A self-perceived high level of physical activity at work and work with back twisted or bent were related to longer duration of sickness absence. We did not find any strong evidence of associations between psychosocial work factors and time to RTW, although higher job insecurity and low reward showed marginal statistical significance. CONCLUSIONS: Hazardous physical working conditions are associated with longer duration of non-work-related sickness absence. Workplace ergonomic interventions could conceivably shorten the length of sickness absence that has not originated at work.

Effectiveness of a clinically integrated e-learning course in evidence-based medicine for reproductive health training: a randomized trial.

CONTEXT: For evidence-based practice to embed culturally in the workplace, teaching of evidence-based medicine (EBM) should be clinically integrated. In low-middle-income countries (LMICs) there is a scarcity of EBM-trained clinical tutors, lack of protected time for teaching EBM, and poor access to relevant databases in languages other than English. OBJECTIVE: To evaluate the effects of a clinically integrated e-learning EBM course incorporating the World Health Organization (WHO) Reproductive Health Library (RHL) on knowledge, skills, and educational environment compared with traditional EBM teaching. DESIGN, SETTING, AND PARTICIPANTS: International cluster randomized trial conducted between April 2009 and November 2010 among postgraduate trainees in obstetrics-gynecology in 7 LMICs (Argentina, Brazil, Democratic Republic of the Congo, India, Philippines, South Africa, Thailand). Each training unit was randomized to an experimental clinically integrated course consisting of e-modules using the RHL for learning activities and trainee assessments (31 clusters, 123 participants) or to a control self-directed EBM course incorporating the RHL (29 clusters, 81 participants). A facilitator with EBM teaching experience was available at all teaching units. Courses were administered for 8 weeks, with assessments at baseline and 4 weeks after course completion. The study was completed in 24 experimental clusters (98 participants) and 22 control clusters (68 participants). MAIN OUTCOME MEASURES: Primary outcomes were change in EBM knowledge (score range, 0-62) and skills (score range, 0-14). Secondary outcome was educational environment (5-point Likert scale anchored between 1 [strongly agree] and 5 [strongly disagree]). RESULTS: At baseline, the study groups were similar in age, year of training, and EBM-related attitudes and knowledge. After the trial, the experimental group had higher mean scores in knowledge (38.1 [95% CI, 36.7 to 39.4] in the control group vs 43.1 [95% CI, 42.0 to 44.1] in the experimental group; adjusted difference, 4.9 [95% CI, 2.9 to 6.8]; P < .001) and skills (8.3 [95% CI, 7.9 to 8.7] vs 9.1 [95% CI, 8.7 to 9.4]; adjusted difference, 0.7 [95% CI, 0.1 to 1.3]; P = .02). Although there was no difference in improvement for the overall score for educational environment (6.0 [95% CI, -0.1 to 12.0] vs 13.6 [95% CI, 8.0 to 19.2]; adjusted difference, 9.6 [95% CI, -6.8 to 26.1]; P = .25), there was an associated mean improvement in the domains of general relationships and support (-0.5 [95% CI, -1.5 to 0.4] vs 0.3 [95% CI, -0.6 to 1.1]; adjusted difference, 2.3 [95% CI, 0.2 to 4.3]; P = .03) and EBM application opportunities (0.5 [95% CI, -0.7 to 1.8] vs 2.9 [95%, CI, 1.8 to 4.1]; adjusted difference, 3.3 [95% CI, 0.1 to 6.5]; P = .04). CONCLUSION: In a group of LMICs, a clinically integrated e-learning EBM curriculum in reproductive health compared with a self-directed EBM course resulted in higher knowledge and skill scores and improved educational environment. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12609000198224.

Long-term cardiac assessment in a sample of adolescent-onset anorexia nervosa.

BACKGROUND: High mortality rates have been reported in patients with anorexia nervosa, mainly due to cardiovascular alterations. The purpose of the present study was to assess cardiac structural and functional abnormalities some 20 years after initial treatment in a sample of adolescent-onset anorexia nervosa (A-AN) and to compare them with matched healthy controls (HC). METHODS: A sample of 29 women diagnosed and treated for AN during adolescence (A-AN) were assessed more than 20 years later. A complete cardiac evaluation was carried out including an electrocardiogram (ECG) and a standard 2D echocardiography. Thirty matched HC were also assessed. RESULTS: In the A-AN group, four subjects had a body mass index lower than 18.5 and met full DSM 5 criteria for AN at follow-up (Low-Weight group). They were compared with the rest of the sample (n = 25) who had normalized their weight (Normal-Weight group), though some still showed some eating disorder symptoms. Both groups were compared with the HC group. Subjects in the Low-Weight group presented statistically significant decreases in the left ventricular end-diastolic and left atrium dimensions and left ventricular mass in comparison with the Normal-Weight group and the HC. No other differences in cardiac parameters were found between groups. CONCLUSIONS: Echocardiographic and ECG parameters of adults who had presented A-AN twenty years earlier and currently maintained normal weight were similar to those of HC who had never been treated or diagnosed with AN. Adult subjects with A-AN who still had low weight in the long term present certain cardiac abnormalities similar to those seen in short-lasting disease. More studies are needed to confirm these results in a larger sample.

Anorexia nervosa is associated with multiple medical complications and high mortality, mainly due to cardiovascular complications. The main objective of the project was to study long-term cardiac abnormalities in a group of patients diagnosed with anorexia nervosa during adolescence. A sample of 29 patients, treated during adolescence for anorexia nervosa, were evaluated 20 years later. We did an echocardiogram and an electrocardiogram to all of them, and compared them with 30 healthy controls. Of the 29 patients with anorexia nervosa, 4 had low weight and 25 had normal weight. Patients who had normalized their weight did not present cardiac alterations and did not differ from the healthy controls. The 4 underweight patients did present cardiac abnormalities similar to those observed in short-term studies, such as decreased dimensions and mass of the left ventricle and the left atrium.