Impact of antiretroviral therapy on fertility desires among HIV-infected persons in rural Uganda

<p>Abstract</p> <p>Background</p> <p>Little is known about the fertility desires of HIV infected individuals on highly active antiretroviral therapy (HAART). In order to contribute more knowledge to this topic we conducted a study to determine if HIV-infected persons on HAART have different fertility desires compared to persons not on HAART, and if the knowledge about HIV transmission from mother-to-child is different in the two groups.</p> <p>Methods</p> <p>The study was a cross-sectional survey comparing two groups of HIV-positive participants: those who were on HAART and those who were not. Semi-structured interviews were conducted with 199 HIV patients living in a rural area of western Uganda. The desire for future children was measured by the question in the questionnaire "Do you want more children in future." The respondents' HAART status was derived from the interviews and verified using health records. Descriptive, bivariate and multivariate methods were used to analyze the relationship between HAART treatment status and the desire for future children.</p> <p>Results</p> <p>Results from the multivariate logistic regression model indicated an adjusted odds ratio (OR) of 1.08 (95% CI 0.40-2.90) for those on HAART wanting more children (crude OR 1.86, 95% CI 0.82-4.21). Statistically significant predictors for desiring more children were younger age, having a higher number of living children and male sex. Knowledge of the risks for mother-to-child-transmission of HIV was similar in both groups.</p> <p>Conclusions</p> <p>The conclusions from this study are that the HAART treatment status of HIV patients did not influence the desire for children. The non-significant association between the desire for more children and the HAART treatment status could be caused by a lack of knowledge in HIV-infected persons/couples about the positive impact of HAART in reducing HIV transmission from mother-to-child. We recommend that the health care system ensures proper training of staff and appropriate communication to those living with HIV as well as to the general community.</p

Investigating associations between maternal stress, smoking and adverse birth outcomes: evidence from the All Our Families cohort

Abstract Background Independently, active maternal and environmental tobacco smoke exposure and maternal stress have been linked to an increased risk of preterm birth and low birth weight. An understudied relationship is the potential for interactive effects between these risk factors. Methods Data was obtained from the All Our Families cohort, a study of 3,388 pregnant women < 25 weeks gestation recruited from those receiving prenatal care in Calgary, Canada between May 2008 and December 2010. We investigated the joint effects of active maternal smoking, total smoke exposure (active maternal smoking plus environmental tobacco smoke) and prenatal stress (Perceived Stress Scale, Spielberger State-Trait Anxiety Inventory), measured at two time points (< 25 weeks and 34–36 weeks gestation), on preterm birth and low birth weight. Results A marginally significant association was observed with the interaction active maternal smoking and Spielberger State-Trait Anxiety Inventory scores in relation to low birth weight, after imputation (aOR = 1.02, 95%CI: 1.00-1.03, p = 0.06). No significant joint effects of maternal stress and either active maternal smoking or total smoke exposure with preterm birth were observed. Active maternal smoking, total smoke exposure, Perceived Stress Scores, and Spielberger State-Trait Anxiety Inventory scores were independently associated with preterm birth and/or low birth weight. Conclusions Findings indicate the role of independent effects of smoking and stress in terms of preterm birth and low birthweight. However, the etiology of preterm birth and low birth weight is complex and multifactorial. Further investigations of potential interactive effects may be useful in helping to identify women experiencing vulnerability and inform the development of targeted interventions

Improving gene set analysis of microarray data by SAM-GS

<p>Abstract</p> <p>Background</p> <p><it>Gene-set </it>analysis evaluates the expression of biological pathways, or <it>a priori </it>defined gene sets, rather than that of individual genes, in association with a binary phenotype, and is of great biologic interest in many DNA microarray studies. Gene Set Enrichment Analysis (GSEA) has been applied widely as a tool for gene-set analyses. We describe here some critical problems with GSEA and propose an alternative method by extending the individual-gene analysis method, Significance Analysis of Microarray (SAM), to gene-set analyses (SAM-GS).</p> <p>Results</p> <p>Using a mouse microarray dataset with simulated gene sets, we illustrate that GSEA gives statistical significance to gene sets that have no gene associated with the phenotype (null gene sets), and has very low power to detect gene sets in which half the genes are moderately or strongly associated with the phenotype (truly-associated gene sets). SAM-GS, on the other hand, performs very well. The two methods are also compared in the analyses of three real microarray datasets and relevant pathways, the diverging results of which clearly show advantages of SAM-GS over GSEA, both statistically and biologically. In a microarray study for identifying biological pathways whose gene expressions are associated with <it>p53 </it>mutation in cancer cell lines, we found biologically relevant performance differences between the two methods. Specifically, there are 31 additional pathways identified as significant by SAM-GS over GSEA, that are associated with the presence vs. absence of <it>p53</it>. Of the 31 gene sets, 11 actually involve <it>p53 </it>directly as a member. A further 6 gene sets directly involve the extrinsic and intrinsic apoptosis pathways, 3 involve the cell-cycle machinery, and 3 involve cytokines and/or JAK/STAT signaling. Each of these 12 gene sets, then, is in a direct, well-established relationship with aspects of <it>p53 </it>signaling. Of the remaining 8 gene sets, 6 have plausible, if less well established, links with <it>p53</it>.</p> <p>Conclusion</p> <p>We conclude that GSEA has important limitations as a gene-set analysis approach for microarray experiments for identifying biological pathways associated with a binary phenotype. As an alternative statistically-sound method, we propose SAM-GS. A free Excel Add-In for performing SAM-GS is available for public use.</p

Improving GSEA for Analysis of Biologic Pathways for Differential Gene Expression across a Binary Phenotype

Gene-set analysis evaluates the expression of biological pathways, or a priori defined gene sets, rather than that of single genes, in association with a binary phenotype, and is of great biologic interest in many DNA microarray studies. Gene Set Enrichment Analysis (GSEA) has been applied widely as a tool for gene-set analyses. We describe here some critical problems with GSEA and propose an alternative method by extending the single-gene analysis method, Significance Analysis of Microarray (SAM), to gene-set analyses (SAM-GS). Specifically, we illustrate, in a simulation study, that GSEA gives statistical significance to gene sets that have no gene associated with the phenotype (null gene sets), and has very low power to detect gene sets in which half the genes are highly associated with the phenotype (truly-associated gene sets). SAM-GS, on the other hand, performs perfectly in the simulation study: none of the null gene sets is identified with statistical significance, while all of the truly-associated gene sets are. The two methods are also compared in the analyses of three real microarray datasets and relevant pathways, the diverging results of which clearly show the advantages of SAM-GS over GSEA, both statistically and biologically

A Biological Evaluation of Six Gene Set Analysis Methods for Identification of Differentially Expressed Pathways in Microarray Data

Gene-set analysis of microarray data evaluates biological pathways, or gene sets, for their differential expression by a phenotype of interest. In contrast to the analysis of individual genes, gene-set analysis utilizes existing biological knowledge of genes and their pathways in assessing differential expression. This paper evaluates the biological performance of five gene-set analysis methods testing “self-contained null hypotheses” via subject sampling, along with the most popular gene-set analysis method, Gene Set Enrichment Analysis (GSEA). We use three real microarray analyses in which differentially expressed gene sets are predictable biologically from the phenotype. Two types of gene sets are considered for this empirical evaluation: one type contains “truly positive” sets that should be identified as differentially expressed; and the other type contains “truly negative” sets that should not be identified as differentially expressed. Our evaluation suggests advantages of SAM-GS, Global, and ANCOVA Global methods over GSEA and the other two methods

Arsenic on the Hands of Children after Playing in Playgrounds

Increasing concerns over the use of wood treated with chromated copper arsenate (CCA) in playground structures arise from potential exposure to arsenic of children playing in these playgrounds. Limited data from previous studies analyzing arsenic levels in sand samples collected from CCA playgrounds are inconsistent and cannot be directly translated to the amount of children’s exposure to arsenic. The objective of this study was to determine the quantitative amounts of arsenic on the hands of children in contact with CCA-treated wood structures or sand in playgrounds. We compared arsenic levels on the hands of 66 children playing in eight CCA playgrounds with levels of arsenic found on the hands of 64 children playing in another eight playgrounds not constructed with CCA-treated wood. The children’s age and duration of playtime were recorded at each playground. After play, children’s hands were washed in a bag containing 150 mL of deionized water. Arsenic levels in the hand-washing water were quantified by inductively coupled plasma mass spectrometry. Our results show that the ages of the children sampled and the duration of play in the playgrounds were similar between the groups of CCA and non-CCA playgrounds. The mean amount of water-soluble arsenic on children’s hands from CCA playgrounds was 0.50 μg (range, 0.0078–3.5 μg). This was significantly higher (p < 0.001) than the mean amount of water-soluble arsenic on children’s hands from non-CCA playgrounds, which was 0.095 μg (range, 0.011–0.41 μg). There was no significant difference in the amount of sand on the children’s hands and the concentration of arsenic in the sand between the CCA and non-CCA groups. The higher values of arsenic on the hands of children playing in the CCA playgrounds are probably due to direct contact with CCA-treated wood. Washing hands after play would reduce the levels of potential exposure because most of the arsenic on children’s hands was washed off with water. The maximum amount of arsenic on children’s hands from the entire group of study participants was < 4 μg, which is lower than the average daily intake of arsenic from water and food

Prospective study of biliary strictures to determine the predictors of malignancy

ORIGINAL ARTICLE BACKGROUND: There have been few prospective studies regarding the investigation of biliary strictures, principally because of rapid technological change. The present study was designed to determine the sensitivity of various imaging studies for the detection of biliary strictures. Serum biochemistry and imaging studies were evaluated for their role in distinguishing benign from malignant strictures. METHODS: Thirty-one patients with suspected noncalculus biliary obstruction were enrolled consecutively in the study. A complete biochemical profile, ultrasound, Disida scan and cholangiogram (endoscopic retrograde cholangiopancreatography [ERCP] or percutaneous cholangiogram) were obtained at study entry. Stricture etiology was determined based on cytology, biopsy and/or clinical follow-up at one year. RESULTS: Twenty-nine of 31 patients had biliary strictures, of which 15 were malignant. The mean age of the malignant cohort was 73.9 years versus 53.9 years in the benign cohort (P&lt;0.001). Statistically significant differences between the malignant and benign groups, respectively, were as follows: alanine transaminase 235.2 versus 66.9 U/L (P=0.004), aspartate transaminase 189.8 versus 84.5 U/L (P=0.011), alkaline phosphatase 840.2 versus 361.1 U/L (P=0.002), bilirubin 317.8 versus 22.1 µmol/L (P&lt;0.001) and bile acids 242.5 versus 73.2 µmol/L (P=0.001). Threshold analysis using receiver operative characteristic (ROC) curves demonstrated that a bilirubin level of 75 µmol/L was most predictive of malignant strictures. Intrahepatic duct dilation was present in 93% of malignant strictures versus 36% of benign strictures (P=0.002). Common hepatic duct dilation was less discriminatory (malignant 13.5 versus benign 9.6 mm; P=0.11). Ultrasound was highly sensitive (93%) in the detection of the primary tumour in the bile duct or pancreas, or in the visualization of nodal or liver metastases. In benign disease, ultrasound failed to detect evidence of intrahepatic or extrahepatic biliary dilation in most cases. Disida scans were not able to distinguish between malignant or benign strictures and could not accurately localize the level of obstruction. The sensitivity of Disida scan for the diagnosis of obstruction was 50%. Cholangiographic characterization of strictures revealed an equal distribution of smooth (eight of 13) and irregular (five of 13) strictures in the malignant group. Ten of 13 benign strictures were characterized as smooth. Malignant strictures were significantly longer than benign ones -30.3 versus 9.2 mm (P=0.001). Threshold analysis using ROC curves showed that strictures greater than or equal to 14 mm were predictive of malignancy (sensitivity 78%, specificity 75%, log odds ratio 11.23). CONCLUSIONS: A serum bilirubin level of 75 µmol/L or higher, or a stricture length of greater than 14 mm was highly predictive of malignancy in patients with a biliary stricture. Ultrasound was useful in predicting malignant strictures by detecting either intrahepatic duct dilation or by visualizing the tumour (primary or metastases). Strictures with a &apos;benign&apos; cholangiographic appearance are frequently malignant. Disida scan did not add additional information. ERCP is necessary to diagnose benign strictures, which tend to be less extensive at presentation. B iliary strictures are a challenging problem for the clinician. By the time that patients with biliary strictures are referred to a specialist, the diagnosis is usually already known or strongly suspected because clinical evaluation and noninvasive investigations alone have a high specificity and sensitivity (1-4). The job of the medical or surgical specialist is not only to confirm the diagnosis of biliary stricture but also, importantly, to define the etiology and the exact anatomic location, which is vital to therapeutic planning. The differentiation between benign and malignant strictures can be difficult but is of obvious importance in regard to prognosis and optimal therapy. Numerous imaging modalities are available for the investigation of biliary strictures, including abdominal ultrasound, computed tomographic (CT) scanning, nuclear imaging, percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopancreatography (ERCP) and most recently magnetic resonance cholangiopancreatography (MRCP). Comparative and descriptive studies in this area are lacking, primarily because rapid technological improvements and developments outdate them. We, therefore, embarked on a prospective descriptive trial with the following aims: · Determine the predictive value of liver enzymes, serum bilirubin, serum bile acids, ultrasound and diethyl-iminodiacetic acid (Disida) nuclear imaging for the presence of malignant biliary strictures. · Measure the ability of ultrasound and nuclear imaging to localize the level of obstruction using direct cholangiography as the gold standard. · Determine the sensitivity of abdominal ultrasound and Disida nuclear scanning for the detection of biliary strictures. · Investigate the utility of various cholangiographic features to distinguish malignant from benign strictures. PATIENTS AND METHODS Patients: All patients with biliary strictures referred to the Division of Gastroenterology at the University of Alberta Hospitals for investigation between January 1, 1995 and December 31, 1995 were prospectively entered into the trial. The inclusion criteria were age 16 years or older and noncalculus biliary obstruction. Patients were excluded if subsequent evaluation did not show a stricture. Ethics committee approval was obtained. sente dans 93 % des sténoses malignes par rapport à 36 % des sténoses béni-gnes (P = 0,002). Une dilatation du canal hépatique commun était moins discriminatoire (13,5 mm en cas de malignité par rapport à 9,6 mm en cas de bénignité, P = 0,11). L&apos;échographie était hautement sensible (93 %) pour déceler la tumeur primaire dans le canal biliaire ou le pancréas, ou pour visualiser les nodules ou les métastases hépatiques. Dans le cas d&apos;une maladie bénigne, l&apos;échogra-phie n&apos;a pas réussi à déceler la présence d&apos;une dilatation biliaire intra-hépa-tique ou extra-hépatique dans la plupart des cas. Les scintigraphies au disida n&apos;ont pas pu différencier les sténoses malignes des sténoses bénignes ou localiser précisément le niveau de l&apos;obstruction. La sensibilité des scintigraphies au disida pour établir un diagnostic d&apos;obstruction était de 50 %. La caractérisation cholangiographique des sténoses a révélé une distribution égale de sténoses lisses (huit sur 13) et irrégulières (cinq sur 13) dans le groupe des sténoses malignes. Dix des 13 sténoses bénignes ont été qualifiées de lisses. Les sténoses malignes étaient nettement plus longues que les sténoses bénignes, soit 30,3 mm par rapport à 9,2 mm (P=0,001). L&apos;analyse des seuils au moyen des courbes ROC a révélé que des sténoses supérieures ou égales à 14 mm étaient un prédicteur de malignité (sensibilité de 78 %, spécificité de 75 %, risque relatif logarithmique de 11,23). CONCLUSIONS : Un niveau de bilirubine sérique de 75 µmol/L ou une longueur de sténose de 14 mm étaient fortement prédictifs de malignité chez les patients atteints d&apos;une sténose biliaire. L&apos;échographie était utile pour prédire les sténoses malignes en décelant soit une dilatation du canal intra-hépatique ou en visualisant la tumeur (primaire ou métastases). Les sténoses d&apos;apparence « bénigne » à la cholangiographie s&apos;avèrent souvent malignes. La scintigraphie au disida n&apos;apportait pas d&apos;informations supplé-mentaires. Une CPRE est nécessaire pour diagnostiquer des sténoses bénignes, qui ont tendance à être moins étendues à l&apos;examen. · Abdominal ultrasound examination with particular attention to intrahepatic biliary dilation, extrahepatic duct calibre, presence or absence of gallbladder and other relevant pathology such as tumour mass or ductal stones. · Disida scan. Patients were examined after a 4 h fast. Opiates were withheld for the proceeding 24 h. In addition to the standard scan, data were collected for deconvolutional analysis to determine hepatic extraction fraction and time activity curve so that the half-life of biliary excretion and time to peak activity could be analyzed. · Cholangiography. ERCP was attempted first in all patients with failures proceeding to PTC. Cefazoline 1 g was administered intravenously 30 to 60 mins before cholangiography. The biliary system was filled as completely as possible using 50% Conray 60 (Mallenchrodt, St Louis, Missouri) contrast injected under low pressure. The information obtained from each cholangiogram included site of stricture, multiplicity, character (smoothly tapered versus irregular or shouldered), stricture(s) length, minimal stricture width, maximal proximal biliary dilation and other information (ampullary mass, primary sclerosing cholangitis, cancer of the pancreas). All data were to be collected within five working days so that the different imaging modalities tested would be comparable. All imaging studies were interpreted by radiologists blinded to the results of the patients&apos; other diagnostic studies. The ERCP data were obtained last so that a biliary stent could be inserted if indicated. The cholangiographic measurements were confirmed by two independent observers. Stricture etiology was defined by cytology or biopsy histology or by clinical outcome after one year. Statistical analysis: Statistical analysis was performed using SPSS. Between-groups differences in mean values of continuous variables were tested by independent samples t tests or by nonparametric Mann-Whitney Rank Sum tests when the distributions were not normal. The differences in frequencies of categorical variables were tested by c 2 test with Yates&apos; correction for continuity or by Fisher&apos;s exact test when the expected number of observations per cell was less than five. Associations between continuous variables were assessed by Pearson correlation coefficient. Logistic regression analysis was used to analyze the association of dichotomous outcome variable (malignant versus benign) with continuous and categorical predictor variables. The statistical inferences were based on the level of significance P&lt;0.05. Receiver operating characteristic (ROC) curves were constructed for the biochemical variables. To determine optimal threshold levels for each diagnostic parameter, ROC plots were constructed using the observed true and false positive rates at each potential threshold level. A best fit ROC curve was constructed according to methods published elsewhere (5,6). The threshold value providing the best compromise between true and false positive rates was estimated from the ROC plot. Likelihood ratios were calculated from the fitted ROC curve. RESULTS Thirty-one patients were enrolled in the study. Two patients were excluded -one because he did not have a stricture and one whose suspected stricture was unevaluable because of previous biliary bypass and contraindication for PTC as a result of coagulopathy. Of the remaining 29 patients, 15 were diagnosed with malignant strictures and 14 with benign strictures. Two patients had primary sclerosing cholangitis, both of whom had multiple strictures. Patient demographics and underlying diagnosis are shown i