Modelling HIV-RNA viral load in vertically infected children

Human immunodeficiency virus (HIV) ribo-nucleic acid (RNA) viral load is a measure of actively replicating virus and is used as a marker of disease progression. For a thorough understanding of the dynamics of the evolution of the virus in the early life of HIV-1 vertically infected children, it is important to elucidate the pattern of HIV-RNA viral load over age. An aspect of assay systems used in the quantification of RNA viral load is that they measure values above particular cut-off values for detection, below which the assays used are not sufficiently sensitive. In this way, measurements are potentially left-censored. Recent adult studies suggest that to adequately model RNA pattern over age, it is necessary to account for within-subject correlation, due to repeated measures, and censoring. The aim of this study, therefore, was to establish whether it is necessary to use complex methods to allow for repeated measures within individuals and censoring of the HIV-RNA viral load in children enrolled in a cohort study. The approach involved the identification of an appropriate model for the basic pattern of RNA viral load by age and subsequent assessment of various estimation procedures accounting for repeated measures and censoring in different ways. Methods developed by Hughes involving the expectation-maximization (EM) algorithm and the Gibbs sampler were taken as the benchmark for comparison of simpler alternatives. Other approaches considered involve linear mixed-effects and ordinary least squares in which censoring is dealt with informally by taking the cut-off value as absolute or taking the mid-point between cut-off and zero. Fractional polynomials provided a substantially superior approach for modelling the dynamics of viral load over age compared to conventional polynomials or change-point models. Allowing for repeated measures was necessary to improve the power of the likelihood ratio tests required to establish the final model, but methods beyond taking the mid-point for censored values did not further improve the fit. Although Hughes' methodology is the best approach, its implementation is not necessary for the identification of the optimal model.     

Lifetime prevalence of sexual abuse in a Swedish pregnant population

BACKGROUND: Our primary purpose was to determine the prevalence of sexual abuse in a non-selected pregnant population. We also endeavored to establish the age at which the abuse had occurred and the identity of the perpetrator and to analyze in sexually abused vis-à-vis non-abused women, various socio-economic and clinical variables. METHODS: Over a period of 6 months, all women registered at antenatal clinics in Uppsala, Sweden, were questioned by their midwives regarding exposure to sexual abuse. Data from antenatal records were used to compare abused with non-abused women concerning socio-economic characteristics, previous ill health, reproductive history, pregnancy complications, and pregnancy outcome. Continuous variables were compared using the Student's t-test or the Mann-Whitney U-test and categorical variables using the chi-square test or Fisher's exact test. RESULTS: Of 1038 women assessed, 84 (8.1%) reported that at some time in their life they had been forced to participate in or subjected to sexual activity against their will. In most cases the perpetrator was someone the woman knew. When compared with non-victims, those abused were more likely to report general health problems, especially gynecologic ill health and surgery, pulmonary disease/asthma, and/or psychiatric care. However, no differences were found regarding pregnancy outcome. CONCLUSIONS: It was found that one pregnant woman in 12 had reported sexual abuse at some time in their life. To midwives and obstetricians who work closely both physically and emotionally with pregnant women, an awareness of the extent of the problem and of possible sequelae is essential.     

A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome

Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, there are no prospective data to support this approach to thromboprophylaxis.     

Pharmacoeconomics of elderly vaccination against invasive pneumococcal infections: cost-effectiveness analyses and implications for The Netherlands

We performed a review of cost-effectiveness of elderly pneumococcal vaccination to prevent invasive disease. It concerns studies in the USA, Canada, Netherlands and Spain and a multinational study of five European countries. Cost-effectiveness of elderly vaccination against invasive pneumococcal infections varies from cost-saving to EUR 33,000 per life-year gained. The Dutch study estimates cost-effectiveness at EUR 10,100 per life-year gained (price level: 1995). This is below the level that has recently been defined for treatment of high cholesterol (EUR 20,000 per life-year gained) and may therefore be considered as favorable. Almost all studies base their estimate of vaccine efficacy on the same case-control study from the USA. We identify a need for a systematic review on the efficacy of the pneumococcal vaccine. Also, we suggest further analysis with respect to potential effects on cost-effectiveness of extended influenza vaccination for the Dutch elderly in recent years and inclusion of pneumococcal re-vaccination. Pending this additional information, we conclude that cost-effectiveness of vaccination against invasive pneumococcal infections for Dutch elderly is favorable (as in several other countries) and justifies implementation from a pharmacoeconomic point of view.     

Endotracheal tube cuff pressure is unpredictable in children

The use of cuffed tracheal tubes in children younger than 8 yr of age has recently increased, although cuff hyperinflation may cause tracheal mucosal damage. In this study, we sought to measure the cuff pressure (P(cuff)) after initial free air inflation (iP(cuff)) and to follow its evolution throughout the duration of 50% nitrous oxide (N(2)O) anesthesia. One-hundred-seventy-four children, aged 0 to 9 yr, fulfilling the following criteria, were studied: 1). weight of 3-35 kg; 2). ASA physical status I or II; 3). elective surgery; 4). anesthesia with tracheal intubation using a cuffed tube and lasting at least 45 min; and 5). gas mixture containing 50% N(2)O. Free air inflation results in variable iP(cuff), with hyperinflation in 39% of cases. Numerous gas removals were required to maintain P(cuff) less than 25 cm H(2)O in 85% of the patients. The number of deflations decreased with the duration of mechanical ventilation and was small after 105 min. No difference was observed among the different cuffed tube sizes. We conclude that iP(cuff) is unpredictable after free air inflation and that numerous gas removals are required to maintain P(cuff) less than 25 cm H(2)O during N(2)O anesthesia in children. IMPLICATIONS: Free inflation of the tracheal tube cuff, controlled only by the palpation of the pilot balloon, is not reliable and results in extremely variable (and sometimes very high) initial cuff pressures in children. In addition, nitrous oxide anesthesia may result in cuff hyperinflation requiring numerous gas removals.     

Expression of somatostatin receptor subtypes 1 to 5 in tumor tissue and intratumoral vessels in malignant endocrine pancreatic tumors

Somatostatin analogs are well established in the treatment of malignant endocrine pancreatic tumors (EPTs). Our goal is to individualize their treatment using receptor-subtype-specific analogs and, therefore, exploring the receptor expression is highly important. We have examined the expression of somatostatin receptor (sst) subtypes 1–5 on tumor cells and in intratumoral vessels in 28 tumor tissues from malignant EPTs with immunohistochemistry using sst-subtype-specific polyclonal antibodies. We found that sst₂ and sst₄ stained positive in 90% and sst₁ in 70% of the tumor tissues, whereas sst₃ and sst₅ stained positive in only 50% of the tumor tissues. Sst expression in intratumoral vessels was high for sst₂ and sst₄ (80%), moderate for sst₁ (40%), and low for sst₃ and sst₅ (10%). The ssts were evenly distributed among the different tumor subtypes. However, tumors belonging to the same subgroup of EPTs showed a variable expression of receptor subtypes. No differences in receptor-subtype expression could be seen between poorly and well-differentiated tumors, nor between primary tumors and metastases. Prior medical treatment did not influence sst expression pattern. In conclusion, sst₂ and sst₄ were expressed in most tumor tissues and intratumoral vessels from EPTs. However, sst₃ and sst₅ were lacking in half of the tumor tissues and in most of the intratumoral vessels. These differences indicate the importance of determining each tumor’s subset of receptors before treatment with receptor-subtype-specific analogs is initiated. The importance of sst expression in intratumoral vessels is not yet known.     

Assessment of the impact of model-based scatter correction on [18F]-FDG 3D brain PET in healthy subjects using statistical parametric mapping

It is recognized that scatter correction can supply more accurate absolute quantification, and that iterative reconstruction results in better noise properties and significantly reduces streak artefacts; however, it is not entirely clear whether they produce significant changes in [18F]-FDG distribution of reconstructed 3D brain PET images relative to not scatter corrected images and analytic reconstruction procedures. The current study assesses the effect of model-based scatter correction using the single-scatter simulation algorithm and iterative reconstruction in 3D brain PET studies, using statistical parametric mapping (SPM) analysis. The study population consisted of 14 healthy volunteers (6 males, 8 females; age 63-80 years). PET images were reconstructed using an analytic 3DRP reprojection algorithm with (SC) and without explicit scatter correction (NSC), as well as using an iterative ordered subset-expectation maximization (OSEM) algorithm. Calculated attenuation correction was performed assuming uniform attenuation (mu = 0.096 cm(-1)) for brain tissues when data are precorrected for scatter. The broad-beam attenuation coefficient (mu = 0.06 cm(-1)) determined from phantom studies was applied to NSC images. The images were coregistered and normalized using the default [15O]-H2O template supplied with SPM99 and an [18F]-FDG template. A t statistic image for the contrast condition effect was then constructed. The contrast comparing SC to NSC images suggest that regional brain metabolic activity decreases significantly in the frontal gyri, in addition to the middle temporal and postcentral gyri. On the other hand, activity increases in the cerebellum, thalamus, insula, brainstem, temporal lobe, and the frontal cortex. No significant changes were detected when comparing images reconstructed using analytic and iterative algorithms. It is concluded that, for some cerebral areas, significant differences in [18F]-FDG distribution arise when images are reconstructed with and without explicit SC. This needs to be considered when interpreting [18F]-FDG 3D brain PET images after applying SC.