Acute internal medicine physicians' clinical intuition based on acute care telephone referral: A prospective study.

INTRODUCTION: In the Netherlands, most emergency department (ED) patients are referred by a general practitioner (GP) or a hospital specialist. Early risk stratification during telephone referral could allow the physician to assess the severity of the patients' illness in the prehospital setting. We aim to assess the discriminatory value of the acute internal medicine (AIM) physicians' clinical intuition based on telephone referral of ED patients to predict short-term adverse outcomes, and to investigate on which information their predictions are based. METHODS: In this prospective study, we included adult ED patients who were referred for internal medicine by a GP or a hospital specialist. Primary outcomes were hospital admission and triage category according to the Manchester Triage System (MTS). Secondary outcome was 31-day mortality. The discriminatory performance of the clinical intuition was assessed using an area under the receiver operating characteristics curve (AUC). To identify which information is important to predict adverse outcomes, we performed univariate regression analysis. Agreement between predicted and observed MTS triage category was assessed using intraclass and Spearman's correlation. RESULTS: We included 333 patients, of whom 172 (51.7%) were referred by a GP, 146 (43.8%) by a hospital specialist, and 12 (3.6%) by another health professional. The AIM physician's clinical intuition showed good discriminatory performance regarding hospital admission (AUC 0.72, 95% CI: 0.66-0.78) and 31-day mortality (AUC 0.73, 95% CI: 0.64-0.81). Univariate regression analysis showed that age ≥65 years and a sense of alarm were significant predictors. The predicted and observed triage category were similar in 45.2%, but in 92.5% the prediction did not deviate by more than one category. Intraclass and Spearman's correlation showed fair agreement between predicted and observed triage category (ICC 0.48, Spearman's 0.29). CONCLUSION: Clinical intuition based on relevant information during a telephone referral can be used to accurately predict short-term outcomes, allowing for early risk stratification in the prehospital setting and managing ED patient flow more effectively.

Optical experimental results using Singer product apertures.

We present the first optical experimental results obtained using the recently developed Singer product apertures. We also show that Fenimore and Cannon's fine sampling and delta decoding techniques can be combined with the fast direct vector decoding algorithm for Singer product apertures. We demonstrate resolutions and decoding speeds comparable to, or better than, those currently reported in the optical literature. Taken together these make possible coded aperture video in the optical domain.

Machine learning for risk stratification in the emergency department (MARS-ED) study protocol for a randomized controlled pilot trial on the implementation of a prediction model based on machine learning technology predicting 31-day mortality in the emergency department.

BACKGROUND: Many prediction models have been developed to help identify emergency department (ED) patients at high risk of poor outcome. However, these models often underperform in clinical practice and their actual clinical impact has hardly ever been evaluated. We aim to perform a clinical trial to investigate the clinical impact of a prediction model based on machine learning (ML) technology. METHODS: The study is a prospective, randomized, open-label, non-inferiority pilot clinical trial. We will investigate the clinical impact of a prediction model based on ML technology, the RISKINDEX, which has been developed to predict the risk of 31-day mortality based on the results of laboratory tests and demographic characteristics. In previous studies, the RISKINDEX was shown to outperform internal medicine specialists and to have high discriminatory performance. Adults patients (18 years or older) will be recruited in the ED. All participants will be randomly assigned to the control group or the intervention group in a 1:1 ratio. Participants in the control group will receive care as usual in which the study team asks the attending physicians questions about their clinical intuition. Participants in the intervention group will also receive care as usual, but in addition to asking the clinical impression questions, the study team presents the RISKINDEX to the attending physician in order to assess the extent to which clinical treatment is influenced by the results. DISCUSSION: This pilot clinical trial investigates the clinical impact and implementation of an ML based prediction model in the ED. By assessing the clinical impact and prognostic accuracy of the RISKINDEX, this study aims to contribute valuable insights to optimize patient care and inform future research in the field of ML based clinical prediction models. TRIAL REGISTRATION: ClinicalTrials.gov NCT05497830. Machine Learning for Risk Stratification in the Emergency Department (MARS-ED). Registered on August 11, 2022. URL: https://clinicaltrials.gov/study/NCT05497830 .

Explainable Machine Learning Models for Rapid Risk Stratification in the Emergency Department: A Multicenter Study.

BACKGROUND: Risk stratification of patients presenting to the emergency department (ED) is important for appropriate triage. Diagnostic laboratory tests are an essential part of the workup and risk stratification of these patients. Using machine learning, the prognostic power and clinical value of these tests can be amplified greatly. In this study, we applied machine learning to develop an accurate and explainable clinical decision support tool model that predicts the likelihood of 31-day mortality in ED patients (the RISKINDEX). This tool was developed and evaluated in four Dutch hospitals. METHODS: Machine learning models included patient characteristics and available laboratory data collected within the first 2 h after ED presentation, and were trained using 5 years of data from consecutive ED patients from the Maastricht University Medical Center (Maastricht), Meander Medical Center (Amersfoort), and Zuyderland Medical Center (Sittard and Heerlen). A sixth year of data was used to evaluate the models using area under the receiver-operating-characteristic curve (AUROC) and calibration curves. The Shapley additive explanations (SHAP) algorithm was used to obtain explainable machine learning models. RESULTS: The present study included 266 327 patients with 7.1 million laboratory results available. Models show high diagnostic performance with AUROCs of 0.94, 0.98, 0.88, and 0.90 for Maastricht, Amersfoort, Sittard and Heerlen, respectively. The SHAP algorithm was utilized to visualize patient characteristics and laboratory data patterns that underlie individual RISKINDEX predictions. CONCLUSIONS: Our clinical decision support tool has excellent diagnostic performance in predicting 31-day mortality in ED patients. Follow-up studies will assess whether implementation of these algorithms can improve clinically relevant end points.

Head-to-head comparison of 19 prediction models for short-term outcome in medical patients in the emergency department: a retrospective study.

INTRODUCTION: Prediction models for identifying emergency department (ED) patients at high risk of poor outcome are often not externally validated. We aimed to perform a head-to-head comparison of the discriminatory performance of several prediction models in a large cohort of ED patients. METHODS: In this retrospective study, we selected prediction models that aim to predict poor outcome and we included adult medical ED patients. Primary outcome was 31-day mortality, secondary outcomes were 1-day mortality, 7-day mortality, and a composite endpoint of 31-day mortality and admission to intensive care unit (ICU).The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC). Finally, the prediction models with the highest performance to predict 31-day mortality were selected to further examine calibration and appropriate clinical cut-off points. RESULTS: We included 19 prediction models and applied these to 2185 ED patients. Thirty-one-day mortality was 10.6% (231 patients), 1-day mortality was 1.4%, 7-day mortality was 4.4%, and 331 patients (15.1%) met the composite endpoint. The RISE UP and COPE score showed similar and very good discriminatory performance for 31-day mortality (AUC 0.86), 1-day mortality (AUC 0.87), 7-day mortality (AUC 0.86) and for the composite endpoint (AUC 0.81). Both scores were well calibrated. Almost no patients with RISE UP and COPE scores below 5% had an adverse outcome, while those with scores above 20% were at high risk of adverse outcome. Some of the other prediction models (i.e. APACHE II, NEWS, WPSS, MEWS, EWS and SOFA) showed significantly higher discriminatory performance for 1-day and 7-day mortality than for 31-day mortality. CONCLUSIONS: Head-to-head validation of 19 prediction models in medical ED patients showed that the RISE UP and COPE score outperformed other models regarding 31-day mortality.

Performance of prediction models for short-term outcome in COVID-19 patients in the emergency department: a retrospective study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has a high burden on the healthcare system. Prediction models may assist in triaging patients. We aimed to assess the value of several prediction models in COVID-19 patients in the emergency department (ED). METHODS: In this retrospective study, ED patients with COVID-19 were included. Prediction models were selected based on their feasibility. Primary outcome was 30-day mortality, secondary outcomes were 14-day mortality and a composite outcome of 30-day mortality and admission to medium care unit (MCU) or intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC). RESULTS: We included 403 patients. Thirty-day mortality was 23.6%, 14-day mortality was 19.1%, 66 patients (16.4%) were admitted to ICU, 48 patients (11.9%) to MCU, and 152 patients (37.7%) met the composite endpoint. Eleven prediction models were included. The RISE UP score and 4 C mortality scores showed very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84, 95% CI 0.79-0.88 for both), significantly higher than that of the other models. CONCLUSION: The RISE UP score and 4 C mortality score can be used to recognise patients at high risk for poor outcome and may assist in guiding decision-making and allocating resources.

Performance of prediction models for short term outcome in COVID-19 patients in the emergency department: a retrospective study

IntroductionCoronavirus disease 2019 (COVID-19) has a high burden on the healthcare system and demands information on the outcome early after admission to the emergency department (ED). Previously developed prediction models may assist in triaging patients when allocating healthcare resources. We aimed to assess the value of several prediction models when applied to COVID-19 patients in the ED. MethodsAll consecutive COVID-19 patients who visited the ED of a combined secondary/tertiary care center were included. Prediction models were selected based on their feasibility. The primary outcome was 30-day mortality, secondary outcomes were 14-day mortality, and a composite outcome of 30-day mortality and admission to the medium care unit (MCU) or the intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC). ResultsA total of 403 ED patients were diagnosed with COVID-19. Within 30 days, 95 patients died (23.6%), 14-day mortality was 19.1%. Forty-eight patients (11.9%) were admitted to the MCU, 66 patients (16.4%) to the ICU and 152 patients (37.7%) met the composite endpoint. Eleven models were included: RISE UP score, 4C mortality score, CURB-65, MEWS, REMS, abbMEDS, SOFA, APACHE II, CALL score, ACP index and Host risk factor score. The RISE UP score and 4C mortality score showed a very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84 respectively, 95% CI 0.79-0.88 for both), for 14-day mortality (AUC 0.83, 95% CI: 0.79-0.88, for both) and for the composite outcome (AUC 0.79 and 0.77 respectively, 95% CI 0.75-0.84). The discriminatory performance of the RISE UP score and 4C mortality score was significantly higher compared to that of the other models. ConclusionThe RISE UP score and 4C mortality score have good discriminatory performance in predicting adverse outcome in ED patients with COVID-19. These prediction models can be used to recognize patients at high risk for short-term poor outcome and may assist in guiding clinical decision-making and allocating healthcare resources.

Validating the RISE UP score for predicting prognosis in patients with COVID-19 in the emergency department, a retrospective study

ObjectiveTo mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed RISE UP score has very good discriminatory value with respect to short-term mortality in older patients in the emergency department (ED). It consists of six items: age, abnormal vital signs, albumin, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and bilirubin. We hypothesized that the RISE UP score could have discriminatory value with regard to 30-day mortality in ED patients with COVID-19. SettingTwo EDs of the Zuyderland Medical Centre (MC), secondary care hospital in the Netherlands. ParticipantsThe study sample consisted of 642 adult ED patients diagnosed with COVID-19 between March 3rd until May 25th 2020. Inclusion criteria were: 1) admission to the hospital with symptoms suggestive of COVID-19, and 2) positive result of the polymerase chain reaction (PCR), or (very) high suspicion of COVID-19 according to the chest computed tomography (CT) scan. OutcomePrimary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU). ResultsWithin 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value with respect to 30-day mortality (AUC 0.77, 95% CI 0.73-0.81), and to the composite outcome (AUC 0.72, 95% CI 0.68-0.76). Patients with RISE UP scores below 10% (121 patients) had favourable outcome (0% mortality and 5% ICU admissions). Patients with a RISE UP score above 30% (221 patients) were at high risk of adverse outcome (46.6% mortality and 19% ICU admissions). ConclusionThe RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome, and may help guiding decision-making and allocating healthcare resources.

An 86-year-old man with acute abdominal pain.

An 86-year-old man presented with severe pain in the upper abdomen along with fever. On physical examination, we found an arterial blood pressure of 84/43 mm Hg, a heart rate of 80 bpm and a temperature of 38.3°C. The abdomen was painful and peristalsis was absent. Empiric antibiotic therapy for sepsis was started with amoxicillin/clavulanate and gentamicin. CT scan of the abdomen revealed an emphysematous cholecystitis. Percutaneous ultrasound-guided cholecystostomy was applied. Bile cultures revealed Clostridium perfringens. Emphysematous cholecystitis is a life-threatening form of acute cholecystitis that occurs as a consequence of ischaemic injury to the gallbladder, followed by translocation of gas-forming bacteria (ie, C. perfringens, Escherichia coli, Klebsiella and Streptococci). The mortality associated with emphysematous cholecystitis is higher than in non-emphysematous cholecystitis (15% vs 4%). Therefore, early diagnosis with radiological imaging is of vital importance.

Symptomatic cholecystolithiasis after cholecystectomy.

A 43-year-old woman was admitted to the gastroenterology department with colicky pain in the upper abdomen. Four years earlier, she had undergone a laparoscopic cholecystectomy because of cholecystitis. She recognised her current complaints from that previous episode. An endoscopic retrograde cholangiopancreatography showed a cavity with a diameter of 2 cm which contained multiple concrements near the liver hilus. An elective surgical exploration was performed. Near the clip of the previous cholecystectomy a bulging of the biliary tract with its own duct was visualised and resected. Histological examination of this "neo" gallbladder showed that the bulging was consistent with the formation of a reservoir secondary to bile leakage, probably caused by a small peroperative lesion of the common bile duct during the previous cholecystectomy. In conclusion, our patient presented with colicky pain caused by concrements inside a 'neo' gallbladder.

Inferring patterns of migration.

The historical movement of organisms, whether recent or in the distant past, forms a central aspect of evolutionary studies. Inferring patterns of migration can be difficult and requires reliance on a large suite of bioinformatic tools. As it is primarily the movement of groups of related individuals or populations that are of interest, population genetic and phylogeographic methods form the core of tools used to decipher migration patterns. Following a description of these tools, we discuss the most critical--and potentially most difficult--aspect of these studies: the inference process used. Designing a study, determining which data to collect, how to analyze the data, and how to coordinate these results into a coherent narrative are all a part of this inference process. Furthermore, using different types of data (e.g., genotypic and DNA sequence) from different types of sources (direct, or from the organisms of interest; and indirect, from symbiotic organisms) produces a powerful suite of techniques that are used to infer patterns of migration.

Geometric morphometric analyses provide evidence for the adaptive character of the Tanganyikan cichlid fish radiations.

The cichlids of East Africa are renowned as one of the most spectacular examples of adaptive radiation. They provide a unique opportunity to investigate the relationships between ecology, morphological diversity, and phylogeny in producing such remarkable diversity. Nevertheless, the parameters of the adaptive radiations of these fish have not been satisfactorily quantified yet. Lake Tanganyika possesses all of the major lineages of East African cichlid fish, so by using geometric morphometrics and comparative analyses of ecology and morphology, in an explicitly phylogenetic context, we quantify the role of ecology in driving adaptive speciation. We used geometric morphometric methods to describe the body shape of over 1000 specimens of East African cichlid fish, with a focus on the Lake Tanganyika species assemblage, which is composed of more than 200 endemic species. The main differences in shape concern the length of the whole body and the relative sizes of the head and caudal peduncle. We investigated the influence of phylogeny on similarity of shape using both distance-based and variance partitioning methods, finding that phylogenetic inertia exerts little influence on overall body shape. Therefore, we quantified the relative effect of major ecological traits on shape using phylogenetic generalized least squares and disparity analyses. These analyses conclude that body shape is most strongly predicted by feeding preferences (i.e., trophic niches) and the water depths at which species occur. Furthermore, the morphological disparity within tribes indicates that even though the morphological diversification associated with explosive speciation has happened in only a few tribes of the Tanganyikan assemblage, the potential to evolve diverse morphologies exists in all tribes. Quantitative data support the existence of extensive parallelism in several independent adaptive radiations in Lake Tanganyika. Notably, Tanganyikan mouthbrooders belonging to the C-lineage and the substrate spawning Lamprologini have evolved a multitude of different shapes from elongated and Lamprologus-like hypothetical ancestors. Together, these data demonstrate strong support for the adaptive character of East African cichlid radiations.

Sampling genetic diversity in the sympatrically and allopatrically speciating Midas cichlid species complex over a 16 year time series.

BACKGROUND: Speciation often occurs in complex or uncertain temporal and spatial contexts. Processes such as reinforcement, allopatric divergence, and assortative mating can proceed at different rates and with different strengths as populations diverge. The Central American Midas cichlid fish species complex is an important case study for understanding the processes of speciation. Previous analyses have demonstrated that allopatric processes led to species formation among the lakes of Nicaragua as well as sympatric speciation that is occurring within at least one crater lake. However, since speciation is an ongoing process and sampling genetic diversity of such lineages can be biased by collection scheme or random factors, it is important to evaluate the robustness of conclusions drawn on individual time samples. RESULTS: In order to assess the validity and reliability of inferences based on different genetic samples, we have analyzed fish from several lakes in Nicaragua sampled at three different times over 16 years. In addition, this time series allows us to analyze the population genetic changes that have occurred between lakes, where allopatric speciation has operated, as well as between different species within lakes, some of which have originated by sympatric speciation. Focusing on commonly used genetic markers, we have analyzed both DNA sequences from the complete mitochondrial control region as well as nuclear DNA variation at ten microsatellite loci from these populations, sampled thrice in a 16 year time period, to develop a robust estimate of the population genetic history of these diversifying lineages. CONCLUSION: The conclusions from previous work are well supported by our comprehensive analysis. In particular, we find that the genetic diversity of derived crater lake populations is lower than that of the source population regardless of when and how each population was sampled. Furthermore, changes in various estimates of genetic diversity within lakes are minimal and provide no evidence for drastic changes during the last 20 years, supporting the hypothesis that the processes which have resulted in rapid speciation are primarily historical. In contrast, there is some evidence for ongoing evolution, particularly selection, in all lakes except crater Lake Masaya, perhaps reflecting the persistence of speciational processes. Importantly, we find that the crater Lake Apoyo population, for which strong evidence of sympatric speciation has been demonstrated, has lower genetic diversity than other crater lakes and the strongest evidence for ongoing selection.

Lineage divergence of a freshwater snail clade associated with post-Tethys marine basin development.

The complex evolutionary history of the Eurasian gastropod lineage Theodoxus reflects the evolution of marine basins following the breakup of the Tethys Sea. Today, this clade inhabits the lakes, rivers, streams, and estuaries of Europe, southwestern Asia, and North Africa. Here we present the first phylogenetic hypothesis for this clade. Based upon extensive geographic and taxonomic sampling, portions of the mitochondrial genes for cytochrome c oxidase subunit I and 16S rRNA were sequenced and analysed using maximum likelihood and maximum parsimony methods. Results from bootstrap analyses, Bayesian analysis, and sensitivity analyses lend support to six deep phylogenetic subdivisions within Theodoxus. These major clades are geographically associated with the major post-Tethyan marine basins. Estimates of divergence times using a penalized likelihood approach indicate that divergence of these major lineages occurred during the Miocene, simultaneous with the breakup of the Mediterranean and Paratethys Seas. The resulting major subclades later diversified during the Pliocene, primarily within geographic regions associated with the eastern and western Mediterranean Sea, the Pannonian Basin, and the Black Sea, thus producing the extant species assemblages. Finally, these phylogenetic results imply that much of the current taxonomy is flawed, therefore we offer recommendations for revising the classification of Theodoxus species based on phylogenetic systematics.

Pan-European phylogeography of the aquatic snail Theodoxus fluviatilis (Gastropoda: Neritidae).

Investigating the geographical distribution of genetic lineages within species is critical to our understanding of how species evolve. As many species inhabit large and complex ranges, it is important that phylogeographical research take into account the entire range of widespread species to clarify how myriad extrinsic variables have affected their evolutionary history. Using phylogenetic, nested clade, and mismatch distribution analyses on a portion of the mitochondrial COI gene, I demonstrate that the wide-ranging freshwater snail Theodoxus fluviatilis possesses in parallel many of the phylogeographical patterns seen in less widespread freshwater species of Europe. Fragmentary forces play a major part in structuring the range of this species, with 12 of 14 geographically structured nested clades displaying a distribution consistent with fragmentation or restricted dispersal. Certain regions of southern Europe harbour the majority of genetic diversity (total haplotype diversity, H = 0.87), particularly Italy (H = 0.87) and areas surrounding the Black Sea (H = 0.81). Post-Pleistocene range expansion is pronounced, with the majority of northern European populations (95% of sample sites) having arisen from northern Italian individuals that initially colonized northern Germany. Additionally, two highly divergent haplotype lineages present in northern Germany imply that there were at least two postglacial recolonization routes. Estuaries may also provide a means of dispersal given that no genetic differentiation was found between estuarine populations and neighbouring freshwater populations. Taken together, these data reveal a species with a complex genetic history resulting from the fragmentary effects of European geology as well as continuous and discrete range expansion related to their aquatic biology.

Identification and first report of Inonotus (Phellinus) tropicalis as an etiologic agent in a patient with chronic granulomatous disease.

Although isolates of filamentous basidiomycetes can usually be recognized in a clinical laboratory setting, identification is problematic, as they seldom exhibit diagnostic morphological features formed in nature. This paper is the first report of Inonotus (Phellinus) tropicalis inciting human disease and describes the methods used to support the identification.

Comparison of CD8(+) T-cell subsets in HIV-infected rapid progressor children versus non--rapid progressor children.

BACKGROUND: CD8(+) T-cell subsets have not been adequately described in HIV-infected (HIV(+)) children classified with respect to disease progression as rapid-progressors (RPs) and non-rapid progressors (non-RPs). OBJECTIVE: The purpose of this investigation was to determine the distribution of CD8(+) T-cell subsets in HIV(+) children and correlate the findings with degree of immunosuppression and HIV viral burden. METHODS: By means of 3-color flow cytometry, percentages of CD38(+)DR(+), CD28(+), and CD57(+) CD8(+) T-cell subsets were examined in RP (n = 15) and non-RP (n = 36) HIV(+) children and in HIV-exposed but uninfected (n = 11) and HIVunexposed (n = 8) children. The CD8(+) T-cell subsets were correlated with mean CD4(+) T-cell percentages and HIV RNA levels. Analysis of covariance was used for group comparisons for the control of the covariate of age. RESULTS: The HIV-exposed and HIV-unexposed controls were not different from each other in CD8(+) T-cell subset percentages, except that the DR(-)CD38(+)CD8(+) T-cell percentages were higher in the exposed controls than in the unexposed controls. RPs had a higher mean percentage of DR(+)CD38(+)CD8(+) T cells than non-RPs and both control groups, and RPs had higher viremia than non-RPs. CD38(+)CD8(+) T-cell percentages did not correlate with viral burden as it has been seen to do in HIV(+) adults. Percentages of CD28(+)CD8(+) T cells were lower in HIV-infected children than in controls. There was a positive correlation of percentage of CD28(+)CD57(-)CD8(+) T cells with CD4(+) T-cell percentages in each HIV-infected group. CONCLUSION: CD8(+) T cells become activated (dual expression of DR and CD38) and lose CD28, some acquiring CD57, in relation to rapidity of disease progression in pediatric HIV infection.

Objective measures of allergic disease in children with human immunodeficiency virus infection.

BACKGROUND: Available information suggests that IgE levels are elevated in adults infected with human immunodeficiency virus (HIV), and that increased IgE levels correlate with allergic disease, with decreased CD4 counts, and with a poor prognosis. Data with respect to these factors in children are scant. OBJECTIVE: We investigated whether serum IgE levels are elevated in children with HIV and, if so, whether the serum IgE level correlates with the degree of immunodeficiency and/or objective indicators of allergic disease. METHODS: Serum IgE levels, CD4 counts, absolute eosinophil counts, and immediate hypersensitivity skin test (IHST) results were collected from 43 children with symptomatic HIV infection (mean age 7.2 years). Associations between serum IgE levels, CD4 counts, and eosinophil counts were investigated by multiple stepwise linear regression analysis. Data were stratified according to IHST positivity, and analysis of variance was used to compare mean values for age, CD4 counts, IgE levels, and eosinophil counts between the two groups. RESULTS: Serum IgE values were elevated more than 2 SDs above control age-matched mean values in 17 of 43 patients (40%). IHST results were positive in 12 of 43 patients (28%). CD4 counts were less than 200/mm3 in 17 of 43 patients (40%). Stepwise linear regression failed to demonstrate any correlation between serum IgE levels and either CD4 or eosinophil counts. With data divided into two groups according to IHST results (positive vs negative), analysis of variance failed to reveal significant differences between means for patient age, CD4 counts, IgE levels, or eosinophil counts. CONCLUSIONS: Our findings confirm that serum IgE levels are increased in children infected with HIV, just as in adults. However, an elevated serum IgE level did not correlate with allergic disease as measured by IHST results and eosinophil counts, nor with the degree of immune dysfunction as approximated by CD4 counts. The mechanism and significance of elevated serum IgE levels remain unclear in children with HIV, and warrant further investigation.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. II. Female reproductive disorders.

Members of the workgroup on female reproductive disorders discussed methods to evaluate five principal functions: menstrual dysfunction, infertility, pregnancy loss, lactation disorders, and pregnancy complications. To test each function, a nested strategy was considered, based on progressive levels of effort available to conduct field investigations. This strategy was analogous to the three-tier classification of biomarkers used by other workshops. The lowest level of effort, corresponding to Tier 1, consists only of questionnaires, diaries, and reviews of maternal and infant medical records. The medium level of effort (Tier 2) collects data from questionnaires and diaries, and some biologic specimens. Suggested laboratory analyses included measurement of progesterone in saliva and several glycoprotein hormones in urine that evaluate menstrual dysfunction, infertility, and pregnancy loss. The highest level of effort (Tier 3) involves prospective collection of diary information and simultaneous collection of biological specimens.