Rapid, real-time detection of acute HIV infection in patients in Africa

BACKGROUND: We conducted a prospective study to evaluate methods of detecting clients with sexually transmitted diseases (STDs) who were acutely coinfected with human immunodeficiency virus (HIV) in Lilongwe, Malawi. METHODS: After informed consent was obtained, all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test-negative or -discordant subjects were pooled (50 : 5 : 1) and tested for HIV RNA. Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA. A subset of specimens received p24 antigen testing with standard and/or ultrasensitive methods. Patients with possible acute HIV infection were followed to confirm seroconversion. RESULTS: A total of 1450 clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had established HIV infection and 21 (1.45%) had acute infection. Discordant rapid antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified 15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA assay was 100%. CONCLUSIONS: Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect approximately 90% of acute cases.     

Incorporation of pulmonary vascular resistance measurement into standard echocardiography: implications for assessment of pulmonary hypertension

Doppler estimation of pulmonary artery systolic pressure (PASP) from tricuspid regurgitation velocity is a simple approach to the detection of pulmonary hypertension but may be influenced by right ventricular stroke volume. We sought the clinical utility of incorporating Doppler calculation of pulmonary vascular resistance (PVR) into determination of pulmonary hypertension in 578 consecutive patients with tricuspid regurgitation. Right atrial pressure was estimated from vena caval dimensions and collapsibility. Pulmonary hypertension was classified on the basis of a) PASP >35 mmHg, b) age-/gender normalized PASP, c) PVR >2 Wood units. The mean PASP was 40 +/- 13 mmHg and PVR was 1.9 +/- 0.8 Wood units. Standard PASP identified pulmonary hypertension in 58%, compared with 36% by age-/gender normalized PASP (P < 0.0001), and 31% by PVR (P < 0.0001). Of patients who had pulmonary hypertension by PASP, 33% were reclassified as normal on the basis of PVR and 6% were reclassified from normal to pulmonary hypertension. PVR is easy to incorporate into a standard echo exam, and identifies a small group with normal PASP as having PAH, and a larger group of apparently increased PASP as normal.     

Reliability,Validity and Responsiveness of the Syncope Functional Status Questionnaire

BACKGROUND: Patients with transient loss of consciousness (TLOC) have poor health-related quality of life (HR-QoL). OBJECTIVE: To test the reliability, validity, and responsiveness of the disease-specific Syncope Functional Status HR-QoL Questionnaire (SFSQ), which yields two summary scales--impairment score (IS) and fear-worry score (FWS). DESIGN: Cohort-study. PARTICIPANTS: 503 adult patients presenting with TLOC. MEASUREMENTS: HR-QoL was assessed using the SFSQ and the Short Form-36 (SF-36) after presentation and 1 year later. To test reliability, score distributions, internal consistency, and test-retest reliability were assessed. To assess validity, scores on the SFSQ and the SF-36 were compared. Clinical validity was tested using known-group comparison. Responsiveness was assessed by comparing changes in SFSQ scores with changes in health status and clinical condition. RESULTS: Response rate was 82% at baseline and 72% at 1-year follow-up. For all scales the full range of scores was seen. Score distributions were asymmetrical. Internal consistency was high (alpha = 0.88 for IS, 0.92 for FWS). Test-retest reliability was moderate to good for individual items and high for summary scales (inter-class correlation = 0.78 for both IS and FWS). Correlations between SFSQ scores and the SF-36 were modest. The SFSQ did not discriminate between patients differing in age and gender but did discriminate between patients differing in number of episodes and comorbid conditions. Changes in SFSQ scores were related to changes in health status and the presence of recurrences but did not vary by TLOC diagnosis. CONCLUSION: The SFSQ is an adequately reliable, valid, and responsive measure to assess HR-QoL in patients with TLOC.     

The effect of HapMap on cardiovascular research and clinical practice

The Haplotype Genetic Map (HapMap) is an invaluable resource to the cardiovascular researcher, enabling a decrease in cost and an increase in the efficiency and speed of discoveries in the laboratory. As cardiologists, we need to understand the vocabulary of genomics because the translation of scientific findings using HapMap could provide insight for improved care and therapeutic guidance of our patients. Genomics is the evaluation of genes as a dynamic system, in which genes interact to influence biologic pathways, networks and physiology. The HapMap promises to increase the efficiency of genomics in identifying cardiovascular-disease-related genes that could become vital for choosing relevant tests and providing preventative and curative therapies. In this Review, the HapMap will be described, to provide insight into the relevance of this work to cardiovascular practice, to clinical research in cardiovascular disease and to future discoveries in diagnostic and therapeutic modalities.     

Diagnosis of diabetic peripheral neuropathy among patients with type 1 and type 2 diabetes in France, Italy, Spain, and the United Kingdom

AIMS: The objective of this study was to describe the proportion and characteristics of patients with type 1 and type 2 diabetes diagnosed with diabetic peripheral neuropathy (DPN) in France, Italy, Spain, and the United Kingdom (UK). METHODS: A cross-sectional survey was administered to general practitioners and diabetes specialists. Existing physicians' records were used to quantify the frequency of DPN diagnoses, and notes from patients' medical charts were used to characterize symptoms. RESULTS: The average number of physicians per country was 41 (range of 34-49). The proportion of diabetes patients diagnosed with DPN ranged from 9.6% (95% CI, 7.1-12.2) in Spain to 23.1% (95% CI, 15.4-30.7) in Italy. Of 913 DPN study patients, 55.0% were male, and 78.5% had type 2 diabetes. Mean age was 64.5+/-12.5 years. A DPN diagnosis was based primarily on symptoms. Approximately 27% of patients had no documented neurological examination. "Prickling" was the most common DPN symptom recorded in France, Italy, and Spain, and "numbness" was the most common in the UK. CONCLUSIONS: Country-specific estimates of DPN diagnosis may reflect clinical management of diabetes and DPN. A substantial number of diagnoses were not associated with a record of a neurological examination.     

Role of dCA3 efferents via the fimbria in the acquisition of a delay nonmatch to place task

Dorsal CA3, but not dorsal CA1, lesioned rats are impaired in the acquisition of a delay nonmatch to place task. In this study, dorsal CA3 efferent fibers in the fimbria were transected; while taking care to spare afferent fibers from the medial septum. Neurophysiological, anatomical tracing, and histochemical data suggest that the transection was selective to dorsal CA3 efferent fibers and spared afferents from the medial septum. Rats showed a deficit for acquisition, but not for performance once learned. One possible explanation is that a small change to the cholinergic inputs to dCA3 caused by a decrease in dorsal CA3 efferent signals reaching the medial septum may impair new learning but not performance of a task once learned.     

Applying theory-driven approaches to understanding and modifying clinicians' behavior: what do we know?

OBJECTIVE: Despite major recent research advances, large gaps exist between accepted mental health knowledge and clinicians' real-world practices. Although hundreds of studies have successfully utilized basic behavioral science theories to understand, predict, and change patients' health behaviors, the extent to which these theories-most notably the theory of reasoned action (TRA) and its extension, the theory of planned behavior (TPB)-have been applied to understand and change clinician behavior is unclear. This article reviews the application of theory-driven approaches to understanding and changing clinician behaviors. METHODS: MEDLINE and PsycINFO databases were searched, along with bibliographies, textbooks on health behavior or public health, and references from experts, to find article titles that describe theory-driven approaches (TRA or TPB) to understanding and modifying health professionals' behavior. RESULTS: A total of 19 articles that detailed 20 studies described the use of TRA or TPB and clinicians' behavior. Eight articles describe the use of TRA or TPB with physicians, four relate to nurses, three relate to pharmacists, and two relate to health workers. Only two articles applied TRA or TPB to mental health clinicians. The body of work shows that different constructs of TRA or TPB predict intentions and behavior among different groups of clinicians and for different behaviors and guidelines. CONCLUSIONS: The number of studies on this topic is extremely limited, but they offer a rationale and a direction for future research as well as a theoretical basis for increasing the specificity and efficiency of clinician-targeted interventions.     

Regulation of adult hippocampal neurogenesis: relevance to depression

Recent hypotheses suggest that depression may involve an inability to mount adaptive structural changes in key neuronal networks. In particular, the addition of new neurons within the hippocampus, a limbic region implicated in mood disorders, is compromised in animal models of depression. Adult hippocampal neurogenesis is also a target for chronic antidepressant treatments, and an increase in adult hippocampal neurogenesis is implicated in the behavioral effects of antidepressants in animal models. The 'neurogenic' hypothesis of depression raises the intriguing possibility that hippocampal neurogenesis may contribute to the pathogenesis and treatment of depressive disorders. While there remains substantial debate about the precise relevance of hippocampal neurogenesis to mood disorders, this provocative hypothesis has been the focus of many recent studies. In this review, we discuss the pathways that may mediate the effects of depression models and antidepressants on adult hippocampal neurogenesis, and the promise of these studies in the development of novel antidepressants.