Immunosuppression among HIV‐1‐positive patients attending for care: experience from two large HIV centres in the United Kingdom

Objectives

The aim of the study was to describe the prevalence of and examine the factors associated with immunosuppression (CD4<200 cells/μL) among HIV‐infected patients attending two large inner London treatment centres.

Methods

Patients attending for care who had a CD4 count <200 cells/μL during a 6‐month period (1 January to 30 June 2007) were identified from the UK national CD4 surveillance database. Corresponding case notes were reviewed and factors associated with the most recent immunosuppressive episode examined. Patients either previously had a CD4 count >200 cells/μL at any time under follow‐up which had decreased (group A) or never had a CD4 count >200 cells/μL (group B; late presenters).

Results

Of 4589 patients, 10.2% (467) had at least one CD4 count <200 cells/μL. In group A (60.1% of patients), 70.4% were not receiving antiretroviral therapy (ART) at the time at which the CD4 count fell to <200 cells/μL. Reasons included: treatment interruption (TI; 32.6%), patient declined ART (20.2%), infrequent attendance (19.1%), physician delay in offer (23.1%) and transient CD4 cell count decrease (3.9%). Among those receiving ART, one in three had poor adherence. In group B, 92.3% had started ART after presentation: most had recently started and were responding virologically. AIDS‐defining diagnoses occurred in the year preceding the decrease in CD4 cell count in 12.6% of patients in group A and 33.3% of those in group B.

Conclusion

The majority of patients became immunosuppressed while under care. Our findings suggest that, in addition to strategies aimed at earlier diagnosis, there are further opportunities to reduce severe immunosuppression in patients already attending for HIV care.     

Lipopolysaccharide produces dose-dependent reductions of the acoustic startle response without impairing prepulse inhibition in male rats

This study examined the dose-dependent effects of Lipopolysaccharide (LPS) on the acoustic startle response and prepulse inhibition (PPI) in male Long-Evans rats. LPS is known to stimulate the innate immune system and result in behavior modifications referred to as "sickness behaviors". The purpose of this study was to assess the ability of LPS to modulate sensorimotor reflexes (Startle-Only trials) and/or sensory processing (PPI trials). Rats were injected intraperitoneally with LPS (50, 100 or 200 microg/kg LPS, n=9/group) or saline vehicle (n=14) on 2 test days 72 h apart. Subjects were placed in a familiar startle box apparatus where startle response magnitudes were recorded following 115 dB Startle-Only trials and PPI trials (with prepulses at +3, +6 and +12 dB above background noise). Analysis of Startle-Only trials indicated a significant dose-dependent effect of LPS on Test Day 1. The 200 microg/kg LPS group exhibited significantly reduced startle response magnitude relative to all other treatments. On the PPI trials no LPS groups displayed significantly different performance from vehicle controls. Also, DayxDrug interactions for both Startle-Only and PPI trial types indicated behavioral tolerance to LPS. LPS reduced the acoustic startle response in a dose-dependent manner on Test Day 1. From the PPI data, it is evident that all treatment groups elicited near-normal inhibition levels indicating adequate sensory function. In combination, the results suggest that the range of sickness behaviors following LPS-administration to adult rats includes decreased non-voluntary motor activity as reflected by reduced startle magnitude.     

MANAGEMENT OPTIONS FOR HYPERTENSION SYNDROME

Hypertension is usually managed on a case-finding basis, and yet continued blood pressure control can be inadequate. Furthermore, hypertension is often a ‘silent’ condition until comorbid events, target organ damage and subsequent heart failure become manifest, leading to a reactive rather than a proactive approach. Management of the hypertension syndrome becomes complex, because blood pressure control may not be just an isolated concern. This review considers the various options, in addition to existing guidelines, that can help to reduce hypertension-related morbidity and mortality.     

Reliability and validity of chest radiograph surveillance programs.

STUDY OBJECTIVES: Due to the lack of consensus in the literature in the use of posteroanterior (PA) vs PA with right and left oblique views as the optimum radiograph surveillance methodology to investigate pleural changes, a study was undertaken to evaluate the reliability, sensitivity, and specificity of these two approaches. DESIGN: Three experienced radiologist B readers used the 1980 International Labor Office classification system for pneumoconiosis to independently read chest radiographs of workers with individual identifiers masked. All radiographs were read first as a PA view only. Unknown to the B readers, each subject's PA was then matched to his or her corresponding right and left oblique views (film triad) and re-read several weeks later. SETTING AND PARTICIPANTS: The respiratory health of 652 workers exposed to refractory ceramic fiber was assessed as part of cross-sectional and longitudinal surveillance programs. MEASUREMENTS AND RESULTS: kappa Statistics for interreader and intrareader reliability between the PA view and film triad methods were calculated. Sensitivity, specificity, and positive predictive value were assessed by comparing the initial cross-sectional study to the longitudinal study. The film triad method had considerably higher interreader reliability (kappa = 0.59) compared to the PA-only method (kappa = 0.44). Results from the initial cross-sectional study were then compared to findings evaluated longitudinally. The film triad again was superior, demonstrating a positive predictive value of 73.7% compared to only 47.8% for the PA method. CONCLUSIONS: It is our recommendation that the film triad method be used in surveillance studies where both parenchymal and pleural changes are anticipated.