Predictors of growth and body composition in HIV‐infected children beginning or changing antiretroviral therapy

Objectives

The aim of the study was to describe growth and body composition changes in HIV‐positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters.

Methods

Ninety‐seven prepubertal HIV‐positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999–2002 (NHANES) to generate z‐scores and with results for HIV‐exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters.

Results

All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height²) z‐scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z‐score decreased (P=0.045), but body mass index and per cent body fat z‐scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid‐thigh circumference and FFM z‐scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z‐scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid‐thigh muscle circumference were also associated with CD4 percentage. Case–control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time.

Conclusions

In these HIV‐positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

Pathogen Profiling: Rapid Molecular Characterization of Staphylococcus aureus by PCR/Electrospray Ionization-Mass Spectrometry and Correlation with Phenotype

There are few diagnostic methods that readily distinguish among community-acquired methicillin (meticillin)-resistant Staphylococcus aureus strains, now frequently transmitted within hospitals. We describe a rapid and high-throughput method for bacterial profiling of staphylococcal isolates. The method couples PCR to electrospray ionization-mass spectrometry (ESI-MS) and is performed on a platform suitable for use in a diagnostic laboratory. This profiling technology produces a high-resolution genetic signature indicative of the presence of specific genetic elements that represent distinctive phenotypic features. The PCR/ESI-MS signature accurately identified genotypic determinants consistent with phenotypic traits in well-characterized reference and clinical isolates of S. aureus. Molecular identification of the antibiotic resistance genes correlated strongly with phenotypic in vitro resistance. The identification of toxin genes correlated with independent PCR analyses for the toxin genes. Finally, isolates were correctly classified into genotypic groups that correlated with genetic clonal complexes, repetitive-element-based PCR patterns, or pulsed-field gel electrophoresis types. The high-throughput PCR/ESI-MS assay should improve clinical management of staphylococcal infections.Invasive infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) are among the most common complications of health care in the United States. Klevens et al. estimate that 94,360 invasive MRSA infections occur in the United States each year, with associated deaths in 18,650 cases (26). Infections are subcategorized as health care-associated MRSA (HA-MRSA) infections or as community-associated MRSA (CA-MRSA) infections; the latter occur in otherwise healthy people who have not experienced a hospital stay within the past 12 months (24, 35). CA-MRSA infections have largely been attributable to a few strains, designated pulsed-field types (PFTs) USA300 and USA400 (26, 29). Once introduced into a health care environment, CA-MRSA strains can be readily transmitted, blending with or replacing entrenched HA-MRSA strains (25, 35).Microbial genotyping analysis allows investigation into the clonality of an outbreak and risk factors associated with infection (5). Methods such as pulsed-field gel electrophoresis (PFGE) (39), repetitive-element-based PCR (rep-PCR) (42), and multilocus sequence typing (MLST) (10, 11) are used for microbial genotyping but are costly and labor-intensive and do not enable specific characterization of acquired genetic elements encoding virulence factors or toxins or of genes that mediate antibiotic resistance (40). A rapid technique for determining the MRSA strain genotype and its broader complement of genetic elements would enable a more comprehensive understanding of transmission dynamics and could lead to more effective actionable decisions related to bed management, prioritization of infection control resources, and treatment.Here, we describe the use of a rapid and high-throughput method to simultaneously genotype and characterize S. aureus specimens with respect to acquired genes encoding virulence factors, toxins, and antibiotic resistance determinants. The method is based on PCR coupled to electrospray ionization-mass spectrometry (ESI-MS) (8, 22, 37).The PCR/ESI-MS assay uses several novel strategies. First, broad-range primers, targeting sites that are highly conserved in all members of a microbe family, are used to amplify PCR products from groupings of microbes rather than single species. These primers are coupled with species- or strain-specific primers for the identification of specific pathogens or antibiotic targets. Second, PCR conditions are, by design, permissive and thus tolerant of mismatches, so that even sequences from novel strains can be amplified. Third, inosine and other “wild-card” nucleotides are used in primers to facilitate PCR analysis of mispaired sequences. Fourth, because MS simply measures the mass-to-charge ratio (m/z), the sequence of the amplicon need not be known in order to detect it. The technology offers advantages over routine single-target and multiplex PCR in that it is a full bioinformatics sequence analysis system.After amplification, MS is used to rapidly determine the precise mass-to-charge ratio for the amplified nucleic acid fragments present, and the A, C, T, and G contents (i.e., the base composition) of each amplicon are determined using proprietary software that creates a signature to allow organism identification and genotyping. This novel MS technology enables the rapid, sensitive, cost-effective, and simultaneous detection of a wide range of typical pathogenic organisms.We used the PCR/ESI-MS assay to analyze a well-characterized set of S. aureus strains from the CDC and geographically distinct clinical isolates from Maryland and Arizona. The PCR/ESI-MS technology effectively combines genotyping and characterization on a single high-throughput platform suitable for surveillance, infection control interventions, and patient management.     

Occurrence of a USA300 vancomycin-intermediate Staphylococcus aureus

A vancomycin-intermediate Staphylococcus aureus (VISA) isolated from the blood of a 46-year-old patient with endocarditis was determined to be pulsed-field type USA300, daptomycin nonsusceptible, and positive for the Panton-Valentine leukocidin genes. Development of the VISA phenotype does not appear limited to traditional health care strains of S. aureus.     

Physiological determinants of residual cerebral arterial pulsatility on best medical treatment after TIA or minor stroke

Cerebral arterial pulsatility is strongly associated with cerebral small vessel disease and lacunar stroke yet its dependence on central versus local haemodynamic processes is unclear. In a population-based study of patients on best medical managment, 4–6 weeks after a TIA or non-disabling stroke, arterial stiffness and aortic systolic, diastolic and pulse pressures were measured (Sphygmocor). Middle cerebral artery peak and trough flow velocities and Gosling’s pulsatility index were measured by transcranial ultrasound. In 981 participants, aortic and cerebral pulsatility rose strongly with age in both sexes, but aortic diastolic pressure fell more with age in men whilst cerebral trough velocity fell more in women. There was no significant association between aortic systolic or diastolic blood pressure with cerebral peak or trough flow velocity but aortic pulse pressure explained 37% of the variance in cerebral arterial pulsatility, before adjustment, whilst 49% of the variance was explained by aortic pulse pressure, arterial stiffness, age, gender and cardiovascular risk factors. Furthermore, arterial stiffness partially mediated the relationship between aortic and cerebral pulsatility. Overall, absolute aortic pressures and cerebral blood flow velocity were poorly correlated but aortic and cerebral pulsatility were strongly related, suggesting a key role for transmission of aortic pulsatility to the brain.     

An australian audit of vaccination status in children and adolescents with inflammatory bowel disease

Background

Pre-existing polyps, especially large polyps, are known to be the major source for colorectal cancer, but there is limited available information about factors that are associated with polyp size and polyp growth. We aim to determine factors associated with polyp size in different age groups.

Methods

Colonoscopy data were prospectively collected from 67 adult gastrointestinal practice sites in the United States between 2002 and 2007 using a computer-generated endoscopic report form. Data were transmitted to and stored in a central data repository, where all asymptomatic white (n = 78352) and black (n = 4289) patients who had a polyp finding on screening colonoscopy were identified. Univariate and multivariate analysis of age, gender, performance site, race, polyp location, number of polyps, and family history as risk factors associated with the size of the largest polyp detected at colonoscopy.

Results

In both genders, size of the largest polyp increased progressively with age in all age groups (P < .0001). In subjects ≥ 80 years the relative risk was 1.55 (95% CI, 1.35-1.79) compared to subjects in the youngest age group. With the exception of family history, all study variables were significantly associated with polyp size (P < .0001), with multiple polyps (≥ 2 versus 1) having the strongest risk: 3.41 (95% CI, 3.29-3.54).

Conclusions

In both genders there is a significant increase in polyp size detected during screening colonoscopy with increasing age. Important additional risk factors associated with increasing polyp size are gender, race, polyp location, and number of polyps, with polyp multiplicity being the strongest risk factor. Previous family history of bowel cancer was not a risk factor.