The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma: IV. Local Treatment Failure and Enucleation in the First 5 Years after Brachytherapy. COMS Report No. 19.

OBJECTIVE: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I125) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. DESIGN: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. METHODS: I125 brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. MAIN OUTCOME MEASURES: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. RESULTS: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08). CONCLUSIONS: Local treatment failure and enucleation were relatively infrequent events after I125 brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe.

Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study.

BACKGROUND: The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment. METHODS: With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function. We controlled for duration of serostatus in a subanalysis, as well as comorbidities and other factors that affect cognition. Analyses were by linear mixed models for longitudinal data. FINDINGS: 5086 participants (47 886 visits) were included in the analytic sample (2278 HIV-seropositive participants contributed 20 477 visits and 2808 HIV-seronegative control participants contributed 27 409 visits). In an a-priori multivariate analysis with control variables including comorbidities and time since seroconversion, significant, direct negative effects of ageing were noted on all neurocognitive domains (p<0·0001 for all). Similar effects were noted for late-stage HIV disease progression on information processing speed (p=0·002), executive function (p<0·0001), motor function (p<0·0001), and working memory (p=0·001). Deleterious interaction effects were also noted in the domains of episodic memory (p=0·03) and motor function (p=0·02). INTERPRETATION: A greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection suggests that these two domains are most susceptible to the progression of neurocognitive impairment caused by ageing in individuals with HIV. This deficit pattern suggests differential damage to the hippocampus and basal ganglia (specifically nigrostriatal pathways). Older individuals with HIV infection should be targeted for regular screening for HIV-associate neurocognitive disorder, particularly with tests referable to the episodic memory and motor domains. FUNDING: National Institute of Mental Health.

Physical Activity and Its Association with Insulin Resistance in Multicenter AIDS Cohort Study Men.

The association between physical activity (PA), degree of insulin resistance (IR), and HIV infection is unclear. We hypothesized that PA might differentially affect the degree of IR through the direct and indirect influences of HIV, antiretroviral medications, and sociodemographic characteristics. The International Physical Activity Questionnaire (IPAQ) was administered to Multicenter AIDS Cohort Study (MACS) participants from 4/2010 to 3/2011 to generate metabolic equivalents (METs) total score and PA category. We determined the concurrent homeostatic model assessment IR (mmol/liter) (HOMA-IR) value from fasting glucose and insulin. We examined the HIV-PA relationship using quantile regression and the HIV-PA-HOMA-IR value relationship using linear regression. Among the 1,281 men, the proportions of men in the low (25% in HIV(+) vs. 23% in HIV(-)), moderate (26% vs. 27%), and high (49% vs. 49%) PA categories were similar by HIV status. The HOMA-IR value was higher among the HIV(+) men (p<0.001), and both HIV infection and low PA were associated with a higher degree of IR (p<0.0001 and p=0.0007). However, the PA-HOMA-IR value interaction was not different by HIV status. The HOMA-IR value was higher among HIV(+) men although the PA was similar. It is unknown if more exercise will overcome the metabolic derangements associated with HIV and its treatment.

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study.

OBJECTIVE: The longitudinal trajectories that individuals may take from a state of normal cognition to HIV-associated dementia are unknown. We applied a novel statistical methodology to identify trajectories to cognitive impairment, and factors that affected the 'closeness' of an individual to one of the canonical trajectories. DESIGN: The Multicenter AIDS Cohort Study (MACS) is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men. METHODS: Using data from 3892 men (both HIV-infected and HIV-uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed Membership Trajectory Model (MMTM) was applied to capture the pathways from normal cognitive function to mild impairment to severe impairment. MMTMs allow the data to identify canonical pathways and to model the effects of risk factors on an individual's 'closeness' to these trajectories. RESULTS: First, we identified three distinct trajectories to cognitive impairment: 'normal aging' (low probability of mild impairment until age 60); 'premature aging' (mild impairment starting at age 45-50); and 'unhealthy' (mild impairment in 20s and 30s) profiles. Second, clinically defined AIDS, and not simply HIV disease, was associated with closeness to the premature aging trajectory, and, third, hepatitis-C infection, depression, race, recruitment cohort and confounding conditions all affected individual's closeness to these trajectories. CONCLUSION: These results provide new insight into the natural history of cognitive dysfunction in HIV disease and provide evidence for a potential difference in the pathophysiology of the development of cognitive impairment based on trajectories to impairment.

No association between Apoε4 alleles, HIV infection, age, neuropsychological outcome, or death.

The ε4 allele of the apolipoprotein E (ApoE) gene may have important interactions with physical health and cognitive function among individuals with HIV disease. The purpose of this study is to examine the relationships between ε4, HIV disease, age, neuropsychological impairment, and death in a large, well-characterized study sample. A total of 2846 men participating in the Multicenter AIDS Cohort Study had ApoE genotyping and neuropsychological test data available for analysis. We found a significant association between HIV infection and time to death (from any cause), as well as older age, race, and education. But, ApoE status was not significantly associated with time to death. Similarly, we found a significant association between HIV infection and time to incident cognitive impairment, as well as age, education, and HIV serostatus; Apoε4 status was not related to incident cognitive impairment. There were no significant interactions between ApoE, HIV infection, and age on cognitive impairment. These data replicate and strengthen prior findings of the lack of association between ApoE ε4 and cognitive outcomes in HIV disease. We conclude that within the specific constraints of an exclusively male study in which the majority of participants were less than 65 years of age (range 22-87 years), it appears reasonable to conclude that the ε4 allele is not significantly interacting with HIV serostatus.

Cohort Profile: Recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study.

The Multicenter AIDS Cohort Study (MACS) is one of the largest and longest running studies of the natural and treated history of HIV disease. The Neuropsychological (NP) substudy was begun in 1988 following reports of significant adverse neurological consequences of HIV disease, including dementia. The goal was to characterize the neuropsychological deficits among individuals with HIV disease, and track the natural history of the neurological complications over time. There were three distinct MACS recruitment stages that focused on different groups of HIV-infected men, or men at risk for infection. Initially, a subcohort was evaluated semi-annually with NP tests but, beginning in 2005, the entire group of MACS participants have had NP examinations biannually, unless closer follow-up was warranted. The participants complete a battery of NP tests, and are classified as either normal, mildly or severely impaired using the Antinori criteria for HIV-Associated Neurocognitive Disorder (HAND). Additional behavioural data, including mood state and psychoactive substance use, are recorded as part of the main MACS data collection. The MACS public data set (PDS) has been available since 1994 and includes baseline and 6-monthly follow-up data. Beginning in October 1995, the PDS has been released annually with new releases superseding previous versions.

Self-reported body fat change in HIV-infected men is a marker of decline in physical health-related quality of life with aging, independent of co-morbidity.

OBJECTIVE: Self-perception of changes in body fat among HIV+ persons is associated with decreased health related quality of life in cross-sectional studies. The longitudinal impact of body fat changes on health related quality of life, while accounting for comorbidity and anatomic location or severity of body fat changes, is unknown. DESIGN: This was a longitudinal analysis of HIV+ and HIV- Multicenter AIDS Cohort Study (MACS) participants who completed questionnaires assessing self-perceived body fat changes (baseline visit) and a health related quality of life (Short Form-36) at baseline and then ≥5 years later. METHODS: Relationships between body fat changes and change in Short Form-36 Physical and Mental Component Summary scores were investigated using mixed-model regression. RESULTS: We studied 270 HIV+ and 247 HIV- men. At baseline, ≥50% of HIV+ men reported body fat changes; physical component but not mental component summary scores were lower among HIV+ men who reported moderate/severe leg or abdominal fat changes (p<0.05). At follow-up, physical component summary scores were significantly lower among men with face, leg, or abdominal fat changes compared to men without perceived fat changes (p<0.05). No significant changes were seen in mental component scores by fat change location or severity. In the final model, body fat changes at any site or severity were significant predictors of a decline in physical component summary score (p<0.05), independent of demographics or comorbidities. Mental component summary score was not associated with body fat changes, but higher mental component summary score was associated with increasing age and time. CONCLUSIONS: Negative self-perceived body fat changes were associated with decline in physical health related quality of life, independent of comorbidities, and may be a marker of an increased risk for physical function decline with aging.

Sleep disordered breathing, fatigue, and sleepiness in HIV-infected and -uninfected men.

STUDY OBJECTIVES: We investigated the association of HIV infection and highly active antiretroviral therapy (HAART) with sleep disordered breathing (SDB), fatigue, and sleepiness. METHODS: HIV-uninfected men (HIV-; n = 60), HIV-infected men using HAART (HIV+/HAART+; n = 58), and HIV-infected men not using HAART (HIV+/HAART-; n = 41) recruited from two sites of the Multicenter AIDS cohort study (MACS) underwent a nocturnal sleep study, anthropometric assessment, and questionnaires for fatigue and the Epworth Sleepiness Scale. The prevalence of SDB in HIV- men was compared to that in men matched from the Sleep Heart Health Study (SHHS). RESULTS: The prevalence of SDB was unexpectedly high in all groups: 86.7% for HIV-, 70.7% for HIV+/HAART+, and 73.2% for HIV+/HAART-, despite lower body-mass indices (BMI) in HIV+ groups. The higher prevalence in the HIV- men was significant in univariate analyses but not after adjustment for BMI and other variables. SDB was significantly more common in HIV- men in this study than those in SHHS, and was common in participants with BMIs <25 kg/m2. HIV+ men reported fatigue more frequently than HIV- men (25.5% vs. 6.7%; p = 0.003), but self-reported sleepiness did not differ among the three groups. Sleepiness, but not fatigue, was significantly associated with SDB. CONCLUSIONS: SDB was highly prevalent in HIV- and HIV+ men, despite a normal or slightly elevated BMI. The high rate of SDB in men who have sex with men deserves further investigation. Sleepiness, but not fatigue, was related to the presence of SDB. Clinicians caring for HIV-infected patients should distinguish between fatigue and sleepiness when considering those at risk for SDB, especially in non-obese men.

The longitudinal and interactive effects of HIV status, stimulant use, and host genotype upon neurocognitive functioning.

Both human immunodeficiency virus (HIV)-1 infection and illicit stimulant use can adversely impact neurocognitive functioning, and these effects can be additive. However, significant variability exists such that as-of-yet unidentified exogenous and endogenous factors affect one's risk for neurocognitive impairment. Literature on both HIV and stimulant use indicates that host genetic variants in immunologic and dopamine-related genes are one such factor. In this study, the individual and interactive effects of HIV status, stimulant use, and genotype upon neurocognitive functioning were examined longitudinally over a 10-year period. Nine hundred fifty-two Caucasian HIV+ and HIV- cases from the Multicenter AIDS Cohort Study were included. All cases had at least two comprehensive neurocognitive evaluations between 1985 and 1995. Pre-highly active antiretroviral therapy (HAART) data were examined in order to avoid the confounding effect of variable drug regimens. Linear mixed models were used, with neurocognitive domain scores as the outcome variables. No four-way interactions were found, indicating that HIV and stimulant use do not interact over time to affect neurocognitive functioning as a function of genotype. Multiple three-way interactions were found that involved genotype and HIV status. All immunologically related genes found to interact with HIV status affected neurocognitive functioning in the expected direction; however, only C-C chemokine ligand 2 (CCL2) and CCL3 affected HIV+ individuals specifically. Dopamine-related genetic variants generally affected HIV-negative individuals only. Neurocognitive functioning among HIV+ individuals who also used stimulants was not significantly different from those who did not use stimulants. The findings support the role of immunologically related genetic differences in CCL2 and CCL3 in neurocognitive functioning among HIV+ individuals; however, their impact is minor. Being consistent with findings from another cohort, dopamine (DA)-related genetic differences do not appear to impact the longitudinal neurocognitive functioning of HIV+ individuals.

Association between systemic inflammation and obstructive sleep apnea in men with or at risk for HIV infection.

BACKGROUND: We sought to determine whether markers of systemic inflammation are associated with the presence of moderate/severe obstructive sleep apnea (OSA) and whether this association differs based on HIV and HIV treatment status. METHODS: HIV-uninfected men (HIV-; n=60), HIV-infected men receiving HAART (HIV+/HAART; n=58) and HIV-infected men not receiving HAART (HIV+/no HAART; n=41) underwent polysomnograpy and measurement of plasma levels of tumour necrosis factor (TNF)-α, soluble TNF-α receptors I and II (sTNFRI and sTNFRII) and interleukin (IL)-6. The relationship between moderate/severe OSA (respiratory disturbance index ≥15 apnea/hypopnea events/h) and inflammatory markers was assessed with multivariable regression models. RESULTS: Compared with the HIV- men, HIV+/HAART men and HIV+/no HAART men had higher levels of TNF-α, sTNFRI and sTNFRII, independent of age, race, smoking status, obstructive lung disease (OLD) and body mass index (BMI). Moderate/severe OSA was present in 48% of the sample (HIV- 57%; HIV+/HAART 41%; HIV+/no HAART 44%). Among the HIV+/no HAART men, but not in the other groups, TNF-α, sTNFRII and IL-6 levels were higher in those with moderate/severe OSA compared to men with no/mild OSA after adjustment for age, race, smoking status, OLD and BMI. Within this group, the association of high TNF-α concentrations with moderate/severe OSA was also independent of CD4(+) T-cell count and plasma HIV RNA concentration. CONCLUSIONS: Compared with HIV+/HAART men and HIV- men, markers of systemic inflammation were higher in HIV+/no HAART men. In these men, TNF-α was significantly related to OSA, independent of HIV-related covariates.

Multiple breast cancer cell-lines derived from a single tumor differ in their molecular characteristics and tumorigenic potential.

BACKGROUND: Breast cancer cell lines are widely used tools to investigate breast cancer biology and to develop new therapies. Breast cancer tissue contains molecularly heterogeneous cell populations. Thus, it is important to understand which cell lines best represent the primary tumor and have similarly diverse phenotype. Here, we describe the development of five breast cancer cell lines from a single patient's breast cancer tissue. We characterize the molecular profiles, tumorigenicity and metastatic ability in vivo of all five cell lines and compare their responsiveness to 4-hydroxytamoxifen (4-OHT) treatment. METHODS: Five breast cancer cell lines were derived from a single patient's primary breast cancer tissue. Expression of different antigens including HER2, estrogen receptor (ER), CK8/18, CD44 and CD24 was determined by flow cytometry, western blotting and immunohistochemistry (IHC). In addition, a Fluorescent In Situ Hybridization (FISH) assay for HER2 gene amplification and p53 genotyping was performed on all cell lines. A xenograft model in nude mice was utilized to assess the tumorigenic and metastatic abilities of the breast cancer cells. RESULTS: We have isolated, cloned and established five new breast cancer cell lines with different tumorigenicity and metastatic abilities from a single primary breast cancer. Although all the cell lines expressed low levels of ER, their growth was estrogen-independent and all had high-levels of expression of mutated non-functional p53. The HER2 gene was rearranged in all cell lines. Low doses of 4-OHT induced proliferation of these breast cancer cell lines. CONCLUSIONS: All five breast cancer cell lines have different antigenic expression profiles, tumorigenicity and organ specific metastatic abilities although they derive from a single tumor. None of the studied markers correlated with tumorigenic potential. These new cell lines could serve as a model for detailed genomic and proteomic analyses to identify mechanisms of organ-specific metastasis of breast cancer.

Genome-wide association study of neurocognitive impairment and dementia in HIV-infected adults.

The neuropathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. Candidate gene studies have implicated genetic susceptibility loci within immune-related genes; however, these have not been reliably validated. Here, we employed genome-wide association (GWA) methods to discover novel genetic susceptibility loci associated with HAND, and validate susceptibility loci implicated in prior candidate gene studies. Data from 1,287 participants enrolled in the Multicenter AIDS Cohort Study between 1985 and 2010 were used. Genotyping was conducted with Illumina 1M, 1MDuo, or 550K platform. Linear mixed models determined subject-specific slopes for change over time in processing speed and executive functioning, considering all visits including baseline and the most recent study visit. Covariates modeled as fixed effects included: time since the first visit, depression severity, nadir CD4+ T-cell count, hepatitis C co-infection, substance use, and antiretroviral medication regimen. Prevalence of HIV-associated dementia (HAD) and neurocognitive impairment (NCI) was also examined as neurocognitive phenotypes in a case-control analysis. No genetic susceptibility loci were associated with decline in processing speed or executive functioning among almost 2.5 million single nucleotide polymorphisms (SNPs) directly genotyped or imputed. No association between the SNPs and HAD or NCI were found. Previously reported associations between specific genetic susceptibility loci, HIV-associated NCI, and HAD were not validated. In this first GWAS of HAND, no novel or previously identified genetic susceptibility loci were associated with any of the phenotypes examined. Due to the relatively small sample size, future collaborative efforts that incorporate this dataset may still yield important findings.

Effect of obesity on falls, injury, and disability.

OBJECTIVES: To examine the effect of obesity on the propensity of older adults to fall, sustain a fall-related injury, and develop disability in activities of daily living (ADLs) after a fall. DESIGN: Longitudinal population-based survey. SETTING: Five waves of the Health and Retirement Study (HRS), 1998-2006. PARTICIPANTS: Ten thousand seven hundred fifty-five respondents aged 65 and older in 31,602 person-intervals. MEASUREMENTS: Falls within any 2-year interval (9,621 falls). Injuries requiring medical attention (3,130 injuries). Increased ADL disability after a fall within any 2-year interval (2,162 events). Underweight and three classes of obesity (body mass index (BMI) 30.0-34.9 kg/m(2) , Class 1) 35.0-39.9 kg/m(2) , Class 2; ≥40.0 kg/m(2) , Class 3), calculated from self-reported height and weight. Self-reported presence of lower body limitation, pain, dizziness, or vision problems. Self-reported doctor's diagnosis of diabetes mellitus, stroke, or arthritis. RESULTS: Compared with normal-weight respondents, the odds ratios (OR) for risk of falling were 1.12 (95% confidence interval (CI) = 1.01-1.24) for obesity Class 1, 1.26 (95% CI = 1.05-1.51) for obesity Class 2, and 1.50 (95% CI = 1.21-1.86) for obesity Class 3. Conditional on falling, only obesity Class 3 was related to a lower propensity for a fall-related injury (OR = 0.62, 95% CI = 0.44-0.87). Obesity Classes 1 and 2 were associated with a higher risk of greater ADL disability after a fall than normal-weight respondents (OR = 1.17, 95% CI = 1.02-1.34; OR = 1.39, 95% CI = 1.10-1.75, respectively). Being underweight was not related to risk of falling or to reported injury or greater ADL limitation after a fall. The presence of measured health problems and chronic conditions was associated with greater risk of falling and, of those who fell, greater ADL limitation but not serious injury. CONCLUSION: Obesity appears to be associated with greater risk of falling in older adults, as well as a higher risk of greater ADL disability after a fall. Obesity (BMI ≥ 40 kg/m(2) ) may reduce the risk of injury from a fall. Further investigation of the mechanisms of obesity on falls and related health outcomes is warranted.

Platelet decline as a predictor of brain injury in HIV infection.

An association between platelet decline and increased risk of progression to dementia has been observed in an advanced HIV infection cohort study. This investigation evaluated the prognostic significance of platelet decline for dementia, for psychomotor slowing, and for brain injury, as quantified in vivo, in a much larger population of HIV+ men. Platelet counts and neurocognitive data were available from biannual visits of 2,125 HIV+ men participating in the prospective, Multicenter AIDS Cohort Study from 1984 to 2009. Brain volumetric data were also available from an imaging substudy of 83 seropositive participants aged 50 and older. The association of platelet counts with neurocognitive outcome was assessed using Cox proportional hazard models where change in platelet count from baseline was a time-updated variable. Marked platelet decline was associated with increased risk of dementia in univariate analysis (hazard ratio [HR] = 2.5, 95% confidence interval [CI] = 1.8-3.5), but not after adjustment for CD4 cell count, HIV viral load, age, study site, hemoglobin, race, education, smoking, and alcohol use (HR = 1.4, 95% CI = 0.78-2.5). Platelet decline did not predict psychomotor slowing in either univariate (HR = 0.79, 95% CI = 0.58-1.08) or multivariate (HR = 1.10, 95% CI = 0.73-1.67) analysis. Analysis of brain volumetric data, however, indicated a relationship between platelet decline and reduced gray matter volume fraction in univariate (p = 0.06) and multivariate (p < 0.05) analyses. Platelet decline was not an independent predictor of dementia or psychomotor slowing, after adjusting for stage of disease. Findings from a structural brain imaging substudy of older participants, however, support a possible relationship between platelet decline and reduced gray matter.

Multisite comparison of high-sensitivity multiplex cytokine assays.

The concentrations of cytokines in human serum and plasma can provide valuable information about in vivo immune status, but low concentrations often require high-sensitivity assays to permit detection. The recent development of multiplex assays, which can measure multiple cytokines in one small sample, holds great promise, especially for studies in which limited volumes of stored serum or plasma are available. Four high-sensitivity cytokine multiplex assays on a Luminex (Bio-Rad, BioSource, Linco) or electrochemiluminescence (Meso Scale Discovery) platform were evaluated for their ability to detect circulating concentrations of 13 cytokines, as well as for laboratory and lot variability. Assays were performed in six different laboratories utilizing archived serum from HIV-uninfected and -infected subjects from the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) and commercial plasma samples spanning initial HIV viremia. In a majority of serum samples, interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor alpha were detectable with at least three kits, while IL-1ß was clearly detected with only one kit. No single multiplex panel detected all cytokines, and there were highly significant differences (P < 0.001) between laboratories and/or lots with all kits. Nevertheless, the kits generally detected similar patterns of cytokine perturbation during primary HIV viremia. This multisite comparison suggests that current multiplex assays vary in their ability to measure serum and/or plasma concentrations of cytokines and may not be sufficiently reproducible for repeated determinations over a long-term study or in multiple laboratories but may be useful for longitudinal studies in which relative, rather than absolute, changes in cytokines are important.

Addressing the well-being of Aboriginal children in out-of-home care: are we there yet?

AIM: Children in out-of-home care (OOHC) have well-documented health and developmental needs. In Australia, Aboriginal children have significantly worse health outcomes than non-Aboriginal children. We wanted to identify the health and well-being of Aboriginal children entering OOHC, placed with an Aboriginal organisation, who accessed a specialised multidisciplinary clinic in south-western Sydney. We wanted to identify children entering care who were doing well and who improved in care. We also wanted to identify enablers and barriers to care. METHODS: We analysed records of the first 100 children attending the OOHC clinic in south-western Sydney. Measures included clinical outcomes and recommendations at first and subsequent visits. Descriptive statistics were calculated using SPSS 16.0 for Windows (SPSS Inc., Chicago, IL, USA). Key stakeholders from the relevant agencies were interviewed about enablers and barriers to care by independent evaluators. RESULTS: A significant proportion of children had health needs identified including speech delay (54%), under-immunisation (50%), behaviour problems (45%), hearing problems (44%), visual problems (35%) and dental problems (36%). Sixteen per cent of the children were doing well at first visit; a third improved in care, and a third remained stable. Significant differences were identified in health and educational needs between the under-5 year olds and the 5-13 year olds. Key barriers identified were systemic issues and lack of resources for intervention. CONCLUSIONS: Children attending this clinic had similar rates of problems identified as other studies. School-age children appear to have significant additional health needs. Targeted developmentally and culturally appropriate interventions need to be provided to address the identified barriers to care.

Patient-reported outcomes among sham vs no-treatment controls from randomized trials.

OBJECTIVE: To compare 2-year changes from baseline scores on the National Eye Institute Visual Function Questionnaire (NEI-VFQ) between similar participants assigned to sham and no-treatment control arms in randomized clinical trials of treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: We retrospectively matched sham controls from a randomized trial to no-treatment controls (no sham or placebo) from another trial on 7 baseline prognostic criteria. Two-year changes in overall and subscale scores were compared using data from those who had 2-year interviews and also using the last follow-up observation carried forward to impute missing 2-year interview scores. RESULTS: A match to a no-treatment control on all 7 criteria was identified for 62 of 238 sham controls. Among the 42 matched pairs of controls interviewed at 2 years, no important difference in 2-year change in NEI-VFQ scores overall or by subscale was observed. Findings were similar for the 56 matched pairs of controls who could be analyzed for 2-year changes in scores using the method of last follow-up observation carried forward. CONCLUSIONS: Findings from this retrospective matched-pairs analysis suggest that sham treatment to mask patient participants in clinical trials may be unnecessary when patient-reported outcomes are of interest and standard instruments are administered by interviewers masked to treatment assignment. This analysis, together with our earlier analysis of visual acuity outcomes, questions the necessity for sham (placebo) controls in randomized clinical trials in ophthalmology when other methods to minimize outcome assessment bias are incorporated into the design.

Anthropometry in the prediction of sleep disordered breathing in HIV-positive and HIV-negative men.

BACKGROUND: Body mass index (BMI), waist circumference (WC) and neck circumference (NC) are important screening tools for sleep disordered breathing (SDB); however, the utility of anthropometry for this purpose has not been evaluated among HIV-positive patients. METHODS: HIV-negative men (n=60), HIV-positive men receiving highly active antiretroviral therapy (HIV-positive/HAART; n=58) and HIV-positive men not receiving HAART (HIV-positive/no HAART; n=41) from the Multicenter AIDS Cohort Study underwent a nocturnal sleep study and anthropomorphic assessment. Moderate-severe SDB was defined as an apnea/hypopnea event rate > or =15 episodes/h. Receiver operating characteristic (ROC) curves were used to compare the ability of different anthropometric measurements to predict SDB within each group. RESULTS: Moderate-severe SDB was found in 48% of men (HIV-negative [57%], HIV-positive/HAART [41%] and HIV-positive/no HAART [44%]). The performance of BMI, WC and NC to predict SDB was excellent among the HIV-negative men (ROC areas under the curve [AUCs] 0.83, 0.88 and 0.88, respectively) and fair among the HIV-positive/HAART group (AUC 0.71, 0.77 and 0.77, respectively). By contrast, these measurements had no predictive value in the HIV-positive/no HAART group (AUC 0.43, 0.41 and 0.45, respectively). Moreover, in the HIV-positive/no HAART group, moderate-severe SDB was independently associated with serum C-reactive protein > or =3.0 mg/l (odds ratio 6.9; P=0.04) and HIV RNA>10,000 copies/ml (odds ratio 7.1; P=0.05). CONCLUSIONS: BMI, WC and NC had a better predictive value for moderate-severe SDB in HIV-positive men compared with HIV-positive [corrected] men, and had no value among HIV-positive/no HAART men. Among this latter group, systemic inflammation might contribute to the pathogenesis of SDB.

TRENDS IN THE ABILITY TO WORK AMONG MEN AND WOMEN IN THE OLDER AMERICAN POPULATION: 1997-2007.

Since the passage of United States (US)' Social Security Amendments in 1983, the age for full Social Security benefits has been increasing from age 65 to 67 depending on one's year of birth. These increases introduce incremental savings in the long-term funding of the US public pension system, but they assume that American workers will be able to continue working past the age of 65. In this study, we examine self-reported work disability for men and women using the 1997 through 2007 National Health Interview Surveys. There are small but significant decreases in work disability and fairly significant increases in labor force activity among men and women in their 60s and for women in their 50s over the 11-year period, and relatively little difference between men's and women's trends. Changes in the educational composition of the population play a major explanatory role in the decrease of work disability. Without this compositional shift, work disability would have increased. Increased obesity over this period exerted an opposite effect; without this change, the decrease in work disability would have been greater.