Clinical and laboratory impact of concomitant syphilis infection during acute HIV.

INTRODUCTION: Cognitive impairment has been reported in people living with HIV-1 (PLWH) with prior syphilis, while PLWH who present with incident syphilis have reduced blood CD4 T-lymphocyte and elevated HIV-1 RNA levels. However, the clinical, virological and neurocognitive effects of syphilis during acute HIV-1 (AHI) remain unknown. METHODS: Pre-antiretroviral therapy laboratory outcomes and neurocognitive performance in a four-test battery in the SEARCH10/RV254 AHI cohort were compared according to syphilis status, determined by serum Treponema pallidum haemagglutination (TPHA), Venereal Disease Research Laboratory (VDRL) and syphilis treatment history. Impaired cognitive performance was defined as having z-scores ≤ -1 in at least two tests or ≤ -2 in at least one test. RESULTS: Out of 595 AHI participants (97% male, median age of 26 years and estimated duration of HIV-1 infection of 19 days), 119 (20%) had history of syphilis (TPHA-positive), of whom 51 (9%) had untreated syphilis (TPHA-positive/VDRL-positive/without prior treatment). Compared with those without syphilis (TPHA-negative), individuals with untreated syphilis had higher CD8 T-lymphocyte levels but not higher plasma HIV-1 RNA or lower CD4 T-lymphocyte levels. Taking into account estimated duration of HIV-1 infection (P < 0.001), and later Fiebig stages (III-V) (P < 0.001), those with untreated syphilis had higher CD8 T-lymphocyte levels (P = 0.049). Individuals with any syphilis (TPHA-positive), but not untreated syphilis, had higher odds of impaired cognitive performance than those without (P = 0.002). CONCLUSIONS: During AHI, individuals with any history of syphilis (TPHA-positive) had poorer cognitive performance than those without syphilis. However, syphilis was not associated with worsened HIV disease measures as described in chronic infection.

Statin use and lung cancer risk in chronic obstructive pulmonary disease patients: a population-based cohort study.

BACKGROUND: Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer. A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins. This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients. METHODS: We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA). We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose). To assess residual confounding, a negative control exposure was used to test the validity of our results. All exposure variables were time-dependent. RESULTS: The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female. There were 12,469 patients who received at least one statin prescription. Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73-1.00) in COPD patients, but this result not statistically significant. Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77-0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96-0.99). Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75-1.10). CONCLUSIONS: The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer. While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy.

Incremental direct medical costs of systemic lupus erythematosus patients in the years preceding diagnosis: A general population-based study.

Objective We estimated the incremental (extra) direct medical costs of a population-based cohort of newly diagnosed systemic lupus erythematosus (SLE) for five years before and after diagnosis, and the impact of sex and socioeconomic status (SES) on pre-index costs for SLE. Methods We identified all adults newly diagnosed with SLE over 2001-2010 in British Columbia, Canada, and obtained a sample of non-SLE individuals from the general population, matched on sex, age, and calendar-year of study entry. We captured costs for all outpatient encounters, hospitalisations, and dispensed medications each year. Using generalised linear models, we estimated incremental costs of SLE each year before/after diagnosis (difference in costs between SLE and non-SLE, controlling for covariates). Similar models were used to examine the impact of sex and SES on costs within SLE. Results We included 3632 newly diagnosed SLE (86% female, mean age 49.6 ± 15.9) and 18,060 non-SLE individuals. Over the five years leading up to diagnosis, per-person healthcare costs for SLE patients increased year-over-year by 35%, on average, with the biggest increases in the final two years by 39% and 97%, respectively. Per-person all-cause medical costs for SLE the year after diagnosis (Year + 1) averaged C$12,019 (2013 Canadian) with 58% from hospitalisations, 24% outpatient, and 18% from prescription medications; Year + 1 costs for non-SLE averaged C$2412. Following adjustment for age, sex, urban/rural residence, socioeconomic status, and prior year's comorbidity score, SLE was associated with significantly greater hospitalisation, outpatient, and medication costs than non-SLE in each year of study. Altogether, adjusted incremental costs of SLE rose from C$1131 per person in Year -5 (fifth year before diagnosis) to C$2015 (Year -2), C$3473 (Year -1) and C$6474 (Year + 1). In Years -2, -1 and +1, SLE patients in the lowest SES group had significantly greater costs than the highest SES. Unlike the non-SLE cohort, male patients with SLE had higher costs than females. Annual incremental costs of SLE males (vs. SLE females) rose from C$540 per person in Year -2, to C$1385 in Year -1, and C$2288 in Year + 1. Conclusion Even years before diagnosis, SLE patients incur significantly elevated direct medical costs compared with the age- and sex-matched general population, for hospitalisations, outpatient care, and medications.

Ten-year trends in direct costs of asthma: a population-based study.

INTRODUCTION: There is little information on recent trends in the economic burden of asthma. Our objective was to estimate the excess costs of asthma and their trend in British Columbia, Canada, from 2002 to 2011. METHODS: A retrospective cohort of individuals aged 5-55 years was constructed from the provincial administrative health databases, consisting of patients with physician-diagnosed asthma and a propensity-score-matched comparison sample from the general population. Total direct medical costs were calculated as the sum of hospitalizations, outpatient visits and medication costs, adjusted to 2012 Canadian dollars ($). Excess costs were defined as the difference in costs between the asthma and comparison groups. RESULTS: A total of 341 457 individuals (mean age at entry 27.3, 54.1% female) were equally divided into the asthma and comparison groups. Excess costs in patients with asthma were $1028.0 (95% CI $982.7-$1073.4) per patient-year (PY). Medications contributed to the greatest share of excess costs ($471.7/PY), whereas hospitalization and outpatient costs were, respectively, $272.2/PY and $284.1/PY. Only $192.9/PY was attributable to asthma itself. There was a 2.9%/year increase in excess costs (P < 0.001), a combination of asthma-attributable costs declining by 0.8%/year while nonasthma excess costs increasing by 3.8%/year. The most dramatic trend was observed in asthma-related outpatient costs, which decreased by %6.6/year. CONCLUSIONS: A significant share of excess costs in asthma is not attributable to the disease itself. The pattern of costs changed significantly during the study period. The burden of comorbid conditions should be considered in developing evidence-based policies for management of patients with asthma.

Clinical and biomarker profiling of prodromal Alzheimer's disease in workpackage 5 of the Innovative Medicines Initiative PharmaCog project: a 'European ADNI study'.

BACKGROUND: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. OBJECTIVE: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). METHODS: A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid ß peptide 1-42 (Aß42), tau and p-tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. RESULTS: Prodromal AD was found in 55 aMCI patients defined by low Aß42 in the cerebrospinal fluid (Aß positive). Compared to the aMCI group with high Aß42 levels (Aß negative), Aß positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO-ERP (P = 0.03). CONCLUSION: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.

International neurocognitive normative study: neurocognitive comparison data in diverse resource-limited settings: AIDS Clinical Trials Group A5271.

Infrastructure for conducting neurological research in resource-limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment and normative data needed for clinical interpretation impedes research and clinical care. Here, we report on ACTG 5271, which provided neurological training of clinical site personnel and collected neurocognitive normative comparison data in diverse settings. At ten sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV- participants from Brazil (n = 240), India (n = 480), Malawi (n = 481), Peru (n = 239), South Africa (480), Thailand (n = 240), and Zimbabwe (n = 240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline and 770 at 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p < 0.0001). There was variation between the age, gender, and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance, and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.

Cognitive status is a determinant of health resource utilization among individuals with a history of falls: a 12-month prospective cohort study.

SUMMARY: Falls are a costly public health problem worldwide. The literature is devoid of prospective data that identifies factors among fallers that significantly drive health care resource utilization. We found that cognitive function--specifically, executive functions--and cognitive status are significant determinants of health resource utilization among older fallers. INTRODUCTION: Although falls are costly, there are no prospective data examining factors among fallers that drive health care resource utilization. We identified key determinants of health resource utilization (HRU) at 6 and 12 months among older adults with a history of falls. Specifically, with the increasing recognition that cognitive impairment is associated with increased falls risk, we investigated cognition as a potential driver of health resource utilization. METHODS: This 12-month prospective cohort study at the Vancouver Falls Prevention Clinic (n = 319) included participants with a history of at least one fall in the previous 12 months. Based on their cognitive status, participants were divided into two groups: (1) no mild cognitive impairment (MCI) and (2) MCI. We constructed two linear regression models with HRU at 6 and 12 months as the dependent variables for each model, respectively. Predictors relating to mobility, global cognition, executive functions, and cognitive status (MCI versus no MCI) were examined. Age, sex, comorbidities, depression status, and activities of daily living were included regardless of statistical significance. RESULTS: Global cognition, comorbidities, working memory, and cognitive status (MCI versus no MCI ascertained using the Montreal Cognitive Assessment (MoCA)) were significant determinants of total HRU at 6 months. The number of medical comorbidities and global cognition were significant determinants of total HRU at 12 months. CONCLUSION: MCI status was a determinant of HRU at 6 months among older adults with a history of falls. As such, efforts to minimize health care resource use related to falls, it is important to tailor future interventions to be effective for people with MCI who fall. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01022866.

Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception.

BACKGROUND AND PURPOSE: Depression is common amongst subjects with multiple sclerosis (MS), and several investigations have explored different determinants of this condition, including physical disability, psychological and psychosocial factors. The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with depression. The aim of this study was to analyze the influence of disease-related factors, BDNF Val66Met polymorphism and perception of disease on the severity of depression in MS. METHOD: In total, 136 MS patients (88 women) were recruited and genotyped for BDNF rs6265 polymorphism at nucleotide 196 (G/A) using 'high resolution melting'. Depressive symptoms were assessed by the Multiple Sclerosis Depression Rating Scale. Perception of health status was assessed using the SF-36 questionnaire. RESULTS: A multivariable linear regression model showed that the best predictors of depression were the SF-36 General health (ß = -0.209; P = 0.013), Mental health (ß = -0.410; P < 0.001) and Social activity (ß = -0.195; P = 0.035) scores; physical disability (assessed by the Extended Disability Status Scale score) was directly correlated to depression severity on univariate analysis, but it was not a relevant predictor of depression on multivariate analysis; other variables directly related to the disease (treatment, annual relapsing rate) and the BDNF Val66Met polymorphism were not significantly associated with depression. CONCLUSION: Perception of the health status is the principal predictor of depressive symptoms in our sample. This result supports the hypothesis that the subjective interpretation of the disease's consequences is one of the main factors in determining depression in MS.

Familiarity for famous faces and names is not equally subtended by the right and left temporal poles. Evidence from an rTMS study.

The aims of the present experiment was to investigate: (a) if transient disruption of neural activity in the right (RTP) or left temporal pole (LTP) can interfere with the development of a familiarity feeling to the presentation of faces/written names of famous/unknown people; and (b) if this interference specifically affects the familiarity for faces after inhibition of the RTP and for names after inhibition of the LTP. Twenty healthy volunteers took part in the study. Repetitive transcranial magnetic stimulation (rTMS) was administered online; it disrupted the neural activity of the right or left TP in concomitance with the presentation of each face and name whose familiarity had to be assessed. Furthermore, in a control group, each participant was submitted to a single experimental session in which rTMS was delivered to the vertex in association with the presentation of faces and written names. Since previous rTMS studies have shown that the temporary inactivation of the right and left TP influences the response latencies, but not the number of correct responses, in this study we took into account both the number of correct responses obtained in different experimental conditions and the corresponding response latencies. A three-way factorial ANOVA carried out on the Response Scores showed only a general effect of the Type of Stimuli, due to better performances on names than on faces. This greater familiarity of names is consistent with previous data reported in the literature. In the three-way factorial ANOVA carried out on the Latency Scores, post-hoc analyses showed an increased latency of responses to faces after right stimulation in Latency Total, Latency on Correct responses and Latency on Unfamiliar faces. None of these results were obtained in the control group. These data suggest that rTMS at the level of the RTP preferentially affects the development of familiarity feelings to the presentation of faces of famous people.

Italian Frontotemporal Dementia Network (FTD Group-SINDEM): sharing clinical and diagnostic procedures in Frontotemporal Dementia in Italy.

In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers.

Brain morphometric correlates of metabolic variables in HIV: the CHARTER study.

Obesity and other metabolic variables are associated with abnormal brain structural volumes and cognitive dysfunction in HIV-uninfected populations. Since individuals with HIV infection on combined antiretroviral therapy (CART) often have systemic metabolic abnormalities and changes in brain morphology and function, we examined associations among brain volumes and metabolic factors in the multisite CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort, cross-sectional study of 222 HIV-infected individuals. Metabolic variables included body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure, random blood glucose, and diabetes. MRI measured volumes of cerebral white matter, abnormal white matter, cortical and subcortical gray matter, and ventricular and sulcal CSF. Multiple linear regression models allowed us to examine metabolic variables separately and in combination to predict each regional volume. Greater BMI was associated with smaller cortical gray and larger white matter volumes. Higher total cholesterol (C) levels were associated with smaller cortex volumes; higher LDL-C was associated with larger cerebral white matter volumes, while higher HDL-C levels were associated with larger sulci. Higher blood glucose levels and diabetes were associated with more abnormal white matter. Multiple atherogenic metabolic factors contribute to regional brain volumes in HIV-infected, CART-treated patients, reflecting associations similar to those found in HIV-uninfected individuals. These risk factors may accelerate cerebral atherosclerosis and consequent brain alterations and cognitive dysfunction.

Management of immunosuppression and antiviral treatment before and after heart transplant for HIV-associated dilated cardiomyopathy.

Infection with HIV may lead to the development of cardiomyopathy as improved antiretroviral regimens continue to prolong patient life. However, advanced therapeutic options, such as heart transplant, have until recently been precluded to HIV-positive persons. A favorable long-term outcome has been obtained after kidney or liver transplant in HIV-positive recipients fulfilling strict virological and clinical criteria. We recently reported the first heart transplant in a HIV-infected patient carried out in our center. In this article, we detail the major challenges we faced with the management of antiretroviral and immunosuppressive treatments over the first 3 years post-transplant. The patient had developed dilated cardiomyopathy while on antiretroviral treatment with zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac resynchronization therapy and maximal drug therapy, the patient progressed to end stage heart failure, requiring heart transplant. He was placed on a standard immune suppressive protocol including cyclosporine A and everolimus. Despite its potential pharmacokinetic interaction with efavirenz, everolimus was chosen to reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs were monitored and remained within the target range, although high doses of everolimus were needed. There were no infectious, neoplastic or metabolic complications during a 3-year follow-up. In summary, our experience supports previous data showing that cardiac transplantation should not be denied to carefully selected HIV patients. Careful management of drug interactions and adverse events is mandatory.

Performance of Fully-Automated High-Throughput Plasma Biomarker Assays for Alzheimer's Disease in Amnestic Mild Cognitive Impairment Subjects.

INTRODUCTION: Novel plasma biomarkers are promising for identifying Alzheimer's disease (AD) pathological processes in vivo, but most currently employed assays have limitations precluding widespread use. METHODS: CSF and plasma samples were collected from seventy amnestic mild cognitive impairment (aMCI) subjects, stratified as A+ and A-. CSF Aß40, Aß42, p-tau181 and t-tau and plasma Aß40, Aß42 and p-tau181 quantification were conducted using the Lumipulse G assays (Fujirebio), to evaluate the diagnostic performance of plasma biomarkers and assess their associations with CSF biomarkers. RESULTS: All plasma biomarkers except Aß40 showed a very good accuracy in distinguishing A+ aMCI from A- aMCI, Aß42/p-tau181 ratio being the most accurate (AUC 0.895, sensitivity 95.1%, specificity 82.8%). Plasma biomarkers levels were significantly associated with CSF biomarkers concentration. DISCUSSION: High-throughput and fully-automated plasma assays could be helpful in discriminating with high accuracy between aMCI in the AD continuum and aMCI unlikely due to AD in clinical settings.

Apolipoprotein E4 genotype does not increase risk of HIV-associated neurocognitive disorders.

This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid.

The Multiple Features Target Cancellation (MFTC): an attentional visual conjunction search test. Normative values for the Italian population.

Several studies, showing that attention disorders during encoding reduce later memory performance, have stressed the critical role of attention for the formation of durable memory traces. Accordingly, some studies suggest that attentive disturbances, together with declarative memory defects, can constitute the earliest cognitive disorders in Alzheimer's disease. Therefore, the analysis of these disorders can contribute to identify different forms of dementia and to detect demented patients characterized by a faster cognitive decline. In this study, we report the normative data (gathered in a large Italian population) of a short test that assess the ability to detect stimuli characterized by a conjunction of features: the 'Multiple Features Targets Cancellation' task (MFTC). Our sample of 465 subjects was composed by urban and rural people. Multiple linear regression analyses revealed significant relation of false alarms with age and educational level, and of time of execution with age, educational level and gender. Regression analyses on accuracy scores did not show any significant correlation with demographics variables. Based on non-parametric techniques, cutoff scores were obtained on the corrected scores of the patients, and equivalent scores were derived for each measure. The MFTC task represents a useful tool that explores attentional disorders (and in particular conjunction search disturbances) and that could be helpful both in discriminating different forms of dementia and to detect mild cognitive impairment patients at risk of conversion to dementia.

Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study.

BACKGROUND: AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. METHODS: Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. RESULTS: The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). CONCLUSIONS: The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. CLINICAL TRIALS REGISTRATION: NCT00096824.

The cost of fall related presentations to the ED: a prospective, in-person, patient-tracking analysis of health resource utilization.

UNLABELLED: We prospectively collected data on elderly fallers to estimate the total cost of a fall requiring an Emergency Department presentation. Using data collected on 102 falls, we found the average cost per fall causing an Emergency Department presentation of $11,408. When hospitalization was required, the average cost per fall was $29,363. INTRODUCTION: For elderly persons, falls are a major source of mortality, morbidity, and disability. Previous Canadian cost estimates of seniors' falls were based upon administrative data that has been shown to underestimate the incidence of falls. Our objective was to use a labor-intensive, direct observation patient-tracking method to accurately estimate the total cost of falls among seniors who presented to a major urban Emergency Department (ED) in Canada. METHODS: We prospectively collected data from seniors (>70 years) presenting to the Vancouver General Hospital ED after a fall. We excluded individuals who where cognitively impaired or unable to read/write English. Data were collected on the care provided including physician assessments/consultations, radiology and laboratory tests, ED/hospital time, rehabilitation facility time, and in-hospital procedures. Unit costs of health resources were taken from a fully allocated hospital cost model. RESULTS: Data were collected on 101 fall-related ED presentations. The most common diagnoses were fractures (n = 33) and lacerations (n = 11). The mean cost of a fall causing ED presentation was $11,408 (SD: $19,655). Thirty-eight fallers had injuries requiring hospital admission with an average total cost of $29,363 (SD: $22,661). Hip fractures cost $39,507 (SD: $17,932). Among the 62 individuals not admitted to the hospital, the average cost of their ED visit was $674 (SD: $429). CONCLUSIONS: Among the growing population of Canadian seniors, falls have substantial costs. With the cost of a fall-related hospitalization approaching $30,000, there is an increased need for fall prevention programs.

SF-6D and EQ-5D result in widely divergent incremental cost-effectiveness ratios in a clinical trial of older women: implications for health policy decisions.

SUMMARY: Using two instruments (SF-6D and EQ-5D) to estimate quality adjusted life years (QALYs), we conducted an economic evaluation of a 12-month randomized controlled trial with a 12-month follow-up study in older women to evaluate the value for money of two doses of resistance training compared with balance and tone classes. We found that the incremental QALYs estimated from the SF-6D were two- to threefold greater than those estimated from the EQ-5D. INTRODUCTION: Decision makers must continually choose between existing and new interventions. Hence, economic evaluations are increasingly prevalent. The impact of quality-adjusted life year (QALY) estimates using different instruments on the incremental cost-effectiveness ratios (ICERs) is not well understood in older adults. Thus, we compared ICERs, in older women, estimated by the EuroQol-5D (EQ-5D) and the Short Form-6D (SF-6D) to discuss implications on decision making. METHODS: Using both the EQ-5D and the SF-6D, we compared the incremental cost per QALY gained in a randomized controlled trial of resistance training in 155 community-dwelling women aged 65 to 75 years. The 12-month randomized controlled trial included a subsequent 12-month follow-up. Our focus, the follow-up study, included 123 of the 155 participants from the Brain Power study; 98 took part in the economic evaluation (twice-weekly balance and tone exercises, n = 28; once-weekly resistance training, n = 35; twice-weekly resistance training, n = 35). Our primary outcome measure was the incremental cost per QALY gained of once- or twice-weekly resistance training compared with balance and tone exercises. RESULTS: At cessation of the follow-up study, the incremental QALY was -0.051 (EQ-5D) and -0.144 (SF-6D) for the once-weekly resistance training group and -0.081 (EQ-5D) and -0.127 (SF-6D) for the twice-weekly resistance training group compared with balance and tone classes. CONCLUSION: The incremental QALYs estimated from the SF-6D were two- to threefold greater than those estimated from the EQ-5D. Given the large magnitude of difference, the choice of preference-based utility instrument may substantially impact health care decisions.

Diagnosing symptomatic HIV-associated neurocognitive disorders: self-report versus performance-based assessment of everyday functioning.

Three types of HIV-associated neurocognitive disorders (HAND) exist that are distinguished by presence and severity of impairment in cognitive and everyday functioning. Although well-validated neurocognitive measures exist, determining impairment in everyday functioning remains a challenge. We aim to determine whether Self-Report measures of everyday functioning are as effective in characterizing HAND as Performance-Based measures. We assessed 674 HIV-infected participants with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via Self-Report and Performance-Based measures. HAND diagnoses were determined according to published criteria using three approaches to assess functional decline: (1) Self-Report measures only, (2) Performance-Based measures only, and (3) Dual-method combining Self-Report and Performance-Based measures. The Dual-method classified the most symptomatic HAND, compared to either singular method. Singular method classifications were 76% concordant with each other. Participants classified as Performance-Based functionally impaired were more likely to be unemployed and more immunosuppressed, whereas those classified as Self-Report functionally impaired had more depressive symptoms. Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. Singular Performance-Based classifications were associated with objective functional and disease-related factors; reliance on Self-Report classifications may be biased by depressive symptoms.

Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias.

AIMS/HYPOTHESIS: Despite the vast body of epidemiological literature on the risk of cancer in people with diabetes, few studies have examined the pattern of cancer risk during different time windows following diabetes onset. The objective of the study was to examine the risks of site-specific cancer in people with incident type 2 diabetes during different time windows following diabetes onset. METHODS: This was a population-based retrospective cohort study. The study period was 1 April 1994 to 31 March 2006; censoring occurred at 31 March 2006, at death or on departure from British Columbia, Canada. Using linked health databases, we identified incident cohorts with and without diabetes, who were matched by age, sex and index year. Following a minimum 2-year cancer washout period, first site-specific cancers were identified prospectively in both cohorts. RESULTS: Within 3 months following diabetes onset, participants with diabetes had significantly increased risks of colorectal, lung, liver, cervical, endometrial, ovarian, pancreatic and prostate cancers. After the initial 3-month period, the risks for colorectal (HR 1.15, 95% CI 1.05, 1.25), liver (HR 2.53, 95% CI 1.93, 3.31) and endometrial (HR 1.58, 95% CI 1.28, 1.94) cancers remained significantly elevated compared with those without diabetes. The diabetes cohort remained at increased risk of pancreatic cancer in later years, but followed a different pattern: HR 3.71 at 3 months-1 year, 2.94 at 1-2 years, 1.78 at 2-3 years and 1.65 at 3-10 years (p value for all <0.01). After an initial period of elevated risk, men with type 2 diabetes subsequently had a decreased risk of prostate cancer (HR 0.82, 95% CI 0.76, 0.88). CONCLUSIONS/INTERPRETATION: People with type 2 diabetes are at increased risk of select cancers; this risk is particularly elevated at the time of diabetes onset, which is likely to be due to increased ascertainment.