Cognitive ageing is premature among a community sample of optimally treated people living with HIV.

Objectives: Evidence of premature cognitive ageing amongst people living with HIV (PLHIV) remains controversial due to previous research limitations including underpowered studies, samples with suboptimal antiretroviral access, varying rate of virological control, high rate of AIDS, over-representation of non-community samples, and inclusion of inappropriate controls. The current study addresses these limitations, while also considering mental health and non-HIV comorbidity burden to determine whether PLHIV showed premature cognitive ageing compared with closely comparable HIV-negative controls.

Methods: This study enrolled 254 PLHIV [92% on antiretroviral therapy; 84% with HIV RNA < 50 copies/mL; 15% with AIDS) and 72 HIV-negative gay and bisexual men [mean (SD) age = 49 (10.

An examination of reliable change methods for measuring cognitive change with the Cogstate Computerized Battery: Research and clinical implications.

Objective: To compare the performance of four reliable change (RC) methods with respect to measuring cognitive change on the Cogstate Computerized Battery (CCB).

Method: We assessed cognitive change in 57 healthy, urban, well-educated males on the CCB at baseline and 6 months (Median age = 50, 65% university-educated). The study CCB version comprised seven measures covering attention, processing speed, verbal learning, and memory.

Associations between CD36 gene polymorphisms, fat tolerance and oral fat preference in a young-adult population.

Background/objectives: CD36 is known to be an orosensory receptor for dietary long-chain fatty acids, as well as being involved in the chemosensory mechanisms within the human gut. Recent data have demonstrated an association between CD36 single-nucleotide polymorphisms (SNPs) and lipid consumption behaviours in humans. This study aimed to test for associations between CD36 SNPs and response to a high-fat meal in a young healthy Australian cohort.

A Screening Strategy for HIV-Associated Neurocognitive Disorders That Accurately Identifies Patients Requiring Neurological Review.

Background: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are not routinely assessed due to the lack of an adequate screening strategy. We aimed to develop a clinically relevant screening procedure for symptomatic HAND, validated against a gold standard neuropsychological (NP) test battery.

Methods: Representative HIV-infected (HIV+) and demographically matched HIV-uninfected (HIV-) participants in an observational study completed a standard evaluation for mood, drug and/or alcohol use, and activities of daily living and a newly designed 20-minute computerized CogState battery that assessed 5 cognitive domains.

Associations between CD36 gene polymorphisms and metabolic response to a short-term endurance-training program in a young-adult population.

Recent studies have shown that CD36 gene variants are associated with an increased prevalence of chronic disease. Although a genetic component to trainability has been proven, no data are available specifically on the influence of CD36 on training response. Two single nucleotide polymorphisms (SNPs) (rs1527479 and rs1984112) were assessed for associations with whole-body substrate oxidation, response to a 75-g dextrose oral glucose tolerance test, fasting plasma lipids, and cardiovascular disease risk factors in a young healthy cohort, both using cross-sectional analysis and following a 4-week endurance-exercise training program.

Change in Dengue and Japanese Encephalitis Seroprevalence Rates in Sri Lanka.

Background: Sri Lanka has been affected by epidemics of dengue infections for many decades and the incidence and severity of dengue infections have been rising each year. Therefore, we investigated the age stratified seroprevalence of dengue infections in order to facilitate future dengue vaccine strategies. In addition, since the symptomatic dengue infections have increased during the past few decades, we also investigated the possible association with Japanese Encephalitis Virus (JEV) antibody seropositivity with symptomatic dengue in a community cohort in Sri Lanka.

Interactions Between Fatty Acid Transport Proteins, Genes That Encode for Them, and Exercise: A Systematic Review.

Long-chain fatty acid (LCFA) movement into skeletal muscle involves a highly mediated process in which lipid rafts are utilized in the cellular membrane, involving numerous putative plasma membrane-associated LCFA transport proteins. The process of LCFA uptake and oxidation is of particular metabolic significance both at rest and during light to moderate exercise. A comprehensive systematic search of electronic databases was conducted to investigate whether exercise alters protein and/or gene expression of putative LCFA transport proteins.

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

Purpose: This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623).

Methods: Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS.

Effectiveness of a team intervention in reducing modifiable cardiovascular disease risk in HIV-infected subjects on antiretroviral therapy.

Introduction: The increasing age, higher modifiable and inherent cardiovascular disease (CVD) risk of HIV-infected patients [1] necessitates improved approaches to reducing co-morbidities. We aimed to assess the effectiveness of a team intervention in reducing modifiable CVD risk.

Materials And Methods: HIV-infected patients ≥50 years attending a large HIV caseload primary-care practice, who were virologically suppressed on antiretroviral therapy (ART), with moderate or severe 10-year CVD Framingham risk (≥10%) were recruited for this prospective case-control study.

The associations between polymorphisms in the CD36 gene, fat oxidation and cardiovascular disease risk factors in a young adult Australian population: a pilot study.

Our pilot study in a young adult Australian cohort aimed to investigate potential associations between CD36 polymorphisms (rs1527479 and rs1984112), fat oxidation and cardiovascular disease risk. CD36 genotype was associated with fat oxidation during sub-maximal exercise, resting heart rate and blood pressure, indicating increased chronic disease risk in this otherwise healthy cohort.

Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children.

Objective: To gain insight into the long-term impact of vagus nerve stimulation (with VNS Therapy) in children with drug-resistant epilepsy, we conducted the largest retrospective multicenter study to date over an extended follow-up period of up to 24 months.

Methods: The primary objective was to assess change in seizure frequency of the predominant seizure type (defined as the most disabling seizure) following VNS device implantation. Treating physicians collected data from patient records from baseline to 6, 12, and 24 months of follow-up.

A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression.

Objective: To compare response and remission rates in depressed patients with chronic treatment-resistant depression (TRD) treated with vagus nerve stimulation (VNS) Therapy(®) plus treatment as usual (VNS + TAU) or TAU alone in a meta-analysis using Bayesian hierarchical models.

Data Sources And Study Selection: Six outpatient, multicenter, clinical trials that have evaluated VNS + TAU or TAU in TRD, including two single-arm studies of VNS + TAU (n = 60 and n = 74), a randomized study of VNS + TAU versus TAU (n = 235), a randomized study of VNS + TAU comparing different VNS stimulation intensities (n = 331), a nonrandomized registry of VNS + TAU versus TAU (n = 636), and a single-arm study of TAU (n = 124) to provide longer-term, control data for comparison with VNS-treated patients.

Data Extraction: A systematic review of individual patient-level data based on the intent-to-treat principle, including all patients who contributed more than one post-baseline visit.

A modified method for determination of lumefantrine in human plasma by HPLC-UV and combination of protein precipitation and solid-phase extraction: application to a pharmacokinetic study.

An HPLC-UV method was developed and validated for the determination of lumefantrine in human plasma. Lumefantrine and its internal standard halofantrine were extracted from plasma samples using protein precipitation with acetonitrile (0.2% perchloric acid) followed by solid-phase extraction with Hypersep C(8) cartridges.

Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.

Introduction: Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing this drug.

Methods: Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals.

Development and validation of a high-performance liquid chromatography/tandem mass spectrometry method for the determination of artemether and its active metabolite dihydroartemisinin in human plasma.

To study the pharmacokinetic profile of artemether in children and in the context of antiviral drugs for HIV infected patients co-infected with malaria, an LC-MS/MS method was developed and validated to simultaneously determine artemether and its metabolite dihydroartemisinin in human plasma. Using artemisinin as the internal standard, 0.5 mL samples were processed with solid phase extraction (Waters Oasis HLB column), the elutes were directly injected onto a C18 LC column (Waters, Symmetry, 150 mm x 4.

Development and validation of a hydrophilic interaction liquid chromatography-tandem mass spectrometry method for determination of isoniazid in human plasma.

An LC-MS/MS method for the determination of isoniazid in human plasma was developed and validated. Human plasma aliquots of 100 microL were used for analysis. The assay used nialamide as the internal standard.

Characterization of nelfinavir binding to plasma proteins and the lack of drug displacement interactions.

Objectives: To determine the characteristics of the binding of nelfinavir and active M8 to alpha1-acid glycoprotein (AAG) and human serum albumin (HSA), and to examine the displacement effects of drugs binding extensively to AAG (ritonavir and saquinavir) or to HSA (salicylic acid and valproic acid).

Methods: Free drugs were separated by equilibrium dialysis after incubation with human plasma or purified plasma proteins and after co-incubation with potential displacers. Association constants were estimated from double-reciprocal plots of the data.

Nelfinavir pharmacokinetics in stable human immunodeficiency virus-positive children: Pediatric AIDS Clinical Trials Group Protocol 377.

Objective: Pharmacokinetic data obtained from children who have human immunodeficiency virus (HIV) infection are essential for the safe and effective use of antiretroviral agents in pediatric populations. The objective of this study was to assess the impact of body weight on the pharmacokinetic disposition of nelfinavir (NFV) in the absence and presence of nevirapine (NVP) and compare the pharmacokinetic profiles of twice-daily (BID) and three-times-daily (TID) NFV regimens.

Methods: This was an intensive pharmacokinetic substudy nested in a phase II, multicenter, randomized, open-label trial.

An LC-MS-MS method for the determination of nevirapine, a non-nucleoside reverse transcriptase inhibitor, in human plasma.

A sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS-MS) method has been developed to measure the levels of the HIV-1 non-nucleoside reverse transcriptase inhibitor nevirapine (NVP) in human plasma. The analyte and internal standard (IS) are isolated from plasma by a simple perchloric acid precipitation of plasma proteins followed by centrifugation. LC-MS-MS in positive mode used pairs of ions at m/z of 267/226 for NVP and 628/421 for the IS, respectively.

Simultaneous determination of five HIV protease inhibitors nelfinavir, indinavir, ritonavir, saquinavir and amprenavir in human plasma by LC/MS/MS.

A sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS-MS) method has been developed to measure the levels of five HIV protease inhibitors nelfinavir (NFV), indinavir (IDV), ritonavir (RTV), saquinavir (SQV) and amprenavir (APV) in human plasma. The analytes and internal standard are isolated from plasma by a simple acetonitrile precipitation of plasma proteins followed by centrifugation. LC-MS-MS in positive mode used pairs of ions at m/z of 568.

Determination of nelfinavir free drug concentrations in plasma by equilibrium dialysis and liquid chromatography/tandem mass spectrometry: important factors for method optimization.

A method was developed and validated for measuring the free fraction of nelfinavir in plasma employing equilibrium dialysis for the separation of free (unbound) drug and liquid chromatography/tandem mass spectrometry for quantitation. Nelfinavir, widely used to treat HIV infection, is a highly bound HIV protease inhibitor with the fraction bound in plasma being greater than 98%. Thus variations in the free fraction may be clinically important when interpreting total drug concentrations.

A direct determination of thymidine triphosphate concentrations without dephosphorylation in peripheral blood mononuclear cells by LC/MS/MS.

A rapid, sensitive and specific analytical method with minimal sample preparation for the measurement of thymidine triphosphate (TTP) in peripheral blood mononuclear cells (PBMC) by LC/MS/MS has been developed. PBMC were separated from whole blood or buffy coat. The analyte and internal standard were extracted from PBMC with 70% methanol (pH 7.