Qualitative and Psychometric Evaluation of 29-Item Patient-Reported Outcomes Measurement Information System® to Assess General Health-Related Quality of Life in Patients With Moderately to Severely Active Inflammatory Bowel Disease.

Objectives: To evaluate content validity and psychometric properties of the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) to determine its suitability in inflammatory bowel disease (IBD) clinical trials.

Methods: Content validity of PROMIS-29 was evaluated using qualitative interviews, including concept elicitation and cognitive debriefing, among patients living with Crohn's disease (Crohn's disease n = 20) or ulcerative colitis (UC, n = 19). PROMIS-29 validity, reliability, and responsiveness were assessed using data from phase II clinical trials of Crohn's disease (N = 360) and UC (N = 518).

Qualitative and psychometric evaluation of the PROMIS®-Fatigue SF-7a scale to assess fatigue in patients with moderately to severely active inflammatory bowel disease.

Background: This study evaluated the content validity and psychometric properties of the Patient-Reported Outcomes Measurement Information System® (PROMIS)-Fatigue Short Form 7a (SF-7a) v1.0 scale to determine its suitability in clinical trials to assess fatigue in patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC).

Methods: A qualitative interview assessed patients' experience living with CD (N = 20) and UC (N = 19).

Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study.

Background & Aims: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy.

Methods: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12.

The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study.

Background: AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ 6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy.

Methods: During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate.

Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis.

Introduction: One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA.

Methods: The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate.

FRET processes of bi-fluorophoric sensor material containing tetraphenylethylene donor and optical-switchable merocyanine acceptor for lead ion (Pb) detection in semi-aqueous media.

A novel aggregation-induced emission (AIE) structure containing a tetraphenylethene (TPE) unit covalently linked with a merocyanine (MC) unit was synthesized and investigated in semi-aqueous solutions with 90% water fraction. The open-form structure of red-emissive MC unit combined with TPE unit was utilized as a bi-fluorophoric sensor to detect lead(II) ion, which could be transformed from the close-form structure of non-emissive SP unit upon UV exposure. Moreover, the TPE unit as an energy donor with the blue-green photoluminescence (PL) emission at 480 nm was combined with the MC unit as an energy acceptor with the red PL emission at 635 nm.

Mapping the drivers of within-host pathogen evolution using massive data sets.

Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses.

The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients With Hematologic Malignancies Requiring Antibiotics.

Background: Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this population remains unknown.

Methods: This was a retrospective cohort study of adult inpatients with hematologic malignancy admitted at 2 tertiary care hospitals from 2010 through 2015.

Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection.

HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood.

Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence.

It is widely believed that epidemics in new hosts diminish in virulence over time, with natural selection favoring pathogens that cause minimal disease. However, a tradeoff frequently exists between high virulence shortening host survival on the one hand but allowing faster transmission on the other. This is the case in HIV infection, where high viral loads increase transmission risk per coital act but reduce host longevity.

Dipstick proteinuria is an independent predictor of high on treatment platelet reactivity in patients on clopidogrel, but not aspirin, admitted for major adverse cardiovascular events.

The effectiveness of aspirin and clopidogrel in patients with chronic kidney disease (CKD) suffering from acute cardiovascular events is unclear. High on treatment platelet reactivity (HTPR) has been associated with worse outcomes. Here, we assessed the association of dipstick proteinuria (DP) and renal function on HTPR and clinical outcomes.

Co-operative additive effects between HLA alleles in control of HIV-1.

Background: HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles--irrespective of linkage disequilibrium--function co-operatively.

HIV control through a single nucleotide on the HLA-B locus.

Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells, and strong linkage disequilibrium between HLA class I alleles complicates the discrimination of individual HLA allelic effects from those of other HLA and non-HLA alleles on the same haplotype.

A molecular assay for sensitive detection of pathogen-specific T-cells.

Here we describe the development and validation of a highly sensitive assay of antigen-specific IFN-γ production using real time quantitative PCR (qPCR) for two reporters--monokine-induced by IFN-γ (MIG) and the IFN-γ inducible protein-10 (IP10). We developed and validated the assay and applied it to the detection of CMV, HIV and Mycobacterium tuberculosis (MTB) specific responses, in a cohort of HIV co-infected patients. We compared the sensitivity of this assay to that of the ex vivo RD1 (ESAT-6 and CFP-10)-specific IFN-γ Elispot assay.

Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations.

We lack the understanding of why HIV-infected individuals in South Africa progress to AIDS. We hypothesised that in end-stage disease there is a shifting dynamic between T cell imposed immunity and viral immune escape, which, through both compensatory and reverting viral mutations, results in increased viral fitness, elevated plasma viral loads and disease progression. We explored how T cell responses, viral adaptation and viral fitness inter-relate in South African cohorts recruited from Bloemfontein, the Free State (n = 278) and Durban, KwaZulu-Natal (n = 775).

HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703.

The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia.

B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection.

HIV can be partially contained by host immunity and understanding the basis of this may inform vaccine design. The importance of B-cell function in long-term control is poorly understood. One method of investigating this is in vivo cellular depletion.

Prevalence of HIV type-1 drug-associated mutations in pre-therapy patients in the Free State, South Africa.

Background: We aimed to characterize the molecular epidemiology of HIV type-1 (HIV-1) and the prevalence of drug-associated mutations prior to initiating highly active antiretroviral therapy (HAART) in the Free State province, South Africa. The Free State has a population of 3 million, an antenatal HIV prevalence of approximately 34% and a well established infrastucture for antiretroviral (ARV) provision.

Methods: HIV-1 polymerase genes were sequenced from 425 HAART-naive HIV-1-positive patients at voluntary primary healthcare HIV testing centres, who were subsequently attending district centres for assessment for commencing ARVs.

Full-length characterization of hepatitis C virus subtype 3a reveals novel hypervariable regions under positive selection during acute infection.

Hepatitis C virus subtype 3a is a highly prevalent and globally distributed strain that is often associated with infection via injection drug use. This subtype exhibits particular phenotypic characteristics. In spite of this, detailed genetic analysis of this subtype has rarely been performed.