A single-arm, open-label study to assess the immunogenicity, safety, and efficacy of etanercept manufactured using the serum-free, high-capacity manufacturing process administered to patients with rheumatoid arthritis

Objective: To evaluate the immunogenicity, safety, and efficacy of etanercept (ETN) manufactured using the serum-free, high-capacity manufacturing (SFHCM) process in patients with rheumatoid arthritis (RA). ----- Methods: In this global, multicenter, open-label, single-arm study (NCT02378506), 187 adult patients with moderate to severe RA received ETN 50 mg once weekly for 24 weeks manufactured using the SFHCM process. Immunogenicity (presence of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs)) was assessed at 12 and 24 weeks. Safety and efficacy were evaluated at 4, 12, and 24 weeks. ----- Results: Eight (4.5%) patients tested positive for ADA, and there were no NAbs detected at any time throughout the study. Ninety (48.1%) patients reported treatment-emergent adverse events (AEs), of which 27 (14.4%) reported injection-site reactions, and 43 (23.0%) reported infections. The majority of AEs were mild or moderate in severity, and the drug was well tolerated. Throughout the duration of the study (week 4 to week 24), there was a progressive increase in the American College of Rheumatology (ACR)-defined responses (ACR20: 55.9%–82.0%, ACR50: 16.1%–57.8%, and ACR70: 3.2%–26.7%) from baseline and the proportion of patients achieving low disease activity and remission, with a corresponding decrease in measures of disease activity. ----- Conclusion: The immunogenicity, safety, and efficacy of ETN manufactured using the SFHCM process were similar to the current approved ETN formulation. ClinicalTrials.gov registration: NCT02378506

Fall history and associated factors among adults living with HIV-1 in the Cape Winelands, South Africa : an exploratory investigation

CITATION: Berner, K., et al. 2019. Fall history and associated factors among adults living with HIV-1 in the Cape Winelands, South Africa : an exploratory investigation. Open Forum Infectious Diseases, 6(10):ofz401, doi:10.1093/ofid/ofz401.The original publication is available at https://academic.oup.com/ofidPublication of this article was funded by the Stellenbosch University Open Access Fund.Background. People with HIV-1 (PWH) exhibit a high fall incidence and increased fracture risk. As little is known about fall frequency and associated factors in PWH residing in lower-middle-income countries (LMIC), we investigated fall frequency, bone quality, and factors associated with fall history in a South African cohort. Methods. Fifty PWH without obvious predisposing factors for mobility impairments attending 2 public primary care clinics in the Western Cape region participated. Demographic, clinical, and physical performance data were collected. Falls were assessed retrospectively over 12 months. Mobility and balance were evaluated using a physical performance battery. Bone mineral density was screened using quantitative ultrasound (QUS). Associations between variables and falls grouping were analyzed using chi-square tests, t tests, and Mann-Whitney U tests, and effect sizes (ES) were calculated. Results. Thirty-four percent of PWH (median age, 36.6 years) reported falling during the past year, and 41.2% of fallers reported multiple falls. Fallers had more mobility problems (P = .013), higher fear of falling (P = .007), higher fracture history (P = .003), worse balance performance (P < .001), higher proportions of detectable viral loads (P = .021), and poorer bone quality (P = .040). Differences were of medium to large ES. Conclusions. This exploratory study is the first to show that relatively young South African PWH without obvious predisposing factors for gait and balance impairments experience falls. The observed fall-associated factors warrant further research using larger samples and longitudinal designs to ascertain fall predictors within this population.https://academic.oup.com/ofid/article/6/10/ofz401/5584296Publisher's versio

Prediction of remission and low disease activity in disease-modifying anti-rheumatic drug-refractory patients with rheumatoid arthritis treated with golimumab

OBJECTIVE: To create a tool to predict probability of remission and low disease activity (LDA) in patients with RA being considered for anti-TNF treatment in clinical practice. METHODS: We analysed data from GO-MORE, an open-label, multinational, prospective study in biologic-naïve patients with active RA (DAS28-ESR ⩾3.2) despite DMARD therapy. Patients received 50 mg s.c. golimumab (GLM) once monthly for 6 months. In secondary analyses, regression models were used to determine the best set of baseline factors to predict remission (DAS28-ESR <2.6) at month 6 and LDA (DAS28-ESR ⩽3.2) at month 1. RESULTS: In 3280 efficacy-evaluable patients, of 12 factors included in initial regression models predicting remission or LDA, six were retained in final multivariable models. Greater likelihood of LDA and remission was associated with being male; younger age; lower HAQ, ESR (or CRP) and tender joint count (or swollen joint count) scores; and absence of comorbidities. In models predicting 1-, 3- and 6-month LDA or remission, area under the receiver operating curve was 0.648-0.809 (R(2) = 0.0397-0.1078). The models also predicted 6-month HAQ and EuroQoL-5-dimension scores. A series of matrices were developed to easily show predicted rates of remission and LDA. CONCLUSION: A matrix tool was developed to show predicted GLM treatment outcomes in patients with RA, based on a combination of six baseline characteristics. The tool could help provide practical guidance in selection of candidates for anti-TNF therapy

Community Engagement newsletter, Faculty of Veterinary Science, Winter, 2012

Mangaung community receives support from Onderstepoort / Willem Engelbrecht, Helzna Krikke, Ingrid Metz, Janine Lombard, Marelize Greyling and Willem Janson -- Fighting animal abuse one school at a time / Ruche Harmse, Taryn Light, Ansu Visser, Este van Coetzen, Megan Naude, Nadia Strydom and Tess Tjasink -- Veterinary education and “Vets for the kids” / Patrick Ntsibande, Nyeleti Manganyi, Noluthando Ndashe, Thapelo Makae, Khulekani Lukhele and Sabelo Magagula -- soVETo k9 Mobile clinic outreach / Daleen Bester, Gideon Stemmet, Ian Gibson, Kobus Rabe, Louw Grobler and Rhynard de RidderNews articles with colour photos about the various community engagement projects of the Faculty of Veterinary Science, University of Pretoria.ab201

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Non-AIDS-, non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.publishedVersio

Attitudes and perceptions of nurses regarding early communication intervention

Although nurses play a vital role during Early Communication Intervention with infants and toddlers 0-2 years, limited research has been conducted regarding this role. Opsomming Alhoewel verpleegkundiges 'n belangrike rol speel in Vroee Kommunikasie Intervensie met hoerisiko-babas en kleuters van 0-2jaar, is beperkte navorsing egter uitgevoer oor hierdie rol. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text

Mobility deviations in adults living with HIV: a cross-sectional assessment using gait analysis, functional performance and self-report

International audienceBackground: Little is known about how HIV affects walking biomechanics, or about associations between HIV-related gait deviations, functional performance and self-reported outcomes. This paper reports on gait biomechanics and -variability in people with HIV (PWH), and associations with clinical tests, self-reported function and falls.Methods: A cross-sectional study tested consecutively-sampled PWH (n=50) and HIV-seronegative participants (SNP, n=50). Participants underwent three-dimensional gait analysis, performed clinical tests (short walk- and single leg stance tests with and without dual tasking, chair-rise tests and a physical performance battery), and completed questionnaires about function and falls. Between-group comparisons were done using analysis of covariance. Linear correlations between gait variability, clinical tests and patient-reported outcomes were established.Results: PWH and SNP had comparable median ages (PWH 36.6 [IQR 32.0–45.6], SNP 31.1 [23.2–45.1]). Compared with SNP, PWH walked slower (adjusted mean difference [MD]=-0.2 m/s, 95% CI=-0.3; -0.1) with greater variability (adjusted MD=14.7, 95% CI=9.9; 19.5). Moreover, PWH were slower in five-times sit-to-stand (5STS) performance (adjusted MD=1.9 seconds, 95% CI=1.00; 2.9). Significant deviations in hip kinematics (increased flexion; adjusted MDs=2.4°–2.8°, P=.012–.016), and knee kinematics (reduced flexion; adjusted MDs=2.3°–3.7°, P=.007–.027) were found in PWH during dual task walking. PWH’s 5STS moderately correlated with larger gait variability (usual pace r=-0.5; dual task r=-0.6), poorer self-reported mobility- (r=0.4) and self-care function (r=0.5), and fear of falling (P=.003).Conclusions: PWH presented with biomechanical deviations suggestive of a slowed and variable gait, especially under cognitive challenges. Five-times STS may be useful to screen for gait deviations in PWH

Can an early 24-hour EEG predict the response to the ketogenic diet?: a prospective study in 34 children and adults with refractory epilepsy treated with the ketogenic diet

AbstractPurposeWe examined whether early EEG changes in a 24-h EEG at 6 weeks of treatment were related to the later clinical response to the ketogenic diet (KD) in a 6-month period of treatment.MethodsWe examined 34 patients with heterogeneous epilepsy syndromes (21 children, 13 adults) and found 9 clinical responders (≥50% seizure reduction); this is a responder rate of 26%. We visually counted the interictal epileptic discharge index (IED index) in % during 2h of wakefulness and in the first hour of sleep (method 1), and also globally reviewed EEG changes (method 2), while blinded to the effect of the KD.ResultsAt group level we saw a correlation between nocturnal reduction of IED-index at 6 weeks and seizure reduction in the follow-up period. A proportional reduction in IED index of 30% from baseline in the sleep EEG, was associated with being a responder to the diet (Pearson Chi-square p=0.04). EEG scoring method 2 observed a significantly larger proportion of patients with EEG-improvement in sleep in KD responders than in non-responders (p=0.03). At individual level, however, EEG changes did not correlate very strongly to the response to the diet, as IED reduction in sleep was also seen in 15% (method 1) to 26% (method 2) of the non-responders.ConclusionNocturnal reduction of IEDs is related to the response to the KD, however in daily clinical practice, an early EEG to predict seizure reduction should not be advised for individual patients