Fourteen-day bactericidal activity, safety, and pharmacokinetics of linezolid in adults with drug-sensitive pulmonary tuberculosis

Linezolid is increasingly used for the treatment of tuberculosis resistant to first-line agents, but the most effective dosing strategy is yet unknown. From November 2014 to November 2016, we randomized 114 drug-sensitive treatment-naive pulmonary tuberculosis patients from Cape Town, South Africa, to one of six 14-day treatment arms containing linezolid at 300 mg once daily (QD), 300 mg twice daily (BD), 600 mg QD, 600 mg BD, 1,200 mg QD, 1,200 mg three times per week (TIW), or a combination of isoniazid, rifampin, pyrazinamide, and ethambutol. Sixteen-hour sputum samples were collected overnight, and bactericidal activity was characterized by the daily percentage change in time to positivity (TTP) and the daily rate of change in log10(CFU). We also assessed the safety and pharmacokinetics of the study treatments. We found that bactericidal activity increased with increasing doses of linezolid. Based on the daily percentage change in TTP, activity was highest for 1,200 mg QD (4.5%; 95% Bayesian confidence interval [BCI], 3.3 to 5.6), followed by 600 mg BD (4.1%; BCI, 2.5 to 5.7), 600 mg QD (4.1%; BCI, 2.9 to 5.3), 300 mg BD (3.3%; BCI, 1.9 to 4.7), 300 mg QD (2.3%; BCI, 1.1 to 3.5), and 1,200 mg TIW (2.2%; BCI, 1.1 to 3.3). Similar results were seen with bactericidal activity characterized by the daily rate of change in CFU count. Antimycobacterial activity correlated positively with plasma drug exposure and percentage time over MIC. There were no unexpected adverse events. All linezolid doses showed bactericidal activity. For the same total daily dose, once-daily dosing proved to be at least as effective as a divided twice-daily dose. An intermittent dosing regimen, with 1,200 mg given three times weekly, showed the least activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02279875.)http://aac.asm.orgpm2020Statistic

Asthma treatment in children: A pragmatic approach

Background. Asthma is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation, with airway reversibility. Management of chronic inflammation with anti-asthma medication improves asthma control and quality of life.Objectives. To provide an evidence-based approach for chronic asthma management in young children and adolescents and provide guidance on the use of new asthma drugs in children.Methods. The South African Childhood Asthma Working Group (SACAWG) convened in January 2017. The asthma treatment task group reviewed the available scientific literature and international asthma treatment guidelines. The evidence was then graded according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system and recommendations were made based on scientific evidence and local context. Asthma management recommendations were made for children Ë‚6 years of age and older children and adolescents, as well as for stepping up and stepping down of therapy. This review does not include biologics or novel asthma drugs, which are covered in another CME article in this edition of SAMJ.Conclusions. To ensure good response, treatment and adherence, type of medication, device and checking of technique are all critical. Stepping up of therapy should be done only after ensuring good adherence and technique. Once therapeutic response is achieved, medication administration has to be stepped down to improve ease of use and avoid unnecessary side-effects

Asthma treatment in children: A pragmatic approach

Background. Asthma is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation, with airway reversibility. Management of chronic inflammation with anti-asthma medication improves asthma control and quality of life.Objectives. To provide an evidence-based approach for chronic asthma management in young children and adolescents and provide guidance on the use of new asthma drugs in children.Methods. The South African Childhood Asthma Working Group (SACAWG) convened in January 2017. The asthma treatment task group reviewed the available scientific literature and international asthma treatment guidelines. The evidence was then graded according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system and recommendations were made based on scientific evidence and local context. Asthma management recommendations were made for children ˂6 years of age and older children and adolescents, as well as for stepping up and stepping down of therapy. This review does not include biologics or novel asthma drugs, which are covered in another CME article in this edition of SAMJ.Conclusions. To ensure good response, treatment and adherence, type of medication, device and checking of technique are all critical. Stepping up of therapy should be done only after ensuring good adherence and technique. Once therapeutic response is achieved, medication administration has to be stepped down to improve ease of use and avoid unnecessary side-effects

Neonatal, infant and child health in South Africa : reflecting on the past towards a better future

CITATION: Goga, A. et al. 2019. Neonatal, infant and child health in South Africa : reflecting on the past towards a better future. South African Medical Journal, 109(11b):83-88, doi:10.7196/SAMJ.2019.v109i11b.14301.The original publication is available at http://www.samj.org.zaAlthough the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living with HIV, expanded immunisation policies, strengthening breastfeeding practices, and health policies to contain tobacco and sugar use. The Sustainable Development Goals (2016 - 2030) have shifted the focus from keeping children alive, as expressed in the Millennium Development Goals (1990 - 2015), to achieving optimal health through the ‘Survive, thrive and transform’ global agenda. This paper focuses on important remaining causes of childhood mortality and morbidity in SA, specifically respiratory illness, environmental pollution, tuberculosis, malnutrition and vaccine-preventable conditions. The monitoring of maternal and child health (MCH) outcomes is crucial, and has improved in SA through both the District Health Information and Civil Registration and Vital Statistics systems, although gaps remain. Intermittent surveys and research augment the routinely collected data. However, availability and use of local data to inform quality and effectiveness of care is critical, and this requires ownership at the collection point to facilitate local redress. Potential game changers to improve MCH outcomes include mobile health and community-based interventions. In SA, improved MCH remains a crucial factor for human capital development. There is a pressing need to focus beyond childhood mortality and to ensure that each child thrives.http://www.samj.org.za/index.php/samj/article/view/12807Publisher's versio

Exposure to the Environmental Endocrine Disruptor TCDD and Human Reproductive Dysfunction: Translating Lessons from Murine Models

Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new "Organ-on-Chip" models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Earlylife exposures to environmental tobacco smoke and indoor air pollution in the Drakenstein Child Health Study: Impact on child health

No Abstrac

The impact of habitual school bag carriage on the health of pubescent scholars

School bag carriage represents a considerable daily occupational load for children. The carriage of heavy school bags is a suspected aetiological factor of the daily physical stress of school pupils which negatively impacts on the health of their vertebral column. The objectives of this study was to determine the prevalence of school bag carriage musculoskeletal pain after the dissemination of the recommendations of Puckree&rsquo;s findings (Puckree et al. 2004) in the eThekwini region of Kwa-Zulu Natal, South Africa, as well as explain the impact of school bag carriage on the pubescent&rsquo;s craniovertebral angle. One hundred and eighty-seven pupils voluntarily participated in a controlled, descriptive, epidemiological retrospective study. Pupils&rsquo; biographical, epidemiological, physical activity and life-style information was gathered by a self-report questionnaire. Digital images were captured in the loaded phase(when pupils were carrying school bags) and unloaded phase (when they were not carrying school bags) in the sagittal and frontal planes. These images were analyzed using biomechanical software, Dartfish. In addition the pupils&rsquo; body mass, stature and mass of their school bags were measured using a Detecto stadiometer scale. The study being retrospective in nature recorded the prevalence of school bag carriage musculoskeletal pain over the last 12 months. Descriptive statistical tests such mean, mode, frequency, percentages and inferential chi-square statistical test (p&le; 0.05) were employed to analyze the data. The result indicated that 64.97% of the cohort experience school bag carriage related musculoskeletal pain (p&lt;0.001). The most prevalent anatomical sites which experienced pain were the vertebral column(40.89%) and shoulders (33.99%) (p&lt;0.001). The predisposing factors of the pain were the mass of the school bag and the reduction in the craniovertebral angle (p&lt;0.001).It was concluded thatpubescent pupils (12.41 &plusmn;0.60 years) residing in the eThekwini region of Kwa-Zulu Natal, South Africa, experience school bag carriage related musculoskeletal pain.Keywords: School bag, pubescent, musculoskeletal pain, craniovertebral angle

Epsilon-aminocaproic acid versus tranexamic acid in total knee arthroplasty: a meta-analysis study

INTRODUCTION: Total knee arthroplasty (TKA) surgery can be associated with significant blood loss. Among the problems associated with such blood loss is the need for transfusions of banked blood [1]. Transfusions not only have a financial consequence but also carry a small risk of disease transmission to the patient. Antifibrinolytics have been successfully used to reduce transfusion requirements in elective arthroplasty patients. The objective of this meta-analysis is to determine which of tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) is more effective for reducing peri-operative blood loss, and lessening the need for blood transfusion following knee arthroplasty surgery. MATERIALS AND METHODS: MEDLINE, Embase and CINAHL databases were searched for relevant articles published between January 1980 to January 2018 for the purpose of identifying studies comparing TXA and EACA for TKA surgery. A double-extraction technique was used, and included studies were assessed regarding their methodological quality prior to analysis. Outcomes analysed included blood loss, pre- and post-operative haemoglobin, number of patients requiring transfusion, number of units transfused, operative and tourniquet time, and complications associated with antifibrinolytics. RESULTS: Three studies contributed to the quantitative analysis of 1691 patients, with 743 patients included in the TXA group and 948 in the EACA group. Estimated blood loss was similar between the two groups [95% confidence interval (CI) -0.50, 0.04; Z = 1.69; P = 0.09]. There were no differences between the two groups regarding the percentage of patients requiring transfusion (95% CI 0.14, 4.13; Z = 0.31; P = 0.76). There was no difference in the pre- and post-operative haemoglobin difference between the two groups (95% CI -0.36, 0.24; Z = 0.38; P = 0.70). There was no difference in the average number of transfused units (95% CI -0.53, 0.25; Z = 0.71; P = 0.48). There was no difference in the operative (95% CI -0.35, 0.36; Z = 0.04; P = 0.97) or tourniquet time (95% CI -0.16, 0.34; Z = 0.72; P = 0.47). Similarly, there was no difference in the percentage of venous thromboembolism between the two groups (95% CI 0.17, 2.80; Z = 0.51; P = 0.61). CONCLUSIONS: This study did not demonstrate TXA to be superior to EACA. In fact, both antifibrinolytic therapies demonstrated similar efficacy in terms of intra-operative blood loss, transfusion requirements and complication rates. Currently EACA has a lower cost, which makes it an appealing alternative to TXA for TKA surgery. LEVEL OF EVIDENCE: 3