Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.

Background: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes.

Caregiver willingness to give TPT to children living with drug-resistant TB patients.

Pediatric household contacts (HHCs) of patients with multidrug-resistant TB (MDR-TB) are at high risk of infection and active disease. Evidence of caregiver willingness to give MDR-TB preventive therapy (TPT) to children is limited. This was a cross-sectional study of HHCs of patients with MDR-TB to assess caregiver willingness to give TPT to children aged <13 years.

Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis.

Background: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis.

Methods: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points.

COVID-19: From health crises to food security anxiety and policy implications.

Like the rest of the world, African countries are reeling from the health, economic and social effects of COVID-19. The continent's governments have responded by imposing rigorous lockdowns to limit the spread of the virus. The various lockdown measures are undermining food security, because stay at home orders have among others, threatened food production for a continent that relies heavily on agriculture as the bedrock of the economy.

Liquid mycobacterial culture outcomes after different sputum collection techniques before and during treatment.

Setting: Mycobacterial sputum culture is a key diagnostic and research tool.

Objective: To compare mycobacterial culture outcomes of three sputum collection methods.

Design: We compared culture results within sets of three sputum samples collected from 18 HIV-infected adult tuberculosis patients at regular intervals up to 84 days after treatment initiation.

C-Tb skin test to diagnose Mycobacterium tuberculosis infection in children and HIV-infected adults: A phase 3 trial.

Background: C-Tb, an ESAT-6/CFP-10-based skin test, has similar sensitivity for active TB compared to tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-Tube (QFT). However, data are limited in children and HIV-infected persons.

Methods: Asymptomatic South African contacts <5 years (n = 87; HIV-uninfected), or symptomatic individuals of all ages presenting to clinics with suspected TB (n = 1003; 30% HIV-infected) were recruited from eight South African centres.

Usefulness of quality indicators for antibiotic use: case study for the Netherlands.

Quality Problem: Inappropriate antibiotic use drives development of antimicrobial resistance. Worldwide, guideline adherence for antibiotic treatment of infectious disease is far from optimal. Insight in prescribing quality is pivotal for healthcare professionals and policy makers to intervene appropriately.

Motherhood and the "Madness of Hunger": "...Want Almal Vra vir My vir 'n Stukkie Brood" ("...Because Everyone Asks Me for a Little Piece of Bread").

It is widely assumed that the social and economic conditions of poverty can be linked to common mental disorders in low-, middle- and high-income countries. Despite the considerable increase in quantitative studies investigating the link between poverty and mental health, the nature of the connection between poverty and emotional well-being/distress is still not fully comprehended. In this qualitative study, exploring how one group of Coloured South African women, diagnosed with depression and residing in a semi-rural low-income South African community, subjectively understand and experience their emotional distress, data was collected by means of in-depth semi-structured interviews and social constructionist grounded theory was used to analyse the data.

Directional Recording of Subthalamic Spectral Power Densities in Parkinson's Disease and the Effect of Steering Deep Brain Stimulation.

Background: A new 32-contacts deep brain stimulation (DBS) lead, capable of directionally steering stimulation, was tested intraoperatively.

Objective: The aim of this pilot study was to perform recordings from the multidirectional contacts and to investigate the effect of directional current steering on the local field potentials (LFPs).

Methods: In eight patients with Parkinson's disease, after standard microelectrode recording and clinical testing, the new lead was temporarily implanted.

Exploiting pallidal plasticity for stimulation in Parkinson's disease.

Objective: Continuous application of high-frequency deep brain stimulation (DBS) often effectively reduces motor symptoms of Parkinson's disease patients. While there is a growing need for more effective and less traumatic stimulation, the exact mechanism of DBS is still unknown. Here, we present a methodology to exploit the plasticity of GABAergic synapses inside the external globus pallidus (GPe) for the optimization of DBS.

Directional steering: A novel approach to deep brain stimulation.

Objective: The aim of this study was to investigate whether directional steering through a novel 32-contact electrode is safe and can modulate the thresholds for beneficial and side effects of stimulation.

Methods: The study is a single-center, performance and safety study. Double-blind intraoperative evaluations of the thresholds for therapeutic benefit and for side effects were performed in 8 patients with Parkinson disease while stimulating in randomized order in spherical mode and in 4 different steering modes with the 32-contact electrode, and in monopolar mode with a commercial electrode.

An exploration of Xhosa speaking patients' understanding of cancer treatment and its influence on their treatment experience.

Cultural beliefs often influence people in seeking appropriate health care. In South Africa, misperceptions and fear about medical interventions contribute to the fact that many indigenous people prefer to make use of traditional healers. This qualitative study explores Xhosa patients' perception of cancer and cancer treatment modalities, and their need for support.

Functional neuronal activity and connectivity within the subthalamic nucleus in Parkinson's disease.

Objective: Characterization of the functional neuronal activity and connectivity within the subthalamic nucleus (STN) in patients with Parkinson's disease (PD).

Methods: Single units were extracted from micro-electrode recording (MER) of 18 PD patients who underwent STN deep brain stimulation (DBS) surgery. The firing rate and pattern of simultaneously recorded spike trains and their coherence were analyzed.

From Parkinsonian thalamic activity to restoring thalamic relay using deep brain stimulation: new insights from computational modeling.

We present a computational model of a thalamocortical relay neuron for exploring basal ganglia thalamocortical loop behavior in relation to Parkinson's disease and deep brain stimulation (DBS). Previous microelectrode, single-unit recording studies demonstrated that oscillatory interaction within and between basal ganglia nuclei is very often accompanied by synchronization at Parkinsonian rest tremor frequencies (3-10 Hz). These oscillations have a profound influence on thalamic projections and impair the thalamic relaying of cortical input by generating rebound action potentials.

The pedunculopontine nucleus as an additional target for deep brain stimulation.

The pedunculopontine nucleus has been suggested as a target for DBS. In this paper we propose a single compartment computational model for a PPN Type I cell and compare its dynamic behavior with experimental data. The model shows bursts after a period of hyperpolarization and spontaneous firing at 8 Hz.

Estimation of expiratory time constants via fuzzy clustering.

Objective: In mechanically ventilated patients the expiratory time constant provides information about respiratory mechanics. In the present study a new method, fuzzy clustering, is proposed to determine expiratory time constants. Fuzzy clustering differs from other methods since it neither interferes with expiration nor presumes any functional relationship between the variables analysed.

Effect of expiratory resistance on gas-exchange and breathing pattern in chronic obstructive pulmonary disease (COPD) patients being weaned from the ventilator.

Background: The majority of patients with severe chronic obstructive pulmonary disease (COPD) have flow limitation, which has deleterious side effects. If these patients are mechanically ventilated, this often results in difficult weaning. Spontaneously breathing COPD patients experience a beneficial effect of pursed lip breathing.

Detection of flow limitation in mechanically ventilated patients.

Objective: In mechanically ventilated patients flow limitation often goes unrecognised. We compared three methods for detection of flow limitation in mechanically ventilated patients: the resistance method, the negative expiratory pressure (NEP) method, and the interrupter method.

Design: Prospective study.

Effect of series of resistance levels on flow limitation in mechanically ventilated COPD patients.

In severe chronic obstructive pulmonary disease (COPD) lung emptying is disturbed by airways compression and expiratory flow limitation. Application of an external resistance has been suggested to counteract airways compression and improve lung emptying. We studied the effect of various resistance levels on lung emptying in mechanically ventilated COPD patients.

Expiratory time constants in mechanically ventilated patients with and without COPD.

Objective: In mechanically ventilated patients, the expiratory time constant provides information about the respiratory mechanics and the actual time needed for complete expiration. As an easy method to determine the time constant, the ratio of exhaled tidal volume to peak expiratory flow has been proposed. This assumes a single compartment model for the whole expiration.

Estimation of respiratory parameters via fuzzy clustering.

The results of monitoring respiratory parameters estimated from flow-pressure-volume measurements can be used to assess patients' pulmonary condition, to detect poor patient-ventilator interaction and consequently to optimize the ventilator settings. A new method is proposed to obtain detailed information about respiratory parameters without interfering with the expiration. By means of fuzzy clustering, the available data set is partitioned into fuzzy subsets that can be well approximated by linear regression models locally.