Treatment fidelity in clinical trials.

In the context of clinical trials, treatment fidelity (TF) has traditionally referred to the extent to which an intervention or treatment is implemented by the clinicians as intended by the researchers who designed the trial. Updated definitions of TF have included an appropriate design of the intervention that was performed in a way that is known to be therapeutically beneficial. This requires careful attention to three key components: (1) protocol and dosage adherence, (2) quality of delivery, and (3) participant adherence.

The Hidden Epidemic of Isoniazid-Resistant Tuberculosis in South Africa.

Isoniazid-resistant tuberculosis (Hr-TB) is often overlooked in diagnostic algorithms because of reliance on first-line molecular assays testing only for rifampicin resistance. To determine the prevalence, outcomes, and molecular mechanisms associated with rifampin-susceptible, isoniazid-resistant TB (Hr-TB) in the Eastern Cape, South Africa. Between April 2016 and October 2017, sputum samples were collected from patients with rifampin-susceptible TB at baseline and at Weeks 7 and 23 of drug-susceptible TB treatment.

Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis.

Background: Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating treatment. We conducted a literature assessment on the efficacy of bedaquiline in treating NTM species in vitro and in vivo (animal models and humans); meta-analyses were performed where possible.

Evaluation of Transparency and Openness Guidelines in Physical Therapist Journals.

Objective: The goals of this study were to evaluate the extent that physical therapist journals support open science research practices by adhering to the Transparency and Openness Promotion (TOP) guidelines and to assess the relationship between journal scores and their respective journal impact factor (JIF).

Methods: Scimago, mapping studies, the National Library of Medicine, and journal author guidelines were searched to identify physical therapist journals for inclusion. Journals were graded on 10 standards (29 available total points) related to transparency with data, code, research materials, study design and analysis, preregistration of studies and statistical analyses, replication, and open science badges.

Site-directed mutagenesis of Mycobacterium tuberculosis and functional validation to investigate potential bedaquiline resistance-causing mutations.

Molecular detection of bedaquiline resistant tuberculosis is challenging as only a small proportion of mutations in candidate bedaquiline resistance genes have been statistically associated with phenotypic resistance. We introduced two mutations, atpE Ile66Val and Rv0678 Thr33Ala, in the Mycobacterium tuberculosis H37Rv reference strain using homologous recombineering or recombination to investigate the phenotypic effect of these mutations. The genotype of the resulting strains was confirmed by Sanger- and whole genome sequencing, and bedaquiline susceptibility was assessed by minimal inhibitory concentration (MIC) assays.

The relationships between pain-associated psychological distress, pain intensity, patient expectations, and physical function in individuals with musculoskeletal pain: A retrospective cohort study.

Introduction: The presence of pain-associated psychological distress (PAPD) in musculoskeletal disorders, including negative mood, fear-avoidance, and lack of positive affect/coping, is associated with prolonged disability. The importance of considering psychological influence on pain is well known, but practical ways of addressing it are not as straightforward. Identifying relationships between PAPD and pain intensity, patient expectations, and physical function may guide the development of future studies that assess causality and inform clinical practice.

COVID-19 detection in cough, breath and speech using deep transfer learning and bottleneck features.

We present an experimental investigation into the effectiveness of transfer learning and bottleneck feature extraction in detecting COVID-19 from audio recordings of cough, breath and speech. This type of screening is non-contact, does not require specialist medical expertise or laboratory facilities and can be deployed on inexpensive consumer hardware such as a smartphone. We use datasets that contain cough, sneeze, speech and other noises, but do not contain COVID-19 labels, to pre-train three deep neural networks: a CNN, an LSTM and a Resnet50.

Automatic cough classification for tuberculosis screening in a real-world environment.

The automatic discrimination between the coughing sounds produced by patients with tuberculosis (TB) and those produced by patients with other lung ailments.We present experiments based on a dataset of 1358 forced cough recordings obtained in a developing-world clinic from 16 patients with confirmed active pulmonary TB and 35 patients suffering from respiratory conditions suggestive of TB but confirmed to be TB negative. Using nested cross-validation, we have trained and evaluated five machine learning classifiers: logistic regression (LR), support vector machines, k-nearest neighbour, multilayer perceptrons and convolutional neural networks.

COVID-19 cough classification using machine learning and global smartphone recordings.

We present a machine learning based COVID-19 cough classifier which can discriminate COVID-19 positive coughs from both COVID-19 negative and healthy coughs recorded on a smartphone. This type of screening is non-contact, easy to apply, and can reduce the workload in testing centres as well as limit transmission by recommending early self-isolation to those who have a cough suggestive of COVID-19. The datasets used in this study include subjects from all six continents and contain both forced and natural coughs, indicating that the approach is widely applicable.

MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era.

Background: Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini.

Methods: We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009-2010; (2) MDR strains from the Nhlangano region, 2014-2017).

Results: MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40).

The correlation between hair and eye colour and contralateral suppression of otoacoustic emissions.

Unlabelled: Genetics and environmental factors frequently influence individual's susceptibility to hearing loss. It is postulated that melanin in the inner ear is related to individual's susceptibility to noise induced hearing loss (NIHL). General pigmentation in turn, suspected to be related to the amount of pigmentation in the inner ear.

A landscape of genomic alterations at the root of a near-untreatable tuberculosis epidemic.

Background: Atypical Beijing genotype Mycobacterium tuberculosis strains are widespread in South Africa and have acquired resistance to up to 13 drugs on multiple occasions. It is puzzling that these strains have retained fitness and transmissibility despite the potential fitness cost associated with drug resistance mutations.

Methods: We conducted Illumina sequencing of 211 Beijing genotype M.

Detection of tuberculosis by automatic cough sound analysis.

Objective: Globally, tuberculosis (TB) remains one of the most deadly diseases. Although several effective diagnosis methods exist, in lower income countries clinics may not be in a position to afford expensive equipment and employ the trained experts needed to interpret results. In these situations, symptoms including cough are commonly used to identify patients for testing.

Isoniazid Resistance and Dosage as Treatment for Patients with Tuberculosis.

Background: The first-line TB antibiotic isoniazid (INH) serves as a central component of combined first-line anti-tuberculosis drug therapy. However, resistance to INH has hindered the functioning of this drug. Resistance is caused by several known and unknown mutations in genes/regions in Mycobacterium tuberculosis (M.

Epistasis between antibiotic resistance mutations drives the evolution of extensively drug-resistant tuberculosis.

Background And Objectives: Multidrug resistant (MDR) bacteria are a growing threat to global health. Studies focusing on single antibiotics have shown that drug resistance is often associated with a fitness cost in the absence of drug. However, little is known about the fitness cost associated with resistance to multiple antibiotics.

Programmatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africa.

Background: South Africa shows one of the highest global burdens of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). Since 2002, MDR-TB in South Africa has been treated by a standardized combination therapy, which until 2010 included ofloxacin, kanamycin, ethionamide, ethambutol and pyrazinamide. Since 2010, ethambutol has been replaced by cycloserine or terizidone.

The rationale for using rifabutin in the treatment of MDR and XDR tuberculosis outbreaks.

Genetically related Mycobacterium tuberculosis strains with alterations at codon 516 in the rpoB gene were observed amongst a substantial number of patients with drug resistant tuberculosis in the Eastern Cape Province (ECP) of South Africa. Mutations at codon 516 are usually associated with lower level rifampicin (RIF) resistance, while susceptibility to rifabutin (RFB) remains intact. This study was conducted to assess the rationale for using RFB as a substitution for RIF in the treatment of MDR and XDR tuberculosis outbreaks.

BDNF Val66Met and DRD2 Taq1A polymorphisms interact to influence PTSD symptom severity: a preliminary investigation in a South African population.

Background: We evaluated the role that selected variants in serotonin transporter (5-HTT), dopamine receptor 2 (DRD2) and brain-derived neurotrophic factor (BDNF) genes play in PTSD symptom severity in an at-risk population. We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms.

Methods: PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population.