Publications by authors named "Bronwyn Smith"

8 Publications

  • Page 1 of 1

Quantitative 18F-FDG PET-CT scan characteristics correlate with tuberculosis treatment response.

EJNMMI Res 2020 Feb 10;10(1). Epub 2020 Feb 10.

Department of Science and Technology/National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Cape Town, South Africa.

Background: There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes.

Results: Quantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions.

Conclusions: Quantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities.
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February 2020

Diagnostic Accuracy of Early Secretory Antigenic Target-6-Free Interferon-gamma Release Assay Compared to QuantiFERON-TB Gold In-tube.

Clin Infect Dis 2019 10;69(10):1724-1730

Statens Serum Institute, Copenhagen, Denmark.

Background: Early secretory antigenic target-6 (ESAT-6) is an immunodominant Mycobacterium tuberculosis (M.tb) antigen included in novel vaccines against tuberculosis (TB) and in interferon-gamma (IFN-γ) release assays (IGRAs). Therefore, the availability of an ESAT-6-free IGRA is essential to determine M.tb infection status following vaccination with ESAT-6-containing vaccines. We aimed to qualify a recently developed ESAT-6-free IGRA and to assess its diagnostic performance in comparison to QuantiFERON-TB Gold In-tube (QFT).

Methods: Participants with different levels of M.tb exposure and TB disease were enrolled to determine the ESAT-6-free IGRA cutoff, test assay performance in independent cohorts compared to standard QFT, and perform a technical qualification of antigen-coated blood collection tubes.

Results: ESAT-6-free IGRA antigen recognition was evaluated in QFT-positive and QFT-negative South African adolescents. The ESAT-6-free IGRA cutoff was established at 0.61 IU/mL, based on receiver operating characteristic analysis in M.tb-unexposed controls and microbiologically confirmed pulmonary TB patients. In an independent cohort of healthy adolescents, levels of IFN-γ released in QFT and ESAT-6-free IGRA were highly correlated (P < .0001, r = 0.83) and yielded comparable positivity rates, 41.5% and 43.5%, respectively, with 91% concordance between the tests (kappa = 0.82; 95% confidence interval, 0.74-0.90; McNemar test P = .48). ESAT-6-free IGRA blood collection tubes had acceptable lot-to-lot variability, precision, and stability.

Conclusions: The novel ESAT-6-free IGRA had diagnostic accuracy comparable to QFT and is suitable for use in clinical trials to assess efficacy of candidate TB vaccines to prevent established M.tb infection.
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October 2019

A systematic review of the experiences of vulnerable people participating in research on sensitive topics.

Int J Nurs Stud 2018 Dec 3;88:85-96. Epub 2018 Sep 3.

Western Sydney University, Locked Bag 1797, Penrith NSW 2751, Australia. Electronic address:

Objective: The aim of this paper is to systematically review studies that discuss the experiences of vulnerable populations participating in research on sensitive topics.

Design: Systematic review performed according to PRISMA guidelines.

Data Sources: Thirteen databases were searched, locating 197 articles. Following removal of duplicates, screening and full text review, 31 studies remained to be critically appraised.

Review Methods: As there was a mix of qualitative and quantitative articles, the Critical Appraisal Skills Program (CASP) toolkit and Effective Public Health Practice Project (EPHPP) tool were used to appraise the methodological quality of the articles. Following critical appraisal, the remaining 11 articles were synthesised narratively to identify common themes across the studies.

Results: Despite some reports of distress, responses from participants were overwhelmingly positive. There was a strong link between symptomatology and potential for distress; however, the majority of those who did experience some level of discomfort stated they would still participate in future research. Three major themes were extracted: "It was worth it"; "Even if it hurt, I would do it again" and "Risk or benefit: fixing the location on the continuum".

Conclusion: Although researchers frequently experience obstacles and the phenomenon known as "gatekeeping" when attempting to conduct research amongst vulnerable populations, there is little evidence of harm to participants. On the contrary, there is evidence of benefit for participants and evidence that they are willing to participate if given the opportunity. Although well-meaning, the actions of gatekeepers are not only paternalistic, they could be further marginalising vulnerable populations by denying them the benefits to be gained from research designed to identify and begin addressing their needs.
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December 2018

Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial.

Gates Open Res 2017 Nov 6;1. Epub 2017 Nov 6.

Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

: By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment. : This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C. : Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified.

Trial Registration: NCT02821832.
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November 2017

Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of Mycobacterium tuberculosis Infection.

Am J Respir Crit Care Med 2017 09;196(5):638-648

1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and.

Rationale: Conversion from a negative to positive QuantiFERON-TB test is indicative of Mycobacterium tuberculosis (Mtb) infection, which predisposes individuals to tuberculosis disease. Interpretation of serial tests is confounded by immunological and technical variability.

Objectives: To improve the consistency of serial QuantiFERON-TB testing algorithms and provide a data-driven definition of conversion.

Methods: Sources of QuantiFERON-TB variability were assessed, and optimal procedures were identified. Distributions of IFN-γ response levels were analyzed in healthy adolescents, Mtb-unexposed control subjects, and patients with pulmonary tuberculosis.

Measurements And Main Results: Individuals with no known Mtb exposure had IFN-γ values less than 0.2 IU/ml. Among individuals with IFN-γ values less than 0.2 IU/ml, 0.2-0.34 IU/ml, 0.35-0.7 IU/ml, and greater than 0.7 IU/ml, tuberculin skin test positivity results were 15%, 53%, 66%, and 91% (P < 0.005), respectively. Together, these findings suggest that values less than 0.2 IU/ml were true negatives. In short-term serial testing, "uncertain" conversions, with at least one value within the uncertainty zone (0.2-0.7 IU/ml), were partly explained by technical assay variability. Individuals who had a change in QuantiFERON-TB IFN-γ values from less than 0.2 to greater than 0.7 IU/ml had 10-fold higher tuberculosis incidence rates than those who maintained values less than 0.2 IU/ml over 2 years (P = 0.0003). By contrast, "uncertain" converters were not at higher risk than nonconverters (P = 0.229). Eighty-seven percent of patients with active tuberculosis had IFN-γ values greater than 0.7 IU/ml, suggesting that these values are consistent with established Mtb infection.

Conclusions: Implementation of optimized procedures and a more rigorous QuantiFERON-TB conversion definition (an increase from IFN-γ <0.2 to >0.7 IU/ml) would allow more definitive detection of recent Mtb infection and potentially improve identification of those more likely to develop disease.
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September 2017

Prevalence and determinants of cessation of exclusive breastfeeding in the early postnatal period in Sydney, Australia.

Int Breastfeed J 2016 8;12:16. Epub 2017 Apr 8.

Ingham Institute for Applied Medical Research, Liverpool, NSW Australia.

Background: Optimal breastfeeding has benefits for the mother-infant dyads. This study investigated the prevalence and determinants of cessation of exclusive breastfeeding (EBF) in the early postnatal period in a culturally and linguistically diverse population in Sydney, New South Wales, Australia.

Methods: The study used routinely collected perinatal data on all live births in 2014 ( = 17,564) in public health facilities in two Local Health Districts in Sydney, Australia. The prevalence of mother's breastfeeding intention, skin-to-skin contact, EBF at birth, discharge and early postnatal period (1-4 weeks postnatal) were estimated. Multivariate logistic regression models that adjusted for confounders were conducted to determine association between cessation of EBF in the early postnatal period and socio-demographic, psychosocial and health service factors.

Results: Most mothers intended to breastfeed (92%), practiced skin-to-skin contact (81%), exclusively breastfed  at delivery (90%) and discharge (89%). However, the prevalence of EBF declined (by 27%) at the early postnatal period (62%). Younger mothers (<20 years) and mothers who smoked cigarettes in pregnancy were more likely to cease EBF in the early postnatal period compared to older mothers (20-39 years) and those who reported not smoking cigarettes, respectively [Adjusted Odds Ratio (AOR) =2.7, 95%CI 1.9-3.8, <0.001 and AOR = 2.5, 95%CI 2.1-3.0, <0.001, respectively]. Intimate partner violence, assisted delivery, low socio-economic status, pre-existing maternal health problems and a lack of partner support were also associated with early cessation of EBF in the postnatal period.

Conclusions: Our findings suggest that while most mothers intend to breastfeed, and commence EBF at delivery and at discharge, the maintenance of EBF in the early postnatal period is sub-optimal. This highlights the need for efforts to promote breastfeeding in the wider community along with targeted actions for disadvantaged groups and those identified to be at risk of early cessation of EBF to maximise impact.
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April 2017

Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure.

Nat Med 2016 10 5;22(10):1094-1100. Epub 2016 Sep 5.

National Medical Center, Seoul, South Korea.

The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.
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October 2016

Nursing practice environment: how does one Australian hospital compare with magnet hospitals?

Int J Nurs Pract 2008 Oct;14(5):366-72

Nursing Research Unit, St Vincents & Mater Health, and Professor of Nursing, School of Nursing (NSW & ACT), ACU National, North Sydney, NSW, Australia.

Magnet hospitals are recognized institutions of nursing excellence that provide an environment for the promotion of nursing and high-quality patient care. The Magnet Recognition Program, developed by the American Nurses Credentialing Centre, acknowledges health-care institutions that not only attract and retain nursing staff but also recognize nursing excellence in the delivery of quality patient care. Our study aimed to adapt the existing Practice Environment Scale to the Australian context and to pilot its use in measuring the nursing practice environment at a metropolitan hospital in Sydney, Australia. Nursing staff from four wards at a 400 bed major metropolitan acute general hospital in Sydney, Australia completed a self-administered questionnaire about their practice environment. Data were compared with the published norms from magnet and non-magnet hospitals in the USA, and means of two subscales were not significantly different from magnet hospital means. Hospitals could benefit from undertaking a similar practice environment baseline measure prior to applying for accreditation, thus enabling targeting of pre-identified service gaps and areas for improvement.
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October 2008