Empiric treatment of pulmonary TB in the Xpert era: Correspondence of sputum culture, Xpert MTB/RIF, and clinical diagnoses.

BackgroundClinical tuberculosis diagnosis and empiric treatment have traditionally been common among patients with negative bacteriologic test results. Increasing availability of rapid molecular diagnostic tests, including Xpert MTB/RIF and the new Xpert Ultra cartridge, may alter the role of empiric treatment.MethodsWe prospectively enrolled outpatients age > = 15 who were evaluated for pulmonary tuberculosis at three health facilities in Kampala, Uganda. Using sputum mycobacterial culture, interviews, and clinical record abstraction, we estimated the accuracy of clinical diagnosis relative to Xpert and sputum culture and assessed the contribution of clinical diagnosis to case detection.ResultsOver a period of 9 months, 99 patients were diagnosed with pulmonary tuberculosis and subsequently completed sputum culture; they were matched to 196 patients receiving negative tuberculosis evaluations in the same facilities. Xpert was included in the evaluation of 291 (99%) patients. Compared to culture, Xpert had a sensitivity of 92% (95% confidence interval 83-97%) and specificity of 95% (92-98%). Twenty patients with negative Xpert were clinically diagnosed with tuberculosis and subsequently had their culture status determined; two (10%) were culture-positive. Considering all treated patients regardless of Xpert and culture data completeness, and considering treatment initiations before a positive Xpert (N = 4) to be empiric, 26/101 (26%) tuberculosis treatment courses were started empirically. Compared to sputum smear- or Xpert-positive patients with positive cultures, empirically-treated, Xpert-negative patients with negative cultures had higher prevalence of HIV (67% versus 37%), shorter duration of cough (median 4 versus 8 weeks), and lower inflammatory markers (median CRP 7 versus 101 mg/L).ConclusionJudged against sputum culture in a routine care setting of high HIV prevalence, the accuracy of Xpert was high. Clinical judgment identified a small number of additional culture-positive cases, but with poor specificity. Although clinicians should continue to prescribe tuberculosis treatment for Xpert-negative patients whose clinical presentations strongly suggest pulmonary tuberculosis, they should also carefully consider alternative diagnoses

Radiation detectors as surveillance monitors for IAEA safeguards

Radiation detectors used for personnel dosimetry are examined for use under IAEA Safeguards as monitors to confirm the passage or nonpassage (YES/NO) of plutonium-bearing nuclear material at barrier penetrations declared closed. In this application where backgrounds are ill defined, no advantage is found for a particular detector type because of intrinsic efficiency. Secondary considerations such as complexity, ease of tamper-proofing, and ease of readout are used to recommend specific detector types for routine monitoring and for data-base measurements. Recommendations are made for applications, data acquisition, and instrument development

The relevance of ERTS-1 data to the state of Ohio

There are no author-identified significant results in this report

Higher cost of implementing Xpert(®) MTB/RIF in Ugandan peripheral settings: implications for cost-effectiveness.

SETTING: Initial cost-effectiveness evaluations of Xpert(®) MTB/RIF for tuberculosis (TB) diagnosis have not fully accounted for the realities of implementation in peripheral settings. OBJECTIVE: To evaluate costs and diagnostic outcomes of Xpert testing implemented at various health care levels in Uganda. DESIGN: We collected empirical cost data from five health centers utilizing Xpert for TB diagnosis, using an ingredients approach. We reviewed laboratory and patient records to assess outcomes at these sites and10 sites without Xpert. We also estimated incremental cost-effectiveness of Xpert testing; our primary outcome was the incremental cost of Xpert testing per newly detected TB case. RESULTS: The mean unit cost of an Xpert test was US$21 based on a mean monthly volume of 54 tests per site, although unit cost varied widely (US$16-58) and was primarily determined by testing volume. Total diagnostic costs were 2.4-fold higher in Xpert clinics than in non-Xpert clinics; however, Xpert only increased diagnoses by 12%. The diagnostic costs of Xpert averaged US$119 per newly detected TB case, but were as high as US$885 at the center with the lowest volume of tests. CONCLUSION: Xpert testing can detect TB cases at reasonable cost, but may double diagnostic budgets for relatively small gains, with cost-effectiveness deteriorating with lower testing volumes

The contributions of fronts, lows and thunderstorms to southern Australian rainfall

This is the final version. Available from the publisher via the DOI in this record.The correction to this article is available in ORE at http://hdl.handle.net/10871/126081A systematic analysis of the main weather types influencing southern Australian rainfall is presented for the period 1979–2015. This incorporates two multi-method datasets of cold fronts and low pressure systems, which indicate the more robust fronts and lows as distinguished from the weaker and less impactful events that are often indicated only by a single method. The front and low pressure system datasets are then combined with a dataset of environmental conditions associated with thunderstorms, as well as datasets of warm fronts and high pressure systems. The results demonstrate that these weather types collectively account for about 86% of days and more than 98% of rainfall in Australia south of 25° S. We also show how the key rain-bearing weather systems vary throughout the year and for different regions, with the co-occurrence of simultaneous lows, fronts and thunderstorm conditions particularly important during the spring and summer months in southeast Australia

Modelling the impact of social protection on tuberculosis: the S-PROTECT project.

BACKGROUND: Tackling the social determinants of Tuberculosis (TB) through social protection is a key element of the post-2015 End TB Strategy. However, evidence informing policies are still scarce. Mathematical modelling has the potential to contribute to fill this knowledge gap, but existing models are inadequate. The S-PROTECT consortium aimed to develop an innovative mathematical modelling approach to better understand the role of social protection to improve TB care, prevention and control. METHODS: S-PROTECT used a three-steps approach: 1) the development of a conceptual framework; 2) the extraction from this framework of three high-priority mechanistic pathways amenable for modelling; 3) the development of a revised version of a standard TB transmission model able to capture the structure of these pathways. As a test case we used the Bolsa Familia Programme (BFP), the Brazilian conditional cash transfer scheme. RESULTS: Assessing one of these pathways, we estimated that BFP can reduce TB prevalence by 4% by improving households income and thus their nutritional status. When looking at the direct impact via malnutrition (not income mediated) the impact was 33%. This variation was due to limited data availability, uncertainties on data transformation and the pathway approach taken. These results are preliminary and only aim to serve as illustrative example of the methodological challenges encountered in this first modelling attempt, nonetheless they suggest the potential added value of integrating TB standard of care with social protection strategies. CONCLUSIONS: Results are to be confirmed with further analysis. However, by developing a generalizable modelling framework, S-PROTECT proved that the modelling of social protection is complex, but doable and allowed to draw the research road map for the future in this field

Multi-decadal increase of forest burned area in Australia is linked to climate change

Fire activity in Australia is strongly affected by high inter-annual climate variability and extremes. Through changes in the climate, anthropogenic climate change has the potential to alter fire dynamics. Here we compile satellite (19 and 32 years) and ground-based (90 years) burned area datasets, climate and weather observations, and simulated fuel loads for Australian forests. Burned area in Australia’s forests shows a linear positive annual trend but an exponential increase during autumn and winter. The mean number of years since the last fire has decreased consecutively in each of the past four decades, while the frequency of forest megafire years (>1 Mha burned) has markedly increased since 2000. The increase in forest burned area is consistent with increasingly more dangerous fire weather conditions, increased risk factors associated with pyroconvection, including fire-generated thunderstorms, and increased ignitions from dry lightning, all associated to varying degrees with anthropogenic climate change

Feasibility of a streamlined tuberculosis diagnosis and treatment initiation strategy.

OBJECTIVE: To assess the feasibility of a streamlined strategy for improving tuberculosis (TB) diagnostic evaluation and treatment initiation among patients with presumed TB. DESIGN: Single-arm interventional pilot study at five primary care health centers of a streamlined, SIngle-saMPLE (SIMPLE) TB diagnostic evaluation strategy: 1) examination of two smear results from a single spot sputum specimen using light-emitting diode fluorescence microscopy, and 2) daily transportation of smear-negative sputum samples to Xpert® MTB/RIF testing sites. RESULTS: Of 1212 adults who underwent sputum testing for TB, 99.6% had two smears examined from the spot sputum specimen. Sputum was transported for Xpert testing within 1 clinic day for 83% (907/1091) of the smear-negative patients. Of 157 (13%) patients with bacteriologically positive TB, 116 (74%) were identified using sputum smear microscopy and 41 (26%) using Xpert testing of smear-negative samples. Anti-tuberculosis treatment was initiated in 142 (90%) patients with bacteriologically positive TB, with a median time to treatment of 1 day for smear-positive patients and 6 days for smear-negative, Xpert-positive patients. CONCLUSION: The SIMPLE TB strategy led to successful incorporation of Xpert testing and rapid treatment initiation in the majority of patients with bacteriologically confirmed TB in a resource-limited setting