Investigation of the comparative cost-effectiveness of different strategies for the management of multidrug-resistant tuberculosis

The tuberculosis epidemic is escalating in South Africa as well as globally. This escalation is exacerbated by the increasing prevalence of multidrug-resistant tuberculosis (MDRTB), which is defined by the World Health Organisation (WHO) as resistance of Mycobacteria to at least isoniazid and rifampicin. Multi-drug resistant tuberculosis is estimated to occur in 1-2% of newly diagnosed tuberculosis (TB) patients and in 4-8% of previously treated patients. MDRTB is both difficult and expensive to treat, costing up to 126 times that of drug-sensitive TB. Resource constrained countries such as South Africa often lack both the money and the infrastructure to treat this disease. The aim of this project was to determine whether the performance of a systematic review with subsequent economic modelling could influence the decision making process for policy makers. Data was gathered and an economic evaluation of MDRTB treatment was performed from the perspective of the South African Department of Health. Three treatment alternatives were identified: a protocol regimen of second line anti-tuberculosis agents, as recommended in the South African guidelines for MDRTB, an appropriate regimen designed for each patient according to the results of culture and drug susceptibility tests, and non-drug management. A decision-analysis model using DATA 3.0 by Treeage® was developed to estimate the costs of each alternative. Outcomes were measured in terms of cost alone as well as the ‘number of cases cured’ and the number of ‘years of life saved’ for patients dying, being cured or failing treatment. Drug, hospital and laboratory costs incurred using each alternative were included in the analysis. A sensitivity analysis was performed on all variables in order to identify threshold values that would change the outcome of the evaluation. Results of the decision analysis indicate that the individualised regimen was both the cheaper and more cost-effective regimen of the two active treatment options, and was estimated to cost R50 661 per case cured and R2 070 per year of life saved. The protocol regimen was estimated to cost R73 609 per case cured and R2 741 per year of life saved. The outcome of the decision analysis was sensitive to changes in some of the variables used to model the disease, particularly the daily cost of drugs, the length of time spent in hospital and the length of treatment received by those patients dying or failing treatment. This modelling exercise highlighted significant deficiencies in the quality of evidence on MDRTB management available to policy makers. Pragmatic choices based on operational and other logistic concerns may need to be reviewed when further information becomes available. A case can be made for the establishment of a national database of costing and efficacy information to guide future policy revisions of the South African MDRTB treatment programme, which is resource intensive and of only moderate efficacy. However, due to the widely disparate range of studies on which this evaluation was based, the outcome of the study may not be credible. In this case, the use of a systematic review with subsequent economic modelling could not validly influence policy-makers to change the decision that they made on the basis of drug availability

Investigation of the comparative cost-effectiveness of different strategies for the management of multidrug-resistant tuberculosis

The tuberculosis epidemic is escalating in South Africa as well as globally. This escalation is exacerbated by the increasing prevalence of multidrug-resistant tuberculosis (MDRTB), which is defined by the World Health Organisation (WHO) as resistance of Mycobacteria to at least isoniazid and rifampicin. Multi-drug resistant tuberculosis is estimated to occur in 1-2% of newly diagnosed tuberculosis (TB) patients and in 4-8% of previously treated patients. MDRTB is both difficult and expensive to treat, costing up to 126 times that of drug-sensitive TB. Resource constrained countries such as South Africa often lack both the money and the infrastructure to treat this disease. The aim of this project was to determine whether the performance of a systematic review with subsequent economic modelling could influence the decision making process for policy makers. Data was gathered and an economic evaluation of MDRTB treatment was performed from the perspective of the South African Department of Health. Three treatment alternatives were identified: a protocol regimen of second line anti-tuberculosis agents, as recommended in the South African guidelines for MDRTB, an appropriate regimen designed for each patient according to the results of culture and drug susceptibility tests, and non-drug management. A decision-analysis model using DATA 3.0 by Treeage® was developed to estimate the costs of each alternative. Outcomes were measured in terms of cost alone as well as the ‘number of cases cured’ and the number of ‘years of life saved’ for patients dying, being cured or failing treatment. Drug, hospital and laboratory costs incurred using each alternative were included in the analysis. A sensitivity analysis was performed on all variables in order to identify threshold values that would change the outcome of the evaluation. Results of the decision analysis indicate that the individualised regimen was both the cheaper and more cost-effective regimen of the two active treatment options, and was estimated to cost R50 661 per case cured and R2 070 per year of life saved. The protocol regimen was estimated to cost R73 609 per case cured and R2 741 per year of life saved. The outcome of the decision analysis was sensitive to changes in some of the variables used to model the disease, particularly the daily cost of drugs, the length of time spent in hospital and the length of treatment received by those patients dying or failing treatment. This modelling exercise highlighted significant deficiencies in the quality of evidence on MDRTB management available to policy makers. Pragmatic choices based on operational and other logistic concerns may need to be reviewed when further information becomes available. A case can be made for the establishment of a national database of costing and efficacy information to guide future policy revisions of the South African MDRTB treatment programme, which is resource intensive and of only moderate efficacy. However, due to the widely disparate range of studies on which this evaluation was based, the outcome of the study may not be credible. In this case, the use of a systematic review with subsequent economic modelling could not validly influence policy-makers to change the decision that they made on the basis of drug availability

The Mysterious Affair of the H2_2 in AU Mic

Molecular hydrogen is the most abundant molecule in the Galaxy and plays important roles for planets, their circumstellar environments, and many of their host stars. We have confirmed the presence of molecular hydrogen in the AU Mic system using high-resolution FUV spectra from HST-STIS during both quiescence and a flare. AU Mic is a $\sim$23 Myr M dwarf which hosts a debris disk and at least two planets. We estimate the temperature of the gas at 1000 to 2000 K, consistent with previous detections. Based on the radial velocities and widths of the H$_2$ line profiles and the response of the H$_2$ lines to a stellar flare, the H$_2$ line emission is likely produced in the star, rather than in the disk or the planet. However, the temperature of this gas is significantly below the temperature of the photosphere ($\sim$3650 K) and the predicted temperature of its star spots ($\gtrsim$2650 K). We discuss the possibility of colder star spots or a cold layer in the photosphere of a pre-main sequence M dwarf.Comment: accepted to ApJ, 20 pages, many figure

A Lyα Transit Left Undetected: The Environment and Atmospheric Behavior of K2-25b

K2-25b is a Neptune-sized exoplanet (3.45R ⊙) that orbits its M4.5 host with a period of 3.48 days. Due to its membership in the Hyades Cluster, the system has a known age (727 ± 75 Myr). K2-25b's youth and its similarities with Gl 436b suggested that K2-25b could be undergoing strong atmospheric escape. We observed two transits of K2-25b at Lyα using HST/STIS in order to search for escaping neutral hydrogen. We were unable to detect an exospheric signature, but placed an upper limit of (R p/R ⊙)|Ly α < 0.56 at 95% confidence by fitting the light curve of the Lyα red wing, or < 1.20 in the blue wing. We reconstructed the intrinsic Lyα profile of K2-25 to determine its Lyα flux, and analyzed XMM-Newton observations to determined its X-ray flux. Based on the total X-ray and extreme ultraviolet irradiation of the planet (8763 ± 1049 erg s-1 cm-2), we estimated the maximum energy-limited mass-loss rate of K2-25b to be 10.6-6.13+15.2}×1010 g s-1 (0.56M ⊙ per 1 Gyr), five times larger than the similarly estimated mass-loss rate of Gl 436b (2.2 ± 1010 g s-1). The photoionization time is about 3 hr, significantly shorter than Gl 436b's 14 hr. A nondetection of a Lyα transit could suggest K2-25b is not significantly losing its atmosphere, or factors of the system are resulting in the mass loss being unobservable (e.g., atmosphere composition or the system's large high-energy flux). Further observations could provide more stringent constraints

Theorising international youth volunteering: training for global (corporate) work?

Ongoing globalisation poses a distinct challenge to how we understand what work ‘is’ in the contemporary world. Theoretical distinctions between the spatialities and temporalities of work as a practice have become blurred, along with understandings of work purely as an economic rather than a socio-cultural phenomenon. Building on theoretical approaches within geography and the ‘new sociology of work’, this paper argues that the transformation of work produced by contemporary globalisation requires a more sophisticated and geographically informed understanding of the spatiality of work as a practice. It develops this contention by presenting research into a specific kind of (unconventional) work – international youth volunteering. It argues that this form of work has a complex spatiality, whose constitution and impacts exceed the specific material location of workers in both space and time. Furthermore, it examines how this ‘multiplex mode’ of work practice destabilises the relationship between work and non-work, and facilitates the development of cultural capital, self-identity and skills in young people. It also contends that this form of voluntary work is embedded in the emerging needs of global labour markets. These arguments are elaborated through the presentation of research from a longitudinal project on the impacts of international youth volunteering. This research consists of data from interviews and focus groups with young people who undertook a range of different types of overseas voluntary work placement, and interviews with corporate recruiters in leading transnational firms concerning their understanding of the value (or otherwise) of international volunteering

TESS Hunt for Young and Maturing Exoplanets (THYME). III. A Two-planet System in the 400 Myr Ursa Major Group

Exoplanets can evolve significantly between birth and maturity as their atmospheres, orbits, and structures are shaped by their environment. Young planets ($<$1 Gyr) offer the opportunity to probe these sculpting processes. However, most of the known young planets orbit prohibitively faint stars. We present the discovery of two planets transiting HD 63433 (TOI 1726, TIC 130181866), a young Sun-like ($M_*=0.99\pm0.03$) star. Through kinematics, lithium abundance, and rotation, we confirm that HD 63433 is a member of the Ursa Major moving group ($\tau=414\pm23$ Myr). Based on the TESS light curve and updated stellar parameters, the planet radii are $2.15\pm0.10R_\oplus$ and $2.67\pm0.12R_\oplus$, the orbital periods are 7.11 and 20.55 days, and the orbital eccentricities are lower than abut 0.2. Using HARPS-N velocities, we measure the Rossiter-McLaughlin signal of the inner planet, demonstrating the orbit is prograde. Since the host star is bright (V=6.9), both planets are amenable to transmission spectroscopy, radial velocity measurements of their masses, and more precise determination of the stellar obliquity. This system is therefore poised to play an important role in our understanding of planetary system evolution in the first billion years after formation

TESS hunt for young and maturing exoplanets (THYME). III. A two-planet system in the 400 Myr Ursa major group

A.W.M. was supported through NASA's Astrophysics Data Analysis Program (80NSSC19K0583). M.L.W. was supported by a grant through NASA's K2 GO program (80NSSC19K0097). This material is based on work supported by the National Science Foundation Graduate Research Fellowship Program under grant No. DGE-1650116 to P.C.T. A.V.'s work was performed under contract with the California Institute of Technology/Jet Propulsion Laboratory funded by NASA through the Sagan Fellowship Program executed by the NASA Exoplanet Science Institute. D.D. acknowledges support from NASA through Caltech/JPL grant RSA-1006130 and through the TESS Guest Investigator Program grant 80NSSC19K1727.Exoplanets can evolve significantly between birth and maturity, as their atmospheres, orbits, and structures are shaped by their environment. Young planets (<1 Gyr) offer an opportunity to probe the critical early stages of this evolution, where planets evolve the fastest. However, most of the known young planets orbit prohibitively faint stars. We present the discovery of two planets transiting HD 63433 (TOI 1726, TIC 130181866), a young Sun-like (M∗=0.99±0.03) star. Through kinematics, lithium abundance, and rotation, we confirm that HD 63433 is a member of the Ursa Major moving group (τ=414±23 Myr). Based on the TESS light curve and updated stellar parameters, we estimate the planet radii are 2.15±0.10R⊕ and 2.67±0.12R⊕, the orbital periods are 7.11 and 20.55 days, and the orbital eccentricities are lower than about 0.2. Using HARPS-N velocities, we measure the Rossiter-McLaughlin signal of the inner planet, demonstrating that the orbit is prograde. Since the host star is bright (V=6.9), both planets are amenable to transmission spectroscopy, radial velocity measurements of their masses, and more precise determination of the stellar obliquity. This system is therefore poised to play an important role in our understanding of planetary system evolution in the first billion years after formation.PostprintPeer reviewe