TSH-CHECK-1 test: diagnostic accuracy and potential application to initiating treatment for hypothyroidism in patients on anti-tuberculosis drugs.

Thyroid-stimulating hormone (TSH) promotes expression of thyroid hormones which are essential for metabolism, growth, and development. Second-line drugs to treat tuberculosis (TB) can cause hypothyroidism by suppressing thyroid hormone synthesis. Therefore, TSH levels are routinely measured in TB patients receiving second-line drugs, and thyroxin treatment is initiated where indicated. However, standard TSH tests are technically demanding for many low-resource settings where TB is prevalent; a simple and inexpensive test is urgently needed

Guidelines for the use of chest radiographs in community-acquired pneumonia in children and adolescents

© 2017, The Author(s). National guidance from the United Kingdom and the United States on community-acquired pneumonia in children states that chest radiographs are not recommended routinely in uncomplicated cases. The main reason in the ambulatory setting is that there is no evidence of a substantial impact on clinical outcomes. However clinical practice and adherence to guidance is multifactorial and includes the clinical context (developed vs. developing world), the confidence of the attending physician, the changing incidence of complications (according to the success of immunisation programs), the availability of alternative imaging (and its relationship to perceived risks of radiation) and the reliability of the interpretation of imaging. In practice, chest radiographs are performed frequently for suspected pneumonia in children. Time pressures facing clinicians at the front line, difficulties in distinguishing which children require admission, restricted bed numbers for admissions, imaging-resource limitations, perceptions regarding risk from procedures, novel imaging modalities and the probability of other causes for the child’s presentation all need to be factored into a guideline. Other drivers that often weigh in, depending on the setting, include cost-effectiveness and the fear of litigation. Not all guidelines designed for the developed world can therefore be applied to the developing world, and practice guidelines require regular review in the context of new information. In addition, radiologists must improve radiographic diagnosis of pneumonia, reach consensus on the interpretive terminology that clarifies their confidence regarding the presence of pneumonia and act to replace one imaging technique with another whenever there is proof of improved accuracy or reliability

The 2010 very high energy gamma-ray flare & 10 years of multi-wavelength observations of M 87

Abridged: The giant radio galaxy M 87 with its proximity, famous jet, and very massive black hole provides a unique opportunity to investigate the origin of very high energy (VHE; E>100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of super-massive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (~day), peak fluxes (Phi(>0.35 TeV) ~= (1-3) x 10^-11 ph cm^-2 s^-1), and VHE spectra. 43 GHz VLBA radio observations of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken ~3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core. The long-term (2001-2010) multi-wavelength light curve of M 87, spanning from radio to VHE and including data from HST, LT, VLA and EVN, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified.Comment: 19 pages, 5 figures; Corresponding authors: M. Raue, L. Stawarz, D. Mazin, P. Colin, C. M. Hui, M. Beilicke; Fig. 1 lightcurve data available online: http://www.desy.de/~mraue/m87

A guide to aid the selection of diagnostic tests

In recent years, a wide range of diagnostic tests has become available for use in resource-constrained settings. Accordingly, a huge number of guidelines, performance evaluations and implementation reports have been produced. However, this wealth of information is unstructured and of uneven quality, which has made it difficult for end-users, such as clinics, laboratories and health ministries, to determine which test would be best for improving clinical care and patient outcomes in a specific context. This paper outlines a six-step guide to the selection and implementation of in vitro diagnostic tests based on Medecins Sans Frontieres practical experience: (i) define the test's purpose; (ii) review the market; (iii) ascertain regulatory approval; (iv) determine the test's diagnostic accuracy under ideal conditions; (v) determine the test's diagnostic accuracy in clinical practice; and (vi) monitor the test's performance in routine use. Gaps in the information needed to complete these six steps and gaps in regulatory systems are highlighted. Finally, ways of improving the quality of diagnostic tests are suggested, such as establishing a model list of essential diagnostics, establishing a repository of information on the design of diagnostic studies and improving quality control and postmarketing surveillanc

Negative, weak positive, and strong positive test results versus quantitative TSH level (TSH units: µIU/mL).

<p>Negative, weak positive, and strong positive test results versus quantitative TSH level (TSH units: µIU/mL).</p

Accuracy of TSH-CHECK-1 test compared against reference standard with >10 µIU/mL as cut-off level for a positive results.

<p>Accuracy of TSH-CHECK-1 test compared against reference standard with >10 µIU/mL as cut-off level for a positive results.</p

Towards more accurate HIV testing in sub-Saharan Africa: a multi-site evaluation of HIV RDTs and risk factors for false positives

Introduction: Although individual HIV rapid diagnostic tests (RDTs) show good performance in evaluations conducted by WHO, reports from several African countries highlight potentially significant performance issues. Despite widespread use of RDTs for HIV diagnosis in resource-constrained settings, there has been no systematic, head-to-head evaluation of their accuracy with specimens from diverse settings across sub-Saharan Africa. We conducted a standardized, centralized evaluation of eight HIV RDTs and two simple confirmatory assays at a WHO collaborating centre for evaluation of HIV diagnostics using specimens from six sites in five sub-Saharan African countries. Methods: Specimens were transported to the Institute of Tropical Medicine (ITM), Antwerp, Belgium for testing. The tests were evaluated by comparing their results to a state-of-the-art reference algorithm to estimate sensitivity, specificity and predictive values. Results: 2785 samples collected from August 2011 to January 2015 were tested at ITM. All RDTs showed very high sensitivity, from 98.8% for First Response HIV Card Test 1–2.0 to 100% for Determine HIV 1/2, Genie Fast, SD Bioline HIV 1/2 3.0 and INSTI HIV-1/HIV-2 Antibody Test kit. Specificity ranged from 90.4% for First Response to 99.7% for HIV 1/2 STAT-PAK with wide variation based on the geographical origin of specimens. Multivariate analysis showed several factors were associated with false-positive results, including gender, provider-initiated testing and the geographical origin of specimens. For simple confirmatory assays, the total sensitivity and specificity was 100% and 98.8% for ImmunoComb II HIV 12 CombFirm (ImmunoComb) and 99.7% and 98.4% for Geenius HIV 1/2 with indeterminate rates of 8.9% and 9.4%. Conclusions: In this first systematic head-to-head evaluation of the most widely used RDTs, individual RDTs performed more poorly than in the WHO evaluations: only one test met the recommended thresholds for RDTs of ≥99% sensitivity and ≥98% specificity. By performing all tests in a centralized setting, we show that these differences in performance cannot be attributed to study procedure, end-user variation, storage conditions, or other methodological factors. These results highlight the existence of geographical and population differences in individual HIV RDT performance and underscore the challenges of designing locally validated algorithms that meet the latest WHO-recommended thresholds

Xpert testing strategies and MTB detection.

<p>Xpert testing strategies and MTB detection.</p