Post-TB lung disease: keep going beyond TB Pontali, E.; Akkerman, O. W.; Zenner, D. ...
The international journal of tuberculosis and lung disease,
03/2024, Letnik:
28, Številka:
3
Journal Article
Linezolid is used to treat patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-tuberculosis (TB) cases, although clinical data on its safety, tolerability and efficacy are ...lacking. We performed a retrospective, nonrandomised, unblinded observational study evaluating the safety and tolerability of linezolid at 600 mg q.d. or b.i.d. in MDR/XDR-TB treatment in four European countries. Efficacy evaluation compared end-points of 45 linezolid-treated against 110 linezolid-nontreated cases. Out of 195 MDR/XDR-TB patients, 85 were treated with linezolid for a mean of 221 days. Of these, 35 (41.2%) out of 85 experienced major side-effects attributed to linezolid (anaemia, thrombocytopenia and/or polyneuropathy), requiring discontinuation in 27 (77%) cases. Most side-effects occurred after 60 days of treatment. Twice-daily administration produced more major side-effects than once-daily dosing (p = 0.0004), with no difference in efficacy found. Outcomes were similar in patients treated with/without linezolid (p = 0.8), although linezolid-treated cases had more first-line (p = 0.002) and second-line (p = 0.02) drug resistance and a higher number of previous treatment regimens (4.5 versus 2.3; p = 0.07). Linezolid 600 mg q.d. added to an individualised multidrug regimen may improve the chance of bacteriological conversion, providing a better chance of treatment success in only the most complicated MDR/XDR-TB cases. Its safety profile does not warrant use in cases for which there are other, safer, alternatives.
The energy source powering the extreme optical luminosity of hydrogen-stripped superluminous supernovae (SLSNe-I) is not known, but recent studies have highlighted the case for a central engine. ...Radio and/or X-ray observations are best placed to track the fastest ejecta and probe the presence of outflows from a central engine. We compile all the published radio observations of SLSNe-I to date and present three new observations of two new SLSNe-I. None were detected. Through modeling the radio emission, we constrain the subparsec environments and possible outflows in SLSNe-I. In this sample, we rule out on-axis collimated relativistic jets of the kind detected in gamma-ray bursts (GRBs). We constrain off-axis jets with opening angles of 5° (30°) to energies of E k < 4 × 10 50 erg ( E k < 10 50 erg ) in environments shaped by progenitors with mass-loss rates of M ˙ < 10 − 4 M yr − 1 ( M ˙ < 10 − 5 M yr − 1 ) for all off-axis angles, assuming fiducial values ϵ e = 0.1 and ϵ B = 0.01 . The deepest limits rule out emission of the kind seen in faint uncollimated GRBs (with the exception of GRB 060218) and from relativistic SNe. Finally, for the closest SLSN-I, SN 2017egm, we constrain the energy of an uncollimated nonrelativistic outflow like those observed in normal SNe to E k 10 48 erg.
The IJTLD - the story continues Migliori, G. B.; Blackbourn, H. D.
The international journal of tuberculosis and lung disease,
08/2022, Letnik:
26, Številka:
8
Journal Article
BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to ...provide guidance on ‘best practice´ for dosing and management of TB drugs.METHODS:
A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS:
Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage
this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition,
consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred
treatment to improve patient care.
Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little ...evidence exists to guide clinicians in treating people with XDR-TB effectively. To summarise the available data on diagnosis and treatment, the current authors performed a systematic review on 13 recent studies of the epidemiology and clinical management of XDR-TB. Studies that met inclusion criteria were reviewed, in order to assess methodology, treatment regimens and treatment outcomes. Meta-analysis of currently available data is not possible because of inconsistent definitions and methodologies. Data show that XDR-TB can be successfully treated in up to 65% of patients, particularly those who are not co-infected with HIV. However, treatment duration is longer and outcomes are in general poorer than for non-XDR TB patients. To strengthen the evidence for extensively drug-resistant tuberculosis diagnosis, treatment and prevention, future studies should: 1) be prospective in design; 2) adopt standardised, internationally accepted definitions; 3) use quality-assured laboratory testing for all first- and second-line drugs; and 4) collect data on an agreed-upon set of standard variables, allowing for comparisons across studies. Early diagnosis and aggressive management of extensively drug-resistant tuberculosis provide the best chance of positive outcome, but prevention is still paramount.
ABSTRACT
We report results on deep Jansky Very Large Array (VLA) A-configuration observations at 22 GHz of the hotspots of the radio galaxies 3C 227 and 3C 445. Synchrotron emission in the optical on ...scales up to a few kpc was reported for the four hotspots. Our VLA observations point out the presence of unresolved regions with upper limit to their linear size of about 100 pc. This is the first time that such compact components in hotspots have been detected in a mini-sample, indicating that they are not a peculiar characteristic of a few individual hotspots. The polarization may reach values up to 70 per cent in compact (about 0.1 kpc scale) regions within the hotspot, indicating a highly ordered magnetic field with size up to a hundred parsecs. On larger scales, the average polarization of the hotspot component is about 30–45 per cent, suggesting the presence of a significant random field component, rather than an ordered magnetic field. This is further supported by the displacement between the peaks in polarized intensity and in total intensity images that is observed in all the four hotspots. The electric vector position angle is not constant, but changes arbitrarily in the central part of the hotspot regions, whereas it is usually perpendicular to the total intensity contours of the outermost edge of the hotspot structure, likely marking the large-scale shock front. The misalignment between X-ray and radio-to-optical emission suggests that the former is tracing the current particle acceleration, whereas the latter marks older shock fronts.
BACKGROUND: The aim of these clinical standards is to provide guidance on ‘best practice’ care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of ...international experts representing scientific societies, associations
and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed
for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life
(QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according
to local health services and tailored to an individual patient’s needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based
set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.
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