Personalised approaches to improve tuberculosis care:Cutting tuberculosis’ many coats according to specific cloths

Tuberculosis (TB) is an infectious disease which records 1 to 1.5 million deaths every year. Persons affected by TB have increased mortality and morbidity, despite advances made in treatment options. This thesis investigated several avenues which could enhance TB clinical care. These avenues include digital health, therapeutic drug monitoring (TDM), interventions geared towards enhancing quality of life, and enhancing policies concerning TB screening and prevention. Concerning digital health, results presented in the thesis indicate that it could be a cost-effective, feasible, and welcomed addition by both medical professionals and persons suffering from TB, to standard of care in multiple steps of the TB care cascade, from screening, to follow up. Concerning TDM, which is a personalised medicine technique informing clinicians of accurate drug dosages (usually) in blood, an international survey described in the thesis indicates that worldwide experts would recommend integrating this technique in standard of care and a retrospective study presents, in a contextualised manner, which patients would best benefit from this technique. This thesis, furthermore, presents an observational study on persons with TB quality of life and wellbeing, in order to quantify the magnitude of effects of TB during, but also after treatment completion so that future interventions could have this crucial human aspect in mind. Last, but not least, part of this thesis research focused on vulnerable persons affected by TB, namely migrants, and how the screening for TB infection is performed on an European level, in order to set the groundwork for future European consensus. Overall, results of this thesis indicate that greater care should be offered to persons at risk of developing side effects of TB or of the treatment for TB and more research should be involved in implementing personalised medicine techniques at all levels of the clinical care cascade.<br/

Patients and Medical Staff Attitudes Toward the Future Inclusion of eHealth in Tuberculosis Management:Perspectives From Six Countries Evaluated using a Qualitative Framework

Background: Digitally delivering healthcare services is very attractive for tuberculosis (TB) management as this disease has a complex diagnosis and lengthy management and involves multiple medical and nonmedical specialists. Especially in low- and middle-income countries, eHealth could potentially offer cost-effective solutions to bridge financial, social, time, and distance challenges. Objective: The goal of the research is to understand what would make eHealth globally applicable and gain insight into different TB situations, opportunities, and challenges. Methods: We performed focus group interviews with TB experts and patients from 6 different countries on 4 different continents. The focus group interviews followed the theory of planned behavior framework to offer structured recommendations for a versatile eHealth solution. The focus group interviews were preceded by a general demographic and technology use questionnaire Questionnaire results were analyzed using basic statistics in Excel (Microsoft Corporation). Focus group interview data were analyzed using ATLAS.ti 8 (ATLAS.ti Scientific Software Development GmbH) by assigning codes to quotations and grouping codes into the 5 domains within the framework. Results: A total of 29 patients and 32 medical staff members were included in our study. All medical staff had used the internet, whereas 31% (9/61) of patients had never been online. The codes with the most quotations were information in relation to eHealth (144 quotations) and communication (67 quotations). The consensus among all participants from all countries is that there are important communication and information gaps that could be bridged by an eHealth app. Participants from different countries also highlighted different challenges, such as a majority of asylum-seeker patients or lack of infrastructure that could be addressed with an eHealth app. Conclusions: Within the 6 countries interviewed, there is high enthusiasm toward eHealth in TB. A potential app could first target information and communication gaps in TB, with additional modules aimed at setting-specific challenges

Tuberculosis impacts multiple aspects in quality of life in a Romanian cohort of drug‐susceptible and drug resistant patients: A patient‐reported outcome measures study

Background: Tuberculosis (TB), and especially its drug resistant forms, is responsible for not only significant mortality, but also considerable morbidity, still under‐quantified. This study used four Patient‐Reported Outcome Measures (PROMS) to assess the status of persons affected by drug‐susceptible and drug‐resistant TB during their TB treatment or after treatment completion, in Romania, the highest TB burden country in the EU. Methods: People affected by TB in two different regions in Romania were included during and after treatment, following a cross‐sectional design. PROMs used were SF‐36, EQ‐5D‐5L, WPAI and the app‐based audiometry screening tool ‘uHear.’ Descriptive statistics and relevant statistical tests were used to compare groups between themselves and with the general Romanian population. Results: Both patients with drug‐susceptible and drug‐resistant TB experience, with drug‐resistant patients experiencing statistically significantly more pain and hearing loss. PROMs show some improvement in the after‐treatment group; however, compared with the general Romanian population for which data were available, all groups scored lower on all outcome measures. Conclusion: PROMs offer the possibility of obtaining a more comprehensive view of patients' status, by involving them directly in the medical process and could guide a rehabilitation strategy

Corrigendum to "Mass spectrometry for therapeutic drug monitoring of anti-tuberculosis drugs" [Clin. Mass Spectrom. 14(Part A) (2019) 34-45]

[This corrects the article DOI: 10.1016/j.clinms.2018.10.002.]

Initiation and completion of treatment for latent tuberculosis infection in migrants globally:a systematic review and meta-analysis

BACKGROUND: Latent tuberculosis infection (LTBI) is one of the most prevalent infections globally and can lead to the development of active tuberculosis disease. In many low-burden countries, LTBI is concentrated within migrant populations often because of a higher disease burden in the migrant's country of origin. National programmes consequently focus on screening and treating LTBI in migrants to prevent future tuberculosis cases; however, how effective these programmes are is unclear. We aimed to assess LTBI treatment initiation and outcomes among migrants, and the factors that influence both. METHODS: For this systematic review and meta-analysis, we searched Embase, MEDLINE, and Global Health, and manually searched grey literature from Jan 1, 2000, to April 21, 2020. We included primary research articles reporting on LTBI treatment initiation or completion, or both, in migrants and excluded articles in which data were not stratified by migrant status, or in which the data were related to outcomes before 2000. There were no geographical or language restrictions. All included studies were quality appraised using recognised tools depending on their design, and we assessed the heterogeneity of analyses using I2. We extracted data on the numbers of migrants initiating and completing treatment. Our primary outcomes were LTBI treatment initiation and completion in migrants (defined as foreign-born). We used random-effects meta-regression to examine the influence of factors related to these outcomes. The study is registered with PROSPERO (CRD42019140338). FINDINGS: 2199 publications were retrieved screened, after which 39 publications from 13 mostly high-income, low-burden countries were included in our analyses, with treatment initiation and completion data reported for 31 598 migrants positive for LTBI, with not all articles reporting the full pathway from initiation to completion. The pooled estimate for the true proportion of migrants testing positive who initiated treatment was 69% (95% CI 51-84; I2= 99·62%; 4409 of 8764). The pooled estimate for the true proportion of migrants on treatment in datasets, who subsequently completed it was 74% (95% CI = 66-81; I2= 99·19%; 15 516 of 25 629). Where data were provided for the entire treatment pathway, the pooled estimate for the true proportion of migrants who initiated and completed treatment after a positive test was only 52% (95% CI 40-64; I2= 98·90%; 3289 of 6652). Meta-regression showed that LTBI programmes are improving, with more recent reported data (2010-20) associated with better rates of treatment initiation and completion, with multiple complex factors affecting treatment outcomes in migrants. INTERPRETATION: Although our analysis highlights that LTBI treatment initiation and completion in migrants has improved considerably from 2010-20, there is still room for improvement, with drop out reported along the entire treatment pathway. The delivery of these screening and treatment programmes will require further strengthening if the targets to eradicate tuberculosis in low-incidence countries are to be met, with greater focus needed on engaging migrants more effectively in the clinic and understanding the diverse and unique barriers and facilitators to migrants initiating and completing treatment. FUNDING: European Society of Clinical Microbiology and Infectious Diseases, the Rosetrees Trust, the National Institute for Health Research, and the Academy of Medical Sciences

Application of 137Cs for measuring soil erosion/deposition rates in Romania

Two methods of monitoring soil redistribution along agroterraces were explored in Tarina basin of the Moldavian Plateau: the classical method of annual or periodic field measurements and the 137C technique. Results obtained by both methods indicate that the aggradation rate of the agroterrace edge averages 5.0-6.0 cm/yr, but the 137C technique is more efficient because it requires only one field visit. Much of the dow n ward movement of soil in these agroterraces can be related to contour ploughing, although some erosion/deposition undoubtedly occurs. The future of using 137C as a tracer of erosion and sedimentation within discontinuous gullies is promising. Some results obtained in the Moldavian Plateau near Barlad support this assumption. A field study, based on a depth - incremental sampling method, was undertaken in two small basins, Roscani and Timbru. Depth distribution of 137Cs from recent sediments deposited along the floor of dis-continuous gullies allowed the establishment of a mean sedimentation rate of 4.4 cm/yr over the period 1963-1996, and 2.5 cm/yr after 1986 for short gullies. In the case of long gullies, after the Chernobyl nuclear accident this value is to 4.9 cm/year. Furthermore, it was possible to estimate: the age of the gullies (23-48 years), the mean gully head advance (0.9 m/yr), the mean total mass of sediment deposited/ eroded within the gully system (up to 124 t/yr) and the main sediment source (the active gully head and banks). Conservation practices and tillage were first implemented during 1982-1983 in the upper Racatau basin of 3,912 hectares. Significant changes in land management practices resulted from the application of the Landed Property Law no.18/1991. The marked shifting from contour to up and down hill farming created a doubling in the amount of soil erosion and deposition. Depth distribution of 137Cs in recent sediments of the Bibiresti reservoir indicates a mean sedimentation rate of 5.0 cm/yr over the period 1986-1992 and 10.0 cm/yr for the period 1993-1996

Adenosine involvement on bronchial reactivity modulation by diesel exhaust

UNLABELLED: In recent decades, epidemiologic investigations have suggested a strong relationship between air pollution and an increase in the prevalence of allergic rhinitis and asthma. AIM: To investigate the possible involvement of adenosine (AD) in bronchomotor effects of diesel exhaust (DE). MATERIAL AND METHOD: Isolated bronchi from ovalbumin (OVA) sensitized rats were challenged in presence or absence of diesel exhaust extract (DEE). AD was delivered on organ bath before or after DEE, at concentrations did not produce significantly contractile effects. RESULTS: AD (0.1 microM) pre-treatment increased bronchomotor effects of DEE: amplified the bronchoconstrictor effects of OVA with more than 35% and decreased Emax of terbutaline induced bronchorelaxation of acetylcholine (Ach) preconstricted bronchial rings (up to 20%), but did not significantly modify ACh-induced contractions. OVA-induced contractions, ACh-induced contractions and terbutaline-induced relaxations have not been significantly modified as compare with DEE alone. On the other hand, DEE amplified AD (cumulative doses) contractile effects. CONCLUSION: These results confirmed our initial hypothesis that AD could partial mediate or at least, modulate DEE effects on airway reactivity