ASST Fatebenefratelli Sacco

The objective of this observational study is to determine how frequently isoniazid (INH) causes liver injury (hepatotoxicity) in adults treated for tuberculosis (TB) or latent tuberculosis infection (LTBI) and to understand which factors increase this risk. The study also aims to describe how hepatotoxicity is managed in real-world clinical practice and whether treatments such as corticosteroids can improve liver function tests.
The main questions this study aims to answer are:
* How frequently does INH-induced hepatotoxicity occur in adults treated for TB or LTBI?
* What demographic, clinical, microbiological, or lifestyle factors increase the risk of developing hepatotoxicity?
* How do different management strategies, including treatment modification or the use of corticosteroids, affect liver recovery and completion of TB/LTBI therapy? This study does not involve experimental treatments. Researchers will analyze information already collected during routine clinical care, both retrospectively (from 2020 to 2025) and prospectively (2026-2028). There is no comparison group, but participants may have different clinical profiles or treatments, which will be compared to understand risk factors and outcomes.
Participants will:
* Receive standard treatment for tuberculosis or LTBI, including isoniazid, as prescribed by their treating physicians.
* Undergo routine assessments, such as blood tests, microbiology, imaging, and clinic visits, as part of their regular care.
* Their clinical data will be recorded in the study database to analyze liver function trends, treatment changes, and outcomes.
The study will contribute to improving understanding of INH-induced hepatotoxicity and supporting safer and more effective treatment strategies for tuberculosis and LTBI.

Multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to global public health.
Globally, the World Health Organization (WHO) estimates the number at 400,000 patients with MDR-TB for 2023. Only 44% were diagnosed and put on treatment, the therapeutic success rate of the 2021 cohort is only 68%.
In Guinea, the number of patients with MDR-TB is estimated at 450, and the treatment success rate is 74% for the 2021 cohort, primarily with the 9-months short oral regimen.
Since 2022, the WHO has recommended the use of the 6-month short course of BPaL/BPaL-M for national tuberculosis control programs and Guinea began implementing this new regime within the programmatic framework starting in January 2025.
Linezolid, a key component of new therapeutic regimens such as BPaL/BPaL-M, shows high bactericidal activity, although it is associated with serious adverse effects in a high percentage of patients, including myelosuppression, neuropathy and, in some cases, fatal lactic acidosis. In particular, peripheral neuropathy, an adverse event often irreversible that may lead to linezolid and the BPaL/BPaL-M regimen discontinuation, is reported in approximately 24% of patients receiving linezolid at 600 mg.
A linezolid blood trough level of above 2 mg/l is associated with side effects, but its pharmacokinetics varies considerably between individuals and over time.
There is little data on the role of therapeutic drug monitoring (TDM) in guiding its administration, some studies showing how the standard dose of 600 mg could exceed the toxicity target and the reduced dose of 300 mg might not achieve the target efficacy.
The main objective of this study is to determine the role of TDM in the optimization of linezolid dosage in TB-MDR patients treated with the BPaL/BPaL-M regimen.
The specific objectives aim to evaluate:
* the variation in the occurrence of adverse events between patients who undergo a modification of the linezolid dose based on the TDM and patients taking linezolid standard dose
* the treatment outcome in patients who undergo a modification of the linezolid dose based on TDM and patients taking linezolid standard dose
* variations in the distribution of TDM throughout treatment in order to identify potential common trends.

The goal of this clinical trial is to investigate if the intervention "Approach Bias Modification" (ABM) can low cocaine craving in people with Cocaine Use Disorder (CUD).
The main question this clinical trial aims to answer is how many days participants can be in abstinence from cocaine after 4 ABM sessions.
ABM is a computerised training aiming to train the participants to:
* avoid drug-related images by pushing a joystick which causes the image to disappear;
* approach positive images by pulling a joystick which causes the image to expand.
Researchers will compare participants treated with ABM to those who receive Treatment As Usual (TAU) condition to see if ABM training for CUD is more effective in increasing the number of abstinent days.
* Participants will attend 1 ABM session per week for a total of 4 sessions, each lasting 15 minutes.
* Both cocaine and non-cocaine positive images relative to the subjective values or interests (i.e. effects, sport, music, nature, work, etc.) are presented to the participant, in portrait or landscape orientation.
* Participants are instructed to push the joystick if the image is portrait-oriented (cocaine-related images) or to pull the joystick if it is landscape-oriented (positive images).
* At 1 and 3-month-follow up, participants will complete self-report questionnaires to measure abstinence days and describe the effect of ABM on cocaine use, dependence symptoms, and approach bias.