João Pedro Ramos

Despite extensive conceptual development, the definition and measurement of Tuberculosis (TB) treatment adherence remain inconsistent. This ambiguity obscures what is being assessed and compared across studies. This scoping review examined how adherence is labelled, defined, and operationalised in observational studies of drug-susceptible TB, assessed consistency with contemporary frameworks, and identified methodological gaps. We conducted a scoping review of observational studies on drug-susceptible TB identified from eight databases up to February 2026. Data were extracted on terminology, measurement approaches, and operational definitions. Content analysis was used to map labels and indicators to the constructs they implicitly presuppose. One hundred and three studies were included. Treatment-taking behaviour was mostly assessed through clinician assessment or self-report. Explicit definitions were uncommon, and operational criteria served as de facto definitions. Multidimensional measures were frequently reduced to binary or ordinal outcomes, and most studies relied on cross-sectional designs, reinforcing static representations of a dynamic process. Thus, TB adherence research faces a fundamental problem of construct conflation: the same label is used to describe behaviours that are conceptually distinct, limiting comparability and weakening the interventions’ evidence base. Standardising reporting requirements would strengthen the evidence base for programmes addressing structural and social drivers of adherence.

Background: Linezolid (LZD) has emerged as a key drug for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) treatment. However, its clinical use is limited by substantial toxicity. This scoping review aimed to synthesise evidence on LZD-associated adverse effects (AEs) to support safer and more effective TB management clinical decisions. Methods: A systematic search of PubMed, Scopus, Web of Science, and EMBASE databases (conducted in October 2024) identified 103 primary studies published between 2005 and 2024 that reported AEs related to LZD use in MDR/XDR-TB. Data on frequency, severity, onset, and management of AEs were extracted and narratively synthesised. Results: Of the 103 included studies, 102 (99%) reported at least one AE. The overall frequency of AEs ranged from 2.8% to 100%. Neurological toxicity was reported in 3.5–91.9% of patients, most commonly presenting as peripheral neuropathy. Haematological toxicity was observed in 1.9–84.6% of participants, mainly reported as anaemia and thrombocytopenia. Gastrointestinal disturbances, metabolic complications, such as lactic acidosis and hyperlactacidaemia, and dermatological events were also reported. Conclusion: LZD-associated toxicity is frequent and often clinically significant, particularly during prolonged treatment. Careful patient assessment, including comorbidities and potential contributing factors such as vitamin deficiencies, along with regular monitoring and, where available, therapeutic drug monitoring, may help optimise safety and treatment outcomes. Future research should focus on standardised toxicity assessment, pharmacokinetic-based dosing strategies, and the inclusion of diverse patient populations to improve the safety and effectiveness of LZD-based regimens.

The co-occurrence of tuberculosis (TB) and diabetes mellitus (DM) presents a growing public global health concern. Managing DM during anti-TB therapy is challenging due to potential drug-drug interactions, especially with rifamycin (RIF). Assess the effects of anti-TB drugs on the pharmacokinetics and pharmacodynamics of novel antidiabetic agents, including DPP-4 inhibitors (DPP4i), SGLT-2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1a). A PRISMA-ScR-based scoping review was conducted among four databases. Ten studies involving 307 participants were included. RIF significantly reduced the plasma exposure of DPP4i (saxagliptin, gemigliptin, evogliptin) and canagliflozin, while other SGLT2i (dapagliflozin, empagliflozin, ertugliflozin) were minimally affected. No direct data was available for GLP-1a. Adverse events were rare in healthy participants but more frequent in elderly patients with poorly controlled DM. Linezolid and dapagliflozin co-administration may lead to severe pancytopenia. RIF co-administration with gemigliptin, evogliptin and canagliflozin requires caution and potential requiring dose adjustments, while saxagliptin, dapagliflozin, ertugliflozin and empagliflozin appear safer alternatives. Haematologic monitoring is recommended when combining linezolid and dapagliflozin. However, current evidence remains limited by small sample sizes, single-dose designs, inclusion of mainly healthy participants, and lack of data on GLP-1a or other anti-TB agents. The limited inclusion of DM patients with TB, restricted to one study with latent TB infection, further reduces generalisability. We developed a clinical decision algorithm to support co-treatment in TB - DM cases, but further dedicated studies are warranted to guide optimal co-treatment.

The rising demand for substance-related treatments results in a persistent increase in human, social, health, and economic costs that affect not only people but also reverberates across families, communities, and societies. Social environment plays a crucial role in substance use as it influences recovery pathways either by fostering drug-free behaviors or hindering them. This review aims to synthesize existing scientific evidence on the social-environmental factors that influence recovery from substance use disorders, excluding alcohol and tobacco. Following the methodological framework proposed by Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, a comprehensive search was conducted in 19 databases and other sources from inception to 2024. Forty-five studies met the inclusion criteria. A multitude of social-environmental factors were shown to influence recovery such as support networks, socioeconomic conditions (i.e., housing, education, employment), spirituality, drug availability in the substance milieu, stigmatization, and the therapeutic setting. The various support networks play a key role in facilitating recovery pathways, with dysfunctional relationships and substance availability hindering recovery progress. Factors that appear to play a protective role under some circumstances could also prove to be risk factors generating feelings of loneliness and alienation. A general lack of evidence directed at post-treatment integration failed to allow an exploration of results akin to other factors. This review highlights that not a single solution appears to apply to everyone's recovery, and continued disregard for varying intersectionalities could result in the support provided being subpar to what is expected by the person involved in a change process. Therapeutic approaches to recovery should seek to be holistic and inclusive of every network by recognizing and mitigating the systemic barriers that surround those in a process of change as a means to sustain treatment's success and facilitate post-treatment integration.

Tuberculosis (TB) remains a major public health challenge, particularly in low- and middle-income countries (LMICs), with treatment adherence being a critical issue. In recent years, digital adherence technologies (DATs) have emerged as a promising approach to enhance TB care and treatment adherence in these settings. Despite their potential to enhance treatment outcomes, their implementation faces challenges, including infrastructure demands, costs, and variability in effectiveness depending on the context. A critical aspect of DATs is their cost-effectiveness, which has shown mixed results across different LMICs. Some technologies, such as the medication sleeves/labels ( e.g. , 99DOTS), demonstrate low-cost alternatives to traditional directly observed therapy (DOT), while others report inconsistent outcomes. Throughout its implementation, DATs can be a source of intervention-generated inequality, where they may disproportionately benefit low-risk populations with better access to technology, potentially widening gaps in healthcare equity. However, when targeted effectively at high-risk groups, DATs can promote equitable health outcomes and enhance TB care delivery. The successful implementation of DATs requires context-specific strategies that address the unique challenges of LMICs, such as technology fatigue, data privacy, and the need for tailored interventions that consider socioeconomic and cultural factors. Leveraging the support of global health initiatives and collaborative funding mechanisms could help scale up DAT adoption and contribute to the global goal of TB elimination.

Objective: Personal experiences, perceptions, and views of patients are crucial in understanding the subjective impacts of diseases. The complexity and duration of tuberculosis treatment impose significant physical, emotional, social, and economic burdens, highlighting the need for person-centered, integrated care strategies that address stigma, fatigue, and accessibility to support well-being. Patient-reported outcomes (PROs) are essential for capturing patient perspectives and improving health care strategies. In this study we explored the multifaceted experiences of patients with tuberculosis, seeking to understand their values and priorities during treatment. Methods: Semistructured interviews with adult tuberculosis patients were conducted at a referral center for tuberculosis diagnosis and management in northern Portugal. After verbatim transcription and anonymization, thematic analysis was performed. Results: Seventeen interviews were conducted. Most (58.8%) of the study participants were male, and most had pulmonary tuberculosis. Our thematic analysis identified five PROs: treatment experiences; health-related quality of life; functional status; symptoms and symptom burden; and health behaviors. People with tuberculosis acknowledged the impact of multiple factors on their overall health, particularly the psychological and physical burdens of tuberculosis and its treatment. Several areas for improvement and opportunities for enhanced support were identified, particularly in communication, emotional support, and management of treatment burden. Conclusions: Our findings highlight the need for tailored PRO measures (PROMs) addressing treatment burden, psychosocial distress, and functional limitations in tuberculosis care. Enhancing communication, psychological support, and multidisciplinary approaches in tuberculosis management could improve patient outcomes and overall well-being. Addressing tuberculosis-related stigma and providing targeted interventions may contribute to a more people-centered approach to care.

Objetivos: O cuidado informal acarreta tarefas e responsabilidades que podem dar origem a uma sobrecarga mental e física para o cuidador. Este estudo procurou explorar as perceções dos cuidadores informais em [localização]. Métodos: Os dados foram recolhidos com base em trabalho de campo de inspiração etnográfica, por meio de entrevistas semiestruturadas, grupo focal, documentos e observação participante e direta, por um período de seis meses. Os dados foram triangulados para Resultados: Os cuidadores informais referem sentir-se "invisíveis" aos olhos da governança pública, uma vez que as suas reais necessidades não se encontram a ser observadas pelas políticas atuais. A maioria dos participantes depende de serviços comunitários para lidar com complicações relacionadas às comorbidades dos idosos, não tendo sido referido nenhum apoio direcionado ao cuidador. Esta lacuna é identificada como a causadora de uma multiplicidade de problemas de saúde física e mental. Os cuidadores mencionam ignorar consecutivamente a sua estabilidade mental, em prol da prestação de cuidados ao idoso. Conclusão: A mitigação do impacto negativo do cuidado pode ser alcançada apenas por meio de esforços adicionais por parte de instituições públicas e organizações do terceiro setor, para a criação ou melhoria da cooperação intersectorial.