Nanomedicine utilises biocompatible nanomaterials for therapeutic as well as imaging purposes, for the treatment of various diseases including cancer, neurological disorders and wound infections. Graphene, a material composed of a single layer of carbon atoms, has recently shown great potential to improve diagnostics and therapeutics, owing to its small size, large surface-area-to-volume ratio and unique physicochemical properties. However, the limited fabrication, in vitro and in vivo functionalities published in the literature indicate inconsistencies regarding the factors affecting metabolic fate, biodistribution as well as toxicity patterns of graphene. This thesis focuses on the biological effects of graphene-based materials, including graphene oxide (GO), reduced graphene oxide (rGO), graphene nanopores (GNPs), graphene quantum dots (GQDs) and three-dimensional graphene foam (GF). These can be used to closely mimic therapeutic functions and thereby open up new pathways to anticancer nanomedicine. In this work, a biocompatible GO-based anti-metastatic enzyme cancer therapy approach has been introduced for the first time to target the extracellular pro-metastatic and pro- tumourigenic enzymes of cathepsin D and cathepsin L, which are typically overexpressed in ovarian and breast cancers. Definitive binding and modulation of cathepsin- D and -L with GO has revealed that both of the enzymes were adsorbed onto the surface of GO through its cationic and hydrophilic residues under the biologically relevant condition of acidic pH. It has been demonstrated that low concentrations of rGO were shown to significantly produce late apoptosis and necrosis rather than early apoptotic events in lung cancer cells (A549 and SKMES-1), suggesting that it was able to disintegrate the cellular membranes in a dose-dependent manner. GNPs at lower concentrations (250μg/ml) induce upregulation of phosphatidylserine on cell surface membrane (i.e. early apoptotic event), which does not significantly disintegrate the cell membrane in the aforementioned lung cancer cells, while higher concentrations of GNPs (5 and 15 mg/kg) in rats (when intraperitoneally injected) exhibited sub-chronic toxicity in a period of 27 days. The interaction of GQDs and trypsin has revealed the strong bonding capacity of GQDs with trypsin, owing to their surface charge and surface functionalities evidencing the high bioavailability of GQDs in enzyme engineering. Finally, 3D GF was developed to probe the role of graphene-based scaffold cues in the field of regenerative medicine revealing their cell attachment to in vitro cell cultures. Furthermore, GF was shown to maintain remarkable biocompatibility with in vitro and in vivo toxicity screening models when exposed for 7 days at doses of 5, 10 and 15 mg/l. Taken together, graphene and its modified structures developed in this thesis promise to revolutionise clinical settings across the board in nanomedicine which include, but are not limited to, ultra-high sensitive enzyme adsorbents, high throughput biosensors, enzyme modulators and smart scaffolds for tissue regeneration.

No description available.

The presented paper deals with the issue of dual diagnosis from the point of view of community/social psychiatry. The main aim of the paper is to introduce readers to the issues of dual diagnosis and ways how to reach recovery and interpret individual case studies to demonstrate approach of case management in social services of community/social psychiatry, to explore the aetiology and interaction of diseases and to map the internal potential and the external sources of recovery of individual clients. The main point of the theoretical part is the analysis of integrative treatment approach of dual diagnosis. The theoretical basis is to introduce readers to the existing system of mental health care in the Czech Republic, which currently undergoes the transformation of medical institutional treatment into developing community/social psychiatry. One of the applied approaches of community/social psychiatry is case management that focuses on recovery of clients and their psychosocial rehabilitation. The last chapter of the theoretical part analyses an example of a specific social service in the Belgian city of Ghent, for people with dual diagnosis, which tries to connect together all the aforementioned concepts and use them in the direct care of clients. The practical basis consists of qualitative...

Introduction: There is a frequent incidence of post-traumatic stress disorder (PTSD) in people with substance use disorder (SUD) and there is also a frequent occurrence of substance use in people with PTSD. Many foreign authors highlight the complications that occur in individuals with this dual diagnosis: higher risk of drop-out from treatment, a higher number of suicide attempts, more serious consequences of substance use, more frequent relapses of both of two diagnoses, etc. The negative impact of this comorbidity on treatment outcomes, highlights the need to focus on improving procedures in the diagnosis of PTSD in people treating from SUD and a need of integrated treatment of both disorders. Many studies also suggest that improving the condition of PTSD increases the likelihood of improvement in substance use. In the Czech Republic, there is a lack of sources that focus on the relationship of these comorbidities and their treatment. Examples of a good practice are also missing. Aims: The aim of this thesis is to introduce the issue of dual diagnosis - PTSD and SUD. The intention of the theoretical part is to present the relationship of these two disorders, with a focus on possible etiology and treatment options. The aim of the practical part is to introduce specific models of integrated...

<p>A difficult issue in stress management is to use biomedical sensor signal in the diagnosis and treatment of stress. Clinicians often make their diagnosis and decision based on manual inspection of physiological signals such as, ECG, heart rate, finger temperature etc. However, the complexity associated with manual analysis and interpretation of the signals makes it difficult even for experienced clinicians. Today the diagnosis and decision is largely dependent on how experienced the clinician is interpreting the measurements.  A computer-aided decision support system for diagnosis and treatment of stress would enable a more objective and consistent diagnosis and decisions.</p><p>A challenge in the field of medicine is the accuracy of the system, it is essential that the clinician is able to judge the accuracy of the suggested solutions. Case-based reasoning systems for medical applications are increasingly multi-purpose and multi-modal, using a variety of different methods and techniques to meet the challenges of the medical domain. This research work covers the development of an intelligent clinical decision support system for diagnosis, classification and treatment in stress management. The system uses a finger temperature sensor and the variation in the finger temperature is one of the key features in the system. Several artificial intelligence techniques have been investigated to enable a more reliable and efficient diagnosis and treatment of stress such as case-based reasoning, textual information retrieval, rule-based reasoning, and fuzzy logic. Functionalities and the performance of the system have been validated by implementing a research prototype based on close collaboration with an expert in stress. The case base of the implemented system has been initiated with 53 reference cases classified by an experienced clinician. A case study also shows that the system provides results close to a human expert. The experimental results suggest that such a system is valuable both for less experienced clinicians and for experts where the system may function as a second option.</p> / IPOS, PROEK

Made available in DSpace on 2016-03-15T19:39:54Z (GMT). No. of bitstreams: 1 Rodrigo Romano de Araujo.pdf: 2203426 bytes, checksum: 9bae67b1181f0d77ed7c6f32a29480ca (MD5) Previous issue date: 2012-08-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Identification of the signs and symptoms of Autism Spectrum Disorders (ASD) in childhood and the search for an accurate diagnosis by health professionals are key factors for early treatment for children with this condition. This study aimed to develop a methodology to analyze the trajectory of parents with children with ASD searching for diagnosis and treatment in health services in the city of Barueri, State of São Paulo. For this purpose, it was developed a quantitative and qualitative questionnaire, gradually improved by the application in a sample of 38 pilot cases, consisting of mothers or primary caregivers of children with ASD and involved in its making the participation of a multidisciplinary team. The composition of the instrument produced a final document, which enabled a definition of educational and socioeconomic profiles of the sample: 89% of families are among the classes D and C and allowed the analysis on the different aspects of this trajectory, such as: the time elapsed until a definitive diagnosis, which is generally delayed; the average number of health professionals involved in this process, which is five; the professional activity related to referrals and guidance, as well as the identification of medical specialty to raise the first suspicion of ASD: despite the pediatricians are the first professionals to observe the child, they are among the last to raise the diagnostic suspicion; the access for an appropriate treatment, which 44% believe that there were no significant difficulties; the degree of satisfaction in the use of public services, 73% are satisfied or completely satisfied; and to answering questions regarding the impact on the family of having a child with ASD, which includes the social isolation that especially mothers may be subject, 66% and the coping strategies used by the families in situations of adversity related to the child: the search for religious and/or spiritual support, 55%, is more frequent than compared to other sources of social support. / A identificação dos sinais e sintomas dos Transtornos do Espectro do Autismo (TEA) na infância e a busca de um diagnóstico preciso por parte dos profissionais da saúde são fatores fundamentais para o tratamento precoce para crianças com essa condição. O presente trabalho teve como objetivo geral desenvolver uma metodologia para a análise da trajetória de pais com filhos com TEA na busca de diagnóstico e tratamento em serviços de saúde no município de Barueri do Estado de São Paulo. Para tanto, desenvolveu-se um questionário quanti-qualitativo, gradativamente aprimorado pela aplicação em uma amostra composta por 38 casospiloto, constituída por mães ou principais responsáveis de filhos com TEA e que envolveu em sua confecção a participação de uma equipe multidisciplinar. A composição do instrumento produziu um documento final otimizado, que viabilizou uma definição do perfil educacional e socioeconômico dos sujeitos de pesquisa, constatando-se que 89% das famílias situam-se entre as classes D e C, e que possibilitou a análise de diversos aspectos componentes dessa trajetória, tais como: o tempo transcorrido até a definição diagnóstica, sendo este de modo geral tardio; a quantidade média de cinco profissionais da saúde envolvidos nesse processo; a atuação profissional referente aos encaminhamentos e orientações assim como a identificação da especialidade médica quanto à primeira suspeita diagnóstica de TEA, verificando-se que os pediatras são os primeiros profissionais a observarem a criança, mas estão entre os últimos a levantarem a suspeita diagnóstica; os desafios para a inserção em um tratamento adequado em que 44% consideram que não existiram dificuldades relevantes; o grau de satisfação na utilização dos serviços públicos e gratuitos onde 73% estão satisfeitos ou completamente satisfeitos; além de responder questões referentes ao impacto no âmbito familiar de se ter um filho com TEA, dentre as quais o isolamento social que especialmente as mães, 66% delas, podem estar sujeitas, e as estratégias de coping utilizadas pelas famílias para enfrentar situações de adversidade em relação ao filho, notando-se que 55% buscam por apoio religioso e/ou espiritual, característica mais frequente do que comparada a outras fontes de apoio social.

A difficult issue in stress management is to use biomedical sensor signal in the diagnosis and treatment of stress. Clinicians often make their diagnosis and decision based on manual inspection of physiological signals such as, ECG, heart rate, finger temperature etc. However, the complexity associated with manual analysis and interpretation of the signals makes it difficult even for experienced clinicians. Today the diagnosis and decision is largely dependent on how experienced the clinician is interpreting the measurements.  A computer-aided decision support system for diagnosis and treatment of stress would enable a more objective and consistent diagnosis and decisions. A challenge in the field of medicine is the accuracy of the system, it is essential that the clinician is able to judge the accuracy of the suggested solutions. Case-based reasoning systems for medical applications are increasingly multi-purpose and multi-modal, using a variety of different methods and techniques to meet the challenges of the medical domain. This research work covers the development of an intelligent clinical decision support system for diagnosis, classification and treatment in stress management. The system uses a finger temperature sensor and the variation in the finger temperature is one of the key features in the system. Several artificial intelligence techniques have been investigated to enable a more reliable and efficient diagnosis and treatment of stress such as case-based reasoning, textual information retrieval, rule-based reasoning, and fuzzy logic. Functionalities and the performance of the system have been validated by implementing a research prototype based on close collaboration with an expert in stress. The case base of the implemented system has been initiated with 53 reference cases classified by an experienced clinician. A case study also shows that the system provides results close to a human expert. The experimental results suggest that such a system is valuable both for less experienced clinicians and for experts where the system may function as a second option. / IPOS, PROEK

Background and Purpose: In 2007, the WHO classification of brain tumors was extended by three new entities of glioneuronal tumors: papillary glioneuronal tumor (PGNT), rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) and glioneuronal tumor with neuropil-like islands (GNTNI). Focusing on clinical characteristics and outcome, the authors performed a comprehensive individual patient data (IPD) meta-analysis of the cases reported in literature until December 2012. Methods: PubMed, Embase and Web of Science were searched for peer-reviewed articles reporting on PGNT, RGNT, and GNTNI using predefined keywords. Results: 95 publications reported on 182 patients (PGNT, 71; GNTNI, 26; RGNT, 85). Median age at diagnosis was 23 years (range 4–75) for PGNT, 27 years (range 6–79) for RGNT, and 40 years (range 2–65) for GNTNI. Ninety-seven percent of PGNT and 69% of GNTNI were located in the supratentorial region, 23% of GNTNI were in the spinal cord, and 80% of RGNT were localized in the posterior fossa. Complete resection was reported in 52 PGNT (73%), 36 RGNT (42%), and 7 GNTNI (27%) patients. Eight PGNT, 3 RGNT, and 12 GNTNI patients were treated with chemo- and/or radiotherapy as the primary postoperative treatment. Follow-up data were available for 132 cases. After a median follow-up time of 1.5 years (range 0.2–25) across all patients, 1.5-year progression-free survival rates were 52±12% for GNTNI, 86±5% for PGNT, and 100% for RGNT. The 1.5-year overall-survival were 95±5%, 98±2%, and 100%, respectively. Conclusions: The clinical understanding of the three new entities of glioneuronal tumors, PGNT, RGNT and GNTNI, is currently emerging. The present meta-analysis will hopefully contribute to a delineation of their diagnostic, therapeutic, and prognostic profiles. However, the available data do not provide a solid basis to define the optimum treatment approach. Hence, a central register should be established.

Searching with the key word “measuring instrument of traditional Chinese medical massage” in CNK, 62 academic literature papers can be found. According to statistics, research of “measuring instrument of traditional Chinese medical massage” are carried out in 5 directions, including normalized operation, high-tech based teaching and training, perception analysis of massage manipulation force, the structural design of robot, and the design of measuring instrument. As the manipulation of traditional Chinese medical massage is a multi-field medical effect, without the supporting of measurement of high-tech based multi-field sensor of massage actions, the quantification, normalized and standardized operation, scientific and modern teaching, microcosmic, precise and quantified perception, robotized and intellectualized actuation implementation, and design of measuring instrument are hard to realize. Meanwhile, the online diagnosis and treatment service model of traditional Chinese medical massage based on “internet plus” depends on the establishment of digital database of massage manipulation, which is based on the creation of high-tech sensor system of traditional Chinese medical massage measurement. Thus, the measuring sensor of the traditional Chinese medical massage manipulation is an unavoidable key scientific problem for scientific, normalized, and internet-enabled traditional Chinese medical massage. Flexible fiber grating sensor array will be a research direction for implementing multi-field measurement of traditional Chinese medical massage manipulation.

Introduction: Au Nigeria, la couverture de la détection et du traitement de la tuberculose pharmaco-résistante (TPR) est toujours faible malgré la mise en place de services gratuits depuis 2011. Le pays se classe au sixième rang mondial avec une proportion de cas de patients résistants aux médicaments de 4,3% et de 15% dans les cas d’une réinitialisation au traitement. Le pays a aussi un fardeau élevé pour la tuberculose, la TPR, et le VIH, avec une prévalence de 219 et 11 pour 100 000 habitants pour la tuberculose et la TPR et de 1,28 pour 1 000 habitants pour le VIH. Sans traitement, la mortalité due à la tuberculose est d'environ 70% en dix ans, augmentant avec la coïnfection par le VIH, et la résistance aux médicaments; et descendant en dessous de 5% avec traitement. Les taux de survie de la tuberculose pharmaco-résistante sont plus faibles et le traitement est plus long, plus coûteux et plus toxique. Cela peut poser des défis différents à la fois pour les patients et les systèmes de santé comparativement à la tuberculose de la forme commune. Cependant, la réponse au traitement et la survie sont influencées par la détection précoce et à l'initiation rapide au traitement, idéalement dans les quatre semaines suivant le diagnostic, en particulier avec la coïnfection par le VIH. Les caractéristiques sociodémographiques interagissent souvent de manière complexe avec des facteurs systémiques, pour accroître la vulnérabilité et les désavantages - ces interactions sont particulièrement bien examinées à travers un cadre conceptuel d'équité à l'accès à la santé, et pourrait offrir des analyses et des recommandations pertinentes pour les politiques. Cette thèse explore les barrières et les facilitateurs à l’accès au diagnostic et au traitement au niveau des patients et du système de santé au Nigéria. Méthodes: Cette thèse est une étude transformative de méthodes mixtes. Nous avons d’abord réalisé une revue systématique mixte pour identifier les obstacles et les facilitateurs influençant l’accès au diagnostic et au traitement de la TPR en Afrique subsaharienne. Nous avons par la suite mené une méta-synthèse qualitative pour examiner en profondeur les obstacles aux soins de la tuberculose auxquels se heurtent les patients, la communauté, et le système de santé. Nous avons utilisé les résultats des deux revues systématiques pour affiner notre cadre conceptuel afin d'orienter la conception et l'analyse de l'étude empirique qui a suivi. Le cadre conceptuel adapté est basé sur le cadre de Levesque. Ce cadre centré sur les patients conceptualise l’accès aux soins selon des dimensions du système de santé et des patients. Cette étude comprenait également une analyse rétrospective d’une cohorte de patients diagnostiqués en 2015 (n = 996) à l'aide de données secondaires nationales et une analyse en cascade des soins de la tuberculose pharmaco-résistante entre 2013 et 2017. Nous avons mené des analyses statistiques descriptives et analytiques. Nous avons effectué une régression logistique et d'autres tests d’association pour mesurer la relation entre les variables catégorielles. L’étude qualitative était une étude de cas qui consistait à examiner la dynamique de soins du point de vue des patients (n = 86 participants, n = 7 groupes de discussions, 5 entretiens approfondis avec des patients diagnostiqués et non traités), leurs familles (n = 19 participants, n = 1 groupe de discussion, 7entretiens approfondis ), membres de la communauté (n = 23 , n=2 groupes de discussion), agents de santé (n = 5 entretiens approfondis) et gestionnaires de programme (n = 29 entretiens approfondis) dans quatre États du Nigéria. Nous avons analysé nos données qualitatives à l'aide d'une analyse thématique. Résultats: Notre revue systématique mixte et notre méta-synthèse qualitative ont indiqué des obstacles et des facilitateurs à l’accès aux soins de la tuberculose pharmaco-résistante au niveau du système de santé et des patients. Les problèmes de fonctionnement des laboratoires et des cliniques, l’absence de connaissances et les attitudes des prestataires de soins, et la gestion de l'information étaient des obstacles à l’accès aux soins de la TPR. Les facteurs facilitateurs comprenaient des outils de diagnostic plus récents, la décentralisation des services et le coût gratuit des soins. Au niveau des patients, la perte de suivi avant ou pendant les soins en raison de la perception négative des soins dans les services publics, le genre, la famille, l’engagement professionnel ou scolaire, et le recours aux soins dans le secteur privé constituaient des obstacles. Les facilitateurs étaient la séropositivité pour VIH, la multitude de symptômes, et le soutien financier des patients. Nos résultats quantitatifs ont révélé une certaine amélioration mais des progrès insuffisants dans le diagnostic et la couverture du traitement au Nigeria entre 2013 et 2017. Notre analyse en cascade a montré des abandons significatifs entre chaque étape des soins, en commençant par les tests et en terminant par l'achèvement du traitement. En moyenne, 80% des cas estimés n'ont pas eu accès au test; 75% de ceux qui ont été testé n'ont pas été diagnostiqués; 36% des personnes diagnostiquées n'ont pas commencé le traitement et 23% d'entre elles n'ont pas terminé le traitement pour la période entre 2013-2017. En 2015, les patients et les enfants atteints de la TB qui résident au nord du Nigéria avaient une probabilité de 0,3 [IC à 95% 0,1-0,7] et 0,4[0,3-0,5] de terminer le traitement une fois la maladie diagnostiquée comparativement aux patients et aux enfants qui résident au sud du pays. Les hommes avaient une probabilité de 1,34 [IC à 95% 1,0-1,7] plus élevée de terminer le traitement après le diagnostic comparativement aux femmes. La localisation géographique et les niveaux de soins étaient associés à un traitement et / ou à un traitement rapide. Notre étude qualitative a identifié des obstacles aux soins aux niveaux individuel, familial, communautaire, et du système de santé. Certains groupes sociodémographiques de patients avaient un accès inéquitable aux soins de la TPR. Alors que les patients étaient pour la plupart traités de manière égale au niveau de l'établissement, certains patients avaient plus de difficulté à accéder aux soins en fonction de leur sexe, de leur âge, de leur profession, de leur niveau d'éducation, et de leur religion. La dynamique familiale et conjugale influencent l’accès aux soins des patients, en particulier des enfants et des femmes. Elle agissait parfois comme un obstacle aux soins. D’autres facteurs qui ont probablement entravé l’accès incluaient l’absence de considérations sur les droits d’accès et la protection des patients dans les directives de traitement et les protocoles de soins. Les patients ignoraient pour la plupart les causes de la tuberculose pharmaco-résistante et la disponibilité des soins gratuits. Le nombre d'agents de santé et les problèmes de formation, la faible performance des laboratoires et des cliniques sont des obstacles aux soins de la tuberculose au niveau du système de santé. Les principaux facilitateurs à l’accès aux soins comprenaient le soutien familial, le soutien financier aux patients et le traitement gratuit. Conclusions: Malgré la gratuité des tests et des traitements de la TB pharmaco-résistante au Nigéria depuis 2011, les couvertures de diagnostic et de traitement restent constamment faibles. Les obstacles à l’accès au diagnostic et au traitement de la TB et de la TB pharmaco-résistante sont similaires. Toutefois, la TB pharmaco-résistante présente des défis particuliers en raison de la complexité des procédures de prétraitement et des toxicités résultant des médicaments eux-mêmes. Notre étude avait pour objectif de mieux comprendre les facteurs qui influencent l’accès à l'initiation au traitement de la TB pharmaco-résistante. Nos résultats montrent que les obstacles les plus importants sont l'accès aux tests et au diagnostic, malgré les progrès technologiques de diagnostic et des protocoles cliniques. Notre étude a identifié plusieurs obstacles liés aux patients et au système de santé. La plupart des patients atteints de TB pharmaco-résistante n'ont pas accès aux tests et ne sont pas diagnostiqués, souvent en raison d'un manque d'information. Les politiques et les programmes de lutte contre la tuberculose pharmaco-résistante ne sont pas toujours équitables, en particulier pour les populations vivant dans les zones rurales, les enfants, et les femmes. Les résultats de notre étude ont généré des données probantes pertinentes pour les décideurs et les partenaires internationaux pour remédier aux disparités systémiques et fournir des services plus équitables. L'élimination des obstacles à l’accès aux soins en temps opportun devrait être une priorité urgente pour améliorer le programme de lutte contre la tuberculose au Nigéria. Dans la faible détection des cas et la couverture thérapeutique, les interventions devraient viser l'équité en facilitant l’accès aux soins des populations vulnérables. / Background: Detection and treatment coverage for drug-resistant tuberculosis (DR-TB) in Nigeria are persistently low despite the implementation of free diagnostic and treatment services since 2011. Nigeria has a high burden for tuberculosis, ranking 6th globally with 4.3% drug resistance in new, and 15% in retreatment cases. The World Health Organization classifies the country as a high burden for TB, DR-TB, and HIV, with a prevalence of 219 and 11 per 100,000 population for TB and DR-TB, and 1.28 per 1,000 population HIV. Without treatment, mortality from tuberculosis is approximately 70% within ten years, increasing with HIV co-infection and drug resistance - and decreasing to below 5% with treatment. DR-TB survival rates are lower, and treatment is longer, costlier, and more toxic; this may pose different challenges to both patients and health systems than is the case for drug-sensitive (DS-) TB. However, treatment response and survival are positively impacted by early detection and treatment initiation, ideally within four weeks of diagnosis, especially with HIV co-infection. Socio-demographic characteristics often interact in complex ways with systemic factors, to increase vulnerability and disadvantage – these interactions are particularly well examined through an equity of health access framework and could offer policy-relevant analyses and recommendations. This study explores patient and health system barriers and facilitators to diagnosis and treatment for DR-TB in Nigeria. Methods: This is a sequential transformative mixed-methods study. First, a mixed-methods systematic review identified barriers and facilitators affecting diagnosis and treatment for DR-TB in sub-Saharan Africa. A subsequent qualitative meta-synthesis was used to examine in more depth the patient, community, and health system barriers to TB care. The results of the systematic reviews were used to refine our conceptual framework and to guide the design and the analysis of the subsequent empirical study. The adapted conceptual framework is based on the Levesque framework for patient-centred healthcare access, which conceptualises access to care as having health system and patient dimensions. This study also included a retrospective cohort analysis of patients diagnosed in 2015 (n= 996 ) using National secondary data, and a DR-TB care cascade analysis of the period between 2013 and 2017. We used descriptive statistics, logistic regression and other tests of association to measure the relationship between variables categorical. The qualitative phase used a case study design to examine the dynamics of care from patients' perspectives (n= 86 participants, N= 7 focus group discussions (FGD), 5 in-depth interviews (IDIs) with diagnosed and untreated patients), their relatives (n= 19 participants, N= 1 FGD, 7 IDIs ), community members (n=23 in 2 FGDs), healthcare workers (n= 5 IDIs ), and program managers (n= 29 IDIs) in four States in Nigeria. We analysed our qualitative data using thematic analysis. Results: Our mixed methods systematic review and qualitative meta-synthesis revealed barriers and facilitators to DR-TB care at the health system and patient levels. Health system laboratory and clinic operational issues, poor provider knowledge and attitudes and information management were some barriers. Facilitators included newer diagnostic tools, decentralisation of services and free cost of care. At the patient level, loss to follow-up before or during care due to negative public sector care perceptions, gender, family, work or school commitments and using private sector care were some barriers. Facilitators were HIV positivity, having more symptoms, and financial support. Our quantitative findings revealed some improvement but inadequate progress in diagnosis and treatment coverage in Nigeria between 2013 and 2017. Our cascade analysis showed significant dropouts between each stage of care, starting with testing and ending with treatment completion. On average, between 2013-2017, 80% of estimated cases did not access testing; 75% of those who test were not diagnosed; 36% of those diagnosed were not initiated on treatment and 23% of these did not finish treatment. In 2015, children and patients in Northern Nigeria had odds of 0.3 [95% CI 0.1-0.7] and 0.4 [0.3-0.5] of completing treatment once diagnosed; compared with adults and patients in Southern Nigeria; while males were shown to have a 1.34 [95% CI 1.0-1.7] times greater chance of completing treatment after diagnosis compared to females.. Geographic locations and levels of care were associated with ever receiving treatment and or timely treatment. Our qualitative data and document review identified barriers to care at individual, family, community, and health systems levels. Some patient socio-demographic groups had inequitable access. While patients were mostly treated equally at the facility level, some patients experienced more difficulty accessing care based on their gender, age, occupation, educational level and religion. Parental and spousal influences affected patients, particularly children, and women, and were sometimes barriers to care. Other factors that likely hampered access include the absence of considerations for patients’ access rights and protection in the treatment guidelines and workers manuals. Patients were mostly unaware of the causes of DR-TB disease and the availability of free care. Health worker numbers and training, clinic, and operational laboratory issues limited patients’ access at the health system level. The main facilitators to care included family support, patient financial support, and free treatment. Conclusions: Despite the provision of free DR-TB testing and treatment in Nigeria since 2011, coverage for diagnosis and treatment remain persistently low. Our literature review identified many of the same access factors affecting both DS-TB and DR-TB. However, DR-TB had peculiar challenges due to complexities in pre- treatment procedures, and in toxicities as a result of the medications themselves. This study was designed to investigate the access factors impacting DR-TB treatment initiation identified in literature. However, our findings showed that the biggest barriers to DR-TB care were essentially in access to testing and diagnosis, making any advances in diagnostic technology and treatment regimens of little benefit to DR-TB patients in Nigeria. Several patient and health system factors were shown to impede access to DR-TB care, particularly for certain groups of patients. Most DR-TB patients are not accessing testing and do not get diagnosed, often due to a lack of information. Also, DR-TB policies, structures and processes are not always equitable, especially for rural dwellers, children and women. Findings from our mixed methods study provided the additional insights needed by policymakers and implementing partners to address systemic disparities and provide more equitable services based on the population's needs. Eliminating barriers that negatively impact timely access to care should be an urgent priority for the TB program in Nigeria. In Nigeria's low case-finding and treatment coverage, interventions should target equity and ease of access, specifically for the barriers identified at the patient and health system levels.