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Calcineurin inhibitors (CNIs) are the mainstay of immunosuppression in kidney transplantation. Interpatient variability in the disposition of calcineurin inhibitors is a well-researched phenomenon and has a well-established genetic contribution. There is great diversity in the makeup of African genomes, but very little is known about the pharmacogenetics of CNIs and transplant outcomes. This review focuses on genetic variants of calcineurin inhibitors' metabolizing enzymes (CYP3A4, CYP3A5), related molecules (POR, PPARA) and membrane transporters involved in the metabolism of calcineurin inhibitors. Given the genetic diversity across the African continent, it is imperative to generate pharmacogenetic data, especially in the era of personalized medicine and emphasizes the need for studies specific to African populations. The study of allelic variants in populations where they have greater frequencies will help answer questions regarding their impact. We aim to fill the knowledge gaps by reviewing existing research and highlighting areas where African research can contribute.
Research on the pharmacogenetics of calcineurin inhibitors in kidney transplant recipients is truly wanting in data from the African continent. Given Africa's vast genetic diversity, it is necessary to intensify efforts to generate data from Africa in this field.
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The gut-liver axis plays a pivotal role in maintaining body homeostasis. Disruption of the gut-liver axis is linked to a multitude of diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Probiotic strains from the Lactobacillaceae family are commonly used to mitigate experimental MASLD. Over the years, numerous studies have demonstrated the efficacy of these probiotics, often focusing on the outcome of liver disease. This review aims to further understand MASLD as a systemic metabolic dysfunction and to highlight the effects of probiotics on multi-organ axis, including organs such as the gastrointestinal tract, pancreas, muscle, adipose tissue, and the immune system. We specifically discuss evidence on how supplementation with Lactobacillaceae strains may alleviate MASLD by not only restoring liver health but also by modulating the physiology of other organ systems.
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[This corrects the article DOI: 10.1016/j.ekir.2024.02.699.].
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Antituberculosos , Diarilquinolinas , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Europa (Continente) , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Diarilquinolinas/uso terapéutico , Diarilquinolinas/farmacología , Linezolid/farmacología , Linezolid/uso terapéutico , Pruebas de Sensibilidad Microbiana , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Rifampin/farmacología , Rifampin/uso terapéutico , Moxifloxacino/uso terapéutico , Moxifloxacino/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Nitroimidazoles/uso terapéutico , Nitroimidazoles/farmacología , OxazolesRESUMEN
BACKGROUND: Tuberculosis (TB) remains a significant public health concern, particularly within prison settings, where the confluence of adverse health factors and high-risk behaviors contribute to a heightened risk of transmission. This study delves into the perspectives of medical doctors, regarding the implementation of the 2014 TB protocol in Portugal. METHODS: The study has a qualitative, descriptive design. Individual semi-structured interviews with medical doctors from TB outpatient centers in Porto and Lisbon were used for data collection. For the analysis thematic analysis method was used. RESULTS: The study population comprised 21 medical doctors with the majority being female (61.9%) and 57.1% specializing in pulmonology. The results indicate varied perceptions of the protocol's usefulness, with positive impacts on coordination reported by some participants. Improved communication and evolving collaboration between TB outpatient centers and prisons were highlighted, although challenges in contact tracing and resource constraints were acknowledged. The study also sheds light on the role of nurses in patient education. CONCLUSION: Despite overall positive perceptions, challenges such as sustaining therapy post-symptomatic improvement and delays in diagnostic methods were identified. The findings underscore the importance of continuous collaboration between prisons and TB control programs to address challenges, improve disease control and prevent TB transmission.
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Responding to a surge in new tuberculosis (TB) cases among migrants from high-incidence countries, low-incidence European nations have heeded World Health Organization recommendations by implementing TB screening in this population. This review aims to synthesise evidence on current screening strategies for active TB and latent tuberculosis infection (LTBI) in European high-income countries, and their main barriers and interventions. PubMed, Web of Science and Scopus were searched from March to April 2023, including articles in English, published in the last decade, pertaining to screening strategies for active TB or LTBI in Europe focused on migrants, excluding those exclusively composed of refugees, asylum seekers or other migrant populations. 32 studies fit the criteria. Screening in migrants varies between countries regarding timing, population, screening location and diagnosis. Furthermore, some barriers prevent migrants from benefiting from screening, namely physical, cultural and professional barriers. Additional research is needed to determine the patterns through which regular migrants adhere to current screening strategies in European countries.
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Patient-reported outcomes (PROs) play a crucial role in understanding the impact of tuberculosis (TB) on both individuals and communities. Despite advances in TB treatment, conventional outcome definitions often overlook essential components of people with TB's experiences, leading to disparities in treatment understanding. The incorporation of PROs in TB scientific research can help bridge the gap between the health system and people's needs and expectations. PROs can offer valuable insights into non-observable constructs like health literacy, self-efficacy and overall wellbeing, contributing to the comprehensive assessment of diagnosis, treatment and research end-points. Participatory community approaches, such as Community-Based Participatory, emphasise the engagement and involvement of relevant stakeholders in designing interventions tailored to their needs. Key stakeholders, including healthcare professionals, researchers, clinical trial investigators, public health officials, and community health workers, TB survivors and people with TB, can play a vital role in promoting patient-centred care and engaging directly with the TB-affected community. An increased and cross-collaborative effort for the inclusion of PROs in TB research can entail their potential role in developing effective treatment regimens and promoting adherence, while maximising community engagement and improving outcomes for those affected by TB.
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OBJECTIVES: Multidrug-resistant/rifampicin-resistant tuberculosis is a major obstacle to successful tuberculosis control. The recommendation by the WHO to use bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaL(M)) for 6 months, based on results of two trials with high efficacy and low toxicity, has revolutionized treatment options. METHODS: In this study, representatives of the Tuberculosis Network European Trials group in 44 of 54 countries of the WHO Europe region documented the availability of the medicines and drug susceptibility testing (DST) of the BPaL(M) regimen through a structured questionnaire between September and November 2023. RESULTS: In total, 24 of 44 (54.5%), 42 of 44 (95.5%), 43 of 44 (97.7%), and 43 of 44 (97.7%) countries had access to pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, 23 of 44 (52.3%) countries had access to all the drugs composing the BPaL(M) regimen. In total, 21 of 44 (47.7%), 37 of 44 (84.1%), 40 of 44 (90.9%), and 41 of 44 (93.2%) countries had access to DST for pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, DST was available for all medicines composing the BPaL(M) regimen in 21 of 44 (47.7%) countries, including countries where pretomanid DST was available at specialized laboratories. The availability of DST for the drugs the countries had access to, varied from 87.5% to 95.3% (pretomanid 21 of 24 (87.5%), bedaquiline 37 of 42 (88.1%), linezolid 40 of 43 (93.1%) and moxifloxacin 41 of 43 (95.3%)). DISCUSSION: In only about half of the countries participating in the survey, clinicians had access to all the BPaL(M) regimen drugs. A complete DST for the BPaL(M) medicines was possible in less than half of the countries, because of the low accessibility of DST for pretomanid. Equal access to new regimens is urgently needed in Europe and a rapid scale up of DST, especially for pretomanid, is important to prevent unnoticed spread of drug resistance.
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Antituberculosos , Diarilquinolinas , Linezolid , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Tuberculosis Resistente a Múltiples Medicamentos , Linezolid/farmacología , Linezolid/uso terapéutico , Europa (Continente) , Humanos , Moxifloxacino/uso terapéutico , Diarilquinolinas/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Rifampin/uso terapéutico , Rifampin/farmacología , Nitroimidazoles/uso terapéutico , Nitroimidazoles/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Encuestas y CuestionariosRESUMEN
The grand discovery of morphogens, or "form-generating substances", revealed that tissue morphogenesis is initiated by soluble molecular signals or morphogens primarily belonging to the transforming growth factor-ß (TGF-ß) supergene family. The regenerative potential of bone rests on its extracellular matrix, which is the repository of several morphogens that tightly control cellular differentiating pathways, cellular matrix deposition and remodeling. Alluringly, the matrix also contains specific factors transferred from the heterotopic implanted bone matrices initiating "Tissue Induction", as provocatively described in Nature in 1945. Later, it was found that selected genes and gene products of the TGF-ß supergene family singly, synchronously, and synergistically mastermind the induction of bone formation. This review describes the phenomenon of the spontaneous and/or intrinsic osteoinductivity of calcium phosphate-based biomaterials and titanium' constructs without the applications of soluble osteogenetic molecular signals. The review shows the spontaneous induction of bone formation initiated by Ca++ activating stem cell differentiation and up-regulation of bone morphogenetic proteins genes. Expressed gene products are embedded into the concavities of the calcium phosphate-based substrata, initiating bone formation as a secondary response. Pure titanium's substrata do not initiate the spontaneous induction of bone formation. The induction of bone is solely dependent on acid, alkali and heat treatments to form apatite layers on the treated titanium surfaces. The induction of bone formation is achieved exclusively by apatite-based biomaterial surfaces. The hydroxyapatite, in its various forms and geometric configurations, finely tunes the induction of bone formation in heterotopic sites. Cellular differentiation by fine-tuning of the cellular molecular machinery is initiated by specific geometric modularity of the hydroxyapatite substrata that push cellular buttons that start the ripple-like cascade of "Tissue Induction", generating newly formed ossicles with bone marrow in heterotopic extraskeletal sites. The highlighted mechanistic insights into the spontaneous induction of bone formation are a research platform invocating selected molecular elements to construct the induction of bone formation.
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Fosfatos de Calcio , Osteogénesis , Titanio , Osteogénesis/genética , Apatitas , Materiales Biocompatibles , Durapatita , Factor de Crecimiento Transformador betaRESUMEN
BACKGROUND: Diagnosis delay contributes to increased tuberculosis (TB) transmission and morbimortality. TB incidence has been decreasing in Portugal, but median patient delay (PD) has risen. Symptom valorisation may determine PD by influencing help-seeking behaviour. We aimed to analyse the association between symptom valorisation and PD, while characterising individuals who disregarded their symptoms. METHODS: A cross-sectional study was conducted among TB patients in Lisbon and Oporto in 2019 - 2021. Subjects who delayed seeking care because they did not value their symptoms or thought these would go away on their own were considered to have disregarded their symptoms. PD was categorised using a 21-day cut-off, and a 30-day cut-off for sensitivity analysis. We estimated the effect of symptom valorisation on PD through a directed acyclic graph. Then, a multivariable regression analysis characterised patients that disregarded their symptoms, adjusting for relevant variables. We fitted Poisson regression models to estimate crude and adjusted prevalence ratios (PR). RESULTS: The study included 75 patients. Median PD was 25 days (IQR 11.5-63.5), and 56.0% of participants had PD exceeding 21 days. Symptom disregard was reported by 38.7% of patients. Patients who did not value their symptoms had higher prevalence of PD exceeding 21 days compared to those who valued their symptoms [PR 1.59 (95% CI 1.05-2.42)]. The sensitivity analysis showed consistent point estimates but wider confidence intervals [PR 1.39 (95% CI 0.77-2.55)]. Being a smoker was a risk factor for symptom disregard [PR 2.35 (95% CI 1.14-4.82)], while living in Oporto [PR 0.35 (95% CI 0.16-0.75)] and having higher household incomes [PR 0.39 (95% CI 0.17-0.94)] were protective factors. CONCLUSIONS: These findings emphasise the importance of symptom valorisation in timely TB diagnosis. Patients who did not value their symptoms had longer PD, indicating a need for interventions to improve symptom recognition. Our findings also corroborate the importance of the socioeconomic determinants of health, highlighting tobacco as a risk factor both for TB and for PD.
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Tuberculosis Pulmonar , Tuberculosis , Humanos , Aceptación de la Atención de Salud , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Estudios Transversales , Portugal/epidemiología , Diagnóstico Tardío , Tuberculosis/epidemiología , Encuestas y CuestionariosRESUMEN
The news media in Portugal played an important role during the COVID-19 pandemic by providing people with important and up-to-date health information. However, the number of news reports did not always correspond to the severity of the pandemic. There was significant media attention at the beginning of the pandemic (in early 2020), but media coverage soon declined, and the Portuguese media began to report on a greater diversity of topics. The present study assessed the evolution of news reports in Portugal during the period of the COVID-19 pandemic by analysis of epidemiological data (cases, deaths, and hospitalizations) and television news lineups from the three major generalist television channels, RTP1, SIC, TVI. The study period was from March 2020 (when the first lockdown was instituted) to March 2021 (when there was the second gradual withdrawal of restrictions). Our results indicated that there was intense media coverage of COVID-19 during the first phase of the pandemic, even though epidemiological data showed there was not a severe health crisis at that time. However, the number of news stories about the pandemic soon declined, and this number was much lower during the worst period of the pandemic. Hence, the intensity of coverage of the COVID-19 pandemic in the Portuguese media provided a distorted image of the actual pandemic. All things considered, we strongly advise for the inclusion of a communication plan that would help address future health emergency crisis. All things considered, we recommend that in future health crisis there is a planned communication strategy that takes into account media relations.
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COVID-19 , Medios de Comunicación Sociales , Humanos , COVID-19/epidemiología , Pandemias , Portugal/epidemiología , Control de Enfermedades Transmisibles , Medios de Comunicación de MasasRESUMEN
BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.
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Tuberculosis , Humanos , Incidencia , Estudios Transversales , Somalia , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Europa (Continente)/epidemiologíaRESUMEN
In the past 2â years, remarkable advances have been made in shortening tuberculosis (TB) treatment. In particular, four clinical trials (Study 31/A5349, Nix-TB, ZeNix and TB-PRACTECAL) have provided evidence of the efficacy of regimens based on new and repurposed drugs: the 4-month regimen for drug-susceptible TB, and the 6-month bedaquiline-pretomanid-linezolid regimen with or without moxifloxacin for multidrug-resistant/rifampicin-resistant TB. Even if the evidence at the basis of these new regimens is compelling, several questions remain open, particularly concerning linezolid dose finding, the upsurging threat of bedaquiline-resistant Mycobacterium tuberculosis and the feasibility of applying these results to the paediatric population. Several ongoing trials may fill the remaining gaps and produce further reliable evidence to address the outstanding questions in TB treatment shortening.
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Black African populations are more genetically diverse than others, but genetic variants have been studied primarily in European populations. The present study examined the association of four single nucleotide polymorphisms (SNPs) of the fibroblast growth factor receptor 2, associated with breast cancer in nonAfrican populations, with breast cancer in Black, southern African women. Genomic DNA was extracted from whole blood samples of 1,001 patients with breast cancer and 1,006 controls (without breast cancer), and the rs2981582, rs35054928, rs2981578, and rs11200014 polymorphisms were analyzed using allelespecific Kompetitive allelespecific PCR™, and the χ2 or Fisher's exact tests were used to compare the genotype frequencies. There was no association between those SNPs and breast cancer in the studied cohort, although an association was identified between the C/C homozygote genotype for rs2981578 and invasive lobular carcinoma. These results show that genetic biomarkers of breast cancer risk in European populations are not necessarily associated with risk in subSaharan African populations. African populations are more heterogenous than other populations, and the information from this population can help focus genetic risks of cancer in this understudied population.
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Neoplasias de la Mama , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Femenino , Humanos , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Población Negra/genética , SudáfricaRESUMEN
People with or affected by tuberculosis (TB) experience complex social and cultural constraints that may affect treatment outcomes by impeding access to proper care or by hindering treatment adherence. Low levels of health literacy which leads to inadequate disease information; stigma, discrimination and other forms of prejudice that may result in marginalisation and ostracisation; and socioeconomic vulnerabilities that hamper one's capacity to access essential goods or increase the risk of exposure to the disease are some of the barriers highlighted. These complex hurdles are also disproportionately felt by people with or affected by TB due to gender-related inequalities that need to be properly addressed. Additionally, TB prevention and care should encompass interventions aimed at improving and promoting mental health, given that mental unhealth may further thwart treatment adherence and success. A multifaceted and multidisciplinary approach to TB is required to answer these complex barriers.
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Background Sarcoidosis is a granulomatous multisystem disease of uncertain aetiology. The disease has major inflammatory and immune components; however, the immunopathogenesis is not well understood. Micro ribonucleic acids (microRNAs) are classes of miniature, single-stranded, non-coding RNAs. Their key recognised role includes mediating the silencing of target genes post-transcriptionally. Recently, the role of miRNAs has gained interest in numerous disorders, suggested as being involved in pathogenesis of those diseases and acting as disease markers. Very little is known about the role of miRNAs in sarcoidosis, with nothing known regarding miRNAs in South African patients. The main objective, therefore, was to investigate the serum expression of approximately 800 miRNAs in patients with sarcoidosis compared with race-, age- and gender-matched healthy controls. Methods A total of six patients and six matched controls participated in this study. Whole blood samples were collected in EDTA tubes, processed and the plasma retained. RNA was extracted from the stored plasma samples using the QIAGEN miRNeasy Mini Kit® and concentrated using a salt-ethanol precipitation. The extracted miRNA was profiled using an nCounter® miRNA human v3 expression assay and data analysed using the nSolver™ Analysis Software. Results After excluding one sample/control pair because of cellular RNA contamination, the remaining five patient and five matched control samples were analysed, and 145 miRNAs were found to be potentially differentially expressed. On applying a Bonferroni correction, the only miRNA that was significantly different was miRNA let-7a-5p, which was significantly overexpressed (141-fold change; p<0.0003) in patients compared with controls. Conclusion This is the first miRNA report of differentially expressed miRNAs in the serum of patients with sarcoidosis and matched healthy controls in South Africa. The results obtained suggest that miRNAs may play a role in sarcoidosis pathogenesis. Whether these molecules have diagnostic or prognostic implications, needs future studies recruiting larger patient cohorts.
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INTRODUCTION: The COVID-19 pandemic is an illustration of how a physical illness can damage people's minds. In this regard, the goal of this study was to see how different sociodemographic and behavioral factors were linked to anxiety and depression symptoms in a group of individuals living in Portugal. METHODS: Between November 2020 and February 2021, a cross-sectional, snowball online study was conducted. The study's target population was adults over the age of 18, residents of the country. For the statistical analysis, the clustering technique - K-means algorithm was applied. The chi-squared test was used to determine the relationships between clusters and sociodemographic and behavioral characteristics. Statistical analyses were conducted in R language, with a significance level of 0.05. A total of 453 participants were included. RESULTS: The majority were female (69.8%), under the age of 40 (60.8%), with a higher education degree (75.3%), and not married (54.4%). Furthermore, the majority were from the country's north region (66%). Cluster 1 (n = 194) was characterized by low or nonexistent levels of anxiety and depression symptoms, which means normal; cluster 2 by severe symptoms (n = 82), meaning case; and cluster 3 by mild symptoms (n = 177), which means borderline. Younger participants (p-value 0.024), female (p-value 0.041), with drinking habits (p-value 0.002), food insecurity (p-value < 0.001), food affordability exacerbation (p-value < 0.001), comorbidity (p-value < 0.001), use of anxiolytics (p-value < 0.001), insufficient household income (p-value 0.017) and income change (p-value < 0.001) were significantly associated with the anxiety-depression clusters. From the three clusters, cluster 2 was mainly represented by younger participants, with more persons stating that their household income was insufficient and that their income has changed as a result of COVID-19 and that they had the highest probability of food insecurity. CONCLUSION: The impacts of a crisis on mental health extend longer than the event itself. We were able to observe that younger women with insufficient household income who suffered a change in income due to COVID-19 and were classified as food insecure presented higher levels of anxiety and depression symptoms. These results highlight the presence of a social gradient where we saw that people who were less advantaged in terms of socioeconomic position presented worse mental health outcomes, stressing, in this sense, the need to bring the best public health responses for these specific groups of the population.
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COVID-19 , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , COVID-19/epidemiología , Depresión/epidemiología , Depresión/etiología , Portugal/epidemiología , Estudios Transversales , Pandemias , Ansiedad/epidemiología , Ansiedad/etiologíaRESUMEN
Deaths from tuberculosis (TB) reached over 1.6 million in 2021 with 10.6 million people becoming ill. Multidrug-resistant TB, defined as the Mycobacterium tuberculosis organism having resistance to at least isoniazid and rifampicin, represented 3.9% of new TB cases and 18% of previously treated cases. While new drug regimens continue to be developed and introduced to improve treatment of drug-resistant forms of TB, diagnostic capability to identify drug resistance lags woefully behind. While significant mortality benefits exist for these newer drug regimens, implementing them without proper drug resistance diagnostic capacity could lead to development of more drug resistances and exhaust these new therapeutic tools. Moving forward, the roll-out of new TB drugs and regimens must be paired with implementation of diagnostics to ensure judicious use of resources and the best chance for improving TB worldwide.