Obstacles in combating multidrug resistant tuberculosis in pediatric patients: a scope review / Obstáculos no combate à tuberculose multidroga resistente em pacientes pediátricos: uma revisão de escopo

Abstract Objectives: to identify the scientific evidence on excessively resistant and multidrug resistant tuberculosis in pediatric patients. Methods: this is a scope review of the literature, with a guiding question: "What is the scientific evidence on multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis in pediatric patients?". The research used the descriptors: "extensively drug-resistant tuberculosis" OR "multidrug-resistant tuberculosis" AND "pediatrics". The research was carried out in a double-blind manner in the following databases of the Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier and International Clinical Trials Registry Platform, with a temporal cut-off from 2011 to 2021, sending a final synthesized sample of 18 articles, which evaluated the methodological content through the level of evidence. Results: the results show the lack of research with a high level of evidence related to MDR-TB in children, the lack of adequate dosage of second-line drugs for the pediatric population and the importance of drug sensitivity testing for the cases of treatment Conclusions: it was identified that the obstacles to MDR-TB treatment were concentrated in the lack of detailed protocols, safe drug dosages with a low side effect, and mainly in the social health determinants and disease process involving MDR-TB.

Resumo Objetivos: identificar as evidências científicas sobre tuberculose excessivamente resistente e multidroga resistente em pacientes pediátricos. Métodos: trata-se de uma revisão de escopo da literatura, tendo como questão norteadora: "Quais as evidências científicas sobre tuberculose multidroga-resistente (TB-MDR) e tuberculose extensivamente resistente em pacientes pediátricos?" A pesquisa usou os descritores: "tuberculose extensivamente resistente a medicamentos" OR "tuberculose resistente a múltiplos medicamentos" AND "pediatria". A pesquisa foi realizada de modo duplo-cego nas bases de dados Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier e International Clinical Trials Registry Platform, com um corte temporal de 2011 a 2021, sendo a amostra final sintetizada de 18 artigos, nos quais avaliou-se o conteúdo metodológico por meio do nível de evidência. Resultados: os resultados mostraram a escassez de pesquisas de alto nível de evidência relacionadas à TB-MDR em crianças, ausência de posologia adequada das drogas de segunda linha para o público pediátrico e a importância do teste de sensibilidade a drogas para o tratamento dos casos. Conclusões: identificou-se que os obstáculos do tratamento TB-MDR se concentraram na ausência de protocolos detalhados, de dosagens medicamentosas seguras e com menor efeito colateral, e, principalmente, nos determinantes sociais do processo saúde e doença que envolvem a TB-MDR.

Prospective Comparative Effectiveness Trial of Multidisciplinary Lung Cancer Care Within a Community-Based Health Care System.

PURPOSE: Multidisciplinary lung cancer care is assumed to improve care delivery by increasing transparency, objectivity, and shared decision making; however, there is a lack of high-level evidence demonstrating its benefits, especially in community-based health care systems. We used implementation and team science principles to establish a colocated multidisciplinary lung cancer clinic in a large community-based health care system and evaluated patient experience and outcomes within and outside this clinic. METHODS: We conducted a prospective frequency-matched comparative effectiveness study (ClinicalTrials.gov identifier: NCT02123797) evaluating the thoroughness of lung cancer staging, receipt of stage-appropriate treatment, and survival between patients receiving care in the multidisciplinary clinic and those receiving usual serial care. Target enrollment was 150 patients on the multidisciplinary arm and 300 on the serial care arm. We frequency-matched patients by clinical stage, performance status, insurance type, race, and age. RESULTS: A total of 526 patients were enrolled: 178 on the multidisciplinary arm and 348 on the serial care arm. After adjusting for other factors, multidisciplinary patients had significantly higher odds (odds ratio [OR]: 2.3 [95% CI, 1.5 to 3.4]) of trimodality staging compared with serial care. Patients on the multidisciplinary arm also had higher odds of receiving invasive stage confirmation (OR: 2.0 [95% CI, 1.4 to 3.1]) and mediastinal stage confirmation (OR: 1.9 [95% CI, 1.3 to 2.8]). Additionally, patients receiving multidisciplinary care were significantly more likely to receive stage-appropriate treatment (OR: 1.8 [95% CI, 1.1 to 3.0]). We found no significant difference in overall or progression-free survival between study arms. CONCLUSION: The multidisciplinary clinic delivered significant improvements in evidence-based quality care on multiple levels. Even in the absence of a demonstrable survival benefit, these findings provide a strong rationale for recommending this model of care.

Lung Cancer Diagnosed Through Screening, Lung Nodule, and Neither Program: A Prospective Observational Study of the Detecting Early Lung Cancer (DELUGE) in the Mississippi Delta Cohort.

PURPOSE: Lung cancer screening saves lives, but implementation is challenging. We evaluated two approaches to early lung cancer detection-low-dose computed tomography screening (LDCT) and program-based management of incidentally detected lung nodules. METHODS: A prospective observational study enrolled patients in the early detection programs. For context, we compared them with patients managed in a Multidisciplinary Care Program. We compared clinical stage distribution, surgical resection rates, 3- and 5-year survival rates, and eligibility for LDCT screening of patients diagnosed with lung cancer. RESULTS: From 2015 to May 2021, 22,886 patients were enrolled: 5,659 in LDCT, 15,461 in Lung Nodule, and 1,766 in Multidisciplinary Care. Of 150, 698, and 1,010 patients diagnosed with lung cancer in the respective programs, 61%, 60%, and 44% were diagnosed at clinical stage I or II, whereas 19%, 20%, and 29% were stage IV (P = .0005); 47%, 42%, and 32% had curative-intent surgery (P < .0001); aggregate 3-year overall survival rates were 80% (95% CI, 73 to 88) versus 64% (60 to 68) versus 49% (46 to 53); 5-year overall survival rates were 76% (67 to 87) versus 60% (56 to 65) versus 44% (40 to 48), respectively. Only 46% of 1,858 patients with lung cancer would have been deemed eligible for LDCT by US Preventive Services Task Force (USPSTF) 2013 criteria, and 54% by 2021 criteria. Even if all eligible patients by USPSTF 2021 criteria had been enrolled into LDCT, the Nodule Program would have detected 20% of the stage I-II lung cancer in the entire cohort. CONCLUSION: LDCT and Lung Nodule Programs are complementary, expanding access to early lung cancer detection and curative treatment to different-risk populations. Implementing Lung Nodule Programs may alleviate emerging disparities in access to early lung cancer detection.

The Relative Survival Impact of Guideline-Concordant Clinical Staging and Stage-Appropriate Treatment of Potentially Curable Non-Small Cell Lung Cancer.

BACKGROUND: Lung cancer management guidelines strive to improve outcomes. Theoretically, thorough staging promotes optimal treatment selection. We examined the association between guideline-concordant invasive mediastinal nodal staging, guideline-concordant treatment, and non-small cell lung cancer survival. RESEARCH QUESTION: What is the current practice of invasive mediastinal nodal staging for patients with lung cancer in a structured multidisciplinary care environment? Is guideline-concordant staging associated with guideline-concordant treatment? How do they relate to survival? STUDY DESIGN AND METHODS: We evaluated patients with nonmetastatic non-small cell lung cancer diagnosed from 2014 through 2019 in the Multidisciplinary Thoracic Oncology Program of the Baptist Cancer Center, Memphis, Tennessee. We examined patterns of mediastinal nodal staging and stage-stratified treatment, grouping patients into cohorts with guideline-concordant staging alone, guideline-concordant treatment alone, both, or neither. We evaluated overall survival with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 882 patients, 456 (52%) received any invasive mediastinal staging. Seventy-four percent received guideline-concordant staging; guideline-discordant staging decreased from 34% in 2014 to 18% in 2019 (P < .0001). Recipients of guideline-concordant staging were more likely to receive guideline-concordant treatment (83% vs 66%; P < .0001). Sixty-one percent received both guideline-concordant invasive mediastinal staging and guideline-concordant treatment; 13% received guideline-concordant staging alone; 17% received guideline-concordant treatment alone; and 9% received neither. Survival was greatest in patients who received both (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.26-0.63), followed by those who received guideline-concordant treatment alone (aHR, 0.60; 95% CI, 0.36-0.99), and those who received guideline-concordant staging alone (aHR, 0.64; 95% CI, 0.37-1.09) compared with neither (P < .0001, log-rank test). INTERPRETATION: Levels of guideline-concordant staging were high, were rising, and were associated with guideline-concordant treatment selection in this multidisciplinary care cohort. Guideline-concordant staging and guideline-concordant treatment were complementary in their association with improved survival, supporting the connection between these two processes and lung cancer outcomes.

The complete chloroplast genome of the threatened Napa False Indigo Amorpha californica var. napensis Jeps. 1925 (Fabaceae) from Northern California, USA.

Amorpha californica var. napensis Jeps. 1925, the Napa false indigo, is a threatened shrub endemic to northern California. Here the complete chloroplast genome of topotype material of var. napensis was assembled and characterized to contribute to the bioinformatics, systematics, and conservation of this variety. The chloroplast genome (GenBank accession OK274088) is 158,294 base pairs (bp) in length, encodes 130 genes including 85 protein-coding, 37 tRNA, 8 rRNA, and shows a high-level of gene synteny to other Papilionoideae. Phylogenetic analysis fully resolved var. napensis in a clade with A. fruticosa L. and A. roemeriana Scheele, sister to the Dalbergieae. The newly sequenced chloroplast genome shows that the genetic differences between var. napensis and Amorpha californica Nutt. var. californica are greater than the variation observed between var. napensis and many other Amorpha spp. sequences deposited in GenBank. These data suggest that var. napensis should be elevated to full species rank.

Impact of a Lymph Node Specimen Collection Kit on the Distribution and Survival Implications of the Proposed Revised Lung Cancer Residual Disease Classification: A Propensity-Matched Analysis.

IMPORTANCE: The International Association for the Study of Lung Cancer (IASLC) has proposed a revision of the residual disease (R-factor) classification, to R0, 'R-uncertain', R1 and R2. We previously demonstrated longer survival after surgical resection with a lymph node specimen collection kit, and now evaluate R-factor redistribution as the mechanism of its survival benefit. OBJECTIVE: We retrospectively evaluated surgical resections for lung cancer in the population-based observational 'Mid-South Quality of Surgical Resection' cohort from 2009-2019, including a full-cohort and propensity-score matched analysis. RESULTS: Of 3,505 resections, 34% were R0, 60% R-uncertain, and 6% R1 or R2. The R0 percentage increased from 9% in 2009 to 56% in 2019 (p < 0.0001). Kit cases were 66% R0 and 29% R-uncertain, compared to 14% R0 and 79% R-uncertain in non-kit cases (p < 0.0001). Compared with non-kit resections, kit resections had 12.3 times the adjusted odds of R0 versus R-uncertainty.Of 2,100 R-uncertain resections, kit cases had lower percentages of non-examination of lymph nodes, 1% vs. 14% (p < 0.0001) and non-examination of mediastinal lymph nodes, 8% vs. 35% (p < 0.0001). With the kit, more R-uncertain cases had examination of stations 7 (43% vs. 22%, p < 0.0001) and 10 (67% vs. 45%, p < 0.0001).The adjusted hazard ratio (aHR) for kit cases versus non-kit cases was 0.75 (confidence interval [CI]: 0.66-0.85, p < 0.0001). In 2,100 subjects with R-uncertain resections, kit cases had an aHR of 0.79 versus non-kit cases ([CI: 0.64-0.99], p=0.0384); however, in the 1,199 R0 resections the survival difference was not significant (aHR: 0.85[0.68-1.07], p = 0.17). CONCLUSIONS AND RELEVANCE: A lymph node kit increased overall survival by increasing R0, reducing the probability of R-uncertain resections, and diminishing extreme R-uncertainty.

Interest in Cessation Treatment Among People Who Smoke in a Community-Based Multidisciplinary Thoracic Oncology Program.

INTRODUCTION: To evaluate the need for tobacco cessation services within a multidisciplinary clinic (MDC), we surveyed patients on their smoking status, interest in quitting, and willingness to participate in a clinic-based cessation program. We further evaluated the association between interest in cessation or willingness to participate in a cessation program and overall survival (OS). METHODS: From 2014 to 2019, all new patients with lung cancer in the MDC at Baptist Cancer Center (Memphis, TN) were administered a social history questionnaire to evaluate their demographic characteristics, smoking status, tobacco dependence, interest in quitting, and willingness to participate in a cessation program. We used chi-square tests and logistic regression to compare characteristics of those who would participate to those who would not or were unsure and Kaplan-Meier curves and Cox regression to evaluate the association between cessation interest or willingness to quit and OS. RESULTS: Of 641 total respondents, the average age was 69 years (range: 32-95), 47% were men, 64% white, 34% black, and 17% college graduates. A total of 90% had ever smoked: 34% currently and 25% quit within the past year. Among the current smokers, 60% were very interested in quitting and 37% would participate in a cessation program. Willingness to participate in a cessation program was associated with greater interest in quitting (p < 0.0001), better OS (p = 0.02), and reduced hazard of death (hazard ratio = 0.52, 95% confidence interval: 0.30-0.88), but no other characteristics. CONCLUSIONS: Patients with lung cancer in an MDC expressed considerable interest in tobacco cessation services; patients willing to participate in a clinic-based cessation program had improved survival.

Survival Impact of an Enhanced Multidisciplinary Thoracic Oncology Conference in a Regional Community Health Care System.

INTRODUCTION: We compared NSCLC treatment and survival within and outside a multidisciplinary model of care from a large community health care system. METHODS: We implemented a rigorously benchmarked "enhanced" Multidisciplinary Thoracic Oncology Conference (eMTOC) and used Tumor Registry data (2011-2017) to evaluate guideline-concordant care. Because eMTOC was located in metropolitan Memphis, we separated non-MTOC patient by metropolitan and regional location. We categorized National Comprehensive Cancer Network guideline-concordant treatment as "preferred," or "appropriate" (allowable under certain circumstances). We compared demographic and clinical characteristics across cohorts using chi-square tests and survival using Cox regression, adjusted for multiple testing. We also performed propensity-matched and adjusted survival analyses. RESULTS: Of 6259 patients, 14% were in eMTOC, 55% metropolitan non-MTOC, and 31% regional non-MTOC cohorts. eMTOC had the highest rates of African Americans (34% versus 28% versus 22%), stages I to IIIB (63 versus 40 versus 50), urban residents (81 versus 78 versus 20), stage-preferred treatment (66 versus 57 versus 48), guideline-concordant treatment (78 versus 70 versus 63), and lowest percentage of nontreatment (6 versus 21 versus 28); all p values were less than 0.001. Compared with eMTOC, hazard for death was higher in metropolitan (1.5, 95% confidence interval: 1.4-1.7) and regional (1.7, 1.5-1.9) non-MTOC; hazards were higher in regional non-MTOC versus metropolitan (1.1, 1.0-1.2); all p values were less than 0.05 after adjustment. Results were generally similar after propensity analysis with and without adjusting for guideline-concordant treatment. CONCLUSIONS: Multidisciplinary NSCLC care planning was associated with significantly higher rates of guideline-concordant care and survival, providing evidence for rigorous implementation of this model of care.

Trends in Accuracy and Comprehensiveness of Pathology Reports for Resected NSCLC in a High Mortality Area of the United States.

INTRODUCTION: Complete and accurate pathology reports are vital to postoperative prognostication and management. We evaluated the impact of three interventions across a diverse group of hospitals on pathology reports of postresection NSCLC. METHODS: We evaluated pathology reports for patients who underwent curative-intent surgical resection for NSCLC, at 11 institutions within four contiguous Dartmouth Hospital Referral Regions in Arkansas, Mississippi, and Tennessee from 2004 to 2020, for completeness and accuracy, before and after the following three quality improvement interventions: education (feedback to heighten awareness); synoptic reporting; and a lymph node specimen collection kit. We compared the proportion of pathology reports with the six most important items for postoperative management (specimen type, tumor size, histologic type, pathologic [p] T-category, pN-category, margin status) across the following six patient cohorts: preintervention control, postintervention with four different combinations of interventions, and a contemporaneous nonintervention external control. RESULTS: In the postintervention era, the odds of reporting all key items were eight times higher than those in the preintervention era (OR = 8.3, 95 % confidence interval [CI]: 6.7-10.2, p < 0.0001). There were sixfold and eightfold increases in the odds of accurate pT- and pN-category reporting in the postintervention era compared with the preintervention era (pT OR = 5.7, 95 % CI: 4.7-6.9; pN OR = 8.0, 95 % CI: 6.5-10.0, both p < 0.0001). Within the intervention groups, the odds of reporting all six key items, accurate pT category, and accurate pN-category were highest in patients who received all three interventions. CONCLUSIONS: Gaps in the quality of NSCLC pathologic reportage can be identified, quantified, and corrected by rationally designed interventions.

Comparative Effectiveness of a Lymph Node Collection Kit Versus Heightened Awareness on Lung Cancer Surgery Quality and Outcomes.

INTRODUCTION: The adverse prognostic impact of poor pathologic nodal staging has stimulated efforts to heighten awareness of the problem through guidelines, without guidance on processes to overcome it. We compared heightened awareness (HA) of nodal staging quality versus a lymph node collection kit. METHODS: We categorized curative-intent lung cancer resections from 2009 to 2020 in a population-based, nonrandomized stepped-wedge implementation study of both interventions, into preintervention baseline, HA, and kit subcohorts. We used differences in proportion and hazard ratios across the subcohorts to estimate the effect of the interventions on poor quality (nonexamination of nodes [pNX] or nonexamination of mediastinal lymph nodes) and attainment of quality recommendations of the National Comprehensive Cancer Network, the Commission on Cancer, and the proposed complete resection definition of the International Association for the Study of Lung Cancer across the three cohorts. RESULTS: Of 3734 resections, 39% were preintervention, 40% kit, and 21% HA cases. Cohort proportions were the following: pNX, 11% (baseline) versus 0% (kit) versus 9% (HA); nonexamination of mediastinal lymph nodes, 27% versus 1% versus 22%; Commission on Cancer benchmark attainment, 14% versus 77% versus 30%; International Association for the Study of Lung Cancer-defined complete resection, 11% versus 58% versus 24%; National Comprehensive Cancer Network attainment, 23% versus 79% versus 35% (p < 0.001 for all, except pNX rate baseline versus HA). Survival rate was significantly higher for both interventions compared with baseline (p < 0.0001). CONCLUSIONS: Resections with HA or the kit significantly improved surgical quality and outcomes, but the kit was more effective. We propose to conduct a prospective, institutional cluster-randomized clinical trial comparing both interventions.