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New tools for controlling tuberculosis are urgently needed. Despite our emerging understanding of the biogeography of Mycobacterium tuberculosis, the implications for development of new diagnostics, drugs, and vaccines is unknown. M tuberculosis has a clonal genetic population structure that is geographically constrained. Evidence suggests strain-specific differences in virulence and immunogenicity in light of this global phylogeography. We propose a strain selection framework, based on robust phylogenetic markers, which will allow for systematic and comprehensive evaluation of new tools for tuberculosis control.

The advent of affordable, portable ultrasound devices has led to increasing interest in the use of point-of-care ultrasound (POCUS) for the detection of pulmonary TB (PTB). We undertook a systematic review of the diagnostic accuracy of POCUS for PTB. Five databases were searched for articles published between January 2010 and June 2020. Risk of bias was assessed using QUADAS-2. Data on sensitivity and specificity of individual lung ultrasound findings were collected, with variable reference standards including PCR and sputum smear microscopy. Six of 3,919 reviewed articles were included: five in adults and one in children, with a total sample size of 564. Studies had high risk of bias in many domains. In adults, subpleural nodule and lung consolidation were the lung ultrasound findings with the highest sensitivities, ranging from 72.5% to 100.0% and 46.7% to 80.4%, respectively. Only one study reported specificity data. Variability in sensitivity may be due to variable reference standards or may imply operator dependence. There is insufficient evidence to judge the diagnostic accuracy of POCUS for PTB. There is also no consensus on the optimal protocols for acquiring and analysing POCUS images for PTB. New studies which minimise potential sources of bias are required to further assess the diagnostic accuracy of POCUS for PTB.

Allergic rhinitis is a common disorder that is strongly linked to asthma and conjunctivitis. It is usually a long-standing condition that often goes undetected in the primary-care setting. The classic symptoms of the disorder are nasal congestion, nasal itch, rhinorrhea and sneezing. A thorough history, physical examination and allergen skin testing are important for establishing the diagnosis of allergic rhinitis. Second-generation oral antihistamines and intranasal corticosteroids are the mainstay of treatment. Allergen immunotherapy is an effective immune-modulating treatment that should be recommended if pharmacologic therapy for allergic rhinitis is not effective or is not tolerated, or if chosen by the patient. This article provides an overview of the pathophysiology, diagnosis, and appropriate management of this disorder.

Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

The effective treatment of tuberculosis is a lifesaving intervention. The global scale-up of tuberculosis therapy has averted 6 million deaths over the past 15 years, making it one of the greatest public health interventions of our lifetime. 1 Unfortunately, by the time most patients are treated, they have already infected many others. 2 This failure to interrupt transmission fuels the global epidemic so that every year there are more new cases of tuberculosis than in the previous year. 1 National tuberculosis programs are particularly challenged by multidrug-resistant tuberculosis. Globally, fewer than 2% of the estimated cases of multidrug-resistant disease are reported to the . . .

Continuing tuberculosis control with current approaches is unlikely to reach the World Health Organization's objective to eliminate TB by 2035. Innovative interventions such as unmanned aerial vehicles (or drones) and digital adherence monitoring technologies have the potential to enhance patient-centric quality tuberculosis care and help challenged National Tuberculosis Programs leapfrog over the impediments of conventional Directly Observed Therapy (DOTS) implementation. A bundle of innovative interventions referred to for its delivery technology as the Drone Observed Therapy System (DrOTS) was implemented in remote Madagascar. Given the potentially increased cost these interventions represent for health systems, a cost-effectiveness analysis was indicated. A decision analysis model was created to calculate the incremental cost-effectiveness of the DrOTS strategy compared to DOTS, the standard of care, in a study population of 200,000 inhabitants in rural Madagascar with tuberculosis disease prevalence of 250/100,000. A mixed top-down and bottom-up costing approach was used to identify costs associated with both models, and net costs were calculated accounting for resulting TB treatment costs. Net cost per disability-adjusted life years averted was calculated. Sensitivity analyses were performed for key input variables to identify main drivers of health and cost outcomes, and cost-effectiveness. Net cost per TB patient identified within DOTS and DrOTS were, respectively,282 and 1,172. The incremental cost per additional TB patient diagnosed in DrOTS was2,631 and the incremental cost-effectiveness ratio of DrOTS compared to DOTS was 177 per DALY averted. Analyses suggest that integrating drones with interventions ensuring highly sensitive laboratory testing and high treatment adherence optimizes cost-effectiveness. Innovative technology packages including drones, digital adherence monitoring technologies, and molecular diagnostics for TB case finding and retention within the cascade of care can be cost effective. Their integration with other interventions within health systems may further lower costs and support access to universal health coverage.

Sebastien Gagneux and colleagues report the genome sequences of 21 phylogeographically diverse Mycobacterium tuberculosis complex strains. Analysis of the global genetic diversity of these strains showed that most of the known human T cell epitopes were highly conserved. Mycobacterium tuberculosis is an obligate human pathogen capable of persisting in individual hosts for decades. We sequenced the genomes of 21 strains representative of the global diversity and six major lineages of the M. tuberculosis complex (MTBC) at 40- to 90-fold coverage using Illumina next-generation DNA sequencing. We constructed a genome-wide phylogeny based on these genome sequences. Comparative analyses of the sequences showed, as expected, that essential genes in MTBC were more evolutionarily conserved than nonessential genes. Notably, however, most of the 491 experimentally confirmed human T cell epitopes showed little sequence variation and had a lower ratio of nonsynonymous to synonymous changes than seen in essential and nonessential genes. We confirmed these findings in an additional data set consisting of 16 antigens in 99 MTBC strains. These findings are consistent with strong purifying selection acting on these epitopes, implying that MTBC might benefit from recognition by human T cells.

Mini gastric bypass is being explored by many bariatric surgeons as a standalone bariatric procedure. Several surgeons from different parts of the world have now published their extensive experience with this procedure. It appears to be an effective bariatric procedure with acceptable weight loss, co-morbidity resolution, and complication rates in the short and medium term. Its proponents claim that it is safer and easier than the gold standard Roux-en-Y gastric bypass. However, concerns with regard to symptomatic gastric or oesophageal biliary reflux requiring revisional surgery and long-term risk of gastric and oesophageal cancers persist. This paper reviews the published experience to date with this procedure and examines the surrounding controversy.

One anastomosis (mini) gastric bypass (OAGB) is believed to be more malabsorptive than Roux-en-Y gastric bypass. A number of patients undergoing this procedure suffer from severe protein-calorie malnutrition requiring revisional surgery. The purpose of this study was to find the magnitude of severe protein-calorie malnutrition requiring revisional surgery after OAGB and any potential relationship with biliopancreatic limb (BPL) length. A questionnaire-based survey was carried out on the surgeons performing OAGB. Data were further corroborated with the published scientific literature. A total of 118 surgeons from thirty countries reported experience with 47,364 OAGB procedures. Overall, 0.37% (138/36,952) of patients needed revisional surgery for malnutrition. The highest percentage of 0.51% (120/23,277) was recorded with formulae using >200 cm of BPL for some patients, and lowest rate of 0% was seen with 150 cm BPL. These data were corroborated by published scientific literature, which has a record of 50 (0.56%) patients needing surgical revision for severe malnutrition after OAGB. A very small number of OAGB patients need surgical correction for severe protein-calorie malnutrition. Highest rates of 0.6% were seen in the hands of surgeons using BPL length of >250 cm for some of their patients, and the lowest rate of 0% was seen with BPL of 150 cm. Future studies are needed to examine the efficacy of a standardised BPL length of 150 cm with OAGB.

IntroductionSleeve gastrectomy (SG) is the commonest bariatric procedure worldwide. Yet there is significant variation in practice concerning its various aspects. This paper report results from the first modified Delphi consensus-building exercise on SG.MethodsWe established a committee of 54 globally recognized opinion makers in this field. The committee agreed to vote on several statements concerning SG. An agreement or disagreement amongst ≥ 70.0% experts was construed as a consensus.ResultsThe committee achieved a consensus of agreement (n = 71) or disagreement (n = 7) for 78 out of 97 proposed statements after two rounds of voting. The committee agreed with 96.3% consensus that the characterization of SG as a purely restrictive procedure was inaccurate and there was 88.7% consensus that SG was not a suitable standalone, primary, surgical weight loss option for patients with Barrett’s esophagus (BE) without dysplasia. There was an overwhelming consensus of 92.5% that the sleeve should be fashioned over an orogastric tube of 36–40 Fr and a 90.7% consensus that surgeons should stay at least 1 cm away from the angle of His. Remarkably, the committee agreed with 81.1% consensus that SG patients should undergo a screening endoscopy every 5 years after surgery to screen for BE.ConclusionA multinational team of experts achieved consensus on several aspects of SG. The findings of this exercise should help improve the outcomes of SG, the commonest bariatric procedure worldwide, and guide future research on this topic.