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INTRODUCTION: Application of whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis highlights a diverse pool of antimicrobial resistance genes: the 'resistome', the clinical significance of which remains unclear. METHODS: Individuals with bronchiectasis were prospectively recruited into cross-sectional and longitudinal cohorts (n=280) including the international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis 2 study (CAMEB 2; n=251) and two independent cohorts, one describing patients experiencing acute exacerbation and a further cohort of patients undergoing P. aeruginosa eradication treatment. Sputum was subjected to metagenomic sequencing and the bronchiectasis resistome evaluated in association with clinical outcomes and underlying host microbiomes. RESULTS: The bronchiectasis resistome features a unique resistance gene profile and elevated counts of aminoglycoside, bicyclomycin, phenicol, triclosan and multi-drug resistance genes. Longitudinally, it exhibits within-patient stability over time and during exacerbations despite between-patient heterogeneity. Proportional differences in baseline resistome profiles including increased macrolide and multi-drug resistance genes associate with shorter intervals to next exacerbation, while distinct resistome archetypes associate with frequent exacerbations, poorer lung function, geographic origin, and the host microbiome. Unsupervised analysis of resistome profiles identified two clinically relevant 'resistotypes' RT1 and RT2, the latter characterized by poor clinical outcomes, increased multi-drug resistance and P. aeruginosa. Successful targeted eradication in P. aeruginosa-colonized individuals mediated reversion from RT2 to RT1, a more clinically favourable resistome profile demonstrating reduced resistance gene diversity. CONCLUSION: The bronchiectasis resistome associates with clinical outcomes, geographic origin, and the underlying host microbiome. Bronchiectasis 'resistotypes' link to clinical disease and are modifiable through targeted antimicrobial therapy. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Objectives: The psychological distress of people living with diabetes is increased and associated with poorer glycemic outcomes and self-care. We aimed to examine the frequency of depression, anxiety, and diabetes-related distress (DRD) of individuals with type 2 diabetes (T2D) in primary care (PC) and their comparative associations with clinical, self-care, and socio-demographic characteristics, testing for possible different roles on glycemic control and self-care. Methods: This is a cross-sectional study of 182 adults with a T2D diagnosis of at least six months, recruited between August 2019-March 2020 and May-October 2020, from an urban PC unit. Participants were screened for symptoms of depression (Patient Health Questionnaire-9 (PHQ-9)), anxiety (Generalized Anxiety Disorder-7 (GAD-7)), and DRD (Diabetes Distress Scale (DDS)). Clinical, self-care, and socio-demographic parameters were recorded. Results: The frequency of clinically significant symptoms of depression was 16.6%, (PHQ-9 score ⩾10), anxiety 17.7% (GAD-7 score ⩾10), and DRD 22.6% (DDS score ⩾2). All PHQ-9, GAD-7, and DDS scores intercorrelated, and higher scores were found to be associated with female gender, lower income, and prior diagnosis of depression. Higher PHQ-9 and GAD-7 scores were found to be associated with lower education, more hypoglycemia episodes, more blood glucose self-tests and antidepressant or benzodiazepine use. The retired/housewives scored significantly lower in GAD-7 and DDS compared to the unemployed participants. Higher DDS scores were associated with higher glycated hemoglobin, higher fasting plasma glucose, and insulin use. It was also noted that higher PHQ-9 scores were associated with lower uric acid levels and were significantly higher in the sedentary lifestyle group. Conclusion: DRD was associated with poorer glycemic outcomes while depressive symptoms were associated with lower physical activity perhaps sharing different roles for glycemic control and self-care. The psychological burden of individuals with T2D may be considered in PC.