The sputum microbiome and clinical outcomes in patients with bronchiectasis: a prospective observational study.

Background: Infection is a key component of bronchiectasis pathophysiology. Characterisation of the microbiome offers a higher degree of sensitivity and resolution than does traditional culture methods. We aimed to evaluate the role of the microbiome in determining the risk of exacerbation and long-term outcomes, including all-cause mortality, in bronchiectasis.

A cuckoo COVID coincidence?

https://bit.ly/2YWAhhl

Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD.

Background: Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).

Estimates of the ongoing need for social distancing and control measures post-"lockdown" from trajectories of COVID-19 cases and mortality.

By 21 May 2020, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) had caused more than 5 million cases of coronavirus 2019 (COVID-19) across more than 200 countries. Most countries with significant outbreaks have introduced social distancing or "lockdown" measures to reduce viral transmission. So the key question now is when, how and to what extent these measures can be lifted.

Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a analysis of the AIR-BX studies.

Introduction: Inhaled antibiotics may improve symptom scores, but it is not known which specific symptoms improve with therapy. Item-level analysis of questionnaire data may allow us to identify which specific symptoms respond best to treatment.

Methods: analysis of the AIR-BX1 studies and two trials of inhaled aztreonam placebo in bronchiectasis.

Relationship between Symptoms, Exacerbations, and Treatment Response in Bronchiectasis.

Bronchiectasis guidelines regard treatment to prevent exacerbation and treatment of daily symptoms as separate objectives. We hypothesized that patients with greater symptoms would be at higher risk of exacerbations and therefore that a treatment aimed at reducing daily symptoms would also reduce exacerbations in highly symptomatic patients. Our study comprised an observational cohort of 333 patients from the East of Scotland (2012-2016).

Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis.

Background: Bronchiectasis guidelines recommend long-term macrolide treatment for patients with three or more exacerbations per year without Pseudomonas aeruginosa infection. Randomised controlled trials suggest that long-term macrolide treatment can prevent exacerbations in adult patients with bronchiectasis, but these individual studies have been too small to do meaningful subgroup analyses. We did a systematic review and individual patient data (IPD) meta-analysis to explore macrolide benefit in subpopulations, including those in which macrolide therapy is not currently recommended.

Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis.

The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. We performed three studies.

Pulmonary rehabilitation after exacerbation of bronchiectasis: a pilot randomized controlled trial.

Background: Pulmonary rehabilitation improves exercise capacity and reduces risk of future exacerbation in COPD when performed after an exacerbation. There have been no previous studies of post-exacerbation rehabilitation in bronchiectasis.

Methods: Parallel group randomized controlled trial compared pulmonary rehabilitation (PR) to standard care (SC) in patients followed an antibiotic treated exacerbation of bronchiectasis.

Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data.

Objective: The choice of therapy for type 2 diabetes after metformin is guided by overall estimates of glycemic response and side effects seen in large cohorts. A stratified approach to therapy would aim to improve on this by identifying subgroups of patients whose glycemic response or risk of side effects differs markedly. We assessed whether simple clinical characteristics could identify patients with differing glycemic response and side effects with sulfonylureas and thiazolidinediones.

Pathogenicity and Penetrance of Germline Variants in Pheochromocytoma and Paraganglioma (PPGL).

Germline mutations are reported in a minority of pheochromocytoma/paraganglioma (PPGL) cases but are associated with an increased risk of malignancy, leading some to advocate cascade genetic testing and surveillance screening of "at-risk" first-degree relatives. However, such approaches rely on accurate estimates of variant pathogenicity and disease penetrance, which may have been subject to ascertainment and reporting biases, although the recent provision of large population-based DNA sequence data sets may provide a potentially unbiased resource to aid variant interpretation. Thus, the aim of the current study was to evaluate the pathogenicity and penetrance of variants reported in literature-based PPGL cases by comparing their frequency to those occurring in the Genome Aggregation Database (GnomAD) data set, which provides high-quality DNA sequence data on 138,632 individuals.

Pharmacokinetics of metformin in patients with gastrointestinal intolerance.

Aims: To assess potential causes of metformin intolerance, including altered metformin uptake from the intestine, increased anaerobic glucose utilization and subsequent lactate production, altered serotonin uptake, and altered bile acid pool.

Methods: For this pharmacokinetic study, we recruited 10 severely intolerant and 10 tolerant individuals, matched for age, sex and body mass index. A single 500-mg dose of metformin was administered, with blood sampling at 12 time points over 24 hours.

Costs and Treatment Pathways for Type 2 Diabetes in the UK: A Mastermind Cohort Study.

Introduction: Medication therapy for type 2 diabetes has become increasingly complex, and there are few reliable data on the current state of clinical practice. We report treatment pathways and associated costs of medication therapy for people with type 2 diabetes in the UK, their variability and changes over time.

Methods: Prescription and biomarker data for 7159 people with type 2 diabetes were extracted from the GoDARTS cohort study, covering the period 1989-2013.

Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users: A GoDarts study.

Aims: Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase the risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin.

Defining drug response for stratified medicine.

The premise for stratified medicine is that drug efficacy, drug safety, or both, vary between groups of patients, and biomarkers can be used to facilitate more targeted prescribing, with the aim of improving the benefit:risk ratio of treatment. However, many factors can contribute to the variability in response to drug treatment. Inadequate characterisation of the nature and degree of variability can lead to the identification of biomarkers that have limited utility in clinical settings.

Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?

Aims: Baseline HbA1c is a major predictor of response to glucose lowering therapy and therefore a potential confounder in studies aiming to identify other predictors. However, baseline adjustment may introduce error if the association between baseline HbA1c and response is substantially due to measurement error and regression to the mean. We aimed to determine whether studies of predictors of response should adjust for baseline HbA1c.

Adherence to Oral Glucose-Lowering Therapies and Associations With 1-Year HbA1c: A Retrospective Cohort Analysis in a Large Primary Care Database.

Objective: The impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired U.K.

Conspecific recognition and aggression reduction to familiars in newly weaned, socially plastic mammals.

Recognising conspecifics and behaving appropriately towards them is a crucial ability for many species. Grey seals () show varying capabilities in this regard: mother-pup recognition has been demonstrated in some geographical populations but is absent in others, yet there is evidence that individuals aggregate with prior associates. The recognition capabilities of newly weaned grey seal pups were investigated using class recognition trials within the habituation/dishabituation paradigm.

Modelling beyond data is uninformative: a comment on "State-space modelling reveals proximate causes of harbour seal population declines" by Matthiopoulos et al.

Detailed models have the potential to reveal important processes underlying patterns in data. However, model fitting depends on the availability of sufficient data, and the results obtained from the models depend on detailed assumptions. In a recent paper, Matthiopoulos et al.

Validation of an enzyme-linked immunoassay (ELISA) for plasma oxytocin in a novel mammal species reveals potential errors induced by sampling procedure.

Background: The neuropeptide oxytocin is increasingly the focus of many studies investigating human and animal social behaviours and diseases. However, interpretation and comparison of results is made difficult by a lack of consistent methodological approaches towards analysing this hormone.

New Method: This study determined the sample collection and analysis protocols that cause the least amounts of protocol dependant variation in plasma oxytocin concentrations detected by ELISA.

Pup mortality in a rapidly declining harbour seal (Phoca vitulina) population.

The harbour seal population in Orkney, off the north coast of Scotland, has reduced by 65% between 2001 and 2010. The cause(s) of this decline are unknown but must affect the demographic parameters of the population. Here, satellite telemetry data were used to test the hypothesis that increased pup mortality could be a primary driver of the decline in Orkney.