Background The delivery of healthcare during the COVID pandemic has had a significant impact on front line staff. Nurses who work with respiratory patients, have been at the forefront of the pandemic response. Lessons can be learnt from these nurses’ experiences in order to support these nurses during the existing pandemic and retain and mobilise this skilled workforce for future pandemics. Methods This study explores UK nurses’ experiences of working in a respiratory environment during the COVID-19 pandemic. An e-survey was distributed via professional respiratory societies the survey included a resilience scale, the GAD7 (anxiety) and the PHQ9 (depression) tools. Demographic data was collected on age, gender, ethnicity, nursing experience and background, clinical role in the pandemic, and home-life and work balance. Results Two hundred and fifty-five responses were received for the survey, predominately women (89%, 226/255), aged over 35 (79%, 202/255). Nearly 21% (40/191) experiencing moderate to severe or severe symptoms of anxiety. Similar levels are seen for depression (15.7%, 30/191). 18.9% (34/180) had a low or very low resilience score. Regression analysis showed that for both depression and anxiety variables, age and years of qualification provided the best model fit.  Younger nurses with less experience have higher levels of anxiety and depression and had lower resilience. Conclusion This cohort experienced significant levels of anxiety and depression, with moderate to high levels of resilience. Support mechanisms and interventions need to be put in place to support all nurses during pandemic outbreaks, particularly younger or less experienced staff.

ObjectiveTo investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.MethodsA total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.ResultsAmong patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.ConclusionPharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

Bronchial responsiveness to inhaled methacholine was measured four to six days before fibreoptic bronchoscopy in 22 asthmatic patients (10 smokers) and 20 control subjects (12 smokers).The asthmatic patients had a baseline FEV, greater than 60% predicted and a PD20FEV, (provocative dose of methacholine causing a 20% fall in FEV,) of 0 006-3-7 mg. The 20 control subjects had normal pulmonary function and a PD20FEV, above the maximum cumulative dose of methacholine of 6-4 mg. Bronchoalveolar lavage of a middle lobe segment (lingula in four subjects) was performed with three sequential 60 ml aliquots of sterile saline. Cellular metabolic activity was stimulated with latex in aliquots of resuspended cells, and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. Mean absolute total cell counts were similar in the asthmatic and control groups but there were differences in differential cell counts, with a significant increase in eosinophil (p < 0 05) and lymphocyte (p < 0 05) counts in asthma. PD20FEV, was negatively correlated with percentage neutrophil counts (p < 0005). Luminol enhanced chemiluminescence/1000 neutrophils was increased about twofold in asthmatic subjects (p < 0 001), but was not correlated with PD20FEV1. Lucigenin enhanced chemiluminescence/1000 macrophages was increased nearly fourfold in asthmatic patients (p < 0-001) and showed a negative correlation with PD20FEV, (p < 0-01). The macrophage count was increased twofold in current smokers in both groups, but other cell numbers were not altered significantly. Smoking did not affect cellular metabolic activity in either group. This study supports the idea that an inflammatory process is present in the airways of those with asthma, and suggests a relation between bronchial responsiveness and both neutrophil numbers and macrophage activity.

ObjeCtive To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs. DesignOpen label pragmatic randomised multicentre two arm non-inferiority trial over 12 months. setting 24 rheumatology clinics in England. PartiCiPantsPatients with rheumatoid arthritis who were eligible for treatment with tumour necrosis factor inhibitors according to current English guidance were randomised to either the tumour necrosis factor inhibitor strategy or the combined disease modifying drug strategy. interventiOns Biologic strategy: start tumour necrosis factor inhibitor; second biologic in six month for nonresponders. Alternative strategy: start combination of disease modifying drugs; start tumour necrosis factor inhibitors after six months in non-responders. Main OutCOMe MeasurePrimary outcome: reduction in disability at 12 months measured with patient recorded heath assessment questionnaire (range 0.00-3.00) with a 0.22 non-inferiority margin for combination treatment versus the biologic strategy. Secondary outcomes: quality of life, joint damage, disease activity, adverse events, and costs. Intention to treat analysis used multiple imputation methods for missing data. results 432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of −0.30 with the tumour necrosis factor inhibitor strategy and −0.45 with the alternative combined drug strategy. The difference between groups in unadjusted linear regression analysis favoured the alternative strategy of combined drugs. The mean difference was −0.14, and the 95% confidence interval (−0.29 to 0.01) was below the prespecified non-inferiority boundary of 0.22. Improvements at 12 months in secondary outcomes, including quality of life and erosive progression, were similar with both strategies. Initial reductions in disease activity were greater with the biologic strategy, but these differences did not persist beyond six months. Remission was seen in 72 patients (44 with biologic strategy; 36 with alternative strategy); 28 patients had serious adverse events (18 and 10, respectively); six and 10 patients, respectively, stopped treatment because of toxicity. The alternative strategy reduced health and social care costs per patient by £3615 (€4930, $5585) for months 0-6 and £1930 for months 6-12. COnClusiOnsIn patients with active rheumatoid arthritis who meet...

Long-term macrolide therapy may reduce the frequency of exacerbations and improve quality of life, although supporting evidence is derived mainly from studies of azithromycin, rather than other macrolides, and predominantly among adults rather than children. However, macrolides should be used with caution, as limited data indicate an associated increase in microbial resistance. Macrolides are associated with increased risk of cardiovascular death and other serious adverse events in other populations, and available data cannot exclude a similar risk among patients with bronchiectasis.