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Spherical silica particles are traditionally made via Stöber and modified-Stöber processes, which commonly use environmental toxins as reagents. Here we report a process to synthesise spherical silica particles using environmentally friendly biomolecules (phosphatidylcholine and soy lecithin) and employing water and soybean oil as solvents, rather than potentially harmful organic solvents. This scalable method represents an important step towards sustainable industrial silica syntheses. Under mildly acidic conditions phosphatidylcholine and soy lecithin can control the condensation of sodium silicate to form discrete, spherical silica particles. Silica particles with diameters ranging between 329 and 2232 nm were readily produced using phosphatidylcholine as the templating agent and soybean oil as the solvent in the presence of sodium silicate. Narrower size distributions (262–1272 nm) were achieved using soy lecithin as the templating agent in an aqueous acetate buffer solution containing sodium silicate. Silica particles grown using low concentrations of phosphatidylcholine and soy lecithin as templating agents formed by a combination of coalescence and Ostwald ripening, whilst particles grown at high concentrations predominantly formed through Ostwald ripening behaviour. The possibility of sustainably producing spherical silica particles in a simple biomolecule-templated synthesis is shown., Data from publication: Appl. Nanosci. 2021, 11 (5), 1721-1735.

Background\ud \ud Pseudomonas aeruginosa (PA) status influences management decisions in cystic fibrosis (CF) but diagnostic approaches vary. We evaluated the ability of the CFHealthHub (CFHH) criteria, which consist of two major and four minor statements, in diagnosing chronic PA infection among adults with CF.\ud \ud \ud \ud Methods\ud \ud In this retrospective cross-sectional analysis, we compared the CFHH criteria against the Leeds criteria. Data were collected between 1st January and 31st December 2016 from all adults with CF receiving care at Sheffield, excluding those with lung transplantation (n = 7) or on ivacaftor (n = 13). The CFHH criteria PA status were cross-tabulated against the Leeds criteria, and clinical outcomes between chronic PA vs non chronic PA for both criteria were compared.\ud \ud \ud \ud Results\ud \ud This analysis included 186 adults with CF (90 females, median age 27 years, median baseline FEV1 78.5%). The CFHH criteria diagnosed more cases of chronic PA (116/186, 62.4% vs 79/186, 42.5%), and 37/107 cases of non-chronic PA according to the Leeds criteria were deemed chronic PA by the CFHH criteria. The magnitude of difference in %FEV1 decline between chronic PA vs non chronic PA was slightly greater for the CFHH criteria (−0.6%, 95% CI –1.8 to 0.6%) compared to the Leeds criteria (−0.2%, 95% CI –1.3 to 1.0%).\ud \ud \ud \ud Conclusions\ud \ud The CFHH criteria detected more chronic PA cases yet still retained similar levels of discrimination for health outcomes in comparison to the Leeds criteria. These findings provide preliminary evidence for the validity of the CFHH criteria among adults with CF.

Background\ud \ud Accurate centre-level medication adherence measurement allows identification of highly performing CF centres, drives shared learning and informs quality improvement. Self-reported adherence is unreliable but data-logging nebulisers can capture objective data. However, adherence levels in current literature are limited by the use of agreed prescriptions and convenience sampling. In this single-centre retrospective study, we quantified the differences in centre-level adherence with different methods of calculating adherence (unadjusted vs normative adherence) and different data sampling frames (convenience sampling vs including difficult to obtain data).\ud \ud \ud \ud Methods\ud \ud Adherence data were objectively captured using I-neb® from 2013-2016 in Sheffield Adult CF Centre. Adults on non data-logging devices, on ivacaftor or with previous lung transplantation were excluded. Adherence was calculated based on agreed regimen (‘unadjusted adherence’) or minimum required regimen (‘normative adherence’). I-nebs® not brought to clinic were downloaded during home visits. Adults not on any inhaled therapy but with chronic Pseudomonas aeruginosa infection were included by counting their adherence as “0”.\ud \ud \ud \ud Results\ud \ud Of the 131 included adults, 126 provided I-neb® data. Calculating unadjusted adherence from I-nebs® brought to clinics resulted in the highest centre-level adherence (median 41.8% in 2013). Median adherence reduced after sequentially accounting for minimum required regimen (40.0% in 2013), I-nebs® not brought to clinics (32.9% in 2013) and adults not on any inhaled therapy (31.0% in 2013).\ud \ud \ud \ud Conclusions\ud \ud Different approaches of calculating adherence produced different adherence levels. Adherence levels based only on agreed regimen among adults who readily brought their nebulisers to clinics can over-estimate the effective adherence of CF centres.

Introduction\ud In CF, people with higher FEV1 are less aggressively treated with intravenous (IV) antibiotics, with resultant negative impact on their health outcomes. This could be entirely clinician-driven, but patient choice may also influence IV use. In this prospective observational study, we explored IV recommendations by clinicians and IV acceptance by adults with CF to understand how clinical presentations consistent with exacerbations resulted in IV use.\ud \ud Methods\ud Clinical presentations consistent with exacerbations, IV recommendation by clinicians and IV acceptance by patients were prospectively identified for every adult with CF in Sheffield throughout 2016, excluding those who had lung transplantation (n = 7) or on ivacaftor (n = 13). Relevant demographic data, e.g. %FEV1, were extracted from medical records. Multi-level mixed-effects logistic regression models were used to compare IV recommendations vs non-recommendations for all clinical encounters, and IV acceptance vs non-acceptance for all IV recommendations.\ud \ud Results\ud Among 186 adults (median age 27 years, median FEV1 78.5%), there were 434 exacerbation events and 318 IV use episodes following 1010 clinical encounters. Only 254 (58.5%) of exacerbations were IV treated. A diagnosis of exacerbation, higher number of symptoms and lower %FEV1 were independent predictors for IV recommendation by clinicians. Higher number of symptoms and lower %FEV1 were also independent predictors for IV acceptance by adults with CF.\ud \ud Conclusions\ud Lower IV use among adults with higher %FEV1 was influenced by both clinicians' and patients’ decisions. Using IV antibiotics as an exacerbation surrogate could under-estimate exacerbation rates and conceal differential treatment decisions according to varying clinical characteristics.

Background: Forced expiratory volume in one second (FEV1) is an important cystic fibrosis (CF) prognostic marker and an established endpoint for CF clinical trials. FEV1 is also used in observation studies, e.g. to compare different centre’s outcomes. We wished to evaluate whether different methods of processing FEV1 data can impact on centre outcome.\ud \ud Methods: This is a single-centre retrospective analysis of routinely collected data from 2013-2016 among 208 adults. Year-to-year %FEV1 change was calculated by subtracting best %FEV1 at Year 1 from Year 2 (i.e. negative values indicate fall in %FEV1), and compared using Friedman test. Three methods were used to process %FEV1 data. First, %FEV1 calculated with Knudson equation was extracted directly from spirometer machines. Second, FEV1 volume were extracted then converted to %FEV1 using clean height data and Knudson equation. Third, FEV1 volume were extracted then converted to %FEV1 using clean height data and GLI equation. In addition, year-to-year variation in %FEV1 calculated using GLI equation was adjusted for baseline %FEV1 to understand the impact of case-mix adjustment.\ud \ud Results: Year-to-year fall in %FEV1 reduced with all three data processing methods but the magnitude of this change differed. Median change in %FEV1 for 2013-2014, 2014-2015 and 2015-2016 was –2.0, –1.0 and 0.0 respectively using %FEV1 in Knudson equation whereas the median change was –1.1, –0.9 and –0.3 respectively using %FEV1 in the GLI equation. A statistically significant p-value (0.016) was only obtained when using %FEV1 in Knudson equation extracted directly from spirometer machines.\ud \ud Conclusions: Although the trend of reduced year-to-year fall in %FEV1 was robust, different data processing methods yielded varying results when year-to-year variation in %FEV1 was compared using a standard related group non-parametric statistical test. Observational studies with year-to-year variation in %FEV1 as an outcome measure should carefully consider and clearly specify the data processing methods used.

Rationale, aims and objective\ud \ud Cross‐country comparisons of cystic fibrosis (CF) outcomes can potentially identify variation in care but are dependent on data quality. An important assumption is that the UK annual review FEV1 is only collected during periods of clinical stability. If this assumption does not hold, results of FEV1 comparisons may be biased in favour of registries with encounter‐based FEV1. We aimed to test the assumption that CF annual reviews in the UK are only performed during periods of clinical stability.\ud \ud \ud \ud Method\ud \ud Prospective encounter‐based data collected in Sheffield (n = 174) was used to establish whether annual review FEV1 were always collected during periods of clinical stability and to determine the group‐level discrepancy between annual review vs best FEV1. We then went on to quantify the group‐level discrepancy between annual review and best annual FEV1 readings within the UK registry (n = 2995) to determine if the differences observed in Sheffield also apply to the wider UK data.\ud \ud \ud \ud Results\ud \ud Sheffield results showed a group‐level discrepancy between best and annual review FEV1 of −2.5% (95% CI −3.95% to −1.2%) for annual reviews performed during periods of clinical stability (n = 50). The group‐level discrepancy is larger at −8.0% (95% CI −11.2% to −4.9%) among annual reviews performed during periods of clinical instability (n = 13). Therefore, the magnitude of this group‐level discrepancy is a surrogate for the proportion of clinically stable annual reviews—smaller discrepancy indicates a higher proportion of clinically stable annual reviews and vice versa.\ud \ud The overall group‐level discrepancy in the UK registry (−5.6%, 95% CI −5.9 to −5.4%) was similar to Sheffield (−6.1%, 95% CI −7.1 to −5.1%). Around 20% of the clinician reviewed, annual reviews in Sheffield were performed during periods of clinically instability.\ud \ud \ud \ud Conclusions\ud \ud Annual review FEV1 underestimates lung health of adults with CF in the UK and may bias cross‐country comparisons.

Pseudomonas aeruginosa status influences cystic fibrosis (CF) clinical management but no 'gold standard' definition exists. The Leeds criteria are commonly used but may lack sensitivity for chronic P. aeruginosa. We compared clinicians' decision with the Leeds criteria in three adult CF centres. Two independent prospective datasets (Sheffield dataset, n = 185 adults; ACtiF pilot dataset, n = 62 adults from two different centres) were analysed. Clinicians involved in deciding P. aeruginosa status were blinded to the study objectives. Clinicians considered more adults with CF to have chronic P. aeruginosa infection compared to the Leeds criteria. This was more so for the Sheffield dataset (106/185, 57.3% with clinicians' decision vs. 80/185, 43.2% with the Leeds criteria; kappa coefficient between these two methods 0.72) compared to the ACtiF pilot dataset (34/62, 54.8% with clinicians' decision vs. 30/62, 48.4% with the Leeds criteria; kappa coefficient between these two methods 0.82). However, clinicians across different centres were relatively consistent once age and severity of lung disease, as indicated by the type of respiratory samples provided, were taken into account. Agreement in P. aeruginosa status was similar for both datasets among adults who predominantly provided sputum samples (kappa coefficient 0.78) or adults > 25 years old (kappa coefficient 0.82). Across three different centres, clinicians did not always agree with the Leeds criteria and tended to consider the Leeds criteria to lack sensitivity. Where disagreement occurred, clinicians tended to diagnose chronic P. aeruginosa infection because other relevant information was considered. These results suggest that a better definition for chronic P. aeruginosa might be developed by using consensus methods to move beyond a definition wholly dependent on standard microbiological results.

Pulmonary exacerbations in adults with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (Psae) infection are usually treated with dual intravenous antibiotics for 14 days, despite the lack of evidence for best practice. Intravenous antibiotics are commonly associated with various systemic adverse effects, including renal failure and ototoxicity. Inhaled antibiotics are less likely to cause systematic adverse effects, yet can achieve airway concentrations well above conventional minimum inhibitory concentrations. Typically one inhaled antibiotic is used at a time, but dual inhaled antibiotics (i.e. concomitant use of two different inhaled antibiotics) may have synergistic effect and achieve better results in the treatment of exacerbations. We presented anecdotal evidence for the use of dual inhaled antibiotics as an acute treatment for exacerbations, in the form of a case report. A female in her early thirties with CF and chronic Psae infection improved her FEV1 by 5% and 2% with two courses of dual inhaled antibiotics to treat exacerbations in 2016. In contrast, her FEV1 changed by 2%, –2%, 0% and 2%, respectively, with four courses of dual intravenous antibiotics in 2016. Baseline FEV1 was similar prior to all six courses of treatments. The greater FEV1 improvements with dual inhaled antibiotics compared to dual intravenous antibiotics suggest the potential role of using dual inhaled antibiotics to treat exacerbations among adults with CF and chronic Psae infection, especially since a greater choice of inhaled anti-pseudomonal antibiotics is now available. A previous study in 1985 has looked at the concomitant administration of inhaled tobramycin and carbenicillin, by reconstituting antibiotics designed for parenteral administration. To our knowledge, this is the first literature to describe the concomitant use of two different antibiotics specifically developed for delivery via the inhaled route.

BACKGROUND: The Epidemiologic Study of Cystic Fibrosis using 1995-1996 and 2003-2005 data found that CF centres with lowest FEV1 tended to use fewer intravenous antibiotics. We repeated the analyses using 2013-2014 UK CF registry data to determine if this was still the case. METHODS: Analysing data for 2013 and 2014 separately, 28 adult CF centres were ranked according to median % age-adjusted FEV1. The top 7 centres were placed in the 'upper quarter' (best FEV1), the bottom 7 centres in 'lower quarter' (lowest FEV1), and the rest in 'middle half'. IV use was stratified according to %FEV1, then compared between the three groups. RESULTS: Centres in the 'upper quarter' and 'middle half' used significantly more IV antibiotics compared to centres in the 'lower quarter' (van Elteren test P-value

Background and objective: Intravenous (i.v.) antibiotics are needed for rescue when preventative therapy fails to achieve stability among adults with cystic fibrosis (CF). Understanding the distribution of i.v. days can provide insight into the care that adults with CF need. We aim to determine the baseline characteristics that are associated with higher i.v. use, in particular to test the hypothesis that prior-year i.v. use is associated with future-year i.v. use. Methods: This is a cross-sectional analysis of the 2013–2014 UK CF registry data. Stepwise logistic regression was performed using current-year i.v. days as the dependent variable, and demographic variables including prior-year i.v. days as the covariates. Based on these results, study sample was divided into clinically meaningful subgroups using analysis similar to tree-based method. Results: Data were available for 4269 adults in 2013 and 4644 adults in 2014. Prior-year i.v. use was the strongest predictor for current-year i.v. use followed by forced expiratory volume in 1 s (FEV1). Adults with high prioryear i.v. use (>14 days) continued to require high levels of i.v., regardless of FEV1. Those with high prior-year i. v. use and FEV1 ≥70% had higher current-year i.v. days compared to adults with low prior-year i.v. use and FEV1