Effects of Methyl Branching on the Properties and Performance of Furandioate-Adipate Copolyesters of Bio-Based Secondary Diols

Furandioate-adipate copolyesters are an emerging class of bio-based biodegradable polymers with great potential to replace fossil-derived terephthalic acid-based copolyesters such as poly(butylene adipate-co-terephthalate) (PBAT). Furandioate-adipate polyesters have almost exclusively been prepared with conventional primary (1°) alcohol diols, while secondary (2°) alcohol diol monomers have largely been overlooked until now, despite preliminary observations that using methyl-branched diols increases the Tg of the resultant polyesters. Little is known of what impact the use of 2° alcohol diols has on other properties such as material strength, hydrophobicity, and rate of enzymatic hydrolysis—all key parameters for performance and end-of-life. To ascertain the effects of using 2° diols on the properties of furandioate-adipate copolyesters, a series of polymers from diethyl adipate (DEA) and 2,5-furandicarboxylic acid diethyl ester (FDEE) using different 1° and 2° alcohol diols was prepared. Longer transesterification times and greater excesses of diol (diol/diester molar ratio of 2:1) were found to be necessary to achieve Mws > 20 kDa using 2° alcohol diols. All copolyesters from 2° diols were entirely amorphous and exhibited higher Tgs than their linear equivalents from 1° diols. Compared to linear poly(1,4-butyleneadipate-co-1,4-butylenefurandioate), methyl-branched, poly(2,5-hexamethyleneadipate-co-2,5-hexamethylenefurandioate) (0:7:0.3 furandioate/adipate ratio) displayed both higher modulus (67.8 vs 19.1 MPa) and higher extension at break (89.7 vs 44.5 mm). All other methyl-branched copolyesters displayed lower modulus but retained higher extension at break compared with their linear analogues. Enzymatic hydrolysis studies using Humicola insolens cutinase revealed that copolyesters from 2° alcohol diols have significantly decreased rates of biodegradation than their linear equivalents synthesized using 1° alcohol diols, allowing for fine-tuning of polymer stability. Hydrophobicity, as revealed by water contact angles, was also found to generally increase through the introduction of methyl branching, demonstrating potential for these materials in coatings applications

Five-year costs from a randomised comparison of bilateral and single internal thoracic artery grafts

Background: The use of bilateral internal thoracic arteries (BITA) for coronary artery bypass grafting (CABG) may improve survival compared with CABG using single internal thoracic arteries (SITA). We assessed the long-term costs of BITA compared with SITA. Methods: Between June 2004 and December 2007, 3102 patients from 28 hospitals in seven countries were randomised to CABG surgery using BITA (n=1548) or SITA (n=1554). Detailed resource use data were collected from the initial hospital episode and annually up to 5 years. The associated costs of this resource use were assessed from a UK perspective with 5 year totals calculated for each trial arm and pre-selected patient subgroups. Results: Total costs increased by approximately £1000 annually in each arm, with no significant annual difference between trial arms. Cumulative costs per patient at 5-year follow-up remained significantly higher in the BITA group (£18 629) compared with the SITA group (£17 480; mean cost difference £1149, 95% CI £330 to £1968, p=0.006) due to the higher costs of the initial procedure. There were no significant differences between the trial arms in the cost associated with healthcare contacts, medication use or serious adverse events. Conclusions: Higher index costs for BITA were still present at 5-year follow-up mainly driven by the higher initial cost with no subsequent difference emerging between 1 year and 5 years of follow-up. The overall cost-effectiveness of the two procedures, to be assessed at the primary endpoint of the 10-year follow-up, will depend on composite differences in costs and quality-adjusted survival

Parental and clinician agreement of illness severity in children with RTIs:Secondary analysis of data from a prospective cohort study

Background: severity assessments of respiratory tract infection (RTI) in children are known to differ between parents and clinicians, but determinants of perceived severity are unknown. Aim: to investigate the (dis)agreement between, and compare the determinants of, parent and clinician severity scores. Design and setting: secondary analysis of data from a prospective cohort study of 8394 children presenting to primary care with acute (≤28 days) cough and RTI. Method: data on sociodemographic factors, parent-reported symptoms, clinician-reported findings, and severity assessments were used. Kappa (κ)-statistics were used to investigate (dis) agreement, whereas multivariable logistic regression was used to identify the factors associated with illness severity. Results: parents reported higher illness severity (mean 5.2 [standard deviation (SD) 1.8], median 5 [interquartile range (IQR) 4–7]), than clinicians (mean 3.1 [SD 1.7], median 3 [IQR 2–4], P&lt;0.0001). There was low positive correlation between these scores (+0.43) and poor inter-rater agreement between parents and clinicians (κ 0.049). The number of clinical signs was highly correlated with clinician scores (+0.71). Parent-reported symptoms (in the previous 24 hours) that were independently associated with higher illness severity scores, in order of importance, were: severe fever, severe cough, rapid breathing, severe reduced eating, moderate-to-severe reduced fluid intake, severe disturbed sleep, and change in cry. Three of these symptoms (severe fever, rapid breathing, and change in cry) along with inter/ subcostal recession, crackles/crepitations, nasal flaring, wheeze, and drowsiness/irritability were associated with higher clinician scores. Conclusion: clinicians and parents use different factors and make different judgements about the severity of children’s RTI. Improved understanding of the factors that concern parents could improve parent–clinician communication and consultation outcomes.</p

Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002-17:population-based cohort study and decision analytic model

BackgroundEfforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed.Methods and findingsWe conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57-82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0-4 years old, the NNT was 29,773 (95% UI 18,458-71,091) in boys and 27,014 (16,739-65,709) in girls; over 85 years old, NNT was 262 (236-293) in men and 385 (352-421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55-64 years, the NNT was 247 (156-459) in men and 343 (234-556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65-74 years, the NNT following RTI was 1,257 (1,112-1,434) in men and 2,278 (1,966-2,686) in women; the NNT following skin infection was 503 (398-646) in men and 784 (602-1,051) in women; following UTI, the NNT was 121 (102-145) in men and 284 (241-342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period.ConclusionsThese stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs

Serious bacterial infections and antibiotic prescribing in primary care: cohort study using electronic health records in the UK

Objective This study evaluated whether serious bacterial infections are more frequent at family practices with lower antibiotic prescribing rates. Design Cohort study. Setting 706 UK family practices in the Clinical Practice Research Datalink from 2002 to 2017. Participants 10.1 million registered patients with 69.3 million patient-years' follow-up. Exposures All antibiotic prescriptions, subgroups of acute and repeat antibiotic prescriptions, and proportion of antibiotic prescriptions associated with specific-coded indications. Main outcome measures First episodes of serious bacterial infections. Poisson models were fitted adjusting for age group, gender, comorbidity, deprivation, region and calendar year, with random intercepts representing family practice-specific estimates. Results The age-standardised antibiotic prescribing rate per 1000 patient-years increased from 2002 (male 423; female 621) to 2012 (male 530; female 842) before declining to 2017 (male 449; female 753). The median family practice had an antibiotic prescribing rate of 648 per 1000 patient-years with 95% range for different practices of 430-1038 antibiotic prescriptions per 1000 patient-years. Specific coded indications were recorded for 58% of antibiotic prescriptions at the median family practice, the 95% range at different family practices was from 10% to 75%. There were 139 759 first episodes of serious bacterial infection. After adjusting for covariates and the proportion of coded consultations, there was no evidence that serious bacterial infections were lower at family practices with higher total antibiotic prescribing. The adjusted rate ratio for 20% higher total antibiotic prescribing was 1.03, (95% CI 1.00 to 1.06, p=0.074). Conclusions We did not find population-level evidence that family practices with lower total antibiotic prescribing might have more frequent occurrence of serious bacterial infections overall. Improving the recording of infection episodes has potential to inform better antimicrobial stewardship in primary care.</p

Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry

Aims: We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). Methods and results: In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [−0.075 (95% confidence interval −0.144, −0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [−0.037 (−0.071, −0.003)], new-onset/worsening heart failure [−0.064 (−0.088, −0.039)], bleeding events [−0.031 (−0.059, −0.003)], thromboembolic events [−0.071 (−0.115, −0.027)], mild symptoms [0.037 (−0.048, −0.026)], or severe/disabling symptoms [−0.090 (−0.108, −0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. Conclusion: Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe

The frequency distribution of presenting symptoms in children aged six months to six years to primary care.

Primary care providers and researchers wishing to estimate study recruitment rates need estimates of illness frequency in primary care. Previous studies of children's symptoms have found that presentations are most common for the symptoms: cough, fever, earache, rash, diarrhoea and vomiting. Since 2000, primary care provision in the United Kingdom has changed with the introduction of Walk-in-Centres (WICs) and new Out of Hours (OoHs) providers. To describe the type and frequency of parent-reported presenting symptoms at a range of primary care sites between 2005 and 2007. Parent-reported presenting symptoms, recorded in their own words, were extracted from data collected from all children aged six months to six years during recruitment to a randomised controlled trial. Presenting symptoms were coded and presented as frequency per 100 'consulting sessions' by type of primary care site. Results were evaluated from 2491 episodes of illness at 35 sites. When grouped by primary care site, respiratory symptoms were the most common at OoHs centres, the WIC and general practitioner (GP) surgeries. Trauma symptoms were common in the Emergency Department, but unexpectedly, diarrhoea and vomiting were more common in the Emergency Department and skin presenting symptoms more common at the WIC than at GP sites. We report the relative frequency of acute symptoms by type of primary care provider. These data may be useful to those planning recruitment to primary care paediatric studies and policy makers for planning primary care service provision