Development of gelatin-alginate hydrogels for burn wound treatment

Hydrogels are interesting as wound dressing for burn wounds to maintain a moist environment. Especially gelatin and alginate based wound dressings show strong potential. Both polymers are modified by introducing photocrosslinkable functionalities and combined to hydrogel films (gel-MA/alg-MA). In one protocol gel-MA films are incubated in alg-MA solutions and crosslinked afterward into double networks. Another protocol involves blending both and subsequent photocrosslinking. The introduction of alginate into the gelatin matrix results in phase separation with polysaccharide microdomains in a protein matrix. Addition of alg(-MA) to gel-MA leads to an increased swelling compared to 100% gelatin and similar to the commercial Aquacel Ag dressing. In vitro tests show better cell adhesion for films which have a lower alginate content and also have superior mechanical properties. The hydrogel dressings exhibit good biocompatibility with adaptable cell attachment properties. An adequate gelatin-alginate ratio should allow application of the materials as wound dressings for several days without tissue ingrowth

Impact of socioeconomic status on participation and outcomes in the Salford Lung Studies

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The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study

Background Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. Methods and findings This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. Conclusions Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment

Predicting the risk of acute kidney injury in primary care: derivation and validation of STRATIFY-AKI

Background: Antihypertensives reduce the risk of cardiovascular disease but are also associated with harms including acute kidney injury (AKI). Few data exist to guide clinical decision making regarding these risks. Aim: To develop a prediction model estimating the risk of AKI in people potentially indicated for antihypertensive treatment. Design and setting: Observational cohort study using routine primary care data from the Clinical Practice Research Datalink (CPRD) in England. Method: People aged ≥40 years, with at least one blood pressure measurement between 130 mmHg and 179 mmHg were included. Outcomes were admission to hospital or death with AKI within 1, 5, and 10 years. The model was derived with data from CPRD GOLD (n = 1 772 618), using a Fine–Gray competing risks approach, with subsequent recalibration using pseudo-values. External validation used data from CPRD Aurum (n = 3 805 322). Results: The mean age of participants was 59.4 years and 52% were female. The final model consisted of 27 predictors and showed good discrimination at 1, 5, and 10 years (C-statistic for 10-year risk 0.821, 95% confidence interval [CI] = 0.818 to 0.823). There was some overprediction at the highest predicted probabilities (ratio of observed to expected event probability for 10-year risk 0.633, 95% CI = 0.621 to 0.645), affecting patients with the highest risk. Most patients (>95%) had a low 1- to 5-year risk of AKI, and at 10 years only 0.1% of the population had a high AKI and low CVD risk. Conclusion: This clinical prediction model enables GPs to accurately identify patients at high risk of AKI, which will aid treatment decisions. As the vast majority of patients were at low risk, such a model may provide useful reassurance that most antihypertensive treatment is safe and appropriate while flagging the few for whom this is not the case

Development and external validation of a risk prediction model for falls in patients with an indication for antihypertensive treatment: retrospective cohort study

Objective To develop and externally validate the STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY)-Falls clinical prediction model to identify the risk of hospital admission or death from a fall in patients with an indication for antihypertensive treatment. Design Retrospective cohort study. Setting Primary care data from electronic health records contained within the UK Clinical Practice Research Datalink (CPRD). Participants Patients aged 40 years or older with at least one blood pressure measurement between 130 mm Hg and 179 mm Hg. Main outcome measure First serious fall, defined as hospital admission or death with a primary diagnosis of a fall within 10 years of the index date (12 months after cohort entry). Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at one, five, and 10 years using pseudo values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves and the observed to expected ratio, C statistic, and D statistic, pooled across general practices, and clinical utility using decision curve analysis at thresholds around 10%. Results Analysis included 1 772 600 patients (experiencing 62 691 serious falls) from CPRD GOLD used in model development, and 3 805 366 (experiencing 206 956 serious falls) from CPRD Aurum in the external validation. The final model consisted of 24 predictors, including age, sex, ethnicity, alcohol consumption, living in an area of high social deprivation, a history of falls, multiple sclerosis, and prescriptions of antihypertensives, antidepressants, hypnotics, and anxiolytics. Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of 0.833 (95% confidence interval 0.831 to 0.835) and 0.843 (0.841 to 0.844) at five and 10 years, respectively. Original model calibration was poor on visual inspection and although this was improved with recalibration, under-prediction of risk remained (observed to expected ratio at 10 years 1.839, 95% confidence interval 1.811 to 1.865). Nevertheless, decision curve analysis suggests potential clinical utility, with net benefit larger than other strategies. Conclusions This prediction model uses commonly recorded clinical characteristics and distinguishes well between patients at high and low risk of falls in the next 1-10 years. Although miscalibration was evident on external validation, the model still had potential clinical utility around risk thresholds of 10% and so could be useful in routine clinical practice to help identify those at high risk of falls who might benefit from closer monitoring or early intervention to prevent future falls. Further studies are needed to explore the appropriate thresholds that maximise the model’s clinical utility and cost effectiveness

Code lists for indicators of consultation complexity in primary care

Read code lists for use with Clinical Practice Research Datalink GOLD databas

Determinants and extent of weight recording in UK primary care: an analysis of 5 million adults' electronic health records from 2000 to 2017

BACKGROUND:Excess weight and unexpected weight loss are associated with multiple disease states and increased morbidity and mortality, but weight measurement is not routine in many primary care settings. The aim of this study was to characterise who has had their weight recorded in UK primary care, how frequently, by whom and in relation to which clinical events, symptoms and diagnoses. METHODS:A longitudinal analysis of UK primary care electronic health records (EHR) data from 2000 to 2017. Descriptive statistics were used to summarise weight recording in terms of patient sociodemographic characteristics, health professional encounters, clinical events, symptoms and diagnoses. Negative binomial regression was used to model the likelihood of having a weight record each year, and Cox regression to the likelihood of repeated weight recording. RESULTS:A total of 14,049,871 weight records were identified in the EHR of 4,918,746 patients during the study period, representing 26,998,591 person-years of observation. Around a third of patients had a weight record each year. Forty-nine percent of weight records were repeated within a year with an average time to a repeat weight record of 1.92 years. Weight records were most often taken by nursing staff (38-42%) and GPs (37-39%) as part of a routine clinical care, such as chronic disease reviews (16%), medication reviews (6-8%) and health checks (6-7%), or were associated with consultations for contraception (5-8%), respiratory disease (5%) and obesity (1%). Patient characteristics independently associated with an increased likelihood of weight recording were as follows: female sex, younger and older adults, non-drinkers, ex-smokers, low or high BMI, being more deprived, diagnosed with a greater number of comorbidities and consulting more frequently. The effect of policy-level incentives to record weight did not appear to be sustained after they were removed. CONCLUSION:Weight recording is not a routine activity in UK primary care. It is recorded for around a third of patients each year and is repeated on average every 2 years for these patients. It is more common in females with higher BMI and in those with comorbidity. Incentive payments and their removal appear to be associated with increases and decreases in weight recording