National trends in heart failure mortality in men and women, United Kingdom, 2000–2017

Aims: To understand gender differences in the prognosis of women and men with heart failure, we compared mortality, cause of death and survival trends over time. Methods and results: We analysed UK primary care data for 26 725 women and 29 234 men over age 45 years with a new diagnosis of heart failure between 1 January 2000 and 31 December 2017 using the Clinical Practice Research Datalink, inpatient Hospital Episode Statistics and the Office for National Statistics death registry. Age-specific overall survival and cause-specific mortality rates were calculated by gender and year. During the study period 15 084 women and 15 822 men with heart failure died. Women were on average 5 years older at diagnosis (79.6 vs. 74.8 years). Median survival was lower in women compared to men (3.99 vs. 4.47 years), but women had a 14% age-adjusted lower risk of all-cause mortality [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.84–0.88]. Heart failure was equally likely to be cause of death in women and men (HR 1.03, 95% CI 0.96–1.12). There were modest improvements in survival for both genders, but these were greater in men. The reduction in mortality risk in women was greatest for those diagnosed in the community (HR 0.83, 95% CI 0.80–0.85). Conclusions: Women are diagnosed with heart failure older than men but have a better age-adjusted prognosis. Survival gains were less in women over the last two decades. Addressing gender differences in heart failure diagnostic and treatment pathways should be a clinical and research priority.</p

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

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

Associations between patient, treatment, or wound-level factors and venous leg ulcer healing: wound characteristics are the key factors in determining healing outcomes

Chronic venous leg ulcers are challenging to heal and often recur. This has a significant impact on older individual health and is a financial burden on health care resources. This study aimed to identify factors associated with the healing of venous leg ulcers via secondary examination of data from a previously published prospective randomized controlled trial of elastic and inelastic compression systems. The data from the 45 patients who finished the trial was reanalyzed for a hypothesis generating study. Larger ulcers, higher exudate levels, larger calf circumferences, and longer ulcer duration at baseline were associated with lack of healing at 12 weeks. There was some evidence that NSAID use was associated with an increased likelihood of nonhealing (unadjusted OR for healing, 0.13, 95% CI (0.02, 0.70)). There was no evidence that other variables, including gender and BMI, were associated with healing. The key risk factors for wound healing are largely wound based or inherent to wound development, as these were found to be the factors with the strongest associations in the analysis. Future research should address how and why these factors are associated with wound healing over a longer time frame and explore how NSAIDs may affect wound healing outcomes

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