Estimating excess mortality and economic burden of <i>Clostridioides difficile</i> infections and recurrences during 2015–2019:The RECUR England study

Objective To generate real-world evidence on all-cause mortality and economic burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. Methods We conducted a cohort study using retrospective data from Clinical Practice Research Datalink linked to Hospital Episode Statistics. Patients diagnosed with CDI in hospital and community settings during 2015–2018 were included and followed for ≥1year. All-cause mortality was described at 6-, 12-, and 24-months. Healthcare resource usage (HCRU) and associated costs were assessed at 12-months of follow-up. A cohort of non-CDI patients, matched by demographic and clinical characteristics including Charlson Comorbidity Index score, was used to assess excess mortality and incremental costs of HCRU. Results All-cause mortality among CDI patients at 6-, 12-, and 24-months was 15.87%, 20.37%, and 27.03%, respectively. A higher proportion of rCDI patients died at any point during follow-up. Compared with matched non-CDI patients, excess mortality was highest at 6-months with 1.81 and 2.53 deaths per 100 patient-months among CDI and ≥1 rCDI patients. Hospitalisations were the main drivers of costs, with an incremental cost of £1,209.21 per CDI patient. HCRU and costs increased with rCDIs. Conclusions CDI poses a substantial mortality and economic burden, further amplified by rCDIs

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

Impact of Changes to National Hypertension Guidelines on Hypertension Management and Outcomes in the United Kingdom.

In recent years, national and international guidelines have recommended the use of out-of-office blood pressure monitoring for diagnosing hypertension. Despite evidence of cost-effectiveness, critics expressed concerns this would increase cardiovascular morbidity. We assessed the impact of these changes on the incidence of hypertension, out-of-office monitoring and cardiovascular morbidity using routine clinical data from English general practices, linked to inpatient hospital, mortality, and socio-economic status data. We studied 3 937 191 adults with median follow-up of 4.2 years (49% men, mean age=39.7 years) between April 1, 2006 and March 31, 2017. Interrupted time series analysis was used to examine the impact of changes to English hypertension guidelines in 2011 on incidence of hypertension (primary outcome). Secondary outcomes included rate of out-of-office monitoring and cardiovascular events. Across the study period, incidence of hypertension fell from 2.1 to 1.4 per 100 person-years. The change in guidance in 2011 was not associated with an immediate change in incidence (change in rate=0.01 [95% CI, -0.18-0.20]) but did result in a leveling out of the downward trend (change in yearly trend =0.09 [95% CI, 0.04-0.15]). Ambulatory monitoring increased significantly in 2011/2012 (change in rate =0.52 [95% CI, 0.43-0.60]). The rate of cardiovascular events remained unchanged (change in rate =-0.02 [95% CI, -0.05-0.02]). In summary, changes to hypertension guidelines in 2011 were associated with a stabilisation in incidence and no increase in cardiovascular events. Guidelines should continue to recommend out-of-office monitoring for diagnosis of hypertension

Using out-of-office blood pressure measurements in established cardiovascular risk scores: implications for practice

YesAbstract Background: Blood pressure (BP) measurement is increasingly carried out through home or ambulatory monitoring, yet existing cardiovascular risk scores were developed for use with measurements obtained in clinic. Aim: To describe differences in cardiovascular risk estimates obtained using ambulatory or home BP measurements instead of clinic readings. Design and setting: Secondary analysis of data from adults aged 30-84 without prior history of cardiovascular disease (CVD) in two BP monitoring studies (BP-Eth and HOMERUS). Method: The primary comparison was Framingham risk calculated using BP measured as in the Framingham study or daytime ambulatory BP measurements. The QRISK2 and SCORE risk equations were also studied. Statistical and clinical significance were determined using the Wilcoxon signed-rank test and scatter plots respectively. Results: In 442 BP-Eth patients (mean age = 58 years, 50% female) the median absolute difference in 10-year Framingham cardiovascular risk calculated using BP measured as in the Framingham study or daytime ambulatory BP measurements was 1.84% (interquartile range 0.65 to 3.63, p=0.67). Only 31/ 442 (7.0%) of patients were reclassified across the 10% risk treatment threshold. In 165 HOMERUS patients (mean age = 56 years, 46% female) the median difference in 10-year risk was 2.76% (IQR 1.19 to 6.39, p<0.001) and only 8/165 (4.8%) of patient were reclassified. Conclusion: Estimates of cardiovascular risk are similar when calculated using BP measurements obtained as in the risk score derivation study or through ambulatory monitoring. Further research is required to determine if differences in estimated risk would meaningfully influence risk score accuracy

Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017:population based cohort study

Objectives To report reliable estimates of short term and long term survival rates for people with a diagnosis of heart failure and to assess trends over time by year of diagnosis, hospital admission, and socioeconomic group. Design Population based cohort study. Setting Primary care, United Kingdom. Participants Primary care data for 55 959 patients aged 45 and overwith a new diagnosis of heart failure and 278 679 age and sex matched controls in the Clinical Practice Research Datalink from 1 January 2000 to 31 December 2017 and linked to inpatient Hospital Episode Statistics and Office for National Statistics mortality data. Main outcome measures Survival rates at one, five, and 10 years and cause of death for people with and without heart failure; and temporal trends in survival by year of diagnosis, hospital admission, and socioeconomic group. Results Overall, one, five, and 10 year survival rates increased by 6.6% (from 74.2% in 2000 to 80.8% in 2016), 7.2% (from 41.0% in 2000 to 48.2% in 2012), and 6.4% (from 19.8% in 2000 to 26.2% in 2007), respectively. There were 30 906 deaths in the heart failure group over the study period. Heart failure was listed on the death certificate in 13 093 (42.4%) of these patients, and in 2237 (7.2%) it was the primary cause of death. Improvement in survival was greater for patients not requiring admission to hospital around the time of diagnosis (median difference 2.4 years; 5.3 v 2.9 years, P<0.001). There was a deprivation gap in median survival of 2.4 years between people who were least deprived and those who were most deprived (11.1 v 8.7 years, P<0.001). Conclusions Survival after a diagnosis of heart failure has shown only modest improvement in the 21st century and lags behind other serious conditions, such as cancer. New strategies to achieve timely diagnosis and treatment initiation in primary care for all socioeconomic groups should be a priority for future research and policy

Patient consultation rate and clinical and NHS outcomes:A cross-sectional analysis of English primary care data from 2.7 million patients in 238 practices

Supplementary results. This file contains additional tables presenting results from the analyses which could not be included in the main manuscript. (DOCX 29 kb

Measuring the complexity of general practice consultations:development and validation of a complexity measure

Background: The complexity of general practice consultations may be increasing and varies in different settings. A measure of complexity is required to test these hypotheses. Aim: To develop a valid measure of general practice consultation complexity applicable to routine medical records. Design and setting: Delphi study to select potential indicators of complexity followed by a cross-sectional study in English general practices to develop and validate a complexity measure. Method: The online Delphi study over two rounds identified potential indicators of consultation complexity. The cross-sectional study used an age–sex stratified random sample of patients and general practice face-to-face consultations from 2013/2014 in the Clinical Practice Research Datalink. The authors explored independent relationships between each indicator and consultation duration using mixed-effects regression models, and revalidated findings using data from 2017/2018. The proportion of complex consultations in different age–sex groups was assessed. Results: A total of 32 GPs participated in the Delphi study. The Delphi panel endorsed 34 of 45 possible complexity indicators after two rounds. After excluding factors because of low prevalence or confounding, 17 indicators were retained in the cross-sectional study. The study used data from 173 130 patients and 725 616 face-to-face GP consultations. On defining complexity as the presence of any of these 17 factors, 308 370 consultations (42.5%) were found to be complex. Mean duration of complex consultations was 10.49 minutes, compared to 9.64 minutes for non-complex consultations. The proportion of complex consultations was similar in males and females but increased with age. Conclusion: The present consultation complexity measure has face and construct validity. It may be useful for research, management and policy, and for informing decisions about the range of resources needed in different practices

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