Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015-2019: The RECUR England study.

OBJECTIVES: 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 ≥1 year. 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. Hospitalizations were the main drivers of costs, with an incremental cost of £1209.21 per CDI patient. HCRU and costs increased with rCDIs. CONCLUSION: CDI poses a substantial mortality and economic burden, further amplified by rCDIs.

Clostridioides difficile infections, recurrences, and clinical outcomes in real-world settings from 2015 to 2019: The RECUR England study.

OBJECTIVE: To estimate the epidemiological and clinical burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. METHODS: This retrospective study included adult patients diagnosed with CDI (community or hospital settings) over 2015-2019 from Clinical Practice Research Datalink and Hospital Episode Statistics databases. Incidences of CDI and rCDI were determined annually. Time to subsequent rCDI was estimated by Kaplan-Meier method. Rates of complications were assessed within 12 months from index episode. Association of risk factors with complications was evaluated using a Cox regression model. RESULTS: A total of 52,443 CDI episodes were recorded among 36,913 patients. Of these, 75% were aged ≥65 years, 59% were women; 73% were treated in community settings. CDI incidence remained stable (111 episodes per 100,000 patients in 2019). Around 21% of patients had ≥1 rCDI. Sepsis (12%) was the most common complication, followed by colectomy and ulcerative colitis. Age, gender, comorbidities, rCDI, preindex medical procedures, hospitalizations and consultations, and CDI treatment in hospital, were found to increase the risk of complication. CONCLUSIONS: CDI remains a concern in England. The study highlights the importance of managing primary and rCDI episodes via effective and improved therapies to prevent fatal complications.

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.

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.

Natriuretic peptide testing and heart failure diagnosis in primary care: diagnostic accuracy study.

BACKGROUND: Natriuretic peptide (NP) testing is recommended for patients presenting to primary care with symptoms of chronic heart failure (HF) to prioritise referral for diagnosis. AIM: To report NP test performance at European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guideline referral thresholds. DESIGN AND SETTING: Diagnostic accuracy study using linked primary and secondary care data (2004 to 2018). METHOD: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NP testing for HF diagnosis was assessed. RESULTS: In total, 229 580 patients had an NP test and 21 102 (9.2%) were diagnosed with HF within 6 months. The ESC NT-proBNP threshold ≥125 pg/mL had a sensitivity of 94.6% (95% confidence interval [CI] = 94.2 to 95.0) and specificity of 50.0% (95% CI = 49.7 to 50.3), compared with sensitivity of 81.7% (95% CI = 81.0 to 82.3) and specificity of 80.3% (95% CI = 80.0 to 80.5) for the NICE NT-proBNP ≥400 pg/mL threshold. PPVs for an NT-proBNP test were 16.4% (95% CI = 16.1 to 16.6) and 30.0% (95% CI = 29.6 to 30.5) for ESC and NICE thresholds, respectively. For both guidelines, nearly all patients with an NT-proBNP level below the threshold did not have HF (NPV: ESC 98.9%, 95% CI = 98.8 to 99.0 and NICE 97.7%, 95% CI = 97.6 to 97.8). CONCLUSION: At the higher NICE chronic HF guideline NP thresholds, one in five cases are initially missed in primary care but the lower ESC thresholds require more diagnostic assessments. NP is a reliable 'rule-out' test at both cut-points. The optimal NP threshold will depend on the priorities and capacity of the healthcare system.

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.

Natriuretic peptide level at heart failure diagnosis and risk of hospitalisation and death in England 2004-2018.

OBJECTIVE: Heart failure (HF) is a malignant condition requiring urgent treatment. Guidelines recommend natriuretic peptide (NP) testing in primary care to prioritise referral for specialist diagnostic assessment. We aimed to assess association of baseline NP with hospitalisation and mortality in people with newly diagnosed HF. METHODS: Population-based cohort study of 40 007 patients in the Clinical Practice Research Datalink in England with a new HF diagnosis (48% men, mean age 78.5 years). We used linked primary and secondary care data between 1 January 2004 and 31 December 2018 to report one-year hospitalisation and 1-year, 5-year and 10-year mortality by NP level. RESULTS: 22 085 (55%) participants were hospitalised in the year following diagnosis. Adjusted odds of HF-related hospitalisation in those with a high NP (NT-proBNP >2000 pg/mL) were twofold greater (OR 2.26 95% CI 1.98 to 2.59) than a moderate NP (NT-proBNP 400-2000 pg/mL). All-cause mortality rates in the high NP group were 27%, 62% and 82% at 1, 5 and 10 years, compared with 19%, 50% and 77%, respectively, in the moderate NP group and, in a competing risks model, risk of HF-related death was 50% higher at each timepoint. Median time between NP test and HF diagnosis was 101 days (IQR 19-581). CONCLUSIONS: High baseline NP is associated with increased HF-related hospitalisation and poor survival. While healthcare systems remain under pressure from the impact of COVID-19, research to test novel strategies to prevent hospitalisation and improve outcomes-such as a mandatory two-week HF diagnosis pathway-is urgently needed.

Consultations for clinical features of possible cancer and associated urgent referrals before and during the COVID-19 pandemic: an observational cohort study from English primary care.

BACKGROUND: It remains unclear to what extent reductions in urgent referrals for suspected cancer during the COVID-19 pandemic were the result of fewer patients attending primary care compared to GPs referring fewer patients. METHODS: Cohort study including electronic health records data from 8,192,069 patients from 663 English practices. Weekly consultation rates, cumulative consultations and referrals were calculated for 28 clinical features from the NICE suspected cancer guidelines. Clinical feature consultation rate ratios (CRR) and urgent referral rate ratios (RRR) compared time periods in 2020 with 2019. FINDINGS: Consultations for cancer clinical features decreased by 24.19% (95% CI: 24.04-24.34%) between 2019 and 2020, particularly in the 6-12 weeks following the first national lockdown. Urgent referrals for clinical features decreased by 10.47% (95% CI: 9.82-11.12%) between 2019 and 2020. Overall, once patients consulted with primary care, GPs urgently referred a similar or greater proportion of patients compared to previous years. CONCLUSION: Due to the significant fall in patients consulting with clinical features of cancer there was a lower than expected number of urgent referrals in 2020. Sustained efforts should be made throughout the pandemic to encourage the public to consult their GP with cancer clinical features.

Long term trends in natriuretic peptide testing for heart failure in UK primary care: a cohort study.

AIMS: Heart failure (HF) is a malignant condition with poor outcomes and is often diagnosed on emergency hospital admission. Natriuretic peptide (NP) testing in primary care is recommended in international guidelines to facilitate timely diagnosis. We aimed to report contemporary trends in NP testing and subsequent HF diagnosis rates over time. METHODS AND RESULTS: Cohort study using linked primary and secondary care data of adult (≥45 years) patients in England 2004-18 (n = 7 212 013, 48% male) to report trends in NP testing (over time, by age, sex, ethnicity, and socioeconomic status) and HF diagnosis rates. NP test rates increased from 0.25 per 1000 person-years [95% confidence interval (CI) 0.23-0.26] in 2004 to 16.88 per 1000 person-years (95% CI 16.73-17.03) in 2018, with a significant upward trend in 2010 following publication of national HF guidance. Women and different ethnic groups had similar test rates, and there was more NP testing in older and more socially deprived groups as expected. The HF detection rate was constant over the study period (around 10%) and the proportion of patients without NP testing prior to diagnosis remained high [99.6% (n = 13 484) in 2004 vs. 76.7% (n = 12 978) in 2017]. CONCLUSION: NP testing in primary care has increased over time, with no evidence of significant inequalities, but most patients with HF still do not have an NP test recorded prior to diagnosis. More NP testing in primary care may be needed to prevent hospitalization and facilitate HF diagnosis at an earlier, more treatable stage.

Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses.

OBJECTIVE: To assess the associations between statins and adverse events in primary prevention of cardiovascular disease and to examine how the associations vary by type and dosage of statins. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Studies were identified from previous systematic reviews and searched in Medline, Embase, and the Cochrane Central Register of Controlled Trials, up to August 2020. REVIEW METHODS: Randomised controlled trials in adults without a history of cardiovascular disease that compared statins with non-statin controls or compared different types or dosages of statins were included. MAIN OUTCOME MEASURES: Primary outcomes were common adverse events: self-reported muscle symptoms, clinically confirmed muscle disorders, liver dysfunction, renal insufficiency, diabetes, and eye conditions. Secondary outcomes included myocardial infarction, stroke, and death from cardiovascular disease as measures of efficacy. DATA SYNTHESIS: A pairwise meta-analysis was conducted to calculate odds ratios and 95% confidence intervals for each outcome between statins and non-statin controls, and the absolute risk difference in the number of events per 10 000 patients treated for a year was estimated. A network meta-analysis was performed to compare the adverse effects of different types of statins. An Emax model based meta-analysis was used to examine the dose-response relationships of the adverse effects of each statin. RESULTS: 62 trials were included, with 120 456 participants followed up for an average of 3.9 years. Statins were associated with an increased risk of self-reported muscle symptoms (21 trials, odds ratio 1.06 (95% confidence interval 1.01 to 1.13); absolute risk difference 15 (95% confidence interval 1 to 29)), liver dysfunction (21 trials, odds ratio 1.33 (1.12 to 1.58); absolute risk difference 8 (3 to 14)), renal insufficiency (eight trials, odds ratio 1.14 (1.01 to 1.28); absolute risk difference 12 (1 to 24)), and eye conditions (six trials, odds ratio 1.23 (1.04 to 1.47); absolute risk difference 14 (2 to 29)) but were not associated with clinically confirmed muscle disorders or diabetes. The increased risks did not outweigh the reduction in the risk of major cardiovascular events. Atorvastatin, lovastatin, and rosuvastatin were individually associated with some adverse events, but few significant differences were found between types of statins. An Emax dose-response relationship was identified for the effect of atorvastatin on liver dysfunction, but the dose-response relationships for the other statins and adverse effects were inconclusive. CONCLUSIONS: For primary prevention of cardiovascular disease, the risk of adverse events attributable to statins was low and did not outweigh their efficacy in preventing cardiovascular disease, suggesting that the benefit-to-harm balance of statins is generally favourable. Evidence to support tailoring the type or dosage of statins to account for safety concerns before starting treatment was limited. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020169955.

Clinical prediction tools to identify patients at highest risk of myeloma in primary care: a retrospective open cohort study.

BACKGROUND: Patients with myeloma experience substantial delays in their diagnosis, which can adversely affect their prognosis. AIM: To generate a clinical prediction rule to identify primary care patients who are at highest risk of myeloma. DESIGN AND SETTING: Retrospective open cohort study using electronic health records data from the UK's Clinical Practice Research Datalink (CPRD) between 1 January 2000 and 1 January 2014. METHOD: Patients from the CPRD were included in the study if they were aged ≥40 years, had two full blood counts within a year, and had no previous diagnosis of myeloma. Cases of myeloma were identified in the following 2 years. Derivation and external validation datasets were created based on geographical region. Prediction equations were estimated using Cox proportional hazards models including patient characteristics, symptoms, and blood test results. Calibration, discrimination, and clinical utility were evaluated in the validation set. RESULTS: Of 1 281 926 eligible patients, 737 (0.06%) were diagnosed with myeloma within 2 years. Independent predictors of myeloma included: older age; male sex; back, chest and rib pain; nosebleeds; low haemoglobin, platelets, and white cell count; and raised mean corpuscular volume, calcium, and erythrocyte sedimentation rate. A model including symptoms and full blood count had an area under the curve of 0.84 (95% CI = 0.81 to 0.87) and sensitivity of 62% (95% CI = 55% to 68%) at the highest risk decile. The corresponding statistics for a second model, which also included calcium and inflammatory markers, were an area under the curve of 0.87 (95% CI = 0.84 to 0.90) and sensitivity of 72% (95% CI = 66% to 78%). CONCLUSION: The implementation of these prediction rules would highlight the possibility of myeloma in patients where GPs do not suspect myeloma. Future research should focus on the prospective evaluation of further external validity and the impact on clinical practice.

Measuring the complexity of general practice consultations: a Delphi and cross-sectional study in English primary care.

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.

Impact of changes to national guidelines on hypertension-related workload: an interrupted time series analysis in English primary care.

BACKGROUND: In 2011, National Institute for Health and Care Excellence (NICE) guidelines recommended the routine use of out-of-office blood pressure (BP) monitoring for the diagnosis of hypertension. These changes were predicted to reduce unnecessary treatment costs and workload associated with misdiagnosis. AIM: To assess the impact of guideline change on rates of hypertension-related consultation in general practice. DESIGN AND SETTING: A retrospective open cohort study in adults registered with English general practices contributing to the Clinical Practice Research Datalink between 1 April 2006 and 31 March 2017. METHOD: The primary outcome was the rate of face-to-face, telephone, and home visit consultations related to hypertension with a GP or nurse. Age- and sex-standardised rates were analysed using interrupted time-series analysis. RESULTS: In 3 937 191 adults (median follow-up 4.2 years) there were 12 253 836 hypertension-related consultations. The rate of hypertension-related consultation was 71.0 per 100 person-years (95% confidence interval [CI] = 67.8 to 74.2) in April 2006, which remained flat before 2011. The introduction of the NICE hypertension guideline in 2011 was associated with a change in yearly trend (change in trend -3.60 per 100 person-years, 95% CI = -5.12 to -2.09). The rate of consultation subsequently decreased to 59.2 per 100 person-years (95% CI = 56.5 to 61.8) in March 2017. These changes occurred around the time of diagnosis, and persisted when accounting for wider trends in all consultations. CONCLUSION: Hypertension-related workload has declined in the last decade, in association with guideline changes. This is due to changes in workload at the time of diagnosis, rather than reductions in misdiagnosis.

Association between antihypertensive treatment and adverse events: systematic review and meta-analysis.

OBJECTIVE: To examine the association between antihypertensive treatment and specific adverse events. DESIGN: Systematic review and meta-analysis. ELIGIBILITY CRITERIA: Randomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up. INFORMATION SOURCES: Searches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020. MAIN OUTCOME MEASURES: The primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (τ2). RESULTS: Of 15 023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280 638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, τ2=0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, τ2=0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, τ2=0.122, n=26), hypotension (1.97, 1.67 to 2.32, τ2=0.132, n=35), and syncope (1.28, 1.03 to 1.59, τ2=0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction. CONCLUSIONS: This meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function. REGISTRATION: PROSPERO CRD42018116860.

Current prevalence of self-monitoring of blood pressure during pregnancy: the BUMP Survey.

OBJECTIVE: To understand the current prevalence of, and attitudes to, self-monitoring of blood pressure (BP) during pregnancy. METHODS: Five thousand, five hundred and fifty-five pregnant women from antenatal clinics in 16 hospitals in England were invited to complete a survey. MAIN OUTCOME MEASURES: The primary outcome was the proportion of women currently BP self-monitoring. Secondary outcomes included self-monitoring schedules and women's interactions with clinicians regarding self-monitoring. Population characteristics including risk factors for preeclampsia, ethnicity and deprivation level were considered. RESULTS: Completed surveys were received and analysed from 5181 pregnant women (93% response rate). Comparison to hospital demographic data suggests that respondents were representative of the UK population. Nine hundred and eighty-three of 5181 (19%) women were currently self-monitoring their BP, constituting 189 of 389 (49%) hypertensive women and 794 of 4792 (17%) normotensive women. However, only 482 of 983 (49%) reported ever sharing this information with antenatal care teams. Of those who self-monitored, 68% (668/983) were able to provide a previous BP reading, compared with 1% (67/5181) of those who did not self-monitor. CONCLUSION: Many women are now choosing to self-monitor their BP during pregnancy and clinicians should enquire about this proactively and consider providing better information on BP monitoring. Those who self-monitor appear to have better knowledge about their blood pressure. If these findings were replicated nationwide, around 125 000 pregnant women would be currently self-monitoring BP in the UK, yet only half of these women may communicate their readings to their antenatal care teams, suggesting a missed opportunity for enhanced care. Current trials will make the place of self-monitoring in pregnancy clearer.

The Long-Term Impact of Vaginal Surgical Mesh Devices in UK Primary Care: A Cohort Study in the Clinical Practice Research Datalink.

PURPOSE: Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) may be treated with surgical mesh devices; evidence of their long-term complications is lacking. PATIENTS AND METHODS: Rates of diagnoses of depression, anxiety or self-harm (composite measure) and sexual dysfunction, and rates of prescriptions for antibiotics and opioids were estimated in women with and without mesh surgery, with a diagnostic SUI/POP code, registered in the Clinical Practice Research Datalink (CPRD) gold database. RESULTS: There were 220,544 women eligible for inclusion; 74% (n = 162,687) had SUI, 37% (n = 82,123) had POP, and 11% (n = 24,266) had both. Women undergoing mesh surgery for SUI or POP had about 1.1 times higher rates of antibiotic use. Women with no previous history of the outcome, who underwent mesh surgery had 2.43 (95% CI 2.19-2.70) and 1.47 (95% CI 1.19-1.81) times higher rates of depression, anxiety, or self-harm, 1.88 (95% CI 1.50-2.36) and 1.64 (95% CI 1.02-2.63) times higher rates of sexual dysfunction and 1.40 (95% CI 1.26-1.56) and 1.23 (95% CI 1.01-1.49) times higher opioid use for SUI and POP, respectively. Women with a history of depression, anxiety and self-harm had 0.3 times lower rates of these outcomes with SUI or POP mesh surgery (HR for SUI 0.70 (95% CI 0.67-0.73), HR for POP 0.72 (95% CI 0.65-0.79)). Women with a history of opioid use who had POP mesh surgery had about 0.09 times lower rates (HR 0.91 (95% CI 0.86-0.96)) of prescriptions. Negative control outcome analyses showed no evidence of an association between asthma consultations and mesh surgery in women with POP, but the rate was 0.09 times lower (HR 0.91 (95% CI 0.87-0.94)) in women with SUI mesh surgery, suggesting that study results are subject to some residual confounding. CONCLUSION: Mesh surgery was associated with poor mental and sexual health outcomes, alongside increased opioid and antibiotic use, in women with no history of these outcomes and improved mental health, and lower opioid use, in women with a previous history of these outcomes. Although our results suggest an influence of residual confounding, careful consideration of the benefits and risk of mesh surgery for women with SUI or POP on an individual basis is required.

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.

Association Between Blood Pressure Control and Coronavirus Disease 2019 Outcomes in 45 418 Symptomatic Patients With Hypertension: An Observational Cohort Study.

Hypertension has been identified as a risk factor for coronavirus disease 2019 (COVID-19) and associated adverse outcomes. This study examined the association between preinfection blood pressure (BP) control and COVID-19 outcomes using data from 460 general practices in England. Eligible patients were adults with hypertension who were tested or diagnosed with COVID-19. BP control was defined by the most recent BP reading within 24 months of the index date (January 1, 2020). BP was defined as controlled (<130/80 mm Hg), raised (130/80-139/89 mm Hg), stage 1 uncontrolled (140/90-159/99 mm Hg), or stage 2 uncontrolled (≥160/100 mm Hg). The primary outcome was death within 28 days of COVID-19 diagnosis. Secondary outcomes were COVID-19 diagnosis and COVID-19-related hospital admission. Multivariable logistic regression was used to examine the association between BP control and outcomes. Of the 45 418 patients (mean age, 67 years; 44.7% male) included, 11 950 (26.3%) had controlled BP. These patients were older, had more comorbidities, and had been diagnosed with hypertension for longer. A total of 4277 patients (9.4%) were diagnosed with COVID-19 and 877 died within 28 days. Individuals with stage 1 uncontrolled BP had lower odds of COVID-19 death (odds ratio, 0.76 [95% CI, 0.62-0.92]) compared with patients with well-controlled BP. There was no association between BP control and COVID-19 diagnosis or hospitalization. These findings suggest BP control may be associated with worse COVID-19 outcomes, possibly due to these patients having more advanced atherosclerosis and target organ damage. Such patients may need to consider adhering to stricter social distancing, to limit the impact of COVID-19 as future waves of the pandemic occur.

Are blood pressure level and variability related to pregnancy outcome? Analysis of control of hypertension in pregnancy study data.

OBJECTIVE: To examine the relationship between pregnancy outcomes and BP level and variability. DESIGN: Secondary analysis of CHIPS trial data (Control of Hypertension In Pregnancy Study, NCT01192412). SETTING: International. POPULATION OR SAMPLE: Women with chronic or gestational hypertension. METHODS: BP measurement was standardised in outpatient clinics. Adjusted (including for allocated group) mixed effects logistic regression was used to assess relationships between major CHIPS outcomes and both BP level (mean of clinic readings) and visit-to-visit within-participant BP variability (standard deviation and average real variability of absolute successive difference of BP values). BP values 7-28 days prior to outcomes (or birth for perinatal outcomes) were excluded in sensitivity analyses. MAIN OUTCOME MEASURES: Major CHIPS outcomes. RESULTS: Among 961 (97.4%) women, higher BP level was associated with more adverse maternal and perinatal outcomes (usually at p < 0.001) except for serious maternal complications. Among 913 (92.5%) women with at least two post-randomisation outpatient visits, higher BP variability was associated with increased odds of severe hypertension and pre-eclampsia (usually at p < 0.01). Sensitivity analyses suggested reverse causality for these maternal outcomes, but greater diastolic BP variability may have been associated with fewer adverse perinatal outcomes. CONCLUSIONS: Higher BP is an adverse prognostic marker, regardless of target BP. While the association between higher BP variability and severe hypertension and pre-eclampsia may be related to higher BP at diagnosis, our results suggest a possible advantage of BP variability for the fetus, through undefined mechanisms. TWEETABLE ABSTRACT: Higher blood pressure (BP) is associated with more adverse pregnancy outcomes, but higher BP variability may be good for the baby.

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.