Background: Evidence for kidney function monitoring intervals in primary care is weak, and based mainly on expert opinion. In the absence of trials of monitoring strategies, an approach combining a model for the natural history of kidney function over time combined with a cost-effectiveness analysis offers the most feasible approach for comparing the effects of monitoring under a variety of policies. This study aimed to create a model for kidney disease progression using routinely collected measures of kidney function. Methods: This is an open cohort study of patients aged \u226518 years, registered at 643 UK general practices contributing to the Clinical Practice Research Datalink between 1 April 2005 and 31 March 2014. At study entry, no patients were kidney transplant donors or recipients, pregnant or on dialysis. Hidden Markov models for estimated glomerular filtration rate (eGFR) stage progression were fitted to four patient cohorts defined by baseline albuminuria stage; adjusted for sex, history of heart failure, cancer, hypertension and diabetes, annually updated for age. Results: Of 1,973,068 patients, 1,921,949 had no recorded urine albumin at baseline, 37,947 had normoalbuminuria (<3mg/mmol), 10,248 had microalbuminuria (3-30mg/mmol), and 2,924 had macroalbuminuria (>30mg/mmol). Estimated annual transition probabilities were 0.75-1.3%, 1.5-2.5%, 3.4-5.4% and 3.1-11.9% for each cohort, respectively. Misclassification of eGFR stage was estimated to occur in 12.1% (95%CI: 11.9-12.2%) to 14.7% (95%CI: 14.1-15.3%) of tests. Male gender, cancer, heart failure and age were independently associated with declining renal function, whereas the impact of raised blood pressure and glucose on renal function was entirely predicted by albuminuria. Conclusions: True kidney function deteriorates slowly over time, declining more sharply with elevated urine albumin, increasing age, heart failure, cancer and male gender. Consecutive eGFR measurements should be interpreted with caution as observed improvement or deterioration may be due to misclassification.
\n \n\n \n \nBackground: Clinical prediction rules (CPRs) can help general practitioners (GPs) address challenges in cardiovascular disease. A survey published in 2014 evaluated GPs' awareness and use of CPRs in the UK. However, many new CPRs have been published since and it is unknown which cardiovascular CPRs are currently recognised and used. Aim: To identify cardiovascular CPRs recognised and used by GPs, and to assess how GPs' familiarity and use have changed over time. Design & setting: An online survey of GPs in the UK was undertaken. Method: Using comparable methods to the 2014 survey, GPs were recruited from a network of doctors in the UK. They were asked how familiar they were with cardiovascular CPRs, how frequently they used them, and why they used them. The results were compared with the 2014 survey. Results: Most of 401 GPs were familiar with QRISK scores, ABCD scores, CHADS scores, HAS-BLED score, Wells scores for deep vein thrombosis, and Wells scores for pulmonary embolism. The proportions of GPs using these CPRs were 96.3%, 65.1%, 97.3%, 93.0%, 92.5%, and 82.0%, respectively. GPs' use increased by 31.2% for QRISK scores, by 13.5% for ABCD scores, by 54.6% for CHADS scores, by 33.2% for Wells scores for deep vein thrombosis, and by 43.6% for Wells scores for pulmonary embolism; and decreased by 45.9% for the Joint British Societies (JBS) risk calculator, by 38.7% for Framingham risk scores, and by 8.7% for New Zealand tables. GPs most commonly used cardiovascular CPRs to guide therapy and referral. Conclusion: The study found GPs' familiarity and use of cardiovascular CPRs changed substantially. Integrating CPRs into guidelines and practice software might increase familiarity and use.
\n \n\n \n \nBACKGROUND: 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.
\n \n\n \n \nThe article entitled \"Systematic Review and Metaanalysis Comparing the Bias and Accuracy of the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration Equations in Community-Based Populations,\"by Emily C. McFadden, Jennifer A. Hirst, Jan Y. Verbakel, Julie H. McLellan, F.D. Richard Hobbs, Richard J. Stevens, Chris A. O'Callaghan, and Daniel S. Lasserson (Clin Chem 2018;64:475-85), published in the March 2018 issue of Clinical Chemistry, contains errors. In the Results section, under \"Difference in Bias between CKD-EPI and MDRD Equations for eGFR\"(page 479), the penultimate sentence of the paragraph should read, \"Bias in the CKD-EPI equation was on average lower than mGFR by 2.8 mL/min/1.73 m2 (95% CI, -0.4 to 6.0) with variation between studies (I2 99.0; P<0.0001) (Fig. 3).\"Figure 3 is correct and unchanged. In the Discussion (page 479), the opening sentence should read, \"In populations relevant to primary care, we found that both the MDRD and CKD-EPI equations underestimated GFR, though the estimate for CKD-EPI was not significantly different from mGFR. Estimates from CKD-EPI were slightly more accurate than those from MDRD.\"In view of these changes, the abstract conclusion should read \"Both equations may underestimate mGFR, but CKD-EPI gave more accurate estimates of GFR.\"The authors regret the errors.
\n \n\n \n \nObjective 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 (\u03c4 2). 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, \u03c4 2 =0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, \u03c4 2 =0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, \u03c4 2 =0.122, n=26), hypotension (1.97, 1.67 to 2.32, \u03c4 2 =0.132, n=35), and syncope (1.28, 1.03 to 1.59, \u03c4 2 =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.
\n \n\n \n \nIntroduction: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published frequent summaries of spontaneous reports of suspected adverse drug reactions (ADRs) (Yellow Cards) to vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The EudraVigilance database has provided similar data for the European Economic Area. Objective: Our objective was to characterize the evolution over time of spontaneous reports of suspected ADRs to coronavirus disease 2019 (COVID-19) vaccines and to observe the effect of a publicized reaction (cerebral venous and sinus thrombosis [CVST]) on reporting rates. Methods: We used publicly available data on reports of suspected ADRs and doses of vaccine administered, published by the MHRA, EudraVigilance, and the European Centre for Disease Prevention and Control to calculate reporting rates. Results: Approximately 4814 Yellow Card reports (23 fatal) per million doses of ChAdOx1 nCoV-19 (AstraZeneca) and 2890 (13 fatal) per million doses of tozinameran (Pfizer/BioNTech) have been lodged. Between 15 March and 31 October 2021, cumulative European reports of CVST rose from 0 to 443 (183 with thrombocytopenia, 72 fatal) with ChAdOx1 nCoV-19 and from 2 to 315 (9 with thrombocytopenia, 28 fatal) with tozinameran. European cases of retinal vein occlusion and thrombosis rose from 0 to 168 with ChAdOx1 nCoV-19 and from 1 to 220 with tozinameran; four of the ChAdOx1 nCoV-19 cases were associated with thrombocytopenia. Conclusion: Reports of fatal adverse reactions to coronavirus vaccines are very rare. Reports of CVST have been made in relation to both vaccines. Most were submitted after the reaction had been publicized. Thrombocytopenia occurred in a minority of cases. Reports linked both vaccines to cases of retinal vein thrombosis, just four\u00a0cases with thrombocytopenia. This suggests two different mechanisms of thrombosis associated with the vaccines.
\n \n\n \n \nBackground 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 \u226540 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\u2013Gray 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.
\n \n\n \n \nObjectives: FRAX uses clinical risk factors, with or without BMD, to calculate 10-year fracture risk. RA is a risk factor for osteoporotic fracture and a FRAX input variable. FRAX predates the current era of RA treatment. We examined how well FRAX predicts fracture in contemporary RA patients. Methods: Administrative data from patients receiving BMD testing were linked to the Manitoba Population Health Research Data Repository. Observed cumulative 10-year major osteoporotic fracture (MOF) probability was compared with FRAX-predicted 10-year MOF probability with BMD for assessing calibration. MOF risk stratification was assessed using Cox regression. Results: RA patients (n\u2002=\u20022099, 208 with incident MOF) and non-RA patients (n\u2002=\u20022099, with 165 incident MOF) were identified. For RA patients, FRAX-predicted 10-year risk was 13.2% and observed 10-year MOF risk was 13.2% (95% CI 11.6, 15.1). The slope of the calibration plot was 0.67 (95% CI 0.53, 0.81) in those with RA vs 0.98 (95% CI 0.61, 1.34) in non-RA patients. Risk was overestimated in RA patients with high FRAX scores (>20%), but FRAX was well calibrated in other groups. FRAX stratified risk in those with and without RA [hazard ratio (HR) 1.52 (95% CI 1.25, 1.72) vs 2.00 (95% CI 1.73, 2.31)], with slightly better performance in the latter (P for interaction\u2002=\u20020.004). Conclusions: FRAX predicts fracture risk in contemporary RA patients but may slightly overestimate risk in those already at high predicted risk. Thus the current FRAX tool continues to be appropriate for fracture risk assessment in RA patients.
\n \n\n \n \nAssociations of adiposity with risks of oesophageal squamous cell carcinoma (ESCC) and non-cardia stomach cancer, both prevalent in China, are still inconclusive. While adiposity is an established risk factor for colorectal cancer, the relevance of fat-free mass and early-adulthood adiposity remains to be explored. The prospective China Kadoorie Biobank study included 0.5 million adults (aged 30\u201379 years) from 10 areas in China. Participants' body size and composition were measured at baseline and at resurveys (amongst a subset). After >10 years of follow-up, 2350, 3345 and 3059 incident cases of oesophageal (EC), stomach (SC) and colorectal (CRC) cancers\u00a0were recorded, respectively. Cox regression was used to estimate hazard ratios (HRs) for these cancers in relation to different adiposity traits. General and central adiposity were inversely associated with EC (primarily ESCC) risk, with HRs of 0.81 (95% CI 0.77\u20130.85), 0.76 (0.72\u20130.81) and 0.87 (0.83\u20130.92) per SD increase in usual levels of BMI, body fat percentage (BF%) and waist circumference (WC), respectively. Adiposity was also inversely associated with SC risk [HR = 0.79 (0.75\u20130.83) and 0.88 (0.84\u20130.92) per SD increase in usual BF% and WC], with heterogeneity by cardia and non-cardia subsites, and positively associated with CRC [HR = 1.09 (1.03\u20131.15) and 1.17 (1.12\u20131.22) per SD higher usual BF% and WC]. Fat-free mass was inversely associated with EC [HR = 0.93 (0.89\u20130.98) per SD increase] but positively associated with CRC [1.09 (1.04\u20131.14)], while BMI at age 25 was positively associated with all three cancers. After mutual adjustment, general adiposity remained inversely associated with EC and SC, while central adiposity remained positively associated with CRC.
\n \n\n \n \nBackground: Restricted activity is a potential early marker of declining health in older adults. Previous studies of this association with patient outcomes have been inconclusive. This review aimed to evaluate the extent to which restricted activity is associated with decline in health. Methods: A search was conducted for studies including people over 65 years old which investigated the association between measures of restricted activity and hospitalisation, cognitive decline, and mortality. Following data extraction by two reviewers, eligible studies were summarised using Inverse Variance Heterogeneity meta-analysis. Results: The search identified 8,434 unique publications, with 11 eligible studies. Three measures of restricted activity were identified: bed rest, restricted movement, and dependency for activities of daily living (ADL). Three studies looked at hospitalisations, with two finding a significant association with bed rest or restricted movement and one showing no evidence of an association. Restricted activity was associated with a significant increase in mortality across all three measures (bed rest odds ratio [OR] 6.34, 95%CI 2.51\u201316.02, I2 = 76%; restricted movement OR 5.38 95%CI 2.60\u201311.13, I2 = 69%; general ADL dependency OR 4.65 95%CI 2.25\u20139.26, I2 = 84%). The significant heterogeneity observed could not be explained by restricting the analysis by length of follow-up, or measure of restricted activity. No meta-analysis was conducted on the limited evidence for cognitive decline outcomes. Conclusions: Limited studies have considered the prognostic value of restricted activity in terms of predicting future declining health. Current evidence suggests restricted activity is associated with hospitalisation and mortality, and therefore could identify a group for whom early intervention might be possible.
\n \n\n \n \nBackground: Little evidence is available on the long-term health effects of nitrogen dioxide (NO2) in low-income and middle-income populations. We investigated the associations of long-term NO2 exposure with the incidence of a wide spectrum of disease outcomes, based on data from the China Kadoorie Biobank. Methods: This prospective cohort study involved 512 724 Chinese adults aged 30\u201379 years recruited from ten areas of China during 2004\u201308. Time-varying Cox regression models yielded adjusted hazard ratios (HRs) for the associations of long-term NO2 exposure with aggregated disease incidence endpoints classified by 14 ICD-10 chapters, and incidences of 12 specific diseases selected from three key ICD-10 chapters (cardiovascular, respiratory, and musculoskeletal diseases) found to be robustly associated with NO2 in the analyses of aggregated endpoints. All models were stratified by age-at-risk (in 1-year scale), study area, and sex, and were adjusted for education, household income, smoking status, alcohol intake, cooking fuel type, heating fuel type, self-reported health status, BMI, physical activity level, temperature, and relative humidity. Findings: The analysis of 512 709 participants (mean baseline age 52\u00b70 years [SD 10\u00b77]; 59\u00b70% female and 41\u00b70% male) included approximately 6\u00b75 million person-years of follow-up. Between 5285 and 144 852 incident events were recorded for each of the 14 aggregated endpoints. Each 10 \u03bcg/m3 higher annual average NO2 exposure was associated with higher risks of chapter-specific endpoints, especially cardiovascular (n=144 852; HR 1\u00b704 [95% CI 1\u00b702\u20131\u00b705]), respiratory (n=73 232; 1\u00b703 [1\u00b701\u20131\u00b705]), musculoskeletal (n=54 409; 1\u00b711 [1\u00b709\u20131\u00b714]), and mental and behavioural (n=5361; 1\u00b712 [1\u00b705\u20131\u00b721]) disorders. Further in-depth analyses on specific diseases found significant positive supra-linear associations with hypertensive disease (1\u00b708 [1\u00b705\u20131\u00b711]), lower respiratory tract infection (1\u00b703 [1\u00b701\u20131\u00b706]), arthrosis (1\u00b715 [1\u00b709\u20131\u00b721]), intervertebral disc disorders (1\u00b713 [1\u00b709\u20131\u00b717]), and spondylopathies (1\u00b705 [1\u00b701\u20131\u00b710]), and linear associations with ischaemic heart disease (1\u00b703 [1\u00b700\u20131\u00b705]), ischaemic stroke (1\u00b708 [1\u00b706\u20131\u00b711]), and asthma (1\u00b715 [1\u00b704\u20131\u00b727]), whereas intracerebral haemorrhage (1\u00b700 [0\u00b795\u20131\u00b706]), other cerebrovascular disease (0\u00b798 [0\u00b796\u20131\u00b701]), acute upper respiratory infection (1\u00b703 [0\u00b796\u20131\u00b709]), and chronic lower respiratory disease (0\u00b798 [0\u00b795\u20131\u00b702]) showed no significant association. NO2 exposure showed robust null association with external causes (n=32 907; 0\u00b798 [0\u00b795\u20131\u00b702]) as a negative control. Interpretation: In China, long-term NO2 exposure was associated with a range of diseases, particularly cardiovascular, respiratory, and musculoskeletal diseases. These associations underscore the pressing need to implement the recently tightened WHO air quality guidelines. Funding: Wellcome Trust, UK Medical Research Council, Cancer Research UK, British Heart Foundation, National Natural Science Foundation of China, National Key Research and Development Program of China, Sino-British Fellowship Trust, and Kadoorie Charitable Foundation.
\n \n\n \n \nBackground: Risk prediction models can identify individuals at high risk of chronic liver disease (CLD), but there is limited evidence on the performance of various models in diverse populations. We aimed to systematically review CLD prediction models, meta-analyze their performance, and externally validate them in 0.5 million Chinese adults in the China Kadoorie Biobank (CKB). Methods: Models were identified through a systematic review and categorized by the target population and outcomes (hepatocellular carcinoma [HCC] and CLD). The performance of models to predict 10-year risk of CLD was assessed by discrimination (C-index) and calibration (observed vs predicted probabilies). Results: The systematic review identified 57 articles and 114 models (28.4% undergone external validation), including 13 eligible for validation in CKB. Models with high discrimination (C-index \u2265 0.70) in CKB were as follows: (1) general population: Li-2018 and Wen 1\u20132012 for HCC, CLivD score (non-lab and lab) and dAAR for CLD; (2) hepatitis B virus (HBV) infected individuals: Cao-2021 for HCC and CAP-B for CLD. In CKB, all models tended to overestimate the risk (O:E ratio 0.55\u20130.94). In meta-analysis, we further identified models with high discrimination: (1) general population (C-index \u2265 0.70): Sinn-2020, Wen 2\u20132012, and Wen 3\u20132012 for HCC, and FIB-4 and Forns for CLD; (2) HBV infected individuals (C-index \u2265 0.80): RWS-HCC and REACH-B IIa for HCC and GAG-HCC for HCC and CLD. Conclusions: Several models showed good discrimination and calibration in external validation, indicating their potential feasibility for risk stratification in population-based screening programs for CLD in Chinese adults.
\n \n\n \n \nBackground : Action on smoking, obesity, excess alcohol, and physical inactivity in primary care is effective and cost-effective, but implementation is low. The aim was to examine the effectiveness of strategies to increase the implementation of preventive healthcare in primary care. Methods: CINAHL, CENTRAL, The Cochrane Database of Systematic Reviews, Dissertations & Theses \u2013 Global, Embase, Europe PMC, MEDLINE and PsycINFO were searched from inception through 5 October 2023 with no date of publication or language limits. Randomised trials, non-randomised trials, controlled before-after studies and interrupted time series studies comparing implementation strategies (team changes; changes to the electronic patient registry; facilitated relay of information; continuous quality improvement; clinician education; clinical reminders; financial incentives or multicomponent interventions) to usual care were included. Two reviewers screened studies, extracted data, and assessed bias with an adapted Cochrane risk of bias tool for Effective Practice and Organisation of Care reviews. Meta-analysis was conducted with random-effects models. Narrative synthesis was conducted where meta-analysis was not possible. Outcome measures included process and behavioural outcomes at the closest point to 12\u00a0months for each implementation strategy. Results: Eighty-five studies were included comprising of 4,210,946 participants from 3713 clusters in 71 cluster trials, 6748 participants in 5 randomised trials, 5,966,552 participants in 8 interrupted time series, and 176,061 participants in 1 controlled before after study. There was evidence that clinical reminders (OR 3.46; 95% CI 1.72\u20136.96; I2 = 89.4%), clinician education (OR 1.89; 95% CI 1.46\u20132.46; I2 = 80.6%), facilitated relay of information (OR 1.95, 95% CI 1.10\u20133.46, I2 = 88.2%), and multicomponent interventions (OR 3.10; 95% CI 1.60\u20135.99, I2 = 96.1%) increased processes of care. Multicomponent intervention results were robust to sensitivity analysis. There was no evidence that other implementation strategies affected processes of care or that any of the implementation strategies improved behavioural outcomes. No studies reported on interventions specifically designed for remote consultations. Limitations included high statistical heterogeneity and many studies did not account for clustering. Conclusions: Multicomponent interventions may be the most effective implementation strategy. There was no evidence that implementation interventions improved behavioural outcomes. Trial registration: PROSPERO CRD42022350912.
\n \n\n \n \nBACKGROUND: Hypertensive disorders of pregnancy are associated with high maternal and fetal morbidity and mortality. There are limited global data on the characteristics of women during and after pregnancy hypertension. METHODS: May Measurement Month is a global campaign to raise awareness of the importance of blood pressure. Adults (\u226518 years) recruited through opportunistic sampling during May 2019 had blood pressure measured and comorbidities and lifestyle data collected. This secondary analysis included 16 519 pregnant women and 529 172 nonpregnant women (16 457 with previous raised blood pressure in pregnancy) from 64 countries. RESULTS: Almost half of the pregnant women (43.3%) reported not having had their blood pressure measured in the past year, and 14.3% (95% CI, 12.1-16.6) had hypertension (blood pressure \u2265140/90 mm\u2005Hg or taking antihypertensive medication). Diabetes was self-reported in 7.6% (5.9-9.3) of pregnant women with hypertension and 2.8% (1.9-3.6) of pregnant women without hypertension. In nonpregnant women with and without a history of pregnancy hypertension, age-standardized proportions with current hypertension were 53.2% (50.8-55.7) versus 33.3% (29.3-37.3); with diabetes were 14.4% (11.8-17.0) versus 8.5% (6.3-10.9); and with body mass index \u226530 kg/m2 were 28.4% (23.5-33.3) versus 16.6% (13.0-20.2). CONCLUSIONS: Hypertension in pregnancy was common in this global sample but many cases had not previously been identified. There was a clustering of cardiovascular risk factors in both pregnant women with current hypertension and previously raised blood pressure in pregnancy. This work highlights the importance of screening pregnant women for hypertension, which remains a challenge in large parts of the world.
\n \n\n \n \nBackground: One-third of people with depression do not respond to antidepressants, and, after two adequate courses of antidepressants, are classified as having treatment-resistant depression (TRD). Some case reports suggest that ketogenic diets (KDs) may improve some mental illnesses, and preclinical data indicate that KDs can influence brain reward signalling, anhedonia, cortisol, and gut microbiome which are associated with depression. To date, no trials have examined the clinical effect of a KD on TRD. Methods: This is a proof-of-concept randomised controlled trial to investigate the efficacy of a six-week programme of weekly dietitian counselling plus provision of KD meals, compared with an intervention involving similar dietetic contact time and promoting a healthy diet with increased vegetable consumption and reduction in saturated fat, plus food vouchers to purchase healthier items. At 12 weeks we will assess whether participants have continued to follow the assigned diet. The primary outcome is the difference between groups in the change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 6 weeks. PHQ-9 will be measured at weeks 2, 4, 6 and 12. The secondary outcomes are the differences between groups in the change in remission of depression, change in anxiety score, functioning ability, quality of life, cognitive performance, reward sensitivity, and anhedonia from baseline to 6 and 12 weeks. We will also assess whether changes in reward sensitivity, anhedonia, cortisol awakening response and gut microbiome may explain any changes in depression severity. Discussion: This study will test whether a ketogenic diet is an effective intervention to reduce the severity of depression, anxiety and improve quality of life and functioning ability for people with treatment-resistant depression.
\n \n\n \n \nObjective: To compare clinic and home blood pressure readings in higher risk pregnancies in the antenatal period from 20 weeks gestation, and to evaluate differences between the two modalities. Study design: A cohort study comprising a secondary analysis of a large randomised controlled trial (BUMP 1). Population: Normotensive women at higher risk of pregnancy hypertension randomised to self-monitoring of blood pressure. Main outcome measures: The primary outcome was the overall mean difference between clinic and home readings for systolic blood pressure (sBP) and diastolic blood pressure (dBP). Blood pressure readings were averaged across each gestational week for each participant and compared within the same gestational week. Calculations of the overall differences were based on the average difference for each week for each participant. Results: The cohort comprised 925 participants. In total, 92 (10 %) developed a hypertensive disorder during the pregnancy. A significant difference in the overall mean sBP (clinic \u2013 home) of 1.1 mmHg (0.5\u20131.6 95 %CI) was noted, whereas no significant difference for the overall mean dBP was found (0.0 mmHg (\u22120.4\u20130.4 95 %CI)). No tendency of proportional bias was noted based on Bland-Altman plots. Increasing body mass index in general increased the difference (clinic \u2013 home) for both sBP and dBP in a multivariate analysis. Conclusions: No clinically significant difference was found between clinic and home blood pressure readings in normotensive higher risk pregnancies from gestational week 20+0 until 40+0. Clinic and home blood pressure readings might be considered equal during pregnancy in women who are normotensive at baseline.
\n \n\n \n \nObjective: Offering advice and support for smoking, obesity, excess alcohol, and physical inactivity is an evidence-based component of primary care. The objective was to quantify the impact of the pandemic on the rate of advice or referral for these four risk factors. Methods: A retrospective cohort study using primary care data from 1847 practices in England and 21,191,389 patients contributing to the Oxford Clinical Informatics Digital Hub. An interrupted time series analysis was undertaken with a single change point (March 2020). Monthly trends were modelled from 1st January 2018 \u2013 30th June 2022 using segmented linear regression. Results: There was an initial step reduction in advice and referrals for smoking, obesity, excess alcohol, and physical inactivity in March 2020. By June 2022, advice on smoking (slope change \u22120.02 events per hundred patient years/month (EPH/month); 95% confidence interval (CI) -0.17, 0.21), obesity (0.06 EPH/month; 95% CI 0.01, 0.12), alcohol (0.02 EPH/month; 95% CI -0.01, 0.05) and physical inactivity (0.05 EPH/month; 95% CI 0.01, 0.09) had not returned to pre-pandemic levels. Similarly, smoking cessation referral remained lower (0.01 EPH/month; 95% CI -0.01, 0.09), excess alcohol referral returned to similar levels (0.0005 EPH/month; 95% CI 0.0002, 0.0008), while referral for obesity (0.14 EPH/month; 95% CI 0.10, 0.19) and physical inactivity (0.01 EPH/month; 95% CI 0.01, 0.02) increased relative to pre-pandemic rates. Conclusion: Advice and support for smoking, and advice for weight, excess alcohol and physical inactivity have not returned to pre-pandemic levels. Clinicians and policy makers should prioritise preventive care in COVID-19 recovery plans.
\n \n\n \n \nObjective: To evaluate the diagnostic accuracy of point-of-care (POC) tests for detecting proteinuria in pregnant women. Design: Systematic review and meta-analysis. Data Sources: MEDLINE and EMBASE databases were searched from inception to 13 November 2020. Eligibility Criteria and Data Analysis: Included studies measured the sensitivity and specificity of POC proteinuria testing compared to laboratory reference standards (protein-creatinine ratio (PCR), 24-hour urine collection). Bivariate meta-analyses determined pooled sensitivity and specificity. Random-effects inverse-variance model determined heterogeneity. Main Outcome Measures: The primary outcome was overall sensitivity and specificity, stratified by method of POC testing and reference standard. Secondary outcomes were sensitivity and specificity within the subgroups test brand, reference standard, and hypertension status. Results: 1078 studies were identified, 17 studies comprising 23 comparisons were included. The meta-analysis included 13 studies with 19 comparisons. Pooled sensitivity and specificity of visual dipsticks against PCR was 72 % (95 % CI: 56 % to 84 %) and 92 % (95 % CI: 76 % to 98 %), respectively. Pooled sensitivity and specificity of visual dipsticks against 24-hour collection was 69 % (55 % to 80 %) and 70 % (51 % to 84 %), respectively. Pooled sensitivity and specificity for automated readers against PCR was 73 % (53 % to 86 %) and 91 % (83 % to 95 %), respectively. Pooled sensitivity and specificity of automated readers against 24-hour collection was 65 % (42 % to 83 %) and 82 % (46 % to 96 %), respectively. Conclusion: Visual dipsticks have comparable accuracy to automated readers, yet are not adequate as a rule-out test for proteinuria. Proteinuria POC testing may be beneficial in antenatal care when repeat follow-up tests are performed. PROSPERO Registration Number: CRD42021231914.
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