Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank.

BACKGROUND: Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education. METHODS: Participants were 181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank. We used a Mendelian randomization design; an approach that uses genetic variants as instrumental variables to interrogate causality. RESULTS: The prevalence of multimorbidity was 55.1%. Mendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in genetically-predicted years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in genetically-predicted BMI increases the risk of multimorbidity by 9.2% (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index increases the risk of multimorbidity by 6.8% (95% CI: 3.3 to 10.4%). Evidence for a causal effect of genetically-predicted alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity. CONCLUSIONS: Education, BMI, smoking and alcohol consumption are intervenable causal risk factors for multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.

Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP): Protocol for a multicentre cluster randomised trial comparing a complex intervention for medication optimization against usual care.

Introduction: Polypharmacy is increasingly common, and associated with undesirable consequences. Polypharmacy management necessitates balancing therapeutic benefits and risks, and varying clinical and patient priorities. Current guidance for managing polypharmacy is not supported by high quality evidence. The aim of the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial is to evaluate the effectiveness of an intervention to optimise medication use for patients with polypharmacy in a general practice setting. Methods: This trial will use a multicentre, open-label, cluster-randomised controlled approach, with two parallel groups. Practices will be randomised to a complex intervention comprising structured medication review (including interprofessional GP/pharmacist treatment planning and patient-facing review) supported by performance feedback, financial incentivisation, clinician training and clinical informatics (intervention), or usual care (control). Patients with polypharmacy and triggering potentially inappropriate prescribing (PIP) indicators will be recruited in each practice using a computerised search of health records. 37 practices will recruit 50 patients, and review them over a 26-week intervention delivery period. The primary outcome is the mean number of PIP indicators triggered per patient at 26 weeks follow-up, determined objectively from coded GP electronic health records. Secondary outcomes will include patient reported outcome measures, and health and care service use. The main intention-to-treat analysis will use linear mixed effects regression to compare number of PIP indicators triggered at 26 weeks post-review between groups, adjusted for baseline (pre-randomisation) values. A nested process evaluation will explore implementation of the intervention in primary care. Ethics and dissemination: The protocol and associated study materials have been approved by the Wales REC 6, NHS Research Ethics Committee (REC reference 19/WA/0090), host institution and Health Research Authority. Research outputs will be published in peer-reviewed journals and relevant conferences, and additionally disseminated to patients and the public, clinicians, commissioners and policy makers. ISRCTN Registration: 90146150 (28/03/2019).

Doctor-patient communication about blood tests: Qualitative interview study in general practice.

Context: Shared decision making is widely advocated, however most research focuses on treatment decisions. Evidence for shared decision-making in relation to diagnostic testing is limited to specific tests such as prostate specific antigen, screening and genetic tests. There is a lack of evidence regarding the relevance of shared decision-making to routine blood tests, despite increasing rates of laboratory testing in primary care. Objectives: To explore shared decision making and communication around routine blood tests in primary care. Study design: Qualitative interview study Setting: UK primary care Population studied: Qualitative interviews were undertaken with patients at two time points: (a) at or soon after their blood test and (b) after they had received their test results. We also undertook interviews with the patients' GPs who requested the tests. This gave us paired data which enabled to us to examine areas of congruence and dissonance between GPs' and patients' expectations, experience and understanding of testing. A total of 80 interviews with 28 patients and 19 doctors were completed, reflecting a range of socioeconomic and demographic characteristics. Interviews were digitally recorded, transcribed and analyzed using thematic analysis using a mixture of inductive and deductive coding and constant comparison. Results: There were no examples of shared decision making identified in any of the interviews, indeed patients were frequently unaware of which blood tests had been done and why. Barriers to a shared understanding of blood testing were identified including the complexity and technical nature of information, a lack of resources for information sharing and a perception that blood tests were low priority for information sharing. Doctors perceived that a paternalistic approach to testing could be justified to protect patients from anxiety. Misunderstanding and a lack of communication around testing and test results led to uncertainty, anxiety and frustration for patients. Conclusions: The results have implications, not just for models of shared decision making, but more fundamentally, informed consent. Shared decision-making for diagnostic testing differs from treatment decisions. Promoting a shared understanding and shared decision-making could help rationalize testing, potentially reducing unnecessary investigations and improving patient-centered care.

Changes in presentations with features potentially indicating cancer in primary care during the COVID-19 pandemic: a retrospective cohort study.

OBJECTIVES: To investigate how the COVID-19 pandemic affected the number of people aged 50+ years presenting to primary care with features that could potentially indicate cancer, and to explore how reporting differed by patient characteristics and in face-to-face vs remote consultations. DESIGN, SETTING AND PARTICIPANTS: A retrospective cohort study of general practitioner (GP), nurse and paramedic primary care consultations in 21 practices in South-West England covering 123 947 patients. The models compared potential cancer indicators reported in April-July 2019 with April-July 2020. MAIN OUTCOME MEASURES: Potential indicators of cancer were identified using code lists for symptoms, signs, test results and diagnoses listed in the National Institute for Health and Care Excellence suspected cancer referral guidance (NG12). RESULTS: During April-July 2019, 17% of registered patients aged 50+ years reported a potential cancer indicator in a consultation with a GP or nurse. During April-July 2020, this reduced to 11% (incidence rate ratio (IRR) 0.64, 95% CI 0.62 to 0.67, p<0.001). Reductions in potential cancer indicators were stable across age group, sex, ethnicity, index of multiple deprivation quintile and shielding status, but less marked in patients with mental health conditions than without (IRR 0.75, 95% CI 0.72 to 0.79, interaction p<0.001). Proportions of GP consultations with potential indicators of cancer reduced between 2019 and 2020 for face-to-face consultations (IRR 0.84, 95% CI 0.76 to 0.92, p<0.001) and increased for remote consultations (IRR 1.17, 95% CI 1.07 to 1.29, p=0.001), although it remained lower in remote consulting than face-to-face in April-July 2020. This difference was greater for nurse/paramedic consultations (face-to-face: IRR 0.61, 95% CI 0.44 to 0.83, p=0.002; remote: IRR 1.60, 95% CI 1.10 to 2.333, p=0.014). CONCLUSION: The number of patients consulting with presentations that could potentially indicate cancer reduced during the first wave of the COVID-19 pandemic. Patients should be encouraged to continue contacting primary care for persistent signs and symptoms, and GPs and nurses should be encouraged to probe patients for further information during remote consulting, in the absence of non-verbal cues.

Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy.

BACKGROUND: Research comparing C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and plasma viscosity (PV) in primary care is lacking. Clinicians often test multiple inflammatory markers, leading to concerns about overuse. AIM: To compare the diagnostic accuracies of CRP, ESR, and PV, and to evaluate whether measuring two inflammatory markers increases accuracy. DESIGN AND SETTING: Prospective cohort study in UK primary care using the Clinical Practice Research Datalink. METHOD: The authors compared diagnostic test performance of inflammatory markers, singly and paired, for relevant disease, defined as any infections, autoimmune conditions, or cancers. For each of the three tests (CRP, ESR, and PV), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under receiver operator curve (AUC) were calculated. RESULTS: Participants comprised 136 961 patients with inflammatory marker testing in 2014; 83 761 (61.2%) had a single inflammatory marker at the index date, and 53 200 (38.8%) had multiple inflammatory markers. For 'any relevant disease', small differences were seen between the three tests; AUC ranged from 0.659 to 0.682. CRP had the highest overall AUC, largely because of marginally superior performance in infection (AUC CRP 0.617, versus ESR 0.589, P<0.001). Adding a second test gave limited improvement in the AUC for relevant disease (CRP 0.682, versus CRP plus ESR 0.688, P<0.001); this is of debatable clinical significance. The NPV for any single inflammatory marker was 94% compared with 94.1% for multiple negative tests. CONCLUSION: Testing multiple inflammatory markers simultaneously does not increase ability to rule out disease and should generally be avoided. CRP has marginally superior diagnostic accuracy for infections, and is equivalent for autoimmune conditions and cancers, so should generally be the first-line test.

Added value and cascade effects of inflammatory marker tests in UK primary care: a cohort study from the Clinical Practice Research Datalink.

BACKGROUND: Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, and plasma viscosity) are commonly used in primary care. Though established for specific diagnostic purposes, there is uncertainty around their utility as a non-specific marker to rule out underlying disease in primary care. AIM: To identify the value of inflammatory marker testing in primary care as a rule-out test, and measure the cascade effects of testing in terms of further blood tests, GP appointments, and referrals. DESIGN AND SETTING: Cohort study of 160 000 patients with inflammatory marker testing in 2014, and 40 000 untested age, sex, and practice-matched controls, using UK primary care data from the Clinical Practice Research Datalink. METHOD: The primary outcome was incidence of relevant disease, including infections, autoimmune conditions, and cancers, among those with raised versus normal inflammatory markers and untested controls. Process outcomes included rates of GP consultations, blood tests, and referrals in the 6 months after testing. RESULTS: The overall incidence of disease following a raised inflammatory marker was 15%: 6.3% infections, 5.6% autoimmune conditions, 3.7% cancers. Inflammatory markers had an overall sensitivity of <50% for the primary outcome, any relevant disease (defined as any infections, autoimmune conditions, or cancers). For 1000 inflammatory marker tests performed, the authors would anticipate 236 false-positives, resulting in an additional 710 GP appointments, 229 phlebotomy appointments, and 24 referrals in the following 6 months. CONCLUSION: Inflammatory markers have poor sensitivity and should not be used as a rule-out test. False-positive results are common and lead to increased rates of follow-on GP consultations, tests, and referrals.

Predictive value of inflammatory markers for cancer diagnosis in primary care: a prospective cohort study using electronic health records.

BACKGROUND: Early identification of cancer in primary care is important and challenging. This study examined the diagnostic utility of inflammatory markers (C-reactive protein, erythrocyte sedimentation rate and plasma viscosity) for cancer diagnosis in primary care. METHODS: Cohort study of 160,000 patients with inflammatory marker testing in 2014, plus 40,000 untested matched controls, using Clinical Practice Research Datalink (CPRD), with Cancer Registry linkage. Primary outcome was one-year cancer incidence. RESULTS: Primary care patients with a raised inflammatory marker have a one-year cancer incidence of 3.53% (95% CI 3.37-3.70), compared to 1.50% (1.43-1.58) in those with normal inflammatory markers, and 0.97% (0.87-1.07) in untested controls. Cancer risk is greater with higher inflammatory marker levels, with older age and in men; risk rises further when a repeat test is abnormal but falls if it normalises. Men over 50 and women over 60 with raised inflammatory markers have a cancer risk which exceeds the 3% NICE threshold for urgent investigation. Sensitivities for cancer were 46.1% for CRP, 43.6% ESR and 49.7% for PV. CONCLUSION: Cancer should be considered in patients with raised inflammatory markers. However, inflammatory markers have a poor sensitivity for cancer and are therefore not useful as 'rule-out' test.

Practice variation in the use of tests in UK primary care: a retrospective analysis of 16 million tests performed over 3.3 million patient years in 2015/16.

BACKGROUND: The UK's National Health Service (NHS) is currently subject to unprecedented financial strain. The identification of unnecessary healthcare resource use has been suggested to reduce spending. However, there is little very research quantifying wasteful test use, despite the £3 billion annual expenditure. Geographical variation has been suggested as one metric in which to quantify inappropriate use. We set out to identify tests ordered from UK primary care that are subject to the greatest between-practice variation in their use. METHODS: We used data from 444 general practices within the Clinical Practice Research Datalink to calculate a coefficient of variation (CoV) for the ordering of 44 specific tests from UK general practices. The coefficient of variation was calculated after adjusting for differences between practice populations. We also determined the tests that had both a higher-than-average CoV and a higher-than-average rate of use. RESULTS: In total, 16,496,218 tests were ordered for 4,078,091 patients over 3,311,050 person-years from April 1, 2015, to March 31, 2016. The tests subject to the greatest variation were drug monitoring 158% (95%CI 153 to 163%), urine microalbumin (52% (95%CI 49.9 to 53.2%)), pelvic CT (51% (95%CI 50 to 53%)) and Pap smear (49% (95%CI 48 to 51%). Seven tests were classified as high variability and high rate (clotting, vitamin D, urine albumin, prostate-specific antigen (PSA), bone profile, urine MCS and C-reactive protein (CRP)). CONCLUSIONS: There are wide variations in the use of common tests, which is unlikely to be explained by clinical indications. Since £3 billion annually are spent on tests, this represents considerable variation in the use of resources and inefficient management in the NHS. Our results can be of value to policy makers, researchers, patients and clinicians as the NHS strives towards identifying overuse and underuse of tests.

Factors associated with consultation rates in general practice in England, 2013-2014: a cross-sectional study.

BACKGROUND: Workload in general practice has risen during the last decade, but the factors associated with this increase are unclear. AIM: To examine factors associated with consultation rates in general practice. DESIGN AND SETTING: A cross-sectional study examining a sample of 304 937 patients registered at 316 English practices between 2013 and 2014, drawn from the Clinical Practice Research Datalink. METHOD: Age, sex, ethnicity, smoking status, and deprivation measures were linked with practice-level data on staffing, rurality, training practice status, and Quality and Outcomes Framework performance. Multilevel analyses of patient consultation rates were conducted. RESULTS: Consultations were grouped into three types: all (GP or nurse), GP, and nurse. Non-smokers consulted less than current smokers (all: rate ratio [RR] = 0.88, 95% CI = 0.87 to 0.89; GP: RR = 0.88, 95% CI = 0.87 to 0.89; nurse: RR = 0.91, 95% CI = 0.90 to 0.92). Consultation rates were higher for those in the most deprived quintile compared with the least deprived quintile (all: RR = 1.18, 95% CI = 1.16 to 1.19; GP: RR = 1.17, 95% CI = 1.15 to 1.19; nurse: RR = 1.13, 95% CI = 1.11 to 1.15). For all three consultation types, consultation rates increased with age and female sex, and varied by ethnicity. Rates in practices with >8 and ≤19 full-time equivalent (FTE) GPs were higher compared with those with ≤2 FTE GPs (all: RR = 1.26, 95% CI = 1.06 to 1.49; GP: RR = 1.36, 95% CI = 1.19 to 1.56). CONCLUSION: The analyses show consistent trends in factors related to consultation rates in general practice across three types of consultation. These data can be used to inform the development of more sophisticated staffing models, and resource allocation formulae.

Patient-level and practice-level factors associated with consultation duration: a cross-sectional analysis of over one million consultations in English primary care.

OBJECTIVES: Consultation duration has previously been shown to be associated with patient, practitioner and practice characteristics. However, previous studies were conducted outside the UK, considered only small numbers of general practitioner (GP) consultations or focused primarily on practitioner-level characteristics. We aimed to determine the patient-level and practice-level factors associated with duration of GP and nurse consultations in UK primary care. DESIGN AND SETTING: Cross-sectional data were obtained from English general practices contributing to the Clinical Practice Research Datalink (CPRD) linked to data on patient deprivation and practice staffing, rurality and Quality and Outcomes Framework (QOF) achievement. PARTICIPANTS: 218 304 patients, from 316 English general practices, consulting from 1 April 2013 to 31 March 2014. ANALYSIS: Multilevel mixed-effects models described the association between consultation duration and patient-level and practice-level factors (patient age, gender, smoking status, ethnic group, deprivation and practice rurality, number of full-time equivalent GPs/nurses, list size, consultation rate, quintile of overall QOF achievement and training status). RESULTS: Mean duration of face-to-face GP consultations was 9.24 min and 5.32 min for telephone consultations. Nurse face-to-face and telephone consultations lasted 9.70 and 5.73 min on average, respectively. Longer GP consultation duration was associated with female patient gender, practice training status and older patient age. Shorter duration was associated with higher deprivation and consultation rate. Longer nurse consultation duration was associated with male patient gender, older patient age and ever smoking; and shorter duration with higher consultation rate. Observed differences in duration were small (eg, GP consultations with female patients compared with male patients were 8 s longer on average). CONCLUSIONS: Small observed differences in consultation duration indicate that patients are treated similarly regardless of background. Increased consultation duration may be beneficial for older or comorbid patients, but the benefits and costs of increased consultation duration require further study.

Identifying possible reasons why female street sex workers have poor drug treatment outcomes: a qualitative study.

AIMS: To explore street sex workers (SSWs) views and experiences of drug treatment, in order to understand why this population tend to experience poor drug treatment outcomes. DESIGN: In-depth interviews. SETTING: Bristol, UK. PARTICIPANTS: 24 current and exited SSWs with current or previous experience of problematic use of heroin and/or crack cocaine. FINDINGS: Participants described how feeling unable to discuss their sex work in drug treatment groups undermined their engagement in the treatment process. They outlined how disclosure of sex work resulted in stigma from male and female service users as well as adverse interactions with male service users. Participants highlighted that non-disclosure meant they could not discuss unresolved trauma issues which were common and which emerged or increased when they reduced their drug use. As trauma experiences had usually involved men as perpetrators participants said it was not appropriate to discuss them in mixed treatment groups. SSWs in recovery described how persistent trauma-related symptoms still affected their lives many years after stopping sex work and drug use. Participants suggested SSW-only services and female staff as essential to effective care and highlighted that recent service changes were resulting in loss of trusted staff and SSW-only treatment services. This was reported to be reducing the likelihood of SSWs engaging in drug services, with the resultant loss of continuity of care and reduced time with staff acting as barriers to an effective therapeutic relationship. CONCLUSIONS: SSWs face many barriers to effective drug treatment. SSW-only treatment groups, continuity of care with treatment staff and contact with female staff, particularly individuals who have had similar lived experience, could improve the extent to which SSWs engage and benefit from drug treatment services. Service engagement and outcomes may also be improved by drug services that include identification and treatment of trauma-related symptoms.

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements. OBJECTIVE: To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE. DESIGN: Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials. SETTING: Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention). PARTICIPANTS: Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE). INTERVENTIONS: NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network. MAIN OUTCOME MEASURES: Efficacy Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness. DATA SOURCES: MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014. REVIEW METHODS: Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models. RESULTS: Apixaban (Eliquis®, Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana®, Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication. CONCLUSIONS: NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE. LIMITATIONS: These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs. FUTURE WORK: Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005324, CRD42013005331 and CRD42013005330. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Telehealth for patients at high risk of cardiovascular disease: pragmatic randomised controlled trial.

OBJECTIVE:  To assess whether non-clinical staff can effectively manage people at high risk of cardiovascular disease using digital health technologies. DESIGN:  Pragmatic, multicentre, randomised controlled trial. SETTING:  42 general practices in three areas of England. PARTICIPANTS:  Between 3 December 2012 and 23 July 2013 we recruited 641 adults aged 40 to 74 years with a 10 year cardiovascular disease risk of 20% or more, no previous cardiovascular event, at least one modifiable risk factor (systolic blood pressure ≥140 mm Hg, body mass index ≥30, current smoker), and access to a telephone, the internet, and email. Participants were individually allocated to intervention (n=325) or control (n=316) groups using automated randomisation stratified by site, minimised by practice and baseline risk score. INTERVENTIONS:  Intervention was the Healthlines service (alongside usual care), comprising regular telephone calls from trained lay health advisors following scripts generated by interactive software. Advisors facilitated self management by supporting participants to use online resources to reduce risk factors, and sought to optimise drug use, improve treatment adherence, and encourage healthier lifestyles. The control group comprised usual care alone. MAIN OUTCOME MEASURES:  The primary outcome was the proportion of participants responding to treatment, defined as maintaining or reducing their cardiovascular risk after 12 months. Outcomes were collected six and 12 months after randomisation and analysed masked. Participants were not masked. RESULTS:  50% (148/295) of participants in the intervention group responded to treatment compared with 43% (124/291) in the control group (adjusted odds ratio 1.3, 95% confidence interval 1.0 to 1.9; number needed to treat=13); a difference possibly due to chance (P=0.08). The intervention was associated with reductions in blood pressure (difference in mean systolic -2.7 mm Hg (95% confidence interval -4.7 to -0.6 mm Hg), mean diastolic -2.8 (-4.0 to -1.6 mm Hg); weight -1.0 kg (-1.8 to -0.3 kg), and body mass index -0.4 ( -0.6 to -0.1) but not cholesterol -0.1 (-0.2 to 0.0), smoking status (adjusted odds ratio 0.4, 0.2 to 1.0), or overall cardiovascular risk as a continuous measure (-0.4, -1.2 to 0.3)). The intervention was associated with improvements in diet, physical activity, drug adherence, and satisfaction with access to care, treatment received, and care coordination. One serious related adverse event occurred, when a participant was admitted to hospital with low blood pressure. CONCLUSIONS:  This evidence based telehealth approach was associated with small clinical benefits for a minority of people with high cardiovascular risk, and there was no overall improvement in average risk. The Healthlines service was, however, associated with improvements in some risk behaviours, and in perceptions of support and access to care.Trial registration Current Controlled Trials ISRCTN 27508731.

Clinical workload in UK primary care: a retrospective analysis of 100 million consultations in England, 2007-14.

BACKGROUND: Primary care is the main source of health care in many health systems, including the UK National Health Service (NHS), but few objective data exist for the volume and nature of primary care activity. With rising concerns that NHS primary care workload has increased substantially, we aimed to assess the direct clinical workload of general practitioners (GPs) and practice nurses in primary care in the UK. METHODS: We did a retrospective analysis of GP and nurse consultations of non-temporary patients registered at 398 English general practices between April, 2007, and March, 2014. We used data from electronic health records routinely entered in the Clinical Practice Research Datalink, and linked CPRD data to national datasets. Trends in age-standardised and sex-standardised consultation rates were modelled with joinpoint regression analysis. FINDINGS: The dataset comprised 101,818,352 consultations and 20,626,297 person-years of observation. The crude annual consultation rate per person increased by 10·51%, from 4·67 in 2007-08, to 5·16 in 2013-14. Consultation rates were highest in infants (age 0-4 years) and elderly people (≥85 years), and were higher for female patients than for male patients of all ages. The greatest increases in age-standardised and sex-standardised rates were in GPs, with a rise of 12·36% per 10,000 person-years, compared with 0·9% for practice nurses. GP telephone consultation rates doubled, compared with a 5·20% rise in surgery consultations, which accounted for 90% of all consultations. The mean duration of GP surgery consultations increased by 6·7%, from 8·65 min (95% CI 8·64-8·65) to 9·22 min (9·22-9·23), and overall workload increased by 16%. INTERPRETATION: Our findings show a substantial increase in practice consultation rates, average consultation duration, and total patient-facing clinical workload in English general practice. These results suggest that English primary care as currently delivered could be reaching saturation point. Notably, our data only explore direct clinical workload and not indirect activities and professional duties, which have probably also increased. This and additional research questions, including the outcomes of workload changes on other sectors of health care, need urgent answers for primary care provision internationally. FUNDING: Department of Health Policy Research Programme.

Improving the management of multimorbidity in general practice: protocol of a cluster randomised controlled trial (The 3D Study).

INTRODUCTION: An increasing number of people are living with multimorbidity. The evidence base for how best to manage these patients is weak. Current clinical guidelines generally focus on single conditions, which may not reflect the needs of patients with multimorbidity. The aim of the 3D study is to develop, implement and evaluate an intervention to improve the management of patients with multimorbidity in general practice. METHODS AND ANALYSIS: This is a pragmatic two-arm cluster randomised controlled trial. 32 general practices around Bristol, Greater Manchester and Glasgow will be randomised to receive either the '3D intervention' or usual care. 3D is a complex intervention including components affecting practice organisation, the conduct of patient reviews, integration with secondary care and measures to promote change in practice organisation. Changes include improving continuity of care and replacing reviews of each disease with patient-centred reviews with a focus on patients' quality of life, mental health and polypharmacy. We aim to recruit 1383 patients who have 3 or more chronic conditions. This provides 90% power at 5% significance level to detect an effect size of 0.27 SDs in the primary outcome, which is health-related quality of life at 15 months using the EQ-5D-5L. Secondary outcome measures assess patient centredness, illness burden and treatment burden. The primary analysis will be a multilevel regression model adjusted for baseline, stratification/minimisation, clustering and important co-variables. Nested process evaluation will assess implementation, mechanisms of effectiveness and interaction of the intervention with local context. Economic analysis of cost-consequences and cost-effectiveness will be based on quality-adjusted life years. ETHICS AND DISSEMINATION: This study has approval from South-West (Frenchay) National Health Service (NHS) Research Ethics Committee (14/SW/0011). Findings will be disseminated via final report, peer-reviewed publications and guidance to healthcare professionals, commissioners and policymakers. TRIAL REGISTRATION NUMBER: ISRCTN06180958; Pre-results.

Patient-doctor continuity and diagnosis of cancer: electronic medical records study in general practice.

BACKGROUND: Continuity of care may affect the diagnostic process in cancer but there is little research. AIM: To estimate associations between patient-doctor continuity and time to diagnosis and referral of three common cancers. DESIGN AND SETTING: Retrospective cohort study in general practices in England. METHOD: This study used data from the General Practice Research Database for patients aged ≥40 years with a diagnosis of breast, colorectal, or lung cancer. Relevant cancer symptoms or signs were identified up to 12 months before diagnosis. Patient-doctor continuity (fraction-of-care index adjusted for number of consultations) was calculated up to 24 months before diagnosis. Time ratios (TRs) were estimated using accelerated failure time regression models. RESULTS: Patient-doctor continuity in the 24 months before diagnosis was associated with a slightly later diagnosis of colorectal (time ratio [TR] 1.01, 95% confidence interval [CI] =1.01 to 1.02) but not breast (TR = 1.00, 0.99 to 1.01) or lung cancer (TR = 1.00, 0.99 to 1.00). Secondary analyses suggested that for colorectal and lung cancer, continuity of doctor before the index consultation was associated with a later diagnosis but continuity after the index consultation was associated with an earlier diagnosis, with no such effects for breast cancer. For all three cancers, most of the delay to diagnosis occurred after referral. CONCLUSION: Any effect for patient-doctor continuity appears to be small. Future studies should compare investigations, referrals, and diagnoses in patients with and without cancer who present with possible cancer symptoms or signs; and focus on 'difficult to diagnose' types of cancer.

Emergency respiratory admissions: influence of practice, population and hospital factors.

OBJECTIVE: To determine the influence of population, hospital and general practice characteristics on practice admission rates for asthma and chronic obstructive pulmonary disease (COPD) in England. METHODS: Cross sectional study using Hospital Episode Statistics (HES), routine population data and primary care data. Admissions for all general practices in England during 2005-06, adjusted for age and sex composition of practice population. Univariable analysis of population, practice and hospital care provision variables, including prevalence and quality data. Significant factors included in multiple regression Poisson model. RESULTS: Admissions from 8169 practices were included. Risk of admission for each condition increased with deprivation, prevalence and smoking. Admission rates were higher in urban than rural practices. Hospital bed availability and distance to the nearest emergency department were also significantly associated with risk of admission. The associations with practice factors including practice size and quality markers varied across conditions. CONCLUSIONS: Practice population, geographic and hospital supply factors are consistently associated with asthma and COPD admissions. Higher smoking rates among such patients in a practice are associated with higher admission rates. There is little evidence from this study that other modifiable general practice factors are important in influencing admission rates.

Vulvovaginal-swab or first-catch urine specimen to detect Chlamydia trachomatis in women in a community setting?

Screening for chlamydia in women is widely recommended. We evaluated the performance of two nucleic acid amplification tests for detecting Chlamydia trachomatis in self-collected vulvovaginal-swab and first-catch urine specimens from women in a community setting and a strategy for optimizing the sensitivity of an amplified enzyme immunoassay on vulvovaginal-swab specimens. We tested 2,745 paired vulvovaginal-swab and urine specimens by PCR (Roche Cobas) or strand displacement amplification (SDA; Becton Dickinson). There were 146 women infected with chlamydia. The assays detected 97.3% (95% confidence interval [CI], 93.1 to 99.2%) of infected patients with vulvovaginal-swab specimens and 91.8% (86.1 to 95.7%) with urine specimens. We tested 2,749 vulvovaginal-swab specimens with both a nucleic acid amplification test and a polymer conjugate-enhanced enzyme immunoassay with negative-gray-zone testing. The relative sensitivities obtained after retesting specimens in the negative gray zone were 74.3% (95% CI, 62.8 to 83.8%) with PCR and 58.3% (95% CI, 46.1 to 69.8%) with SDA. In community settings, both vulvovaginal-swab and first-catch urine specimens from women are suitable substrates for nucleic acid amplification tests, but enzyme immunoassays, even after negative-gray-zone testing, should not be used in screening programs.

Opportunistic and systematic screening for chlamydia: a study of consultations by young adults in general practice.

BACKGROUND: Opportunistic screening for genital chlamydia infection is being introduced in England, but evidence for the effectiveness of this approach is lacking. There are insufficient data about young peoples' use of primary care services to determine the potential coverage of opportunistic screening in comparison with a systematic population-based approach. AIM: To estimate use of primary care services by young men and women; to compare potential coverage of opportunistic chlamydia screening with a systematic postal approach. DESIGN OF STUDY: Population based cross-sectional study. SETTING: Twenty-seven general practices around Bristol and Birmingham. METHOD: A random sample of patients aged 16-24 years were posted a chlamydia screening pack. We collected details of face-to-face consultations from general practice records. Survival and person-time methods were used to estimate the cumulative probability of attending general practice in 1 year and the coverage achieved by opportunistic and systematic postal chlamydia screening. RESULTS: Of 12 973 eligible patients, an estimated 60.4% (95% confidence interval [CI] = 58.3 to 62.5%) of men and 75.3% (73.7 to 76.9%) of women aged 16-24 years attended their practice at least once in a 1-year period. During this period, an estimated 21.3% of patients would not attend their general practice but would be reached by postal screening, 9.2% would not receive a postal invitation but would attend their practice, and 11.8% would be missed by both methods. CONCLUSIONS: Opportunistic and population-based approaches to chlamydia screening would both fail to contact a substantial minority of the target group, if used alone. A pragmatic approach combining both strategies might achieve higher coverage.

Enhanced enzyme immunoassay with negative-gray-zone testing compared to a single nucleic Acid amplification technique for community-based chlamydial screening of men.

We evaluated a low-cost diagnostic strategy for detecting Chlamydia trachomatis in a low-prevalence population. We used an amplified enzyme immunoassay (EIA) with a reduced-cutoff "negative gray zone" to identify reactive specimens for confirmation by a nucleic acid amplification test. As part of the Chlamydia Screening Studies project, men provided a first-pass urine specimen, which they returned by post for testing. We tested 1,003 specimens by IDEIA PCE EIA (Dako) and Cobas PCR (Roche). There were 32 (3.2%) true positive specimens according to a combined standard using an algorithm requiring concordant results from at least two independent tests. All of these were positive by Cobas PCR and 24 were confirmed to be positive by PCE EIA, including 2 that gave results in the negative gray zone. There were 971 true negative specimens, 2 of which were positive by Cobas PCR and 19 of which were initially inhibitory for PCR. The relative sensitivity, specificity, positive predictive value, and negative predictive value of PCE EIA with PCR confirmation were 75.0% (95% confidence interval [CI], 56.6 to 88.5%), 100% (95% CI, 99.7 to 100%), 100% (95% CI, 88.3 to 100%), and 99.2% (95% CI, 98.4 to 99.6%), respectively. The corresponding values for Cobas PCR were 100% (95% CI, 89.1 to 100%), 99.8% (95% CI, 99.3 to 100%), 94.1% (95% CI, 76.9 to 98.2%), and 100% (95% CI, 99.6 to 100%), respectively, with 1.9% (19/1003) of the samples being initially indeterminate. When the prevalence of C. trachomatis is low, the use of an amplified EIA on urine specimens, with confirmation of results in the negative gray zone by use of a nucleic acid amplification technique, is not suitable for screening asymptomatic men. In addition, positive nucleic acid amplification test results should be confirmed and an inhibition control should be used.