Kimberley Horspool

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.

Being Human: A Qualitative Interview Study Exploring Why a Telehealth Intervention for Management of Chronic Conditions Had a Modest Effect

Background Evidence of benefit for telehealth for chronic conditions is mixed. Two linked randomized controlled trials tested the Healthlines Service for 2 chronic conditions: depression and high risk of cardiovascular disease (CVD). This new telehealth service consisted of regular telephone calls from nonclinical, trained health advisers who followed standardized scripts generated by interactive software. Advisors facilitated self-management by supporting participants to use Web-based resources and helped to optimize medication, improve treatment adherence, and encourage healthier lifestyles. Participants were recruited from primary care. The trials identified moderate (for depression) or partial (for CVD risk) effectiveness of the Healthlines Service. Objective An embedded qualitative study was undertaken to help explain the results of the 2 trials by exploring mechanisms of action, context, and implementation of the intervention. Methods Qualitative interview study of 21 staff providing usual health care or involved in the intervention and 24 patients receiving the intervention. Results Interviewees described improved outcomes in some patients, which they attributed to the intervention, describing how components of the model on which the intervention was based helped to achieve benefits. Implementation of the intervention occurred largely as planned. However, contextual issues in patients’ lives and some problems with implementation may have reduced the size of effect of the intervention. For depression, patients’ lives and preferences affected engagement with the intervention: these largely working-age patients had busy and complex lives, which affected their ability to engage, and some patients preferred a therapist-based approach to the cognitive behavioral therapy on offer. For CVD risk, patients’ motivations adversely affected the intervention whereby some patients joined the trial for general health improvement or from altruism, rather than motivation to make lifestyle changes to address their specific risk factors. Implementation was not optimal in the early part of the CVD risk trial owing to technical difficulties and the need to adapt the intervention for use in practice. For both conditions, enthusiastic and motivated staff offering continuity of intervention delivery tailored to individual patients’ needs were identified as important for patient engagement with telehealth; this was not delivered consistently, particularly in the early stages of the trials. Finally, there was a lack of active engagement from primary care. Conclusions The conceptual model was supported and could be used to develop further telehealth interventions for chronic conditions. It may be possible to increase the effectiveness of this, and similar interventions, by attending to the human as well as the technical aspects of telehealth: offering it to patients actively wanting the intervention, ensuring continuity of delivery by enthusiastic and motivated staff, and encouraging active engagement from primary care staff.

Implementing street triage: a qualitative study of collaboration between police and mental health services

BackgroundStreet Triage is a collaborative service between mental health workers and police which aims to improve the emergency response to individuals experiencing crisis, but peer reviewed evidence of the effectiveness of these services is limited. We examined the design and potential impact of two services, along with factors that hindered and facilitated the implementation of the services.MethodsWe conducted 14 semi-structured interviews with mental health and police stakeholders with experience of a Street Triage service in two locations of the UK. Framework analysis identified themes related to key aspects of the Street Triage service, perceived benefits of Street Triage, and ways in which the service could be developed in the future.ResultsStakeholders endorsed the Street Triage services which utilised different operating models. These models had several components including a joint response vehicle or a mental health worker in a police control room. Operating models were developed with consideration of the local geographical and population density. The ability to make referrals to the existing mental health service was perceived as key to the success of the service yet there was evidence to suggest Street Triage had the potential to increase pressure on already stretched mental health and police services. Identifying staff with skills and experience for Street Triage work was important, and their joint response resulted in shared decision making which was less risk averse for the police and regarded as in the interest of patient care by mental health professionals. Collaboration during Street Triage improved the understanding of roles and responsibilities in the ‘other’ agency and led to the development of local information sharing agreements. Views about the future direction of the service focused on expansion of Street Triage to address other shared priorities such as frequent users of police and mental health services, and a reduction in the police involvement in crisis response.ConclusionThe Street Triage service received strong support from stakeholders involved in it. Referral to existing health services is a key function of Street Triage, and its impact on referral behaviour requires rigorous evaluation. Street Triage may result in improvement to collaborative working but competing demands for resources within mental health and police services presented challenges for implementation.

The DiPEP (Diagnosis of PE in Pregnancy) biomarker study: An observational cohort study augmented with additional cases to determine the diagnostic utility of biomarkers for suspected venous thromboembolism during pregnancy and puerperium

This study aimed to estimate the diagnostic utility of biomarkers for suspected venous thromboembolism (VTE) in pregnancy and the puerperium. Research nurses/midwives collected blood samples from 310 pregnant/postpartum women with suspected pulmonary emboli (PE) and 18 with diagnosed deep vein thrombosis (DVT). VTE was diagnosed using imaging, treatment and adverse outcome data. Primary analysis was limited to women with conclusive imaging (36 with VTE, 247 without). The area under the curve (AUC) for each biomarker was: activated partial thromboplastin time 0·669 (95% confidence interval 0·570–0·768), B‐type natriuretic peptide 0·549 (0·453–0·645), C‐reactive protein 0·542 (0·445–0·639), Clauss fibrinogen 0·589 (0·476–0·701), D‐Dimer (by enzyme‐linked immunosorbent assay) 0·668 (0·561–0·776), near‐patient D‐Dimer 0·651 (0·545–0·758), mid‐regional pro‐atrial natriuretic peptide 0·524 (0·418–0·630), prothrombin fragment 1 + 2 0·562 (0·462–0·661), plasmin‐antiplasmin complexes 0·639 (0·536–0·742), prothombin time 0·613 (0·508–0·718), thrombin generation lag time 0·702 (0·598–0·806), thrombin generation endogenous potential 0·559 (0·437–0·681), thrombin generation peak 0·596 (0·478–0·715), thrombin generation time to peak 0·655 (0·541–0·769), soluble tissue factor 0·531 (0·424–0·638) and serum troponin 0·597 (0·499–0·695). No diagnostically useful threshold for diagnosing or ruling out VTE was identified. In pregnancy and the puerperium, conventional and candidate biomarkers have no utility either for their negative or positive predictive value in the diagnosis of VTE.

The DiPEP study: an observational study of the diagnostic accuracy of clinical assessment, D-dimer and chest x-ray for suspected pulmonary embolism in pregnancy and postpartum.

To identify clinical features associated with pulmonary embolism (PE) diagnosis and determine the accuracy of decision rules and D‐dimer for diagnosing suspected PE in pregnant/postpartum women

Selecting pregnant or postpartum women with suspected pulmonary embolism for diagnostic imaging: the DiPEP diagnostic study with decision-analysis modelling

BACKGROUND Pulmonary embolism (PE) is a leading cause of death in pregnancy and post partum, but the symptoms of PE are common in normal pregnancy. Simple diagnostic tests are needed to select women for diagnostic imaging. OBJECTIVE To estimate the accuracy, effectiveness and cost-effectiveness of clinical features, decision rules and biomarkers for selecting pregnant or postpartum women with a suspected PE for imaging. DESIGN An expert consensus study to develop new clinical decision rules, a case-control study of women with a diagnosed PE or a suspected PE, a biomarker study of women with a suspected PE or diagnosed deep-vein thrombosis (DVT) and decision-analysis modelling. SETTING Emergency departments and consultant-led maternity units. PARTICIPANTS Pregnant/postpartum women with a diagnosed PE from any hospital reporting to the UK Obstetric Surveillance System research platform and pregnant/postpartum women with a suspected PE or diagnosed DVT at 11 prospectively recruiting sites. INTERVENTIONS Clinical features, decision rules and biomarkers. MAIN OUTCOME MEASURES Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, quality-adjusted life-years (QALYs) and health-care costs. RESULTS The primary analysis involved 181 women with PE and 259 women without PE in the case-control study and 18 women with DVT, 18 with PE and 247 women without either in the biomarker study. Most clinical features showed no association with PE. The AUROC curves for the clinical decision rules were as follows: primary consensus, 0.626; sensitive consensus, 0.620; specific consensus, 0.589; PE rule-out criteria, 0.621; simplified Geneva score, 0.579; Wellss PE criteria (permissive), 0.577; and Wellss PE criteria (strict), 0.732. The sensitivities and specificities of the D-dimer measurement were 88.4% and 8.8%, respectively, using a standard threshold, and 69.8% and 32.8%, respectively, using a pregnancy-specific threshold. Previous venous thromboembolism, long-haul travel, multiple pregnancy, oxygen saturation, recent surgery, temperature and PE-related chest radiograph abnormality were predictors of PE on multivariable analysis. We were unable to derive a rule through multivariable analysis or recursive partitioning with adequate accuracy. The AUROC curves for the biomarkers were as follows: activated partial thromboplastin time - 0.669, B-type natriuretic peptide - 0.549, C-reactive protein - 0.542, Clauss fibrinogen - 0.589, enzyme-linked immunosorbent assay D-dimer - 0.668, Innovance D-dimer (Siemens Healthcare Diagnostics Products GmbH, distributed by Sysmex UK Ltd, Milton Keynes, UK) - 0.651, mid-regional pro-atrial natriuretic peptide (MRproANP) - 0.524, prothrombin fragment 1 + 2 - 0.562, plasmin-antiplasmin - 0.639, Prothombin time - 0.613, thrombin generation lag time - 0.702, thrombin generation endogenous potential - 0.559, thrombin generation peak - 0.596, thrombin generation time to peak - 0.655, tissue factor - 0.531 and troponin - 0.597. The repeat analysis excluding women who had received anticoagulation was limited by the small number of women with PE (n = 4). The health economic analysis showed that a strategy of scanning all women with a suspected PE accrued more QALYs and incurred fewer costs than any selective strategy based on a clinical decision rule and was therefore the dominant strategy. LIMITATIONS The findings apply specifically to the diagnostic assessment of women with a suspected PE in secondary care. CONCLUSIONS Clinical features, decision rules and biomarkers do not accurately, effectively or cost-effectively select pregnant or postpartum women with a suspected PE for diagnostic imaging. FUTURE WORK New diagnostic technologies need to be developed to detect PE in pregnancy. TRIAL REGISTRATION Current Controlled Trials ISRCTN21245595. FUNDING DETAILS This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 47. See the NIHR Journals Library website for further project information.

19 Accuracy of biomarkers for venous thromboembolism in pregnancy: the diagnosis of pulmonary embolism in pregnancy (DiPEP) biomarker study

Objective To estimate the accuracy of biomarkers for venous thromboembolism (VTE) in pregnant and postpartum women with suspected pulmonary embolism (PE). Design Observational cohort study augmented with additional cases with VTE. Setting Emergency departments and maternity units at eleven prospectively recruiting sites. Participants Pregnant or postpartum women presenting with suspected PE or diagnosed DVT. Interventions Research nurses/midwives collected a blood sample from women with suspected PE or diagnosed DVT and data relating to diagnostic imaging, treatment and adverse outcomes. Blood samples were centrifuged, stored and then transported to Guy’s St Thomas Trust for analysis. Main outcome measures Women were classified as having or not having VTE on the basis of diagnostic imaging, treatment and subsequent adverse outcomes. Primary analysis was limited to women with conclusive diagnostic imaging. Secondary analyses included women with clinically diagnosed or ruled out PE. Results Usable blood samples were taken from 18 women with diagnosed DVT and 310 women with suspected PE, of whom 18 had PE confirmed by imaging and 247 had PE ruled out after imaging and were included in the primary analysis. Mean biomarker levels only significantly differed between women with and without PE for Clauss Fibrinogen (p=0.007), ELISA D-Dimer (p=0.001), Innovance D-Dimer (p=0.004), Thrombin Generation Lag Time (p<0.001), Thrombin Generation Time to Peak (p=0.001) and Plasmin Antiplasmin (p=0.004). The AUC (95% CI) for each biomarker was APTT 0.669 (0.570 to 0.768), BNP 0.549 (0.453 to 0.645), C-Reactive Protein 0.542 (0.445 to 0.639), Clauss Fibrinogen 0.589 (0.476 to 0.701), ELISA D-Dimer 0.668 (0.561 to 0.776), Innovance D-Dimer 0.651 (0.545 to 0.758), MRproANP 0.524 (0.418 to 0.630), PF1 +2 00.562 (0.462 to 0.661), Plasmin-antiplasmin 0.639 (0.536 to 0.742), Prothombin Time 0.613 (0.508 to 0.718), Thrombin Generation Lag Time 0.702 (0.598 to 0.806), Thrombin Generation Endogenous Potential 0.559 (0.437 to 0.681), Thrombin Generation Peak 0.596 (0.478 to 0.715), Thrombin Generation Time to Peak 0.655 (0.541 to 0.769), Tissue Factor 0.531 (0.424 to 0.638) and Troponin 0.597 (0.499 to 0.695). ROC analysis showed that only thrombin generation lag time had any potential to rule out PE with sufficient sensitivity while achieving meaningful specificity, with sensitivity of 97% and specificity of 25% at the threshold that optimised sensitivity. Repeat analysis excluding women who had received anticoagulation was limited by the small number (n=4) who had PE. Conclusion Currently available biomarkers show little potential for aiding the diagnosis of suspected PE in pregnancy and postpartum. Figure 1 Figure 2 Figure 3

27 The DiPEP (Diagnosis of PE in Pregnancy) study: can clinical assessment, d-dimer or chest x-ray be used to select pregnant or postpartum women with suspected PE for diagnostic imaging?

Objective To determine whether clinical features (in the form of a clinical decision rule) or d-dimer can be used to select pregnant or postpartum women with suspected PE for diagnostic imaging. Design Observational cohort study augmented with additional cases. Setting Consultant-led maternity units participating in the UK Obstetric Surveillance System (UKOSS) and emergency departments and maternity units at eleven prospectively recruiting sites. Participants 198 pregnant or postpartum women with diagnosed PE identified through UKOSS and 324 pregnant or postpartum women with suspected PE from prospectively recruiting sites. Interventions Data were collected relating to clinical features, elements of clinical decision rules, d-dimer measurements, diagnostic imaging, treatment for PE and adverse outcomes. Main outcome measures Women were classified as having or not having PE on the basis of diagnostic imaging, treatment and subsequent adverse outcomes. Primary analysis was limited to women with conclusive diagnostic imaging. Secondary analyses included women with clinically diagnosed or ruled out PE. Results The primary analysis included 181 women with PE and 259 without. Most clinical features showed no association with PE. The only exceptions were number of previous pregnancies over 24 weeks (p=0.017), no varicose veins (p=0.045), no recent long haul travel (p=0.006), recent surgery including caesarean section (p=0.001), increased temperature (p=0.003), low oxygen saturation (p<0.001), PE-related chest x-ray abnormality (p=0.01) and other chest x-ray abnormality (p=0.001). Clinical decision rules had areas under the receiver-operator characteristic curve ranging from 0.577 to 0.732. No clinically useful threshold for decision-making was identified for any rule. The sensitivities and specificities of d-dimer were 88.4% and 8.8% using the standard laboratory threshold and 69.8% and 32.8% using a pregnancy-specific threshold. Conclusions Clinical decision rules, d-dimer and chest x-ray should not be used to select pregnant or postpartum women with suspected PE for diagnostic imaging.