Joe Kai

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial.

BACKGROUND Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. OBJECTIVES To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of womens perspectives on treatment. DESIGN A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. SETTING Women who presented in primary care. PARTICIPANTS A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. INTERVENTIONS LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. OUTCOME MEASURES The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. RESULTS The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that womens experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. CONCLUSIONS The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in womens assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. TRIAL REGISTRATION Current Controlled Trials ISRCTN86566246. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information.

Networks for research in primary health care

Editorial by Green and Dovey The evolution of the academic discipline of primary care throughout the world is resulting in more primary care practitioners taking part in research. Primary care has a generalist nature,1 and several research approaches are therefore required to understand the complex interplay between medical and psychosocial factors in the discipline.2 Collaboration is needed between primary care professionals (general practitioners, nurses, health visitors, etc) and a variety of academics with a breadth of expertise.3 In this article we give an overview of primary care research networks. These networks were established as a way to enable diverse practitioners to engage in research. We start by outlining what these networks are and what they do, using examples from the United Kingdom and elsewhere. We then go on to discuss the lessons learnt from UK experience and suggest how these lessons can be built on through better integration with emerging primary care structures. Primary care research networks began to develop in the United Kingdom in the 1960s (box), but until recently there has been little political recognition of their importance. Primary care research was specifically included in the NHS research and development strategy for England and Wales for the first time in 1997. Before then there was no acknowledgement in government of the need to address the low research capacity of primary care. In 1997, the research and development in primary care national working group recommended an investment in care research networks to “achieve an evidence based culture in primary care.”4 #### Summary box Research networks have been established throughout the United Kingdom and internationally to develop research and education in primary health care and implement research evidence These networks can enable multidisciplinary coalitions of researchers to address diverse research agendas Networks may use different organisational approaches including bottom …

Understanding influences on smoking in Bangladeshi and Pakistani adults: community based, qualitative study

Abstract Objective: To gain detailed understanding of influences on smoking behaviour in Bangladeshi and Pakistani communities in the United Kingdom to inform the development of effective and culturally acceptable smoking cessation interventions. Design: Qualitative study using community participatory methods, purposeful sampling, one to one interviews, focus groups, and a grounded approach to data generation and analysis. Setting: Newcastle upon Tyne, during 2000-2. Participants: 87 men and 54 women aged 18–80 years, smokers and non-smokers, from the Bangladeshi and Pakistani communities. Results: Four dominant, highly inter-related themes had an important influence on smoking attitudes and behaviour: gender, age, religion, and tradition. Smoking was a widely accepted practice in Pakistani, and particularly Bangladeshi, men and was associated with socialising, sharing, and male identity. Among women, smoking was associated with stigma and shame. Smoking in women is often hidden from family members. Peer pressure was an important influence on smoking behaviour in younger people, who tended to hide their smoking from elders. There were varied and conflicting interpretations of how acceptable smoking is within the Muslim religion. Tradition, culture, and the family played an important role in nurturing and cultivating norms and values around smoking. Conclusion: Although there are some culturally specific contexts for smoking behaviour in Bangladeshi and Pakistani adults—notably the influence of gender and religion—there are also strong similarities with white people, particularly among younger adults. Themes identified should help to inform the development and appropriate targeting of smoking cessation interventions. What is already known on this topic Smoking is common among Bangladeshi and Pakistani men in Britain but rare among the women Smoking is particularly common in Bangladeshi men Socioeconomic status is thought to influence smoking uptake in Bangladeshi men Influences on smoking in South Asians in Britain are poorly understood What this study adds Smoking among Pakistani and Bangladeshi men is strongly seen as socially acceptable—a “normal” part of being a man Smoking in Bangladeshi men is more deeply socially ingrained than in Pakistanis, contributing to group cohesion and identity Smoking in Bangladeshi and Pakistani women is associated with a strong sense of cultural taboo, stigma, and non-acceptance Islam forbids addiction and intoxicants, but opinions differ on whether the Muslim religion allows smoking Culturally sensitive smoking cessation interventions for Bangladeshis and Pakistanis are needed

Effect of Adding Systematic Family History Enquiry to Cardiovascular Disease Risk Assessment in Primary Care : A Matched-Pair, Cluster Randomized Trial

BACKGROUND Evidence of the value of systematically collecting family history in primary care is limited. OBJECTIVE To evaluate the feasibility of systematically collecting family history of coronary heart disease in primary care and the effect of incorporating these data into cardiovascular risk assessment. DESIGN Pragmatic, matched-pair, cluster randomized, controlled trial. (International Standardized Randomized Controlled Trial Number Register: ISRCTN 17943542). SETTING 24 family practices in the United Kingdom. PARTICIPANTS 748 persons aged 30 to 65 years with no previously diagnosed cardiovascular risk, seen between July 2007 and March 2009. INTERVENTION Participants in control practices had the usual Framingham-based cardiovascular risk assessment with and without use of existing family history information in their medical records. Participants in intervention practices also completed a questionnaire to systematically collect their family history. All participants were informed of their risk status. Participants with high cardiovascular risk were invited for a consultation. MEASUREMENTS The primary outcome was the proportion of participants with high cardiovascular risk (10-year risk ≥ 20%). Other measures included questionnaire completion rate and anxiety score. RESULTS 98% of participants completed the family history questionnaire. The mean increase in proportion of participants classified as having high cardiovascular risk was 4.8 percentage points in the intervention practices, compared with 0.3 percentage point in control practices when family history from patient records was incorporated. The 4.5-percentage point difference between groups (95% CI, 1.7 to 7.2 percentage points) remained significant after adjustment for participant and practice characteristics (P = 0.007). Anxiety scores were similar between groups. LIMITATIONS Relatively few participants were from ethnic minority or less-educated groups. The potential to explore behavioral change and clinical outcomes was limited. Many data were missing for anxiety scores. CONCLUSION Systematically collecting family history increases the proportion of persons identified as having high cardiovascular risk for further targeted prevention and seems to have little or no effect on anxiety. PRIMARY FUNDING SOURCE Genetics Health Services Research program of the United Kingdom Department of Health.

Levonorgestrel Intrauterine System versus Medical Therapy for Menorrhagia

BACKGROUND Menorrhagia is a common problem, yet evidence to inform decisions about therapy is limited. In a pragmatic, multicenter, randomized trial, we compared the levonorgestrel-releasing intrauterine system (levonorgestrel-IUS) with usual medical treatment in women with menorrhagia who presented to their primary care providers. METHODS We randomly assigned 571 women with menorrhagia to treatment with levonorgestrel-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined estrogen-progestogen, or progesterone alone). The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) (ranging from 0 to 100, with lower scores indicating greater severity), assessed over a 2-year period. Secondary outcomes included general quality-of-life and sexual-activity scores and surgical intervention. RESULTS MMAS scores improved from baseline to 6 months in both the levonorgestrel-IUS group and the usual-treatment group (mean increase, 32.7 and 21.4 points, respectively; P<0.001 for both comparisons). The improvements were maintained over a 2-year period but were significantly greater in the levonorgestrel-IUS group than in the usual-treatment group (mean between-group difference, 13.4 points; 95% confidence interval, 9.9 to 16.9; P<0.001). Improvements in all MMAS domains (practical difficulties, social life, family life, work and daily routine, psychological well-being, and physical health) were significantly greater in the levonorgestrel-IUS group than in the usual-treatment group, and this was also true for seven of the eight quality-of-life domains. At 2 years, more of the women were still using the levonorgestrel-IUS than were undergoing the usual medical treatment (64% vs. 38%, P<0.001). There were no significant between-group differences in the rates of surgical intervention or sexual-activity scores. There were no significant differences in serious adverse events between groups. CONCLUSIONS In women with menorrhagia who presented to primary care providers, the levonorgestrel-IUS was more effective than usual medical treatment in reducing the effect of heavy menstrual bleeding on quality of life. (Funded by the National Institute of Health Research Health Technology Assessment Programme; ECLIPSE Controlled-Trials.com number, ISRCTN86566246.).

Learning to value ethnic diversity - what, why and how?

 Learning to value ethnic diversity is the appreciation of how variations in culture and background may affect health care. It involves acknowledging and responding to an individual’s culture in its broadest sense. This requires learning the skills to negotiate effective communication, a heightened awareness of one’s own attitudes, and sensitivity, to issues of stereotyping, prejudice and racism. This paper aims to contribute to debate about some of the key issues that learning to value ethnic diversity creates.

Comparison of reporting of ethnicity in US and European randomised controlled trials

Increasing evidence shows that different ethnic groups respond differently to educational, psychosocial, and pharmacological interventions. If diverse communities are to benefit from the implementation of appropriately derived evidence then it is imperative that the ethnic diversity of populations under study are reflected in clinical trials. In the United States, since 1993, the National Institutes of Health have instituted policy insisting that minority groups are represented in study samples unless there is a compelling reason not to do so.1 However, no comparable legislation exists in Europe. We sought to compare reporting of ethnicity in published reports of US and European randomised controlled studies. We searched Medline for reports of trials published in 2002 using the Cochrane optimal search strategy.2 We downloaded titles and abstracts of study reports into the reference manager database and randomly …

Quitting smoking and experience of smoking cessation interventions among UK Bangladeshi and Pakistani adults: the views of community members and health professionals.

Objective: To explore attitudes to quitting smoking and experience of smoking cessation among Bangladeshi and Pakistani ethnic minority communities. Design: Qualitative study using community participatory methods, purposeful sampling, interviews and focus groups, and a grounded approach to data generation and analysis. Setting: Newcastle upon Tyne, UK, 2000–2002. Participants: 53 men and 20 women aged 18–80 years, including smokers, former smokers, and smokers’ relatives, from the Bangladeshi and Pakistani communities; and eight health professionals working with these communities. Results: Motivation to quit was high but most attempts had failed. “Willpower” was the most common approach to quitting. For some, the holy month of Ramadan was used as an incentive, however few had been successful in quitting. Perceived barriers to success included being tempted by others, everyday stresses, and withdrawal symptoms. Few participants had sought advice from health services, or received cessation aids, such as nicotine replacement therapy (NRT) or buproprion. Family doctors were not viewed as accessible sources of advice on quitting. Health professionals and community members identified common barriers to accessing effective smoking cessation, including: language, religion and culture; negative attitudes to services; and lack of time and resources for professionals to develop necessary skills. Conclusions: High levels of motivation do not seem to be matched by effective interventions or successful attempts to quit smoking among Bangladeshi and Pakistani adults in the UK. There is a need to adapt and test effective smoking cessation interventions to make them culturally acceptable to ethnic minority communities. UK tobacco control policies need to give special attention to the needs of ethnic minority groups.

Can machine-learning improve cardiovascular risk prediction using routine clinical data?

Background Current approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention. Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors. We assessed whether machine-learning can improve cardiovascular risk prediction. Methods Prospective cohort study using routine clinical data of 378,256 patients from UK family practices, free from cardiovascular disease at outset. Four machine-learning algorithms (random forest, logistic regression, gradient boosting machines, neural networks) were compared to an established algorithm (American College of Cardiology guidelines) to predict first cardiovascular event over 10-years. Predictive accuracy was assessed by area under the ‘receiver operating curve’ (AUC); and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to predict 7.5% cardiovascular risk (threshold for initiating statins). Findings 24,970 incident cardiovascular events (6.6%) occurred. Compared to the established risk prediction algorithm (AUC 0.728, 95% CI 0.723–0.735), machine-learning algorithms improved prediction: random forest +1.7% (AUC 0.745, 95% CI 0.739–0.750), logistic regression +3.2% (AUC 0.760, 95% CI 0.755–0.766), gradient boosting +3.3% (AUC 0.761, 95% CI 0.755–0.766), neural networks +3.6% (AUC 0.764, 95% CI 0.759–0.769). The highest achieving (neural networks) algorithm predicted 4,998/7,404 cases (sensitivity 67.5%, PPV 18.4%) and 53,458/75,585 non-cases (specificity 70.7%, NPV 95.7%), correctly predicting 355 (+7.6%) more patients who developed cardiovascular disease compared to the established algorithm. Conclusions Machine-learning significantly improves accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment, while avoiding unnecessary treatment of others.

Improving identification of familial hypercholesterolaemia in primary care: Derivation and validation of the familial hypercholesterolaemia case ascertainment tool (FAMCAT)

OBJECTIVE Heterozygous familial hypercholesterolaemia (FH) is a common autosomal dominant disorder. The vast majority of affected individuals remain undiagnosed, resulting in lost opportunities for preventing premature heart disease. Better use of routine primary care data offers an opportunity to enhance detection. We sought to develop a new predictive algorithm for improving identification of individuals in primary care who could be prioritised for further clinical assessment using established diagnostic criteria. METHODS Data were analysed for 2,975,281 patients with total or LDL-cholesterol measurement from 1 Jan 1999 to 31 August 2013 using the Clinical Practice Research Datalink (CPRD). Included in this cohort study were 5050 documented cases of FH. Stepwise logistic regression was used to derive optimal multivariate prediction models. Model performance was assessed by its discriminatory accuracy (area under receiver operating curve [AUC]). RESULTS The FH prediction model (FAMCAT), consisting of nine diagnostic variables, showed high discrimination (AUC 0.860, 95% CI 0.848-0.871) for distinguishing cases from non-cases. Sensitivity analysis demonstrated no significant drop in discrimination (AUC 0.858, 95% CI 0.845-0.869) after excluding secondary causes of hypercholesterolaemia. Removing family history variables reduced discrimination (AUC 0.820, 95% CI 0.807-0.834), while incorporating more comprehensive family history recording of myocardial infraction significantly improved discrimination (AUC 0.894, 95% CI 0.884-0.904). CONCLUSION This approach offers the opportunity to enhance detection of FH in primary care by identifying individuals with greatest probability of having the condition. Such cases can be prioritised for further clinical assessment, appropriate referral and treatment to prevent premature heart disease.