Patient-reported outcome measures for asthma:a systematic review

BACKGROUND: Patient-reported outcome measures (PROMs) are measures of the outcome of treatment(s) reported directly by the patient or carer. There is increasing international policy interest in using these to assess the impact of clinical care. AIMS: To identify suitably validated PROMs for asthma and examine their potential for use in clinical settings. METHODS: We systematically searched MEDLINE, EMBASE and Web of Science databases from 1990 onwards to identify PROMs for asthma. These were critically appraised, then narratively synthesised. We also identified the generic PROMs commonly used alongside asthma-specific PROMs. RESULTS: We identifi ed 68 PROMs for asthma, 13 of which were selected through screening as being adequately developed to warrant full-quality appraisal: 8 for adults, 4 for children and 1 for a child's caregiver. The PROMs found to be sufficiently well validated to offer promise for use in clinical settings were the Asthma Quality of Life Questionnaire (AQLQ) and mini-AQLQ for adults, and Pediatric Asthma Quality of Life Questionnaire for children. Rhinasthma was considered promising in simultaneously assessing the impact of asthma and rhinitis in those with coexistent disease. We identified 28 generic PROMs commonly used in conjunction with asthma-specific instruments. CONCLUSIONS: We identified asthma PROMs that offer the greatest potential for use in clinical settings. Further work is needed to assess whether these are fit-for-purpose for use in clinical practice with individual patients. In particular, there is a need to ensure these are validated for use in clinical settings, acceptable to patients, caregivers and clinicians, and yield meaningful outcomes. © 2014 Primary Care Respiratory Society/Macmillan Publishers Limited.

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.)

Value of glycaemic control in diabetes

Full text: Several Lancet publications have questioned the value of glycaemic control in diabetic patients. For example, in their Comment (Sept 29, p 1103),1 John Cleland and Stephen Atkin state that “Improved glycaemic control is not a surrogate for effective care of patients who have diabetes”, and Victor Montori and colleagues (p 1104)2 claim that “HbA1c loses its validity as a surrogate marker when patients have a constellation of metabolic abnormalities”. We are concerned that the reaction against “glucocentricity” in the field of diabetes has gone too far. Even the UK's National Prescribing Centre website, carrying the National Health Service logo, includes comments that undermine the value of glycaemic control. For example, referring to the United Kingdom Prospective Diabetes Study (UKPDS), this site states that “Compared with ‘conventional control’ there was no benefit from tight control of blood glucose with sulphonylureas or insulin with regard to total mortality, diabetes-related death, macrovascular outcomes or microvascular outcomes, including all the most serious ones such as blindness or kidney failure”.3 It is well established that better glycaemic control reduces long-term microvascular complications in type 1 and type 2 diabetes.4 In type 2 diabetes, the UKPDS reported that a composite microvascular endpoint (retinopathy requiring photocoagulation, vitreous haemorrhage, and fatal or non-fatal renal failure) was reduced by 25% in patients randomised to intensive glucose control (p=0·0099).4 To imply that these are not patient-relevant outcomes is to distort the evidence. Many studies have also found that improved glycaemic control reduces macrovascular complications.5 Do not be misled: glycaemic control remains a crucial component in the care of people with diabetes. The authors have received research support and undertaken ad hoc consultancies and speaker engagements for several pharmaceutical companies.

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 women's 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 women's 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 women's 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.

Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding:long-term randomised pragmatic trial in primary care

Background: Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. Aim: To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. Design and setting: A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. Method: In total, 571 women aged 25–50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen–progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. Results: At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = −0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Conclusion: Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery.

Midterm to long-term longitudinal outcome of autologous chondrocyte implantation in the knee joint:a multilevel analysis

Background Autologous chondrocyte implantation is a cell therapeutic approach for the treatment of chondral and osteochondral defects in the knee joint. The authors previously reported on the histologic and radiologic outcome of autologous chondrocyte implantation in the short- to midterm, which yields mixed results. Purpose The objective is to report on the clinical outcome of autologous chondrocyte implantation for the knee in the midterm to long term. Study Design Cohort study; Level of evidence, 3. Methods Eighty patients who had undergone autologous chondrocyte implantation of the knee with mid- to long-term follow-up were analyzed. The mean patient age was 34.6 years (standard deviation, 9.1 years), with 63 men and 17 women. Seventy-one patients presented with a focal chondral defect, with a median defect area of 4.1 cm2 and a maximum defect area of 20 cm2. The modified Lysholm score was used as a self-reporting clinical outcome measure to determine the following: (1) What is the typical pattern over time of clinical outcome after autologous chondrocyte implantation; and (2) Which patient-related predictors for the clinical outcome pattern can be used to improve patient selection for autologous chondrocyte implantation? Results The average follow-up time was 5 years (range, 2.7–9.3). Improvement in clinical outcome was found in 65 patients (81%), while 15 patients (19%) showed a decline in outcome. The median preoperative Lysholm score of 54 increased to a median of 78 points. The most rapid improvement in Lysholm score was over the 15-month period after operation, after which the Lysholm score remained constant for up to 9 years. The authors were unable to identify any patient-specific factors (ie, age, gender, defect size, defect location, number of previous operations, preoperative Lysholm score) that could predict the change in clinical outcome in the first 15 months. Conclusion Autologous chondrocyte implantation seems to provide a durable clinical outcome in those patients demonstrating success at 15 months after operation. Comparisons between other outcome measures of autologous chondrocyte implantation should be focused on the clinical status at 15 months after surgery. The patient-reported clinical outcome at 15 months is a major predictor of the mid- to long-term success of autologous chondrocyte implantation.

Deep brain stimulation for chronic pain investigated with magnetoencephalography

Deep brain stimulation has shown remarkable potential in alleviating otherwise treatment-resistant chronic pain, but little is currently known about the underlying neural mechanisms. Here for the first time, we used noninvasive neuroimaging by magnetoencephalography to map changes in neural activity induced by deep brain stimulation in a patient with severe phantom limb pain. When the stimulator was turned off, the patient reported significant increases in subjective pain. Corresponding significant changes in neural activity were found in a network including the mid-anterior orbitofrontal and subgenual cingulate cortices; these areas are known to be involved in pain relief. Hence, they could potentially serve as future surgical targets to relieve chronic pain. © 2007 Lippincott Williams & Wilkins, Inc.

Changing faces

News & Comment. Many influential models of prefrontal cortex function suggest that activity within this area is often associated with additional activity in posterior regions of the cortex that support perception. The purpose of this cortical ‘coupling’ is to ensure that a perceptual representation is generated and then maintained within the working memory system. Areas in the right ventrolateral prefrontal cortex (vlPFC) and the fusiform gyrus have been implicated as associate areas involved in face processing. In an interesting case study by Vignal, Chauvel and Halgren the functional relationship between these two areas was tested1. In order to confirm the epileptogenic foci prior to resective surgery in a 30-year-old male patient, depth electrodes were implanted into sites around prefrontal, anterior temporal and premotor cortices. While the patient was looking at a blank screen, 50-Hz electrical stimulation of two probes implanted into the right anterior frontal gyrus resulted in the patient’s reporting the perception of a series of colourful faces. These facial hallucinations were described as being ‘…like passing slides, one after the after, linked together’. When asked to look at an actual face during stimulation at the same sites the patient reported transformation of that face (such as appearing without spectacles or with a hat). These findings were related to activity of a cortical network involving the vlPFC and the fusiform gyrus. This paper thus suggests a role in face processing for the vlPFC, evoking working memory processes to maintain facial representations.

Levonorgestrel intrauterine system versus medical therapy for menorrhagia

ABSTRACT: Menorrhagia is a common problem that interferes with a woman’s physical, emotional, and social life. Evidence to guide physicians for decision about therapy for heavy menstrual bleeding is lacking. One treatment option, the levonorgestrel-releasing intrauterine system (levonorgestrel-IUS), has been available in the United States since 2009. Updated meta-analyses comparing the levonorgestrel-IUS with nonhormonal and hormonal treatments showed that the levonorgestrel-IUS produced a greater reduction in menstrual blood loss at 3 to 12 months of follow-up. It is not clear whether these short-term benefits persist. Moreover, the rates of discontinuation of the levonorgestrel-IUS at 2 years are as high as 28%, and effects on bleeding-related quality of life are not known. This pragmatic, multicenter, randomized trial compared the effectiveness of the levonorgestrel-IUS with that of usual medical treatment among women with menorrhagia in a primary care setting. A total of 571 women with menorrhagia were randomized to treatment with levonorgestrel-IUS (n = 285) or usual medical treatment (n = 286). Usual treatment was tranexamic acid, mefenamic acid, combined estrogen-progestogen, or progesterone alone. The primary study outcome measure was the patient-reported score on the condition-specific Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period. The MMAS scores range from 0 to 100, with lower scores indicating greater severity. Summary MMAS scores were assessed at 6, 12, and 24 months. Secondary outcome measures included general health-related quality of life, sexual-activity scores, and surgical intervention. There was a significant improvement in total MMAS scores from baseline to 6 months in both the levonorgestrel-IUS group and the usual-treatment group; the mean increase was 32.7 and 21.4 points, respectively; P < 0.001 for both comparisons. Over the 2-year follow-up, improvements were maintained in both groups but were significantly greater in the levonorgestrel-IUS group (mean between-group difference, 13.4 points; 95% confidence interval, 9.9–16.9; P < 0.001). Significantly greater improvements in all MMAS domains (practical difficulties, social life, psychological health, physical health, work and daily routine, and family life and relationships) occurred with the levonorgestrel-IUS than with the usual treatment (P < 0.001 with the use of a test for trend). This was also found for 7 of the 8 quality-of-life domains. At the 2-year end point, almost twice as many women were still using the levonorgestrel-IUS than were those receiving the usual medical treatment (64% vs 38%, P < 0.001). No significant between-group differences were noted in the rates of surgical intervention or sexual-activity scores as well as in the frequency of serious adverse events. These data show that levonorgestrel-IUS is more effective than usual medical treatment in improving the quality of life of women with menorrhagia in a primary care setting.

Randomised trial of levonorgestrel intrauterine system compared to usual medical treatment for heavy menstrual bleeding:the ECLIPSE Trial

Objective: Heavy menstrual bleeding (menorrhagia) is a common problem, yet evidence is limited to inform therapeutic decisions.We compared the levonorgestrel-releasing intrauterine system(LNG-IUS) to usual medical treatment in a pragmatic randomised trial in primary care. Methods: We randomly assigned 571 women consulting their primary care providers with menorrhagia to LNG-IUS or to usual medical treatment as clinically appropriate (tranexamic acid, mefenamic acid, combined estrogen/progestogen or progestogen only). The primary outcome was a patient-reported measure ofimpact of menorrhagia, the validated Menorrhagia Multi-Attribute Scale (MMAS), assessed over 2 years. Secondary measures included generic quality of life (SF-36), sexual activity and surgical intervention.Results MMAS scores improved from baseline in both the LNG-IUS and usual medical treatment groups by 6 months (mean increases 32.7 points versus 21.4 points, respectively; P < 0.001for both) and were maintained over 2 years, but improvements were significantly greater with LNG-IUS (mean between-group difference 13.4 points, 95%CI, 9.9–16.9; P < 0.001).All domains of MMAS (practical difficulties, social life, family life,work/daily routine, psychological well being and physical health)improved significantly more with LNG-IUS, as were seven of the eight domains of SF-36. More women were still using LNG-IUSthan usual medical treatment at 2 years (64% versus 38%,P < 0.001). There were no significant between-group differences in surgical intervention rates or sexual activity scores. There were no serious adverse events in either group.Conclusions Among women presenting to primary care providers with menorrhagia, LNG-IUS was more effective than usual medical treatment at reducing the impact of this problem on their quality of life. In practice therefore, conventional treatments, such as tranexamic and mefenamic acid, remain helpful choices in women for whom LNG-IUS is considered unsuitable, or due to individual preference. For other women, LNG-IUS can be confidently recommended as an effective initial medical therapy for menorrhagia. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project number 02/06/02)

A study of outcomes measures in forensic mental health

Outcomes measures, which is the measurement of effectiveness of interventions and services has been propelled onto the health service agenda since the introduction of the internal market in the 1990s. It arose as a result of the escalating cost of inpatient care, the need to identify what interventions work and in what situations, and the desire for effective information by service users enabled by the consumerist agenda introduced by Working for Patients white paper. The research reported in this thesis is an assessment of the readiness of the forensic mental health service to measure outcomes of interventions. The research examines the type, prevalence and scope of use of outcomes measures, and further seeks a consensus of views of key stakeholders on the priority areas for future development. It discusses the theoretical basis for defining health and advocates the argument that the present focus on measuring effectiveness of care is misdirected without the input of users, particularly patients in their care, drawing together the views of the many stakeholders who have an interest in the provision of care in the service. The research further draws on the theory of structuration to demonstrate the degree to which a duality of action, which is necessary for the development, and use of outcomes measures is in place within the service. Consequently, it highlights some of the hurdles that need to be surmounted before effective measurement of health gain can be developed in the field of study. It concludes by advancing the view that outcomes research can enable practitioners to better understand the relationship between the illness of the patient and the efficacy of treatment. This understanding it is argued would contribute to improving dialogue between the health care practitioner and the patient, and further providing the information necessary for moving away from untested assumptions, which are numerous in the field about the superiority of one treatment approach over another.

Applying quantitative methods in the assessment of outcomes of pharmacotherapy of psoriasis

Healthcare providers and policy makers are faced with an ever-increasing number of medical publications. Searching for relevant information and keeping up to date with new research findings remains a constant challenge. It has been widely acknowledged that narrative reviews of the literature are susceptible to several types of bias and a systematic approach may protect against these biases. The aim of this thesis was to apply quantitative methods in the assessment of outcomes of topical therapies for psoriasis. In particular, to systematically examine the comparative efficacy, tolerability and cost-effectiveness of topical calcipotriol in the treatment of mild-to-moderate psoriasis. Over the years, a wide range of techniques have been used to evaluate the severity of psoriasis and the outcomes from treatment. This lack of standardisation complicates the direct comparison of results and ultimately the pooling of outcomes from different clinical trials. There is a clear requirement for more comprehensive tools for measuring drug efficacy and disease severity in psoriasis. Ideally, the outcome measures need to be simple, relevant, practical, and widely applicable, and the instruments should be reliable, valid and responsive. The results of the meta-analysis reported herein show that calcipotriol is an effective antipsoriatic agent. In the short-tenn, the pooled data found calcipotriol to be more effective than calcitriol, tacalcitol, coal tar and short-contact dithranol. Only potent corticosteroids appeared to have comparable efficacy, with less short-term side-effects. Potent corticosteroids also added to the antipsoriatic effect of calcipotriol, and appeared to suppress the occurrence of calcipotriol-induced irritation. There was insufficient evidence to support any large effects in favour of improvements in efficacy when calcipotriol is used in combination with systemic therapies in patients with severe psoriasis. However, there was a total absence of long-term morbidity data on the effectiveness of any of the interventions studied. Decision analysis showed that, from the perspective of the NHS as payer, the relatively small differences in efficacy between calcipotriol and short-contact dithranol lead to large differences in the direct cost of treating patients with mildto-moderate plaque psoriasis. Further research is needed to examine the clinical and economic issues affecting patients under treatment for psoriasis in the UK. In particular, the maintenance value and cost/benefit ratio for the various treatment strategies, and the assessment of patient's preferences has not yet been adequately addressed for this chronic recurring disease.

Use of flucinolone acetonide for patients with diabetic macular oedema:patient selection criteria and early outcomes in real world setting

Introduction: Fluocinolone acetonide slow release implant (Iluvien®) was approved in December 2013 in UK for treatment of eyes which are pseudophakic with DMO that is unresponsive to other available therapies. This approval was based on evidence from FAME trials which were conducted at a time when ranibizumab was not available. There is a paucity of data on implementation of guidance on selecting patients for this treatment modality and also on the real world outcome of fluocinolone therapy especially in those patients that have been unresponsive to ranibizumab therapy. Method: Retrospective study of consecutive patients treated with fluocinolone between January and August 2014 at three sites were included to evaluate selection criteria used, baseline characteristics and clinical outcomes at 3-month time point. Results: Twenty two pseudophakic eyes of 22 consecutive patients were included. Majority of patients had prior therapy with multiple intravitreal anti-VEGF injections. Four eyes had controlled glaucoma. At baseline mean VA and CRT were 50.7 letters and 631 μm respectively. After 3 months, 18 patients had improved CRT of which 15 of them also had improved VA. No adverse effects were noted. One additional patient required IOP lowering medication. Despite being unresponsive to multiple prior therapies including laser and anti-VEGF injections, switching to fluocinolone achieved treatment benefit. Conclusion: The patient level selection criteria proposed by NICE guidance on fluocinolone appeared to be implemented. This data from this study provides new evidence on early outcomes following fluocinolone therapy in eyes with DMO which had not responded to laser and other intravitreal agents.