Behavioural modification interventions for medically unexplained symptoms in primary care: systematic reviews and economic evaluation.

BACKGROUND: The term 'medically unexplained symptoms' is used to cover a wide range of persistent bodily complaints for which adequate examination and appropriate investigations do not reveal sufficiently explanatory structural or other specified pathologies. A wide range of interventions may be delivered to patients presenting with medically unexplained symptoms in primary care. Many of these therapies aim to change the behaviours of the individual who may have worsening symptoms. OBJECTIVES: An evidence synthesis to determine the clinical effectiveness and cost-effectiveness of behavioural modification interventions for medically unexplained symptoms delivered in primary care settings was undertaken. Barriers to and facilitators of the effectiveness and acceptability of these interventions from the perspective of patients and service providers were evaluated through qualitative review and realist synthesis. DATA SOURCES: Full search strategies were developed to identify relevant literature. Eleven electronic sources were searched. Eligibility criteria - for the review of clinical effectiveness, randomised controlled trials were sought. For the qualitative review, UK studies of any design were included. For the cost-effectiveness review, papers were restricted to UK studies reporting outcomes as quality-adjusted life-year gains. Clinical searches were conducted in November 2015 and December 2015, qualitative searches were conducted in July 2016 and economic searches were conducted in August 2016. The databases searched included MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and EMBASE. Updated searches were conducted in February 2019 and March 2019. PARTICIPANTS: Adult participants meeting the criteria for medically unexplained symptoms, including somatoform disorders, chronic unexplained pain and functional somatic syndromes. INTERVENTIONS: Behavioural interventions were categorised into types. These included psychotherapies, exercise-based interventions, multimodal therapies (consisting of more than one intervention type), relaxation/stretching/social support/emotional support, guided self-help and general practitioner interventions, such as reattribution. Evidence synthesis: a network meta-analysis was conducted to allow a simultaneous comparison of all evaluated interventions in a single coherent analysis. Separate network meta-analyses were performed at three time points: end of treatment, short-term follow-up (< 6 months since the end of treatment) and long-term follow-up (≥ 6 months after the end of treatment). Outcomes included physical and psychological symptoms, physical functioning and impact of the illness on daily activities. Economic evaluation: within-trial estimates of cost-effectiveness were generated for the subset of studies where utility values (or quality-adjusted life-years) were reported or where these could be estimated by mapping from Short Form questionnaire-36 items or Short Form questionnaire-12 items outcomes. RESULTS: Fifty-nine studies involving 9077 patients were included in the clinical effectiveness review. There was a large degree of heterogeneity both between and within intervention types, and the networks were sparse across all outcomes. At the end of treatment, behavioural interventions showed some beneficial effects when compared with usual care, in particular for improvement of specific physical symptoms [(1) pain: high-intensity cognitive-behavioural therapy (CBTHI) standardised mean difference (SMD) 0.54 [95% credible interval (CrI) 0.28 to 0.84], multimodal SMD 0.52 (95% CrI 0.19 to 0.89); and (2) fatigue: low-intensity cognitive-behavioural therapy (CBTLI) SMD 0.72 (95% CrI 0.27 to 1.21), relaxation/stretching/social support/emotional support SMD 0.87 (95% CrI 0.20 to 1.55), graded activity SMD 0.51 (95% CrI 0.14 to 0.93), multimodal SMD 0.52 (95% CrI 0.14 to 0.92)] and psychological outcomes [(1) anxiety CBTHI SMD 0.52 (95% CrI 0.06 to 0.96); (2) depression CBTHI SMD 0.80 (95% CrI 0.26 to 1.38); and (3) emotional distress other psychotherapy SMD 0.58 (95% CrI 0.05 to 1.13), relaxation/stretching/social support/emotional support SMD 0.66 (95% CrI 0.18 to 1.28) and sport/exercise SMD 0.49 (95% CrI 0.03 to 1.01)]. At short-term follow-up, behavioural interventions showed some beneficial effects for specific physical symptoms [(1) pain: CBTHI SMD 0.73 (95% CrI 0.10 to 1.39); (2) fatigue: CBTLI SMD 0.62 (95% CrI 0.11 to 1.14), relaxation/stretching/social support/emotional support SMD 0.51 (95% CrI 0.06 to 1.00)] and psychological outcomes [(1) anxiety: CBTHI SMD 0.74 (95% CrI 0.14 to 1.34); (2) depression: CBTHI SMD 0.93 (95% CrI 0.37 to 1.52); and (3) emotional distress: relaxation/stretching/social support/emotional support SMD 0.82 (95% CrI 0.02 to 1.65), multimodal SMD 0.43 (95% CrI 0.04 to 0.91)]. For physical functioning, only multimodal therapy showed beneficial effects: end-of-treatment SMD 0.33 (95% CrI 0.09 to 0.59); and short-term follow-up SMD 0.78 (95% CrI 0.23 to 1.40). For impact on daily activities, CBTHI was the only behavioural intervention to show beneficial effects [end-of-treatment SMD 1.30 (95% CrI 0.59 to 2.00); and short-term follow-up SMD 2.25 (95% CrI 1.34 to 3.16)]. Few effects remained at long-term follow-up. General practitioner interventions showed no significant beneficial effects for any outcome. No intervention group showed conclusive beneficial effects for measures of symptom load (somatisation). A large degree of heterogeneity was found across individual studies in the assessment of cost-effectiveness. Several studies suggested that the interventions produce fewer quality-adjusted life-years than usual care. For those interventions that generated quality-adjusted life-year gains, the mid-point incremental cost-effectiveness ratios (ICERs) ranged from £1397 to £129,267, but, where the mid-point ICER fell below £30,000, the exploratory assessment of uncertainty suggested that it may be above £30,000. LIMITATIONS: Sparse networks meant that it was not possible to conduct a metaregression to explain between-study differences in effects. Results were not consistent within intervention type, and there were considerable differences in characteristics between studies of the same type. There were moderate to high levels of statistical heterogeneity. Separate analyses were conducted for three time points and, therefore, analyses are not repeated-measures analyses and do not account for correlations between time points. CONCLUSIONS: Behavioural interventions showed some beneficial effects for specific medically unexplained symptoms, but no one behavioural intervention was effective across all medically unexplained symptoms. There was little evidence that these interventions are effective for measures of symptom load (somatisation). General practitioner-led interventions were not shown to be effective. Considerable heterogeneity in interventions, populations and sparse networks mean that results should be interpreted with caution. The relationship between patient and service provider is perceived to play a key role in facilitating a successful intervention. Future research should focus on testing the therapeutic effects of the general practitioner-patient relationship within trials of behavioural interventions, and explaining the observed between-study differences in effects within the same intervention type (e.g. with more detailed reporting of defined mechanisms of the interventions under study). STUDY REGISTRATION: This study is registered as PROSPERO CRD42015025520. FUNDING: 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. 24, No. 46. See the NIHR Journals Library website for further project information.

The term 'medically unexplained symptoms' is used in relation to individuals who present to their general practitioner with persistent symptoms that cannot easily be explained, even after adequate physical examination and appropriate investigations. Common interventions delivered in primary care tend to be psychological interventions, behaviour therapies or physical exercise therapies. These therapies often aim to change the behaviours of the individual that may make symptoms worse. We conducted systematic reviews of existing evidence to evaluate the effectiveness and acceptability of behavioural interventions delivered in primary care, and a cost-effectiveness analysis to see whether or not they offer good value. Studies measured improvement in outcomes, such as physical or psychological symptoms, or health-related quality of life. There were large differences in the nature of the behavioural interventions delivered and so we grouped them into 'types'. These included intervention types involving exercise (e.g. aerobic or strengthening, or graded activity); different types of psychotherapy, for example cognitive­behavioural therapy; interventions focused on relaxation or social/emotional support; interventions offering education and information; and interventions by general practitioners, for example receiving training on how to implement a behavioural approach to treating medically unexplained symptoms. Statistical analyses were conducted to investigate which, if any, of the intervention types were effective when compared with usual care. Results indicated that some of the behavioural intervention types showed beneficial effects at the end of treatment and at short-term follow-up. In particular, cognitive­behavioural therapy at a higher intensity, and therapies consisting of components of more than one intervention type (i.e. multimodal therapies), showed beneficial effects for specific physical symptoms such as pain, fatigue or bowel symptoms. High-intensity cognitive­behavioural therapy, other types of psychotherapies and interventions focusing on relaxation and social/emotional support showed some beneficial effects on mood outcomes such as depression and anxiety. By long-term follow-up, effects had diminished. More complex measures of symptom load or 'somatisation' showed fewer beneficial effects. We found that no one intervention improved outcomes across all medically unexplained symptoms. However, the results of the statistical analyses should be interpreted with caution. Not only were there differences in the types of behavioural interventions trialled in the included studies, but there were also differences in the characteristics of interventions within the same type. Participants of the studies had a range of symptoms and syndromes, of varying severity and duration. Interventions of the same type varied in how they were delivered, for example the qualifications of the therapist and the contact time spent between therapist and patient. Owing to the limited number of studies in each intervention type, it has not been possible to identify how these differences influenced the results. Interventions delivered by general practitioners themselves did not generally show beneficial effects. However, the relationship between general practitioner and patient was perceived to be important. Patients valued receiving explanations for their symptoms and learning self-management techniques. This was facilitated by good relationships with their health-care practitioner. Health-care practitioners reported a need for training and supervision, but patients reported that the primary care setting was both appropriate and helpful. A successful behavioural intervention should allow a patient and their care provider to maintain a relationship where the patient feels supported. Analyses of the cost-effectiveness of the interventions showed a wide variation in costs. Costs varied between different intervention types, but also between interventions of the same type. Differences in the nature of interventions within the same intervention type, for example whether delivery is to groups or to individuals, make comparisons difficult. Future research should focus on identifying how the relationship between the general practitioner and their patient can influence the effectiveness of a behavioural intervention when it is conducted in the primary care setting. In addition, more research is needed to explore which aspects of the more promising interventions are influencing their effectiveness.

Selective laser trabeculoplasty versus drops for newly diagnosed ocular hypertension and glaucoma: the LiGHT RCT.

BACKGROUND: Newly diagnosed open-angle glaucoma (OAG) and ocular hypertension (OHT) are habitually treated with intraocular pressure (IOP)-lowering eyedrops. Selective laser trabeculoplasty (SLT) is a safe alternative to drops and is rarely used as first-line treatment. OBJECTIVES: To compare health-related quality of life (HRQoL) in newly diagnosed, treatment-naive patients with OAG or OHT, treated with two treatment pathways: topical IOP-lowering medication from the outset (Medicine-1st) or primary SLT followed by topical medications as required (Laser-1st). We also compared the clinical effectiveness and cost-effectiveness of the two pathways. DESIGN: A 36-month pragmatic, unmasked, multicentre randomised controlled trial. SETTINGS: Six collaborating specialist glaucoma clinics across the UK. PARTICIPANTS: Newly diagnosed patients with OAG or OHT in one or both eyes who were aged ≥ 18 years and able to provide informed consent and read and understand English. Patients needed to qualify for treatment, be able to perform a reliable visual field (VF) test and have visual acuity of at least 6 out of 36 in the study eye. Patients with VF loss mean deviation worse than -12 dB in the better eye or -15 dB in the worse eye were excluded. Patients were also excluded if they had congenital, early childhood or secondary glaucoma or ocular comorbidities; if they had any previous ocular surgery except phacoemulsification, at least 1 year prior to recruitment or any active treatment for ophthalmic conditions; if they were pregnant; or if they were unable to use topical medical therapy or had contraindications to SLT. INTERVENTIONS: SLT according to a predefined protocol compared with IOP-lowering eyedrops, as per national guidelines. MAIN OUTCOME MEASURES: The primary outcome was HRQoL at 3 years [as measured using the EuroQol-5 Dimensions, five-level version (EQ-5D-5L) questionnaire]. Secondary outcomes were cost and cost-effectiveness, disease-specific HRQoL, clinical effectiveness and safety. RESULTS: Of the 718 patients enrolled, 356 were randomised to Laser-1st (initial SLT followed by routine medical treatment) and 362 to Medicine-1st (routine medical treatment only). A total of 652 (91%) patients returned the primary outcome questionnaire at 36 months. The EQ-5D-5L score was not significantly different between the two arms [adjusted mean difference (Laser-1st - Medicine-1st) 0.01, 95% confidence interval (CI) -0.01 to 0.03; p = 0.23] at 36 months. Over 36 months, the proportion of visits at which IOP was within the target range was higher in the Laser-1st arm (93.0%, 95% CI 91.9% to 94.0%) than in the Medicine-1st arm (91.3%, 95% CI 89.9% to 92.5%), with IOP-lowering glaucoma surgery required in 0 and 11 patients, respectively. There was a 97% probability of Laser-1st being more cost-effective than Medicine-1st for the NHS, at a willingness to pay for a quality-adjusted life-year of £20,000, with a reduction in ophthalmology costs of £458 per patient (95% of bootstrap iterations between -£585 and -£345). LIMITATION: An unmasked design, although a limitation, was essential to capture any treatment effects on patients' perception. The EQ-5D-5L questionnaire is a generic tool used in multiple settings and may not have been the most sensitive tool to investigate HRQoL. CONCLUSIONS: Compared with medication, SLT provided a stable, drop-free IOP control to 74.2% of patients for at least 3 years, with a reduced need for surgery, lower cost and comparable HRQoL. Based on the evidence, SLT seems to be the most cost-effective first-line treatment option for OAG and OHT, also providing better clinical outcomes. FUTURE WORK: Longitudinal research into the clinical efficacy of SLT as a first-line treatment will specify the long-term differences of disease progression, treatment intensity and ocular surgery rates between the two pathways. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32038223. FUNDING: 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. 23, No. 31. See the NIHR Journals Library website for further project information.

Glaucoma is an eye condition in which the optic nerve becomes damaged and, if left untreated, will lead to loss of vision. Ocular hypertension (OHT) is the medical name for high pressure in the eye that increases the risk of getting glaucoma. Lowering the eye pressure is the only known way to prevent glaucoma from getting worse. Before this trial, the standard initial treatment of these conditions was the prescription of eyedrops to lower the pressure in the eye. An alternative is a laser therapy that is known to reduce the eye pressure. This study investigated if starting treatment of glaucoma or OHT with laser therapy (using eyedrops later, if needed) affected the patients' quality of life (QoL) more or less than starting treatment with eyedrops alone. The study also investigated if initial treatment with laser and initial treatment with eyedrops are equally good at controlling eye pressure and are equally safe and how much they cost the NHS. Patients were randomly assigned to starting treatment with either laser or eyedrops and the two groups were then compared. The study found that for the first 3 years QoL was similar regardless of treatment. However, three-quarters of patients initially treated with laser did not need any eyedrops to control their eye pressure for 3 years. Patients initially treated with laser were less likely to require cataract surgery, and none needed any glaucoma surgery in the first 3 years. In contrast, among those patients treated with eyedrops, glaucoma surgery was required in 11 eyes (out of 622 eyes). Initial treatment with laser was cheaper than initial treatment with eyedrops. The results of this study suggest that laser is an efficient, safe and cheaper alternative to eyedrops, and that three-quarters of the patients initially treated with laser do not need any eyedrops for the first 3 years of treatment.

Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial.

BACKGROUND: Primary open angle glaucoma and ocular hypertension are habitually treated with eye drops that lower intraocular pressure. Selective laser trabeculoplasty is a safe alternative but is rarely used as first-line treatment. We compared the two. METHODS: In this observer-masked, randomised controlled trial treatment-naive patients with open angle glaucoma or ocular hypertension and no ocular comorbidities were recruited between 2012 and 2014 at six UK hospitals. They were randomly allocated (web-based randomisation) to initial selective laser trabeculoplasty or to eye drops. An objective target intraocular pressure was set according to glaucoma severity. The primary outcome was health-related quality of life (HRQoL) at 3 years (assessed by EQ-5D). Secondary outcomes were cost and cost-effectiveness, disease-specific HRQoL, clinical effectiveness, and safety. Analysis was by intention to treat. This study is registered at controlled-trials.com (ISRCTN32038223). FINDINGS: Of 718 patients enrolled, 356 were randomised to the selective laser trabeculoplasty and 362 to the eye drops group. 652 (91%) returned the primary outcome questionnaire at 36 months. Average EQ-5D score was 0·89 (SD 0·18) in the selective laser trabeculoplasty group versus 0·90 (SD 0·16) in the eye drops group, with no significant difference (difference 0·01, 95% CI -0·01 to 0·03; p=0·23). At 36 months, 74·2% (95% CI 69·3-78·6) of patients in the selective laser trabeculoplasty group required no drops to maintain intraocular pressure at target. Eyes of patients in the selective laser trabeculoplasty group were within target intracoluar pressure at more visits (93·0%) than in the eye drops group (91·3%), with glaucoma surgery to lower intraocular pressure required in none versus 11 patients. Over 36 months, from an ophthalmology cost perspective, there was a 97% probability of selective laser trabeculoplasty as first treatment being more cost-effective than eye drops first at a willingness to pay of £20 000 per quality-adjusted life-year gained. INTERPRETATION: Selective laser trabeculoplasty should be offered as a first-line treatment for open angle glaucoma and ocular hypertension, supporting a change in clinical practice. FUNDING: National Institute for Health Research, Health and Technology Assessment Programme.

Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology.

PURPOSE: The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). DESIGN: The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. CONCLUSIONS: The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. TRIAL REGISTRATION NUMBER: ISRCTN32038223, Pre-results.

Increasing awareness of gynaecological cancer symptoms: a GP perspective.

BACKGROUND: In the UK there has been an effort, through the National Awareness and Early Diagnosis Initiative (NAEDI), to increase early stage diagnoses and ultimately cancer survival. Encouraging early symptom presentation through awareness-raising activities in primary care is one method to achieve this goal. Understanding GPs' views about this type of activity, however, is crucial prior to implementation. AIM: To describe GPs' attitudes to raising public awareness of gynaecological cancers, and their views about the potential impact on primary care services. DESIGN AND SETTING: An online survey with a convenience sample recruited from 1860 UK general practices. METHOD: An invitation was emailed to GPs via practice managers and included a weblink to a draft education leaflet and an online survey about the impact of sending a leaflet giving information about symptoms associated with gynaecological cancers to all women on GPs' lists. Participants could offer additional free text comments which were coded using content analysis. RESULTS: A total of 621 GPs participated. Most (77%, 477) felt that raising awareness of cancers was important. Only half (50%, 308), however, indicated that they would distribute such a leaflet from their practice. Barriers to implementation included concerns about financial costs; emotional impact on patients; increased demand for appointments and diagnostic services, such as ultrasound. CONCLUSIONS: GPs were generally positive about an intervention to improve patients' awareness of gynaecological cancers, but had concerns about increasing rates of presentation. There is a need for research quantifying the benefits of earlier diagnosis against resource costs such as increased consultations, investigations, and referrals.

Carer-led health interventions to monitor, promote and improve the health of adults with intellectual disabilities in the community: a systematic review.

Using carers to help assess, monitor, or promote health in people with intellectual disabilities (ID) may be one way of improving health outcomes in a population that experiences significant health inequalities. This paper provides a review of carer-led health interventions in various populations and healthcare settings, in order to investigate potential roles for carers in ID health care. We used rapid review methodology, using the Scopus database, citation tracking and input from ID healthcare professionals to identify relevant research. 24 studies were included in the final review. For people with ID, the only existing interventions found were carer-completed health diaries which, while being well received, failed to improve health outcomes. Studies in non-ID populations show that carers can successfully deliver screening procedures, health promotion interventions and interventions to improve coping skills, pain management and cognitive functioning. While such examples provide a useful starting point for the development of future carer-led health interventions for people with ID, the paucity of research in this area means that the most appropriate means of engaging carers in a way that will reliably impact on health outcomes in this population remains, as yet, unknown.

Assessment of an incentivised scheme to provide annual health checks in primary care for adults with intellectual disability: a longitudinal cohort study.

BACKGROUND: People with intellectual disabilities (ID) have many comorbidities but experience inequities in access to health care. National Health Service England uses an opt-in incentive scheme to encourage annual health checks of patients with ID in primary care. We investigated whether the first 3 years of the programme had improved health care of people with ID. METHODS: We did a longitudinal cohort study that used data from The Health Improvement Network primary care database. We did multivariate logistic regression to assess associations between various characteristics and whether or not practices had opted in to the incentivised scheme. FINDINGS: We assessed data for 8692 patients from 222 incentivised practices and those for 918 patients in 48 non-incentivised practices. More blood tests (eg, total cholesterol, odds ratio [OR] 1·88, 95% CI 1·47-2·41, p<0·0001) general health measurements (eg, smoking status, 6·0, 4·10-8·79, p<0·0001), specific health assessments (eg, hearing, 24·0, 11·5-49·9, p<0·0001), and medication reviews (2·23, 1·68-2·97, p<0·0001) were done in incentivised than in non-incentivised practices, and more health action plans (6·15, 1·41-26·9, p=0·0156) and secondary care referrals (1·47, 1·05-2·05, p=0·0256) were made. Identification rates were higher in incentivised practices for thyroid disorder (OR 2·72, 95% CI 1·09-6·81, p=0·0323), gastrointestinal disorders (1·94, 1·03-3·65, p=0·0390), and obesity (2·49, 1·76-3·53, p<0·0001). INTERPRETATION: Targeted annual health checks for people with ID in primary care could reduce health inequities. FUNDING: National Institute for Health Research.

Facilitating access to voluntary and community services for patients with psychosocial problems: a before-after evaluation.

BACKGROUND: Patients with psychosocial problems may benefit from a variety of community, educational, recreational and voluntary sector resources, but GPs often under-refer to these through lack of knowledge and time. This study evaluated the acceptability and effectiveness of graduate primary care mental health workers (GPCMHWs) facilitating access to voluntary and community sector services for patients with psychosocial problems. METHODS: Patients with psychosocial problems from 13 general practices in London were referred to a GPCMHW Community Link scheme providing information and support to access voluntary and community resources. Patient satisfaction, mental health and social outcomes, and use of primary care resources, were evaluated. RESULTS: 108 patients consented to take part in the study. At three-month follow-up, 63 (58%) had made contact with a community service identified as suitable for their needs. Most were satisfied with the help provided by the GPCMHW in identifying and supporting access to a suitable service. There was a reduction in the number of patients with a probable mental health problem on the GHQ-12 from 83% to 52% (difference 31% (95% CI, 17% - 44%). Social adjustment improved and frequencies of primary care consultations and of prescription of psychotropic medications were reduced. CONCLUSION: Graduates with limited training in mental health and no prior knowledge of local community resources can help patients with psychosocial problems access voluntary and community services, and patients value such a scheme. There was some evidence of effectiveness in reducing psychosocial and mental health problems.