Hepatitis C Virus Infection in Persons Who Inject Drugs in the Middle East and North Africa: Intervention Strategies.

There is a high incidence and prevalence of hepatitis C viral infection in persons with or without substance use disorders (SUDs) in the Middle East and North Africa (MENA) region, but only a small number receive comprehensive care. Highly effective direct-acting antiviral (DAA) medications are available at substantially lower costs; however, complete elimination of the hepatitis C virus (HCV) can only be achieved if integrated care strategies target those at highest risk for HCV infection and transmission and improve access to care. Due to the high prevalence of SUD in the MENA region, strategies to eliminate HCV must focus on integrated healthcare across multiple subspecialties, including addiction medicine, psychiatry, infectious diseases, hepatology, and social work. In this invited manuscript, we review the epidemiology of HCV in the MENA region and highlight intervention strategies to attain the WHO's goal of HCV eradication by 2030.

Maternal-focused interventions to improve infant growth and nutritional status in low-middle income countries: A systematic review of reviews.

BACKGROUND: Small and nutritionally at-risk infants under 6 months (<6m) are a vulnerable group at increased risk of mortality, morbidity, poor growth and sub-optimal development. Current national and international (World Health Organization) management guidelines focus mainly on infants' needs, yet growing evidence suggests that maternal factors also influence infant outcomes. We aimed to inform future guidelines by exploring the impacts of maternal-focused interventions on infant feeding and growth. METHODS: We conducted a systematic review of reviews published since 2008 (PROSPERO, register number CRD 42019141724). We explored five databases and a wide variety of maternal-focused interventions based in low- and middle-income countries. Infant outcomes of interest included anthropometric status, birthweight, infant mortality, breastfeeding and complementary feeding practices. Given heterogenous interventions, we present a narrative synthesis of the extracted data. RESULTS: We included a total of 55 systematic reviews. Numerous maternal interventions were effective in improving infant growth or feeding outcomes. These included breastfeeding promotion, education, support and counselling interventions. Maternal mental health, while under-researched, showed potential to positively impact infant growth. There was also some evidence for a positive impact of: women's empowerment, m-health technologies, conditional cash transfers, water, sanitation and hygiene and agricultural interventions. Effectiveness was increased when implemented as part of a multi-sectoral program. Antenatal supplementation with macronutrient, multiple micronutrients, Vitamin D, zinc, iron folic acid and possibly calcium, iodine and B12 in deficient women, improved birth outcomes. In contrast, evidence for postnatal supplementation was limited as was evidence directly focusing on small and nutritionally at-risk infants; most reviews focused on the prevention of growth faltering. CONCLUSION: Our findings suggest sufficient evidence to justify greater inclusion of mothers in more holistic packages of care for small and nutritionally at-risk infants aged <6m. Context specific approaches are likely needed to support mother-infant dyads and ensure infants survive and thrive.

Transesophageal echocardiography detection of air embolism during endoscopic surgery and validity of hyperbaric oxygen therapy: Case report.

INTRODUCTION: Air embolism has the potential to be serious and fatal. In this paper, we report 3 cases of air embolism associated with endoscopic medical procedures in which the patients were treated with hyperbaric oxygen immediately after diagnosis by transesophageal echocardiography. In addition, we systematically review the risk factors for air embolism, clinical presentation, treatment, and the importance of early hyperbaric oxygen therapy efficacy after recognition of air embolism. PATIENT CONCERNS: We present 3 patients with varying degrees of air embolism during endoscopic procedures, one of which was fatal, with large amounts of gas visible in the right and left heart chambers and pulmonary artery, 1 showing right heart enlargement with increased pulmonary artery pressure and tricuspid regurgitation, and 1 showing only a small amount of gas images in the heart chambers. DIAGNOSES: Based on ETCO2 and transesophageal echocardiography (TEE), diagnoses of air embolism were made. INTERVENTIONS: The patients received symptomatic supportive therapy including CPR, 100% O2 ventilation, cerebral protection, hyperbaric oxygen therapy and rehabilitation. OUTCOMES: Air embolism can causes respiratory, circulatory and neurological dysfunction. After aggressive treatment, one of the 3 patients died, 1 had permanent visual impairment, and 1 recovered completely without comorbidities. CONCLUSIONS: While it is common for small amounts of air/air bubbles to enter the circulatory system during endoscopic procedures, life-threatening air embolism is rare. Air embolism can lead to serious consequences, including respiratory, circulatory, and neurological impairment. Therefore, early recognition of severe air embolism and prompt hyperbaric oxygen therapy are essential to avoid its serious complications.

Brazilian women's use of evidence-based practices in childbirth after participating in the Senses of Birth intervention: A mixed-methods study.

Brazil has a cesarean rate of 56% and low use of Intrapartum Evidence-based Practices (IEBP) of 3.4%, reflecting a medically centered and highly interventionist maternal health care model. The Senses of Birth (SoB) is a health education intervention created to promote normal birth, use of EBP, and reduce unnecessary c-sections. This study aimed to understand the use of intrapartum EBP by Brazilian women who participated in the SoB intervention. 555 women answered the questionnaire between 2015 and 2016. Bivariate analysis and ANOVA test were used to identify if social-demographic factors, childbirth information, and perceived knowledge were associated with the use of EBP. A qualitative analysis was performed to explore women's experiences. Research participants used the following EBP: birth plan (55.2%), companionship during childbirth (81.6%), midwife care (54.2%), freedom of mobility during labor (57.7%), choice of position during delivery (57.2%), and non-pharmacological pain relief methods (74.2%). Doula support was low (26.9%). Being a black woman was associated with not using a birth plan or having doula support. Women who gave birth in private hospitals were more likely not to use the EBP. Barriers to the use of EBP identified by women were an absence of individualized care, non-respect for their choices or provision of EBP by health care providers, inadequate structure and ambiance in hospitals to use EBP, and rigid protocols not centered on women's needs. The SoB intervention was identified as a potential facilitator. Women who used EBP described a sense of control over their bodies and perceived self-efficacy to advocate for their chosen practices. Women saw the strategies to overcome barriers as a path to become their childbirth protagonist. Health education is essential to increase the use of EBP; however, it should be implemented combined with changes in the maternal care system, promoting woman-centered and evidence-based models.

Effects of non-drug interventions on depression, anxiety and sleep in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVE: Patients with Coronavirus Disease 2019 (COVID-19) suffer from anxiety, depression and sleep disorders due to isolation treatment, among other reasons. Whether non-drug interventions can be alternative therapies for COVID-19 patients with anxiety, depression and sleep disorders is controversial. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of non-drug interventions on anxiety, depression and sleep in patients with COVID-19 to provide guidance for clinical application. MATERIALS AND METHODS: We searched the following databases for randomized controlled trials (RCTs) from December 2019 to July 2020: China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP Chinese Science and Technology Periodical Database (VIP), Wanfang, Cochrane Library, Web of Science, PubMed, MEDLINE and Embase. Two investigators independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 5 articles with 768 subjects were included. Meta-analysis results indicated that non-drug interventions can reduce anxiety [SMD=-1.40, 95% CI (-1.62, -1.17), p<0.00001] and depression [SMD=-1.22, 95% CI (-2.01, -0.43), p=0.002] scores in patients with COVID-19. Descriptive analysis indicated that non-drug interventions can improve the sleep status of COVID-19 patients. Sensitivity analysis indicated that the meta-analysis results were stable. Egger's test and Begg's test showed no publication bias. CONCLUSIONS: This meta-analysis found that non-drug interventions can reduce the anxiety and depression scores of patients with COVID-19. Due to the limitations of this study, more high-quality studies are needed to verify the findings, especially the effect of non-drug interventions on improving the sleep status of COVID-19 patients.

Effectiveness of a home-based early cognitive-motor intervention provided in daycare, home care, and foster care settings: Changes in motor development and context affordances.

BACKGROUND: Appropriate opportunities within the context are crucial to affect the motor trajectory positively. OBJECTIVE: To investigate the effectiveness of professional-parental/caregivers' early motor-cognitive intervention on infants' motor development in Daycare (DC), Home Care (HC), and Foster Care (FC). Secondary objectives were to examine if parents and caregivers modified the context to meet the infants' needs and if making modifications was positively associated with infants' development. METHODS: Participants were 176 infants (DC = 48; HC = 58, FC = 70). Infants' were randomly assigned to intervention (IG) or comparison (CG) groups within each context. The Alberta Infant Motor Scale and Affordances in the Daycare and Home Environment for Motor Development were used. A cognitive-motor intervention was provided for infants in the intervention groups; and, a home-based support protocol for all caregivers and parents. RESULTS: IGs showed higher motor scores at post-test than CGs (p values from 0.018 to 0.026) and positive changes were observed from the pre-to-post intervention for all IGs (p ≤ .0001), and for two CGs (DC p ≤ .0001; HC p = .028). Maternal daily care and home opportunities improved for all infants. CONCLUSIONS: Parents/caregivers' protocol combined with the cognitive-motor intervention lead to better motor outcomes and changes in the context for the IGs. Only the parent/caregivers' protocol was not strong to improve CGs motor outcomes, although changes in context were found. Intensive intervention is need for infants living in vulnerability.

Megaloblastic anaemia in a 9-weeks old infant: A case report.

Megaloblastic anaemia due to vitamin B12 and folic acid deficiency is uncommon in infancy and rarely reported in infants below 3 months of age. We hereby report a case of megaloblastic anaemia in a 9-weeks old infant having fever from 7th week of life. Blood picture showed pancytopenia and diagnosis was confirmed on bone marrow biopsy and serum level of vitamins. Patient positively responded to vitamin B12 and folic acid supplementation. Infants with pancytopenia even younger than 2 months, should also be investigated for vitamin B12 and folate deficiency. Mother of the baby was not antenatally investigated for anaemia. Prompt antenatal diagnosis and treatment of mothers can reduce the incidence in the infants.

Efficacy of Supporting Play Exploration and Early Development Intervention in the First Months of Life for Infants Born Very Preterm: 3-Arm Randomized Clinical Trial Protocol.

OBJECTIVE: The aim of this project is to study the effect of a physical therapist intervention provided in the first months of life on developmental outcomes of infants born very preterm. Secondary aims are to investigate the impact of intervention timing on the efficacy and impact of the intervention on infants with and without cerebral palsy. METHODS: This study is a multisite longitudinal controlled trial comparing developmental outcomes from infants in the Supporting Play, Exploration, and Early Development Intervention (SPEEDI)_Late or SPEEDI_Early group to a usual care group. SETTINGS ARE URBAN: Urban and rural areas surrounding 2 academic medical centers. There will be 90 preterm infants enrolled in this study born at <29 weeks of gestation. SPEEDI is a developmental intervention provided by collaboration between a physical therapist and parent to support a child's motor and cognitive development. The primary outcome measure is the Bayley Scale of Infant and Toddler Development Cognitive and Gross Motor Scaled Scores. Secondary measures include behavioral coding of early problem solving skills, the Gross Motor Function Measure, and Test of Infant Motor Performance. IMPACT: More than 270,000 infants are born very preterm in the United States each year, 50% of whom will have neurological dysfunction that limits their ability to keep pace with peers who are typically developing. This study is a step toward understanding the impact that intensive developmental intervention could have in this population in the first months of life.

Efficacy of a brief mindfulness intervention upon anxiety in early psychosis patients.

AIM: To examine the efficacy of a brief mindfulness intervention in reducing anxiety in early psychosis patients, and to determine whether symptom burden mitigates therapeutic response. METHODS: Our study included patients who had experienced an initial episode of psychosis, with less than 30 months of antipsychotic exposure. First, the prescriber completed the COMPASS Clinician Rating Form (measuring symptom burden), and patients completed the POMS questionnaire (measuring anxiety). A 3-minute mindfulness exercise was administered, and patients again completed the POMS scale. The differences between the pre- and postintervention anxiety scores were analysed using a paired t test. RESULTS: A total of 20 subjects participated. The mean Anxiety Subscale of the POMS scores decreased from 4.6 to 1.7. The change was statistically significant, and not influenced by symptom burden. CONCLUSIONS: A brief mindfulness exercise, conducted in a routine office visit, produced a significant reduction in state anxiety for early psychosis patients, regardless of symptom burden.

WHO antenatal care recommendations for a positive pregnancy experience Nutritional interventions update: Vitamin D supplements during pregnancy

The World Health Organization's comprehensive antenatal care (ANC) guideline WHO recommendations on antenatal care for a positive pregnancy experience was first published in 2016 with the objective of improving the quality of routine health care that all women and adolescent girls receive during pregnancy. The overarching principle ­ to provide pregnant service users with a positive pregnancy experience ­ aims to encourage countries to expand their health-care agendas beyond survival, with a view to maximizing health, human rights and the potential of their populations. Recognizing that ANC provides a strategic platform for important health-care functions, including health promotion and disease prevention, 14 out of the 49 recommendations in the WHO 2016 ANC guideline relate to nutritional interventions in pregnancy. In April 2019, the Executive Guideline Steering Group (GSG) prioritized two of these antenatal nutrition recommendations for updating in response to new evidence on these interventions, namely: 1. Vitamin D supplements during pregnancy 2. Multiple micronutrient supplements during pregnancy. Evidence on these interventions was evaluated by a Guideline Development Group (GDG) composed of an international group of experts convened during an online GDG meeting held on 4­5 December 2019. The respective recommendations were updated in accordance with WHO's living guidelines approach. For consistency and continuity, the GDG, including the chair, comprised the same members as the ANC guideline GDG. This guideline presents that evidence and updated recommendation on antenatal vitamin D supplements, whichupdates and does not alter the corresponding recommendation previously issued.

The Human-Animal Relationship as the Focus of Animal-Assisted Interventions: A One Health Approach.

BACKGROUND: Animal-assisted intervention (AAIs) represent an adequate expression of integrated medicine, according to the One Health approach. We argue that AAIs are interventions based on interspecific relationships between humans and animals. Although there are many studies on the effects of AAIs on animal and human health and wellbeing, research is still needed to give us more data. For example, information is still lacking on the aspects characterizing and influencing the interspecific relationships occurring in AAIs. The efficacy of an intervention based on interspecific relationships will be influenced by different factors, such as attachment styles and personalities of both the animal and the handler, an appropriate choice of animal species and their individuality, animal educational training techniques, the relationship between the handler and the animal, and relational reciprocity between animal, the patients, and members of the working team. METHOD: This article aims to contribute to the study of interspecific relationships in AAIs via theoretical considerations. An interspecific relationship determines the result of safe interventions, which directly influences the welfare of the animal. Results and considerations: AAIs should be evaluated systemically as a network within a process in which every component interacts with and influences other components. Standardized methods using appropriate tests and parameters are needed to better select appropriate animals (i.e., species and individual subjects) using interspecific relational competences as well as appropriate educational training methods and health protocols to assess potential risks.

Chronic Headache: a Review of Interventional Treatment Strategies in Headache Management.

PURPOSE OF THE REVIEW: To provide an overview of current interventional pain management techniques for primary headaches with a focus on peripheral nerve stimulation and nerve blocks. RECENT FINDINGS: Despite a plethora of treatment modalities, some forms of headaches remain intractable to conservative therapies. Interventional pain modalities have found a niche in treating headaches. Individuals resistant to common regimens, intolerant to pharmaceutical agents, or those with co-morbid factors that cause interactions with their therapies are some instances where interventions could be considered in the therapeutic algorithm. In this review, we will discuss these techniques including peripheral nerve stimulation, third occipital nerve block (TON), lesser occipital nerve block (LON), greater occipital nerve block (GON), sphenopalatine block (SPG), radiofrequency ablation (RFA), and cervical epidural steroid injections (CESI). Physicians have used several interventional techniques to treat primary headaches. While many can be treated pharmacologically, those who continue to suffer from refractory or severe headaches may see tremendous benefit from a range of more invasive treatments which focus on directly inhibiting the painful nerves. While there is a plethora of evidence suggesting these methods are effective and possibly durable interventions, there is still a need for large, prospective, randomized trials to clearly demonstrate their efficacy.

Vaccine discussions in pregnancy: interviews with midwives to inform design of an intervention to promote uptake of maternal and childhood vaccines.

Presumptive and Motivational Interviewing communication styles have successfully promoted childhood and adolescent vaccination to parents, but less is known about effective communication approaches during pregnancy to promote maternal vaccination and childhood vaccines. In Australian public antenatal settings, midwives provide a substantial proportion of care and are highly accessed and trusted sources of vaccine information for expectant parents. However, there are no evidence-based interventions incorporating communication strategies and resources for midwives to optimize discussions and promote acceptance of maternal and childhood vaccines. This study aimed to gather qualitative data from midwives to inform the design of a feasible and acceptable vaccine communication intervention package building on an evidence-based model utilized with US obstetricians. We explored midwives' attitudes and values regarding maternal and childhood vaccination, their perceived role in vaccine advocacy and delivery, and barriers and enablers to implementation of a potential communication intervention. We recruited 12 midwives for semi-structured interviews at two Australian tertiary public hospitals (one with antenatal vaccines onsite, one without). Interviews were analyzed using thematic template analysis. Midwives supported vaccination but expressed varied views regarding its centrality to their role. Most reported receiving minimal or no training on vaccine communication. Their communication practices focused primarily on vaccine information provision rather than persuasion, although some midwives shared personal views and actively encouraged vaccination. More vaccine and communication training and resources were requested. Findings highlight the need for communication tools that align with midwifery standards for practice to support midwives to address parents' questions and concerns about maternal and childhood vaccines.

Meals, Mindfulness, & Moving Forward: A feasibility study to a multi-modal lifestyle approach in early psychosis.

AIM: The primary aim was to demonstrate adherence to a novel 6-week lifestyle intervention program ("Meals, Mindfulness, & Moving Forward" [M3 ]) designed to help improve lifestyle practices of youth with a history of at least 1 psychotic episode. METHODS: M3 used a non-equivalent control group design involving clients from a community early intervention program. Seventeen individuals in the active M3 program and 16 controls were assessed for secondary outcomes at baseline, 6-weeks, and 12-weeks (6 weeks post-intervention) on cardiometabolic and symptomatic outcomes. RESULTS: The program met its primary aim with 88% (15/17) of participants meeting adherence criteria. Compared with the controls, M3 participants showed significant improvement in positive psychotic symptoms (P = .002). CONCLUSION: This pilot study showed that young people involved in a community early intervention program adhered to an activity-based lifestyle program which included mindfulness meditation, yoga and nutrition education, warranting further evaluation with a larger sample size.

Impact of tobacco, alcohol and cannabis use on treatment outcomes among patients experiencing first episode psychosis: Data from the national RAISE-ETP study.

AIM: The primary aim of this study was to examine the effect of recent tobacco, alcohol and cannabis use on treatment outcomes among participants experiencing first episode psychosis (FEP). METHODS: Secondary data analyses were conducted on 404 participants enrolled in the Recovery After an Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study. RAISE-ETP investigated the effectiveness of a coordinated specialty care (CSC) intervention for FEP in community mental health agencies in the United States. Generalized estimating equations were used to examine whether recent tobacco smoking, alcohol, and cannabis use at baseline were associated with illness severity, number of antipsychotic pills missed, psychiatric symptoms and quality of life during the 24-month treatment period, after controlling for duration of untreated psychosis and treatment group. RESULTS: At baseline, roughly 50% (n = 209) of participants reported recent tobacco, 28% (n = 113) alcohol and 24% (n = 95) cannabis use. Tobacco smokers had higher levels of illness severity (ß = .24; P < .005), a higher number of missed pills (ß = 2.89; P < .05), higher psychiatric symptoms and lower quality of life during treatment relative to non-smokers. Alcohol users had a higher number of missed pills (ß = 3.16; P < .05) during treatment and cannabis users had higher levels of illness severity (ß = .18; P < .05) and positive symptoms (ß = 1.56; P < .05) relative to non-users. CONCLUSIONS: Tobacco, alcohol and cannabis use are common in youth seeking treatment for FEP. Tobacco smoking was associated with more negative clinical outcomes. These findings have implications for including interventions targeting these areas of substance use within current CSC models.

Perioperative Anxiety and Stress in Children Undergoing Congenital Cardiac Surgery and Their Parents: Effect of Brief Intervention-A Randomized Control Trial.

OBJECTIVE: To know the effects of psychological preparation on perioperative stress, anxiety, and mood in children undergoing cardiac surgery and their parents. DESIGN: Prospective randomized control nonblinded trial. SETTING: Single-center tertiary teaching hospital. PARTICIPANTS: A total of 60 children aged 5 to 15 years undergoing cardiac surgery were included in the study. One of the parents, preferably the father, was selected from the respective children. INTERVENTIONS: Subjects were randomized into 2 groups: noninterventional (group 1) and interventional (group 2). Intervention was in the form of toys and video games in children, and counseling and information in parents. Preoperative and postoperative anxiety in parents was measured using the State-Trait Anxiety Inventory (STAI), stress using the Index of Clinical Stress (ICS) scale by Abell, and the Ottawa mood scale. In children, the STAI-C (child version of STAI), Ottawa mood and Ottawa stress scales, and Wong-Baker faces pain scale were applied and serum cortisol was measured. MEASUREMENTS AND MAIN RESULTS: Group 2 children had significantly less (p < 0.001) stress, anxiety, and pain and improved mood. Group 2 parents had a significant reduction in state anxiety (42 ± 4.4 v 54.5 ± 7.8; p < 0.001) and ICS score (68.1±9.6 v 84.2 ± 9.2; p < 0.001) and an improvement in mood (7.5 ± 0.7 v 5.9 ± 1; p < 0.001) compared with group 1. Postoperatively, cortisol levels in group 2 were lower than group 1 (571.3 nmol/L [123.3 -1247.14] v 718.9 nmol/L [53-1642.0]). CONCLUSION: Providing video games and toys preoperatively reduced postoperative stress and anxiety and improved mood in children undergoing congenital cardiac surgery. Parents were relieved of anxiety and stress with proper counseling and information.

Smartphone Applications for Mindfulness Interventions with Suicidality in Asian Older Adults: A Literature Review.

Elderly suicide is a rising concern. Despite the advent of mobile technology, there remained a gap in the evidence base as to whether smartphone applications could be used for mindfulness intervention for suicidality in Asian older adults. This paper aimed to review recent research relevant to smartphone applications that could be used in providing mindfulness interventions for suicidality to Asian older adults. The inclusion criteria for this review were papers published in peer-reviewed journals from 2008 to 2018 with the usage of specific search terms, namely, 'smartphone application', 'mobile application', and 'mindfulness', assessed against the inclusion criteria and screened by an experienced Asian clinician to be of clinical utility for mindfulness intervention for suicidality with Asian older adults. Initial search on databases yielded 236 results. A total of 35 full text papers that fit the inclusion criteria were assessed for eligibility and 10 papers were included in the current review. This review highlighted the paucity of rigorous empirically validated research into effective smartphone applications that can be used for mindfulness interventions for suicidality with Asian older adults.

Early motion and directed exercise (EMADE) versus usual care post ankle fracture fixation: study protocol for a pragmatic randomised controlled trial.

BACKGROUND: Following surgical fixation of ankle fractures, the traditional management has included immobilisation for 6 weeks in a below-knee cast. However, this can lead to disuse atrophy of the affected leg and joint stiffness. While early rehabilitation from 2 weeks post surgery is viewed as safe, controversy remains regarding its benefits. We will compare the effectiveness of early motion and directed exercise (EMADE) ankle rehabilitation, against usual care, i.e. 6 weeks' immobilisation in a below-knee cast. METHOD/DESIGN: We have designed a pragmatic randomised controlled trial (p-RCT) to compare the EMADE intervention against usual care. We will recruit 144 independently living adult participants, absent of tissue-healing comorbidities, who have undergone surgical stabilisation of isolated Weber B ankle fractures. The EMADE intervention consists of a non-weight-bearing progressive home exercise programme, complemented with manual therapy and education. Usual care consists of immobilisation in a non-weight-bearing below-knee cast. The intervention period is between week 2 and week 6 post surgery. The primary outcome is the Olerud and Molander Ankle Score (OMAS) patient-reported outcome measure (PROM) at 12 weeks post surgery. Secondary PROMs include the EQ-5D-5 L questionnaire, return to work and return to driving, with objective outcomes including ankle range of motion. Analysis will be on an intention-to-treat basis. An economic evaluation will be included. DISCUSSION: The EMADE intervention is a package of care designed to address the detrimental effects of disuse atrophy and joint stiffness. An advantage of the OMAS is the potential of meta-analysis with other designs. Within the economic evaluation, the cost-utility analysis, may be used by commissioners, while the use of patient-relevant outcomes, such as return to work and driving, will ensure that the study remains pertinent to patients and their families. As it is being conducted in the clinical environment, this p-RCT has high external validity. Accordingly, if significant clinical benefits and cost-effectiveness are demonstrated, EMADE should become a worthwhile treatment option. A larger-scale, multicentre trial may be required to influence national guidelines. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN11212729 . Registered retrospectively on 20 March 2017.