Using a Combination of Indirect Calorimetry, Infrared Thermography, and Blood Glucose Levels to Measure Brown Adipose Tissue Thermogenesis in Humans.

In mammals, brown adipose tissue (BAT) is activated rapidly in response to cold in order to maintain body temperature. Although BAT has been studied greatly in small animals, it is difficult to measure the activity of BAT in humans. Therefore, little is known about the heat-generating capacity and physiological significance of BAT in humans, including the degree to which components of the diet can activate BAT. This is due to the limitations in the currently most used method to assess the activation of BAT-radiolabeled glucose (fluorodeoxyglucose or 18FDG) measured by positron emission tomography-computerized tomography (PET-CT). This method is usually performed in fasted subjects, as feeding induces glucose uptake by the muscles, which can mask the glucose uptake into the BAT. This paper describes a detailed protocol for quantifying total-body human energy expenditure and substrate utilization from BAT thermogenesis by combining indirect calorimetry, infrared thermography, and blood glucose monitoring in carbohydrate-loaded adult males. To characterize the physiological significance of BAT, measures of the impact of BAT activity on human health are critical. We demonstrate a protocol to achieve this by combining carbohydrate loading and indirect calorimetry with measurements of supraclavicular changes in temperature. This novel approach will help to understand the physiology and pharmacology of BAT thermogenesis in humans.

5-HT3 Receptors on Mitochondria Influence Mitochondrial Function.

The 5-hydroxytryptamine 3 (5-HT3) receptor belongs to the pentameric ligand-gated cation channel superfamily. Humans have five different 5-HT3 receptor subunits: A to E. The 5-HT3 receptors are located on the cell membrane, but a previous study suggested that mitochondria could also contain A subunits. In this article, we explored the distribution of 5-HT3 receptor subunits in intracellular and cell-free mitochondria. Organelle prediction software supported the localization of the A and E subunits on the inner membrane of the mitochondria. We transiently transfected HEK293T cells that do not natively express the 5-HT3 receptor with an epitope and fluorescent protein-tagged 5HT3A and 5HT3E subunits. Fluorescence microscopy and cell fractionation indicated that both subunits, A and E, localized to the mitochondria, while transmission electron microscopy revealed the location of the subunits on the mitochondrial inner membrane, where they could form heteromeric complexes. Cell-free mitochondria isolated from cell culture media colocalized with the fluorescent signal for A subunits. The presence of A and E subunits influenced changes in the membrane potential and mitochondrial oxygen consumption rates upon exposure to serotonin; this was inhibited by pre-treatment with ondansetron. Therefore, it is likely that the 5-HT3 receptors present on mitochondria directly impact mitochondrial function and that this may have therapeutic implications.

Both caffeine and Capsicum annuum fruit powder lower blood glucose levels and increase brown adipose tissue temperature in healthy adult males.

Using a combination of respiratory gas exchange, infrared thermography, and blood glucose (BGL) analysis, we have investigated the impact of Capsicum annuum (C. annuum) fruit powder (475 mg) or caffeine (100 mg) on metabolic activity in a placebo controlled (lactose, 100 mg) double-blinded three-way cross-over-design experiment. Metabolic measurements were made on day 1 and day 7 of supplementation in eight adult male participants (22.2 ± 2 years of age, BMI 23 ± 2 kg/m2, x̅ ± SD). Participants arrived fasted overnight and were fed a high carbohydrate meal (90 g glucose), raising BGL from fasting baseline (4.4 ± 0.3 mmol/L) to peak BGL (8.5 ± 0.3 mmol/L) 45 min after the meal. Participants consumed the supplement 45 min after the meal, and both caffeine and C. annuum fruit powder restored BGL (F (8,178) = 2.2, p = 0.02) to near fasting levels within 15 min of supplementation compared to placebo (120 min). In parallel both supplements increased energy expenditure (F (2, 21) = 175.6, p < 0.001) over the 120-min test period (caffeine = 50.74 ± 2 kcal/kg/min, C. annuum fruit = 50.95 ± 1 kcal/kg/min, placebo = 29.34 ± 1 kcal/kg/min). Both caffeine and C. annuum fruit powder increased supraclavicular fossa temperature (F (2,42) = 32, p < 0.001) on both day 1 and day 7 of testing over the 120-min test period. No statistical difference in core temperature or reference point temperature, mean arterial pressure or heart rate was observed due to supplementation nor was any statistical difference seen between day 1 and day 7 of intervention. This is important for implementing dietary ingredients as potential metabolism increasing supplements. Together the results imply that through dietary supplements such as caffeine and C. annuum, mechanisms for increasing metabolism can be potentially targeted to improve metabolic homeostasis in people.

A novel movement system screen for primary care providers: a multisite, observational study.

CONTEXT: Movement of the human body is essential for the interaction of an individual within their environment and contributes to both physical and emotional quality of life. Movement system disorders (MSDs) are kinesiopathologic conditions that result from either altered movement patterns, trauma, or pathology. A screening tool may facilitate earlier diagnosis and treatment of acute MSDs. This tool could prevent progression to chronic conditions, leading to better patient outcomes and quality of life. OBJECTIVES: Our study evaluated whether a screening tool would be able to accurately screen individuals for MSDs, explore comorbidities that may predict the prevalence of MSDs, and identify why people do not discuss these problems with their primary care provider (PCP). METHODS: A multisite, observational study in a primary care setting. Data were analyzed to determine the psychometric properties of the screening question. Logistic regression was performed to explore the relationship of comorbidities with MSDs. Thematic analysis was performed to explore why patients do not discuss these issues with their PCP. RESULTS: The point prevalence of MSDs was determined to be 78%. The sensitivity of the screening question was determined to be good (70%). Arthritis, obesity, sleep disorders, and gastroesophageal reflux disease (GERD) were significant predictors for an MSD. Thematic analysis regarding why patients do not discuss the MSD with their physician revealed: (1) the perceived lack of importance of the problem; (2) the lack of access to healthcare, and (3) the acuity of the problem. CONCLUSIONS: Screening for an MSD and associated comorbidities could prevent the transition of acute conditions to chronic conditions. If PCPs can identify predictors and factors associated with an MSD, they may be able to screen for MSDs more effectively. Earlier identification of MSDs may facilitate earlier treatment and prevent costs associated with resulting chronic disorders and persistent pain and disability.

A review on various explanations of Ponzo-like illusions.

This article reviews theoretical and empirical arguments for and against various theories that explain the classic Ponzo illusion and its variants from two different viewpoints concerning the role of perceived depth in size distortions. The first viewpoint argues that all Ponzo-like illusions are driven by perceived depth. The second viewpoint argues that the classic Ponzo illusion is unrelated to depth perception. This review will give special focus to the first viewpoint and consists of three sections. In the first section, the role of the number of pictorial depth cues and previous experience in the strength of all Ponzo-like illusions are discussed. In the second section, we contrast the first viewpoint against the theories that explain the classic Ponzo illusion with mechanisms that are unrelated to depth perception. In the last section, we propose a Bayesian-motivated reconceptualization of Richard Gregory's misapplied size constancy theory that explains Ponzo-variant illusions in terms of prior information and prediction errors. The new account explains why some studies have provided inconsistent evidence for misapplied size constancy theory.

Corrigendum: Both caffeine and Capsicum annuum fruit powder lower blood glucose levels and increase brown adipose tissue temperature in healthy adult males.

[This corrects the article DOI: 10.3389/fphys.2022.870154.].

Tapping into 5-HT3 Receptors to Modify Metabolic and Immune Responses.

5-hydroxytryptamine type 3 (5-HT3) receptors are ligand gated ion channels, which clearly distinguish their mode of action from the other G-protein coupled 5-HT or serotonin receptors. 5-HT3 receptors are well established targets for emesis and gastrointestinal mobility and are used as adjunct targets in treating schizophrenia. However, the distribution of these receptors is wider than the nervous system and there is potential that these additional sites can be targeted to modulate inflammatory and/or metabolic conditions. Recent progress in structural biology and pharmacology of 5-HT3 receptors have provided profound insights into mechanisms of their action. These advances, combined with insights into clinical relevance of mutations in genes encoding 5-HT3 subunits and increasing understanding of their implications in patient's predisposition to diseases and response to the treatment, open new avenues for personalized precision medicine. In this review, we recap on the current status of 5-HT3 receptor-based therapies using a biochemical and physiological perspective. We assess the potential for targeting 5-HT3 receptors in conditions involving metabolic or inflammatory disorders based on recent findings, underscoring the challenges and limitations of this approach.

Effects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review.

The impact of brown adipose tissue (BAT) metabolism on understanding energy balance in humans is a relatively new and exciting field of research. The pathogenesis of obesity can be largely explained by an imbalance between caloric intake and energy expenditure, but the underlying mechanisms are far more complex. Traditional non-selective sympathetic activators have been used to artificially elevate energy utilization, or suppress appetite, however undesirable side effects are apparent with the use of these pharmacological interventions. Understanding the role of BAT, in relation to human energy homeostasis has the potential to dramatically offset the energy imbalance associated with obesity. This review discusses paradoxical effects of caffeine on peripheral adenosine receptors and the possible role of adenosine in increasing metabolism is highlighted, with consideration to the potential of central rather than peripheral mechanisms for caffeine mediated BAT thermogenesis and energy expenditure. Research on the complex physiology of adipose tissue, the embryonic lineage and function of the different types of adipocytes is summarized. In addition, the effect of BAT on overall human metabolism and the extent of the associated increase in energy expenditure are discussed. The controversy surrounding the primary ß-adrenoceptor involved in human BAT activation is examined, and suggestions as to the lack of translational findings from animal to human physiology and human in vitro to in vivo models are provided. This review compares and distinguishes human and rodent BAT effects, thus developing an understanding of human BAT thermogenesis to aid lifestyle interventions targeting obesity and metabolic syndrome. The focus of this review is on the effect of BAT thermogenesis on overall metabolism, and the potential therapeutic effects of caffeine in increasing metabolism via its effects on BAT.

The conceptual understanding of depth rather than the low-level processing of spatial frequencies drives the corridor illusion.

Our objective was to determine how different spatial frequencies affect the perceptual size rescaling of stimuli in the corridor illusion. Two experiments were performed using the method of constant stimuli. In experiment 1, the task required participants to compare the size of comparison and standard rings displayed over the same background image. ANOVA on the points of subject equality (PSEs) revealed that the perceived size of the top and bottom standard rings changed as a function of the availability of the high, medium, and low spatial frequency information. In experiment 2, the task required participants to compare the size of a comparison ring presented outside of the background image with a standard ring presented inside it. ANOVA on the PSEs revealed that the apparent size of the top and not the bottom standard ring changed depending on the availability of medium spatial frequency information. Eye-tracking revealed that the spatial frequency range of the background image in the periphery affected participants' eye positioning, which may explain why the effects of different spatial frequencies fluctuated across experiments. Nonetheless, when we consider these findings together, we propose that the conceptual understanding of depth plays a more important role in explaining the corridor illusion than the low-level processing of depth information extracted from different spatial frequencies along separate channels.

Interocular transfer effects of linear perspective cues and texture gradients in the perceptual rescaling of size.

Our objective was to determine whether the influence of linear perspective cues and texture gradients in the perceptual rescaling of stimulus size transfers from one eye to the other. In experiment 1, we systematically added linear perspective cues and texture gradients in a background image of the corridor illusion. To determine whether perceptual size rescaling takes place at earlier or later stages, we tested how the perceived size of top and bottom rings changed under binocular (rings and background presented to both eyes), monocular (rings and background presented to the dominant eye only), and dichoptic (rings and background presented separately to the dominant and nondominant eyes, respectively) viewing conditions. We found differences between viewing conditions in the perceived size of the rings when linear perspective cues, but not texture gradients, were presented. Specifically, linear perspective cues produced a stronger illusion under the monocular compared to the dichoptic viewing condition. Hence, there was partial interocular transfer from the linear perspective cues, suggesting a dominant role of monocular neural populations in mediating the corridor illusion. In experiment 2, we repeated similar procedures with a more traditional Ponzo illusion background. Contrary to findings from experiment 1, there was a full interocular transfer with the presence of the converging lines, suggesting a dominant role of binocular neural populations. We conclude that higher order visual areas, which contain binocular neural populations, are more involved in the perceptual rescaling of size evoked by linear perspective cues in the Ponzo compared to the corridor illusion.

Innervation of supraclavicular adipose tissue: A human cadaveric study.

Functional brown adipose tissue (BAT) was identified in adult humans only in 2007 with the use of fluorodeoxyglucose positron emission tomography imaging. Previous studies have demonstrated a negative correlation between obesity and BAT presence in humans. It is proposed that BAT possesses the capacity to increase metabolism and aid weight loss. In rodents it is well established that BAT is stimulated by the sympathetic nervous system with the interscapular BAT being innervated via branches of intercostal nerves. Whilst there is evidence to suggest that BAT possesses beta-3 adrenoceptors, no studies have identified the specific nerve branch that carries sympathetic innervation to BAT in humans. The aim of this study was to identify and trace the peripheral nerve or nerves that innervate human BAT in the supraclavicular region. The posterior triangle region of the neck of cadaveric specimens were dissected in order to identify any peripheral nerve branches piercing and/or terminating in supraclavicular BAT. A previously undescribed branch of the cervical plexus terminating in a supraclavicular adipose depot was identified in all specimens. This was typically an independent branch of the plexus, from the third cervical spinal nerve, but in one specimen was a branch of the supraclavicular nerve. Histological analysis revealed the supraclavicular adipose depot contained tyrosine hydroxylase immunoreactive structures, which likely represent sympathetic axons. This is the first study that identifies a nerve branch to supraclavicular BAT-like tissue. This finding opens new avenues for the investigation of neural regulation of fat metabolism in humans.

The difference between a clinical technician and clinical practitioner is in the scope of practice: the need for a bioscience understanding in paramedicine.

"Only teach me what I need to know!" This commonly heard refrain is often spoken by allied health students while studying preclinical sciences (physiology, anatomy, pharmacology). Here we use a clinical scenario undertaken by second-year Bachelor of Paramedic Practice students of acute coronary syndrome to demonstrate the difference in clinical decision making when using a clinical reasoning approach to treatment rather than relying exclusively on a practice guidelines approach. We hope to demonstrate that understanding basic bioscience concepts, such as the Frank-Starling mechanism and the anatomy and physiology of the autonomic nervous system, are key to providing good clinical care in response to ambiguous patient symptoms. Students who understand these concepts underlying their patient care guideline will make better clinical decisions and better provide quality of care than students who follow the guideline exclusively. We aim this as a practical demonstration of the value of detailed understanding of human bioscience in allied health education. As health care providers transition from "technician" to "practitioner," the key distinguishing feature of the role is the ability to practice independently, using "best judgment" rather than clinical guidelines (alone). Evidence suggests that complex case management requires detailed bioscience understanding.

The contribution of linear perspective cues and texture gradients in the perceptual rescaling of stimuli inside a Ponzo illusion corridor.

We examined the influence of linear perspective cues and texture gradients in the perceptual rescaling of stimuli over a highly-salient Ponzo illusion of a corridor. We performed two experiments using the Method of Constant Stimuli where participants judged the size of one of two rings. In experiment 1, one ring was presented in the upper visual-field at the end of the corridor and the other in the lower visual-field at the front of the corridor. The perceived size of the top and bottom rings changed as a function of the availability of linear perspective and textures. In experiment 2, only one ring was presented either at the top or the bottom of the image. The perceived size of the top but not the bottom ring changed as a function of the availability of linear perspective and textures. In both experiments, the effects of the cues were additive. Perceptual rescaling was also stronger for the top compared to the bottom ring. Additional eye-tracking revealed that participants tended to gaze more in the upper than the lower visual-field. These findings indicate that top-down mechanisms provide an important contribution to the Ponzo illusion. Nonetheless, additional maximum likelihood estimation analyses revealed that linear perspective fulfilled a greater contribution in experiment 2, which is suggestive of a bottom-up mechanism. We conclude that both top-down and bottom-up mechanisms play important roles. However, the former seems to fulfil a more prominent role when both stimuli are presented in the image.

Labial trauma post birth: A delphi study of classification and suturing requirements.

OBJECTIVES: Primary objectives were to establish consensus of opinion for classification of post birth labial trauma and which types of post birth labial trauma require suturing. Secondary objectives were to establish optimal method, material and anaesthetic for suturing labial trauma. DESIGN: Delphi study consisting of 3 rounds. SETTING: UK and Europe PARTICIPANTS: 8 midwives, 4 obstetricians, 7 specialist perineal midwives, 1 consultant midwife and 2 midwifery lecturers all with relevant expertise and or recent, regular clinical experience of assessing and suturing labial trauma from 2 United Kingdom (UK) universities, 12 UK healthcare trusts and 1 European healthcare organisation. METHODS: A Delphi study consisting of an initial round of 6 professional medical illustrations of labial trauma with 6 open questions attached to each sent to panel members. 2 further rounds developed from the first round with between 2 and 10 opt-in statements for the 6 questions for each illustration to 20 and 22 panel members respectively. Consensus was set at 70% opt-in for each statement. FINDINGS: Consensus was reached that unilateral or bilateral vertical skin separation with minimal trauma to underlying tissues was described as a graze and does not require suturing. Consensus was reached that unilateral or bilateral deeper vertical trauma with involvement of the underlying tissue and horizontal trauma across the labia does require suturing with interrupted technique, injected local anaesthetic and using Vicryl Rapide 3.0 or equivalent. CONCLUSION: A pilot study and definitive randomised controlled trial are required to establish in vivo whether labial tears including those which are transverse, are less painful and heal better with interrupted suturing compared to continuous or subcuticular sutures.

The capacity for oestrogen to influence obesity through brown adipose tissue thermogenesis in animal models: A systematic review and meta-analysis.

Pharmacological interventions to aid weight loss have historically targeted either appetite suppression or increased metabolic rate. Brown adipose tissue (BAT) possesses the capacity to expend energy in a futile cycle, thus increasing basal metabolic rate. In animal models, oestrogen has been implicated in the regulation of body weight, and it is hypothesized that oestrogen is acting by modulating BAT metabolism. A systematic search was performed, to identify research articles implementing in vivo oestrogen-related interventions and reporting outcome measures that provide direct or indirect measures of BAT metabolism. Meta-analyses were conducted where sufficient data were available. The final library of 67 articles were predominantly in rodent models and provided mostly indirect measures of BAT metabolism. Results of this review found that oestrogen's effects on body weight, in rats and possibly mice, are likely facilitated by both metabolic and appetitive mechanisms but are largely only found in ovariectomized models. There is a need for further studies to clarify the potential effects of oestrogen on BAT metabolism in gonad-intact and castrated male animal models.

A molecular approach in drug development for Alzheimer's disease.

An increase in dementia numbers and global trends in population aging across the world prompts the need for new medications to treat the complex biological dysfunctions, such as neurodegeneration associated with dementia. Alzheimer's disease (AD) is the most common form of dementia. Cholinergic signaling, which is important in cognition, is slowly lost in AD, so the first line therapy is to treat symptoms with acetylcholinesterase inhibitors to increase levels of acetylcholine. Out of five available FDA-approved AD medications, donepezil, galantamine and rivastigmine are cholinesterase inhibitors while memantine, a N-methyl d-aspartate (NMDA) receptor antagonist, blocks the effects of high glutamate levels. The fifth medication consists of a combination of donepezil and memantine. Although these medications can reduce and temporarily slow down the symptoms of AD, they cannot stop the damage to the brain from progressing. For a superior therapeutic effect, multi-target drugs are required. Thus, a Multi-Target-Directed Ligand (MTDL) strategy has received more attention by scientists who are attempting to develop hybrid molecules that simultaneously modulate multiple biological targets. This review highlights recent examples of the MTDL approach and fragment based strategy in the rational design of new potential AD medications.

Omega 3 polyunsaturated fatty acids and the treatment of depression.

Depression is a common, recurrent, and debilitating illness that has become more prevalent over the past 100 years. This report reviews the etiology and pathophysiology of depression, and explores the role of omega 3 polyunsaturated fatty acids (n-3 PUFA) as a possible treatment. In seeking to understand depression, genetic factors and environmental influences have been extensively investigated. Research has led to several hypotheses for the pathophysiological basis of depression but a definitive pathogenic mechanism, or group thereof, has hitherto remained equivocal. To date, treatment has been based on the monoamine hypothesis and hence, selective serotonin reuptake inhibitors have been the most widely used class of medication. In the last decade, there has been considerable interest in n-3 PUFAs and their role in depression. These fatty acids are critical for development and function of the central nervous system. Increasing evidence from epidemiological, laboratory, and randomized placebo-controlled trials suggests deficiency of dietary n-3 PUFAs may contribute to development of mood disorders, and supplementation with n-3 PUFAs may provide a new treatment option. Conclusions based on systematic reviews and meta-analyses of published trials to date vary. Research into the effects of n-3 PUFAs on depressed mood is limited. Furthermore, results from such have led to conflicting conclusions regarding the efficacy of n-3 PUFAs in affecting reduction in symptoms of depression. PUFAs are generally well tolerated by adults and children although mild gastrointestinal effects are reported. There is mounting evidence to suggest that n-3 PUFAs play a role in depression and deserve greater research efforts.

An obstetric sphincter injury risk identification system (OSIRIS): is this a clinically useful tool?

INTRODUCTION AND HYPOTHESIS: To establish the contribution of maternal, fetal and intrapartum factors to the risk of incidence of obstetric anal sphincter injuries (OASIS) and assess the feasibility of an OASIS risk prediction model based on variables available to clinicians prior to birth. METHODS: This was a population-based, retrospective cohort study using single-site data from the birth database of Aarhus University Hospital, Denmark. The participants were all women who had a singleton vaginal birth during the period 1989 to 2006. Univariate and multivariate logistic regression analyses were performed using multiple imputations for missing data and internally validated using bootstrap methods. The main outcome measures were the contributions of maternal, fetal and intrapartum events to the incidence of OASIS. RESULTS: A total of 71,469 women met the inclusion criteria, of whom 1,754 (2.45 %) sustained OASIS. In the multivariate analysis of variables known prior to birth, maternal age 20 - 30 years (OR 1.65, 95 % CI 1.44 - 1.89) and ≥30 years (OR 1.60, 95 % CI 1.39 - 1.85), occipitoposterior fetal position (OR 1.34, 95 % CI 1.06 - 1.70), induction/augmentation of labour (OR 1.46, 95 % CI 1.32 - 1.62), and suspected macrosomia (OR 2.20, 95 % CI 1.97 - 2.45) were independent significant predictors of OASIS, with increasing parity conferring a significant protective effect. The 'prebirth variable' model showed a 95 % sensitivity and a 24 % specificity in predicting OASIS with 1 % probability, and a 3 % sensitivity and a 99 % specificity in predicting OASIS with a 10 % probability. CONCLUSIONS: Our model identified several significant OASIS risk factors that are known prior to actual birth. The prognostic model shows potential for ruling out OASIS (high sensitivity with a low risk cut-off value), but is not useful for ruling in the event.

Evaluating acupuncture and standard care for pregnant women with back pain: the EASE Back pilot randomised controlled trial (ISRCTN49955124).

BACKGROUND: Low back pain (LBP) and pelvic girdle pain (PGP) during pregnancy are common and often accepted as a 'normal' part of pregnancy. Many women receive little in the way of treatment, and yet pain interferes with sleep, daily activities and work and leads to increasing requests for induction of labour or elective caesarean section. The aim of this study was to assess the feasibility of a full RCT evaluating the benefit of acupuncture for pregnancy-related back pain. METHODS: This study is a single-centre, three-arm pilot RCT in one large maternity unit and associated antenatal and physiotherapy clinics. Women were eligible if they had pregnancy-related LBP with or without PGP. Exclusions included a history of miscarriage, high risk of early labour or pre-eclampsia, PGP only and previous acupuncture. Interventions were standard care (SC): a self-management booklet with physiotherapy if needed. SC+TA: the booklet and physiotherapy comprising true (penetrating) acupuncture, advice and exercise. SC+NPA: the booklet and physiotherapy comprising non-penetrating acupuncture, advice and exercise. Remote telephone randomisation used a 1:1:1 allocation ratio stratified by gestational weeks. Three measures of pain/function were compared to inform the primary outcome measure in a full RCT: the Pelvic Girdle Questionnaire (PGQ), Oswestry Disability Index (ODI) and 11-point 0-10 numerical rating scale for pain. Analysis focused on process evaluation of recruitment, retention, descriptive information on outcomes, adherence to treatment, occurrence of adverse events and impact of physiotherapist training. RESULTS: One hundred twenty-five women were randomised (45% of those eligible) between April and October 2013; 73% (n = 91) provided 8-week follow-up data. Three of six recruitment methods accounted for 82% of total uptake: screening questionnaire at the 20-week scan, community midwives issuing study cards, and self-referral following local awareness initiatives. Physiotherapists' self-confidence on managing pregnancy-related LBP improved post training. The PGQ is suitable as the primary outcome in a full trial. The average number of treatment sessions in both SC+TA and SC+NPA was six (in line with treatment protocols). No serious adverse events attributable to the trial treatments were reported. CONCLUSIONS: A full RCT is feasible and would provide evidence about the effectiveness of acupuncture and inform treatment choices for women with pregnancy-related LBP. TRIAL REGISTRATION: ISRCTN49955124.

Evaluating Acupuncture and Standard carE for pregnant women with Back pain (EASE Back): a feasibility study and pilot randomised trial.

BACKGROUND: Many pregnant women experience low back pain. Acupuncture appears to be a safe, promising intervention but evidence is needed about its clinical effectiveness and cost-effectiveness. OBJECTIVES: To assess the feasibility of a future large randomised controlled trial (RCT) testing the additional benefit of adding acupuncture to standard care (SC) for pregnancy-related back pain. DESIGN: Phase 1: a questionnaire survey described current care for pregnancy-related back pain. Focus groups and interviews with midwives, physiotherapists and pregnant women explored acceptability and feasibility of acupuncture and the proposed RCT. Phase 2: a single-centre pilot RCT. Participants were identified using six methods and randomised to SC, SC plus true acupuncture or SC plus non-penetrating acupuncture. PARTICIPANTS: Phase 1: 1093 physiotherapists were surveyed and 15 midwives, 21 physiotherapists and 17 pregnant women participated in five focus groups and 20 individual interviews. Phase 2: 125 women with pregnancy-related back pain participated. INTERVENTIONS: SC: a self-management booklet and onward referral for one-to-one physiotherapy (two to four sessions) for those who needed it. SC plus true acupuncture: the self-management booklet and six to eight treatments with a physiotherapist comprising true (penetrating) acupuncture, advice and exercise. SC plus non-penetrating acupuncture: the self-management booklet and six to eight treatments with a physiotherapist comprising non-penetrating acupuncture, advice and exercise. MAIN OUTCOME MEASURES: Pilot RCT outcomes included recruitment rates, treatment fidelity, follow-up rate, patient-reported pain and function, quality of life and health-care resource use. Birth and neonatal outcomes were also assessed. Staff overseeing outcome data collection were blind to treatment allocation. RESULTS: Phase 1: 629 (57.5%) physiotherapists responded to the survey, 499 were experienced in treating pregnancy-related back pain and reported 16 advice and 18 treatment options. Typical treatment comprised two to four individual sessions of advice and exercise over 6 weeks. Acupuncture was reported by 24%. Interviews highlighted the impact of back pain and paucity of effective interventions. Women and midwives strongly supported a RCT and expressed few concerns. Physiotherapists' concerns about acupuncture in pregnancy informed a training programme prior to the pilot RCT. Phase 2: We recruited 125 of 280 potentially eligible women (45%) in 6 months and randomised 41 to SC and 42 each to the SC plus true acupuncture and SC plus non-penetrating acupuncture arms. Analysis was conducted with 124 participants (41, 42 and 41, respectively) as one participant was randomised in error. Three of six recruitment methods were the most successful. In total, 10% of women (n = 4) randomised to SC alone accessed one-to-one physiotherapy and received an average of two treatments. The average number of treatments was six for both SC plus true acupuncture and SC plus non-penetrating acupuncture. Treatments were in line with protocols. Eight-week follow-up was 74%. Patient-reported outcomes (pain, function and quality of life) favoured the addition of acupuncture. There was no evidence of serious adverse events on mothers or birth and neonatal outcomes. The Pelvic Girdle Questionnaire was found to be an appropriate outcome measure for a future trial. CONCLUSIONS: A future main RCT is feasible and would be welcomed by women and clinicians. Longer-term follow-up and further follow-up efforts are recommended for a main trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49955124. FUNDING: This project was funded by the National Institute of Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 33. See the NIHR Journals Library website for further project information.