Optogenetic recruitment of hypothalamic corticotrophin-releasing-hormone (CRH) neurons reduces motivational drive.

Impaired motivational drive is a key feature of depression. Chronic stress is a known antecedent to the development of depression in humans and depressive-like states in animals. Whilst there is a clear relationship between stress and motivational drive, the mechanisms underpinning this association remain unclear. One hypothesis is that the endocrine system, via corticotropin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN; PVNCRH), initiates a hormonal cascade resulting in glucocorticoid release, and that excessive glucocorticoids change brain circuit function to produce depression-related symptoms. Another mostly unexplored hypothesis is that the direct activity of PVNCRH neurons and their input to other stress- and reward-related brain regions drives these behaviors. To further understand the direct involvement of PVNCRH neurons in motivation, we used optogenetic stimulation to activate these neurons 1 h/day for 5 consecutive days and showed increased acute stress-related behaviors and long-lasting deficits in the motivational drive for sucrose. This was associated with increased Fos-protein expression in the lateral hypothalamus (LH). Direct stimulation of the PVNCRH inputs in the LH produced a similar pattern of effects on sucrose motivation. Together, these data suggest that PVNCRH neuronal activity may be directly responsible for changes in motivational drive and that these behavioral changes may, in part, be driven by PVNCRH synaptic projections to the LH.

The effect of clinical guidelines on the utilisation of radiographs in chiropractic clinics in Denmark - an interrupted time series analysis.

BACKGROUND: In Denmark, chiropractors have a statutory right to use radiography and the government-funded national Health Insurance provides partial reimbursement. Danish National Clinical Guidelines recommends against routine use of imaging for uncomplicated spinal pain; however, it is not clear if clinical imaging guidelines recommendations have had an effect on the utilisation of spinal radiography. This study aimed to describe the utilisation rate of radiographs in Danish chiropractic clinics in the period from 2010 to 2020 and to assess the impact of clinical guidelines and policy changes on the utilisation of radiographs in Danish chiropractic clinics. METHODS: Anonymised data from January 1st, 2010, to December 31st, 2020, were extracted from the Danish Regions register on health contacts in primary care. Data consisted of the total number of patients consulting one of 254 chiropractic clinics and the total number of patients having or being referred for radiography. Data were used to investigate the radiography utilisation per month from 2010 to 2020. An 'interrupted time series' analysis was conducted to determine if two interventions, the dissemination of 1) Danish clinical imaging guidelines recommendations and policy changes related to referral for advanced imaging for chiropractors in 2013 and 2) four Danish clinical guidelines recommendations in 2016, were associated with an immediate change in the level and/or slope of radiography utilisation. RESULTS: In total, 336,128 unique patients consulted a chiropractor in 2010 of which 55,449 (15.4%) had radiography. In 2020, the number of patients consulting a chiropractor had increased to 366,732 of which 29,244 (8.0%) had radiography. The pre-intervention utilisation decreased by two radiographs per 10,000 patients per month. Little absolute change, but still statistically significant for Intervention 1, in the utilisation was found after the dissemination of the clinical guidelines and policy changes in 2013 or 2016. CONCLUSIONS: The proportion of Danish chiropractic patients undergoing radiography was halved in the period from 2010 to 2020. However, the dissemination of clinical imaging guidelines recommendations and policy changes related to referrals for advanced imaging showed little meaningful change in the monthly utilisation of radiographs in the same period.

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Drivers, barriers, and response to care of Australian pregnant women seeking chiropractic care for low back and pelvic girdle pain: a qualitative case study.

BACKGROUND: Pregnancy-related low back and/or pelvic girdle pain is common, with a prevalence rate of up to 86% in pregnant women. Although 19.5% of Australian pregnant women visit a chiropractor for pelvic girdle pain, little is known about the experience of pregnant women who seek this care. The aim of this study was to describe and explore the experiences of Australian pregnant women who seek chiropractic care for their current pregnancy-related low back and/or pelvic girdle pain. METHODS: A qualitative case study approach with purposive sampling from 27 chiropractic practices was used. A grounded theory approach was informed by a constructivist and interpretivist stance, which provided understanding and meaning to the pregnant women's experiences. Online unstructured interviews were recorded, transcribed, and anonymised. A thematic analysis was subsequently conducted on the primary data. Codes and major themes were developed with the use of critical self- reflection (memos), survey finding triangulation and respondent validation. RESULTS: Sixteen potential respondents expressed interest in participating. After eligibility screening and data saturation, nine interviews were undertaken. Four key themes were identified: "Care drivers: what drives care seeking?", "Care barriers: what barriers are encountered?", "Chiropractic treatment: what does treatment consist of?" and "Response to care: what response was there to care?". CONCLUSION: Four key themes: care drivers, care barriers, chiropractic treatment, and response to care support an emergent substantive-level theory in women's care seeking experiences for pregnancy-related back pain and chiropractic care. This theory is that chiropractic care for pregnant women experiencing low back pain and pelvic girdle pain may improve pain and function, while reducing pregnancy-related biopsychosocial concerns. The findings may inform antenatal health providers and the chiropractic profession about pregnant women's experience seeking chiropractic care as well as directing future research.

Patient and provider characteristics associated with therapeutic intervention selection in a chiropractic clinical encounter: a cross-sectional analysis of the COAST and O-COAST study data.

BACKGROUND: Chiropractors use a variety of therapeutic interventions in clinical practice. How the selection of interventions differs across musculoskeletal regions or with different patient and provider characteristics is currently unclear. This study aimed to describe how frequently different interventions are used for patients presenting for chiropractic care, and patient and provider characteristics associated with intervention selection. METHODS: Data were obtained from the Chiropractic Observation and Analysis STudy (COAST) and Ontario (O-COAST) studies: practice-based, cross-sectional studies in Victoria, Australia (2010-2012) and Ontario, Canada (2014-2015). Chiropractors recorded data on patient diagnosis and intervention selection from up to 100 consecutive patient visits. The frequency of interventions selected overall and for each diagnostic category (e.g., different musculoskeletal regions) were descriptively analysed. Univariable multi-level logistic regression (provider and patient as grouping factors), stratified by diagnostic category, was used to assess the association between patient/provider variables and intervention selection. RESULTS: Ninety-four chiropractors, representative of chiropractors in Victoria and Ontario for age, sex, and years in practice, participated. Data were collected on 7,966 patient visits (6419 unique patients), including 10,731 individual diagnoses (mean age: 43.7 (SD: 20.7), 57.8% female). Differences in patient characteristics and intervention selection were observed between chiropractors practicing in Australia and Canada. Overall, manipulation was the most common intervention, selected in 63% (95%CI:62-63) of encounters. However, for musculoskeletal conditions presenting in the extremities only, soft tissue therapies were more commonly used (65%, 95%CI:62-68). Manipulation was less likely to be performed if the patient was female (OR:0.74, 95%CI:0.65-0.84), older (OR:0.79, 95%CI:0.77-0.82), presenting for an initial visit (OR:0.73, 95%CI:0.56-0.95) or new complaint (OR:0.82, 95%CI:0.71-0.95), had one or more comorbidities (OR:0.63, 95%CI:0.54-0.72), or was underweight (OR:0.47, 95%CI:0.35-0.63), or obese (OR:0.69, 95%CI:0.58-0.81). Chiropractors with more than five years clinical experience were less likely to provide advice/education (OR:0.37, 95%CI:0.16-0.87) and exercises (OR:0.17, 95%CI:0.06-0.44). CONCLUSION: In more than 10,000 diagnostic encounters, manipulation was the most common therapeutic intervention for spine-related problems, whereas soft tissue therapies were more common for extremity problems. Different patient and provider characteristics were associated with intervention selection. These data may be used to support further research on appropriate selection of interventions for common musculoskeletal complaints.

Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.

A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode-retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life.

Circular Medicine - Being Mindful of Resources and Waste Recycling in Healthcare Systems.

In the light of the COP27 Climate Change Conference, the concept of the circular economy has come to the fore with promotion of reuse and recycling of appliances and materials from electronics to clothes. This concept has not been widely taken up by healthcare systems. In this perspective article, we discuss the idea of the circular economy and how, by extension, the concept of "circular medicine" with optimised hospital and medical clinic waste recycling might be promoted in the context of better stewardship of resources in healthcare management.

Linear endovenous energy density (LEED) should always be quoted with the power used in endovenous thermal ablation - results from an in-vitro porcine liver model study.

BACKGROUND: Linear Endovenous Energy Density (LEED) is the energy used per cm of vein in endovenous thermal ablation (EVTA) but does not include time. This study examines the effect of time during EVTA. METHOD: EVTA was performed in a previously validated porcine liver model. LEEDs of 40, 60, 80 and 100 J/cm, using different powers were repeated 5 times each. Thermal spread, tissue carbonisation and device-tissue sticking during treatment were recorded. RESULT: LEED positively correlated to thermal spread and carbonisation of the tissue. Power was correlated with carbonisation but not thermal spread. Pullback had no correlations with thermal spread or carbonisation. Catheter sticking found occurred in powers >= 15 W or LEED >= 80 J/cm. CONCLUSION: LEED is a good measure of EVTA but does not include time. Power, which does include time, correlates with carbonisation and with device-tissue sticking. The power used must be quoted with the LEED.

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.

European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Adulteration Detection of Edible Bird's Nests Using Rapid Spectroscopic Techniques Coupled with Multi-Class Discriminant Analysis.

Edible bird's nests (EBNs) are vulnerable to adulteration due to their huge demand for traditional medicine and high market price. Presently, there are pressing needs to explore field-deployable rapid screening techniques to detect adulteration of EBNs. The objective of this study is to explore the feasibility of using a handheld near-infrared (VIS/SW-NIR) spectroscopic device for the determination of EBN authenticity against the benchmark performance of a benchtop mid-infrared (MIR) spectrometer. Forty-nine authentic EBNs from the different states in Malaysia and 13 different adulterants (five types) were obtained and used to simulate the adulteration of EBNs at 1, 5 and 10% adulteration by mass (a total of 15 adulterated samples). The VIS/SW-NIR and MIR spectra collated were subsequently processed, modelled and classified using multi-class discriminant analysis. The VIS/SW-NIR results showed 100% correct classification for the collagen and nutrient agar classes in authenticity classification, while for the other classes, the lowest correct classification rate was 96.3%. For MIR analysis, only the karaya gum class had 100% correct classification whilst for the other four classes, the lowest rate of correct classification was at 94.4%. In conclusion, the combination of spectroscopic analysis with chemometrics can be a powerful screening tool to detect EBN adulteration.

European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

Sleep deprivation as a treatment for major depressive episodes: A systematic review and meta-analysis.

Sleep deprivation, alone or in combination with pharmacological treatment and as part of a chronotherapy package, is of potential use for people with major depressive episodes, however the evidence base is still conflicting. The aim of this systematic review and meta-analysis is to assess the clinical effects of sleep deprivation in comparison to any other intervention for the acute and long-term treatment of mood disorders. We searched electronic databases and trial registries (last update: 16th October 2021) for published and unpublished randomised controlled trials recruiting participants with a major depressive episode in unipolar or bipolar affective disorder. The clinical outcomes of interest were the reduction in depressive symptoms at different timepoints and the number of participants experiencing at least one side effect. Overall, 29 trials (1246 participants) were included. We did not find any difference in change in symptoms or all-cause discontinuation between interventions including SD compared to a control of the same intervention except without SD. In the included studies there were no available data for adverse events. Using the most methodologically rigorous approach, we did not find evidence that the addition of sleep deprivation to treatment packages leads to enhanced depressive outcomes.

Exploring factors influencing chiropractors' adherence to radiographic guidelines for low back pain using the Theoretical Domains Framework.

BACKGROUND: The inappropriate use of lumbar spine imaging remains common in primary care despite recommendations from evidence-based clinical practice guidelines to avoid imaging in the absence of red flags. This study aimed to explore factors influencing ordering behaviours and adherence to radiographic guidelines for low back pain (LBP) in chiropractors in Newfoundland and Labrador (NL), Canada. METHODS: We conducted two focus groups in December 2018 with chiropractors in different regions of NL (eastern, n = 8; western, n = 4). An interview guide based on the Theoretical Domains Framework (TDF) served to identify perceived barriers to, and enablers of, target behaviours of guideline adherence and managing LBP without X-rays. We conducted thematic analysis of chiropractors' statements into relevant theoretical domains, followed by grouping of similar statements into specific beliefs. Domains key to changing radiographic guideline adherence, LBP imaging behaviours, and/or informing intervention design were identified by noting conflicting beliefs and their reported influence on the target behaviours. RESULTS: Six of the 14 TDF domains were perceived to be important for adherence to radiographic guidelines and managing non-specific LBP without imaging. Participating chiropractors reported varying levels of knowledge and awareness of guidelines for LBP imaging (Knowledge). Many chiropractors based their decision for imaging on clinical presentation, but some relied on "gut feeling" (Memory, attention, and decision processes). While chiropractors thought it was their role to manage LBP without imaging, others believed ordering imaging was the responsibility of other healthcare providers (Social/professional role and identity). Contrasting views were found regarding the negative consequences of imaging or not imaging LBP patients (Beliefs about consequences). Communication was identified as a skill required to manage LBP without imaging (Skills) and a strategy to enable appropriate imaging ordering behaviours (Behavioural regulation). Chiropractors suggested that access to patients' previous imaging and a system that facilitated better interprofessional communication would likely improve their LBP imaging behaviours (Behavioural regulation). CONCLUSION: We identified potential influences, in six theoretical domains, on participating chiropractors' LBP imaging behaviours and adherence to radiographic guidelines. These beliefs may be targets for theory-informed behaviour change interventions aimed at improving these target behaviours for chiropractors in NL.

Patients with low back pain presenting for chiropractic care who want diagnostic imaging are more likely to receive referral for imaging: a cross-sectional study.

BACKGROUND: It is unclear if the use of imaging for low back pain (LBP) is impacted by patient beliefs. This study aimed to: (1) describe beliefs about the importance of imaging and whether patients wanted imaging when presenting for chiropractic care for LBP; (2) describe associations between baseline patient characteristics and imaging beliefs and whether patients wanted imaging; and (3) determine whether patients who believed imaging to be important in the management of LBP, or who wanted to receive imaging, were more likely to receive an imaging referral. METHODS: Cross-sectional observational data was collected between November 2016 to December 2019 from 10 primary care chiropractic clinics in Denmark. Consecutive patients aged 18 or older and presenting with a new episode of LBP were included (N = 2818). Beliefs about the importance of imaging (two questions) and whether imaging was wanted (one question) were collected at the initial visit, together with baseline participant characteristics and whether an imaging referral was provided. Associations between imaging beliefs/desire to receive imaging and participant characteristics were explored using multivariable logistic regression analysis. The relationships between imaging beliefs and desire to receive imaging with subsequent imaging referral were assessed using multivariable logistic regression analysis adjusted for pre-selected confounder variables. RESULTS: Approximately one third of participants believed imaging to be important for the management of LBP (29.5% (95%CI 27.8, 31.3) or 41.5% (95%CI 39.6, 43.3) depending on the two imaging beliefs questions). Approximately one quarter (26.1%, 95%CI 24.5, 27.7) of participants wanted to receive an imaging referral. Participants were more likely to believe in the importance of imaging or want an imaging referral if they had a longer duration of LBP, history of previous imaging for LBP, or a lower completed education level. Participants who wanted imaging at the initial consult were more likely to receive an imaging referral (Odds ratio; 95%CI 1.6; 1.2, 2.1). CONCLUSIONS: Approximately one third of patients presenting for chiropractic care in Denmark believed imaging to be important in the management of LBP. One quarter wanted imaging at the initial consult. Patients' desire for imaging appeared to impact the use of diagnostic imaging.

Improving adherence to acute low back pain guideline recommendations with chiropractors and physiotherapists: the ALIGN cluster randomised controlled trial.

BACKGROUND: Acute low back pain is a common condition, has high burden, and there are evidence-to-practice gaps in the chiropractic and physiotherapy setting for imaging and giving advice to stay active. The aim of this cluster randomised trial was to estimate the effects of a theory- and evidence-based implementation intervention to increase chiropractors' and physiotherapists' adherence to a guideline for acute low back pain compared with the comparator (passive dissemination of the guideline). In particular, the primary aim of the intervention was to reduce inappropriate imaging referral and improve patient low back pain outcomes, and to determine whether this intervention was cost-effective. METHODS: Physiotherapy and chiropractic practices in the state of Victoria, Australia, comprising at least one practising clinician who provided care to patients with acute low back pain, were invited to participate. Patients attending these practices were included if they had acute non-specific low back pain (duration less than 3 months), were 18 years of age or older, and were able to understand and read English. Practices were randomly assigned either to a tailored, multi-faceted intervention based on the guideline (interactive educational symposium plus academic detailing) or passive dissemination of the guideline (comparator). A statistician independent of the study team undertook stratified randomisation using computer-generated random numbers; four strata were defined by professional group and the rural or metropolitan location of the practice. Investigators not involved in intervention delivery were blinded to allocation. Primary outcomes were X-ray referral self-reported by clinicians using a checklist and patient low back pain-specific disability (at 3 months). RESULTS: A total of 104 practices (43 chiropractors, 85 physiotherapists; 755 patients) were assigned to the intervention and 106 practices (45 chiropractors, 97 physiotherapists; 603 patients) to the comparator; 449 patients were available for the patient-level primary outcome. There was no important difference in the odds of patients being referred for X-ray (adjusted (Adj) OR: 1.40; 95% CI 0.51, 3.87; Adj risk difference (RD): 0.01; 95% CI - 0.02, 0.04) or patient low back pain-specific disability (Adj mean difference: 0.37; 95% CI - 0.48, 1.21, scale 0-24). The intervention did lead to improvement for some key secondary outcomes, including giving advice to stay active (Adj OR: 1.96; 95% CI 1.20, 3.22; Adj RD: 0.10; 95% CI 0.01, 0.19) and intending to adhere to the guideline recommendations (e.g. intention to refer for X-ray: Adj OR: 0.27; 95% CI 0.17, 0.44; intention to give advice to stay active: Adj OR: 2.37; 95% CI 1.51, 3.74). CONCLUSIONS: Intervention group clinicians were more likely to give advice to stay active and to intend to adhere to the guideline recommendations about X-ray referral. The intervention did not change the primary study outcomes, with no important differences in X-ray referral and patient disability between groups, implying that hypothesised reductions in health service utilisation and/or productivity gains are unlikely to offset the direct costs of the intervention. We report these results with the caveat that we enrolled less patients into the trial than our determined sample size. We cannot recommend this intervention as a cost-effective use of resources. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609001022257 . Retrospectively registered on 25 November 2009.

Assessment of rapid low-cost isotope (δ15 N, δ18 O) analyses of nitrate in fruit extracts by Ti(III) reduction to differentiate organic from conventional production.

RATIONALE: The isotopic composition (δ15 N, δ18 O) of nitrate in fruits and vegetables differentiates organic from conventional food production practices. Organic systems do not use synthetic nitrate fertilizers high in 18 O and low in 15 N and thereby help reveal producers' fertilization claims. Isotope analyses of nitrate extracted from fruits and vegetables are done by bacterial reduction which is costly and by specialized laboratories. Rapid, low-cost methods are needed to promulgate nitrate isotope analyses of food products to support organic food product certification and to verify the authenticity of production claims. METHODS: Fresh strawberry samples were obtained from certified organic and conventional growers in Andalucía, Spain. We applied a new, rapid, one-step Ti(III) reduction method to convert the nitrate from strawberry extracts to N2 O gas for headspace isotope analyses using isotope-ratio mass spectrometry. Using the Ti(III) reduction method, 70 samples, controls and references were prepared and analyzed for NO3 - , δ15 N and δ18 O per 48 h. We also analyzed extracts and solids for anions and cations and for bulk δ15 N for multivariate chemometric evaluation. RESULTS: The Ti(III)-based isotope analyses of nitrate in strawberry extracts revealed clear differentiation between organic and conventional production with mean δ18 O and δ15 N values of +18.3 ± 1.2 ‰ and +17.6 ± 1.2 ‰ versus +28.2 ± 4.5 ‰ and +14.9 ± 3.0 ‰, respectively. The δ15 N of strawberry dry mass differed slightly (+3.0 ± 1.4 ‰ versus +4.0 ± 1.4 ‰) between organic and conventional samples, respectively. Chemometric analyses of nitrate isotopes and extract chemistry revealed that the δ18 O of nitrate along with δ15 N and Ca2+ fully differentiated organic from conventional strawberry production. CONCLUSIONS: Our results show the Ti(III) reduction method provides a new low-cost and rapid analytical method to facilitate compound-specific δ15 N and δ18 O isotope analyses of nitrate in selected fruit types, and likely other food products, for the purposes of assessing nitrate fertilization practices of organic versus conventional production claims and to support authenticity investigations.

Psychological and behavioural interventions in bipolar disorder that target sleep and circadian rhythms: A systematic review of randomised controlled trials.

Sleep and circadian disruptions are prominent symptoms of bipolar disorder (BD) and potential targets for adjunctive interventions. The aim of this review was to appraise the effectiveness of psychological and behavioural interventions in BD that target sleep and circadian rhythms, as reported by randomised controlled trials. Nineteen studies met the inclusion/exclusion criteria. They were summarised via narrative synthesis and meta-analysis wherever appropriate. Six studies delivered bright light therapy, five interpersonal and social rhythm therapy, two blue-light blocking glasses, one cognitive behavioural therapy for insomnia, one total sleep deprivation, and four combination treatments. More than half of the studies (N = 10, 52 %) did not measure sleep or circadian rhythms despite being the principal target of the intervention. Overall, the evidence base for the effectiveness of these interventions was limited. There was a small number of studies for each intervention, and a lack of consistency in protocols and outcomes. Meta-analysis was possible for the effect of bright light therapy on depression, revealing a medium-to-large post-treatment effect (Nc = 6; g=-0.74 [95 % CI=-1.05 to -0.42], p < 0.001).