Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

Background: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation

The microRNA-29 family in cartilage homeostasis and osteoarthritis

MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways

Nicotine Protects Kidney from Renal Ischemia/Reperfusion Injury through the Cholinergic Anti-Inflammatory Pathway

Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the α7 nicotinic acetylcholine receptor (α7nAChR). Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the α7nAChR, as attested by the absence of protection in α7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-α and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic α7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation

Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

High susceptibility to lipopolysaccharide-induced lethal shock in encephalomyocarditis virus-infected mice

Secondary bacterial infection in humans is one of the pathological conditions requiring clinical attention. In this study, we examined the effect of lipopolysaccharide (LPS) on encephalomyocarditis virus (EMCV) infected mice. All mice inoculated with EMCV at 5 days before LPS challenge died within 24 h. LPS-induced TNF-α mRNA expression was significantly increased in the brain and heart at 5 days after EMCV infection. CD11b+/TLR4+ cell population in the heart was remarkably elevated at 5 days after EMCV infection, and sorted CD11b+ cells at 5 days after EMCV infection produced a large amount of TNF-α on LPS stimulation in vivo and in vitro. In conclusion, we found that the infiltration of CD11b+ cells into infected organs is involved in the subsequent LPS-induced lethal shock in viral encephalomyocarditis. This new experimental model can help define the mechanism by which secondary bacterial infection causes a lethal shock in viral encephalomyocarditis

Trends in suicide in Scotland 1981 – 1999: age, method and geography

BACKGROUND: Male suicide rates continued to increase in Scotland when rates in England and Wales declined. Female rates decreased, but at a slower rate than in England and Wales. Previous work has suggested higher than average rates in some rural areas of Scotland. This paper describes trends in suicide and undetermined death in Scotland by age, gender, geographical area and method for 1981 – 1999. METHODS: Deaths from suicide and undetermined cause in Scotland from 1981 – 1999 were identified using the records of the General Registrar Office. The deaths of people not resident in Scotland were excluded from the analysis. Death rates were calculated by area of residence, age group, gender, and method. Standardised Mortality Ratios (SMRs) and 95% confidence intervals were calculated for rates by geographical area. RESULTS: Male rates of death by suicide and undetermined death increased by 35% between 1981 – 1985 and 1996 – 1999. The largest increases were in the youngest age groups. All age female rates decreased by 7% in the same period, although there were increases in younger female age groups. The commonest methods of suicide in men were hanging, self-poisoning and car exhaust fumes. Hanging in males increased by 96.8% from 45 per million to 89 per million, compared to a 30.7% increase for self-poisoning deaths. In females, the commonest method of suicide was self-poisoning. Female hanging death rates increased in the time period. Male SMRs for 1981 – 1999 were significantly elevated in Western Isles (SMR 138, 95% CI 112 – 171), Highland (135, CI 125 – 147), and Greater Glasgow (120, CI 115 – 125). The female SMR was significantly high only in Greater Glasgow (120, CI 112 – 128). CONCLUSION: All age suicide rates increased in men and decreased in women in Scotland in 1981 – 1999. Previous findings of higher than expected male rates in some rural areas were supported. Rates were also high in Greater Glasgow, one of the most deprived areas of Scotland. There were changes in the methods used, with an increase in hanging deaths in men, and a smaller increase in hanging in women. Altered choice of method may have contributed to the increased male deaths

The working alliance in a randomized controlled trial comparing online with face-to-face cognitive-behavioral therapy for depression

Background: Although numerous efficacy studies in recent years have found internet-based interventions for depression to be effective, there has been scant consideration of therapeutic process factors in the online setting. In face-to face therapy, the quality of the working alliance explains variance in treatment outcome. However, little is yet known about the impact of the working alliance in internet-based interventions, particularly as compared with face-to-face therapy. Methods: This study explored the working alliance between client and therapist in the middle and at the end of a cognitive-behavioral intervention for depression. The participants were randomized to an internet-based treatment group (n = 25) or face-to-face group (n = 28). Both groups received the same cognitive behavioral therapy over an 8-week timeframe. Participants completed the Beck Depression Inventory (BDI) post-treatment and the Working Alliance Inventory at mid- and post- treatment. Therapists completed the therapist version of the Working Alliance Inventory at post-treatment. Results: With the exception of therapists' ratings of the tasks subscale, which were significantly higher in the online group, the two groups' ratings of the working alliance did not differ significantly. Further, significant correlations were found between clients' ratings of the working alliance and therapy outcome at post-treatment in the online group and at both mid- and post-treatment in the face-to-face group. Correlation analysis revealed that the working alliance ratings did not significantly predict the BDI residual gain score in either group. Conclusions: Contrary to what might have been expected, the working alliance in the online group was comparable to that in the face-to-face group. However, the results showed no significant relations between the BDI residual gain score and the working alliance ratings in either group

The Spatial Expansion and Ecological Footprint of Fisheries (1950 to Present)

Using estimates of the primary production required (PPR) to support fisheries catches (a measure of the footprint of fishing), we analyzed the geographical expansion of the global marine fisheries from 1950 to 2005. We used multiple threshold levels of PPR as percentage of local primary production to define ‘fisheries exploitation’ and applied them to the global dataset of spatially-explicit marine fisheries catches. This approach enabled us to assign exploitation status across a 0.5° latitude/longitude ocean grid system and trace the change in their status over the 56-year time period. This result highlights the global scale expansion in marine fisheries, from the coastal waters off North Atlantic and West Pacific to the waters in the Southern Hemisphere and into the high seas. The southward expansion of fisheries occurred at a rate of almost one degree latitude per year, with the greatest period of expansion occurring in the 1980s and early 1990s. By the mid 1990s, a third of the world's ocean, and two-thirds of continental shelves, were exploited at a level where PPR of fisheries exceed 10% of PP, leaving only unproductive waters of high seas, and relatively inaccessible waters in the Arctic and Antarctic as the last remaining ‘frontiers.’ The growth in marine fisheries catches for more than half a century was only made possible through exploitation of new fishing grounds. Their rapidly diminishing number indicates a global limit to growth and highlights the urgent need for a transition to sustainable fishing through reduction of PPR

Internet-based treatment for PTSD reduces distress and facilitates the development of a strong therapeutic alliance: a randomized controlled clinical trial

BACKGROUND: The present study was designed to evaluate the efficacy of an internet-based therapy (Interapy) for Posttraumatic Stress Disorder (PTSD) in a German speaking population. Also, the quality of the online therapeutic relationship, its development and its relevance as potential moderator of the treatment effects was investigated. METHOD: Ninety-six patients with posttraumatic stress reactions were allocated at random to ten sessions of Internet-based cognitive behavioural therapy (CBT) conducted over a 5-week period or a waiting list control group. Severity of PTSD was the primary outcome. Secondary outcome variables were depression, anxiety, dissociation and physical health. Follow-up assessments were conducted at the end of treatment and 3 months after treatment. RESULTS: From baseline to post-treatment assessment, PTSD severity and other psychopathological symptoms were significantly improved for the treatment group (intent-to-treat group x time interaction effect size d = 1.40). Additionally, patients of the treatment condition showed significantly greater reduction of co-morbid depression and anxiety as compared to the waiting list condition. These effects were sustained during the 3-months follow-up period. High ratings of the therapeutic alliance and low drop-out rates indicated that a positive and stable therapeutic relationship could be established online. Significant improvement of the online working alliance in the course of treatment and a substantial correlation between the quality of the online relationship at the end of treatment and treatment outcome emerged. CONCLUSION: Interapy proved to be a viable treatment alternative for PTSD with large effect sizes and sustained treatment effects. A stable and positive online therapeutic relationship can be established through the Internet which improved during the treatment process. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN012606000401550