Effects of a Supplement Containing Cannabidiol (CBD) on Sedation and Ataxia Scores and Health.

Supplements containing Cannabidiol (CBD) are available for horses, however, few studies have been published on their effects on behavior and health parameters. The purpose of this study was to determine if a daily oral supplement containing CBD would cause sedation, ataxia or alterations in other health parameters during administration for 56 days. Twenty clinically healthy adult Thoroughbred horses were housed in stalls. Before treatment was initiated, a complete physical examination, complete blood count (CBC) and biochemical panel were evaluated. In addition, horses were examined for sedation and ataxia using standard scoring systems. Horses were randomly divided into two treatment groups, treated (supplement pellets containing CBD as Hemp Extract, 150 mg) or control (supplement pellets without CBD). Horses were treated daily and sedation and ataxia scores were assigned by two masked observers once weekly for 56 days. Horses were monitored daily for clinical signs or adverse events and body weights were recorded weekly. A CBC and biochemical panel were repeated on days 28 and 56, two hours after administration of the supplement. The supplement was readily consumed by the horses and no adverse effects were seen over the treatment period. Sedation and ataxia scores ranged from zero to two for all horses during the weekly examinations and there was no statistical difference between treatment groups. There were no treatment effects on blood values, including indicators of anemia and blood proteins, liver enzymes, kidney values, electrolytes or calcium. Body weight significantly increased in all horses, by Day 56 compared to Day zero but no treatment by day effect was noted. The CBD supplement (150 mg) was readily consumed and safe and did not result in changes in mentation, gait, or other health parameters, and no adverse clinical signs were observed during 56 days of oral administration.

Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis.

Biologic therapies have transformed the management of psoriasis, but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. Here we perform in-depth immunomonitoring of blood immune cells of 67 patients with psoriasis, before and during therapy with the anti-TNF drug adalimumab, to identify immune mediators of clinical response and evaluate their predictive value. Enhanced NF-κBp65 phosphorylation, induced by TNF and LPS in type-2 dendritic cells (DC) before therapy, significantly correlates with lack of clinical response after 12 weeks of treatment. The heightened NF-κB activation is linked to increased DC maturation in vitro and frequency of IL-17+ T cells in the blood of non-responders before therapy. Moreover, lesional skin of non-responders contains higher numbers of dermal DC expressing the maturation marker CD83 and producing IL-23, and increased numbers of IL-17+ T cells. Finally, we identify and clinically validate LPS-induced NF-κBp65 phosphorylation before therapy as a predictive biomarker of non-response to adalimumab, with 100% sensitivity and 90.1% specificity in an independent cohort. Our study uncovers important molecular and cellular mediators underpinning adalimumab mechanisms of action in psoriasis and we propose a blood biomarker for predicting clinical outcome.

Maternity service organisational interventions that aim to reduce caesarean section: a systematic review and meta-analyses.

BACKGROUND: Caesarean sections (CSs) are associated with increased maternal and perinatal morbidity, yet rates continue to increase within most countries. Effective interventions are required to reduce the number of non-medically indicated CSs and improve outcomes for women and infants. This paper reports findings of a systematic review of literature related to maternity service organisational interventions that have a primary intention of improving CS rates. METHOD: A three-phase search strategy was implemented to identify studies utilising organisational interventions to improve CS rates in maternity services. The database search (including Cochrane CENTRAL, CINAHL, MEDLINE, Maternity and Infant Care, EMBASE and SCOPUS) was restricted to peer-reviewed journal articles published from 1 January 1980 to 31 December 2017. Reference lists of relevant reviews and included studies were also searched. Primary outcomes were overall, planned, and unplanned CS rates. Secondary outcomes included a suite of birth outcomes. A series of meta-analyses were performed in RevMan, separated by type of organisational intervention and outcome of interest. Summary risk ratios with 95% confidence intervals were presented as the effect measure. Effect sizes were pooled using a random-effects model. RESULTS: Fifteen articles were included in the systematic review, nine of which were included in at least one meta-analysis. Results indicated that, compared with women allocated to usual care, women allocated to midwife-led models of care implemented across pregnancy, labour and birth, and the postnatal period were, on average, less likely to experience CS (overall) (average RR 0.83, 95% CI 0.73 to 0.96), planned CS (average RR 0.75, 95% CI 0.61 to 0.93), and episiotomy (average RR 0.84, 95% CI 0.74 to 0.95). Narratively, audit and feedback, and a hospital policy of mandatory second opinion for CS, were identified as interventions that have potential to reduce CS rates. CONCLUSION: Maternity service leaders should consider the adoption of midwife-led models of care across the maternity episode within their organisations, particularly for women classified as low-risk. Additional studies are required that utilise either audit and feedback, or a hospital policy of mandatory second opinion for CS, to facilitate the quantification of intervention effects within future reviews. PROSPERO REGISTRATION: CRD42016039458 ; prospectively registered.

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial.

BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3-5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. FINDINGS: Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1-26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9-30·1), p=0·001. INTERPRETATION: Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. FUNDING: NIHR Health Technology Assessment Programme.

Improving the uptake of preconception care and periconceptional folate supplementation: what do women think?

BACKGROUND: Despite strong evidence of the benefits of preconception interventions to improve pregnancy outcomes, the delivery and uptake of preconception care in general and periconceptional folate supplementation in particular remains low. The aim of this study was to determine women's views of the barriers and enablers to the uptake of preconception care and periconceptional folate supplementation. METHODS: Focus groups were undertaken in 2007 with 17 women of reproductive age (18-45 years). To identify key issues and themes within the data, focus groups were analysed using an inductive process of thematic analysis. RESULTS: Most women were unaware of the need to attend for preconception care and were surprised at the breadth of issues involved. Women also felt general practitioners (GPs) should be more proactive in promoting preconception care availability but acknowledged that they themselves had to be thinking about pregnancy or becoming pregnant to be receptive to it. Barriers to periconceptional folate supplementation included confusion about reasons for use, dose, duration, timing and efficacy of folate use. Enablers included the desire to do anything they could to ensure optimum pregnancy outcomes, and promotional material and letters of invitation from their GP to advise them of the availability and the need for preconception care. CONCLUSION: A number of important barriers and enablers exist for women regarding the delivery and uptake of preconception care and periconceptional folate supplementation. It is essential that these patient perspectives are addressed in both the implementation of evidence based clinical practice guidelines and in the systematic design of an intervention to improve preconception care delivery.

Dispersal of Trichogramma ostriniae (Hymenoptera: Trichogrammatidae) in potato fields.

The dispersal ability of Trichogramma ostriniae Pang and Chen, a biological control agent of Ostrinia nubilalis Hübner, was studied in commercial potato fields on the Eastern Shore of Virginia. The purpose was to quantify dispersal of T. ostriniae after an inundative release to aid in determining the number of release points needed per unit area for effective biological control of O. nubilalis in solanaceous crops. A single release of approximately 0.5 million wasps was made in two spatially separate potato fields in summer 2005 and 2006. Each release area contained 25 monitoring points at distances from 5 to 45 m from the release point bearing a yellow sticky card and O. nubilalis egg sentinels to observe for adult parasitoids and parasitism, respectively. Results showed that movement of T. ostriniae adults from the release point was rapid with individuals captured at 45 m within 1 d of emergence. High rates of parasitization (20-50%) also were observed at this distance, but the levels decreased with increasing distance from the release point. The distances that encompassed 98% recaptured T. ostriniae adults (x(98)) were 27.5 and 12.9 m from the release point in 2005 and 2006, respectively. The (x(98)) distances for parasitization of O. nubilalis were 21-26 m in 2005 and 8-10 m in 2006. However, the highest levels of parasitization in both years occurred nearest the release point. T. ostriniae showed uniform dispersal within an area of approximately 0.1 ha, indicating that multiple release points should be used for effective dispersal of T. ostriniae and control of O. nubilalis in solanaceous crops. Based on the assumption that a distance of 16 m represents the radius around a release point in which T. ostriniae activity was at its maximum, we estimate that approximately 12 release points/ha would be required in potato fields.