Prevention Of Flares Research Articles

Stand-alone Emollient Treatment Reduces Flares After Discontinuation of Topical Steroid Treatment in Atopic Dermatitis: A Double-blind, Randomized, Vehicle-controlled, Left-right Comparison Study

Prevention of the flares is a main goal in the long-term treatment of atopic dermatitis (AD). Therefore we investigated the efficacy of a water-in-oil emollient, containing licochalcone A, omega-6-fatty acids, ceramide 3 and glycerol, for prevention of the flares in adults with mild to moderately severe AD, treated with topical steroids, that led to clearing of the inflammatory lesions and had been discontinued prior to inclusion. The study was a 12-week, double-blind, randomized, vehicle-controlled, left-right comparison test with the number of relapses, defined as re-occurrence of erythema for at least 3 consecutive days, considered the primary outcome. Compared with the vehicle, the active formulation significantly reduced the number of relapses and maintained the barrier homeostasis of the respective arm. To the best of knowledge, this is the first study to show prevention of the AD flares by the use of stand-alone emollient treatment, based on comparison with the corresponding vehicle while excluding concomitant/rescue medications.

A Case-Crossover Study of Urological Chronic Pelvic Pain Syndrome Flare Triggers in the MAPP Research Network

Although many factors have been proposed to trigger symptom exacerbations (flares) in patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, few studies have investigated these factors empirically. Therefore, we embedded a case-crossover study in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain longitudinal study to evaluate a range of patient reported triggers. We assessed exposure to proposed triggers, including diet, physical activities, sedentary behaviors, stress, sexual activities, infection-like symptoms and allergies, by questionnaire a maximum of 3 times when participants reported flares and at 3 randomly selected times. We compared participant preflare to nonflare exposures by conditional logistic regression. In our full analytical sample of 292 participants only 2 factors, including recent sexual activity (OR 1.44, 95% CI 1.06-1.96) and urinary tract infection symptoms (OR 3.39, 95% CI 2.02-5.68), which may overlap with those of flares, were associated with flare onset. On subanalyses restricted to flares with specific suspected triggers additional positive associations were observed for some factors such as certain dietary factors, abdominal muscle exercises, and vaginal infection-like symptoms and fever, but not for other factors (eg stress). Except for sexual activity our findings suggest that patient reported triggers may be individual or group specific, or they may not contribute to flares. These findings suggest caution in following rigid, global flare prevention strategies and support additional research to develop evidence-based strategies.

Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: results from FORTUNE-1, a prospective, multicentre randomised study

ObjectivesTo determine whether febuxostat with stepwise dose increase is as useful as colchicine prophylaxis in reducing gout flares during the initial introduction of urate-lowering therapy in patients with gout in...

Atopic Dermatitis: Early Treatment in Children.

Therapeutic regimens for the treatment and long-term management of AD traditionally had a two-fold objective of decreasing skin inflammation and repairing the defective skin barrier. Essential treatments for AD in children should include topical moisturizers for skin hydration and prevention of flares, topical anti-inflammatory medications (e.g. corticosteroids, calcineurin inhibitors, PDE4 inhibitor), allergen/irritant avoidance, and treatment of skin infections. Treatment regimens should be severity-based, and implemented in a stepwise approach tailored to the individual patient. This stepwise approach includes initial use of emollients, gentle skin care, and escalating to more potent anti-inflammatory treatments as the disease severity increases. Currently available systemic medications should be reserved for the presence of recalcitrance to topical therapies due to associated toxicities. We believe that early treatment of AD is not only essential in treating the skin disease, but also in preventing the development of additional atopic diseases, such as food allergy, asthma and allergic rhinitis. The defective skin barrier of AD permits a route of entry for food and environmental allergens, and upon exposure, keratinocytes secrete TSLP, which activates the TH2 pathway. This TH2 differentiation sets off the atopic march and the subsequent diseases that are seen. This review highlights treatment options and strategies in pediatric AD therapy with an emphasis on early therapy. Supporting evidence on the efficacy and safety of each intervention will be discussed.

Performance and Tolerability of the Moisturizers Cetaphil® and Excipial® in Atopic Dermatitis: What is the Evidence Based on Randomized Trials?

IntroductionMoisturizers play a prominent role in the management of atopic dermatitis by improving the impaired skin barrier function and enhancing skin hydration. Their efficacy was evaluated in a recently published Cochrane Review ‘Emollients and moisturizers for eczema’.ObjectiveIn the present review, we summarize the performance and safety of Cetaphil® and Excipial® moisturizing products.MethodsThis review was carried out in compliance with standard Cochrane methodological procedures, which means independent study selection, data extraction, assessment of risk of bias, and analyses by two review authors. The quality of evidence for the predefined outcomes was rated with the GRADE approach. The prespecified outcomes of the review included participant assessments, satisfaction, adverse events, investigator assessments, prevention of flares, change in use of topical active treatment, skin barrier function and quality of life.ResultsFour randomized controlled studies examining these moisturizers were included in the previously published Cochrane Review. For the performance and tolerability of these moisturizers, there was very low to moderate quality evidence for the prespecified outcomes.ConclusionThe results from these four studies are in line with those of the Cochrane Review that moisturizers themselves have beneficial effects, and that combining moisturizers with active topical treatment produced better results when compared to active topical treatment alone.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-017-0184-3) contains supplementary material, which is available to authorized users.

Topical Therapy of AD: How to Reach Better Results

This review summarizes the current state-of-the-art in topical therapy of atopic dermatitis (atopic eczema), a clinically defined, highly variable, pruritic chronic skin disease characterized by age-dependent distribution patterns and lesion morphology. Current emollient treatment should be performed at least once daily, using about 250 g of emollient per week. Commonly used topical anti-inflammatory treatment is based on topical corticosteroids and the topical calcineurin inhibitors tacrolimus and pimecrolimus. Acute intervention for flares works best with topical corticosteroid creams, which may be applied in a wet-wrap technique. Proactive therapy is defined as long-term intermittent, anti-inflammatory therapy of the frequently relapsing problem zones. This new regimen works with mid-potent topical corticosteroid (TCS) and tacrolimus ointment, may prevent flares, improves the quality of life significantly, and is cost-effective. Topical phosphodiesterase 4 inhibitors may become a treatment alternative for mild to moderate forms. All management should consider the above findings and individual course of disease, with special aim of flare prevention.

Evaluation of modified nasal to oral endotracheal tube switch—For modified alar base cinching after maxillary orthognathic surgery

BackgroundSoft tissue changes secondary to Maxillary orthognathic surgery are many fold. The alar flare is one among them, which affects the appearance of the patient. Cinch suture has been used to prevent alar flare; but the presence of anaesthetic tube hinders cinching. So, the study was aimed to assess an efficacy of modified nasal to oral tube switch technique for modified alar cinching to prevent alar flare after orthognathic and nasal corrective surgeries. Materials and methodsPatients were randomly allocated in each group, who underwent modified alar base cinching with and without nasal to oral tube switch. Changes in alar base width, upper lip length was measured with Digital Vernier Caliper and nasolabial angle (Cotg-Sn-Ls) on lateral cephalogram at 1st, 3rd, 6th, and 12th months after surgery. The time taken and ease of tube switch were noted. The data obtained were tabulated and interpreted using a test of significance. ResultsStudy results showed no statistical significant difference in perinasal soft changes among both groups. But tube switch appears to be beneficial to prevent alar flare. ConclusionModified alar base cinching was performed effectively in patients with a modified tube switch technique. It increased positive results in comparison with non-shift. The technique of tube switch used is effective in prevention of alar flare. Because of small sample size and limited period of follow up, our study suggests multi centre, randomized studies to know the technical difficulties of tube switch for cinching and aesthetic results with varying anaesthetist and the surgeon’s experience.

Prevention of Flares in Children with Atopic Dermatitis with Regular Use of an Emollient Containing Glycerol and Paraffin: A Randomized Controlled Study

Emollients are part of the standard treatment for atopic dermatitis (AD), although there is limited evidence that regular use of emollients as management therapy reduces the frequency of flares and corticosteroid consumption. The objective of this study was to evaluate the benefit of emollient use in the management of mild to moderate AD in children by assessing the ability of two different emollients (particularly V0034CR) to prevent flares and to reduce the use of corticosteroids. In this randomized, open-label study, patients with a current flare were treated with a potent topical corticosteroid. After flare resolution, patients were centrally randomized to V0034CR emollient, reference emollient, or no emollient (1:1:1 ratio) for 12 weeks. New flares were medically assessed before being treated with a moderately potent corticosteroid. A total of 335 children 2 to 6 years of age were randomized. At 12 weeks, the percentage of patients with one or more flares was statistically significantly lower with V0034CR (35.1%) than without emollient (67.6%; p < 0.001). Fewer patients treated with V0034CR required any corticosteroids or immunosuppressants (23.6%) than patients with no emollient (43.3%) at 12 weeks. The difference was significant at all time points (p = 0.002). Patients treated with emollients had a longer time to first flare, fewer flares, higher complete remission rates, less corticosteroid consumption, lower Investigator Global Assessment scores, and lower Scoring Atopic Dermatitis scores than those who were not. V0034CR was well tolerated, with no specific safety concerns. Regular emollient use in children with mild to moderate AD reduces flares and corticosteroid consumption.

Emollients and moisturisers for eczema.

Emollients and moisturisers for eczema.

Flares in systemic lupus erythematosus: diagnosis, risk factors and preventive strategies.

Despite advances in the treatment, patients with systemic lupus erythematosus (SLE) often experience disease exacerbations (flares) of varying severity. Their diagnosis is primarily made on clinical grounds after exclusion of other diseases or disturbances, primarily infections, and can be assisted by the use of validated clinical indices. Serological tests such as serum complement fractions and anti-dsDNA autoantibodies, are helpful in monitoring SLE activity, but they lack high diagnostic accuracy. Flares are more frequent in patients with persistent immunological and clinical activity, and have been described as significant risk factor for development of irreversible end-organ damage. Accordingly, prevention of flares has been recognized as a distinct therapeutic target in SLE and involves adequate control of disease activity, use of hydroxychloroquine, maintaining immunosuppressive or biologic therapy for several years, and avoiding non-compliance issues. The future holds promise for the discovery of biomarkers that will accurately predict or diagnose SLE flares, thus allowing for the implementation of patient-tailored preventive strategies.

Economics of gas to wire technology applied in gas flare management

Our environment is increasingly being endangered by the introduction of greenhouse gases which are continuously produced from gas flaring processes. Currently, total volume of gas flared globally amounts to 100 billion cubic meters (BCM) annually. Nigeria flares about 18.27 BCM and loses approximately $2 billion yearly. This statistics indicates the urgent need to conduct research aimed at addressing both the environmental impact of gas flaring and the economic implications. This research studies the economic viability of using gas to wire (GTW) technology as an integral component of gas flare management. The investigation critically evaluates the cost implications and impact of the GTW technology. The research method involves the interview of key experts and practitioners in the field. The interviews are structured to obtain information on the total volume of gas produced, utilised and flared in two major gas and electricity producing firms in Nigeria. The data obtained show that the gas producing company flares about 8.33% of its total production which is in excess of the 6.6 million cubic meters (MCM) utilised daily. This study demonstrates that in the Nigerian oil and gas sector, one unit of gas turbine having 0.93 MCM gas consumption capacity generates 150MW of electricity daily. It is found in result evaluation that 50 turbines are sufficient to consume an average of 46.5 MCM of gas daily to generate 7500MW of electricity. Economic analysis shows that there is an annual net profit of £2.68 billion gained from flare prevention and overall environmental protection.

Treat-to-target (T2T) recommendations for gout

ObjectivesThe treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of...

Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial

Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids. We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged ≥18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov number NCT01124838. Between Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8·3 months; hazard ratio 0·57, 95% CI 0·39-0·84; p=0·004). The 40th percentile for time to treatment failure was 4·8 months in the placebo group and 10·2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group). Adalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis. AbbVie.

Using the topical moisturizing agent in children whit atopic dermatitis is the cornerstone of the successful preventive treatment

Summary.This article describes the management of pediatric atopic dermatitis (AD) of all severities and covers the use of nonpharmacologic approaches (eg, moisturizers, bathing practices, and wet wraps). Atopic dermatitis is a chronic, pruritic, inflammatory dermatitis that affects up to 25% of children. Xerosis is one of the cardinal clinical features of AD and results from a dysfunctional epidermal barrier. Topical moisturizers are used to combat xerosis and transepidermal water loss, with traditional agents containing different amounts of emollient, occlusive, and/or humectant ingredients. Although they often include water as well, this only delivers a transient effect, whereas the other components provide the main benefits.Moisturizers can be the main primary treatment for mild disease and should be a part of the regimen for moderate and severe disease. They are also an important component of maintenance treatment and prevention of flares. Moisturizers are therefore a cornerstone of AD therapy and should be included in to the management plans especially in children.There are a few systematic studies to define an optimal amount or frequency of application of moisturizers. It is generally thought that liberal and frequent reapplication is necessary to reduce xerosis to minimal. Traditional moisturizers are formulated into a variety of delivery systems, including creams, ointments, oils, gels, and lotions. Although most ointments have the advantage of not containing preservatives, which may cause stinging when applied to inflamed skin, they may be too greasy for some patients with AD. Lotions have a higher water content that can evaporate and may be less ideal in those with significant xerosis.Head-to-head trials between specific moisturizing products are few, and the published information has not demonstrated the preference of one emollient to others. Therefore, the choice of moisturizing agent highly depends on the individual preference. In our clinic we also have a long experience of using emollients in children with AD, including young children. Very often in our practice we use Topicrem, Physiogel and Oilatum. Analyzing efficiency of each, we have identified 24 children aged from 6 months to 2 years with a diagnosis of atopic dermatitis in remission and divided them into three equal groups. Observation period lasted 14 days. Evaluation of efficacy was performed using SCORAD index, determined not only objective criteria but also subjective marks sleep disorders and severity of itching. During the study, accurately clinical observation refers to the third level of evidence (C), we were able to demonstrate again the high efficiency of moisturizers. Analyzing the results, first of all, we want to emphasize the good clinical efficacy of all three emollients.To conclude, the choice of moisturizers demands an individual approach. The ideal agent should be safe, effective, inexpensive, and free of additives, fragrances, perfumes, and other potentially sensitizing agents.

Scoping systematic review of treatments for eczema

BackgroundEczema is a very common chronic inflammatory skin condition.ObjectivesTo update the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) systematic review of treatments for atopic eczema, published in 2000, and to inform health-care professionals, commissioners and patients about key treatment developments and research gaps.Data sourcesElectronic databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Skin Group Specialised Register, Latin American and Caribbean Health Sciences Literature (LILACS), Allied and Complementary Medicine Database (AMED) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from the end of 2000 to 31 August 2013. Retrieved articles were used to identify further randomised controlled trials (RCTs).Review methodsStudies were filtered according to inclusion criteria and agreed by consensus in cases of uncertainty. Abstracts were excluded and non-English-language papers were screened by international colleagues and data were extracted. Only RCTs of treatments for eczema were included, as other forms of evidence are associated with higher risks of bias. Inclusion criteria for studies included availability of data relevant to the therapeutic management of eczema; mention of randomisation; comparison of two or more treatments; and prospective data collection. Participants of all ages were included. Eczema diagnosis was determined by a clinician or according to published diagnostic criteria. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. We used a standardised approach to summarising the data and the assessment of risk of bias and we made a clear distinction between what the studies found and our own interpretation of study findings.ResultsOf 7198 references screened, 287 new trials were identified spanning 92 treatments. Trial reporting was generally poor (randomisation method: 2% high, 36% low, 62% unclear risk of bias; allocation concealment: 3% high, 15% low, 82% unclear risk of bias; blinding of the intervention: 15% high, 28% low, 57% unclear risk of bias). Only 22 (8%) trials were considered to be at low risk of bias for all three criteria. There was reasonable evidence of benefit for the topical medications tacrolimus, pimecrolimus and various corticosteroids (with tacrolimus superior to pimecrolimus and corticosteroids) for both treatment and flare prevention; oral ciclosporin; oral azathioprine; narrow band ultraviolet B (UVB) light; Atopiclair™ and education. There was reasonable evidence to suggest no clinically useful benefit for twice-daily compared with once-daily topical corticosteroids; corticosteroids containing antibiotics for non-infected eczema; probiotics; evening primrose and borage oil; ion-exchange water softeners; protease inhibitor SRD441 (Serentis Ltd); furfuryl palmitate in emollient; cipamfylline cream; andMycobacterium vaccaevaccine. Additional research evidence is needed for emollients, bath additives, antibacterials, specialist clothing and complementary and alternative therapies. There was no RCT evidence for topical corticosteroid dilution, impregnated bandages, soap avoidance, bathing frequency or allergy testing.LimitationsThe large scope of the review coupled with the heterogeneity of outcomes precluded formal meta-analyses. Our conclusions are still limited by a profusion of small, poorly reported studies.ConclusionsAlthough the evidence base of RCTs has increased considerably since the last NIHR HTA systematic review, the field is still severely hampered by poor design and reporting problems including failure to register trials and declare primary outcomes, small sample size, short follow-up duration and poor reporting of risk of bias. Key areas for further research identified by the review include the optimum use of emollients, bathing frequency, wash products, allergy testing and antiseptic treatments. Perhaps the greatest benefit identified is the use of twice weekly anti-inflammatory treatment to maintain disease remission. More studies need to be conducted in a primary care setting where most people with eczema are seen in the UK. Future studies need to use the same core set of outcomes that capture patient symptoms, clinical signs, quality of life and the chronic nature of the disease.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

Simplified Technique to Change the Endotracheal Tube from Nasal to Oral Cavity.

We introduce modified nasal to oral tube switch technique for modified alar cinching to prevent alar flare after orthognathic and nasal corrective surgeries. The technique is beneficial to prevent alar flare. Modified alar base cinching is effective in patients with modified tube switch technique. It increased positive results. The technique of tube switch is effective in prevention of alar flare. We suggest multi center randomized studies to know the technical difficulties of tube switch for cinching.

ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients.

Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic inflammatory skin disease of children and adults. The diagnosis is made using evaluated clinical criteria. Disease activity is best measured with a composite score assessing both objective signs and subjective symptoms, such as SCORAD. The management of AD must consider the clinical and pathogenic variabilities of the disease and also target flare prevention. Basic therapy includes hydrating topical treatment, as well as avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment of visible skin lesions is based on topical glucocorticosteroids and the topical calcineurin inhibitors tacrolimus and pimecrolimus. Topical calcineurin inhibitors are preferred in sensitive locations. Tacrolimus and mid-potent steroids are proven for proactive therapy, which is long-term intermittent anti-inflammatory therapy of the frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is indicated for severe refractory cases. Biologicals targeting key mechanisms of the atopic immune response are promising emerging treatment options. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) may diminish pruritus, but do not have sufficient effect on lesions. Adjuvant therapy includes UV irradiation, preferably UVA1 or narrow-band UVB 311 nm. Dietary recommendations should be patient specific and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. 'Eczema school' educational programmes have been proven to be helpful for children and adults.

A Primary Care Perspective on Gout

Gout causes patients’ significant morbidity, work-related disability, loss of productivity, increased health care costs, and even all-cause hospital admissions. As a result, primary care providers must be armed with the knowledge to properly diagnose and manage gout. While many aspects of care remain the same, some key updates that primary care providers must consider when treating their patients with gout will be discussed. In this perspective we will highlight and discuss acceptable circumstances for empiric treatment, renewed emphasis on treat to target, access to commonly used medications, recommended first line agents, and the role of primary care physicians in gout flare prevention among other topics. These strategies will aid primary care physicians treat all but the most complex cases of gout.

Efficacy of proactive long-term maintenance therapy of canine atopic dermatitis with 0.0584% hydrocortisone aceponate spray: a double-blind placebo controlled pilot study.

Long-term remission between flares of canine atopic dermatitis (CAD) can be difficult to achieve. Therefore, additional strategic forms of treatment are needed in order to target flare prevention. The concept of proactive therapy is recommended in the European guidelines for the treatment of human atopic eczema. To evaluate the efficacy of a proactive treatment regimen with a 0.0584% hydrocortisone aceponate (HCA) spray for CAD. Client-owned dogs with spontaneous atopic dermatitis (AD) (n = 41). This pilot study was conducted as a randomised, placebo-controlled, double-blinded clinical trial with an end-point of treatment failure. Dogs were treated once daily to remission, then randomly assigned to receive either the HCA spray (n = 21) or a placebo (n = 20) spray on two consecutive days each week. All dogs were on appropriate flea control. No topical or systemic anti-inflammatory or antimicrobial agents were permitted. Intention-to-treat analysis was used. At Day 0, all the dogs were in remission or had mild AD based on their Canine Atopic Dermatitis Extent and Severity Index, version 3 (CADESI-03) scores. The time to relapse was significantly higher in the HCA group (median 115 d; range 31-260 d) compared to the placebo group (median 33 d; range 15-61 d) (P < 0.0001). No adverse events were attributable to the HCA spray. Four dogs were lost to follow-up and four were withdrawn after receiving prohibited medication. These results indicate that proactive long-term therapy of CAD with an HCA spray administered on two consecutive days each week is effective and well-tolerated.

Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial

Pain flare occurs after palliative radiotherapy, and dexamethasone has shown potential for prevention of such flare. We aimed to compare the efficacy of dexamethasone with that of placebo in terms of reduction of incidence of pain flare. In this double-blind, randomised, placebo-controlled phase 3 trial, patients from 23 Canadian centres were randomly allocated (1:1) with a web-based system and minimisation algorithm to receive either two 4 mg dexamethasone tablets or two placebo tablets taken orally at least 1 h before the start of radiation treatment (a single 8 Gy dose to bone metastases; day 0) and then every day for 4 days after radiotherapy (days 1-4). Patients were eligible if they had a non-haematological malignancy and bone metastasis (or metastases) corresponding to the clinically painful area or areas. Patients reported their worst pain scores and opioid analgesic intake before treatment and daily for 10 days after radiation treatment. They completed the European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C15-PAL, the bone metastases module (EORTC QLQ-BM22), and the Dexamethasone Symptom Questionnaire at baseline, and at days 10 and 42 after radiation treatment. Pain flare was defined as at least a two-point increase on a scale of 0-10 in the worst pain score with no decrease in analgesic intake, or a 25% or greater increase in analgesic intake with no decrease in the worst pain score from days 0-10, followed by a return to baseline levels or below. Primary analysis of incidence of pain flare was by intention-to-treat (patients with missing primary data were classified as having pain flare). This study is registered with ClinicalTrials.gov, number NCT01248585, and is completed. Between May 30, 2011, and Dec 11, 2014, 298 patients were enrolled. 39 (26%) of 148 patients randomly allocated to the dexamethasone group and 53 (35%) of 150 patients in the placebo group had a pain flare (difference 8·9%, lower 95% confidence bound 0·0, one-sided p=0·05). Two grade 3 and one grade 4 biochemical hyperglycaemic events occurred in the dexamethasone group (without known clinical effects) compared with none in the placebo group. The most common adverse events were bone pain (61 [41%] of 147 vs 68 [48%] of 143), fatigue (58 [39%] of 147 vs 49 [34%] of 143), constipation (47 [32%] of 147 vs 37 [26%] of 143), and nausea (34 [23%] of 147 vs 34 [24%] of 143), most of which were mild grade 1 or 2. Dexamethasone reduces radiation-induced pain flare in the treatment of painful bone metastases. The NCIC CTG's programmatic grant from the Canadian Cancer Society Research Institute.