Basophil sensitivity reflects long-term clinical outcome of subcutaneous immunotherapy in grass pollen-allergic patients.

BACKGROUND: Allergic rhinoconjunctivitis is a public health problem. Allergen Immunotherapy is an effective and safe treatment, that modifies the natural course of allergic disease and induces long-term tolerance. OBJECTIVE: To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue. METHODS: Adults suffering from allergic rhinoconjunctivitis due to grass pollen allergy were randomized to receive subcutaneous immunotherapy (n = 18) or to an open control group (n = 6). Patients reported daily symptom and medication scores and weekly rhinitis related quality of life scores during four pollen seasons. Biomarkers were measured every 3 months for three years treatment and every 6 months in the follow-up year. Nasal and cutaneous allergen challenge tests were performed annually. Leukocyte subsets were assessed in nasal mucosa biopsies at baseline and after treatment. RESULTS: Subcutaneous immunotherapy led to a 447-fold decrease in basophil sensitivity during the first treatment year. This remained 100-fold lower than baseline during the 3 year-treatment period and 10-fold lower during the follow-up year (n = 18, P = .03). Decrease in basophil sensitivity after three weeks of treatment predicted long-term improvement in seasonal combined symptom and medication scores (á¿¥=-0.69, P = .0027) during three years of treatment. AUC of IgE-blocking factor correlated to nasal allergen challenge (á¿¥ = 0.63, P = .0012) and SPT (á¿¥ = 0.45, P = .03). Plasma cell numbers in the nasal mucosa increased during treatment (P = .02). CONCLUSION: Decrease in basophil sensitivity after three weeks of subcutaneous allergen immunotherapy predicted the clinical outcome of this treatment.

Evaluating the effect on asthma quality of life of added reflexology or homeopathy to conventional asthma management - an investigator-blinded, randomised, controlled parallel group study.

BACKGROUND: Asthma is a common chronic disease worldwide without any known cure. Despite remarkable improvement in asthma treatment, better education and guideline implementation strategies, there is growing interest in using complementary and alternative medicine, like reflexology and homeopathy. However, evidence supporting the effectiveness of homeopathy and reflexology in asthma treatment is not available. OBJECTIVE: The aim of this study was to evaluate the effect of reflexology and homeopathy as adjunctive therapies in asthma. METHODS: In a single centre, randomised, investigator blinded, controlled study 86 asthma patients were enrolled. They were assigned to one of three study groups (conventional treatment alone or conventional treatment with addition of either homeopathy or reflexology). All patients received their asthma treatment during the study and were followed as usual by their general practitioner. The study assignment group of individual patients were blinded to the investigators, who made the clinical evaluation of asthma control. The primary outcome was the change in the asthma quality of life questionnaire (AQLQ) scores after 26 weeks. Secondary outcomes included asthma control questionnaire, EuroQol, forced expiratory volume in 1 sec, morning and evening peak expiratory flow, asthma symptoms, rescue medication use, and total medication score. RESULTS: Minor improvements in the AQLQ score were observed in all three groups. However, no statistically significant changes in AQLQ scores were seen within or between groups. Likewise, secondary outcomes did not differ between groups. CONCLUSIONS: In this study, the addition of homeopathy or reflexology to conventional treatment did not result in improved quality of life in asthma.

The impact of reflexology and homeopathy added to conventional asthma treatment on markers of airway inflammation - a randomised study.

Background: Asthma is a common chronic airway disease associated with hyperresponsiveness and airway inflammation. Anti-inflammatory medication especially inhaled corticosteroids are important for control of airway inflammation, decrease of airway hyperresponsiveness and lung function variability, reduce asthma symptoms, and improve lung function as well as quality of life. Most studies investigating the influence of complementary and alternative medicine (CAM) in asthma measure clinical effectiveness, but only few evaluate the impact on markers of airway inflammation. Objective: The aim of this study was to investigate the effect of reflexology and homeopathy added to conventional treatment on different markers of airway inflammation in asthma. Methods: Eighty-four patients with asthma were randomized to receive conventional treatment alone or conventional treatment with addition of homeopathy or reflexology in a single center, investigator blinded, controlled, one-year trial. During the study period, patients regularly consulted their general practitioner for evaluation and asthma treatment. At randomization, and after 6 and 12 months, methacholine challenge test and measurement of exhaled nitric oxide were performed. Blood samples were collected for eosinophil count and measurement of serum eosinophil cationic protein. Results: No significant differences between groups for any of the inflammatory markers were demonstrated. Methacholine responsiveness improved in all three groups but improvements were not statistically significant within and between groups. Conclusions: This randomized controlled study of reflexology and homeopathy failed to show significant improvement on selected markers of inflammation and airway hyperresponsiveness in asthma.

Who benefits from adolescent sleep interventions? Moderators of treatment efficacy in a randomized controlled trial of a cognitive-behavioral and mindfulness-based group sleep intervention for at-risk adolescents.

BACKGROUND: The aim of this study was to test moderators of therapeutic improvement in an adolescent cognitive-behavioral and mindfulness-based group sleep intervention. Specifically, we examined whether the effects of the program on postintervention sleep outcomes were dependent on participant gender and/or measures of sleep duration, anxiety, depression, and self-efficacy prior to the interventions. METHOD: Secondary analysis of a randomized controlled trial conducted with 123 adolescent participants (female = 59.34%; mean age = 14.48 years, range 12.04-16.31 years) who had elevated levels of sleep problems and anxiety symptoms. Participants were randomized into either a group sleep improvement intervention (n = 63) or group active control 'study skills' intervention (n = 60). The sleep intervention ('Sleep SENSE') was cognitive behavioral in approach, incorporating sleep education, sleep hygiene, stimulus control, and cognitive restructuring, but also had added anxiety-reducing, mindfulness, and motivational interviewing elements. Components of the active control intervention ('Study SENSE') included personal organization, persuasive writing, critical reading, referencing, memorization, and note taking. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Spence Children's Anxiety Scale (SCAS), Center for Epidemiologic Studies Depression Scale (CES-D), and General Self-Efficacy Scale (GSE) and wore an actigraph and completed a sleep diary for five school nights prior to the interventions. Sleep assessments were repeated at postintervention. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001177842; http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12612001177842&isBasic=True). RESULTS: The results showed that compared with the active control intervention, the effect of the sleep intervention on self-reported sleep quality (PSQI global score) at postintervention was statistically significant among adolescents with relatively moderate to high SCAS, CES-D, and GSE prior to the intervention, but not among adolescents with relatively low SCAS, CES-D, and GSE prior to the intervention. The results were consistent across genders. However, the effects of the sleep intervention on actigraphy-measured sleep onset latency and sleep diary-measured sleep efficiency at postintervention were not dependent on actigraphy-measured total sleep time, SCAS, CES-D, or GSE prior to the intervention. CONCLUSIONS: This study provides evidence that some sleep benefits of adolescent cognitive-behavioral sleep interventions are greatest among those with higher levels of anxiety and depressive symptoms, suggesting that this may be an especially propitious group to whom intervention efforts could be targeted. Furthermore, adolescents with lower levels of self-efficacy may need further targeted support (e.g. additional motivational interviewing) to help them reach treatment goals.

A cognitive-behavioral and mindfulness-based group sleep intervention improves behavior problems in at-risk adolescents by improving perceived sleep quality.

OBJECTIVE: The aim of this study was to test whether a cognitive-behavioral and mindfulness-based group sleep intervention would improve behavior problems in at-risk adolescents, and whether these improvements were specifically related to improvements in sleep. METHOD: Secondary analysis of a randomized controlled trial conducted with 123 adolescent participants (female = 60%; mean age = 14.48, range 12.04-16.31 years) who had high levels of sleep problems and anxiety symptoms. Participants were randomized into either a sleep improvement intervention (n = 63) or an active control "study skills" intervention (n = 60). Participants completed sleep and behavior problems questionnaires, wore an actiwatch and completed a sleep diary for five school nights, both before and after the intervention. RESULTS: Parallel multiple mediation models showed that postintervention improvements in social problems, attention problems, and aggressive behaviors were specifically mediated by moderate improvements in self-reported sleep quality on school nights, but were not mediated by moderate improvements in actigraphy-assessed sleep onset latency or sleep diary-measured sleep efficiency on school nights. CONCLUSION: This study provides evidence, using a methodologically rigorous design, that a cognitive-behavioral and mindfulness-based group sleep intervention improved behavior problems in at-risk adolescent by improving perceived sleep quality on school nights. These findings suggest that sleep interventions could be directed towards adolescents with behavior problems. CLINICAL TRIAL REGISTRATION: This study was part of The SENSE Study (Sleep and Education: learning New Skills Early). URL: ACTRN12612001177842; http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12612001177842&isBasic=True.

The SENSE Study: Treatment Mechanisms of a Cognitive Behavioral and Mindfulness-Based Group Sleep Improvement Intervention for At-Risk Adolescents.

Objectives: The aim of this study was to test whether a cognitive behavioral and mindfulness-based group sleep intervention would improve sleep and anxiety on school nights in a sample of at-risk adolescents. We also examined whether benefits to sleep and anxiety would be mediated by improvements in sleep hygiene awareness and presleep hyperarousal. Methods: Secondary analysis of a randomized controlled trial conducted with 123 adolescent participants (female = 60%; mean age = 14.48) who had high levels of sleep problems and anxiety symptoms. Participants were randomized into a sleep improvement intervention (n = 63) or active control "study skills" intervention (n = 60). Preintervention and postintervention, participants completed the Pittsburgh Sleep Quality Index (PSQI), Spence Children's Anxiety Scale (SCAS), Sleep Beliefs Scale (SBS), and Presleep Hyperarousal Scale (PSAS) and wore an actiwatch and completed a sleep diary for five school nights. Results: The sleep intervention condition was associated with significantly greater improvements in actigraphy-measured sleep onset latency (SOLobj), sleep diary measured sleep efficiency (SEsubj), PSQI, SCAS, SBS, and PSAS, with medium to large effect sizes. Improvements in the PSQI and SCAS were specifically mediated by the measured improvements in the PSAS that resulted from the intervention. Improvements in SOLobj and SEsubj were not specifically related to improvements in any of the putative treatment mechanisms. Conclusions: This study provides evidence that presleep arousal but not sleep hygiene awareness is important for adolescents' perceived sleep quality and could be a target for new treatments of adolescent sleep problems.

Pharmacokinetic Profile of Oral Magnesium Hydroxide.

Despite the presumption of a beneficial effect of magnesium (Mg) supplementation on various diseases, little is known concerning the pharmacokinetics of Mg hydroxide. This study was designed to provide a pharmacokinetic profile of Mg hydroxide after a single oral dose. Ten healthy male adults participated in this cross-over study with three 24-hr study days. Interventions were (i) none (baseline), (ii) oral intake of three (3 × 360 mg) tablets of Mg hydroxide (Mablet® ) and (iii) IV bolus infusion of 2 g Mg sulphate (index drug). Blood samples were collected before the single dose, after (i.e. after treatment administration) 15, 30, 60, 90 and 120 min. and after 3, 4, 6, 8, 12 and 24 hr. Urine was collected in four 6-hr periods per study day. Blood (N = 10) and urine (N = 6) Mg were analysed by descriptive statistics. Bioavailability was 14.9% (CI: 8.3; 26.8), blood clearance was 5.1 L/hr (CI: 2.1; 17.0), apparent volume of distribution was 60.2 L (CI: 35.6; 102.0), elimination constant was 0.08 per hour (CI: 0.05; 0.14), half-life was 8.3 hr (CI: 4.8; 14.1), Cmax was 0.11 mmol/L (CI: 0.07; 0.14), and AUC[0-24] was 92.3 mmol/L × min. (CI: 45.5; 139.1). Urine Mg excretion augmented by 17.7% (CI: 8.9; 35.0) from baseline. No severe side effects were observed. The bioavailability of Mg hydroxide was 15%, and it constitutes a clinically relevant option for oral Mg supplementation. No severe side effects were seen.

Fish oil supplementation during pregnancy and allergic respiratory disease in the adult offspring.

BACKGROUND: Maternal supplementation with long-chain n-3 polyunsaturated fatty acids can have immunologic effects on the developing fetus through several anti-inflammatory pathways. However, there is limited knowledge of the long-term programming effects. OBJECTIVE: In a randomized controlled trial from 1990 with 24 years of follow-up, our aim was to determine whether supplementation with 2.7 g of long-chain n-3 polyunsaturated fatty acids in pregnancy can reduce the risk of asthma in offspring and allergic respiratory disease. METHODS: The randomized controlled trial included 533 women who were randomly assigned to receive fish oil during the third trimester of pregnancy, olive oil, or no oil in the ratio 2:1:1. The offspring were followed in a mandatory national prescription register, with complete follow-up for prescriptions related to the treatment of asthma and allergic rhinitis as primary outcomes. Furthermore, the offspring were invited to complete a questionnaire (74% participated) and attend a clinical examination (47% participated) at age 18 to 19 years. RESULTS: In intention-to-treat analyses the probability of having had asthma medication prescribed was significantly reduced in the fish oil group compared with the olive oil group (hazard ratio, 0.54, 95% CI, 0.32-0.90; P = .02). The probability of having had allergic rhinitis medication prescribed was also reduced in the fish oil group compared with the olive oil group (hazard ratio, 0.70, 95% CI, 0.47-1.05; P = .09), but the difference was not statistically significant. Self-reported information collected at age 18 to 19 years supported these findings. No associations were detected with respect to lung function outcomes or allergic sensitization at 18 to 19 years of age. CONCLUSION: Maternal supplementation with fish oil might have prophylactic potential for long-term prevention of asthma in offspring.

The SENSE study: Post intervention effects of a randomized controlled trial of a cognitive-behavioral and mindfulness-based group sleep improvement intervention among at-risk adolescents.

OBJECTIVE: Sleep problems are a major risk factor for the emergence of mental health problems in adolescence. The aim of this study was to investigate the post intervention effects of a cognitive-behavioral/mindfulness-based group sleep intervention on sleep and mental health among at-risk adolescents. METHOD: A randomized controlled trial (RCT) was conducted across High schools in Melbourne, Australia. One hundred forty-four adolescents (aged 12-17 years) with high levels of anxiety and sleeping difficulties, but without past or current depressive disorder, were randomized into either a sleep improvement intervention or an active control 'study skills' intervention. Both programs consisted of 7 90-min-long group sessions delivered over 7 weeks. One hundred twenty-three participants began the interventions (female = 60%; mean age = 14.48, SD = 0.95), with 60 in the sleep condition and 63 in the control condition. All participants were required to complete a battery of mood and sleep questionnaires, 7 days of wrist actigraphy (an objective measure of sleep), and sleep diary entry at pre- and-post intervention. RESULTS: The sleep intervention condition was associated with significantly greater improvements in subjective sleep (global sleep quality [with a medium effect size], sleep onset latency, daytime sleepiness [with small effect sizes]), objective sleep (sleep onset latency [with a medium effect size]), and anxiety (with a small effect size) compared with the control intervention condition. CONCLUSION: The SENSE study provides evidence that a multicomponent group sleep intervention that includes cognitive-behavioral and mindfulness-based therapies can reduce sleep initiation problems and related daytime dysfunction, along with concomitant anxiety symptoms, among at-risk adolescents. (PsycINFO Database Record

SQ grass sublingual allergy immunotherapy tablet for disease-modifying treatment of grass pollen allergic rhinoconjunctivitis.

BACKGROUND: Allergy immunotherapy is a treatment option for allergic rhinoconjunctivitis (ARC). It is unique compared with pharmacotherapy in that it modifies the immunologic pathways that elicit an allergic response. The SQ Timothy grass sublingual immunotherapy (SLIT) tablet is approved in North America and throughout Europe for the treatment of adults and children (≥5 years old) with grass pollen-induced ARC. OBJECTIVE: The clinical evidence for the use of SQ grass SLIT-tablet as a disease-modifying treatment for grass pollen ARC is discussed in this review. METHODS: The review included the suitability of SQ grass SLIT-tablet for patients with clinically relevant symptoms to multiple Pooideae grass species, single-season efficacy, safety, adherence, coseasonal initiation, and cost-effectiveness. The data from the long-term SQ grass SLIT-tablet clinical trial that evaluated a clinical effect 2 years after a continuous 3-year treatment period were presented in the context of regulatory criteria that define a clinically meaningful effect. RESULTS: This trial demonstrated that the clinical effect of the SQ grass SLIT-tablet is maintained, which is also supported by the immunologic findings. CONCLUSION: Therefore, the SQ grass SLIT-tablet has an indication as a disease-modifying therapy in Europe, and a sustained effect is recognized in the United States.

Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract.

BACKGROUND: Allergen immunotherapy is an effective treatment of allergic rhinoconjunctivitis. Clinical efficacy is associated with improvement of basophil sensitivity and an increase in allergen-specific immunoglobulin concentration. OBJECTIVE: We sought to determine whether changes in allergen component-specific serum IgE and IgG4 levels during the updosing phase of subcutaneous immunotherapy (SCIT) are biomarkers of the immunologic changes that can lead to treatment efficacy. METHODS: Twenty-four subjects with grass pollen-induced allergic rhinoconjunctivitis were randomized 3:1 to receive SCIT (Alutard SQ) or to an open control group. IgE and IgG4 concentrations were determined for the major allergens Phl p 1 or Phl p 5 by using ImmunoCAP and for 8 grass pollen molecules by using Immuno Solid-phase Allergy Chip (ISAC) before treatment and after updosing. RESULTS: Levels of specific IgE against the dominant major allergens Phl p 1 and Phl p 5 increased from a mean of 23.0 to 48.8 kU/L (P = .01, n = 18) during the updosing phase in ImmunoCAP measurements but decreased from a median of 4.6 ISAC specific units (ISU) to 2.14 ISU (P < .0001, n = 102) when measured by using ISAC against 8 grass allergen components. The updosing phase induced a specific IgG4 level increase from a median of 0 ISU before treatment to 0.83 ISU after 12 weeks (P < .0001, n = 102) but only for allergen molecules to which pretreatment-specific IgE antibodies were detected (Spearman σ = 0.72, P < .0001, n = 102). CONCLUSION: Pretreatment allergen component-specific IgE appears to determine the induction of IgG4 in the updosing phase. Induced IgG4 seems to suppress IgE levels on ISAC, resulting in a marked decrease in ISAC-measured specific IgE levels after updosing of SCIT. Thus this decrease in ISAC IgE levels can be used to monitor the blocking effect of allergen-specific immunotherapy-induced non-IgE antibodies.

[Methotrexate may be a useful corticosteroid reducing treatment of severe asthma]. / Methotrexat kan anvendes som steroidbesparendebehandling af svær astma.

Asthma is a chronic airway disease affecting many people worldwide. Less than 1% suffers from difficult-to-treat asthma and requires systemic corticosteroid treatment to achieve symptom control. The therapeutic options for these patients are limited and often we have to accept a lesser degree of symptom control. Methotrexate has been evaluated in 13 studies, where the mean corticosteroid dose reduction was 35%. Despite the adverse effects, we find that methotrexate may be a useful treatment of severe asthma in certain patients under close observation.

The SENSE Study (Sleep and Education: learning New Skills Early): a community cognitive-behavioural therapy and mindfulness-based sleep intervention to prevent depression and improve cardiac health in adolescence.

BACKGROUND: Sleep problems are a major risk factor for the emergence of depression in adolescence. The aim of this study was to test whether an intervention for improving sleep habits could prevent the emergence of depression, and improve well-being and cardiovascular indices amongst at-risk adolescents. METHODS/DESIGN: A longitudinal randomised controlled trial (RCT) is being conducted across Victorian Secondary Schools in Melbourne, Australia. Adolescents (aged 12-17 years) were defined as at-risk for depression if they reported high levels of anxiety and sleep problems on in-school screening questionnaires and had no prior history of depression (assessed by clinical diagnostic interview). Eligible participants were randomised into either a sleep improvement intervention (based on cognitive behavioral and mindfulness principles) or an active control condition teaching study skills. Both programs consisted of seven 90 minute-long sessions over seven weeks. All participants were required to complete a battery of mood and sleep questionnaires, seven-days of actigraphy, and sleep diary entry at pre- and post-intervention. Participants also completed a cardiovascular assessment and two days of saliva collection at pre-intervention. Participants will repeat all assessments at two-year follow up (ongoing). DISCUSSION: This will be the first efficacy trial of a selective group-based sleep intervention for the prevention of depression in an adolescent community sample. If effective, the program could be disseminated in schools and greatly improve health outcomes for anxious adolescents. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612001177842. Date of Registration: 06-Nov-2012.

Serum magnesium and not vitamin D is associated with better QoL in COPD: A cross-sectional study.

BACKGROUND: Deficiency of serum levels of vitamin D3 (se vitD), magnesium (se Mg) and calcium (se Ca) may be associated with increased exacerbation risk in chronic obstructive pulmonary disease (COPD). However, associations with other aspects of COPD, e.g. lung function and quality of life (QoL), have been studied less extensively. AIM: To investigate se vitD, se Mg and se Ca in COPD and their associations with both forced expiratory volume in 1st second (FEV1) and QoL. METHODS: FEV1 and se vitD (assessed by 25-(OH)-D3), se Mg and se Ca were measured during summertime. Generic and health related QoL were characterized. RESULTS: This cross-sectional study included 143 participants with COPD. Women had a significantly higher se vitD than men (P = 0.0028), and 27% of participants were se vitD deficient. FEV1 was not correlated with se vitD, se Mg or se Ca in COPD. Mg deficiency group reported significantly impaired mobility, usual activities, pain/discomfort and COPD-related QoL. Se vitD and se Ca were not associated with QoL. CONCLUSION: Serum levels of vitD, Mg and Ca were not related to FEV1. Most participants in this study were vitD-, Mg- and Ca sufficient. Women had higher se vitD than men. Se Mg, but not se vitD and se Ca, was associated with QoL in COPD. Prospective randomized studies are needed to substantiate these finding. Clinical trials ID at www.clinicaltrials.gov: NCT01564953.

[Methotrexate may be a useful corticosteroid reducing treatment of severe asthma].

Asthma is a chronic airway disease affecting many people worldwide. Less than 1% suffers from difficult-to-treat asthma and requires systemic corticosteroid treatment to achieve symptom control. The therapeutic options for these patients are limited and often we have to accept a lesser degree of symptom control. Methotrexate has been evaluated in 13 studies, where the mean corticosteroid dose reduction was 35%. Despite the adverse effects, we find that methotrexate may be a useful treatment of severe asthma in certain patients under close observation.

Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study.

INTRODUCTION: The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting ß2-agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237), in development for the treatment of patients with chronic obstructive pulmonary disease (COPD), compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY). METHODS: In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010) were randomized (1:1) to once-daily QVA149 (110 µg indacaterol/50 µg glycopyrronium) or concurrent administration of indacaterol (150 µg) and glycopyrronium (50 µg) via the Breezhaler® device (Novartis AG, Basel, Switzerland) for 4 weeks. The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1) after 4 weeks of treatment. The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0-4 hours) at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period. RESULTS: Of 193 patients randomized, 187 (96.9%) completed the study.Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.5 L ± 0.02 [DOSAGE ERROR CORRECTED] and 1.46 L ± 0.18, respectively. The FEV1 AUC0-4 hours at day 1 and week 4 were similar between the two treatment groups. Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period. Overall, 25.6% of patients in QVA149 group and 25.2% in the IND+GLY group experienced an adverse event, with the majority being mild-to-moderate in severity. No deaths were reported during the study or during the 30 days follow-up period. CONCLUSION: The BEACON study demonstrated that once-daily QVA149 provides an efficacy and safety profile similar to the concurrent administration of its monocomponents indacaterol and glycopyrronium.

SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial.

BACKGROUND: The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials. OBJECTIVE: To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU,(∗) ALK, Denmark) or placebo. METHODS: A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters. RESULTS: The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% (P ≤ .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by 20% to 45% (P ≤ .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% (P ≤ .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% (P ≤ .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified. CONCLUSION: The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis.

Double trouble? The effects of sleep deprivation and chronotype on adolescent affect.

BACKGROUND: Two understudied risk factors that have been linked to emotional difficulties in adolescence are chronotype and sleep deprivation. This study extended past research by using an experimental design to investigate the role of sleep deprivation and chronotype on emotion in adolescents. It was hypothesized that sleep deprivation and an evening chronotype would be associated with decreased positive affect (PA), increased negative affect (NA), and lower positivity ratios. METHODS: Forty-seven healthy adolescents (aged 10-15 for girls, 11-16 for boys) participated in a sleep deprivation and a rested condition. A subsample of 24 adolescents was selected on the basis of extreme morningness or eveningness scores (based on outer quartiles of scores on the Children's Morningness-Eveningness Preferences Scale). PA and NA were measured using the Positive and Negative Affect Schedule for Children, and positivity ratios were calculated by dividing PA by NA. RESULTS: Participants reported less positive affect and lower positivity ratios when sleep deprived, relative to when rested. Evening chronotypes reported less positive affect and lower positivity ratios than morning chronotypes in both rested and sleep deprivation conditions. CONCLUSIONS: These findings extend previous research by suggesting that adolescents are adversely impacted by sleep deprivation, and that an evening chronotype might serve as a useful marker of emotional vulnerability. Early intervention and prevention strategies can focus on improving sleep and on using chronotherapy principles to reduce eveningness.

Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet.

BACKGROUND: Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial. OBJECTIVE: We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abelló, Hørsholm, Denmark). METHODS: A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events. RESULTS: Significant improvements in efficacy were consistently shown during 3 years' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified. CONCLUSION: Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment, which is indicative of disease modification and associated long-term benefits.