***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : In r and omized , double‐blind , placebo‐controlled clinical trials the efficacy of immunotherapy for allergic rhinoconjunctivitis is evaluated using the Average Rhinoconjunctivitis Total Symptom Score ( ARTSS ) . Effective treatment is associated with lower ARTSS relative to placebo . For ethical reasons patients are provided with registered rescue medication , which may alleviate symptoms and thus reduce symptom scores . This effect biases the mean difference in ARTSS between effective treatment and placebo towards zero . Therefore , when rescue medication is taken by a patient , the ARTSS needs to be adjusted appropriately Background The optimal dose of grass pollen tablets for sublingual immunotherapy ( SLIT ) in allergic rhinoconjunctivitis patients was previously established in a multinational , r and omized , double‐blind , placebo‐controlled study in 628 adults . Patients were r and omized to receive once‐daily 5‐grass pollen sublingual tablets of 100 IR ( index of reactivity ) , 300 IR or 500 IR , or placebo starting 4 months before the pollen season Background Although the prevalence of allergic rhinitis ( AR ) is increasing , relatively little is known about patient characteristics in Spain . The aim of this study was to investigate the clinical profile and therapeutic strategies in patients attending Spanish specialists for AR caused by grass pollen or house-dust mites ( HDMs . Methods This was a multicenter cross-sectional epidemiological study of consecutive patients aged ≥5 years with confirmed diagnosis of AR caused by grass pollen or HDMs attending allergy specialists throughout Spain . Demographic and clinical data and information on treatment were collected . Results Data from 1043 patients were analyzed ( 524 with grass pollen allergy and 519 with HDM allergy ; mean age , 27.1 years ) . Three-quarters had persistent AR as per the Allergic Rhinitis and Its Impact on Asthma ( ARIA ) definition , with disease duration of > 2 years in 94.3 % of those with pollen allergy and 85.5 % of those with HDM allergy . Approximately 38 % had concurrent asthma . Over one-half of the patients were considered to have gotten worse since the first onset of symptoms . In total , 51.5 % did not achieve good disease control with pharmacotherapy and 47.7 % were treated with immunotherapy ( 52.2 % of HDM allergic patients and 43.2 % of grass pollen-allergic patients . Conclusion The duration of AR in patients attended for the first time by specialists is long and , in general , the disease does not improve over time and is often not well controlled with pharmacologic interventions . Less than one-half of patients receive allergen-specific immunotherapy that is more often prescribed in HDM allergy Although many patients with allergic rhinoconjunctivitis have symptoms due to sensitization with more than one pollen allergen , and mixed pollen extracts are widely used for allergen immunotherapy in practice , there are few published trials BACKGROUND Mite sensitivity is highly prevalent in tropical and subtropical regions , such as the Canary Isl and s. OBJECTIVES To evaluate the clinical efficacy and safety of a depigmented polymerized allergen vaccine containing a 50 % mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae . METHODS Sixty-four patients participated in the study . It was prospect i ve , double-blind , and placebo-controlled , with r and om allocation of patients to receive active treatment or placebo . The active group received a mixture of modified allergen extracts containing 50 % D pteronyssinus and 50 % D farinae ; the control group received placebo .  All individuals were diagnosed with mild/moderate asthma and rhinoconjunctivitis caused by sensitization to D pteronyssinus and D farinae .  Bronchial provocation test ( BPT ) was considered the main outcome to document clinical efficacy . RESULTS Fifty-four patients completed the study . The active group experienced a significant improvement in BPT ( P < .001 ) , whereas the placebo group did not ( P = .648 ) . At the end of the study , 20 patients in the active versus 9 in the placebo group ( P = .013 ; odds ratio , 5.71 [ 1.76 , 18.51 ] ) needed more than twice the amount of allergen to obtain a positive BPT . The median improvement in the active group over placebo was 53.76 % in total symptom and 58.09 % in medication scores . CONCLUSION Immunotherapy with a mixture of modified allergen extracts of D pteronyssinus and D farinae is safe and efficacious to treat mite-allergic asthma . CLINICAL IMPLICATION S This immunotherapy modifies the natural course of the illness because it improves all clinical outcomes measured and prevents the worsening of specific bronchial hyperreactivity BACKGROUND Allergen immunotherapy ( AIT ) has been thoroughly documented in r and omized controlled trials ( RCTs ) . It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis , allergic asthma and insect sting allergy . However , there is a high degree of clinical and method ological heterogeneity among the endpoints in clinical studies on AIT , for both subcutaneous and sublingual immunotherapy ( SCIT and SLIT ) . At present , there are no commonly accepted st and ards for defining the optimal outcome parameters to be used for both primary and secondary endpoints . METHODS As elaborated by a Task Force ( TF ) of the European Academy of Allergy and Clinical Immunology ( EAACI ) Immunotherapy Interest Group , this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis . RESULTS Based on a thorough literature review , the TF members have outlined recommendations for nine domains of clinical outcome measures . As the primary outcome , the TF recommends a homogeneous combined symptom and medication score ( CSMS ) as a simple and st and ardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner . All outcomes , grouped into nine domains , are review ed . CONCLUSION A st and ardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required . The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis Background Immunotherapy ( IT ) with modified allergens reduces allergic rhinitis ( AR ) symptoms and medications requirements . Improvement of quality of life ( QOL ) is a key point in the treatment of AR . The aim of this study was to provide evidence of changes related to the patient 's QOL ( well‐being ) induced by a modified ( depigmented glutaraldehyde‐polymerized ) therapeutic vaccine and of its safety Background : Four administration schedules of immunotherapy have been reported : conventional , cluster , rush and ultra-rush . Objectives : To evaluate the safety and the clinical advantage of using st and ardized modified allergen extracts in an ultra-rush protocol without premedication and /or hospitalization . Material and Methods : One thous and and sixty-eight patients with rhinoconjunctivitis and /or asthma sensitized to mites and /or pollen were included in a prospect i ve observational study . Patients received a therapeutic vaccine containing depigmented and glutaraldehyde-modified extracts ( mites and /or pollens ) adsorbed onto alum prescribed by a specialist . The schedule of administration consisted of injecting 0.2 and 0.3 ml of the vial of maximum concentration during the first day of immunotherapy , separated by a time interval of 30 min . All patients reached the maximum dose ( 0.5 ml ) after 2 injections . Tolerance was assessed by recording all side reactions related to immunotherapy , classified according to the criteria of the EAACI . Results : The total number of injections was 2,136 . All patients reached the maximum established dose on the 1st day . No premedication was used . Seven clinical ly relevant local reactions were recorded . The systemic reactions were 5 grade -1 ( 2 immediate and 3 delayed ) and 3 delayed grade -2 reactions . Conclusions : The therapeutic vaccines containing chemically modified extracts can be administered using an alternative ultra-rush schedule in an immunotherapy unit , reaching the maximum dose on the 1st day with 2 injections , without the need of premedication and /or hospitalization To cite this article : Pfaar O , Urry Z , Robinson DS , Sager A , Richards D , Hawrylowicz CM , Bräutigam M , Klimek L. A r and omized placebo‐controlled trial of  rush preseasonal depigmented  polymerized grass pollen immunotherapy . Allergy 2012 ; 67 : 272–279 Background : A r and omized double‐blind , placebo‐controlled study was conducted in patients allergic asthma sensitized to Dermatophagoides pteronyssinus BACKGROUND The inhalation of Salsola kali pollen is a common cause of respiratory diseases in Europe and North America . OBJECTIVE To evaluate the efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic vaccine of S kali . METHODS The trial was r and omized , double-blind , and placebo-controlled using a rush protocol in the build-up phase . Sixty patients with rhinoconjunctivitis ( 19 also had mild asthma ) were r and omly allocated to receive either active treatment ( polymerized extract ) or placebo . The final distribution was 41 patients in the active and 19 in the placebo group .  Side effects were registered . Symptom and medication scores and the number of days free of symptoms during the pollen season were assessed to evaluate the clinical efficacy . A Rhinoconjunctivitis Quality of Life Question naire was completed in the previous pollen season ( before treatment ) and during the pollen season 1 year later ( in the trial ) . Dose-response skin tests were performed at baseline and at the end of the trial . RESULTS There was a significant difference ( P < .05 ) in symptom and medication scores between both groups during the pollen season , with the active group the one that had fewer symptoms and lower intake of medication . The number of days without symptoms was higher in the active group ( P < .05 ) . This group also had a significant improvement in the Rhinoconjunctivitis Quality of Life Question naire and a reduction in skin sensitivity . No moderate or severe systemic reactions were registered . CONCLUSION Immunotherapy with this modified vaccine of S kali pollen is safe and efficacious to treat patients clinical ly sensitive to this pollen . CLINICAL IMPLICATION S Patients allergic to S kali ( Russian thistle ) can be successfully treated with immunotherapy to improve symptoms of allergic rhinitis and asthma , reduce medication use , and improve quality of life parameters Background Rhinoconjunctivitis due to birch pollen sensitization is common in Northern Europe . A depigmented polymerized birch pollen extract – Depigoid ® has been developed for immunotherapy 
    Output:
    
An exploratory analysis of cSMS and RCSS suggested that the efficacy of AIT treatment with  DPAEs  was higher in trials including patients with more severe rhinoconjunctivitis and asthma .
Conclusions Compared to placebo , AIT with DPAEs is  effective in patients with pollen- or HDM-induced rhinoconjunctivitis with or without allergic asthma  and improves health-related quality of life .
It does not differ significantly in safety and tolerability