***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 
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    ***EXAMPLES*** 
    Input: We performed a prospect i ve , multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season . The study was carried out in eight centers and included 191 patients ( children and adults ) with allergic respiratory disease due to sensitization to olive tree and /or grass pollen . Of these , 34 patients acted as controls and the remaining patients received  immunotherapy  administered in the initiation phase according to a cluster schedule of eight doses injected on four visits . After 3 months of treatment , significant differences were found between the two groups in medication consumption ( antihistamines in drops and oral formulations : p = 0.045 and p = 0.001 , respectively ; short-acting beta2-agonist treatments : p = 0.004 ) and respiratory symptoms ( wheezing and coughing : p = 0.035 and 0.014 , respectively ) . The cytokine profile ( interleukin [IL]-4 , 5 , 10 and 2 , interferon [ IFN-gamma ] , and tumor necrosis factor [ TNF-alpha ] ) was determined before the start of treatment and at the end of follow-up ( 4 - 5 months ) . Levels of IL-4 , 5 and 10 ( Th2 profile ) decreased while those of IL-2 , IFN-gamma , and TNF-alpha ( Th1 profile ) decreased . These differences were more marked in the active group than in the control group but were not statistically significant . No severe adverse effects were recorded . This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment . A double-blind , placebo-controlled study is needed to confirm these results BACKGROUND Sensitivity to Salsola kali is a frequent cause of allergic respiratory disease in various regions of Spain . However , there are very few articles in which this allergen has been studied . METHODS AND RESULTS In order to evaluate the tolerance of this extract , a prospect i ve study has been performed . This study was observational , multi-centred and open , involving 88 patients with allergic respiratory disease due to sensitivity to Salsola , aged between 5 and 52 years . The administration of the extract was performed subcutaneously , through one of two treatment schedules : cluster ( 8 doses in 4 visits ) or conventional ( 13 doses in 12 visits ) . A total of 42 adverse reactions were registered , in 26 patients ( 35 local reactions in 21 patients and 7 systemic reactions in 6 patients ) . Among the 7 systemic reactions , 4 were registered with the cluster protocol and 2 with the conventional protocol ( p = 0.329 ) . In no patients were serious adverse reactions registered . CONCLUSION The subcutaneous administration of a Salsola extract is safe and well tolerated , both when administered using a conventional schedule and when using a cluster schedule The st and ardisation of allergenic extracts in micrograms of the major allergen has encouraged the search for new treatment schedules , with the purpose of shortening the number of visits and doses required to reach the maintenance dose without eliciting a greater risk of adverse reactions for the patients . With this objective , a prospect i ve multicentre pharmacovigilance study was design ed that included 200 patient with allergic rhinoconjunctivitis and /or allergic asthma sensitised to mites ( Dermatophagoides pteronyssinu and /or farinae ) . The dose increment period was carried out using a cluster schedule , where the optimal dose wa reached after 4 visits , administering two doses in each visit . The duration of the study was 5 months and a total o 1902 doses were administered . At the end of the trial , 31  adverse reactions in 23 patients were recorded . Six of these were systemic ( 0.3 % of t administered doses ) recorded in 6 patients ( 3 % of the sample ) . One was an immediate reaction ( grade 1 ) and delayed ( 4 mild and 1 moderate ) . Two were asthmatic exacerbations , 2 cutaneous reactions , 1 rhinitis and 1 an unspecific symptom ( not IgE-mediated ) . Two appeared upon administration of the first vial and the remaining 4 after administration of the third cluster . Therefore , the schedule tested presents an adequate tolerance profile , suggesting savings ( compared to th conventional schedule of 13 doses per patient ) of 1800 visits and 1000 treatment doses in the whole study Twenty‐seven patients with allergy to house‐dust mite and the clinical symptoms of perennial rhinitis and /or mild asthma were treated with specific immunotherapy ( SIT ) with st and ardized extracts of house‐dust mite for 3 years . The success of therapy was evaluated in yearly intervals BACKGROUND Short-term immunotherapy ( STI ) can be beneficial for patients who are noncompliant with long-term specific immunotherapy . OBJECTIVE The efficacy and tolerance of STI with seven preseasonal injections of molecular st and ardized allergens from grass and rye pollen has been investigated in a double-blind , placebo-controlled multicenter study with 87 patients at 12 German University hospitals . METHODS Symptoms of the eyes , nose , and bronchi and use of symptomatic drugs were documented daily in diaries by patients with allergic rhinitis to grass and /or rye pollen and without bronchial asthma . Patients were monitored by skin prick test titration and measurement of levels of specific IgE and IgG4 . RESULTS The median nasal score for the 10 weeks with the strongest symptoms during the grass pollen season was significantly lower ( p = 0.014 ) with 35.0 for STI ( n = 41 ) versus 69.0 for placebo ( n = 40 ) ; the overall symptom score was 54.0 for STI versus 97.5 for placebo ( p = 0.020 ) . Only STI-treated patients exposed to less than 40 pollen grains per cubic meter per week showed a significantly lower nasal symptom score of 39.0 versus 75.0 for placebo ( p = 0.006 ) ; these patients also had fewer nasal symptoms and less use of topical nasal drugs ( p < 0.001 ) . The threshold dose in skin prick tests was significantly higher , being 9.06 histamine equivalent for skin prick test ( HEP ) for STI-treated patients who received the maximum dose ( n = 22 ) versus 4.33 HEP for placebo ( p = 0.005 ) . Specific IgE levels were significantly higher , being 55.9 SU/ml for STI versus 39.2 SU/ml for placebo after seven injections ( p = 0.006 ) and level of specific IgG4 was 5.36 % for STI versus 1.28 % for placebo ( p < 0.001 ) . No severe systemic reactions were observed . CONCLUSION STI with seven preseasonal injections with molecular st and ardized allergens is effective and well tolerated Background and Objectives : Allergy to house dust mite is one of the most common causes of allergic rhinitis ( AR ) in China . We sought to compare the efficacy and safety of a 6-week cluster schedule of specific immunotherapy with that of a 14-week conventional schedule for the treatment of subjects with persistent AR . Methods : The trial was a prospect i ve and r and omized study involving 96 patients with persistent AR , aged 14–60 years , who were allergic to Dermatophagoides pteronyssinus . While 48 patients were r and omly assigned to the cluster schedule reaching the maintenance dose within 6 weeks , the other 48 were r and omly assigned to the conventional schedule reaching the maintenance dose within 14 weeks . Eighty-nine patients completed a 1-year treatment course . While kinetic changes in clinical efficacy and adverse reactions were observed during the treatment , quality of life , cutaneous reactivity and serum-specific immunoglobulin E to Dermatophagoides pteronyssinus were measured before and after treatment . Results : The cluster schedule reduced the time to reach the maintenance dose by 57 % and caused mild systemic adverse reactions after 1.0 % of injections ( 6.7 % of patients ) , with no differences in comparison with the conventional schedule . Cluster specific immunotherapy led to decreases in clinical symptoms and earlier use of medication than did the conventional schedule . Similar improvements in quality of life and reduced cutaneous reactivity without significant changes in specific immunoglobulin E were observed in both groups after 1 year . Conclusions : The cluster schedule is a safe alternative to the conventional schedule with the advantage of achieving clinical effectiveness sooner 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 Background : Subcutaneous immunotherapy ( SCIT ) usually requires a long titration phase , which can be associated with various adverse events ( AEs ) . Objectives : It was the aim of this study to determine the safety of 2 cluster regimens for SCIT in patients with allergic rhinitis , with or without mild or moderate allergic asthma , who were sensitized to grass and /or tree pollen , or house dust mites ( HDM ) . Patients and Methods : Adult patients were included in a European , open-label , prospect i ve trial . Pollen-allergic patients received grass pollen , grass and olive pollen , or hazel , alder and birch pollen according to a 3-week titration cluster .  HDM-allergic patients received HDM extract according to a 2-week titration cluster . The safety of the titration phase was assessed in terms of local and systemic AEs . Results : The safety analysis included 157 patients : 110 received pollen and 47 HDM extract .  During the cluster titration , 248 AE episodes were reported in the pollen group and 113 in the HDM group ; these were mainly local reactions . Around one third of patients ( 30.9 % pollen and 38.3 % HDM ) did not experience any AE . In most cases ( 67.1 % of pollen and 71.1 % of HDM patients ) , AEs did not lead to a change in titration schedule . No anaphylactic reaction or other serious life-threatening systemic AEs were reported . Only 2 patients in the HDM group discontinued treatment because of AEs . Conclusions : Rapid cluster titration was well tolerated in adults with allergic rhinitis , with or without mild to moderate allergic asthma , due to pollen or HDM . This short-titration , high-dose cluster regime may allow better patient compliance and cost savings BACKGROUND Specific immunotherapy ( SIT ) represents the only specific treatment that can be offered to allergic patients apart from allergen avoidance . SIT has been widely used in pollen allergic rhinitis . Clinical efficacy has been demonstrated in several controlled clinical trials and depends on the specific allergen the individual patient is sensitive to , the quality and total amount of allergen applied , and the SIT schedule . In classic SIT , gradually increasing dosages of the allergen extract are injected subcutaneously . Several dosage schedules for subcutaneous SIT can be applied . In Cluster-SIT , 2 - 3 injections per day of treatment are given once a week during induction treatment . PATIENTS In this study , we investigated 64 patients ( 33 female , 31 male ) from 18 to 54 years ( 26.9 + /- 5.1 years ) in terms of side-effects of Cluster-SIT during induction treatment . RESULTS The total amount of enlarged local reactions ( > grade 1 ) was n = 77 or 15.2 % of all injections . Of these , 68 ( 88 % ) were classified as immediate reactions , 8 ( 11 % ) were late phase reactions and 1 ( 1 % ) was immediate as well as late phase reaction . Of all enlarged local reactions , 48 ( 62 % ) were grade 1 reactions , 13 ( 17 % ) were grade 2 reactions , 13 ( 17 % ) were grade 3 reactions and 1 ( 1 % ) was a grade 4 reaction . The total amount 
    Output:
    
Our meta- analysis showed that cluster SCIT have similar effect in reduction of both rhinitis symptoms and the requirement for anti-allergic medication compared with conventional SCIT , but when comparing cluster SCIT with placebo , no statistic significance were found in reduction of symptom scores or medication scores .
Based on the current limited evidence , we still could not conclude affirmatively that cluster SCIT was a safe and efficacious option for the treatment of AR patients .