***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 Grass pollen allergy is one of the most common allergies worldwide , and patients often show sensitization to an array of phylogenetically related species . OBJECTIVE To determine the effect of specific immunotherapy ( SIT ) with Phleum pratense extract on induction of the immune response to a mixture composed of 5 grass pollen extracts . METHODS Forty-six adult patients suffering from rhinitis and sensitized to a mix of grass pollen allergen extracts  were r and omized 3:1 to receive a short course of SIT with P. pratense or to an open control group without SIT . At baseline and after 3 - 4 months , we evaluated levels of specific immunoglobulin ( Ig ) E and IgG4 , as well as the immediate and delayed cutaneous responses to the grass mix and P. pratense . IgG4 to Lolium perenne was also determined . RESULTS Levels of IgE and IgG4 to grass mix and P. pratense  increased significantly during treatment ( P<.001 ) . However , this increase was only significantly higher in the SIT group than in the control group for IgG4 ( P<.001 ) . The levels of IgG4 to Phl p 5 and Lol p 5 were highly correlated ( r=0.99 , P<.001 ) . The immediate and delayed cutaneous responses were significantly diminished to both extracts after SIT ( P<.001 ) . CONCLUSIONS Patients with rhinoconjunctivitis diagnosed using skin prick testing with a grass mix allergen extract and treated with a short course of SIT based on a single species P. pratense allergen extract are able to develop an immune response that targets not only the immunizing species , but also the grass mix allergen extract Background : Both sublingual and subcutaneous immunotherapies have a documented clinical efficacy , but only a few comparative studies have been performed . Objectives : To evaluate and compare the long-term efficacies of subcutaneous and sublingual immunotherapy . Methods : One hundred and ninety-three patients with house dust mite allergies , out of an original total of 230 , were treated with subcutaneous and sublingual house dust mite-specific immunotherapies for 3 years and also observed for 3 years after discontinuation of the treatment . The patients were r and omized into 2 groups : the sublingual group ( 97 patients ) and the subcutaneous group ( 96 patients ) . The therapy ’s success was evaluated using the symptom score , skin prick test results , and the nasal allergen challenge score . The patients were evaluated at the beginning of the study , at the end of years 1 , 2 , and 3 , and also at the end of the 1st and 3rd years after discontinuation of the specific immunotherapy treatment . Results : Immunotherapy induced a significant improvement during the treatment and the follow-up period . We found a greater improvement in the subcutaneous group compared to the sublingual group when we looked at the comparative results of the total 6 years . Conclusion : We suggest subcutaneous immunotherapy for patients with perennial allergic rhinitis due to the better results that were obtained during our study period . Nevertheless , sublingual immunotherapy is now accepted by WHO as a valid alternative to the subcutaneous route and should be used in all patients who require immunotherapy and do not accept the subcutaneous route of allergen administration Background : Local application of allergen extracts in specific immunotherapy is accompanied by increased compliance and significantly reduced side effects . However , efficacy of local immunotherapy in children has yet not been sufficiently demonstrated . This study was performed to determine clinical efficacy of high dose sublingual swallow immunotherapy ( SLIT ) by a double‐blind placebo‐controlled study in children with grass pollen allergy using high dose allergen extracts Background Modification of allergens by glutaraldehyde in extracts used for immunotherapy reduces the risk for side effects , but therapeutic efficacy of such extracts requires further evaluation . The aim of this study was to evaluate the efficacy and safety of immunotherapy with PURETHAL Mites ( PM ) , a single-strength glutaraldehyde-modified aluminum hydroxide – adsorbed extract of house-dust mites ( HDM ) . Methods In a multicenter , r and omized , placebo-controlled double-blind setting , HDM-allergic subjects ( n = 140 ) were treated with modified allergen extract or placebo over a 1-year period . The primary outcome parameter was a combined symptom and medication score ( clinical index score [ CIS ] ) . Secondary efficacy parameters were the result of a titrated conjunctival provocation test ( CPT ) , rhinitis/rhinoconjunctivitis quality of life ( RQL ) score , and serum concentrations of IgE and IgG against specific HDM allergens and a documentation of adverse events ( AE ) . Results We evaluated 140 patients ( 66 treatment and 74 placebo ) for clinical efficacy . The allergoid treatment for 1 year result ed in significantly greater CIS improvement and higher RQL scores . The response threshold in the titrated CPT ( p = 0.009 ) and the serum concentrations of IgG4 ( p < 0.001 ) against Dermatophagoides pteronyssinus allergens after treatment were also significantly different between groups . In total , 88 patients ( 46 PM/42 placebo ) out of a safety population of 145 reported 278 ( 158 PM/120 placebo ) AE . Except for local reactions , no specific AE appeared to be associated with PURETHAL Mites ( HAL-Allergy , Leiden , The Netherl and s ) . Conclusion The findings of this study indicate that allergen injection therapy with modified HDM extract is superior to placebo in allergic rhinitis therapy . The treatment was well tolerated and no serious drug-related AE were observed Background : The efficacy of st and ardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens . Methods : Forty adults with European cypress-allergic rhinoconjunctivitis were r and omized to receive immunotherapy or a matched placebo . Specific immunotherapy was performed with a st and ardized , aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR ( arbitrary index of reactivity ) containing 54 µg of Jun a 1/ml ( Alustal , Stallergenes , France ) . Subcutaneous injections started in October 2000 . The maintenance dose was 0.30 ml of the 100-IR concentration per month . Rhinitis and conjunctivitis symptoms were rated according to a 4-point score . Results : Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001 ; 14 in each group completed year 2002 . A statistically significant improvement ( 41 % , p < 0.02 ) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season . Improvement in rhinitis ( 17 % ) was not significant . This significant improvement was greater at the peak of the 2002 pollen season ( 63 % , p < 0.01 ) . Conclusions : This study therefore indirectly vali date s the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted The objective of this study was to develop and test a health‐related quality of life question naire for clinical trials in rhinoconjunctivitis . The Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) was developed by asking patients to identify areas of their lives affected by rhinoconjunctivitis . The result ant RQLQ was tested for reproducibility , responsiveness and validity in a r and omized , double‐blind trial of regular versus ‘ as required ’ aqueous beclomethasone dipropionate ( BDP ) nasal spray in ragweed pollen‐induced rhinoconjunctivitis . Eighty‐five patients from previous rhinoconjunctivitis studies participated in the developmental survey . Sixty ragweed‐sensitive patients , from previous trials and media notices , were enrolled in the clinical trial . Aqueous BDP ( 800 μg ) nasal spray was administered regularly or ‘ as required ’ throughout the ragweed pollen season . The survey revealed that , in addition to local symptoms of rhinoconjunctivitis , patients experienced impairment of quality of life through systemic symptoms , sleep disturbance , practical problems , activity limitations and emotional problems . The RQLQ includes 28 questions related to these dimensions . Repeated administration of the RQLQ demonstrated good reproducibility . During the clinical trial , the RQLQ proved responsive in its ability to distinguish between regular and ‘ as required ’ medication use . Validity was shown by moderate to strong relations between changes in symptom diary scores and changes in RQLQ scores . In conclusion the RQLQ is likely to prove useful as a measure of health‐related quality of life in clinical trials in both rhinoconjunctivitis and rhinitis Evidence -based clinical practice guidelines can reduce the delivery of inappropriate care and support the introduction of new knowledge into clinical practice ( 1 - 3 ) . In many cases , guidelines encapsulate the most current knowledge about best practice s. Rigorously developed guidelines can translate complicated research findings into actionable recommendations for clinical care ( 4 ) . Over the past decade , a plethora of guidelines has been created and published by a multitude of organizations at substantial cost . Despite the enormous energies invested in guideline authoring , the quality of individual guidelines varies considerably . In its l and mark report , the Institute of Medicine ( IOM ) defined 8 desirable attributes of clinical practice guidelines : validity , reliability and reproducibility , clinical applicability , clinical flexibility , clarity , documentation , development by a multidisciplinary process , and plans for review ( 5 ) . However , critical information that would attest to validity or would document fulfillment of the other IOM criteria is regularly absent from published guidelines . In an evaluation of 279 guidelines developed by U.S. medical specialty societies , Shaneyfelt and colleagues ( 6 ) found that guidelines published in the peer- review ed medical literature do not adhere to established method ologic st and ards . Likewise , Grilli and colleagues ( 7 ) found that of 431 guidelines produced by specialty societies , 82 % did not apply explicit criteria to grade the scientific evidence that supported their recommendations , 87 % did not report whether a systematic literature search was performed , and 67 % did not describe the type of professionals involved in guideline development . Systematic review s of guidelines for drug therapy ( 8) , management of depression ( 9 ) , and osteoporosis ( 10 ) have confirmed marked variation in quality . Both nonadherence to method ologic st and ards and failure to document development activities contribute to this variation . We convened the Conference on Guideline St and ardization ( COGS ) to define a st and ard for guideline reporting that would promote guideline quality and facilitate implementation . The proposed st and ard provides a checklist of components necessary for evaluation of validity and usability . The checklist is intended to minimize the quality defects that arise from failure to include essential information and to promote development of recommendation statements that are more easily implemented . In contrast to other instruments that have been developed for post hoc evaluation of guideline quality , the COGS checklist is intended to be used prospect ively by developers to improve their product by improving documentation . The COGS panel used a systematic and rigorous process to define content of the proposed st and ard and to achieve consensus . The COGS panel also included a wide variety of perspectives , deliberately bringing together representatives from medical specialty societies , government agencies , and private groups that develop guidelines ; journal editors and the National Guideline Clearinghouse ( NGC ) , which disseminate guidelines ; guideline implementers , including managed care representatives and informaticians ; and academicians . Methods We actively sought people with diverse background s from wide-ranging geographic areas to participate in the meeting . Selection criteria for participants were 1 ) activity in a wide variety of guidelines initiatives , 2 ) recognition as leaders in their field , and 3 ) willingness to collaborate . To maximize interaction , the number of participants in the Conference was limited . We set as a task for the panelists the specification and definition of a set of necessary guideline components that should be considered for reporting in all evidence -based practice guidelines . We defined necessary items as those that establish the validity of the guideline recommendations or facilitate practical application of the recommendations . We noted that many additional items might be considered appropriate components in guidelines , but sought to define a minimal set of essential elements . We assembled a list of c and i date guideline components from the IOM Provisional Instrument for Assessing Clinical Guidelines ( 5 ) , the NGC ( 11 ) , and the Guideline Elements Model ( 12 ) , a hierarchical model of guideline content that was created from a systematic review of published guideline descriptions . These items were supplemented with items highlighted in the literature , for example , structured abstract ( 13 ) and conflict of interest ( 14 ) . We applied a modified Delphi approach to help focus group discussion . This approach has been widely applied for evaluation of expert opinion on appropriateness ( 15 ) and medical necessity ( 16 ) , for policy development ( 17 ) , and for prioritization ( 18 ) . The technique has been described in detail ( 19 ) . In brief , after we secured agreement to participate in the COGS panel , we gave all participants a bibliography of re sources regarding guideline quality and its appraisal , guideline implementation , and the modified Delphi consensus development approach . Panelists were asked to rate their agreement with the statement that [ Item name ] is a necessary component of practice guidelines on a 9-point scale . Rating an item with a 9 indicated strong agreement with the statement that this item was necessary . Rating an item with a 1 indicated strong disagreement with the statement and suggested that the item was absolutely unnecessary in a guideline . A rating of 5 indicated neutrality or indifference . We developed a password-protected Web site that panelists used to complete the first round of ratings online before the 
    Output:
    
CONCLUSION Subcutaneous immunotherapy improves symptom and /or medication scores and vali date d quality of life measures .
In addition , associated changes in surrogate markers of immunologic protection are observed .
Subcutaneous immunotherapy is safe when administered to carefully selected patients and in setting s capable of responding to systemic reactions .