***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 Treatment of primary acquired cold urticaria ( CU ) is quite difficult because of variable clinical effectiveness and side effects of classic antihistamines . OBJECTIVE The objective of the study was to assess the efficacy and safety of mizolastine , an antihistaminic with antiallergic properties , versus placebo in primary acquired CU . METHODS This study was a phase II , multicenter , r and omized , double-blind , crossover , placebo-controlled study of mizolastine ( 10 mg , once daily ) versus placebo in 28 patients with primary acquired CU .  Efficacy was measured by the cold-stimulation time test , the wheal response , and pruritus intensity after an ice-cube test . RESULTS Mizolastine delayed the cold-induced wheal reaction , reduced wheal response at 3 and 10 minutes , and reduced pruritus intensity . Statistically significant differences were observed versus placebo for the cold-stimulation time test , wheal response at 3 and 10 minutes , and pruritus intensity ( P = .006,.015,.009 , and .005 , respectively ) . No clinical ly relevant adverse events were reported . CONCLUSIONS Mizolastine ( 10 mg , once daily ) was shown to be superior to placebo for both delaying and reducing the cold-induced wheal reaction without significant adverse events . Results suggest that mizolastine may be effective in the treatment of CU BACKGROUND Patients with acquired cold urticaria ( ACU ) show itchy wheals during cold exposure . This disturbing condition involves histamine and platelet-activating factor in its pathogenesis . Rupatadine is a dual antagonist of both histamine and platelet-activating factor . OBJECTIVE To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU . METHODS A crossover , r and omized , double-blind , placebo-controlled study in which 21 patients with ACU received rupatadine , 20 mg/d , or placebo for 1 week each is presented . The main outcome was the critical stimulation time threshold ( CSTT ) determined by ice cube challenge . Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device ( TempTest 3.0 ) , as well as scores for wheal reactions , pruritus , burning sensations , and subjective complaints after cold challenge . RESULTS After rupatadine treatment , 11 ( 52 % ) of 21 patients exhibited a complete response ( ie , no urticaria lesions after ice cube provocation ) . A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge ( P = .03 and P = .004 , respectively ) . A significant reduction of critical temperature threshold ( P < .001 ) and reduced scores for cold provocation-induced wheal reactions ( P = .01 ) , pruritus ( P = .005 ) , burning sensation ( P = .03 ) , and subjective complaints ( P = .03 ) after rupatadine treatment were also found . Mild fatigue ( n = 4 ) , somnolence ( n = 1 ) , and moderate headache ( n = 1 ) were reported during active treatment . CONCLUSION Rupatadine , 20 mg/d , shows high efficacy and is well tolerated in the treatment of ACU symptoms The efficacy of the new nonsedating antihistamines loratadine and cetirizine was compared in a r and omized , single-blind , crossover , controlled study with that of the classical antihistamines cyproheptadine and ketotifen in seven patients with primary acquired cold urticaria ( ACU ) . The patients received each of the four drugs for 14 consecutive days with a 7-day interval between drugs . We evaluated clinical symptomatology , adverse effects , minimum time of cold contact stimulation required to induce an immediate coalescent wheal ( CSTT ) , and inhibition of histamine-induced wheal response . Both loratadine and cetirizine showed suppression of symptoms with infrequent adverse effects . Important side-effects were observed in patients receiving cyproheptadine . Improvement in CSTT was statistically significant for all drugs compared with baseline values , without differences among them . The histamine-induced skin test was significantly inhibited by all antihistamines . Wheal reductions were 34.6 % for loratadine and 50.9 % for cetirizine . This study suggests that both loratadine and cetirizine may be effective in the treatment of primary ACU A double-blind , crossover trial with a new triprolidine derivative , acrivastine ( BW 825C ; 8 mg 3 times daily ) , cyproheptadine ( 4 mg 3 times daily ) and placebo was carried out in 18 patients suffering from idiopathic cold urticaria .  Acrivastine and cyproheptadine significantly ( p less than 0.01 ) reduced weal areas following ice cube challenge when compared to placebo . Acrivastine was found to be significantly more effective ( p less than 0.01 ) than cyproheptadine in reducing weal areas . Furthermore , cyproheptadine caused significantly more drowsiness than acrivastine ( p = 0.021 ) or placebo ( p = 0.013 ) , which did not differ from each other . This study shows that acrivastine is an effective agent in the treatment of cold urticaria and suggests that acrivastine in the dose used lacks adverse effects , such as drowsiness , traditionally associated with antihistamine therapy Eleven patients with primary acquired cold-induced urticaria were treated with ketotifen ( 1 mg b.i.d . ) or placebo in a double-blind , crossover design trial . After seven days of ketotifen treatment , reaction times to a cold stimulus were significantly delayed in ten of the 11 subjects . No effect was seen after placebo treatment . It is concluded that ketotifen may have a place in the treatment of primary acquired cold urticaria The study was performed in 6 Thai children with primary acquired cold urticaria . They all suffered from generalized urticaria and two of them also had angioedema . All of them had normal erythrocyte sedimentation rate , complement 3 and negative VDRL , TPHA , hepatitis B screen and cold agglutinin titer . Cryoglobulin was checked in 3 cases and showed negative results A double-blind cross-over study to compare the effectiveness of cyproheptadine and ketotifen demonstrated that the efficacy of cyproheptadine and ketotifen on clinical symptoms and ice cube test was not significantly different ( p > 0.05 ) . Both of them showed good results in the treatment of cold urticaria with mild side effects . During the follow up , 5 cases showed complete recovery while the other one developed one or two exacerbations per year upon cold exposure . However , the symptoms were mild and subsided on administration of one or two doses of H1 antihistamine . Our data demonstrated that ketotifen was as effective as cyproheptadine in the treatment of cold urticaria in Thai children BACKGROUND Proof-of-concept studies with omalizumab in patients with chronic idiopathic urticaria ( CIU ) have shown significant decreases in mean urticaria activity scores ( UASs ) . OBJECTIVE We sought to evaluate the efficacy and safety of omalizumab in patients with CIU who remain symptomatic despite concomitant H(1)-antihistamine therapy . METHODS This phase II , prospect i ve , double-blind , placebo-controlled , dose-ranging study investigated  omalizumab in patients aged 12 to 75 years in the United States and 18 to 75 years in Germany with a UAS over 7 days ( UAS7 ) of 12 or greater despite antihistamine therapy . Patients were r and omized 1:1:1:1 to receive a single subcutaneous dose of 75 , 300 , or 600 mg of omalizumab or placebo added to a stable dose of H(1)-antihistamine . The primary efficacy outcome was change from baseline to week 4 in UAS7 . Patients were followed for an additional 12 weeks to monitor safety . RESULTS Ninety patients from the United States or Germany were enrolled . Both the 300-mg omalizumab group ( -19.9 vs -6.9 , P < .001 ) and the 600-mg omalizumab group ( -14.6 vs -6.9 , P = .047 ) showed greater improvement versus the placebo group in UAS7 . No meaningful difference was observed for the 75-mg omalizumab group . Similar results were seen for key secondary end points of weekly hive and itch scores . Onset of effect occurred after 1 to 2 weeks . Omalizumab was well tolerated , and the incidence of adverse events was similar across treatment groups . CONCLUSION This study demonstrated that a fixed dose of 300 or 600 mg of omalizumab provides rapid and effective treatment of CIU in patients who are symptomatic despite treatment with H(1)-antihistamines Eight subjects with primary -acquired cold urticaria were treated with chlorpheniramine maleate , cyproheptadine hydrochloride , and placebo in a double-blind clinical trial . During three separate seven-day treatment periods , each patient took 4 mg of either active drug or lactose placebo three times a day . Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time ( MT ) of cold stimulus application required to provoke urtication . In addition , the spontaneous appearance of cold urticaria lesions was recorded during each treatment period . The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo ( P less than .01 ) . The study demonstrated that cyproheptadine had a significant suppressive action on experimental cold-induced urticaria , while placebo and chlorpheniramine proved ineffective Chronic cold urticaria ( ColdU ) is a rare disease characterized by mast cell-mediated wheals and angioedema following cold exposure . Second-generation H1-antihistamines , such as rupatadine , are the recommended first-line therapy . As of yet , the effects of rupatadine up-dosing on development of ColdU symptom have only been partially characterized . Two-centre , r and omized , double-blind , 3-way crossover , placebo-controlled study in patients with a confirmed ColdU was design ed to assess the effects of up-dosing of rupatadine . A total of 23 patients were r and omized to receive placebo , rupatadine 20 mg/day , and rupatadine 40 mg/day for 1 week . The primary outcome was change in critical temperature thresholds and critical stimulation time thresholds after treatment . Secondary endpoints included assessment of safety and tolerability of rupatadine  . Both 20 and 40 mg rupatadine were highly effective in reducing critical temperature thresholds ( p < 0.001 ) and critical stimulation time thresholds ( p < 0.001 ) . In conclusion , rupatadine 20 and 40 mg significantly reduced the development of chronic cold urticaria symptom without an increase in adverse effects BACKGROUND Increased dosing of nonsedating antihistamines is recommended by the current European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum guidelines on patients with acquired cold urticaria ( ACU ) who do not respond satisfactorily to the st and ard dose . Prospect i ve data supporting this recommendation are scant . OBJECTIVE We sought to assess the effects of 5 and 20 mg of desloratadine and placebo on cold-induced urticarial reactions in patients with ACU . METHODS In this prospect i ve , r and omized , double-blind , 3-way crossover trial , patients with ACU ( n = 30 ) received placebo , 5 mg of desloratadine , and 20 mg of desloratadine every day each for 7 days separated by 14-day washout periods . At the end of each treatment , patients underwent cold provocation with the TempTest 2.0/2.1 system , and urticarial reactions were assessed by using digital 3-dimensional time-lapse photography and thermography ; the critical temperature threshold ( CTT ) and critical stimulation time threshold ( CSTT ) were measured . Adverse events ( AEs ) reported during the study were assessed . RESULTS Compared with placebo , 7 days of desloratadine at 5 and 20 mg/d significantly reduced the volume of cold-induced wheals and areas of hyperthermic skin and improved CTT and CSTT results .  Desloratadine at 20 mg/d significantly reduced cold-induced wheal volume and CTT and CSTT values versus desloratadine at 5 mg/d . Desloratadine was well tolerated , with no increased rate of somnolence or other AEs with 20 mg of desloratadine . CONCLUSIONS Desloratadine at st and ard and high doses significantly improved objective signs of ACU provoked by cold exposure . Desloratadine at 4 times the st and ard dose significantly reduced ACU lesion severity versus 5 mg of desloratadine without an increase in AEs . This study supports current guidelines that increased desloratadine dosing might benefit patients with urticaria who do not respond to st and ard doses Background : Omalizumab , a recombinant anti‐IgE antibody , effectively treats chronic spontaneous urticaria . 
    Output:
    
Results Our pooled meta‐analyses showed that nonsedating second‐generation H1‐antihistamines ( nsAHs ) are effective in the treatment of ColdU and that updosing of nsAHs significantly reduced CTTs relative to their own st and ard doses and placebos .
Omalizumab result ed in a marked reduction of CTTs in H1‐antihistamine – resistant patients .
Of 118 adverse events in 8 studies , st and ard‐dose nsAHs , updosed nsAHs , and omalizumab produced lower numbers of adverse events than first‐generation antihistamines .
Conclusions Our study showed that greater dosages of nsAHs were more effective than st and ard dosages in controlling ColdU symptoms .
Increasing the dosages was not significantly associated with higher adverse event rates .
Omalizumab at 150 and 300 mg every 4 weeks was shown to be effective for patients with ColdU refractory to antihistamines