***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: Abstract A four-month , double-blind , crossover study of 22 patients with familial Mediterranean fever was undertaken to study the effect of colchicine in decreasing acute attacks of that disease . T Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results BACKGROUND About a quarter of familial Mediterranean fever ( FMF ) patients are partially or totally resistant to colchicine . A previous observation reported that acute attacks may be shortened by administration of interferon alpha ( IFN ) . OBJECTIVE We design ed a double-blind , placebo-controlled trial to test our initial observations of a beneficial response with IFN in FMF attacks . METHODS We treated 34 acute abdominal attacks with IFN 5 million IU or placebo sc in the early phase of the attack . Leucocytes , thrombocytes , the erythrocyte sedimentation rate , fibrinogen , C-reactive protein ( CRP ) , serum amyloid A protein ( SAA ) , haptoglobin , transferrin , IL-1beta and TNF-alpha were measured at hours 0 , 6 , 12 , 24 and 48 . RESULTS The median time to recovery in those treated with IFN and placebo was not significantly different , while the leucocytosis and high levels of fibrinogen were significantly more prolonged in placebo-treated patients . CRP and SAA were extremely elevated and peaked at 24h , remaining less marked in the IFN-treated patients but the difference was not statistically significant . Observations regarding the other parameters were unremarkable . CONCLUSIONS Although there were some clues indicating a depressed inflammatory response with IFN , we could not demonstrate a definitive effect of this agent in this double-blind trial . The drug may suppress the acute inflammation of FMF only if administered at the earliest phase . CRP and SAA may be more sensitive indicators of an attack than ESR or fibrinogen Familial Mediterranean fever ( FMF ) , the most common monogenic autoinflammatory disease , is characterized by recurrent self-limited attacks of fever and serositis . Between 5 % and 10 % of patients are resistant to or intolerant of colchicine , the current st and ard of care ( 1 ) . Pyrin , the mutated protein in FMF , has an important role in the regulation of interleukin-1 ( IL-1 ) activation . This knowledge has led to the effective use of IL-1 inhibitors in 50 reported patients with colchicine-resistant FMF , including in one controlled study ( 2,3 ) . In the present study we assessed the efficacy and safety of canakinumab , a selective , fully human anti – IL-1 monoclonal antibody with a terminal half-life of 26 days , in the treatment of children with colchicine-resistant FMF . This 6-month , phase II , open-label , single-arm study ( clinical trials.gov identifier NCT01148797 ) was conducted in 7 Caucasian children with FMF ( 5 boys and 2 girls ; median age 9.5 years [ range 6.8–14.9 ] ) at 2 centers in Israel ( Rambam Medical Center and Shaare Zedek Medical Center ) . The study was approved by the ethics committees at both hospitals , and informed consent was obtained from the parents/legal guardians of the participants . Patients were diagnosed according to the Tel-Hashomer criteria ( 4 ) , with 2 exon 10 mutations on the MEFV gene ( M694V/M694V in 5 , M694V/ V726A in 1 , and M694V/M680I in 1 ) . Participants were all colchicine resistant , having had 3 well-documented acute FMF attacks  during the 3 months prior to screening despite treatment with colchicine at 1–2 mg/day ( based on age ) for at least 3 months . Following successful screening , participants were enrolled in a 30-day run-in period . Those who experienced 1 investigator-confirmed FMF attack during this time were eligible for treatment . In addition to continuing daily colchicine treatment at the usual dosage , participants received 3 subcutaneous injections ( 4 weeks apart ) of canakinumab 2 mg/kg ( maximum 150 mg ) , with the first injection ( day 1 ) administered during the next attack following the run-in period . The dose was doubled to 4 mg/kg ( maximum 300 mg ) if an attack occurred between the day 1 and day 29 visits . Day 86 was considered the end of the treatment period ( 4 weeks after administration of the last dose of canakinumab ) . Participants were followed up for another 2 visits ( that occurred between day 126 and 160 ) or until an attack occurred ( whichever occurred first ) . Attacks were then treated with acetaminophen and /or nonsteroidal antiinflammatory drugs only . The primary outcome measure was the proportion of participants with 50 % reduction in the frequency of FMF attacks during the treatment period versus the pretreatment period . Secondary outcome measures included acute-phase reactant levels , health-related quality of life ( Child Health Question naire— Parent Form 50 [ CHQ-PF50 ] ) ( 5 ) , physician ’s global assessment of FMF control , time to attack following the last canakinumab injection ( day 57 ) , and safety and tolerability of canakinumab .  Six participants met the primary outcome measure with a 50 % reduction ( range 76–100 % ) in the rate of FMF attacks ( Figure 1 ) . The median 28-day time-adjusted attack rate decreased from 2.7 to 0.3 ( 89 % ) . Three participants did not experience any attacks during the treatment phase . The canakinumab dose was doubled for the second and third injections in 2 participants : a responder who experienced 1 additional brief attack after dose escalation and the single nonresponder , who experienced 3 additional attacks ( 4 attacks overall ) . Compared with 34 attacks over 374 patient-days of followup during the pretreatment phase , only 8 attacks in 601 patient-days were reported during the treatment phase . The proportion of days that participants were experiencing an attack decreased from 24.2 % to 3.6 % . Eighteen of 34 attacks ( 53 % ) were rated as severe or very severe during the pretreatment phase , compared with 0 of 8 during the treatment phase . Following the first injection , clinical manifestations resolved the same day in 4 participants and within 24 hours in 3 . Five participants developed an attack after the last canakinumab  injection , within a median of 25 days ( range 5–34 ) . Median C-reactive protein levels normalized by day 8 ( from 74 mg/liter at baseline to 2 mg/liter on day 8 and 1.3 mg/liter on day 86 ) , the erythrocyte sedimentation rate by day 29 ( from 83 mm/hour at baseline to 17 mm/hour on days 29 and 86 ) , and serum amyloid A levels by day 57 ( from 500 mg/liter at baseline to 2.5 mg/liter on day 57 and 12.2 mg/liter on day 86 ) . Health-related quality of life also improved , with an increase in CHQ-PF50 summary scores for both the physical domain ( from a median of 21 at baseline to 46 on day 86 [ mean 50 in the healthy population ] ) and the psychosocial domain ( 31 to 40 ) . The physician ’s global assessment of FMF control at baseline was rated as very poor in 3 participants , poor in 3 , and fair in 1 . By day 86 this had improved to very good in 4 participants and good in 3 . Eleven adverse events ( AEs ) were reported in 4 participants ; 2 were infections . All were mild except for 1 moderate streptococcal throat infection . There were no serious AEs , opportunistic infections , malignancies , or deaths . No significant laboratory abnormalities occurred , and formation of neutralizing antibodies to canakinumab was not observed . No participants discontinued the study or missed a treatment dose because of an AE . The major limitation of this study , which was primarily a proof-of-concept study , was the small sample size . Of note , the proportion of complete responders ( with no attacks ) was lower than has been reported in studies of other autoinflammatory conditions treated with canakinumab , such as cryopyrin-associated periodic syndrome ( 6 ) and tumor necrosis factor receptor – associated periodic syndrome ( 7 ) , but higher than has been reported in systemic juvenile idiopathic arthritis ( 8) . This may be due in part to the selection , for the present study , of patients whose FMF was severe and resistant to colchicine treatment . The proportion of complete responders was slightly greater in this study than in a r and omized trial of rilonacept treatment in a similar FMF population ( 3 ) OBJECTIVES Modified adult disease severity scoring systems are being used for childhood FMF . We aim to test the clinical consistency of two common severity scoring systems and to evaluate the correlation of scores with the type of FMF mutations in paediatric FMF patients since certain mutations are prone to severe disease . METHODS Two hundred and fifty-eight children with FMF were cross-sectionally studied . Assessment of the disease severity was performed by using the modified scoring systems of Mor et al. and Pras et al. Genetic analysis was performed using PCR and restriction endonuclease digestion methods for the presence of 15 FMF gene mutations . FMF mutations were grouped into three based on well-known genotypic-phenotypic associations . Correlation between the mutation groups and the severity scoring systems was assessed . The consistency of the severity scoring systems was evaluated . RESULTS The results of two scoring systems were not statistically consistent with each other ( κ = 0.171 ) . This inconsistency persisted even in a more homogeneous subgroup of patients with only homozygote mutations of M694V , M680I and M694I ( κ = 0.125 ) . There was no correlation between the mutation groups and either of the scoring systems ( P = 0.002 , r = 0,196 for scoring systems of Mor et al. ; P = 0.009 , r = 0.162 for Pras et al. ) . CONCLUSIONS The inconsistency of the two scoring systems and lack of correlation between the scoring systems and mutation groups raises concerns about the reliability of these scoring systems in children . There is a need to develop a scoring system in children based on a prospect i ve registry Nine patients with familial Mediterranean fever ( FMF ) were admitted to a controlled , double-blind trial to determine if there are patients with this disease who are able to abort their acute episodes of pain and fever with short courses of colchicine taken at the onset of attacks . Five patients completed their treatment assignments , and colchicine was significantly effective in aborting the attacks of three but was ineffective in two . The remaining four patients could not be assessed because of insufficient numbers of courses . During the 10 months of the trial , 28 courses of colchicine and 31 of placebo were taken during the early stages of FMF attacks . Twenty-one ( 75 % ) colchicine courses were followed by attacks considered to have been aborted , compared to only three ( 10 % ) placebo courses . This trial shows that patients can recognize the prodrome of their FMF attacks and that some patients can consistently abort their attacks with short courses of colchicine taken at the very onset of symptoms Double blind , r and omized , placebo controlled pilot study of ImmunoGuard -- a st and ardized fixed combination of And rographis paniculata Nees . , Eleutherococcus senticosus Maxim . , Schiz and ra chinensis Bail . , and Glycyrrhiza glabra L. special extracts st and ardized for the content of And rographolide ( 4 m 
    Output:
    
Colchicine is an effective treatment in FMF