***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 Surgical castration in male piglets is painful and methods that reduce this pain are requested . This study evaluated the effect of local anaesthesia and analgesia on vocal , physiological and behavioural responses during and after castration . A second purpose was to evaluate if herdsmen can effectively administer anaesthesia . Methods Four male piglets in each of 141 litters in five herds were r and omly assigned to one of four treatments : castration without local anaesthesia or analgesia ( C , controls ) , analgesia ( M , meloxicam ) , local anaesthesia ( L , lidocaine ) , or both local anaesthesia and analgesia ( LM ) . Lidocaine ( L , LM ) was injected at least three minutes before castration and meloxicam ( M , LM ) was injected after castration . During castration , vocalisation was measured and resistance movements judged . Behaviour observations were carried out on the castration day and the following day . The day after castration , castration wounds were ranked , ear and skin temperature was measured , and blood sample s were collected for analysis of acute phase protein Serum Amyloid A concentration ( SAA ) . Piglets were weighed on the castration day and at three weeks of age . Sickness treatments and mortality were recorded until three weeks of age . Results Piglets castrated with lidocaine produced calls with lower intensity ( p < 0.001 ) and less resistance movements ( p < 0.001 ) during castration . Piglets that were given meloxicam displayed less pain-related behaviour ( huddled up , spasms , rump-scratching , stiffness and prostrated ) on both the castration day ( p = 0.06 , n.s . ) and the following day ( p = 0.02 ) . Controls had less swollen wounds compared to piglets assigned to treatments M , L and LM ( p < 0.001 ) . The proportion of piglets with high SAA concentration ( over threshold values 200 , 400 mg/l ) was higher ( p = 0.005 ; p = 0.05 ) for C + L compared to M + LM . Ear temperature was higher ( p < 0.01 ) for controls compared to L and LM . There were no significant treatment effects for skin temperature , weight gain , sickness treatments or mortality . Conclusions The study concludes that lidocaine reduced pain during castration and that meloxicam reduced pain after castration . The study also concludes that the herdsmen were able to administer local anaesthesia effectively In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence OBJECTIVE We evaluated the inter-rater reliability ( IRR ) of assessing the quality of evidence ( QoE ) using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) approach . STUDY DESIGN AND SETTING On completing two training exercises , participants worked independently as individual raters to assess the QoE of 16 outcomes . After recording their initial impression using a global rating , raters grade d the QoE following the GRADE approach . Subsequently , r and omly paired raters su bmi tted a consensus rating . RESULTS The IRR without using the GRADE approach for two individual raters was 0.31 ( 95 % confidence interval [ 95 % CI ] = 0.21 - 0.42 ) among Health Research Methodology students ( n = 10 ) and 0.27 ( 95 % CI = 0.19 - 0.37 ) among the GRADE working group members ( n = 15 ) . The corresponding IRR of the GRADE approach  in assessing the QoE was significantly higher , that is , 0.66 ( 95 % CI = 0.56 - 0.75 ) and 0.72 ( 95 % CI = 0.61 - 0.79 ) , respectively . The IRR further increased for three ( 0.80 [ 95 % CI = 0.73 - 0.86 ] and 0.74 [ 95 % CI = 0.65 - 0.81 ] ) or four raters ( 0.84 [ 95 % CI = 0.78 - 0.89 ] and 0.79 [ 95 % CI = 0.71 - 0.85 ] ) . The IRR did not improve when QoE was assessed through a consensus rating . CONCLUSION Our findings suggest that trained individuals using the GRADE approach improves reliability in comparison to intuitive judgments about the QoE and that two individual raters can reliably assess the QoE using the GRADE system 
    Output:
    
The panel strongly recommended against the use of a CO2/O2 general anesthesia mixture , weakly recommended for the use of NSAIDs and weakly recommended against the use of lidocaine for pain mitigation during castration of 1- to 28-day-old piglets