***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 To study the patterns of supraspinal pain processing in neonates , we hypothesized that acute pain causes haemodynamic changes associated with activation of the primary somatosensory cortex . Forty preterm neonates at 28–36 weeks of gestation ( mean = 32.0 ) and at 25–42 h ( mean = 30.7 ) of age were studied following st and ardized tactile ( skin disinfection ) and painful ( venipuncture ) stimuli .  Changes in regional cerebral haemodynamics were monitored by near infrared spectroscopy ( NIRS ) over both somatosensory cortices in 29 newborns , and over the contralateral somatosensory and occipital areas in 11 newborns . Heart rate ( HR ) and peripheral oxygen saturation ( SaO2 ) were recorded simultaneously with NIRS parameters : oxygenated [ HbO2 ] , deoxygenated , and total hemoglobin . Tactile stimulation produced no changes in HR or SaO2 . HR increased in the first 20 s ( p < 0.001 ) , while SaO2 decreased during the 40 s after venipuncture ( p < 0.0001 ) . Following tactile or painful stimulation , [ HbO2 ] increased bilaterally regardless of which h and was stimulated ( p < 0.0001 ) . Pain‐induced [ HbO2 ] increases in the contralateral somatosensory cortex ( p < 0.05 ) were not mirrored in the occipital cortex ( p > 0.1 ) . Pain‐related [ HbO2 ] increases were more pronounced in male neonates ( p < 0.05 on left , p < 0.001 on right ) , inversely correlated with gestational age ( r = −0.53 on left , p < 0.01 ; r = −0.42 on right , p < 0.05 ) and directly correlated with postnatal age ( r = 0.75 on left , p < 0.0001 ; r = 0.67 on right , p < 0.0001 ) . Painful and tactile stimuli elicit specific haemodynamic responses in the somatosensory cortex , implying conscious sensory perception in preterm neonates . Somatosensory cortical activation occurs bilaterally following unilateral stimulation and these changes are more pronounced in male neonates or preterm neonates at lower gestational ages CONTEXT Effective strategies to improve pain management in neonates require a clear underst and ing of the epidemiology and management of procedural pain . OBJECTIVE To report epidemiological data on neonatal pain collected from a geographically defined region , based on direct bedside observation of neonates . DESIGN , SETTING , AND PATIENTS Between September 2005 and January 2006 , data on all painful and stressful procedures and corresponding analgesic therapy from the first 14 days of admission were prospect ively collected within a 6-week period from 430 neonates admitted to tertiary care centers in the Paris region of France ( 11.3 millions inhabitants ) for the Epidemiology of Procedural Pain in Neonates ( EPIPPAIN ) study . MAIN OUTCOME MEASURE Number of procedures considered painful or stressful by health personnel and  corresponding analgesic therapy . RESULTS The mean ( SD ) gestational age and intensive care unit stay were 33.0 ( 4.6 ) weeks and 8.4 ( 4.6 ) calendar days , respectively . Neonates experienced 60,969 first-attempt procedures , with 42,413 ( 69.6 % ) painful and 18,556 ( 30.4 % ) stressful procedures ; 11,546 supplemental attempts were performed during procedures including 10,366 ( 89.8 % ) for painful and 1180 ( 10.2 % ) for stressful procedures . Each neonate experienced a median of 115 ( range , 4 - 613 ) procedures during the study period and 16 ( range , 0 - 62 ) procedures per day of hospitalization . Of these , each neonate experienced a median of 75 ( range , 3 - 364 ) painful procedures during the study period and 10 ( range , 0 - 51 ) painful procedures per day of hospitalization . Of the 42,413 painful procedures , 2.1 % were performed with pharmacological-only therapy ; 18.2 % with nonpharmacological-only interventions , 20.8 % with pharmacological , nonpharmacological , or both types of therapy ; and 79.2 % without specific analgesia , and 34.2 % were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons . Prematurity , category of procedure , parental presence , surgery , daytime , and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia , whereas mechanical ventilation , noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia . CONCLUSION During neonatal intensive care in the Paris region , large numbers of painful and stressful procedures were performed , the majority of which were not accompanied by analgesia Despite the recent increase in our underst and ing of the development of pain processing , it is still not known whether premature infants are capable of processing pain at a cortical level . In this study , changes in cerebral oxygenation over the somatosensory cortex were measured in response to noxious stimulation using real-time near-infrared spectroscopy in 18 infants aged between 25 and 45 weeks postmenstrual age . The noxious stimuli were heel lances performed for routine blood sampling ; no blood tests were performed solely for the purpose of the study . Noxious stimulation produced a clear cortical response , measured as an increase in total hemoglobin concentration [ HbT ] in the contralateral somatosensory cortex , from 25 weeks ( mean Δ[HbT ] = 7.74 μmol/L ; SE , 1.10 ) . Cortical responses were significantly greater in awake compared with sleeping infants , with a mean difference of 6.63 μmol/L [ 95 % confidence interval ( CI ) limits : 2.35 , 10.91 μmol/L ; mean age , 35.2 weeks ] . In awake infants , the response in the contralateral somatosensory cortex increased with age ( regression coefficient , 0.698 μmol/L/week ; 95 % CI limits : 0.132 , 1.265 μmol/L/week ) and the latency decreased with age ( regression coefficient , −0.9861 μmol/L/week ; 95 % CI limits : −1.5361 , −0.4361 μmol/L/week ; age range , 25–38 weeks ) . The response was modality specific because no response was detected after non-noxious stimulation of the heel , even when accompanied by reflex withdrawal of the foot . We conclude that noxious information is transmitted to the preterm infant cortex from 25 weeks , highlighting the potential for both higher-level pain processing and pain-induced plasticity in the human brain from a very early age Background Procedural pain relief is sub-optimal in infants , especially small and vulnerable ones .  Tetracaine gel 4 % ( Ametop ® , Smith-Nephew ) provides pain relief in children and larger infants , but its efficacy in smaller infants and for peripherally inserted central catheters ( PICC ) remains uncertain . The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight ( VLBW ) infants during insertion of a PICC . Methods Medically stable infants greater than or equal to 24 weeks gestation , requiring a non-urgent PICC , were included . Following r and omization and double blinding , 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes . The PICC was inserted according to a st and ard protocol . Pain was assessed using the Premature Infant Pain Profile ( PIPP ) . A 3-point change in the pain score was considered clinical ly significant , leading to a sample size of 54 infants , with 90 % statistical power . Local skin reactions and immediate adverse cardiorespiratory events were noted . The primary outcome , PIPP score at 1 minute , was analysed using an independent Student 's t-test . Results Fifty-four infants were included , 27 + /- 2 weeks gestation , 916 + /- 292 grams and 6.5 + /- 3.2 days of age . Baseline characteristics were similar between groups . The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group ( difference 0.86 , 95 % CI -1.86 , 3.58 ) . Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group ( difference -78 , 95 % CI -539 , 117 ) . Local skin erythema was observed transiently in 4 infants ( 3 in the treatment and 1 in the placebo group ) . No serious harms were observed . Conclusion Tetracaine 4 % when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants 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 most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVE Inadequate assessment of  pain in premature infants is a persistent clinical problem . The objective of this research was to develop and vali date a measure for assessing pain in premature infants that could be used by both clinicians and research ers . DESIGN The  Premature Infant Pain Profile ( PIPP ) was developed and vali date d using a prospect i ve and retrospective design . Indicators of pain were identified from clinical experts and the literature . Indicators were retrospectively tested using four existing data sets . PATIENTS AND SETTING S Infants of varying gestational ages undergoing different painful procedures from three different setting s were utilized to develop and vali date the measure . METHODS AND RESULTS The largest data set ( n = 124 ) was used to develop the PIPP . The development process included determining the factor structure of the data , developing indicators and indicator scales and establishing internal consistency . The remaining three data sets were utilized to establish beginning construct validity . CONCLUSIONS The PIPP is a newly developed pain assessment measure for premature infants with beginning content and construct validity . The practicality and feasibility for using the PIPP in clinical practice will be determined in prospect i ve research in the clinical setting Objective : Preterm neonates undergo numerous painful procedures in the neonatal intensive care unit ( NICU ) .  Sucrose , with and without pacifiers , is effective and safe for relieving pain from single painful events . However , repeated use of sucrose for multiple painful procedures has not been adequately evaluated . The study objectives were to : 1 ) determine the efficacy and safety of consistent management of repeated procedural pain with sucrose ; and 2 ) explore the impact of consistent pain management on clinical outcomes and neurobiological risk status . Methods : Sixty-six preterm infants were r and omized to receive st and ard care ( positioning and swaddling ; n = 21 ) , sterile water plus pacifier ( n = 23 ) , or 24 % sucrose plus pacifier ( n = 22 ) prior to all painful procedures in the NICU during the first 28 days of life . Also , at a routine heel lance at 7 , 14 , 21 , and 28 days of life , data were collected to determine efficacy and immediate and long-term adverse events . Data on clinical outcomes and neurobiological risk status were collected at 28 days or NICU discharge . Results : There was no intervention by time interaction ( P = 0.60 ) . There was a significant main effect of intervention ( P = 0.03 ) between the sucrose plus pacifier group , and the st and ard care group ( P = 0.01 ) , but there was no main effect of time ( P = 0.72 ) . No group differences existed for adverse events , clinical outcomes , or neurobiological risk status . Discussion : Consistent management of painful procedures with sucrose plus pacifier was effective and safe for preterm neonates during their stay in the NICU . Further exploration of consistent pain management with sucrose on clinical , developmental , and neurobiological outcomes is required & NA ; The responses of preterm neonates to acute tissue‐damaging stimuli have been described . However , factors which influence these responses have received little attention . In this study , we observed 124 premature infants before , during and after a 
    Output:
    
Sucrose is safe and effective for reducing procedural pain from single events .