***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 
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    Input: AIMS This study examined the effectiveness of non-nutritive sucking on  preterm infant pain , changes in infant behaviour and frequency of abnormal physiological signals during heel stick procedures in Taiwan . BACKGROUND Preterm infants ' repetitive exposure to painful procedures may result in changes to brain organisation . Pain management should be a priority in neonatal care . DESIGN R and omised control trial . METHODS Preterm infants ( gestational age 28.9 - 37 weeks ) were r and omised to two groups : those receiving ( experimental , n = 52 ) or not receiving non-nutritive sucking ( control , n = 52 ) during heel stick procedures .  Pain was measured before ( for three minutes ) , during and after ( during 10-minute recovery ) heel stick procedures by the Premature Infant Pain Profile , changes in infant behaviour and abnormal physiological parameters . Results . Infants in both groups had similar odds ratios for pain and moderate-to-severe pain ( 0.57 and 0.58 , respectively ) , after adjusting for time effects , postconceptional age , heel stick duration , painful experiences and baseline Premature Infant Pain Profile score . The pain scores of infants with non-nutritive sucking were significantly lower than those of non-nutritive sucking infants at all eight phases of the heel stick procedures . Infants undergoing heel stick procedures in the experimental group had lower rates ratios for ' grimace ' and ' h and to mouth or face ' behaviours than control infants ( 0.73 and 0.78 , respectively ) . CONCLUSION Non-nutritive sucking effectively reduced pain , particularly mild to moderate pain and behavioural responses to pain in infants receiving heel stick procedures , suggesting that nurses can offer this intervention to relieve pain in preterm infants undergoing invasive procedures . RELEVANCE TO CLINICAL PRACTICE Infants should be given an appropriate-sized pacifier for comfort during painful procedures . Nurses need to be informed about the effectiveness of non-nutritive sucking , its analgesic mechanisms and how to use and incorporate it into practice BACKGROUND : Eye examinations for retinopathy of prematurity ( ROP ) are painful to the neonate . The use of topical anesthetic for eye examinations to evaluate ROP is routine in our neonatal intensive care unit ( NICU ) , but does not completely suppress painful responses . Sweet solutions have been shown to reduce procedural pain in newborns . OBJECTIVE : To examine whether the addition of sucrose 24 % to topical anesthetic improves procedural pain control during the ROP eye examination . METHODS : Neonates born at ⩽30 weeks ' gestation were included in this placebo-controlled , double-blind , crossover study . Patients were r and omly assigned to receive treatment with either proparacaine HCl ophthalmic solution 0.5 % plus 2 mL of sucrose 24 % or proparacaine HCl ophthalmic solution 0.5 % plus 2 mL of sterile water ( placebo ) prior to an eye examination . In a subsequent eye examination , each patient received the alternate treatment . Oral sucrose and sterile water were prepared in the pharmacy in identical syringes , and physicians , nurses , and pharmacists in the NICU were blinded to the treatment given . Pain was measured using the Premature Infant Pain Profile ( PIPP ) scoring system , which measures both physical and physiologic measures of pain , and the scores were simultaneously assessed by 2 study nurses . PIPP scores were recorded 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum . The same ophthalmologist performed all eye examinations . Several different definitions of a pain response were investigated . RESULTS : Twenty-three infants were studied , with 12 receiving sucrose and 11 receiving placebo  as the first treatment . For 3 of the 5 definitions of pain response , patients experienced significantly less pain at speculum insertion with sucrose than with placebo . After the ROP examination , pain responses were similar with either sucrose or placebo . CONCLUSIONS : Oral sucrose may reduce the immediate pain response in premature infants undergoing eye examination for ROP Objective : The objective of this study was to evaluate and compare the efficacy of combined sucrose and non-nutritive sucking ( NNS ) for analgesia in newborn infants undergoing heel-stick procedures . Study Design : This r and omized control trial was conducted in the neonatal intensive care unit of a tertiary care hospital over a period of 1 year . One hundred and eighty full-term neonates with birth weight > 2200 g and age > 24 h were r and omized to one of four interventions administered 2 min before the procedure : 2 ml of 30 % sucrose ( group I , n=45 ) or NNS ( group II , n=45 ) or both ( group III , n=45 ) or none ( group IV , n=45 ) . Primary outcome was composite score based on Premature Infant Pain Profile ( PIPP ) score . Result : Baseline variables were comparable among the groups . Median ( interquartile range ) PIPP score was 3 ( 2 to 4 ) in group III as compared with 7 ( 6.5 to 8) in group I , 9 ( 7 to 11 ) in group II and 13 ( 10.5 to 15 ) in group IV . Group III had significant decrease in the median PIPP score compared with other groups ( P=0.000 ) . Median PIPP score also decreased significantly with any intervention as compared with no intervention ( P=0.000 ) . Conclusion : Sucrose and /or NNS are effective in providing analgesia in full-term neonates undergoing heel-stick procedures , with the combined intervention being more effective compared with any single intervention OBJECTIVE To determine the efficacy of sucrose analgesia for procedural pain during the first week of life in preterm neonates in neonatal intensive care units on enhancing later clinical outcomes . METHODS A total of 107 preterm neonates who were born at < 31 weeks ' postconceptional age ( PCA ) entered this double-blind , r and omized , controlled trial within 48 hours of birth at 3 level III university-affiliated neonatal intensive care units in Canada , and 103 completed the study .  Sucrose ( 0.1 mL of 24 % ) or sterile water was administered orally up to 3 times , 2 minutes apart , for every invasive procedure during a 7-day period . Motor development and vigor , and alertness and orientation components of the Neurobehavioral Assessment of the Preterm Infant were measured at 32 , 36 , and 40 weeks ' PCA ; Score for Neonatal Acute Physiology was measured on the last day of intervention ; and Neuro-Biological Risk Score ( NBRS ) was measured at 2 weeks of age and at discharge . Primary analyses of covariance were applied for each outcome to compare group differences followed by secondary analyses using st and ard linear regression within each group to determine predictors of outcomes . RESULTS Although there were no differences between the groups on any outcomes , there were significant dose-related effects within each group . In the sucrose group only , higher number of doses of sucrose predicted lower scores on motor development and vigor , and alertness and orientation at 36 weeks ' , lower motor development and vigor at 40 weeks ' , and higher NBRS at 2 weeks ' postnatal age . Higher number of invasive procedures was predictive of higher NBRS both times in the water group . CONCLUSIONS Repeated use of sucrose analgesia in infants < 31 weeks ' PCA may put infants at risk for poorer neurobehavioral development and physiologic outcomes . Additional study is needed to determine the most appropriate age and duration of sucrose analgesia in preterm infants BACKGROUND Despite an increasing awareness regarding pain management in neonates and the availability of published guidelines for the treatment of procedural pain , preterm neonates experience pain leading to short- and long-term detrimental effects . OBJECTIVE To assess the frequency of use of analgesics  in invasive procedures in neonates and the associated pain burden in this population . METHODS For 151 neonates , we prospect ively recorded all painful procedures , including the number of attempts required , and analgesic therapy used during the first 14 days of neonatal intensive care unit admission . These data were linked to estimates of the pain of each procedure , obtained from the opinions of experienced clinicians . RESULTS On average , each neonate was subjected to a mean + /- SD of 14 + /- 4 procedures per day . The highest exposure to painful procedures occurred during the first day of admission , and most procedures ( 63.6 % ) consisted of suctioning . Many procedures ( 26 of 31 listed on a question naire ) were estimated to be painful ( pain scores > 4 on a 10-point scale ) . Preemptive analgesic therapy was provided to fewer than 35 % of neonates per study day , while 39.7 % of the neonates did not receive any analgesic therapy in the neonatal intensive care unit . CONCLUSIONS Clinicians estimated that most neonatal intensive care unit procedures are painful , but only a third of the neonates received appropriate analgesic therapy . Despite the accumulating evidence that neonatal procedural pain is harmful , analgesic treatment for painful procedures is limited . Systematic approaches are required to reduce the occurrence of pain and to improve the analgesic treatment of repetitive pain in neonates A r and omized study was done to compare non pharmacological methods to reduce the pain of heel pricks in 104 stable term neonates .  Non-nutritive sucking ( NNS ) , rocking , massage , sucrose ( 20 percent ) , distilled water ( DW ) and expressed breast milk ( EBM ) were used as pain reducing agents . Duration of cry and Douleur Aiguë du Nouveau né ( DAN ) score were used to assess pain . Physiological parameters were also recorded before and after the stimulus . At 30 seconds after the stimulus , the pain scores were lowest in the sucrose group but this was not sustained at 1 , 2 and 4 minutes . At 2 and 4 minutes pain scores were lowest in the NNS and rocking groups as compared to sucrose , distilled water , expressed breast milk and massage . The total duration of crying was also lowest in the NNS and rocking groups . Physiological parameters were comparable in all groups . Babies who were in Prechtl State 1 and 2 ( sleeping ) at the time of stimulus showed significantly lesser response to pain compared to babies who were awake . This was seen in all the intervention groups . In conclusion , our study suggests that rocking or giving a baby a pacifier are more effective non-pharmacological analgesics than EBM , DW , sucrose or massage for the pain of heel pricks in neonates . A calm or sleeping state before a painful procedure also appears to decrease crying and pain scores 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 To assess the characteristics of sucrose as a pain-reducing substance , crying in 72 newborn humans during and after blood collection via heel prick was determined . In the first study infants drank 2 ml of water or 2 ml of a 0.17 - 0.34- or 0.51-M sucrose solution 1 min prior to blood collection . In the second experiment , a delay of 30 , 60 , 90 , 120 or 240 s was imposed between sucrose intake and the initiation of blood collection . The dose-response function for concentration was flat . The most effective time delay was 120 s. The effectiveness of the 2-min interval accords with previous findings of endogenous opioid release caused by sucrose taste . The flat dose-response function extends findings in rats and humans that the calming and pain-reducing effects of sucrose are not influenced by either concentration or volume , suggesting that the transduction from gustatory afferent to opioid-mediated efferent is of an on-off nature and not grade Premature infants are at risk for adverse motor outcomes , including cerebral palsy and developmental coordination disorder . The purpose of this study was to examine the relationship of antenatal , perinatal , and postnatal risk factors for abnormal development of the corticospinal tract , the major voluntary motor pathway , during the neonatal period . In a prospect i ve cohort study , 126 premature neonates ( 24 - 32 weeks ' gestational age ) underwent serial brain imaging near birth and at term-equivalent age . With diffusion tensor tractography , mean diffusivity and fractional anisotropy of the corticospinal tract were measured to reflect microstructural development . Generalized estimating equation models examined associations of risk factors on corticospinal tract development . The perinatal risk factor of greater early illness severity ( as measured by the 
    Output:
    
Conclusion : The pooled evidence indicates that the combination measures may serve as an evidence -based guideline for pain relief among patients having minor pain .
Besides , it also indicates that OS combined with NNS can be an alternative for better prevention and management of procedure pain in NICU newborns .