***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 : The analgesic effect of oral sucrose in newborn infants undergoing painful procedures is generally accepted . For blood sampling , some studies have shown that venepuncture ( VP ) is less painful than heel lance ( HL ) . Objective : To determine the least painful and most effective method among blood sampling by VP or HL with or without sucrose . Design : R and omised , double blind , placebo controlled trial . Subjects : A total of 100 healthy , full term newborn infants being screened for inborn errors of metabolism were r and omly allocated to one of four experimental groups ( 25 infants in each ) . Intervention and outcome measure : Seven specially trained nurses took turns to carry out blood sampling two minutes after administration of oral sucrose or water .  Neonatal pain was assessed by the neonatal facial coding system ( NFCS ) , as well as by crying . Results : Without sucrose , the NFCS score was higher in the HL group than the VP group during blood sampling ( median 58 v 23 , p<0.001 ) . Oral sucrose significantly reduced the score of the HL group ( 58 v 47 , p<0.01 ) and also tended to reduce the score of the VP group ( 23 v 2 , p<0.1 ) . However , the HL with sucrose group still had a higher score than the VP without sucrose group ( 47 v 23 , p<0.01 ) . Crying and the total procedure time showed the same trends as the NFCS score . Conclusions : VP is less painful and more effective than HL for blood sampling in newborn infants . Although oral sucrose may have an additive analgesic effect , it is not necessarily required if VP is used for blood sampling Intraoral sucrose induces rapid and sustained calm in  crying newborns  and transiently increases mouthing and h and -mouth contact . To determine whether these effects are specific to sucrose and to explore which properties of orogustatory stimuli might contribute to this effect , 60 crying newborns were r and omized to receive 250 ul of 24 % sucrose solution , 0.25 % quinine hydrochloride solution , or corn oil as well as water in a mixed parallel crossover design . Relative to water , sucrose persistently reduced crying , and transiently increased mouthing and h and -mouth contact as previously demonstrated . While quinine produces a " disgust " face in calm infants , in crying infants it transiently decreased crying and increased mouthing , but did not affect h and -mouth contact .  Corn oil had no specific effect on crying , mouthing or h and -mouth contact . The results imply that crying newborns respond differentially to orogustatory stimuli , that taste " salience " rather than positive hedonic valence may account for initial crying reduction and increased mouthing , and that these behavioral effects are not induced by at least one lipid nutrient This experiment had three goals : 1 . To identify the basis of sucking-induced analgesia in healthy , term , newborn humans undergoing the painful , routine , procedure of heel lance and blood collection . 2 . To evaluate how taste-induced and sucking-induced analgesias combine to combat pain . 3 . To determine whether facial grimacing was an accurate index of diminished pain , or whether it was linked to tissue trauma . We report that : 1 . Sucking an unflavored pacifier was analgesic when and only when suck rate exceeded 30 sucks/min . 2 . The combination of sucrose and nonnutritive sucking was remarkably analgesic ; we saw no behavioral indication in nine of the ten infants that the heel lance had even occurred . 3 . Grimacing was reduced to almost naught by procedures that essentially eliminated crying and markedly reduced heart rate during the blood harvesting procedure There is evidence that newborn babies feel pain even at the lowest gestational ages when they can survive . Because sweet solutions such as sucrose , given orally , may relieve pain in neonates , we decided to compare the effects of two concentrations of glucose ( normally used for intravenous infusions ) and of breast milk in a r and omized controlled trial in 120 babies requiring heel‐prick tests .  Glucose solutions and breast milk are readily available in the neonatal department . No other treatment was given . Our results strongly suggest that 1 ml of a 30 % glucose solution given orally alleviates mild pain significantly and can be used for this purpose in newborns . Breast milk and 10 % glucose did not have a similar effect Aim : Increases in heart rate have been widely utilized as pain responses in different studies . In a previous study , we found an increase in heart rate in newborns when they received glucose as pain relief . Other research groups have shown a smaller increase in heart rate on administration of sweet solutions . We therefore investigated the question as to whether or not oral glucose itself can cause an increased heart rate in healthy infants . Method : This was a r and omized , controlled , double‐blind study comprising 70 healthy newborns . They were r and omly allocated to receive 1 ml 30 % glucose or 1 ml placebo solution ( sterile water ) orally without undergoing any painful procedure . The heart rate was recorded during and at different times after this administration . Results : The heart rate was significantly higher in the glucose than in the placebo group ( p=0.020 ) . The highest heart rate was noted during treatment , and the heart rate subsequently decreased in both groups ( p = 0.002 ) Abstract  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size 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 To investigate interventions that affect pain reduction during vaccination in infants and children attending a well-child unit . STUDY DESIGN A consecutive sample of 243 children between age 0 and 48 months receiving their routine vaccinations was r and omly assigned to 1 of the study groups . A total of 158 infants under age 6 months were r and omly assigned to breast-feeding or no breast-feeding during immunization , and 85 children age 6 to 48 months were r and omly assigned to receive 12 % sucrose solution , lidocaine-prilocaine cream , or no intervention . All children were evaluated for crying time and pain score by a pediatrician using the Neonatal Infant Pain Scale ( NIPS ) for those under age 12 months and the Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) for those over age 12 months . RESULTS Breast-feeding in infants under age 6 months and use of sucrose or lidocaine-prilocaine in children age 6 to 48 months significantly reduced crying time and pain scores compared with controls . No difference in outcome was seen between the sucrose and lidocaine-prilocaine treatment groups . CONCLUSIONS Here we exp and on previous findings by demonstrating that breast-feeding may have an analgesic effect up to age 6 months and that in older children , both sucrose and lidocaine-prilocaine reduce vaccination pain AIM To compare the efficacies of non-nutritive sucking and glucose solution as pain-relief interventions for neonates undergoing a venipuncture procedure . BACKGROUND Neonates may be subjected to painful procedures . The individual efficacies of non-nutritive sucking or oral glucose solution used alone on pain-relief for neonates still remain controversial . DESIGN A r and omised , parallel-group controlled trial was design ed . METHODS A total of 105 neonates were r and omly assigned to one of the three groups : non-nutritive sucking , glucose solution , or control group . When a neonate underwent a venipuncture during a newborn screening test , his/her pain manifestations were videotaped and subsequently measured using the Neonatal Infant Pain Scale . Both the stability analysis and the analysis of repeated relationships were performed by generalised estimating equations . RESULTS The level of pain was regressed over the study variables ( time and group ) and covariate ( gestational age ) . Both the non-nutritive sucking and glucose solution groups had significantly lower pain scores than the control group during the venipuncture and recovery phases . Furthermore , non-nutritive sucking seemed to be more effective than glucose solution . CONCLUSION Nurses can use a pain assessment tool and the pain-relief intervention to improve the quality of neonatal care in clinical practice . This study indicates that either non-nutritive sucking or glucose solution can effectively decrease the level of pain . RELEVANCE TO CLINICAL PRACTICE If a painful procedure on neonates is inevitable , simple , convenient and effective pain-relief methods such as non-nutritive sucking or glucose solution can be provided alone . Based on a neonate 's condition , nurses can provide 2 ml of 25 % glucose solution through a syringe for a breastfeeding infant before an invasive procedure if nipple confusion is the concern 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 
    Output:
    
However , most of the individual studies that measured pain found sucrose to significantly reduce pain compared with the control group .
Due to the differences between the studies , we were unable to identify the optimal concentration , volume or method of administration of sweet-tasting solutions in infants aged one to 12 months .
There is insufficient evidence to confidently judge the effectiveness of sweet-tasting solutions in reducing  needle-related pain in infants ( one month to 12 months of age ) .
The treatments do , however , appear promising .
Data from a series of individual trials are promising , as are the results from a subset meta- analysis of studies measuring duration of crying .