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Background: Combination therapy with multiple phosphate binders is prescribed to reduce elevated serum phosphorus (sP) concentrations among patients on maintenance hemodialysis. Sucroferric oxyhydroxide (SO), an iron-based phosphate binder, has demonstrated efficacy at reducing sP while also being associated with a low pill burden. Whereas the effects of SO monotherapy have been well characterized in clinical trials and observational cohorts, little is known about the effects of SO-containing combination therapy., Methods: Patients on hemodialysis ( N =234) at Fresenius Kidney Care (FKC) who received ≥120 days of uninterrupted phosphate binder combination therapy with SO were included in this retrospective study. Patient data were censored after SO discontinuation, end of care at FKC, or completion of 12 months of follow-up. Quarterly (Q) changes in phosphate binder pill burden, mean sP, and proportion of patients achieving National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI)-recommended sP levels (≤5.5 mg/dl) were compared between baseline (-Q1) and follow-up (Q1-Q4)., Results: Phosphate binder combination therapy with SO was associated with significant increase in the proportion of patients with sP ≤5.5 mg/dl (from 19% at baseline to up to 40% at follow-up; P <0.001) and reduction in sP at all postbaseline time points (from 6.7 mg/dl to 6.2-6.3 mg/dl; P <0.001). Patients on calcium acetate ( N =54) and sevelamer ( N =94) who added SO therapy at follow-up resulted in a ≥250% increase in patients achieving sP ≤5.5 mg/dl (all P <0.001). Whereas mean phosphate binder pill burden increased with initiation of phosphate binder combination therapy with SO (15.8 pills/d at Q1 versus 12.3 pills/d at -Q1), continued use of SO was associated with down-titration of non-SO phosphate binders such that, by Q4, mean total PB pill burden reduced to 12.3 pills/d., Conclusions: For patients on hemodialysis with uncontrolled hyperphosphatemia, combination therapy with SO may allow for sustained improvements in sP control without adversely affecting phosphate binder pill burden., Competing Interests: L. Ficociello, R. Kossmann, C. Mullon, and V. Parameswaran are employees of Fresenius Medical Care Renal Therapies Group. R. Kossmann and C. Mullon own stock in Fresenius Medical Care North America. R. Kossmann is on the board of directors of Advanced Renal Technologies. D. Molony is professor of medicine at the McGovern Medical School, University of Texas Houston, and reports personal fees from Fresenius Medical Care outside the submitted work., (Copyright © 2020 by the American Society of Nephrology.)

To compare the efficacy of low dose fentanyl infusion and 24% oral sucrose in providing optimal pain relief during laser for retinopathy of prematurity (ROP), we enrolled fifty-eight spontaneously breathing preterm infants undergoing laser. The preterm infants were randomized to either fentanyl infusion (1 mcg/kg/hr) or 24% oral sucrose (2 ml). We evaluated and compared the proportion of time spent crying during the procedure, salivary cortisol before and after the procedure, premature infant pain profile- revised (PIPP-R) scores during the procedure, apnoea during and after the procedure, need for mechanical ventilation, and feed intolerance and urinary retention 24 h after the procedure between the two groups. We found that the proportion of time spent crying during the procedure was significantly less in the fentanyl group [62.5% (50.7-74.2) vs 73.8% (55.6-83.4); P = 0.02]. Average PIPP-R score during the procedure was significantly less in the fentanyl group [7.2 vs 9.0; (mean difference of - 1.8; P = 0.01)]. There was no difference in other outcomes between the two groups.Conclusion: During laser for ROP, low dose fentanyl infusion was found to be efficacious in reducing pain as compared with 24% sucrose.What is Known:• Preterm infants undergoing laser photocoagulation for ROP suffer significant amount of pain.• Standard of care for pain relief in infants undergoing laser therapy in developed countries is general anesthesia (GA) or combination of sedation, analgesia, and paralysis (SAP).What is New:• During laser photocoagulation for ROP, fentanyl infusion at low dose (1 mcg/kg/hr) is efficacious in reducing pain as compared to 24% oral sucrose.

Objectives: The aim of the present study was to evaluate the growth and acid synthesis of cariogenic pathogens in vitro when rebaudioside A was the sole source of carbon, compared to sucrose, xylitol, and a commercial sweetener containing rebaudioside A., Materials and Methods: First, sucrose or sugar substitutes were added to human saliva and the pH was measured over 10 h. Subsequently, the growth and acid synthesis efficiency of Streptococcus mutans, Streptococcus sobrinus, Streptococcus oralis, Lactobacillus rhamnosus, Lactobacillus paracasei, and Candida albicans were investigated: after adding them to minimal culture media containing only one of the carbon sources, the optical density and pH were determined over 10 h., Results: A significant pH drop only occurred in the sucrose group of human saliva whereas no differences were found between the sugar substitute groups. The individual strains of caries pathogens showed significantly lower growth rates and less acid synthesis in the sugar replacement groups, in comparison to sucrose. However, these groups also showed bacterial growth and a decline in pH., Conclusion: Xylitol appeared to be superior to rebaudioside A regarding the inhibition of mutans streptococci. The results for the remaining microorganisms indicate that rebaudioside A causes a similar or lower acid synthesis than xylitol. As saliva contains buffer systems, the metabolism of rebaudioside A did not seem to shift the equilibrium to demineralization., Clinical Relevance: Rebaudioside A may not be suitable as a targeted Streptococcus mutans treatment, but it could contribute to a reduction of caries risk as a replacement for sucrose.

Objective: To compare the analgesic effects of sucrose, music, and their combination on venipuncture's pain in preterm neonates., Methodology: A double-blinded randomized control trial conducted at a Neonatal Intensive Care Unit (NICU) affiliated to Tehran University of Medical Sciences (TUMS) in Tehran, Iran. One hundred and twenty preterm neonates were randomly allocated into three experimental (sucrose, music and combination of sucrose and music) and one control groups (n = 30 for each group). Two minutes before the venipuncture, 0.5 ml of oral 24% sucrose was provided for the sucrose and combination groups. The combination group additionally received lullaby music as same as the music group. The control group had headphones without playing music and received sterile water. Blinded assessment of the Premature Infant Pain Profile (PIPP) was performed before and during venipuncture, as well as 30 s and 10 min and 10 min after its completion., Results: The pain scores during venipuncture in the sucrose and combination groups were significantly lower than the control group (p = .003, p < .001, respectively) but not in the music group. Thirty seconds after the end of the venipuncture, the pain score in the three intervention groups was significantly lower than the control group (sucrose, music and, combination group, p < .001, p = .009, p < .001, respectively). Ten min after the venipuncture, there was no significant difference in pain scores among the four groups., Conclusion: Music could relief pain 30 s after the venipuncture completion but not during the venipuncture. A more prolonged period of playing music is recommended to evaluate the analgesic effects of music in preterm neonates in future studies., Competing Interests: Declaration of Competing Interest There is no conflict of interest to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Sucroferric oxyhydroxide (SOH) is an iron-based phosphate binder (PB), and its use has been widely expanded since its initial approval in 2014. Based on the existing data, however, it remains yet unclear whether its long-term administration is followed by iron overload in dialysis patients. The purpose of this observational study was to evaluate the longstanding effects of SOH on the anemia and iron indices in patients on dialysis., Methods: A total of 110 patients from 3 dialysis centers were included in the study; 49 were under chronic treatment with SOH (cohort A), while 61 were either receiving other PB or no treatment for hyperphosphatemia (cohort B). We initially compared the hematologic profile of patients in 2 cohorts (phase I), and subsequently, we evaluated modifications of the above parameters in the SOH treated patients over a period of 6 months (phase II)., Results: There were no statistically significant differences between 2 cohorts in terms of hemoglobin (Hb; 11.4 ± 1.3 vs. 11.6 ± 0.9 g/dL, p = 0.375), ferritin (473 ± 230 vs. 436 ± 235 ng/mL, p = 0.419) and transferrin saturation (TSAT;26.6 ± 13.2 vs. 26.5 ± 10.6%, p = 0.675), serum phosphate concentration (4.57 ± 1.05 vs. 4.3 ± 0.96 mg/dL, p = ns), and intact PTH (286 ± 313 vs. 239 ± 296 pg/mL, p = ns). Marginally, but significantly higher calcium levels were found in cohort A compared to cohort B (9.18 ± 0.58 vs. 8.9 ± 0.51 mg/dL, respectively, p = 0.008). In phase II, no significant changes were observed in hematological parameters after a 6-month treatment with SOH (Hb: from 11.5 ± 1.1 to 11.4 ± 1.3 g/dL, p = 0.4, serum ferritin levels: from 475 ± 264 to 473 ± 230 ng/mL, p = 0.951, TSAT: from 26.5 ± 16.7 to 26.6 ± 13.2%, p = 0.933). There were also no significant changes in the administration of iron supplements or erythropoietin dose during this period., Conclusions: SOH is an effective PB, and its long-term use is not complicated by iron overload., (© 2020 S. Karger AG, Basel.)

Introduction: Control of hyperphosphatemia in patients on dialysis remains a major challenge., Objective: This study evaluated predictors of serum phosphorus (sP) control among dialysis patients treated with noncalcium, oral phosphate binder therapy in a phase 3 clinical trial., Methods: Post hoc analyses were performed using data for patients with hyperphosphatemia who received 52 weeks of treatment with sucroferric oxyhydroxide (SFOH) or sevelamer carbonate (sevelamer). Patients were categorized into those who achieved sP control (n = 302; defined as sP ≤ 5.5 mg/dL at week 52), and those with uncontrolled sP (n = 195; sP >5.5 mg/dL at week 52). Because SFOH and sevelamer have previously demonstrated similar effects on chronic kidney disease-mineral-bone disorder parameters in this study, the treatment groups were pooled., Results: Average age at baseline was higher among sP-controlled versus sP-uncontrolled patients (56.9 vs. 53.4 years; p = 0.005). Baseline sP levels were significantly lower among sP-controlled versus sP-uncontrolled patients (7.30 vs. 7.85 mg/dL; p < 0.001), and sP reductions from baseline were significantly greater in the sP-controlled group (-2.89 vs. -0.99 mg/dL at week 52; p < 0.001). Logistic regression analysis identified higher baseline sP levels (odds ratio [OR] = 0.86, 95% confidence interval [CI]: 0.765-0.960), no concomitant active vitamin D therapy use (OR = 0.51, 95% CI: 0.328-0.804), and higher body mass index at baseline (OR = 0.96, 95% CI: 0.937-0.992) as significant predictors of uncontrolled sP., Conclusion: This analysis indicates that sP control may be more challenging in younger patients with high sP levels. Closer monitoring and management of serum phosphorus levels may be required in this population., (The Author(s). Published by S. Karger AG, Basel.)

Objective: Diabetes is one of the most widespread diseases in Germany. Common complications are diabetic foot ulcers (DFU), which are associated with a cost-intensive treatment and serious adverse events, such as infections, amputations. This cost-effectiveness analysis compares two treatment options for patients with DFU: a TLC-NOSF dressing versus a neutral dressing, assessed through a European double-blind randomised controlled trial (RCT), Explorer., Methods: The evaluation of the clinical outcomes was associated to direct costs (costs for dressings, nursing time, hospitalisation etc.) of both dressings, from the perspective of the statutory health insurance in Germany. Due to the long mean healing time of a DFU, the observation period was extended from 20 to 100 weeks in a Markov model., Results: After 20 weeks, and with complete closure as a primary endpoint, the model revealed direct treatment costs for DFU of €2,864.21 when treated with a TLC-NOSF dressing compared with €2,958.69 with the neutral control dressing (cost-effectiveness: €6,017.25 versus €9,928.49). In the Markov model (100 weeks) the costs for the TLC-NOSF dressing were €5,882.87 compared with €8,449.39 with the neutral dressing (cost-effectiveness: €6,277.58 versus €10,375.56). The robustness of results was underlined by several sensitivity analyses for varying assumptions. The frequency of weekly dressing changes had the most significant influence in terms of parameter uncertainty., Conclusion: Overall, the treatment of DFU with a TLC-NOSF dressing is supported from a health economic perspective, because both the treatment costs and the cost-effectiveness were superior compared with the neutral wound dressing.

Infants undergo painful procedures involving skin puncture as part of routine medical care. Pain from needle puncture procedures is suboptimally managed. Numerous nonpharmacologic interventions are available that may be used for these painful procedures, including swaddling/containment, pacifier/non-nutritive sucking, rocking/holding, breastfeeding and breastmilk, skin-to-skin care, sweet tasting solutions, music therapy, sensorial saturation, and parental presence. Adoption these interventions into routine clinical practice is feasible and should be a standard of care in quality health care for infants. This review summarizes the epidemiology of pain from common needle puncture procedures in infants, the effectiveness of nonpharmacologic interventions, implementation considerations, and unanswered questions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period., Design: Historical cohort analyses of de-identified electronic medical records., Subjects: In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12 months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse., Main Outcome Measures: Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (≤5.5 mg/dL) and mean number of PB pills/day., Results: Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1 year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P < .0001 for all). Reductions in serum phosphorus were observed at all follow-up timepoints (P < .0001), irrespective of baseline PB. From a mean baseline PB pill burden of 8.5 pills/day, patients experienced an average 50% pill burden reduction during SO treatment (P < .0001). Phosphorus-attuned albumin and phosphorus-attuned protein intake (normalized protein catabolic rate) improved significantly after transition to SO (P < .0001). The effectiveness of SO was evident in prespecified subgroups of interest (i.e., black/African-American patients, Hispanic/Latino patients, and women)., Conclusion: Among patients on hemodialysis, switching to SO resulted in a 2-fold greater likelihood of achieving target phosphorus levels while halving daily PB pill burden. Increases in phosphorus-attuned albumin and protein intake suggest improved nutritional status., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Procedural pain is one of the most significant problems in neonates, especially in premature babies. Harmless and effective pain relief modalities in newborns should thus be applied. Although sucrose is the most commonly used agent, the most effective dose and concentration of sucrose is not clear. In this study, we compared the efficacy of two different doses of sucrose during venepuncture in neonates., Methods: This was a prospective, randomized, double-blind study. The study was conducted during venous sampling. Oral 24% sucrose (Tool sweet ™ Natus Medical, San Carlos, CA, USA) was given by sterile syringe onto the anterior part of the tongue. Group 1 (n = 65) received 0.2 mL/kg 24% sucrose and group 2 (n = 64) received 0.5 mL/kg 24% sucrose. The Bernese Pain Scale for Neonates (BPSN) was used to assess the pain scores before, during and after the procedure., Results: One hundred and twenty-nine premature infants were enrolled in the study, consisting of 67 girls (51.9%) and 62 boys (48.1%) aged 1-24 days (mean age, 8.34 ± 6.25 days). There was no significant difference in BPSN score between the groups (P > 0.05). There was also no statistically significant difference in BPSN subscale scores between the groups (P > 0.05)., Conclusions: Twenty-four percent sucrose 0.2 mL/kg may be the minimum effective dose to relieve pain during venepuncture procedures in premature babies., (© 2019 Japan Pediatric Society.)

Management of neonatal pain is not only ethical but is also essential. Barriers to pain management in infants include lack of safe and effective medications and fear of adverse effects of conventional pain medications. Sweet solutions given intraorally have been shown to reduce pain behaviors and associated symptoms. Sucrose and other sweet solutions are being increasingly used at the NICUs and immunization clinics. Sucrose for mild invasive procedures is effective and safe for those procedures that need to be repeated multiple times during the day. Only few studies examine the efficacy of sucrose for the management of inflammatory pain during infancy. In this study, Complete Freund's Adjuvant (CFA) was used to induce inflammation in 5-day-old rat pups; CFA also produces inflammation that lasts for more than a day, thus can also be a model for chronic pain. Sucrose or ibuprofen was given to subset of pups shortly after CFA intraplantar injections. Thermal as well as mechanical pain sensitivity was assessed on subsequent days as well as during adolescence and early adulthood. Sucrose and ibuprofen were both effective in preventing hyperalgesia and allodynia produced by CFA. Interestingly, sucrose was even more effective than ibuprofen, and the analgesic effects continued further to adolescence and adult life of the rats. Thus, and according to the results of this study, sucrose seems to be just as effective for inflammatory pain as Ibuprofen. In addition, sucrose protects against later-in-life hypersensitivity consequences to neonatal pain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or sevelamer carbonate ('sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia., Methods: After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis., Results: Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment., Conclusions: Overall, 1 year of sucroferric oxyhydroxide or sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.)

Objective: In March 2018, the Explorer study, an international, double-blind, randomised controlled trial (RCT), established that adding a TLC-NOSF (UrgoStart Contact, Laboratoires Urgo, France) dressing to good local standard of care (SoC) significantly and substantially increases wound closure and reduces the healing time of neuroischaemic diabetic foot ulcers (DFU). Besides the TLC-NOSF treatment, the wound duration was the only other covariate that had an influence on the wound closure rate in the regression model used in the original study. The purpose of this work was to further document the impact of wound duration on the healing outcomes of the DFUs included in the Explorer study and to discuss complementary pragmatic observations on the TLC-NOSF effect., Method: In this post-hoc analysis of the Explorer data, the wound closure rates by week 20 are reported for the global cohort (n=240, Intention-to-treat population) and for the treated (n=126) and control groups (n=114) according to DFU duration and location., Results: For the combined group, wound closure rates decreased with the increase of wound duration at baseline (from 57% in wounds ≤2 months to 19% in wounds >11 months). Whatever the wound duration subgroups analysed, higher closure rates were reported in the TLC-NOSF group than in the control group. However, the maximal difference between the two treatments was reported in wounds with a duration of ≤2 months (71% versus 41%, 30 percentage points difference, Relative Risk 1.7, 95% Confidence Interval 1.1 to 2.8). Regarding wound location subgroup analyses, the outcomes were always in favour of the TLC-NOSF treatment, with closure rates ranging between 43% and 61% within the TLC-NOSF group, and between 25% and 40% within the control group., Conclusion: This clinical evidence supports that treating DFUs with TLC-NOSF dressing and good SoC results in higher wound closure rates than with a neutral dressing and the same good standard of care, whatever the duration and the location of the treated wounds. However, the earlier the TLC-NOSF dressing is initiated in DFU treatment, the greater the benefits.

The taste of sucrose is commonly used to provide pain relief in newborn humans and is innately analgesic to neonatal rodents. In adulthood, sucrose remains a strong motivator to feed, even in potentially hazardous circumstances (ie, threat of tissue damage). However, the neurobiological mechanisms of this endogenous reward-pain interaction are unclear. We have developed a simple model of sucrose drinking-induced analgesia in Sprague-Dawley rats (6-10 weeks old) and have undertaken a behavioral and pharmacological characterization using the Hargreaves' test of hind-paw thermal sensitivity. Our results reveal an acute, potent, and robust inhibitory effect of sucrose drinking on thermal nociceptive behaviour that unlike the phenomenon in neonates is independent of endogenous opioid signalling and does not seem to operate through classical descending inhibition of the spinal cord circuitry. Experience of sucrose drinking had a conditioning effect whereby the apparent expectancy of sucrose enabled water alone (in euvolemic animals) to elicit a short-lasting placebo-like analgesia. Sweet taste alone, however, was insufficient to elicit analgesia in adult rats intraorally perfused with sucrose. Instead, the sucrose analgesia phenomenon only appeared after conditioning by oral perfusion in chronically cannulated animals. This sucrose analgesia was completely prevented by systemic dosing of the endocannabinoid CB1 receptor antagonist rimonabant. These results indicate the presence of an endogenous supraspinal analgesic circuit that is recruited by the context of rewarding drinking and is dependent on endocannabinoid signalling. We propose that this hedonic sucrose-drinking model may be useful for further investigation of the supraspinal control of pain by appetite and reward.

Introduction: Hyperphosphatemia is a serious consequence of chronic kidney disease and has been associated with an increased risk for cardiovascular disease. Controlling serum phosphorus levels in patients on dialysis is a challenge for the clinicians and implies, in most cases, the use of phosphate binders (PB). Part of the reason for this challenge is poor adherence to treatment because of the high pill burden in this patient group., Objective: To assess the real-world effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus levels and determine the associated pill burden., Methods: A multicenter, quantitative, retrospective, before-after study was conducted with patients receiving online hemodiafiltration. Patients who switched to SO as a part of routine care were included in the study. PB treatment, number of pills, serum phosphorus levels, and intravenous iron medication and dosage were collected monthly during the six months of treatment with either PB or SO., Results: A total of 42 patients were included in the study. After switching from a PB to SO, the prescribed pills/day was reduced 67% from 6 pills/day to 2 pills/day (p < 0.001) and the frequency of pill intake was lowered from 3 times/day to 2 times/day (p < 0.001). During the treatment with SO, the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 33.3% at baseline to 45% after six months of treatment., Conclusion: During the six-month follow-up with SO, serum phosphorus levels were controlled with one third of the pills/day compared to other PB.

Introduction: Despite a better management of hyperphosphatemia in haemodialysis patients observed during the past years, most of them remain insufficiently treated and exposed to bone and cardiovascular complications that are associated with this biological abnormality. The availability of calcium-free phosphate binders among therapeutical options is confirmed to significantly reduce serum phosphate levels without the risk of excess exposure to calcium. Currently sucroferric oxyhydroxyde (SO) is the only iron-based phosphate binder available in France., Methods: A cohort of patients prescribed OHS has been extracted from the EUCLID 5 database between June 2016 and December 2017. The effects on bone mineral metabolism and ferritin have been retrospectively studied., Results: Two hundred and sixty-two patients with OHS prescription have been identified. The OHS treatment duration median was 4.3 months (1.84-10.99). The average midweek phosphatemia decreased significantly after OHS prescription (from 1.99 to 1.83 mmol/L ; P<0.0001) with a significant increase of the proportion of patients (12.1 to 25.7% ; P<0.0001) reaching the phosphate target of 1.5 mmol/L, without significant change in calcemia and PTH. Ferritinemia significantly increased from 362 to 427 μg/L in 3 months (P=0.0049). OHS therapy has been stopped and replaced in 18% of the cases., Discussion: Among the NephroCare cohort, OHS therapy was efficient to decrease phosphatemia and to increase significantly the proportion of patients in target. There were no short term changes in calcemia and PTH. The slight increase in ferritin confirms the findings of the phase III study and its extension. The effects on the pills count and the OHS side-effects are analyzed from literature. The risk of iron overload and the impact on the anemia management including EPO sparing are currently under study., Conclusion: OHS therapy appears to be a new efficient alternative to non-calcium phosphate binders. A better knowledge of its side effects will help the patients and the physician to optimize the phosphate balance management. The slight increase in ferritin can be considered as an epiphenomenon because of the important iron needs and frequent check of this parameter in the anemia management., (Copyright © 2018 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Background: Treating pain during immunization should be a part of pediatric primary healthcare around the world, as untreated pain in children has short- and long-term consequences. Few studies of pharmacologic and nonpharmacologic methods of pain relief during immunization have been conducted in low- and middle-income countries. Finding pain-mitigating interventions that are low-cost, effective, and feasible across all settings, including with low-resourced settings could improve primary healthcare., Purpose: To evaluate the effectiveness of oral sucrose versus breastfeeding as methods of pain management during immunization of infants through 6 months of age., Methods: A randomized controlled experimental design was used; 120 infants were randomly assigned to control, sucrose, or breastfeeding groups. Data were collected in an Egyptian primary health center. Outcome measures including pain (as per the FLACC pain scale), crying time, and heart rate were measured at three time points., Results: There were significant differences in pain scores and crying duration during and after immunization (p < .001) for the breastfeeding group compared with the sucrose and control groups., Implications for Practice: Health staff and parents need education and support in use of breastfeeding for pain management during immunization. More studies are needed to evaluate effectiveness of breastfeeding versus other pain management methods for managing infants' immunization-related pain.

Background: Parents have reported that they want to learn how to reduce pain in infants during vaccinations. Our objective was to compare different levels of intensity of postnatal education about pain mitigation on parental self-reported use of interventions at future infant vaccinations., Methods: We conducted a longitudinal, 3-group parallel, add-on, randomized controlled trial on the postnatal ward of a hospital. New mothers, unaware of the hypothesis, were randomly assigned to 1 of 3 intervention groups and 3 follow-up groups (i.e., 9 groups, 3 × 3). The 3 intervention groups were control (general immunization information), pain pamphlet (pain mitigation information), and pain pamphlet and pain video (pain mitigation information). Both pain mitigation education groups also received general immunization information. The 3 follow-up groups were 2-, 4- and 6-month infant vaccinations. Mothers reported use of breastfeeding, sucrose and topical anesthetics during infant vaccinations in a telephone survey., Results: Of 3420 participants, follow-up was available for 2549 (75%): 36.1%, 34.2% and 29.7% reported on pain mitigation practices at 2-, 4- and 6-month vaccinations, respectively ( p = 0.9). Maternal characteristics did not differ ( p > 0.05): mean age, 33.6 years; 58% were primipara. Utilization of any intervention (breastfeeding, sucrose or topical anesthetics) was 53.2%, 61.4% and 63.0% for control, pain pamphlet, and pain pamphlet and pain video groups, respectively ( p < 0.001); both pain education groups had higher utilization than the control group, but did not differ from one another. Uptake differed among intervention groups at 2 and 4 months but not at 6 months., Interpretation: Hospital-based postnatal education increased parental use of pain interventions at infant vaccinations and can be added to existing education., Trial Registration: ClinicalTrials.gov, no. NCT01937143., Competing Interests: Competing interests: Anna Taddio has received a research grant from Pfizer (investigator initiated) and supplies for a separate study from Natus Medical and Ferndale Pharma Group. Lucie Bucci has received research grants from Pfizer Canada, Merck Canada, Sanofi Pasteur, GlaxoSmithKline and Seqirus Canada. No other competing interests were declared., (© 2018 Joule Inc. or its licensors.)

Introduction: Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based phosphate binder that demonstrated sustained serum phosphorus (sP) control, good tolerability, and lower pill burden, vs. sevelamer carbonate ("sevelamer"), in a Phase 3 study conducted in dialysis patients with hyperphosphatemia. This analysis evaluates the efficacy and safety of SFOH and sevelamer among African American (AA) patients participating in the trial., Methods: Post hoc analysis of a 24-week, Phase 3, open-label trial (NCT01324128) and its 28-week extension study (NCT01464190). Patients were randomized 2:1 to SFOH (1.0-3.0 g/day) or sevelamer (2.4-14.4 g/day) for up to 52 weeks., Findings: Of 549 patients who completed the Phase 3 study and extension, 100 (18.2%) AA patients were eligible for efficacy analysis (SFOH, n = 48; sevelamer, n = 52). sP concentrations decreased rapidly and comparably with both treatments by Week 8 (mean ± standard deviation change from baseline: -1.9 ± 1.9 mg/dL for SFOH and -2.2 ± 1.8 mg/dL for sevelamer). These reductions were maintained for 52 weeks (-2.1 ± 2.6 and -2.1 ± 1.6 mg/dL) and achieved with a lower mean pill burden (3.4 ± 1.4 vs. 7.6 ± 2.9 tablets/day) with SFOH vs. sevelamer. Treatment adherence rates (adherence within 70%-120% of expected medication intake) were 79.2% with SFOH and 59.6% with sevelamer. The proportion of patients reporting serious adverse events (AEs) was 27.7% with SFOH and 30.7% with sevelamer. More patients withdrew due to treatment-emergent AEs with SFOH vs. sevelamer (18.5% vs. 8.0%). The most common AEs with both treatments were gastrointestinal-related: diarrhea and discolored feces with SFOH, and nausea, vomiting, and constipation with sevelamer., Discussion: SFOH is an efficacious and well-tolerated treatment for hyperphosphatemia in AA dialysis patients, with a lower pill burden and an improved adherence rate vs. sevelamer. These findings were consistent with the wider US patient population and the overall study population., (© 2018 The Authors Hemodialysis International published by Wiley Periodicals, Inc. on behalf of International Society for Hemodialysis.)

Objectives: Pain in hospitalized children remains under-assessed and undertreated. With this study, we aim to describe results from a repeat single-day, hospital-wide survey of children's pain and its treatment after the initiation of a hospital-wide quality improvement initiative used to reduce or eliminate pain caused by needle procedures., Methods: All patients and parents listed on the inpatient morning census, in emergency department and outpatient surgery registration lists, were invited to participate in a brief single-day point prevalence survey of their experience with pain and its management in the hospital setting. Results were compared with a survey conducted 2 years earlier, before implementation of a system-wide Children's Comfort Promise needle pain treatment and prevention protocol., Results: A total of 194 children and their parents participated in the current survey. A higher percentage of children reported having no pain compared with the previous survey (33% vs 24%; P = .07; not significant) and fewer experienced severe pain (score ≥7 out of 10). Fewer children identified pain caused by needles as the cause of the worst pain (21% vs 30%), although it remained the highest reported cause of the most painful experience overall. The number of pain management strategies administered and offered to children with needle pain (distraction, positioning, numbing cream, and sucrose and/or breastfeeding for infants) increased., Conclusions: The implementation of a mandatory Comfort Promise protocol used to minimize or prevent pain caused by elective needle procedures was associated with a significant reduction in overall pain prevalence and improved use of evidence-based practices for needle pain management., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Several studies have evidenced the association between high serum phosphorus concentrations and adverse events especially in patients on dialysis. Recent K-DIGO guidelines suggest lowering elevated phosphate levels toward the normal range. This goal should be achieved by combining dietary counseling, optimizing dialysis procedures and prescribing phosphate binders. Despite the availability of several binders, the "ideal" phosphate binder that combines high efficacy, low pills burden, minimal side effects and low cost is still not available. In clinical practice it is crucial to reach a high patient's compliance to therapy. The pill burden is the most relevant factor contributing to low compliance. This is the case of phosphate binder therapy that represents almost 50% of total pills prescribed to patients on dialysis. It has been evidenced an association between pills of phosphate binder and poor control of phosphorus and PTH. In recent years sucroferric oxyhydroxide is available as a new phosphate binder. Its peculiarity is an high phosphate binding capability that requires prescription of low number of pills per day. This characteristic has been confirmed by several randomized controlled trials. These trials have also evidenced that sucroferric oxyhydroxide may cause some gastrointestinal side effects. There is an ongoing study to confirm in "the real world" the incidence of side effects reported by controlled trials., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Background: In dialysis patients, mortality risk due to cardiovascular diseases is remarkably high and prognosis is poor; coronary artery calcification is considered one of the major contributing factors. It is known that hyperphosphatemia is associated with coronary artery calcification. Therefore, controlling serum phosphate level and thereby mitigating vascular calcification could improve the poor prognosis of dialysis patients. However, the optimal phosphate level in dialysis patients remains unknown; hence, this study was planned to compare the effects of two types of non-calcium-based phosphate binders, and examine the effect of strict control of phosphate on coronary artery calcification., Methods: EPISODE is a randomized, open-label, multi-center, interventional trial with a two-by-two factorial design (UMIN ID: UMIN000023648). This trial will enroll hemodialysis patients who have been on dialysis for at least 3 months with a pre-dialysis serum phosphate level of at least 5.0 mg/dL or at least 6.1 mg/dL, respectively, in those taking or not taking a phosphate binder, as measured during the observation period. Registered patients will be randomized to the sucroferric oxyhydroxide or lanthanum carbonate arm and will receive the assigned drug to reduce serum phosphate to two target levels (3.5-4.5 mg/dL in strict arm and 5.0-6.0 mg/dL in standard arm) for 12 months. The primary endpoint will be percent change in coronary artery calcification score, and the secondary endpoints will include change from baseline serum phosphate and calcium levels, change in renal anemia-related factors, etc. The desired sample size has been calculated to be 200 patients.

Background: Preterm infants (PI) requiring the neonatal intensive care unit are exposed to early repetitive pain/distress. Little is known about how pain relief strategies interact with infants' clinical health status, such as severity of illness with pain responses. This study aimed to examine main and interactive effects of routine sucrose intervention and neonatal clinical risk (NCR) on biobehavioral pain reactivity-recovery in PI during painful blood collection procedures., Methods: Very low birth weight PI (<1500 g; n=104) were assigned to low and high clinical risk groups, according to the Clinical Risk Index for Babies. Sucrose group (n=52) received sucrose solution (25%; 0.5 mL/kg) 2 minutes before the procedures and control group received standard care. Biobehavioral pain reactivity-recovery was assessed according to the Neonatal Facial Coding System, sleep-wake state scale, crying time, and heart rate at 5 phases (baseline, antisepsis, puncture (P), recovery-dressing, and recovery-resting [R]). Repeated measure ANOVA with mixed-design was performed considering pain assessment phases, intervention group, and NCR., Results: Independent of NCR, sucrose presented main effect in decreasing neonates' facial activity pain responses and crying time, during P and R. Independent of NCR level or routine sucrose intervention, all neonates displayed activated state in P and decreased biobehavioral responses in R phase. Although no sucrose or NCR effects were observed on physiological reactivity, all neonates exhibited physiological recovery 10 minutes after P, reaching the same heart rate patterns as the baseline., Conclusions: Independent of NCR level, sucrose intervention for pain relief during acute painful procedures was effective to reduce pain intensity and increase biobehavioral regulation.

Introduction: Sucroferric oxyhydroxide is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphatemia in patients with chronic kidney disease undergoing dialysis. Areas covered: Herein, the preclinical development and clinical data for sucroferric oxyhydroxide are reviewed, including the key data from the Phase III registration study and the latest evidence from the real-world clinical setting. Expert opinion: Sucroferric oxyhydroxide displays potent phosphate-binding capacity and clinical studies demonstrate its effectiveness for the long-term reduction of serum phosphorus levels in dialysis patients. Observational study data also show that sucroferric oxyhydroxide provides effective serum phosphorus control for hyperphosphatemic patients in the real-world clinical setting. The serum phosphorus reductions with sucroferric oxyhydroxide can be achieved with a relatively low pill burden in comparison with other phosphate binders, which may translate into better treatment adherence in clinical practice. The Phase III data also indicate that sucroferric oxyhydroxide has a favorable impact on other chronic kidney disease-related mineral bone disease parameters, including a fibroblast growth factor-23-lowering effect. Sucroferric oxyhydroxide is well tolerated and associated with low systemic iron absorption, minimizing the potential for iron accumulation or overload. These attributes render sucroferric oxyhydroxide an attractive non-calcium-containing phosphate binder for the treatment of hyperphosphatemia.

Objective: Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients., Results: Hemodialysis patients, receiving existing hyperphosphatemia drugs with insufficient benefit, were administered sucroferric oxyhydroxide with/without calcium carbonate for 16 weeks. Serum phosphorus level declined rapidly in Week 8 (p < 0.0001) and this decrease persisted until Week 16 (p < 0.0001). FGF23 decreased (p = 0.0412, Week 16), and hemoglobin increased (p < 0.0001, Week 16). Cumulative dose of erythropoiesis-stimulating agents (p = 0.0122, Week 16), and intravenous iron (p = 0.0233, Week 12) decreased. All adverse reactions were mild, and diarrhea was the most frequently observed adverse reaction (16.7%). Therefore, hyperphosphatemia treatment with sucroferric oxyhydroxide may safely improve serum phosphorus level, renal anemia, FGF23, and other factors that affect the prognosis of hemodialysis patients.

Background: Orally administered sucrose is effective and safe in reducing pain intensity during single, tissue-damaging procedures in neonates, and is commonly recommended in neonatal pain guidelines. However, there is wide variability in sucrose doses examined in research, and more than a 20-fold variation across neonatal care settings. The aim of this study was to determine the minimally effective dose of 24% sucrose for reducing pain in hospitalized neonates undergoing a single skin-breaking heel lance procedure., Methods: A total of 245 neonates from 4 Canadian tertiary neonatal intensive care units (NICUs), born between 24 and 42 weeks gestational age (GA), were prospectively randomized to receive one of three doses of 24% sucrose, plus non-nutritive sucking/pacifier, 2 min before a routine heel lance: 0.1 ml (Group 1; n = 81), 0.5 ml (Group 2; n = 81), or 1.0 ml (Group 3; n = 83). The primary outcome was pain intensity measured at 30 and 60 s following the heel lance, using the Premature Infant Pain Profile-Revised (PIPP-R). The secondary outcome was the incidence of adverse events. Analysis of covariance models, adjusting for GA and study site examined between group differences in pain intensity across intervention groups., Results: There was no difference in mean pain intensity PIPP-R scores between treatment groups at 30 s (P = .97) and 60 s (P = .93); however, pain was not fully eliminated during the heel lance procedure. There were 5 reported adverse events among 5/245 (2.0%) neonates, with no significant differences in the proportion of events by sucrose dose (P = .62). All events resolved spontaneously without medical intervention., Conclusions: The minimally effective dose of 24% sucrose required to treat pain associated with a single heel lance in neonates was 0.1 ml. Further evaluation regarding the sustained effectiveness of this dose in reducing pain intensity in neonates for repeated painful procedures is warranted., Trial Registration: ClinicalTrials.gov : NCT02134873. Date: May 5, 2014 (retrospectively registered).

Noncaloric sweeteners (NCS) are food additives used to provide sweetness without adding calories. Their consumption has become more widespread around the world in all age groups, including children. The aim of this study is to show the state of the art about the intake of noncaloric sweeteners in children, as well as their benefits and consumption risk. Scientific searchers were used (PUBMED, Scopus, and Scielo) to analyze articles that included keywords (noncaloric sweeteners/saccharin/cyclamate/acesulfame potassium/aspartame/sucralose/stevia/children) in English, Spanish, and Portuguese. Authors conclude that it is imperative that health professionals judiciously and individually evaluate the overall benefits and risks of NCS use in consumers before recommending their use. Different subgroups of the population incorporate products containing NCS in their diet with different objectives, which should be considered when recommending a diet plan for the consumer. In childhood, in earlier age groups, this type of additives should be used as a dietary alternative when other forms of prevention in obesity are not sufficient.

Background: Few clinical trials evaluating the efficacy of oral sweet solutions for procedures in the emergency department (ED) have been published., Objectives: To compare the efficacy of an oral sucrose solution vs. a placebo in reducing pain in infants undergoing venipuncture without cannulation., Methods: A randomized, double-blinded clinical trial was conducted in a pediatric ED. Infants 1 to 3 months old were randomly allocated to receive 2 mL of 88% sucrose or 2 mL of placebo, 2 min prior to venipuncture. The outcome measures were the difference in pain levels as assessed by the Face, Legs, Activity, Cry and Consolability Pain Scale (FLACC) and Neonatal Infant Pain Scale (NIPS) scores, crying time, and variations in heart rate., Results: Eighty-two participants were recruited. Data were analyzed for 38 patients from each group (excluding protocol deviations). The mean difference in FLACC scores 1 min post venipuncture compared with baseline was 2.84 ± .64 (sucrose) vs. 2.71 ± .62 (placebo) (p = 0.98). For the NIPS score, it was 2.32 ± .47 (sucrose) vs. 1.63 ± .49 (placebo) (p = 0.60). The difference in the median crying time was not statistically significant between the two groups: 63.0 ± 3 (sucrose) vs. 48.5 ± 5 s (placebo) (p = 0.17). No significant difference was found in participants' heart rates 1 min post venipuncture compared with baseline: 33 ± 6 (sucrose) vs. 24 ± 5 beats per minute (placebo) (p = 0.44)., Conclusions: In infants 1 to 3 months of age undergoing simple venipuncture, administration of an oral sweet solution did not statistically decrease pain scores, and participants' heart rate variations and crying time were not significantly changed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Sucroferric oxyhydroxide (P-TOL ® chewable tablets, 250 and 500 mg) is a phosphate binder for oral use; it is composed of polynuclear iron (III)-oxyhydroxide, sucrose, and starches, and is currently indicated for alleviating hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. The results of non-clinical pharmacological studies have suggested that P-TOL consistently decreases serum phosphorus levels in the aqueous environment at pH levels similar to those in the gastrointestinal tract, thereby suppressing the progression of secondary hyperparathyroidism, aberrant calcification, and abnormal bone metabolism associated with hyperphosphatemia. Since the diameter of the P-TOL tablet exceeds 15 mm, it is manufactured with a doughnut-shape to minimize choking hazards. From the results of pharmaceutical studies, it was indicated that the P-TOL tablets promptly disintegrated in the gastrointestinal tract and excessive iron uptake from this product is unlikely to occur. In clinical studies, P-TOL (one tablet/dose, t.i.d.) decreased serum phosphorus levels during treatment Week 1 and allowed stable, long-term control of serum phosphorus levels. Furthermore, P-TOL was expected to reduce the tablet burden on patients and to improve medication adherence. The most common adverse reaction was diarrhea. However, in most cases, the symptoms were mild and oral administration of P-TOL could be continued. Although iron-related parameters tended to increase, iron uptake from this product was low, and the risk of iron overload was considered to be low. These findings confirm the efficacy and safety of P-TOL in CKD patients with hyperphosphatemia. Therefore, sucroferric oxyhydroxide therapy is a potentially useful treatment option for hyperphosphatemia.

The use of sugar for treating wounds which are difficult to heal and positive to resistant pathogens has already been documented. The authors describe the successful treatment by direct instillation of granular sugar in the antibiotic-resistant infected surgical site wound of a child with sarcoma. Sugar instillation in the extended spectrum beta-lactamase (ESBL)-producing Enterobacter cloacae positive wound, in addition to systemic treatment with meropenem and levofloxacin, allowed culture negativization in six days and complete wound healing in 30 days. These results make the use of sugar an attractive option for wounds which are difficult to treat, even in an immunocompromised child.

Objectives: There is no consensus on the most effective pain management for neonatal circumcision. We sought to compare different modalities., Methods: This is a double-blinded randomized controlled trial comparing 3 combination analgesics used during circumcision (EMLA + sucrose; EMLA + sucrose + dorsal penile nerve block [DPNB]; EMLA + sucrose + ring block [RB]) with the traditional topical analgesic cream EMLA alone. The trial was set in the normal nursery of a teaching hospital. The sample included 70 healthy male newborns, randomly assigned to intervention and control groups at a 2:1 ratio. Infants were videotaped (face and torso) during the procedure for assessment of pain by 2 blinded, independent reviewers. The primary outcome measure is the Neonatal Infant Pain Scale score. Secondary outcomes include heart rate, oxygen saturation, and crying time., Results: Neonatal Infant Pain Scale scores were significantly lower in the intervention groups (EMLA + sucrose, mean [SD]: 3.1 [1.33]; EMLA + sucrose + DPNB: 3 [1.33]; EMLA + sucrose + RB: 2.45 [1.27]) compared with the control (5.5 [0.53]). Between-group analyses showed RB + EMLA + sucrose to be significantly more effective than EMLA + sucrose; EMLA + sucrose + DPNB ( P = .009 and P = .002, respectively). Interrater reliability was κ = 0.843. Significant increase in heart rate (139.27 [9.63] to 163 [13.23] beats per minute) and crying time (5.78 [6.4] to 45.37 [12.39] seconds) were noted in the EMLA group., Conclusions: During neonatal circumcision in boys, the most effective analgesia is RB combined with oral sucrose and EMLA cream., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Background: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with sevelamer carbonate (sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and sevelamer in the peritoneal dialysis (PD) patient population., Methods: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total., Results: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with sevelamer., Conclusions: Sucroferric oxyhydroxide is noninferior to sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Breastfeeding (BF), skin-to-skin care (SSC), and sucrose effectively reduce babies' pain during newborn blood work, but these strategies are infrequently used. Our team developed a parent-targeted video intervention showing the effectiveness of the 3 pain management strategies., Purpose: To evaluate neonatal intensive care unit (NICU) parents' (1) baseline knowledge and previous use of BF, SSC, and sucrose for procedural pain management; (2) intention to advocate/use BF, SSC, or sucrose for their infants' future blood work after viewing the video; (3) intention to recommend the video to other parents; and (4) perceptions of the video and identify areas for improvement., Methods: Cross-sectional survey of parents in an NICU., Results: Fifty parents were enrolled: 33 mothers and 17 fathers. More than two-thirds (68%) of parents had prior knowledge of analgesic effects of sucrose; knowledge of SSC and BF as pain-reduction strategies was lower: 44% and 34%, respectively. Eighty-six percent of parents felt the video was the right length; 7 (14%) felt the video was too long. After viewing the video, 96% of parents intended to advocate for BF, SSC, or sucrose for pain management and 88% parents would recommend the video to other parents., Implications for Practice: The video is acceptable to parents, is feasible to deliver to parents in an NICU, and has potential to increase parents' intent to advocate for pain management strategies for their infants., Implications for Research: Future studies are required to evaluate the effectiveness of this parent-targeted intervention on increasing actual use of pain management in clinical practice.

Objective: The objective of this article was to assess the safety and efficacy of long-term administration of PA21., Design and Methods: Phase III, open-label, long-term study in 15 sites in Japan., Subjects: Japanese hemodialysis patients (N = 161) with hyperphosphatemia aged ≥20 years undergoing stable maintenance hemodialysis 3 times weekly, for ≥12 weeks., Intervention: After a 2-week observation period with their previous hyperphosphatemia therapy, patients began the 52-week treatment with PA21, which was administered orally at an initial dose of 250 mg, 3 times daily, immediately before every meal (dosing range between 750 and 3,000 mg/day)., Main Outcome Measure: Safety was evaluated based on the development of adverse events and adverse drug reactions (ADRs). Efficacy was evaluated according to serum phosphorus concentration, corrected serum calcium concentration, and serum intact-parathyroid hormone concentration., Results: The mean serum phosphorus concentration decreased from 5.46 ± 1.06 mg/dL at baseline to 5.00 ± 1.17 mg/dL at end of treatment. The serum phosphorus concentration was maintained within the target range (3.5-6.0 mg/dL) throughout the 52 weeks of the study period with a mean of 3.3 tablets per day of PA21. Most ADRs were mild, transient, and developed early during treatment, and the incidence was not shown to increase with long-term treatment. The most frequently reported ADR was diarrhea (22.4%)., Conclusion: Treatment with PA21 was effective in lowering and maintaining target serum phosphorus concentrations in Japanese hemodialysis patients with hyperphosphatemia over 52 weeks. PA21 was generally well tolerated in the long term., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sucroferric oxyhydroxide is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphataemia in adult dialysis patients. This post hoc analysis of a randomized, 24-week Phase 3 study and its 28-week extension was performed to evaluate the long-term effect of sucroferric oxyhydroxide on iron parameters., Methods: A total of 1059 patients were randomized to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or sevelamer carbonate ('sevelamer') 2.4-14.4 g/day (n = 349) for up to 52 weeks. The current analysis only included patients who completed 52 weeks of continuous treatment (n = 549). Changes in iron-related parameters and anti-anaemic product use during the study were measured., Results: Some changes in iron-related parameters across both treatment groups were observed during the first 24 weeks of the study, and to a lesser extent with longer-term treatment. There were small, but significantly greater increases in mean transferrin saturation (TSAT) and haemoglobin levels with sucroferric oxyhydroxide versus sevelamer during the first 24 weeks (change in TSAT: +4.6% versus +0.6%, P = 0.003; change in haemoglobin: +1.6 g/L versus -1.1 g/L, P = 0.037). Mean serum ferritin concentrations also increased from Weeks 0 to 24 with sucroferric oxyhydroxide and sevelamer (+119 ng/mL and +56.2 ng/mL respectively; no statistically significant difference between groups). In both treatment groups, ferritin concentrations increased to a greater extent in the overall study population [>70% of whom received concomitant intravenous (IV) iron], compared with the subset of patients who did not receive IV iron therapy during the study. The pattern of anti-anaemic product use was similar in both treatment groups, with a trend towards higher use of IV iron and erythropoiesis-stimulating agents with sevelamer., Conclusions: Initial increases in some iron-related parameters were observed in both treatment groups but were more pronounced with sucroferric oxyhydroxide. These differences between treatment groups with respect to changes in iron parameters are likely due to minimal iron absorption from sucroferric oxyhydroxide., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.)

Aims: Hyperphosphatemia has been associated with an increased risk of mortality in patients with end-stage renal disease. We sought to assess the real-world effectiveness of sucroferric oxyhydroxide (SO), an iron-based phosphate binder (PB), in control of serum phosphorus levels, and to determine the associated pill burden in hemodialysis patients., Materials and Methods: Adult, in-center hemodialysis patients first prescribed SO through a renal pharmacy service as part of routine clinical care between April 1, 2014 and March 31, 2015 were included in the analysis. The proportion of patients with phosphorus levels ≤ 5.5 mg/dL and the mean prescribed PB pills/day were compared between baseline (3 months prior to SO) and SO follow-up at 3 (SO 1 - 3) and 6 months (SO 4 - 6). Mineral bone disease markers, hemoglobin, iron indices, and erythropoiesis-stimulating agents and intravenous iron use were assessed., Results: At baseline, all patients (n = 1,029) were prescribed PB, and 13.9% had mean serum phosphorus ≤ 5.5 mg/dL. Comparing baseline to SO 1 - 3, the mean prescribed PB pills/day declined from 9.6 to 3.8 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 13.9 to 26.1% (+88%). Comparing baseline to SO 4 - 6 (n = 424), the mean prescribed PB pills/day declined from 9.7 to 4.0 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 15.6 to 30.4% (+95%)., Conclusions: Prescription of SO was associated with an increase in the proportion of patients achieving serum phosphorus levels ≤ 5.5 mg/dL along with fewer prescribed PB pills/day.
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Aim: We aimed to investigate the non-inferiority of PA21 (sucroferric oxyhydroxide) to sevelamer hydrochloride (sevelamer) in terms of efficacy and safety in Japanese haemodialysis patients with hyperphosphataemia., Methods: In this Phase III, open-label, multicentre study, 213 haemodialysis patients with hyperphosphataemia were randomized to PA21 or sevelamer treatment for 12 weeks. The primary outcome was adjusted serum phosphorus concentration at the end of treatment; the non-inferiority of PA21 was confirmed if the upper limit of the two-sided 95% confidence interval (CI) is ≤0.32 mmol/L. Secondary outcomes were corrected serum calcium and intact-parathyroid hormone concentrations. Adverse events (AEs) and adverse drug reactions (ADRs) were evaluated., Results: The adjusted mean serum phosphorus concentration at the end of treatment confirmed the non-inferiority of PA21 for lowering serum phosphorus compared with sevelamer (1.62 vs 1.72 mmol/L; difference, -0.11 mmol/L; 95% CI, -0.20 to -0.02 mmol/L). The mean daily tablet intake was 5.6 ± 2.6 and 18.7 ± 7.1 tablets in the PA21 and sevelamer groups, respectively. The incidences of AEs and ADRs were not significantly different between the two groups., Conclusion: The non-inferiority of PA21 to sevelamer was confirmed for the treatment of Japanese haemodialysis patients with hyperphosphataemia. PA21 was effective, safe, and well tolerated, while having a considerably lower pill burden than sevelamer., (© 2016 The Authors Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Pain management in the neonatal ICU remains challenging for many clinicians and in many complex care circumstances. The authors review general pain management principles and address the use of pain scales, non-pharmacologic management, and various agents that may be useful in general neonatal practice, procedurally, or at the end of life. Chronic pain and neonatal abstinence are also noted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Vaccine injections can cause acute pain and distress in infants, which can contribute to dissatisfaction with the vaccination experience and vaccine hesitancy. We sought to compare the effectiveness of additive pain interventions administered consistently during vaccine injections in the first year of life., Methods: We conducted a multicentre, longitudinal, double-blind, add-on, randomized controlled trial. Healthy infants were randomly assigned to 1 of 4 levels of pain management for all vaccine injections at 2, 4, 6 and 12 months: (i) placebo control; (ii) parent-directed video education about infant soothing; (iii) the video plus sucrose administered orally or (iv) the video plus sucrose plus liposomal lidocaine applied topically. All infants benefit from injection techniques that minimize pain. We used a double-dummy design; hence all parents watched a video (active psychological intervention or placebo) and all infants received oral solution (sucrose or placebo) and topical cream (lidocaine or placebo). We assessed infant distress during 3 phases - preinjection (baseline), vaccine injection (needle), and 1 minute postinjection (recovery) - using the Modified Behavioural Pain Scale (range 0-10). We compared scores between groups and across infant ages using a mixed-model repeated-measures analysis., Results: A total of 352 infants participated in the study, from Jan. 17, 2012, to Feb. 2, 2016. Demographics did not differ among intervention groups ( p > 0.05). Baseline pain scores did not differ among intervention groups ( p = 0.4), but did differ across ages ( p < 0.001). Needle pain scores differed among groups ( p = 0.003) and across ages ( p < 0.001). The mean (± standard deviation) needle score was 6.3 (± 0.8) in the video-sucrose-lidocaine group compared with 6.7 (± 0.8) in each of the other groups. There were no other between-group differences. Recovery scores did not differ among groups ( p = 0.98), but did differ across ages ( p < 0.001)., Interpretation: Only liposomal lidocaine provided consistent analgesia within an additive pain intervention regimen during vaccinations in infants. Trial registration: ClinicalTrials.gov, no. NCT01503060., Competing Interests: Anna Taddio declares a research grant from Pfizer, and study supplies from Natus and Ferndale. The other authors declare no conflicts of interest., (© 2017 Canadian Medical Association or its licensors.)

Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphatemia in adult dialysis patients. Studies in Japan about the side effects of SFOH treatment indicate that the incidence of diarrhea (25%) is greater while that of constipation (2.9%) is lesser in comparison to that observed upon treatment with an existing phosphate binder. In the present study, the effect of treatment with a combination of the existing phosphate binders and SFOH on the serum phosphorus level and digestive symptoms was observed in hemodialysis patients with hyperphosphatemia, which is untreatable using only the existing phosphate binders. We evaluated the serum phosphorus levels and gastrointestinal symptoms (using the gastrointestinal symptom rating scale) of 6 patients (2 men, 4 women) before and 2, 4, 6, and 8 weeks after continuous administration. The serum phosphorus levels before and 2, 4, 6, and 8 weeks after combination treatment were 7.4±1.0 mg/dL, 5.9±1.3 mg/dL, 5.8±1.5 mg/dL, 5.8±1.4 mg/dL, and 5.8±1.3 mg/dL, respectively, with significant reduction in the levels being observed 2 weeks after administration (p<0.05) and persisting even 8 weeks after continuous administration. The constipation scores before and 2, 4, and 8 weeks after drug administration were 2.39±0.85, 2.34±1.93, 2.56±1.44, and 3.28±2.19, respectively, with no changes observed during the investigation period. The diarrhea scores before and 2, 4, and 8 weeks after drug administration were 2.22±0.91, 2.06±1.16, 1.28±0.39, and 1.06±0.13 respectively. The scores improved significantly, 4 weeks after drug administration (p<0.05), and the improvement persisted, even 8 weeks after continuous administration. Thus, by using a combination of the existing phosphate binders and SFOH, we were able to reduce the serum phosphorus level in patients with hyperphosphatemia, which is untreatable using the existing phosphate binder alone, with no sign of exacerbation of the gastrointestinal symptoms despite a few contradictory case reports.

Aim: To study the analgesic effect of oral 25% glucose as compared with oral 24% sucrose during heel lance in preterm neonates., Methods: Stable preterm neonates within first 48 hours of life were randomized to receive either 24% sucrose or 25% glucose before heel lance. Primary outcome assessed was painful response by the Premature Infant Pain Profile (PIPP) score at 30 seconds after heel lance, and the secondary outcome was immediate adverse events associated with the administration of two solutions and duration of crying immediately following the procedure., Results: A total of 94 neonates were randomly assigned into 24% sucrose and 25% glucose group. The baseline characteristics between the two groups were comparable. No significant difference was observed between the two study groups with respect to PIPP scores, duration of crying and rate of adverse events., Conclusions: When assessed by PIPP score, 25% glucose and 24% sucrose provided comparable analgesia during heel lance in preterm neonates., (© The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Both oral sucrose (OS) and nonnutritive sucking (NNS) are effective nonpharmacological methods to alleviate procedures pain in neonatal intensive care unit (NICU) newborns when they were used alone, but the combined effect of OS+NNS remains controversial. So, we conducted this study to evaluate the efficiency of NNS combined with oral sucrose on pain relief in NICU newborns undergoing painful procedures., Methods: We searched PubMed, Ovid (Medline), Embase (Medline), Cochrane Central Library, and other resources such as Google Scholar, bibliographies of included literatures for all available articles. Two reviewers screened literatures and extracted data independently. The fixed effects model was used to pool the results using Reviewer Manager (RevMan) 5.3. As each study included in our meta-analysis had been approved by Ethics Committee or institutional review board, thus our study did not need ethical approval., Results: Seven randomized controlled trials, including 599 participants, were contained in our meta-analysis. The combination of oral sucrose and NNS is associated with reduced pain scores (mean difference [MD], -0.52; 95% confidence interval [CI], -0.68 to -0.36); shortened crying time (MD,-0.92; 95% CI, -1.39 to -0.44); but the 2 groups did not differ significantly in reducing bradycardia (MD, 0.73; 95% CI, 0.32-1.68), tachycardia (MD, 0.65; 95% CI, 0.38-1.10), or desaturations (MD, 0.73; 95% CI, 0.32-1.68)., 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. Nevertheless, the results may be limited due to incomplete data, and thus, more randomized controlled trials or well-designed studies are required to determine the effects of OS+NNS in the future.

Purpose: To determine whether 24% sucrose solution given orally before insertion of a peripheral intravenous (PIV) catheter decreases neonatal pain., Background: Prior studies of pain caused by heel and arterial needlesticks found oral administration of 24% sucrose to significantly blunt pain during these painful procedures. No studies have evaluated this treatment with needlestick pain associated with PIV catheter insertion., Methods: Oral 24% sucrose or placebo solution was administered 2 minutes prior to PIV catheter insertion. Outcome measures were obtained prior to, during, and for 5 minutes after PIV catheter insertion. Investigators and caregivers were blinded to group assignment. Data were analyzed with longitudinal analysis of repeated measures, with P < .05 for significance., Results: A total of 40 neonates (24% sucrose: N = 20; placebo: N = 20) were studied. Pain scores significantly increased from 3.2 ± 1.6 to a maximum of 7.6 ± 3.8 at the time of catheter insertion, returning to baseline levels 8 minutes after PIV catheter insertion (P < .001). No significant differences were found in pain, heart rate, or noninvasive oxygen saturation (SpO2) between the sucrose and placebo groups (P > 0.05)., Implications for Practice: Results from this study did not find that 24% sucrose administered prior to PIV catheter insertion altered the infant's pain response., Implications for Research: Since this is the first study to evaluate the pain-blunting effects of 24% sucrose administration before PIV catheter insertion, replication of this study is needed before widespread application of findings.

Background: Applied mechanical vibration in pediatric and adult populations has been shown to be an effective analgesic for acute and chronic pain, including needle pain. Studies among the neonatal population are lacking. According to the Gate Control Theory, it is expected that applied mechanical vibration will have a summative effect with standard nonpharmacologic pain control strategies, reducing behavioral and physiologic pain responses to heel lancing., Purpose: To determine the safety and efficacy of mechanical vibration for relief of heel lance pain among neonates., Methods: In this parallel design randomized controlled trial, eligible enrolled term or term-corrected neonates (n = 56) in a level IV neonatal intensive care unit were randomized to receive either sucrose and swaddling or sucrose, swaddling, and vibration for heel lance analgesia. Vibration was applied using a handheld battery-powered vibrator (Norco MiniVibrator, Hz = 92) to the lateral aspect of the lower leg along the sural dermatome throughout the heel lance procedure. Neonatal Pain, Agitation, and Sedation Scale (N-PASS) scores, heart rate, and oxygen saturations were collected at defined intervals surrounding heel lancing., Results: Infants in the vibration group (n = 30) had significantly lower N-PASS scores and more stable heart rates during heel stick (P = .006, P = .037) and 2 minutes after heel lance (P = .002, P = .016) than those in the nonvibration group. There were no adverse behavioral or physiologic responses to applied vibration in the sample., Implications for Practice and Research: Applied mechanical vibration is a safe and effective method for managing heel lance pain. This pilot study suggests that mechanical vibration warrants further exploration as a nonpharmacologic pain management tool among the neonatal population.

Introduction: Systemic chemotherapy remains the standard of care for patients with advanced pancreatic ductal adenocarcinoma (PDAC). The introductions of FOLFIRINOX and nab-paclitaxel/gemcitabine combinations have improved the first-line treatment outcomes of patients with metastatic PDAC; while second-line therapy options are limited. Based on the results of pivotal NAPOLI-1 study, nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) became the first US Food and Drug Administration (FDA) approved regimen for patients with metastatic PDAC with previous gemcitabine-based chemotherapy in November 2015., Areas Covered: We reviewed and summarized the rationale, pharmacokinetics, therapeutic efficacy and adverse events of nal-IRI alone or combined with 5-FU/LV for metastatic PDAC with previous gemcitabine-based chemotherapy., Expert Opinion: In the NAPOLI study, nal-IRI plus 5-FU/LV significantly improved the overall survival, progression-free survival and objective response rate compared to 5-FU/LV alone. The nal-IRI plus 5-FU/LV treatment was associated with a manageable toxicity profile and comparable outcomes in patients with negative demographic characteristics. The relatively sparse of neurotoxicity makes nal-IRI plus 5-FU/LV as a more favorable option than oxaliplatin-containing regimens and the current recommended standard treatment for patients with metastatic PDAC after frontline nab-paclitaxel/gemcitabine treatment. The front-line therapeutic role of nal-IRI is currently under investigation.

Background: Non-pharmacological interventions are effective neonatal pain reduction strategies. We aimed to study the effects of non-nutritive sucking (NNS) and swaddling on infants' behavioural and physiological parameters during shallow or deep heel stick procedures., Method: In this prospective, multi-centred, randomized controlled clinical trial, we enrolled 671 newborns. The infants undergoing shallow or deep heel stick procedures were randomized into four groups: oral sucrose (routine care, group S), oral sucrose combined with NNS (group NS), oral sucrose combined with swaddling (group SS) and oral sucrose combined with NNS and swaddling (group NSS). The behavioural responses were evaluated by the Revised Neonatal Facial Coding System and the physiological signals were monitored by electrocardiogram monitors., Results: A significant synergistic analgesic effect was observed between the NS and SS groups in both the shallow (F = 5.952, p = 0.015) and deep heel stick (F = 7.452, p = 0.007) procedure. NSS group exhibited the lowest pain score. For the deep heel stick procedure, the NS group had a significantly lower increase in heart rate (HR)% and decrease in SPO2 % than the S group (F = 17.540, p = 0.000, F = 10.472, p = 0.001), while this difference was not observed in the shallow heel stick procedure. No difference was found between the S and SS groups, in terms of different physiological parameters., Conclusion: Non-nutritive sucking and swaddling had synergistic effects on pain relief when used with oral sucrose. For the deep heel stick procedure, oral sucrose combined with NNS and swaddling provided the best pain relief effect. For the shallow heel stick procedure, addition of NNS and swaddling did not improve the effects., (© 2015 European Pain Federation - EFIC®)

Several factors influence the choice of phosphate binder for patients, including older age, male gender, post-menopause, diabetes, low bone turnover, vascular/valvular calcification and inflammation. Unlike calcium-based phosphate binders, non-calcium-based phosphate binders, such as sevelamer and lanthanum carbonate, have been able to reduce the progression of bone disease to adynamic bone among patients with CKD. New iron-based phosphate binders are now available. With multiple options available for the reduction of phosphate, the focus has been on agents that do not contain calcium. This is because it is thought that calcium itself functions as a substrate for calcification.

Hyperphosphatemia is common in chronic kidney disease (CKD) and is treated by dietary measures, dialysis techniques and/or phosphate binders. For the present review PubMed was searched for new publications on phosphate binders appearing between January 2010 and October 2015. This review summarizes the latest information on non-pharmacological measures and their problems in lowering phosphate in CKD patients, effects of phosphate binders on morbidity and mortality, adherence to phosphate binder therapy as well as new information on specific aspects of the various phosphate binders on the market: calcium acetate, calcium carbonate, magnesium-containing phosphate binders, polymeric phosphate binders (sevelamer, bixalomer, colestilan), lanthanum carbonate, ferric citrate, sucroferric oxyhydroxide, aluminum-containing phosphate binders, and new compounds in development. The review also briefly covers the emerging field of drugs targeting intestinal phosphate transporters.

Background: Although many hypotheses have been suggested, the pathophysiology of restless legs syndrome (RLS) has not been fully understood. In this case series, we describe eleven cases with RLS whose symptoms subsided by the use of crystallized sucrose. This kind of sugar, known as nabat, is used in traditional Iranian medicine., Methods: Case series., Results: All patients felt relief 30-60 min after taking 100 grams of dissolved nabat., Conclusions: Sucrose seems to carry a special benefit for patients with RLS, and it provides evidence for growing literature demonstrating the different underlying mechanisms of RLS. Possible causes for this concurrence are also discussed.

The prevention of pain in neonates should be the goal of all pediatricians and health care professionals who work with neonates, not only because it is ethical but also because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor, yet painful procedures. Therefore, every health care facility caring for neonates should implement (1) a pain-prevention program that includes strategies for minimizing the number of painful procedures performed and (2) a pain assessment and management plan that includes routine assessment of pain, pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and measures for minimizing pain associated with surgery and other major procedures., (Copyright © 2016 by the American Academy of Pediatrics.)