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Objectives: Research specifically addressing implementation strategies regarding nursing guidelines is limited. The objective of this review was to provide an overview of strategies used to implement nursing guidelines in all nursing fields, as well as the effects of these strategies on patient-related nursing outcomes and guideline adherence. Ideally, the findings would help guideline developers, healthcare professionals and organizations to implement nursing guidelines in practice. Design: Systematic review. PROSPERO registration number: CRD42018104615. Data sources: We searched the Embase, Medline, PsycINFO, Web of Science, Cochrane, CINAHL and Google Scholar databases until August 2019 as well as the reference lists of relevant articles. Review methods: Studies were included that described quantitative data on the effect of implementation strategies and implementation outcomes of any type of a nursing guideline in any setting. No language or date of publication restriction was used. The Cochrane Effective Practice and Organisation of Care taxonomy was used to categorize the implementation strategies. Studies were classified as effective if a significant change in either patient-related nursing outcomes or guideline adherence was described. Strength of the evidence was evaluated using the ‘Cochrane risk of bias tool’ for controlled studies, and the ‘Newcastle-Ottawa Quality Assessment form’ for cohort studies. Results: A total of 54 articles regarding 53 different guideline implementation studies were included. Fifteen were (cluster) Randomized Controlled Trials or controlled before-after studies and 38 studies had a before-after design. The topics of the implemented guidelines were diverse, mostly concerning skin care (n = 9) and infection prevention (n = 7). Studies were predominantly performed in hospitals (n = 34) and nursing homes (n = 11). Thirty studies showed a positive significant effect in either patient-related nursing outcomes or guideline adherence (

Aim: To explore the perspectives of patients, their relatives and nurses on rooming-in for adult patients. Background: The practice of having family stay overnight with an adult patient in hospital is quite new. To support rooming-in programs, the perspectives from all stakeholders should be taken into account. Methods: All types of studies on rooming-in in adult healthcare settings were included in this scoping review. Rooming-in has been defined as the practice where ‘family members or trusted others are facilitated to continuously stay with the patient and are provided with facilities to sleep in the patient's room’. Results: Seven studies were included: one randomized controlled trial, three qualitative studies, and three correspondence articles. Generally, patients felt safe in the presence of a family member, but could also feel restricted in their freedom and privacy. Family members saw a benefit for the patient, considered rooming-in a moral duty, and were happy to help. Nonetheless, family members reported rooming-in as physically and emotionally stressful. Nurses described that patients were less anxious and more easily adjusted to the hospital environment. Conclusions: The reviewed studies suggest that patients, family members, and nurses have both positive and negative experiences with rooming-in. The concept o

BACKGROUND: Minimally invasive sampling methods are important to facilitate therapeutic drug monitoring and pharmacokinetic research in children with behavioral problems. This study assessed the feasibility and pain of dried blood spot (DBS) sampling in this population. METHODS: Repeated DBS sampling was performed in children with autism spectrum disorder (ASD) and severe behavioral problems using antipsychotic drugs, aged between 6 and 18 years. The child, guardian, and DBS performer assessed pain using the numeric rating scale (NRS-11) or 5-face Faces Pain Scale. The influence of age, sex, and the fingerprick performer on the child's pain intensity was analyzed using linear mixed models. RESULTS: Overall, 247 fingerpricks were performed in 70 children. Seven children refused all DBS sampling. The median (interquartile range) NRS-11 pain scores were 2 (3) rated by children, 3 (2.5) by guardians, and 2 (2) by fingerprick performers. The child's age and sex, and fingerprick performer had no significant influence on pain intensity. CONCLUSIONS: DBS sampling could be performed in most children with ASD and severe behavioral problems. However, 1 in 5 children refused one or more DBS fingerpricks owing to distress. Most expressed minimal pain (NRS < 4). Repeated sampling with DBS is feasible in children with ASD and severe behavioral problems.

Titrating analgesic and sedative drugs in pediatric intensive care remains a challenge for caregivers due to the lack of pharmacodynamic knowledge in this population. The aim of the current study is to explore the concentration-effect relationship for morphine-associated oversedation after ca

Background: In the last decade, there is an increasing focus on detecting and compiling lists of low-value nursing procedures. However, less is known about effective de-implementation strategies

Objectives: Neonates born extremely prematurely are at high risk of acute and prolonged pain. Effective treatment requires reliable pain assessment, which is currently missing. Our study explored whether existing pain assessment tools and physiological indicators measure pain and comfort accurately in this population. Materials and Methods: We prospectively collected data in 16 neonates born at less than 29 weeks’ gestational age during 3 conditions: skin-to-skin care, rest, and heelstick procedure for capillary blood sampling in the incubator. The neonates were video recorded in these situations, and recordings were coded using 5 observational pain assessment tools and numeric rating scales for pain and distress. We simultaneously collected heart rate, respiratory rate, arterial oxygen saturation, regional cerebral oxygenation, and the number of skin conductance peaks. All measures across the 3 conditions were compared using general linear modeling. Results: The median gestational age was 27.1 weeks (range: 24.1 to 28.7). Forty measurement periods across the 3 conditions were analyzed. Heart rate was significantly higher during heelstick procedures compared with during rest, with a mean difference of 10.7 beats/min (95% confidence interval [CI]: 2.7-18.6). Oxygen saturation was significantly higher during skin-to-skin care compared with during heelstick procedures with a mean difference of 5.5% (95% CI: 0.2-10.8). The Premature Infant Pain Profile-revised (PIPP-R) score was significantly higher during heelstick procedures compared with skin-to-skin care with a mean difference of 3.2 points (95% CI: 1.6-5.0). Discussion: Pain measurement in clinical practice in prematurely born infants below 29 weeks remains challenging. The included behavioral and physiological indicators did not adequately distinguish between a painful situation, rest, and skin-to-skin care in premature neonates.

Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.

Background: Pain in children and adolescents with cancer has been identified as an area where many healthcare professionals seek guidance. This protocol details a systematic review whose aim is to explore current knowledge regarding measurement instruments to assess pain (and pain-related distress) in children and adolescents with cancer. After completion of the review, the information will be used in the development of a clinical practice guideline. Methods: We will search four electronic databases (MEDLINE via PubMed, CINAHL, PsycINFO and HaPI). Additional relevant studies will be identified by reference checking and expert consultation. All citations will be screened independently by two reviewers in a three-step approach: first selection based on title, second selection based on abstract, third selection based on full-text. Studies in children and adolescents with cancer that aimed to evaluate the clinimetric properties of an existing pain measurement instrument or to develop a new pain measurement instrument and that include at least one relevant outcome (reliability, validity, responsiveness, interpretability, clinical utility) are eligible for inclusion. For all steps of evidence selection, a detailed list with eligibility criteria will be determined a priori. Data extraction and quality assessment of included studies (according to the COnsensus-based Standards for the selection of health Measurement INstruments, COSMIN criteria) will be conducted independently by two authors. Discussion: This systematic review will provide an overview of the current literature regarding measurement instruments to assess pain in children and adolescents with cancer. This knowledge synthesis will be used to formulate recommendations for clinical p

Background: Premedication for neonatal intubation facilitates the procedure and reduces stress and physiological disturbances. However, no validated scoring system to assess the effect of premedication prior to intubation is available. Objective: To evaluate the usefulness of an Intubation Readiness Score (IRS) to assess the effect of premedication prior to intubation in newborn infants. Methods: Two-center prospective study in neonates who needed endotracheal intubation. Intubation was performed using a standardized procedure with propofol 1-2 mg/kg as premedication. The level of sedation was assessed with the IRS by evaluating the motor response to a firm stimulus (1 = spontaneous movement; 2 = movement on slight touch; 3 = movement on firm stimulus; 4 = no movement). Intubation was proceeded if an adequate effect, defined as an IRS of 3 or 4, was reached. IRS was compared to the quality of intubation measured with the Viby-Mogensen intubation score. Results: A total of 115 patients, with a median gestational age of 27.7 weeks (interquartile range 5.3) and a median birth weight of 1,005 g (interquartile range 940), were included. An adequate IRS was achieved in 105 patients, 89 (85%) of whom also had a good Viby-Mogensen intubation score and 16 (15%) had an inadequate Viby-Mogensen intubation score. The positive predictive value of the IRS was 85%. Conclusions: Preintubation sedation assessment using the IRS can adequately predict optimal conditions during intubation in the majority of neonates. We suggest using the IRS in routine clinical care. Further research combining the IRS with other parameters could further improve the predictability of adequate sedation during intubation.

BACKGROUNDS: Reports of increasing incidence rates of delirium in critically ill children are reason for concern. We evaluated the measurement properties of the pediatric delirium component (PD-scale) of the Sophia Observation Withdrawal Symptoms scale Pediatric Delirium scale (SOS-PD scale). METHODS: In a multicenter prospective observational study in four Dutch pediatric ICUs (PICUs), patients aged ≥ 3 months and admitted for ≥ 48 h were assessed with the PD-scale thrice daily. Criterion validity was assessed: if the PD-scale score was ≥ 4, a child psychiatrist clinically assessed the presence or absence of PD according to the Diagnostic and statistical manual of mental disorders (DSM)-IV. In addition, the child psychiatrist assessed a randomly selected group to establish the false-negative rate. The construct validity was assessed by calculating the Pearson coefficient (rp) for correlation between the PD-scale and Cornell Assessment Pediatric Delirium (CAP-D) scores. Interrater reliability was determined by comparing paired nurse-researcher PD-scale assessments and calculating the intraclass correlation coefficient (ICC). RESULTS: Four hundred eighty-five patients with a median age of 27.0 months (IQR 8-102) were included, of whom 48 patients were diagnosed with delirium by the child psychiatrist. The PD-scale had overall sensitivity of 92.3% and specificity of 96.5% compared to the psychiatrist diagnosis for a cutoff score ≥4 points. The rp between the PD-scale and the CAP-D was 0.89 (CI 95%, 0.82-0.93; p < 0.001). The ICC of 75 paired nurse-researcher observations was 0.99 (95% CI, 0.98-0.99). CONCLUSIONS: The PD-scale has good reliability and validity for early screening of PD in critically ill children. It can be validly and reliably used by nurses to this aim.

Background: Accurate measurement of preoperative anxiety is important for pediatric surgical patients’ care as well as for monitoring anxiety-reducing interventions. The modified Yale Preoperative Anxiety Scale-short form is well validated for this purpose in children aged 2 years and above, but not in younger children. Aims: We aimed to validate the Dutch version of the modified Yale Preoperative Anxiety Scale-short form for measuring preoperative anxiety in children less than 2 years old. Methods: Two investigators independently assessed infants’ anxiety at the holding area and during induction of anesthesia with the modified Yale Preoperative Anxiety Scale-short form and the COMFORT-Behavior scale—live and from video observations. Construct validity and responsiveness of both scales were tested with Pearson correlation coefficient. Internal cons

Background: Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement. Methods: This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0-36months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n=208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%. Discussion: This study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0-36months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0-36months old.

__Background:__ In palliative care, administration of opioids is often indispensable for pain treatment. Pain assessment may help recognize pain and guide treatment in non-communicative patients. In the Netherlands the Rotterdam Elderly Pain Observation Scale (REPOS) is recommended to this aim, but not yet validated. Therefore the objective of this study was to validate the REPOS in non-communicative or unconscious end-of-life patients. __Methods:__ In this observational study, the primary researcher applied the REPOS, while both the researcher and a nurse applied the Numeric Rating Scale (NRS). If possible, the patient in question applied the NRS as well. The NRS scores were compared with the REPOS scores to determine concurrent validity. REPOS scores obtained before and after a pain-reducing intervention were analysed to establish the scale's sensitivity to change. __Results:__ A total of 183 REPOS observations in 100 patients were analysed. Almost 90% of patients had an advanced malignancy; observations were done a median of 3 days (IQR 1 to 13) before death. Internal consistency of the REPOS was 0.73. The Pearson product moment correlation coefficient ranged from 0.64 to 0.80 between REPOS and NRS scores. REPOS scores declined with median 2 points (IQR 1 to 4) after a pain-reducing intervention (p < 0.001). Optimal sensitivity (0.81) and specificity (0.62) were found at cut-off score 3. __Conclusions:__ This study demonstrates that the REPOS has promising psychometric properties for pain assessment in non-communicative end-of-life patients. Its application may be of additional value to relieve suffering, including pain, in palliative care.

Objectives: Support from healthcare professionals in a PICU is highly valuable for parents of dying children. The way they care for the patients and their families affects the parents’ initial mourning process. This study explores what interaction with hospital staff is meaning

Objective: This review addresses sedation management on paediatric intensive care units and possible gaps in the knowledge of optimal sedation strategies. We present an overview of the commonly used sedatives and their pharmacokinetic and pharmacodynamic considerations in children, as well as the ongoing studies in this field. Also, sedation guidelines and current sedation strategies and assessment methods are addressed. Key findings: This review shows that evidence and pharmacokinetic data are scarce, but fortunately, there is an active research scene with promising new PK and PD data of sedatives in children using new study designs with application of advanced laboratory methods and modelling. The l

Introduction: Pharmacologic pain management in newborns and infants is often based on limited scientific data. To close the knowledge gap, drug-related research in this population is increasingly supported by the authorities, but remains very challenging. This review summarizes the challenges of analgesic studies in newborns and infants on morphine and paracetamol (acetaminophen). Areas covered: Aspects such as the definition and multimodal character of pain are reflected to newborn infants. Specific problems addressed include defining pharmacodynamic endpoints, performing clinical trials in this population and assessing developmental changes in both pharmacokinetics and pharmacodynamics. Expert commentary: Neonatal and infant pain management research faces two major challenges: lack of clear biomarkers and very heterogeneous pharmacokinetics and pharmacodynamics of analgesics. There is a clear call for integral research addressing the multimodality of pain in this population and further developing population pharmacokinetic models towards physiology-based models.

__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different paracetamol doses in preterm infants are lacking. __Objectives:__ To determine the analgesic effects of different single intravenous paracetamol doses on pain from peripherally inserted central catheter (PICC) placement in preterm infants. __Methods:__ In a blinded randomized controlled trial, the ana

__Background__ Worldwide, oral sucrose is standard of care in many neonatal intensive care units to relieve procedural pain in neonates. This study aims to determine if time interval between sucrose administration and heelstick correlates with pain scores. __Methods__ Neonates were prospectively studied with variable time intervals and assessed with the Premature Infant Pain Profile-Revised (PIPP-R). __Results__ 150 neonates were included with a median gestational age of 30 +6 (IQR 27 +6-33 +2) weeks and a median time interval of 72 (IQR 39-115) seconds between sucrose administration and heelstick. In multiple regression analysis, this time interval was not significantly related to the PIPP-R (B=0.004, 95% CI â '0.005 to 0.013, p=0.37). Providing non-nutritive sucking combined with sucrose was significantly related to lower PIPP-R scores (B=â '3.50, 95% CI A '4.7 to â '2.3, p<0.001). __Conclusions__ Our study suggests that there is no need to wait 2â €.min after sucrose administration before a painful procedure. Sucrose-induced non-nutritive sucking shows a fast pain-relieving effect in neonates.

Background. Trauma is the leading cause of mortality and morbidity worldwide. Blood transfusions play an incremental role in the acute phase, yet practice varies owing to variations in transfusion thresholds and concerns about potential complications, especially in children. Objectives. To evaluate protocol adherence to blood transfusion thresholds in paediatric trauma patients and determine the degree of blood product wastage, as defined by discarded units. Methods. A retrospective, descriptive study of trauma patients (age 0 - 13 years) who received a blood transfusion in the trauma unit at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa, over a 5.5-year period (1 January 2009 - 1 July 2014). Haemoglobin (Hb) transfusion thresholds were defined as 10 g/dL for neurotrauma patients and patients requiring skin grafting or a musculocutaneous flap (group 1). All other trauma patients had an Hb transfusion threshold of 7 g/dL (group 2). Results. A total of 144 patients were included (mean age 5.2 years (standard deviation (SD) 3.3), 68.1% male). The mean Hb increase after transfusion was 3.5 g/dL (SD 1.7). Adherence to the transfusion Hb threshold protocol was 96.7% for group 1 v. 34.0% for group 2. No complications were reported. Average blood wastage was 3.5 units per year during the study period. Conclusions. Adherence to paediatric blood transfusion protocol was low in the Hb threshold group <7 g/dL. However, transfusion-related complications and wastage were minimal. Further prospective research is required to determine optimal blood transfusion guidelines for paediatric trauma patients.

Pain is a complex biopsychosocial phenomenon of which the intensity, location and duration depends on various underlying components. Treatment of pain is associated with considerable inter-individual variability, and as such, requires a personalized approach. However, a priori prediction of optimal analgesic treatment for individual patients is still challenging. Another challenge is the assessment and treatment of pain in patients unable to self-report pain. In this mini-review, we first provide a brief overview of the various components underlying pain, and their associated biomarkers. These include clinical, psychosocial, neurophysiological, and biochemical components. We then discuss the use of empirical and mechanism-based pharmacokinetic-pharmacodynamic modelling to support personalized treatment of pain. Finally, we propose how these concepts can be extended to a quantitative systems pharmacology (QSP) approach that integrates the components of clinical pain and treatment response. This integrative approach can support predictions of optimal pharmacotherapy of pain, compared with approaches that focus on single components of pain. Moreover, combination of QSP modelling with state-of-the-art metabolomics approaches may offer unique possibilities to identify novel pain biomarkers. Such biomarkers could support both the personalized treatment of pain and translational drug development of novel analgesic agents. In conclusion, a QSP approach will likely improve our ability to predict pain and treatment response, paving the way for personalized treatment of pain.

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Background: Quantitative sensory testing (QST) is often used to measure children's and adults' detection- and pain thresholds in a quantitative manner. In children especially the Thermal Sensory Analyzer (TSA-II) is often applied to determine thermal detection and pain thresholds. As comparisons between studies are hampered by the different testing protocols used, we aimed to present a standard protocol and reference values for thermal detection- and pain thresholds in children. Methods: Our standard testing protocol includes reaction time dependent and independent tests and takes about 14-18 min to complete. Reference values were obtained from a sample of 69 healthy term born children and adolescents with a median age of 11.2 years (range 8.2 to 17.9 years old). Seventy-one children were recruited and data of 28 males and 41 females was obtained correctly. We studied possible age and sex differences. Results: This study provides Dutch reference values and presents a standard quantitative sensory testing protocol for children with an age from 8 years onwards. This protocol appeared to be feasible, since only two out of 71 participants were not able to correctly complete the protocol due to attention deficits and were therefore excluded. We found some significant age and sex differences: females were statistically significantly more sensitive for both cold and heat pain compared to males, and the youngest children (8-9 years old) were less sensitive to detect a warm stimulus. The youngest children tend to be more sensitive to heat pain in comparison to older participants, although the difference was not statistically significant. Conclusions: We present a feasible thermal quantitative sensory testing protocol for children and reference values that are easy to interpret and may serve as normative values for future studies.

__Introduction__ Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. __Methods and analysis__ The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2-18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. __Ethics__ Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community.

The gold standard for quantification of pain is a person's self-report. However, we need objective parameters for pain measurement when intensive care patients, for example, are not able to report pain themselves. An increase in pain is currently thought to coincide with an increase in stress hormones. This observational study investigated whether procedure-related pain is associated with an increase of plasma cortisol, adrenaline, and noradrenaline. In 59 patients receiving intensive care after cardiac surgery, cortisol, adrenaline, and noradrenaline plasma levels were measured immediately before and immediately after patients were turned for washing, either combined with the removal of chest tubes or not. Numeric rating scale scores were obtained before, during, and after the procedure. Unacceptably severe pain (numeric rating scale ≥ 4) was reported by seven (12%), 26 (44%), and nine (15%) patients, before, during and after the procedure, respectively. There was no statistically significant association between numeric rating scale scores and change in cortisol, adrenaline, and noradrenaline plasma levels during the procedure. Despite current convictions that pain coincides with an increase in stress hormones, procedural pain was not associated with a significant increase in plasma stress hormone levels in patients who had undergone cardiac surgery. Thus, plasma levels of cortisol, adrenaline, and noradrenaline seem unsuitable for further research on the measurement of procedural pain.

Background: This position statement provides clinical recommendations for the assessment of pain, level of sedation, iatrogenic withdrawal syndrome and delirium in critically ill infants and children. Admission to a neonatal or paediatric intensive care unit (NICU, PICU) exposes a child to a series of painful and stressful events. Accurate assessment of the presence of pain and non-pain-related distress (adequacy of sedation, iatrogenic withdrawal syndrome and delirium) is essential to good clinical management and to monitoring the effectiveness of interventions to relieve or prevent pain and distress in the individual patient. Methods: A multidisciplinary group of experts was recruited from the members of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). The group formulated clinical questions regarding assessment of pain and non-pain-related distress in critically ill and nonverbal children, and searched the PubMed/Medline, CINAHL and Embase databases for studies describing the psychometric properties of assessment instruments. Furthermore, level of evidence of selected studies was assigned and recommendations were formulated, and grade or recommendations were added on the basis of the level of evidence. Results: An ESPNIC position statement was drafted which provides clinical recommendations on assessment of pain (n = 5), distress and/or level of sedation (n = 4), iatrogenic withdrawal syndrome (n = 3) and delirium (n = 3). These recommendations were based on the available evidence and consensus amongst the experts and other members of ESPNIC. Conclusions: This multidisciplinary ESPNIC position statement guides professionals in the assessment and reassessment of the effectiveness of treatment interventions for pain, distress, inadequate sedation, withdrawal syndrome and delirium.

__Background__ Ongoing rationing of healthcare threatens services that are well established, and cripples others that desperately require investment. Burn, for one, remains a neglected epidemic in South Africa (SA), despite the magnitude of the problem. __Objective__ To identify the prominent components contributing to the cost of hospital admission with paediatric burn injury. Determining the true costs of specialist services is important, so that resources can be allocated appropriately to achieve the greatest possible impact. __Methods__ A retrospective study was undertaken over 1 year to determine patient demographics and injury details of 987 patients admitted with burn injuries to Red Cross War Memorial Children’s Hospital, Cape Town, SA. The in-hospital financial records of 80 randomly selected patients were examined. This was followed by a prospective study to determine the financial implications of four cost drivers, i.e. bed cost per day, costs of medications received, costs of dressings for wound care, and costs of surgical intervention. A random selection of 37 dressing changes (in 31 pa

Background Worldwide, oral sucrose is standard of care in many neonatal intensive care units to relieve procedural pain in neonates. This study aims to determine if time interval between sucrose administration and heelstick correlates with pain scores. Methods Neonates were prospectively studied with variable time intervals and assessed with the Premature Infant Pain Profile-Revised (PIPP-R). Results 150 neonates were included with a median gestational age of 30+6 (IQR 27+6-33+2) weeks and a median time interval of 72 (IQR 39-115) seconds between sucrose administration and heelstick. In multiple regression analysis, this time interval was not significantly related to the PIPP-R (B=0.004, 95% CI -0.005 to 0.013, p=0.37). Providing non-nutritive sucking combined with sucrose was significantly related to lower PIPP-R scores (B=-3.50, 95% CI -4.7 to -2.3, p<0.001). Conclusions Our study suggests that there is no need to wait 2 min after sucrose administration before a painful procedure. Sucrose-induced non-nutritive sucking shows a fast pain-relieving effect in neonates.

Objective: Neonatal intensive care units (NICU) around the world increasingly use music interventions. The most recent systematic review of randomized controlled trials (RCT) dates from 2009. Since then, 15 new RCTs have been published. We provide an updated systematic review on the possible benefits of music interventions on premature infants' well-being. Methods: We searched 13 electronic databases and 12 journals from their first available date until August 2016. Included were all RCTs published in English with at least 10 participants per group, including infants born prematurely and admitted to the NICU. Interventions were either recorded music interventions or live music therapy interventions. All control conditions were accepted as long as the effects of the music intervention could be analysed separately. A meta-analysis was not possible due to incompleteness and heterogeneity of the data. Results: After removal of duplicates the searches retrieved 4893 citations, 20 of which fulfilled the inclusion/exclusion criteria. The 20 included studies encompassed 1128 participants receiving recorded or live music interventions in the NICU between 24 and 40 weeks gestational age. Twenty-six different outcomes were reported which we classified into three categories: physiological parameters; growth and feeding; behavioural state, relaxation outcomes and pain. Live music interventions were shown to improve sleep in three out of the four studies and heart rate in two out of the four studies. Recorded music improved heart rate in two out of six studies. Better feeding and sucking outcomes were reported in one study using live music and in two studies using recorded music. Conclusions: Although music interventions show promising results in some studies, the variation in quality of the studies, age groups, outcome measures and timing of the interventions across the studies makes it difficult to draw strong conclusions on the effects of music in premature infants.

Background: Traditionally, 10 years ago, children born preterm often routinely received morphine, especially during mechanical ventilation. Studies in neonatal rats, whose stage of brain development roughly corresponds to that of children born preterm, found negative long-term effects after pain and opioid exposure. Objectives: We studied possible effects of prematurity, procedural pain and opioids in humans 10 years later. We hypothesized that these factors would negatively influence neurobiological, neuropsychological and sensory development later in life. Methods: We included 19 children born preterm who as neonates participated in an RCT on the short-term effects of morphine administration and who previously participated in our follow-up studies at ages 5 and 8/9 years. We assessed associations between brain morphology (n = 11), neuropsychological functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid exposure and neonatal pain. Results: Significant correlations (coefficients 0.60-0.85) of gestational age, number of painful procedures and morphine exposure with brain volumes were observed. Significant correlations between these factors and thermal sensitivity were not established. Neuropsychological outcome was significantly moderately correlated with morphine exposure in only two subtests, and children performed in general 'average' by Dutch norms. Conclusions: Although prematurity, opioid exposure and neonatal pain were significantly associated with brain volume, no major associations with neuropsychological functioning or thermal sensitivity were detected. Our findings suggest that morphine administration during neonatal life does not affect neurocognitive performance or thermal sensitivity during childhood in children born preterm without brain damage during early life. Future studies with larger sample sizes are needed to confirm these findings.

Background In end-of-life care, symptoms of discomfort are mainly managed by drug therapy, the guidelines for which are mainly based on expert opinions. A few papers have inventoried drug prescriptions in palliative care settings, but none has reported the frequency of use in combination with doses and route of administration. Objective To describe doses and routes of administration of the most frequently used drugs at admission and at day of death. Setting Palliative care centre in the Netherlands. Method In this retrospective cohort study, prescription data of deceased patients were extracted from the electronic medical records. Main outcome measure Doses, frequency and route of administration of prescribed drugs Results All regular medication prescriptions of 208 patients, 89 % of whom had advanced cancer, were reviewed. The three most prescribed drugs were morphine, midazolam and haloperidol, to 21, 11 and 23 % of patients at admission, respectively. At the day of death these percentages had increased to 87, 58 and 50 %, respectively. Doses of these three drugs at the day of death were statistically significantly higher than at admission. The oral route of administration was used in 89 % of patients at admission versus subcutaneous in 94 % at the day of death. Conclusions Nearing the end of life, patients in this palliative care centre receive discomfort-relieving drugs mainly via the subcutaneous route. However, most of these drugs are unlicensed for this specific application and guidelines are based on low level of evidence. Thus, there is every reason for more clinical research on drug use in palliative care.

This critical opinion article deals with the challenges of finding the most effective pharmacotherapeutic options for the management of pain in intellectually disabled children and provides recommendations for clinical practice and research. Intellectual disability can be caused by a wide variety of underlying diseases and may be associated with congenital anomalies such as cardiac defects, small-bowel obstructions or limb abnormalities as well as with comorbidities such as scoliosis, gastro-esophageal reflux disease, spasticity, and epilepsy. These conditions themselves or any necessary surgical interventions are sources of pain. Epilepsy often requires chronic pharmacological treatment with antiepileptic drugs. These antiepileptic drugs can potentially cause drug–drug interactions with analgesic drugs. It is unfortunate that children with intellectual disabilities often cannot communicate pain to caregivers. Although these children are at high risk of experiencing pain, researchers nevertheless often have to exclude them from trials on pain management because of ethical considerations. We therefore make a plea for prescribers, researchers, patient organizations, pharmaceutical companies, and policy makers to study evidence-based, safe and effective pharmacotherapy in these children through properly designed studies. In the meantime, parents and clinicians must resort to validated pain assessment tools such as the revised FLACC scale.

Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3–7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 251/7 weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %. Conclusion: In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective.What is known:• The ductus arteriosus fails to close after birth in 30 to 60 % of prematurely born neonates and is a significant cause of morbidity and mortality in these infants.• Paracetamol gained importance as an alternative drug in PDA closure.What is new:• Paracetamol for PDA closure after ibuprofen treatment failure was not effective in VLBW infants.• Effect of paracetamol on PDA closure was observed when given as primary treatment.

Objective: Music interventions are widely used, but have not yet gained a place in guidelines for pediatric surgery or pediatric anesthesia. In this systematic review and meta-analysis we examined the effects of music interventions on pain, anxiety and distress in children undergoing invasive surgery. Data Sources: We searched 25 electronic databases from their first available date until October 2014. Study Selection: Included were all randomized controlled trials with a parallel group, crossover or cluster design that included pediatric patients from 1 month to 18 years old undergoing minimally invasive or invasive surgical procedures, and receiving either live music therapy or recorded music. Data Extraction and Synthesis: 4846 records were retrieved from the searches, 26 full text reports were evaluated and data was extracted by two independent investigators. Main Outcome Measures: Pain was measured with the Visual Analogue Scale, the Coloured Analogue Scale and the Facial Pain Scale. Anxiety and distress were measured with an emotional index scale (not validated), the Spielberger short State Trait Anxiety Inventory and a Facial Affective Scale. Results: Three RCTs were eligible for inclusion encompassing 196 orthopedic, cardiac and day surgery patients (age of 1 day to 18 years) receiving either live music therapy or recorded music. Overall a statistically significant positive effect was demonstrated on postoperative pain (SMD -1.07; 95%CI-2.08; -0.07) and on anxiety and distress (SMD -0.34 95% CI -0.66; -0.01 and SMD -0.50; 95% CI -0.84; - 0.16. Conclusions and Relevance: This systematic review and meta-analysis indicates that music interventions may have a statistically significant effect in reducing post-operative pain, anxiety and distress in children undergoing a surgical procedure. Evidence from this review and other reviews suggests music therapy may be considered for clinical use.

Objective: To study whether new pharmacological and nonpharmacological guidelines lowered numbers of painful procedures in neonates and changed the amount and frequency of analgesic therapy as compared to the results of our previous study in 2001. Design: A prospective observational study. Setting: Level III NICU of the Erasmus MC-Sophia Children's Hospital, Rotterdam. Participants: Neonates admitted at postnatal ages less than 3 days with length of stay at least 72 h. Main Outcome Measures: Number of all potentially painful procedures and analgesic therapy recorded at the bedside during the first 14 days of NICU stay. Results: A total number of 21,076 procedures were performed in the 175 neonates studied during 1,730 patient-days (mean 12.2). The mean number of painful procedures per neonate per day was 11.4 (SD 5.7), significantly lower than the number of 14.3 (SD 4.0) in 2001 (p < 0.001). The use of analgesics was 36.6% compared to 60.3% in 2001. Sixty-three percent of all peripheral arterial line insertions failed versus 37.5% in 2001 and 9.1% venipunctures failed versus 21% in 2001. Conclusions: The mean number of painful procedures per NICU patient per day declined. Nonpharmacological pain- or stress-reducing strategies like NIDCAP and sucrose were fully embedded in our pain management. As further reduction of the number of painful procedures is unlikely, we should apply more nonpharmacological interventions and explore newer pharmacological agents.

Polytrauma is a major cause of mortality and morbidity in both developed and developing countries. The primary goal of this review is to provide a comprehensive overview on current knowledge in the management of pediatric polytrauma patients (PPPs). A database review was con- ducted based on a search in the Embase, Medline OVID-SP, Web of Science, Cochrane central, and Pubmed databases. Only studies with “paediatric population” and “polytrauma” as criteria were included. A total of 3310 citations were retrieved. Of these, 3271 were excluded after screening, based on title and abstract. The full texts of 39 articles were assessed; further selection left 25 articles to be included in this review. The most crucial point in the management of PPPs is preparedness of the staff and an emergency room furnished with age-appropriate drugs and equipment combined with a systemic approach.

Objective and Background: Bile leakage is a serious postoperative complication and percutaneous transhepatic biliary drainage (PTBD) may be an option when endoscopic treatment is not feasible. In this retrospective study, we established technical and clinical success rates as well as the complication rates of PTBD in a large group of patients with postoperative bile leakage. Methods: Data on all patients with nondilated intrahepatic bile ducts who underwent a PTBD procedure for the treatment of bile leakage between January 2000 and August 2012 were retrospectively assessed. Data included type of surgery, site of bile leak, previous attempts of bile leak repair, interval between surgery and PTBD placement. Outcome measures were the technical and clinical success rates, the procedure-related complications, and mortality rate. Results: A total of 63 patients were identified; PTBD placement was technically successful in 90.5% (57/63) after one to three attempts. The clinical success rate was 69.8% (44/63). Four major complications were documented (4/63; 6.3%): liver laceration, pneumothorax, pleural empyema, and prolonged hemobilia. One minor complication involved pain. Conclusions

Background. The major paediatric public health problem worldwide is injury or trauma. In 2004, 950 000 children died as a result of injury. Objective. The aim of this study was to evaluate the logistics of medical care after paediatric polytrauma within the first hours after arrival into a trauma unit - the so-called Golden Hour. Methods. Children presenting with polytrauma to the Trauma Unit at the Red Cross War Memorial Children's Hospital between May 2011 and August 2011 were considered for inclusion in the study. Results. Fifty-five children were included in the final analysis. The median duration of stay in the Trauma Unit was 205 minutes (interquartile range 135 - 274). Conclusion. Several factors were identified that unnecessarily prolonged the time that patients stayed in the trauma unit following arrival in hospital for

Background: The reason for this review is the lack of data on the management of physical abused children in Africa. The primary goal of the first part is to outline the management of physical child abuse in (South) Africa and provide suggestions for other governments in Africa on which to base their management of physical child abuse, at both governmental and hospital management level. The main aim of the second part is to outline the extent of the problem as seen at the Red Cross Memorial Children's Hospital (RCH) in Cape Town. Material and Methods: The National Library of Medicine's PubMed database was searched for articles specifically about the management of physical child abuse. Hospital data were analysed in two phases: one addressed various types of assault in order to assess the number of patients admitted to the trauma unit of RCH between 1991 and 2009, and the other to identify all children with suspected non-accidental injury (NAI) presenting to the trauma unit at RCH from January 2008 until December 2010. Results: Information on physical abuse of children in Africa in the English scientific literature remains disappointing with only two articles focusing on its management. RCH data for the period 1991-2009 recorded a total number of 6415 children hospitalised with injuries following assault, who accounted for 4.2% of all trauma admissions. Types of abuse included assault with a blunt or sharp instrument, rape/ sexual assault and human bite wounds. Over the last 2 decades, there has been a minor decline in the number of cases of severe abuse requiring admission; admissions for other injuries have remained stable. More detailed analysis of hospital data for 2008-2010, found that boys were far more commonly assaulted than girls (70.5% vs 29.5%). Physical abuse appeared to be the most common cause of abuse; 89.9% of all boys and 60.5% of all girls presented after physical abuse. Conclusion: In order to eradicate child abuse, awareness of it has to be promote

Purpose. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. We tested the hypothesis that VA-ECMO therapy improves the microcircu- lation in neonates wit

BackgroundReports conflict on optimal postoperative analgesic treatment in children with intellectual disability. We retrospectively compared postoperative analgesics consumption between neonates with and without Downs syndrome in relation to anaesthesia requirements and pain scores. MethodsWe analysed hypnotic and analgesic drug administration, pain scores [COMFORT-Behaviour (COMFORT-B) scale], and duration of mechanical ventilation during the first 48 h after surgical repair of congenital duodenal obstruction in neonates, between 1999 and 2011. Data of 15 children with Downs syndrome were compared with data of 30 children without Downs syndrome. ResultsGeneral anaesthesia requirements did not differ. The median (inter-quartile range) maintenance dose of morphine during the first 24 h after operation was 9.5 (7.810.1) g kg -1 h -1 in the Downs syndrome group vs 7.7 (5.010.0) g kg -1 h -1 in the control group (P0.46). Morphine doses at postoperative day 2 and COMFORT-B scores at day 1 did not significantly differ between the two groups. COMFORT-B scores at day two were lower in children with Downs syndrome (P0.04). The duration of postoperative mechanical ventilation did not statistically differ between the two groups (P0.89). ConclusionsIn this study, neonates with and without Downs syndrome received adequate postoperative analgesia, as judged from comparable analgesic consumption and pain scores. We recommend prospective studies in children of different age groups with Downs syndrome and in other groups of intellectually disabled children to provide further investigation of the hypothesis that intellectual disability predisposes to different analgesic requirements.

The objectives of this study are to describe the number and nature of adverse events occurring in general pediatric practice, to describe factors contributing to the occurrence of these adverse events, and to report on the experience of pediatricians with reporting adverse events. It is a prospective study on 11 pediatric units in a 3-month period; adverse events were registered for all newly admitted patients. Ninety-four adverse events were registered in 88 of 5,669 patients, amounting to a 1.6 per 100 admissions rate and a 0.4 per 100 patient days rate. Ninety percent of the adverse events did not cause serious harm. Failed diagnostic procedures were most common. Conclusion: Adverse event registration in general pediatric practice is a first step in assessing quality and safety of care. It yields a considerable number of adverse events. Compliance to adverse event registration in daily practice is difficult but also key to optimal monitoring of quality of care.

Assessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g., pain intensity, time to first (rescue) analgesia, total analgesic consumption, adverse effects, and long-term effects] in studies on the effects of analgesic drugs. Here, we review current and promising new endpoints used in pediatric pain assessment studies.

__Background:__ Children with major anatomical congenital anomalies (CA) often need prolonged hospitalization with surgical interventions in the neonatal period and thereafter. Better intensive care treatment has reduced mortality rates, but at the cost of more morbidity. __Aim:__ To study motor-function and exercise capacity in five-year-old children born with CA, and to determine whether motor-function and exercise capacity differ according to primary diagnosis. __Study design:__ Descriptive study. __Subjects:__ One-hundred-and-two children with the following CA: congenital diaphragmatic hernia (CDH) n=24, esophageal atresia (EA) n=29, small intestinal anomalies (SIA) n=25, and abdominal wall defects (AWD) n=24. __Outcome measures:__ Overall and subtest percentile scores of the Movement-Assessment Battery for Children (M-ABC) were used to measure motor skills. Endurance time on the Bruce treadmill test was used to determine maximal exercise capacity. __Results:__ Motor-function: Seventy-three children (71.6%) had an overall percentile score within the normal range, 18 (17.6%) were classified as borderline, and 11 (10.8%) had a motor problem. This distribution was different from that in the reference population (Chi square: p=0.001). Most problems were encountered in children with CDH and EA (p=0.001 and 0.013, respectively). Ball skills and balance were most affected. __Exercise capacity:__ Mean standard deviation score (SDS) endurance time=-. 0.5 (SD: 1.3); p=0.001; due to poor exercise performance in CDH and EA patients. __Conclusions:__ Children with major anatomical CA and especially those with CDH and EA are at risk for delayed motor-function and disturbed exercise capacity.

Background: Assessing pain in mechanically ventilated critically ill patients is a great challenge. There is a need for an adequate pain measurement tool for use in conscious sedated patients because of their questionable communicative abilities. In this study, we evaluated the use of the Behavioral Pain Scale (BPS) in conscious sedated patients in comparison with its use in deeply sedated patients, for whom the BPS was developed. Additionally, in conscious sedated patients, the combination of the BPS and the

__Purpose:__ The aim of the study was to compare long-term respiratory morbidity in children after repair of esophageal atresia (EA) or congenital diaphragmatic hernia (CDH). __Patients and Methods:__ Children were seen at 6, 12, and 24 months and 5 years within a prospective longitudinal follow-up program in a tertiary children's hospital. Respiratory morbidity and physical condition were evaluated at all moments. At age 5 years, pulmonary function and maximal exercise performance were tested. __Results:__ In 3 of 23 atresia patients and 10 of 20 hernia patients, bronchopulmonary dysplasia was developed. Seventeen atresia and 11 hernia patients had recurrent respiratory tract infections mainly in the first years of life. At age 5, 25% of EA and CDH patients measured showed reduced forced expiratory volume in 1 second (z-score < -2). Both atresia and hernia patients showed impaired growth, with catch-up growth at 5 years in patients with EA but not in those with hernia. Maximal exercise performance was significantly below normal for both groups.

Several observation scales have been developed to measure pain in elderly persons with cognitive impairments. Most scales, however, do not provide cut-off scores for pain, and previous studies do not include data on non-verbal patients with diagnoses other than dementia. Objective: The development of an easy-to-use, reliable and valid pain observation scale, the Rotterdam Elderly Pain Observation Scale (REPOS), for use in nursing home residents incapable of reporting pain themselves. Methods: In this multicenter case-control study 174 residents of various cognitive levels were videotaped at rest and during a potentially painful activity. Prevalences and co- occurrences of behaviors were examined, and interrelationships were identified. To reduce number of items, multiple linear regression analysis was used. Interrater-, and intrarater agreements and internal consistency were investigated. To estimate validity, REPOS was related to Numeric Rating Scale (NRS) and Pain Assessment in Advanced Dementia-Scale (PAINAD), and activity and rest situations were compared. Results: A one- dimensional model with a good fit was found. After redundancy analysis, ten items remained. Interrater- and intrarater agreements of two observers were good. Internal consistency was moderate. Correlations between REPOS and NRS were small to medium, and between REPOS and PAINAD large. REPOS-scores for the two situations differed significantly. A total score of 3 and hig

Objective: To construct a reliable and clinically practical instrument for monitoring opioids and benzodiazepine withdrawal symptoms in pediatric ICU patients. Design: Instrument development. Setting: Intensive care unit in an academic children's hospital. Patients and participants: 79 patients up to age 16 years on intravenous midazolam and/or opioids for ≥5 days. An expert panel of 85 physicians and nurses rated clinical relevance of withdrawal symptoms. Intervention: During drug weaning repeated observations were performed with a checklist of 24 withdrawal symptoms described in the literature. Measurements and results: For 76 children, 932 observations were obtained within 24 h after decrease and/or discontinuation of midazolam or opioids. Most frequent symptoms were tachypnea, agitation, motor disturbance, diarrhea, fever, anxiety, sleep disturbance and hypertension (14.6-29.6%). Multidimensional scaling (MDS) was performed to detect the underlying empirical structure of co-occurrences of symptoms. An expert panel judged clinical relevance of each withdrawal symptom on a four-point scale ranging from 'definitively so' to 'definitively not'. Agitation, anx