Pain assessment tools in paediatric palliative care: A systematic review of psychometric properties and recommendations for clinical practice.

BACKGROUND: Assessing pain in infants, children and young people with life-limiting conditions remains a challenge due to diverse patient conditions, types of pain and often a reduced ability or inability of patients to communicate verbally. AIM: To systematically identify pain assessment tools that are currently used in paediatric palliative care and examine their psychometric properties and feasibility and make recommendations for clinical practice. DESIGN: A systematic literature review and evaluation of psychometric properties of pain assessment tools of original peer-reviewed research published from inception of data sources to April 2021. DATA SOURCES: PsycINFO via ProQuest, Web of Science Core, Medline via Ovid, EMBASE, BIOSIS and CINAHL were searched from inception to April 2021. Hand searches of reference lists of included studies and relevant reviews were performed. RESULTS: From 1168 articles identified, 201 papers were selected for full-text assessment. Thirty-four articles met the eligibility criteria and we examined the psychometric properties of 22 pain assessment tools. Overall, the Faces Pain Scale-Revised (FPS-R) had high cross-cultural validity, construct validity (hypothesis testing) and responsiveness; while the Faces, Legs, Activity, Cry and Consolability (FLACC) scale and Paediatric Pain Profile (PPP) had high internal consistency, criterion validity, reliability and responsiveness. The number of studies per psychometric property of each pain assessment tool was limited and the methodological quality of included studies was low. CONCLUSION: Balancing aspects of feasibility and psychometric properties, the FPS-R is recommended for self-assessment, and the FLACC scale/FLACC Revised and PPP are the recommended observational tools in their respective age groups.

Carer preferences of route of administration of transmucosal diamorphine and willingness to take part in a randomised controlled trial: an interview study (DIPPER).

BACKGROUND: Children and young people are usually given liquid morphine by mouth for breakthrough pain, which can take thirty minutes to work. A faster-acting, quickly absorbed, needle-free pain medicine, that is easy to administer is needed such as transmucosal (sublingual, buccal, intranasal) diamorphine. Research evidence relating to the administration of medication for breakthrough pain in children and young people is limited. This study aims to describe the experiences and preferences of parents and/or children and young people regarding the route of administration of diamorphine, barriers and facilitators comparative to oral morphine, and participation in a randomised controlled trial. METHODS: In-depth, semi-structured interviews with parents and/or children and young people at home or hospital/hospice. RESULTS: Thirteen interviews with: nine mothers, one father, and three sets of parents jointly. No interviews took place with a child/young person. Most families had experience of the buccal route which was effective in ease of administration and time to control pain. The intranasal route was preferred by parents irrespective of experience. Parents' willingness for their child to take part in a trial depended on the time commitment, their child's pain trajectory and the stability of analgesic requirements. CONCLUSION: A randomised controlled trial of oral morphine versus transmucosal diamorphine would need to consider trial logistics, especially time commitment. Parents felt that the trial should be introduced initially by the clinical team, with written information from the research team, and sufficient time to ask questions. Patients who had discontinued oral morphine because of side effects, or those with gastrointestinal failure, should be excluded. Maintaining stability in pain management was essential to families, so the timing of the trial is a potential issue.

Healthcare professionals' views of the use of oral morphine and transmucosal diamorphine in the management of paediatric breakthrough pain and the feasibility of a randomised controlled trial: A focus group study (DIPPER).

BACKGROUND: Oral morphine is frequently used for breakthrough pain but the oral route is not always available and absorption is slow. Transmucosal diamorphine is administered by buccal, sublingual or intranasal routes, and rapidly absorbed. AIM: To explore the perspectives of healthcare professionals in the UK caring for children with life-limiting conditions concerning the assessment and management of breakthrough pain; prescribing and administration of transmucosal diamorphine compared with oral morphine; and the feasibility of a comparative clinical trial. DESIGN/ PARTICIPANTS: Three focus groups, analysed using a Framework approach. Doctors, nurses and pharmacists (n = 28), caring for children with life-limiting illnesses receiving palliative care, participated. RESULTS: Oral morphine is frequently used for breakthrough pain across all settings; with transmucosal diamorphine largely limited to use in hospices or given by community nurses, predominantly buccally. Perceived advantages of oral morphine included confidence in its use with no requirement for specific training; disadvantages included tolerability issues, slow onset, unpredictable response and unsuitability for patients with gastrointestinal failure. Perceived advantages of transmucosal diamorphine were quick onset and easy administration; barriers included lack of licensed preparations and prescribing guidance with fears over accountability of prescribers, and potential issues with availability, preparation and palatability. Factors potentially affecting recruitment to a trial were patient suitability and onerousness for families, trial design and logistics, staff time and clinician engagement. CONCLUSIONS: There were perceived advantages to transmucosal diamorphine, but there is a need for access to a safe preparation. A clinical trial would be feasible provided barriers were overcome.

A mixed-methods systematic review and meta-analysis of barriers and facilitators to paediatric symptom management at end of life.

BACKGROUND: Symptom management for infants, children and young people at end of life is complex and challenging due to the range of conditions and differing care needs of individuals of different ages. A greater understanding of these challenges could inform the development of effective interventions. AIM: To investigate the barriers and facilitators experienced by patients, carers and healthcare professionals managing symptoms in infants, children and young people at end of life. DESIGN: A mixed-methods systematic review and meta-analysis was undertaken (PROSPERO ID: CRD42019124797). DATA SOURCES: The Cochrane Library, PROSPERO, CINAHL, MEDLINE, PsycINFO, Web of Science Core Collection, ProQuest Dissertations & Theses Database, Evidence Search and OpenGrey were electronically searched from the inception of each database for qualitative, quantitative or mixed-methods studies that included data from patients, carers or healthcare professionals referring to barriers or facilitators to paediatric end-of-life symptom management. Studies underwent data extraction, quality appraisal, narrative thematic synthesis and meta-analysis. RESULTS: A total of 64 studies were included (32 quantitative, 18 qualitative and 14 mixed-methods) of medium-low quality. Themes were generated encompassing barriers/facilitators experienced by carers (treatment efficacy, treatment side effects, healthcare professionals' attitudes, hospice care, home care, families' symptom management strategies) and healthcare professionals (medicine access, treatment efficacy, healthcare professionals' demographics, treatment side effects, specialist support, healthcare professionals' training, health services delivery, home care). Only one study included patients' views. CONCLUSION: There is a need for effective communication between healthcare professionals and families, more training for healthcare professionals, improved symptom management planning including anticipatory prescribing, and urgent attention paid to the patients' perspective.

Pediatric Erythromelalgia and SCN9A Mutations: Systematic Review and Single-Center Case Series.

OBJECTIVES: To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Nav1.7 voltage-gated sodium channel, we conducted a systematic review of pediatric presentations of erythromelalgia related to SCN9A mutations, and compared pediatric clinical presentations of symptomatic erythromelalgia, with or without SCN9A mutations. STUDY DESIGN: PubMed, Embase, and PsycINFO Databases were searched for reports of inherited erythromelalgia in childhood. Clinical features, management, and genotype were extracted. Case notes of pediatric patients with erythromelalgia from the Great Ormond Street Hospital Pain Service were reviewed for clinical features, patient-reported outcomes, and treatments. Children aged over 10 years were recruited for quantitative sensory testing. RESULTS: Twenty-eight publications described erythromelalgia associated with 15 different SCN9A gene variants in 25 children. Pain was severe and often refractory to multiple treatments, including nonspecific sodium channel blockers. Skin damage or other complications of cold immersion for symptomatic relief were common (60%). SCN9A mutations resulting in greater hyperpolarizing shifts in Nav1.7 sodium channels correlated with symptom onset at younger ages (P = .016). Variability in reporting, and potential publication bias toward severe cases, limit any estimations of overall prevalence. In our case series, symptoms were similar but comorbidities were more common in children with SCN9A mutations. Quantitative sensory testing revealed marked dynamic warm allodynia. CONCLUSIONS: Inherited erythromelalgia in children is associated with difficult-to-manage pain and significant morbidity. Standardized reporting of outcome and management in larger series will strengthen identification of genotype-phenotype relationships. More effective long-term therapies are a significant unmet clinical need.

Sensitivity and Specificity of a Neuropathic Screening Tool (Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, S-LANSS) in Adolescents With Moderate-Severe Chronic Pain.

Neuropathic screening tools improve recognition of neuropathic pain in adults. Although utilized in pediatric populations, the sensitivity, specificity and methodology of screening tool delivery have not been compared in children. We evaluated the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) in adolescents (10-18 years) referred to a tertiary pediatric pain clinic. History and examination by specialist clinicians and multidisciplinary assessment informed classification of the primary pain type. In a prospective cohort, scores were obtained at interview (S-LANSS interview; n = 161, 70% female), and following substitution of self-reported signs with examination findings in the primary pain region (Leeds Assessment of Neuropathic Symptoms and Signs, LANSS examination). Secondly, we retrospectively retrieved questionnaires self-completed by adolescents at their initial clinic appointment (S-LANSS self-completed; n = 456, 73% female). Thirdly, we explored relationships between patient-reported outcomes and S-LANSS scores. S-LANSS interview scores varied with pain classification, and S-LANSS self-completed scores were similarly highest with neuropathic pain (median [interquartile range]: 18 [11, 21]) and complex regional pain syndrome (21 [14, 24]), variable with musculoskeletal pain (13 [7, 19]) and lowest with visceral pain (6.5 [2, 11.5]) and headache (8.5 [4, 14]). As in adults, the cutpoint score of 12/24 was optimal. Sensitivity was highest with inclusion of examination findings and lowest with self-completion (LANSS examination vs S-LANSS interview vs S-LANSS self-completed: 86.3% vs 80.8% vs 74.7%), but specificity was relatively low (37.8% vs 36.7% vs 48%). High S-LANSS scores in non-neuropathic groups were associated with female sex and high pain catastrophizing. The S-LANSS is a sensitive screening tool for pain with neuropathic features in adolescents, but needs to be interpreted in the context of clinical evaluation (clinicaltrials.gov NCT03312881). PERSPECTIVE: This article reports high sensitivity of the S-LANSS screening tool for identifying pain with neuropathic features in adolescents with moderate-severe chronic pain. However, as sensitivity is lower than in adult populations, further interdisciplinary evaluation is necessary to inform diagnosis and management.

Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain:systematic review.

BACKGROUND: Intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation. AIM: To determine an intranasal diamorphine dose in children through an understanding of pharmacokinetics. DESIGN: A systematic review of the literature was undertaken to seek diamorphine pharmacokinetic parameters in neonates, children and adults. Parenteral and enteral diamorphine bioavailability were reviewed with respect to formation of the major metabolite, morphine. Clinical data quantifying equianalgesic effects of diamorphine and morphine were reviewed. REVIEW SOURCES: PubMed (1960-2020); EMBASE (1980-2020); IPA (1973-2020) and original human research studies that reported diacetylmorphine and metabolite after any dose or route of administration. RESULTS: The systematic review identified 19 studies: 16 in adults and 1 in children and 2 neonatal reports. Details of study participants were extracted. Age ranged from premature neonates to 67 years and weight 1.4-88 kg. Intranasal diamorphine bioavailability was predicted as 50%. The equianalgesic intravenous conversion ratio of morphine:diamorphine was 2:1. There was heterogeneity between pharmacokinetic parameter estimates attributed to routes of administration, lack of size standardisation, methodology and pharmacokinetic analysis. Estimates of the pharmacokinetic parameters clearance and volume of distribution were reduced in neonates. There were insufficient paediatric data to characterise clearance or volume maturation of either diamorphine or its metabolites. CONCLUSIONS: We estimate equianalgesic ratios of intravenous morphine:diamorphine 2:1, intravenous morphine:intranasal diamorphine 1:1 and oral morphine:intranasal diamorphine of 1:3. These ratios are based on adult literature, but are reasonable for deciding on an initial dose of 0.1 mg/kg in children 4-13 years.

Clinical outcome of a randomized controlled blinded trial of open versus laparoscopic Nissen fundoplication in infants and children.

OBJECTIVE: To compare the clinical outcome and endocrine response in children who were randomized to open or laparoscopic Nissen fundoplication using minimization. BACKGROUND: It is assumed that laparoscopic surgery is associated with less pain, quicker recovery and dampened endocrine response. Few randomized studies have been performed in children. METHODS: Parents gave informed consent, and this study was approved and registered (ClinicalTrials.gov Identifier: NCT00231543). Anesthesia, postoperative analgesia and feeding were standardized. Parents and staff were blinded to allocation. Blood was taken for markers of endocrine response. RESULTS: Twenty open and 19 laparoscopic patients were comparable with respect to age, weight, neurological status, and presence of congenital anomalies. Median time to full feeds was 2 days in both groups (P = 0.85); hospital stay was 4.5 days in the open group versus 5.0 days in the laparoscopic group (P = 0.57). Pain was adequately managed in both groups and there was no difference in morphine requirements. Median follow-up was 22 (range 12-34) months. Dysphagia, recurrence and need for redo fundoplication were not different between groups; retching was higher after open surgery (56% vs. 6%; P = 0.003). Insulin levels decreased at 24 hours, and was 54% lower (P = 0.02) after laparoscopy. Cortisol was elevated immediately postoperative, but was 42% lower (P = 0.02) after laparoscopy. CONCLUSIONS: There was no difference in the postoperative analgesia requirements and recovery. Laparoscopy decreased insulin levels to a greater extent, but caused less of a response in cortisol. Early postoperative outcome confirmed equal efficacy, but fewer children with retching after laparoscopy.

A Systematic Review of Measures of Breakthrough Pain and Their Psychometric Properties.

CONTEXT: Breakthrough pain (BTP) is common in cancer and other conditions yet there is a lack of validated BTP measurement tools. OBJECTIVES: We aimed to identify all tools assessing or characterising BTP in patients of any age with any condition, and to critically appraise their psychometric properties. METHODS: The Cochrane Library, PROSPERO, Embase, CINAHL, Medline, PsycINFO, Web of Science, Google Scholar, ProQuest, Evidence Search and OpenGrey were searched to identify all available tools used to assess BTP. A second search identified studies that had evaluated psychometric properties of tools identified in Search 1. Databases were searched from inception to November 2020. Studies were assessed using COSMIN criteria and GRADE guidelines. RESULTS: Search 1 found 51 tools used to assess BTP. Search 2 found six tools that had a development study and/or a study evaluating a tool psychometric property. No tool had more than one study evaluating psychometric properties so a meta-analysis could not be conducted. Studies were of inadequate to very good quality. Only the Breakthrough Pain Assessment Tool (BAT) had sufficient content validity and at least low-quality evidence for sufficient internal consistency. CONCLUSION: The BAT is recommended to characterise BTP in adults with cancer; its applicability to other conditions is unknown. The remaining tools need further evaluation. Only the Breakthrough Pain Questionnaire for Children was designed for children with cancer, but no psychometric properties were evaluated. There is a need for a tool to assess and characterise BTP in children with non-cancer diagnoses and those who cannot self-report.

Oral morphine versus transmucosal diamorphine for breakthrough pain in children: methods and outcomes: UK (DIPPER study) consensus.

OBJECTIVES: No randomised controlled trials have been conducted for breakthrough pain in paediatric palliative care and there are currently no standardised outcome measures. The DIPPER study aims to establish the feasibility of conducting a prospective randomised controlled trial comparing oral and transmucosal administration of opioids for breakthrough pain. The aim of the current study was to achieve consensus on design aspects for a small-scale prospective study to inform a future randomised controlled trial of oral morphine, the current first-line treatment, versus transmucosal diamorphine. METHODS: The nominal group technique was used to achieve consensus on best practice for mode of administration, dose regimen and a range of suitable pain intensity outcome measures for transmucosal diamorphine in children and young people with breakthrough pain. An expert panel of ten clinicians in paediatric palliative care and three parent representatives participated. Consensus was achieved when agreement was reached and no further comments from participants were forthcoming. RESULTS: The panel favoured the buccal route of administration, with dosing according to the recommendations in the Association for Paediatric Palliative Medicine formulary (fifth Edition, 2020). The verbal Numerical Rating Scale was selected to measure pain in children 8 years old and older, the Faces Pain Scale-Revised for children between 4 and 8 years old, and Face, Legs, Activity, Cry and Consolability (FLACC)/FLACC-Revised as the observational tools. CONCLUSIONS: The nominal group technique allowed consensus to be reached for a small-scale, prospective, cohort study and provided information to inform the design of a randomised controlled trial.

The addition of ketamine to a morphine nurse- or patient-controlled analgesia infusion (PCA/NCA) increases analgesic efficacy in children with mucositis pain.

AIM: To assess the efficacy of adding ketamine to morphine nurse- or patient-controlled analgesia (NCA/PCA) infusions in treating mucositis pain in children. BACKGROUND: Mucositis pain can be very difficult to control in some patients despite the use of parenteral opioids. In our institution, we have started adding low-dose ketamine to the morphine NCA/PCA in these children in an effort to improve analgesic efficacy. METHODS/MATERIALS: The records of all children receiving a morphine/ketamine PCA or NCA for mucositis pain in our institution from 1999 to 2007 were reviewed. At the time of treatment, details of the analgesic management and consumption, pain scores and side effects were prospectively recorded and then entered on to an electronic database. Ketamine was added at a concentration of 20 or 40 microg x kg(-1) per ml with our standard morphine NCA/PCA infusions and protocols being used. RESULTS: In 28 patients, there was no difference between average morphine consumption in the 24 h pre and post the addition of ketamine (33.1 (+/-10.7) vs 35.2 (+/-14.3) microg x kg(-1) per hour, P = 0.45) but in those with recorded pain scores (n = 16), the median percentage of pain scores > or =4 was 48% (13-100%) preketamine versus 33% (0-82%) postketamine (P = 0.01). In all patients, there was no change in the rates of nausea and vomiting and pruritus pre and post the addition of ketamine and no other significant side effects were reported. No difference was seen between those who had 20 or 40 microg x kg(-1) per ml of ketamine added. CONCLUSION: The addition of ketamine to a morphine NCA/PCA improves analgesic efficacy in children with mucositis pain with no increase in the incidence of side effects.

Nurse-controlled analgesia (NCA) following major surgery in 10,000 patients in a children's hospital.

BACKGROUND AND OBJECTIVES: Patients who received NCA with morphine following major surgery between 1996 and 2008 at Great Ormond Street Hospital, London, UK, were prospectively studied in the postoperative period to determine effectiveness, morphine requirements, incidence of common side effects, and serious adverse events. METHODS: The morphine NCA regimen and monitoring was according to standard hospital protocols. Data were collected prospectively and subsequently entered by trained personnel into a secure database. Patient demographics, effectiveness and satisfaction rates, morphine requirements, side effects, and serious complications were recorded. RESULTS: 10,079 patients were included. The average age was 4 years old (range 1 day to 20.5 years, median 2.3 years). There were 510 neonates. The average NCA duration was 43.7 h. 1.8% of morphine NCAs were replaced by other methods because analgesia was unsatisfactory. Satisfaction ratings were 'good' or 'very good' for 98% of the remainder. Average daily morphine requirement (mcg x kg(-1) x h(-1)) was related to age, surgical category, and postoperative time. Side effects included PONV (25%), itching (9.4%), depression of respiration, and sedation (4.5%); incidences varied with age, morphine dose, and type of surgery. Serious, potentially life-threatening adverse effects (SAE) were 0.4%. There were no deaths. SAE were significantly greater in neonates (2.5%), relative risk 9.4, P < 0.001. Morphine dose in neonates who experienced SAE was not significantly different from other neonates. CONCLUSION: NCA with morphine is an acceptable, safe, and effective method of postoperative analgesia for a wide range of ages and types of surgery in our practice. Morphine requirements increase with age, but there was also considerable inter-individual variation within age groups. PONV, itching, sedation, and respiratory depression are expected side effects. SAE are uncommon but the incidence is greatest in neonates.

Tapentadol Prolonged Release for Long-Term Treatment of Pain in Children.

PURPOSE: Investigation of the efficacy and safety of tapentadol prolonged release (PR) compared with morphine PR for long-term treatment of pain in children. PATIENTS AND METHODS: Children aged 6 to <18 years requiring long-term treatment with opioids were studied in a 12-month, 2-part, multi-center trial: Part 1, 14-day open-label, randomized, active-controlled, parallel group non-inferiority trial comparing twice daily tapentadol PR with morphine PR; Part 2, open-label treatment with tapentadol PR for up to 12 months or no treatment "safety observation period". Pain intensity was rated with visual analogue scale or Faces Pain Scale-Revised, and non-inferiority was assessed by comparison of "treatment responders" (those completing the 14-day treatment period and showing pre-defined changes in pain rating) in each group. RESULTS: Twenty-three of 48 centers enrolled 73 patients. In Part 1, 45 and 24 patients received tapentadol or morphine, respectively, of which 40 and 22 completed 14-day treatment. In Part 2, thirty-six and 58 patients entered the tapentadol PR or observation periods, respectively, with 20/36 completing at least 12 weeks of treatment; 10 of the 36 had received morphine in Part 1. Forty-four of the 58 patients in the safety observation period had received tapentadol. Tapentadol PR was non-inferior to morphine PR (lower limit of confidence interval above negative non-inferiority margin of -0.2) in Part 1. Rates of adverse events were as expected with nausea (22.2%) and constipation (15.6%) in the tapentadol PR group, and with vomiting (33.3%), nausea and constipation (each 16.7%) in the morphine PR group. No new safety issues were identified; the safety profile of tapentadol over the 12 months treatment and observation periods was comparable to that established in subjects >18 years old. CONCLUSION: Tapentadol PR was well tolerated and equivalent to morphine PR for both efficacy and safety in children (6 to <18 years old) requiring long-term treatment with opioids.

Prospective observational study of adverse drug reactions to diclofenac in children.

AIM: The aim of this study was to investigate the type of common (occurring in >1% of patients) adverse reactions caused by diclofenac when given to children for acute pain. METHODS: A prospective observational study was undertaken on paediatric surgical patents aged < or =12 years at Great Ormond Street and University College London Hospitals. All adverse events were recorded, and causality assessment used to judge the likelihood of them being due to diclofenac. Prospective recruitment meant not all patients were prescribed diclofenac, allowing an analysis of utilization. Causality of all serious adverse events was reviewed by an expert panel. RESULTS: Children prescribed diclofenac were significantly older, and stayed in hospital for shorter periods than those who were not. Diclofenac was not avoided in asthmatic patients. Data on 380 children showed they suffer similar types of nonserious adverse reactions to adults. The incidence (95% confidence interval) of rash was 0.8% (0.016, 2.3); minor central nervous system disturbance 0.5% (0.06, 1.9); rectal irritation with suppositories 0.3% (0.009, 1.9); and diarrhoea 0.3% (0.007, 1.5). No serious adverse event was judged to be caused by diclofenac, meaning the incidence of serious adverse reactions to diclofenac in children is <0.8%. CONCLUSION: Children given diclofenac for acute pain appeared to suffer similar types of adverse reactions to adults; the incidence of serious adverse reaction is <0.8%.

Pharmacological interventions for chronic pain in children: an overview of systematic reviews.

We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with CNCP or CCRP. We extracted the review characteristics and primary outcomes of ≥30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with CNCP or CCRP. Seven of those 23 reviews included 6 trials that involved children with CNCP. There were no randomised controlled trials in reviews relating to reducing pain in CCRP. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.

Population pharmacokinetics of oral diclofenac for acute pain in children.

AIMS: To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml(-1)) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children. METHODS: Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg(-1) dose; these were pooled with rich (14 post-dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults. RESULTS: A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and V(D)/F were 53.98 l h(-1) 70 kg(-1) and 4.84 l 70 kg(-1) respectively. Allometric size models appeared to predict adequately changes in CL and V(D) with age. Of the simulated doses investigated, 1 mg kg(-1) gave paediatric AUC((0,12 h)) to adult 50 mg AUC((0,12 h)) ratios of 1.00, 1.08 and 1.18 for ages 1-3, 4-6 and 7-12 years respectively. CONCLUSIONS: This study has shown 1 mg kg(-1) diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses.

The effectiveness of online pain resources for health professionals: a systematic review with subset meta-analysis of educational intervention studies.

Online educational interventions are increasingly developed for health professionals and students, although graduate and undergraduate medical curricula often contain limited information about how to assess and manage pain. This study reviews the literature on the effectiveness of pain-related online educational resources. Studies were identified through a search of Medline, PsychINFO, Web of Science, CINAHL, PubMed, Scopus, Cochrane Library, Google Scholar, and OpenGrey databases. Search terms included 3 concept blocks: (1) type of intervention-online education, computer-based, e-learning, web-based, and internet-based; (2) population-pediatrician, physician, nurse, psychologist, and medical; and (3) outcome-pain*. Thirty-two studies (13 randomised controlled trials, 5 nonrandomised controlled trials, and 14 single-group pre-post studies) were included. Ten provided data for inclusion in a series of between-groups meta-analyses. After intervention, participants receiving online instruction had significantly greater knowledge compared with those receiving training as usual/alternative training (Hedges' g = 0.80, 95% confidence interval [CI]: 0.12-1.49), and students had significantly greater skills compared with students receiving training as usual (g = 1.34, CI: 0.38-2.30). No significant differences were found for confidence/competence (g = 0.02, CI: -0.79 to 0.84) or attitudes/beliefs (g = 0.16, CI: -0.48 to 0.79). Although online educational resources show promise in improving learner knowledge, considerable heterogeneity exists between studies in quality, design, educational content, and outcomes. Furthermore, methodologically robust RCTs are required to establish the effectiveness of online educational interventions and a greater understanding of the key features of successful online resources, including cognitive interactivity. Few studies assessed health outcomes for patients, remaining a major priority for future investigations.

Persistent postsurgical pain in children and young people: prediction, prevention, and management.

Ensuring optimum preoperative and postoperative pain management should always be a priority in children.

Development of research priorities in paediatric pain and palliative care.

Priority setting for healthcare research is as important as conducting the research itself because rigorous and systematic processes of priority setting can make an important contribution to the quality of research. This project aimed to prioritise clinical therapeutic uncertainties in paediatric pain and palliative care in order to encourage and inform the future research agenda and raise the profile of paediatric pain and palliative care in the United Kingdom. Clinical therapeutic uncertainties were identified and transformed into patient, intervention, comparison and outcome (PICO) format and prioritised using a modified Nominal Group Technique. Members of the Clinical Studies Group in Pain and Palliative Care within National Institute for Health Research (NIHR) Clinical Research Network (CRN)-Children took part in the prioritisation exercise. There were 11 clinically active professionals spanning across a wide range of paediatric disciplines and one parent representative. The top three research priorities related to establishing the safety and efficacy of (1) gabapentin in the management of chronic pain with neuropathic characteristics, (2) intravenous non-steroidal anti-inflammatory drugs in the management of post-operative pain in pre-schoolers and (3) different opioid formulations in the management of acute pain in children while at home. Questions about the long-term effect of psychological interventions in the management of chronic pain and various pharmacological interventions to improve pain and symptom management in palliative care were among the 'top 10' priorities. The results of prioritisation were included in the UK Database of Uncertainties about the Effects of Treatments (DUETS) database. Increased awareness of priorities and priority-setting processes should encourage clinicians and other stakeholders to engage in such exercises in the future.