Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - Evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: Study protocol for a randomized controlled trial

Background: Gabapentin has shown efficacy in the treatment of chronic neuropathic or mixed pain in adults. Although pediatric pain specialists have extensive experience with gabapentin for the treatment of neuropathic pain, its use is off-label. Its efficacy and safety in this context have never been shown. The aim of this trial is to compare gabapentin with placebo as add-on to morphine for the treatment of severe chronic mixed or neuropathic pain in children. This trial is part of the European Union Seventh Framework Programme project Gabapentin in Paediatric Pain (GAPP) to develop a pediatric use marketing authorization for a new gabapentin suspension. Methods/design: The GAPP-2 study is a randomized, double-blind, placebo-controlled, multicenter superiority phase II study in children with severe chronic neuropathic or mixed pain. Its primary objective is to evaluate the efficacy of a gabapentin liquid formulation as adjunctive therapy to morphine. Sixty-six eligible children 3 months to 18 years of age with severe pain (pain scores ≥ 7), stratified in three age groups, will be randomized to receive gabapentin (to an accumulating dose of 45 to 63 mg/kg/day, dependent on age) or placebo, both in addition to morphine, for 12 weeks. Randomization will be preceded by a short washout period, and treatment will be initiated by a titration period of 3 weeks. After the treatment period, medication will be tapered during 4 weeks. The primary endpoint is the average pain scores in the two treatment groups (average of two measures each day for 3 days before the end-of-study visit [V10] assessed by age-appropriate pain scales (Face, Legs, Activity, Cry, Consolability scale; Faces Pain Scale-Revised; Numeric Rating Scale). Secondary outcomes include percentage responders to treatment (subjects with 30% reduction in pain scale), number of episodes of breakthrough pain, number of rescue interventions, number of pain-free days, participant dropouts, quality of life (Pediatric Quality of Life Inventory), and acceptability of treatment. Outcomes will be measured at the end-of-study visit after 12 weeks of treatment at the optimal gabapentin dose. Groups will be compared on an intention-to-treat basis. Discussion: We hope to provide evidence that the combination of morphine and gabapentin will provide better analgesia than morphine alone and will be safe. We also aim to obtain confirmation of the recommended pediatric dose. Trial registration: EudractCT, 2014-004897-40. Registered on 7 September 2017. ClinicalTrials.gov, NCT03275012. Registered on 7 September 2017

The research gap in chronic paediatric pain: A systematic review of randomised controlled trials

Background and Objective: Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. Methods: We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. Results: A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Conclusions: Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. Significance: There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases

[The effect of periodontal treatment on diabetes-related healthcare costs. A retrospective study]

Periodontitis has been considered the sixth complication of diabetes. The aim of this study was to assess the impact of periodontal treatment on diabetes-related healthcare costs in patients with diabetes. Data on 41,598 adults (45.7% female) with at least 1 insurance claim in 2012 for diabetes-related treatment were included in the analysis. The impact of periodontal treatment on diabetes-related healthcare costs was analysed by means of fixed effect models for panel data. The median diabetes-related healthcare costs per patient in 2012, including costs for diagnosis, treatment, medication, and hospitalisation, were €38.45 per quarter (interquartile range €11.52 - €263.14). The fixed effects models showed a reduced expenditure on diabetes-related costs of €12.03 [95%CI €-15.77; €-8.29] per quarter following periodontal treatment. These results support the relevance and necessity of good periodontal care for patients with diabetes

Effect of periodontal treatment on diabetes-related healthcare costs: a retrospective study

Contains fulltext : 229148.pdf (publisher's version ) (Open Access)INTRODUCTION: Periodontitis has been considered a sixth complication of diabetes. The aim of this study was to assess the impact of periodontal treatment on diabetes-related healthcare costs in patients with diabetes. RESEARCH DESIGN AND METHODS: A retrospective analysis was done, exploiting unique and large-scale claims data of a Dutch health insurance company. Data were extracted for a cohort of adults who had been continuously insured with additional dental coverage for the years 2012-2018. Individuals with at least one diabetes-related treatment claim in 2012 were included for analysis. A series of panel data regression models with patient-level fixed effects were estimated to assess the impact of periodontal treatment on diabetes-related healthcare costs. RESULTS: A total of 41 598 individuals with diabetes (age range 18-100 years; 45.7% female) were included in the final analyses. The median diabetes-related healthcare costs per patient in 2012 were €38.45 per quarter (IQR €11.52-€263.14), including diagnoses, treatment, medication and hospitalization costs. The fixed effect models showed €12.03 (95% CI -€15.77 to -€8.29) lower diabetes-related healthcare costs per quarter of a year following periodontal treatment compared with no periodontal treatment. CONCLUSIONS: Periodontitis, a possible complication of diabetes, should receive appropriate attention in diabetes management. The findings of this study provide corroborative evidence for reduced economic burdens due to periodontal treatment in patients with diabetes

Once bitten, twice shy? Lessons learned from an experiment to liberalize price regulations for dental care

Contains fulltext : 218781.pdf (Publisher’s version ) (Open Access

Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bowel preparation: development and validation of a prediction score

Contains fulltext : 152602.pdf (Publisher’s version ) (Closed access)BACKGROUND: Adequate bowel preparation is important for optimal colonoscopy. It is important to identify patients at risk for inadequate bowel preparation because this allows taking precautions in this specific group. OBJECTIVE: To develop a prediction score to identify patients at risk for inadequate bowel preparation who may benefit from an intensified bowel cleansing regimen. DESIGN: Patient and colonoscopy data were prospectively collected, whereas clinical data were retrospectively collected for a total of 1996 colonoscopies in participants who received split-dose bowel preparation. Multivariate logistic regression analyses were conducted in a random two-thirds of the cohort to develop a prediction model. Validation and evaluation of the discriminative power of the prediction model were performed within the remaining one-third of the cohort. SETTING: Four centers, including one academic and three medium-to-large size nonacademic centers. PATIENTS: Consecutive colonoscopies in November and December 2012. Mean age was 57.3 +/- 15.9 years, 45.8% were male and indications for colonoscopy were screening and/or surveillance (27%), abdominal symptoms and/or blood loss and/or anemia (60%), inflammatory bowel disease (9%), and others (4%). INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Inadequate bowel preparation defined as Boston Bowel Preparation Scale score /=3, use of tricyclic antidepressants, use of opioids, diabetes, chronic constipation, history of abdominal and/or pelvic surgery, history of inadequate bowel preparation, and current hospitalization. The discriminative ability of the scale was good, with an area under the curve of 0.77 in the validation cohort. LIMITATIONS: Study design partially retrospective, no data on patient compliance. CONCLUSION: We developed a validated, easy-to-use prediction scale that can be used to identify subjects with an increased risk of inadequate bowel preparation with good accuracy

Influence of two pedalling rate conditions on mechanical output and physiological responses during all-out intermittent exercise

BACKGROUND AND STUDY AIMS: Cecal intubation rate (CIR) and adenoma detection rate (ADR) have been found to be inversely associated with the occurrence of post-colonoscopy colorectal cancer. Depicting differences in CIR and ADR between hospitals could provide incentives for quality improvement. The aim of this study was to compare quality parameters of routine colonoscopies between seven hospitals in The Netherlands in order to determine the extent to which possible differences were attributable to procedural and institutional factors. PATIENTS AND METHODS: Consecutive patients undergoing colonoscopy were prospectively included between November 2012 and January 2013 at two academic and five nonacademic hospitals. Patients with inflammatory bowel disease or hereditary colorectal cancer syndromes were excluded. Main outcome measures were CIR and ADR. RESULTS: A total of 3129 patients were included (mean age 59 +/- 15 years; 45.5 % male). The majority of patients (86.2 %) had a Boston Bowel Preparation Scale (BBPS) score >/= 6. Overall CIR was 94.8 %, ranging from 89.4 % to 99.2 % between hospitals. After adjustment for case mix (age, sex, American Society of Anesthesiologists score, and indication for colonoscopy), factors associated with CIR were hospital and a BBPS score >/= 6. Overall ADR was 31.8 % and varied between hospitals, ranging from 24.8 % to 46.8 %. Independent predictors for ADR were hospital, BBPS score >/= 6, and cecal intubation. By combining CIR and ADR for each hospital, a colonoscopy quality indicator (CQI) was developed, which can be used by hospitals to stimulate quality improvement. CONCLUSION: Differences in the quality of colonoscopy between hospitals can be demonstrated using CIR and ADR. As both indicators are affected by institution and bowel preparation, a comparison between hospitals based on the newly developed CQI could assist in further improving the quality of colonoscopy

Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: The GABA-1 trial-a study protocol

Introduction Gabapentin is currently used â € off-label' in children and adolescents with chronic neuropathic pain, and reliable evidence of its effects and optimal dosing are lacking. Objectives The GABA-1 trial aims to compare the efficacy and safety of gabapentin liquid formulation relative to tramadol and to explore the pharmacokinetics of both drugs in the treatment of chronic, neuropathic or mixed pain in the paediatric population. Methods and analysis The trial is a multicentre, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial. Participants aged from 3 months to <18 years of age with moderate to severe (≥4/10 in age-appropriate pain scales) chronic neuropathic or mixed pain will be recruited in 14 clinical sites in eight European countries. A total of 94 subjects will be randomised to receive gabapentin and tramadol placebo or tramadol and gabapentin placebo throughout 16-19 weeks (including 3 weeks of titration [optimisation period], 12 weeks of treatment at a stable dose [maintenance period] and 1-4 weeks of tapering [discontinuation period]). The primary objective is to assess the efficacy of gabapentin relative to tramadol for the treatment of moderate to severe chronic neuropathic or mixed pain by comparing the difference in average pain scores (assessed by age-appropriate pain scales) between intervention arms after 15 weeks of treatment. Secondary objectives include the assessment of the safety, quality of life and global satisfaction with treatment and the description of the pharmacokinetic-pharmacodynamic relationship of gabapentin liquid formulation and tramadol oral drops to validate the recommended paediatric doses. Only rescue pain medication by paracetamol and/or ibuprofen is allowed during the trial. Ethics and dissemination Ethic approval was obtained in the eight participating countries. Results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. Trial registration numbers 2014-004851-30 and NCT02722603. Trial status Ongoing research study, currently recruiting