Bioavailability of Oral Curcumin in Systematic Reviews: A Methodological Study.

Curcumin is a natural compound found in turmeric that exhibits diverse biological activities. However, its poor bioavailability limits its therapeutic application, which has led to the development of various bioavailability-improved formulations. In this methodological study, we analyzed whether systematic reviews on curcumin considered the bioavailability of systemic oral curcumin formulations when synthesizing evidence from human clinical trials. A total of 171 systematic reviews published between 2003 and 2022 were included in the study. From the included studies, we extracted data on study characteristics; type of curcumin; methods; and reporting regarding bioavailability, funding, and conflict of interest. Our results show that systematic reviews rarely consider the variable bioavailability of tested curcumin formulations. Relevant statistical subgroup and/or sensitivity analyses were reported in the methods and results of only 3.5% and 6.4% of reviews, respectively. However, more reviews mentioned bioavailability in their discussion (57%) or conclusion (13%). The detailed analysis of the included systematic reviews suggests that there is broad recognition of product bioavailability as a crucial factor affecting the health effects of curcumin, which is not accompanied by adequate evidence synthesis. Therefore, the results of most systematic reviews on orally administered curcumin should be taken with caution.

Characteristics of the Inflammatory Bowel Disease in Children: A Croatian Single-Centre Retrospective Study.

Inflammatory bowel diseases (IBDs), encompassing ulcerative colitis (UC) and Crohn's disease (CD), are chronic gastrointestinal disorders often diagnosed in youth, presenting unique features compared to adult-onset cases. We aimed to profile pediatric IBD patients in Croatia through a retrospective analysis of children up to 18 years old diagnosed with IBD at the University Hospital of Split from 1 January 2012, to 31 December 2021, utilizing data collected during hospitalization for diagnosis. Over a decade, 107 children were diagnosed, with 43.9% having UC, 55.1% CD, and 0.9% IBD-unclassified. Median age at diagnosis was 14.1 years, with UC patients being older (14.8 vs. 13.7 years, p = 0.044). Males constituted 60.7% of patients. Median symptom duration was 2.0 months, with CD patients experiencing a longer diagnostic delay (3.0 vs. 2.0 months, p = 0.003). The median incidence rate was 9.89 (95% CI 5.93-13.84) per 100,000 children/year, varying across age groups. Median (IQR) BMI z-score was -0.34 (-0.97-0.45). Common symptoms included diarrhea (60.7%) and abdominal pain (50.5%), with rectal bleeding more prevalent in UC (72.3% vs. 32.2%, p < 0.001). While our study offers valuable insights into pediatric IBD in Croatia, further prospective research is needed to clarify disease progression and development.

Most systematic reviews that used the term "update" in title/abstract were not an updated version.

OBJECTIVES: To analyze whether articles labelled as systematic reviews or meta-analyses (SRs/MAs) in the title and used terms "updated" or "update" in the title or abstract are indeed a report of an updated version of a previously existing SR/MA. STUDY DESIGN AND SETTING: We searched PubMed for SRs/MAs, using descriptors updated/update in the title/abstract published in 2018-2019. We analyzed how the articles used the term "update"/"updated" and whether the previous version of SR was referenced. We surveyed authors who indicated that the SR was an updated version, but there was no reference to the original SR. RESULTS: Among 1,118 included articles, most (N = 716; 64%) used the term "update" only to denote that an SR includes recent data. Among 47 authors eligible for survey, 15 replied (32%). Six authors (40%) stated that their article was an updated version and gave reference to the previous version, while 9 authors (60%) stated that their SR was not an updated version of a previous SR. CONCLUSION: Most SRs that used the term "update" in title/abstract were not an updated version of an SR. Authors should use the descriptor "update"/"updated" in their title/abstract only to refer to a new version of an SR to avoid ambiguity.

Clinical and Cytogenetic Characteristics of Children With Leukemia 20-Year Retrospective Study.

Acute leukemias are the most common malignant diseases in childhood. The aims of this retrospective cohort study were to investigate the frequency of cytogenetic abnormalities in acute pediatric leukemia; the correlation between cytogenetic abnormalities and 5-year survival; and the correlation between cytogenetic abnormalities and clinical and laboratory features. We included 105 patients; acute lymphoblastic leukemia (ALL) had 80.9% patients, B-cell lineage ALL (B-ALL) 84.7% of them, and T-cell lineage (T-ALL) 15.3%. The overall 5-year survival for B-ALL was 85.9% and for T-ALL was 84.6%. The most common cytogenetic abnormalities in patients with B-ALL were t(12;21)(p13.2;q22.1); ETV6-RUNX1 with 22.2% and hyperdiploidy with 19.4%. Our survival analysis showed that t(12;21)(p13.2;q22.1); ETV6-RUNX1 and t(1;19)(q23;p13.3); TCF3-PBX1 had the best 5-year survival with 100% of patients surviving, whereas t(v;11q23.3); KMT2A rearranged had the worst 5-year survival of just 33.3% of patients surviving after 5 years. We found no difference in 5-year survival in B-ALL when comparing clinical features. Acute myelogenous leukemia had 20 patients with 70.6% 5-year survival. The most common cytogenetic abnormality in acute myelogenous leukemia was t(8;21)(q21;q22.1); RUNX1-RUNX1T1 (20%). In conclusion, this study showed the correlation of different cytogenetic abnormalities with 5-year survival in B-ALL patients. Such correlation was not found when comparing clinical features and 5-year survival of patients with B-ALL. This emphasized the significance of cytogenetic analysis in pediatric leukemia.

Knowledge and Practice of Pediatricians Regarding Hypovitaminosis D-A Survey across 33 European Countries.

Hypovitaminosis D has been recognized as a worldwide pandemic, but there are disagreements regarding its diagnosis and treatment. This study aimed to evaluate the knowledge and practice of European pediatricians concerning vitamin D (VD) and hypovitaminosis D and their adherence to relevant guidelines. A cross-sectional study was conducted through an anonymous survey via SurveyMonkey on 304 European pediatricians. Most of the participants were general pediatricians, followed by endocrinologists and neonatologists. ESPGHAN's and the national guidelines were the most frequently used. VD testing was mostly performed in patients with skeletal, chronic kidney, and autoimmune diseases. Participants predominantly answered the questions regarding the definition of hypovitaminosis D and VD supplementation correctly, especially in children younger than 12 months. They showed the least knowledge regarding the cut off-point for the initiation of the therapy and therapeutic doses used to treat confirmed hypovitaminosis D. Participants' conflicting answers could be related to the differences between the guidelines. We consider that experts in this field should create uniform guidelines, and that those guidelines should also be promoted by national or local pediatric associations.

Methods Used for Enhancing the Bioavailability of Oral Curcumin in Randomized Controlled Trials: A Meta-Research Study.

It is unknown how randomized controlled trials (RCTs) approach the problem related to curcumin bioavailability. We analyzed methods and reporting regarding the bioavailability of systemic oral curcumin used in RCTs. We searched PubMed on 12 September 2020, to find articles reporting RCTs that used curcumin as an intervention. We extracted data about trial characteristics, curcumin products used, methods for improving curcumin bioavailability, and mentions of curcumin bioavailability. We included 165 RCTs. The most common category of intervention was simply described as "curcumin" or "curcuminoids" without a commercial name. There were 107 (64%) manuscripts that reported that they used methods to enhance the oral bioavailability of curcuminoids used in their intervention; 25 different methods were reported. The most common method was the addition of piperine (23%). Phospholipidated curcumin, a combination of curcumin and turmeric oils, nanomicellar curcumin, and colloidal dispersion of curcumin were the next most common methods. Fourteen trials (8.4%) compared more than one different curcumin product; nine (7.9%) trials compared the bioavailability/pharmacokinetics of curcumin products. In conclusion, a high number of diverse methods were used, and very few trials compared different curcumin products. More studies are needed to explore the comparative bioavailability and efficacy of different curcumin products.

Percutaneous Endoscopic Gastrostomy Tubes Can Be Considered Safe in Children: A Single-Center 11-Year Retrospective Analysis.

Background and Objectives: When the human body is disabled to naturally ingest food through the mouth, enteral or parenteral nutritional support should be started. Percutaneous gastrostomy (PEG) is a flexible feeding tube that is inserted into the stomach through the abdominal wall in patients who will need long-term enteral nutrient intake. The aim of this study is to analyze clinical characteristic of children at the time of PEG placement as well as to determine indications, complications and outcomes associated with PEG at the Department of Pediatrics of the University Hospital of Split. Materials and Methods: Retrospective analysis of the medical records of patients treated from 2010 to 2020 was performed. The following data were collected from medical records: age, gender, information about nasogastric feeding before PEG placement, indication for PEG insertion, duration of PEG, procedure-related complications and treatment outcomes. Malnutrition was determined according to the z-score range for BMI for age and sex. According to the indication for PEG placement, patients were divided into five categories: central nervous system (CNS) diseases, neuromuscular diseases, genetic disorders, metabolic diseases, and group of children with polytrauma. Results: A total of 40 patients with median age of 110 months were included in study. At the time of PEG placement, most patients had deviations in body weight and height compared to expected values for age and sex. The most common underlying diagnoses were diseases of the central nervous system. Minor complications were found in 13 (35%) of patients. One patient (2.7%) developed major complication (gastrocolic fistula) and consequently underwent reoperation. The median duration of PEG in patients with complications before the need for replacement was 27 months, and in patients without complications, 43 months. Conclusions: Negative deviations of z-score body weight, body height, and body mass index could indicate the need for possible earlier placement of PEG. PEG can be considered as a safe therapeutic option in children since PEG-related complications, mostly in minor forms, were found in a small number of patients.

The impact of the COVID-19 pandemic on resident physicians: A cross-sectional study.

BACKGROUND: COVID-19 presents a threat to the mental health of the medical staff working with COVID-19 patients. OBJECTIVE: To investigate the impact of working during the COVID-19 pandemic on resident physicians. METHODS: The study was conducted via anonymous online survey and included resident physicians. The survey contained questions about sociodemographic information, general job satisfaction during the COVID-19 pandemic, and the impact of the COVID-19 pandemic on their personal lives. RESULTS: This study included a response from 728 resident physicians. The majority of residents rated that the COVID-19 pandemic had a mostly negative impact on their satisfaction with professional life (59.9%) and quality of work (62.8%), their personal lives (44.7%) and quality of life (57.1%). Half of all residents indicated that they did not have enough personal protective equipment (PPE). About one-third of residents indicated that the level of stress at work during the COVID-19 pandemic was higher. CONCLUSIONS: Working as resident physicians during COVID-19 pandemic had a negative effect on participants' professional and personal lives. Residents did not have all the necessary PPE nor felt safe working with patients with suspected or proven COVID-19. Further action is needed to provide support for physician residents working during the COVID-19 pandemic.

Adequacy of risk of bias assessment in surgical vs non-surgical trials in Cochrane reviews: a methodological study.

BACKGROUND: Bias in randomized controlled trials (RCTs) can lead to underestimation or overestimation of the true effects of interventions. Surgical RCTs may suffer from the risk of bias (RoB) that is avoidable in trials of other interventions, and vice versa. We aimed to compare the adequacy of RoB assessments in surgical versus non-surgical RCTs included in Cochrane reviews and to assess the most common differences in those RoB assessments. Due to specificities of surgical trials, i.e. difficulties associated with blinding of surgical interventions, we hypothesized that assessments of surgical trials may be more adequate, compared to RCTs of non-surgical interventions. METHODS: This was a methodological study, analyzing methods of published Cochrane systematic reviews. Data were extracted from RoB tables in Cochrane reviews (judgments and accompanying explanatory comment) for the following four RoB domains used in the 2011 Cochrane RoB tool: randomization, allocation concealment, blinding of participants and personnel, and blinding of outcome assessors. We defined adequate assessments as those that were in line with instructions from the Cochrane Handbook for Systematic Reviews of Interventions. The prevalence of adequate assessments was compared in surgical versus non-surgical trials. The most common differences in both groups of reviews were presented. RESULTS: In 729 analyzed Cochrane reviews, there were 10,537 included trials. The prevalence of adequate RoB judgments made by Cochrane authors ranged from 87.9, 95%CI (87.3 to 88.6%) for randomization to 70.7, 95%CI (69.8 to 71.5%) for blinding of participants and personnel. For all analyzed RoB domains, the prevalence of adequate RoB domains was higher in surgical trials than in non-surgical trials. For two RoB domains assessing blinding, this difference between surgical and non-surgical trials was statistically significant (P < 0.001), while the difference was not significant for the RoB domain regarding randomization (P = 0.124) and allocation concealment (P = 0.039, ß < 0.8). CONCLUSIONS: RoB judgments were more in line with instructions from the Cochrane Handbook when Cochrane reviews assessed surgical trials, compared to those that analyzed non-surgical interventions. However, further steps are warranted to scrutinize RoB assessment in trials of both surgical and non-surgical interventions.

Assessing risk of bias judgments for blinding of outcome assessors in Cochrane reviews.

Aim: Adequate judging of risk of bias (RoB) for blinding of outcome assessors (detection bias) is important for supporting highest level of evidence. Materials & methods: Judgments and supporting comments for detection bias were retrieved from RoB tables reported in Cochrane reviews. We categorized comments, and then compared judgment and supporting comment with instructions from the Cochrane Handbook. Results: We analyzed 8656 judgments for detection bias from 7626 trials included in 575 reviews. Overall, 1909 judgments (22%) were not in line with the Cochrane Handbook. In 9% of trials, the authors split the detection bias domain according to outcomes. Here, prevalence of inadequate judgments was 19%. Conclusion: Interventions to improve RoB assessments in systematic reviews should be explored.

Research methodology used in the 50 most cited articles in the field of pediatrics: types of studies that become citation classics.

BACKGROUND: One of the frequently used methods for assessing research trends and the impact of published scientific literature in a particular discipline is citation analysis. Journals may strive to improve their metrics by choosing manuscripts and study designs that are more likely to be cited. The aim of this study was to identify the 50 most-cited articles in the field of pediatrics, analyze their study design and other characteristics of those articles, and assess the prevalence of systematic reviews among them. METHODS: In December 2017, we searched Web of Science (WoS) for all articles published in the field of pediatrics. Two authors screened articles independently and in the further analysis included 50 articles with the highest number of citations. To avoid bias for scientific papers published earlier, the citation density was calculated. We also analyzed Journal Impact Factor (JIF) of journals where citation classics were published. RESULTS: The citation density in top 50 cited articles in the field of pediatrics ranged from 33.16 to 432.8, with the average of 119.95. Most of the articles reported clinical science. Median 2016 JIF for journals that published them was 6.226 (range: 2.778 to 72.406). Half of the top 10 highly cited articles in pediatrics were published in a journal with JIF below 5. Most of the studies among the citation classics in pediatrics were cross-sectional studies (N = 22), followed by non-systematic narrative reviews (N = 10), randomized controlled trials (N = 5), cohort studies (N = 5), systematic reviews (N = 2), case-control studies (N = 2), case reports (N = 2), and there was one study protocol and one expert opinion. CONCLUSION: Few randomized controlled trials and systematic reviews were among citation classics in the field of pediatrics. Articles that use observational research methodology, and are published in journals with lower impact factors, can become citation classics.

Conference abstracts describing systematic reviews on pain were selectively published, not reliable, and poorly reported.

OBJECTIVE: The objective of the study was to determine the reporting quality of systematic review (SR) abstracts presented at World Congresses on Pain (WCPs) and to quantify agreement in results presented in those abstracts with their corresponding full-length publications. STUDY DESIGN AND SETTING: We screened abstracts of five WCPs held from 2008 to 2016 to find abstracts describing SRs. Two authors searched for corresponding full publications using PubMed and Google Scholar in April 2018. Methods and outcomes extracted from abstracts were compared with their corresponding full publications. The reporting quality of abstracts was evaluated against the PRISMA for Abstracts (PRISMA-A) checklist. RESULTS: We identified 143 conference abstracts describing SRs. Of these, 90 (63%) were published as full-length articles in peer-reviewed journals by April 2018, with a median time from conference presentation to publication of 5 months (interquartile range: -0.25 to 14 months). Among 79 abstract-publication pairs evaluable for discordance, there was some form of discordance in 40% of pairs. Qualitative discordance (different direction of the effect) was found in 13 analyzed pairs (16%). The median adherence by abstracts to each PRISMA-A checklist item was 33% (interquartile range: 29% to 42%). CONCLUSION: Conference abstracts of pain SRs are selectively published, not reliable, and poorly reported.

Efficacy and safety of oral and inhalation commercial beta-glucan products: Systematic review of randomized controlled trials.

BACKGROUND & AIMS: Beta-glucans are advertised as biologically active compounds, with various health claims. We aimed to summarize results about efficacy and safety of commercial oral and inhalation beta-glucan products on human health from randomized controlled trials (RCTs). METHODS: We conducted systematic review of RCTs. We searched MEDLINE, CENTRAL and ClinicalTrials.gov. Any commercial product, any types of participants and any health-related outcomes were eligible. Two authors independently screened studies and extracted data. Cochrane risk of bias tool was used. This review did not have any extramural funding. Registration: PROSPERO record no. 42016043539. RESULTS: We included 30 RCTs that were conducted on healthy or ill participants. Most of the trials reported beneficial effect of beta-glucan, but among the 105 different outcome domains and measures that were used, only three could be considered clinically relevant, while others were various biomarkers and surrogate outcomes such as complete blood count. Included studies on average had 33 participants per study arm, high or unclear risk of bias of at least one domain, and only half of them reported data for safety. More than half of trials that reported source of funding indicated commercial sponsorship from producers of beta-glucan. Only five RCTs reported trial registration. CONCLUSIONS: Commercial beta-glucan products were studied in a number of RCTs whose results can be considered only as preliminary, as they used small number of participants and surrogate outcomes. The quality of many studies was poor and further research and trials on bigger population should be performed before a final conclusion can be made.

Outcome Domains, Outcome Measures, and Characteristics of Randomized Controlled Trials Testing Nonsurgical Interventions for Osteoarthritis.

OBJECTIVE: Core outcome set (COS) is the minimum set of outcome domains that should be measured and reported in clinical trials. We analyzed outcome domains, prevalence of use of COS published by Outcome Measures in Rheumatology (OMERACT) initiative, outcome measures for outcome domains recommended by OMERACT COS, duration and size of randomized controlled trials (RCT) testing nonsurgical interventions for osteoarthritis (OA). METHODS: We searched PubMed and analyzed RCT about nonsurgical interventions for OA published from June 2012 to June 2017. We extracted data about trial type, use of OMERACT COS, efficacy outcome domains, safety outcome domains, outcome measures used for COS assessment, duration, and sample size. RESULTS: Among 334 analyzed trials, complete OMERACT-recommended COS was used by 14% of trials. Higher median prevalence of using OMERACT COS was found in trials explicitly described as phase III, and trials of pharmacological interventions with followup ≥ 1 year, but both with wide range of COS usage. Trialists used numerous different outcome measures for analyzing core outcome domains: 50 different outcome measures for pain, 74 for physical function, 9 for patient's global assessment, and 5 for imaging. CONCLUSION: Suboptimal use of recommended COS and heterogeneity of outcome measures is reducing quality and comparability of OA trials and hinders conclusions about efficacy and comparative efficacy of nonsurgical interventions. Interventions for improving study design of trials in this field would be beneficial.

Selective reporting bias due to discrepancies between registered and published outcomes in osteoarthritis trials.

Aim: Outcome reporting bias (ORB) occurs when outcomes planned in a study protocol are subsequently not reported or are partially reported. Our aim was to analyze ORB in randomized controlled trials (RCTs) about conservative interventions for osteoarthritis (OA) by comparing registered protocols and published manuscripts, as well as association between study funding type and intervention type, and ORB in those RCTs. Materials & methods: We analyzed RCTs that were published in a peer-review journal and analyzed any type of conservative intervention for treatment of OA in humans that reported in the manuscript registration in a public clinical trial registry and provided unique registration identifier. We extracted data indicating ORB by comparing outcomes in protocol and published article, and characteristics of trials. Results: In 190 (57%) of 334 included RCTs, it was indicated in the manuscript that a trial was registered. In 48% of trials we found discrepancies in number, type or time point of primary efficacy outcome between protocol and manuscript. Significantly less discrepancies in primary efficacy outcomes between protocols and published articles were found in trials funded by a commercial sponsor (p = 0.0062) and trials of pharmacological interventions (p = 0.0016). Conclusion: Trials about conservative therapies for OA have high prevalence of discrepancies between protocol and publication, and frequent ORB. This may mislead readers of published results because it has been shown that ORB can lead to both overestimation and underestimation of effects of interventions, depending on the intervention and outcome. Efforts to prevent nonregistration of protocols and selective reporting are needed.

Awareness and acceptability of Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials core outcome set for chronic pain among surveyed neuropathic pain authors.

Aim: We assessed the knowledge and adoption of Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT)-recommended core outcome set (COS) and core outcome measures (COM) among authors of systematic reviews (SR) and randomized controlled trials (RCT) about interventions for neuropathic pain (NeuP). Methods: NeuP SR and RCT authors identified via a systematic literature search were surveyed. Results: The response rate was low. Although majority of respondents were familiar with the IMMPACT COS, only 61% of SR authors and 40% of RCT authors used the COS. The main perceived obstacle that prevented the adoption of the COS was the lack of awareness of the full IMMPACT COS. Conclusion: The adoption of IMMPACT-recommended COS and COM among NeuP authors was inadequate and their appropriateness needs to be further evaluated.

Revisiting established medicines: An overview of systematic reviews about ibuprofen and paracetamol for treating pain in children.

BACKGROUND AND OBJECTIVE: We explored how systematic reviews evaluated paracetamol and ibuprofen for treating pain in children, as these two non-opioid analgesics are well-established medicines included in most national essential medicines lists. DATABASES AND DATA TREATMENT: We carried out an overview of systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions (PROSPERO registration: 42016045367). We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR) and Database of Reviews of Effects (DARE) up to 23 August 2017. We used AMSTAR checklist to analyse methodological quality of included SRs. RESULTS: We found 17 SRs with 72 unique RCTs; the majority of those trials included under 100 children. Positive conclusive evidence was found in only one SR, regarding safety of paracetamol. Conclusions of other SRs for efficacy and safety of ibuprofen and paracetamol were inconclusive, unclear, or there was no opinion. Only one SR analysed efficacy of ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) in chronic pain and the conclusion was that there was no evidence from RCTs that NSAIDs were effective for chronic non-cancer pain in children and adolescents. Most of the SRs addressed very narrow questions, included few trials, with few children and were of low or medium methodological quality. CONCLUSIONS: Most SRs on two relevant medicines have inconsistent conclusions and doubt upon their effectiveness. Instead of focusing on very narrow questions, SRs should examine more comprehensive research topics to obtain a general sense of consistency, particularly when analysing established medicines. SIGNIFICANCE: Evidence behind two analgesics-ibuprofen and paracetamol-that are well-established medicines for children in most countries appears limited, judging by the systematic reviews. The discrepancy between clinical use and the extensive evidence we reviewed may be a result of the selective criteria in the reviews examined. We need new, and better evidence syntheses supporting the use of these two medicines in wide indications regarding pain in children.

Outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain in children and adolescents.

BACKGROUND: We analysed outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain management in children and adolescents and compared them to the core outcome set recommended by the Pediatric Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (PedIMMPACT). METHODS: Systematic literature search was conducted in MEDLINE, CDSR, DARE, CINAHL and PsycINFO up to 31 January 2017. One author extracted data and second verified the extraction. Outcome domains and pain outcome measures were analysed and compared with the PedIMMPACT core outcome set. RESULTS: We included 337 trials. Median number of reported outcomes was five (range 1-11) for the included trials and two (range 0-6) for PedIMMPACT. The most commonly analysed PedIMMPACT outcome domains were pain intensity (93%) and "symptoms and adverse events" (83%). The remaining four PedIMMPACT outcomes were present in under 30% of included randomized controlled trials. Proportion of PedIMMPACT outcome domains did not change after the PedIMMPACT was published in 2008. Of the 312 trials that reported pain intensity, 303 (97%) also specified pain assessment tools, in which the most common was the visual analogue scale (24%) followed by the Children's Hospital of Eastern Ontario Pain Scale (18%). CONCLUSION: Analysed trials about interventions for pediatric postoperative pain insufficiently used the recommended core outcome set for acute pain in children. Relevance of the PedIMMPACT core outcome set, as well as the reasons behind its limited uptake, need to be further evaluated. SIGNIFICANCE: Recommended core outcomes have been insufficiently used in randomized controlled trials about postoperative pain in children, which hinders comparability of studies and makes synthesis of evidence difficult.

Comparison of methodological quality rating of systematic reviews on neuropathic pain using AMSTAR and R-AMSTAR.

BACKGROUND: Systematic reviews (SRs) in the field of neuropathic pain (NeuP) are increasingly important for decision-making. However, methodological flaws in SRs can reduce the validity of conclusions. Hence, it is important to assess the methodological quality of NeuP SRs critically. Additionally, it remains unclear which assessment tool should be used. We studied the methodological quality of SRs published in the field of NeuP and compared two assessment tools. METHODS: We systematically searched 5 electronic databases to identify SRs of randomized controlled trials of interventions for NeuP available up to March 2015. Two independent reviewers assessed the methodological quality of the studies using the Assessment of Multiple Systematic Reviews (AMSTAR) and the revised AMSTAR (R-AMSTAR) tools. The scores were converted to percentiles and ranked into 4 grades to allow comparison between the two checklists. Gwet's AC1 coefficient was used for interrater reliability assessment. RESULTS: The 97 included SRs had a wide range of methodological quality scores (AMSTAR median (IQR): 6 (5-8) vs. R-AMSTAR median (IQR): 30 (26-35)). The overall agreement score between the 2 raters was 0.62 (95% CI 0.39-0.86) for AMSTAR and 0.62 (95% CI 0.53-0.70) for R-AMSTAR. The 31 Cochrane systematic reviews (CSRs) were consistently ranked higher than the 66 non-Cochrane systematic reviews (NCSRs). The analysis of individual domains showed the best compliance in a comprehensive literature search (item 3) on both checklists. The results for the domain that was the least compliant differed: conflict of interest (item 11) was the item most poorly reported on AMSTAR vs. publication bias assessment (item 10) on R-AMSTAR. A high positive correlation between the total AMSTAR and R-AMSTAR scores for all SRs, as well as for CSRs and NCSRs, was observed. CONCLUSIONS: The methodological quality of analyzed SRs in the field of NeuP was not optimal, and CSRs had a higher quality than NCSRs. Both AMSTAR and R-AMSTAR tools produced comparable quality ratings. Our results point out to weaknesses in the methodology of existing SRs on interventions for the management NeuP and call for future improvement by better adherence to analyzed quality checklists, either AMSTAR or R-AMSTAR.

Authors' lack of awareness and use of core outcome set on postoperative pain in children is hindering comparative effectiveness research.

AIM: To analyze awareness about and acceptability of core outcome set (COS) for pediatric pain recommended by the PedIMMPACT. METHODS: We invited authors of systematic reviews and randomized controlled trials about interventions for postoperative pain in children to participate in a survey. RESULTS: Only a third of surveyed authors of systematic reviews and randomized controlled trials about postoperative pain in children had heard about the PedIMMPACT COS for acute pediatric pain. Problems indicated as preventing them from using the COS were lack of awareness, difficulties with implementation, and lack of resources. CONCLUSION: Further discussions about the adequacy of COS for acute pediatric pain, as well as interventions to increase the uptake of COS may be warranted.