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.

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.

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.

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.

Treatment of acute migraine attacks in children with analgesics on the World Health Organization Essential Medicines List: A systematic review and GRADE evidence synthesis.

Background The World Health Organization Essential Medicines List (WHO EML) contains two analgesics for treatment of acute migraine attacks in children, ibuprofen and paracetamol. Methods The Embase, CDSR, CENTRAL, DARE and MEDLINE databases were searched up to 18 April 2017. We analyzed randomized controlled trials (RCTs) and systematic reviews (SRs) that investigate the efficacy and safety of ibuprofen or paracetamol for treatment of acute migraine attacks in children. We conducted meta-analysis and assessments of evidence with GRADE, Cochrane risk of bias tool, and AMSTAR. Results Three RCTs (201 children) and 10 SRs on ibuprofen and/or paracetamol for acute migraine attacks in children were included. Meta-analysis indicated that ibuprofen was superior to placebo for pain-free at 2 h or pain relief at 2 h, without difference in adverse events. There were no differences between paracetamol and placebo, or ibuprofen and paracetamol. Ten SRs that analyzed various therapies for migraine in children were published between 2004 and 2016, with discordant conclusions. Conclusion Limited data from poor quality RCTs indicate that ibuprofen and paracetamol might be effective analgesics for treating migraine attacks in children. Inclusion of ibuprofen and paracetamol as antimigraine medicines for children in the WHO EML is supported by indirect evidence from studies in adults.

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.

Efficacy and Safety Outcomes in Systematic Reviews of Interventions for Postoperative Pain in Children: Comparison Against the Recommended Core Outcome Set.

Objective: To investigate the range of efficacy and safety outcomes used in systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions for postoperative pain in children and compare them with outcome domains recommended in the Pediatric Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (PedIMMPACT). Methods: Five electronic databases were searched: MEDLINE, Cochrane Database of Systematic Reviews, DARE, CINAHL, and PsycINFO. Two review authors extracted outcome data independently. Efficacy and safety outcomes were extracted and categorized. The type and number of outcomes were analyzed and compared against the outcomes recommended by PedIMMPACT. The study protocol was registered in PROSPERO (CRD42015029654). Results: We included 48 systematic reviews with data from 816 trials. The median number of all outcomes was 4, while the median number of the PedIMMPACT core outcomes was three out of six. The most commonly reported outcome of the PedIMMPACT Core Outcome set (COS) was "symptoms and adverse events," followed by pain intensity, which was reported in 75% of the included SRs. Just over half of the SRs that included a pain intensity outcome also indicated the specific pain assessment tool used in the methods section. Conclusions: Systematic reviews in the field of pediatric pain do not use the recommended COS. Nor do they consistently include pain as an outcome. This makes comparisons of efficacy and safety across interventions very difficult. Future studies should explore whether the authors are aware of the COS and whether the recommended COS is appropriate.

Interventions for Neuropathic Pain: An Overview of Systematic Reviews.

Numerous interventions for neuropathic pain (NeuP) are available, but its treatment remains unsatisfactory. We systematically summarized evidence from systematic reviews (SRs) of randomized controlled trials on interventions for NeuP. Five electronic databases were searched up to March 2015. Study quality was analyzed using A Measurement Tool to Assess Systematic Reviews. The most common interventions in 97 included SRs were pharmacologic (59%) and surgical (15%). The majority of analyzed SRs were of medium quality. More than 50% of conclusions from abstracts on efficacy and approximately 80% on safety were inconclusive. Effective interventions were described for painful diabetic neuropathy (pregabalin, gabapentin, certain tricyclic antidepressants [TCAs], opioids, antidepressants, and anticonvulsants), postherpetic neuralgia (gabapentin, pregabalin, certain TCAs, antidepressants and anticonvulsants, opioids, sodium valproate, topical capsaicin, and lidocaine), lumbar radicular pain (epidural corticosteroids, repetitive transcranial magnetic stimulation [rTMS], and discectomy), cervical radicular pain (rTMS), carpal tunnel syndrome (carpal tunnel release), cubital tunnel syndrome (simple decompression and ulnar nerve transposition), trigeminal neuralgia (carbamazepine, lamotrigine, and pimozide for refractory cases, rTMS), HIV-related neuropathy (topical capsaicin), and central NeuP (certain TCAs, pregabalin, cannabinoids, and rTMS). Evidence about interventions for NeuP is frequently inconclusive or completely lacking. New randomized controlled trials about interventions for NeuP are necessary; they should address safety and use clear diagnostic criteria.

Methodological and Reporting Quality of Systematic Reviews Published in the Highest Ranking Journals in the Field of Pain.

BACKGROUND: Systematic reviews (SRs) are important for making clinical recommendations and guidelines. We analyzed methodological and reporting quality of pain-related SRs published in the top-ranking anesthesiology journals. METHODS: This was a cross-sectional meta-epidemiological study. SRs published from 2005 to 2015 in the first quartile journals within the Journal Citation Reports category Anesthesiology were analyzed based on the Journal Citation Reports impact factor for year 2014. Each SR was assessed by 2 independent authors using Assessment of Multiple Systematic Reviews (AMSTAR) and Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) tools. Total score (median and interquartile range, IQR) on checklists, temporal trends in total score, correlation in total scores between the 2 checklists, and variability of those results between journals were analyzed. RESULTS: A total of 446 SRs were included. Median total score of AMSTAR was 6/11 (IQR: 4-7) and of PRISMA 18.5/27 (IQR: 15-22). High compliance (reported in over 90% SRs) was found in only 1 of 11 AMSTAR and 5 of 27 PRISMA items. Low compliance was found for the majority of AMSTAR and PRISMA individual items. Linear regression indicated that there was no improvement in the methodological and reporting quality of SRs before and after the publication of the 2 checklists (AMSTAR: F(1,8) = 0.22; P = .65, PRISMA: F(1,7) = 0.22; P = .47). Total scores of AMSTAR and PRISMA had positive association (R = 0.71; P < .0001). CONCLUSIONS: Endorsement of PRISMA in instructions for authors was not a guarantee of compliance. Methodological and reporting quality of pain-related SRs should be improved using relevant checklists. This can be remedied by a joint effort of authors, editors, and peer reviewers.

Celecoxib for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is a systemic auto-immune disorder that causes widespread and persistent inflammation of the synovial lining of joints and tendon sheaths. Presently, there is no cure for rheumatoid arthritis and treatment focuses on managing symptoms such as pain, stiffness and mobility, with the aim of achieving stable remission and improving mobility. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID) used for treatment of people with rheumatoid arthritis. OBJECTIVES: To assess the benefits and harms of celecoxib in people with rheumatoid arthritis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials registers (ClinicalTrials.gov and the World Health Organization trials portal) to May 18, 2017. We also searched the reference and citation lists of included studies. SELECTION CRITERIA: We included prospective randomized controlled trials (RCTs) that compared oral celecoxib (200 mg and 400 mg daily) versus no intervention, placebo or a traditional NSAID (tNSAID) in people with confirmed rheumatoid arthritis, of any age and either sex. We excluded studies with fewer than 50 participants in each arm or had durations of fewer than four weeks treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included eight RCTs with durations of 4 to 24 weeks, published between 1998 and 2014 that involved a total of 3988 adults (mean age = 54 years), most of whom were women (73%). Participants had rheumatoid arthritis for an average of 9.2 years. All studies were assessed at high or unclear risk of bias in at least one domain. Overall, evidence was assessed as moderate-to-low quality. Five studies were funded by pharmaceutical companies. Celecoxib versus placeboWe included two studies (N = 873) in which participants received 200 mg daily or 400 mg daily or placebo. Participants who received celecoxib showed significant clinical improvement compared with those receiving placebo (15% absolute improvement; 95% CI 7% to 25%; RR 1.53, 95% CI 1.25 to 1.86; number needed to treat to benefit (NNTB) = 7, 95% CI 5 to 13; 2 studies, 873 participants; moderate to low quality evidence).Participants who received celecoxib reported less pain than placebo-treated people (11% absolute improvement; 95% CI 8% to 14%; NNTB = 4, 95% CI 3 to 6; 1 study, 706 participants) but results were inconclusive for improvement in physical function (MD -0.10, 95% CI 0.29 to 0.10; 1 study, 706 participants).In the celecoxib group, 15/293 participants developed ulcers, compared with 4/99 in the placebo group (Peto OR 1.26, 95% CI 0.44 to 3.63; 1 study, 392 participants; low quality evidence). Nine (of 475) participants in the celecoxib group developed short-term serious adverse events, compared with five (of 231) in the placebo group (Peto OR 0.87 (0.28 to 2.69; 1 study, 706 participants; low quality evidence).There were fewer withdrawals among people who received celecoxib (163/475) compared with placebo (130/231) (22% absolute change; 95% CI 16% to 27%; RR 0.61, 95% CI 0.52 to 0.72; 1 study, 706 participants).Cardiovascular events (myocardial infarction, stroke) were not reported. However, regulatory agencies warn of increased cardiovascular event risk associated with celecoxib. Celecoxib versus tNSAIDsSeven studies (N = 2930) compared celecoxib and tNSAIDs (amtolmetin guacyl, diclofenac, ibuprofen, meloxicam, nabumetone, naproxen, pelubiprofen); one study included comparisons of both placebo and tNSAIDs (N = 1149).There was a small improvement, which may not be clinically significant, in numbers of participants achieving ACR20 criteria response in the celecoxib group compared to tNSAIDs (4% absolute improvement; 95% CI 0% less improvement to 8% more improvement; RR 1.10, 95% CI 0.99 to 1.23; 4 studies, 1981 participants). There was a lack of evidence of difference between participants in the celecoxib and tNSAID groups in terms of pain or physical function. Results were assessed at moderate-to-low quality evidence (downgraded due to risk of bias and inconsistency).People who received celecoxib had a lower incidence of gastroduodenal ulcers ≥ 3 mm (34/870) compared with those who received tNSAIDs (116/698). This corresponded to 12% absolute change (95% CI 11% to 13%; RR 0.22, 95% CI 0.15 to 0.32; 5 studies, 1568 participants; moderate quality evidence). There were 7% fewer withdrawals among people who received celecoxib (95% CI 4% to 9%; RR 0.73, 95% CI 0.62 to 0.86; 6 studies, 2639 participants).Results were inconclusive for short-term serious adverse events and cardiovascular events (low quality evidence). There were 17/918 serious adverse events in people taking celecoxib compared to 42/1236 among people who received placebo (Peto OR 0.71; 95% CI 0.39 to 1.28; 5 studies, 2154 participants). Cardiovascular events were reported in both celecoxib and placebo groups in one study (149 participants). AUTHORS' CONCLUSIONS: Celecoxib may improve clinical symptoms, alleviate pain and contribute to little or no difference in physical function compared with placebo. Celecoxib was associated with fewer numbers of participant withdrawals. Results for incidence of gastroduodenal ulcers (≥ 3 mm) and short-term serious adverse events were uncertain; however, there were few reported events for either.Celecoxib may slightly improve clinical symptoms compared with tNSAIDs. Results for reduced pain and improved physical function were uncertain. Particpants taking celecoxib had lower incidence of gastroduodenal ulcers (≥ 3 mm) and there were fewer withdrawals from trials. Results for cardiovascular events and short-term serious adverse events were also uncertain.Uncertainty about the rate of cardiovascular events between celecoxib and tNSAIDs could be due to risk of bias; another factor is that these were small, short-term trials. It has been reported previously that both celecoxib and tNSAIDs increase cardiovascular event rates. Our confidence in results about harms is therefore low. Larger head-to-head clinical trials comparing celecoxib to other tNSAIDs is needed to better inform clinical practice.

Interventions for postoperative pain in children: An overview of systematic reviews.

The aim of this study was to conduct an overview of systematic reviews that summarizes the results about efficacy and safety from randomized controlled trials involving the various strategies used for postoperative pain management in children. We searched the Cochrane Database of Systematic Reviews, CINAHL, Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest date to January 24, 2016. This overview included 45 systematic reviews that evaluated interventions for postoperative pain in children. Out of 45 systematic reviews that investigated various interventions for postoperative pain in children, 19 systematic reviews (42%) presented conclusive evidence of efficacy. Positive conclusive evidence was reported in 18 systematic reviews (40%) for the efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal anti-inflammatory drugs and transversus abdominis plane block. Only one systematic review reported conclusive evidence of equal efficacy that involved a comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions was reported as conclusive in 14 systematic reviews (31%), with positive conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia, transversus abdominis plane block, and clonidine. Seven systematic reviews reported equal conclusive safety for epidural infusion, diclofenac intravenous vs ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and dexmedetomidine vs intravenous infusions of various opioid analgesics, oral suspension and suppository of diclofenac, only opioid, normal saline, no treatment, placebo, and midazolam. Negative conclusive statement for safety was reported in one systematic review for caudal analgesia vs noncaudal regional analgesia. More than half of systematic reviews included in this overview were rated as having medium methodological quality. Of 45 included systematic reviews, 10 were Cochrane reviews and they had higher methodological quality than non-Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for most of the analyzed interventions, our review points out the need for more rigorous trials concerning pain management in children.

Proliferative injection therapy for osteoarthritis: a systematic review.

PURPOSE: To systematically analyse randomised controlled trials (RCTs) about efficacy and safety of proliferative injection therapy (prolotherapy) for treatment of osteoarthritis (OA). METHODS: CENTRAL, Embase and MEDLINE were searched. Two reviewers independently conducted screening and data extraction. RCTs were assessed with the Cochrane risk of bias tool. Type of treatment, study design, dosing, efficacy outcomes and safety outcomes were analysed. The protocol was registered in PROSPERO (CRD42016035258). RESULTS: Seven RCTs were included, with 393 participants aged 40-75 years and mean OA pain duration from three months to eight years. Follow-up was 12 weeks to 12 months. Studies analysed OA of the knee joint (n = 5), first carpometacarpal joint (n = 1) and finger joints (n = 1). Various types of prolotherapy were used; dextrose was the most commonly used irritant agent. All studies concluded that prolotherapy was effective treatment for OA. No serious adverse events were reported. The studies had considerable methodological limitations. DISCUSSION: Limited evidence from low-quality studies indicates a beneficial effect of prolotherapy for OA management. The number of participants in these studies was too small to provide reliable evidence. CONCLUSIONS: Current data from trials about prolotherapy for OA should be considered preliminary, and future high-quality trials on this topic are warranted.

Cochrane plain language summaries are highly heterogeneous with low adherence to the standards.

BACKGROUND: The aim of this study was to analyze whether Cochrane plain language summaries (PLSs) adhere to the Standards for the reporting of Plain Language Summaries in new Cochrane Intervention Reviews (PLEACS). METHODS: A systematic analysis of adherence to the measurable PLEACS items was performed for Cochrane PLSs published from March 2013 to the end of January 2015. Duplicate independent data extraction was performed. An adherence score was calculated for each PLS and for the Cochrane Review Groups (CRGs) that published them. RESULTS: Of the 1738 analyzed PLSs, not a single one adhered fully to the measured PLEACS items. The highest adherence was found for absence of details of the search strategy (99 % adherence), and the lowest adherence for an item mandating to address quality according to the GRADE system (0.7 % adherence). Overall adherence percentage of PLSs reporting reviews with included studies was 57 %. Different CRGs had a wide range of adherence scores. CONCLUSIONS: Cochrane plain language summaries are highly heterogeneous with a low adherence to the PLEACS standards. Therefore, there is much room for improving the content and consistency of the PLS. A standardization of PLSs is necessary to ensure delivery of proper and consistent information for consumers.

Changes in epidermal thickness and cutaneous innervation during maturation in long-term diabetes.

AIM: Peripheral nerve fiber depletion in patients with chronic diabetes mellitus (DM) was linked to neuropathic symptoms, development of pain, foot ulcerations and lower extremity amputation. The aim of this study was to analyze cutaneous changes, including paw epidermal thickness and intraepidermal nerve fiber (IENF) density in long-term diabetes, in rats 6 months and 12 months after induction of diabetes. MATERIALS AND METHODS: Epidermal thickness and IENF density were studied in Sprague-Dawley diabetic rats 6 months and 12 months after diabetes induction with streptozotocin. Epidermal thickness was evaluated using hematoxylin and eosin staining. Peripheral nerve fibers were stained with polyclonal antiserum against protein gene product 9.5 (PGP 9.5). Successful diabetes induction was validated by measuring plasma glucose and body mass regularly throughout the experiment. RESULTS: This study showed that long-term diabetes, induced in Sprague-Dawley rats with streptozotocin, is characterized with significant epidermal thinning and reduction of intraepidermal nerve fibers, 6 months and 12 months after induction of diabetes. CONCLUSION: Long-term studies of streptozotocin models of diabetes could be used for making normative IENF densities that can be later used as age-dependent normative values for studying new treatment modalities.

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.

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.

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.