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Systematic review on TRPA1. repository for script used on data retrieval and analysis.

Background and Objective: Chronic pain represents a major global health issue in terms of psycho-physiological, therapeutic, and economic burden, not limited to adults but also to the pediatric age. Despite its great impact, its molecular mechanisms have still not been completely unraveled. Focusing on the impact of epigenetics in the pain complex trait, we assessed the association between chronic pain and the methylation pattern of TRPA1, a key gene related to pain sensitivity. Methods: We conducted a systematic review retrieving articles from three different databases. After deduplication, 431 items were subjected to manual screening, and then 61 articles were selected and screened again. Of these, only six were maintained for meta-analysis and analyzed using specific R packages. Results: Six articles were divided into two groups (group 1: comparison of mean methylation levels between healthy subjects and patients with chronic pain; group 2: correlation between mean methylation levels and pain sensation). A non-significant mean difference was obtained from the analysis of group 1 with a value of 3.97 (95% C.I. −7.79; 15.73). Analysis of group 2 showed a high level of variability between studies (correlation = 0.35, 95% C.I. −0.12; 0.82) due to their heterogeneity (I2 = 97%, p < 0.01). Conclusions: Despite the high variability observed in the different studies analyzed, our results suggest that hypermethylation and increased pain sensitivity could be connected, possibly due to the variation of TRPA1 expression.

Purpose: Compare ibuprofen and ketorolac for children with trauma-related acute pain. Methods: We conducted a multicentre randomized, double-blind, controlled trial in the Paediatric Emergency Department setting. We enrolled patients aged 8 to 17 who accessed the emergency department for pain related to a limb trauma that occurred in the previous 48 hours. At the admission, patients were classified based on numeric rating scale-11 (NRS-11) in moderate (NRS 4-6) and severe (NRS 7-10) pain groups. Each patient was randomized to receive either ibuprofen (10 mg/kg) or ketorolac (0.5 mg/kg) and the placebo of the not given drug in a double dummies design. NRS-11 was asked every 30 minutes until 2 hours after drug and placebo administration. The primary outcome was NRS-11 reduction at 60 minutes. Results: Among 125 patients with severe pain, NRS-11 reduction after 60 minutes from drug administration was 2.0 (IQR 1.0-4.0) for ibuprofen and 1.0 (IQR 1.0-3.0) for ketorolac (p=0.36). Ibuprofen was significantly better, considering secondary outcomes, at 90 minutes with a lower median of NRS-11 (p 0.008), more patients with NRS-11 less than 4 (p 0.01) and a reduction of pain score of more than 3 NRS-11 points (p 0.01). Among 87 patients with moderate pain, the NRS-11 reduction after 60 minutes from drug administration was 1.63 (±1.8) for ibuprofen and 1.8 (±1.6) for ketorolac, with no statistically significant difference. Conclusions: Oral ibuprofen and ketorolac are similarly effective in children and adolescents with acute traumatic musculoskeletal pain. ClinicalTrial.gov registration number: NCT04133623

Aim Children and adolescents affected by somatization and somatic symptom disorder commonly refer to emergency services. Due to the absence of specific guidelines for the emergency setting and to a possible lack of knowledge, these patients are at risk of being unrecognized and mismanaged. This study aims at proposing a clinical practice to approach and manage these patients and their families in the emergency setting. Methods This manuscript derived from the work of a research group of italian pediatric emergency physicians and anesthesiologists, with an expertise in pain management, members of the PIPER group. The research group reviewed the literature about psychosomatic pain and somatic symptom disorder and developed a clinical practice specific for the pediatric emergency setting. Results The manuscript provides information about the main clinical features shared by patients with psychosomatic pain and about current diagnostic criteria and appropriate management in the emergency setting. Furthermore, it highlights the possible pitfalls in which the emergency physician may run into dealing with these patients. Conclusion This clinical practice should be seen as a starting point toward a better understanding of patients with psychosomatic pain and a standardization of care in the pediatric emergency setting.

Objectives Venipuncture is one of the most frequently performed painful procedures in children. The aim of this study was to investigate the effectiveness of 2 analgesic strategies for venipuncture in children in a specific setting like a blood-drawing center. Methods This was a prospective randomized controlled trial. It was conducted in the blood-drawing center of a tertiary level children's hospital in Italy, between November 2014 and February 2015. Eligible patients were children aged from 4 to 12 years referred to the blood-drawing center for venipuncture. Enrolled children were randomized to be distracted by Buzzy device or by playing with a handheld computer. The procedural pain was measured with the faces pain scale-revised by children aged from 4 to 7 years and with a numerical rating scale by children aged from 8 to 12 years. Results Two hundred children with a median age of 8 years were enrolled in the study. The self-reported procedural pain was not statistically different between the Buzzy group and the handheld computer group: median (interquartile range) = 3.0 (1.0-4.8) and 2.0 (1.0-4.8), respectively (P = 0.72). Children reported significant pain in 25% of cases with both distraction strategies. The procedural success rate at the first attempt was not significantly different in the 2 groups. Conclusions Analgesia provided by Buzzy or by a handheld computer was not significantly different in children undergoing venipuncture in a blood-drawing center, with the great proportion of them reporting no or mild pain during procedure.

BackgroundBone fractures are a common reason for children and adolescents to seek evaluation in the ED. Little is known about the pain experienced after cast immobilisation and discharge from the ED and its optimal management. We aimed to investigate the administration of pharmacological analgesia in the first days after cast immobilisation and to identify possible influencing variables.MethodsA prospective observational cross-sectional study was conducted at the ED of the children’s hospital, Institute for Maternal and Child Health of Trieste, Italy, from October 2019 to June 2020. Patients aged 0–17 years with bone fractures were included. The primary outcome was the administration of analgesia during the 10 days following discharge, while secondary outcomes were the associated variables, including age, gender, fracture type and location, the mean limitation in usual activities and the frequency of re-evaluation at the ED for pain. Data were recorded through a questionnaire, completed by caregivers and collected by the researchers mainly through a telephone interview. The primary endpoint was evaluated as the ratio between the number of children who took at least one analgesic dose and the total enrolled children, while Χ2 or Fisher’s exact tests were used to assess secondary outcomes.ResultsDuring the study period, 213 patients, mean age 10 years (IQR: 8–13), were enrolled. Among them, 137 (64.3%) did not take any analgesic during follow-up. Among children who were administered analgesia, 22 (28.9%) received it only on the first day, and 47 (61.8%) for less than 5 days. One hundred and sixty one patients (75.6%) did not report any limitation in usual activities because of pain. The administration of analgesia was not related to the child’s age, gender or fracture site. Displaced fractures were associated with significantly more frequent analgesia being taken (OR 5.5, 95% CI 1.4 to 21.0).ConclusionAlthough some studies recommend scheduled analgesic treatment after discharge for bone fractures, this study would suggest analgesia on demand in children with non-displaced fractures, limiting scheduled analgesia to children with displaced fractures.

OBJECTIVES Injuries are one of the most common causes of pediatric emergency department (ED) visit. The aim of this study was to investigate the relationship between the intensity of pain at the ED visit of children presenting with an extremity injury and the risk of fracture. METHODS We conducted a retrospective study, considering all patients presenting to the ED of a children's hospital in Italy, with an accidental extremity injury, between May and December 2015. We selected all children aged 8 to 17 years who underwent an x-ray. Children with major, multiple, or nonextremity injuries were excluded. Age, sex, spontaneous and palpation pain, local swelling, time between injury, and medical evaluation were recorded. Sensibility and specificity of spontaneous and palpation pain in detecting a fracture were calculated. RESULTS We reviewed 994 medical records; of these, 344 (34.6%) reported a fracture. Children's median age was 12 years (interquartile range [IQR], 10-14). Median spontaneous pain at the ED visit was not significantly different between children with and without a fracture: 4.0 (1.0-6.0) and 5 (1.0-6.0), respectively (P = 0.129). Children with mild palpation pain and children without an increase of pain of at least 2 points between spontaneous and palpation pain were fractured in 3.2% and 0.97% of cases, respectively. CONCLUSIONS In this series, pain intensity in children with a minor extremity injury was not a good marker of fracture. Nevertheless, children with mild palpation pain or with a mild increase of pain between spontaneous and palpation pain had a low risk of fracture.

Children with intellectual disability frequently undergo needle-related procedures for diagnosis or treatment. Nevertheless, only a few studies deal with pain and distress management during the procedure in this population of children. This study aimed to investigate the number of anxiety and pain management techniques performed during needle procedure in children with intellectual disability (cases) compared to a population of children without intellectual disability (controls). This multicenter cohort study was performed from July 2016 to January 2018 in the pediatric ward of four urban hospitals in Italy. Eligible subjects were children with and without intellectual disability, from 4 to 17 years old, who needed venipuncture or intravenous cannulation for diagnosis or treatment. Use of topical anesthesia, distraction techniques, and physical or verbal comfort during procedures were recorded. Pain and anxiety scores were also recorded. Forty-seven cases and 94 controls were recruited. Three pain- and anxiety-relieving techniques were performed during the procedure in 12 (25%) cases and in 10 controls (11%); two techniques were performed in 23 (50%) cases and in 26 (28%) controls; 12 (25%) cases and 52 (55%) controls received only one.Conclusion: In this series, children with intellectual disability received significantly more relieving techniques, but experienced more pain and anxiety when compared to children without intellectual disability. What is Known: • Children with intellectual disability experience more episodes of pain than cognitively healthy ones, and almost 10% of these episodes are due to medical procedures. What is New: • Children with intellectual disability despite receiving more relieving techniques during a needle-related procedure experienced more pain and anxiety when compared to healthy children.

OBJECTIVE: Needle-related procedures are the most common sources of pain for children in the hospital setting. The most used topical anesthetic, eutectic mixture of local anesthetic (EMLA) cream, may cause transient vasoconstriction. It has been postulated that this vasoconstriction may decrease vein visualization. The application of heat gel pack after removal of EMLA cream in the site of venipuncture counteracts the vasoconstriction, improving vein visualization. We assessed using a prospective randomized controlled trial whether the application of heat gel pack increases the needle procedure success rate. The primary study outcome was procedural success rate at the first attempt. METHODS: The study enrolled 400 children, 200 of whom applied heat gel pack after removing EMLA (treatment group) and 200 did not (control group). Procedural success rate at the first attempt, vein perception before procedure, procedural pain, and adverse events were recorded in both groups. RESULTS: Eighty-eight percent of the procedures were successful at the first attempt in the treatment group and 89% in the control group (P = 0.876). Vein perception was not significantly different in the 2 groups (P = 0.081). Pain score after the procedure was similar in the 2 groups. CONCLUSIONS: This study shows that the application of heat gel pack after removal of EMLA cream does not improve venipuncture or intravenous cannulation success rate.

Aim More than 50% of children report apian during venepuncture or intravenous cannulation and using local anaesthetics before needle procedures can lead to different success rates. This study examined how many needle procedures were successful at the first attempt when children received either a warm lidocaine and tetracaine patch or an eutectic mixture of lidocaine and prilocaine (EMLA) cream. Methods We conducted this multicentre randomised controlled trial at three tertiary-level children's hospitals in Italy in 2015. Children aged three to 10 years were enrolled in an emergency department, paediatric day hospital and paediatric ward and randomly allocated to receive a warm lidocaine and tetracaine patch or EMLA cream. The primary outcome was the success rate at the first attempt. Results The analysis included 172 children who received a warm lidocaine and tetracaine patch and 167 who received an EMLA cream. The needle procedure was successful at the first attempt in 158 children (92.4%) who received the warm patch and in 142 children (85.0%) who received the cream (p = 0.03). The pain scores were similar in both groups. Conclusion This study showed that the first-time needle procedure success was 7.4% higher in children receiving a warm lidocaine and tetracaine patch than EMLA cream.

Aim The aim of this study was to quantify the prevalence of somatic pain in a paediatric emergency department (ED). Methods We conducted a prospective observational study using patients admitted to the ED of an Italian children's hospital between December 2014 and February 2015. We enrolled children aged 7–17 who turned up at the ED complaining of pain. Patients and parents were asked to fill in a questionnaire to allow the analysis of the patients’ medical history and provide contact details for follow-up. We divided the enrolled patients into four groups: post-traumatic pain, organic pain, functional pain and somatic pain. The questionnaire was used to define pain characteristics and to generate an impairment score. Results Of the 713 patients who met inclusion criteria, 306 (42.9%) were enrolled in the study. Of these, 135 (44.0%) suffered from post-traumatic pain, 104 (34.0%) from organic pain, 41 (13.4%) from functional pain and 26 (8.6%) from somatic pain. Somatic pain patients had endured pain longer, had missed more school days and had suffered severe functional impairment. Conclusion This study highlighted that somatic pain was a significant contributor to paediatric emergency room visits and should be suspected and diagnosed in children reporting pain.

Aim Children with cognitive impairment experience pain more frequently than healthy children and are more likely to require venipuncture or intravenous cannulation for various procedures. They are frequently unable to report pain and often receive poor pain assessment and management. This study assessed the effectiveness of physical analgesia during vascular access in children with cognitive impairments. Methods We conducted a prospective randomised controlled study at a tertiary-level children's hospital in Italy from April to May 2015 to assess whether a cooling vibration device called Buzzy decreased pain during venipuncture and intravenous cannulation in children with cognitive impairment. None of the children had verbal skills and the main cognitive impairments were cerebral palsy, epileptic encephalopathy and genetic syndromes. Results We tested 70 children with a median age of nine years: 34 in the Buzzy group and 36 in the no-intervention group. Parents were trained in the use of the Noncommunicating Children's Pain Checklist – postoperative version scale, and they reported no or mild procedural pain in 32 cases (91.4%) in the Buzzy group and in 22 cases (61.1%) in the no-intervention group (p = 0.003). Conclusion Cooling vibration analgesia during vascular access reduced pain in children with cognitive impairment.