The effect of recorded music on pain endurance (CRESCENDo) - A randomized controlled trial.

INTRODUCTION: Clarifying the effect of music on pain endurance in an experimental design could aid in how music should be applied during both surgical and non-surgical interventions. This study aims to investigate the effect of music on pain endurance and the involvement of the sympathetic adrenomedullary axis (SAM) and the hypothalamic-pituitary-adrenocortical axis (HPA). MATERIALS AND METHODS: In this randomized controlled trial all participants received increasing electric stimuli through their non-dominant index finger. Participants were randomly assigned to the music group (M) receiving a 20-minute music intervention or control group (C) receiving a 20-minute resting period. The primary outcome was pain endurance, defined as amount milliampere tolerated. Secondary outcomes included anxiety level, SAM-axis based on heart rate variability (HRV) and salivary alpha-amylase, and HPA-axis activity based on salivary cortisol. RESULTS: In the intention-to-treat analysis, the effect of music on pain tolerance did not statistically differ between the M and C group. A significant positive effect of music on pain endurance was noted after excluding participants with a high skin impedance (p = 0.013, CI 0.35; 2.85). Increased HRV was observed in the M-group compared to the C-group for SDNN (B/95%CI:13.80/2.22;25.39, p = 0.022), RMSSD (B/95%CI:15.97/1.64;30.31, p = 0.032), VLF (B/95%CI:212.08/60.49;363.67, p = 0.008) and HF (B/95%CI:821.15/150.78;1491.52, p = 0.0190). No statistical significance was observed in other secondary outcomes. CONCLUSIONS: The effect of the music intervention on pain endurance was not statistically significant in the intention-to-treat analysis. The subgroup analyses revealed an increase in pain endurance in the music group after correcting for skin impedance, which could be attributed to increased parasympathetic activation.

Music to prevent deliriUm during neuroSurgerY (MUSYC): a single-centre, prospective randomised controlled trial.

OBJECTIVES: Delirium is a serious complication following neurosurgical procedures. We hypothesise that the beneficial effect of music on a combination of delirium-eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes. DESIGN: Prospective randomised controlled trial. SETTING: Single centre, conducted at the neurosurgical department of the Erasmus Medical Center, Rotterdam, the Netherlands. PARTICIPANTS: Adult patients undergoing craniotomy were eligible. INTERVENTIONS: Patients in the intervention group received preferred recorded music before, during and after the operation until day 3 after surgery. Patients in the control group were treated according to standard of clinical care. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was presence or absence of postoperative delirium within the first 5 postoperative days measured with the Delirium Observation Screening Scale (DOSS) and, in case of a daily mean score of 3 or higher, a psychiatric evaluation with the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Secondary outcomes included anxiety, heart rate variability (HRV), depth of anaesthesia, delirium severity and duration, postoperative complications, length of stay and location of discharge. RESULTS: We enrolled 189 patients (music=95, control=94) from July 2020 through September 2021. Delirium, as assessed by the DOSS, was less common in the music (n=11, 11.6%) than in the control group (n=21, 22.3%, OR:0.49, p=0.048). However, after DSM-5 confirmation, differences in delirium were not significant (4.2% vs 7.4%, OR:0.47, p=0.342). Moreover, music increased the HRV (root mean square of successive differences between normal heartbeats, p=0.012). All other secondary outcomes were not different between groups. CONCLUSION: Our results support the efficacy of music in reducing the incidence of delirium after craniotomy, as found with DOSS but not after DSM-5 confirmation, substantiated by the effect of music on preoperative autonomic tone. Delirium screening tools should be validated and the long-term implications should be evaluated after craniotomy. TRIAL REGISTRATION NUMBER: Trialregister.nl: NL8503 and ClinicalTrials.gov: NCT04649450.

Study protocol for a multicentre randomised controlled trial studying the effect of a music intervention on anxiety in adult critically ill patients (The RELACS trial).

INTRODUCTION: Anxiety is common in critically ill patients and has likely become more prevalent in the recent decade due to the imperative of the recent Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients (PADIS) to use low levels of sedation and strive for wakefulness. However, management of anxiety has not been included in the PADIS guidelines, and there is lack of evidence to treat it in spite of its growing importance. Administration of sedative and analgesic medication is often chosen to reduce anxiety, especially when associated with agitation. Sedatives are associated with prolonged mechanical ventilation, delirium and muscle wasting and are therefore preferably minimised. Previous studies have suggested positive effects of music interventions on anxiety in the critically ill. Therefore, we aim to study the effect of music intervention on anxiety in adult critically ill patients. METHODS AND DESIGN: A multicentre randomised controlled trial was designed to study the effect of a music intervention on the level of anxiety experienced by adult patients admitted to the intensive care unit (ICU). One hundred and four patients will be included in three centres in the Netherlands. Patient recruitment started on 24-08-2020 and is ongoing in three hospitals. The primary outcome is self-reported anxiety measured on the visual analogue scale. Secondary outcomes include anxiety measured using the six-item State-Trait Anxiety Inventory, sleep quality, agitation and sedation level, medication requirement, pain, delirium, complications, time spend on mechanical ventilation, physical parameters and ICU memory and experience. ETHICS AND DISSEMINATION: The Medical Ethics Review Board of Erasmus MC University Medical Centre Rotterdam, The Netherlands, has approved this protocol. The study is being conducted in accordance with the Declaration of Helsinki. Results of this trial will be published in peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT04796389.

Implementation of music in the perioperative standard care of colorectal surgery: study protocol of the IMPROVE Study.

INTRODUCTION: Perioperative music intervention has been proven effective in reducing anxiety, pain, neurohormonal stress response and medication requirement. Unfortunately, there is a gap between new effective interventions and their (interventions) integration in standard care protocols. The aim of this preimplementation and postimplementation study is to investigate the adherence to a music intervention in a tailored, multilevel, systematic implementation strategy and the initial impact of the implementation on postoperative pain in patients undergoing colorectal surgery. METHODS AND DESIGN: A monocentre prospective preimplementation and postimplementation study was set up using The Consolidated Framework for Implementation Research to conduct a systematic implementation of music intervention in three phases. Primary outcomes are adherence to the music intervention and the initial impact of the music intervention implementation on postoperative pain scores on the first postoperative day. At least 100 patients will be included in the study. Secondary outcomes include adherence to the implementation strategy, penetration of music intervention in the standard care, assessment of the determinants for implementation, impact of the implemented music intervention on pain during the entire admission, anxiety, medication usage, complications, hospital and intensive care unit (ICU) length of stay. ETHICS AND DISSEMINATION: The Medical Ethics Review Board of Erasmus MC University Medical Centre Rotterdam, The Netherlands, has approved this protocol. The study is being conducted in accordance with the Declaration of Helsinki. Results of this trial will be published in peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION: Dutch Trial Register NL8071.

Music intervention for sleep quality in critically ill and surgical patients: a meta-analysis.

OBJECTIVE: Sleep disruption occurs frequently in hospitalised patients. Given the potential of music intervention as a non-pharmacological measure to improve sleep quality, we aimed to assess and quantify current literature on the effect of recorded music interventions on sleep quality and quantity in the adult critical care and surgical populations. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, MEDLINE Ovid, Cochrane Central, Web of Science and Google Scholar. ELIGIBILITY CRITERIA FOR STUDIES: Randomised controlled trials assessing the effect of music on sleep quality in critically ill and surgical patients. METHODS: The electronic databases were systematically searched from 1 January 1981 to 27 January 2020. Data were screened, extracted and appraised by two independent reviewers. Primary outcomes were sleep quality and quantity, assessed with validated tools. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Random effects meta-analysis was performed, and pooled standardised mean differences (SMDs) with 95% CIs were reported. RESULTS: Five studies (259 patients) were included in qualitative (risk of bias) and quantitative analysis (meta-analysis). Pooled data showed a significant effect of recorded music on subjective sleep quality in the critical care and surgical population (SMD=1.21 (95% CI 0.50 to 1.91), p<0.01, excluding one non-English study; SMD=0.87 (95% CI 0.45 to 1.29), p<0.01). The SMD of 1.21 corresponded to a 27.1% (95% CI 11.2 to 42.8) increase in subjective sleep quality using validated questionnaires. A significant increase in subjective sleep quantity of 36 min was found in one study. Objective measurements of sleep assessed in one study using polysomnography showed significant increase in deeper sleep stage in the music group. CONCLUSIONS: Recorded music showed a significant improvement in subjective sleep quality in some critical care and surgical populations. Therefore, its use may be relevant to improve sleep, but given the moderate potential for bias, further research is needed. PROSPERO REGISTRATION NUMBER: CRD42020167783.

Music intervention to relieve anxiety and pain in adults undergoing cardiac surgery: a systematic review and meta-analysis.

OBJECTIVES: Previous studies have reported beneficial effects of perioperative music on patients' anxiety and pain. We performed a systematic review and meta-analysis of randomised controlled trials investigating music interventions in cardiac surgery. METHODS: Five electronic databases were systematically searched. Primary outcomes were patients' postoperative anxiety and pain. Secondary outcomes were hospital length of stay, opioid use, vital parameters and time on mechanical ventilation. PRISMA guidelines were followed and PROSPERO database registration was completed (CRD42020149733). A meta-analysis was performed using random effects models and pooled standardised mean differences (SMD) with 95% confidence intervals were calculated. RESULTS: Twenty studies were included for qualitative analysis (1169 patients) and 16 (987 patients) for meta-analysis. The first postoperative music session was associated with significantly reduced postoperative anxiety (SMD = -0.50 (95% CI -0.67 to -0.32), p<0.01) and pain (SMD = -0.51 (95% CI -0.84 to -0.19), p<0.01). This is equal to a reduction of 4.00 points (95% CI 2.56 to 5.36) and 1.05 points (95% CI 0.67 to 1.41) on the State-Trait Anxiety Inventory and Visual Analogue Scale (VAS)/Numeric Rating Scale (NRS), respectively, for anxiety, and 1.26 points (95% CI 0.47 to 2.07) on the VAS/NRS for pain. Multiple days of music intervention reduced anxiety until 8 days postoperatively (SMD = -0.39 (95% CI -0.64 to -0.15), p<0.01). CONCLUSIONS: Offering recorded music is associated with a significant reduction in postoperative anxiety and pain in cardiac surgery. Unlike pharmacological interventions, music is without side effects so is promising in this population.

Interventions with Music in PECTus excavatum treatment (IMPECT trial): a study protocol for a randomised controlled trial investigating the clinical effects of perioperative music interventions.

INTRODUCTION: Pectus excavatum repair is associated with substantial postoperative pain, despite the use of epidural analgesia and other analgesic regimens. Perioperative recorded music interventions have been shown to alleviate pain and anxiety in adults, but evidence for children and adolescents is still lacking. This study protocol describes a randomised controlled trial that evaluates the effects of recorded music interventions on postoperative pain relief in children and adolescents after pectus excavatum repair. METHODS: A multicentre randomised controlled trial was set up comparing the effects of perioperative recorded music interventions in addition to standard care with those of standard care only in patients undergoing a Nuss procedure for pectus excavatum repair. One hundred and seventy subjects (12-18 years of age) will be included in three centres in the Netherlands. Patient inclusion has started in November 2018, and is ongoing. The primary outcome is self-reported perceived pain measured on the visual analogue scale. Secondary outcomes are anxiety level, analgesics consumption, vital parameters such as heart rate, blood pressure and respiratory rate, length of hospital stay, postoperative complications, quality of life and cost-effectiveness. ETHICS AND DISSEMINATION: This study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Centre Rotterdam, The Netherlands, has approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: NL6863.

Music Interventions in Pediatric Surgery (The Music Under Surgery In Children Study): A Randomized Clinical Trial.

BACKGROUND: Perioperative music interventions have been shown to reduce anxiety and pain in adults. This inexpensive, easily applicable intervention could be of benefit to children as well. Our objective was to determine the effects of music interventions on distress, anxiety, and postoperative pain in infants undergoing surgery. METHODS: The Music Under Surgery In Children study was designed as a parallel, single-blind, randomized controlled trial with an a priori formulated hypothesis. Data were collected between August 2015 and October 2016 in a single tertiary care children's hospital. There was a 24-hour follow-up with blind primary outcome assessment. A random sample of 432 eligible 0-3 years of age infants admitted for orchidopexy, hypospadias, or inguinal hernia repair receiving general anesthesia and caudal block were asked for participation. Subjects were assigned to a preoperative music intervention, pre- and intraoperative music intervention, or no music intervention (control) via random allocation using a computer-generated list with the use of opaque envelopes. The main outcome measure was the postoperative level of distress assessed with the COMFORT-Behavior scale, which is an observational scale; furthermore, preoperative level of distress, preoperative anxiety, and physiological measurements such as heart rate (HR) and blood pressure were measured. The trial was registered at the Dutch Trial Register, number NTR5402 (www.trialregister.nl). RESULTS: One hundred ninety-five infants with median age 6.9 months (interquartile range, 3.3-11.1) were randomized, 178 of whom were included in the primary analysis. A nonsignificant difference in COMFORT-Behavior scale scores between the pre- and intraoperative music intervention group and control group at 4 hours after surgery was found (mean difference, -1.22; 95% CI, 2.60-0.17; P = .085). Additional analysis showed weak nonsignificant evidence for an interaction effect between music exposure and COMFORT-Behavior score at baseline (P = .027 with a Bonferroni-adjusted significance level of .025). General linear modeling showed a statistically significantly reduced HR after the preoperative music intervention in the holding area in the combined preoperative music intervention and intraoperative music intervention group compared to the control group (P = .003). The differences in HR among the 3 study arms at all time points were not statistically significant (P = .069). CONCLUSIONS: Music interventions do not seem to benefit all young infants undergoing surgery. The potential benefits of music interventions in the preoperative period and in more distressed children warrant further exploration.

The Effect of Perioperative Music on Medication Requirement and Hospital Length of Stay: A Meta-analysis.

OBJECTIVE: To assess and quantify the effect of perioperative music on medication requirement, length of stay and costs in adult surgical patients. SUMMARY BACKGROUND DATA: There is an increasing interest in nonpharmacological interventions to decrease opioid analgesics use, as they have significant adverse effects and opioid prescription rates have reached epidemic proportions. Previous studies have reported beneficial outcomes of perioperative music. METHODS: A systematic literature search of 8 databases was performed from inception date to January 7, 2019. Randomized controlled trials investigating the effect of perioperative music on medication requirement, length of stay or costs in adult surgical patients were eligible. Meta-analysis was performed using random effect models, pooled standardized mean differences (SMD) were calculated with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42018093140) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. RESULTS: The literature search yielded 2414 articles, 55 studies (N = 4968 patients) were included. Perioperative music significantly reduced postoperative opioid requirement (pooled SMD -0.31 [95% CI -0.45 to -0.16], P < 0.001, I = 44.3, N = 1398). Perioperative music also significantly reduced intraoperative propofol (pooled SMD -0.72 [95% CI -1.01 to -0.43], P < 0.00001, I = 61.1, N = 554) and midazolam requirement (pooled SMD -1.07 [95% CI -1.70 to -0.44], P < 0.001, I = 73.1, N = 184), while achieving the same sedation level. No significant reduction in length of stay (pooled SMD -0.18 [95% CI -0.43 to 0.067], P = 0.15, I = 56.0, N = 600) was observed. CONCLUSIONS: Perioperative music can reduce opioid and sedative medication requirement, potentially improving patient outcome and reducing medical costs as higher opioid dosage is associated with an increased risk of adverse events and chronic opioid abuse.

Can live music therapy reduce distress and pain in children with burns after wound care procedures? A randomized controlled trial.

OBJECTIVE: Burn wound care procedures are very painful and lead to distress. Live music therapy has shown beneficial effects on distress and pain in specific pediatric patient populations. In this study we measured whether live music therapy has beneficial effects in terms of less distress and pain in children with burns after wound care procedures. METHODS: This randomized assessor-blinded controlled trial (RCT) took place at the burns unit of the Red Cross War Memorial Children's Hospital, Cape Town, South Africa. It included newly admitted inpatients between the ages of 0 and 13 years undergoing their first or second wound care procedures. Excluded were children with a hearing impairment or low level of consciousness. The intervention group received one live music therapy session directly after wound care in addition to standard care. The control group received standard care only. The primary outcome was distress measured with the Observational Scale of Behavioral Distress-revised (OSBD-r). The secondary outcome was pain measured with the COMFORT-behavioral scale (COMFORT-B). In addition, in children older than 5 years self-reported distress with the validated Wong-Baker scale (FACES) and pain with the Faces Pain Scale-Revised (FPS-R) were measured. Patients in both groups were videotaped for three minutes before wound care; during the music therapy or the control condition; and for two minutes thereafter. Two researchers, blinded to the study condition, independently scored the OSBD-r and the COMFORT-B from the video footage before and after music therapy. RESULTS: We included 135 patients, median age 22.6 months (IQR 15.4-40.7 months). Change scores did not significantly differ between the intervention and the control groups for either distress (p=0.53; d=0.11; 95% CI -0.23 to 0.45) or pain (p=0.99; d=0.04; 95% CI -0.30 to 0.38). Self-reported distress in a small group of children (n=18) older than 5 years indicated a significant reduction in distress after live music therapy (p=0.05). CONCLUSIONS: Live music therapy was not found effective in reducing distress and pain in young children after burn wound care. Older children might be more responsive to this intervention.

Short-term effect of preoperative intravenous iron therapy in colorectal cancer patients with anemia: results of a cohort study.

BACKGROUND: In the treatment of preoperative anemia, which is associated with increased postoperative morbidity, iron supplementation can replace blood transfusion and erythropoiesis-stimulating agents. The aim of this study was to assess the efficacy of preoperative intravenous (IV) iron infusion in optimizing hemoglobin (Hb) levels in anemic colorectal cancer patients. STUDY DESIGN AND METHODS: A retrospective cohort study was performed on patients who underwent surgery for colorectal cancer between 2010 and 2016 in a single teaching hospital. The primary outcome measure, the change in Hb level, was assessed by comparing anemic patients receiving usual care (UC; i.e. no iron therapy and no blood transfusion) with anemic patients receiving IV iron therapy (no blood transfusion). RESULTS: A total of 758 patients with colorectal cancer were eligible, of whom 318 (41.9%) had anemia. The IV and the UC groups included 52 and 153 patients with mean Hb levels at diagnosis of 6.3 and 6.9 mmol/L, respectively. In the IV group, preoperative Hb level was significantly increased compared to the UC group (0.65 mmol/L vs. 0.10 mmol/L, p < 0.001). High increase in Hb level after iron infusion was associated with initial higher transferrin and lower ferritin levels (high vs. poor responders: median transferrin 2.9 g/L vs. 2.7 g/L, median ferritin 12 µg/L vs. 27 µg/L). CONCLUSION: Implementation of IV iron therapy in anemic colorectal cancer patients leads to a distinct increase of preoperative Hb level. IV iron therapy is most effective in patients presenting with more severe anemia, and with higher transferrin and lower ferritin levels, markers for an absolute iron deficiency (ID), compared to functional ID.

Oxygen therapies and their effects on wound healing.

Oxygen is an important factor for wound healing. Although several different therapies investigated the use of oxygen to aid wound healing, the results of these studies are not unequivocal. This systematic review summarizes the clinical and experimental studies regarding different oxygen therapies for promoting wound healing, and evaluates the outcomes according the methodological details. A systematic literature search was conducted using Embase, Medline, Web of Science, Cochrane, PubMed publisher, and Google Scholar libraries. Clinical and experimental studies investigating oxygen for wound healing were selected. Included articles were categorized according to the kind of therapy, study design, and wound type. The methodological details were extracted and analyzed. Sixty-five articles were identified and divided in three different oxygen therapies: Local oxygen therapy, hyperbaric oxygen therapy, and supplemental inspired oxygen therapy. More than half of the included local oxygen and hyperbaric oxygen studies had one or more significant positive outcomes, 77 and 63%, respectively. Supplemental inspired oxygen therapy during gastrointestinal and vascular surgery was more likely to have a positive result than during other surgical interventions reducing surgical site infections. These many positive outcomes promote the use of oxygen treatment in the stimulation of wound healing. However, the lack of clinical studies and vast methodological diversity made it impossible to perform a proper comparison within and between the different therapies. Further randomized clinical studies are warranted to examine the value of these therapies, especially studies that investigate the more patient-friendly oxygen dressings and topical wound oxygen therapies. Also, to achieve more solid and consistent data, studies should use more standardized methods and subjects.

Do Hospitalized Premature Infants Benefit from Music Interventions? A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: Neonatal intensive care units (NICU) around the world increasingly use music interventions. The most recent systematic review of randomized controlled trials (RCT) dates from 2009. Since then, 15 new RCTs have been published. We provide an updated systematic review on the possible benefits of music interventions on premature infants' well-being. METHODS: We searched 13 electronic databases and 12 journals from their first available date until August 2016. Included were all RCTs published in English with at least 10 participants per group, including infants born prematurely and admitted to the NICU. Interventions were either recorded music interventions or live music therapy interventions. All control conditions were accepted as long as the effects of the music intervention could be analysed separately. A meta-analysis was not possible due to incompleteness and heterogeneity of the data. RESULTS: After removal of duplicates the searches retrieved 4893 citations, 20 of which fulfilled the inclusion/exclusion criteria. The 20 included studies encompassed 1128 participants receiving recorded or live music interventions in the NICU between 24 and 40 weeks gestational age. Twenty-six different outcomes were reported which we classified into three categories: physiological parameters; growth and feeding; behavioural state, relaxation outcomes and pain. Live music interventions were shown to improve sleep in three out of the four studies and heart rate in two out of the four studies. Recorded music improved heart rate in two out of six studies. Better feeding and sucking outcomes were reported in one study using live music and in two studies using recorded music. CONCLUSIONS: Although music interventions show promising results in some studies, the variation in quality of the studies, age groups, outcome measures and timing of the interventions across the studies makes it difficult to draw strong conclusions on the effects of music in premature infants.

Systematic review and meta-analysis of music interventions in hypertension treatment: a quest for answers.

BACKGROUND: Adverse effects, treatment resistance and high costs associated with pharmacological treatment of hypertension have led to growing interest in non-pharmacological complementary therapies such as music interventions. This meta-analysis aims to provide an overview of reported evidence on the efficacy of music interventions in the treatment of hypertension. METHODS: A systematic literature search was conducted for publications on the effect of music interventions on blood pressure in adult hypertensive subjects published between January 1990-June 2014. Randomized controlled trials with a follow-up duration ≥28 days were included. Blood pressure measures were pooled using inverse variance weighting. RESULTS: Of the 1689 abstracts reviewed, 10 randomized controlled trials were included. Random-effects pooling of the music intervention groups showed a trend toward a decrease in mean systolic blood pressure (SBP) from 144 mmHg(95 % CI:137-152) to 134 mmHg(95 % CI:124-144), and in mean diastolic blood pressure (DBP) from 84 mmHg(95 % CI:78-89) to 78 mmHg(95 % CI:73-84). Fixed-effect analysis of a subgroup of 3 trials with valid control groups showed a significant decrease in pooled mean SBP and DBP in both intervention and control groups. A comparison between music intervention groups and control groups was not possible due to unavailable measures of dispersion. CONCLUSIONS: This systematic review and meta-analysis revealed a trend towards a decrease in blood pressure in hypertensive patients who received music interventions, but failed to establish a cause-effect relationship between music interventions and blood pressure reduction. Considering the potential value of this safe, low-cost intervention, well-designed, high quality and sufficiently powered randomized studies assessing the efficacy of music interventions in the treatment of hypertension are warranted.

The Effects of Perioperative Music Interventions in Pediatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Music interventions are widely used, but have not yet gained a place in guidelines for pediatric surgery or pediatric anesthesia. In this systematic review and meta-analysis we examined the effects of music interventions on pain, anxiety and distress in children undergoing invasive surgery. DATA SOURCES: We searched 25 electronic databases from their first available date until October 2014. STUDY SELECTION: Included were all randomized controlled trials with a parallel group, crossover or cluster design that included pediatric patients from 1 month to 18 years old undergoing minimally invasive or invasive surgical procedures, and receiving either live music therapy or recorded music. DATA EXTRACTION AND SYNTHESIS: 4846 records were retrieved from the searches, 26 full text reports were evaluated and data was extracted by two independent investigators. MAIN OUTCOME MEASURES: Pain was measured with the Visual Analogue Scale, the Coloured Analogue Scale and the Facial Pain Scale. Anxiety and distress were measured with an emotional index scale (not validated), the Spielberger short State Trait Anxiety Inventory and a Facial Affective Scale. RESULTS: Three RCTs were eligible for inclusion encompassing 196 orthopedic, cardiac and day surgery patients (age of 1 day to 18 years) receiving either live music therapy or recorded music. Overall a statistically significant positive effect was demonstrated on postoperative pain (SMD -1.07; 95%CI-2.08; -0.07) and on anxiety and distress (SMD -0.34 95% CI -0.66; -0.01 and SMD -0.50; 95% CI -0.84; - 0.16. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis indicates that music interventions may have a statistically significant effect in reducing post-operative pain, anxiety and distress in children undergoing a surgical procedure. Evidence from this review and other reviews suggests music therapy may be considered for clinical use.

Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled trial.

BACKGROUND: Success of surgical treatment for pancreatic and periampullary cancer is often limited due to locoregional recurrence and/or the development of distant metastases. OBJECTIVE: The survival benefit of celiac axis infusion (CAI) and radiotherapy (RT) versus observation after resection of pancreatic or periampullary cancer was investigated. METHODS: In a randomized controlled trial, 120 consecutive patients with histopathologically proven pancreatic or periampullary cancer received either adjuvant treatment consisting of intra-arterial mitoxantrone, 5-FU, leucovorin, and cisplatinum in combination with 30 x 1.8 Gy radiotherapy (group A) or no adjuvant treatment (group B). Groups were stratified for tumor type (pancreatic vs. periampullary tumors). RESULTS: After surgery, 120 patients were randomized (59 patients in the treatment group, 61 in the observation group). The median follow-up was 17 months. No significant overall survival benefit was seen (median, 19 vs. 18 months resp.). Progressive disease was seen in 86 patients: in 37 patients in the CAI/RT group, and in 49 patients in the observation group (log-rank P < 0.02). Subgroup analysis showed significantly less liver metastases after adjuvant treatment in periampullary tumors (log-rank P < 0.03) without effect on local recurrence. Nonetheless, there was no significant effect on overall survival in these patients (log-rank P = 0.15). In patients with pancreatic cancer, CAI/RT had no significant effect on local recurrence (log-rank P = 0.12) neither on the development of liver metastases (log-rank P = 0.76) and consequently, no effect on overall survival. CONCLUSION: This adjuvant treatment schedule results in a prolonged time to progression. For periampullary tumors, CAI/RT induced a significant reduction in the development of liver metastases, with a possible effect on overall survival. Especially in these tumors, CAI/RT might prove beneficial in larger groups and further research is warranted.

Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891.

BACKGROUND: The role of adjuvant chemoradiation in pancreatic cancer remains unclear. This report presents the long-term follow-up results of EORTC trial 40891, which assessed the role of chemoradiation in resectable pancreatic cancer. METHODS: Two hundred eighteen patients were randomized after resection of the primary tumor. Eligible patients had T1-2 N0-N1a M0 pancreatic cancer or T1-3 N0-N1a M0 periampullary cancers, all histologic proven. Patients in the treatment group (n = 110) underwent postoperative chemoradiation (40 Gy plus 5-FU). Patients in the control group (n = 108) had no further adjuvant treatment. FINDINGS: After a median follow-up of 11.7 years, 173 deaths (79%) have been reported. The overall survival did not differ between the 2 treatment groups (Chemoradiation treatment vs. CONTROLS: death rate ratio 0.91, 95% CI: 0.68-1.23, P value 0.54). The 10-year overall survival was 18% in the whole population of patients (8% in the pancreatic head cancer group and 29% in the periampullary cancer group). INTERPRETATION: These results confirm the previous short-term analysis, indicating no benefit of adjuvant chemoradiation over observation in patients with resected pancreatic cancer or periampullary cancer. Patients with pancreatic cancer may survive more than 10 years. Only 1 of 31 cases recurred after year 7.

Adjuvant 5-FU-based chemoradiotherapy for patients undergoing R-1/R-2 resections for pancreatic cancer.

BACKGROUND: Pancreatic cancer is the fifth leading cause of cancer-related death worldwide. Among patients treated with surgery alone, liver metastasis occurs in up to 50%, peritoneal recurrence in 25%, and local recurrence occurs in 50-80% of all patients who underwent resection. Even after a macroscopically curative resection, tumour cells might be observed by microscopy at one or more edges of the resected specimen in 20-51% (R-1) which might account for the high local recurrence. AIM OF THE STUDY: An analysis was performed in 54 patients who underwent an irradical resection (R-1 and R-2) for pancreatic cancer. 33 patients were treated with chemoradiotherapy. To evaluate the effect of therapy on survival and recurrence, this group was retrospectively compared to a group of 21 patients that did not receive chemoradiotherapy. METHODS: Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses of 3 weeks, concomitant with intravenous 5-FU 25 mg/kg/24 h continuously on the first 4 days of each treatment course. Follow-up was performed mainly by CT scanning and occasionally by US and was completed for all but 1 patient. RESULTS: The treatment protocol was completed in all patients without complications. Local recurrence was found in 6 (18%) patients in the group of patients who received adjuvant therapy versus 16 (48%) patients in the group that did not receive adjuvant therapy (p = 0.001). The median survival time for the treated group was 12.8 vs. 13.7 months in the group that did not receive chemoradiotherapy (p = 0.9). Three (9%) patients are still alive 140, 88 and 70 months after receiving surgery and adjuvant treatment. CONCLUSION: Adjuvant chemoradiotherapy clearly gives a significant better local control. However, treatment with 5-FU and radiotherapy does not improve survival due to distant metastases. This therapy probably prolongs survival in only a few patients. More effective treatment methods have to be designed to prevent metastatic disease and improve survival.

Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil: a first step to neoadjuvant treatment?

AIM OF THE STUDY: In two institutions, a retrospective analysis was performed on patients with histologically proven locally advanced pancreatic cancer without distant metastases. The aim of this analysis is to assess whether chemoradiotherapy provides survival benefit for patients with locally advanced pancreatic cancer. METHODS: Forty-five patients from the Erasmus Medical Centre (Erasmus MC), Rotterdam, received 5-fluorouracil (5-FU) and radiotherapy and, 38 patients from the Academic Medical Centre Amsterdam (AMC) were offered the best supportive care. Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 25 mg/kg/ 24 h continuously on the first 4 days of each treatment course. RESULTS: The treatment protocol was completed in 38 of 45 patients (84%) without complications. Radiological response was evaluated in 38 patients. Ten patients (26%) showed a partial response, stable disease was seen in 6 (16%) patients and progressive disease in 22 (58%) patients. A second-look operation was performed in 8 of 10 patients (72%) showing a radiological response, in 3 patients the tumour could be resected. Median overall survival time for the Erasmus MC group (n = 45) was 9.8 months compared to 7.6 months when the best supportive care was given (AMC group, p = 0.04). CONCLUSION: Although overall survival remains poor, treatment with 5-FU and radiotherapy might benefit some patients with locally advanced pancreatic cancer.