Olanzapine as a prophylactic antiemetic for preventing postoperative nausea and vomiting after general anesthesia: A systematic review and meta-analysis.

BACKGROUND: The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic review and meta-analysis, the authors evaluate the efficacy and side effects of olanzapine as a prophylactic antiemetic in adult patients who undergo general anesthesia and assess adverse effects. METHODS: A systematic search was done on electronic bibliographic databases in July 2023. Randomized controlled trials of olanzapine as a prophylactic antiemetic for PONV in adults who underwent general anesthesia were included. The authors excluded non-RCTs and retracted studies. The authors set no date of publication or language limits. The outcomes were the incidence of PONV within 24 h postoperatively and the safety of olanzapine. The risk of bias was assessed according to the tool suggested by the National Heart, Lung, and Blood Institute. RESULTS: Meta-analysis included 446 adult patients. Olanzapine reduced on average 38 % the incidence of PONV. The estimated risk ratio (95 % CI) of olanzapine versus control was 0.62 (0.42-0.90), p = 0.010, I2 = 67 %. In the subgroup meta-analysis, doses of olanzapine (10 mg) reduced on average 49 % of the incidence of PONV (RR = 0.51 [0.34-0.77], p = 0.001, I2 = 31 %). CONCLUSIONS: This systematic review with meta-analysis indicated that olanzapine as a prophylactic antiemetic alone or combined with other antiemetic agents reduced the incidence of postoperative nausea and vomiting. However, this conclusion must be presented with some degree of uncertainty due to the small number of studies included. There was a lack of any evidence to draw conclusions on side effects.

Natural Language Processing of Referral Letters for Machine Learning-Based Triaging of Patients With Low Back Pain to the Most Appropriate Intervention: Retrospective Study.

BACKGROUND: Decision support systems (DSSs) for suggesting optimal treatments for individual patients with low back pain (LBP) are currently insufficiently accurate for clinical application. Most of the input provided to train these systems is based on patient-reported outcome measures. However, with the appearance of electronic health records (EHRs), additional qualitative data on reasons for referrals and patients' goals become available for DSSs. Currently, no decision support tools cover a wide range of biopsychosocial factors, including referral letter information to help clinicians triage patients to the optimal LBP treatment. OBJECTIVE: The objective of this study was to investigate the added value of including qualitative data from EHRs and referral letters to the accuracy of a quantitative DSS for patients with LBP. METHODS: A retrospective study was conducted in a clinical cohort of Dutch patients with LBP. Patients filled out a baseline questionnaire about demographics, pain, disability, work status, quality of life, medication, psychosocial functioning, comorbidity, history, and duration of pain. Referral reasons and patient requests for help (patient goals) were extracted via natural language processing (NLP) and enriched in the data set. For decision support, these data were considered independent factors for triage to neurosurgery, anesthesiology, rehabilitation, or minimal intervention. Support vector machine, k-nearest neighbor, and multilayer perceptron models were trained for 2 conditions: with and without consideration of the referral letter content. The models' accuracies were evaluated via F1-scores, and confusion matrices were used to predict the treatment path (out of 4 paths) with and without additional referral parameters. RESULTS: Data from 1608 patients were evaluated. The evaluation indicated that 2 referral reasons from the referral letters (for anesthesiology and rehabilitation intervention) increased the F1-score accuracy by up to 19.5% for triaging. The confusion matrices confirmed the results. CONCLUSIONS: This study indicates that data enriching by adding NLP-based extraction of the content of referral letters increases the model accuracy of DSSs in suggesting optimal treatments for individual patients with LBP. Overall model accuracies were considered low and insufficient for clinical application.

1. Lumbosacral radicular pain.

INTRODUCTION: Patients suffering lumbosacral radicular pain report radiating pain in one or more lumbar or sacral dermatomes. In the general population, low back pain with leg pain extending below the knee has an annual prevalence that varies from 9.9% to 25%. METHODS: The literature on the diagnosis and treatment of lumbosacral radicular pain was reviewed and summarized. RESULTS: Although a patient's history, the pain distribution pattern, and clinical examination may yield a presumptive diagnosis of lumbosacral radicular pain, additional clinical tests may be required. Medical imaging studies can demonstrate or exclude specific underlying pathologies and identify nerve root irritation, while selective diagnostic nerve root blocks can be used to confirm the affected level(s). In subacute lumbosacral radicular pain, transforaminal corticosteroid administration provides short-term pain relief and improves mobility. In chronic lumbosacral radicular pain, pulsed radiofrequency (PRF) treatment adjacent to the spinal ganglion (DRG) can provide pain relief for a longer period in well-selected patients. In cases of refractory pain, epidural adhesiolysis and spinal cord stimulation can be considered in experienced centers. CONCLUSIONS: The diagnosis of lumbosacral radicular pain is based on a combination of history, clinical examination, and additional investigations. Epidural steroids can be considered for subacute lumbosacral radicular pain. In chronic lumbosacral radicular pain, PRF adjacent to the DRG is recommended. SCS and epidural adhesiolysis can be considered for cases of refractory pain in specialized centers.

Role of non-invasive objective markers for the rehabilitative diagnosis of central sensitization in patients with fibromyalgia: A systematic review.

BACKGROUND: Central sensitization cannot be demonstrated directly in humans. Therefore, studies used different proxy markers (signs, symptoms and tools) to identify factors assumed to relate to central sensitization in humans, that is, Human Assumed Central Sensitization (HACS). The aims of this systematic review were to identify non-invasive objective markers of HACS and the instruments to assess these markers in patients with fibromyalgia (FM). METHODS: A systematic review was conducted with the following inclusion criteria: (1) adults, (2) diagnosed with FM, and (3) markers and instruments for HACS had to be non-invasive. Data were subsequently extracted, and studies were assessed for risk of bias using the quality assessment tools developed by the National Institute of Health. RESULTS: 78 studies (n= 5234 participants) were included and the findings were categorized in markers identified to assess peripheral and central manifestations of HACS. The identified markers for peripheral manifestations of HACS, with at least moderate evidence, were pain after-sensation decline rates, mechanical pain thresholds, pressure pain threshold, sound 'pressure' pain threshold, cutaneous silent period, slowly repeated evoked pain sensitization and nociceptive flexion reflex threshold. The identified markers for central manifestations of HACS were efficacy of conditioned pain modulation with pressure pain conditioning and brain perfusion analysis. Instruments to assess these markers are: pin-prick stimulators, cuff-algometry, repetitive pressure stimulation using a pressure algometer, sound, electrodes and neuroimaging techniques. CONCLUSIONS: This review provides an overview of non-invasive markers and instruments for the assessment of HACS in patients with FM. Implementing these findings into clinical settings may help to identify HACS in patients with FM.

Validity of the Central Sensitization Inventory to Address Human Assumed Central Sensitization: Newly Proposed Clinically Relevant Values and Associations.

Central sensitization cannot be directly demonstrated in humans and thus a gold standard is missing. Therefore, we used human assumed central sensitization (HACS) when associated with humans. The central sensitization inventory (CSI) is a screening questionnaire for addressing symptoms that are associated with HACS. This cross-sectional study compared patients with chronic pain and at least one central sensitivity syndrome with healthy, pain-free controls via ROC analyses. Analyses were performed for all participants together and for each sex separately. Regression analyses were performed on patients with chronic pain with and without central sensitivity syndromes. Based on 1730 patients and 250 healthy controls, cutoff values for the CSI for the total group were established at 30 points: women: 33 points; men: 25 points. Univariate and multivariate regression analyses were used to identify possible predictors for the CSI score in 2890 patients with chronic pain. The CSI score is associated with all independent factors and has a low association with pain severity in women and a low association with pain severity, age, and body mass index in men. The newly established CSI cutoff values are lower than in previous studies and different per sex, which might be of clinical relevance in daily practice and importance in research.

2. Cervical radicular pain.

INTRODUCTION: Cervical radicular pain is pain perceived in the upper limb, caused by irritation or compression of a cervical spine nerve, the roots of the nerve, or both. METHODS: The literature on the diagnosis and treatment of cervical radicular pain was retrieved and summarized. RESULTS: The diagnosis is made by combining elements from the patient's history, physical examination, and supplementary tests. The Spurling and shoulder abduction tests are the two most common examinations used to identify cervical radicular pain. MRI without contrast, CT scanning, and in some cases plain radiography can all be appropriate imaging techniques for nontraumatic cervical radiculopathy. MRI is recommended prior to interventional treatments. Exercise with or without other treatments can be beneficial. There is scant evidence for the use of paracetamol, nonsteroidal anti-inflammatory drugs, and neuropathic pain medications such as gabapentin, pregabalin, tricyclic antidepressants, and anticonvulsants for the treatment of radicular pain. Acute and subacute cervical radicular pain may respond well to epidural corticosteroid administration, preferentially using an interlaminar approach. By contrast, for chronic cervical radicular pain, the efficacy of epidural corticosteroid administration is limited. In these patients, pulsed radiofrequency treatment adjacent to the dorsal root ganglion may be considered. CONCLUSIONS: There is currently no gold standard for the diagnosis of cervical radicular pain. There is scant evidence for the use of medication. Epidural corticosteroid injection and pulsed radiofrequency adjacent to the dorsal root ganglion may be considered. [Correction added on 12 June 2023, after first online publication: The preceding sentence was corrected.].

The C4EB study-Transvamix (10% THC / 5% CBD) to treat chronic pain in epidermolysis bullosa: A protocol for an explorative randomized, placebo controlled, and double blind intervention crossover study.

Patients with the genetic blistering skin condition epidermolysis bullosa (EB) report severe pain as a consequence of skin and mucous membrane lesions including blisters, wounds, and scars. Adequate symptom alleviation is not often achieved using conventional pharmacologic interventions. Finding novel approaches to pain care in EB is imperative to improve the quality of life of patients living with EB. There are several anecdotal reports on the use of cannabinoid-based medicines (CBMs) by EB patients to reduce the burden of symptoms. However, controlled clinical investigations assessing these reported effects are lacking. As the pain quality "unpleasantness" delineates EB pain, we hypothesize the modulation of affective pain processing in the brain by way of intervention with CBMs comprising the cannabinoids Δ-9-tetrahydrocannabinol and cannabidiol-objectified by functional magnetic resonance imaging (fMRI). The C4EB study is an investigator-initiated, single-centre, randomized, double-blind, placebo-controlled and crossover trial. Adult patients with the diagnosis epidermolysis bullosa, reporting chronic pain will be eligible to participate. Following baseline measurements, participants will be randomized to receive the sublingually administered interventions placebo and Transvamix® in forward or reversed orders, each for two weeks and separated by a washout. The primary outcome is the difference in numeric rating scale pain scores between grouped interventions, using affective descriptors within the Short-form McGill Pain Questionnaire-2. Secondary outcomes include pain self-efficacy, concomitant analgesic medication-use and adverse events. Additionally, fMRI will be employed to assess brain connectivity related to neuroanatomic pain circuits at baseline, placebo and Transvamix® interventions. The study was approved by the ethical committee at the University Medical Center of Groningen in the Netherlands. Results will be submitted for publication in a peer-reviewed journal. Trial registration number: Netherlands Trial Register: NL9347 (Acronym: C4EB).

A guide for standardized interpretation of lumbar multifidus ultrasonography; an observational study.

BACKGROUND: Inconsistent descriptions of Lumbar multifidus (LM) morphology were previously identified, especially in research applying ultrasonography (US), hampering its clinical applicability with regard to diagnosis and therapy. The aim of this study is to determine the LM-sonoanatomy by comparing high-resolution reconstructions from a 3-D digital spine compared to standard LM-ultrasonography. METHODS: An observational study was carried out. From three deeply frozen human tissue blocks of the lumbosacral spine, a large series of consecutive photographs at 78 µm interval were acquired and reformatted into 3-D blocks. This enabled the reconstruction of (semi-)oblique cross-sections that could match US-images obtained from a healthy volunteer. Transverse and oblique short-axis views were compared from the most caudal insertion of LM to L1. RESULTS: Based on the anatomical reconstructions, we could distinguish the LM from the adjacent erector spinae (ES) in the standard US imaging of the lower spine. At the lumbosacral junction, LM is the only dorsal muscle facing the surface. From L5 upwards, the ES progresses from lateral to medial. A clear distinction between deep and superficial LM could not be discerned. We were only able to identify five separate bands between every lumbar spinous processes and the dorsal part of the sacrum in the caudal anatomical cross-sections, but not in the standard US images. CONCLUSION: The detailed cross-sectional LM-sonoanatomy and reconstructions facilitate the interpretations of standard LM US-imaging, the position of the separate LM-bands, the details of deep interspinal muscles, and demarcation of the LM versus the ES. Guidelines for electrode positioning in EMG studies should be refined to establish reliable and verifiable findings. For clinical practice, this study can serve as a guide for a better characterisation of LM compared to ES and for a more reliable placement of US-probe in biofeedback.

Reply to Jensen, O.K. On the Use of Quantitative Sensory Testing to Estimate Central Sensitization in Humans. Comment on "Schuttert et al. The Definition, Assessment, and Prevalence of (Human Assumed) Central Sensitisation in Patients with Chronic Low Back Pain: A Systematic Review. J. Clin. Med. 2021, 10, 5931".

We thank Dr. Jensen for his interest [...].

What can we learn from long-term studies on chronic low back pain? A scoping review.

PURPOSE: A scoping review was conducted with the objective to identify and map the available evidence from long-term studies on chronic non-specific low back pain (LBP), to examine how these studies are conducted, and to address potential knowledge gaps. METHOD: We searched MEDLINE and EMBASE up to march 2021, not restricted by date or language. Experimental and observational study types were included. Inclusion criteria were: participants between 18 and 65 years old with non-specific sub-acute or chronic LBP, minimum average follow-up of > 2 years, and studies had to report at least one of the following outcome measures: disability, quality of life, work participation, or health care utilization. Methodological quality was assessed using the Effective Public Health Practice Project quality assessment. Data were extracted, tabulated, and reported thematically. RESULTS: Ninety studies met the inclusion criteria. Studies examined invasive treatments (72%), conservative (21%), or a comparison of both (7%). No natural cohorts were included. Methodological quality was weak (16% of studies), moderate (63%), or strong (21%) and generally improved after 2010. Disability (92%) and pain (86%) outcomes were most commonly reported, followed by work (25%), quality of life (15%), and health care utilization (4%). Most studies reported significant improvement at long-term follow-up (median 51 months, range 26 months-18 years). Only 10 (11%) studies took more than one measurement > 2 year after baseline. CONCLUSION: Patients with persistent non-specific LBP seem to experience improvement in pain, disability and quality of life years after seeking treatment. However, it remains unclear what factors might have influenced these improvements, and whether they are treatment-related. Studies varied greatly in design, patient population, and methods of data collection. There is still little insight into the long-term natural course of LBP. Additionally, few studies perform repeated measurements during long-term follow-up or report on patient-centered outcomes other than pain or disability.

Human assumed central sensitisation (HACS) in patients with chronic low back pain radiating to the leg (CLaSSICO study).

INTRODUCTION: Patients with chronic low back pain radiating to the leg (CLBPr) are sometimes referred to a specialised pain clinic for a precise diagnosis based, for example, on a diagnostic selective nerve root block. Possible interventions are therapeutic selective nerve root block or pulsed radiofrequency. Central pain sensitisation is not directly assessable in humans and therefore the term 'human assumed central sensitisation' (HACS) is proposed. The possible existence and degree of sensitisation associated with pain mechanisms assumed present in the human central nervous system, its role in the chronification of pain and its interaction with diagnostic and therapeutic interventions are largely unknown in patients with CLBPr. The aim of quantitative sensory testing (QST) is to estimate quantitatively the presence of HACS and accumulating evidence suggest that a subset of patients with CLBPr have facilitated responses to a range of QST tests.The aims of this study are to identify HACS in patients with CLBPr, to determine associations with the effect of selective nerve root blocks and compare outcomes of HACS in patients to healthy volunteers. METHODS AND ANALYSIS: A prospective observational study including 50 patients with CLBPr. Measurements are performed before diagnostic and therapeutic nerve root block interventions and at 4 weeks follow-up. Data from patients will be compared with those of 50 sex-matched and age-matched healthy volunteers. The primary study parameters are the outcomes of QST and the Central Sensitisation Inventory. Statistical analyses to be performed will be analysis of variance. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee of the University Medical Center Groningen, Groningen, the Netherlands, approved this study (dossier NL60439.042.17). The results will be disseminated via publications in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: NTR NL6765.

Increased adherence to perioperative safety guidelines associated with improved patient safety outcomes: a stepped-wedge, cluster-randomised multicentre trial.

BACKGROUND: National Dutch guidelines have been introduced to improve suboptimal perioperative care. A multifaceted implementation programme (IMPlementatie Richtlijnen Operatieve VEiligheid [IMPROVE]) has been developed to support hospitals in applying these guidelines. This study evaluated the effectiveness of IMPROVE on guideline adherence and the association between guideline adherence and patient safety. METHODS: Nine hospitals participated in this unblinded, superiority, stepped-wedge, cluster RCT in patients with major noncardiac surgery (mortality risk ≥1%). IMPROVE consisted of educational activities, audit and feedback, reminders, organisational, team-directed, and patient-mediated activities. The primary outcome of the study was guideline adherence measured by nine patient safety indicators on the process (stop moments from the composite STOP bundle, and timely administration of antibiotics) and on the structure of perioperative care. Secondary safety outcomes included in-hospital complications, postoperative wound infections, mortality, length of hospital stay, and unplanned care. RESULTS: Data were analysed for 1934 patients. The IMPROVE programme improved one stop moment: 'discharge from recovery room' (+16%; 95% confidence interval [CI], 9-23%). This stop moment was related to decreased mortality (-3%; 95% CI, -4% to -1%), fewer complications (-8%; 95% CI, -13% to -3%), and fewer unscheduled transfers to the ICU (-6%; 95% CI, -9% to -3%). IMPROVE negatively affected one other stop moment - 'discharge from the hospital' - possibly because of the limited resources of hospitals to improve all stop moments together. CONCLUSIONS: Mixed implementation effects of IMPROVE were found. We found some positive associations between guideline adherence and patient safety (i.e. mortality, complications, and unscheduled transfers to the ICU) except for the timely administration of antibiotics. CLINICAL TRIAL REGISTRATION: NTR3568 (Dutch Trial Registry).

Identifying Epidermolysis Bullosa Patient Needs and Perceived Treatment Benefits: An Explorative Study Using the Patient Benefit Index.

Epidermolysis bullosa (EB) is a genetic blistering skin condition for which no cure exists. Symptom alleviation and quality of life are therefore central to EB care. This study aimed to gain insight into EB patient needs and benefits from current clinical care. Two questionnaires were administered cross-sectionally to adult EB patients at the Dutch expertise centre for blistering diseases. Patient needs and benefits were analyzed using the patient benefit index survey (PBI-S). Ancillary data were compiled pertaining to self-reported EB severity, pain and pruritus, as well as current and previous treatments. In total, 104 participants were included (response rate 69.8%). Sixty-eight participants comprised the analyzed cohort (n = 36 omitted from analysis). The needs given the highest importance were to get better skin quickly (64.7%) and to be healed of all skin alterations (61.8%). A positive correlation between pain and EB severity and the importance of most needs was observed. Minimal clinically important differences within the PBI-S, relating to reported benefits from clinical care, were reported by 60.3% of the cohort. This study highlights a discrepancy between patient needs and feasible treatment outcomes. Utilizing the PBI-S in conjunction with well-established multidisciplinary care may catalyze the process of tailoring treatments to the needs of individual patients.

The Definition, Assessment, and Prevalence of (Human Assumed) Central Sensitisation in Patients with Chronic Low Back Pain: A Systematic Review.

Central sensitisation is assumed to be one of the underlying mechanisms for chronic low back pain. Because central sensitisation is not directly assessable in humans, the term 'human assumed central sensitisation' (HACS) is suggested. The objectives were to investigate what definitions for HACS have been used, to evaluate the methods to assess HACS, to assess the validity of those methods, and to estimate the prevalence of HACS. Database search resulted in 34 included studies. Forty different definition references were used to define HACS. This review uncovered twenty quantitative methods to assess HACS, including four questionnaires and sixteen quantitative sensory testing measures. The prevalence of HACS in patients with chronic low back pain was estimated in three studies. The current systematic review highlights that multiple definitions, assessment methods, and prevalence estimates are stated in the literature regarding HACS in patients with chronic low back pain. Most of the assessment methods of HACS are not validated but have been tested for reliability and repeatability. Given the lack of a gold standard to assess HACS, an initial grading system is proposed to standardize clinical and research assessments of HACS in patients with a chronic low back.

Music and low-frequency vibrations for the treatment of chronic musculoskeletal pain in elderly: A pilot study.

BACKGROUND: Transcutaneous vagal nerve stimulation has analgesic potential and might be elicited by abdominally administered low-frequency vibrations. The objective was to study the safety and effect of a combination of music and abdominally administered low-frequency vibrations on pain intensity in elderly patients with chronic musculoskeletal pain. METHODS: This trial was an international multicenter, randomized controlled pilot study. Patients at age ≥ 65 years with musculoskeletal pain for ≥ 3 months and a daily pain score ≥ 4 out of 10 were recruited at three centers. They were randomized to receive either a combination of music and low-frequency (20-100 Hz) vibrations administered to the abdomen, or a combination with the same music but with higher frequency (200-300 Hz) vibrations administered to the abdomen. Low-frequency vibrations were expected to result in pain reduction measured with a numeric pain rating scale (NRS). Patients in both groups received eight treatments of the music combined with the vibrations in three weeks. Primary outcomes were safety (Serious Adverse Events) and pain intensity measured at baseline, after the last treatment and at six weeks follow-up. Multilevel linear model analyses were performed to study group and time effects. RESULTS: A total of 45 patients were analyzed according to intention-to-treat principle. After 344 treatments, 1 Adverse Event was found related to the intervention, while 13 Adverse Events were possibly related. A multilevel linear model showed that the interaction effect of group by time did not predict pain intensity (F[1, 45.93] = 0.002, p = 0.97) when comparing pain intensity at baseline, after the last treatment and at follow-up. CONCLUSIONS: The combination of music and abdominally administered vibrations was found to be safe and well tolerated by the elderly patients. However, over time, neither the low-frequency treatment group nor the high-frequency treatment group provided clinically meaningful pain relief. There is no evidence that the low-frequency treatment elicited vagal nerve stimulation. TRIAL REGISTRATION: The trial was prospectively registered in the Netherlands Trial Register (NTR: NL7606) on 21-03-2019.

Complexity and involvement as implementation challenges: results from a process analysis.

BACKGROUND: The study objective was to analyse the implementation challenges experienced in carrying out the IMPROVE programme. This programme was designed to implement checklist-related improvement initiatives based on the national perioperative guidelines using a stepped-wedge trial design. A process analysis was carried out to investigate the involvement in the implementation activities. METHODS: An involvement rating measure was developed to express the extent to which the implementation programme was carried out in the hospitals. This measure reflects the number of IMPROVE-implementation activities executed and the estimated participation in these activities in all nine participating hospitals. These data were compared with prospectively collected field notes. RESULTS: Considerable variation between the hospitals was found with involvement ratings ranging from 0 to 6 (mean per measurement = 1.83 on a scale of 0-11). Major implementation challenges were respectively the study design (fixed design, time planning, long duration, repeated measurements, and data availability); the selection process of hospitals, departments and key contact person(s) (inadequately covering the entire perioperative team and stand-alone surgeons); the implementation programme (programme size and scope, tailoring, multicentre, lack of mandate, co-interventions by the Inspectorate, local intervention initiatives, intervention fatigue); and competitive events such as hospital mergers or the introduction of new IT systems, all reducing involvement. CONCLUSIONS: The process analysis approach helped to explain the limited and delayed execution of the IMPROVE-implementation programme. This turned out to be very heterogeneous between hospitals, with variation in the number and content of implementation activities carried out. The identified implementation challenges reflect a high complexity with regard to the implementation programme, study design and setting. The involvement of the target professionals was put under pressure by many factors. We mostly encountered challenges, but at the same time we provide solutions for addressing them. A less complex implementation programme, a less fixed study design, a better thought-out selection of contact persons, as well as more commitment of the hospital management and surgeons would likely have contributed to better implementation results. TRIAL REGISTRATION: Dutch Trial Registry: NTR3568 , retrospectively registered on 2 August 2012.

Cannabinoid use and effects in patients with epidermolysis bullosa: an international cross-sectional survey study.

BACKGROUND: Epidermolysis bullosa (EB) patient anecdotes and case reports indicate that cannabinoid-based medicines (CBMs) may alleviate pain and pruritus and improve wound healing. CBM use has not been characterized in the EB patient population. OBJECTIVES: To evaluate CBM use among EB patients, including CBM types, effects on symptoms (e.g., pain and pruritus), disease process (e.g., blistering, wounds, and inflammation), well-being (e.g., sleep, appetite) and concomitant medications. METHODS: English-speaking EB patients or caregivers completed an online international, anonymous, cross-sectional survey regarding CBM use. Respondents reported the types of CBMs, subsequent effects including perceived EB symptom alteration, changes in medication use, and side effects. RESULTS: Seventy-one EB patients from five continents reported using or having used CBMs to treat their EB. Missing question responses ranged between 0 (0%) and 33 (46%). Most used more than one CBM preparation (mean: 2.4 ± 1.5) and route of administration (mean: 2.1 ± 1.1). Topical and ingested were the most common routes. Pain and pruritus were reported retrospectively to decrease by 3 points (scale: 0-10; p < 0.001 for both) after CBM use. Most reported that CBM use improved their overall EB symptoms (95%), pain (94%), pruritus (91%) and wound healing (81%). Most participants (79%) reported decreased use of pain medications. The most common side-effect was dry mouth (44%). CONCLUSIONS: CBMs improve the perception of pain, pruritus, wound healing, and well-being in EB patients and reduced concomitant medication use. Nevertheless, a direct relation between the use of CBMs and reduction of the above-mentioned symptoms cannot be proven by these data. Therefore, future controlled studies using pharmaceutically standardised CBM preparations in EB are warranted to delineate the risks and benefits of CBMs.