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Small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia
(2018)
Background:
Chemotherapy-induced Peripheral Neuropathy (CIPN) of large-fibers affects up to 20% of survivors of pediatric acute lymphoblastic leukemia (ALL). We aimed to describe small-fiber toxicity and pain sensitization in this group.
Methods:
In a cross-sectional, bicentric study we assessed 46 survivors of pediatric ALL (Mean age: 5.7 ± 3.5 years at diagnosis, median 2.5 years after therapy; males: 28). Inclusion criteria: ≥6 years of age, ≥3 months after last administration of Vincristine, and cumulative dose of Vincristine 12 mg/m2. We used a reduced version of the Pediatric-modified Total Neuropathy Score (Ped-mTNS) as bedside test and Quantitative Sensory Testing (QST) for assessment of small- and large-fiber neuropathy as well as pain sensitization. We employed Nerve Conduction Studies (NCS) as the most accurate tool for detecting large-fiber neuropathy.
Results:
Fifteen survivors (33%) had abnormal rPed-mTNS values (≥4 points) and 5 survivors (11%) reported pain. In QST, the survivor group showed significant (p < 0.001) inferior large-fiber function and pain sensitization when compared to healthy matched peers. We identified deficits of vibration in 33 (72%) and tactile hypoesthesia in 29 (63%), hyperalgesia to blunt pressure in 19 (41%), increased mechanical pain sensitivity in 12 (26%) and allodynia in 16 (35%) of 46 survivors. Only 7 survivors (15%) had pathologic NCS.
Conclusion:
QST is a sensitive tool that revealed signs of large-fiber neuropathy in two thirds, small-fiber neuropathy and pain sensitization in one third of survivors. Prospective studies using QST in pediatric oncology may help to elucidate the pathophysiology of small-fiber neuropathy and pain sensitization as well as their relevance for quality of survival.
Hintergrund:
Wenn Kinder Schmerzen haben, reagieren Eltern kognitiv-affektiv und verhaltensbezogen. Dysfunktionale Reaktionen wie elterliches Katastrophisieren können zur Chronifizierung kindlicher Schmerzen beitragen.
Ziel der Arbeit:
Ziele der Online-Studie sind (1) die erstmalige psychometrische Überprüfung existierender Fragebögen zu kognitiv-affektiven (Pain Catastrophizing Scale for Parents; PCS-P) und verhaltensbezogenen Reaktionen (Inventar zum schmerzbezogenen Elternverhalten; ISEV-E) an 105 schmerzfreien Eltern, (2) der Vergleich der Reaktionen mit existierenden (inter-)nationalen klinischen und schmerzfreien Samples sowie mit 80 Eltern mit selbstberichteten chronischen Schmerzen.
Methode:
Die teilnehmenden Eltern machten per Online-Fragebogen Angaben zu ihren elterlichen Reaktionen auf kindlichen Schmerz.
Ergebnisse:
Die Faktoren des ISEV-E konnten nicht bestätigt werden; die Faktorenstruktur des PCS-P war replizierbar. Das elterliche Katastrophisieren der schmerzfreien Eltern war geringer als in klinischen Samples. Unterschiede zwischen schmerzfreien Eltern und Eltern mit selbstberichteten chronischen Schmerzen aus der Allgemeinbevölkerung zeigten sich nicht.
Diskussion:
Die Ergebnisse bieten eine Basis zur Einordnung des elterlichen Katastrophisierens, um Risikogruppen mit starker Katastrophisierungsneigung frühzeitig zu identifizieren.
Introduction:
Many patients with cerebral palsy (CP) suffer chronic pain as one of the most limiting factors in their quality of life. In CP patients, pain mechanisms are not well understood, and pain therapy remains a challenge. Quantitative sensory testing (QST) might provide unique information about the functional status of the somatosensory system and therefore better guide pain treatment.
Objectives:
To understand better the underlying pain mechanisms in pediatric CP patients, we aimed to assess clinical and pain parameters, as well as QST profiles, which were matched to the patients' cerebral imaging pathology.
Patients and methods:
Thirty CP patients aged 6–20 years old (mean age 12 years) without intellectual impairment underwent standardized assessments of QST. Cerebral imaging was reassessed. QST results were compared to age- and sex-matched controls (multiple linear regression; Fisher's exact test; linear correlation analysis).
Results:
CP patients were less sensitive to all mechanical and thermal stimuli than healthy controls but more sensitive to all mechanical pain stimuli (each p < 0.001). Fifty percent of CP patients showed a combination of mechanical hypoesthesia, thermal hypoesthesia and mechanical hyperalgesia; 67% of CP patients had periventricular leukomalacia (PVL), which was correlated with mechanic (r = 0.661; p < 0.001) and thermal (r = 0.624; p = 0.001) hypoesthesia.
Conclusion:
The combination of mechanical hypoesthesia, thermal hypoesthesia and mechanical hyperalgesia in our CP patients implicates lemniscal and extralemniscal neuron dysfunction in the thalamus region, likely due to PVL. We suspect that extralemniscal tracts are involved in the original of pain in our CP patients, as in adults.
Objective:
The German version of the Social Phobia and Anxiety Inventory (SPAI-G) is avalidated measure for the detection of social anxiety disorder (SAD). The aim of the presentstudy was to develop optimal cut points (OC) for remission and response to treatment for theSPAI-G.
Methods:
We used Receiver Operating Characteristic methods and bootstrapping to analysethe data of 359 patients after psychotherapeutic treatment. OCs where defined as the cut pointswith the highest sensitivity and specificity after bootstrapping.
Results:
For remission, an OC of 2.79 was found, and for response, a change in score frompre- to posttreatment by 11% yielded best results.
Conclusions:
The OC we identified for remission may be used to improve the diagnostic utilityof the SPAI-G. However, the cut point for response achieved only borderline-acceptable levelsof sensitivity and specificity, calling into doubt their utility in clinical and research setting.
The Liebowitz Social Anxiety Scale (LSAS) is the most frequently used instrument to assess social anxiety disorder (SAD) in clinical research and practice. Both a self‐reported (LSAS‐SR) and a clinician‐administered (LSAS‐CA) version are available. The aim of the present study was to define optimal cut‐off (OC) scores for remission and response to treatment for the LSAS in a German sample.
Data of N = 311 patients with SAD were used who had completed psychotherapeutic treatment within a multicentre randomized controlled trial. Diagnosis of SAD and reduction in symptom severity according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, served as gold standard. OCs yielding the best balance between sensitivity and specificity were determined using receiver operating characteristics. The variability of the resulting OCs was estimated by nonparametric bootstrapping.
Using diagnosis of SAD (present vs. absent) as a criterion, results for remission indicated cut‐off values of 35 for the LSAS‐SR and 30 for the LSAS‐CA, with acceptable sensitivity (LSAS‐SR: .83, LSAS‐CA: .88) and specificity (LSAS‐SR: .82, LSAS‐CA: .87). For detection of response to treatment, assessed by a 1‐point reduction in the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, rating, a reduction of 28% for the LSAS‐SR and 29% for the LSAS‐CA yielded the best balance between sensitivity (LSAS‐SR: .75, LSAS‐CA: .83) and specificity (LSAS‐SR: .76, LSAS‐CA: .80).
To our knowledge, we are the first to define cut points for the LSAS in a German sample. Overall, the cut points for remission and response corroborate previously reported cut points, now building on a broader data basis.
Objectives: The aims of this study were to define the Faces Pain Scale-Revised (FPS-R) and Color Analog Scale (CAS) scores associated with no pain, mild pain, moderate pain, and severe pain in children with acute pain, and to identify differences based on age, sex, and ethnicity.
Methods: We conducted a prospective observational study in 2 pediatric emergency departments of children aged 4 to 17 years with painful and nonpainful conditions. We assessed their pain intensity using the FPS-R, CAS, and qualitative measures. Pain score cut points that best differentiated adjacent categories of pain were identified using a receiver operating characteristic-based method. Cut points were compared within subgroups based on age, sex, and ethnicity.
Results: We enrolled 620 patients, of whom 314 had painful conditions. The mean age was 9.2 years; 315 (50.8%) were in the younger age group (aged 4-7 years); 291 (46.8%) were female; and 341 (55%) were Hispanic. The scores best representing categories of pain for the FPS-R were as follows: no pain, 0 and 2; mild pain, 4; moderate pain, 6; and severe pain, 8 and 10. For the CAS, these were 0 to 1, 1.25 to 2.75, 3 to 5.75, and 6 to 10, respectively. Children with no pain frequently reported nonzero pain scores. There was considerable overlap of scores associated with mild and moderate pain. There were no clinically meaningful differences of scores representing each category of pain based on age, ethnicity, and race.
Conclusions: We defined pain scores for the FPS-R and CAS associated with categories of pain intensity in children with acute pain that are generalizable across subgroups based on patient characteristics. There were minor but potentially important differences in pain scores used to delineate categories of pain intensity compared to prior convention.