Hans Timmerman

Physical Exercise for Patients Undergoing Hematopoietic Stem Cell Transplantation: Systematic Review and Meta-Analyses of Randomized Controlled Trials

Background The treatment-related burden for patients undergoing hematopoietic stem cell transplantation (HSCT) may be relieved by physical exercises. Purpose The purpose of this study was to summarize and analyze the evidence provided by randomized controlled trials (RCTs) on physical exercise interventions among patients with cancer undergoing HSCT. Data Sources PubMed, CINAHL, EMBASE, the Cochrane Library, and PEDro were searched for relevant RCTs up to October 1, 2011. Study Selection Two reviewers screened articles on inclusion criteria and indentified relevant RCTs. Data Extraction Two authors assessed the selected articles for risk of bias. Data extraction was performed by 1 reviewer. Meta-analyses were undertaken to estimate the outcomes quality of life (QOL), psychological well-being and distress, and fatigue. Data Synthesis Eleven studies were included, with study populations consisting of recipients undergoing either an allogeneic or autologous HSCT (n=734). Four studies had low risk of bias. The exercise interventions were performed before, during, and after hospitalization for the HSCT. Different exercise programs on endurance, resistance and/or activities of daily living training, progressive relaxation, and stretching were used. Meta-analyses showed that exercise during hospitalization led to a higher QOL (weighted mean difference=8.72, 95% confidence interval=3.13, 14.31) and less fatigue (standardized mean difference=0.53, 95% confidence interval=0.16, 0.91) in patients with an allogeneic HSCT at the moment of discharge from the hospital. No marked effects were found for psychological well-being and distress. Individual study results suggested significant positive effects on QOL, fatigue, psychological well-being and distress, and physical functioning. Limitations Prevalent shortcomings in the included studies were the heterogeneity among studies and the lack of blinding of participants, personnel, and outcome assessment. Conclusions The results suggest that recipients of HSCT may benefit from physical exercise.

Feasibility and preliminary effectiveness of preoperative therapeutic exercise in patients with cancer: A pragmatic study

The aim of this pilot study is to determine the feasibility and preliminary effectiveness of an individually designed preoperative therapeutic exercise program (PreTEP), in patients recently diagnosed with cancer and awaiting elective surgery. The purpose is to improve their physical fitness levels during this waiting period with the intention of decreasing postoperative morbidity. A preexperimental pilot study was performed at the University Medical Center Utrecht, The Netherlands. Thirty-nine patients diagnosed with cancer, scheduled for elective abdominal/thoracic surgery, were referred to a multidisciplinary preoperative screening. Fifteen patients (38%) participated in PreTEP. Participants were satisfied and motivated during the period of training (on average 5 weeks) in which they attended 84% of the sessions. Cardiorespiratory fitness (Åstrand-test) and muscle strength (Handheld Dynamometry) increased significantly, from 25 to 33 mL/kg/min, respectively (p<0.01; 95% confidence interval [CI]=−0.011 to −0.004) and from 894 Newton (N) to 961 N (p<0.01; 95% CI=−94.53 to −39.0). No adverse events occurred during the training period. PreTEP was shown to be feasible, safe, and well-tolerated and appreciated by participants. Despite the relatively short period of training, physical fitness improved in all participants.

Cross-Cultural Adaptation to the Dutch Language of the PainDETECT-Questionnaire

Background:  The PainDETECT‐Questionnaire (PDQ) helps to identify neuropathic components in patients suffering from pain. It can be used by clinicians in daily practice and in clinical trials.

Multi-modal Quantitative Sensory Testing in Patients with Unilateral Chronic Neck Pain: An Exploratory Study

Objectives The main objective of this study was to evaluate the pattern of altered pain processing in patients with chronic idiopathic neck pain, with particular emphasis on the interaction between pain sensitivity and modulation. Methods This cross-sectional study systematically evaluates patients with unilateral chronic idiopathic neck pain using a comprehensive, multi-modal quantitative sensory testing [QST] protocol. Only patients with unilateral idiopathic neck pain present without radicular symptoms for more than six months were invited to participate. The QST measurements consists of pressure pain threshold testing, thermal threshold testing, electrical pain threshold testing, wind-up response testing using electrical stimulation, and measurement of descending inhibitory modulation using the Conditioned Pain Modulation paradigm. For a control group, we randomly selected age- and gender-matched control values from our center database consisting of reference values of 118 pain-free healthy volunteers. Results Eighteen patients with unilateral neck pain participated in this study. The control group was represented by previously stored data from 18 demographically matched pain-free individuals. When data from the non-painful side and the non-painful reference area of the patients were compared with data from the pain-free healthy volunteers, we found preliminary evidence of 1. ongoing descending tonic inhibition, 2. less effective inhibitory modulation in the trigeminal compared to the spinal sensory system, and 3. segmental sensitization over the chronic nociceptive source in the neck. Conclusions Using our multi-modal QST battery which incorporates dynamic and static tests, we demonstrate a possibly on-going interaction between intact descending inhibitory modulation and segmental sensitization in patients with chronic idiopathic neck pain. This enables not only better insight into the underlying neurophysiology but may also provide a means to better evaluate treatment and management interventions.

Investigating the validity of the DN4 in a consecutive population of patients with chronic pain

Neuropathic pain is clinically described as pain caused by a lesion or disease of the somatosensory nervous system. The aim of this study was to assess the validity of the Dutch version of the DN4, in a cross-sectional multicentre design, as a screening tool for detecting a neuropathic pain component in a large consecutive, not pre-stratified on basis of the target outcome, population of patients with chronic pain. Patients’ pain was classified by two independent (pain-)physicians as the gold standard. The analysis was initially performed on the outcomes of those patients (n = 228 out of 291) in whom both physicians agreed in their pain classification. Compared to the gold standard the DN4 had a sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the DN4-signs (three examination items) it was respectively 75% and 75%. In conclusion, because it seems that the DN4 helps to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way, a comprehensive (physical-) examination by the physician is still obligate.

Qualitative and Quantitative Aspects of Pain in Patients With Myotonic Dystrophy Type 2

Pain is a common but often ignored symptom in patients with myotonic dystrophy type 2 (DM2). In this explorative study, we assessed qualitative and quantitative aspects of pain in DM2 using 4 questionnaires and quantitative sensory testing. A disease control group (fibromyalgia [FMS]) as well as healthy controls were used to compare the results, because pain in DM2 shows many clinical similarities to pain in FMS. Thirty-four patients with genetically confirmed DM2 (71% female, mean age 54 years), 28 patients with FMS, and 33 healthy controls were included, age- as well as sex-matched. Pain prevalence was 65% in DM2, 100% in FMS (P < .001), and 15% in healthy controls (P < .001). The mean of the pressure pain thresholds was lower in DM2 than in healthy controls (P = .016), with the largest differences in the rectus femoris, trapezius, and thenar muscles. Mechanical and electric pain thresholds were significantly higher in DM2 than in FMS, and no differences were found in electric pain thresholds between DM2 and healthy controls. These results confirm that pain is a frequent and important symptom in patients with DM2, affecting quality of life. Peripheral mechanisms of pain seem to play a role in DM2. The widespreadness of the hyperalgesia suggests central sensitization, but this finding was not supported by the other results. This study opens new avenues for further research and eventually novel treatment strategies, in DM2 as well as in other muscular disorders. PERSPECTIVE This article presents qualitative as well as quantitative aspects of pain in patients with DM2. Pain is a frequent and important symptom in patients with DM2, affecting quality of life. We found mechanical hyperalgesia, indicative of a peripheral mechanism of pain. The widespreadness of hyperalgesia may suggest central sensitization, but this finding was not supported by other results and needs further exploration.

A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and lower quality of life. Persistent postsurgical pain is relatively refractory to treatment hence generating a high need for preventive strategies and treatments. Therefore, the identification of patients at risk of developing persistent pain is an area of active ongoing research. Recently it was demonstrated that peri-operative disruptions in central pain processing may be able to predict persistent postsurgical pain at long term follow-up in breast cancer patients. The aim of the current report is to present a short protocol to obtain pain thresholds to different stimuli at multiple sites and a measure of endogenous analgesia in breast cancer patients. We have used this method successfully in a clinical context and detail some representative results from a clinical study.

The added value of bedside examination and screening QST to improve neuropathic pain identification in patients with chronic pain

Background The assessment of a neuropathic pain component (NePC) to establish the neurological criteria required to comply with the clinical description is based on history taking, clinical examination, and quantitative sensory testing (QST) and includes bedside examination (BSE). The objective of this study was to assess the potential association between the clinically diagnosed presence or absence of an NePC, BSE, and the Nijmegen–Aalborg screening QST (NASQ) paradigm in patients with chronic (≥3 months) low back and leg pain or with neck shoulder arm pain or in patients with chronic pain due to suspected peripheral nerve damage. Methods A total of 291 patients participated in the study. Pain (absence or presence of neuro-pathic pain) was assessed independently by two physicians and compared with BSE (measurements of touch [finger, brush], heat, cold, pricking [safety pin, von Frey hair], and vibration). The NASQ paradigm (pressure algometry, electrical pain thresholds, and conditioned pain modulation) was assessed in 58 patients to generate new insights. Results BSE revealed a low association of differences between patients with either absent or present NePC: heat, cold, and pricking sensations with a von Frey hair were statistically significantly less common in patients with present NePC. NASQ did not reveal any differences between patients with and without an NePC. Conclusion Currently, a standardized BSE appears to be more useful than the NASQ paradigm when distinguishing between patients with and without an NePC.

Avoiding Catch-22: Validating the PainDETECT in a in a population of patients with chronic pain

BackgroundNeuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and is a major therapeutic challenge. Several screening tools have been developed to help physicians detect patients with neuropathic pain. These have typically been validated in populations pre-stratified for neuropathic pain, leading to a so called “Catch-22 situation:” “a problematic situation for which the only solution is denied by a circumstance inherent in the problem or by a rule”. The validity of screening tools needs to be proven in patients with pain who were not pre-stratified on basis of the target outcome: neuropathic pain or non-neuropathic pain. This study aims to assess the validity of the Dutch PainDETECT (PainDETECT-Dlv) in a large population of patients with chronic pain.MethodsA cross-sectional multicentre design was used to assess PainDETECT-Dlv validity. Included where patients with low back pain radiating into the leg(s), patients with neck-shoulder-arm pain and patients with pain due to a suspected peripheral nerve damage. Patients’ pain was classified as having a neuropathic pain component (yes/no) by two experienced physicians (“gold standard”). Physician opinion based on the Grading System was a secondary comparison.ResultsIn total, 291 patients were included. Primary analysis was done on patients where both physicians agreed upon the pain classification (n = 228). Compared to the physician’s classification, PainDETECT-Dlv had a sensitivity of 80% and specificity of 55%, versus the Grading System it achieved 74 and 46%.ConclusionDespite its internal consistency and test-retest reliability the PainDETECT-Dlv is not an effective screening tool for a neuropathic pain component in a population of patients with chronic pain because of its moderate sensitivity and low specificity. Moreover, the indiscriminate use of the PainDETECT-Dlv as a surrogate for clinical assessment should be avoided in daily clinical practice as well as in (clinical-) research. Catch-22 situations in the validation of screening tools can be prevented by not pre-stratifying the patients on basis of the target outcome before inclusion in a validation study for screening instruments.Trial registrationThe protocol was registered prospectively in the Dutch National Trial Register: NTR 3030.