Monitoring Opioids in Europe: The Need for Shared Definitions and Measuring Drivers of Opioid Use and Related Harms.

The past 20 years, the USA is facing a serious opioid crisis initiated by an increase in prescription opioid use. Europe has also seen an increase in prescription opioid use, but the extent of related harm is still largely unknown. Given the impact of the US opioid epidemic, it is important to closely monitor signs of emerging opioid-related problems to guarantee early warnings and timely actions. Shared and meaningful definitions for opioid use and related harms, and relevant information about specific drivers for opioid use and related problems are needed for an adequate policy response. In this commentary, we discuss these definitions, the need to know more about the specific drivers for increased opioid use, its related harm, and proposals for strategies to move forward. Policy recommendations include making a distinction between licit and illicit opioids when monitoring and reporting on opioid-related harm, and using oral morphine equivalents to quantify prescription opioid use in a clinically relevant and comparable manner. A major topic of further research is exploring unique and universal drivers of prescription opioid (mis)use across Europe, in particular the role of opioid diversion.

Pain education and pain management skills in virtual reality in the treatment of chronic low back pain: A multiple baseline single-case experimental design.

Chronic lower back pain is a major health problem and current treatments do not always lead to adequate pain control. Virtual reality (VR) is an upcoming technology that has shown to be effective in reducing acute pain. However, the value of VR in reducing chronic pain is still unknown. Therefore, the current study focuses on the effects of a recently developed VR application 'Reducept' using a multiple baseline single-case experimental design in 8 patients (N = 8). Reducept is a VR-training program aiming to improve pain management skills and providing pain education in patients with (chronic lower) back pain. Results based on visual and statistical analyses indicated that Reducept has the potential to reduce chronic lower back pain, although its clinical relevance was small. This study is one of the first that focuses on the possible effects of Reducept using sophisticated visual and statistical analyses. Our study shows a detailed overview of individual changes in pain intensity over time. Further research is necessary to investigate the working mechanism of Reducept and its impact on chronic pain conditions.

Multimodal and widespread somatosensory abnormalities in persistent shoulder pain in the first 6 months after stroke: an exploratory study.

OBJECTIVE: To explore the role of multimodal and widespread somatosensory abnormalities in the development of persistent poststroke shoulder pain (pPSSP) in the first 6 months after stroke. DESIGN: Prospective inception cohort study. SETTING: Stroke units of 2 teaching hospitals. PARTICIPANTS: The data of a strict selection of patients (N=31) with a clinical diagnosis of stroke were analyzed. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The development of pPSSP within the first 6 months after stroke. Bilateral sensation and pain thresholds at 3 (t1) and 6 (t2) months, and conditioned pain modulation (CPM) at 3 months after stroke. Clinical examination within 2 weeks after stroke (t0), at t1, and at t2. RESULTS: pPSSP (n=9) was associated with increased sensation and pain threshold ratios at the affected side (t1, t2), and with reduced cold pain tolerance at the unaffected side (t1). CPM was not different from patients without pPSSP (n=22). Notably, in patients with pPSSP reporting increased sensation on clinical examination, multiple body sites across multiple stimulus modalities were involved, and increased sensation persisted from t1 to t2. CONCLUSIONS: pPSSP in the first 6 months after stroke was associated with somatosensory loss to both innocuous and noxious stimuli (affected side). In addition, pPSSP was associated with sensitization to cold pain (unaffected side) and with widespread sensitization to multimodal innocuous stimuli (affected side). The results support the notion that central somatosensory sensitization could play an important role in the development of pPSSP, the maintenance of pPSSP, or both.

The effectiveness and cost evaluation of pain exposure physical therapy and conventional therapy in patients with complex regional pain syndrome type 1. Rationale and design of a randomized controlled trial.

BACKGROUND: Pain Exposure Physical Therapy is a new treatment option for patients with Complex Regional Pain Syndrome type 1. It has been evaluated in retrospective as well as in prospective studies and proven to be safe and possibly effective. This indicates that Pain Exposure Physical Therapy is now ready for clinical evaluation. The results of an earlier performed pilot study with an n = 1 design, in which 20 patients with Complex Regional Pain Syndrome type 1 were treated with Pain Exposure Physical Therapy, were used for the design and power calculation of the present study.After completion and evaluation of this phase III study, a multi-centre implementation study will be conducted.The aim of this study is to determine whether Pain Exposure Physical Therapy can improve functional outcomes in patients with Complex Regional Pain Syndrome type 1. METHODS/DESIGN: This study is designed as a single-blinded, randomized clinical trial. 62 patients will be randomized with a follow-up of 9 months to demonstrate the expected treatment effect. Complex Regional Pain Syndrome type 1 is diagnosed in accordance with the Bruehl/International Association for the Study of Pain criteria. Conventional therapy in accordance with the Dutch guideline will be compared with Pain Exposure Physical Therapy. Primary outcome measure is the Impairment level SumScore, restricted version. DISCUSSION: This is the first randomized controlled study with single blinding that has ever been planned in patients with Complex Regional Pain Syndrome type 1 and does not focus on a single aspect of the pain syndrome but compares treatment strategies based on completely different pathophysiological and cognitive theories.

Changes in quantitative sensory testing and patient perspectives following spinal cord stimulation for persistent spinal pain syndrome: An observational study with long-term follow-up.

BACKGROUND: Spinal cord stimulation (SCS) can impact sensory, pain and tolerance thresholds in various ways, which can be accessed via quantitative sensory testing (QST). The objectives of this study were to (1) assess the subjective sensory responses using QST in patients following SCS therapy for PSPS and (2) to get a clinical impression of the results of SCS during an interview of these patients with PSPS and SCS during long term follow-up. METHODS: Forty patients with PSPS who received SCS treatment underwent QST via electrical and mechanical pressure stimuli. QST was performed at four different moments (1) pre-implantation SCS, (2) two weeks postoperatively, (3) three months after permanent SCS implantation and (4) six months after permanent SCS implantation. Patients' perspectives on pain, use of drugs and quality of life were assessed via semi-structured interviews during a follow-up between 5 and 11 years. RESULTS: We found statistical significant differences in the changes of sensory, pain and tolerance thresholds. A decrease in pain complaints and analgesics use were reported by the patients during follow-up. The quality of life in patients increased from three to eight (NRS 0 [worst QoL imaginable] -10 [best QoL imaginable]) after receiving SCS. CONCLUSIONS: The increased thresholds on areas without pain or being covered by the SCS induced paresthesias may indicate that there are central changes contributing to these deviations in thresholds. The overall QoL in patients improved greatly after receiving SCS. SIGNIFICANCE: This study provides an overview of the effect of SCS on sensory, pain and tolerance thresholds in patients with PSPS throughout the SCS treatment process. In addition, this study presents data from 40 patients with PSPS treated with SCS, analysing several long-term patient-reported outcome measures. The results serve to give more insight into the mechanism of SCS and document SCS as a possible treatment for PSPS.

Persistent shoulder pain in the first 6 months after stroke: results of a prospective cohort study.

OBJECTIVE: To identify factors associated with persistent poststroke shoulder pain (pPSSP) in the first 6 months after stroke. DESIGN: Prospective inception cohort study. SETTING: Stroke units of 2 teaching hospitals. PARTICIPANTS: Patients (N=31) with a clinical diagnosis of stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The development of pPSSP within the first 6 months after stroke. Clinical assessment of motor, somatosensory, cognitive, emotional, and autonomic functions, undertaken within 2 weeks (t0), at 3 months (t1), and at 6 months (t2) after stroke. RESULTS: Patients with pPSSP (n=9) were compared with patients without pPSSP (n=22). Bivariate logistic regression analyses showed that pPSSP was significantly associated with impaired voluntary motor control (t0, t1, t2), diminished proprioception (t0, t1), tactile extinction (t0), abnormal sensation (t1, t2), spasticity of the elbow flexor muscles (t1, t2), restricted range of motion (ROM) for both shoulder abduction (t2) and shoulder external rotation (t1, t2), trophic changes (t1), and type 2 diabetes mellitus (t0). CONCLUSIONS: These findings suggest a multifactorial etiology of pPSSP. The association of pPSSP with restricted, passive, pain-free ROM and signs indicative of somatosensory sensitization may implicate a vicious cycle of repetitive (micro)trauma that can establish itself rapidly after stroke. Intervention should therefore be focused on maintaining and restoring joint ROM as well as preventing injury and somatosensory sensitization. In this perspective, strategies that aim to intervene simultaneously at various levels of function can be expected to be more effective than treatment directed at merely 1 level.

The use of laminectomy for the placement of a percutaneous spinal cord stimulation electrode.

OBJECTIVE: The placement of a percutaneous electrode for trial stimulation to evaluate the effectiveness of spinal cord stimulation can be impossible because of epidural adhesions from previous spinal surgeries. The authors would like to describe a combination of techniques in order to place a percutaneous lead for a test phase. MATERIALS AND METHODS: Technical report of an illustrative case where a partial laminectomy was used to assist a percutaneous lead placement. RESULTS: Adequate trial spinal cord stimulation with a single lead electrode at the right target area was possible. CONCLUSION: This case demonstrates the possibility to use a combination of an open and percutaneous technique for trial spinal cord stimulation in patients with prior operations in the target area of stimulation.

Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial.

BACKGROUND: Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS could serve as an effective treatment for patients with MICCH. METHODS: The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks' baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and near-discomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25-48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21-24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631). FINDINGS: Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15·75; IQR 9·44 to 24·75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7·38 (2·50 to 18·50; p<0·0001) in weeks 21-24, a median change of -5·21 (-11·18 to -0·19; p<0·0001) attacks per week. In the 100% ONS stimulation group, mean attack frequency decreased from 17·58 (9·83 to 29·33) at baseline to 9·50 (3·00 to 21·25) at 21-24 weeks (median change from baseline -4·08, -11·92 to -0·25), and for the 30% ONS stimulation group, mean attack frequency decreased from 15·00 (9·25 to 22·33) to 6·75 (1·50 to 16·50; -6·50, -10·83 to -0·08). The difference in median weekly mean attack frequency between groups at the end of the masked phase in weeks 21-24 was -2·42 (95% CI -5·17 to 3·33). In the masked study phase, 129 adverse events occurred with 100% ONS and 95 occurred with 30% ONS. None of the adverse events was unexpected but 17 with 100% ONS and eight with 30% ONS were labelled as serious, given they required brief hospital admission for minor hardware-related issues. The most common adverse events were local pain, impaired wound healing, neck stiffness, and hardware damage. INTERPRETATION: In patients with MICCH, both 100% ONS intensity and 30% ONS intensity substantially reduced attack frequency and were safe and well tolerated. Future research should focus on optimising stimulation protocols and disentangling the underlying mechanism of action. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

Pain exposure physical therapy may be a safe and effective treatment for longstanding complex regional pain syndrome type 1: a case series.

OBJECTIVE: To determine if treatment of longstanding complex regional pain syndrome type 1, focusing on functional improvement only while neglecting pain, results in clinical improvement of this syndrome. DESIGN: Prospective description of a case series of 106 patients. SETTING: Outpatient clinic for rehabilitation. INTERVENTIONS: Physical therapy of the affected limb directed at a functional improvement only while neglecting the pain, was performed following an extensive explanation. Normal use of the limb between the treatments was encouraged despite pain. A maximum of five of these sessions were performed in three months. MEASURES: Radboud Skills Test was used to monitor functional improvement of the arms. Speed and walking distance was used as the measure of outcome for the legs. RESULTS: The function of the affected arm or leg improved in 95 patients. Full functional recovery was experienced in 49 (46%) of them. A reduction in pain presented in 75 patients. In 23 patients functional recovery was reached despite an increase in pain. Four patients stopped early due to pain increase. CONCLUSIONS: Our results suggest that 'pain exposure physical therapy' is effective and safe for patients who are unresponsive to accepted standard therapies. Avoiding the use of a limb due to pain will result in loss of function. Forced usage of limbs restores the function, reverses these adaptive processes and leads to regain of control by practice with a reduction of pain in most cases.

Trends in use and misuse of opioids in the Netherlands: a retrospective, multi-source database study.

BACKGROUND: The USA is currently facing a serious opioid misuse epidemic that started with increased prescribing of oxycodone and the inclusion of pain as a fifth vital sign, and eventually resulted in massive overdose mortality. In Europe, including the Netherlands, the medical use of opioids (mainly oxycodone) has also increased since 2009, but an increase in proxies for opioid misuse has not yet been described. METHODS: For this retrospective, multi-source database study, data were requested from several national databases in the Netherlands to evaluate the following time trends: (1) number of people with opioid prescriptions, (2) number of hospital admissions related to opioid intoxication, (3) number of people treated for opioid use disorder, and (4) number of people who died from opioid poisoning. Data were presented as the number per 100 000 inhabitants, using population data over the years 2008-17 from Statistics Netherlands (Centraal Bureau voor de Statistiek). Data about the number of people with opioid prescriptions was obtained from the Drug Information Project (Genees- en hulpmiddelen Informatie Project) database hosted by the Dutch National Health Care Institute (Zorginstituut Nederland). Data about opioid-related hospital admissions between 2008 and 2017 were obtained from the Dutch National Hospital Care Basic Registration (Landelijke Basisregistratie Ziekenhuiszorg), a database managed by Dutch Hospital Data. Data about addiction treatment were obtained from the National Alcohol and Drugs Information System (Landelijk Alcohol en Drugs Informatie Systeem). Data on opioid mortality between 2008 and 2017 were obtained from the cause-of-death statistics database hosted by Statistics Netherlands. Each database covered almost the entire population of the Netherlands. FINDINGS: Between 2008 and 2017, the overall number of prescription opioid users nearly doubled from 4109 per 100 000 inhabitants to 7489 per 100 000 inhabitants, mainly because the number of oxycodone users quadrupled from 574 to 2568 per 100 000 inhabitants. In the same period, the number of opioid-related hospital admissions tripled from 2·5 to 7·8 per 100 000 inhabitants, and between 2008 and 2015 the number of patients in addiction care for opioid use disorders other than heroin increased from 3·1 to 5·6 per 100 000 inhabitants. Opioid-related mortality was stable between 2008 and 2014 with 0·21 deaths per 100 000 inhabitants, but after 2014 it increased to 0·65 per 100 000 inhabitants in 2017. INTERPRETATION: Prescription opioid use increased substantially between 2008 and 2017, and several proxies for misuse show a parallel increasing trend. Although the Netherlands is far from the opioid epidemic faced by the USA, safe opioid prescribing guidelines should be implemented to prevent further escalation and to keep opioid painkillers available for those in need. FUNDING: Radboud University Nijmegen Medical Centre.

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.

Severity of Neuropathy Is Associated With Long-term Spinal Cord Stimulation Outcome in Painful Diabetic Peripheral Neuropathy: Five-Year Follow-up of a Prospective Two-Center Clinical Trial.

OBJECTIVE: Evidence from prospective studies for long-term treatment efficacy of spinal cord stimulation (SCS) in painful diabetic peripheral neuropathy (PDPN) is not available. We report prospective data on the effect of SCS on pain ratings, treatment success and failure, and complications during a 5-year follow-up in patients with PDPN. RESEARCH DESIGN AND METHODS: Patients with PDPN (n = 48) were included in this prospective multicenter study. The Michigan Diabetic Neuropathy Score (MDNS) was used to assess the severity of neuropathy. Numerical rating scale (NRS) score for pain, Patient's Global Impression of Change (PGIC), and treatment success (50% reduction of NRS score or significant PGIC) during 5 years of follow-up were evaluated. Complications of SCS were reported, and associations between baseline characteristics and SCS trial success or failure during a 5-year follow-up were investigated by using survival analyses. RESULTS: Treatment success was observed in 55% of patients after 5 years. Median duration of SCS treatment was 60 months (minimum 1 month, maximum 60 months), and 80% of patients with a permanent implant still used their SCS device after 5 years. Higher MDNS was associated with treatment failure during the 5-year follow-up (hazard ratio 3.9 [95% CI 1.3-11.6]; P = 0.014). CONCLUSIONS: SCS is successful in reducing chronic pain symptoms in the lower extremities of patients with PDPN up to 5 years after initiation of treatment. Furthermore, 80% of patients with PDPN still use their SCS device after 5 years. Moreover, the severity of neuropathy is associated with a higher chance of long-term treatment failure during a 5-year follow-up.

A Trial-Based Economic Evaluation Comparing Spinal Cord Stimulation With Best Medical Treatment in Painful Diabetic Peripheral Neuropathy.

The objective was to perform an economic evaluation comparing spinal cord stimulation (SCS) in combination with best medical treatment (BMT) with BMT in painful diabetic peripheral neuropathy patients. Alongside a prospective 2-center randomized controlled trial, involving 36 painful diabetic peripheral neuropathy patients with severe lower limb pain not responding to conventional therapy, an economic evaluation was performed. Incremental cost-effectiveness ratios were based on: 1) societal costs and quality-adjusted life years (QALYs), and 2) direct health care costs and the number of successfully treated patients, respectively, both with a time horizon of 12 months. Bootstrap and secondary analyses were performed to address uncertainty. Total societal cost amounted to €26,539.18 versus €5,313.45 per patient in the SCS and BMT group, respectively. QALYs were .58 versus .36 and the number of successfully treated patients was 55% versus 7% for the SCS and BMT group, respectively. This resulted in incremental cost-effectiveness ratios of €94,159.56 per QALY and €34,518.85 per successfully treated patient, respectively. Bootstrap analyses showed that the probability of SCS being cost-effective ranges from 0 to 46% with willingness to pay threshold values ranging between €20,000 and €80,000 for a QALY. Secondary analyses showed that cost-effectiveness of SCS became more favorable after correcting for baseline cost imbalance between the 2 groups, extending the depreciation period of SCS material to 4 years, and extrapolation of the data up to 4 years. Although SCS was considerably more effective compared with BMT, the substantial initial investment that is required resulted in SCS not being cost-effective in the short term. Cost-effectiveness results were sensitive to baseline cost imbalances between the groups and the depreciation period of the SCS material. PERSPECTIVE: Painful diabetic peripheral neuropathy is a common complication of diabetes mellitus and the humanistic and economic burden is high. This article presents the cost-effectiveness of SCS in patients suffering from painful diabetic peripheral neuropathy from a societal and health care perspective with a time horizon of 12 months.

[Complex regional pain syndrome type 1: negating the myth]. / Complex regionaal pijnsyndroom type 1: de mythe ontkracht.

Complex regional pain syndrome type 1 (CRPS-1) was identified in the Netherlands more than 30 years ago, but since then the arguments supporting this diagnosis have become weaker. Incidence has decreased, it is often not possible to make a definite diagnosis, the pathophysiology remains unclear and treatments are extremely diverse. Since the patient group is so heterogeneous, it is often unclear exactly which patients should be included. Disuse due to immobilization can give an identical clinical picture, including the inflammatory parameters that are seen in CRPS-1. CRPS-1 following injury can be prevented with exercise, and incidence is declining dramatically. Taking these factors into consideration, we support the view that CRPS-1 is not an illness but rather a 'disuse syndrome' as a result of immobilization, or there may be a missed underlying diagnosis.

[Neuromodulation in severe neuropathic pain]. / Neuromodulatie bij ernstige neuropathische pijn.

Pain relief in patients with chronic neuropathic pain can be difficult to accomplish. If pharmacological treatment combined with a form of physical therapy and psychological support does not lead to improvement, nerve blocks and rehabilitation can be considered. Appropriately screened patients with persistent incapacitating pain may respond to neuromodulation. A specific form of this technique - spinal cord stimulation - delivers electric pulses via an implanted electrode connected to a battery in the epidural space around the spinal cord. We describe three patients, two of whom had persistent leg pain after disc surgery. The third patient suffered from diabetic neuropathy. Despite thorough pre-procedural screening by an anaesthetist-pain specialist, psychologist, physical therapist and specialised nurse, spinal cord stimulation failed in one patient. Psycho-social factors, inadequate coping skills and depression may lead to inadequate improvement and failure of this therapy.

Pain exposure physical therapy (PEPT) compared to conventional treatment in complex regional pain syndrome type 1: a randomised controlled trial.

OBJECTIVE: To compare the effectiveness of pain exposure physical therapy (PEPT) with conventional treatment in patients with complex regional pain syndrome type 1 (CRPS-1) in a randomised controlled trial with a blinded assessor. SETTING: The study was conducted at a level 1 trauma centre in the Netherlands. PARTICIPANTS: 56 adult patients with CRPS-1 participated. Three patients were lost to follow-up. INTERVENTIONS: Patients received either PEPT in a maximum of five treatment sessions, or conventional treatment following the Dutch multidisciplinary guideline. MEASUREMENTS: Outcomes were assessed at baseline and at 3, 6 and 9 months after randomisation. The primary outcome measure was the Impairment level Sum Score--Restricted Version (ISS-RV), consisting of visual analogue scale for pain (VAS-pain), McGill Pain Questionnaire, active range of motion (AROM) and skin temperature. Secondary outcome measures included Pain Disability Index (PDI); muscle strength; Short Form 36 (SF-36); disability of arm, shoulder and hand; Lower Limb Tasks Questionnaire (LLTQ); 10 m walk test; timed up-and-go test (TUG) and EuroQol-5D. RESULTS: The intention-to-treat analysis showed a clinically relevant decrease in ISS-RV (6.7 points for PEPT and 6.2 points for conventional treatment), but the between-group difference was not significant (0.96, 95% CI -1.56 to 3.48). Participants allocated to PEPT experienced a greater improvement in AROM (between-group difference 0.51, 95% CI 0.07 to 0.94; p=0.02). The per protocol analysis showed larger and significant between-group effects on ISS-RV, VAS-pain, AROM, PDI, SF-36, LLTQ and TUG. CONCLUSIONS: We cannot conclude that PEPT is superior to conventional treatment for patients with CRPS-1. Further high-quality research on the effects of PEPT is warranted given the potential effects as indicated by the per protocol analysis. TRIAL REGISTRATION NUMBERS: NCT00817128 and NTR 2090.

Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-center randomized controlled trial.

OBJECTIVE: Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes mellitus. Unfortunately, pharmacological treatment is often partially effective or accompanied by unacceptable side effects, and new treatments are urgently needed. Small observational studies suggested that spinal cord stimulation (SCS) may have positive effects. RESEARCH DESIGN AND METHODS: We performed a multicenter randomized clinical trial in 36 PDPN patients with severe lower limb pain not responding to conventional therapy. Twenty-two patients were randomly assigned to SCS in combination with the best medical treatment (BMT) (SCS group) and 14 to BMT only (BMT group). The SCS system was implanted only if trial stimulation was successful. Treatment success was defined as ≥50% pain relief during daytime or nighttime or "(very) much improved" for pain and sleep on the patient global impression of change (PGIC) scale at 6 months. RESULTS: Trial stimulation was successful in 77% of the SCS patients. Treatment success was observed in 59% of the SCS and in 7% of the BMT patients (P < 0.01). Pain relief during daytime and during nighttime was reported by 41 and 36% in the SCS group and 0 and 7% in the BMT group, respectively (P < 0.05). Pain and sleep were "(very) much improved" in 55 and 36% in the SCS group, whereas no changes were seen in the BMT group, respectively (P < 0.001 and P < 0.05). One SCS patient died because of a subdural hematoma. CONCLUSIONS: Treatment success was shown in 59% of patients with PDPN who were treated with SCS over a 6-month period, although this treatment is not without risks.