Standards for the diagnosis and management of complex regional pain syndrome: Results of a European Pain Federation task force.

BACKGROUND: Complex regional pain syndrome is a painful and disabling post-traumatic primary pain disorder. Acute and chronic complex regional pain syndrome (CRPS) are major clinical challenges. In Europe, progress is hampered by significant heterogeneity in clinical practice. We sought to establish standards for the diagnosis and management of CRPS. METHODS: The European Pain Federation established a pan-European task force of experts in CRPS who followed a four-stage consensus challenge process to produce mandatory quality standards worded as grammatically imperative (must-do) statements. RESULTS: We developed 17 standards in 8 areas of care. There are 2 standards in diagnosis, 1 in multidisciplinary care, 1 in assessment, 3 for care pathways, 1 in information and education, 4 in pain management, 3 in physical rehabilitation and 2 on distress management. The standards are presented and summarized, and their generation and consequences were discussed. Also presented are domains of practice for which no agreement on a standard could be reached. Areas of research needed to improve the validity and uptake of these standards are discussed. CONCLUSION: The European Pain Federation task force present 17 standards of the diagnosis and management of CRPS for use in Europe. These are considered achievable for most countries and aspirational for a minority of countries depending on their healthcare resource and structures. SIGNIFICANCE: This position statement summarizes expert opinion on acceptable standards for CRPS care in Europe.

Medical cannabis: A forward vision for the clinician.

Medical cannabis has entered mainstream medicine and is here to stay. Propelled by public advocacy, the media and mostly anecdote rather than sound scientific study, patients worldwide are exploring marijuana use for a vast array of medical conditions including management of chronic pain. Contrary to the usual path of drug approval, medical cannabis has bypassed traditional evidence-based study and has been legalized as a therapeutic product by legislative bodies in various countries. While there is a wealth of basic science and preclinical studies demonstrating effects of cannabinoids in neurobiological systems, especially those pertaining to pain and inflammation, clinical study remains limited. Cannabinoids may hold promise for relief of symptoms in a vast array of conditions, but with many questions as yet unanswered. Rigorous study is needed to examine the true evidence for benefits and risks for various conditions and in various patient populations, the specific molecular effects, ideal methods of administration, and interaction with other medications and substances. In the context of prevalent use, there is an urgency to gather pertinent clinical information about the therapeutic effects as well as risks. Even with considerable uncertainties, the health care community must adhere to the guiding principle of clinical care 'primum non nocere' and continue to provide empathetic patient care while exercising prudence and caution. The health care community must strongly advocate for sound scientific evidence regarding cannabis as a therapy. SIGNIFICANCE: Legalization of medical cannabis has bypassed usual drug regulatory procedures in jurisdictions worldwide. Pending sound evidence for effect in many conditions, physicians must continue to provide competent empathetic care with attention to harm reduction. A vision to navigate the current challenges of medical cannabis is outlined.

Using a multimedia presentation to improve patient understanding and satisfaction with informed consent for minimally invasive vascular procedures.

OBJECTIVE: As vascular procedures become more complex, patient understanding of their treatment(s) can become more difficult. We wished to evaluate the utility of multimedia presentations (MPs) to improve patient understanding of their vascular interventions. METHODS: Patients undergoing endovascular aneurysm repair (EVAR), peripheral angioplasty, Hickman catheter and peripherally inserted central catheter (PICC) insertion were randomized into a control group receiving traditional verbal consent, and a MP group that were shown a two minute simplified video of their procedure on an iPad™ computer in addition to the traditional verbal consent. After obtaining consent, all patients completed a questionnaire assessing their comprehension of the procedure, and satisfaction with the consent process. Satisfaction was rated on a 5 point Likert scale with 5 being 'very helpful' in understanding the procedure. RESULTS: Ninety-three patients were recruited for this study, 62% of which were male. The intervention significantly increased total comprehension in all procedure types controlling for procedure type (multimedia vs. control; F = 9.14, P = .003). A second ANOVA showed there was a significant main effect by intervention (F = 44.06, p < .000) with those in the intervention group showing higher overall satisfaction scores after controlling for surgery type. CONCLUSION: This study suggests that patients find the use of MP during the consent process to be helpful in patient understanding and that there is improved satisfaction. Given the rapid rate of innovation in vascular interventions, increased regular use of MPs to help patients understand their procedures would be beneficial in the care of patients undergoing vascular interventions.

Amputation in patients with complex regional pain syndrome: a comparative study between amputees and non-amputees with intractable disease.

AIMS: Amputation in intractable cases of complex regional pain syndrome (CRPS) remains controversial. The likelihood of recurrent Complex Regional Pain Syndrome (CRPS), residual and phantom limb pain and persistent disability after amputation is poorly described in the literature. The aims of this study were to compare pain, function, depression and quality of life between patients with intractable CRPS who underwent amputation and those in whom amputation was considered but not performed. PATIENTS AND METHODS: There were 19 patients in each group, with comparable demographic details. The amputated group included 14 men and five women with a mean age of 31 years (sd 12) at the time of CRPS diagnosis. The non-amputated group consisted of 12 men and seven women and their mean age of 36.8 years (sd 8) at CRPS diagnosis. The mean time from CRPS diagnosis to (first) amputation was 5.2 years (sd 4.3) and the mean time from amputation to data collection was 6.6 years (sd 5.8). All participants completed the following questionnaires: Short-Form (SF) 36, Short Form McGill Pain questionnaire (SF-MPQ), Pain Disability Index (PDI), the Beck Depression Inventory (BDI) and a clinical demographic questionnaire. RESULTS: The amputation group showed consistently better results compared to the non-amputation group in the following parameters: median pain intensity (VAS): 80 (inter-quartile range (IQR) 13 to 92) vs 91 (IQR 85 to 100); p = 0.007; median SF-MPQ score 28 (IQR 9 to 35) vs 35 (IQR 31 to 38), p = 0.025; median PDI: 42 (IQR 11 to 64) vs 58 (IQR 50 to 62), p = 0.031; median BDI: 19 (IQR 5 to 28) vs 27 (IQR 21 to 32), p = 0.061 (borderline significant) and in six of the eight SF-36 domains. TAKE HOME MESSAGE: Amputation should be considered as a form of treatment for patients with intractable CRPS.

Who can benefit from virtual reality to reduce experimental pain? A crossover study in healthy subjects.

BACKGROUND: The present study aimed to identify predicting factors affecting experimental pain stimuli reduction by using 'EyeToy', which is an Immersive Virtual Reality System (IVRS). METHODS: Sixty-two healthy subjects (31 M, 31 F) underwent a battery of pain tests to determine each participant's baseline sensitivity to nociceptive. The battery included thermal pain tests (hot and cold) as well as a paradigm to induce conditioned pain modulation (CPM). Later on, each subject participated in two study conditions in random order: (1) An exposure to tonic heat stimulation (46.5 °C/135 s) to the ankle while participating in VR environment which included an activity requiring limb movements; (2) Same heat stimulation with no exposure to VR. Six pain measures were taken during each study condition (baseline, test 1-5). RESULTS: An interaction of time × treatment was found (RM ANOVA, F(5, 305)  = 24.33, p < 0.001, η² = 0.28). Specifically, the reduction in pain score between baseline and test 1 was significantly greater in VR condition than in control (p < 0.001). The maximal pain reduction in both conditions was between baseline and test 1. Hierarchical regression revealed gender and the extent of CPM as predictive factors for pain reduction in the VR condition (6.1% and 7.5%, respectively). CONCLUSIONS: It can be concluded that VR can serve as an effective manipulation for pain reduction in individuals with efficient CPM and in women. These findings constitute a promising platform for future research and hold potential for the improvement and facilitation of clinical treatment.

Long-term outcomes in children conceived with assisted reproductive technologies.

Over five million children have been born worldwide through assisted reproductive technology (ART) and access to ART treatment is increasing yearly. Investigations of the health, disease, cognitive, developmental and behavioral outcomes in the children conceived with ART are often confounded by parental and other social, environmental and medical factors, including multiplicity, prematurity and low birth weight. Reports of the long-term health and psychosocial adjustment of children conceived with ART show generally good outcomes. Many of the major long-term conditions observed in the children may be associated with multiple gestations, preterm delivery and low birth weight, or with subfertility of the parents. Evidence in the male infants conceived with the aid of intracytoplasmic injection (ICSI) suggests an increased risk of reproductive tract anomalies such as hypospadias. Health-related outcomes of children born after cryopreservation of cleavage stage embryos are reassuring. Currently, our knowledge and understanding of the long-term health risks and/or benefits to the children conceived is incomplete. Measuring long-term outcomes is the first step to improving and optimizing health in the offspring conceived with medical and technological assistance.

Jamming, relaxation, and crystallization of a supercooled fluid in a three-dimensional lattice.

Off-equilibrium dynamics of a three-dimensional lattice model with nearest- and next-nearest-neighbors exclusions is studied. At equilibrium, the model undergoes a first-order fluid-solid transition. Nonequilibrium filling, through random sequential adsorption with diffusion, creates amorphous structures and terminates at a disordered state with random closest packing density that lies in the equilibrium solid regime. The approach toward random closest packing is characterized by two distinct power-law regimes, reflecting the formation of small densely packed grains in the long-time regime of the filling process. We then study the fixed-density relaxation of these amorphous structures toward the solid phase. The route to crystallization for the high-density, deeply supercooled regime is shown to deviate from the simple grain growth proposed by classical nucleation theory. Our measurements suggest that relaxation in this regime is driven mainly by coalescence of neighboring crystallized grains which exist in the initial amorphous state.

Finite-temperature liquid-quasicrystal transition in a lattice model.

We consider a tiling model of the two-dimensional square lattice, where each site is tiled with one of the 16 Wang tiles. The ground states of this model are all quasiperiodic. The systems undergoes a disorder to quasiperiodicity phase transition at finite temperature. Introducing a proper order parameter, we study the system at criticality and extract the critical exponents characterizing the transition. The exponents obtained are consistent with hyperscaling.

Complex diel cycles of gene expression in coral-algal symbiosis.

Circadian regulation of plant-animal endosymbioses is complicated by a diversity of internal and external cues. Here, we show that stress-related genes in corals are coupled to the circadian clock, anticipating major changes in the intracellular milieu. In this regard, numerous chaperones are "hard-wired" to the clock, effectively preparing the coral for the consequences of oxidative protein damage imposed by symbiont photosynthesis (when O(2) > 250% saturation), including synexpression of antioxidant genes being light-gated. Conversely, central metabolism appears to be regulated by the hypoxia-inducible factor system in coral. These results reveal the complexity of endosymbiosis as well as the plasticity regulation downstream of the circadian clock.

Direct measurements of the dynamical correlation length indicate its divergence at an athermal glass transition.

The supercooled N3 model exhibits an increasingly slow dynamics as density approaches the random closest packing density. Here, we present a direct measurement of the dynamical correlation function G4(r,t), showing the emergence of a growing length scale ξ(4) across which the dynamics is correlated. The correlation length measured, up to 120 lattice sites, power law diverges as the density approaches ρ(t), the density at which the fluid phase of the model is predicted to terminate. The four-point susceptibility, often used as an agent to estimate ξ(4), does not depend simply on the latter. Rather, it depends strongly on the short-range behavior of G4(r,t). Consequently, χ(4) peaks before ξ(4) reaches its maximal value. The two quantities should therefore be studied independently.

Critical exponents from cluster coefficients.

For a large class of repulsive interaction models, the Mayer cluster integrals can be transformed into a tridiagonal real symmetric matrix R_{mn} , whose elements converge to two constants. This allows for an effective extrapolation of the equation of state for these models. Due to a nearby (nonphysical) singularity on the negative real z axis, standard methods (e.g., Padé approximants based on the cluster integrals expansion) fail to capture the behavior of these models near the ordering transition, and, in particular, do not detect the critical point. A recent work [E. Eisenberg and A. Baram, Proc. Natl. Acad. Sci. U.S.A. 104, 5755 (2007)] has shown that the critical exponents sigma and sigma;{'} , characterizing the singularity of the density as a function of the activity, can be exactly calculated if the decay of the R matrix elements to their asymptotic constant follows a 1/n;{2} law. Here we employ renormalization group (RG) arguments to extend this result and analyze cases for which the asymptotic approach of the R matrix elements toward their limiting value is of a more general form. The relevant asymptotic correction terms (in RG sense) are identified, and we then present a corrected exact formula for the critical exponents. We identify the limits of usage of the formula and demonstrate one physical model, which is beyond its range of validity. The formula is validated numerically and then applied to analyze a number of concrete physical models.

Ideal glass transition in a simple two-dimensional lattice model.

We present a simple lattice model showing a glassy behavior. R matrix analysis predicts critical termination of the supercooled fluid branch at density rho(g)=0.1717. This prediction is confirmed by dynamical numerical simulations, showing power-law divergences of relaxation time tau1/2, as well as the four-susceptibility chi4 peak's location and height exactly at the predicted density. The power-law divergence of chi4 continues up to chi4 as high as 10(4). Finite-size scaling study reveals the divergence of the correlation length accompanying the transition.

Estimation of critical exponents from cluster coefficients and the application of this estimation to hard spheres.

For a large class of repulsive interaction models, the Mayer cluster integrals can be transformed into a tridiagonal real symmetric matrix R(mn), whose elements converge to two constants with 1/n(2) correction. We find exact expressions in terms of these correction terms for the two critical exponents describing the density near the two singular termination points of the fluid phase. We apply the method to the hard-spheres model and find that the metastable fluid phase terminates at rho(t) = 0.751[5]. The density near the transition is given by rho(t)-rho approximately (z(t) - z)(sigma'), where the critical exponent is predicted to be sigma' = 0.0877[25]. Interestingly, the termination density is close to the observed glass transition; thus, the above critical behavior is expected to be associated with the onset of glassy behavior in hard spheres.

Opioids for neuropathic pain.

BACKGROUND: The use of opioids for neuropathic pain remains controversial. Studies have been small, have yielded equivocal results, and have not established the long-term risk-benefit ratio of this treatment. OBJECTIVES: To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (2nd Quarter 2005), MEDLINE (1966 to June 2005), and EMBASE (1980 to 2005 Week 27) for articles in any language, and reference lists of reviews and retrieved articles. SELECTION CRITERIA: Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects. MAIN RESULTS: Twenty-three trials met the inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = eight to 70 days; n = 9). The short-term trials had contradictory results. In contrast all nine intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. Meta-analysis of seven intermediate-term studies showed mean post-treatment visual analog scale scores of pain intensity after opioids to be 13 points lower on a scale from zero to 100 than after placebo (95% confidence interval -16 to -9; P < 0.00001). The most common adverse events were nausea (33% opioid versus 9% control: number needed to treat to harm (NNH) 4.2) and constipation (33% opioid versus 10% control: NNH 4.2), followed by drowsiness (29% opioid versus 12% control: NNH 6.2), dizziness (21% opioid versus 6% control: NNH 7.1), and vomiting (15% opioid versus 3% control: NNH 8.3). Where reported, 23 (11%) of 212 participants withdrew because of adverse events during opioid therapy versus nine (4%) of 202 receiving placebo. AUTHORS' CONCLUSIONS: Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain, whereas intermediate-term studies demonstrate significant efficacy of opioids over placebo, which is likely to be clinically important. Reported adverse events of opioids are common but not life threatening. Further randomized controlled trials are needed to establish long-term efficacy, safety (including addiction potential), and effects on quality of life.

Analysis of the ordering transition of hard disks through the Mayer cluster expansion.

The available virial coefficients for the two-dimensional hard-disks model are transformed into a matrix representation of the thermodynamic potentials, which allows for an accurate description of the whole fluid phase, up to the phase transition. We find that the fluid phase terminates at the transition point, implying a second-order phase transition in accordance with the Kosterlitz-Thouless-Halperin-Nelson-Young scenario of a transition into a hexatic phase. The density and pressure at the transition are calculated from the available first ten virial coefficients, and are found to be in excellent agreement with recent Monte-Carlo calculations. Finally, we calculate the equation of state in the critical region.

Random matrix theory for closed quantum dots with weak spin-orbit coupling.

To lowest order in the coupling strength, the spin-orbit coupling in quantum dots results in a spin-dependent Aharonov-Bohm flux. This flux decouples the spin-up and spin-down random matrix theory ensembles of the quantum dot. We employ this ensemble and find significant changes in the distribution of the Coulomb blockade peak height, in particular, a decrease of the width of the distribution. The puzzling disagreement between standard random matrix theory and the experimental distributions by Patel et al. [Phys. Rev. Lett. 81, 5900 (1998)]] might possibly be attributed to these spin-orbit effects.