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While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed outcomes of people with rheumatoid arthritis (RA), a proportion of patients are refractory to multiple bDMARDs. Definitions of refractory RA thus far have been arbitrary, and outcome data and impact of such cohorts remain limited. Extrapolation from randomised controlled trial and some real-life data suggest approximately 20% progress onto a third bDMARD with a more modest proportion failing additional bDMARDs. This viewpoint discusses an opinion of refractory RA disease and proposes key principles to accurately identify refractory cohorts. These include demonstrating presence of persistent inflammation despite multiple therapies and acknowledging development of antidrug antibody. Potential basis of refractory disease is summarised, and suggestions for an initial approach in the future evaluation of refractory disease are offered. Specific investigation of refractory RA disease is necessary to inform the clinical need and provide a basis for robust investigation of underlying mechanisms.

Study design: This study was designed as an experimental study (trial). Objectives: To verify the effects of the association between conventional pharmacological treatment and osteopathic manipulative treatment (OMT) for chronic pain management in spinal cord injury (SCI). Setting: This study was carried out at Spinal Unit, Ospedale Niguarda Ca’ Granda, Milan, Italy. Istituto Superiore di Osteopatia, Milan, Italy. Methods: We enrolled 47 patients with SCI, 26 with pain of both nociceptive and neuropathic origin, and 21 with pure neuropathic pain. In all, 33 patients had a complete spinal cord lesion (ASIA level A) and 14 had incomplete lesion (ASIA level B, C and D). The patients were subdivided in a pharmacological group (Ph), a pharmacological osteopathic (PhO) group and a osteopathic (Os) group. The verbal numeric scale (VNS) was used at various time intervals to evaluate treatment outcomes. Results: Ph patients reached a 24% improvement in their pain perception, assessed by the VNS scale after 3 weeks of treatment, whereas Os patients reached a 16% improvement in their pain perception for the same weeks. Both treatments per se failed to induce further improvements at later time points. In contrast, the combination of the two approaches yielded a significantly better pain relief both in patients with nociceptive or pure neuropathic pain in the PhO group. Conclusions: Our results suggest the OMT is a feasible approach in patients in whom available drugs cannot be used. Moreover, a benefit can be expected by the association of OMT in patients treated according to existing pharmacological protocols.

To improve patient care and help clinical research, the Neuropathic Pain Special Interest Group of the Italian Neurological Society appointed a task force to elaborate a consensus statement on pharmacoresistant neuropathic pain. The task force included 19 experts in neuropathic pain. These experts participated in a Delphi survey consisting of three consecutive rounds of questions and a face-to-face meeting, designed to achieve a consensus definition of pharmacoresistant neuropathic pain. In the three rounds of questions, the participants identified and described the main distinguishing features of pharmacoresistance. In the face-to-face meeting the participants discussed the clinical features determining pharmacoresistance. They finally agreed that neuropathic pain is pharmacoresistant when “the patient does not reach the 50% reduction of pain or an improvement of at least 2 points in the Patient Global Impression of Change, having used all drug classes indicated as first, second, or third line in the most recent and widely agreed international guidelines, for at least 1 month after titration to the highest tolerable dose.” Our consensus statement might be useful for identifying eligible patients for invasive treatments, and selecting patients in pharmacological trials, thus improving patient care and helping clinical research.

Background Best current estimates of neuropathic pain (NeuP) prevalence come from studies using various screening detecting pain with probable neuropathic features; the proportion experiencing significant, long-term NeuP, and the proportion not responding to standard treatment are unknown. These “refractory” cases are the most clinically important to detect, being the most severe, requiring specialist treatment. Methods We report an international Delphi survey of experts in NeuP, aiming for consensus on the features required to define, for epidemiological research: (1) neuropathic pain; and (2) when NeuP is “refractory”. A web-based questionnaire was developed and data collected from three rounds of questionnaires from nineteen experts. Results There was good consensus on essential inclusion of six items to identify NeuP (“prickling, tingling, pins & needles”, “pain evoked by light touch”, “electric shocks or shooting pain”, “hot or burning” pain, “brush allodynia on self-examination”, and “relevant history”) and on some items that were non-essential. Consensus was also reached on components of a “refractory NeuP” definition: minimum duration (one year); number of trials of drugs of known effectiveness (four); adequate duration of these trials (three months / maximum tolerated); outcomes of treatment (pain severity, quality of life). Further work needs to validate these proposed criteria in general population research. Conclusions This paper presents an international consensus on measuring the epidemiology of refractory neuropathic pain. This will be valuable in reaching an agreed estimate of the prevalence of neuropathic pain, and the first estimate of refractory neuropathic pain prevalence.

Background: Many pain scales exist today; however, a comprehensive, easy-to-analyze test has yet to be available to evaluate a patient’s pain and understand the sociocultural, cognitive, and affective factors contributing to a patient’s overall pain experience. Many scales have attempted to create an all-encompassing pain assessment but remain incomplete in their assessment of pain and the contributing aspects of pain. Objective: To present the Global Pain Scale (GPS) as an alternative to current pain assessments and evaluate the reliability and construct validity of the GPS. Methods: Two hundred sixty-two undergraduates with chronic pain at a large midwestern university participated in this survey study. Participants reported in which of 14 specific body regions they have pain, the frequency of pain, and treatment history for their pain. Participants completed 4 scales— GPS, the West Haven Yale Scale (WHY), the Perceived Stress Scale (PSS), and the short form McGill (SF-MPQ) — in a randomized order. Results: The GPS demonstrated high criterion validity and high construct validity (including both convergent and discriminant validity). The total GPS scale and each of the subscales were reliable. The total GPS score was significantly correlated with all other subscales, excluding those for which there is a theoretical reason for them to not be correlated with our participant population. Limitations: A sample of college students was used, thus decreasing the generalizability of these findings to patients approximating our sample. Conclusions: The GPS is a valid scale that is concise and easily interpreted. The GPS is a comprehensive assessment of pain evaluating pain, emotions, clinical outcomes, and daily activities. This may be a valuable tool for evaluation and treatment planning for interventional pain management physicians. Key words: chronic pain, pain assessment comprehensive pain scale, pain scales

Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity on a baseline pain of moderate intensity in patients on regularly administered analgesic treatment. This review provides updated information about the classification, assessment, and treatment of BTcP, with special emphasis on the use of opioids. Due to its slow onset to effect, oral opioids cannot be considered an efficacious treatment of BTcP. More recently, different technologies have been developed to provide fast pain relief with potent opioid drugs, such as fentanyl, delivered by noninvasive routes. Transmucosal, buccal, sublingual, and intranasal fentanyl have been shown to provide rapid analgesia in comparison with oral morphine or placebo and are available for clinical use in most countries. All the studies performed with these delivery systems have recommended that these drugs should be administered to opioid-tolerant patients receiving doses of oral morphine equivalents of at least 60 mg. The need of titrating opioid doses for BTcP has been commonly recommended in all the controlled studies, but never has been substantiated in appropriate studies.

Patients affected by chronic forms of headache are often very difficult to treat. Refractory patients are so defined when adequate trials of specific drugs (for acute or prophylactic treatment) failed both to reduce the burden of disease and to improve headache-related quality of life. An escalating approach is suggested to test different kinds of therapies. All comorbid factors should be addressed. More invasive modalities (such as neurostimulation) or promising approaches such as repetitive transcranial magnetic stimulation (rTMS) could be a future major step as third line therapies.