Long-term efficacy of OROS® hydromorphone combined with pregabalin for chronic non-cancer neuropathic pain.

BACKGROUND AND OBJECTIVES: Treatment for chronic non-cancer neuropathic pain can be complicated by side effects and drug interactions. Combining opioid analgesics and calcium channel modulators may overcome these and improve efficacy. The objective of the present study was to evaluate the efficacy and safety of OROS® hydromorphone combined with pregabalin in patients with chronic non-cancer neuropathic pain. METHODS: This retrospective observational study was conducted on clinical records from patients aged ≥18 years with chronic non-cancer neuropathic [>4 on the Douleur Neuropathique en 4 questions (DN4) scale] pain of ≥6 months duration, with severe intensity [>4 on the Numerical Rating Scale (NRS); range 0-10], who attended all visits and had ≥12 months of follow-up at the Tor Vergata University Polyclinic Hospital, from November 2008 to February 2011. Patients received an oral combination of OROS® hydromorphone and pregabalin. Pain was evaluated at each visit (months 1, 3, 6, 9, and 12) using the NRS and DN4 scale; Patients' Global Impression of Change (PGIC) was administered at months 1, 6, and 12. Dosage and side effects were recorded at each visit. RESULTS: Of 1,292 patients (32 % men, mean ± SD age 67.6 ± 11.9 years), 1,126 attended all visits. Seventeen percent (n = 224) had purely neuropathic pain. Initial mean dosage was 6.06 ± 2.00 mg/day for OROS® hydromorphone, 113.02 ± 21.94 mg/day for pregabalin. Dosages increased up to month 6, and returned to near initial dosages at month 12 (range 4-120 mg/day for OROS® hydromorphone; 75-600 mg/day for pregabalin). NRS pain scores (mean ± standard deviation) were 7.25 ± 1.34 at baseline and 1.85 ± 1.36 at 12 months (p < 0.0001); DN4 scores were 6.19 ± 1.65 at baseline, reduced to 1.84 ± 1.25 at 12 months (p < 0.0001), reductions of 74.4 and 70.2 %, respectively. More than 90 % of patients had a ≥50 % score reduction on both scales after 12 months. The PGIC scale showed that >75 % of patients felt improvement at 1 month, increasing to 91 % and 93 % at 6 and 12 months. The incidence of side effects was similar between elderly (aged >65 years) and younger subjects; there were no cases of addiction. CONCLUSIONS: The OROS® hydromorphone and pregabalin combination was efficacious for chronic non-cancer neuropathic pain and well tolerated, providing significant pain reduction without the risk of addiction and with a good tolerability profile, regardless of age

Controlled-release oxycodone and pregabalin in the treatment of neuropathic pain: results of a multicenter Italian study

Abstract AIMS: The aim of our study was to compare the efficacy, safety, and quality of life of combination therapy with controlled-release (CR) oxycodone plus pregabalin versus monotherapy with either CR oxycodone or pregabalin in patients with neuropathic pain. MATERIALS AND METHODS: Patients with moderate to severe neuropathic pain, despite the use of various pharmacologic treatments prior to study entry, were enrolled (n = 409) and treated with CR oxycodone plus pregabalin (n = 169), CR oxycodone (n = 106), and pregabalin (n = 134). Pain intensity was rated on an 11-point numerical rating scale (NRS). RESULTS: The combination of CR oxycodone plus pregabalin and CR oxycodone monotherapy were both more effective for alleviating neuropathic pain than pregabalin monotherapy (reduction in NRS value: 80, 76, and 46%, respectively; p </= 0.003). Significantly greater improvements from baseline in quality of life were reported with combination therapy than with monotherapy (p = 0.0009). At the end of treatment, the majority (91.2%) of patients receiving CR oxycodone plus pregabalin found that the treatment had been 'effective' or 'very effective'. Combination therapy also allowed a dose reduction of both agents (22% for CR oxycodone and 51% for pregabalin) compared with the dosages of the respective monotherapies. Combination therapy had a superior safety profile compared with pregabalin monotherapy. CONCLUSIONS: The combination of CR oxycodone plus pregabalin may represent a valuable addition to the existing pharmacotherapy for neuropathic pain and warrants further investigation

Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences

Background: Gabapentin and pregabalin inhibit Ca2+ currents via high-voltage-activated channels containing the α2δ-1 subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used also for the chronic pain treatment. A large number of clinical trials indicate that gabapentin and pregabalin could be effective as postoperative analgesics. This systematic-narrative review aims to analyse the most recent evidences regarding the effect of gabapentinoids on postoperative pain treatment. Methods: Medline, The Cochrane Library, EMBASE and CINHAL were searched for recent (2006-2009) randomized clinical trials (RCTs) of gabapentin-pregabalin for postoperative pain relief in adults. Quality of RCTs was evaluated according to Jadad method. Visual analogue scale (VAS), opioid consumption and side-effects (nausea, vomiting, dizziness and sedation) were considered the most important outcomes. Results: An overall of 22 gabapentin (1640 patients), 8 pregabalin (707 patients) RCTs and seven meta-analysis were involved in this review. Gabapentin provided better post-operative analgesia and rescue analgesics sparing than placebo in 6 of the 10 RCTs that administered only pre-emptive analgesia. Fourteen RCTs suggested that gabapentin did not reduce PONV when compared with placebo, clonidine or lornoxicam. Pregabalin provided better post-operative analgesia and rescue analgesics sparing than placebo in two of the three RCTs that evaluated the effects of pregabalin alone vs placebo. Four studies reported no pregabalin effects on preventing the PONV. Conclusion: Gabapentin and pregabalin reduce pain and opioid consumption after surgery in confront with placebo, but comparisons with other standard post-operative regimens are not sufficient. Gabapentin and pregabalin seem not to have any influence on the prevention of PONV

Clinical and psychosocial correlates of post-herpetic neuralgia

Post-herpetic neuralgia is the most challenging and debilitating complication of herpes zoster in the immunocompetent host. Because the effect of treatment is disappointing once the syndrome has developed, it is important to know which factors predict post-herpetic neuralgia occurrence to facilitate selection of herpes zoster patients with a higher risk of developing neuralgia and undertake preventative strategies. The present study aimed at identifying demographic, clinical and psychosocial correlates of post-herpetic neuralgia in a sample of 219 immunocompetent patients, who were examined by dermatologists in private practice in Italy and who completed a questionnaire designed to evaluate their clinical and psychosocial profile at the time of clinical diagnosis of herpes zoster and at a follow-up visit 6 months later. In a univariate analysis, post-herpetic neuralgia was associated significantly with older age, longer duration of prodromal pain, greater acute pain intensity, greater extent of rash, presence of abnormal sensations and use of systemic antiviral therapy. Compared to the values at herpes zoster onset, at the follow-up visit patients with post-herpetic neuralgia presented with similar high mean scores of pain intensity, anxiety and depression and greatly reduced quality of life, whereas patients without neuralgia presented with improved scores. In a multivariate model, older age, greater acute pain intensity, greater extent of rash and longer duration of prodromal pain were independently associated with post-herpetic neuralgia. The results of this study may help physicians to identify patients with a higher risk of developing post-herpetic neuralgia and undertaking preventative strategies

No evidence of family history as a risk factor for herpes zoster in patients with post-herpetic neuralgia

Little is known about reactivation of latent varicella zoster virus as herpes zoster in individuals with no underlying immunosuppression. Risk factors include age, sex, ethnicity, exogenous boosting of immunity from varicella contacts, underlying cell-mediated immune disorders, mechanical trauma, psychological stress, and immunotoxin exposure. An association between herpes zoster and family history of zoster has been proposed. A case-control study involving patients affected by post-herpetic neuralgia, which usually follows more severe acute herpes zoster, was performed. The patients with post-herpetic neuralgia were enrolled at the Pain Clinic of the Policlinico Tor Vergata in Rome, Italy, within 1 year from the onset of acute zoster. The controls matched for sex and age were chosen among healthy subjects without a history of herpes zoster presenting at the Internal Medicine Outpatient Clinic for hypertension in the same time period. All the participants in the study gave informed consent and were interviewed by medically trained and blinded investigators using a questionnaire. Similar proportions of the patients and the controls reported a family history of herpes zoster irrespective of the degree of relationship, i.e., 17.4% and 18.2%, respectively, by analyzing only the first-degree relatives [RR 1.03 (CI 95%: 0.78-1.37)], and 28.4% and 29.6%, respectively, by analyzing the total number of relatives [RR 1.03 (CI 95%: 0.81-1.31)]. Further and larger prospective cohort studies are needed to ascertain whether a family history of herpes zoster is really an independent predictor of zoster in different geographical settings

Italian Oncological Pain Survey (IOPS) A Multicentre Italian Study of Breakthrough Pain Performed in Different Settings

Objective: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC). Methods: A standard algorithm was used to confirm the diagnosis of BTP of patients refereed to different settings. Results: 1,412 evaluable cancer patients were enrolled. 53.9% were males and the mean age was 63.7±13.1 years. The mean intensity of background pain was 2.8±0.73. Patients reported 2.4±1.1 BTP episodes/day with a mean intensity of 7.37±1.28. 80.6% patients reported that the BTP had a significant negative impact in everyday life. The majority of patients reported a fast onset of BTP, which was predictable in 50.7% of cases, while BTP with a gradual onset (>10 min) was less predictable (29%) (P=0.001). PCU patients were older, had lower Karnofsky levels, a lower number of BTP episodes/day, a slow onset of BTP onset, and a less predictable BTP. Cancer diagnosis was performed a mean of 23.5 months (SD±32.8) before the assessment. The mean duration of background pain was 3.5 months (SD±3.5), and the mean duration of any analgesic treatment was 2.5 months (SD±3). BTP started a mean of 2.2 months (SD±1.9) before the assessment. Characteristics of BTP were influenced by the course of disease, as well as the duration of background pain and initiation of BTP. Most patients took rapid onset opioids and were satisfied with the treatment. BTP diagnosis was prevalently made by ONC and OPC physicians, and rarely by GPs. Conclusion: This survey performed by an Italian observatory expert review group, has confirmed that the BTP represents a clinically relevant condition with a negative impact on the patient’s quality of life. BTP was detected in all settings involved. A number of factors are associated with the BTP. Also factors regarding the course of disease and setting of care have been assessed. This information may help in stratifying patients or predicting the risk of development of BTP with specific characteristics

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level