title: The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies A randomized trial of behavioral physical therapy interventions for acute and sub-acute low back pain (NCT00373867) Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial Effect of Transversus Abdominis Plane Block With and Without Clonidine on Post–Cesarean Delivery Wound Hyperalgesia and Pain The effects of gabapentin on acute and chronic pain after inguinal herniorrhaphy The Analgesic Properties of Scalp Infiltrations with Ropivacaine After Intracranial Tumoral Resection Health-resource use and costs associated with fibromyalgia in France, Germany, and the United States A Multicenter, Randomized, Controlled Study Evaluating Preventive Etanercept on Postoperative Pain After Inguinal Hernia Repair Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy Effect of early administration of the N-methyl-d-aspartate receptor antagonist amantadine on the development of postmastectomy pain syndrome: a prospective pilot study. Gabapentin does not improve multimodal analgesia outcomes for total knee arthroplasty: a randomized controlled trial Information and advice to patients with back pain can have a positive effect. A randomized controlled trial of a novel educational booklet in primary care. Control of the Lumbar Neutral Zone Decreases Low Back Pain and Improves Self-Evaluated Work Ability: A 12-Month Randomized Controlled Study Risk factors for postherpetic neuralgia in patients with herpes zoster A Comparison of Gabapentin and Ketamine in Acute and Chronic Pain After Hysterectomy The Effects of Three Different Analgesia Techniques on Long-Term Postthoracotomy Pain Preventing chronic postsurgical pain: how much of a difference makes a difference? Secondary Prevention of Low‐Back Pain: A Clinical Trial CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial Evaluation of Efficacy of the Perioperative Administration of Venlafaxine or Gabapentin on Acute and Chronic Postmastectomy Pain Effects of epidural anesthesia on acute and chronic pain after coronary artery bypass grafting. Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2) Perioperative Oral Pregabalin Reduces Chronic Pain After Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial A longitudinal study on the predictive validity of the fear–avoidance model in low back pain A randomized, placebo-controlled trial of oxycodone and of gabapentin for acute pain in herpes zoster Effect of early stellate ganglion blockade for facial pain from acute herpes zoster and incidence of postherpetic neuralgia. Herpes zoster: risk categories for persistent pain. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Pain education to prevent chronic low back pain: a study protocol for a randomised controlled trial Perioperative gabapentin for the prevention of persistent pain after thoracotomy: a randomized controlled trial. Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain Perioperative ketamine does not prevent chronic pain after thoracotomy Evaluation of a program to reduce back pain in nursing personnel. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. Postherpetic neuralgia: impact of famciclovir, age, rash severity, and acute pain in herpes zoster patients. Perioperative Pregabalin Improves Pain and Functional Outcomes 3 Months After Lumbar Discectomy Antidepressant therapy in patients undergoing coronary artery bypass grafting: the MOTIV-CABG trial. The STarT Back Screening Tool and Individual Psychological Measures: Evaluation of Prognostic Capabilities for Low Back Pain Clinical Outcomes in Outpatient Physical Therapy Settings Stress doses of hydrocortisone reduce chronic stress symptoms and improve health-related quality of life in high-risk patients after cardiac surgery: a randomized study. Efficacy of paracetamol for acute low-back pain: a double-blind, randomised controlled trial Polymorphic Variation of the Guanosine Triphosphate Cyclohydrolase 1 Gene Predicts Outcome in Patients Undergoing Surgical Treatment for Lumbar Degenerative Disc Disease Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation. A randomized, multicenter, double-blind, placebo-controlled, dose-finding study of ORG 2766 in the prevention or delay of cisplatin-induced neuropathies in women with ovarian cancer. Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. A Randomized Study of the Effects of Gabapentin on Postamputation Pain Local Administration of Morphine for Analgesia After Autogenous Anterior or Posterior Iliac Crest Bone Graft Harvest for Spinal Fusion: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study North Central Cancer Treatment Group/Alliance trial N08CA—the use of glutathione for prevention of paclitaxel/carboplatin‐induced peripheral neuropathy: A phase 3 randomized, double‐blind, placebo‐controlled study Perioperative Intravenous Lidocaine Decreases the Incidence of Persistent Pain After Breast Surgery Gabapentin Improves Postcesarean Delivery Pain Management: A Randomized, Placebo-Controlled Trial Perioperative Intravenous Ketamine Infusion for the Prevention of Persistent Post-amputation Pain: A Randomized, Controlled Trial Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial Preoperative gabapentin for acute post-thoracotomy analgesia: a randomized, double-blinded, active placebo-controlled study. Comparison of Classification-Based Physical Therapy With Therapy Based on Clinical Practice Guidelines for Patients with Acute Low Back Pain: A Randomized Clinical Trial Early Intervention Options for Acute Low Back Pain Patients: A Randomized Clinical Trial with One-Year Follow-Up Outcomes Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Amitriptyline in the prevention of chemotherapy-induced neuropathic symptoms. A randomized placebo-controlled trial of two doses of pregabalin for postoperative analgesia in patients undergoing abdominal hysterectomy Prevention of post‐herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone Assessment of diclofenac or spinal manipulative therapy, or both, in addition to recommended first-line treatment for acute low back pain: a randomised controlled trial Famciclovir for the Treatment of Acute Herpes Zoster: Effects on Acute Disease and Postherpetic Neuralgia: A Randomized, Double-Blind, Placebo-Controlled Trial The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial. Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation Postoperative Pain and Long-Term Functional Outcome After Administration of Gabapentin and Pregabalin in Patients Undergoing Spinal Surgery Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. Chemotherapy-induced peripheral neuropathy as a predictor of neuropathic pain in breast cancer patients previously treated with paclitaxel. [Preventive analgesic effect of intraoperative administration of ibuprofen-arginine on postmastectomy pain syndrome]. The effects of gabapentin on acute and chronic postoperative pain after coronary artery bypass graft surgery. Gabapentin Attenuates Late but Not Early Postoperative Pain After Thyroidectomy with Superficial Cervical Plexus Block High dose alfentanil pre-empts pain after abdominal hysterectomy The Analgesic Effect of Gabapentin and Mexiletine After Breast Surgery for Cancer Active back school: prophylactic management for low back pain. A randomized, controlled, 1-year follow-up study. Outcome of low back pain in general practice: a prospective study The Effectiveness of Repetitive Paravertebral Injections with Local Anesthetics and Steroids for the Prevention of Postherpetic Neuralgia in Patients with Acute Herpes Zoster A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose‐modification guideline Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). The efficacy of a glial inhibitor, minocycline, for preventing persistent pain after lumbar discectomy: A randomized, double-blind, controlled study
abstract: Background Adjustment for prognostic covariates can lead to increased power in the analysis of r and omized trials . However , adjusted analyses are not often performed in practice . Methods We used simulation to examine the impact of covariate adjustment on 12 outcomes from 8 studies across a range of therapeutic areas . We assessed ( 1 ) how large an increase in power can be expected in practice ; and ( 2 ) the impact of adjustment for covariates that are not prognostic . Results Adjustment for known prognostic covariates led to large increases in power for most outcomes . When power was set to 80 % based on an unadjusted analysis , covariate adjustment led to a median increase in power to 92.6 % across the 12 outcomes ( range 80.6 to 99.4 % ) . Power was increased to over 85 % for 8 of 12 outcomes , and to over 95 % for 5 of 12 outcomes . Conversely , the largest decrease in power from adjustment for covariates that were not prognostic was from 80 % to 78.5 % . Conclusions Adjustment for known prognostic covariates can lead to substantial increases in power , and should be routinely incorporated into the analysis of r and omized trials . The potential benefits of adjusting for a small number of possibly prognostic covariates in trials with moderate or large sample sizes far outweigh the risks of doing so , and so should also be considered Abstract Psychological factors consistent with fear‐avoidance models are associated with the development of chronic low back pain ( LBP ) . As a result , grade d activity ( GA ) and grade d exposure ( GX ) have been suggested as behavioral treatment options . This clinical trial compared the effectiveness of treatment‐based classification ( TBC ) physical therapy alone to TBC augmented with GA or GX for patients with acute and sub‐acute LBP . Our primary hypothesis was that GX would be most effective for those with elevated pain‐related fear . In total , 108 patients enrolled in this clinical trial and were r and omly assigned to receive TBC , GA , or GX . Outcomes were assessed by a blinded evaluator at 4 weeks and by mail at 6 months . The primary outcomes for this trial were disability and pain intensity , and the secondary outcomes were fear‐avoidance beliefs , pain catastrophizing , and physical impairment . There were no differences in 4‐week and 6‐month outcomes for reduction of disability , pain intensity , pain catastrophizing , and physical impairment . GX and TBC were associated with larger reductions in fear‐avoidance beliefs at 6 months only . Six‐month reduction in disability was associated with reduction in pain intensity , while 6‐month reduction in pain intensity was associated with reductions in fear‐avoidance beliefs and pain catastrophizing . This trial suggests that supplementing TBC with GA or GX was not effective for improving important outcomes related to the development of chronic LBP Background Perioperative administration of pregabalin , which is effective for neuropathic pain , might reduce early postoperative and chronic pain . This r and omized , double-blinded , placebo-controlled trial ( Clinical Trials.gov ID NCT00905580 ) was design ed to investigate the efficacy and safety of pregabalin for reducing both acute postoperative pain and the development of chronic pain in patients after robot-assisted endoscopic thyroidectomy . Methods Ninety-nine patients were r and omly assigned to groups that received pregabalin 150 mg or placebo 1 h before surgery , with the dose repeated after 12 h. Assessment s of pain and side effects were performed 48 h postoperatively . The incidences of chronic pain and hypoesthesia in the anterior chest were recorded 3 months after surgery . Results Ninety-four patients completed the study .  Verbal numerical rating scale scores for pain and the need for additional analgesics were lower in the pregabalin group ( n = 47 ) than the placebo group ( n = 47 ) during 48 h postoperatively ( P < 0.05 ) . However , incidences of sedation and dizziness were higher in the pregabalin group ( P < 0.05 ) . There were no differences between the groups in the incidences of chronic pain and chest hypoesthesia at 3 months after surgery . Conclusions Perioperative administration of pregabalin ( 150 mg twice per day ) was effective in reducing early postoperative pain but not chronic pain in patients undergoing robot-assisted endoscopic thyroidectomy . Caution should be taken regarding dizziness and sedation Background and Objectives The transversus abdominis plane ( TAP ) block is an established technique to manage post – cesarean delivery pain .  Transversus abdominis plane blocks with a local anesthetic only offer no analgesic benefits compared with intrathecal morphine . Adjuvants to extend TAP block duration and possibly reduce wound hyperalgesia , known to be a risk factor for chronic pain , have not been studied . We hypothesized that a TAP block with clonidine will affect postsurgical wound hyperalgesia and improve pain outcomes . Methods Ninety women were r and omly assigned to receive 1 of 3 TAP blocks after cesarean delivery  : saline ( placebo ) , bupivacaine ( BupTAP ) , or bupivacaine + clonidine ( CloTAP ) . The primary outcome was wound hyperalgesia index at 48 hours . Secondary outcomes included pain scores , analgesic consumption , and pain descriptors up to 12 months . Results Wound hyperalgesia index at 48 hours ( median [ 25th–75th percentiles ] ) was 1.07 ( 0.48–3.26 ) in the placebo group , 1.27 ( 0.59–2.95 ) in the BupTAP group , and 0.74 ( 0.09–2.25 ) in the CloTAP group ( P = 0.48 ) . Morphine request in the postanesthesia care unit was significantly higher in the placebo group compared with the other TAP groups ( P = 0.01 ) . Postoperative pain scores and requests for breakthrough medication at 48 hours ( 30 % in the placebo group , 24 % in the BupTAP group , and 12 % in the CloTAP group , P = 0.25 ) or chronic pain descriptors reported up to 12 months did not differ significantly among groups . Conclusions Adding clonidine to a TAP block with bupivacaine did not affect wound hyperalgesia index and it did not improve short-term or long-term pain scores in women undergoing elective cesarean delivery . Further studies are warranted to determine the benefits of antihyperalgesic adjuvants in TAP solutions for specific individuals at risk for chronic pain Background and objective To find out whether preoperative gabapentin use had a favourable effect on long-term postoperative pain in patients undergoing inguinal herniorrhaphy . Methods Sixty male patients – aged 20–40 years – who were scheduled for unilateral inguinal herniorrhaphy under spinal anaesthesia  were included in this prospect i ve , r and omized , double-blind study . The patients were r and omly allocated to two groups : the gabapentin group ( n = 30 ) received single-dose 1.2 g oral gabapentin 1 h before surgery , and the placebo group received a placebo capsule instead . Spinal anaesthesia was performed with heavy bupivacaine , and all operations were performed by the same surgeon with the same technique . Postoperative analgesia was evaluated during sitting and lying with a visual analogue scale . Assessment of postoperative pain at 1 , 3 and 6 months was carried out with an 11-point numerical rating scale ; 0 indicating ‘ no pain ’ and 10 indicating ‘ worst pain imaginable ’ . Patients who had numerical rating scale scores of more than 0 were further evaluated with regard to the impact of pain on their daily activities . Results When compared with the placebo group , the gabapentin group displayed significantly lower visual analogue scale scores ( lying and sitting ) and total tramadol consumption at 8 , 12 , 16 , 20 and 24 h after surgery ( P < 0.05 ) and higher postoperative patient satisfaction scores ( P < 0.05 ) . Numerical rating scale scores at 1 , 3 and 6 months after surgery were lower in the gabapentin group than in the placebo group ( P < 0.05 ) . The number of patients whose daily activities were adversely affected by pain was smaller in the gabapentin group at the first month ; however , the two groups were found to be similar at 3 and 6 months . Conclusion We conclude that preoperative single-dose gabapentin decreases the intensity of acute postoperative pain , tramadol consumption and the incidence and intensity of pain in the first 6 months after inguinal herniorrhaphy BACKGROUND : The issue of postoperative pain after neurosurgery is controversial . It has been reported as mild to moderate and its treatment may be inadequate . Infiltration of the surgical site with local anesthetics has provided transient benefit after craniotomy , but its effect on chronic pain has not been evaluated . Accordingly , we design ed the present study to test the hypothesis that ropivacaine infiltration of the scalp reduces acute and persistent postoperative pain after intracranial tumor resection . METHODS : This was a prospect i ve , single-blinded study . Inclusion criteria were intracranial tumor resection , age ≥18 or ≤80 yr , and ability to underst and and use a visual analog scale ( VAS ) . Exclusion criteria were history of craniotomy , chronic drug abuse , and neurologic disorders . All eligible patients were r and omly included in Group I ( infiltration ) or C ( control ) . Postoperative analgesia was IV acetaminophen combined with nalbuphine . At the end of the surgery , Group I received an infiltration of the surgical site with 20 mL of ropivacaine 0.75 % . Acute pain was evaluated hourly by VAS during the first 24 h. The analgesic effect of ropivacaine was evaluated based on total consumption of nalbuphine and VAS scores . The incidence of persistent pain and neuropathic pain was assessed at the 2-mo postoperative evaluation . We used the Student ’s t-test to compare total nalbuphine consumption , repeated measures analysis of variance with post hoc Bonferroni t-test for VAS score and the Fisher ’s exact test for chronic and neuropathic pain . RESULTS : Fifty-two patients were enrolled , 25 in Group I and 27 in Group C. Demographic and intraoperative data were similar between groups . Group I showed a nonsignificant trend toward reduced nalbuphine consumption during the first postoperative day , 11.2 ± 9.2 mg vs 16.6 ± 11.0 mg for Group C ( mean ± sd , P = 0.054 ) . VAS scores were significantly higher in Group C. Two months after surgery , persistent pain was significantly lower in Group I , 2/24 ( 8 % ) vs 14/25 ( 56 % ) , P = 0.0003 . One patient ( 4.1 % ) in Group I versus six ( 25 % ) patients in Group C ( P = 0.04 ) experienced neuropathic pain . CONCLUSIONS : Because pain is moderate after intracranial tumor resection , there is limited interest in scalp infiltrations with ropivacaine in the acute postoperative period . Nevertheless , these infiltrations may be relevant for the rehabilitation of neurosurgical patients and their quality of life by limiting the development of persistent pain and particularly neuropathic pain Background Fibromyalgia ( FM ) is a chronic disorder characterized by widespread , persistent pain . Prospect i ve and retrospective studies have demonstrated substantial health-care costs associated with FM in a number of countries . This study evaluated and compared health-re source use ( HRU ) and associated costs related to FM in routine clinical practice across the US , France , and Germany . Methods Two separate , cross-sectional , observational studies of subjects with FM were conducted : one in the US and one in France and Germany .  HRU related to prescription medication , physician office visits , diagnostic tests , and hospitalizations was abstract ed from chart review ; patient out-of-pocket costs and lost productivity were collected via subject self-report . Costs were assigned to HRU based on st and ard algorithms . Direct and indirect costs were evaluated and compared by simple linear regression . Results A total of 442 subjects ( 203 US , 70 France , 169 Germany ) with FM were analyzed . The mean ( st and ard deviation ) age in the US , France , and Germany was 47.9 ( 10.9 ) , 51.2 ( 9.5 ) , and 49.2 ( 9.8 ) , respectively ( P = 0.085 ) . Most subjects were female ( 95 % US , 83 % France , 80 % Germany ) ( P < 0.001 ) . Adjusted annual direct costs per subject for FM were significantly higher in the US ( $ 7087 ) than in France ( $ 481 , P < 0.001 ) or Germany ( $ 2417 , P < 0.001 ) . Adjusted mean annual indirect costs per subject for FM were lower in the US ( $ 6431 ) than in France ( $ 8718 ) or Germany ( $ 10,001 ) , but represented a significant proportion of total costs in all countries . Conclusion The significant HRU and costs associated with FM in the US , France , and Germany documented in this study highlight the substantial global economic burden of FM . Indirect costs represented a significant proportion of the total costs , particularly in Europe . Comparisons between the three countries show differences in HRU , with significantly higher direct costs in the US compared with France and Germany BACKGROUND :  Chronic postsurgical pain ( CPSP )  affects between 5 % and 70 % of surgical patients , depending on the surgery . There is no reliable treatment for CPSP , which has led to an increased emphasis on prevention . In this study , we sought to determine whether preventive etanercept can decrease the magnitude of postoperative pain and reduce the incidence of CPSP . METHODS : We performed a multicenter , r and omized study in 77 patients comparing subcutaneous etanercept 50 mg administered 90 minutes before inguinal hernia surgery with saline .  Patients , surgeons , anesthesiologists , the injecting physician , nursing staff , and evaluators were blinded . The primary outcome measure was a 24-hour numerical rating scale pain score . Secondary outcome measures were postanesthesia care unit pain scores , 24-hour opioid requirements , time to first analgesic , and pain scores recorded at 1 month , 3 months , 6 months , and 12 months . RESULTS : Mean 24-hour pain scores were 3.3 ( 95 % confidence interval [ CI ] , 3.2–4.6 ) in the etanercept and 3.9 ( 95 % CI , 2.6–4.0 ) in the control group ( P = 0.22 ) . The mean number of analgesic pills used in the first 24 hours was 4.0 ( SD , 2.8 ) in the treatment versus 5.8 ( SD , 4.2 ) in the control group ( P = 0.03 ) . At 1 month , 10 patients ( 29 % ) in the treatment group reported pain versus 21 ( 49 % ) control patients ( P = 0.08 ) . The presence of pain at 1 month was significantly associated with pain at 3 months ( hazard ratio , 0.74 ; 99 % CI , 0.52–0.97 ; P = 0.03 ) . CONCLUSION : Although preventive etanercept was superior to saline in reducing postoperative pain on some measures , the effect sizes were small , transient , and not statistically significant . Different dosing regimens in a larger population should be explored in future studies Background : Ketamine potentiates intravenous or epidural morphine analgesia . The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain . Methods : Forty-nine patients scheduled to undergo open thoracotomy were r and omly assigned to receive one of two anesthesia regimens : continuous epidural infusion of ropivacaine and morphine , along with intravenous infusion of ketamine ( 0.05 mg · kg−1 · h−1 [ approximately 3 mg/h ] , ketamine group , n = 24 ) or placebo ( saline , control group , n = 25 ) . Epidural analgesia was continued for 2 days after surgery , and infusion of ketamine or placebo was continued for 3 days . Pain was assessed at 6 , 12 , 24 , and 48 h after surgery . Patients were asked about their pain , abnormal sensation on the wound , and inconvenience in daily life at 7 days and 1 , 3 , and 6 months after surgery . Results : The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group ( pain at rest , 9 ± 11 vs. 25 ± 20 and 9 ± 11 vs. 18 ± 13 ; pain on coughing , 26 ± 16 vs. 50 ± 17 and 30 ± 18 vs. 43 ± 18 , mean ± SD ; P = 0.002 and P = 0.01 , P < 0.0001 and P = 0.02 , respectively ) . The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group ( 0.5 [ 0–4 ] vs. 2 [ 0–5 ] and 0 [ 0–5 ] vs. 1.5 [ 0–6 ] , median [ range ] , respectively ; P = 0.02 ) . Three months after surgery , a higher number of control patients were taking pain medication ( 2 vs. 9 ; P = 0.03 ) . Conclusions : Very-low-dose ketamine ( 0.05 mg · kg−1 · h−1 ) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain UNLABELLED Postmastectomy pain syndrome ( PMPS ) is a neuropathic pain syndrome that might develop after breast surgery . Like many other forms of neuropathic pain , it is relatively resistant to treatment and negatively affects the quality of life . A double-blind , r and omized , placebo-controlled pilot trial was conducted to study the analgesic efficacy of perioperative administration of the N-methyl-D-aspatrate ( NMDA ) receptor antagonist amantadine in preventing PMPS after mastectomy plus axillary lymph node dissection ( ALND ) . In the study group , a regimen of 200 mg/day of amantadine was started 1 day before surgery and continued for 14 days , whereas the control group received a placebo .  Patients were required to indicate the exact location of their pain and to record its level at 1 , 3 , and 6 months after surgery . Neurologic examination and Quantitative Thermal Testing ( QTT ) were performed 1 and 6 months after surgery . On both the neurologic examination and the QTT , all patients , regardless of the perioperative intervention ( amantadine or placebo ) , presented evidence for nerve injury , manifested primarily by painful hypoesthesia ( anesthesia dolorosa ) in the axilla or inner arm . PMPS persisted for the entire duration of the study in 82 % of the patients who were available for follow-up . The average intensity of the pain was moderate in both groups and tended not to decline over time . No differences between the 2 groups in any of the outcome parameters reached statistical significance . According to the results of the present pilot study , the NMDA antagonist amantadine does not prevent the development of PMPS in patients who undergo breast surgery with ALND . PERSPECTIVE Breast surgery that involves ALND seems to uniformly cause nerve injury , which can not be prevented by the perioperative administration of 200 mg of amantadine . It is most commonly presented by painful hypoesthesia or anesthesia dolorosa in the axillary/inner arm area , which is moderate in intensity and likely to persist for at least 6 months Purpose This study assessed whether gabapentin given preoperatively and for two days postoperatively ( in addition to patient-controlled analgesia [ PCA ] morphine , acetaminophen , and ketorolac ) is effective in reducing morphine requirements and moderating pain scores when compared with placebo for primary total knee arthroplasty . Methods This single-centre double-blind r and omized controlled trial was undertaken in patients who underwent primary total knee arthroplasty . All subjects received acetaminophen 1,000 mg and ketorolac 15 mg po preoperatively . Postoperatively , subjects received PCA morphine , acetaminophen 1,000 mg every six hours , and ketorolac 15 mg po every six hours . Subjects received either gabapentin 600 mg po preoperatively followed by 200 mg po every eight hours for two days or matching placebo . The primary outcome was cumulative morphine consumption at 72 hr following surgery . Secondary outcome measures included pain scores and patient satisfaction . Results There were 52 subjects in the gabapentin group and 49 subjects in the placebo group .  The average cumulative morphine consumption at 72 hr postoperatively was 66.3 mg in the gabapentin group and 72.5 mg in the placebo group ( difference −6.2 mg ; 95 % confidence interval −29.1 to 16.8 mg ; P = 0.59 ) . Mean pain scores at rest , with passive movement , or with weight bearing were similar in both groups at corresponding time periods for the first three days following surgery . In addition , mean patient satisfaction scores and hospital length of stay were similar in the two groups . Conclusion Gabapentin 600 mg po given preoperatively followed by 200 mg po every eight hours for two days has no effect on postoperative morphine consumption , pain scores , patient satisfaction , or length of hospital stay . This trial is registered at Clinical Trials.gov NCT01307202.RésuméObjectifCette étude a consisté à déterminer si la gabapentine , donnée en préopératoire et pendant deux jours après l’opération ( en addition à de la morphine en analgésie contrôlée par le patient [ ACP ] , de l’acétaminophène et du kétorolac ) , était efficace pour réduire les besoins en morphine ainsi que pour diminuer les scores de douleur par rapport à un placebo pour une arthroplastie totale du genou . MéthodeCette étude r and omisée contrôlée à double insu a été réalisée dans un seul centre , auprès de patients subissant une arthroplastie totale du genou primaire . Tous les patients ont reçu 1000 mg d’acétaminophène et 15 mg de kétorolac po avant l’opération . En postopératoire , les patients ont reçu de la morphine en ACP , 1000 mg d’acétaminophène toutes les six heures et 15 mg de kétorolac po toutes les six heures . Les patients ont reçu soit 600 mg de gabapentine po en préopératoire suivis de 200 mg po aux huit heures durant deux jours , soit un placebo correspondant . Le critère d’évaluation principal était la consommation cumulée de morphine à 72 h après la chirurgie . Les critères d’évaluation secondaires étaient les scores de douleur et la satisfaction des patients .RésultatsLe groupe gabapentine  comptait 52 patients et le groupe placebo en comptait 49 . La consommation cumulée moyenne de  morphine  à 72 h postopératoires était de 66,3 mg dans le groupe gabapentine et de 72,5 mg dans le groupe placebo ( différence −6,2 mg ; intervalle de confiance 95 % −29,1 à 16,8 mg ; P = 0,59 ) . Les scores moyens de douleur au repos , avec un mouvement passif ou avec un mouvement contre résistance , étaient semblables dans les deux groupes à des points dans le temps correspondants au cours des trois premiers jours postopératoires . En outre , les scores moyens de satisfaction des patients et la durée du séjour à l’hôpital étaient semblables dans les deux groupes . Conclusion La gabapentine 600 mg po en préopératoire suivie de 200 mg po toutes les huit heures pendant deux jours n’a aucun effet sur la consommation postopératoire de morphine , les scores de douleur , la satisfaction des patients ou la durée du séjour à l’hôpital . Cette étude est enregistrée sous Clinical Trials.gov NCT01307202 STUDY DESIGN A double-blind , r and omized controlled trial of a novel educational booklet compared with a traditional booklet for patients seeking treatment in primary care for acute or recurrent low back pain . OBJECTIVE To test the impact of a novel educational booklet on patients ' beliefs about back pain and functional outcome . SUMMARY OF BACKGROUND DATA The information and advice that health professionals give to patients may be important in health care intervention , but there is little scientific evidence of their effectiveness . A novel patient educational booklet , The Back Book , has been developed to provide evidence -based information and advice consistent with current clinical guidelines . METHODS One hundred sixty-two patients were given either the experimental booklet or a traditional booklet . The main outcomes studied were fear-avoidance beliefs about physical activity , beliefs about the inevitable consequences of back trouble , the Rol and Disability Question naire , and visual analogue pain scales . Postal follow-up response at 1 year after initial treatment was 78 % . RESULTS Patients receiving the experimental booklet showed a statistically significant greater early improvement in beliefs which was maintained at 1 year . A greater proportion of patients with an initially high fear-avoidance beliefs score who received the experimental booklet had clinical ly important improvement in fear-avoidance beliefs about physical activity at 2 weeks , followed by a clinical ly important improvement in the Rol and Disability Question naire score at 3 months . There was no effect on pain . CONCLUSION This trial shows that carefully selected and presented information and advice about back pain can have a positive effect on patients ' beliefs and clinical outcomes , and suggests that a study of clinical ly important effects in individual patients may provide further insights into the management of low back pain Study Design . A r and omized controlled study with 12 months intervention . Objective . To study the effectiveness of a training intervention with emphases on the control of lumbar neutral zone ( NZ ) and behavior modeling as secondary prevention of  low back pain ( LBP ) and disability .  Summary of Background Data . Improving the control of lumbar NZ and enhancing muscle activation patterns ensuring spinal stability have been proposed as means for secondary prevention of LBP and disability . In addition , cognitive behavior interventions have been shown to lower the risk of recurrence of LBP and long-term disability . Methods . Middle-aged working men with recent LBP but without severe disability were r and omly allocated to either a training ( TG , n = 52 ) or control group ( CG , n = 54 ) . The aim was to exercise twice a week for 12 months , once guided and once independently . The outcome measures were the changes in intensity of LBP , disability , self-evaluated future work ability , and neuromuscular fitness . Results . The intensity of LBP decreased significantly more ( 39 % ) in the TG than in CG at 12 months . The proportion of subjects with negative expectations about their future work ability decreased in both groups at 6 and 12 months ; however , the proportion was significantly bigger in TG compared with CG ( P = 0.028 ) . There effects on disability indexes and fitness were not statistically significant . Conclusions . Controlling lumbar NZ is a specific form of exercise and daily self-care with potential for prevention of recurrent nonspecific LBP and disability among middle aged working men Objectives : To identify risk factors for postherpetic neuralgia ( PHN ) using a vali date d definition of this chronic neuropathic pain syndrome , to determine combinations of risk factors that identify patients with a high risk of developing PHN , and to examine the characteristics of patients with subacute herpetic neuralgia , that is , pain that persists beyond the acute phase of herpes zoster but that resolves before PHN can be diagnosed . Methods : The authors examined baseline and follow-up data from 965 herpes zoster patients enrolled within 72 hours of rash onset in two clinical trials of famciclovir .  Results : Univariate and multivariate analyses indicated that older age , female sex , presence of a prodrome , greater rash severity , and greater acute pain severity made independent contributions to identifying which patients developed PHN . Patients with subacute herpetic neuralgia who did not develop PHN were significantly younger and had less severe acute pain than PHN patients but were significantly more likely to have severe and widespread rash than patients without persisting pain . Conclusions : The independent contributions to the prediction of PHN made by older age , female sex , presence of a prodrome , greater rash severity , and greater acute pain severity suggest that these risk factors reflect different mechanisms that each contribute to the development of PHN . Subacute herpetic neuralgia that does not progress to PHN may reflect peripheral tissue damage and inflammation caused by a particularly severe or widespread rash BACKGROUND : Gabapentin and ketamine are popular analgesic adjuvants for improving perioperative pain management . We design ed this double-blind , placebo-controlled study to test and compare the preventive effects of perioperative ketamine and gabapentin on early and chronic pain after elective hysterectomy . METHODS : Sixty patients undergoing abdominal hysterectomy were r and omly assigned to 1 of the following 3 groups : control group received oral placebo capsules and bolus plus infusion of saline ; ketamine group received oral placebo capsules and , before incision , 0.3 mg/kg IV bolus and 0.05 mg·kg−1·h−1 infusion of ketamine until the end of surgery ; and gabapentin group received oral gabapentin 1.2 g and bolus plus infusion of saline . The anesthetic technique was st and ardized , and the postoperative assessment s included verbal rating scales for pain and sedation , IV morphine usage , quality of recovery assessment , recovery of bowel function , resumption of normal activities , and patient satisfaction with their pain management . Patients were question ed at 1 , 3 , and 6 mo after surgery for chronic postoperative pain . RESULTS : Postoperative pain scores were significantly lower in the gabapentin group compared with the ketamine and control groups , and patient-controlled analgesia morphine use was significantly reduced in both treatment groups ( versus control group ) ( P < 0.001 ) . Total patient-controlled analgesia morphine use was decreased by 35 % and 42 % in the ketamine and gabapentin groups , respectively , compared with the control group ( P < 0.001 ) . Patient satisfaction with pain treatment was significantly improved in the ketamine and gabapentin groups compared with the control group ( P < 0.001 ) . The incidence of incisional pain and related pain scores at the 1- , 3- , and 6-mo follow-up were significantly lower in the gabapentin group compared with the ketamine and control groups ( P < 0.001 ) . CONCLUSION : Gabapentin and ketamine are similar in improving early pain control and in decreasing opioid consumption ; however , gabapentin also prevented chronic pain in the first 6 postoperative months In this clinical , r and omized , prospect i ve study , we compared the effects of three different analgesia techniques ( thoracic epidural analgesia [ TEA ] with and without preoperative initiation and IV patient-controlled analgesia [ IV-PCA ] ) on postthoracotomy pain in 69 patients . In two groups , a thoracic epidural catheter was inserted preoperatively . Group Pre-TEA had bupivacaine and morphine solution preoperatively and intraoperatively . Postoperative analgesia was maintained with epidural PCA with a similar solution . Group Post-TEA , with no intraoperative medication , had the same postoperative analgesia as Group Pre-TEA plus the bolus dose . Group IV-PCA received only IV-PCA with morphine for postoperative analgesia . Pain was evaluated every 4 h during the first 48 h at rest , cough , and movement . Pre-TEA was associated with decreased pain compared with the other groups . Six months later , the patients were asked about their pain . The incidence and the intensity of pain were most frequent in Group IV-PCA ( 78 % ) and were the least in Group Pre-TEA ( 45 % ) ( Group Pre-TEA versus Group IV-PCA , P = 0.0233 ; Group Pre-TEA versus Group IV-PCA , P = 0.014 ) . Patients having pain on the second postoperative day had 83 % chronic pain . TEA with preoperative initiation is a preferable method in preventing acute and long-term thoracotomy pain AFTER surgical procedures such as amputation , mastectomy , and thoracotomy , as many as 60 % of patients continue to experience pain for at least 6 months , with approximately 10 % reporting severe pain . These chronic postsurgical pain conditions have major adverse effects on health-related quality of life , including physical functioning and emotional well-being . Unfortunately , the efficacy of existing treatments is limited and many patients remain refractory to currently available therapies . For this reason , the development of interventions that prevent chronic pain after surgery has the potential to have a major impact on public health . Substantial attention has been devoted to the hypothesis that the incidence of chronic postsurgical pain can be reduced by “ preventive ” analgesia , and the benefits of preoperative , intraoperative , and postoperative analgesic interventions have been investigated alone and in various combinations . Although the results of these studies suggest that reduced acute pain and analgesic consumption can extend beyond the duration of action of the preventive analgesic interventions , there is little evidence that chronic postsurgical pain can be prevented . Placebocontrolled r and omized clinical trials are needed to determine what specific analgesic interventions are efficacious for preventing chronic pain after what types of surgery for which patients . – 6 A critical component of future clinical trials will involve determining the clinical importance of the benefits of preventive analgesia . The results of recent studies and consensus recommendations provide a foundation for interpreting the benefits of chronic pain treatment ; however , little attention has been paid to determining what magnitudes of chronic pain prevention are clinical ly meaningful . As is true of treatment benefits , evaluating the importance of preventive benefits involves a frequently misunderstood distinction between the interpretation of the clinical importance of individual patient benefits and the interpretation of the clinical importance of group differences . The results of multiple studies have shown that individual patients consider chronic pain reductions of at least 30 % on numerical or visual analog scales to be moderately clinical ly important , whereas reductions of at least 50 % represent substantial improvements . These thresholds are based on ratings by patients of their own improvement at the end of chronic pain trials , and consistent results have been found across different chronic pain conditions and in patients administered active treatments as well as placebo . Criteria for identifying clinical ly meaningful individual improvements are necessary to categorize patients as “ responders ” or “ nonresponders , ” which makes it possible to compare the percentages of patients who achieve clinical ly important outcomes between different treatment and comparison groups . Unfortunately , criteria for determining clinical ly important improvements in patients being treated for chronic pain can not be extrapolated to those undergoing perioperative analgesic interventions to prevent chronic pain . Currently , there are no data that make it possible to determine whether patients who have not experienced chronic pain would consider its prevention after surgery important enough to undergo preoperative , intraoperative , and postoperative analgesic interventions . Evaluations of individual patient improvements associated with chronic pain treatments have emphasized pain reduction , but patients considering the prevention of conditions for which their risk is relatively low can also be expected to be particularly concerned with the adverse effects , safety risks , inconvenience , and costs of the preventive intervention . It is likely that an efficacious preventive analgesia would not completely prevent chronic pain but would instead partially reduce its incidence , intensity , or duration . Such partial preventive benefits would , of course , be even harder for patients to evaluate ; for example , would patients consider reducing pain intensity 6 months after surgery from a daily average of 4 to 2 on a 0–10 scale a clinical ly important benefit ? Would this evaluation change if this reduction in pain intensity at 6 months is known to last for another 2 yr , or if the preventive intervention requires that patients take a medication that causes sedation , nausea , and constipation for 7 days before and 30 days after their operation ? Evaluations of the clinical importance of preventive analgesia must reflect the magnitude of the reductions in chronic pain incidence , intensity , or duration that the intervention would provide . However , even small reductions in the incidence or intensity of a chronic pain condition that can last for months or even years might be considered clinical ly important by patients if Accepted for publication November 17 , 2009 . The authors are not supported by , nor maintain any financial interest in , any commercial activity that may be associated with the topic of this article A clinical trial , aim ed at secondary prevention of low-back pain , was performed in 142 hospital employees reporting at least three annual episodes of this condition . Participants were r and omly assigned to one of three groups : a calisthenics program ( CAL ) for 3 months with biweekly sessions of flexion exercises , a back school program ( 5 sessions ) , and a control group . The effectiveness of the two intervention programs was evaluated over a 1-year period . Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected . A monthly surveillance for the whole year showed a mean of 4.5 “ painful months ” in the CAL group versus 7.3 and 7.4 months in the back school and control groups , respectively ( P < 0.0001 ) . The superiority of the CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength . The increased trunk flexion was associated with the rate of participation in the CAL sessions . Further research is needed to answer the question of “ intensity versus type of exercise ” by comparing different intervention programs , with similar intensity The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . OBJECTIVE Long-term pain is a common sequela of thoracotomy , occurring in approximately 50 % of patients 2 years after thoracic surgery . Despite this alarming statistic , little is known about the factors responsible for the transition of acute to chronic pain . The aim of the present study is to identify predictors of long-term post-thoracotomy pain . DESIGN Follow-up was for 1.5 years for patients who had participated in a prospect i ve , r and omized , controlled trial of preemptive , multimodal analgesia .  SETTING Subjects were recruited from a tertiary care center . PATIENTS Thirty patients who had undergone lateral thoracotomy  were followed up by telephone , administered a structured interview , and classified according to long-term pain status . MAIN OUTCOME MEASURES Present pain status was measured by a verbal rating scale ( VAS ) . Measures obtained within the first 48 h after surgery were compared between patients with and without pain 1.5 years later . These include VAS pain scores at rest and after movement , McGill Pain Question naire data , patient-controlled morphine consumption ( mg ) , and pain thresholds to pressure applied to a rib contralateral to the thoracotomy incision . RESULTS Fifty-two percent of patients reported long-term pain . Early postoperative pain was the only factor that significantly predicted long-term pain . Pain intensity 24 h after surgery , at rest , and after movement was significantly greater among patients who developed long-term pain compared with pain-free patients . A significant predictive relationship was also found at 24 and 48 h using the McGill Pain Question naire . Cumulative morphine was comparable for the two groups . Pain thresholds to pressure applied to a rib contralateral to the incision did not differ significantly between the groups . CONCLUSION Aggressive management of early postoperative pain may reduce the likelihood of long-term post-thoracotomy pain Background Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel . Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy . Methods This study was a r and omized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy ( PIPN ) .  Eligible patients with breast cancer r and omly assigned to take omega-3 fatty acid pearls  , 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo .  Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on " reduced Total Neuropathy Score " . Results Twenty one patients ( 70 % ) of the group taking omega-3 fatty acid supplement ( n = 30 ) did not develop PN while it was 40.7 % ( 11 patients ) in the placebo group(n = 27 ) . A significant difference was seen in PN incidence ( OR = 0.3 , .95 % CI = ( 0.10 - 0.88 ) , p = 0.029 ) . There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group ( 0.95 % CI = ( −2.06 -0.02 ) , p = 0.054 ) . Conclusions Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN . Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents . Finding a way to solve the disabling effects of PIPN would significantly improve the patients ’ quality of life . Trial registration This trial was registered at Clinical Trials.gov ( NCT01049295 Objectives Postmastectomy pain syndrome is a neuropathic pain syndrome that is known to develop after breast surgery . Preemptive analgesia has been shown to be efficacious in reducing postoperative pain , and may be effective in reducing the incidence of certain types of neuropathic pain . We investigated the analgesic efficacy of Venlafaxine and gabapentin on acute and chronic pain associated with cancer breast surgery . Patients and Methods The study was carried out on 150 patients scheduled for either partial or radical mastectomy with axillary dissection . They were r and omized in a double-blinded manner to receive , extended release Venlafaxine 37.5 mg/d , gabapentin 300 mg/d , or placebo for 10 days starting the night before operation . Pain scores were recorded at rest and movement ( visual analog scale ) at 4 , 12 , and 24 hours on the first day postoperatively , daily from the second to tenth day postoperatively and visual analog scale in addition to pain character 6 months later . Analgesic requirements were compared between the 3 groups . Results Pain after movement was reduced by gabapentin from the second to tenth postoperative day and venlafaxine group in the last 3 days but no difference was found between the groups regarding pain during rest . Gabapentin reduced morphine consumed in the first 24 hours postoperatively . The analgesic requirements from the second to tenth days for codeine and paracetamol were reduced in venlafaxine and gabapentin groups compared to the control group . Six months later , the incidence of chronic pain , its intensity , and need for analgesics were reduced in venlafaxine compared to gabapentin and the placebo group . However , burning pain was more frequent in the control groups than in the gabapentin . Conclusion Venlafaxine 37.5 mg/d extended release or gabapentin 300 mg/d have equipotent effects ( except on the first day in venlafaxine group ) in reducing analgesic requirements , although gabapentin is more effective in reducing pain after movement . Venlafaxine significantly reduced the incidence of postmastectomy pain syndromes ( chronic pain ) 6 months in women having breast cancer surgery . Gabapentin had no effect on chronic pain except decreasing incidence of burning pain OBJECTIVE To evaluate the effects of thoracic epidural anesthesia ( TEA ) as an adjunct to general anesthesia ( GA ) on postoperative pain after coronary artery bypass grafting ( CABG ) . METHODS Between April 2009 and March 2010 , 40 patients with ischemic heart disease scheduled for elective CABG were prospect ively r and omized to receive either GA ( n = 20 ) or GA + TEA ( n = 20 ) . Through epidural catheters , patients received an infusion of ( 10 - 20 mg/h ) 0.25%-bupivacaine intraoperatively and during the first 24 hours after surgery . Study endpoints included assessment of postoperative pain at rest and with coughing , rescue analgesic need , and postoperative course . RESULTS The differences in pain scores were decreased at rest during 6 ( 0.1 ± 0.3 vs. 2.4 ± 1.8 ; p < 0.05 ) and 12 hours ( 0.1 ± 0.3 vs. 3.9 ± 2.3 ; p < 0.05 ) and with coughing at 6 ( 0.1 ± 0.3 vs. 5.6 ± 2.2 ; p < 0.05 ) , 12 ( 0.1 ± 0.3 vs. 5.9 ± 2.3 ; p < 0.05 ) , and 24 hours ( 0.05 ± 0.2 vs. 4.6 ± 2.9 ; p < 0.05 ) in the GA + TEA group . At one-month follow-up , pain scores were decreased in GA + TEA group ( 0.3 ± 0.7 vs. 1.6 ± 1.3 ; p = 003 ) . There was no significant difference at three and six months . Mechanical ventilation time ( 4.7 ± 1.2 vs. 2.9 ± 1.1 hours ; p < 0.05 ) , intensive care unit stay ( 28.4 ± 9.0 vs. 22.4 ± 3.4 hours ; p < 0.05 ) , and hospital stay ( 7.2 ± 1.1 vs. 6.1 ± 0.3 days ; p = 0.001 ) were reduced in the GA + TEA group . CONCLUSIONS TEA significantly reduced the intensity of postoperative pain and analgesic consumption in the early postoperative period following CABG . The delivery of effective analgesia along with conventional medications may prevent chronic pain after surgery ABSTRACT The objective of the present research was to develop a single measure of the major symptoms of both neuropathic and non‐neuropathic pain that can be used in studies of epidemiology , natural history , pathophysiologic mechanisms , and treatment response . We exp and ed and revised the Short‐form McGill Pain Question naire1 ( SF‐MPQ ) pain descriptors by adding symptoms relevant to neuropathic pain and by modifying the response format to a 0–10 numerical rating scale to provide increased responsiveness in longitudinal studies and clinical trials . The reliability , validity , and subscale structure of the revised SF‐MPQ ( SF‐MPQ‐21 )  were examined in responses from 882 individuals with diverse chronic pain syndromes and in 226 patients with painful diabetic peripheral neuropathy who participated in a r and omized clinical trial . The data suggest that the SF‐MPQ‐2 has excellent reliability and validity , and the results of both exploratory and confirmatory factor analyses provided support for four readily interpretable subscales — continuous pain , intermittent pain , predominantly neuropathic pain , and affective descriptors . These results provide a basis for use of the SF‐MPQ‐2 in future clinical research , including clinical trials of treatments for neuropathic and non‐neuropathic pain conditions BACKGROUND : Despite the enormous success of total knee arthroplasty ( TKA ) , chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established . We hypothesized that perioperative treatment with pregabalin , a chronic pain medication , would reduce the incidence of postsurgical neuropathic pain . METHODS : We performed a r and omized , placebo-controlled , double-blind trial of pregabalin ( 300 mg ) administered before TKA and for 14 days after TKA ( 150–50 mg twice daily ) . Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale . Secondary outcomes included postsurgical recovery and rehabilitation measures , including knee range of motion , opioid consumption , postoperative pain scores , sleep disturbance , and time to discharge as well as the occurrence of postoperative systemic complications . RESULTS : Of the 240 patients r and omly assigned to the 2 treatment groups ( 120 in each ) , data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients . At both 3 and 6 mo postoperatively , the incidence of neuropathic pain was less frequent in the pregabalin group ( 0 % ) compared with the placebo group ( 8.7 % and 5.2 % at 3 and 6 mo , respectively ; P = 0.001 and P = 0.014 ) . Patients receiving pregabalin also consumed less epidural opioids ( P = 0.003 ) , required less oral opioid pain medication while hospitalized ( P = 0.005 ) , and had greater active flexion over the first 30 postoperative days ( P = 0.013 ) . There were no differences in the actual recorded duration of hospitalization between the 2 groups , although time to achieve hospital discharge criteria was longer for placebo patients , 69.0 ± 16.0 h ( mean ± sd ) , than that of pregabalin patients , 60.2 ± 15.8 h ( P = 0.001 ) . Sedation ( P = 0.005 ) and confusion ( P = 0.013 ) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin . CONCLUSION : Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA , with less opioid consumption and better range of motion during the first 30 days of rehabilitation . However , in the doses tested , it is associated with a higher risk of early postoperative sedation and confusion & NA ; Recently , fear – avoidance models have been quite influential in underst and ing the transition from acute to chronic low back pain ( LBP ) . Not only has pain‐related fear been found to be associated with disability and increased pain severity , but also treatment focused at reducing pain‐related fear has shown to successfully reduce disability levels . In spite of these developments , there is still a lack in well‐ design ed prospect i ve studies examining the role of pain‐related fear in acute back pain . The aim of the current study was to prospect ively test the assumption that pain‐related fear in acute stages successfully predicts future disability .  Subjects were primary care acute LBP patients consulting because of a new episode of LBP ( ≤3 weeks ) . They completed question naires on background variables , fear – avoidance model variables and LBP outcome ( Grade d Chronic Pain Scale , GCPS ) at baseline , 3 , 6 , and 12 months follow‐up and at the end of the study . Two‐hundred and twenty‐two acute LBP patients were included , of whom 174 provided full follow‐up information ( 78.4 % ) . A backward ordinal regression analysis showed previous LBP history and pain intensity to be the most important predictors of end of study GCPS . Of the  fear – avoidance model  variables , only negative affect added to this model . Our results do not really support the longitudinal validity of the fear – avoidance model , but they do feed the discussion on the role of pain‐related fear in early stages of LBP ABSTRACT Although acute pain in patients with herpes zoster can be severe and has a substantial impact on health‐related quality of life , there have been no r and omized clinical trials of oral medications specifically for its ongoing treatment . A r and omized clinical trial was conducted in which 87 subjects ⩾50 years of age with herpes zoster within 6 calendar days of rash onset and with worst pain in the past 24 h ⩾ 3 on a 0–10 rating scale initiated 7 days of treatment with famciclovir in combination with 28 days of treatment with either controlled‐release ( CR ) oxycodone , gabapentin , or placebo . Subjects were evaluated for adverse effects of treatment , acute pain , and health‐related quality of life . The results showed that CR‐oxycodone and gabapentin were generally safe and were associated with adverse events that reflect well‐known effects of these medications . Discontinuing participation in the trial , primarily associated with constipation , occurred more frequently in subjects r and omized to CR‐oxycodone ( 27.6 % ) compared with placebo ( 6.9 % ) . Treatment with CR‐oxycodone reduced the mean worst pain over days 1–8 ( p = 0.01 ) and days 1–14 ( p = 0.02 ) relative to placebo but not throughout the entire 28‐day treatment period as pain resolved in most subjects . Gabapentin did not provide significantly greater pain relief  than placebo , although the data for the first week were consistent with a modest benefit . By demonstrating that CR‐oxycodone is safe , generally adequately tolerated , and appears to have efficacy for relieving acute pain , the results of this clinical trial provide a foundation for evidence ‐based treatment for acute pain in herpes zoster BACKGROUND The incidence of postherpetic neuralgia ( PHN ) has been reported to be 25 % among those over the age of 50 years treated with antiviral medication . The role of sympathetic block in its prevention remains question able . OBJECTIVES The aim of this study is to determine whether early stellate ganglion blockade for acute herpes zoster of the face will reduce the intensity and duration of acute herpetic pain , and if the blockade has the potential to prevent or reduce the incidence and /or severity of PHN . STUDY DESIGN R and omized , controlled , double blind trial . SETTING Hospital , outpatient setting . METHODS Sixty-four patients over 50 years were assigned to receive a stellate ganglion block using either 8 mL saline ( Group 1 ) or 6 mL bupivacaine 0.125 % and 8 mg dexamethasone in a total volume of 8 mL ( Group 2 ) . All procedures were performed under fluoroscopy . All patients received pregabalin in a dose of 150 mg twice daily . Acetaminophen was available as needed . Pain assessment using the visual analog scale and amount of analgesic being taken was measured at the initial visit ( basal ) , weekly for 6 weeks after the procedure and after 2 , 3 , and 6 months . Once a patient reported mild pain during the trial , pregabalin was tapered by 75 mg every other day ; the patients who succeeded in this step were recorded in each group . The time of complete resolution of pain and incidence of persistent postherpetic pain was reported . Each patient 's satisfaction was evaluated . RESULTS There was a significantly shorter duration of pain noticed in Group 2 ( P = 0.002 ) . A significantly lower incidence of PHN was encountered in Group 2 after 3 months ( P = 0.043 ) and 6 months ( P = 0.035 ) . Significantly more patient satisfaction was reported in Group 2 after 3 and 6 months . By the fourth week , 29 patients in Group 2 reported no pain . Two patients reported mild pain after 3 months which was resolved by the sixth month . In Group 1 , 22 patients reported no pain by the sixth week and 8 patients reported moderate pain after 2 and 3 months ; by the sixth month , 4 out of those 8 patients showed spontaneous remission of pain . There was a significant reduction in the total doses of pregabalin and acetaminophen  in Group 2 ( P < 0.001 ) . No serious adverse effects were reported during the study period . LIMITATIONS The sample size was determined using the incidence of PHN ( chronic pain ) as a main hypothesis . Meanwhile , this study determined the incidence of acute pain as well , which may lead to bias to the results of acute pain . CONCLUSION Early stellate ganglion blockade , in combination with an antiviral agent , is a very effective treatment modality ; it dramatically decreases the intensity of acute pain and shortens its duration and reduces the incidence of postherpetic neuralgia Acute neuritis and persistent pain are the most significant clinical manifestations of herpes zoster and are end points for clinical trials therapy . In an acyclovir and prednisone study , patients were categorized according to pain severity and number of lesions at presentation  . Risk categories were defined according to the magnitude of risk ratios ( RRs ) and a comparison of Kaplan-Meier survival estimates . For acute neuritis and zoster-associated pain , RRs defined rate of resolution . Patients who presented with  severe or incapacitating pain  and a large number of lesions were less likely to achieve resolution of both acute neuritis and zoster-associated pain ( RR , 18.0 ; 95 % confidence interval [ CI ] , 6 . 6 - 48.6 , and RR , 5.3 ; 95 % CI , 4.2 - 17.2 , respectively ) . These analyses identify the subgroups of patients for whom aggressive interventions are most strongly indicated BACKGROUND Early clinical trials have suggested that glutathione ( GSH ) offers protection from the toxic effects of cisplatin . PATIENTS AND METHODS One hundred fifty-one patients with ovarian cancer ( stage I-IV ) were evaluated in a clinical trial of cisplatin ( CDDP ) + /- glutathione ( GSH ) . The objective was to determine whether GSH would enhance the feasibility of giving six cycles of CDDP at 100 mg/m2 without dose reduction due to toxicity . RESULTS When considering the proportion of patients receiving six courses of CDDP at any dose , GSH produced a significant advantage over control--58 % versus 39 % , ( P = 0.04 ) . For these patients there was a significant difference between the reduction in creatinine clearance for GSH treated patients compared with control--74 % versus 62 % ( P = 0.006 ) . Quality of life scores demonstrated that for patients receiving GSH there was a statistically significant improvement in depression , emesis , peripheral neurotoxicity , hair loss , shortness of breath and difficulty concentrating . As an indication of overall activity , these patients were statistically significantly more able to undertake housekeeping and shopping . Clinical ly assessed response to treatment demonstrated a trend towards a better outcome in the GSH group ( 73 % versus 62 % ) but this was not statistically significant ( P = 0.25 ) . CONCLUSIONS The results demonstrate that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient 's quality of life is improved Introduction Low back pain ( LBP ) is the leading cause of disability worldwide . Of those patients who present to primary care with acute LBP , 40 % continue to report symptoms 3 months later and develop chronic LBP . Although it is possible to identify these patients early , effective interventions to improve their outcomes are not available . This double-blind ( participant/ outcome assessor ) r and omised controlled trial will investigate the efficacy of a brief educational approach to prevent chronic LBP in ‘ at-risk ’ individuals . Methods / analysis Participants will be recruited from primary care practice s in the Sydney metropolitan area . To be eligible for inclusion participants will be aged 18–75 years , with acute LBP ( < 4 weeks ’ duration ) preceded by at least a 1 month pain-free period and at-risk of developing chronic LBP . Potential participants with chronic spinal pain and those with suspected serious spinal pathology will be excluded . Eligible participants who agree to take part will be r and omly allocated to receive 2 × 1 h sessions of pain biology education or 2 × 1 h sessions of sham education from a specially trained study physiotherapist . The study requires 101 participants per group to detect a 1-point difference in pain intensity 3 months after pain onset . Secondary outcomes include the incidence of chronic LBP , disability , pain intensity , depression , healthcare utilisation , pain attitudes and beliefs , global recovery and recurrence and are measured at 1 week post-intervention , and at 3 , 6 and 12 months post LBP onset . Ethics/dissemination Ethical approval was obtained from the University of New South Wales Human Ethics Committee in June 2013 ( ref number HC12664 ) . Outcomes will be disseminated through publication in peer- review ed journals and presentations at international conference meetings . Trial registration number https://www.anzctr.org.au/Trial/ Registration /Trial Review OBJECTIVES To evaluate the effect of perioperative gabapentin treatment for the prevention of persistent  post-thoracotomy pain  and to establish whether gabapentin has a significant therapeutic impact on acute postoperative pain . METHODS Consecutive patients with pulmonary malignancies scheduled for anterior thoracotomy were enrolled in this r and omized , double-blinded , placebo-controlled trial . Patients were given 1200 mg gabapentin or placebo 2 h before surgery followed by increasing doses during 5 postoperative days : 600 mg for day 1 ; 900 mg for day 2 ; and 1200 mg for days 3 - 5 . Effective pain relief was provided with perioperative multimodal analgesia with epidural infusion of bupivacaine and morphine for 72 h , and oral acetaminophen , ibuprofen and morphine . The main outcome was persistent post-thoracotomy pain at 6 months . Secondary outcomes included measures of early postoperative post-thoracotomy pain , morphine requirements , recovery and analgesia-related adverse effects over the first 3 weeks as well as persistent post-thoracotomy pain at 3 months . RESULTS A total of 104 patients were r and omly assigned to the intervention or control group ; 86 ( 83 % ) patients were available for the 14-day analysis , 76 ( 73 % ) for the 3-month analysis and 67 ( 64 % ) for the 6-month follow-up . At 6 months postoperatively , 47 % of patients treated with gabapentin reported persistent post-thoracotomy pain compared with 49 % in the placebo group ( P = 0.9 ) . No overall clinical ly or statistically significant differences were observed between groups receiving placebo and gabapentin , respectively , for the secondary outcome measures and treatment-related adverse events . CONCLUSIONS We found no evidence for the superiority of gabapentin over placebo for the treatment of acute pain following thoracotomy or for the prevention of persistent post-thoracotomy pain Purpose To investigate interindividual variability in response to pain treatment , we characterized postoperative patients for morphine metabolism and for COMT , OPRM1 and UGT2B7 polymorphisms . Methods A total of 109 patients treated with morphine  were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT , OPRM1 and UGT2B7 genes . The plasma concentration of morphine and of M3G/M6 G metabolites were evaluated by means of reversed phase high-performance liquid chromatography coupled with mass spectrometry . Results An association between average morphine consumption during the first 24 postoperative hours by patient-controlled analgesia ( PCA ) and COMT haplotypes was found . Specifically , patients with the diplotype for average pain intensity ( APS/APS ) required the lowest  morphine doses compared to the other subjects ( p = 0.011 ) . The APS haplotype contains an adenine corresponding to methionine , instead of valine , at position 158 of the COMT protein . Met/Met homozygous patients consumed significantly lower morphine doses than other subjects ( p = 0.014 ) ; accordingly , Val158Met genotyping alone might be used in the clinical setting to predict PCA morphine need . Considering both COMT Val158Met and OPRM1 A118 G polymorphisms , carriers of both the Met/Met and AA genotypes required less morphine than other subjects , although the difference was not significant . The analysis of UGT2B7 revealed the occurrence of two common haplotypes ( G_C_C_A_C and A_T_T_G_T ) that did not prove to be related with plasma morphine and M3G/M6 G concentration . Conclusions By considering COMT , OPRM1 , and UGT2B7 genotypes , as well as pharmacokinetic results , only COMT polymorphisms appear to be predictive of morphine need in postoperative pain therapy Thoracotomy is often responsible for chronic pain , possibly of neuropathic origin . To confirm pre clinical studies , the preventive effects of perioperative ketamine were tested in a r and omized , double‐blind , placebo‐controlled clinical trial on persistent neuropathic pain after thoracotomy . Eighty‐six patients scheduled for thoracotomy under st and ardised general anaesthesia were r and omised to receive either ketamine ( 1mgkg−1 at the induction , 1mgkg−1h−1 during surgery , then 1mgkg−1 during 24h ; n=42 ) or normal saline ( n=44 ) . Postoperative analgesia included a single dose of intrapleural ropivacaine , intravenous paracetamol and nefopam , and patient‐controlled intravenous morphine . Vital parameters and analgesia were recorded during the 48 first postoperative hours . Seventy‐three patients were followed up . The patient 's chest was examined 1–2 weeks , 6 weeks and 4 months after surgery . At the last two observations , spontaneous pain score over a one‐week period ( visual analogue scale ) , neuropathic pain score ( NPSI ) , and intake of analgesics , were assessed . No drug affecting neuropathic pain ( except opiates ) was given during the follow‐up . Two patients in each group were lost to follow‐up after the 6 week visit . Ketamine  improved immediate postoperative pain , but the groups were similar in terms of neuropathic pain and intake of analgesics , 6 weeks ( NPSI score : ketamine : 1.25 [ 0–4.125 ] ; placebo : 1 [ 0–4 ] ) and 4 months after surgery . Thus , ketamine given in 24‐h infusion failed to prevent chronic neuropathic pain after thoracotomy . Other perioperative preventive long‐lasting treatments or techniques could be tested in this context OBJECTIVE To evaluate the effectiveness of a program design ed to reduce back pain in nursing aides . METHODS Female nursing aides from a university hospital who had suffered episodes of back pain for at least six months were included in the study . Participants were r and omly divided into a control group and an intervention group . The intervention program involved a set of exercises and an educational component stressing the ergonomic aspect , administered twice a week during working hours for four months . All subjects answered a structured question naire and the intensity of pain was assessed before and after the program using a visual analogue scale ( VAS ) . Student 's t-test or the Wilcoxon Rank Sum Test for independent sample s , and Chi-square test or the Exact Fisher test for categorical analysis , were used . The McNemar test and the Wilcoxon matched pairs test were used to compare the periods before and after the program . RESULTS There was a statistically significant decrease in the frequency of cervical pain in the last two months and in the last seven days in the intervention group . There was also a reduction in cervical pain intensity in the two periods ( 2 months , 7 days ) and lumbar pain intensity in the last 7 days . CONCLUSIONS The results suggest that a program of regular exercise with an emphasis on ergonomics can reduce musculoskeletal symptoms in nursing personnel BACKGROUND The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus ( VZV ) . We tested the hypothesis that vaccination against VZV would decrease the incidence , severity , or both of herpes zoster and postherpetic neuralgia among older adults . METHODS We enrolled 38,546 adults 60 years of age or older in a r and omized , double-blind ,  placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ( " zoster vaccine " ) . Herpes zoster was diagnosed according to clinical and laboratory criteria . The pain and discomfort associated with herpes zoster were measured repeatedly for six months . The primary end point was the burden of illness due to herpes zoster , a measure affected by the incidence , severity , and duration of the associated pain and discomfort . The secondary end point was the incidence of postherpetic neuralgia . RESULTS More than 95 percent of the subjects continued in the study to its completion , with a median of 3.12 years of surveillance for herpes zoster . A total of 957 confirmed cases of herpes zoster ( 315 among vaccine recipients and 642 among placebo recipients ) and 107 cases of postherpetic neuralgia ( 27 among vaccine recipients and 80 among placebo recipients ) were included in the efficacy analysis . The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent ( P<0.001 ) , reduced the incidence of postherpetic neuralgia by 66.5 percent ( P<0.001 ) , and reduced the incidence of herpes zoster by 51.3 percent ( P<0.001 ) . Reactions at the injection site were more frequent among vaccine recipients but were generally mild . CONCLUSIONS The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults BACKGROUND In this prospect i ve , r and omized , double-blind , placebo-controlled study , we investigated the effect of pregabalin on oxycodone consumption , postoperative confusion , and pain in elderly cardiac surgery patients . METHODS Seventy patients , aged ≥75 yr , were r and omized to receive either 150 mg of pregabalin before operation and 75 mg of pregabalin twice daily for 5 postoperative days or placebo . Pain intensity was measured with the Verbal Rating Scale ( VRS ) . When pain intensity was ≥2 on the VRS , patients received oxycodone either i.v . ( 0.05 mg kg(-1 ) ) or orally ( 0.10 - 0.15 mg kg(-1 ) ) . Postoperative confusion was measured with the Confusion Assessment Method for the intensive care unit ( CAM-ICU ) . Postoperative pain was assessed by a telephone interview 1 and 3 months after operation . RESULTS Cumulative consumption of parenteral oxycodone  during 16 h after extubation was reduced by 44 % and total oxycodone consumption from extubation to the end of the fifth postoperative day was reduced by 48 % in the pregabalin  group . Time to extubation was 138 min shorter and CAM-ICU scores were significantly lower on the first postoperative day in the placebo group , although there was no significant difference with respect to the Mini-Mental State Examination or the Richmond Agitation Sedation Score . The incidence of pain during movement was significantly lower in the pregabalin group at 3 months postoperative . CONCLUSIONS The administration of pregabalin  reduced postoperative opioid consumption after cardiac surgery reduced the incidence of confusion on the first postoperative day and increased time to extubation when compared with placebo . Three months after operation , patients in the pregabalin group experienced less pain during movement New and previously reported analyses of the data from a placebo-controlled trial of famciclovir are review ed in light of recently proposed recommendations for the analysis of pain in herpes zoster trials . The analyses examined the effect of famciclovir treatment on the duration of postherpetic neuralgia ( PHN )  , which was defined as pain persisting after rash healing , pain persisting > 30 days after study enrollment , or pain persisting > 3 months after study enrollment ; the baseline characteristics of patients in the famciclovir and placebo groups who developed PHN  ; the impact of famciclovir treatment on the duration of PHN , while controlling for significant covariates ; and the prevalence of PHN at monthly intervals from 30 to 180 days after enrollment . The results of these analyses indicated that greater age , rash severity , and acute pain severity are risk factors for prolonged PHN . In addition , they demonstrated that treatment of acute herpes zoster patients with famciclovir significantly reduces both the duration and prevalence of PHN BACKGROUND : Patient outcome after lumbar discectomy for radicular low back pain is variable and the benefit is inconsistent . Many patients continue to experience pain 3 months after surgery . Pregabalin , a membrane stabilizer , may decrease perioperative central sensitization and subsequent persistent pain . METHODS : Forty patients undergoing lumbar discectomy were r and omly allocated to receive either pregabalin ( 300 mg at 90 minutes preoperatively and 150 mg at 12 and 24 hours postoperatively ) or placebo at corresponding times in a double-blinded manner . Our primary outcome was the change in the present pain intensity ( PPI ) ( visual analog scale [ VAS ] , 0–100 mm [ PPI-VAS , McGill Pain Question naire ] ) from preoperatively to 3 months postoperatively . RESULTS : The decrease in PPI-VAS score at 3 months was greater in patients who received pregabalin ( 37.6 ± 19.6 mm ) ( mean ± SD ) than those who received placebo ( 25.3 ± 21.9 mm ) ( P = 0.08 ) . The Rol and Morris disability score at 3 months was less in patients who received pregabalin ( 2.7 ± 2.4 ) than in those who received placebo ( 5.6 ± 4.8 ) ( P = 0.032 ) . Pregabalin administration was associated with greater pain tolerance thresholds in both lower limbs compared with placebo at 24 hours postoperatively . CONCLUSION : Perioperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy BACKGROUND The efficacy of antidepressant therapy in patients undergoing coronary artery bypass grafting ( CABG ) is not clearly established . METHODS This double-blind trial was conducted at University Hospital , Besançon , France . Adult CABG patients were r and omized ( 1:1 ) to receive escitalopram ( 10 mg daily ) or placebo from 2 to 3 weeks before to 6 months after surgery , including 12 months post-surgery follow-up . The primary composite endpoint was the occurrence of mortality or predefined morbidity events . Secondary endpoints included measures of depression , mental and physical health using Beck Depression Inventory Short Form ( BDI ) , and quality of life 36-Item Short Form ( SF-36 ) self assessment s. RESULTS The treated cohort contained 361 patients with mean age 67 years . At 12 months , the proportions of patients with the composite morbidity and mortality endpoint were not different between escitalopram and placebo ( 110 of 182 [ 60.4 % ] vs 108 of 179 [ 60.3 % ] , p = 0.984 ) . However , over the 6 months postoperative period , the BDI and SF-36 Mental Component Summary scores were better overall in the escitalopram group than in the placebo group for all patients ( p = 0.015 and p = 0.014 , respectively ) and preoperatively depressed ( BDI > 3 ) patients ( p = 0.002 and p = 0.005 , respectively ) . Moreover , the SF-36 Pain score was better overall in the escitalopram group than in the placebo group in the preoperatively-depressed subset ( p = 0.026 ) . CONCLUSIONS Antidepressant therapy had no effect on morbidity and mortality events up to 1 year after CABG . However , antidepressant therapy may provide faster improvements to mental health aspects of quality of life and reduce postoperative pain in patients with preoperative depression . Subject to contra-indications , we recommend antidepressant therapy in coronary revascularization patients who are preoperatively depressed Background Psychologically informed practice emphasizes routine identification of modifiable psychological risk factors being highlighted . Objective The purpose of this study was to test the predictive validity of the STarT Back Screening Tool ( SBT ) in comparison with single-construct psychological measures for 6-month clinical outcomes . Design This was an observational , prospect i ve cohort study . Methods Patients ( n=146 ) receiving physical therapy for low back pain were administered the SBT and a battery of psychological measures ( Fear-Avoidance Beliefs Question naire physical activity scale and work scale [ FABQ-PA and FABQ-W , respectively ] , Pain Catastrophizing Scale [ PCS ] , 11-item version of the Tampa Scale of Kinesiophobia [ TSK-11 ] , and 9-item Patient Health Question naire [ PHQ-9 ] ) at initial evaluation and 4 weeks later . Treatment was at the physical therapist 's discretion . Clinical outcomes consisted of pain intensity and self-reported disability . Prediction of 6-month clinical outcomes was assessed for intake SBT and psychological measure scores using multiple regression models while controlling for other prognostic variables . In addition , the predictive capabilities of intake to 4-week changes in SBT and psychological measure scores for 6-month clinical outcomes were assessed . Results Intake pain intensity scores ( β=.39 to .45 ) and disability scores ( β=.47 to .60 ) were the strongest predictors in all final regression models , explaining 22 % and 24 % and 43 % and 48 % of the variance for the respective clinical outcome at 6 months . Neither SBT nor psychological measure scores improved prediction of 6-month pain intensity . The SBT overall scores ( β=.22 ) and SBT psychosocial scores ( β=.25 ) added to the prediction of disability at 6 months . Four-week changes in TSK-11 scores ( β=−.18 ) were predictive of pain intensity at 6 months . Four-week changes in FABQ-PA scores ( β=−.21 ) , TSK-11 scores ( β=−.20 ) and SBT overall scores ( β=−.18 ) were predictive of disability at 6 months . Limitations Physical therapy treatment was not st and ardized or accounted for in the analysis . Conclusions Prediction of clinical outcomes by psychology-based measures was dependent upon the clinical outcome domain of interest . Similar to studies from the primary care setting , initial screening with the SBT provided additional prognostic information for 6-month disability and changes in SBT overall scores may provide important clinical decision-making information for treatment monitoring OBJECTIVES Improvement in health-related quality of life is a major object of cardiac surgery . However , high stress exposure during the perioperative period of cardiac surgery can result in the formation of traumatic memories and symptoms of chronic stress or even posttraumatic stress disorder , which can have negative effects on health-related quality -of-life outcome . In this controlled study we examined whether exogenously administered stress doses of hydrocortisone during cardiac surgery reduce perioperative stress exposure and the long-term incidence of chronic stress symptoms and improve health-related quality of life after cardiac surgery . METHODS Thirty-six high-risk patients undergoing cardiac surgery were prospect ively r and omized to receive either stress doses of hydrocortisone or placebo . Of 28 available patients at 6 months after cardiac surgery , 14 had received hydrocortisone , and 14 had received placebo .  Traumatic memories , chronic stress symptoms ( posttraumatic stress disorder scores ) , and health-related quality of life were measured by using vali date d question naires . RESULTS Compared with patients from the placebo group , patients from the hydrocortisone group had a significantly shorter duration of intensive care unit treatment , required lower doses of the stress hormone norepinephrine during cardiac surgery , and had significantly fewer stress symptoms and a better health-related quality of life regarding physical function , chronic pain , general health , vitality , and mental health during follow-up . The groups did not differ with regard to the number or type of intensive care unit-related traumatic memories . CONCLUSIONS The use of stress doses of hydrocortisone in high-risk cardiac surgical patients reduces perioperative stress exposure , decreases chronic stress symptoms , and improves health-related quality of life at 6 months after cardiac surgery BACKGROUND Regular paracetamol is the recommended first-line analgesic for acute low-back pain ; however , no high- quality evidence supports this recommendation . We aim ed to assess the efficacy of paracetamol taken regularly or as-needed to improve time to recovery from pain , compared with placebo , in patients with low-back pain . METHODS We did a multicentre , double-dummy , r and omised , placebo controlled trial across 235 primary care centres in Sydney , Australia , from Nov 11 , 2009 , to March 5 , 2013 . We r and omly allocated patients with acute low-back pain in a 1:1:1 ratio to receive up to 4 weeks of regular doses of paracetamol ( three times per day ; equivalent to 3990 mg paracetamol per day ) , as-needed doses of paracetamol ( taken when needed for pain relief ; maximum 4000 mg paracetamol per day ) , or placebo . R and omisation was done according to a central ised r and omisation schedule prepared by a research er who was not involved in patient recruitment or data collection . Patients and staff at all sites were masked to treatment allocation . All participants received best- evidence advice and were followed up for 3 months . The primary outcome was time until recovery from low-back pain , with recovery defined as a pain score of 0 or 1 ( on a 0 - 10 pain scale ) sustained for 7 consecutive days . All data were analysed by intention to treat . This study is registered with the Australian and New Zeal and Clinical Trial Registry , number ACTN 12609000966291 . FINDINGS 550 participants were assigned to the regular group ( 550 analysed ) , 549 were assigned to the as-needed group ( 546 analysed ) , and 553 were assigned to the placebo group ( 547 analysed ) . Median time to recovery was 17 days ( 95 % CI 14 - 19 ) in the regular group , 17 days ( 15 - 20 ) in the as-needed group , and 16 days ( 14 - 20 ) in the placebo group ( regular vs placebo hazard ratio 0·99 , 95 % CI 0·87 - 1·14 ; as-needed vs placebo 1·05 , 0·92 - 1·19 ; regular vs as-needed 1·05 , 0·92 - 1·20 ) . We recorded no difference between treatment groups for time to recovery ( adjusted p=0·79 ) . Adherence to regular tablets ( median tablets consumed per participant per day of maximum 6 ; 4·0 [ IQR 1·6 - 5·7 ] in the regular group , 3·9 [ 1·5 - 5·6 ] in the as-needed group , and 4·0 [ 1·5 - 5·7 ] in the placebo group ) , and number of participants reporting adverse events ( 99 [ 18·5 % ] in the regular group , 99 [ 18·7 % ] in the as-needed group , and 98 [ 18·5 % ] in the placebo group ) were similar between groups . INTERPRETATION Our findings suggest that regular or as-needed dosing with paracetamol does not affect recovery time compared with placebo in low-back pain , and question the universal endorsement of paracetamol in this patient group . FUNDING National Health and Medical Research Council of Australia and GlaxoSmithKline Australia Study Design . Prospect i ve observational study . Objective . To determine whether polymorphic variations of the guanosine triphosphate ( GTP ) cyclohydrolase 1 gene ( GCH1 ) are associated with different outcomes in patients undergoing surgical treatment for lumbar degenerative disc disease ( DDD ) . Summary of Background Data . GCH1 , the gene encoding the rate-limiting enzyme in tetrahydrobiopterin synthesis , has been strongly implicated as a determinant of pain experience in previous animal and human studies . Methods . A total of 69 patients undergoing surgical treatment for lumbar DDD were prospect ively enrolled .  Genomic DNA was extracted from a venous blood sample , and DNA sequence analysis was performed of GCH1 . Surgery included 65 instrumented fusions and 4 disc arthroplasty  procedures . Patients were observed prospect ively for 1 year following surgery . Allelic and genotype frequencies were calculated for each of 14 single nucleotide polymorphisms ( SNPs ) . One-year postoperative Oswestry Disability Index ( ODI ) scores were compared to preoperative scores and the absolute change in ODI score was used to perform genetic association analyses on the basis of both individual SNP markers as well as commonly observed haplotypes for the entire gene sequence . Results . Single marker analysis revealed 1 SNP ( rs998259 ; minor allele T ) that was significantly associated with improvement in both absolute ODI score ( P = 0.030 ) and Numerical Rating Scale back pain scores ( P = 0.033 ) following surgery . Haplotype analysis identified a common GCH1 haplotype ( “ CACTTGTTTGAC ” ) with a sample frequency of 12.3 % , which was highly associated with improvement in absolute ODI score ( P = 0.04 ) . This haplotype frequency reflects the existence of both heterozygous and homozygous individuals in the study population . The presence of 1 unit of this haplotype was associated with an improvement in postoperative ODI score of 15.34 relative to the absence of this haplotype ( P = 0.04 ) . Conclusion . Preliminary results from this pilot genetic study of patients undergoing surgery for DDD suggests that the T allele at rs998259 of GCH1 may be associated with improved outcomes 1 year following surgery A r and omized , controlled trial was performed to assess the efficacy and safety of vitamin E supplementation for prophylaxis against paclitaxel-induced peripheral neuropathy ( PIPN ) .  Thirty-two patients undergoing six courses of paclitaxel-based chemotherapy  were r and omly assigned to receive either chemotherapy with vitamin E ( 300 mg twice a day , Group I ) or chemotherapy without vitamin E supplementation ( Group II ) . A detailed neurological examination and electrophysiological study was performed during and 3 months after chemotherapy . The severity of PIPN was summarized by means of a modified Peripheral Neuropathy ( PNP ) score . The incidence of neurotoxicity differed significantly between groups , occurring in 3/16 ( 18.7 % ) patients assigned to the vitamin E supplementation group and in 10/16 ( 62.5 % ) controls ( P=0.03 ) . The relative risk ( RR ) of developing PIPN was significantly higher in controls than in vitamin E group patients ( RR=0.3 , 95 % confidence interval (CI)=0.1 - 0.9 ) . Mean PNP scores were 2.25+/-5.1 ( range 0 - 15 ) for patients in Group I and 11+/-11.63 ( range 0 - 32 ) for those in Group II ( P=0.01 ) . Vitamin E supplementation was well tolerated and showed an excellent safety profile . This study shows that vitamin E effectively and safely protects patients with cancer from the occurrence of paclitaxel-induced peripheral nerve damage . A double-blind , placebo-controlled trial is needed to confirm these results OBJECTIVE The objective was to evaluate the efficacy of Org 2766 ( a hexapeptide analogue of ACTH ) in the prevention or delay of cisplatin-induced neuropathy during chemotherapy in women with ovarian cancer as measured by vibration perception threshold ( VPT ) . METHODS In this r and omized , multicenter , double-blind , placebo-controlled study , 196 women with ovarian cancer were treated with cisplatin 75 - 100 mg/m2 , cyclophosphamide 600 - 1000 mg/m2 plus placebo or two dose levels of Org 2766 . The cisplatin-induced neuropathies were monitored by determining the  VPT with the Vibratron II .  VPT was determined for both the most sensitive great toe and the index finger on a monthly basis during treatment and months 1 , 2 , and 3 postchemotherapy . Once the blind was broken , it was found that 174 women ( 59 in placebo , 58 in 2 mg , and 57 in 4 mg ) had enough data to allow evaluation . RESULTS Over the course of follow-up , the VPT was found to increase . This is consistent with the development of cisplatin-induced peripheral neuropathies . The baseline VPT for the index finger was less than that of the great toe ( 0.65 vs 2.13 ) , but the percentage change in VPT was the same for both ( percentage increase in VPT of about 350 % ) . When the VPTs are compared according to the dose of Org 2766 given , there appears to be no difference in the rate of change or degree of neuropathies that developed in these women receiving cisplatin and cyclophosphamide . CONCLUSIONS The development of cisplatin-induced neuropathies is confirmed by measurement of the VPT . The rate of development of neuropathies seems to accelerate after the sixth course of cisplatin . When the development of neuropathies is evaluated on the basis of Org 2766 dosage , it is found that there is no difference in the rate or degree of neuropathies seen . Instead of providing protection from and delay of onset of peripheral neuropathies caused by cisplatin , these results suggest that the administration of Org 2766 appears to cause an increase in the rate of change and degree of neuropathies ( P > 0.05 ) Abstract Though it is clear that genomic variability plays an integral role in accounting for pain sensitivity , controversy exists over which genes are involved . While recent data suggest a “ protective ” ( i.e. , less pain ) haplotype in the GTP cyclohydrolase ( GCH1 ) gene , other research has failed to confirm this association . Possibly , the effects of single nucleotide polymorphisms ( SNPs ) vary depending on the pain task . The current investigation analyzed the association of five previously identified GCH1 SNPs with ratings of pain induced by topical high concentration ( 10 % ) capsaicin applied to the skin of 39 healthy human volunteers . Each of the GCH1 polymorphisms was associated with lower pain ratings . When combined , three of the five accounted for a surprisingly high 35 % of the inter‐individual variance in pain ratings . We conclude that SNPs of the GCH1 gene may profoundly affect the ratings of pain induced by capsaicin IMPORTANCE There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy . OBJECTIVE To determine the effect of duloxetine , 60 mg daily , on average pain severity . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled crossover trial at 8 National Cancer Institute (NCI)-funded cooperative research networks that enrolled 231 patients who were 25 years or older being treated at community and academic setting s between April 2008 and March 2011 . Study follow-up was completed July 2012 . Stratified by chemotherapeutic drug and comorbid pain risk , patients were r and omized to receive either duloxetine followed by placebo or placebo followed by duloxetine .  Eligibility required that patients have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events and at least 4 on a scale of 0 to 10 , representing average chemotherapy-induced pain , after paclitaxel , other taxane , or oxaliplatin treatment . INTERVENTIONS The initial treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or placebo for the first week and 2 capsules of either 30 mg of duloxetine or placebo daily for 4 additional weeks . MAIN OUTCOME MEASURES The primary hypothesis was that duloxetine would be more effective than placebo in decreasing chemotherapy-induced peripheral neuropathic pain . Pain severity was assessed using the Brief Pain Inventory-Short Form " average pain " item with 0 representing no pain and 10 representing as bad as can be imagined . RESULTS Individuals receiving duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 ( 95 % CI , 0.72 - 1.40 ) vs 0.34 ( 95 % CI , 0.01 - 0.66 ) among those who received placebo ( P = .003 ; effect size , 0.513 ) . The observed mean difference in the average pain score between duloxetine and placebo was 0.73 ( 95 % CI , 0.26 - 1.20 ) . Fifty-nine percent of those initially receiving duloxetine vs 38 % of those initially receiving placebo reported decreased pain of any amount . CONCLUSION AND RELEVANCE Among patients with painful chemotherapy-induced peripheral neuropathy , the use of duloxetine compared with placebo for 5 weeks result ed in a greater reduction in pain . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00489411 Background : Pain after amputation is common but difficult to treat . Therefore , the authors examined whether postoperative treatment with gabapentin could reduce postamputation stump and phantom pain . Methods : Forty-six patients scheduled to undergo lower limb amputation were r and omly assigned to receive oral gabapentin or placebo . Treatment was started on the first postoperative day and continued for 30 days . The daily dose of gabapentin or placebo was gradually increased to 2,400 mg/day . The intensity of stump and phantom pain was recorded every day on a numeric rating scale ( 0–10 ) during the 30-day treatment period . Five interviews were performed after 7 , 14 , and 30 days and after 3 and 6 months . Results : Results from 41 patients were included in the data analysis . The risk of phantom pain  ( gabapentin vs. placebo ) was 55.0 % versus 52.6 % ( risk difference , 2.4 % ; 95 % confidence interval , −28.9 to 33.7 % ; P = 0.88 ; 30 days ) and 58.8 % versus 50.0 % ( risk difference , 8.8 % ; 95 % confidence interval , −23.3 to 40.9 % ; P = 0.59 ; 6 months ) . The median intensity of phantom pain  ( gabapentin vs. placebo ) was 1.5 ( range , 0–9.0 ) versus 1.2 ( range , 0–6.6 ) ( P = 0.60 ; 30 days ) and 1.0 ( range , 0–6.0 ) versus 0.5 ( range , 0–5.0 ) ( P = 0.77 ; 6 months ) . The median intensity of stump pain was 0.85 ( range , 0–8.2 ) versus 1.0 ( range , 0–5.4 ) ( P = 0.68 ; 30 days ) and 0 ( range , 0–8.0 ) versus 0 ( range , 0–5.0 ) ( P = 0.58 ; 6 months ) . Conclusion : Gabapentin administered in the first 30 postoperative days after amputation does not reduce the incidence or intensity of postamputation pain BACKGROUND : Harvesting of iliac crest graft for spinal fusions is associated with a number of patients reporting residual or chronic pain at the harvest site . Various interventions , including morphine infiltration , have been proposed to minimize the associated pain . METHODS : We performed a prospect i ve , double-blind , r and omized , placebo-controlled study comparing intraoperative infiltration of 5 mg morphine ( treatment ) versus saline ( placebo ) into the iliac crest harvest site for patients undergoing elective spinal surgery . Patients with myelopathy , excessive perioperative opioid use ( 60 mg equivalent morphine/d or more ) , or multilevel ( > 3 levels ) spinal surgery were excluded . Postoperative administration of morphine ( recovery room and patient-controlled analgesia ) was st and ardized . Numerical pain scores specific for the iliac crest site were determined in the immediate postoperative period and at 3 , 6 , and 12 months . RESULTS : Of the 54 patients r and omized , 47 ( 87 % ) were available for review with a minimum of 1-year follow-up . The groups were similar in baseline age , gender , and comorbidities . There was no significant difference between groups in total use of postoperative morphine during the first 24 hours ( P = 0.48 ) . Repeated measures analysis of variance demonstrated no interacting effect of group over time for hip pain at rest ( P = 0.94 ) , hip pain while moving ( P = 0.90 ) , spine pain at rest ( P = 0.99 ) , or spine pain while moving ( P = 0.83 ) . The proportion of patients reporting iliac crest pain at 1-year follow-up was the same between groups ( P = 0.95 ) . CONCLUSIONS : This study has demonstrated that there are no additional benefits for the use of intraoperative infiltration of morphine into the iliac crest harvest site during spinal fusions Chemotherapy‐induced peripheral neuropathy ( CIPN ) is a significant side effect of taxane and platinum‐based chemotherapy . Several studies have supported the potential benefit of glutathione for the prevention of platinum‐induced CIPN . The current trial was design ed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy Objectives : Breast cancer surgery is associated with a high incidence of persistent postsurgical pain ( PPSP ) . The aim of this study was to evaluate the impact of intravenous ( IV ) lidocaine on acute and PPSP , analgesic requirements , and sensation abnormalities in patients undergoing surgery for breast cancer . Methods : Thirty-six patients participated in this r and omized , double-blinded study . Before induction of general anesthesia , patients received a bolus of intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of lidocaine 1.5 mg/kgh ( lidocaine group ) or an equal volume of saline ( control group ) . The infusion was stopped 1 hour after the skin closure . Pain scores and analgesic consumption were recorded at 2 , 4 , 24 hours , and then daily for 1 week postoperatively . Three months later , patients were assessed for PPSP and secondary hyperalgesia . Results : Two ( 11.8 % ) patients in the lidocaine group and 9 ( 47.4 % ) patients in the control group reported PPSP at 3 months follow-up ( P=0.031 ) . McGill Pain Question naire revealed greater present pain intensity-visual analog scale in the control group ( 14.6±22.5 vs. 2.6±7.5 ; P=0.025 ) . Secondary hyperalgesia ( area of hyperalgesia/length of surgical incision ) was significantly less in the lidocaine group compared with control group ( 0.2±0.8 vs. 3.2±4.5 cm ; P=0.002 ) . The 2 groups were similar in terms of analgesic consumption during the early postoperative period . Discussion : Intravenous perioperative lidocaine decreases the incidence and severity of PPSP after breast cancer surgery . Prevention of the induction of central hyperalgesia is a potential mechanism BACKGROUND : Gabapentin is effective for preventing and treating acute and chronic postoperative pain ; however , it has not been described for use in cesarean delivery . We hypothesized that preoperative gabapentin would reduce  postcesarean delivery pain . METHODS : Women undergoing scheduled cesarean delivery were r and omized to receive preoperative gabapentin 600 mg , or placebo . Spinal anesthesia was achieved with 0.75 % hyperbaric bupivacaine 12 mg , fentanyl 10 & mgr;g , and morphine 100 & mgr;g . Postoperative analgesia was initiated with intraoperative ketorolac and acetaminophen , and continued with postoperative diclofenac , acetaminophen , and morphine . Patients were assessed at 6 , 12 , 24 , and 48 hours after spinal anesthesia for pain at rest and on movement using a visual analog scale ( 0 to 100 mm ) , satisfaction , opioid consumption , and side effects . Neonatal interventions , Apgar scores , umbilical artery blood gases , and breastfeeding difficulties were assessed . Chronic pain was assessed 3 months after delivery . Maternal and umbilical vein gabapentin plasma concentrations were measured in a subgroup of patients . Mixed-model analysis was used to compare the primary outcome of visual analog scale pain scores at 24 hours between groups . RESULTS : Forty-six patients were r and omized , and 2 were excluded from analysis . The mean ( 95 % confidence interval , CI ) pain scores on movement at 24 hours were 21 mm ( CI = 13–28 ) in the gabapentin and 41 mm ( CI = 31–50 ) in the placebo group ( P = 0.001 ) . Maternal satisfaction was higher in the gabapentin group . There was no difference in opioid consumption . Severe maternal sedation was more common in the gabapentin group ( 19 % vs. 0 % , P = 0.04 ) . There was no difference in neonatal Apgar scores , interventions , or umbilical artery pH. The mean ( SD ) maternal vein : umbilical vein plasma gabapentin ratio was 0.86 ( 0.12 ) . The incidence of pain at 3 months was similar in both groups . CONCLUSION : Preoperative gabapentin 600 mg in the setting of multimodal analgesia reduces postcesarean delivery pain and increases maternal satisfaction in comparison with placebo We hypothesized that perioperative ketamine administration would modify acute central sensitization following amputation and hence reduce the incidence and severity of persistent post-amputation pain ( both phantom limb and stump pain ) . In a r and omized , controlled trial , 45 patients undergoing above- or below-knee amputation received ketamine 0.5 mg.kg–1 or placebo as a pre-induction bolus followed by an intravenous infusion of ketamine 0.15 mg.kg–1.h–1 or normal saline for 72 hours postoperatively . Both groups received st and ardized general anaesthesia followed by patient-controlled intravenous morphine . The surface area of allodynia over the stump was mapped at days 3 and 6 . Postamputation pain was assessed at days 3 and 6 and at 6 months postoperatively . We found no significant difference between groups in the surface area of stump allodynia or in morphine consumption . There was an unexplained , but significant , increase in the incidence of stump pain in the ketamine group at day 3 . At six-month review , the incidence of phantom pain was 47 % in the ketamine group and 71 % in the control group . This did not reach statistical significance ( P=0.28 ) as the power of the study was based on the search for a large treatment effect . The incidence of stump pain at six months was 47 % in the ketamine group and 35 % in the control group ( P=0.72 ) . There were no significant between-group differences in pain severity throughout the study period . Ketamine at the dose administered did not significantly reduce acute central sensitization or the incidence and severity of post-amputation pain Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications . The limited oral bioavailability of acyclovir necessitates frequent dosing . Valaciclovir , the l-valyl ester of acyclovir , is rapidly and almost completely converted to acyclovir in vivo and gives three- to fivefold increases in acyclovir bioavailability . In a r and omized , double-blind , multicenter study , the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged > or = 50 years with herpes zoster . Patients were evaluated for 6 months . The intent-to-treat analysis ( 1,141 patients ) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain ( P = 0.001 and P = 0.03 , respectively ) compared with acyclovir ;  median pain duration s were 38 and 44 days , respectively , versus 51 days for acyclovir . Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months ( 19.3 versus 25.7 % ) . However , there were no differences between treatments in pain intensity or quality -of-life measures . Cutaneous manifestations resolved at similar rates in all groups . Adverse events were similar in nature and prevalence among groups , and no clinical ly important changes occurred in hematology or clinical chemistry parameters . Thus , in the management of immunocompetent patients > or = 50 years of age with localized herpes zoster , valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing , while it maintains the favorable safety profile of acyclovir BACKGROUND Postherpetic neuralgia is the most frequent complication of herpes zoster . Treatment of this neuropathic pain syndrome is difficult and often disappointing . We assessed the effectiveness of a single epidural injection of steroids and local anaesthetics for prevention of postherpetic neuralgia in older patients with herpes zoster . METHODS We r and omly assigned 598 patients older than 50 years , with acute herpes zoster ( rash < 7 days ) below dermatome C6 , to receive either st and ard therapy ( oral antivirals and analgesics ) or st and ard therapy with one additional epidural injection of 80 mg methylprednisolone acetate and 10 mg bupivacaine . The primary endpoint was the proportion of patients with zoster-associated pain 1 month after inclusion . Analyses were by intention-to-treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N32866390 . FINDINGS At 1 month , 137 ( 48 % ) patients in the epidural group reported pain compared with 164 ( 58 % ) in the control group ( relative risk [ RR ] 0.83 , 95 % CI 0.71 - 0.97 , p=0.02 ) . After 3 months these values were 58 ( 21 % ) and 63 ( 24 % ) respectively ( 0.89 , 0.65 - 1.21 , p=0.47 ) and , at 6 months , 39 ( 15 % ) and 44 ( 17 % ; 0.85 , 0.57 - 1.13 , p=0.43 ) . We detected no subgroups in which the relative risk for pain 1 month after inclusion substantially differed from the overall estimate . No patient had major adverse events related to epidural injection . INTERPRETATION A single epidural injection of steroids and local anaesthetics in the acute phase of herpes zoster has a modest effect in reducing zoster-associated pain for 1 month . This treatment is not effective for prevention of long-term postherpetic neuralgia BACKGROUND The role of preoperative gabapentin in postoperative pain management is not clear , particularly in patients receiving regional blockade . Patients undergoing thoracotomy benefit from epidural analgesia but still may experience significant postoperative pain . We examined the effect of preoperative gabapentin in thoracotomy patients . METHODS Adults undergoing elective thoracotomy were enrolled in this prospect i ve , r and omized , double-blinded , placebo-controlled study , and r and omly assigned to receive 600 mg gabapentin or active placebo ( 12.5 mg diphenhydramine ) orally within 2 hours preoperatively . St and ardized management included thoracic epidural infusion , intravenous patient-controlled opioid analgesia , acetaminophen and ketorolac .  Pain scores , opioid use and side effects were recorded for 48 hours . Pain was also assessed at 3 months . RESULTS One hundred twenty patients ( 63 placebo and 57 gabapentin ) were studied .  Pain scores did not significantly differ at any time point ( P = 0.53 ) . Parenteral and oral opioid consumption was not significantly different between groups on postoperative day 1 or 2 ( P > 0.05 in both cases ) . The frequency of side effects such as nausea and vomiting or respiratory depression was not significantly different between groups , but gabapentin was associated with decreased frequency of pruritus requiring nalbuphine ( 14 % gabapentin vs. 43 % control group , P < 0.001 ) . The frequency of patients experiencing pain at 3 months post-thoracotomy was also comparable between groups ( 70 % gabapentin vs. 66 % placebo group , P = 0.72 ) . CONCLUSIONS A single preoperative oral dose of gabapentin ( 600 mg ) did not reduce pain scores or opioid consumption following elective thoracotomy , and did not confer any analgesic benefit in the setting of effective multimodal analgesia that included thoracic epidural infusion Study Design . A r and omized clinical trial was conducted . Objective . To compare the effectiveness of classification-based physical therapy with that of therapy based on clinical practice guidelines for patients with acute , work-related low back pain . Summary of Background Data . Clinical practice guidelines recommend minimal intervention during the first few weeks after acute low back injury . However , studies supporting this recommendation have not attempted to identify which patients are likely to respond to particular interventions . Methods . For this study , 78 subjects with work-related low back pain of less than 3 weeks duration were r and omized to  receive therapy  based on a classification system that attempts to match patients to specific interventions or therapy based on the Agency for Health Care Policy and Research guidelines . The subjects were followed for 1 year . Outcomes included the impairment index , Oswestry scale , SF-36 component scores , satisfaction , medical costs , and return to work status . Results . After adjustment for baseline factors , subjects receiving classification-based therapy showed greater change on the Oswestry ( P = 0.023 ) and the SF-36 physical component ( P = 0.029 ) after 4 weeks . Patient satisfaction was greater ( P = 0.006 ) and return to full-duty work status more likely ( P = 0.017 ) after 4 weeks in the classification-based group . After 1 year , there was a trend toward reduced Oswestry scores in the classification-based group ( P = 0.063 ) . Median total medical costs for 1 year after injury were $ 1003.68 for the guideline -based group and $ 774.00 for the classification-based group ( P = 0.13 ) . Conclusions . For patients with acute , work-related low back pain , the use of a classification-based approach result ed in improved disability and return to work status after 4 weeks , as compared with therapy based on clinical practice guidelines . Further research is needed on the optimal timing and methods of intervention for patients with acute low back pain Introduction In an earlier study , Gatchel et al. ( J Occup Rehabil 13:1–9 , 2003 ) demonstrated that participants at high risk for developing chronic low back pain disability ( CLBPD ) , who received a biopsychosocial early intervention treatment program , displayed significantly more symptom improvement , as well as cost savings , relative to participants receiving st and ard care . The purpose of the present study was to exp and on these results by examining whether the addition of a work-transition component would further strengthen the effectiveness of this early intervention treatment . Methods Using an existing algorithm , participants were identified as being high-risk ( HR ) or low-risk ( LR ) for developing CLBPD . HR participants were then r and omly assigned to one of three groups : early intervention ( EI ) ; early intervention with work transition ( EI/WT ) ; or st and ard care ( SC ) . Participants provided information regarding pain , disability , work status , and psychosocial functioning at baseline , periodically during treatment , and again 1 year following completion of treatment . Results At 1-year follow-up , no significant differences were found between the EI and EI/WT groups in terms of occupational status , self-reports of pain and disability , coping ability or psychosocial functioning . However , significant differences in all these outcomes were found comparing these groups to st and ard care . Conclusion The addition of a work transition component to an early intervention program for the treatment of ALBP did not significantly contribute to improved work outcomes . However , results further support the effectiveness of early intervention for high-risk ALBP patients OBJECTIVE To compare the efficacy and safety of valacyclovir hydrochloride and famciclovir for the treatment of  herpes zoster .  DESIGN A double-blind , r and omized , controlled , multicenter clinical trial in which patients received 7 days of treatment and were followed up for 24 weeks . SETTING S Patients reported directly to specialist centers or were referred from primary care centers . PATIENTS There were 597 otherwise healthy immunocompetent out patients , aged 50 years and older , who presented within 72 hours of onset of zoster rash . INTERVENTIONS Treatment with valacyclovir hydrochloride ( 1 g 3 times daily ) or famciclovir ( 500 mg 3 times daily ) for 7 days . MAIN OUTCOME MEASURES Resolution of zoster-associated pain and postherpetic neuralgia , rash healing , and treatment safety . RESULTS Intent-to-treat analysis did not detect statistically significant differences for valacyclovir vs famciclovir on resolution of zoster-associated pain ( hazard ratio , 1 . 02 ; 95 % confidence interval , 0.84 - 1.23 ; P = .84 ) . Furthermore , no differences were evident between treatments on rash healing rates and on a range of analyses of postherpetic neuralgia . Safety profiles for valacyclovir and famciclovir were similar , with headache and nausea being the more common adverse events . CONCLUSIONS Valacyclovir treatment is comparable to famciclovir treatment in speeding the resolution of zoster-associated pain and postherpetic neuralgia . Current wholesale prices indicate that valacyclovir is the more cost-effective treatment for herpes zoster ( $ 83.90 vs $ 140.70 per course ) BACKGROUND Neuropathy is a common adverse effect of chemotherapy . The tricyclic antidepressant , amitriptyline , is a gold st and ard in the treatment of neuropathic pain . This double-blind , r and omized placebo-controlled trial assessed the efficacy of amitriptyline to prevent chemotherapy-induced neuropathic symptoms . PATIENTS AND METHODS Patients without previous neuropathy , who started chemotherapy with vinca alcaloids , platina derivatives or taxanes  , were r and omized to receive amitriptyline ( target dose , 100 mg daily ) or placebo for the duration of their chemotherapy . Chemotherapy-induced neuropathic symptoms were evaluated with a patient diary and after every third chemotherapy cycle with clinical examination . The diary data were transformed to a neuropathy score . A total of 114 patients fulfilling the inclusion criteria were r and omly assigned to the treatment or control arm . RESULTS There was no difference in the appearance of chemotherapy-induced neuropathic symptoms between the groups . In general , the intensity of neuropathic symptoms was mild . CONCLUSION Amitriptyline does not prevent chemotherapy-induced neuropathy Purpose  Acute pain after open abdominal hysterectomy limits the function of patients in the postoperative period , but data regarding the analgesic efficacy of a low dose of pregabalin ( 75 or 150 mg ) have been conflicting . This study was performed to determine if a low dose of pregabalin could decrease postoperative opioid use following abdominal hysterectomy when compared with placebo . Methods American Society of Anesthesiologists I-II patients older than 18 yr and scheduled for open elective abdominal hysterectomy were recruited for participation and r and omized to one of three groups : pregabalin 75 mg ( P75 ) , pregabalin 150 mg ( P150 ) , or placebo . The study drug was administered two hours prior to surgery and 12 hr following the initial dose . Anesthetic technique and postoperative analgesia were st and ardized . Postoperative pain was managed using patient-controlled analgesia with morphine .  Pain at rest and movement as well as nausea were assessed with an 11-point numeric rating scale . Results One hundred and one patients were recruited , and 89 patients completed the study .  Mean ( SD ) cumulative morphine consumption at 24 hr postoperatively was 54.0 ( 26.2 ) mg for the placebo group , 53.1 ( 22.7 ) mg for the P75 group , and 44.3 ( 20.9 ) mg for the P150 group . Independent Student ’s t tests indicated no difference between the placebo group and either the P75 group ( 95 % confidence interval [ CI ] : −11.75 to 13.44 ; P = 0.8937 ) or the P150 group ( 95 % CI : −2.74 to 22.15 ; P = 0.1238 ) . Conclusions At the doses used in this study , pregabalin treatment may not be effective in reducing opioid use up to 24 hr postoperatively following abdominal hysterectomy . This trial was registered at www . Clinical Trials.gov : NCT00781131.RésuméObjectifLa douleur aiguë faisant suite à une hystérectomie par voie abdominale limite les fonctions des patients au cours de la période postopératoire , mais les données concernant l’efficacité analgésique d’une faible dose de prégabaline ( 75 ou 150 mg ) ont été contradictoires . Cette étude a été menée pour déterminer si une faible dose de prégabaline pouvait diminuer l’utilisation postopératoire des morphiniques après hystérectomie par voie abdominale , comparativement au placebo . MéthodesDes patientes , âgées de plus de 18 ans , de type I-II selon les critères de l’American Society of Anesthesiologists , et devant subir une hystérectomie programmée par voie abdominale ont été recrutées et r and omisées dans l’un des trois groupes suivants : prégabaline 75 mg ( P75 ) , prégabaline 150 mg ( P150 ) , ou placebo . Le médicament étudié a été administré deux heures avant l’intervention chirurgicale et 12 h après la dose initiale . La technique anesthésique et l’analgésie postopératoire ont été st and ardisées . La douleur postopératoire a été gérée en utilisant une analgésie par morphine contrôlée par le patient . La douleur au repos et au mouvement ainsi que les nausées ont été évaluées au moyen d’une échelle d’évaluation numérique de 11 points . RésultatsCent une patientes ont été incluses et 89 patientes ont terminé l’étude . Les consommations cumulées moyennes ( ET ) de morphine à 24 heures en postopératoire étaient de 54,0 ( 26,2 ) mg pour le groupe placebo , 53,1 ( 22,7 ) mg pour le groupe P75 et 44,3 ( 20,9 ) mg pour le groupe P150 . Des tests t de Student indépendants n’ont pas fait apparaître de différence entre le groupe placebo et soit le groupe P75 ( intervalle de confiance [ IC ] à 95 % : −11,75 à 13,44 ; p = 0,8937 ) , soit le groupe P150 ( IC à 95 % : −2,74 à 22,15 ; p = 0,1238 ) . Conclusions Aux doses utilisées dans cette étude , le traitement par prégabaline ne semble pas être efficace dans la réduction de la consommation de morphine à 24 heures postopératoires après hystérectomie par voie abdominale . Cette étude a été enregistrée sur le site www . clinical trials.gov : NCT00781131 Background : Treatment of herpes zoster ( HZ ) includes the use of acyclovir with or without steroids . An alternative therapy is the epidural administration of local anesthetics with or without steroids . This trial compared the efficacy of these two treatment regimens in the prevention of  post‐herpetic neuralgia ( PHN ) BACKGROUND We aim ed to investigate whether the addition of non-steroidal anti-inflammatory drugs or spinal manipulative therapy , or both , would result in faster recovery for patients with acute low back pain receiving recommended first-line care . METHODS 240 patients with acute low back pain who had seen their general practitioner and had been given advice and paracetamol were r and omly allocated to one of four groups in our community-based study : diclofenac 50 mg twice daily and placebo manipulative therapy ( n=60 ) ; spinal manipulative therapy and placebo drug ( n=60 ) ; diclofenac 50 mg twice daily and spinal manipulative therapy ( n=60 ) ; or double placebo ( n=60 ) . The primary outcome was days to recovery from pain assessed by survival curves ( log-rank test ) in an intention-to-treat analysis . This trial was registered with the Australian Clinical Trials Registry , ACTRN012605000036617 . FINDINGS Neither diclofenac nor spinal manipulative therapy appreciably reduced the number of days until recovery compared with placebo drug or placebo manipulative therapy ( diclofenac hazard ratio 1.09 , 95 % CI 0.84 - 1.42 , p=0.516 ; spinal manipulative therapy hazard ratio 1.01 , 95 % CI 0.77 - 1.31 , p=0.955 ) . 237 patients ( 99 % ) either recovered or were censored 12 weeks after r and omisation . 22 patients had possible adverse reactions including gastrointestinal disturbances , dizziness , and heart palpitations . Half of these patients were in the active diclofenac group , the other half were taking placebo . One patient taking active diclofenac had a suspected hypersensitivity reaction and ceased treatment . INTERPRETATION Patients with acute low back pain receiving recommended first-line care do not recover more quickly with the addition of diclofenac or spinal manipulative therapy Herpes zoster ( shingles ) develops in as many as 20 % of all persons [ 1 ] . The characteristic zoster rash is often accompanied by substantial pain , dysesthesias , and skin hypersensitivity . The unmet challenge in the management of patients with acute zoster is the alleviation of chronic pain . In many patients , pain resolves once the affected area of skin returns to normal . However , some patients continue to experience pain long after the lesions have healed ; this pain is commonly called postherpetic neuralgia . Postherpetic neuralgia is by far the most common complication of herpes zoster and is one of the most intractable pain disorders [ 2 , 3 ] . The incidence of postherpetic neuralgia increases sharply with increasing age [ 4 , 5 ] ; nearly half of patients older than 60 years have this complication [ 2 , 5 ] . Postherpetic neuralgia is also more severe and persists longer in older than in younger patients [ 3 ] . The disorder is clearly the most distressing component of the disease process for both the patient and the physician . Although for many years acyclovir has been the only oral antiviral agent approved for the treatment of patients with acute herpes zoster  , its effect on postherpetic neuralgia remains controversial [ 6 - 10 ] . Famciclovir , a new antiviral agent , was approved for marketing by the Food and Drug Administration in June 1994 for the management of acute herpes zoster . Famciclovir is the well-absorbed ( 77 % bioavailable ) [ 11 ] oral form of penciclovir , with activity against varicella-zoster virus , herpes simplex virus types 1 and 2 , and Epstein-Barr virus [ 12 - 15 ] . Penciclovir is selectively activated in virus-infected cells through phosphorylation to the antiviral compound penciclovir triphosphate . Viral thymidine kinase converts penciclovir to penciclovir monophosphate , which is converted by cellular enzymes to penciclovir triphosphate [ 12 , 16 , 17 ] . Penciclovir triphosphate inhibits viral DNA polymerase , thereby halting DNA synthesis and viral replication [ 16 - 19 ] . The in vitro potencies of penciclovir and acyclovir depend on the tissue culture cell line and assay method used but are generally similar [ 14 , 15 , 20].The 50 % plaque inhibitory concentrations in human lung fibroblasts infected with varicella-zoster virus were 4.0 1.5 g/mL for penciclovir and 4.0 1.1 g/mL for acyclovir [ 14 ] . A potentially clinical ly important characteristic of penciclovir triphosphate is that it persists in virus-infected host cells longer than acyclovir triphosphate [ 19 ] . For cells infected with varicella-zoster virus , the intracellular half-life of penciclovir triphosphate is 9.1 hours ; in contrast , the half-life for acyclovir triphosphate is 0.8 hours [ 19 , 21 ] . Thus , penciclovir triphosphate has the potential to continue to inhibit viral replication even if serum concentrations are below the inhibitory level . Consistent oral bioavailability linked to a favorable intracellular half-life of penciclovir triphosphate in cells infected with varicella-zoster virus suggested that famciclovir could offer clinical ly important advantages in the management of herpes zoster over currently available therapy . These advantages include a reduced total daily dose and a reduced dosing frequency . Because persistent antiviral activity throughout each day of dosing was expected to lead to improved clinical efficacy , especially with regard to postherpetic neuralgia , we examined the effects of famciclovir on acute herpes zoster and postherpetic neuralgia . Methods Study Design In our r and omized , double-blind , placebo-controlled , multicenter trial , we compared the efficacy and safety of famciclovir , 500 mg or 750 mg , given three times daily for 7 days , with that of placebo in the treatment of patients with uncomplicated acute herpes zoster . Eligible participants were immunocompetent patients 18 years or older with clinical ly diagnosed uncomplicated herpes zoster who gave written informed consent . Exclusion criteria included zoster rash that had been present for more than 72 hours ; complications of herpes zoster ( for example , ocular or visceral involvement , disseminated herpes zoster ) ; presence of crusts at enrollment ; other serious underlying disease ( such as immune disorders or human immunodeficiency virus [ HIV ] infection ) ; or pregnancy or lactation . Patients were prohibited from receiving any concomitant antiviral or immunomodifying therapy and any topical medication that would be applied to zoster lesions during the study . Patient Assessment s Patients were instructed to return to the clinic for evaluation of lesions and pain on each of the 7 therapy days and every day for the 7 days after therapy . Patients with lesions that were fully crusted by day 7 were examined every other day during the week after therapy . After day 14 , weekly visits were required of all patients until all lesions had lost their crusts . After the lesions had healed , patients were assessed for the presence of postherpetic neuralgia ( defined as pain after healing ) at monthly intervals for an additional 5 months . These monthly pain assessment s continued for all patients , even if postherpetic neuralgia had resolved before completion of the study period . Patients attending the clinic for fewer than 80 % of required visits were deemed noncompliant . The number of papules , vesicles , ulcers , and crusts within the primary dermatome was classified as none , mild ( < 25 lesions ) , moderate ( 25 to 50 lesions ) , or severe ( > 50 lesions ) . A specimen for viral culture was obtained at baseline and daily thereafter while vesicles were present . Patients were asked to rate the intensity of their pain as none , mild , moderate , or severe . Definitions for mild , moderate , and severe pain were not prospect ively provided . Adverse events were assessed at each visit according to the time of onset , duration , severity , and investigator-defined relation to the study medication . Blood sample s were obtained for chemical and hematologic assessment , and urine sample s were obtained for dipstick analysis before initiation of therapy and at the last therapy visit . Statistical Analysis Efficacy end points were analyzed by st and ard survival methods . We used the Cox proportional-hazards regression model in our analyses [ 22 ] . Time-dependent covariates were modeled to evaluate the proportional hazards assumption , and a model that included the main effects of treatment was used to examine efficacy . Statistical conclusions were based on the significance of estimated hazard ratios . Hazard ratios greater than 1 indicated a faster rate of event occurrence in patients receiving famciclovir than in those receiving placebo . An estimated hazard ratio of 2 indicated that the event of interest occurred twice as rapidly in patients receiving famciclovir as it did in placebo recipients . Two comparisons were made for each end point : 500-mg famciclovir compared with placebo and 750-mg famciclovir compared with placebo . We also used Kaplan-Meier estimates of the cumulative proportion of patients achieving an event to graphically illustrate the trial results . We used the Fisher exact test ( two-tailed ) to analyze proportion data . The primary efficacy variable was the time to full crusting of the lesions . Secondary variables included duration of viral shedding ; time to resolution of vesicles , ulcers , crusts , and acute pain ; and duration of postherpetic neuralgia ( that is , the time to resolution of pain after the lesions had healed ) . Healing was defined as the first time in which a patient had no papules , vesicles , ulcers , or crusts and after which did not develop them at any later visit . Similarly , the time to the resolution of a clinical variable was the time to the complete cessation of that variable with no further occurrence at any later date . Duration of viral shedding was measured as the number of days from the first dose of the study medication to the last positive culture . The enrollment objective before the study was 400 patients ; this number was selected to ensure a target of 300 evaluable patients ( 100 per group ) . The sample provided an 80 % power to detect a significant difference from placebo , assuming a true hazard ratio of 1.5 and exponential time to full crusting ( or time to event ) . We analyzed data from both the intention-to-treat group ( patients receiving at least one dose of study medication ) and the efficacy-evaluable group ( patients complying with the protocol ) . We prospect ively defined the efficacy-evaluable group before unblinding the r and omization code . Because the results of both analyses were generally similar , we present data for the intention-to-treat group , unless otherwise specified . We also examined prospect ively defined subgroups with respect to age , duration of rash at enrollment , and severity of rash at enrollment . The safety analysis included all patients who had received at least one dose of the study medication . Each analysis included all patients who provided information for the respective end point . For example , the analysis for the time to resolution of crusts included all patients who presented with crusts during the study . Therefore , the number of patients in each analysis of the time to resolution of a condition may vary because only patients experiencing the specific condition were included in the analysis . Results Demographic Characteristics Characteristics of patients in the intention-to-treat group ( n = 419 ) , including sex , age , duration of rash , location of rash , severity of rash , and severity of pain , are shown in Table 1 . Of the 419 patients enrolled , 138 received 500 mg of famciclovir , 135 received 750 mg of famciclovir , and 146 received placebo . Approximately half of the patients were female , and the mean age was 50 years . More than half of the patients had severe rash ( > 50 lesions ) at enrollment , and more than 60 % had moderate or severe zoster pain  at enrollment . Table 1 . Patient Characteristics at Study Enrollment The intention-to-treat group and the efficacy-evaluable group ( n = 323 ) had similar Seventy-two patients older than 60 years of age who received a diagnosis of herpes zoster ( HZ ) were entered into a r and omized , double-blind , placebo-controlled trial of daily amitriptyline 25 mg . Treatment with either amitriptyline or placebo continued for 90 days after diagnosis . Pain prevalence at 6 months was the primary outcome . Results showed that early treatment with low-dose amitriptyline  reduced pain prevalence by more than one-half ( p < 0.05 ; odds ratio , 2.9:1 ) This finding makes a strong case for the pre-emptive administration of amitriptyline , in combination with an antiviral drug , to elderly patients with acute herpes zoster BACKGROUND Epidural analgesia before limb amputation is commonly used to reduce postamputation pain . But there have been no controlled studies with large numbers of patients to prove such a pre-emptive effect . We investigated whether postamputation stump and phantom pain in the first year is reduced by preoperative epidural blockade with bupivacaine and morphine . METHODS In a r and omised , double-blind trial , 60 patients scheduled for lower-limb amputation were r and omly assigned epidural bupivacaine ( 0.25 % 4 - 7 mL/h ) and morphine ( 0.16 - 0.28 mg/h ) for 18 h before and during the operation ( 29 patients ; blockade group ) or epidural saline ( 4 - 7 mL/h ) and oral or intramuscular morphine ( 31 patients ; control group ) . All patients had general anaesthesia for the amputation  and were asked about stump and phantom pain after 1 week and then after 3 , 6 , and 12 months by two independent examiners . Study endpoints were rate of stump and phantom pain , intensity of stump and phantom pain , and consumption of opioids . FINDINGS Two patients in each group were withdrawn before amputation . The groups were well matched in baseline characteristics . Median duration of preoperative saline treatment was 18.5 h ( IQR 17 - 20 ) . Median duration of preoperative epidural blockade  in the blockade group was 18 h ( 15 - 20.3 ) . The combined median duration of postoperative epidural pain treatment in both groups was 166 h ( 89.3 - 308.3 ) . After 1 week , 14 ( 52 % ) patients in the blockade group and 15 ( 56 % ) in the control group had phantom pain ( 95 % CI - 30.6 to 22.7 , p = 0.9 ) . The figures for blockade versus control group were : 14 ( 82 % ) vs ten ( 50 % ; 4.0 to 60.8 , p = 0.09 ) at 3 months ; 13 ( 81 % ) vs 11 ( 55 % ; -2.7 to 55.3 , p = 0.2 ) at 6 months ; and nine ( 75 % ) vs 11 ( 69 % ; -27.0 to 39.6 , p = 1.0 ) at 12 months . Intensity of stump and phantom pain and consumption of opioids were similar in both groups at all four postoperative interviews . INTERPRETATION Perioperative epidural blockade started a median of 18 h ( 15 - 20.3 ) before the amputation and continued into the postoperative period does not prevent phantom or stump pain Study Design . Prospect i ve , double-blind study , r and omized control trial . Objective . To evaluate and compare the analgesic efficacy , adverse effects , and clinical utility of gabapentin and pregabalin in postoperative pain management , long-term functional outcome , and quality of life in patients undergoing spinal surgery . Summary of Background Data . Patient outcome after lumbar discectomy for radicular low back pain is variable and the benefit is inconsistent . The most common persistent symptoms are pain , motor deficit , and decreased functional status . Methods . This study was conducted in 90 patients belonging to the 18 to 75 age group of either sex undergoing spinal surgery under general anesthesia . Group A received 300 mg of gabapentin , group B received 75 mg of pregabalin , whereas group C received placebo 1 dose 1 hour before surgery and 8 hourly for 7 days , thereafter . The outcome of postoperative static and dynamic pain and functional outcome was recorded using 3 question naires — visual analogue scale , Prolo functional and economic score , Oswestry Disability Index score from preoperative period to 3 months postoperatively . Results . Among the 3 groups , subjects receiving pregabalin showed consistently reduced static and dynamic pain intensity and also required lesser amount of rescue drug throughout the postoperative period . There was statistically significant difference ( P < 0.05 ) in the Prolo score and Oswestry Disability Index score at all time intervals between group B and group C. Although , significant difference in the functional outcome between group A and group B was seen at 3 months . Conclusion . Preoperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy followed by gabapentin and then placebo . Level of Evidence : PURPOSE The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy .  METHODS Between April 1999 and October 2000 , forty-seven patients were r and omly assigned to either group one , which received vitamin E supplementation during cisplatin chemotherapy , or to group two , which received cisplatin chemotherapy alone . Alpha-tocopherol ( vitamin E ; 300 mg/d ) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment . For pre clinical studies , nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E. RESULTS Twenty-seven patients completed six cycles of cisplatin chemotherapy : 13 patients in group one and 14 patients in group two . The incidence of neurotoxicity was significantly lower in group one ( 30.7 % ) than it was in group two ( 85.7 % ; P < .01 ) . The severity of neurotoxicity , measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters , was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E ( 2 v 4.7 , P < .01 ) . The results of the pre clinical studies showed that when cisplatin was combined with vitamin E , no differences were observed in tumor weight inhibition , tumor growth delay , or life span as compared with treatment with cisplatin alone . CONCLUSION Supplementation of patients receiving cisplatin chemotherapy  with vitamin E decreases the incidence and severity of peripheral neurotoxicity e20505 Background : Neuropathic pain ( NP ) remains difficult to control for a significant proportion of patients with cancer . Chemotherapy induced peripheral neuropathy ( CIPN ) is postulated as an initial stage to the development of NP . Among breast cancer patients , taxanes , platinum agents , and vinca alkaloids are most likely to cause NP . The purpose of this study was to assess the extent to which those who experienced CIPN ( NCI toxicity criteria ≥ grade 2 sensory neuropathy ) during paclitaxel chemotherapy were at risk of developing chronic NP , controlling for disease- and treatment-related variables ( e.g. , stage of disease , location of tumor chemotherapy and other cancer therapies , dose of chemotherapy and duration of treatment ) , clinical health status ( e.g. , comorbid conditions ) , and sociodemographic characteristics ( e.g. , age , race ) . METHODS We conducted a follow-up survey of breast cancer patients who previously participated in clinical trials for paclitaxel .  Patients were asked if they have ever been diagnosed by the physician or healthcare provider for NP during the survey . Clinical trial data ( NCI Toxicity , cummulative dose ) were abstract ed from a clinical data base . RESULTS Of the 430 potential respondents , 240 responded to the survey . Mean follow-up time was 9.5 years ( SD=2.1 ) . Sixty three percent of the respondents had grade 2 or greater sensory neuropathy during their previous treatment with paclitaxel . Follow-up data showed that 18 % ( 43/240 ) were subsequently diagnosed by their physician to have NP . Logistic regression analysis showed that those with CIPN during the trial were 3 times more likely to having been diagnosed with NP ( OR=3 ; 95%CI=1.2 ; 7.2 ; p<0.001 ) , which persisted in the multivariable model . Other variables found to be associated with NP included cummulative dose of paclitaxel , and comorbid conditions such as diabetes and osteoarthritis . Patients with NP reported twice as many visits to their health care provider ( p=0.028 ) ; had taken more prescription ( 50 % versus 19 % ; p=0.0001 ) for pain relative to those without NP . CONCLUSIONS We provide empirical evidence on the importance CIPN as a risk factor for NP in breast cancer patients . Prospect i ve studies with larger cohorts are needed to vali date our findings . No significant financial relationships to disclose The efficacy of preemptive analgesia on postoperative pain is discussed . From experimental neurophysiological data , the present policy of preventive analgesia aims at precluding modifications of the nervous system secondary to a nervous lesion and the appearance of chronic pain , particularly of the neurogenic kind . The post-mastectomy pain syndrome ( PMPS ) falls within the realm of neurogenic pain and is still poorly understood and underestimated . This study evaluated the preemptive effect of a perioperative administration of an oral non steroid anti-inflammatory , the ibuprofen-arginine , on PMPS . Thirty patients scheduled for partial or total mastectomy with axillary dissection were prospect ively and r and omly assigned to 2 groups . The ibuprofen-arginine group ( group I ) ( n = 15 ) , received an oral administration of 400 mg of ibuprofen-arginine , 90 min before surgery , 2 h after surgery and then every 8 h in the first 32 postoperative hours . The control group ( group C ) received in doubled blind a placebo at the same time . At 6 months , we looked after pain or dysesthesia . We confirmed the diagnosis of PMPS in presence of association of diagnosis criteria s. Fourteen patients in each group have been included . Eighty-six percent of the patients ( 13 patients in group I and 11 patients in group C ) presented at 6 months dysesthesia of the upper member ipsilateral to the mastectomy and /or the operated breast , appearing either immediately or after a laps of time . Nine patients ( group I ) and 6 patients ( group C ) had PMPS . Postoperative radiotherapy and lymphoedema were statistically associated with PMPS ( p = 0.019 and p = 0.011 ) . The perioperative preventive administration of a non-steroid anti-inflammatory drug reduces neither the incidence of pain in the first post-operative months , nor the appearance of PMPS at 6 months . These results suggest that others factors than the nervous lesion may play a role in the occurrence of PMPS , as radiotherapy , lymphoedema , but also psychosocials factors OBJECTIVES The purpose of this study was to evaluate the analgesic effects of perioperative gabapentin on postoperative acute and chronic pain after coronary artery bypass graft ( CABG ) surgery with median sternotomy and internal mammary artery harvesting . DESIGN A double-blind r and omized clinical study . SETTING A single-academic hospital . PARTICIPANTS Patients with ischemic heart disease who were scheduled to undergo CABG surgery . INTERVENTIONS Forty patients were allocated r and omly into 2 groups ; the gabapentin group ( n = 20 ) received 1.2 g/d of oral gabapentin before and for 2 days after surgery , and the placebo group ( n = 20 ) received a placebo capsule instead . The primary outcome was to evaluate the effects of gabapentin on acute and chronic pain after surgery . The postoperative evaluation included the assessment of pain at rest and when coughing , intravenous tramadol usage , postoperative morbidities , and side effects of gabapentin . Postoperative analgesia at 6 , 12 , 18 , 24 , 48 , and 72 hours after extubation and at discharge was evaluated with the visual analog scale . The assessment of postoperative pain at the 1- and 3-month follow-ups was performed using a numeric rating scale . MAIN RESULTS Postoperative pain scores at 1 , 2 , and 3 days were significantly lower in the gabapentin group when compared with the placebo group ( p < 0.05 ) . Pain scores at 1 and 3 months postoperatively were lower in the gabapentin group than in the placebo group ( p > 0.05 ) . Consumption of intravenous tramadol given as rescue analgesic within 24 hours after extubation in the gabapentin group was 99.0 ± 53.8 mg versus 149.4 ± 72.5 mg in the placebo group ( p < 0.05 ) . There were no differences in the incidence of side effects and time to extubation between the groups . CONCLUSIONS Gabapentin significantly reduced the intensity of pain and tramadol consumption in the early postoperative period after CABG surgery . Pain scores at 1 and 3 months after surgery were low in both groups , with no significant difference between the groups BACKGROUND : Preoperative oral gabapentin has been shown to reduce postoperative pain . However , the effects of gabapentin as an adjunct to regional anesthesia is unclear and its effects on chronic pain remains unknown . In patients undergoing thyroidectomy , we investigated the effects on early and late ( at 6 mo ) postoperative pain of preoperative oral gabapentin as an adjunct to superficial cervical plexus block ( SCPB ) . METHOD : Fifty consecutive consenting patients were r and omized to receive either 1200 mg of gabapentin ( Group G ) or placebo ( Group P ) 2 h preoperatively . Preoperative anxiety was assessed on a numeric scale from 0 to 6 . A SCPB was performed after a st and ardized induction of anesthesia . The primary outcome , analgesic drug consumption , was assessed during the procedure and postoperatively in the postanesthesia care unit and after discharge to the ward . Over the first 24 h , pain levels at rest and during swallowing were measured on a numeric scale from 0 to 10 . If the pain level was more than 4/10 at rest , patients received 1 g/6 h of IV paracetamol and /or 50 mg/6 h of IV tramadol as a rescue analgesic treatment in the interval . The day before operation and 6 mo after thyroidectomy , included patients were asked to answer a neuropathic pain diagnostic question naire . RESULTS : Population characteristics , preoperative anxiety , intraoperative drug consumption , procedure duration , and postoperative care unit stay were comparable in both groups . Analgesic consumption during the first 24 postoperative hours was similar in both groups ( G : 3 [ 0–5 ] doses/24 h ; P : 3 [ 1–5 ] doses/24 h ; P = NS ) , as well as pain at rest ( G : 2,2 [ 0.2–3.7 ] ; P : 2 [ 0–6.3 ] ; P = NS ) , and during swallowing ( G : 2.8 [ 0.4–8.9 ] ; P : 3 [ 1.4–6.3 ] ; P = NS ] ) . Eight patients had a diagnostic question naire score more than 3 , 6 mo after operation versus 2 in preoperative period ( P = 0.04 ) . Such delayed neuropathic pain complaints were reported in seven patients receiving SCPB alone and only in one patient receiving both SCPB and preoperative adjunctive oral gabapentin . ( P = 0.01 ) . CONCLUSION : Oral preoperative administration of gabapentin did not modify immediate pain management in thyroidectomy patients receiving SCPB , but prevented delayed neuropathic pain at 6 mo & NA ; This study tested the hypothesis that high dose systemic alfentanil administered before and during abdominal hysterectomy would pre‐empt post‐operative pain to a greater extent than administration of either low dose alfentanil or no alfentanil perioperatively . Patients ( ASA 1 or 2 ) were r and omly assigned to group 1 ( n = 15 ) , no opioid ; group 2 ( n = 15 ) , low dose alfentanil ; or group 3 ( n = 15 ) , high dose alfentanil . Anaesthesia was induced in group 1 with midazolam and thiopentone and was maintained with isoflurane and 70 % N2O in O2 . Anaesthesia was induced in group 2 with midazolam , thiopentone and i.v . alfentanil ( 30 & mgr;g kg−1 ) , and was maintained with isoflurane , 70 % N2O in O2 , and bolus doses of i.v . alfentanil ( 10–20 & mgr;g kg−1 ) every hour . Anaesthesia was induced in group 3 with midazolam and i.v . alfentanil ( 100 & mgr;g kg−1 ) , and was maintained with 70 % N2O in O2 , and an infusion of i.v . alfentanil ( 1–2 & mgr;g kg−1 min−1 ) . Blood sample s were drawn at 30 and 120 min after surgery and assayed for plasma alfentanil . Morphine consumption and VAS pain scores were consistently lowest in group 3 over the 48 h study period . A composite measure of pain and morphine consumption was significantly lower in group 3 than group 2 up to 6 h after surgery , and siificantly lower than group 1 up to 12 h. No adverse effects were observed . A 6‐month follow‐up did not reveal any significant differences among the three groups . It is concluded that intra‐operative high dose alfentanil anaesthetic pre‐empts post‐operative pain after abdominal hysterectomy , but the effects are small and of short duration . Surgical procedures carried out under general anaesthesia using st and ard ( and even high ) doses of opioids intraoperatively provide sub‐optimal protection from the injury barrage brought about by incision and subsequent noxious surgical events We investigated the analgesic efficacy of mexiletine and gabapentin on  acute and chronic pain associated with cancer breast surgery in 75 patients . They were r and omized to receive , in a double-blinded manner , mexiletine 600 mg/d , gabapentin 1200 mg/d , or placebo for 10 days . Anesthesia was st and ardized , and all patients had access to routine postoperative analgesics on dem and . The visual analog scale score assessed pain at rest and after movement . Three months later , all patients were interviewed to identify intensity of chronic pain and analgesic requirements .  Mexiletine and gabapentin  reduced codeine  consumed from the second to tenth day by 50 % ( P = 0.029;P = 0.018 and P = 0.035 for mexiletine versus control and gabapentin versus control comparisons , respectively ) . Total paracetamol consumption was also reduced during the same time ( P = 0.0085;P = 0.007 and P = 0.011 for the mexiletine and gabapentin groups when compared with the control , respectively ) . Pain at rest and after movement was reduced by both drugs on the third postoperative day . Pain after movement also was reduced by gabapentin between the second and fifth postoperative day . Three months later , the incidence of chronic pain , its intensity , and need for analgesics were not affected by either treatment . However , burning pain was more frequent in the control group ( P = 0.033 ) STUDY DESIGN A r and omized , controlled , single-center trial with a stratified group design . OBJECTIVE To investigate the secondary prophylactic effect of the Active Back School program on minimizing recurrences of low back pain episodes . SUMMARY OF BACKGROUND DATA The results of back school interventions are controversial . Previous work often used short intervention periods and low doses of practical training . However , studies with the highest method ologic scores have shown the best results , especially when conducted in occupational setting s and coupled with a comprehensive rehabilitation program . METHODS By block r and omization , 19 men and 24 women were allocated to Active Back School , with 18 men and 20 women as control subjects . The Slumps test and number of low back pain episodes during the previous 36 months were used as stratification factors . There were no significant differences between the groups with regard to demographic factors and initially observed variables . Active Back School consisted of 20 lessons over a 13-week period . Each lesson was divided into a 20-minute theoretical part and a 40-minute exercise part . All participants were examined on enrollment , then 5 and 12 months after initiation of the program . Outcome measures were recurrence of low back pain episodes and number of days of sick leave . RESULTS The recurrence of new low back pain episodes was significantly lower ( P < 0.05 ) and the time from inclusion to the first new episode significantly longer ( P < 0.01 ) in the Active Back School group than in the control group . In the Active Back School group , seven participants took sick leave because of low back pain episodes during the first 12 months of follow-up compared with 11 among the control subjects . The number of sick leave days was significantly lower ( P < 0.05 ) in the Active Back School group than in the control group . CONCLUSION Active Back School reduced the recurrence and severity of new low back pain episodes according to results of follow-up examinations performed 5 and 12 months after enrollment Abstract Objectives : To investigate the cl aim that 90 % of episodes of low back pain that present to general practice have resolved within one month . Design : Prospect i ve study of all adults consulting in general practice because of low back pain over 12 months with follow up at 1 week , 3 months , and 12 months after consultation . Setting : Two general practice s in south Manchester . Subjects : 490 subjects ( 203 men , 287 women ) aged 18 - 75 years . Main outcome measures : Proportion of patients who have ceased to consult with low back pain  after 3 months ; proportion of patients who are free of pain and back related disability at 3 and 12 months . Results : Annual cumulative consultation rate among adults in the practice s was 6.4 % . Of the 463 patients who consulted with a new episode of low back pain , 275 ( 59 % ) had only a single consultation , and 150 ( 32 % ) had repeat consultations confined to the 3 months after initial consultation . However , of those interviewed at 3 and 12 months follow up , only 39/188 ( 21 % ) and 42/170 ( 25 % ) respectively had completely recovered in terms of pain and disability . Conclusions : The results are consistent with the interpretation that 90 % of patients with low back pain in primary care will have stopped consulting with symptoms within three months . However most will still be experiencing low back pain and related disability one year after consultation . Key messages It is widely believed that 90 % of episodes of low back pain seen in general practice resolve within one month In a large population based study we examined the outcome of episodes of low back pain in general practice with respect to both consultation behaviour and self reported pain and disability While 90 % of subjects consulting general practice with low back pain ceased to consult about the symptoms within three months , most still had substantial low back pain and related disability Only 25 % of the patients who consulted about low back pain had fully recovered 12 months later Since most consulters continue to have long term low back pain and disability , effective early treatment could reduce the burden of these symptoms and their social , economic , and medical BACKGROUND : The treatment of postherpetic neuralgia ( PHN ) continues to be a challenge in clinical pain management . In this r and omized , controlled study , we assessed the effectiveness of repetitive paravertebral injections with local anesthetics and steroids for the prevention of PHN in patients with acute herpes zoster . METHODS : One hundred thirty-two patients with acute herpes zoster diagnosed 1–7 days after the onset of the rash were r and omly assigned to receive either st and ard therapy ( oral antivirals and analgesics ) or st and ard therapy with additional repetitive paravertebral injections of a mixture of 10 mL 0.25 % bupivacaine and 40 mg methylprednisolone acetate every 48 h for a week . Efficacy was evaluated at 1 , 3 , 6 , and 12 mo after the end of the treatments . The primary end point was the proportion of patients with zoster-associated pain and /or allodynia 1 mo after inclusion . Statistical analysis was performed based on the intent-to-treat population . RESULTS : One hundred thirteen patients completed the 1-yr follow-up . At 1 mo posttherapy , 13 % of patients in the paravertebral group reported zoster-related pain , compared with 45 % in the st and ard group ( P < 0.001 ) . At 3 , 6 , and 12 mo posttherapy , the incidence of PHN was still significantly lower in the paravertebral group than in the st and ard group . The quality of life improved in both groups at each follow-up time point with no significant difference between groups . CONCLUSION : Repetitive paravertebral anesthetic block in combination with steroids plus st and ard treatment with acyclovir and analgesics significantly reduced the incidence of PHN than the st and ard treatment alone In a r and omized , double-blind , placebo-controlled pilot study , we examined the effect of Org 2766 - -a corticotropin ( 4 - 9 ) analogue -- on neurotoxicity  in 28 patients with lymphoma who were treated with combination chemotherapy containing Vinca alkaloids ( vincristine and vinblastine ) .  The patients received a total dose of 12 mg of vincristine in the case of non-Hodgkin 's lymphoma and a total dose of 16 mg of vincristine in the case of Hodgkin 's disease . Moreover , the patients with Hodgkin 's disease received a mean total dose of 84 mg of vinblastine . Subcutaneous injections of 2 mg of Org 2766 or placebo were administered to patients with non-Hodgkin 's lymphoma on days 1 and 10 of each chemotherapy course and to patients with Hodgkin 's disease on days 1 and 8 of each chemotherapy course . The first injection was always given before the administration of vincristine .  Assessment of neurologic symptoms and signs and measurement of sensory thresholds ( vibration sense and temperature sense ) were performed on day 1 of the first , fourth , and sixth ( or eighth ) courses and 6 weeks after cessation of chemotherapy . Thirteen patients ( mean age , 44.7 years ) received  Org 2766 and 15 patients ( mean age , 54.7 years ) received placebo . More symptoms occurred in the placebo group , but only numbness and autonomic complaints occurred significantly more often in the placebo group . Motor deficit and sensory disturbances were more severe and also occurred significantly more often in the placebo group . There was no difference with respect to reflex examination findings and sensory thresholds . ( ABSTRACT TRUNCATED AT 250 WORDS The frequency , characteristics and reversibility of bortezomib‐associated peripheral neuropathy were evaluated in the phase III APEX ( Assessment of Proteasome Inhibition for Extending Remissions ) trial in patients with relapsed myeloma , and the impact of a dose‐modification guideline on peripheral neuropathy severity and reversibility was assessed . Patients received bortezomib 1·3 mg/m2 ( days 1 , 4 , 8 , 11 , eight 21‐d cycles , then days 1 , 8 , 15 , 22 , three 35‐d cycles ) ; bortezomib was held , dose‐reduced or discontinued depending on peripheral neuropathy severity , according to a protocol ‐specified dose‐modification guideline . Overall , 124/331 patients ( 37 % ) had treatment‐emergent peripheral neuropathy , including 30 ( 9 % ) with grade ≥3 ; incidence and severity were not affected by age , number/type of prior therapies , baseline glycosylated haemoglobin level , or diabetes history . Grade ≥3 incidence appeared lower versus phase II trials ( 13 % ) that did not specifically provide dose‐modification guidelines . Of patients with grade ≥2 peripheral neuropathy , 58/91 ( 64 % ) experienced improvement or resolution to baseline at a median of 110 d , including 49/72 ( 68 % ) who had dose modification versus 9/19 ( 47 % ) who did not . Efficacy did not appear adversely affected by dose modification for grade ≥2 peripheral neuropathy . Bortezomib‐associated peripheral neuropathy is manageable and reversible in most patients with relapsed myeloma . Dose modification using a specific guideline improves peripheral neuropathy management without adversely affecting outcome Oxaliplatin is a promising drug for cancer therapy and the oxaliplatin/5-fluorouracil/leucovorin ( FOLFOX ) regimen has become the st and ard adjuvant treatment for colorectal cancer . However , the oxaliplatin-induced neurotoxicity still represents a clinical problem leading to a discontinuation of the therapy . Many strategies have been proposed in order to manage the neurotoxicity , but their effect on antitumoral efficacy is still unclear . In this study , we investigated the effect of reduced glutathione administration on neurotoxicity , oxaliplatin pharmacokinetics , and platinum-DNA ( Pt-DNA ) adduct formation in patients affected by colorectal cancer treated with FOLFOX4 adjuvant regimen . Twenty-seven patients were r and omized to receive GSH 1500 mg/m2 or saline solution before oxaliplatin infusion . Evaluation of neurotoxicity , pharmacokinetics of plasmatic total and ultrafiltered Pt , and determination of Pt-DNA adduct formation on white blood cells was performed during the 5th , 9th , and 12th cycles . At the end of all cycles of therapy , the patients in the GSH arm showed a statistically significant reduction of neurotoxicity ( P=0.0037 ) compared with the placebo arm . There were no significant differences in the main pharmacokinetic parameters between the two arms except a lower area under the plasma concentration – time curve and a smaller apparent steady-state volume of distribution ( Vss ) when GSH was coadministered . This difference can be explained by the natural function of GSH in the detoxification of oxaliplatin and by its ability to remove the Pt bound to plasma proteins . The determination of Pt-DNA adduct formation shows no statistically significant differences between the two arms . In conclusion , this study indicates that coadministration of GSH is an effective strategy to reduce the oxaliplatin-induced neurotoxicity without impairing neither the pharmacokinetics of oxaliplatin , nor the Pt-DNA adduct formation PURPOSE Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy . Intravenous calcium and magnesium have been extensively used to reduce oxaliplatin-induced neurotoxicity . This trial was design ed to definitively test whether calcium/magnesium decreases oxaliplatin-related neurotoxicity . PATIENTS AND METHODS In all , 353 patients with colon cancer undergoing adjuvant therapy with FOLFOX ( fluorouracil , leucovorin , and oxaliplatin )  were r and omly assigned to intravenous calcium/magnesium before and after oxaliplatin , a placebo before and after , or calcium/magnesium before and placebo after . The primary end point was cumulative neurotoxicity measured by the sensory scale of the European Organisation for Research and Treatment of Cancer Quality of Life Question naire-Chemotherapy-Induced Peripheral Neuropathy 20 tool . RESULTS There were no statistically significant neuropathy differences among the study arms as measured by the primary end point or additional measures of neuropathy , including clinician-determined measurement of the time to grade 2 neuropathy by using the National Cancer Institute Common Terminology Criteria for Adverse Events scale or an oxaliplatin-specific neuropathy scale . In addition , calcium/magnesium did not substantially decrease oxaliplatin-induced acute neuropathy . CONCLUSION This study does not support using calcium/magnesium to protect against oxaliplatin-induced neurotoxicity & NA ; Perioperative minocycline administration for 8 days after lumbar discectomy does not improve persistent pain . & NA ; Minocycline strongly inhibits microglial activation , which contributes to central sensitization , a major mechanism underlying chronic pain development . We hypothesized that the perioperative administration of minocycline might decrease persistent pain after lumbar discectomy . We r and omly assigned 100 patients undergoing scheduled lumbar discectomy to placebo and minocycline groups . The minocycline group received 100 mg minocycline orally , twice daily , beginning the evening before surgery and continuing for 8 days . The primary outcome was the change in lower limb pain intensity at rest between baseline and 3 months . Secondary outcomes were pain intensity on movement , the incidence of persistent pain and chronic neuropathic pain , back pain intensity at rest and on movement , and changes in Neuropathic Pain Symptom Inventory , Brief Pain Inventory , and Rol and ‐Morris scores at 3 months . An intention‐to‐treat analysis was performed for patients assessed from the day before surgery to 3 months . The decrease in lower limb pain intensity was similar in the placebo and minocycline groups , both at rest −1.7 ± 1.6 vs −2.3 ± 2.4 and on movement −2.5 ± 2.1 vs −3.4 ± 2.9 . The incidence and intensity of neuropathic pain and functional scores did not differ between the minocycline and placebo groups . Exploratory analysis suggested that minocycline might be effective in a subgroup of patients with predominantly deep spontaneous pain at baseline . Perioperative minocycline administration for 8 days does not improve persistent pain after lumbar discectomy
target: Such interventions would have the potential to reduce the prevalence of chronic pain in the population .
background: Although certain risk factors can identify individuals who are most likely to develop chronic pain , few interventions to prevent chronic pain have been identified .
  To facilitate the identification of preventive interventions , an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain .
  We present general design considerations for prevention trials in population s that are at relatively high risk for developing chronic pain .