Greater Pain Relief Research Articles

Decreased postoperative pain after reduction of fractured nasal bones using a nerve block of the anterior ethmoidal nerve

There is consensus that all patients should experience minimal pain following reduction of a fractured nasal bone. The issue requiring further study is what technique will provide patients with the greatest pain relief following the reduction of nasal fractures. This study investigated the use of an anterior ethmoidal nerve block as preemptive analgesia for the management of postoperative pain associated with reduction of nasal bone fractures. The medical documents of 85 patients were reviewed for a retrospective case-controlled comparative study. Patients in the nerve block group (n=45) were injected with 2% lidocaine containing epinephrine into the anterior ethmoidal nerve and dorsal periosteum, and those in the control group (n=40) were not. The rate of patients requiring postoperative injectable analgesics was compared between the two groups. The rate of patients who received a postoperative analgesic injection was significantly lower in the nerve block group than in the control group (P=0.034). The use of an anterior ethmoidal nerve block and dorsal periosteal injection of anaesthetic solution during reduction of fractured nasal bones under general anaesthesia resulted in the effective reduction of postoperative pain. Thus, this is regarded as a good method for enhancing patient quality of care and compliance in the reduction of fractured nasal bones.

Cost Comparisons of Various Diagnostic Medial Branch Block Protocols and Medial Branch Neurotomy in a Private Practice Setting

We calculated the average total facility and professional cost of medial branch neurotomy (MBN) procedure and diagnostic medial branch blocks (MBBs), based on increments of MBB results (50-100% cutoff values), to determine the most cost-effective protocol that correlates with positive MBN outcome. We evaluated both actual cost and the theoretical cost of procedures in three groups: 0, single and double MBB. We calculated costs assuming MBB success rates at incrementally higher levels by incrementally raising the cutoff values for a successful diagnostic MBB by 10% increments (from 50% to 100%). We analyzed each cutoff value using the preposition that all patients meeting the cutoff value would proceed to MBN. Those not meeting the cutoff value would not have the cost of MBN added to the cost calculations. A cost per successful procedure was also analyzed. Cost savings were noted when ≥70% cutoff MBB values were utilized and additionally when patients declined MBN for reasons other than their MBB outcome, although these dropouts lowered the cost-effectiveness of MBB when analyzed as cost per successful procedure. Costs over 5 years per successful procedure using 0, 1 and 2 diagnostic MBB protocol (x) and MBB protocol (o) were, however, similar at all MBB cutoff values. Diagnostic MBB using progressively stringent MBB cutoff values incrementally excluded patients without posterior element pain as evidenced by incremental increase in positive outcomes following MBN. The exclusion of patients from MBN due to failure to report 70% or greater pain relief following MBB resulted in cost savings in favor of performing diagnostic MBB.

Treatment of Chronic, Intractable Pain With a Conventional Implantable Pulse Generator

To provide further short-term (6 mo) and long-term (1 y) evidence for the use of spinal cord stimulation (SCS) with a conventional implantable pulse generator in the management of chronic, intractable pain. We conducted a meta-analysis of 4 prospective, multicenter studies that collected outcome data from patients implanted with SCS to treat chronic pain of the trunk and/or limbs (Genesis IPG system). Two of these were conducted as long-term studies lasting 1 year, and 2 as shorter term studies lasting 6 months. A total of 300 patients from 28 investigational sites were prospectively evaluated for efficacy at 3 months after implant and safety at 6 months after implant. None of the sites participated in more than one study. Outcome measures included patient-reported percent of pain relief, patient satisfaction, quality of life improvement, pain evaluation (0 to 10 rating), pain relief rating, Short-Form McGill Pain Questionnaire, visual analog scale, the Short Form-36, and the total number of adverse events (AEs). At 3 months after implantation of the permanent system, 75.4% of the patients (190/252) reported a 50% or greater pain relief as determined by the patient-reported degree of pain relief. Similarly, assessment of patient satisfaction with SCS therapy showed that 86.1% of patients (217/252) in all 4 studies were satisfied or very satisfied with the therapy at 3 months. In the 2 long-term studies, 80.9% of patients (140/173) were satisfied or very satisfied with the therapy at the 1-year evaluation point. Quality-of-life (QoL) data indicated that at 3 months after implant, 77.8% of patients (196/252) reported QoL as improved or greatly improved. Similarly, QoL was improved or greatly improved for 74.0% patients in the long-term study at 1 year (128/173). In the safety analysis, AEs were reviewed for all 4 studies. A total of 190 AEs were reported in 117 of 300 patients during all studies. This analysis provides further evidence of the safety and effectiveness of SCS in treating chronic intractable pain of the trunk and/or limbs. Specifically, it underscores a high level of effectiveness and acceptable safety concerns in the use of nonrechargeable SCS devices.

Correlation of Lumbar Medial Branch Neurotomy Results with Diagnostic Medial Branch Block Cutoff Values to Optimize Therapeutic Outcome

We sought an optimal medial branch block (MBB) cutoff value for both single and double MBB protocols that would best correlate with a positive outcome of medial branch neurotomy (MBN). We analyzed the percentage of subjective pain relief following MBB, confirmed by numerical rating scale (NRS) in aggravating positions before and 45 minutes after MBB. The percentage of overall pain relief following MBB was plotted against the following outcome variables: degree of subjective pain relief, duration of relief, patient satisfaction and activity level, no other doctor's visits, and reduction in medications use. Using the percent of pain relief post-MBB plotted in 10% increments in the double-MBB group, patients reporting 70% or greater pain relief following MBB showed statistically favorable outcome for the following four criteria: percentage of pain relief, duration of relief, patient satisfaction, and pain medications reduction. In the single MBB group, patients reporting 80% or greater pain relief following MBB had favorable outcomes for improvement in activity level and patient satisfaction. The double MBB protocol better correlated with favorable MBN outcomes compared with a single MBB protocol. Using a double MBB protocol, a 70% cutoff value for reported subjective pain relief post-MBB best predicted overall outcome following MBN. Without a confirmatory MBB, an 80% cutoff value was the optimal value.

Comparison of Four Different Analgesic Discogram Protocols Comparing the Incidence of Reported Pain Relief Following Local Anesthetic Injection into Concordantly Painful Lumbar Intervertebral Discs

To compare the incidence of pain relief following injection of local anesthetic (LA) into lumbar discs that caused concordant pain during provocation testing. Prospective collected data review from two centers and compare with published results. We compared subjective reported pain relief following provocative testing using the following protocols at three separate facilities: 23 patients undergoing routine provocative discography using contrast alone (PD); 47 patients undergoing provocative discography performed using an equal combination of LA and contrast (CPD); 120 patients injected with LA following routine PD (ADPD); 33 patients undergoing stand-alone analgesic discography (SAAD); and 28 patients injected with LA through a catheter (FAD) placed during provocative discogaphy testing. Pressure-controlled PD showed a positive response rate of 34% per disc in patients with a clinical diagnosis of discogenic pain. None of the PD group without LA had pain relief and less than 10% of the CPD group reported pain relief. Forty percent of the SAAD group with positive pain reproduction reported ≥50% relief and 20% reporting ≥80% relief. Forty-six percent of the ADPD group reported ≥50% relief and 30% reporting ≥80% relief. The FAD group had a greater 80% patients reporting ≥50% pain relief although fewer 26% reporting more convincing ≥80% relief. If the criterion standard to confirm painful annular tears is concordant pain provocation and 80% or greater pain relief following LA injected into lumbar discs, the SAAD, ADPD, and FAD protocols show statistically similar 20% to 30% prevelance.

Glenoid or not glenoid component in primary osteoarthritis

The optimal choice for the treatment of end-stage primary glenohumeral osteoarthritis remains controversial, with alternatives including total shoulder replacement (TSR) and humeral head replacement (HHR). The objective of this review is to analyze the effect of TSR compared with HHR on rates of pain relief, range of motion, patient satisfaction and revision surgery in patients with primary glenohumeral osteoarthritis. Compared with HHR, TSR provided significantly greater pain relief, gain in forward elevation, and gain in external rotation and patient satisfaction. Furthermore, TSR required significantly less revision surgery glenoid component loosening than patients undergoing HHR (progression of osteoarthritis changes with subchondral sclerosis, joint space narrowing and glenoid subsidence). A convex-back pegged glenoid component with a modern instrumented cement pressurization technique achieves risk of loosening. For 10 years, a high interest regarding new designs of un-cemented metal back glenoid components has developed with promising results, because they allow glenoid bone graft in case of glenoid erosion or dysplasia and a one-stage glenoid bone reconstruction in case of revision surgery.

A Randomized Controlled Trial of Patient-controlled Analgesia Compared with Boluses of Analgesia for the Control of Acute Traumatic Pain in the Emergency Department

BackgroundThe use of patient-controlled analgesia (PCA) has been reported to provide effective pain relief, often resulting in less opioid consumption, and is associated with greater patient satisfaction when it is compared to other techniques of analgesia delivery. ObjectivesThis study was done to compare the effectiveness of pain relief and patient satisfaction between PCA and the conventional method of administering boluses of analgesia for acute pain of traumatic origin in the Emergency Department (ED). MethodsStudy patients were randomized into two groups after being given a bolus of morphine. The PCA group was then given morphine via the PCA system, whereas the control group was given the conventional boluses of morphine via titration method. Pain levels were measured using the visual analogue scale at intervals of 0, 15, 30, 45, 60, 90, and 120 min. Any adverse events were also noted. Finally, within 24 h, these patients completed questionnaires regarding their experience with regard to the pain relief they experienced. ResultsThe PCA group experienced faster and greater pain relief. No life-threatening events were encountered. The satisfaction questionnaire revealed that the PCA group was more satisfied using the PCA method of pain relief than those receiving standard boluses for delivery of analgesia. ConclusionPCA provides more effective pain relief and more patient satisfaction when compared to the conventional method of titrated bolus intravenous injection for the relief of traumatic pain in the ED setting.

Elucidation of Pathophysiology and Treatment of Neuropathic Pain

Neuropathic pain, pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, is relatively common, occurring in about 1% of the population. Studies in animal models describe a number of peripheral and central pathophysiological processes after nerve injury that would be the basis of underlying neuropathic pain mechanism. Additionally, neuro-imaging (positron emission tomography and functional magnetic resonance imaging) provides insights in brain mechanisms corresponding with mechanistic processes including allodynia, hyperalgesia, altered sensation, and spontaneous pain. A change in function, chemistry, and structures of neurons (neural plasticity) underlie the production of the altered sensitivity characteristics of neuropathic pain. Peripheral processes in neuropathic pain involve production of mediators (cytokines, protons, nerve growth factor), alterations in calcium channels, sodium channels, hyperpolarisation-activated nucleotide-gated ion channels, and potassium channels, phenotypic switches and sprouting of nerves endings, and involvement of the sympathetic nervous system. Stimulation of the N-Methyl-D-Aspartate receptor, activation of microglia, oligodendrocytes, and astrocytes, increased production of nerve growth factor and brain-derived neurotrophic factor together with loss of spinal inhibitory control are responsible for central neuron hyperexcitability and maintenance of neuropathic pain. Recent advances, including functional imaging techniques, in identification of peripheral and central sensitization mechanisms related to nervous system injury have increased potential for affecting pain research from both diagnostic as well as therapeutic view. Key brain regions involved in generating pharmacologically induced analgesia may be identified. Despite the progress in pain research, neuropathic pain is challenge to manage. Although numerous treatment options are available for relieving neuropathic pain, there is no consensus on the most appropriate treatment. However, recommendations can be proposed for first-line, second-line, and third-line pharmacological treatments based on the level of evidence for the different treatment strategies. Available therapies shown to be effective in managing neuropathic pain include opioids and tramadol, anticonvulsants, antidepressants, topical treatments (lidocaine patch, capsaicin), and ketamine. Tricyclic antidepressants are often the first drugs selected to alleviate neuropathic pain (first-line pharmacological treatment). Although they are very effective in reducing pain in several neuropathic pain disorders, treatment may be compromised (and outweighed) by their side effects. In patients with a history of cardiovascular disorders, glaucoma, and urine retention, pregabalin and gabapentine are emerging as first-line treatment for neuropathic pain. In addition these anti-epileptic drugs have a favourable safety profile with minimal concerns regarding drug interactions and showing no interference with hepatic enzymes. Alternatively, opioids (oxycodone and methadone) and tramadol may alleviate nociceptive and neuropathic pain. Despite the numerous treatment options available for relieving neuropathic pain, no more than half of patients experience clinically meaningful pain relief, which is almost always partial but not complete relief. In addition, patients frequently experience burdensome adverse effects and as a consequence are often unable to tolerate the treatment. In the remaining patients, combination therapies using two or more analgesics with different mechanisms of action may also offer adequate pain relief. Although combination treatment is clinical practice and may result in greater pain relief, trials regarding different combinations of analgesics (which combination to use, occurrence of additive or supra-additive effects, sequential or concurrent treatment, adverse-event profiles of these analgesics, alone and in combination) are scarce. If medical treatments have failed, invasive therapies such as intrathecal drug administration and neurosurgical stimulation techniques (spinal cord stimulation, deep brain stimulation, and motor cortex stimulation) may be considered.

A Randomized, Prospective Study of Efficacy and Safety of Oral Tramadol in the Management of Post‐Herpetic Neuralgia in Patients from North India

To evaluate the safety and efficacy of oral tramadol therapy (50 to 200 mg/day) in the treatment for post-herpetic neuralgia (PHN). The study was a prospective, single-blind, non-responder vs. responder, randomized trial conducted in 100 outpatients of PHN after oral administration of tramadol for 4 weeks. Those patients who had achieved 50% or greater pain relief after 14 days of oral tramadol treatment were categorized as responders and those reporting < 50% pain relief were categorized as non-responders. Rescue analgesia was provided by the topical application of a cream consisting of the combination of 3.33% doxepin and 0.05% capsaicin to the affected areas of PHN patients of both groups for at least 14 days, along with tramadol therapy. The rescue analgesia was extended to 4 weeks in patients of the non-responder group. The primary endpoints were measured using a numerical rating scale (NRS) at rest and with movement. Secondary endpoints included additional pain ratings such as global perceived effect (GPE), Neuropathic Pain Symptom Inventory scores (NPSI), daily sleep interference score (DSIS), quality of life (QOL) as per WHO QOL-BREF Questionnaire scores, patient and clinician ratings of global improvement. The 2 groups were compared on the basis of pain intensity scores, encompassing primary as well as secondary endpoints, and QOL after 28 days of the treatment regimen. Pain intensity scores measured by NRS (at resting and with movement), NPSI, and DSIS were consistently reduced (P < 0.001) over 28 days at varying intervals in both the groups, but the magnitude of reduction was higher in responders than non-responders. A concomitant improvement (P < 0.001) was observed in GPE on days 3, 14, and 28 as compared to the respective baseline scores in both the groups. Although the WHO QOL-BREF scores showed significant (P < 0.001) improvement in QOL of PHN patients at days 14 and 28 in both the groups, the magnitude of improvement was higher in responders as compared to non-responders. Significant improvement in pain intensity scores and QOL in non-responders is mainly attributed to the use of rescue analgesia for 28 days rather than recommended tramadol therapy. Treatment with tramadol 50 to 200 mg per day was associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side-effect profile, and improved QOL in PHN patients from North India. Further categorization of PHN patients may be helpful so that additional or alternative therapy may be prescribed to non-responders.

Dismembered Laparoscopic Anderson-Hynes Pyeloplasty Versus Nondismembered Laparoscopic Y-V Pyeloplasty in the Treatment of Patients with Primary Ureteropelvic Junction Obstruction: A Prospective Study

An attempt has been made to prospectively compare the results of two laparoscopic pyeloplasties: Dismembered Anderson-Hynes (A-H) plasty and nondismembered Y-V plasty. Complications following the procedures have been studied as well. Fifty patients with primary ureteropelvic junction obstruction (UPJO) were prospectively selected at random to undergo dismembered A-H (25 patients-even numbers) and nondismembered Y-V (25 patients-odd numbers) laparoscopic pyeloplasty. UPJO was diagnosed on the basis of ultrasonography, excretory urography, and diuretic renography (DR). The intensity of pain was assessed according to a visual analog pain scale (VAS). Success was defined by three factors taken collectively: 80% or greater pain relief in comparison with the preoperative VAS score, no obstruction on DR (decreasing renographic excretion curve, T(1/2) <12 min), and improved or stable differential renal function. The mean follow-up was 26.2 months for the A-H group and 26.6 months for Y-V group (P=0.865). Both groups were comparable in terms of preoperative data, except for the presence of the crossing vessel, which was more often observed in the Y-V group. No statistically significant differences between the studied groups were found in operative times, morbidity, and hospitalization length. The success rate in the A-H group was 95% and 86% in the Y-V group, the difference being not statistically significant. Laparoscopic A-H pyeloplasty achieved a higher success rate then Y-V pyeloplasty; however, the difference was not statistically significant.

Ultrasound guided corticosteroid injection for plantar fasciitis: randomised controlled trial

Objective To investigate the effectiveness of ultrasound guided corticosteroid injection in the treatment of plantar fasciitis.Design Randomised, investigator and participant blinded, placebo controlled trial.Setting University clinic in Melbourne, Australia.Participants 82...

Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study

Background and objectives:A number of transmucosal fentanyl formulations have been developed for the management of breakthrough cancer pain (BTCP). Sublingual delivery of fentanyl, formulated as fentanyl sublingual spray, offers the potential for more rapid and greater absorption of fentanyl and associated onset of analgesic effect compared with other formulations. The objective of this study was to assess the efficacy and safety of fentanyl sublingual spray for the treatment of BTCP.Research design and methods:This was a randomized, double-blind, placebo-controlled phase III trial conducted in opioid-tolerant patients with BTCP. An open-label titration period was followed by a double-blind treatment period during which patients received fentanyl sublingual spray (100–1600 mcg) or placebo.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00538850.Main outcome measures:The primary efficacy measure was summed pain intensity difference at 30 minutes (SPID30). Secondary efficacy measures included total pain relief at 30 minutes (TOTPAR30) and patient global evaluation of study medication at 30 minutes. Efficacy measures were also assessed at various time points from 5–60 minutes postdose. Adverse events were monitored throughout the study.Results:A total of 130 patients were treated during the titration period, of whom 98 (75.4%) entered the double-blind period. Relative to placebo, fentanyl sublingual spray significantly improved mean SPID scores from 5 minutes (p = 0.0219) through 60 minutes (p < 0.0001), including the primary endpoint at 30 minutes (p < 0.0001). Fentanyl sublingual spray produced significantly greater pain relief (expressed in terms of TOTPAR) from 5 through 60 minutes (p < 0.0001), and significantly greater global evaluation of treatment effectiveness (p < 0.0001), compared with placebo. During double-blind treatment, the most frequently reported adverse events were nausea (7.1%), hyperhidrosis (5.1%), and peripheral edema (5.1%). Serious adverse events occurred in seven patients (5.4%) during titration and six (6.1%) during double-blind treatment; none were considered related to treatment.Conclusions:These findings indicate that treatment with fentanyl sublingual spray results in effective relief of BTCP, with a rapid onset of action, and is well tolerated.

Extended-release tramadol/paracetamol in moderate-to-severe pain: a randomized, placebo-controlled study in patients with acute low back pain

Objective:Combinations of oral analgesics may offer several potential benefits compared with an individual agent. The objective of this study was to investigate the efficacy and safety of an extended-release, twice-daily fixed combination of 75 mg tramadol/650 mg paracetamol (DDS-06C) in the treatment of moderate-to-severe pain, using acute low back pain as a model.Research design and methods:In this phase III study, 277 patients with moderate-to-severe acute low back pain were randomized to 1–2 tablets of DDS-06C or placebo every 10–12 h for 2.5 days during the double-blind phase. Following the double-blind phase, patients had the option to continue for a 2.5-day open-label phase.Clinical trial registration:Clinicaltrials.gov (Identifier: NCT00643383)Main outcome measures:The primary end point was the sum of pain intensity differences (SPID) over the 50-h double-blind phase (SPID50). Secondary end points included total pain relief score over the 50-h double-blind phase (TOTPAR50), patient’s global impression of medication, and SPID over the first 4 h.Results:A statistically significant (p = 0.038) greater decrease in pain intensity was observed in the DDS-06C group (median SPID50: −6.0) versus placebo (median SPID50: −4.0). Greater pain relief was also observed in patients randomized to DDS-06C: the median TOTPAR50 was 13.0 for the DDS-06C group and 11.0 for placebo (p = 0.026). DDS-06C demonstrated statistically significant superior efficacy compared with placebo for the majority of the other secondary end points. Overall, 38% of patients treated with DDS-06C experienced at least one adverse event; the intensity was mild-to-moderate in 81% of cases. The most commonly reported adverse events (>5% of patients receiving DDS-06C) were nausea, dizziness, vomiting, and somnolence.Conclusions:Using acute low back pain, a model with a high degree of heterogeneity and intrinsic variability, DDS-06C was superior to placebo on measures of pain intensity and relief, and was well-tolerated.

Efficacy of Botulinum Toxin Type A for Treating Chronic Low Back Pain

Background: Low back pain is a major cause of disability and can result in substantial morbidity and high healthcare costs. Botulinum toxin has been used successfully to alleviate pain for a number of conditions caused by muscle contractions or spasms. Objectives: The aim of this study was to investigate the efficacy of botulinum toxin type A (BoNT-A; Dysport®, Ipsen, UK) for treating chronic low back pain (CLBP). Patients and Methods: This was a single-blind, randomized clinical trial study. Fifty patients with CLBP received either BoNT-A (40 Ipsen units per injection) or saline in 5 sites in the paraspinal muscles (n = 25 per group). A visual analogue system (VAS) was used to measure pain levels at baseline and at 4 and 8 weeks post-injection. Disability was assessed using the Oswestry low back pain disability questionnaire at baseline and at 8 weeks post-injection. Results: After 4 weeks, 76% of patients in the BoNT-A group reported pain relief compared to 20% in the saline group (P < 0. 005). Additionally, greater pain relief was experienced by patients in the BoNT-A group at 8 weeks (64% vs. 12%; P < 0. 001). By week 8, significant functional improvement (a minimum two-grade improvement between baseline and post-treatment assessments) was demonstrated in a higher number of patients receiving BoNT-A than in the saline group (68% vs. 12% , respectively; P < 0. 005). Patients experienced only minor side effects. Conclusions: BoNT-A improves CLBP with a low incidence of side effects and can be used as a therapeutic tool in the management of these patients.

Evaluation of fentanyl buccal soluble film (FBSF) in opioid tolerant cancer patients with neuropathic breakthrough cancer pain (BTP)

Neuropathic pain, in particular neuropathic breakthrough cancer pain (BTP), is poorly understood and difficult to effectively control. Pain clinicians generally use agents that are not ordinarily used as analgesics, such as anticonvulsants and antidepressants, alpha-2 adrenergic agonists and NMDA receptor antagonists in combination with opioids as treatments. In 2009, a fentanyl buccal soluble film (FBSF) was approved for the management of BTP in opioid-tolerant cancer patients ≥18 years of age. The safety and efficacy of FBSF was studied in a multicenter, randomized, double-blind, placebo-controlled, multiple-crossover study in adult cancer patients on stable opioid therapy who reported ≤4 BTP episodes per day. A subgroup of patients from that trial was analyzed to evaluate the efficacy and safety of FBSF in patients with neuropathic BTP pain. The primary variable evaluated was the sum of pain intensity differences (SPID) at 30 minutes with higher scores correlating with greater pain relief. Adverse events were recorded and summarized. Fourteen females and nine males (mean age ∼51 years) were included in the subgroup analysis and breast cancer (n=6) was the most prevalent type of cancer among these patients. Pain reduction after treatment with FBSF was greater than after treatment with placebo. SPID values in patients with neuropathic BTP were significantly higher for FBSF-treated episodes than for those episodes treated with placebo beginning 15 minutes after dosing. FBSF was as effective in this subgroup as in the entire population. The most commonly reported adverse events included somnolence, nausea, and dizziness. The results of this subgroup analysis indicate that FBSF may aid in the management of breakthrough cancer pain in patients experiencing neuropathic pain. This subgroup analysis was supported by a grant from Meda Pharmaceuticals, Inc.

Diclofenac Epolamine plus Heparin Plaster versus Diclofenac Epolamine Plaster in Mild to Moderate Ankle Sprain

In general sports, ankle sprain is the most frequently reported ankle injury and can cause chronic lateral ankle pain and tenderness. Treatment with NSAIDs is preferred, and several topical NSAID formulations are now available, helping to avoid the systemic adverse events typically associated with oral preparations. To compare the efficacy and tolerability of a newly developed fixed-dose diclofenac epolamine (diclofenac hydroxyethylpyrrolidine, DHEP)/heparin plaster (Flectoparin® Tissugel) with that of a DHEP (Flector EP Tissugel®) or placebo plaster in the treatment of mild to moderate ankle sprain in adults. This was a randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase III study conducted in the emergency medical centres of hospitals or private clinics in Europe. Outpatients aged 18-65 years who had suffered an acute ankle sprain (O'Donoghue grade I or II in severity, with external lateral ligament involvement) within the previous 48 hours and had peri-malleolar oedema were eligible for inclusion. A total of 430 patients were randomized to receive a DHEP/heparin 1.3%/5600 IU (n = 142), DHEP 1.3% (n = 146) or placebo (n = 142) plaster, applied once daily to the injured ankle for a total of 7 days. The primary endpoint was the mean change from baseline in pain on movement on day 3, as measured by a visual analogue scale (VAS). The DHEP/heparin plaster was associated with a significantly (p = 0.002) greater mean reduction from baseline in pain on movement after 3 days of treatment than the DHEP plaster (-24.2 vs -18.8 mm VAS), with each active treatment providing significantly (p ≤ 0.005) greater pain relief than placebo (-13.7 mm VAS). Both DHEP/heparin and DHEP were also effective in relieving other measures of pain, with DHEP/heparin recipients experiencing significantly less daily pain while leaning on the injured limb than DHEP recipients (p < 0.001). In addition, oedema was reduced to a significantly greater extent with DHEP/heparin than with placebo (day 7 only; p = 0.012). The DHEP/heparin plaster and DHEP plaster were both well tolerated, with adverse event profiles similar to that of placebo. Local adverse events were infrequent and generally mild in severity and there were no systemic adverse effects. The fixed-dose DHEP/heparin plaster is effective and has advantages over the DHEP plaster in relieving pain, and possibly also swelling, associated with mild to moderate acute ankle sprains with oedema in adults.

Efficacy of botulinum toxin type a for treating chronic low back pain.

Background:Low back pain is a major cause of disability and can result in substantial morbidity and high healthcare costs. Botulinum toxin has been used successfully to alleviate pain for a number of conditions caused by muscle contractions or spasms.Objectives:The aim of this study was to investigate the efficacy of botulinum toxin type A (BoNT-A; Dysport®, Ipsen, UK) for treating chronic low back pain (CLBP).Patients and Methods:This was a single-blind, randomized clinical trial study. Fifty patients with CLBP received either BoNT-A (40 Ipsen units per injection) or saline in 5 sites in the paraspinal muscles (n = 25 per group). A visual analogue system (VAS) was used to measure pain levels at baseline and at 4 and 8 weeks post-injection. Disability was assessed using the Oswestry low back pain disability questionnaire at baseline and at 8 weeks post-injection.Results:After 4 weeks, 76% of patients in the BoNT-A group reported pain relief compared to 20% in the saline group (P < 0. 005). Additionally, greater pain relief was experienced by patients in the BoNT-A group at 8 weeks (64% vs. 12%; P < 0. 001). By week 8, significant functional improvement (a minimum two-grade improvement between baseline and post-treatment assessments) was demonstrated in a higher number of patients receiving BoNT-A than in the saline group (68% vs. 12% , respectively; P < 0. 005). Patients experienced only minor side effects.Conclusions:BoNT-A improves CLBP with a low incidence of side effects and can be used as a therapeutic tool in the management of these patients.

A Double-Blind Placebo-Controlled Comparison of a Novel Formulation of Intravenous Diclofenac and Ketorolac for Postoperative Third Molar Extraction Pain

Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N = 51 for all groups, except N = 47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P = .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia.

Cardiovascular Effects of Cocaine

The use of cocaine has evolved from chewing the leaves of the Erythroxylon coca bush thousands of years ago, to purification of cocaine hydrochloride over 100 years ago and its use in tonics and elixirs (at one time in popular cola drinks), to insufflating and injecting the fine, white, water-soluble, powder form, to a smokable freebase form called “crack,” which became popular in the 1980s.1 In 2007, 2.1 million Americans had recent cocaine use; 1.6 million met criteria for cocaine dependence or abuse.1 Cocaine accounted for 31% of all visits to the emergency department related to drug misuse or abuse.1 From 1971 to 1987, the incidence of deaths caused by cocaine overdose increased 20-fold in Dade County, Florida.2 In a consecutive series of 233 emergency visits by cocaine-using patients, 56% presented with cardiovascular complaints, including 40% with chest pain.3 A minority of these patients have acute myocardial infarction (MI) (≈6%),4,–,7 and overall mortality is low (<1%).3,–,5,8,–,10 However, cocaine is associated with a number of cardiovascular diseases, including MI, heart failure, cardiomyopathies, arrhythmias, aortic dissection, and endocarditis. Identifying patients with acute disease is challenging. This review describes the relationship between cocaine and various cardiovascular diseases, as well as appropriate diagnostic evaluation and therapies. ### Molecular Cocaine stimulates the sympathetic nervous system by inhibiting catecholamine reuptake at sympathetic nerve terminals,11,12 stimulating central sympathetic outflow,11 and increasing the sensitivity of adrenergic nerve endings to norepinephrine (Figure 1).12 Cocaine also acts like a class I antiarrhythmic agent (local anesthetic) by blocking sodium and potassium channels, which depresses cardiovascular parameters.13 Of these 2 primary, opposing actions, enhanced sympathetic activity predominates at low cocaine doses, whereas the local anesthetic actions …

Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial

Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures. Patients were recruited to this open-label prospective randomised trial from the radiology departments of six hospitals in the Netherlands and Belgium. Patients were aged 50 years or older, had vertebral compression fractures on spine radiograph (minimum 15% height loss; level of fracture at Th5 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 5 or more. Patients were randomly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated randomisation codes with a block size of six. Masking was not possible for participants, physicians, and outcome assessors. The primary outcome was pain relief at 1 month and 1 year as measured by VAS score. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00232466. Between Oct 1, 2005, and June 30, 2008, we identified 431 patients who were eligible for randomisation. 229 (53%) patients had spontaneous pain relief during assessment, and 202 patients with persistent pain were randomly allocated to treatment (101 vertebroplasty, 101 conservative treatment). Vertebroplasty resulted in greater pain relief than did conservative treatment; difference in mean VAS score between baseline and 1 month was -5·2 (95% CI -5·88 to -4·72) after vertebroplasty and -2·7 (-3·22 to -1·98) after conservative treatment, and between baseline and 1 year was -5·7 (-6·22 to -4·98) after vertebroplasty and -3·7 (-4·35 to -3·05) after conservative treatment. The difference between groups in reduction of mean VAS score from baseline was 2·6 (95% CI 1·74-3·37, p<0·0001) at 1 month and 2·0 (1·13-2·80, p<0·0001) at 1 year. No serious complications or adverse events were reported. In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost. ZonMw; COOK Medical.