Global Impression Of Change Scores Research Articles

Long-Term Outcomes After Ventral Rectopexy With Sacrocolpo- or Hysteropexy for the Treatment of Concurrent Rectal and Pelvic Organ Prolapse.

The primary objective is to describe the long-term anatomic and subjective outcomes in women undergoing ventral rectopexy with sacrocolpo- or hysteropexy. The secondary objective is to describe the perioperative adverse events. This is a retrospective cohort of women who underwent ventral rectopexy with either concurrent sacrocolpo- or hysteropexy at a tertiary care center between 2009 and 2015. A composite outcome for recurrent pelvic organ prolapse and rectal prolapse was defined as subjective failure (vaginal or rectal prolapse symptoms), objective failure (prolapse to or beyond the hymen or full thickness rectal prolapse), or any retreatment for prolapse. Patient's Global Impression of Change was recorded at baseline and at all follow-up visits. Perioperative adverse events were defined a priori and collected up to 6 weeks after surgery. A total of 59 patients underwent a ventral rectopexy, either a sacrocolpopexy (48/59, 81.3%) or sacrohysteropexy (11/59, 18.6%). The median follow-up after surgery for all patients was 17 months (range, 1-76) with a composite success rate for both pelvic organ prolapse and rectal prolapse (estimated by Kaplan-Meier method) of 57.4%. Forty (91%) of 44 patients reported a Patient's Global Impression of Change score of 6 or 7, indicating significant improvement after surgery. Of the patients, 15 (25.4%) experienced a perioperative adverse event. Use of biologic graft was associated with a higher rate of adverse event (40.0% [95% confidence interval, 24.6-57.5] vs 10.3% [95% confidence interval, 3.6-26.3]; P < 0.01). Ventral rectopexy with sacrocolpo- or hysteropexy is associated with significant improvement in anatomic and subjective outcomes. One in 4 women experienced a perioperative adverse event.

Effect of Nitrous Oxide as a Treatment for Subjective, Idiopathic, Nonpulsatile Bothersome Tinnitus

The tinnitus research literature suggests that N-methyl-d-aspartate (NMDA) receptor antagonists may be useful in reducing tinnitus. Nitrous oxide, a member of the NMDA receptor antagonist class, is a widely used general anesthetic and sedative with a proven safety record. To investigate whether nitrous oxide can reduce bothersome tinnitus. Randomized, placebo-controlled crossover trial conducted between October 15, 2016, and June 22, 2017. Participants attended 2 interventional sessions separated by at least 14 days and were randomized to receive either placebo first or nitrous oxide first. Participants were followed up through completion of the second arm of the study. The setting was a clinical research unit at an academic medical center. Adults aged 18 to 65 years with subjective, idiopathic, nonpulsatile bothersome tinnitus of 6 months' duration or longer were recruited from 2 clinical research databases. Seventy-one individuals were screened, of whom 40 were enrolled. Of those enrolled, 37 participants completed all components of the study. The placebo session consisted of 50% nitrogen and 50% oxygen inhaled for 40 minutes, and the treatment session consisted of 50% nitrous oxide and 50% oxygen inhaled for 40 minutes. Tinnitus was assessed before and after intervention, with the change in the Tinnitus Functional Index (TFI) as the primary outcome measure. Secondary outcome measures included the Patients' Global Impression of Change score and the change in the Global Bothersome Scale score. Among 40 participants in this intent-to-treat randomized clinical trial with 20 participants randomly assigned to each group, the mean (SD) age of participants was 52.9 (11.1) years, with equal numbers of male and female participants. The TFI after intervention was a mean (SD) of 1.8 (8.8) points lower than before intervention in the placebo arm and a mean (SD) of 2.5 (11.0) points lower than before intervention in the nitrous oxide arm. The within-participant mean difference in the change in the TFI of the placebo arm compared with the nitrous oxide arm was -1.1 points (95% CI, -5.6 to 3.4 points). The difference between the placebo and nitrous oxide arms was neither clinically meaningful nor statistically significant. Nitrous oxide was no more effective than placebo for the treatment of subjective, idiopathic tinnitus. ClinicalTrials.gov identifier: NCT03365011.

Efficacy and safety of single-dose onabotulinumtoxinA in the treatment of symptoms of osteoarthritis of the knee: results of a placebo-controlled, double-blind study

To evaluate intraarticular onabotulinumtoxinA 400U and 200U in reducing symptoms of knee osteoarthritis (OA) in patients with nociceptive pain. A multicenter, double-blind, randomized, placebo-controlled study was conducted in adults with knee OA and a painDETECT questionnaire score of ≤12 (indicating nociceptive pain). Patients were randomized to receive intraarticular onabotulinumtoxinA 400U or 200U or placebo (saline) in the study knee on a 1:1:2 ratio and were followed-up for 24 weeks posttreatment. The primary efficacy measure was the daily average numeric rating scale pain score for the study knee over 7 days at week 8. Secondary efficacy measures included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function scores, the patient global impression of change score and the 7-day average worst pain score. Of the 176 enrolled patients, 158 completed the study. The daily average pain score was reduced by approximately two points for all treatments (week 8); the reduction was sustained throughout follow-up, with no significant between-group difference between onabotulinumtoxinA and placebo (both doses: 0.22 [95% confidence interval (CI):-0.33, 0.76]; 400U: 0.42 [95% CI:-0.26, 1.10]; 200U:-0.03 [95% CI:-0.70, 0.64]). Similar results were found for all secondary efficacy measures. Treatment-related adverse events occurred in 3.4% of the pooled onabotulinumtoxinA group and placebo group; none were serious. There were no significant differences between onabotulinumtoxinA and placebo in reducing average pain score at week 8 compared with baseline in patients with knee OA. No safety concerns were identified. CLINICALTRIALS. NCT02230956.

A longitudinal study of painless and painful intercostobrachial neuropathy after breast cancer surgery.

Intercostobrachial neuropathy, often resulting in neuropathic pain, is a common complication of breast cancer surgery. In this 1-year longitudinal study, we aimed at seeking information on the frequency, clinical features, and course of painless and painful intercostobrachial neuropathy. We enrolled 40 women previously undergoing breast cancer surgery. In these patients, we collected, at 3, 6 and 12months after surgery, clinical and quantitative sensory testing (QST) variables to diagnose intercostobrachial neuropathy, DN4 questionnaire to identify neuropathic pain, Neuropathic Pain Symptom Inventory to assess the different neuropathic pain symptoms, the Beck Depression Inventory to assess depressive symptoms, and SF36 to assess quality of life and Patient Global Impression of Change. Clinical and QST examination showed an intercostobrachial neuropathy in 23 patients (57.5%). Out of the 23 patients, five experienced neuropathic pain, as assessed with clinical examination and DN4. Axillary surgery clearance was associated with an increased risk of intercostobrachial neuropathy. Whereas sensory disturbances improved during the 1-year observation, neuropathic pain did not. Nevertheless, Beck Depression Inventory, SF36, and the Patient Global Impression of Change scores significantly improved over time. Our study shows that although intercostobrachial neuropathy is a common complication of breast cancer surgery, neuropathic pain affects only a minor proportion of patients. After 1year, sensory disturbances partially improve and have only a mild impact on mood and quality of life.

Effects of Pregabalin in Patients with Neuropathic Pain Previously Treated with Gabapentin: A Pooled Analysis of Parallel-Group, Randomized, Placebo-controlled Clinical Trials.

This analysis compared the therapeutic response of pregabalin in patients with neuropathic pain (NeP) who had been previously treated with gabapentin to the therapeutic response in patients who had not received gabapentin previously. Data were pooled from 18 randomized, double-blind, placebo-controlled trials of pregabalin in patients with NeP. Pregabalin-mediated changes in pain and pain-related sleep interference scores, patient global impression of change scores at endpoint, and the occurrence of adverse events were compared between patients who had received gabapentin previously (+GBN) and patients who had not received gabapentin previously (-GBN). There were no significant differences between the -GBN and +GBN cohorts with regard to the extent of pain relief and relief of pain-related sleep interference for any dose of pregabalin (150, 300, 600, or 150 to 600 mg/day) at any time point (6, 8, or 12 weeks). Additionally, there was no significant difference in the distribution of patient global impression of change scores at study endpoint, or the occurrence of adverse events, between the -GBN and +GBN cohorts. The findings presented here support the idea that pregabalin may be used successfully to treat patients with NeP who may be refractory, respond inadequately, or are intolerant to gabapentin. These findings highlight the importance of tailoring treatment of NeP based on individual patient response to different treatments, including the trial of multiple agents within the same mechanistic class.

Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies.

Serum monoclonal anti-myelin-associated glycoprotein (anti-MAG) antibodies may be pathogenic in some people with immunoglobulin M (IgM) paraprotein and demyelinating neuropathy. Immunotherapies aimed at reducing the level of these antibodies might be expected to be beneficial. This is an update of a review first published in 2003 and previously updated in 2006 and 2012. To assess the effects of immunotherapy for IgM anti-MAG paraprotein-associated demyelinating peripheral neuropathy. On 1 February 2016 we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for randomised controlled trials (RCTs). We also checked trials registers and bibliographies, and contacted authors and experts in the field. We included randomised controlled trials (RCTs) or quasi-RCTs involving participants of any age treated with any type of immunotherapy for anti-MAG antibody-associated demyelinating peripheral neuropathy with monoclonal gammopathy of undetermined significance and of any severity.Our primary outcome measures were numbers of participants improved in disability assessed with either or both of the Neuropathy Impairment Scale (NIS) or the modified Rankin Scale (mRS) at six months after randomisation. Secondary outcome measures were: mean improvement in disability, assessed with either the NIS or the mRS, 12 months after randomisation; change in impairment as measured by improvement in the 10-metre walk time, change in a validated linear disability measure such as the Rasch-built Overall Disability Scale (R-ODS) at six and 12 months after randomisation, change in subjective clinical scores and electrophysiological parameters at six and 12 months after randomisation; change in serum IgM paraprotein concentration or anti-MAG antibody titre at six months after randomisation; and adverse effects of treatments. We followed standard methodological procedures expected by Cochrane. We identified eight eligible trials (236 participants), which tested intravenous immunoglobulin (IVIg), interferon alfa-2a, plasma exchange, cyclophosphamide and steroids, and rituximab. Two trials of IVIg (22 and 11 participants, including 20 with antibodies against MAG), had comparable interventions and outcomes, but both were short-term trials. We also included two trials of rituximab with comparable interventions and outcomes.There were very few clinical or statistically significant benefits of the treatments used on the outcomes predefined for this review, but not all the predefined outcomes were used in every included trial and more responsive outcomes are being developed. A well-performed trial of IVIg, which was at low risk of bias, showed a statistical benefit in terms of improvement in mRS at two weeks and 10-metre walk time at four weeks, but these short-term outcomes are of questionable clinical significance. Cyclophosphamide failed to show any benefit in the single trial's primary outcome, and showed a barely significant benefit in the primary outcome specified here, but some toxic adverse events were identified.Two trials of rituximab (80 participants) have been published, one of which (26 participants) was at high risk of bias. In the meta-analysis, although the data are of low quality, rituximab is beneficial in improving disability scales (Inflammatory Neuropathy Cause and Treatment (INCAT) improved at eight to 12 months (risk ratio (RR) 3.51, 95% confidence interval (CI) 1.30 to 9.45; 73 participants)) and significantly more participants improve in the global impression of change score (RR 1.86, 95% CI 1.27 to 2.71; 70 participants). Other measures did not improve significantly, but wide CIs do not preclude some effect. Reported adverse effects of rituximab were few, and mostly minor.There were few serious adverse events in the other trials. There is inadequate reliable evidence from trials of immunotherapies in anti-MAG paraproteinaemic neuropathy to form an evidence base supporting any particular immunotherapy treatment. IVIg has a statistically but probably not clinically significant benefit in the short term. The meta-analysis of two trials of rituximab provides, however, low-quality evidence of a benefit from this agent. The conclusions of this meta-analysis await confirmation, as one of the two included studies is of very low quality. We require large well-designed randomised trials of at least 12 months' duration to assess existing or novel therapies, preferably employing unified, consistent, well-designed, responsive, and valid outcome measures.

Pregabalin for Neuropathic Pain: Why Benefits Could Be Expected for Multiple Pain Conditions.

Limited research exists to support the extrapolation of the analgesic efficacy of pregabalin from one neuropathic pain condition to another. This retrospective analysis evaluated similarities in the efficacy of pregabalin for treating neuropathic pain associated with post-herpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI) in a Japanese population, as a basis for considering the extrapolation of these data to other neuropathic pain conditions. Data were analysed across pregabalin doses within each pain condition, from three comparable 13- to 16-week, randomized, double-blind, placebo-controlled trials (RCTs) and the corresponding 52-week, open-label extension trials of pregabalin in Japanese patients with PHN, DPN or SCI. Efficacy outcomes in the RCTs included endpoint and weekly mean pain and sleep interference scores; endpoint proportions of responders in pain; Patient Global Impression of Change scores; and 36-Item Short Form Health Survey (SF-36) scores or Hospital Anxiety and Depression Scale (HADS) assessments. Study discontinuation rates were compared between treatment groups. The extension trials assessed pain intensity, using the Short-Form McGill Pain Questionnaire. In the RCTs for all pain conditions, significant improvements in comparison with placebo in mean pain and sleep interference scores were evident after 1 week with pregabalin and were sustained throughout the treatment periods (p < 0.05). At the study endpoint, in comparison with placebo, a significantly greater percentage of pregabalin-treated patients experienced a ≥30 % reduction in pain across the RCTs (p < 0.05), and pregabalin significantly improved six of 16 SF-36 subscale scores in the PHN and DPN trials (p < 0.05). In the SCI trial, pregabalin-treated patients had numerically better outcomes of HADS scores. In the extension trials, improvements in pain intensity were maintained over a 52-week period. Similarities in the pregabalin efficacy profiles, including time to onset and magnitude of response, were confirmed regardless of the neuropathic pain condition. These data support the potential for extrapolating analgesic efficacy to other neuropathic pain conditions. CLINICALTRIALS. NCT00394901, NCT00553475, NCT00407745, NCT00424372, NCT00553280, NCT01202227.

Adipose derived mesenchymal stem cell therapy in the treatment of isolated knee chondral lesions: design of a randomised controlled pilot study comparing arthroscopic microfracture versus arthroscopic microfracture combined with postoperative mesenchymal stem cell injections

IntroductionThe management of intra-articular chondral defects in the knee remains a challenge. Inadequate healing in areas of weight bearing leads to impairment in load transmission and these defects predispose to...

An open-label study to assess safety, tolerability, and effectiveness of dextromethorphan/quinidine for pseudobulbar affect in dementia: PRISM II results.

Dextromethorphan (DM)/quinidine (Q) is an approved treatment for pseudobulbar affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported. This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study-Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C). 134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint (P<.001) vs. baseline. PBA episodes were reduced 67.7% (P<.001) vs. baseline; global measures showed 77.5% CGI-C and 76.5% PGI-C "much"/"very much" improved. Adverse events included headache (7.5%), urinary tract infection (4.5%), and diarrhea (3.7%); few patients dropped out for adverse events (10.4%). DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q. Trial Registration clinicaltrials.gov identifier: NCT01799941.

Oral tapentadol for cancer pain.

A large proportion of people with advanced cancer will experience moderate to severe pain. Tapentadol is a novel, centrally acting analgesic medicine acting at the μ-opioid receptor and inhibiting noradrenaline reuptake. The efficacy of tapentadol is stated to be comparable to morphine and oxycodone. To assess the analgesic efficacy of tapentadol for the relief of cancer pain in adults, and the adverse events associated with its use in clinical trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from January 2005 to July 2015, together with reference lists of retrieved papers and review articles, and two clinical trial registries. Searches started from 2005 because this covered the period during which clinical trials were conducted. We contacted the manufacturer of tapentadol in the UK to find additional trials not identified by electronic searches. We did not restrict searches by language. We included randomised controlled trials (RCTs) of tapentadol compared with placebo or active controls in adults with moderate to severe cancer pain. Pain had to be measured using a validated assessment tool, and studies had to include at least 10 participants per treatment arm. Two review authors independently extracted data using a standard form and assessed risk of bias. We extracted available data on study design, participant details, interventions, and outcomes, including analgesic outcome measures, withdrawals, and adverse events. We included four studies with 1029 participants. All the studies used a parallel-group design, and included an initial titration phase to determine the maximum effective and tolerated dose, followed by a maintenance phase. Tapentadol medication was taken twice daily and doses ranged from 50 to 500 mg per day. Rescue medication (morphine or oxycodone immediate-release) was available to participants in all studies.Overall, 440 participants were randomised in classically designed RCTs, and 589 participants were enrolled in enriched-enrolment, randomised-withdrawal (EERW) trials. A total of 476 participants were randomised to titration with tapentadol and 338 participants took tapentadol throughout the maintenance phase of their trial.All studies used numerical rating scores, Patient Global Impression of Change scores, and use of rescue medication as measures of efficacy, and all reported on adverse events and withdrawals.All studies enrolled fewer than 200 participants per treatment arm and were therefore at risk of overestimating efficacy. One study was terminated early due to problems with supply of rescue medication, with fewer than 20 participants enrolled per treatment arm in the maintenance phase of the trial. We judged another study at high risk of bias due to an open-label design.There were insufficient data for pooling and statistical analysis. Response rates for pain intensity were comparable across treatment groups in each study. In one EERW study, response rates were high across both treatment and placebo arms during the maintenance phase (62% tapentadol, 69% morphine, 50% placebo). For pain relief, tapentadol is no more and no less effective than oxycodone or morphine (low quality evidence).Treatment emergent adverse event rates were high, approximately 50% to 90%. The most common adverse events were gastrointestinal (nausea, vomiting, constipation) (low quality evidence). There was no advantage of tapentadol over morphine or oxycodone in terms of serious adverse events. The number of people experiencing effects on consciousness, appetite, or thirst was low. Information from RCTs on the effectiveness and tolerability of tapentadol was limited. The available studies were of moderate or small size and used different designs, which prevented pooling of data. Pain relief and adverse events were comparable between the tapentadol and morphine and oxycodone groups.

Memantine for Lewy Body Disorders: Systematic Review and Meta-Analysis

To clarify whether memantine is more efficacious in several outcomes and safer than placebo in patients with Lewy body disorders, we performed a meta-analysis of memantine in patients with Lewy body disorders. The meta-analysis included randomized controlled trials of memantine for Lewy body disorders in all patients with Lewy body disorders. Motor function, activities of daily living, Neuropsychiatric Inventory, Mini-Mental State Exam, discontinuation rate, and individual side effects were evaluated. No significant effects of memantine on motor function scores, Mini-Mental State Exam scores, Neuropsychiatric Inventory scores, and activity of daily living scores were found. However, memantine was superior to placebo in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change scores (standardized mean difference:-0.26; 95% confidence interval:-0.51 to-0.02; z= 2.08; p= 0.04; two studies; N= 258). Dropout due to all causes, inefficacy, or adverse events were similar in both groups. Moreover, no significant differences in serious adverse events, somnolence/tiredness, stroke, dizziness/vertigo, and confusion were found between the groups. Our results suggest that memantine did not have a benefit for the treatment of Lewy body disorders in cognition and motor function. However, memantine may be superior to placebo for the overall impression of the disorders. Further, memantine is well tolerated.

Relationship Between Pain Relief and Improvements in Patient Function/Quality of Life in Patients With Painful Diabetic Peripheral Neuropathy or Postherpetic Neuralgia Treated With Pregabalin

BackgroundIn patients with chronic pain due to diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN), pregabalin treatment results in pain relief and improved patient function/quality of life (QoL). Few studies, however, have examined the exact relationship between pain relief and improvements in patient function/QoL. It is unclear, for example, whether pregabalin has a direct independent effect on patient function/QoL or whether improvements in function/QoL are an indirect consequent of pain relief. ObjectivesTo determine whether improvements in function/QoL in response to pregabalin treatment are related to the extent of pain relief in patients with neuropathic pain due to DPN or PHN and to determine whether pregabalin has a direct independent effect on patient function/QoL that is distinct from its effects on pain. MethodsData from 11 randomized, double-blind, placebo-controlled trials of pregabalin for the treatment of DPN or PHN were pooled for this analysis. Changes in patient function/QoL scores were plotted according to the extent of pain relief to assess whether greater levels of pain relief were associated with greater improvement in function/QoL. A novel mediation analysis was used to asses to what extent the effects of pregabalin on function/QoL scores are a direct treatment effect as opposed to an indirect effect mediated through improvements in pain or sleep. ResultsModerate-to-substantial pain relief (a ≥30% decrease in pain) in response to pregabalin treatment was associated with significant (P < 0.05) improvements in 36-Item Short Form Health Survey (SF-36) scores (used to assess patient function/QoL). In many patients, greatest improvement in SF-36 scores was reported by patients achieving ≥50% decrease in pain. Analysis of Patient Global Impression of Change scores revealed a similar trend, where >80% of patients who achieved substantial pain relief also reported their status as much or very much improved. A substantial direct pregabalin treatment effect was evident for many SF-36 domains that could not be explained by pain relief or improvement in sleep. ConclusionsIn patients with chronic pain due to DPN or PHN, improvements in patient function/QoL in response to pregabalin treatment are correlated with the extent of pain relief. However, such improvements in function/QoL are not mediated entirely through pain relief but are the result of a combination of pregabalin's effects on pain and sleep disturbance and a direct effect on patient function itself.

A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury

To assess the efficacy and tolerability of pregabalin for the treatment of central neuropathic pain after spinal cord injury (SCI). Patients with chronic, below-level, neuropathic pain due to SCI were randomized to receive 150 to 600 mg/d pregabalin (n = 108) or matching placebo (n = 112) for 17 weeks. Pain was classified in relation to the neurologic level of injury, defined as the most caudal spinal cord segment with normal sensory and motor function, as above, at, or below level. The primary outcome measure was duration-adjusted average change in pain. Key secondary outcome measures included the change in mean pain score from baseline to end point, the percentage of patients with ≥30% reduction in mean pain score at end point, patient global impression of change scores at end point, and the change in mean pain-related sleep interference score from baseline to end point. Additional outcome measures included the medical outcomes study-sleep scale and the Hospital anxiety and depression scale. Pregabalin treatment resulted in statistically significant improvements over placebo for all primary and key secondary outcome measures. Significant pain improvement was evident as early as week 1 and was sustained throughout the treatment period. Adverse events were consistent with the known safety profile of pregabalin and were mostly mild to moderate in severity. Somnolence and dizziness were most frequently reported. This study demonstrates that pregabalin is effective and well tolerated in patients with neuropathic pain due to SCI. This study provides class I evidence that pregabalin, 150 to 600 mg/d, is effective in reducing duration-adjusted average change in pain compared with baseline in patients with SCI over a 16-week period (p = 0.003, 95% confidence interval = -0.98, -0.20).

Maintenance of the efficacy of desvenlafaxine in menopausal vasomotor symptoms

The purpose of this study was to assess the 1-year maintenance of the efficacy of desvenlafaxine 100 mg/day (administered as desvenlafaxine succinate) established on week 12 in a 1-year, double-blind, randomized, placebo-controlled trial in postmenopausal women seeking treatment of bothersome vasomotor symptoms. Primary efficacy endpoints were changes in hot flush (HF) frequency and severity on weeks 12, 26, and 52 in an efficacy substudy population (≥50 moderate and severe HFs per week at baseline). Secondary endpoints were Greene climacteric scale, patient global impression symptom rating, and patient global impression of change scores (weeks 12, 26, and 52) for the main study efficacy population. Safety was assessed throughout the trial. The mean baseline HF frequency (efficacy substudy population, n = 365) was 12 moderate and severe HFs per day; the mean baseline severity score was 2.4. At 1 year, women treated with desvenlafaxine maintained the efficacy established on week 12. Desvenlafaxine reduced HF frequency by 7.47 moderate and severe HFs per day on week 12 (adjusted mean difference from placebo, -2.48; 95% CI, -3.47 to -1.50; P < 0.001) and by 7.70 moderate and severe HFs per day on month 12 (adjusted mean difference from placebo, -2.86; 95% CI, -4.14 to -1.57; P < 0.001). Desvenlafaxine reduced the mean severity score by 0.63 on week 12 (placebo, -0.30; P < 0.001) and by 0.75 on month 12 (placebo, -0.44; P = 0.003). Reductions in Greene Climacteric Scale total score (main study efficacy population, n = 1,950) were significantly greater for desvenlafaxine than for placebo on months 3, 6, and 12 (all P < 0.001). Treatment-emergent adverse event rates were 84% for desvenlafaxine and 79% for placebo (P = 0.006). Full safety results are reported separately. The treatment efficacy of desvenlafaxine 100 mg/day achieved on week 12 in postmenopausal women with vasomotor symptoms is maintained for 1 year.

Lacosamide as Add-On to Monotherapy in Patients with Partial-Onset Seizures: Interim Results of the Post-Marketing VITOBA Study (VImpaT Added to One Baseline AED) (P06.126)

Objective: To evaluate the efficacy and safety of lacosamide when added to a single antiepileptic drug (AED) in patients with partial-onset seizures (POS). Background Lacosamide was approved as adjunctive treatment for adults with POS based on results from three pivotal Phase II/III trials in which highly refractory patients (45.2% had >7 lifetime AEDs) were treated according to strict dosing regimens and titration schedules. Design/Methods: VITOBA is a 6-month prospective, non-interventional study with a planned enrollment of 500 evaluable adult patients. Efficacy measures include seizure freedom and Clinical Global Impression of Change score. Safety and tolerability are also being evaluated. Results: Efficacy data are available for 99 patients (FAS) and safety data for 109 (SS). Patients were less refractory than those in the pivotal trials with 73.4% (SS) having a history of 1–3 lifetime AEDs, and only 6.4% (SS) having >6. Over the final three months of the study period, 77.8% and 64.6% of patients experienced a ≥50% and ≥75% reduction in seizure frequency and 43.4% were seizure free at study endpoint. Patients with a history of one lifetime AED experienced greater benefit with lacosamide than the overall population: 86.7% and 80.0% showed a ≥50% and ≥75% reduction in seizure frequency, and 66.7% experienced seizure freedom. Overall, treating physicians judged symptoms in 23.2% and 40.4% of patients as “very much improved” or “much improved.” The incidence of TEAEs (50.5%) was lower than in the pooled pivotal Phase II/III trials (81.0% for all doses). The most common TEAEs (≥5%) were fatigue (11.9%), dizziness (10.1%) and convulsion (5.5%). The mean lacosamide maintenance dose was 250mg/day and the median was 200mg/day. Conclusions: In this interim analysis, patients with less refractory POS treated with lacosamide as add-on to monotherapy derived therapeutic benefits that exceed those observed in the pivotal controlled trials of lacosamide for POS. Supported by: UCB Pharma. Disclosure: Dr. Noack-Rink has received personal compensation for activities with UCB Pharma. Dr. Mayer has nothing to disclose. Dr. Arnold has received personal compensation for activities with DESITIN, Eisai, Inc., and UCB Pharma. Dr. Kumke has received personal compensation for activities with UCB Pharma as an employee. Dr. Runge has received personal compensation for activities with Eisai and UCB.Dr. Runge has received research support from UCB.

Longterm Therapeutic Response to Milnacipran Treatment for Fibromyalgia. A European 1-Year Extension Study Following a 3-Month Study

This double-blind, 1-year extension study investigated the longterm efficacy and safety of milnacipran 100, 150, and 200 mg/day in the treatment of fibromyalgia (FM) in completers of a 3-month European double-blind lead-in study of milnacipran 200 mg/day versus placebo. A total of 468 patients with FM successfully completing the lead-in study were either blindly maintained on milnacipran 200 mg/day (MLN200:MLN200, n = 198) or (if previously receiving placebo) rerandomized to milnacipran 100 mg/day (PBO:MLN100, n = 91), 150 mg/day (PBO:MLN150, n = 92), or 200 mg/day (PBO:MLN200, n = 87) for an additional 12 months (including a 4-week dose escalation). The main efficacy endpoint was a 2-measure composite responder rate (relative to lead-in study baseline) incorporating the weekly-recall pain score recorded on a visual analog scale and the Patient Global Impression of Change score. A panel of other assessments including the Fibromyalgia Impact Questionnaire explored the multidimensional aspects of FM. Descriptive analyses using the last observation carried forward approach were performed. At the 1-year endpoint, the proportion of composite responders (relative to the lead-in study baseline) ranged from 27.5% (PBO:MLN100) to 35.9% (MLN200:MLN200), and had increased from the extension study baseline by 15.2% (PBO:MLN150) to 20.7% (PBO:MLN200 and MLN200:MLN200). At endpoint, an improvement from both baselines was shown in all groups on pain, fatigue, sleep, and quality of life measures. Up to 1 year, all doses of milnacipran were safe and well tolerated. The most common drug-related adverse events were hyperhidrosis and nausea. Over 1 year, milnacipran 100, 150, and 200 mg/day exhibited sustained and safe therapeutic effects on predominant symptoms of FM. Registered as trial no. NCT00757731.

Prospective review of medium term outcomes following interpositional arthroplasty for hammer toe deformity correction

Hammer toe is a common lesser toe deformity that is usually found to affect the second toe. A number of procedures have been applied in its surgical management with varying results but there is still no consensus on the best technique. We prospectively reviewed a consecutive series of patients treated with interpositional arthroplasty, early mobilisation and with a minimal follow up of 6 months. We measured outcome using the Manchester Oxford foot and ankle questionnaire and a global impression of change score. There was a high level of satisfaction with the resulting pain relief and the type of footwear worn thereafter. We had no complications in terms of infection or chronic pain. There were no early recurrences within our follow up period. Overall we demonstrate good to excellent results with this surgical tactic allowing pain relief, early mobilisation and a low risk of infection.

Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial

Previous studies have suggested that patients with Lewy-body-related dementias might benefit from treatment with the N-methyl D-aspartate receptor antagonist memantine, but further data are needed. Therefore, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB). Patients (≥50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey. They were randomly assigned to placebo or memantine (20 mg per day) according to a computer-generated list. Patients and all physicians who had contact with them were masked to treatment assignment. No primary endpoint was defined. Safety analyses were done for all patients who took at least one dose of memantine or placebo, and efficacy analyses were done for all patients who had at least one valid postbaseline assessment. This trial is registered with ClinicalTrials.gov, number NCT00855686. Of the 199 patients randomly assigned to treatment, 34 with DLB and 62 with PDD were given memantine, and 41 with DLB and 58 with PDD were given placebo. 159 (80%) patients completed the study: 80 in the memantine group and 79 in the placebo group. 93 patients treated with memantine and 97 patients treated with placebo were included in the efficacy analysis. At week 24, patients with DLB who received memantine showed greater improvement according to Alzheimer's disease cooperative study (ADCS)-clinical global impression of change scores than did those who received placebo (mean change from baseline 3·3 vs 3·9, respectively, difference -0·6 [95% CI -1·2 to -0·1]; p=0·023). No significant differences were noted between the two treatments in patients with PDD (3·6 with memantine vs 3·8 with placebo, -0·1 [-0·6 to 0·3]; p=0·576) or in the total population (3·5 with memantine vs 3·8 with placebo, -0·3 [-0·7 to 0·1]; p=0·120). Neuropsychiatric-inventory scores showed significantly greater improvement in the memantine group than in the placebo group (-4·3 vs 1·7, respectively, -5·9 [-11·6 to -0·2]; p=0·041) in patients with DLB, but not in those with PDD (-1·6 vs -0·1, respectively, -1·4 [-5·9 to 3·0]; p=0·522) or in the total patient population (-2·6 vs 0·4, respectively, -2·9 [-6·3 to 0·5]; p=0·092). In most of the cognitive test scores, ADCS-activities of daily living, and Zarit caregiver burden scores, there were no significant differences between the two treatment groups in any of the study populations. The incidence of adverse events and number of discontinuations due to adverse events were similar in the two groups. The most common serious adverse events were stroke (n=3 in memantine group), falls (n=2 in memantine group; n=1 in placebo group), and worsening of dementia (n=2 in memantine group). Memantine seems to improve global clinical status and behavioural symptoms of patients with mild to moderate DLB, and might be an option for treatment of these patients. Lundbeck.

Pregabalin in fibromyalgia - responder analysis from individual patient data

BackgroundPopulation mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores.MethodsWe obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (≥ 0%), minimal improvement (≥ 15%), moderate improvement (≥ 30%), substantial improvement (≥ 50%), and extensive improvement (≥ 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo.ResultsInformation from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs (with 95% confidence intervals) for ≥ 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for ≥ 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response.ConclusionsResponder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects.

Milnacipran

Milnacipran is an orally administered selective serotonin and norepinephrine (noradrenaline) reuptake inhibitor indicated for the management of fibromyalgia in adults. In adults, milnacipran was generally effective in the treatment of fibromyalgia in four well designed trials of 3 or 6 months' duration. Composite responder rates for the treatment of fibromyalgia and fibromyalgia pain (co-primary efficacy variables) were generally higher with milnacipran 100 or 200 mg/day (in two divided doses) than with placebo after 12 weeks of fixed-dose treatment. In one study, the composite responder rate for fibromyalgia pain (co-primary efficacy variable) was also higher with milnacipran 200 mg/day than with placebo after 24 weeks of fixed-dose treatment. Furthermore, the benefits of milnacipran therapy were sustained in a 6-month extension of an initial double-blind trial. Improvements from baseline in mean 24-hour recall pain scores, mean weekly recall pain scores, Patient Global Impression of Change scores and in several items of the Fibromyalgia Impact Questionnaire were observed in patients receiving continuous milnacipran for up to 12 months, as well as in patients who switched from placebo to milnacipran therapy at the start of the extension phase. Milnacipran was generally well tolerated in adults with fibromyalgia, with most adverse events being mild to moderate in severity. Nausea was the most common adverse event reported in milnacipran recipients.