Pain Intensity Visual Analogue Scale Research Articles

Open-Label Treatment with Desvenlafaxine in Postmenopausal Women with Major Depressive Disorder Not Responding to Acute Treatment with Desvenlafaxine or Escitalopram

Preliminary clinical evidence indicates that menopausal status might impact on the efficacy of certain classes of antidepressants. The aim of this study was to evaluate open-label desvenlafaxine treatment (administered as desvenlafaxine succinate) in postmenopausal women who did not achieve clinical response to acute, double-blind treatment with desvenlafaxine or escitalopram. This phase IIIb, multicentre study included a 6-month open-label extension phase of patients who did not respond in the initial 8-week, randomized, double-blind acute phase. Postmenopausal women aged 40-70 years with a primary diagnosis of major depressive disorder were recruited. PRIMARY INTERVENTION: Non-responders to acute treatment with double-blind desvenlafaxine or escitalopram received flexible-dose, open-label desvenlafaxine 100-200 mg/day for the 6-month extension phase. The primary efficacy assessment was the 17-item Hamilton Rating Scale for Depression (HAM-D(17)) total score. Secondary efficacy outcome measures were the Clinical Global Impressions-Improvement (CGI-I) and -Severity scales, Hamilton Rating Scale for Anxiety, Quick Inventory of Depressive Symptomatology-Self-Report, Visual Analogue Scale-Pain Intensity and the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary health assessments were the Changes in Sexual Functioning Questionnaire, 5-Dimension EuroQoL Index, Health State Today, Menopause Rating Scale, Sheehan Disability Scale, treatment response (≥ 50% decrease in total HAM-D(17) and MADRS score from acute-phase baseline and CGI-I total score ≤ 2), HAM-D(17) remission (total score ≤ 7) and safety. Descriptive statistics were used to summarize outcomes. The efficacy analysis included 123 patients (desvenlafaxine/desvenlafaxine = 64; escitalopram/desvenlafaxine = 59). At final evaluation of the open-label extension phase, mean reductions from acute-phase baseline in HAM-D(17) total scores were -11.33 for the desvenlafaxine/desvenlafaxine group and -11.41 for the escitalopram/desvenlafaxine group. HAM-D(17) response or remission after 6 months of open-label extension phase desvenlafaxine treatment were achieved in 56-58% and 41-48% of patients, respectively. The results of the other secondary efficacy outcome measures and other definitions of treatment response were generally consistent with the primary analyses. The observed adverse events were similar to those reported during previous desvenlafaxine clinical trials. Postmenopausal women with major depressive disorder who did not respond to acute, double-blind treatment with escitalopram or desvenlafaxine achieved modest, continued improvement with long-term, open-label desvenlafaxine therapy. Further interpretation of these findings is limited by aspects of the study design (i.e. open-label, non-placebo-controlled) and the lack of randomized comparison groups in the extension phase, which prevents statistical assessment of the efficacy of longer term treatment with desvenlafaxine. Clinicaltrials.gov identifier: NCT00406640.

Duodenum-preserving pancreatic head resection in treating patients with chronic pancreatitis

To evaluate the therapeutic efficacy of duodenum-preserving pancreatic head resection (DPPHR) for severe chronic pancreatitis (CP). From February 2004 to March 2010, duodenum-preserving resection of pancreatic head was performed in 21 patients with severe CP. A "modified-DPPHR" was carried out in 14 patients of them and a "Frey's DPPHR" in the other 7 patients. The values of fasting plasma blood (FPB), oral glucose tolerance test (OGTT), body weight (BW), visual analogue pain intensity scale (VAS score) and the quality of life indices were evaluated before and 6(th) month after surgery. There was no hospital mortality. The complications from adjacent organs were resolved definitively. Pancreatic fistula was the major and the most frequent morbidity occurring in 23.8% of the patients. After operation 85.7% of the patients were completely pain-free and 14.3% had continuing abdominal pain. The VAS score decreased more after surgery comparing with before and there was a significant difference (81.1 ± 5.6 vs 7.8 ± 3.6, P < 0.05). The value of FPB in post-operative patients was similar to that in pre-operative ones and there was no significant difference [(5.3 ± 0.4) mmol/L vs (5.4 ± 0.4) mmol/L, P > 0.05]. The value of 2 h-OGGT in post-operative patients was also similar to that in pre-operative ones and it did not differ significantly [(8.0 ± 0.6) mmol/L vs (7.9 ± 0.6) mmol/L, P > 0.05]. After operation 77.8% of patients gained more than 5% of their pre-operative body weight with a mean increment of (4.8 ± 0.7) kg (58.8 ± 1.8 vs 53.9 ± 2.0, P < 0.05). A significant rise of the overall quality of life index was observed after surgery (78.1 ± 7.3 vs 61.0 ± 6.2, P < 0.05). DPPHR is both safe and effective with regard to pain relief, a definitive control of complications affecting adjacent organs and an improvement of overall quality of life. It leads to no further deterioration of pancreatic functions.

Oral acetaminophen (paracetamol) for additional analgesia in phacoemulsification cataract surgery performed using topical anesthesia: Randomized double-masked placebo-controlled trial

To evaluate the clinical analgesic efficacy of 1.0 g oral acetaminophen (paracetamol) given in addition to topical anesthesia before phacoemulsification cataract surgery. Inpatient and outpatient ophthalmology clinics, Bydgoszcz, Poland. Consecutive patients with age-related cataract having phacoemulsification under topical anesthesia (tetracaine 0.5%) were enrolled in a prospective double-blind randomized placebo-controlled study. Patients were randomly assigned to preoperative oral administration of a placebo medication or to oral administration of 1.0 g acetaminophen. The main outcome measure was intensity of pain during and after surgery. Pain intensity was measured using a 10 cm baseline visual analog scale and a discrete 5-category verbal rating scale. The study comprised 160 consecutive patients (80 in each group). Intraoperatively, the mean visual analog scale pain intensity score was 2.17 +/- 1.81 in the placebo group and 1.45 +/- 1.17 in the acetaminophen group and the mean verbal rating scale score, 1.11 +/- 0.73 and 0.67 +/- 0.66, respectively (P<.01). Postoperatively, the mean visual analog scale score for pain was 1.47 +/- 1.39 in the placebo group and 0.56 +/- 0.61 in the acetaminophen group and the mean verbal rating scale score, 0.94 +/- 0.79 and 0.28 +/- 0.41, respectively (P<.01). There was no significant difference in patient behavior during surgery and no significant adverse effects of acetaminophen use. Preoperative oral administration of acetaminophen 1.0 g was effective, convenient, safe, and cost effective in reducing intraoperative and postoperative pain in phacoemulsification performed using topical anesthesia.

Correlation of pain relief with physical function in hand osteoarthritis: randomized controlled trial post hocanalysis

IntroductionNonsteroidal anti-inflammatory drugs are recommended for the relief of pain associated with hand osteoarthritis (OA) but do not alter the underlying structural changes that contribute to impaired physical function. The current analysis examined the relationship of pain relief with measures of function and global rating of disease in patients with hand OA.MethodsThis was a combined analysis of 2 prospective, randomized, double-blind, 8-week, multicenter, parallel-group studies comparing diclofenac sodium 1% gel with placebo gel (vehicle) in patients with radiographically confirmed mild to moderate hand OA. Patients (n = 783) aged ≥ 40 years applied diclofenac sodium 1% gel (2 g) or vehicle to each hand 4 times daily for 8 weeks. Outcome measures included pain intensity assessed on a 100-mm Visual Analog Scale (VAS); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscales for pain, stiffness, and physical function (100-mm VAS); and a global rating of disease (100-mm VAS). Change in VAS pain intensity from baseline to week 8 was categorized (<0%, 0%-<15%, 15%-<30%, 30%-<50%, 50%-<70%, and ≥ 70%) without regard to treatment and compared in each category with the mean change from baseline in each AUSCAN subindex and the global rating of disease. Pearson correlations between changes in outcome measures from baseline to week 8 were calculated.ResultsChanges in VAS pain intensity were accompanied by similar changes in AUSCAN scores and global rating of disease. Pearson correlations confirmed significant associations (P < 0.001) between change in VAS pain intensity and changes in AUSCAN pain (correlation coefficient [r] = 0.81), AUSCAN function (r = 0.75), AUSCAN stiffness (r = 0.66), and global rating of disease (r = 0.76).ConclusionsPain relief correlated with improvements in physical function, stiffness, and global rating of disease in patients with hand OA, irrespective of treatment. This suggests that pain or anticipation of pain inhibits physical function and influences patient perception of disease severity in hand OA. These results also suggest that any intervention to relieve the pain of hand OA may improve function and patient perception of disease severity, despite the absence of a disease-modifying mechanism of action.Trial registrationClinicaltrials.gov NCT00171652, NCT00171665.

Augmented Cerebral Activation by Lumbar Mechanical Stimulus in Chronic Low Back Pain Patients

Cerebral activation by lumbar mechanical stimulus was investigated by functional magnetic resonance imaging in healthy subjects and patients with chronic low back pain (LBP). To characterize the cerebral substrates of LBP, and to explore a possible pathologic pattern of cerebral activation in chronic LBP patients. The cerebral substrates of LBP have been poorly defined in contrast to those of cutaneous somatic pain. Eight healthy volunteers and 6 patients with idiopathic, chronic LBP were recruited. Each subject was placed in the prone position on a 3 Tesla MRI scanner, and stimulated by manual pressure with the tail of an air-filled, 20-mL syringe at 5 cm left of the fourth-fifth lumbar spinal interspace. Three blocks of 30-second painful stimulus, calibrated at either 3 or 5 on the 10-cm visual analog scale (VAS), were applied with intervening 30-second rest conditions during whole-brain echo-planar imaging. VAS of pain intensity and unpleasantness were evaluated after each session. Functional imaging was analyzed using a multisubject general linear model with Bonferroni multiple comparisons at P < 0.05. Pain thresholds were smaller (P < 0.05) and VAS of unpleasantness was larger in LBP patients than in healthy subjects. Activation was observed at the prefrontal, insular, posterior cingulate cortices (PCC), supplementary motor, and premotor areas predominantly in the right hemisphere, but not at the somatosensory cortices. LBP patients showed augmented activation compared with healthy volunteers specifically at the right insula, supplementary motor, and PCC. Chronic LBP patients showed increased tenderness at the lower back, higher aversive reaction to pain, and augmented LBP-related cerebral activation. The LBP-related activation is characterized by the absence of sensory-discriminative component and the involvement of PCC.

Botulinum Neurotoxin-A for Treatment of Refractory Neck Pain: A Randomized, Double-Blind Study

To investigate the efficacy and tolerability of Botulinum neurotoxin-A (BoNT-A) in the patients with refractory neck pain. An analgesic effect is suggested for BoNT-A by a number of animal studies. Two blinded studies suggested efficacy of BoNT-A in a chronic neck pain. Forty-seven subjects were enrolled in a prospective, double-blind, placebo-controlled study. A total of 150 to 300 units of BoNT-A were injected into the neck and shoulder muscles based on pain localization. Subjects completed the visual analog scale (VAS), Pain Frequency Questionnaire and the Modified Oswestry Pain Questionnaire (MOPQ) at baseline, 3 and 8 weeks after the treatment. The primary outcomes consisted of: 1) > or =50% improvement on the VAS; and 2) > or =30% reduction in pain day frequency. The secondary outcome was an improvement of ADL in MOPQ. Excellent responders (ERs) were those who met all three outcomes. At 2 months, a significant reduction in the mean VAS (pain intensity) was noted in the BoNT-A group compared with the placebo (P = 0.0018, CI 95% from 2.51 to 7.89). At 2 months, there were six ERs in the BoNT-A group and one ER in the placebo group (P = 0.0152). Administration of BoNT-A into the neck and shoulder muscles for treatment of chronic refractory neck pain met one of the two primary outcomes: reduction in pain intensity. More ERs were noted in the Botox group.

Intravenous Paracetamol or Morphine for the Treatment of Renal Colic: A Randomized, Placebo-Controlled Trial

This randomized, placebo-controlled trial evaluates the analgesic efficacy and safety of intravenous single-dose paracetamol and morphine for the treatment of renal colic. We conducted a randomized, double-blind, placebo-controlled clinical trial comparing single intravenous doses of paracetamol (1 g), morphine (0.1 mg/kg), and placebo (normal saline solution) for patients presenting to the emergency department (ED) with suspected renal colic. Subjects with inadequate pain relief at 30 minutes received rescue fentanyl (0.75 microg/kg). We compared changes in pain intensity 30 minutes after treatment among the 3 arms, as well as the need for rescue medication and the presence of adverse effects. Six hundred forty-five consecutive patients were screened for study and 165 were entered. Eight subjects were subsequently excluded from analysis because of protocol violations and 11 were excluded because of uncertain diagnoses, leaving 146 subjects available for analysis. The mean reduction in visual analogue scale pain intensity scores at 30 minutes was 43 mm for paracetamol (95% confidence interval [CI] 35 to 51 mm), 40 mm for morphine (95% CI 29 to 52 mm), and 27 mm for placebo (95% CI 19 to 34 mm). Statistically significant mean differences in pain intensity reductions compared with those for placebo were observed for paracetamol (16; 95% CI 5 to 27; P=.005) and morphine (14; 95% CI 0.4 to 27; P=.05); however, no difference was found between paracetamol and morphine (2; 95% CI -13 to 16; P=.74). Rescue analgesics at 30 minutes were required by 21 subjects (45%) receiving paracetamol, 24 subjects (49%) receiving morphine, and 34 subjects (67%) receiving placebo (P=.08). At least 1 adverse effect was experienced by 11 (24%) receiving paracetamol, 16 (33%) receiving morphine, and 8 (16%) in the placebo group (P=.14). There were no serious adverse events. Intravenous paracetamol is an efficacious and safe treatment for ED patients with renal colic.

Influence of Time, Activities, and Memory on the Assessment of Chronic Low Back Pain Intensity

A prospective study. To identify factors potentially influencing patient self-evaluation of chronic low back pain (CLBP) and their interactions. The impact of the time, context, and/or recall on the self-assessment of chronic pain intensity remains poorly understood. A prospective study investigated patients' CLBP intensity over 29 days. Patients were evaluated on days 1 and 29 by the investigator with a pain intensity visual analog scale (0-100), and interviewed by phone on days 8, 15, and 22 to 28 to evaluate pain intensity with a numerical rating scale (0-10), either thrice daily (time-associated group), or during rest/activities (activity-associated group). Current and/or recalled pain intensities were also assessed. Means of recorded pain intensity and overall assessment of patient's pain intensity of the day were subjected to statistical analyses with analysis of variance and test of correlation. Among the 203 patients included, 194 (56.2% women; mean age: 47.5 +/- 12.1 year) were considered in the analysis (9 patients were not followed until day 24). Strong correlations were obtained between mean pain intensity (time-associated group = 44 patients) and overall assessment of pain intensity of the day. Strong correlations were also obtained between overall assessment of pain intensity of the day and intensity measured during each activity, but not between current pain intensity and remembered pain 24 of 48 hours earlier (activity-associated group = 150 patients). Recalled pain intensities for the last 7 or 28 days were strongly correlated with current pain intensity, but the correlations were markedly weaker after adjustment for day 29-pain intensity. For CLBP patients, overall assessment of pain intensity of the day at evening is accurate to assess pain on 1 day. Overall assessment of pain intensity of the day is very close with usual pain. Furthermore, 24 and 48 hours remembered pain intensity are not accurate measures. Recalls of pain on the 7 or 28 last days were very dependant of the pain intensity of the day of the assessment. These findings could contribute to improving pain intensity assessment in CLBP patients avoiding multiple assessments, especially during clinical trials.

Cost-effectiveness of ziconotide in intrathecal pain management for severe chronic pain patients in the UK

ABSTRACTObjective: To examine the cost-effectiveness of using intrathecal ziconotide in the treatment of severe chronic pain compared to best supportive care for patients with intractable chronic pain in the United Kingdom.Methods: Using a simulation model, the analysis evaluated the cost and health economic consequences of using ziconotide as a treatment for severe chronic pain. The modelled population and clinical data were based on a randomised controlled trial in which the main outcome was reduction in pain as measured by the visual analogue scale of pain intensity (VASPI). Resource use data were elicited using a modified Delphi panel and costed using published sources. Utility values were derived from a separate research study. The main outcome measure was the cost per quality-adjusted life-year (QALY). Extensive scenario analysis was conducted to evaluate parameter uncertainty.Results: Overall, findings were robust to most assumptions. The cost-effectiveness of ziconotide compared to best supportive care (BSC) was £27 443 per QALY (95% CI £18 304–38 504). Scenarios were investigated in which discount rates, the time horizon, the threshold for qualifying as a responder, pump-related assumptions, utilities, ziconotide drug dose, and the patient discontinuation rate with ziconotide were varied. The most sensitive parameter was the dosage of ziconotide: using the lower and upper bounds of the average ziconotide dosage observed in the long-term open-label study changed the incremental cost-effectiveness ratio (ICER) to £15 500 [£8206–25 405] and £44 700 [£30 541–62 670].Conclusions: Ziconotide may offer an economically feasible alternative solution for patients for whom current treatment is inappropriate or ineffective. The main study limitation is that some model inputs, mainly related to resource use, are based on assumptions or expert interviews.

Anemia-Related Hemogram, Uterine Artery Pulsatility Index, and Blood Pressure for the Effects of Four-Agents-Decoction (Si Wu Tang) in the Treatment of Primary Dysmenorrhea

We previously reported pain intensity as the primary outcome of Four-Agents-Decoction (Si Wu Tang) for treating primary dysmenorrhea. We further explored other effects of this formula in accordance with the theory of Traditional Chinese Medicine on anemia-related hemogram parameters for "nourishing blood" and uterine artery pulsatility index (PI) for "blood stagnation." Data were assessed for post-hoc analysis from 76 young women from the Taipei metropolitan area of Taiwan who participated in the randomized double-blind clinical trial. Analysis of variance and t test were used to examine the treatment effect between and within the Four-Agents-Decoction and placebo groups. In addition to pain intensity, anemia-related hemogram parameters, uterine artery PI, menstruation characteristics, and blood pressure were compared. Compared to placebo, biochemical indicators for anemic status did not change differently after the treatment with Four-Agents-Decoction (Si Wu Tang). The changes in uterine artery PI, menstrual pain intensity, and blood pressure were statistically greater in the active treatment group than in the placebo group. In the 25 women receiving ultrasound examination on the same menstruation day, the directions of the changes in both PI and in visual analog scale (VAS) pain intensity aligned well. The changes in the left PI, right PI, and VAS pain intensity in the Four-Agents-Decoction group were -0.391 +/- 0.861, -0.344 +/- 1.03, and -0.251 +/- 2.02 cm; those in the placebo group were 0.208 +/- 1.10, 0.372 +/- 1.06, and 0.438 +/- 2.98 cm, respectively. Inversely, the changes in blood pressure were 11.4 +/- 10.5 mm Hg for systolic blood pressure and 8.36 +/- 8.65 mm Hg for diastolic pressure for the Four-Agents-Decoction group and 6.36 +/- 8.66 and 2.91 +/- 11.2 mm Hg, respectively, for the placebo group. The directions of the changes did not shift, nor did the values change drastically, after adjusting for the level at screening cycle. The anemia status evaluated in conventional medicine does not readily explain the effect of "nourishing blood" by Four-Agents-Decoction (Si Wu Tang) from this exploratory study. Although we did not find strong statistical significance of treatment effect, the decreased PI and extra blood pressure elevation may indicate an improvement of "blood stagnation" in the Four-Agents-Decoction group. The added information warrants a further larger clinical trial with an increased power to enhance our understanding of the efficacy, the dose-response relationship, and the mode of action of this ancient formula for treating primary dysmenorrhea.

What factors predict full or partial return to work among sickness absentees with spinal pain participating in rehabilitation?

Purpose. To identify the factors that predict full or partial return to work among long-term (≥90 days) sickness absentees due to spinal pain who begin a multidisciplinary rehabilitation programme.Method. In a prospective cohort study, 312 patients with neck, thoracic and/or lumbar pain, aged 20–64, participated in a 4-week multidisciplinary rehabilitation programme in Sweden. Questionnaire data at inclusion were used. Factors included in logistic regressions were as follows: age, gender, type of work, pain location, pain intensity (visual analogue scale), activity limitations [Disability Rating Index (DRI)], health-related quality of life (SF-36), pain-related fear of movement (Tampa Scale of Kinesiophobia), motivation (Self Motivation Inventory), sickness absence at baseline and number of sick-leave days during the previous 2 years. Outcome factor was increased versus not increased working time at follow-up 6 months later.Results. Most patients (68%) reported two or three pain locations. At baseline, 56% were full-time sickness absent and 23% at follow-up; 61% had increased their working time. Predictors for increased working time were age below 40 years, low activity limitation (DRI < 50), low SF-36 bodily pain (>30) and high SF-36 social functioning (>60). Number of sick-leave days during the previous 2 years (md 360; range 90–730) had no influence.Conclusions. Even patients with long previous sick leave can increase working time after a multidisciplinary rehabilitation programme, especially if they are younger, have lower levels of activity limitations and pain and better social functioning. To include information on part-time work is useful when evaluating work ability following rehabilitation programmes.

Preemptive combined preventive delivery of flurbiprofen axetil produced effective analgesia after lumpectomy

Summary Background Preoperative and intraoperative administration of analgesics was considered an effective way to suppress postoperative pain. The aim of this study was to investigate the analgesic efficacy of flurbiprofen axetil administered preemptively plus preventively in the earlier period of lumpectomy. Methods Four hundred ASA I–II patients, undergoing lumpectomy, were screened and 236 were randomly assigned into one of two groups ( n = 118). In the flurbiprofen group, patients received an i.v. injection of flurbiprofen 50 mg 15 min before the start and the end of the operation, separately. The placebo group received the same volumes of saline before the start and the end of the operation. The Visual Analog Scale (VAS) pain intensity at rest, overall satisfaction score, additional morphine consumption and side effects were recorded. Results A total of 196 patients completed the study. Subjects received flurbiprofen experienced significant pain relief and improvement of the feeling of satisfaction at the first 24 h after surger. The additional morphine was consumed [8.5 mg (95% CI 4.2–12.4) in the saline group vs. 1.1 mg (95% CI 0.7–2.5) in the flurbiprofen group, p = 0.046]. No intergroup difference was observed in the incidence of side effects. Conclusion Preemptive combined preventive administration of flurbiprofen axetil showed effective analgesia significantly up to 24 h after lumpectomy and suggested it is a reliable analgesic for acute postoperative pain therapy.

Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder

ABSTRACTObjective: To assess the efficacy, safety, and tolerability of 50- and 100-mg/day doses of desvenlafaxine (administered as desvenlafaxine succinate), a serotonin-norepinephrine reuptake inhibitor, for the treatment of major depressive disorder (MDD).Research design and methods: Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) MDD and 17-item Hamilton Rating Scale for Depression (HAM-D17) scores ≥20 were randomly assigned to double-blind placebo or desvenlafaxine treatment (fixed dose of 50 mg/day or 100 mg/day) for 8 weeks. The primary efficacy measure was the HAM-D17. Changes from baseline in HAM-D17 scores were analyzed using analysis of covariance. The final on-therapy evaluation was the primary endpoint for efficacy analyses, using last-observation-carried-forward data.Main outcomes measures and results: The intent-to-treat population included 447 patients. Desvenlafaxine 50 mg was associated with a significantly greater adjusted mean change from baseline on the HAM-D17 (−11.5) compared with placebo (−9.5, p = 0.018); the 100-mg dose group (−11.0) did not achieve statistical significance (p = 0.065). The 100-mg dose group experienced significant improvements compared with placebo on several secondary efficacy measures, including the 6-item Hamilton Depression Rating Scale (p = 0.038) and the Visual Analog Scale–Pain Intensity total score (p = 0.041). Both desvenlafaxine doses were generally well-tolerated. The most common adverse events (incidence ≥10% in either desvenlafaxine group and twice the rate of placebo) were dry mouth, constipation, insomnia, decreased appetite, hyperhidrosis, and dizziness.Conclusions: These results demonstrate efficacy, safety, and tolerability of desvenlafaxine 50 mg/day for treating MDD. The significant findings on secondary measures support the efficacy of desvenlafaxine 100 mg, as seen in other trials. Conclusions may be limited by the exclusion of MDD patients with comorbid conditions and the short-term desvenlafaxine treatment duration.

An Open-Label, Multicenter Study of the Safety and Efficacy of Intrathecal Ziconotide for Severe Chronic Pain When Delivered via an External Pump

Objectives. The study aims to assess the safety and efficacy of intrathecal (IT) ziconotide when delivered via an external infusion system. Materials and Methods. Patients with severe chronic pain were implanted with an external infusion system, and IT ziconotide was titrated over one to four weeks. Safety was evaluated via adverse event (AE) reports, and efficacy measures included the visual analog scale of pain intensity (VASPI), categorical pain relief scale (CPRS), and clinical global impression (CGI). Results. Sixty-four of the 71 patients (90.1%) experienced an AE during titration; five patients developed meningitis after completing at least two weeks of therapy. A significant (p≤0.005) median percentage improvement in VASPI scores was seen at week 1 and maintained through week 4 (range: 11.0-32.6%); 53.6% of patients reported good to excellent pain control on the CGI and 52.2% of patients reported moderate to complete pain relief on the CPRS. Conclusions. The study results suggest that a short-term trial of IT ziconotide using an external infusion system may be sufficient to assess patient response. High rates of AEs were noted; however, ziconotide-related AEs were consistent with those reported in previous trials.

Tubeless Percutaneous Nephrolithotomy: What about Replacing the Double-J Stent with a Ureteral Catheter?

To evaluate the feasibility and safety of replacing the Double-J stent with a ureteral catheter in tubeless percutaneous nephrolithotomy (PCNL). From August 1998 to February 2007, 33 patients underwent tubeless PCNL for renal calculi by the same surgeon. A retrograde 7F ureteral catheter was placed at the beginning of the surgery in all patients. A nephrostomy tube was not used in any patient. At the end of the procedure, the working tract was electrocauterized using a 26F resectoscope with a rollerball electrode; no hemostatic sealant was used. The ureteral catheter was the sole means of drainage left in place. The incidence and type of complications, the operative time, the length of hospitalization, the rate of transfusion, and the degree of pain were obtained by chart review. In this group of patients, the mean stone burden was 17.25 mm. The mean operative time was 71.5 min. The mean length of hospitalization was 1.9 day (range 1 to 7 days). The mean hemoglobin decrease was 0.8 g/dL. No blood transfusions were needed. The mean visual analog pain intensity scale was 1.87. Complications developed in five (15%) patients, of whom one needed a Double-J stent placement. The complications were pyelonephritis, urinary extravasation, sustained hematuria, and renal colic. The ureteral catheter was removed by postoperative day 1 in 91% of patients. Replacing the Double-J stent with a ureteral catheter in tubeless PCNL is an effective procedure and can be performed in patients with a moderate stone burden. The electrocauterization of the bleeding points at the end of percutaneous renal surgery with a rollerball resectoscope is safe.

A Randomized, Double‐Blind, Crossover Comparison of the Efficacy and Safety of Oral Controlled‐Release Tramadol and Placebo in Patients with Painful Osteoarthritis

To compare the efficacy and safety of controlled-release (CR) tramadol (Zytram XL, Purdue Pharma, Canada) and placebo in patients with painful osteoarthritis. Patients underwent analgesic washout for two to seven days before random assignment to 150 mg daily of CR tramadol or placebo, and were titrated weekly to 200 mg, 300 mg or a maximum of 400 mg once daily. After four weeks, patients crossed over to the alternate treatment for another four weeks. Plain acetaminophen was provided as a rescue analgesic. All patients who completed the crossover study were eligible to receive open label CR tramadol for six months. Seventy-seven of 100 randomly assigned patients were evaluable for efficacy. CR tramadol resulted in significantly lower visual analogue scale pain intensity scores (37.4+/-23.9 versus 45.1+/-24.3, P=0.0009). Western Ontario and McMaster Universities osteoarthritis index subscale scores for pain (189.0+/-105.0 versus 230.0+/-115.4; P=0.0001) and physical function (632.4+/-361.3 versus 727.4+/-383.4; P=0.0205) were significantly better with CR tramadol. Total pain and disability (22.8+/-14.5 versus 27.2+/-14.8; P=0.0004), and overall pain and sleep (104.7+/-98.0 versus 141.0+/-108.2; P=0.0005) scores in the Pain and Sleep Questionnaire were significantly lower for CR tramadol. Short-form 36 Health Survey scores were significantly better during CR tramadol treatment for the pain index (38.8+/-10.8 versus 35.6+/-9.0; P=0.0100), general health perception (46.5+/-11.2 versus 44.4+/-11.6; P=0.0262), vitality (43.1+/-13.2 versus 40.2+/-13.7; P=0.0255) and overall physical components (40.8+/-8.9 versus 37.8+/-7.7; P=0.0002). CR tramadol treatment was preferred by 55.8% of patients (P=0.0005) versus 20.8% and 23.4% of patients who chose placebo or had no preference, respectively. These improvements were sustained for up to six months, and 86.5% of patients reported at least moderate benefit from CR tramadol during long-term treatment. CR tramadol is effective for the management of painful osteoarthritis.

Interactions between glutamate and capsaicin in inducing muscle pain and sensitization in humans

The aim of the study was to investigate the interaction between glutamate and capsaicin in inducing muscle pain and sensitization in humans. Fifteen male volunteers participated. Glutamate or capsaicin or isotonic saline, in a paired-sequence order, was injected randomly into the right or left masseter muscle. Two injections were given in a double-blinded design 25 min apart in 1 session/week over 4 weeks: saline (A1) followed by glutamate (A2), capsaicin (B1) followed by glutamate (B2), saline (C1) followed by capsaicin (C2), and glutamate (D1) followed by capsaicin (D2). The subjects drew the area of perceived pain and scored pain intensity on a 0–10 visual analogue scale (VAS). Pressure pain threshold (PPT) at the injection site, at a site 2-cm away, and on the contralateral side, as well as pressure pain tolerance (PPTol) at the injection site and contralateral site, were also measured before and after injection and subsequently at 5-min intervals. Paired t-test analyses showed that the pain drawing area was significantly smaller in the B2 compared to the A2 condition ( P = 0.028), and significantly larger in the D2 compared to the C2 condition ( P = 0.027). It also revealed significantly lower VAS peak pain intensity ( P = 0.008) and smaller VAS area under the curve ( P = 0.003) for the B2 compared to the A2 condition, and significantly higher VAS peak pain ( P = 0.015) and larger VAS area under the curve ( P = 0.037) for the D2 compared to the C2 condition. There was a significant PPT and PPTol decrease at the injection site after glutamate or capsaicin injection (ANOVA: P < 0.028). The percentage decrease in PPT or PPTol (at the injection site) was not significantly different for the B2 compared to the A2 condition (Paired t-test: P > 0.682) or for the D2 compared to the C2 condition ( P > 0.133). Significant PPT changes were also observed at the site 2 cm away, but not on the contralateral side. In conclusion, these findings indicate that intramuscular administrations of glutamate and capsaicin interact and influence pain and sensitization of muscle nociceptors: glutamate causes a sensitization to subsequent administration of capsaicin, whereas capsaicin is associated with a desensitization to subsequent injection of glutamate. These findings support previous animal data.

Acupuncture in the Treatment of Fibromyalgia in Tertiary Care – a Case Series

Fibromyalgia is a common cause of chronic widespread pain. The benefit of medication is often limited by its side effects, and the improvements obtained with exercise and education are inconsistent. Many patients seek acupuncture treatment, which is reported to be helpful in some cases. This study aimed to explore the acceptability and benefits of acupuncture offered in the setting of a tertiary referral clinic. An open, uncontrolled observational study was conducted among patients who met the usual fibromyalgia criteria and who had a pain score of at least 30 on a 100mm Visual Analogue Scale (VAS). Patients were allowed to continue other treatments but not to introduce new ones. Acupuncture was given using a Western approach according to a protocol developed by consensus. Patients were offered eight treatments in eight weeks. Outcome measures included VAS of pain intensity and Fibromyalgia Impact Questionnaire (range 0 - 100), and were taken before and after treatment, and at 14, 20 and 34 weeks from enrolment. Twenty four eligible patients were enrolled in a 12 month period. Baseline mean pain VAS score for these 24 patients was 74 (SD 18) and mean Fibromyalgia Impact Questionnaire score 78 (SD 12.4). Only 14 patients completed the course of treatment within about 10 weeks. Compliance was poor in the remaining patients because of difficulty attending clinic, and in two cases because of exacerbation of pain. Completion of outcome measures was variable and therefore the analysis of data is limited. Five patients scored at least 20% reduction in Fibromyalgia Impact Questionnaire score which is a clinically relevant improvement. Two of these scored at least 50% reduction. Acupuncture appears to offer symptomatic improvement to some patients with fibromyalgia in a tertiary clinic who have failed to respond to other treatments. In view of its safety, further acupuncture research is justified in this population.

A Randomized, Double-Blind, Placebo-Controlled Trial of Desvenlafaxine Succinate in Adult Outpatients With Major Depressive Disorder

This study evaluated the efficacy and tolerability of desvenlafaxine succinate (desvenlafaxine) in the treatment of major depressive disorder (MDD). In this 8-week, multicenter, randomized, double-blind, placebo-controlled trial, adult outpatients (aged 18-75 years) with a primary diagnosis of MDD (DSM-IV criteria) were randomly assigned to treatment with desvenlafaxine (100-200 mg/day) or placebo. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression (HAM-D(17)) score at final on-therapy evaluation. The Clinical Global Impressions-Improvement scale (CGI-I) was the key secondary measure. Other secondary measures included the Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions-Severity of Illness scale, Visual Analog Scale-Pain Intensity (VAS-PI) overall and subcomponent scores, and HAM-D(17) response and remission rates. The study was conducted from June 2003 to May 2004. Of the 247 patients randomly assigned to treatment, 234 comprised the intent-to-treat population. Following titration, mean daily desvenlafaxine doses ranged from 179 to 195 mg/day. At endpoint, there were no significant differences in scores between the desvenlafaxine (N = 120) and placebo (N = 114) groups on the HAM-D(17) or CGI-I. However, the desvenlafaxine group had significantly greater improvement in MADRS scores (p = .047) and in VAS-PI overall pain (p = .008), back pain (p = .006), and arm, leg, or joint pain (p < .001) scores than the placebo group. The most common treatment-emergent adverse events (at least 10% and twice the rate of placebo) were nausea, dry mouth, constipation, anorexia, somnolence, and nervousness. Desvenlafaxine was generally safe and well tolerated. In this study, it did not show significantly greater efficacy than placebo on the primary or key secondary efficacy endpoints, but it did demonstrate efficacy on an alternate depression scale and pain measure associated with MDD. ClinicalTrials.gov identifier NCT00063206.

A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder

The antidepressant efficacy and safety of desvenlafaxine succinate (desvenlafaxine) were evaluated in a phase III, double-blind, placebo-controlled study. Outpatients with a primary diagnosis of major depressive disorder were treated with fixed once-daily doses of desvenlafaxine 200 or 400 mg for 8 weeks. The primary efficacy measure was change from baseline on the 17-item Hamilton Rating Scale for Depression. At the final on-therapy evaluation, adjusted mean change from baseline in 17-item Hamilton Rating Scale for Depression total score was greater for desvenlafaxine 200 and 400 mg/day vs. placebo. Both desvenlafaxine doses showed greater efficacy than placebo on the secondary efficacy measures, including the Clinical Global Impressions-Improvement scale scores, Montgomery-Asberg Depression Rating Scale scores, CGI-Severity, and 17-item Hamilton Rating Scale for Depression response rate. Desvenlafaxine 200 mg/day was also significantly better than placebo on remission, Visual Analog Scale-Pain Intensity overall scores, and some Visual Analog Scale-Pain Intensity subscale scores. Desvenlafaxine 400 mg/day was significantly better than placebo on selected Visual Analog Scale-Pain Intensity subscale scores. Most adverse events were mild or moderate in severity, and safety assessments revealed few clinically significant changes in vital signs, laboratory tests, and electrocardiogram results. These data provide support for the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder.