Intravenous immunoglobulin in the treatment of primary trigeminal neuralgia refractory to carbamazepine: a study protocol[ISRCTN33042138]

BACKGROUND: We have recently reported successful treatment of patients with chronic pain syndromes using human pooled intravenous immunoglobulin (IVIG) in a prospective, open-label cohort study. A randomised, placebo controlled, double blinded study is needed to confirm these results. We chose to study patients with carbamazepine resistant primary Trigeminal Neuralgia (rpTN), as these had responded particularly well to IVIG. A protocol involving the use of IVIG in rpTN is complex for three reasons: 1. The effect of IVIG does not follow simple dose-response rules; 2. The response pattern of patients to IVIG was variable and ranged between no effect at all and pain free remission between two weeks and >1 year; 3. TN is characterized by extremely severe pain, for which operative intervention is (if temporarily) helpful in most patients. DESIGN: A placebo controlled, parallel, add-on model was developed and the primary outcome variable defined as the length of time during which patients remain in the study. Study groups are compared using Kaplan-Maier survival analysis. Patients record their response to treatment ("severe, moderate, slight, no pain"). The study coordinator monitors pain diaries. Severe or moderate pain of three days duration will result in termination of the study for that patient. CONCLUSIONS: This study design utilizes a method of survival analysis and is novel in chronic pain research. It allows for both early departure from the study and voluntary crossover upon non-response. It may be applicable to the analysis of IVIG efficacy in other chronic pain syndromes

Azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy

INTRODUCTION: The first-line therapy for the intermittent preventive treatment of malaria in pregnancy (IPTp) is sulphadoxine-pyrimethamine (SP). There is an urgent need to identify safe, well-tolerated and efficacious alternatives to SP due to widespread Plasmodium falciparum resistance. Combination therapy using azithromycin and chloroquine is one possibility that has demonstrated adequate parasitological response > 95% in clinical trials of non-pregnant adults in sub-Saharan Africa and where IPTp is a government policy in 33 countries. AREAS COVERED: Key safety, tolerability and efficacy data are presented for azithromycin and chloroquine, alone and/or in combination, when used to prevent and/or treat P. falciparum, P. vivax, and several curable sexually transmitted and reproductive tract infections (STI/RTI). Pharmacokinetic evidence from pregnant women is also summarized for both compounds. EXPERT OPINION: The azithromycin-chloroquine regimen that has demonstrated consistent efficacy in non-pregnant adults has been a 3-day course containing daily doses of 1 g of azithromycin and 600 mg base of chloroquine. The pharmacokinetic evidence of these compounds individually suggests that dose adjustments may not be necessary when used in combination for treatment efficacy against P. falciparum, P. vivax, as well as several curable STI/RTI among pregnant women, although clinical confirmation will be necessary. Mass trachoma-treatment campaigns have shown that azithromycin selects for macrolide resistance in the pneumococcus, which reverses following the completion of therapy. Most importantly, no evidence to date suggests that azithromycin induces pneumococcal resistance to penicillin

Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia

<p>Abstract</p> <p>Background</p> <p>Postherpetic neuralgia (PHN) is a painful and difficult to treat complication of acute herpes zoster. Current treatment options provide only partial relief and are often limited by poor tolerability. We evaluated the safety and efficacy of a single 60-minute application of NGX-4010, an 8% capsaicin patch, in patients with PHN.</p> <p>Methods</p> <p>This multicenter, double-blind, controlled study randomized 155 patients 2:1 to receive either NGX-4010 or a 0.04% capsaicin control patch. Patients were at least 18 years old with PHN for at least 3 months, and an average Numeric Pain Rating Scale (NPRS) score of 3 to 9. The primary efficacy endpoint was the percentage change in NPRS score from baseline to weeks 2-8.</p> <p>Results</p> <p>The mean percent reduction in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 was greater in the NGX-4010 group (36.5%) compared with control (29.9%) although the difference was not significant (p = 0.296). PGIC analysis demonstrated that more NGX-4010 recipients considered themselves improved (much, or very much) compared with control at weeks 8 and 12, but the differences did not reach statistical significance. Post hoc analyses of patients with PHN for at least 6 months showed significantly greater reductions in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 in NGX-4010 patients compared to controls (37.6% versus 23.4%; p = 0.0291). PGIC analysis in this subgroup demonstrated that significantly more NGX-4010 recipients considered themselves much or very much improved compared with control at week 12 (40% versus 20%; p = 0.0403;).</p> <p>Conclusions</p> <p>Although treatment appeared to be safe and well tolerated, a single 60-minute application of NGX-4010 failed to show efficacy in this study which included patients with PHN for less than 6 months. Large reductions in pain observed among control patients with pain for less than 6 months may have been due to spontaneous resolution of PHN, may have confounded the results of the prespecified analyses, and should be taken into account when designing PHN studies.</p> <p>Trial Registration</p> <p>NCT00068081</p

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Early reduction in painful physical symptoms is associated with improvements in long-term depression outcomes in patients treated with duloxetine

<p>Abstract</p> <p>Background</p> <p>To investigate the association of the change of painful physical symptoms (PPS) after 4 weeks, with the 6-month treatment outcomes of depressive symptoms in patients treated with duloxetine in clinical practice.</p> <p>Methods</p> <p>Multicenter, prospective, 6-month, non-interventional study in adult outpatients with a depressive episode and starting treatment with duloxetine. Depression severity was assessed by the clinician (Inventory for Depressive Symptomatology [IDS-C]) and patient (Kurz-Skala Stimmung/Aktivierung [KUSTA]). Somatic symptoms and PPS were assessed using the patient-rated Somatic Symptom Inventory (SSI) and visual analog scales (VAS) for pain items. Association of change in PPS with outcomes of depressive symptoms was analyzed based on mean KUSTA scores (mean of items mood, activity, tension/relaxation, sleep) and achievement of a 50% reduction in the total IDS-C score after 6 months using linear and logistic regression models, respectively.</p> <p>Results</p> <p>Of the 4,517 patients enrolled (mean age: 52.2 years, 71.8% female), 3,320 patients (73.5%) completed the study. 80% of the patients had moderate to severe overall pain (VAS > 30 mm) at baseline. A 50% VAS overall pain reduction after 4 weeks was associated with a 13.32 points higher mean KUSTA score after 6 months, and a 50% pain reduction after 2 weeks with a 6.33 points improvement. No unexpected safety signals were detected in this naturalistic study.</p> <p>Conclusion</p> <p>Pain reduction after 2 and 4 weeks can be used to estimate outcomes of long-term treatment with duloxetine. PPS associated with depression have a potential role in predicting remission of depressive symptoms in clinical practice.</p

Clinical characteristics and patterns of healthcare utilization in patients with painful neuropathic disorders in UK general practice: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Clinical characteristics and patterns of healthcare utilization in patients with painful neuropathic disorders (PNDs) who are under the care of general practitioners (GPs) in the UK are not well understood.</p> <p>Methods</p> <p>Using a large electronic UK database, we identified all adults (age ≥ 18 years) with any GP encounters between 1 January 2006 - 31 December 2006 at which a diagnosis of PND was noted ("PND patients"). An age-and gender-matched comparison group also was constituted consisting of randomly selected patients with one or more GP encounters-but no mention of PNDs-during this period. Characteristics and patterns of healthcare utilization of patients in the two groups were then examined over the one-year study period.</p> <p>Results</p> <p>The study sample consisted of 31,688 patients with mention of PNDs and an equal number of matched comparators; mean age was 56 years, and 62% were women. The prevalence of various comorbidities was higher among patients in the PND group, including digestive disorders (31% vs. 17% for comparison group), circulatory disorders (29% vs. 22%), and depression (4% vs. 3%) (all <it>p </it>< 0.01). Receipt of prescriptions for pain-related pharmacotherapy also was higher among PND patients, including nonsteroidal anti-inflammatory drugs (56% of PND patients had one or more such prescriptions vs. only 22% in the comparison group), opioids (49% vs. 12%), tricyclic antidepressants (20% vs. 1%), and antiepileptics (12% vs. 1%) (all <it>p </it>< 0.01). PND patients also averaged significantly more GP visits (22.8 vs. 14.2) and referrals to specialists (2.8 vs. 1.4) over one year (both comparisons <it>p </it>< 0.01).</p> <p>Conclusions</p> <p>Patients with PNDs under the care of GPs in the UK have relatively high levels of use of healthcare services and pain-related pharmacotherapy.</p

Patient-reported-outcomes in subjects with painful lumbar or cervical radiculopathy treated with pregabalin: evidence from medical practice in primary care settings

The objective of this study was to evaluate the effect of pregabalin in painful cervical or lumbosacral radiculopathy treated in Primary Care settings under routine clinical practice. An observational, prospective 12-week secondary analysis was carried-out. Male and female above 18 years, naïve to PGB, with refractory chronic pain secondary to cervical/lumbosacral radiculopathy were enrolled. SF-MPQ, Sheehan Disability Inventory, MOS Sleep Scale, Hospital Anxiety and Depression Scale and the EQ-5D were administered. A total of 490 (34%) patients were prescribed PGB-monotherapy, 702 (48%) received PGB add-on, and 159 (11%) were administered non-PGB drugs. After 12 weeks, significant improvements in pain, associated symptoms of anxiety, depression and sleep disturbances, general health; and level of disability were observed in the three groups, being significantly greater in PGB groups. In routine medical practice, monotherapy or add-on pregabalin is associated with substantial pain alleviation and associated symptoms improvements in painful cervical or lumbosacral radiculopathy

A Novel Tool for the Assessment of Pain: Validation in Low Back Pain

Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain