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Head-to-head Comparisons (head-to-head + comparison)
Selected AbstractsIndustry sponsorship and selection of comparators in randomized clinical trialsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2010D. N. Lathyris Eur J Clin Invest 2010; 40 (2): 172,182 Abstract Background, Most clinical trials on medical interventions are sponsored by the industry. The choice of comparators shapes the accumulated evidence. We aimed to assess how often major companies sponsor trials that involve only their own products. Methods, Studies were identified by searching ClinicalTrials.gov for trials registered in 2006. We focused on randomized trials involving the 15 companies that had sponsored the largest number of registered trials in ClinicalTrials.gov in that period. Results, Overall, 577 randomized trials were eligible for analysis and 82% had a single industry sponsor [89% (166/187) of the placebo-control trials, 87% (91/105) of trials comparing different doses or ways of administration of the same intervention, and 78% (221/285) of other active control trials]. The compared intervention(s) belonged to a single company in 67% of the trials (89%, 81% and 47% in the three categories respectively). All 15 companies strongly preferred to run trials where they were the only industry sponsor or even the only owner of the assessed interventions. Co-sponsorship typically reflected co-ownership of the same intervention by both companies. Head-to-head comparison of different active interventions developed by different companies occurred in only 18 trials with two or more industry sponsors. Conclusions, Each company generates a clinical research agenda that is strongly focused on its own products, while comparisons involving different interventions from different companies are uncommon. This diminishes the ability to understand the relative merits of different interventions for the same condition. [source] Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trialINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2008A. D. Anastasilakis Summary Aims:, We aimed to compare the effect of risedronate (RIS) and teriparatide (TPTD) (recombinant human parathyroid hormone 1,34) on bone turnover markers in women with postmenopausal osteoporosis. Methods:, Forty-four Caucasian women (age 65.1 ± 1.6 years) with postmenopausal osteoporosis were randomly assigned to receive either RIS 35 mg once weekly (n = 22) or TPTD 20 ,g once daily (n = 22) for 12 months. Serum N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTx), total alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were obtained from all women before, 3 and 6 months after treatment initiation. Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry before and 12 months after treatment initiation. Results:, P1NP, CTx and total ALP levels decreased in RIS group (p < 0.001) and increased in TPTD group (p < 0.001) throughout the treatment. iPTH increased significantly in RIS group (p < 0.05) and decreased in TPTD group (p < 0.001). Finally, lumbar spine BMD increased significantly in both RIS (p = 0.003) and TPTD groups (p < 0.001) without significant differences between them. Conclusions:, Our data suggest that both serum P1NP and CTx are reliable markers of RIS and TPTD action in women with postmenopausal osteoporosis. In a similar way, serum total ALP can be used as an alternative marker for monitoring both RIS and TPTD action, while iPTH can be used only for TPTD-treated women. The increase in P1NP and CTx after 3 months of treatment with RIS or TPTD can predict the increase in BMD after 12 months of treatment. [source] "Head-to-head comparison between sirolimus-eluting and paclitaxel-eluting stents in patients with complex coronary artery disease: An intravascular ultrasound study"CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 6 2006FSCAI, Pavel, ervinka MD Abstract Background: The aim of this study was to assess neointimal hyperplasia following sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) implantation in a patients with complex coronary disease. Method: Between January to December 2004, 70 patients were enrolled in this study (SES = 37; PES = 33. The primary objective was to assess the efficacy of SES and PES on neointimal proliferation inhibition in patients with complex coronary lesions by volumetric 3D intravascular ultrasound (IVUS) assessment at six-month follow-up. Results: Baseline clinical, demographic or angiographic characteristics were well balanced in both groups. All procedures as well as hospitalisation were uneventful. The percentage of B2/C lesions in our study was >90% in both groups. The IVUS-assessed in-stent mean neointimal hyperplasia volume was significantly lower in lesions treated with SES compared to PES (4.1 ± 11 mm3 vs. 17.4 ± 23 mm3, p < 0.002) at 6 month follow-up. No difference in both MACE (3.0 versus 6.0%, p = NS) and restenosis (5.4 versus 9.1%, p = NS) were found. The in-segment late loss at six month was 0.26 mm in the SES and 0.48 mm in the PES group (p = NS). Conclusions: The present study showed reduced neointimal proliferation after sirolimuseluting as compared to paclitaxel-eluting stents in patients with complex coronary artery disease. Both SES and PES were associated with low rate of angiographic restenosis or major adverse cardiovascular events. © 2006 Wiley-Liss, Inc. [source] Meta-analysis comparing clinical effectiveness of drug-eluting stents, bare metal stents and coronary artery bypass surgeryINTERNATIONAL JOURNAL OF EVIDENCE BASED HEALTHCARE, Issue 3 2007Eun-Hwan Oh PhD MPH MHA BA Abstract Objective, To compare clinical outcomes among patients receiving drug-eluting stents, bare metal stents, or coronary artery bypass grafting surgery (CABG) to treat coronary artery disease. Data sources, Randomised controlled trials were systematically selected from electronic database for head-to-head comparisons. The results from these head-to-head comparisons were used for an adjusted indirect comparison. Methods, Published randomised controlled trials were reviewed for outcome data in patients treated for coronary artery disease with drug-eluting stents, bare metal stents, or CABG. Head-to-head comparisons were conducted for drug-eluting stents versus bare metal stents and for CABG versus bare metal stents. Adjusted indirect comparison was used to compare drug-eluting stents and CABG. Mid-term clinical outcomes (range: 6,12 months) were investigated and included rates of mortality, myocardial infarction, thrombosis, target lesion revascularisation, target vessel revascularisation, restenosis and major adverse cardiac events. Results, Systematic literature search identified 23 randomised controlled trials (15 for drug-eluting stents vs. bare metal stents, 8 for CABG vs. bare metal stents). Head-to-head comparisons for both single and multiple vessel disease demonstrated that compared with bare metal stents, drug-eluting stents had better outcomes for target lesion revascularisation, target vessel revascularisation, restenosis and major adverse cardiac events. Except target lesion revascularisation, data were similarly favourable for CABG when compared with bare metal stents. Adjusted indirect comparison between drug-eluting stents and CABG in single vessel disease failed to detect significant differences in any of the measured outcomes. Multiple vessel disease data analysis demonstrated that target vessel revascularisation (odds ratio 3.41 [95% CI 2.29,5.08]) and major adverse cardiac events (1.89 [1.28,2.79]) were superior to drug-eluting stents in patients undergoing CABG. Conclusions, Drug-eluting stents and CABG were superior to bare metal stents in terms of target lesion revascularisation (drug-eluting stents only), target vessel revascularisation, restenosis and major adverse cardiac events. There was no difference in clinical outcomes when comparing CABG and drug-eluting stents in patients with single vessel disease, and CABG may be superior to drug-eluting stents for target vessel revascularisation and major adverse cardiac events in patients with multiple vessel disease. However, results may vary between subpopulations with different clinical or socioeconomic differences. [source] Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2004Darren M. Ashcroft PhD Abstract Objective To evaluate the comparative efficacy and tolerability of naratriptan in the treatment of acute attacks of migraine. Design Meta-analysis of randomised controlled trials using a random effects model. Subjects A total of 4499 patients suffering from moderate or severe attacks of acute migraine reported in ten trials. Main outcome measures Response rate ratios for headache relief, pain-free response and sustained relief (4,24 hours). Adverse events were estimated with the rate ratio (RR), risk difference and number needed to harm. Results Pooled RRs relative to placebo for pain-free response at 2 and 4 hours for naratriptan 2.5,mg were 2.52 (95%,CI: 1.78,3.57) and 2.58 (1.99,3.35). Naratriptan 2.5,mg was more effective than naratriptan 1,mg; the corresponding RRs for pain-free response at 2 and 4 hours were 1.54 (95%,CI: 1.28,1.86) and 1.35 (1.20,1.51). In contrast, naratriptan 2.5,mg was less effective in pain-free response than either rizatriptan 10,mg at 4,hours (RR: 0.68; 95%,CI: 0.55,0.85) or sumatriptan 100,mg at 4,hours (RR: 0.79; 95%,CI: 0.67,0.93). However, significantly fewer patients experienced adverse effects with naratriptan 2.5,mg than with rizatriptan 10,mg (RR: 0.73; 95%,CI: 0.56,0.97) or sumatriptan 100,mg (RR: 0.68; 95%,CI: 0.55,0.86). Conclusions Naratriptan is an effective and well-tolerated treatment for acute attacks of migraine. Head-to-head comparisons suggest that naratriptan 2.5,mg is significantly more effective than the 1,mg dose. Rizatriptan 10,mg and sumatripatn 100,mg were superior to naratriptan in terms of headache relief, while zolmitriptan 2.5,mg seemed to have comparable efficacy. Randomised controlled trials have shown that at licensed doses (1 and 2.5,mg), naratriptan is associated with a lower incidence of adverse effects than rizatriptan, sumatriptan and zolmitriptan. The incidence rates of adverse effects were similar to placebo. Copyright © 2003 John Wiley & Sons, Ltd. [source] Antidepressants in the Treatment of Neuropathic PainBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2005Søren H. Sindrup Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2,3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4,5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class , may among the antidepressants , favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain. [source] EFNS guidelines on pharmacological treatment of neuropathic painEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2006N. Attal Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools. [source] The relation between personality and prejudice: a variable- and a person-centred approachEUROPEAN JOURNAL OF PERSONALITY, Issue 6 2003Bo Ekehammar The relationship between Big Five personality (measured by the NEO-PI) and prejudice was examined using a variable- and a person-centred approach. Big Five scores were related to a generalized prejudice factor based on seven different prejudice scales (racial prejudice, sexism, etc). A correlation analysis disclosed that Openness to Experience and Agreeableness were significantly related to prejudice, and a multiple regression analysis showed that a variable-centred approach displayed a substantial cross-validated relationship between the five personality factors and prejudice. A cluster analysis of the Big Five profiles yielded, in line with previous research, three personality types, but this person-centred approach showed a low cross-validated relationship between personality and prejudice, where the overcontrolled type showed the highest prejudice and the undercontrolled the lowest, with the resilient falling in between. A head-to-head comparison sustained the conclusion that, based on people's Big Five personalities, their generalized prejudice could be predicted more accurately by the variable- than the person-centred approach. Copyright © 2003 John Wiley & Sons, Ltd. [source] Screening for Wound-induced Oxylipins in Arabidopsis thaliana by Differential HPLC-APCI/MS Profiling of Crude Leaf Extracts and Subsequent Characterisation by Capillary-scale NMRPHYTOCHEMICAL ANALYSIS, Issue 3 2008Aly Thiocone Abstract A simple non-targeted differential HPLC-APCI/MS approach has been developed in order to survey metabolome modifications that occur in the leaves of Arabidopsis thaliana following wound-induced stress. The wound-induced accumulation of metabolites, particularly oxylipins, was evaluated by HPLC-MS analysis of crude leaf extracts. A generic, rapid and reproducible pressure liquid extraction procedure was developed for the analysis of restricted leaf samples without the need for specific sample preparation. The presence of various oxylipins was determined by head-to-head comparison of the HPLC-MS data, filtered with a component detection algorithm, and automatically compared with the aid of software searching for small differences in similar HPLC-MS profiles. Repeatability was verified in several specimens belonging to different series. Wound-inducible jasmonates were efficiently highlighted by this non-targeted approach without the need for complex sample preparation as is the case for the ,oxylipin signature' procedure based on GC-MS. Furthermore this HPLC-MS screening technique allowed the isolation of induced compounds for further characterisation by capillary-scale NMR (CapNMRTM) after HPLC scale-up. In this paper, the screening method is described and applied to illustrate its potential for monitoring polar and non-polar stress-induced constituents as well as its use in combination with CapNMR for the structural assignment of wound-induced compounds of interest. Copyright © 2008 John Wiley & Sons, Ltd. [source] A modified tandem affinity purification strategy identifies cofactors of the Drosophila nuclear receptor,dHNF4PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 3 2006Ping Yang Abstract With the completion of numerous genome projects, new high-throughput methods are required to ascribe gene function and interactions. A method proven successful in yeast for protein interaction studies is tandem affinity purification (TAP) of native protein complexes followed by MS. Here, we show that TAP, using Protein,A and CBP tags, is not generally suitable for the purification and identification of proteins from tissues. A head-to-head comparison of tags shows that two others, FLAG and His, provide protein yields from Drosophila tissues that are an order of magnitude higher than Protein,A and CBP. FLAG-His purification worked sufficiently well so that two cofactors of the Drosophila nuclear receptor protein,dHNF4 could be purified from whole animals. These proteins, Hsc70 and Hsp83, are important chaperones and cofactors of other nuclear receptor proteins. However, this is the first time that they have been shown to interact with a non-steroid binding nuclear receptor. We show that the two proteins increase the ability of dHNF4 to bind DNA in,vitro and to function in,vivo. The tags and approaches developed here will help facilitate the routine purification of proteins from complex cells, tissues and whole organisms. [source] Meta-analysis comparing clinical effectiveness of drug-eluting stents, bare metal stents and coronary artery bypass surgeryINTERNATIONAL JOURNAL OF EVIDENCE BASED HEALTHCARE, Issue 3 2007Eun-Hwan Oh PhD MPH MHA BA Abstract Objective, To compare clinical outcomes among patients receiving drug-eluting stents, bare metal stents, or coronary artery bypass grafting surgery (CABG) to treat coronary artery disease. Data sources, Randomised controlled trials were systematically selected from electronic database for head-to-head comparisons. The results from these head-to-head comparisons were used for an adjusted indirect comparison. Methods, Published randomised controlled trials were reviewed for outcome data in patients treated for coronary artery disease with drug-eluting stents, bare metal stents, or CABG. Head-to-head comparisons were conducted for drug-eluting stents versus bare metal stents and for CABG versus bare metal stents. Adjusted indirect comparison was used to compare drug-eluting stents and CABG. Mid-term clinical outcomes (range: 6,12 months) were investigated and included rates of mortality, myocardial infarction, thrombosis, target lesion revascularisation, target vessel revascularisation, restenosis and major adverse cardiac events. Results, Systematic literature search identified 23 randomised controlled trials (15 for drug-eluting stents vs. bare metal stents, 8 for CABG vs. bare metal stents). Head-to-head comparisons for both single and multiple vessel disease demonstrated that compared with bare metal stents, drug-eluting stents had better outcomes for target lesion revascularisation, target vessel revascularisation, restenosis and major adverse cardiac events. Except target lesion revascularisation, data were similarly favourable for CABG when compared with bare metal stents. Adjusted indirect comparison between drug-eluting stents and CABG in single vessel disease failed to detect significant differences in any of the measured outcomes. Multiple vessel disease data analysis demonstrated that target vessel revascularisation (odds ratio 3.41 [95% CI 2.29,5.08]) and major adverse cardiac events (1.89 [1.28,2.79]) were superior to drug-eluting stents in patients undergoing CABG. Conclusions, Drug-eluting stents and CABG were superior to bare metal stents in terms of target lesion revascularisation (drug-eluting stents only), target vessel revascularisation, restenosis and major adverse cardiac events. There was no difference in clinical outcomes when comparing CABG and drug-eluting stents in patients with single vessel disease, and CABG may be superior to drug-eluting stents for target vessel revascularisation and major adverse cardiac events in patients with multiple vessel disease. However, results may vary between subpopulations with different clinical or socioeconomic differences. [source] A systematic review and meta-analysis on the therapeutic equivalence of statinsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2010T.-C. Weng MSc (Clin Pharm) Summary Background:, Statins are the most commonly prescribed agents for hypercholesterolemia because of their efficacy and tolerability. As the number of patients in need of statin therapy continues to increase, information regarding the relative efficacy and safety of statins is required for decision-making. Objective:, This study will use systematic review to compare the efficacy and safety profiles of different statins at different doses and determine the therapeutically equivalent doses of statins to achieve a specific level of low-density lipoprotein cholesterol (LDL-C) lowering effect. Methods:, Publications of head-to-head randomized controlled trials (RCTs) of statins were retrieved from the Oregon state database (1966,2004), MEDLINE (2005-April of 2006), EMBASE (2005-April of 2006), and the Cochrane Controlled Trials Registry (up to the first quarter of 2006). The publications were evaluated with predetermined criteria by a reviewer before they were included in the review. The mean change in cholesterol level of each statin was calculated and weighted by number of subjects involved in each RCT. Where possible, meta-analysis was performed to generate pooled estimates of the cholesterol lowering effect of statins and the difference between statins. Results:, Seventy-five studies reporting RCTs of head-to-head comparisons on statins were included. Most studies had similar baseline characteristics, except the rosuvastatin related studies. A daily dose of atorvastatin 10 mg, fluvastatin 80 mg, lovastatin 40,80 mg, and simvastatin 20 mg could decrease LDL-C by 30,40%, and fluvastatin 40 mg, lovastatin 10,20 mg, pravastatin 20,40 mg, and simvastatin 10 mg could decrease LDL-C by 20,30%. The only two statins that could reduce LDL-C more than 40% were rosuvastatin and atorvastatin at a daily dose of 20 mg or higher. Meta-analysis indicated a statistically significant but clinically minor difference (<7%) between statins in cholesterol lowering effect. Comparisons of coronary heart disease prevention and safety could not be made because of insufficient data. Conclusions:, At comparable doses, statins are therapeutically equivalent in reducing LDL-C. [source] Systematic review: pancreatic enzyme treatment of malabsorption associated with chronic pancreatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009A. K. WALJEE Summary Background, Pancreatic enzyme supplementation is standard treatment for malabsorption caused by chronic pancreatitis. The FDA recently required all manufacturers to submit New Drug Applications to continue to market these agents because published data demonstrated variation in formulation, bioavailability and shelf-life while providing limited data about efficacy and safety. Aim, To review systematically the design and results of randomized, parallel-design trials of pancreatic enzyme supplements in chronic pancreatitis patients with steatorrhea. Methods, A computer-assisted search of MEDLINE and EMBASE was performed to identify relevant studies. Two authors performed duplicate data extraction on study design, improvement in coefficient of fat absorption (CFA), diarrhoea and adverse events using pre-specified forms. Agreement between investigators for data extraction was greater than 95%. Results, Of 619 articles found through literature searching, 20 potentially relevant articles were identified and four manuscripts met inclusion criteria. No studies performed head-to-head comparisons of different supplements. Enzyme supplementation is more likely to improve CFA compared with placebo, but fat malabsorption remained abnormal. Important differences in patient population, study endpoint, study design, pancreatic enzyme dosage and measurement of CFA were present across trials, which precluded comparison of different agents. Conclusions, Enzyme supplementation improves CFA compared to placebo, but may not abolish steatorrhoea. [source] Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000,2007,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2008Alexander M. Walker MD, DrPH Abstract Background The risk of coronary heart disease (CHD) in users of antidiabetic agents must be quantified to permit reasoned therapeutic choices. Objectives To assess the risk of myocardial infarction (MI) and coronary revascularization (CR), in diabetic patients who began rosiglitazone, pioglitazone, metformin, or sulfonylureas. Methods We conducted a retrospective cohort study of MI and CR in the PharMetrics database. We performed head-to-head comparisons using propensity-score-stratified Cox proportional hazards models, examining risks both on-treatment and during total follow-up before regimen switches. Results For the combined outcome (MI and CR), the crude rates per 1000 person years were 9 on monotherapy, 13 on dual therapy, and 21 on therapies combined with insulin. In the absence of insulin, regimens containing thiazolidinediones (TZDs) tended toward lower risk than comparable regimens containing sulfonylureas and higher risk than those containing metformin. The summary hazard ratio for rosiglitazone versus pioglitazone was 1.04 (95%CI: 0.94,1.14) for total follow-up and 1.05 (0.92,1.19) for on-treatment time. For MI, the hazard ratios were 1.07 (0.89,1.27) for total follow-up and 1.21 (0.95,1.54) for on-treatment time. Conclusions The present data indicate that the risk of CHD in patients using TZDs appears to lie between the risks associated with sulfonylureas and metformin. Neither the risk of MI and CR together nor the risk of MI alone was significantly different between rosiglitazone and pioglitazone. A nonsignificant observed excess risk of 21% for MI during on-treatment time will require combination with the results of other studies to provide a reliable assessment. Copyright © 2008 John Wiley & Sons, Ltd. [source] Antidepressants in the Treatment of Neuropathic PainBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2005Søren H. Sindrup Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2,3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4,5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class , may among the antidepressants , favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain. [source] 2154: Are all glaucoma drugs equally effective?ACTA OPHTHALMOLOGICA, Issue 2010L SCHMETTERER Purpose It is only in the recent years that we have got evidence that reducing intraocular pressure (IOP) is beneficial in terms of preventing glaucoma progression in all types of glaucomatous disease. Nowadays we do have numerous data from large clinical outcomes trials clearly indicating that the lower the IOP the better the visual field preservation. There is, however, less data available comparing outcomes of different pharmacological regimen. Methods Only few head-to-head comparisons of two drugs that are equally effective in lowering IOP have been published. It is generally assumed that such trials would yield similar results in visual field preservation with both regimen. Looking into the literature there is, however, some evidence for the opposite. Results One clinical trial indicates that betaxolol may be superior to timolol in terms of visual field perservation. Another trial indicates that a combination of dorzolamide and timolol is assocaited with less visual field detoriation than a combination of brinzolamide and timolol. In this study the risk of disease progression was closely linked to low blood velocities in retrobulbar vessels. Conclusion In light of these results and the lessons we have learned from other fields there is a need for further studies comparing the outcomes of different antiglaucoma drugs head-to-head. Given that the pathophysiology of glaucoma is only poorly understood it can not generally be expected that all glaucoma drugs are equally effective in perserving visual fields. Commercial interest [source] | |||||||||||||||||||||||||