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Comparator
Kinds of Comparator Terms modified by Comparator Selected AbstractsMulticenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder,DEPRESSION AND ANXIETY, Issue 5 2010Vladimir Coric M.D. Abstract Background: Antagonism of corticotropin-releasing factor (CRF) receptors has been hypothesized as a potential target for the development of novel anxiolytics. This study was designed to determine the safety and efficacy of pexacerfont, a selective CRF-1 receptor antagonist, in the treatment of generalized anxiety disorder (GAD). Method: This was a multicenter, randomized, double-blind, placebo-controlled and active comparator trial. Two hundred and sixty patients were randomly assigned to pexacerfont 100,mg/day (after a 1 week loading dose of 300,mg/day), placebo or escitalopram 20,mg/day in a 2:2:1 ratio. The primary outcome was the mean change from baseline to end point (week 8) in the Hamilton Anxiety Scale total score. Results: Pexacerfont 100,mg/day did not separate from placebo on the primary outcome measure. The half-powered active comparator arm, escitalopram 20,mg/day, demonstrated efficacy with significant separation from placebo at weeks 1, 2, 3, 6, and 8 (P<.02). Response rates for pexacerfont, placebo, and escitalopram were 42, 42, and 53%, respectively. Genetic and psychometric rating scale data was obtained in 175 randomized subjects. There was a significant association between a single nucleotide polymorphism (SNP) of the gene encoding plexin A2 (PLXNA2-2016) with the HAM-A psychic subscale score for the entire cohort at baseline (FDR-adjusted P=.015). Conclusions: Pexacerfont did not demonstrate efficacy compared to placebo for the treatment of GAD. Whether these findings are generalizable to this class of agents remains to be determined. Our preliminary genetic finding of an association between a SNP for the gene encoding plexin A2 and an anxiety phenotype in this study merits further exploration. The trial was registered at clinicaltrials.gov (NCT00481325) before enrollment. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [source] Is bipolar II depression phenotypically distinctive?ACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009G. B. Parker Objective:, We examine the depressive symptom profile of bipolar II disorder patients compared with a comparator (composite) group of those with unipolar depression, with stratification by melancholic and non-melancholic subtypes. Method:, Out-patients (n = 394) attending a specialist depression clinic comprised the sample. Data on severity and prototypic status of depressive symptoms were analysed. Results:, Age-matched analyses revealed minimal differentiation between bipolar II and composite unipolar groups. Stratified analyses suggested that ,bipolar II depression' more closely approximated melancholic depression in terms of psychomotor and cognitive slowing. Severity-based analyses and prototypic symptom patterns yielded differing results, suggesting that definition of bipolar II depression is influenced by rating strategies, and age. Conclusion:, We found limited differentiation of bipolar II depression from unipolar, melancholic and non-melancholic depression. Differences suggested previously may reflect age, gender and severity differences, highlighting the need for appropriately matched groups in defining bipolar II depression. [source] Ontogenetic scaling of scansorial surface area and setal dimensions of Chondrodactylus bibronii (Gekkota: Gekkonidae): testing predictions derived from cross-species comparisons of gekkotansACTA ZOOLOGICA, Issue 1 2009Nicole B. Webster Abstract Little is known of how the adhesive apparatus of gekkotans scales with growth. Cross-species comparisons of certain characteristics, using size as a comparator to investigate scaling relationships, suggest certain relationships between subdigital pad area and body size. The manner in which the adhesive apparatus grows and scales within any one species, however, remains unknown, and it is unclear whether interspecific and intraspecific patterns are similar. To address this, we examined a post-hatching ontogenetic series of the southern African gecko Chondrodactylus bibronii and demonstrate that setal density, setal basal diameter and setal spacing remain relatively constant in relation to size, indicating conserved subdigital pad assembly rules that are independent of size. Conversely, however, average and maximal setal lengths increase slightly and isometrically with size, an outcome that is probably explained by setal row recruitment, and the surface area of the subdigital pads scales close to, but below, isometry with respect to body mass and snout,vent length, it therefore does not increase sufficiently with size to compensate for the increase in mass. As a result, relative adhesive capacity decreases with growth with a regression slope of ,0.45. [source] Rat hippocampal theta rhythm during sensory mismatchHIPPOCAMPUS, Issue 4 2009D. Zou Abstract It has been suggested that sensory mismatch induces motion sickness, but its neural mechanisms remain unclear. To investigate this issue, theta waves in the hippocampal formation (HF) were studied during sensory mismatch by backward translocation in awake rats. A monopolar electrode was implanted into the dentate gyrus in the HF, from which local field potentials were recorded. The rats were placed on a treadmill affixed to a motion stage translocated along a figure 8-shaped track. The rats were trained to run forward on the treadmill at the same speed as that of forward translocation of the motion stage (a forward condition) before the experimental (recording) sessions. In the experimental sessions, the rats were initially tested in the forward condition, and then tested in a backward (mismatch) condition, in which the motion stage was turned around by 180° before translocation. That is, the rats were moved backward by translocation of the stage although the rats ran forward on the treadmill. The theta (6,9 Hz) power was significantly increased in the backward condition compared with the forward condition. However, the theta power gradually decreased by repeated testing in the backward condition. Furthermore, backward translocation of the stage without locomotion did not increase theta power. These results suggest that the HF might function as a comparator to detect sensory mismatch, and that alteration in HF theta activity might induce motion sickness. © 2008 Wiley-Liss, Inc. [source] Regional differences in hippocampal PKA immunoreactivity after training and reversal training in a spatial Y-maze taskHIPPOCAMPUS, Issue 5 2007Robbert Havekes Abstract It is suggested that the hippocampus functions as a comparator by making a comparison between the internal representation and actual sensory information from the environment (for instance, comparing a previously learned location of a food reward with an actual novel location of a food reward in a Y-maze). However, it remains unclear to what extent the various hippocampal regions contribute to this comparator function. One of the proteins known to be crucially involved in the formation of hippocampus-dependent long-term memory is the adenosine 3,,5, cyclic monophosphate dependent protein kinase (PKA). Here, we examined region-specific changes in immunoreactivity (ir) of the regulatory II,,, subunits of PKA (PKA RII,,,-ir) in the hippocampus during various stages of spatial learning in a Y-maze reference task. Thereafter, we compared changes in hippocampal PKA RII,,,-ir induced by training and reversal training in which the food reward was relocated to the previously unrewarded arm. We show that: (1) There was a clear correlation between behavioral performance and elevated PKA RII,,,-ir during the acquisition phase of both training and reversal training in area CA3 and dentate gyrus (DG), (2) PKA RII,,,-ir was similarly enhanced in area CA1 during the acquisition phase of reversal training, but did not correlate with behavioral performance, (3) PKA RII,,,-ir did not change during training or reversal training in the subiculum (SUB), (4) No changes in PKA RII,,, protein levels were found using Western blotting, and (5) AMPA receptor phosphorylation at serine 845 (S845p; the PKA site on the glutamate receptor 1 subunit (GluR1)), was enhanced selectively during the acquisition phase of reversal training. These findings reveal that training and reversal training induce region-specific changes in hippocampal PKA RII,,,-ir and suggest a differential involvement of hippocampal subregions in match-mismatch detection in case of Y-maze reference learning. Alterations in AMPA receptor regulation at the S845 site seems specifically related to the novelty detector function of the hippocampus important for match-mismatch detection. © 2007 Wiley-Liss, Inc. [source] A placebo controlled investigation into the effects of paroxetine and mirtazapine on measures related to car driving performanceHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2003F. Ridout Abstract Objective To assess the effects of paroxetine and mirtazapine on psychometric performance related to car driving, including an on-the-road test of BRT. Method In a 4-way, double blind randomised crossover study, 12 healthy volunteers received paroxetine 20,mg mane, mirtazapine 15,mg/30,mg nocte (comparator), mirtazapine 15,mg mane/15,mg b.i.d.(verum) and placebo over a 5 day period with a washout period of 7 days between treatments. Psychometric assessments included ,on-the-road' BRT (BRT), CFF (CFF), CRT (CRT) and subjective measures of sedation and sleep parameters. Results Paroxetine had no significant effect on BRT compared with placebo. Although subjective ratings of sleep quality and sedation were impaired, there were significant improvements in both CFF and the recognition reaction component of CRT with paroxetine. Mirtazapine 15,mg/30,mg nocte impaired laboratory performance and some subjective tests. Mirtazapine 15 mg mane/15,mg b.i.d. improved sleep, but significantly impaired all other measures. Conclusion Paroxetine 20,mg/day has no psychomotor or behavioural toxicity and has no negative impact on BRT. Further research into the chronic and sub-chronic effects of mirtazapine is needed to establish the clinical significance of these results. Copyright © 2003 John Wiley & Sons, Ltd. [source] Nonagenarian surgical admissions for the acute abdomen: who benefits?INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2010Z. Toumi Summary Introduction:, Patients 90 years and older form an increasing proportion of the general population. Outcomes of their acute surgical admissions are not well documented. Methods and materials:, Surgical management of 49 consecutive nonagenarian admissions (median age: 92 years) with an acute abdomen was compared with the management and outcome of 50 younger patients (median age: 53.5) admitted with a suspected acute abdomen over the same period. Results:, Nonagenarian group consisted of mainly women (71% vs. 50%; p = 0.003). The use of laboratory investigations and imaging was similar for the patients aged over 90 and the younger patients, although proportionately fewer nonagenarians were investigated by abdominal CT scan (8% vs. 24%). Of the 49 nonagenarian patients admitted, only 4% (n = 2) were operated on. In contrast, 38% (n = 19) of patients aged 50,59 (p = 0.0001) underwent a surgical intervention. A much greater proportion of nonagenarians died in hospital than patients in the 50,59 comparator group (16% nonagenarians vs. 4% comparator patients; p = 0.04). The very large majority of survivors in both age groups were discharged back to their preadmission domicile [39 (95%) nonagenarians vs. 46 (96%) comparator 50,59 year group]. Conclusions:, In this study, when compared with younger patients, very few nonagenarian patients (2%) with a suspected acute abdomen benefited from surgical admission. Instead, the large majority of nonagenarians either died or were discharged back to their home address without surgery. [source] A double blind, randomized clinical trial assessing the efficacy and safety of augmenting standard antidepressant therapy with nimodipine in the treatment of ,vascular depression'INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2001Fernando E. Taragano Abstract Background ,Vascular depression' may be caused by cerebrovascular disease. Calcium channel blockers, which are putative treatments for cerebrovascular disease, might be expected to improve depression reduction and to prevent recurrence of depression in this patient population. This clinical trial was designed to test these hypotheses. Design This was a controlled, double blind, randomized clinical trial in which 84 patients with vascular depression (Alexopoulos criteria) were treated with antidepressants at standard doses. Patients were also randomized to nimodipine (n,=,40) or an inactive comparator, vitamin C (n,=,44). Treatment outcomes were assessed using the Hamilton depression rating scale (HDRS) regularly up to 300 days after treatment initiation. Results As expected, depression reduction was successful in most patients. In addition, those treated with nimodipine plus an antidepressant had greater improvements in depression overall in repeated measures ANCOVA (F(1,81),=,8.64, p,=,0.004). As well a greater proportion of nimodipine-treated participants (45 versus 25%) exhibited a full remission (HDRS,,10) (,2(df, 1),=,3.71, p,=,0.054). Among those experiencing a substantial response in the first 60 days (50% reduction in HDRS), fewer patients on nimodipine (7.4%) had a recurrence of major depression when compared to those on antidepressant alone (32%) (,2(df, 1),=,3.59, p,=,0.058). Conclusions In treating vascular depression, augmentation of antidepressant therapy with a calcium-channel blocker leads to greater depression reduction and lower rates of recurrence. These findings support the argument that cerebrovascular disease is involved in the pathogenesis and recurrence of depression in these patients. Copyright © 2001 John Wiley & Sons, Ltd. [source] Across the EU Studies,New Regionalism Frontier: Invitation to a DialogueJCMS: JOURNAL OF COMMON MARKET STUDIES, Issue 4 2010ALEX WARLEIGH-LACK This article notes a lack of communication between two broad schools of scholarship on regional integration: EU studies and analyses of the ,new regionalism'. It is argued that the existence of this divide, which is perpetrated by proponents of both schools, is an impediment to the elaboration of useful theory as well as being a missed opportunity. The benefits and problems of using the EU as a comparator in studies of regionalism are assessed. While the mistake of giving the EU analytical primacy as a benchmark or model is to be avoided, it is argued that careful treatment of accumulated insights from EU studies (including a proper re-inspection of classical integration theory) brings clear methodological and meta-theoretical benefits for the project of comparative regional integration scholarship. [source] A novel lattice-spacing comparator with resolution of 10,8JOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 2 2003Xiaowei Zhang A novel, fast and stable system for measuring the lattice spacing of a silicon crystal with a precision of 10,8 is described. Self selection of monochromatic X-rays by a monolithic double channel-cut crystal monochromator (MDCM), producing silicon 264 and 624 diffraction, may lead to a stable, highly collimated and narrow-bandwidth beam. When utilizing the 264 and 624 Bragg reflections of a silicon sample, the angular distance between the two associated Bragg peaks must be extremely small, so that the diffraction angle can be determined with high precision and the traveling time from one peak to the other can be considerably reduced by the order of at least three compared with the established classical Bond method. This so-called self-reference comparator method can dramatically save measurement time and can provide an absolute measurement on the basis of the known X-ray wavelength available from the MDCM. Thus a lattice-spacing measurement with resolution of 10,8, within a few tens of seconds for an area of 1,mm2 on a silicon sample, has been realised. [source] A systematic review of honey uses and its potential value within oncology careJOURNAL OF CLINICAL NURSING, Issue 19 2008Joy Bardy Aim., To synthesise the evidence regarding honey's role in health care and to identify whether this evidence applies more specifically to cancer care. Design., Systematic review. Methods., The inclusion and exclusion criteria were agreed by two reviewers and a keyword strategy was developed. EMBASE, CINAHL, AMED, MEDLINE, COCHRANE and PUBMED databases were screened to identify suitable articles. The citation list from each included study was also screened for potentially suitable papers. The key findings from each study were entered onto a data extraction sheet. Results., In total, 43 studies were included in the systematic review, which included studies in relation to wounds (n = 19), burns (n = 11), skin (n = 3), cancer (n = 5) and others (n = 5). In addition, a systematic review regarding honey use in wound care was also included. While the majority of studies noted the efficacy of honey in clinical use, five studies found honey to be equally as effective as the comparator and three found honey to be less effective than the comparator treatment. Other research did not illustrate any significant difference between standard treatment regimes vs. honey treatment. Studies were generally poor in quality because of small sample sizes, lack of randomisation and absence of blinding. Conclusions., Honey was found to be a suitable alternative for wound healing, burns and various skin conditions and to potentially have a role within cancer care. Relevance to clinical practice., In the cancer setting, honey may be used for radiation-induced mucositis, radiotherapy-induced skin reactions, hand and foot skin reactions in chemotherapy patients and for oral cavity and external surgical wounds. [source] Comparison of the technical and clinical performance of the Elecsys® HBsAg II assay with the Architect®, AxSym®, and Advia® Centaur HBsAg screening assaysJOURNAL OF MEDICAL VIROLOGY, Issue 5 2010S. Louisirirotchanakul Abstract South East Asia has some of the highest prevalence rates of hepatitis B virus (HBV) infection (,8%) in the world, and the emergence of hepatitis B surface antigen (HBsAg) mutant strains is a growing problem. Assays with the highest levels of sensitivity, including mutant detection, should be used for routine HBsAg screening. In this large multicenter study, the clinical and technical performance of the fully automated Elecsys HBsAg II assay was compared with the Architect, AxSYM, and Advia Centaur HBsAg assays for HBsAg screening. Nine laboratories (three each from Thailand, Korea, and Singapore) compared the Elecsys HBsAg II assay with their routine HBsAg screening assay against a range of stored and routine clinical samples, including recombinant mutants. The Elecsys HBsAg II assay demonstrated equivalent sensitivity and specificity to the Architect HBsAg assay. However, the Elecsys HBsAg II assay recognized a native mutant sample (L94S, L97V, L98V, T123A) that the Architect HBsAg assay failed to detect. The AxSYM and Advia Centaur HBsAg assays appeared less sensitive for the detection of early HBV infection and also failed to detect some of the recombinant mutant strains. There was almost complete agreement between the Elecsys HBsAg II assay and comparator assays with respect to routine serum samples. The results of this study demonstrate that the Elecsys HBsAg II assay is a highly sensitive and specific screening assay for HBsAg and detects reliably the most important and clinically relevant HBV mutants and genotypes. It is suitable for routine HBsAg screening in Asia. J. Med. Virol. 82: 755,762, 2010. © 2010 Wiley-Liss, Inc. [source] Biowaiver monographs for immediate release solid oral dosage forms: Doxycycline hyclate,,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2010E. Jantratid Abstract Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing doxycycline hyclate are reviewed. According to the Biopharmaceutics Classification System (BCS), doxycycline hyclate can be assigned to BCS Class I. No problems with BE of IR doxycycline formulations containing different excipients and produced by different manufacturing methods have been reported and hence the risk of bioinequivalence caused by these factors appears to be low. Doxycycline has a wide therapeutic index. Further, BCS-based dissolution methods have been shown to be capable of identifying formulations which may dissolve too slowly to generate therapeutic levels. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing doxycycline hyclate as the single Active Pharmaceutical Ingredient (API) provided that (a) the test product contains only excipients present in doxycycline hyclate IR solid oral drug products approved in the International Conference on Harmonization (ICH) or associated countries; and (b) the comparator and the test products comply with the BCS criteria for "very rapidly dissolving" or, alternatively, when similarity of the dissolution profiles can be demonstrated and the two products are "rapidly dissolving.". © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1639,1653, 2010 [source] Biowaiver monographs for immediate release solid oral dosage forms: Diclofenac sodium and diclofenac potassium,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2009B. Chuasuwan Abstract Literature data are reviewed regarding the scientific advisability of allowing a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing either diclofenac potassium and diclofenac sodium. Within the biopharmaceutics classification system (BCS), diclofenac potassium and diclofenac sodium are each BCS class II active pharmaceutical ingredients (APIs). However, a biowaiver can be recommended for IR drug products of each salt form, due to their therapeutic use, therapeutic index, pharmacokinetic properties, potential for excipient interactions, and performance in reported BE/bioavailability (BA) studies, provided: (a) test and comparator contain the same diclofenac salt; (b) the dosage form of the test and comparator is identical; (c) the test product contains only excipients present in diclofenac drug products approved in ICH or associated countries in the same dosage form, for instance as presented in this paper; (d) test drug product and comparator dissolve 85% in 30 min or less in 900 mL buffer pH 6.8, using the paddle apparatus at 75 rpm or the basket apparatus at 100 rpm; and (e) test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1206,1219, 2009 [source] Biowaiver monographs for immediate release solid oral dosage forms: AciclovirJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2008J. Arnal Abstract Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. However, in some countries also 800 mg tablets are available which fall just within BCS Class IV. Aciclovir seems not to be critical with respect to a risk for bioinequivalence, as no examples of bioinequivalence have been identified. It has a wide therapeutic index and is not used for critical indications. Hence, if: (a) the test product contains only excipients present in aciclovir solid oral IR drug products approved in ICH or associated countries, for instance as presented in this article; and (b) the comparator and the test product both are very rapidly dissolving, a biowaiver for IR aciclovir solid oral drug products is considered justified for all tablet strengths. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5061,5073, 2008 [source] Physicochemical interactions between drugs and superdisintegrantsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2008Nelly Fransén We have evaluated the interactions between superdisintegrants and drugs with different physicochemical characteristics, which may affect the in-vivo absorption e.g. after mucosal administration. The binding of sodium salicylate, naproxen, methyl hydroxybenzoate (methylparaben), ethyl hydroxybenzoate (ethylparaben), propyl hydroxybenzoate (propylparaben), atenolol, alprenolol, diphenhydramine, verapamil, amitriptyline and cetylpyridinium chloride monohydrate (CPC) to different superdisintegrants (sodium starch glycolate (SSG), croscarmellose sodium (CCS) and crospovidone) and one unsubstituted comparator (starch) was studied spectrophotometrically. An indication of the in-vivo effect was obtained by measuring the interactions at physiological salt concentrations. SSG was investigated more thoroughly to obtain release profiles and correlation between binding and ionic strength. The results showed that the main interactions with the anionic hydrogels formed by SSG and CCS were caused by ion exchange, whereas the neutral crospovidone exhibited lipophilic interactions with the non-ionic substances. The effect of increased ionic strength was most pronounced at low salt concentrations and the ion exchange interactions were almost completely eradicated at physiological conditions. The release profile of diphenhydramine was significantly affected by the addition of salt. It was thus concluded that the choice of buffer was of great importance for in-vitro experiments with ionic drugs. At physiological salt concentrations the interactions did not appear to be strong enough to influence the in-vivo bioavailability of any of the drug molecules. [source] Effect of chitosan on the intranasal absorption of salmon calcitonin in sheepJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2005Michael Hinchcliffe The effects of a chitosan-based delivery system on the pharmacokinetics of intranasally administered salmon calcitonin (sCT) were investigated in a sheep model. In particular, the feasibility of producing a formulation with a comparable or improved bioavailability and/or less variability than the currently marketed nasal product (Miacalcin nasal spray, Novartis Pharmaceuticals) was assessed. A comparator (control) formulation comprising sCT solution was also tested. Sheep (n = 6) were dosed intranasally according to a randomized crossover design. The intranasal sCT dose was 1100 IU (equivalent to approximately 17 IU kg,1). After completion of the nasal dosing legs, five of the sheep received 300 IU sCT (equivalent to approximately 5 IU kg,1) by subcutaneous injection to estimate relative bioavailability. After intranasal or subcutaneous dosing, serial blood samples were taken and plasma separated by centrifugation before measuring sCT concentrations by ELISA. Pharmacokinetic (non-compartmental) and statistical (analysis of variance or non-parametric alternative) analyses were performed. No systemic or local adverse effects were observed following intranasal or subcutaneous administration of sCT. The mean relative bioavailability of sCT from the chitosan solution was improved twofold compared with Miacalcin nasal spray and threefold compared with sCT control solution. Inter-animal variability in sCT absorption appeared to be lower with use of the chitosan-based solution compared with the control solution or commercial product. Based on the reported sheep data, a chitosan delivery system could offer the potential to significantly improve the intranasal absorption of sCT and reduce the variability in absorption. In the clinical setting, this may allow relatively lower doses of the drug to be given intranasally and/or lead to improvements in the efficacy or quality of intranasal therapy. [source] Clinical trial: ulcerative colitis maintenance treatment with 5-ASA: a 1-year, randomized multicentre study comparing MMX® with Asacol®ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009C. PRANTERA Summary Background, 5-ASA-MMX® (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis. Aim, To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol® (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study. Methods, In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for ,1 month prior to the trial, with ,1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment. Results, In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated. Conclusions, Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis. [source] Health-economic analysis: cost-effectiveness of scheduled maintenance treatment with infliximab for Crohn's disease , modelling outcomes in active luminal and fistulizing disease in adultsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2008J. LINDSAY Summary Background, Infliximab has been shown to be efficacious in moderate-to-severe Crohn's disease (CD). Aim, To evaluate the cost-effectiveness of scheduled maintenance treatment with infliximab in luminal and fistulizing CD patients. Methods, Markov models were constructed to simulate the progression of adult CD patients with and without fistulae during treatment with infliximab (5 mg/kg). Transitions were estimated from published clinical trials of infliximab. Standard care, comprising immunomodulators and/or corticosteroids was used as a comparator. An average weight of 60 kg was used to estimate the dose of infliximab. The costs and outcomes were discounted at 3.5% over 5 years. The primary effectiveness measurement was quality-adjusted life years (QALYs) estimated using EQ-5D. One-way and probabilistic sensitivity analyses were performed by varying the infliximab efficacy estimates, costs and utilities. Results, The incremental cost per QALY gained was £26 128 in luminal CD and £29 752 in fistulizing CD at 5 years. Results were robust and remained in the range of £23 752,£38 848 for luminal CD and £27 047,£44 206 for fistulizing CD. Patient body weight was the most important factor affecting cost-effectiveness. Conclusion, Eight-week scheduled maintenance treatment with infliximab is a cost-effective treatment for adult patients suffering from active luminal or fistulizing CD. [source] Doctors' reasons for rejecting initial choices of specialties as long-term careersMEDICAL EDUCATION, Issue 4 2003Trevor W Lambert Objectives, To report on rejected choices of specialty as long-term careers and reasons for rejection. Design, Postal questionnaire survey. Setting, United Kingdom. Participants, All graduates of 1996 and 1999 from UK medical schools during their first year after qualification. Main outcome measures, Any career choice which had been seriously considered and rejected and the reason for its rejection. Results, In all, 33·1% (1871) of respondents named a rejected choice and gave reasons for its rejection. Disproportionately high numbers rejected the surgical specialties, paediatrics and obstetrics and gynaecology (O&G), using the specialty distribution of positive choices as the comparator. Relatively few doctors rejected general practice (GP) after giving it serious consideration. Doctors rejecting the hospital medical and surgical specialties or paediatrics were most likely to specify reasons relating to quality of life. Three-quarters of the graduates of 1999 who rejected O&G did so because of poor career prospects. Conclusions, Quality of life issues, and concerns about working relationships, are sufficiently influential to persuade many doctors to abandon an initial choice of medical career. It is unlikely that much of the decline in entry to GP is attributable to rejection of GP by doctors who initially chose it. The decline must therefore represent an increase in the number of doctors who had never seriously considered it as a long-term career choice. [source] Comparing the impact of conventional pesticide and use of a transgenic pest-resistant crop on the beneficial carabid beetle Pterostichus melanariusPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 10 2006Evan A Mulligan Abstract The potential impact of a chemical pesticide control method has been compared with that of transgenic plants expressing a protease inhibitor conferring insect resistance by utilising a tritrophic system comprising the crop plant Brassica napus (L.) (Oilseed rape), the pest mollusc Deroceras reticulatum (Müller) and the predatory carabid beetle Pterostichus melanarius (Illiger). Cypermethrin, as the most widely used pesticide in UK oilseed rape (OSR) cultivation, was selected as the conventional treatment. OSR expressing a cysteine protease inhibitor, oryzacystatin-1 (OC-1), was the transgenic comparator. In feeding trials, D. reticulatum showed no significant long-term effects on measured life history parameters (survival, weight gain, food consumption) as a result of exposure to either the cypermethrin or OC-1 treatment. However, D. reticulatum was able to respond to the presence of the dietary inhibitor by producing two novel proteases following exposure to OC-1-expressing OSR. Similarly, P. melanarius showed no detectable alterations in mortality, weight gain or food consumption when feeding on D. reticulatum previously fed either pesticide-contaminated or GM plant material. Furthermore, as with the slug, a novel form of protease, approximately Mr 27 kDa, was induced in the carabid in response to feeding on slugs fed OC-1-expressing OSR. Copyright © 2006 Society of Chemical Industry [source] Concurrent validity of the NK hand dexterity testPHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 2 2001Joy C MacDermid BSc, PT PhD Co-Director Abstract Background and Purpose The present study evaluated the concurrent validity of the NK hand dexterity test (NKHDT) by use of three separate analyses: (1) the correlation between the NKHDT and a criterion comparator (Jebson's Hand Function Test (JHFT)); (2) the correlation between both dexterity tests and a patient-rated function questionnaire; and (3) the ability of subscales to differentiate between subjects with and without upper extremity pathology. Method The study population included 40 individuals with a variety of musculoskeletal problems affecting the upper extremity and 10 individuals without any history of upper extremity problems. Both dexterity tests were administered on a single occasion according to a standard protocol. Subjects also completed a rating scale which evaluated self-care, household work, work and recreation on an 0,10-point scale. Results The validity of the NKHDT was supported in all three analyses because: (1) the correlation between the NKHDT and JHFT subtests was moderate to strong (Pearson's r=0.47,0.87) and stronger when the objects were more similar in size; (2) both scales correlated to a similar extent with patient-rated function (Pearson's r=,0.34,0.67); and (3) all subscales were statistically different between subjects with and without upper extremity pathology (p<0.01). Conclusions The present study supports the use of the NKHDT as a measure of hand dexterity. Copyright © 2001 Whurr Publishers Ltd. [source] The quality of questions and use of resources in self-directed learning: Personal learning projects in the maintenance of certificationTHE JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS, Issue 2 2009T. Horsley PhD Abstract Introduction: To engage effectively and efficiently in self-directed learning and knowledge-seeking practices, it is important that physicians construct well-formulated questions; yet, little is known about the quality of good questions and their relationship to self-directed learning or to change in practice behavior. Methods: Personal learning projects (PLPs) submitted to the Canadian Maintenance of Certification program were examined to include underlying characteristics, quality of therapeutic questions (population, intervention, comparator, outcome [PICO] mnemonic), and relationships between stage of change and level of evidence used to resolve questions. Results: We assessed 1989 submissions (from 559 Fellows of the Royal College of Physicians and Surgeons of Canada [RCPSC]). The majority of submissions were by males (69.2%) aged 40,59 (59.4%) with an average of 24.3 (range 6,58, SD 11.1) years since graduation. The most frequent submissions were treatment (36.6%) and diagnosis (22.3%) questions. Half of all questions described ,2 components (PICO), and only 3.7% of questions included all 4 components. Cross tabulations indicated only 1 significant trend for the use of narrative reviews and the outcome "integrating new knowledge' (P < .000). Discussion: Self-directed learning skills comprise an important strategy for specialists maintaining or expanding their expertise in patient care, but an important obstacle to answering patient care questions is the ability to formulate good ones. Engagement in most major learning activities is stimulated by management of a single patient: formal accredited group learning events are of limited value in starting episodes of self-directed learning. Low levels of evidence used to address learning projects. Future research should determine how best to improve the quality of questions submitted and whether or not these changes result in increased efficiencies, more appropriate uses of evidence, and increased changes in practice behaviors. [source] Trends of spinal fusion surgery in Australia: 1997 to 2006ANZ JOURNAL OF SURGERY, Issue 11 2009Ian Andrew Harris Abstract Background:, This study aims to explore the trend in spine fusion surgery in Australia over the past 10 years, and to explore the possible influence of health insurance status (private versus public) on the rate of surgery. Methods:, Data pertaining to the rate of lumbar spine fusion from 1997 to 2006 were collected from Inpatient Statistics Collection of NSW Health, Medicare Australia Statistics and the Australian Bureau of Statistics. Data on total hip and total knee arthroplasties were collected to provide a comparator. Results:, The number of publicly performed spinal fusion procedures increased by 2% from 1997 to 2006. In comparison, privately performed spinal fusion procedures increased by 167% over the same 10-year period. In 2006, spine fusion surgery was 10.8 times more likely to be done in the private sector than in the public sector, compared with corresponding figures of 4.2 times and 3.0 times for knee replacement and hip replacement, respectively. Waiting list data showed no increase in demand for spine fusion surgery in the public sector. Conclusion:, There is a disproportionately high rate of lumbar spine fusion surgery performed in the private sector, given the rate of private insurance. The rate of increase was found to be higher than that for hip or knee arthroplasty procedures. Possible explanations for this difference include: over-servicing in the private sector, under-servicing in the public sector, differences in medical referral patterns, surgeon and patient preferences and financial incentives. [source] Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator,ARTHRITIS & RHEUMATISM, Issue 2 2007Gabriel Herrero-Beaumont Objective To assess the effects of the prescription formulation of glucosamine sulfate (1,500 mg administered once daily) on the symptoms of knee osteoarthritis (OA) during a 6-month treatment course. Methods Three hundred eighteen patients were enrolled in this randomized, placebo-controlled, double-blind trial in which acetaminophen, the currently preferred medication for symptomatic treatment of OA, was used as a side comparator. Patients were randomly assigned to receive oral glucosamine sulfate 1,500 mg once daily (n = 106), acetaminophen 3 gm/day (n = 108), or placebo (n = 104). The primary efficacy outcome measure was the change in the Lequesne index after 6 months. Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and response according to the Osteoarthritis Research Society International criteria. These outcome measures were assessed using an intent-to-treat analysis. Results At baseline, the study patients had moderately severe OA symptoms (mean Lequesne index ,11 points). Glucosamine sulfate was more effective than placebo in improving the Lequesne score, with a final decrease of 3.1 points, versus 1.9 with placebo (difference between glucosamine sulfate and placebo ,1.2 [95% confidence interval ,2.3, ,0.8]) (P = 0.032). The 2.7-point decrease with acetaminophen was not significantly different from that with placebo (difference ,0.8 [95% confidence interval ,1.9, 0.3]) (P = 0.18). Similar results were observed for the WOMAC. There were more responders to glucosamine sulfate (39.6%) and acetaminophen (33.3%) than to placebo (21.2%) (P = 0.004 and P = 0.047, respectively, versus placebo). Safety was good, and was comparable among groups. Conclusion The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms. Although acetaminophen also had a higher responder rate compared with placebo, it failed to show significant effects on the algofunctional indexes. [source] Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trialsBIPOLAR DISORDERS, Issue 2 2010Christoph U Correll Correll CU, Sheridan EM, DelBello MP. Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials. Bipolar Disord 2010: 12: 116,141. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objective:, To compare antipsychotic and mood stabilizer (MS) efficacy and tolerability in youth and adults with bipolar mania. Methods:, Medline/PubMed search for studies including: (i) youth (< 18 years) or adults (, 18 years); (ii) bipolar I disorder; (iii) double-blind, randomized, placebo-controlled trial (DB-RPCT); (iv) , 12 weeks of treatment; and (v) calculable effect sizes (ES) and/or numbers needed to treat/harm (NNT/NNH) ± 95% confidence intervals (CI). Non-overlapping 95% CIs determined significant group differences. Results:, We identified nine DB-RPCTs in youth (n = 1,609), 5 evaluating second-generation antipsychotics (SGAs) (n = 1,140) and 4 evaluating MSs (n = 469). We also identified 23 DB-RPCTs in adults (n = 6,501), 14 including SGAs (n = 3,297), 5 using haloperidol as an active comparator (n = 580), and 11 including MSs (n = 2,581). Young Mania Rating Scale scores improved significantly more with SGAs than MSs in youth (ES = 0.65, CI: 0.53,0.78 versus 0.24, CI: 0.06,0.41) and adults (ES = 0.48, CI: 0.41,0.55 versus 0.24, CI: 0.17,0.31). After excluding topiramate studies, SGAs had larger ES than MSs only in youth (ES = 0.65, CI: 0.53,0.78 versus 0.20, CI: 0.02,0.39), but not adults (ES = 0.48, CI: 0.41,0.55 versus 0.46, CI: 0.37,0.55). However, in adults SGAs had significantly larger ES regarding Clinical Global Impressions scores than MSs, even without topiramate (ES = 0.75, CI: 0.68,0.82 versus 0.24, CI: 0.07,0.41). Rates of response, remission, and discontinuation due to any reason compared to placebo were similar between medication and age groups, except for more favorable NNTs for remission with SGAs than MSs in adults after excluding topiramate. SGAs caused more weight gain than MSs in youth (ES = 0.53, CI: 0.41,0.66 versus 0.10, CI: ,0.12,0.33), but not in adults (ES = 0.13, CI: 0.05,0.22 versus 0.00, CI: ,0.08,0.08). However, results were heterogeneous and not significant in either age group after excluding topiramate. Nevertheless, SGA-related weight gain was significantly greater in youth than adults. In youth, SGA-related somnolence was greater than with MSs (NNH = 4.7, CI: 3.9,6.0 versus 9.5, CI: 6.3,23.5), and more likely than in adults (NNH = 7.1, CI: 6.1,8.8). Conversely, youth experienced less akathisia with SGAs than adults (NNH = 20.4, CI: 14.1,36.5 versus 10.2, CI: 8.1,13.7), likely due to lower doses/slower titration. Conclusions:, In treating mania, potentially greater short-term efficacy compared to placebo with SGAs versus MS needs to be balanced against increased adverse events, especially in youth. [source] Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trialsBIPOLAR DISORDERS, Issue 1 2006Stuart F Kushner Objective:, To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder. Methods:, In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of ,1 previous manic or mixed episodes, and ,20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study. Results:, Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, ,5.1 to ,8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p , 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo. Conclusions:, These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population. [source] Effect of single doses of maraviroc on the QT/QTc interval in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2008John D. Davis AIMS To assess the effect of a single dose of maraviroc on the QTc interval in healthy subjects and to evaluate the QTc interval,concentration relationship. METHODS A single-dose, placebo- and active-controlled, five-way crossover study was conducted to investigate the effects of maraviroc (100, 300, 900 mg) on QTc in healthy subjects. Moxifloxacin (400 mg) was used as the active comparator. The study was double-blind with respect to maraviroc/placebo and open label for moxifloxacin. There was a 7-day wash-out period between each dose. QT interval measurements obtained directly from the electrocardiogram (ECG) recorder were corrected for heart rate using Fridericia's correction (QTcF). A placebo run-in day was conducted before period 3, when ECGs were collected at intervals while subjects were resting or during exercise. These ECGs plus other predose ECGs were used to evaluate the QT/RR relationship for each subject to enable calculation of an individual's heart rate correction for their QT measurements (QTcI). ECGs were taken at various intervals pre- and postdose in each study period. Pharmacokinetic parameters were determined for each maraviroc dose. The end-points that were evaluated were QTcF at median time to maximum concentration (Tmax) based on the machine readings and QTcI at median Tmax based on manual over-reads of the QT/RR data. A separate analysis of variance was used for each of the pair-wise comparisons for each end-point. The relationship between QTc interval and plasma concentration was also investigated using a mixed-effects modelling approach, as implemented by the NONMEM software system. A one-stage model was employed in which the relationship between QT and RR and the effects of maraviroc plasma concentration on QT were estimated simultaneously. RESULTS The mean difference from placebo in machine-read QTcF at median Tmax for maraviroc 900 mg was 3.6 ms [90% confidence interval (CI) 1.5, 5.8]. For the active comparator, moxifloxacin, the mean difference from placebo in machine-read QTcF was 13.7 ms. The changes from placebo for each of the end-points were similar for men and women. No subjects receiving maraviroc or placebo had a QTcF ,,450 ms (men) or QTcF ,,470 ms (women), nor did any subject experience a QTcF increase ,,60 ms from baseline at any time point. Analysis based on the QTcI data obtained from the manual over-readings of the ECGs gave numerically very similar results. The QT:RR relationship was similar pre- and postdose and was not related to maraviroc concentration. The population estimate of the QT:RR correction factor was 0.324 (95% CI 0.309, 0.338). The population estimate of the slope describing the QT,concentration relationship was 0.97 ,s ml ng,1 (95% CI ,0.571, 2.48), equivalent to an increase of 0.97 ms in QT per 1000 ng maraviroc plasma concentration. Most adverse events were mild to moderate in severity. CONCLUSIONS Single doses of maraviroc, up to and including 900 mg, had no clinically relevant effect on QTcF or QTcI. At all maraviroc doses and for both end-points, the mean difference from placebo for QTc was <4 ms. There was no apparent relationship between QT interval and maraviroc plasma concentration up to 2363 ng ml,1. This conclusion held in both male and female subjects, and there was no evidence of a change in the QT/RR relationship with concentration. [source] Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosisBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004A.K. Gupta Summary Background Onychomycosis is a common nail disease that is often chronic, difficult to eradicate, and has a tendency to recur. The most common oral therapies for dermatophyte toenail onychomycosis include terbinafine, itraconazole and fluconazole. Objectives A cumulative meta-analysis of the randomized controlled trials (RCTs) for antimycotic agents was performed to determine whether the pooled estimate of the cure rates has remained consistent over the years. Furthermore, for each agent we compared the overall meta-analytical average of both mycological and clinical response rates of RCTs vs. open studies. Methods We searched MEDLINE (1966 to November 2002) for relevant studies evaluating the efficacy of the oral antifungal agents terbinafine, itraconazole (pulse or continuous), fluconazole and griseofulvin for treating dermatophyte toenail onychomycosis. Studies included in this meta-analysis required a standard accepted dosage regimen, treatment duration and follow-up period. To determine the cumulative meta-analytical average, studies were sequentially pooled by adding one study at a time according to the date of publication (i.e. earliest to the most recent). Results There were 36 studies included in the analyses. For RCTs the change in efficacy of mycological cure rates from the first trial to the overall cumulative meta-average for each drug comparator is as follows (with 95% confidence interval): terbinafine, 78 ± 6% (n = 2 studies, 79 patients) to 76 ± 3% (n = 18 studies, 993 patients) (P = 0·68); itraconazole pulse, 75 ± 10% (n = 1 study, 20 patients) to 63 ± 7% (n = 6 studies, 318 patients) (P = 0·25); itraconazole continuous, 63 ± 5% (n = 1 study, 84 patients) to 59 ± 5% (n = 7 studies, 1131 patients) (P = 0·47); fluconazole, 53 ± 6% (n = 1 study, 72 patients) to 48 ± 5% (n = 3 studies, 131 patients) (P = 0·50); and griseofulvin, 55 ± 8% (n = 2 studies, 109 patients) to 60 ± 6% (n = 3 studies, 167 patients) (P = 0·41). The cumulative meta-analytical average of mycological cure rates when comparing RCTs vs. open studies was: terbinafine, 76 ± 3% (n = 18 studies, 993 patients) vs. 83 ± 12% (n = 2 studies, 391 patients) (P = 0·0028); itraconazole pulse, 63 ± 7% (n = 6 studies, 318 patients) vs. 84 ± 9% (n = 3 studies, 194 patients) (P = 0·0001); and fluconazole, 48 ± 5% (n = 3 studies, 131 patients) vs. 79 ± 3% (n = 3 studies, 208 patients) (P = 0·0001). Conclusions The cumulative meta-analysis of cure rates for RCTs suggests that over time, as new RCTs have been conducted, the efficacy rates have remained consistent. The efficacy rates of open studies are substantially higher compared with RCTs and may therefore overestimate cure rates. [source] Antipsychotic combination therapy in schizophrenia.ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002A review of efficacy, risks of current combinations Objective:, To review the literature on efficacy and risks of combining antipsychotics (atypical with atypical or conventional) and suggest a rationale and strategies for future clinical trials. Method:, A computerized Medline search supplemented by an examination of cross-references and reviews was performed. Results:, Empirical evidence for the efficacy of combining antipsychotics is too limited to draw firm conclusions. The practice of augmenting clozapine with more ,tightly bound' D2 receptor antagonists as exemplified by risperidone augmentation of clozapine has some empirical and theoretical support. The risks of augmentation strategies have not been studied systematically. No study has examined the economic impact of combination treatment. Conclusion:, Further trials of antipsychotic combination therapies are needed before this currently unsupported practice can be recommended. Rationales for combination treatment include a broadening of the range of receptor activity or an increase in D2 receptor occupancy with certain atypical agents. Trial methodology needs to take into account subject characteristics, duration of treatment, optimization of monotherapy comparators, and appropriate outcome measures. [source] | |||||||||||||||||||||||||||||||||||||||||||