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Trial Data (trial + data)
Kinds of Trial Data Selected AbstractsOpen retropubic colposuspension for urinary incontinence in women: A short version cochrane review,,NEUROUROLOGY AND URODYNAMICS, Issue 6 2009Marie Carmela M. Lapitan Abstract Background Urinary incontinence is a common and potentially debilitating problem. Open retropubic colposuspension is a surgical treatment which involves lifting the tissues near the bladder neck and proximal urethra in the area behind the anterior pubic bones to correct deficient urethral closure. Objectives To assess the effects of open retropubic colposuspension for the treatment of urinary incontinence. Search Strategy We searched the Cochrane Incontinence Group Specialized Register (searched June 30, 2008) and reference lists of relevant articles. We contacted investigators to locate extra studies. Selection Criteria Randomized or quasi-randomized controlled trials in women with symptoms or urodynamic diagnoses of stress or mixed urinary incontinence that included open retropubic colposuspension surgery in at least one trial group. Data Collection and Analysis Studies were evaluated for methodological quality/susceptibility to bias and appropriateness for inclusion and data extracted by two of the reviewers. Trial data were analyzed by intervention. Where appropriate, a summary statistic was calculated. Main Results This review included 46 trials involving a total of 4,738 women. Overall cure rates were 68.9,88.0% for open retropubic colposuspension. Two small studies suggest lower failure rates after open retropubic colposuspension compared with conservative treatment. Similarly, one trial suggests lower failure rates after open retropubic colposuspension compared to anticholinergic treatment. Evidence from six trials showed a lower failure rate for subjective cure after open retropubic colposuspension than after anterior colporrhaphy. Such benefit was maintained over time (RR of failure 0.51; 95% CI 0.34,0.76 before the first year, RR 0.43; 95% CI 0.32,0.57 at 1,5 years, RR 0.49; 95% CI 0.32,0.75 in periods beyond 5 years). In comparison with needle suspensions there was a lower failure rate after colposuspension in the first year after surgery (RR 0.66; 95% CI 0.42,1.03), after the first year (RR 0.48; 95% CI 0.33,0.71), and beyond 5 years (RR 0.32; 95% CI 15,0.71). Evidence from 12 trials in comparison with suburethral slings found no significant difference in failure rates in all time periods assessed. Patient-reported failure rates in short, medium and long-term follow-up showed no significant difference between open and laparoscopic retropubic colposuspension, but with wide confidence intervals. In two trials failure was less common after Burch (RR 0.38 95% CI 0.18,0.76) than after the Marshall-Marchetti-Krantz procedure at 1,5-year follow-up. There were few data at any other follow-up time. In general, the evidence available does not show a higher morbidity or complication rate with open retropubic colposuspension, compared to the other open surgical techniques, although pelvic organ prolapse is more common than after anterior colporrhaphy and sling procedures. Authors' Conclusions The evidence available indicates that open retropubic colposuspension is an effective treatment modality for stress urinary incontinence especially in the long term. Within the first year of treatment, the overall continence rate is approximately 85,90%. After 5 years, approximately 70% of patients can expect to be dry. Newer minimal access procedures such as tension free vaginal tape look promising in comparison with open colposuspension but their long-term performance is not known and closer monitoring of their adverse event profile must be carried out. Laparoscopic colposuspension should allow speedier recovery but its relative safety and effectiveness is not known yet. Neurourol. Urodyn. 28:472,480, 2009. © 2009 Wiley-Liss, Inc. [source] A CRITICAL LOOK AT PAP ADEQUECY: ARE OUR CRITERIA SATISFACTORY?CYTOPATHOLOGY, Issue 2006D.R. Bolick Liquid based Pap (LBP) specimen adequacy is a highly documented, yet poorly understood cornerstone of our GYN cytology practice. Each day, as cytology professionals, we make adequacy assessments and seldom wonder how the criteria we use were established. Are the criteria appropriate? Are they safe? What is the scientific data that support them? Were they clinically and statistically tested or refined to achieve optimal patient care? In this presentation, we will take a fresh look at what we know about Pap specimen adequacy and challenge some of the core assumptions of our daily practice. LBP tests have a consistent, well-defined surface area for screening, facilitating the quantitative estimates of slide cellularity. This provides an unprecedented opportunity to establish reproducible adequacy standards that can be subjected to scientific scrutiny and rigorous statistical analysis. Capitalizing on this opportunity, the TBS2001 took the landmark step to define specimen adequacy quantitatively, and set the threshold for a satisfactory LBP at greater than 5,000 well visualized squamous epithelial cells. To date, few published studies have attempted to evaluate the validity or receiver operator characteristics for this threshold, define an optimal threshold for clinical utility or assess risks of detection failure in ,satisfactory' but relatively hypocellular Pap specimens. Five years of cumulative adequacy and cellularity data of prospectively collected Pap samples from the author's laboratory will be presented, which will serve as a foundation for a discussion on ,Pap failure'. A relationship between cellularity and detection of HSIL will be presented. Risk levels for Pap failure will be presented for Pap samples of different cellularities. The effect of different cellularity criterion on unsatisfactory Pap rates and Pap failure rates will be demonstrated. Results from this data set raise serious questions as to the safety of current TBS2001 adequacy guidelines and suggest that the risk of Pap failure in specimens with 5,000 to 20 000 squamous cells on the slide is significantly higher than those assumed by the current criteria. TBS2001 designated all LBP to have the same adequacy criterion. Up to this point, it has been assumed that ThinPrep, SurePath, or any other LBP would be sufficiently similar that they should have the same adequacy criteria. Data for squamous cellularity and other performance characteristics of ThinPrep and SurePath from the author's laboratory will be compared. Intriguing data involving the recently approved MonoPrep Pap Test will be reviewed. MonoPrep clinical trial data show the unexpected finding of a strong correlation between abundance of endocervical component and the detection of high-grade lesions, provoking an inquiry of a potential new role for a quantitative assessment of the transition zone component. The current science of LBP adequacy criteria is underdeveloped and does not appear to be founded on statistically valid methods. This condition calls us forward as a body of practitioners and scientists to rigorously explore, clarify and define the fundamental nature of cytology adequacy. As we forge this emerging science, we will improve diagnostic performance, guide the development of future technologies, and better serve the patients who give us their trust. Reference:, Birdsong GG: Pap smear adequacy: Is our understanding satisfactory? Diagn Cytopathol. 2001 Feb; 24(2): 79,81. [source] Insulin glargine and receptor-mediated signalling: clinical implications in treating type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2007Derek Le Roith Abstract Most patients with type 2 diabetes mellitus will eventually require insulin therapy to achieve or maintain adequate glycaemic control. The introduction of insulin analogues, with pharmacokinetics that more closely mimic endogenous insulin secretion, has made physiologic insulin replacement easier to achieve for many patients. However, there are also concerns regarding alteration of binding affinities for the insulin receptor (IR) or insulin-like growth factor-1 receptor (IGF-1R) may increase the mitogenic potential of some analogues. Therefore, this article will review the relevant preclinical and clinical data to assess the mitogenic potential of insulin glargine, a basal insulin analogue, compared with regular human insulin (RHI). Searches of the PubMed database were performed using terms that included ,IR,' ,insulin-like growth factor-1,' ,IGF-1R,' ,type 2 diabetes mellitus,' and ,insulin glargine.' Original articles and reviews of published literature were retrieved and reviewed. Although one study reported increased binding affinity of insulin glargine for the IGF-1R and increased mitogenic potential in cells with excess IGF-1Rs (Saos/B10 osteosarcoma cells), most in vitro binding-affinity and cell-culture studies have demonstrated behaviour of insulin glargine comparable to that of RHI for both IR and IGF-1R binding, insulin signalling, and metabolic and mitogenic potential. Currently published in vivo carcinogenic studies and human clinical trial data have shown that insulin glargine is not associated with increased risk for either cancer or the development or progression of diabetic retinopathy. Copyright © 2007 John Wiley & Sons, Ltd. [source] Changing aspirin use in patients with Type 2 diabetes in the UKPDSDIABETIC MEDICINE, Issue 12 2004C. A. Cull Abstract Aims To examine the proportion of UK Prospective Diabetes Study (UKPDS) patients with Type 2 diabetes taking aspirin regularly for the primary and secondary prevention of cardiovascular disease (CVD) before and after publication of the 1997 American Diabetes Association (ADA) Clinical Practice Recommendations and the 1998 Joint British Recommendations on the Prevention of Coronary Disease in Clinical Practice. Methods UKPDS annual review data from 1996/7 (n = 3190) and 2000/1 (n = 2467) were used to determine the prevalence of patients taking aspirin regularly in relation to known CVD risk factors and pre-existing CVD. Results Patients taking aspirin regularly were more often male than female (24 vs. 20%, P = 0.0033), older (66 ± 8 vs. 62 ± 9 years, P < 0.0001) and less often Afro-Caribbean than White Caucasian or Indian Asian (11 vs. 23 vs. 22%, respectively, P < 0.0001). Between 1996/7 and 2000/1 aspirin use in patients without pre-existing CVD increased from 17 to 31% (P < 0.0001) and for those with pre-existing CVD from 76 to 82% (P = 0.032). Conclusion The majority of patients with pre-existing CVD were taking aspirin regularly. Although aspirin use in those without pre-existing CVD approximately doubled after publication of the ADA and Joint British Recommendations, less than two-thirds of these high-risk patients were being treated according to guidelines. This may relate to a lack of convincing evidence for primary CVD prevention or failure to adhere to guidelines. It may be that more trial data is needed to convince clinicians of the value of aspirin therapy in Type 2 diabetes. [source] Modeling Passing Rates on a Computer-Based Medical Licensing Examination: An Application of Survival Data AnalysisEDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 3 2004André F. de Champlain The purpose of this article was to model United States Medical Licensing Examination (USMLE) Step 2 passing rates using the Cox Proportional Hazards Model, best known for its application in analyzing clinical trial data. The number of months it took to pass the computer-based Step 2 examination was treated as the dependent variable in the model. Covariates in the model were: (a) medical school location (U.S. and Canadian or other), (b) primary language (English or other), and (c) gender. Preliminary findings indicate that examinees were nearly 2.7 times more likely to experience the event (pass Step 2) if they were U.S. or Canadian trained. Examinees with English as their primary language were 2.1 times more likely to pass Step 2, but gender had little impact. These findings are discussed more fully in light of past research and broader potential applications of survival analysis in educational measurement. [source] Varenicline in prevention of relapse to smoking: effect of quit pattern on response to extended treatmentADDICTION, Issue 9 2009Peter Hajek ABSTRACT Aim While older behavioural and pharmacological approaches to preventing relapse to smoking show little efficacy, a recent randomized trial of an extended course of varenicline reported positive results. In this secondary analysis, trial data were examined to see whether smokers who manage to achieve abstinence only later in the original course of treatment are more likely to benefit from having the course extended. Methods A total of 1208 patients abstinent for at least the last week of 12 weeks' treatment with varenicline were randomized to 3 months continued varenicline or placebo. Overall, 44% of the 12-week abstainers were abstinent from the target quit date (TQD), while the rest stopped smoking later. We examined the relationship between quit pattern and the varenicline versus placebo difference in continuous abstinence rates at week 52 and contributions of baseline patient characteristics. Results With increasing delay in initial quitting, 12-month success rates declined. Participants who had their last cigarette at week 11 of open-label treatment had quit rates at 52 weeks of 5.7% compared with 54.9% in those who last smoked in week 1 [odds ratio (OR) 20.3 (6.3, 65.9); P < 0.0001]. Patients who failed to initiate abstinence in the first week benefited more from extended treatment than patients continuously abstinent from week 1 [OR 1.7 (1.2, 2.4); P = 0.0015 versus OR 1.1 (0.8, 1.5); P = 0.6995, respectively; with the interaction of the quit pattern with treatment effect reaching borderline significance (P = 0.0494)]. No other patient characteristics were related to treatment effect. Conclusions Compared with smokers who quit smoking on their TQD, those who have an initial delay in achieving sustained abstinence have increased risk of relapse even several months later, and may be more likely to benefit from extended treatment with varenicline. [source] An overview of the clinical trial data presented at the 44th American Society of Clinical Oncology Annual Meeting (ASCO) and the 9th Annual European Congress of Rheumatology (EULAR)FUTURE PRESCRIBER, Issue 2 2008Rhonda Siddall No abstract is available for this article. [source] Antithrombotic therapy for congestive heart failureINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2006I. Chung Summary Patients with congestive heart failure (CHF) are at increased risk of thromboembolic events. However, there is much debate and uncertainty over the use of antithrombotic therapy in these patients. The evidence for oral anticoagulation is limited, although large randomised trial data are forthcoming. Aspirin may be detrimental for heart failure due to a possible interaction with angiotensin-converting enzyme inhibitors, leading to increased hospitalisations from decompensated heart failure. The objective of this review article is to summarise the available evidence regarding the risk of stroke and thromboembolic events in CHF patients, as well as the effectiveness and risks of antithrombotic therapy in these patients. [source] Emerging Insights in the First-Step Use of Antihypertensive Combination TherapyJOURNAL OF CLINICAL HYPERTENSION, Issue 2007Keith Norris MD The blood pressure (BP) goals set by hypertension management guidelines (<140/90 mm Hg in uncomplicated hypertension; <130/80 mm Hg in type 2 diabetes or kidney disease) are not being achieved in a high proportion of patients, partly because monotherapy is insufficient in many patients. In particular, patients with uncontrolled moderate or severe hypertension and/or associated cardiovascular risk factors remain at high risk for cardiovascular events and hypertensive emergency. In recognition of the urgency of treating moderate and severe hypertension, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) advocates the initial use of 2-drug therapies in patients with systolic BP levels >20 mm Hg above goal or diastolic BP level >10 mm Hg above goal. Regimens should usually include a thiazide diuretic and, for patients with diabetes or kidney disease, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Recently, clinical trial data have shown that first-step antihypertensive treatment of moderate and severe hypertension with carefully chosen fixed-dose combinations provides a high rate of BP goal achievement, a simplified dosing regimen, and superior tolerability compared with monotherapy. [source] Angiotensin-Converting Enzyme Inhibitors in the Treatment of Hypertension: An UpdateJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2007William B. White MD Angiotensin-converting enzyme inhibitors are an important treatment option for hypertension, especially when elevated blood pressure exists in the presence of diabetes mellitus, chronic kidney disease, or congestive heart failure. This article reviews some of the pathophysiologic mechanisms involved in patients with hypertension and these comorbidities and how they relate to the renin-angiotensin system (RAS). Inhibition of the RAS when utilized along with other antihypertensive medications has been particularly effective in hypertensive patients with type 2 diabetes, chronic kidney disease, and vascular disorders; consensus group guidelines have reflected this in their treatment recommendations. Clinical trial data demonstrate that the effectiveness of RAS blockers is enhanced by maximizing the daily dose and combining these medications with thiazide diuretics. [source] Phytotherapeutics: an evaluation of the potential of 1000 plantsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2010G. Cravotto MD Summary Objective:, The aim of this review is to evaluate and summarize the available scientific information on the commonest plant extracts marketed in Western countries. In view of the intense, ongoing search for new plant extracts with powerful anti-inflammatory activity, we paid particular attention to this topic. The aim is to provide broad coverage of as many potentially useful plants as possible and then to focus on those with the greatest therapeutic potential. Methods:, Our bibliographic sources were the SciFinder databases: CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS (update to October 2007). In order to assess the value of clinical trials, we focused a specific search on clinical investigations concerning nine plants with the most trial data, viz., Althaea officinalis, Calendula officinalis, Centella asiatica, Echinacea purpurea, Passiflora incarnata, Punica granatum, Vaccinium macrocarpon, Vaccinium myrtillus, Valeriana officinalis. This was carried out in several databases (update to June 2008): ISI Web of KnowledgeSM (ISI WoK), SciFinder (CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS) and PubMed (indexed for MEDLINE). Results:, Our survey covers roughly a 1000 plants, although clinical trials have been published only for 156 plants supporting specific pharmacological activities and therapeutic applications. However, for about half of the plants, in vitro and in vivo studies provide some support for therapeutic use. For one-fifth of the plants included in our search, only phytochemical studies were found. Their properties and indications were often attributed to the presence of certain compounds, but no evidence concerning the activities of the whole extracts was presented. We found that for about 12% of the plants, currently available on the Western market, no substantial studies on their properties had been published, while there was strong evidence that 1 in 200 were toxic or allergenic, so that their use ought to be discouraged or forbidden. Nine plants had considerable evidence of therapeutic effect, viz., A. officinalis, Calendula officinalis, Centella asiatica, E. purpurea, Passiflora incarnata, Punica granatum, Vaccinium macrocarpon, Vaccinium myrtillus, Valeriana officinalis. Conclusion:, The present review provides a baseline on the level of evidence available on many herbal preparations and should be of help to those intending to research further on these topics. [source] Lenalidomide in the treatment of multiple myeloma: a reviewJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2008X. Armoiry PharmD PhD Summary Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined anti-inflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and overall survival. The most commonly reported adverse events include haematological toxicity with manageable neutropenia and thrombopenia. Lenalidomide does not trigger the limiting toxicities of thalidomide: somnolence, neuropathy and constipation. Lenalidomide, in combination with dexamethasone, is indicated for the treatment of MM patients who have received at least one prior therapy and is administered orally at the dose of 25 mg q.d. for 21 days of 28-day cycles. The drug is being investigated for the treatment of newly diagnosed MM. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical trial data on lenalidomide. [source] Secondary prevention of ischemic stroke: Challenging patient scenarios,JOURNAL OF HOSPITAL MEDICINE, Issue S4 2008Kiwon Lee MD Abstract The risk for recurrent stroke following a stroke or transient ischemic attack (TIA) is high. Prevention of a secondary event is a priority, as the associated morbidity and mortality are great. Antiplatelet agents have been shown to reduce this risk, but the choice of treatment modality depends on a number of factors, including the underlying cause of the stroke and the patient's comorbidities. For example, a cardioembolic stroke is best treated with anticoagulants, whereas one of noncardioembolic origin requires antiplatelet therapy. A number of challenging patient scenarios are explored in this article, and appropriate medical management is discussed, with the goal of examining the most recent trial data and information in the context of an actual case. Eight sample cases are presented: stroke prevention in a patient with recent stent placement, low ejection fraction, intracranial stenosis, carotid stenosis, atherosclerosis of the aortic arch, symptomatic coronary artery disease, antiplatelet failure, and stroke prevention in a patient already on warfarin. Journal of Hospital Medicine 2008;3(4 Suppl):S20,S28. © 2008 Society of Hospital Medicine. [source] Management of Multivessel Coronary Disease: Let Us Not Shortchange Drug-Eluting StentsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 3 2008F.A.C.C., KISHORE J. HARJAI M.D. A recent observational study of coronary artery graft (CABG) versus drug-eluting stents (DES) performed in the state of New York reported that CABG was superior to DES for multivessel disease. Our comment provides rational criticism of this study, reviews the data that support a role for DES in the management of multivessel coronary disease, and emphasizes the need for ongoing prospective clinical trials in this area. Till randomized trial data become available, physicians should continue to use their clinical judgment based on existing evidence in managing their patients with multivessel coronary artery disease (CAD). [source] Polymer-Based Paclitaxel-Eluting Stents in Percutaneous Coronary Intervention:JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2004A Review of the TAXUS Trials Drug-eluting stents have altered the practice of interventional cardiology by dramatically reducing the risk of angiographic and clinical restenosis following percutaneous coronary intervention. Based on extensive preclinical study and clinical trial data, the polymer-based, slow rate-release paclitaxel-eluting TAXUS stent has recently received Food and Drug Administration approval for sale in the United States. In the current article, we review the available data from the TAXUS trials that have demonstrated that implantation of the slow rate-release TAXUS stent is safe and, in terms of restenosis, markedly superior to bare metal stenting for the treatment of de novo lesions <28 mm in length in arteries 2.5,3.75 mm in diameter. Additional trials in the TAXUS program are currently examining the role of slow and moderate rate-release polymer-based, paclitaxel-eluting stents in a broader range of clinical settings and lesion subsets. [source] Multicentre quality assurance of intensity-modulated radiation therapy plans: A precursor to clinical trialsJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 5 2007MJ Williams Summary A multicentre planning study comparing intensity-modulated radiation therapy (IMRT) plans for the treatment of a head and neck cancer has been carried out. Three Australian radiotherapy centres, each with a different planning system, were supplied a fully contoured CT dataset and requested to generate an IMRT plan in accordance with the requirements of an IMRT-based radiation therapy oncology group clinical trial. Plan analysis was carried out using software developed specifically for reviewing multicentre clinical trial data. Two out of the three plans failed to meet the prescription requirements with one misinterpreting the prescription and the third failed to meet one of the constraints. Only one plan achieved all of the dose objectives for the critical structures and normal tissues. Although each centre used very similar planning parameters and beam arrangements the resulting plans were quite different. The subjective interpretation and application of the prescription and planning objectives emphasize one of the many difficulties in carrying out multicentre IMRT planning studies. The treatment prescription protocol in a clinical trial must be both lucid and unequivocally stated to avoid misinterpretation. Australian radiotherapy centres must show that they can produce a quality IMRT plan and that they can adhere to protocols for IMRT planning before using it in a clinical trial. [source] Glycemic Targets for Patients with Type 2 Diabetes MellitusMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Ole-Petter R. Hamnvik MB Abstract Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins. Mt Sinai J Med 76:227,233, 2009. © 2009 Mount Sinai School of Medicine [source] Dietary Calcium and Dairy Modulation of Adiposity and Obesity RiskNUTRITION REVIEWS, Issue 4 2004Michael B. Zemel Ph.D. Dietary calcium plays a key role in the regulation of energy metabolism and obesity risk. This appears to be mediated primarily by dietary calcium modulation of circulating calcitriol, which in turn regulates adipocyte intracellular calcium ([Ca2+]i). Increased [Ca2]i stimulates lipogenic gene expression and activity and inhibits lipolysis, resulting in increased adipocyte lipid accumulation. Since calcitriol stimulates adipocyte Ca2+ influx, low calcium diets promote adiposity, while dietary calcium-suppression of calcitriol reduces adiposity. These concepts are confirmed in controlled rodent studies as well as by epidemiological and clincial trial data, all of which confirm protection from obesity with high calcium intakes. Moreover, dairy sources of calcium exert markedly greater effects which are most likely attributable to additional bioactive compounds in dairy which act synergistically with calcium to attenuate adiposity. [source] First-line therapy for chronic myeloid leukemia: Past, present, and future,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Carolina Pavlovsky The development of Bcr-Abl tyrosine kinase inhibitors has dramatically changed the prognosis of patients with newly diagnosed chronic myeloid leukemia (CML). Standard-dose imatinib (400 mg/day in chronic phase, 600 mg/day in advanced CML) now dominates the management of this disease, producing considerably higher hematologic, cytogenetic, and molecular response rates than seen with previous drug therapies. However, although many patients respond well to standard-dose imatinib initially, some patients do not achieve adequate levels of response or discontinue therapy because of resistance. One approach to improving treatment response with first-line imatinib may be to increase the imatinib dose (800 mg/day), although recent trial data indicate that overall increases in response rates may be modest. Newer Bcr-Abl tyrosine kinase inhibitors can induce responses in patients with all phases of imatinib-resistant CML, even those with imatinib-resistant mutations in the BCR-ABL gene. Furthermore, in initial studies, first-line dasatinib or nilotinib treatment has produced response rates that compare favorably with historical controls treated with imatinib, although confirmation is required from head-to-head clinical trials. Future clinical approaches may include drug combinations, which may allow quiescent leukemia stem cells to be eradicated. Further improvements in drug treatment for first-line CML are expected during the next few years. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Pesticide residues in food,acute dietary exposure,PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 4 2004Denis Hamilton Abstract Consumer risk assessment is a crucial step in the regulatory approval of pesticide use on food crops. Recently, an additional hurdle has been added to the formal consumer risk assessment process with the introduction of short-term intake or exposure assessment and a comparable short-term toxicity reference, the acute reference dose. Exposure to residues during one meal or over one day is important for short-term or acute intake. Exposure in the short term can be substantially higher than average because the consumption of a food on a single occasion can be very large compared with typical long-term or mean consumption and the food may have a much larger residue than average. Furthermore, the residue level in a single unit of a fruit or vegetable may be higher by a factor (defined as the variability factor, which we have shown to be typically ×3 for the 97.5th percentile unit) than the average residue in the lot. Available marketplace data and supervised residue trial data are examined in an investigation of the variability of residues in units of fruit and vegetables. A method is described for estimating the 97.5th percentile value from sets of unit residue data. Variability appears to be generally independent of the pesticide, the crop, crop unit size and the residue level. The deposition of pesticide on the individual unit during application is probably the most significant factor. The diets used in the calculations ideally come from individual and household surveys with enough consumers of each specific food to determine large portion sizes. The diets should distinguish the different forms of a food consumed, eg canned, frozen or fresh, because the residue levels associated with the different forms may be quite different. Dietary intakes may be calculated by a deterministic method or a probabilistic method. In the deterministic method the intake is estimated with the assumptions of large portion consumption of a ,high residue' food (high residue in the sense that the pesticide was used at the highest recommended label rate, the crop was harvested at the smallest interval after treatment and the residue in the edible portion was the highest found in any of the supervised trials in line with these use conditions). The deterministic calculation also includes a variability factor for those foods consumed as units (eg apples, carrots) to allow for the elevated residue in some single units which may not be seen in composited samples. In the probabilistic method the distribution of dietary consumption and the distribution of possible residues are combined in repeated probabilistic calculations to yield a distribution of possible residue intakes. Additional information such as percentage commodity treated and combination of residues from multiple commodities may be incorporated into probabilistic calculations. The IUPAC Advisory Committee on Crop Protection Chemistry has made 11 recommendations relating to acute dietary exposure. Copyright © 2004 Society of Chemical Industry [source] Developing tools for the safety specification in risk management plans: lessons learned from a pilot project,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2008Andrew J. P. Cooper BSc Abstract Purpose Following the adoption of the ICH E2E guideline, risk management plans (RMP) defining the cumulative safety experience and identifying limitations in safety information are now required for marketing authorisation applications (MAA). A collaborative research project was conducted to gain experience with tools for presenting and evaluating data in the safety specification. This paper presents those tools found to be useful and the lessons learned from their use. Methods Archive data from a successful MAA were utilised. Methods were assessed for demonstrating the extent of clinical safety experience, evaluating the sensitivity of the clinical trial data to detect treatment differences and identifying safety signals from adverse event and laboratory data to define the extent of safety knowledge with the drug. Results The extent of clinical safety experience was demonstrated by plots of patient exposure over time. Adverse event data were presented using dot plots, which display the percentages of patients with the events of interest, the odds ratio, and 95% confidence interval. Power and confidence interval plots were utilised for evaluating the sensitivity of the clinical database to detect treatment differences. Box and whisker plots were used to display laboratory data. Conclusions This project enabled us to identify new evidence-based methods for presenting and evaluating clinical safety data. These methods represent an advance in the way safety data from clinical trials can be analysed and presented. This project emphasises the importance of early and comprehensive planning of the safety package, including evaluation of the use of epidemiology data. Copyright © 2008 John Wiley & Sons, Ltd. [source] Improving the precision of cotton performance trials conducted on highly variable soils of the southeastern USA coastal plainPLANT BREEDING, Issue 6 2007B. T. Campbell Abstract Reliable agronomic and fibre quality data generated in Upland cotton (Gossypium hirsutum L.) cultivar performance trials are highly valuable. The most common strategy used to generate reliable performance trial data uses experimental design to minimize experimental error resulting from spatial variability. However, an alternative strategy uses a posteriori statistical procedures to account for spatial variability. In this study, the efficiency of the randomized complete block (RCB) design and nearest neighbour adjustment (NNA) were compared in a series of cotton performance trials conducted in the southeastern USA to identify the efficiency of each in minimizing experimental error for yield, yield components and fibre quality. In comparison to the RCB, relative efficiency of the NNA procedure varied amongst traits and trials. Results show that experimental analyses, depending on the trait and selection intensity employed, can affect cultivar or experimental line selections. Based on this study, we recommend researchers conducting cotton performance trials on variable soils consider using NNA or other spatial methods to improve trial precision. [source] Identification of novel QTL for resistance to crown rot in the doubled haploid wheat population ,W21MMT70' × ,Mendos'PLANT BREEDING, Issue 6 2006W. D. Bovill Abstract Crown rot (causal agent Fusarium pseudograminearum) is a fungal disease of major significance to wheat cultivation in Australia. A doubled haploid wheat population was produced from a cross between line ,W21MMT70', which displays partial seedling and adult plant (field) resistance to crown rot, and ,Mendos', which is moderately susceptible in seedling tests but partially resistant in field trials. Bulked segregant analysis (BSA) based on seedling trial data did not reveal markers for crown rot resistance. A framework map was produced consisting of 128 microsatellite markers, four phenotypic markers, and one sequence tagged site marker. To this map 331 previously screened AFLP markers were then added. Three quantitative trait loci (QTL) were identified with composite interval mapping across all of the three seedling trials conducted. These QTL are located on chromosomes 2B, 2D and 5D. The 2D and 5D QTL are inherited from the line ,W21MMT70', whereas the 2B QTL is inherited from ,Mendos'. These loci are different from those associated with crown rot resistance in other wheat populations that have been examined, and may represent an opportunity for pyramiding QTL to provide more durable resistance to crown rot. [source] Contingent screening for Down syndrome,results from the FaSTER trialPRENATAL DIAGNOSIS, Issue 2 2008Howard S. Cuckle Abstract Objective Comparison of contingent, step-wise and integrated screening policies. Methods Mid-trimester Down syndrome risks were retrospectively calculated from FaSTER trial data. For contingent screening, initial risk was calculated from ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free ,-human chorionic gonadotrophin (hCG) at 11,13 weeks, and classified positive (>1 in 30), borderline (1 in 30,1500) or negative. Borderline risks were recalculated using ,-fetoprotein, hCG, unconjugated estriol (uE3) and inhibin at 15,18 weeks, and reclassified as positive (>1 in 270) or negative. For step-wise screening, initial negative risks were also recalculated. For integrated screening, a single risk was calculated from NT, PAPP-A and the second trimester markers. Results There were 86 Down syndrome and 32 269 unaffected pregancies. The detection rate for contingent screening was 91% and false-positive rate was 4.5%; initial detection rate was 60%, initial false-positive rate was 1.2% and borderline risk was 23%. Step-wise screening had 92% detection rate and 5.1% false-positive rate; integrated screening had 88% and 4.9% respectively. Conclusion As predicted by modelling, the contingent screening detection rate for a fixed false-positive rate is comparable with step-wise and integrated screening, but substantially reduces the number needing to return for second trimester testing. Copyright © 2008 John Wiley & Sons, Ltd. [source] Fluticasone furoate (Avamys): new intranasal steroid sprayPRESCRIBER, Issue 11 2009MRPharmS, Steve Chaplin MSc Fluticasone furoate (Avamys) is a new intranasal steroid spray for the treatment of allergic rhinitis. Our New product review presents the clinical trial data and describes how this new formulation might be preferred by patients. Copyright © 2009 Wiley Interface Ltd [source] Immunosuppressive Agents and CMV Risk in the VICTOR StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010R. K. Avery Post-hoc analysis of the VICTOR trial data concerning immunosuppressive agents yields some anticipated and some unexpected results. See Article by Ĺsberg et al on page 1881. [source] An ethical hierarchy for decision making during medical emergenciesANNALS OF NEUROLOGY, Issue 4 2010Patrick D. Lyden MD Evidence from well-designed clinical trials may guide clinicians, reduce regional variation, and lead to improved outcomes. Many physicians choose to ignore evidence-based practice guidelines. Using unproven therapies outside of a randomized trial slows recruitment in clinical trials that could yield information on clinical and economic efficacy. Using acute stroke therapy as an illustration, we present an ethical hierarchy for therapeutic decision making during medical emergencies. First, physicians should offer standard care. If no standard care option exists, the physician should consider enrollment in a randomized clinical trial. If no trial is appropriate, the physician should consider a nonrandomized registry, or consensus-based guidelines. Finally, only after considering the first 3 options, the physician should use best judgment based on previous personal experience and any published case series or anecdotes. Given the paucity of quality randomized clinical trial data for most medical decisions, the "best judgment" option will be used most frequently. Nevertheless, such a hierarchy is needed because of the limited time during medical emergencies for consideration of general principles of clinical decision making. There should be general agreement in advance as to the hierarchy to follow in selecting treatment for critically ill patients. Were more clinicians to follow this hierarchy, and choose to participate in clinical trials, the generation of new knowledge would accelerate, yielding rigorous data supporting or refuting the efficacy and safety of new interventions more quickly, thus benefiting far more patients over time. ANN NEUROL 2010;67:434-440 [source] Is Rhythm-Control Superior to Rate-Control in Patients with Atrial Fibrillation and Diastolic Heart Failure?ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2010Melissa H. Kong M.D. Background: Although no clinical trial data exist on the optimal management of atrial fibrillation (AF) in patients with diastolic heart failure, it has been hypothesized that rhythm-control is more advantageous than rate-control due to the dependence of these patients' left ventricular filling on atrial contraction. We aimed to determine whether patients with AF and heart failure with preserved ejection fraction (EF) survive longer with rhythm versus rate-control strategy. Methods: The Duke Cardiovascular Disease Database was queried to identify patients with EF > 50%, heart failure symptoms and AF between January 1,1995 and June 30, 2005. We compared baseline characteristics and survival of patients managed with rate- versus rhythm-control strategies. Using a 60-day landmark view, Kaplan-Meier curves were generated and results were adjusted for baseline differences using Cox proportional hazards modeling. Results: Three hundred eighty-two patients met the inclusion criteria (285 treated with rate-control and 97 treated with rhythm-control). The 1-, 3-, and 5-year survival rates were 93.2%, 69.3%, and 56.8%, respectively in rate-controlled patients and 94.8%, 78.0%, and 59.9%, respectively in rhythm-controlled patients (P > 0.10). After adjustments for baseline differences, no significant difference in mortality was detected (hazard ratio for rhythm-control vs rate-control = 0.696, 95% CI 0.453,1.07, P = 0.098). Conclusions: Based on our observational data, rhythm-control seems to offer no survival advantage over rate-control in patients with heart failure and preserved EF. Randomized clinical trials are needed to verify these findings and examine the effect of each strategy on stroke risk, heart failure decompensation, and quality of life. Ann Noninvasive Electrocardiol 2010;15(3):209,217 [source] Associations between the American College of Rheumatology pediatric response measures and the continuous measures of disease activity used in adult rheumatoid arthritis: A secondary analysis of clinical trial data from children with Polyarticular-Course Juvenile Idiopathic ArthritisARTHRITIS & RHEUMATISM, Issue 12 2009Sarah Ringold Objective To measure associations between the American College of Rheumatology (ACR) pediatric criteria for improvement and the continuous measures of disease activity used for rheumatoid arthritis in adult patients with polyarticular-course juvenile idiopathic arthritis (JIA). Methods In this retrospective analysis of 2 etanercept trials, disease activity was calculated at baseline, 3 months, and 6 months using the Disease Activity Score (DAS), the DAS based on 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). The ACR pediatric response and the European League Against Rheumatism (EULAR) response were also determined for the 3-month and 6-month evaluations. Data were analyzed in 94 patients with JIA independent of the treatment arm. Correlation coefficients between measures were calculated for each visit. The areas under the receiver operating characteristic curve (AUC of ROC) were calculated to assess the discriminative properties of the scores for the ACR pediatric response measures. Results The mean DAS, DAS28, CDAI score, and SDAI score were 3.7, 4.7, 30.8, and 36.4, respectively, at baseline, corresponding to high levels of disease activity (CDAI/SDAI) or moderate levels of disease activity (DAS/DAS28). At 3 months, the mean scores corresponded to low (DAS/DAS28) or moderate (CDAI/SDAI) disease activity. At 6 months, the mean scores corresponded to low disease activity (DAS/DAS28/CDAI) or moderate disease activity (SDAI). Most children met the criteria for a good or moderate EULAR response at 3 months and 6 months. The correlation between continuous outcome measures and each pediatric core set component was moderate to very good. The AUC of ROC values for each measure were high (range 0.76,0.98). Conclusion Good correlation and discriminative abilities were seen between the DAS, DAS28, CDAI, and SDAI for the ACR pediatric criteria for improvement. These disease activity measures may be useful for research and clinical care in polyarticular-course JIA. [source] Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenonARTHRITIS & RHEUMATISM, Issue 9 2002Peter A. Merkel Objective To document disease activity and functional status in patients with scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to determine the sensitivity to change, reliability, ease of use, and validity of various outcome measures in these patients. Methods Patients with SSc and moderate-to-severe RP participating in a multicenter RP treatment trial completed daily diaries documenting the frequency and duration of RP attacks and recorded a daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior to baseline (week 0), end of trial (week 6), and posttrial followup (week 12) were calculated. At weeks 0, 6, and 12, physicians completed 3 global assessment scales and performed clinical assessments of digital ulcers and infarcts; patients completed the Health Assessment Questionnaire (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2) mood and tension subscales, 5 specific SSc/RP-related visual analog scales (VAS), and 3 other VAS global assessments. We used these measures to document baseline disease activity and to assess their construct validity, sensitivity to change, and reliability in trial data. Results Two hundred eighty-one patients (248 women, 33 men; mean age 50.4 years [range 18,82 years]) from 14 centers participated. Forty-eight percent had limited cutaneous SSc; 52% had diffuse cutaneous SSc. Fifty-nine patients (21%) had digital ulcers at baseline. Patients had 3.89 ± 2.33 (mean ± SD) daily RP attacks (range 0.8,14.6), with a duration of 82.1 ± 91.6 minutes/attack. RCS for RP activity (possible range 0,10) was 4.30 ± 1.92. HAQ scores (0,3 scale) indicated substantial disability at baseline (total disability 0.86, pain 1.19), especially among the subscales pertaining to hand function (grip, eating, dressing). AIMS2 mood and tension scores were fairly high, as were many of the VAS scores. Patients with digital ulcers had worse RCS, pain, HAQ disability (overall, grip, eating, and dressing), physician's global assessment, and tension, but no significant difference in the frequency of RP, duration of RP, patient's global assessment, or mood, compared with patients without digital ulcers. VAS scores for digital ulcers as rated by the patients were not consistent with the physician's ratings. Factor analysis of the 18 measures showed strong associations among variables in 4 distinct domains: disease activity, RP measures, digital ulcer measures, and mood/tension. Reliability of the RCS, HAQ pain and disability scales, and AIMS2 mood and tension subscales was high. The RP measures demonstrated good sensitivity to change (effect sizes 0.33,0.76). Conclusion Our findings demonstrate that the significant activity, disability, pain, and psychological impact of RP and digital ulcers in SSc can be measured by a small set of valid and reliable outcome measures. These outcome measures provide information beyond the quantitative metrics of RP attacks. We propose a core set of measures for use in clinical trials of RP in SSc patients that includes the RCS, patient and physician VAS ratings of RP activity, a digital ulcer/infarct measure, measures of disability and pain (HAQ), and measures of psychological function (AIMS2). [source] | |||||||||||||||||||||||||||||||||||||