Home About us Contact
|
Home About us Contact | ||
|
|
||
Primary Analysis (primary + analysis)
Selected AbstractsNegligible Analgesic Tolerance Seen with Extended Release Oxymorphone: A Post Hoc Analysis of Open-Label Longitudinal DataPAIN MEDICINE, Issue 8 2010R. Norman Harden MD Abstract Objective., To examine the development of analgesic tolerance in patients on oxymorphone extended-release (OxymER). Design.,Post hoc analysis of data from a previously conducted prospective 1 year multi-center open-label extension study in which patients were able to titrate as needed. Patients., Sample of 153 hip and knee osteoarthritis (OA) subjects on OxymER. Primary analyses were limited to study completers (n = 62) due to the large amount of missing data for the noncompleters (n = 91). Outcome Measures., Main outcome measures included OxymER doses (pill counts) and pain intensity ratings using a visual analog scale at monthly visits. Results., There were significant dose increases from weeks 1 to 2 and 2 to 6 (P < 0.05). Doses stabilized around week 6, suggesting the completion of what we defined as "titration." Both doses and pain ratings were stable when this titration phase was excluded from the analysis (P = 0.751; P = 0.056, respectively). Only 28% of the patients had any dose changes following this titration. While there was a significantly greater dose at week 52 compared with week 10 (P = 0.010), the increase in dose became insignificant after excluding four subjects who required two dose increases (P = 0.103). Conclusions., The results showed that most of the titration/dose stabilization changes occurred within the first 10 weeks. A minority (28%) of subjects required dosage increases after this (defined) titration period. Pain reports stabilized statistically after 2 weeks. The findings of this post hoc analysis suggest a lack of opioid tolerance in the majority (72%) of these OA patients who completed this study following a defined titration period on OxymER. Summary., This post hoc analysis of oxymorphone ER consumption in osteoarthritis pain vs pain report showed that most dose changes occurred during an initial "titration period" as defined. Following this titration few subjects increased dose and analgesia remained stable. These findings suggest a lack of longitudinal opioid tolerance in the majority of those OA subjects who completed the trial. [source] Efficacy and safety of once-daily fluticasone furoate nasal spray in children with seasonal allergic rhinitis treated for 2 wkPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2009Eli O. Meltzer The objective of this study was to evaluate the efficacy and safety of fluticasone furoate (FF) nasal spray 55 and 110 ,g once daily in children with seasonal allergic rhinitis (SAR). Patients (n = 554) received placebo nasal spray or FF, administered using a unique side-actuated device, in a 2-wk, randomized, double-blind study. Symptoms were evaluated by patients using a 4-point categorical scale. Efficacy assessments included reflective and instantaneous total nasal symptom scores (r/iTNSS). Primary analyses were conducted in patients aged 6,11 yr in the intent-to-treat population (ITT); the 2,11 yr group provided supportive analyses. In patients aged 6,11 yr, FF 110 ,g once daily significantly improved the daily rTNSS compared with placebo. FF 55 ,g once daily was only numerically better for rTNSS and iTNSS. Secondary pre-dose iTNSS and overall response to therapy were significant with FF 110 ,g. The significant findings for FF 110 ,g were supported by analyses in the entire ITT population of 2,11 yr olds. Both doses of FF were well tolerated. These study results suggest that FF nasal spray administered once daily for 2 wk is well tolerated and effective for the treatment of SAR symptoms in children aged 2,11 yr. [source] Treatment of symptomatic diabetic polyneuropathy with the antioxidant ,-lipoic acid: a meta-analysisDIABETIC MEDICINE, Issue 2 2004D. Ziegler Abstract Aims To determine the efficacy and safety of 600 mg of ,-lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy. Methods We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of ,-lipoic acid according to the following prerequisites: randomized, double-masked, placebo-controlled, parallel-group trial using ,-lipoic acid infusions of 600 mg i.v. per day for 3 weeks, except for weekends, in diabetic patients with positive sensory symptoms of polyneuropathy which were scored by the Total Symptom Score (TSS) in the feet on a daily basis. Four trials (ALADIN I, ALADIN III, SYDNEY, NATHAN II) comprised n = 1258 patients (,-lipoic acid n = 716; placebo n = 542) met these eligibility criteria and were included in a meta-analysis based on the intention-to-treat principle. Primary analysis involved a comparison of the differences in TSS from baseline to the end of i.v. Treatment between the groups treated with ,-lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (, 50% improvement in TSS), individual TSS components, Neuropathy Impairment Score (NIS), NIS of the lower limbs (NIS-LL), individual NIS-LL components, and the rates of adverse events. Results After 3 weeks the relative difference in favour of ,-lipoic acid vs. placebo was 24.1% (13.5, 33.4) (geometric mean with 95% confidence interval) for TSS and 16.0% (5.7, 25.2) for NIS-LL. The responder rates were 52.7% in patients treated with ,-lipoic acid and 36.9% in those on placebo (P < 0.05). On a daily basis there was a continuous increase in the magnitude of TSS improvement in favour of ,-lipoic acid vs. placebo which was noted first after 8 days of treatment. Among the individual components of the TSS, pain, burning, and numbness decreased in favour of ,-lipoic acid compared with placebo, while among the NIS-LL components pin-prick and touch-pressure sensation as well as ankle reflexes were improved in favour of ,-lipoic acid after 3 weeks. The rates of adverse events did not differ between the groups. Conclusions The results of this meta-analysis provide evidence that treatment with ,-lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both positive neuropathic symptoms and neuropathic deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy. Diabet. Med. 21, 114,121 (2004) [source] Decreased Dopamine D2/D3-Receptor Binding in Temporal Lobe Epilepsy: An [18F]Fallypride PET StudyEPILEPSIA, Issue 8 2006Konrad J. Werhahn Summary:,Purpose: Although animal data are suggestive, evidence for an alteration of the extrastriatal dopaminergic system in human focal epilepsy is missing. Methods: To quantify D2/D3-receptor density, we studied seven patients with temporal lobe epilepsy (TLE) and nine age-matched controls with positron emission tomography (PET) by using the high-affinity dopamine D2/D3-receptor ligand [18F]Fallypride ([18F]FP) suitable for imaging extrastriatal binding. TLE was defined by interictal and ictal video-EEG, magnetic resonance imaging (MRI), and [18F]fluorodeoxyglucose ([18F]FDG)-PET and was due to hippocampal sclerosis (HS), based on histology in all patients. Primary analysis was based on regions of interest (ROIs) defined on individual MRIs. For each patient, binding potential (BP) was calculated by using the simplified reference tissue model, and the epileptogenic was compared with the unaffected hemisphere in each ROI. To confirm the results, an additional voxel-based group analysis was performed by using statistical parametric mapping. Results: Compared with controls, [18F]FP BP was significantly decreased in the epileptogenic temporal lobe in all patients. On ROI analysis, this reduction was evident in areas surrounding the seizure-onset zone at the pole (,34.2%) and lateral aspects (,32.9%) of the temporal lobe. Although the hippocampus [18F]FDG uptake (,8.1%) and hippocampal MR volume (,35.1%) were significantly reduced, no significant decrease of [18F]FP BP was found. Reduction of [18F]FP BP did not correlate with hippocampal atrophy. Conclusions: D2/D3-receptor binding is reduced at the pole and in lateral aspects of the epileptogenic temporal lobe in patients with mesial TLE and HS. This area might correspond to "the irritative zone," indicating that D2/D3 receptors might play a specific role in the pathophysiology of mesial TLE. [source] Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010K. K. SNOW Aliment Pharmacol Ther,31, 719,734 Summary Background, Primary analysis of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial showed long-term peginterferon therapy did not reduce complications in patients with chronic hepatitis C and advanced fibrosis or cirrhosis. Aim, To assess the effects of long-term peginterferon therapy and disease progression on health-related quality of life (HRQOL), symptoms and sexual health in HALT-C patients. Methods, A total of 517 HALT-C patients received peginterferon alfa-2a (90 ,g/week); 532 received no additional treatment for 3.5 years. Patients were followed up for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF-36 scores and symptoms were serially assessed by repeated-measures analyses of covariance. Results, Patients with cirrhosis (n = 427) reported lower general well-being and more fatigue (P < 0.001) than patients with fibrosis (n = 622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF-36 and symptom scores. Among men, Sexual Health scores were significantly worse in treated patients and in those with a clinical outcome. Conclusion, Clinical progression of chronic hepatitis C and maintenance peginterferon therapy led to worsening of symptoms, HRQOL and, in men, sexual health in a large patient cohort followed up over 4 years (NCT00006164). [source] International migration and the Rainbow NationPOPULATION, SPACE AND PLACE (PREVIOUSLY:-INT JOURNAL OF POPULATION GEOGRAPHY), Issue 1 2006David Lucas Abstract Recent statistics suggest that emigration from South Africa is accelerating while documented immigration remains at low levels. Primary analysis of a 10% sample of the overseas-born in South Africa from the 1996 census confirmed that Black immigrants to South Africa were shown to be predominantly unskilled males, who were no better qualified than the Black population in general. This contrasts with the apartheid era when South Africa built up a stock of overseas-born skilled workers, mostly Whites, which was not replenished in the 1990s, partly because of restrictive immigration policies. The UK is the major destination for South Africans but lacks detailed data on the characteristics of the immigrants. The second destination is Australia and New Zealand combined. Comparisons are made with published census data on the South Africa-born in Australia and New Zealand. A majority of emigrants have post-school qualifications and professional occupations, reflecting the selective immigration criteria of Australia and New Zealand. The analysis confirms the importance of human capital to potential emigrants even though they may wish to move for non-economic reasons. It also supports the view that South Africa had moved from a brain exchange of Whites to a brain drain, thus compounding a national shortage of skilled workers. Copyright © 2006 John Wiley & Sons, Ltd. [source] Epidural versus Non-Epidural or No Analgesia in LabourBIRTH, Issue 1 2006Article first published online: 28 JUN 200 A substantive amendment to this systematic review was last made on 16 August 2005. Cochrane reviews are regularly checked and updated if necessary. Abstract Background:, Epidural analgesia is a central nerve block technique achieved by injection of a local anaesthetic close to the nerves that transmit pain and is widely used as a form of pain relief in labour. However, there are concerns regarding unintended adverse effects on the mother and infant. Objectives:, To assess the effects of all modalities of epidural analgesia (including combined-spinal-epidural) on the mother and the baby, when compared with non-epidural or no pain relief during labour. Search strategy:, We searched the Cochrane Pregnancy and Childbirth Group Trials Register (June 2005). Selection criteria:, Randomised controlled trials comparing all modalities of epidural with any form of pain relief not involving regional blockade, or no pain relief in labour. Data collection and analysis Two of the review authors independently assessed trials for eligibility, methodological quality and extracted all data. Data were entered into RevMan and double checked. Primary analysis was by intention-to-treat; sensitivity analyses excluded trials with >30% of women receiving un-allocated treatment. Main results:, Twenty-one studies involving 6664 women were included, all but one study compared epidural analgesia with opiates. For technical reasons, data on women's perception of pain relief in labour could only be included from one study, which found epidural analgesia to offer better pain relief than non-epidural analgesia (weighted mean difference (WMD),2.60, 95% confidence interval (CI),3.82 to ,1.38, 1 trial, 105 women). However, epidural analgesia was associated with an increased risk of instrumental vaginal birth (relative risk (RR) 1.38, 95% CI 1.24 to 1.53, 17 trials, 6162 women). There was no evidence of a significant difference in the risk of caesarean delivery (RR 1.07, 95% CI 0.93 to 1.23, 20 trials, 6534 women), long-term backache (RR 1.00, 95% CI 0.89 to 1.12, 2 trials, 814 women), low neonatal Apgar scores at 5 minutes (RR 0.70, 95% CI 0.44 to 1.10, 14 trials, 5363 women), and maternal satisfaction with pain relief (RR 1.18 95% CI 0.92 to 1.50, 5 trials, 1940 women). No studies reported on rare but potentially serious adverse effects of epidural analgesia. Authors' conclusions:, Epidural analgesia appears to be effective in reducing pain during labour. However, women who use this form of pain relief are at increased risk of having an instrumental delivery. Epidural analgesia had no statistically significant impact on the risk of caesarean section, maternal satisfaction with pain relief and long-term backache and did not appear to have an immediate effect on neonatal status as determined by Apgar scores. Further research may be helpful to evaluate rare but potentially severe adverse effects of epidural analgesia on women in labour and long-term neonatal outcomes. Citation:, Anim-Somuah M, Smyth R, Howell C. Epidural versus non-epidural or no analgesia in labour. The Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD000331.pub2. DOI: 10.1002/14651858.CD000331.pub2. *** The preceding report is an abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of the review is available in The Cochrane Library (ISSN 1465,1858). Abstracts of Cochrane reviews are compiled and produced by Update Software Ltd on behalf of the publisher, John Wiley & Sons Ltd. [source] Oxygen and Hydrogen Isotopes of Waters in the Ordos Basin, China: Implications for Recharge of Groundwater in the North of Cretaceous Groundwater BasinACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 1 2009Yuncheng YANG Abstract: Hundreds of precipitation samples collected from meteorological stations in the Ordos Basin from January 1988 to December 2005 were used to set up a local meteoric water line and to calculate weighted average isotopic compositions of modern precipitation. Oxygen and hydrogen isotopes, with averages of ,7.8, and ,53.0, for ,18O and ,D, respectively, are depleted in winter and rich in spring, and gradually decrease in summer and fall, illustrating that the seasonal effect is considerable. They also show that the isotopic difference between south portion and north portion of the Ordos Basin are not obvious, and the isotope in the middle portion is normally depleted. The isotope compositions of 32 samples collected from shallow groundwater (less than a depth of 150 m) in desert plateau range from ,10.6, to ,6.0, with an average of ,8.4, for ,18O and from ,85, to ,46, with an average of ,63, for ,D. Most of them are identical with modern precipitation. The isotope compositions of 22 middle and deep groundwaters (greater than a depth of 275 m) fall in ranges from ,11.6, to ,8.8, with an average of ,10.2, for ,18O and from ,89, to ,63, with an average of ,76, for ,D. The average values are significantly less than those of modern precipitation, illustrating that the middle and deep groundwaters were recharged at comparatively lower air temperatures. Primary analysis of 14C shows that the recharge of the middle and deep groundwaters started at late Pleistocene. The isotopes of 13 lake water samples collected from eight lakes define a local evaporation trend, with a relatively flat slope of 3.77, and show that the lake waters were mainly fed by modern precipitation and shallow groundwater. [source] Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia,,§HEPATOLOGY, Issue 5 2010Mark H. Kuniholm Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1,2.6), B*5701 (PR=2.0; 95% CI = 1.0,3.1), B*5703 (PR = 1.7; 95% CI = 1.0,2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0,3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2,0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2,11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. Conclusion: HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized. (HEPATOLOGY 2010.) [source] Health-related quality of life and sexual function in women with stress urinary incontinence and overactive bladderINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2008Seung-June Oh Background: We evaluated the impact of stress urinary incontinence (SUI) and overactive bladder (OAB) on health-related quality of life (HRQOL) and sexual function. Methods: A total of 245 women (SUI; n = 123 and OAB; n = 122) from 21 to 79 years old (mean 50.4) were included in the primary analyses. To obtain HRQOL and sexual function assessments, patients were asked to fill in the ,Bristol Female Lower Urinary Tract Symptoms (BFLUTS)' and the ,Medical Outcomes Study Short Form (SF-36)' questionnaires. Results: Of the eight domains in the SF-36 questionnaire, only ,general health' was significantly different between the groups. Patients with SUI had a better general health than those with OAB (P = 0.016). When comparing the BFLUTS scores in the two groups, the score for ,BFLUTS-filling symptoms' was higher in the OAB group (P = 0.002) but that for ,BFLUTS-incontinence symptoms' was higher in the SUI group (P < 0.001). The score for ,BFLUTS-sex' was higher in the SUI group than in the OAB group but this was not statistically significant (P = 0.096). Of the 169 patients who had a sex life, the SUI group had experienced pain (P = 0.033) and leakage (P = 0.056) more frequently during intercourse than the OAB group. Conclusion: Both SUI and OAB have a detrimental impact on patient HRQOL in Korean women. In addition, our findings suggest that women with SUI had more frequently experienced pain during intercourse and coital incontinence than those with OAB. [source] Effect of a ,centralized intensive education system' for clean intermittent self-catheterization in patients with voiding dysfunction who start catheterization for the first timeINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2006SEUNG-JUNE OH Background:, This study evaluated the effects of a ,centralized intensive education system' (CIES) in terms of acquiring a proper clean intermittent self-catheterization (CISC) technique by patients with voiding dysfunction. Methods:, Between March 2002 and March 2003, we prospectively and consecutively enrolled 132 hospitalized patients who learnt and started CISC for the first time due to voiding dysfunction. Patients were enrolled either of two groups (the CIES group vs the ,individualized ward education system'[IWES] group) at the time of the urologic consultation for voiding dysfunction. Out of 132 patients who enrolled in the study, 112 (45 males and 67 females, mean age 57.3 with a range of 18,81) were included in the primary analyses. The questionnaire was applied immediately before discharge. Results:, There were similar patient demographics and clinical parameters for the CIES (n = 62) and the IWES groups (n = 50). Of 10 items including the methodology of CISC, six items discriminated significantly in favor of the CIES (P < 0.05). The patient satisfaction with CISC education was significantly different for the two groups in terms of response to the questionnaire. The CIES group was found to be more satisfied with the education received than the IWES group (P < 0.05). Moreover, the number of trials to gain confidence to perform CISC in CIES group was significantly fewer than that of IWES group (P < 0.001). Conclusion:, Our results demonstrate that CIES might be a superior training program for the patients with voiding dysfunction to acquire a proper CISC technique to the conventional IWES. [source] Timing of ibuprofen use and bone mineral density adaptations to exercise trainingJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010Wendy M Kohrt Abstract Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the bone-formation response to loading when administered before, but not immediately after, loading. The aim of this proof-of-concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n,=,73) aged 21 to 40 years completed a supervised 9-month weight-bearing exercise training program. They were randomized to take (1) ibuprofen (400,mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi-W dual-energy X-ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n,=,17; PLAC/PLAC, n,=,23; and PLAC/IBUP, n,=,14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p,<,.001; neck, p,=,.026; trochanter, p,=,.040; shaft, p,=,.019) but not the spine (p,=,.242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total-hip BMD changes averaged ,0.2%,±,1.3%, 0.4%,±,1.8%, and 2.1%,±,1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response. © 2010 American Society for Bone and Mineral Research [source] L-type calcium channel blockers and Parkinson disease in DenmarkANNALS OF NEUROLOGY, Issue 5 2010Beate Ritz MD Objective This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood,brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk. Methods We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis. Results Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54,0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications. Interpretation Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers. ANN NEUROL 2010;67:600,606 [source] N1S3: A revised staging system for head and neck cutaneous squamous cell carcinoma with lymph node metastasesCANCER, Issue 5 2010Results of 2 Australian Cancer Centers Abstract BACKGROUND. A staging system was designed for metastatic cutaneous squamous cell carcinoma (SCC) that would incorporate the parotid as a regional level and facilitate a better prognostic discrimination between subgroups. METHODS. A retrospective review of clinical and pathological information of patients treated for metastatic cutaneous SCC to the parotid and/or neck was conducted. Potential prognostic factors were analyzed using univariate and multivariate analyses. A staging system was elaborated and externally validated. RESULTS. Two hundred fifteen patients were included. All patients had surgery as their primary treatment; 148 had parotidectomy with neck dissection, 50 parotidectomy alone, and 18 neck dissection alone. One hundred seventy-five patients received postoperative radiotherapy. On univariate analysis, the number of involved lymph nodes (P < .001), maximal size (P = .01), and extracapsular spread (P = .003) were found to be significant predictors of survival. On Cox regression, the number of involved lymph nodes as single or multiple (P = .006) was significant. The N1S3 staging system incorporates involved lymph nodes from parotid and neck (single or multiple) and the size (< or >3 cm). This system demonstrates significant predictive capacity for locoregional control (P < .001), disease-specific survival (P<.0001), and overall survival (P<.0001). N1S3 was tested on a different cohort of 250 patients, and the results confirmed those obtained from our primary analyses. CONCLUSIONS. The N1S3 system stages patients according to the number of involved lymph nodes and size, and incorporates parotid as 1 of the regional levels. These 2 predictors are easily applied on both clinical and pathological data. Cancer 2010. © 2010 American Cancer Society. [source] Funding and Publishing Trends of Original Research by Emergency Medicine Investigators over the Past DecadeACADEMIC EMERGENCY MEDICINE, Issue 1 2006Robert H. Birkhahn MD Abstract Objectives: To update the profile of author-reported funding of reports of original research published since 1994 in the four U.S. peer-reviewed general emergency medicine (EM) journals. Methods: For the primary analysis, articles published in Academic Emergency Medicine, American Journal of Emergency Medicine, Annals of Emergency Medicine, and Journal of Emergency Medicine between 1994 and 2003 were reviewed by two emergency physicians trained in abstracting from the literature. Original research was identified; case reports, case series, abstracts, and meta-analysis were excluded. Articles were classified by author report of extramural funding as government (public), private nonprofit (foundation), for profit (industry), or multiple. Data are reported as percent per year per journal. A secondary analysis of MEDLINE was performed to identify publishing trends by EM investigators outside of these four journals over the same period. Results: The primary analysis identified 5,728 articles; 3,278 (57%) were considered original research, with 32% of these reporting extramural funding. In 1994, there were 292 articles with 28% funded (28% public, 43% foundation, 17% industry, and 12% multiple). By 2003, there were 358 articles with 36% funded (42% public, 30% foundation, 18% industry, and 10% multiple). There was a trend toward increased extramural funding in all four journals (p = 0.007), with an estimated growth of 3.6% (95% confidence interval = 1.0% to 6.3%) per year over the past decade. The primary review identified 48% of all articles published by EM investigators. Conclusions: Author-reported extramural funding rates for original research have increased in the EM literature over the past decade. Foundations have funded the largest number of studies, with public (government) sources increasing in 2003. [source] The changing association between prenatal participation in WIC and birth outcomes in New York CityJOURNAL OF POLICY ANALYSIS AND MANAGEMENT, Issue 4 2005Ted Joyce We analyze the relationship between prenatal WIC participation and birth outcomes in New York City from 1988,2001. The analysis is unique for several reasons. First, we have over 800,000 births to women on Medicaid, the largest sample ever used to analyze prenatal participation in WIC. Second, we focus on measures of fetal growth distinct from preterm birth, since there is little clinical support for a link between nutritional supplementation and premature delivery. Third, we restrict the primary analysis to women on Medicaid who have no previous live births and who initiate prenatal care within the first four months of pregnancy. Our goal is to lessen heterogeneity between WIC and non-WIC participants by limiting the sample to highly motivated women who have no experience with WIC from a previous pregnancy. Fourth, we analyze a large sub-sample of twin deliveries. Multifetal pregnancies increase the risk of anemia and fetal growth retardation and thus may benefit more than singletons from nutritional supplementation. We find no relationship between prenatal WIC participation and measures of fetal growth among singletons. We find a modest pattern of association between WIC and fetal growth among U.S.-born Black twins. Our findings suggest that prenatal participation in WIC has had a minimal effect on adverse birth outcomes in New York City. © 2005 by the Association for Public Policy Analysis and Management [source] The Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT) scoreJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2008T. GEISLER Summary.,Background:,Recent studies suggest a high interindividual variability of response to clopidogrel associated with adverse cardiovascular outcome. Different clinical factors are considered to influence a persistent residual platelet aggregation (RPA) despite conventional antiplatelet therapy. Objectives:,To investigate clinical factors that affect RPA after 600-mg clopidogrel loading in a large unselected cohort of patients with symptomatic CAD. Methods:,The study population included a consecutive cohort of 1092 patients treated with coronary stenting for stable angina and acute coronary syndromes (ACS). Residual platelet activity was assessed by ADP (20 ,mol L,1)-induced platelet aggregation , 6 h after LD. Eleven clinical factors were included in the primary analysis. Results:,In multivariate regression analysis increased RPA was significantly influenced by ACS, reduced LV-function, diabetes mellitus, renal failure (creatinine > 1.5 mg dL,1), and age > 65 years. In a factor-weighed model the risk for high RPA increased with higher score levels (OR for patients with a score of 1,3, 1.21, 95% CI 0.7,2.1; score 4,6, OR 2.0, 95% CI 1.17,3.5; P = 0.01; score 7,9, OR 3.3, 95% CI 1.8,6.0). During a 30-day follow-up the incidence of major adverse events was higher in patients with RPA in the upper tertile (4.8% vs. 2.5% in the 2nd and 1.5% in the 1st tertile; P < 0.05). Conclusions:,The PREDICT score provides a good tool to estimate residual platelet activity after clopidogrel LD by easily available patient details. Additionally, we demonstrate its association with short-term outcome. Thus, patients with a high score may benefit from intensified antiplatelet therapy by improved platelet inhibition and risk reduction for thromboischemic events. [source] Double-blind study of pardoprunox, a new partial dopamine agonist, in early Parkinson's disease,MOVEMENT DISORDERS, Issue 6 2010Juliana Bronzova MD Abstract This study examined the efficacy and safety of the partial dopamine agonist, pardoprunox (SLV308), in the treatment of patients with early Parkinson's disease (PD). Patients were randomized to receive pardoprunox (n = 69) or placebo (n = 70). Pardoprunox was titrated to each patient's optimal dose (9,45 mg/d) over 2 to 6 weeks and then maintained at this dose for a further 3 weeks. Concomitant anti-Parkinson treatment was not permitted. In the primary analysis, Unified PD Rating Scale (UPDRS)-Motor score was improved in pardoprunox-treated patients (overall mean dose 23.8 mg/d; ,7.3 points), as compared with placebo (,3.0 points; P = 0.0001), from baseline to end point. At end point, there were more responders (,30% reduction in UPDRS-Motor score) in the pardoprunox group (50.7%) than in the placebo group (15.7%; P < 0.0001). In other secondary analyses, UPDRS-activities of daily living (ADL) and -ADL+Motor scores were also significantly more improved in the pardoprunox group. Nausea was reported by 32 of 68 (47.1%) pardoprunox-treated patients (vs. 3/70, 4.3%, placebo-treated patients), with dizziness, somnolence, headache, and asthenia also reported by ,10 patients. In this exploratory proof-of-concept study, pardoprunox significantly improved motor function in patients with early PD. The efficacy and safety profile of pardoprunox justifies its further investigation in PD. © 2010 Movement Disorder Society [source] Latest news and product developmentsPRESCRIBER, Issue 18 2008Article first published online: 3 OCT 200 Inhaled steroids for all children with asthma? Some children with mild well-controlled asthma may not need a daily inhaled steroid, a Scandinavian study suggests (Arch Dis Child 2008;93:654-9). A total of 176 children aged 5-10 years were randomised to treatment with cromoglicate (Intal) or budesonide. Initially high doses of budesonide (400,g twice daily) were reduced after one month to 200,g twice daily for four months; subsequent treatment for a further year was 100,g twice daily as required for exacerbations or 100,g twice daily regularly. Budesonide was associated with greater improvement in lung function and fewer exacerbations compared with cromoglicate, but after 18 months lung function improvements did not differ. Regular budesonide was associated with fewer exacerbations than as-required administration (0.97 vs 1.69 per patient in months 7-18) but no difference in asthma-free days or use of rescue medication. Growth suppression was slightly greater with continuous budesonide. Interventions to reduce atypicals weight gain A systematic review has found that techniques such as cognitive behaviour therapy and nutritional counselling can reduce weight gain associated with atypical antipsychotics (Br J Psychiatry 2008;193:101-7). Analysis of 10 randomised trials lasting eight weeks to six months found that nonpharmacological intervention increased mean weight loss by about 2.5kg compared with usual care. Check flu vaccine delivery Production of flu vaccine is proceeding according to plan, the Director of Immunisation has told GPs. Practices should now contact their suppliers to confirm a delivery schedule so that clinics can be arranged. New BNF for Children The fourth BNF for Children has been published, containing new sections on HPV vaccination, contraception, treatment of pelvic inflammatory disease and the use of continuous iv infusions in neonates. BNFC 2008 is available online at bnfc.org/bnfc. MMR catch-up ,urgent' The DoH has called for urgent action to reduce the risk of a measles epidemic. Following years of relatively low uptake of MMR vaccine, the pool of unprotected children is now large enough to raise the prospect of 30 000-100 000 measles cases in England. A catch-up campaign will now target children and young people who have never been vaccinated, followed by those who have not completed their course of immunisation. Resource materials are available at www.immunisation.nhs.uk. , A new brand of MMR vaccine is now available. Sanofi Pasteur MSD has replaced MMRII with a new formulation and presentation, MMRvaxPro. The new vaccine is equivalent to its predecessor and interchangeable with Priorix. Early primary prevention with low-dose aspirin? GPs should consider prescribing low-dose aspirin for primary prevention for men aged 48 and women aged 57, say UK researchers (Heart 2008; published online 15 August 2008. doi:10.1136/hrt.2008.150698). Using data from the THIN network of electronic patient records, they modelled the age at which 10-year coronary risk changed from <10 per cent to >10 per cent in men and women without diabetes, not taking lipid-lowering therapy and with no history of cardiovascular disease. Does COPD therapy slow progression? Treatment with an inhaled steroid and long-acting beta-agonist may slow progression of COPD, according to a new analysis of the TORCH study (Am J Respir Crit Care Med 2008;178:332-8). TORCH was designed to determine the effects of COPD treatment on mortality; the primary analysis found no significant difference between fluticasone/salmeterol (Seretide) and placebo (N Engl J Med 2007;356:775-89). This analysis found that the rate of decline in FEV1 (a marker of disease progression) was significantly greater with placebo (55ml per year) than with salmeterol or fluticasone monotherapy (both 42ml per year) or their combination (39ml per year). Faster decline in FEV1 was associated with current smoking, lower BMI and more frequent exacerbations. Copyright © 2008 Wiley Interface Ltd [source] Standardized discharge orders after stroke: Results of the quality improvement in stroke prevention (QUISP) cluster randomized trial,ANNALS OF NEUROLOGY, Issue 5 2010S. Claiborne Johnston MD Objective Proven strategies to reduce risk of stroke recurrence are under-utilized. We sought to evaluate the impact of standardized stroke discharge orders on treatment practices in a cluster-randomized trial. Methods The Quality Improvement in Stroke Prevention (QUISP) trial randomized 12 hospitals to continue usual care or to receive assistance in the development and implementation of standardized stroke discharge orders. All patients with ischemic stroke were identified during a 12-month period prior to implementation and for 12 months afterward, and were followed for 6 months after discharge. The primary outcome was optimal treatment at 6 months, defined as taking a statin, having blood pressure <140/90mmHg, and receiving anticoagulation if atrial fibrillation was diagnosed. The primary analysis treated the hospital as the unit of analysis, comparing optimal treatment rates,adjusted for race, age, dementia, atrial fibrillation, and history of bleeding,between intervention and non-intervention hospitals using a paired t test. Results In the primary analysis with hospital as the unit of analysis, the odds of optimal treatment was not significantly increased at intervention compared to non-intervention hospitals (odds ratio, 1.39; 95% confidence interval, 0.71,2.76; p = 0.27). However, in analyses conducted at the level of the individual patients (N = 3,361), rates of optimal treatment increased from 37% to 45% in the intervention hospitals (p = 0.001) and did not change significantly in the non-intervention hospitals (39% to 40%; p = 0.27). Interpretation Implementation of standardized discharge orders after stroke was associated with increased rates of optimal secondary prevention; this improvement was not significant in the primary analysis at the hospital level. ANN NEUROL 2010;67:579,589 [source] Safety and Efficacy of Bivalirudin in High-risk Patients Admitted Through the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 8 2009Chadwick D. Miller MD Abstract Objectives:, The objective was to assess the safety and efficacy of bivalirudin monotherapy in patients with high-risk acute coronary syndrome (ACS) presenting to the emergency department (ED). Methods:, Data from the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial were used to conduct a post hoc subgroup analysis of high-risk ACS patients (cardiac biomarker elevation or ST-segment deviation) who initially presented to the ED. The ACUITY trial randomized patients to receive heparin (unfractionated [UFH] or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Endpoints included composite ischemia, major bleeding (not coronary artery bypass graft (CABG) related), and net clinical outcome (major bleeding plus composite ischemia). Results:, Of 13,819 participants in the ACUITY trial, 6,441 presented initially to the ED, met high-risk criteria, and were included in the primary analysis. Bivalirudin alone when compared to heparin plus GPI, after adjusting for covariates, was associated with an improvement in net clinical outcome (12.3% vs. 14.3%, adjusted odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.66 to 0.99), similar composite ischemia (9.3% vs. 9.1%, adjusted OR = 0.98, 95% CI = 0.77 to 1.24), and less major bleeding (4.0% vs. 6.8%, adjusted OR = 0.57, 95% CI = 0.42 to 0.75). Bivalirudin plus GPI when compared to heparin plus GPI had similar net clinical outcome (13.8% vs. 14.3%, adjusted OR = 0.91, 95% CI = 0.75 to 1.11), composite ischemia (8.8% vs. 9.1%, adjusted OR = 0.87, 95% CI = 0.69 to 1.11), and major bleeding (6.8% vs. 6.8%, adjusted OR = 1.01, 95% CI = 0.79 to 1.30). Conclusions: Bivalirudin monotherapy decreases major bleeding while providing similar protection from ischemic events compared to heparin plus GPI in patients with high-risk ACS admitted through the ED. [source] Crystallization and preliminary X-ray crystallographic analysis of a bacterial tyrosinase from Bacillus megateriumACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2010Mor Sendovski Tyrosinases are type 3 copper enzymes that are involved in the production of melanin and have two copper ions in the active site. Here, the crystallization and primary analysis of a tyrosinase from Bacillus megaterium is reported. The purified protein was crystallized in the absence or presence of zinc ions and the crystals diffracted to a resolution of 2.0,Å. Crystals obtained in the presence of zinc belonged to space group P212121, while crystals grown in the absence of zinc belonged to space group P21. In both space groups the asymmetric unit contained a dimer, with minor differences in the crystal density and in packing interactions. [source] A Latent-Class Mixture Model for Incomplete Longitudinal Gaussian DataBIOMETRICS, Issue 1 2008Caroline Beunckens Summary In the analyses of incomplete longitudinal clinical trial data, there has been a shift, away from simple methods that are valid only if the data are missing completely at random, to more principled ignorable analyses, which are valid under the less restrictive missing at random assumption. The availability of the necessary standard statistical software nowadays allows for such analyses in practice. While the possibility of data missing not at random (MNAR) cannot be ruled out, it is argued that analyses valid under MNAR are not well suited for the primary analysis in clinical trials. Rather than either forgetting about or blindly shifting to an MNAR framework, the optimal place for MNAR analyses is within a sensitivity-analysis context. One such route for sensitivity analysis is to consider, next to selection models, pattern-mixture models or shared-parameter models. The latter can also be extended to a latent-class mixture model, the approach taken in this article. The performance of the so-obtained flexible model is assessed through simulations and the model is applied to data from a depression trial. [source] 3253: Ocular neurovascular coupling in glaucoma patientsACTA OPHTHALMOLOGICA, Issue 2010K GUGLETA Purpose Defining property of glaucoma, cupping of the optic disc in parallel to loss of retinal ganglion cells and their axon, implies tissue remodeling of the optic nerve head which in turns requires involvement of astrocytes. Their malfunction may lead not only to cupping, but also to disturbance in ocular neurovascular coupling. Methods We analyzed 122 glaucoma patients, ocular hypertensives and healthy controls who all received no IOP-lowering therapy at least four weeks prior to the study examination. One eye per subject entered the primary analysis: in the POAG group, an eye with the biggest damage, in the OHT group an eye with the highest average IOP was selected. Relative vessel diameter increase in response to flicker light was used as the measure of neurovascular coupling. Results This response was impaired in untreated POAG patients, affecting both superior and inferior temporal retinal vessels. In general, inferior vessel dilated more than superior ones. The dilation amplitude was inversely correlated to the level of morphological (retinal nerve fiber layer thickness) and functional (visual field mean defect) glaucomatous damage. Despite the relatively high level of inter- and intraocular correlation of vessel responses, in a separate analysis of contralateral eyes, they seem to display higher dilation amplitudes than the more damaged eyes which were included in the original analysis. Conclusion Neurovascular coupling is impaired in untreated glaucoma patients. Prospective studies are underway in an attempt to clarify the cause versus consequence relationship between the glaucomatous damage and disturbance of neurovascular coupling. [source] | |||||||||||||