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Study Termination (study + termination)
Selected AbstractsOpen trial of nefazodone among Hispanics with major depression: Efficacy, tolerability, and adherence issuesDEPRESSION AND ANXIETY, Issue 3 2001J. Arturo Sánchez-Lacay M.D., M.P.H. Abstract The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score ,18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with ,1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58,69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD=170), also within the range of previous trials (321,472mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by >6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21,33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports. Depression and Anxiety 13:118,124, 2001. © 2001 Wiley-Liss, Inc. [source] Dose-related effects following oral exposure of 2,4-dinitrotoluene on the western fence lizard, Sceloporus occidentalisENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008Jamie G. Suski Abstract 2,4-dintitrotoluene (2,4-DNT) is an explosive frequently found in the soil of military installations. Because reptiles can be common on these sites, ecological risk assessments for compounds such as 2,4-DNT could be improved with toxicity data specific to reptiles. Western fence lizards, Sceloporus occidentalis, were used to develop a laboratory toxicity model for reptiles. A hierarchical approach was used; acute to subchronic studies were conducted to provide toxicity data relevant to short- and long-term exposures. First, a modified median lethal dose (LD50) study was conducted on male and female lizards using a stage-wise probit model. The LD50 was 577 mg/kg for female and 380 mg/kg for male lizards. Subsequently, a subacute experiment was conducted to further assess 2,4-DNT toxicity to male lizards and to define exposure levels for a longer term, subchronic study. The subchronic study was conducted for 60 consecutive days; male lizards were exposed to 0, 9, 15, 25, 42, 70 mg/kg/d. Dose-dependent mortality was observed in the three highest dose groups (25, 42, and 70 mg/kg/d); all other animals survived the study duration. Benchmark dose model calculations based on mortality indicated a 5% effect level of 15.8 mg/kg/d. At study termination, a gross necropsy was performed, organ weights were taken, and blood was collected for clinical and hematological analysis. Body weight, kidney weight, food consumption, postdose observations, and blood chemistries all were found to be significantly different from controls at doses above 9 mg/kg/d. Also, preliminary results suggest behavioral observations, and reduced food consumption may be a sensitive indicator of toxicity. The present study indicates Sceloporus occidentalis is suitable for evaluating toxicity of compounds to reptilian species. [source] Time Trends in Incidence, Mortality, and Case-Fatality after First Episode of Status EpilepticusEPILEPSIA, Issue 8 2001Giancarlo Logroscino Summary: ,Purpose: Status epilepticus (SE) is a medical emergency associated with a high mortality. Clinical series have suggested that mortality after SE has decreased. No studies have systematically examined trends in incidence, mortality, and case fatality after SE in a well-defined population. Methods: All first episodes of SE receiving medical attention between January 1, 1935, and December 31, 1984, were ascertained through the Rochester Epidemiology Project Records-Linkage System and followed up until death or study termination (February 1, 1996). We calculated incidence rates in the 50-year period (1935,1984), while we considered mortality and case-fatality in the last 30-year period (1955,1984). Results: Incidence of SE increased over time to 18.1/100,000 (1975 through 1984). The increase was related to an increased incidence in the elderly and to the advent of myoclonic SE after cardiac arrest, a condition not seen in the early decades. In the last decade, ,16% of the incidence was due to myoclonic SE. The mortality rates increased from 3.6 per year in the decade 1955,1965 to 4.0/100,000 per year between 1975 and 1984. The 30-day case-fatality (CF) was unchanged, although a trend toward improvement was shown after excluding myoclonic SE. Conclusions: Incidence and mortality rates of SE have increased in the last 30 years. Case fatality remained the same. The increased incidence and mortality are due to the occurrence in the last decade of myoclonic SE after cardiac arrest. The mortality in the elderly was twice that of the youngest age group, across all study periods. Changes in the age and cause distribution of SE over time are responsible for the stable survivorship. There is improvement in survivorship in the last decade when myoclonic SE is excluded. [source] Long-Term Dosing of Arzoxifene Lowers Cholesterol, Reduces Bone Turnover, and Preserves Bone Quality in Ovariectomized Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2002Yanfei L. Ma M.D. Abstract Long-term effects of a new selective estrogen receptor modulator (SERM) arzoxifene were examined in ovariectomized (OVX) rats. Arzoxifene was administered postoperatively (po) at 0.1 mg/kg per day or 0.5 mg/kg per day to 4-month-old rats, starting 1 week after OVX for 12 months. At study termination, body weights for arzoxifene groups were 16,17% lower than OVX control, which was caused by mainly reduced gain of fat mass. Longitudinal analysis of the proximal tibial metaphysis (PTM) by computed tomography (CT) at 0, 2, 4, 6, 9, and 12 months showed that OVX induced a 22% reduction in bone mineral density (BMD) at 2 months, which narrowed to a 12% difference between sham-operated (sham) and OVX rats by 12 months. Both doses of arzoxifene prevented the OVX-induced decline in BMD. Histomorphometry of the PTM showed that arzoxifene prevented bone loss by reducing osteoclast number in OVX rats. Arzoxifene maintained bone formation indices at sham levels and preserved trabecular number above OVX controls. Micro-CT analysis of lumbar vertebrae showed similar preservation of BMD compared with OVX, which were not different from sham. Compression testing of the vertebra and three-point bending testing of femoral shaft showed that strength and toughness were higher for arzoxifene-treated animals compared with OVX animals. Arzoxifene reduced serum cholesterol by 44,59% compared with OVX. Uteri wet weight from arzoxifene animals was 38,40% of sham compared with OVX rats, which were 29% of sham. Histology of the uterine endometrium showed that cell heights from both doses of arzoxifene were not significantly different from OVX controls. In summary, treatment of OVX rats with arzoxifene for nearly one-half of a lifetime maintained beneficial effects on cholesterol and the skeleton. These data suggest that arzoxifene may be a useful therapeutic agent for osteoporosis in postmenopausal women. [source] A chlorhexidine varnish implemented treatment strategy for chronic periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2005Short-term clinical observations Abstract Objectives: The aim of this study was to investigate the clinical outcome of a subgingivally applied chlorhexidine varnish when used as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis. Material and methods: A randomized controlled, single blind, parallel trial was conducted on the basis of 16 volunteers suffering from chronic periodontitis. The control group received oral hygiene instructions and was scaled and root planed in two sessions. The test group received the same instructions and treatment, however, all pockets were additionally disinfected using a chlorhexidine varnish. The gingival index, plaque index, bleeding on probing, probing pocket depth (PPD) and clinical attachment level (CAL) were recorded at baseline and subsequently after 1 and 3 months. Results: Both treatment strategies showed significant reductions in PPD and CAL at both follow-up visits by comparison with baseline levels (p<0.001). Yet, at study termination, combination therapy resulted in additional pocket reductions between 0.73 and 1.23 mm (p<0.02), and clinical attachment gains between 0.63 and 1.09 mm (p<0.02). Conclusions: These findings suggest that a varnish-implemented strategy may improve the clinical outcome for the treatment of chronic periodontitis in comparison with SRP alone. [source] One-year treatment of chronic urticaria with mizolastine: efficacy and safetyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2000G Lorette Abstract Aim,To assess the long-term safety and efficacy of the H1-receptor antagonist mizolastine in the symptomatic treatment of chronic urticaria (CU). Background,Mizolastine is a novel second generation antihistamine with additional anti-inflammatory properties which has been shown to be effective in this condition as well as in allergic rhinitis. As the drug is used for chronic treatment, a detailed study of its efficacy and safety over a prolonged period was warranted. Methods,This open label multicentre trial recruited 211 patients suffering from CU (67% female; mean age 40 ± 13 years), with , 1 episode/week if untreated. After a 7-day placebo run-in period, patients received mizolastine (10 or 15 mg) for 12 months. Efficacy was assessed by the patient using daily diary cards and overall condition evaluation at study visits. Clinicians also assessed the same parameters at each visit, and gave a global assessment at study termination. Safety was assessed by monitoring adverse events and laboratory parameters. Cardiac safety was monitored every 4 months using 12-lead ECGs, with particular attention to QT intervals. Results,The trial was completed by 127 patients. Mizolastine reduced overall discomfort from the second week of therapy, and reduced itching and the number and size of wheals, as assessed by the patients. The clinician's assessment of the proportion of patients with > 10 wheals decreased from 42% to 28% after 2 months. Clinical assessment also indicated that itch intensity and angioedema were improved by mizolastine, and the improvement was sustained throughout the trial. The investigators estimated that 70% of patients benefited from therapy. There were no drug-related serious adverse events during the study. The cardiac repolarization assessed according to the QTc intervals was not modified during prolonged administration. Conclusion,Mizolastine improves CU symptoms, and these improvements are sustained over 12 months with no loss of drug sensitivity. No specific side-effects are associated with its long-term use in the current study. [source] A Randomized Double-Blind, Placebo Controlled Trial of Steroid Withdrawal after Pediatric Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010M. R. Benfield In an effort to reduce rejection, extend allograft survival and minimize complications, we hypothesized that robust immunosuppression during the first 6 months after transplantation would allow for the safe withdrawal of steroids. A total of 274 pediatric subjects were enrolled and received an anti-CD25 antibody, sirolimus, calcineurin inhibitor and steroids. At 6 months after transplantation, subjects were randomized to steroid withdrawal (n = 73) versus continued low-dose steroids (n = 59). This study was stopped prior to target enrollment because of the incidence of post-transplant lymphoproliferative disorder. At the time of study termination, 132 subjects had been randomized and were available for analysis. At 18 months after transplantation, there was no difference in the standardized height z score; however, the standardized height velocity was greater in the steroid withdrawal group compared to the control group (p = 0.033). There were no differences in acute rejection episodes between treatment groups. The 3-year allograft survival rate was 84.5% in the control group and 98.6% in the steroid withdrawal group (p = 0.002). The immunosuppressive protocol utilized in this study allowed for the withdrawal of steroids without an increased risk of rejection or allograft loss. However, the complications associated with the use of this immunosuppressive protocol were too high to recommend its routine use in pediatric patients. [source] An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupusARTHRITIS & RHEUMATISM, Issue 5 2008Frances Rena Bahjat Objective To assess whether R788, an orally bioavailable small molecule inhibitor of spleen tyrosine kinase (Syk),dependent signaling, could modulate disease in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice via inhibition of Fc receptor (FcR) and B cell receptor signaling. Methods R788 was administered to NZB/NZW mice before and after disease onset. Proteinuria, blood urea nitrogen levels, and autoantibody titers were examined periodically, and overall survival and renal pathologic features were assessed following long-term treatment (24,34 weeks). The distribution and immunophenotype of various splenic T cell and B cell subpopulations were evaluated at the time of study termination. Arthus responses in NZB/NZW mice pretreated with R788 or Fc-blocking antibody (anti-CD16/32) were also examined. Results When R788 was administered prior to or after disease onset, it delayed the onset of proteinuria and azotemia, reduced renal pathology and kidney infiltrates, and significantly prolonged survival of lupus-prone NZB/NZW mice; autoantibody titers were minimally affected throughout the study. Dose-dependent reductions in the numbers of CD4+ activated T cells expressing high levels of CD44 or CD69 were apparent in spleens from R788-treated mice. Minimal effects on the numbers of naive T cells expressing CD62 ligand and total CD8+ T cells per spleen were observed following long-term drug treatment. R788 pretreatment resulted in reduced Arthus responses in NZB/NZW mice, similar to results obtained in mice pretreated with FcR-blocking antibody. Conclusion We demonstrate that a novel Syk-selective inhibitor prevents the development of renal disease and treats established murine lupus nephritis. These data suggest that Syk inhibitors may be of therapeutic benefit in human lupus and related disorders. [source] Early elevation in circulating levels of C-telopeptides of type II collagen predicts structural damage in articular cartilage in the rodent model of collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 9 2006Svetlana Oestergaard Objective To investigate changes in the circulating levels of the C-telopeptide of type II collagen (CTX-II) with relation to disease onset and structural damage of cartilage in a rodent model of collagen-induced arthritis (CIA), and to investigate immunolocalization of the CTX-II epitope in the articular cartilage of affected joints. Methods Seven-week-old female Lewis rats were immunized with type II collagen and monitored using blood sampling at weekly intervals. At study termination (day 23), the animals were killed, synovial fluid was collected, and the affected joints were scored macroscopically for disease severity and underwent immunohistochemical evaluation. Results At the time of disease onset (day 15), which was characterized by redness and swelling of the affected joints (mean ± SD macroscopic severity score 9.1 ± 1.6), there was a 355% increase in serum CTX-II levels. The early change in serum CTX-II from day 0 to day 15 showed a significant association with the severity of cartilage damage (r = 0.61, P < 0.01). Immunostaining revealed extensive presence of the CTX-II epitope in the damaged, uncalcified cartilage tissue. Conclusion The elevation in serum CTX-II concomitant with the onset of disease and proportional to cartilage damage demonstrates that CTX-II is a sensitive diagnostic tool for monitoring joint disease in the rodent model of CIA. Furthermore, the immunohistochemical findings are consistent with the concept that the major source of serum CTX-II is the damaged articular cartilage. [source] | ||||||||||