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1

Long-term efficacy and safety of human papillomavirus vaccination  

PubMed Central

In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV) vaccines and their safety profile. Two prophylactic HPV vaccines – bivalent (bHPV) and quadrivalent (qHPV) – are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman’s sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs), serious AEs, and discontinuations due to a serious AE reported in clinical studies are similar between the two vaccines and their control groups. In particular, no increased risk of autoimmune disease has been shown among HPV-vaccinated subjects in long-term observation studies. As these are crucial topics in HPV vaccination, it is important to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time. PMID:25587221

De Vincenzo, Rosa; Conte, Carmine; Ricci, Caterina; Scambia, Giovanni; Capelli, Giovanni

2014-01-01

2

Long-term safety and efficacy of continuous intrathecal baclofen.  

PubMed

Long-term continuous intrathecal baclofen (CITB) infusion is a treatment option used to manage otherwise intractable spasticity and is delivered via an implantable pump. The purpose of this single-center multidisciplinary review was to report on the long-term safety and efficacy of CITB in the treatment of 21 children with intractable severe spasticity of cerebral origin. Nineteen recipients had spastic quadriplegia and two had spastic diplegia. Seven recipients had level IV severity on the Gross Motor Functional Classification System and 14 had level V. Median age at implantation was 12 years (range 4 to 20). Fifteen recipients were male, 6 were female. Seventeen recipients were alive at the end of the follow-up period (31 to 78 months; mean 53, SD 4). The Ashworth scale showed a substantial decrease in spasticity in the upper and lower extremities at 6 months and at the most recent follow-up. The Gross Motor Function Measure and Pediatric Evaluation of Disability Inventory showed no functional change. Most treatment goals were at least partly achieved. Caregivers reported a reduction in use of oral medication for spasticity, and improvements in comfort, function, and ease of care. Caregiver satisfaction was high. During 80 recipient-years of pump operation, 153 treatment-associated adverse events occurred: 27 of these were device-related. There were four deaths unrelated to CITE, including one from acute pancreatitis. Our findings might assist in establishing patient selection criteria and treatment goals, improving patient follow-up, and monitoring adverse events. PMID:12418790

Campbell, William M; Ferrel, Anne; McLaughlin, John F; Grant, Gerald A; Loeser, John D; Graubert, Catherine; Bjornson, Kristie

2002-10-01

3

Safety and Efficacy of Rivastigmine in Adolescents with Down Syndrome: Long-Term Follow-Up  

PubMed Central

Abstract Following the completion of a 20-week, open-label study of the safety and efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10 adolescents in the clinical trial continued long-term rivastigmine therapy and 5 did not. After an average period of 38 months, all 10 subjects returned for a follow-up assessment to determine the safety and efficacy of long-term rivastigmine use. Rivastigmine was well tolerated and overall health appeared to be unaffected by long-term rivastigmine use. Performance change on cognitive and language measures administered at the termination of the open-label clinical trial was compared between the two groups. No between-group difference in median performance change across the long-term period was found, suggesting that the long-term use of rivastigmine does not improve cognitive and language performance. However, two subjects demonstrated remarkable improvement in adaptive function over the long-term period. Both subjects had received long-term rivastigmine therapy. The discussion addresses the challenge of assessing cognitive change in clinical trials using adolescents with Down syndrome as subjects and the use of group versus individual data to evaluate the relevance of medication effects. PMID:21186971

Spiridigliozzi, Gail A.; Crissman, Blythe G.; McKillop, Jane Anne; Yamamoto, Haru; Kishnani, Priya S.

2010-01-01

4

Long-term efficacy and safety of biphasic insulin aspart in patients with type 2 diabetes  

Microsoft Academic Search

BackgroundIn this study, we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 (BIAsp30) with that of biphasic human insulin 30 (BHI30) over a period of 24 months in patients with type 2 diabetes.

Bernhard O. Boehm; Julius A. Vaz; Lise Brøndsted; Philip D. Home

2004-01-01

5

Long-term safety and efficacy study of adapalene 0.3% gel.  

PubMed

The efficacy and safety of adapalene 0.1% gel in the treatment of acne vulgaris has been demonstrated in multiple controlled clinical trials. A higher concentration formulation, adapalene 0.3% gel, has been developed to provide a broader range of treatment options for acne management. Phase 3 clinical studies have demonstrated the superior efficacy of adapalene 0.3% gel compared to adapalene 0.1% gel and its vehicle at the end of a 12-week treatment period. The goal of this study was to evaluate the long-term safety of adapalene 0.3% gel in subjects treated once daily for 52 weeks, with a secondary objective to evaluate long-term efficacy. Subjects 12 years of age or older (N=551) with acne vulgaris participated in a multicenter, open-label study of the long-term (up to 52 weeks) efficacy and safety of once-daily applications of adapalene 0.3% gel. Of those enrolled, 167 subjects completed 12 months of treatment. Expected signs and symptoms of local cutaneous irritation (erythema, dryness, scaling, and stinging/burning) were mostly mild or moderate, with mean tolerability scores below 1 (mild) at all time points for the parameters assessed. Treatment-related, dermatologic adverse events were experienced by 21% of subjects and dry skin, skin discomfort, and scaling were reported by 10.5%, 8.3% and 3.3% of subjects, respectively. Most of the adverse events reported occurred in the first quarter of treatment. Adverse events were mostly mild to moderate in severity. Subjects treated with adapalene 0.3% gel for 52 weeks achieved a >75% median reduction in total, inflammatory, and noninflammatory lesions in this open-label study by the end of the treatment period. Adapalene 0.3% gel was safe and effective in the long-term (up to 1 year) treatment of subjects with acne vulgaris. PMID:18575223

Weiss, Jonathan S; Thiboutot, Diane M; Hwa, Joyce; Liu, Yin; Graeber, Michael

2008-06-01

6

Long-term efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol.  

PubMed

Beclomethasone dipropionate (BDP) nasal aerosol has an established efficacy and safety profile for short-term allergic rhinitis (AR) treatment. However, managing perennial AR (PAR) symptoms often requires long-term treatment. This study evaluates efficacy and safety of long-term treatment with BDP nasal aerosol in PAR patients. In this double-blind, placebo-controlled study, patients (?12 years [n = 529]) were randomized 4:1 to once-daily treatment with BDP nasal aerosol at 320 ?g or placebo. The primary efficacy end point was change from baseline in weekly averages of patient-reported 24-hour reflective total nasal symptom score (rTNSS) over 30 weeks. Safety and tolerability of BDP nasal aerosol were also assessed. Ocular safety, including changes in intraocular pressure and severity of lens opacities (nuclear opalescence, nuclear color, cortical lens opacity, and posterior subcapsular lens opacity), was measured for patients who completed 52 weeks of treatment (n = 245). Across 30 and 52 weeks, BDP nasal aerosol significantly improved rTNSS and instantaneous TNSS (iTNSS) versus placebo (least-squares mean treatment difference, rTNSS, -0.97 for 30 weeks and -1.09 for 52 weeks, p < 0.001 for both; iTNSS, -0.96 for 30 weeks and -1.10 for 52 weeks], p < 0.001 for both). BDP nasal aerosol was well tolerated. Incidence of most adverse events with BDP nasal aerosol was similar to that with placebo, except for epistaxis, which occurred more frequently with active treatment. Severity of changes from baseline in ocular lens opacities was comparable between treatments. BDP nasal aerosol at 320 ?g once daily was safe and effective for long-term PAR treatment, with no evidence of clinically adverse systemic safety events. This study was a part of the clinical trial NCT00988247 registered at www.ClinicalTrials.gov. PMID:24992552

Weinstein, Steven F; Andrews, Charles P; Shah, Shailen R; Chylack, Leo T; Tankelevich, Alexander; Ding, Yu; Tantry, Sudeesh K

2014-01-01

7

Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis  

PubMed Central

Ulcerative colitis (UC) is a chronic, relapsing, and remitting inflammatory disease involving the large intestine (colon). Treatment seeks to break recurrent inflammation episodes by inducing and maintaining remission. Historically, oral systemic corticosteroids played an important role in inducing remission of this chronic disease; however, their long-term use is limited and can lead to adverse events. Budesonide is a synthetic steroid with potent local anti-inflammatory effects and low systemic bioavailability due to high first-pass hepatic metabolism. Several studies have demonstrated oral budesonide’s usefulness in treating active mild to moderate ileocecal Crohn’s disease and microscopic colitis and in an enema formulation for left sided UC. However, there is limited information regarding oral budesonide’s efficacy in UC. A novel oral budesonide formulation using a multimatrix system (budesonide-MMX) to extend drug release throughout the colon has been developed recently and seems to be an effective treatment in active left sided UC patients. This article summarizes budesonide’s long-term safety and efficacy in treating UC. PMID:24523594

Iborra, Marisa; Álvarez-Sotomayor, Diego; Nos, Pilar

2014-01-01

8

Long-term efficacy, safety, and patient acceptability of ibandronate in the treatment of postmenopausal osteoporosis  

PubMed Central

Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using “ibandronate”, “postmenopausal osteoporosis”, “fracture”, and “bone mineral density” (BMD) revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score ? ?3.0; RRR 69%) and a meta-analysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent) were superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data are limited by patient selection, statistical power, under-dosing, and absence of placebo groups in high dose studies. Ibandronate treatment offers different doses and modalities of administration which could translate into higher adherence rates, an important factor when the two main limitations of BP treatment are initiation and adherence rates. However, lack of consistency in NVF reduction and absence of hip fracture data limits more generalized use of this agent. PMID:25565901

Inderjeeth, Charles A; Glendenning, Paul; Ratnagobal, Shoba; Inderjeeth, Diren Che; Ondhia, Chandni

2015-01-01

9

Long-term efficacy, safety, and patient acceptability of ibandronate in the treatment of postmenopausal osteoporosis.  

PubMed

Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using "ibandronate", "postmenopausal osteoporosis", "fracture", and "bone mineral density" (BMD) revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score ? -3.0; RRR 69%) and a meta-analysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent) were superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data are limited by patient selection, statistical power, under-dosing, and absence of placebo groups in high dose studies. Ibandronate treatment offers different doses and modalities of administration which could translate into higher adherence rates, an important factor when the two main limitations of BP treatment are initiation and adherence rates. However, lack of consistency in NVF reduction and absence of hip fracture data limits more generalized use of this agent. PMID:25565901

Inderjeeth, Charles A; Glendenning, Paul; Ratnagobal, Shoba; Inderjeeth, Diren Che; Ondhia, Chandni

2015-01-01

10

Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria  

PubMed Central

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival. PMID:23617322

Hillmen, Peter; Muus, Petra; Röth, Alexander; Elebute, Modupe O; Risitano, Antonio M; Schrezenmeier, Hubert; Szer, Jeffrey; Browne, Paul; Maciejewski, Jaroslaw P; Schubert, Jörg; Urbano-Ispizua, Alvaro; de Castro, Carlos; Socié, Gérard; Brodsky, Robert A

2013-01-01

11

Long term efficacy and safety of etanercept in the treatment of psoriasis and psoriatic arthritis  

PubMed Central

Psoriasis is a chronic, immune-mediated inflammatory disease affecting both the skin and joints. Approximately 20% of patients suffer a moderate to severe form of skin disease and up to 30% have joint involvement. Standard therapies for psoriasis include topical medications, phototherapy, and both oral systemic and biological therapies whereas therapies for psoriatic arthritis include nonsteroidal anti-inflammatory drugs followed by disease modifying antirheumatic drugs and/or tumor necrosis factor (TNF)-? inhibitors and interleukin-12/23p40 inhibitors. Treatment of both diseases is typically driven by disease severity. In the past decade, major advances in the understanding of the immunopathogenesis of psoriasis and psoriatic arthritis have led to the development of numerous biological therapies, which have revolutionized the treatment for moderate to severe plaque psoriasis and psoriatic arthritis. Anti-TNF-? agents are currently considered as first line biological therapies for the treatment of moderate to severe psoriasis and psoriatic arthritis. Currently approved anti-TNF-? agents include etanercept, adalimumab, and infliximab for psoriasis and psoriatic arthritis as well as golimumab and certolizumab for psoriatic arthritis. In this article, we aim to evaluate the long term safety and efficacy of etanercept in psoriasis and psoriatic arthritis. PMID:24790410

Kivelevitch, Dario; Mansouri, Bobbak; Menter, Alan

2014-01-01

12

Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma  

PubMed Central

Objective: To report long-term efficacy and safety data for everolimus for the treatment of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC). Methods: This was an open-label extension phase of a prospective, phase 1–2 trial (NCT00411619) in patients ?3 years of age with SEGA associated with TSC. Patients received oral everolimus starting at 3 mg/m2 per day and subsequently titrated, subject to tolerability, to attain whole blood trough concentrations of 5–15 ng/mL. Change in SEGA volume, seizures, and safety assessments were the main outcome measures. Results: Of 28 patients enrolled, 25 were still under treatment at the time of analysis. Median dose was 5.3 mg/m2/day and median treatment duration was 34.2 months (range 4.7–47.1). At all time points (18, 24, 30, and 36 months), primary SEGA volume was reduced by ?30% from baseline (treatment response) in 65%–79% of patients. All patients reported ?1 adverse event (AE), mostly grade 1/2 in severity, consistent with that previously reported, and none led to everolimus discontinuation. The most commonly reported drug-related AEs were upper respiratory infections (85.7%), stomatitis (85.7%), sinusitis (46.4%), and otitis media (35.7%). No drug-related grade 4 or 5 events occurred. Conclusion: Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA. Classification of evidence: This study provides Class III evidence that everolimus, titrated to trough serum levels of 5–15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months. PMID:23325902

Krueger, Darcy A.; Care, Marguerite M.; Agricola, Karen; Tudor, Cindy; Mays, Maxwell

2013-01-01

13

Efficacy, Long-Term Safety, and Tolerability of Ziprasidone in Children and Adolescents with Bipolar Disorder  

PubMed Central

Abstract Objective The purpose of this study was to evaluate the short- and long-term efficacy and safety of ziprasidone in children and adolescents with bipolar I disorder. Methods Subjects 10–17 years of age with a manic or mixed episode associated with bipolar I disorder participated in a 4 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE). Subjects were randomized 2:1 to initially receive flexible-dose ziprasidone (40–160?mg/day, based on weight) or placebo. Primary outcome was the change in Young Mania Rating Scale (YMRS) scores from baseline. Safety assessments included weight and body mass index (BMI), adverse events (AEs), vital signs, laboratory measures, electrocardiograms, and movement disorder ratings. Results In the RCT, 237 subjects were treated with ziprasidone (n=149; mean age, 13.6 years) or placebo (n=88; mean age, 13.7 years). The estimated least squares mean changes in YMRS total (intent-to-treat population) were ?13.83 (ziprasidone) and ?8.61 (placebo; p=0.0005) at RCT endpoint. The most common AEs in the ziprasidone group were sedation (32.9%), somnolence (24.8%), headache (22.1%), fatigue (15.4%), and nausea (14.1%). In the OLE, 162 subjects were enrolled, and the median duration of treatment was 98 days. The mean change in YMRS score from the end of the RCT to the end of the OLE (last observation carried forward) was ?3.3 (95% confidence interval, ?5.0 to ?1.6). The most common AEs were sedation (26.5%), somnolence (23.5%), headache (22.2%), and insomnia (13.6%). For both the RCT and the OLE, no clinically significant mean changes in movement disorder scales, BMI z-scores, liver enzymes, or fasting lipids and glucose were observed. One subject on ziprasidone in the RCT and none during the OLE had Fridericia-corrected QT interval (QTcF) ?460?ms. Conclusion These results demonstrate that ziprasidone is efficacious for treating children and adolescents with bipolar disorder. Ziprasidone was generally well tolerated with a neutral metabolic profile. Clinical Trials Registry NCT00257166 and NCT00265330 at ClinicalTrials.gov. PMID:24111980

Çavu?, Idil; Pappadopulos, Elizabeth; Vanderburg, Douglas G.; Schwartz, Jeffrey H.; Gundapaneni, Balarama K.; DelBello, Melissa P.

2013-01-01

14

Long-term efficacy and safety outcomes with OROS-MPH in adults with ADHD.  

PubMed

Methylphenidate (MPH) is widely prescribed for adults with attention deficit hyperactivity disorder (ADHD), but data on long-term treatment and maintenance of effect are lacking. Osmotic release oral system-methylphenidate (OROS-MPH) was evaluated in a 52-wk open-label study in subjects who had previously completed a short-term placebo-controlled trial and short-term open-label extension. Efficacy was assessed using the investigator- and subject-rated Conners' Adult ADHD Rating Scales (CAARS:O-SV and CAARS:S-S), and the Clinical Global Impression - Severity (CGI-S), Sheehan Disability Scale (SDS) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Subjects completing ?52 wk of treatment were eligible for a 4-wk randomized, placebo-controlled withdrawal phase in which loss of treatment effect was assessed using CAARS:O-SV and CGI-S. In the open-label phase (n=156), mean CAARS:O-SV score decreased from baseline by 1.9±7.8 (p<0.01), and small, statistically significant improvements from baseline were observed for CAARS:S-S, CGI-S and SDS. In the double-blind phase (OROS-MPH, n=23; placebo, n=22), CAARS:O-SV increased from double-blind baseline in the OROS-MPH and placebo arms (4.0±7.6 vs. 6.5±7.8, not statistically significant). Long-term OROS-MPH treatment was well tolerated, and there was no evidence of withdrawal or rebound after discontinuation. In conclusion, the short-term benefits of OROS-MPH continue during long-term open-label treatment. Maintenance of efficacy in a placebo-controlled withdrawal design remains to be confirmed in larger patient populations. PMID:21798108

Buitelaar, Jan K; Trott, Götz-Erik; Hofecker, Maria; Waechter, Sandra; Berwaerts, Joris; Dejonkheere, Joachim; Schäuble, Barbara

2012-02-01

15

Endoscopic treatment of bleeding gastric varices by N-butyl-2-cyanoacrylate (Histoacryl) injection: Long-term efficacy and safety  

Microsoft Academic Search

Background: The long-term efficacy and safety of the endoscopic injection of N-butyl-2-cyanoacrylate (Histoacryl) were evaluated to define its role as the initial treatment for bleeding gastric varices. Methods: Ninety patients with bleeding gastric varices underwent endoscopic injections of Histoacryl for hemostasis within a 6-year period. Histoacryl was injected intravariceally as a 1:1 mixture with Lipiodol. Among the 90 patients, 5

Yi-Hsiu Huang; Hong-Zen Yeh; Gran-Hum Chen; Chi-Sen Chang; Chun-Ying Wu; Sek-Kwong Poon; Han-Chung Lien; Sheng-Shun Yang

2000-01-01

16

Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?  

PubMed Central

Background For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1) there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2) the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods Scientometric analysis of the articles representing clinical research in this area was performed to assess (1) the quality of presented evidence (type of study); and (2) the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1) editorials; (2) articles in the top specialty journals; and (3) articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles). Results Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ?6 months (n = 16) were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present. PMID:23874119

Kissin, Igor

2013-01-01

17

Long-term belatacept exposure maintains efficacy and safety at 5 years: results from the long-term extension of the BENEFIT study.  

PubMed

The Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial randomized patients receiving a living or standard criteria deceased donor kidney transplant to a more (MI) or less intensive (LI) regimen of belatacept or cyclosporine A (CsA). The 5-year results of the long-term extension (LTE) cohort are reported. A total of 456 (68.5% of intent-to-treat) patients entered the LTE at 36 months; 406 patients (89%) completed 60 months. Between Months 36 and 60, death occurred in 2%, 1% and 5% of belatacept MI, belatacept LI and CsA patients, respectively; graft loss occurred in 0% belatacept and 2% of CsA patients. Acute rejection between Months 36 and 60 was rare: zero belatacept MI, one belatacept LI and one CsA. Rates for infections and malignancies for Months 36-60 were generally similar across belatacept groups and CsA, respectively: fungal infections (14%, 15%, 12%), viral infections (21%, 18%, 16%) and malignancies (6%, 6%, 9%). No new posttransplant lymphoproliferative disorder cases occurred after 36 months. Mean calculated GFR (MDRD, mL/min/1.73?m(2) ) at Month 60 was 74 for belatacept MI, 76 for belatacept LI and 53 for CsA. These results show that the renal function benefit and safety profile observed in belatacept-treated patients in the early posttransplant period was sustained through 5 years. PMID:24047110

Rostaing, L; Vincenti, F; Grinyó, J; Rice, K M; Bresnahan, B; Steinberg, S; Gang, S; Gaite, L E; Moal, M-C; Mondragón-Ramirez, G A; Kothari, J; Pupim, L; Larsen, C P

2013-11-01

18

Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy.  

PubMed

Romiplostim was effective, safe, and well-tolerated over 6-12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP). This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin/fibrosis), platelet response (platelet count >50 × 10(9) per litre), and the proportion of patients requiring rescue treatments. Treatment-related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5% of patients and were not associated with platelet count. Median platelet counts of 50-200 × 10(9) per litre were maintained with stable doses of romiplostim (mean 5-8 ?g/kg; generally self-administered at home) throughout the study. A platelet response was achieved at least once by 95% of patients, with a platelet response maintained by all patients on a median 92% of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and well-tolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment. PMID:23432528

Kuter, David J; Bussel, James B; Newland, Adrian; Baker, Ross I; Lyons, Roger M; Wasser, Jeffrey; Viallard, Jean-Francois; Macik, Gail; Rummel, Mathias; Nie, Kun; Jun, Susie

2013-05-01

19

Long-term efficacy and safety of exemestane in the treatment of breast cancer  

PubMed Central

Exemestane, a steroidal aromatase inhibitor, is licensed for postmenopausal patients with estrogen receptor (ER)-positive breast cancer as second-line therapy in metastatic disease following antiestrogen failure and as part of sequential adjuvant therapy following initial tamoxifen. This study is a systematic literature review, evaluating exemestane in different clinical settings. The Ovid Medline (1948–2012), Embase (1980–2012), and Web of Science (1899–2012) databases were searched. Forty-two relevant articles covering randomized controlled trials were reviewed for efficacy and safety, and three for adherence. With regard to efficacy in metastatic disease, exemestane is superior to megestrol acetate after progression on tamoxifen. There is evidence for noninferiority to fulvestrant (following a prior aromatase inhibitor) and to nonsteroidal aromatase inhibitors in the first-line setting. Combined use with everolimus is shown to be more efficacious than exemestane alone following previous aromatase inhibitor use. In the adjuvant setting, a switch to exemestane after 2–3 years of tamoxifen is superior to 5 years of tamoxifen. Exemestane is noninferior to 5 years of tamoxifen as upfront therapy, and may have a role as an extended adjuvant therapy. Used as neoadjuvant therapy, increased breast conservation is achievable. As chemoprevention, exemestane significantly reduces the incidence of breast cancer in “at-risk” postmenopausal women. Exemestane is associated with myalgias and arthralgias, as well as reduced bone mineral density and increased risk of fracture, which do not appear to persist at follow-up, with subsequent return to pretreatment values. Compared with tamoxifen, there is a reduced incidence of endometrial changes, thromboembolic events, and hot flashes. Limited evidence shows nonadherence in 23%–32% of patients. Evidence is growing in support of exemestane in all clinical settings. It is generally more efficacious and has a better safety profile than tamoxifen. How it compares with the nonsteroidal aromatase inhibitors remains to be established. Further studies are required on adherence to ensure that maximum benefit is obtained. PMID:23569364

Walker, GA; Xenophontos, M; Chen, LC; Cheung, KL

2013-01-01

20

Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis  

PubMed Central

To date, anti-tumor necrosis factor alfa (anti-TNF-?) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn’s disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept therapy in patients with ankylosing spondylitis. PMID:24101863

Senabre-Gallego, José Miguel; Santos-Ramírez, Carlos; Santos-Soler, Gregorio; Salas-Heredia, Esteban; Sánchez-Barrioluengo, Mabel; Barber, Xavier; Rosas, José

2013-01-01

21

Long-term efficacy, safety and tolerability of Remoxy for the management of chronic pain.  

PubMed

Historically, chronic pain generally went under-treated for a variety of objective and subjective reasons, including difficulty to objectively diagnose and manage over a long period of time, potential serious adverse effects of commonly available medications, and patient, healthcare and societal concerns over opioid medications. More recently, in an effort to redress the under-treatment of pain, the number of prescriptions of opioid analgesics has risen dramatically. However, paralleling the increased legitimate use has been a concomitant increase in opioid abuse, misuse and diversion. Pharmaceutical companies have responded by developing a variety of opioid formulations designed to deter abuse by making the products more difficult to tamper with. One such product is Remoxy(®), an extended-release formulation of the strong opioid oxycodone. We review the efficacy, safety and tolerability of this formulation based on the available published literature. PMID:25683255

Pergolizzi, Joseph V; Zampogna, Gianpietro; Taylor, Robert; Raffa, Robert B

2015-03-01

22

Long-term safety and efficacy of telmisartan/amlodipine single pill combination in the treatment of hypertension.  

PubMed

The use of multiple drug regimens is increasingly recognized as a tacit requirement for the management of hypertension, a necessity fueled in part by rising rates of metabolic syndrome and diabetes. By targeting complementary pathways, combinations of antihypertensive drugs can be applied to provide effective blood pressure control while minimizing side effects and reducing exposure to high doses of individual medications. In addition, combination therapies, including angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs), have the added benefit of reducing cardiovascular mortality and morbidity over other dual therapies while providing equivalent blood pressure control. It is possible that angiotensin receptor blockers (ARBs), which unlike ACE inhibitors are minimally affected by upregulation of alternative pathways for angiotensin II accumulation following long-term treatment, would also provide such outcome benefits. At issue, however, is maintaining patient compliance, as adding medications is known to reduce adherence to treatment regimens. The purpose of this review is to summarize existing trial data for the long-term safety and efficacy of a recent addition to the armamentarium of dual-antihypertensive therapeutic options, the telmisartan/amlodipine single pill combination. The areas where long-term data are lacking, notably clinical information regarding minorities and women, will also be discussed. PMID:23662062

Billecke, Scott S; Marcovitz, Pamela A

2013-01-01

23

Long-term Efficacy and Safety of Questionnaire-based Initiation of Urgency Urinary Incontinence Treatment  

PubMed Central

Objectives To determine the longer-term efficacy and safety of initiating treatment for urgency-predominant urinary incontinence (UUI) in women diagnosed using a simple questionnaire rather than an extensive evaluation. Study Design Women completing a 12-week randomized controlled trial of fesoterodine therapy for UUI diagnosed by questionnaire were invited to participate in a 9-month open label continuation study. UUI and voiding episodes were collected using voiding diaries. Participant satisfaction was measured by questionnaire. Safety was assessed by measurement of post void residual volume and adverse event monitoring; if necessary, women underwent specialist evaluation. Longitudinal changes in UUI and voiding episodes were evaluated using linear mixed models adjusting for baseline. Results Of the 567 women completing the randomized trial, 498 (87.8%) took at least one dose of medication during this open label study. Compared to the enrollment visit in the randomized trial, fesoterodine was associated with a reduction in total incontinence episodes/day and urgency incontinence episodes/day at the end of the open label study [adjusted mean (standard error (SE)) 4.6 (0.12) to 1.2 (0.13) and 3.9 (0.11) to 0.9 (0.11) respectively, p-value<.0001 for both]. Most women were satisfied with treatment (89%, 92%, and 93% at 3, 6, and 9 months). Twenty-six women experienced 28 serious adverse events, one of which was considered possibly treatment-related. Twenty-two women had specialist evaluation: 5 women’s incontinence was misclassified by the 3IQ; none experienced harm due to misclassification. Conclusions Using a simple validated questionnaire to diagnose and initiate treatment for UUI in community dwelling women is safe and effective, allowing timely treatment by primary care practitioners. PMID:23659987

HESS, Rachel; HUANG, Alison J.; RICHTER, Holly E.; GHETTI, Chiara C.; SUNG, Vivian W.; BARRETT-CONNOR, Elizabeth; GREGORY, W. Thomas; PINKERTON, JoAnn V.; BRADLEY, Catherine S.; KRAUS, Stephen R.; ROGERS, Rebecca G.; SUBAK, Leslee L.; JOHNSON, Karen C.; ARYA, Lily A.; SCHEMBRI, Michael; BROWN, Jeanette S.

2014-01-01

24

Multicentric cohort study on the long-term efficacy and safety of electronic cigarettes: study design and methodology  

PubMed Central

Background While electronic cigarettes are forbidden in several countries, their sales are exploding in many others. Although e-cigarettes have been proposed as long-term substitutes for traditional smoking or as a tool for smoking cessation, very scarce data are available on their efficacy and safety. We describe the protocol of a 5-year multicentric prospective study aimed to evaluate short- and long-term adherence to e-cigarette smoking and the efficacy of e-cigarettes in reducing and/or quitting traditional cigarette smoking. The study will also compare the health effects of electronic vs traditional vs mixed cigarette smoking. Methods/design From June to December 2013, we will enroll adult smokers of: (EC) e-cigarettes (self-reported inhaling ??50 puffs per week since ??6 months); (TC) traditional cigarettes (??1 per day since ??6 m); (Mixed) both electronic and traditional cigarettes (?1 per day since ??6 m). Eligible subjects will be requested participation through newspaper advertisements and direct contact at the shops. Each subject will have to compile a structured questionnaire at enrolment and after 6, 12, 24, 36 and 60 months. The level of carbon monoxide in expired after breath will be evaluated in all subjects declaring no traditional cigarette smoking in any follow-up phase, using portable carbon monoxide analyzers. The primary outcomes are traditional smoking cessation rates and number of smoked cigarettes. Secondary outcomes include adherence to e-cigarettes, self-reported adverse events, quality of life, and time to hospital admission for one among cardiovascular diseases, chronic obstructive pulmonary diseases, cancer of the lung, esophagus, larynx, oral cavity, bladder, pancreas, kidney, stomach, cervix, and myeloid leukemia. Admissions will be checked using official discharge data of the Abruzzo Region. A minimum of 500 subjects in each group will be enrolled, for a total of 1500 participants. Cox proportional hazards analysis will be used to calculate adjusted relative hazards of smoking cessation by each variable. Discussion Data on long-term efficacy and safety of e-cigarettes will be of utmost importance to form the basis for guidelines and regulatory decisions on e-cigarettes. Trial registration The protocol has been registered (NCT01785537) and approved by the Ethics Committee of the University of Chieti (Record n. 6; 25-03-2013). PMID:24063569

2013-01-01

25

Efficacy and safety of topiramate in refractory epilepsy: a long-term prospective trial.  

PubMed

The effects of topiramate in 15 patients with drug refractory epilepsy or Lennox-Gastaut syndrome were assessed in an open, add-on prospective study. After a follow-up of 14-21 months, six patients are still on topiramate (mean dosage 583 mg/day, range 400-800 mg/day), and nine have discontinued treatment because of adverse events (n = 6), inefficacy (n = 2) or poor compliance (n = 1). Nine patients (69%) continued to have > or = 50% reduction in seizure frequency during the last two months of treatment, and one has been seizure-free for the last 19 months. The most common adverse events were somnolence, weight loss, mental slowing, fatigue, ataxia and irritability. Most of these events were reversible, but withdrawal of treatment was required in six cases as a result of ataxia (two patients), somnolence, metabolic acidosis, irritability or psychotic symptoms (one patient each). It is concluded that topiramate is a valuable agent for long-term management of refractory epilepsy. PMID:8978450

Tartara, A; Sartori, I; Manni, R; Galimberti, C A; Di Fazio, M; Perucca, E

1996-12-01

26

Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal  

PubMed Central

Background Prolonged-release melatonin (PRM) 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation. Objective To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment. Methods Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary), adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]). Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM. Results Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as “good” or “very good” was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production. Conclusion Results support the efficacy and safety of PRM in primary insomnia patients aged 20–80 throughout 6–12 months of continuous therapy. PRM discontinuation even after 12 months was not associated with adverse events, withdrawal symptoms, or suppression of endogenous melatonin production. PMID:21845053

Lemoine, Patrick; Garfinkel, Doron; Laudon, Moshe; Nir, Tali; Zisapel, Nava

2011-01-01

27

Efficacy and safety of itraconazole in the long-term treatment of onychomycosis.  

PubMed

Sixty-one patients with a clinical diagnosis of onychomycosis in finger or toe nails were treated with itraconazole 100 mg/day or griseofulvin 500 mg/day for six to nine months. The infective causes were Trichophyton rubrum, Trichophyton mentagrophytes, or Trichophyton violaceum, and in two cases Candida albicans. A total of 27 finger and 390 toe nails were infected. Statistically significant intragroup reductions from baseline symptom severity values were seen at endpoint (month 6 or 9) for both treatment groups for all parameters: colour change, thickness, brittleness and unaffected area. No clinically or statistically significant differences between the treatment groups were seen at endpoint. However, the itraconazole group continued to improve during the follow-up, while the mean symptom severity ratings remained the same in the griseofulvin group. All itraconazole patients and 85% of griseofulvin patients were rated as cured or markedly improved at endpoint. Nineteen out of 26 evaluable itraconazole patients (73%) remained cured during the three month follow-up period, compared with 12 out of 17 griseofulvin patients (71%). The rather large number of drop-outs, especially among griseofulvin patients, makes it difficult to draw definitive conclusions of the symptom recurrence. Two itraconazole patients stopped medication due to an adverse event, compared to four patients in the griseofulvin group. The clinical laboratory data on itraconazole-treated patients did not show any statistically or clinically significant changes. In conclusion, itraconazole was at least as effective as griseofulvin in the treatment of onychomycosis. The itraconazole group continued to improve after the treatment was stopped. The results show that itraconazole 100 mg/day is safe and efficient in the long-term treatment of fungal nail infections. PMID:1324238

Piepponen, T; Blomqvist, K; Brandt, H; Havu, V; Hollmen, A; Kohtamäki, K; Lehtonen, L; Turjanmaa, K

1992-02-01

28

Long-Term Treatment Efficacy and Safety of Clevudine Therapy in Naïve Patients with Chronic Hepatitis B  

PubMed Central

Background/Aims Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naïve patients with CHB were investigated. Methods In this retrospective study, 152 naïve Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated. Results The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level ?6 log10 IU/mL (p=0.032) and detectable serum HBV DNA (?12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients. Conclusions The results of long-term CLV therapy for the treatment of naïve patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naïve patients given the availability of other more potent, safer antiviral agents. PMID:23170155

Choung, Bum Su; Jeon, Byung Jun; Lee, Seok; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae-Ghon

2012-01-01

29

Long-term outcome of patients with active ankylosing spondylitis with etanercept-sustained efficacy and safety after seven years  

PubMed Central

Introduction Data from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-? therapy in patients with ankylosing spondylitis (AS) are scarce. This is the first report on continuous treatment with the TNF? fusion protein etanercept over seven years (y). Methods Overall, 26 patients with active AS were initially treated with etanercept 2 × 25 mg s.c./week with no concomitant disease modifying anti-rheumatic drugs (DMARDs) or steroids. The clinical response was assessed by standardized parameters. The primary outcome was the proportion of patients in the Spondyloarthritis International Society (ASAS) partial remission at seven years. AS disease activity scores (ASDAS) for status and improvement were compared to conventional outcome measures. Results Overall, 21/26 patients (81%) completed two years of treatment and 16/26 patients (62%) completed seven years. In the completer analysis, 31% patients were in ASAS partial remission at seven years, while 44% patients showed an ASDAS inactive disease status. Mean Bath AS activity index (BASDAI) scores, which were elevated at baseline (6.3 ± 0.9), showed constant improvement and remained low: 3.1 ± 2.5 at two years and 2.5 ± 2.2 at seven years, while ASDAS also improved (3.9 ± 0.7 at baseline, 1.8 ± 0.9 at two years, 1.6 ± 0.8 at seven years), all P <0.001. From the 10 dropouts, only 5 patients discontinued treatment due to adverse events. Patients who completed the study had lower baseline Bath AS function index (BASFI) scores vs. patients who discontinued. No other clinical parameter at baseline could predict any long-term outcome. Conclusions This study confirms the clinical efficacy and safety of etanercept in patients with active AS over seven years of continuous treatment. After seven years, more than half of the initially treated patients remained on anti-TNF therapy, and one-third were in partial remission. Trial Registration ClinicalTrials.gov: NCT01289743 PMID:23786760

2013-01-01

30

Long-term safety and efficacy of natalizumab in relapsing-remitting multiple sclerosis: impact on quality of life  

PubMed Central

Natalizumab was the first monoclonal antibody to be approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) based on its short-term efficacy and overall tolerability. However, the incidence of treatment-associated progressive multifocal leukoencephalopathy (PML), an infection of the brain caused by the John Cunningham virus, jeopardized this efficacious treatment from the beginning. Eight years after licensing of natalizumab, long-term studies confirm the considerable and sustained efficacy of natalizumab, although the PML complication still threatens one of the most successful treatments available for RRMS. During these years, considerable progress has been made in identification of risk factors that allow more effective management of PML risk. In addition, long-term studies to define better when to start or stop treatment and to optimize treatment strategies after cessation of natalizumab are ongoing, and hopefully will improve management and will allow natalizumab to remain as a valuable therapeutic option for patients with highly active RRMS. PMID:24741337

Planas, Raquel; Martin, Roland; Sospedra, Mireia

2014-01-01

31

The long-term efficacy and safety of a testosterone mucoadhesive buccal tablet in testosterone-deficient men.  

PubMed

What's known on the subject? and What does the study add? Striant® SR is the only available buccal delivery system for testosterone replacement therapy. Previous pharmacokinetic studies have shown that Striant SR effectively produces physiological serum testosterone levels in hypogonadal men. Efficacy and safety data from previously unpublished studies over 2 years of continuous use indicate that Striant SR is effective long term in maintaining serum testosterone within a physiological range, is well tolerated and has a high level of patient acceptance. Striant® sustained-release (SR) is a mucoadhesive buccal tablet (30 mg testosterone, The Urology Company) that adheres to the gum surface in the mouth providing controlled- and sustained-release of testosterone over a 12-h dosing period, offering a unique and rational method of testosterone delivery. Striant SR is indicated for testosterone-replacement therapy (TRT) for male hypogonadism when testosterone deficiency has been confirmed by clinical features and biochemical tests. Pharmacokinetic studies have shown that testosterone is released from Striant SR in a manner similar to the normal daily rhythm of endogenous testosterone secretion, with serum levels rising rapidly after insertion and peak levels reached by the second 12-hourly dose with no accumulation over time. In clinical trials involving hypogonadal men receiving Striant SR for up to 2 years, mean serum testosterone levels have always remained within the normal range. Striant SR is well tolerated, with gum-related disorders (such as irritation, inflammation and gingivitis) and taste perversion being the most commonly reported adverse events, reported by 5.6-16.3% and 3.0-4.1% of patients, respectively. Once patients have become accustomed to it, Striant SR has a high level of patient acceptance. In a long-term study, 90% of patients rated the twice-daily dosing as acceptable, just under half preferred it to other forms of TRT that they have used and 96% found it to be cosmetically acceptable. There is no clinically significant risk of testosterone transfer from Striant SR, as any testosterone that may be present in the saliva when swallowed is subject to extensive first-pass hepatic metabolism. It is pertinent to note that the saliva of eugonadal men contains similar levels of endogenous testosterone. Buccal delivery is particularly suitable where easy and rapid reversal of treatment might be required (such as in late-onset hypogonadism) and where there is a need to avoid the potential for transfer of testosterone to women and young children. PMID:22288877

Dinsmore, Wallace W; Wyllie, Michael G

2012-07-01

32

Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis  

PubMed Central

In 1977, 5-aminosalicylic acid (5-ASA) was discovered as a therapeutically active moiety of sulfasalazine (SASP) and was launched for topical and oral therapy of ulcerative colitis (UC) in 1984. As a first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release). In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release) were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix®, nor MMX 5-ASA, nor Pentasa® granules have initially been developed for once-daily (OD) dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests. Thus, patents for minor changes to the formulation may serve as protection against drug companies trying to launch generic versions. Randomized controlled trials performed on OD dosing in induction of remission have demonstrated that OD administration of 5-ASA is as effective as conventional dosing in mild to moderate active UC. The three 5-ASA products MMX, Salofalk®, and Pentasa® employed in those studies so far have not shown differences in efficacy between OD and conventional dosing. No differences regarding safety outcomes have been detected between OD and conventional dosing, including incidence of adverse events, serious adverse events, or withdrawal from treatment due to an adverse event. Although the majority of patients prefer OD dosing to conventional dosing, it was not possible to detect differences in adherence between OD and multiple dose regimens in the clinical trial setting. Well-designed and controlled large-scale community-based studies are necessary to further investigate and prove the point of improved long-term adherence and treatment efficacy in OD dosing. PMID:25285021

Böhm, Stephan Karl; Kruis, Wolfgang

2014-01-01

33

The long-term safety and efficacy of brinzolamide 1.0% (Azopt) in patients with primary open-angle glaucoma or ocular hypertension  

Microsoft Academic Search

PURPOSE: Oral carbonic anhydrase inhibitors used to treat glaucoma have significant systemic side effects. Brinzolamide 1.0%, a new topical ocular carbonic anhydrase inhibitor, is effective apparently without significant systemic side effects. This study was performed to establish the long-term safety and efficacy of brinzolamide 1.0% two and three times daily for primary open-angle glaucoma and ocular hypertension.METHODS: An 18-month, multicenter,

Wayne F March; Katherine I Ochsner

2000-01-01

34

A Study of the Safety and Efficacy of Calcipotriol and Betamethasone Dipropionate Scalp Formulation in the Long-Term Management of Scalp Psoriasis  

PubMed Central

Background Effective and safe products are needed for long-term management of scalp psoriasis. This study investigated the long-term safety and efficacy of a two-compound formulation (calcipotriol 50 ?g/g plus betamethasone dipropionate 0.5 mg/g) for scalp psoriasis. Methods In this 52-week, international, double-blind study, 869 patients with moderate-to-severe scalp psoriasis were randomized to either a two-compound scalp formulation (n = 429) or calcipotriol (n = 440). Results Adverse drug reactions were less frequent in the two-compound group compared with the calcipotriol group (17.2 vs. 29.5%; p < 0.001). Incidences of adverse events possibly associated with long-term corticosteroid use were low in both the two-compound (2.6%) and the calcipotriol (3.0%) groups. Disease was satisfactorily controlled in 92.3% of visits in the two-compound group versus 80.0% in the calcipotriol group (p < 0.001). Conclusion The two-compound scalp formulation demonstrated a high level of safety and efficacy in long-term management of scalp psoriasis. PMID:18787325

Luger, T.A.; Cambazard, F.; Larsen, F.G.; Bourcier, M.; Gupta, G.; Clonier, F.; Kidson, P.; Shear, N.H.

2008-01-01

35

Long-term efficacy and safety of otilonium bromide in the management of irritable bowel syndrome: a literature review  

PubMed Central

Irritable bowel syndrome (IBS) is a very common functional gastrointestinal disorder characterized by abdominal pain or discomfort and altered bowel habits. The disease affects a large part of the world population. The clinical course is mostly characterized by a cyclic recurrence of symptoms. Therefore, IBS patients should receive, as an initial therapeutic approach, a short course of treatment, and long-term treatment should be reserved for those patients with recurrent symptoms. The available clinical trials show that significant improvement of the symptoms over placebo could be achieved with various drugs, although this improvement is frequently time dependent and with high relapse rates after the cessation of the treatment. In a proportion of patients, clinically obvious relapse could appear long after stopping the treatment. Some of the available pharmacologic agents, including otilonium bromide (OB), are able to significantly prolong the time to the appearance of relapse, compared with placebo. As a consequence, some authors suggest that a cyclic treatment could be of benefit. Antispasmodic drugs have been used for many years in an effort to control the symptoms of IBS. OB is a poorly absorbed spasmolytic drug, exerting significantly greater control of the symptoms of IBS compared with placebo. Recent data suggest that the drug could effectively be used for the long-term management of patients with IBS. The aim of this review is to provide the reader with an evidence-based overview of the efficacy and tolerability of OB in the long-term management of IBS patients, based on the results of the clinical trials published so far. PMID:24741324

Triantafillidis, John K; Malgarinos, George

2014-01-01

36

Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques  

SciTech Connect

Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of {delta}vpuSHIV{sub PPC}, a live virus vaccine derived from SHIV{sub PPC}. Macaques were administered two inoculations of {delta}vpuSHIV{sub PPC}, three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years.

Yankee, Thomas M. [Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, 3025 WHW - MS 3029, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)], E-mail: tyankee@kumc.edu; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia [Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, 3025 WHW - MS 3029, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Stephens, Edward B. [Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, 3025 WHW - MS 3029, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Narayan, Opendra [Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, 3025 WHW - MS 3029, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)

2009-01-05

37

Long-term safety and efficacy of radiofrequency ablation in the treatment of sleep disordered breathing: a meta-analysis.  

PubMed

Radiofrequency ablation (RFA) is used in the treatment of sleep disordered breathing (SDB), particularly in the alleviation of snoring. The literature provides evidence that the short-term results are promising; however, the long-term efficacy is a matter of contention. In this article, we present the results of a literature search of studies that use RFA in the treatment of SDB which have a follow-up time of greater than a year. RFA was found to be a safe technique with minimal morbidity. The overall Visual Analogue score from six studies showed the overall mean improvement to be 4.3 (confidence intervals 3.4-5.12). Apnea Hypopnea Index (AHI), improved significantly in five of the studies analysed. Epworth Sleepiness Score (ESS), improved significantly in six of the studies analysed. In conclusion, the evidence suggests that RFA for SDB results in a significant improvement in follow-up times of at least a year. Since RFA can be applied in a clinic setting and leads to minimal disruption to daily life, this treatment option can be considered for those unwilling to participate in the more traditional surgical options for SDB. PMID:24510179

Veer, Vik; Yang, Woo-Young; Green, Richard; Kotecha, Bhik

2014-11-01

38

Long-term efficacy and safety of topical tacrolimus in the management of ulcerative/erosive oral lichen planus.  

PubMed

The long-term safety and clinical benefit of topical tacrolimus for the management of erosive or ulcerative oral lichen planus has not been evaluated. 50 adults (39 female 11 male; group median age 59, range 29-88 years) with symptomatic, erosive or ulcerative lichen planus recalcitrant to topical corticosteroids applied 0.1% topical tacrolimus ointment twice daily to symptomatic mucosal lesions. Topical tacrolimus was applied for a median time of 19.8 months (range 2-39 months) in this patient group. Fourteen percent of the patients had complete resolution of ulcers or erosions, 80% partial resolution and 6% reported no clinical benefit. The most common adverse effects were a burning sensation (16%) at the site of application and transient taste disturbance (8%). No significant, long-standing changes in hepatic or renal biochemistry were observed. The mean tacrolimus level decreased with duration of therapy from 2.7 microg/l (week 1) to 0.5 microg/l (week 32). 0.1% topical tacrolimus is an effective means of controlling the symptoms and signs of erosive or ulcerative oral lichen planus and has no notable adverse effects over a mean duration of application of 19.8 months. PMID:14693491

Hodgson, Tim A; Sahni, Neeraj; Kaliakatsou, Fotini; Buchanan, John A G; Porter, Stephen R

2003-01-01

39

Safety and Efficacy of Endoscopic Retrograde Cholangiopancreatography in Patients with Post-Liver Transplant Biliary Complications: Results of a Cohort Study with Long-Term Follow-Up  

PubMed Central

Background/Aims Endoscopic retrograde cholangiopancreatography (ERCP) is the standard approach for the management of biliary complications in liver transplant patients; however, its safety and efficacy have not been established in this setting. This study was performed to evaluate the safety and long-term efficacy of ERCP in transplant patients. Methods The case reports of 1,500 liver transplant patients were reviewed. Orthotopic liver transplantation (OLT) patients were matched 1:2 with non-OLT patients and followed-up for long-term outcome (median, 7.4 years). Results Of the 1,500 liver transplant patients, 94 (6.3%) underwent 150 ERCPs after OLT. Anastomotic strictures were present in 45 patients, biliary stones in 24, biliary leaks in 7, papillary stenosis in 2, and primary sclerosing cholangitis in 1. An ERCP success rate of 90.7% was achieved; biliary stenting led to resolution of the bile leak in 7/7 (100%) patients, and biliary stones were removed in 21/24 (87.5%) patients. In addition, 34 of 45 patients with anastomotic stricture underwent endoscopic dilation. We obtained complete resolution in 22/34 (64.7%) patients. OLT patients did not show a higher probability of complications (odds ratio [OR], 1.04), of pancreatitis (OR, 0.80) or of bleeding (OR, 1.34). Conclusions ERCP is safe and effective for the treatment of post-OLT biliary complications, has a low rate of pancreatitis and results in a durable effect. PMID:21927662

Sanna, Claudia; Giordanino, Chiara; Giono, Ilaria; Barletti, Claudio; Ferrari, Arnaldo; Recchia, Serafino; Reggio, Dario; Repici, Alessandro; Ricchiuti, Alessandro; Salizzoni, Mauro; Baldi, Ileana; Ciccone, Giovannino; Rizzetto, Mario

2011-01-01

40

Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis  

PubMed Central

Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i) systematically review the evidence regarding the long-term efficacy of omalizumab in patients with persistent uncontrolled allergic asthma, and to (ii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A comprehensive search for randomized controlled trials (RCTs; ?52 weeks) was performed, and six studies met our final inclusion criteria (n = 2,749). Omalizumab was associated with significant improvements in quality of life and the Global Evaluation of Treatment Effectiveness. Omalizumab also allowed patients to completely withdraw from inhaled corticosteroid therapy and did not increase the overall incidence of adverse events. However, there was insufficient evidence that omalizumab reduced the incidence of exacerbations, and the cost-effectiveness of omalizumab varied across studies. Our data indicated that omalizumab use for at least 52 weeks in patients with persistent uncontrolled allergic asthma was accompanied by an acceptable safety profile, but it lacked effect on the asthma exacerbations. Use of omalizumab was associated with a higher cost than conventional therapy, but these increases may be cost-effective if the medication is used in patients with severe allergic asthma. PMID:25645133

Lai, Tianwen; Wang, Shaobin; Xu, Zhiwei; Zhang, Chao; Zhao, Yun; Hu, Yue; Cao, Chao; Ying, Songmin; Chen, Zhihua; Li, Wen; Wu, Bin; Shen, Huahao

2015-01-01

41

Efficacy and Safety of Omeprazole in the Long-Term Treatment of Peptic Ulcer and Reflux Oesophagitis Resistant to Ranitidine  

Microsoft Academic Search

A total of 143 patients with peptic ulceration of the duodenum, stomach and oesophagus who did not respond to 3 or more months of high-dose treatment with ranitidine, 450 mg or more daily, were treated with oral omeprazole, 40 mg daily. In 94% of the patients, ulcers healed within 2–8 weeks. After healing, 133 patients underwent long-term maintenance treatment with

G. H. G. Brunner; R. Lamberts; W. Creutzfeldt

1990-01-01

42

Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension  

PubMed Central

Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were ?28, ?27, ?27, and ?28%; and in apolipoprotein B ?29, ?28, ?30, and ?31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6–12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. Clinicaltrials.gov NCT00694109. PMID:24366918

Santos, Raul D.; Duell, P. Barton; East, Cara; Guyton, John R.; Moriarty, Patrick M.; Chin, Wai; Mittleman, Robert S.

2015-01-01

43

Safety and Efficacy of the Long-term Adjuvant Treatment of Primary Intermediate to High-Risk Malignant Melanoma (UICC\\/AJCC Stage II and III) with a Standardized Fermented European Mistletoe (Viscum album L.)  

Microsoft Academic Search

Summary Background: Mistletoe therapy is the most frequently used complementary treatment in cancer patients in Germany and Switzerland. However, its safety and efficacy were controversially discussed, also in case of malignant melanoma (MM). Objectives: The present study should evaluate the therapeutic safety and effi- cacy of a long-term therapy with a stand- ardized fermented European mistletoe (Viscum album L.) extract

Matthias Augustina; Paul R. Bockb; Marita Karasmann; Berthold Schneider

44

Phase III safety and efficacy study of long-term brinzolamide/timolol fixed combination in Japanese patients with open-angle glaucoma or ocular hypertension  

PubMed Central

Background The purpose of this study was to evaluate the safety and efficacy of a long-term, twice-daily brinzolamide 1%/timolol 0.5% fixed combination ophthalmic suspension (BRINZ/TIM-FC) in Japanese patients with open-angle glaucoma (primary open-angle, normal-tension, exfoliation, or pigmentary) or ocular hypertension. Methods This was a prospective, nonrandomized, multicenter, open-label, Phase III study of Japanese patients aged ?20 years with diagnoses of open-angle glaucoma or ocular hypertension. Patients were treated with topical BRINZ/TIM-FC twice daily for 52 weeks. The primary endpoint was mean reduction from baseline in intraocular pressure. Data were analyzed using repeated-measures analysis of variance and t-tests. Adverse events and ophthalmic, physiologic, and laboratory parameters were measured throughout the study as safety endpoints. A total of 126 patients (mean ± SD age, 63±12 years) were enrolled, and 125 received BRINZ/TIM-FC. Results Mean intraocular pressure was significantly reduced from baseline at weeks 4 through 52, with changes ranging from ?4.1 mmHg to ?5.7 mmHg (P<0.0001, all time points). Adverse events related to BRINZ/TIM-FC treatment were observed in 22% of patients. No substantial changes from baseline were observed in ophthalmic, physiologic, or laboratory variables. Conclusion Long-term, twice-daily BRINZ/TIM-FC therapy produced and maintained significant intraocular pressure reductions and was generally well tolerated in Japanese patients with open-angle glaucoma or ocular hypertension. PMID:24403818

Nakajima, Masayuki; Iwasaki, Naoki; Adachi, Masaki

2014-01-01

45

Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis: findings from an open-label treatment extension  

PubMed Central

Objective To assess the long-term efficacy and safety of infliximab plus methotrexate in juvenile rheumatoid arthritis (JRA). Methods Patients eligible for the open-label extension (OLE, weeks 52–204) received infliximab 3–6 mg/kg every 8 weeks plus methotrexate. Results Of the 78/122 (64%) children entering the OLE, 42 discontinued infliximab, most commonly due to consent withdrawal (11 patients), lack of efficacy (eight patients) or patient/physician/sponsor requirement (eight patients). Infliximab (mean dose 4.4 mg/kg per infusion) was generally well tolerated. Infusion reactions occurred in 32% (25/78) of patients, with a higher incidence in patients positive for antibodies to infliximab (58%, 15/26). At week 204, the proportions of patients achieving ACR-Pedi-30/50/70/90 response criteria and inactive disease status were 44%, 40%, 33%, 24% and 13%, respectively. Conclusions In the limited population of JRA patients remaining in the study at 4 years, infliximab was safe and effective but associated with a high patient discontinuation rate. Clinical trials registration number NCT00036374. PMID:20237125

Ruperto, Nicolino; Lovell, Daniel J; Cuttica, Ruben; Woo, Patricia; Meiorin, Silvia; Wouters, Carine; Silverman, Earl D; Balogh, Zsolt; Henrickson, Michael; Davidson, Joyce; Foeldvari, Ivan; Imundo, Lisa; Simonini, Gabriele; Oppermann, Joachim; Xu, Stephen; Shen, Yaung-Kaung; Visvanathan, Sudha; Fasanmade, Adedigbo; Mendelsohn, Alan; Martini, Alberto; Giannini, Edward H

2010-01-01

46

Combination therapy of hydroxycarbamide with anagrelide in patients with essential thrombocythemia in the evaluation of Xagrid® efficacy and long-term safety study  

PubMed Central

Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid® Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received hydroxycarbamide + anagrelide. Monotherapies received before this combination were hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581×109/L and 411×109/L before and after starting hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400×109/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600×109/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory. (Clinicaltrials.gov identifier:NCT00567502) PMID:24334294

Gugliotta, Luigi; Besses, Carlos; Griesshammer, Martin; Harrison, Claire; Kiladjian, Jean-Jacques; Coll, Ruth; Smith, Jonathan; Abhyankar, Brihad; Birgegård, Gunnar

2014-01-01

47

Long-term efficacy and safety of once-daily fosamprenavir 1400 mg boosted by ritonavir 100 mg: the BOLD100 study.  

PubMed

In a retrospective database study at two HIV treatment centres, medical records were accessed to evaluate long-term efficacy and safety parameters in all HIV-infected adults who had achieved HIV-1 RNA <50 copies/mL following the initiation of fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once-daily (QD)-containing regimens between January 2004 and January 2006. Data were available for 20 antiretroviral (ARV)-naïve patients (baseline median HIV-1 RNA 5.0 log(10) copies/mL; CD4+ cell count 307 cells/mm(3)), 30 protease inhibitor (PI)-naïve, ARV-experienced patients (HIV-1 RNA 3.6 log(10) copies/mL; CD4+ count 348 cells/mm(3)) and 25 PI-experienced patients switching to FPV/RTV100 for reasons other than virological failure (HIV-1 RNA 2.7 log(10) copies/mL; CD4+ count 328 cells/mm(3)). HIV-1 RNA <50 copies/mL was achieved in 100% of the ARV-naïve cohort (median monitoring period, 2.4 years; range, 1.4-3.2 years), 87% of the PI-naïve cohort (2.4 years; range, 1.2-3.4 years) and 88% of the PI-experienced cohort (2.2 years; range, 1.0-3.2 years). Virological failure occurred in 0%, 7% and 8% of the cohorts, respectively, and median CD4+ count increased above baseline by 224, 155 and 115 cells/mm(3), respectively. Change from baseline in median fasting lipids was: total cholesterol +12, -6, -2 mg/dL; low-density lipoprotein-cholesterol 0, -5, +12 mg/dL; high-density lipoprotein-cholesterol +4, +2, +7 mg/dL; triglycerides +9, -21, -65 mg/dL, respectively. In conclusion, FPV/RTV 1400/100 mg QD-containing regimens remained effective long-term in all ARV-naïve and most PI-naïve and PI-experienced HIV-infected patients. PMID:22581890

Blick, G; Greiger-Zanlungo, P; Gretz, S; Han, J; Dupree, D; Garton, T; Yau, L H; Wine, B C; Pakes, G E

2012-03-01

48

Long term efficacy, safety, and tolerabilitity of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF100) in the treatment of functional chronic constipation  

Microsoft Academic Search

AIMSTo assess the long term therapeutic effectiveness, safety, and tolerability of low daily doses of isosmotic PEG electrolyte solutions (PMF-100) administered for a six month period for the treatment of functional constipation, in a double blind, placebo controlled, parallel group study.METHODSAfter an initial four week run in period with PMF-100 (250 ml twice daily; PEG 14.6 g twice daily), 70

E Corazziari; D Badiali; G Bazzocchi; G Bassotti; P Roselli; G Mastropaolo; M G Lucà; R Galeazzi; E Peruzzi

2000-01-01

49

Open-label infliximab therapy in Crohn's disease: a long-term multicenter study of efficacy, safety and predictors of response  

Microsoft Academic Search

BackgroundEfficacy of infliximab in Crohn's disease (CD) showed by randomized controlled trials must be confirmed in clinical practice. We aimed to evaluate efficacy and safety of infliximab in CD patients of the Madrid area, looking for clinical predictors of response.

Yago González-Lama; Antonio López-San Román; Ignacio Marín-Jiménez; Begoña Casis; Isabel Vera; Fernando Bermejo; José Lázaro Pérez-Calle; Carlos Taxonera; Francisca Martínez-Silva; Luis Menchén; Pilar Martínez-Montiel; Marta Calvo; José Antonio Carneros; Pilar López; Juan Luis Mendoza; José María Milicua; Alaín Huerta; Fernando Sánchez; Luis Abreu; Natalia López-Palacios; José Maté; Javier P. Gisberta

2008-01-01

50

Long-term efficacy of biologics in dermatology  

PubMed Central

Chronic dermatologic diseases affect millions of people. The long-term nature of these diseases creates psychological and financial burden as well as substantially impacts patients' quality of life. Biologics, including adalimumab, etanercept, alefacept, efalizumab, and infliximab, are the newest therapeutic agents in the treatment of moderate-to-severe psoriasis and psoriatic arthritis and have been used in a variety of other dermatologic diseases. These agents act relatively quickly and effectively in 12-week clinical trials. Because these agents are used to treat patients for longer than 12 weeks, there is a need to review the safety and efficacy of these agents over longer periods of time. Many levels of evidence are available for biologics including high level of evidence from large, randomized, double-blind, placebo-controlled clinical studies. This review focuses on the available data for efficacy and safety for greater than 24 weeks of therapy. The studies supporting the use of rituximab and intravenous immunoglobulin in autoimmune blistering diseases are also presented in this review. PMID:19222514

Castelo-Soccio, Leslie; Van Voorhees, Abby S.

2010-01-01

51

Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial.  

PubMed

We describe the 2-year follow-up of an open-label trial (CT-AMT-011-01) of AAV1-LPL(S447X) gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis. The LPL(S447X) gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis. Primary objectives were to assess the long-term safety of alipogene tiparvovec and achieve a ?40% reduction in fasting median plasma triglyceride (TG) at 3-12 weeks compared with baseline. Cohorts 1 (n=2) and 2 (n=4) received 3 × 10(11)?gc?kg(-1), and cohort 3 (n=8) received 1 × 10(12)?gc?kg(-1). Cohorts 2 and 3 also received immunosuppressants from the time of alipogene tiparvovec administration and continued for 12 weeks. Alipogene tiparvovec was well tolerated, without emerging safety concerns for 2 years. Half of the patients demonstrated a ?40% reduction in fasting TG between 3 and 12 weeks. TG subsequently returned to baseline, although sustained LPL(S447X) expression and long-term changes in TG-rich lipoprotein characteristics were noted independently of the effect on fasting plasma TG. PMID:22717743

Gaudet, D; Méthot, J; Déry, S; Brisson, D; Essiembre, C; Tremblay, G; Tremblay, K; de Wal, J; Twisk, J; van den Bulk, N; Sier-Ferreira, V; van Deventer, S

2013-04-01

52

Biologic safety in psoriasis: review of long-term safety data.  

PubMed

The development of targeted biologic agents has revolutionized the treatment of psoriasis. In this review, the authors focus on the published long-term (? one year) safety data for the use of tumor necrosis factor-? antagonists etanercept, infliximab, and adalimumab, as well as the IL-12/IL-23 antagonist ustekinumab, in adult patients with moderate-to-severe psoriasis. The efficacy of these currently available biologic therapies has been demonstrated in several studies, and their safety profiles are also reassuring. PMID:25741401

Mansouri, Yasaman; Goldenberg, Gary

2015-02-01

53

Long-term safety and efficacy of olanzapine long-acting injection in patients with schizophrenia or schizoaffective disorder: a 6-year, multinational, single-arm, open-label study  

PubMed Central

The objective of this study was to assess the long-term safety and efficacy of olanzapine long-acting injection (LAI). A 6-year, single-arm, open-label extension study of olanzapine LAI was conducted at 127 sites in 25 countries. Patients were 18–76 years of age, were diagnosed with schizophrenia or schizoaffective disorder (N=931), and had been previously enrolled in one of three clinical trials of olanzapine LAI. Patients received flexibly dosed (45-405 mg) olanzapine LAI every 2–4 weeks. The mean duration of exposure was ?3 years. A total of 393 (42.2%) patients completed the study. The mean weight change was +2.1 kg (P<0.001), with 40.6% of patients experiencing 7% or higher weight gain. Treatment-emergent categorical changes occurred in fasting glucose, total cholesterol, and triglyceride levels. Pharmacokinetic analyses revealed no systemic accumulation of olanzapine after long-term treatment. There were 36 occurrences of post-injection delirium/sedation syndrome, all resolving within 72 h. The mean Positive and Negative Syndrome Scale total and subscale scores did not change significantly over the course of the study, indicating clinical stability. Olanzapine LAI appeared effective as a long-term maintenance treatment, with a safety profile generally consistent with the known profile of oral olanzapine, except for injection-related events (including post-injection delirium/sedation syndrome). PMID:24850228

Landry, John; Detke, Holland C.

2014-01-01

54

METFORMIN: an efficacy, safety and pharmacokinetic study on the short-term and long-term use in obese children and adolescents – study protocol of a randomized controlled study  

PubMed Central

Background The prevalence of childhood obesity and insulin resistance is rising, increasing the risk of diabetes mellitus type 2. To prevent these complications, lifestyle intervention is the corner stone in treatment. However, long-term efficacy of lifestyle intervention is questionable. In addition to lifestyle intervention, pharmacological treatments have been explored. Metformin has been shown to be moderately effective to reduce BMI in obese adolescents with hyperinsulinemia. However, data on pharmacokinetics and long-term efficacy and safety are lacking as well as an evidence-based dosing regimen for this age group. The primary objective of the METFORMIN study is to determine the effect of adding metformin treatment to lifestyle intervention in reducing BMI in obese adolescents with insulin resistance. In addition, the pharmacokinetics of metformin in obese adolescents will be studied. Methods/design The METFORMIN study is a multi-centre prospective study that consists of two 18-month phases: a double-blind randomized placebo-controlled trial (part 1) and an open-label follow-up study (part 2). During part 1, the participants will be given metformin 1,000 mg or placebo twice daily and will be offered a lifestyle intervention programme; 144 participants will be included, 72 in each arm. Primary endpoints are reduction in body mass index, insulin resistance, and percentage body fat. Discussion This study will provide data on short- and long-term efficacy and safety of metformin and on the pharmacokinetics of metformin in obese adolescents. Trial registration ClinicalTrials.gov number NCT01487993; EudraCT nr. 2010-023980-17. Registration date: 06-01-2011 PMID:24899137

2014-01-01

55

Long-term developmental progression in infants and young children taking sapropterin for phenylketonuria: a two-year analysis of safety and efficacy.  

PubMed

Purpose:Sapropterin is an oral synthetic formulation of tetrahydrobiopterin prescribed as adjunctive therapy for phenylketonuria. The efficacy of sapropterin in reducing blood phenylalanine levels has been demonstrated in clinical studies of individuals with phenylketonuria older than 4 years of age. Its effect on neurocognitive functioning in younger children has not been examined.Methods:A 2-year interim analysis of blood phenylalanine levels, prescribed dietary phenylalanine intake, and neurocognitive functioning was performed in children who started receiving sapropterin at 0-6 years of age and responded with a ?30% mean blood phenylalanine reduction. Children were evaluated at baseline and 2-year follow-up.Results:Sapropterin had a favorable safety profile and lowered blood phenylalanine levels with increased prescribed dietary phenylalanine intakes. Mean full-scale intelligence quotient was 103?±?12 at baseline and 104?±?10 at 2-year follow-up (P = 0.50, paired t-test, n = 25). For children younger than 30 months of age, the cognitive composite score from the Bayley Scales of Infant and Toddler Development, Third Edition, remained within the average range.Conclusion:Sapropterin had a favorable safety profile, was effective in lowering blood phenylalanine levels while clinically requiring dietary adjustment, resulting in increased phenylalanine intake, and preserved neurocognitive performance in children who started therapy between 0 and 6 years of age.Genet Med advance online publication 18 September 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.109. PMID:25232857

Longo, Nicola; Siriwardena, Komudi; Feigenbaum, Annette; Dimmock, David; Burton, Barbara K; Stockler, Sylvia; Waisbren, Susan; Lang, William; Jurecki, Elaina; Zhang, Charlie; Prasad, Suyash

2014-09-18

56

A multi-centre, randomised, double-blind 14-week extension study examining the long-term safety and efficacy profile of the ezetimibe/simvastatin combination tablet.  

PubMed

The objective of this study was to compare the efficacy and safety profile of ezetimibe/simvastatin (EZE/SIMVA) tablet and SIMVA monotherapy. This was an extension study of a randomised, double-blind, placebo-controlled study in patients with primary hypercholesterolaemia. Protocol-compliant patients who completed the 12-week base study were eligible to enter a randomised, double-blind, 14-week extension study and were administered 1 of 8 daily treatments: EZE/SIMVA 10/10-, 10/20-, 10/40- or 10/80-mg, or SIMVA 10-, 20-, 40- or 80-mg. Patients receiving these treatments during the base study remained on the same treatment in the extension. Patients administered placebo or EZE 10-mg monotherapy during the base study were re-randomised to EZE/SIMVA 10/10 mg or SIMVA 80 mg. The primary analysis was mean per cent change in low-density lipoprotein cholesterol (LDL-C) from baseline to extension study end-point. Mean changes from baseline in LDL-C of -38.8% and -53.7% were observed for pooled SIMVA and pooled EZE/SIMVA respectively. The between treatment difference of -14.9% (95% confidence interval: -16.4, -13.3) was statistically significant (p < 0.001). The incremental LDL-C lowering effect of EZE/SIMVA compared with the corresponding dose of SIMVA alone was consistent across the dose range (p < 0.001 for each between-group comparison). More patients receiving EZE/SIMVA than SIMVA achieved LDL-C concentrations < 100 mg/dl and < 70 mg/dl (p < 0.001 for both goals). EZE/SIMVA was generally well tolerated with a safety profile similar to SIMVA monotherapy. There were no significant between-group differences in the incidences of clinically significant elevations in liver transaminase or creatine kinase levels. In conclusion, EZE/SIMVA had a comparable safety and tolerability profile and was more efficacious than SIMVA monotherapy for up to 6 months. PMID:17655686

Ose, L; Johnson-Levonas, A; Reyes, R; Lin, J; Shah, A; Tribble, D; Musliner, T

2007-09-01

57

Clinical efficacy, radiographic and safety findings through 5?years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of a randomised, placebo-controlled trial (the GO-REVEAL study)  

PubMed Central

Objectives Assess golimumab's long-term efficacy/safety in psoriatic arthritis (PsA). Methods Adults with active PsA (?3 swollen and tender joints, active psoriasis) were randomly assigned to subcutaneous placebo, golimumab 50?mg, or golimumab 100?mg every 4?weeks (q4wks) through wk20. All patients received golimumab 50?mg or 100?mg q4wks from wk24 forward. Methotrexate was allowed and taken by approximately half the patients. Findings through 5?years are reported herein. Efficacy assessments included ?20% improvement in American College of Rheumatology (ACR20) response, C-reactive-protein-based, 28-joint-count Disease Activity Score (DAS28-CRP) response, ?75% improvement in Psoriasis Area and Severity Index (PASI75) scores, and PsA-modified Sharp/van der Heijde scores (SHSs). Results 126/405 (31%) randomised patients discontinued treatment through wk252. Golimumab was effective in maintaining clinical improvement through year-5 (ACR20: 62.8–69.9%, DAS28-CRP: 75.2-84.9% for randomised patients; PASI75: 60.8–72.2% among randomised patients with ?3% body surface area involvement) and inhibiting radiographic progression (mean changes in PsA-modified SHS: 0.1–0.3) among patients with radiographic data. While concomitant methotrexate did not affect ACR20/PASI75, it appeared to reduce radiographic progression. No new safety signals were identified. Antibodies-to-golimumab occurred in 1.8%/10.0% of patients with/without methotrexate). Conclusions Long-term golimumab safety/efficacy in PsA was demonstrated through 5?years. Trial registration number NCT00265096. PMID:24748630

Kavanaugh, Arthur; McInnes, Iain B; Mease, Philip; Krueger, Gerald G; Gladman, Dafna; van der Heijde, Désirée; Zhou, Yiying; Lu, Jiandong; Leu, Jocelyn H; Goldstein, Neil; Beutler, Anna

2014-01-01

58

Long-term safety, efficacy and side-effects of continuous subcutaneous insulin infusion treatment for Type 1 (insulin-dependent) diabetes mellitus: a one centre experience  

Microsoft Academic Search

Summary  A follow-up study of 116 Type 1 (insulin-dependent) diabetic patients on long-term continuous subcutaneous insulin infusion was conducted after 4.5±0.2 years. The average HbA1c-value of these patients decreased by 1% to 6.7±0.1% during this observation period. Typical side effects of continuous subcutaneous insulin infusion such as skin inflammation at the catheter insertion site occurred with similar frequency as has been

E. Chantelau; M. Spraul; I. Miahlhauser; R. Gause; M. Berger

1989-01-01

59

Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe  

PubMed Central

Background The objective of these two GCP multicentre European clinical field studies was to evaluate the long-term efficacy and safety of a new imidacloprid/flumethrin collar (Seresto®, Bayer AnimalHealth, Investigational Veterinary Product(IVP)) in dogs and cats naturally infested with fleas and/or ticks in comparison to a dimpylat collar ("Ungezieferband fuer Hunde/fuer Katzen", Beaphar, Control Product (CP)). Methods 232 (IVP) and 81 (CP) cats and 271(IVP) and 129 (CP) dogs were treated with either product according to label claims and formed the safety population. Flea and tick counts were conducted in monthly intervals for up to 8 months in the efficacy subpopulation consisting of 118 (IVP) + 47 (CP) cats and 197 (IVP) + 94 (CP) dogs. Efficacy was calculated as reduction of infestation rate within the same treatment group and statistically compared between the two treatment groups. Results Preventive efficacy against fleas in cats/dogs varied in the IVP group between 97.4%/94.1% and 100%/100% (overall mean: 98.3%/96.7%) throughout the 8 month period and in the CP group between 57.1%/28.2% and 96.1%/67.8% (overall mean: 79.3%/57.9%). Preventive efficacy against ticks in cats/dogs varied in the IVP group between 94.0%/91.2% and 100%/100% (overall mean: 98.4%/94.7%) throughout the 8 month period and in the CP group between 90.7%/79.9% and 100%/88.0% (overall mean: 96.9%/85.6%). The IVP group was statistically non-inferior to the CP group, and on various assessment days, statistical superiority was proven for flea and tick count reduction in dogs and cats. Both treatments proved to be safe in dogs and cats with mainly minor local observations at the application site. There was moreover, no incidence of any mechanical problem with the collar in dogs and cats during the entire study period. Conclusions The imidacloprid/flumethrin collar proved to reduce tick counts by at least 90% and flea counts by at least 95% for a period of at least 7-8 months in cats and dogs under field conditions. Therefore, it can be used as sustainable long-term preventative, covering the whole flea and tick season. PMID:22463745

2012-01-01

60

Comparative Evaluation of the Safety and Efficacy of Long-Term Use of Imidafenacin and Solifenacin in Patients with Overactive Bladder: A Prospective, Open, Randomized, Parallel-Group Trial (the LIST Study)  

PubMed Central

Objectives. Overactive bladder (OAB) is a chronic disease, but comparative trials of anticholinergics, which are commonly used for treatment of OAB, have generally been performed for up to 12 weeks only. There is no comparative study of a long-term intervention. Methods. We conducted a 52-week prospective randomized comparative study to evaluate the efficacy and tolerability of two anticholinergics. Results. Forty-one Japanese patients with untreated OAB were randomly assigned to imidafenacin and solifenacin groups. There was no difference in OABSS and KHQ scores between the two groups, but the severity and incidence of adverse events caused by the anticholinergics showed increased differences between the groups with time. The severity of dry mouth and the incidence of constipation were significantly lower in the imidafenacin group (P = 0.0092 and P = 0.0013, resp.). Conclusions. This study is the first long-term trial to show differences in the properties of anticholinergics that were not detected in short-term studies. Since OAB is a chronic disease, we conclude that imidafenacin is preferable to solifenacin from a perspective of safety. PMID:22046182

Zaitsu, Masayoshi; Mikami, Koji; Ishida, Noriko; Takeuchi, Takumi

2011-01-01

61

Efficacy and safety of long-term tadalafil 5 mg once daily combined with sildenafil 50 mg as needed at the early stage of treatment for patients with erectile dysfunction.  

PubMed

This study aimed to evaluate the efficacy and safety of long-term and low-dose tadalafil combined with sildenafil as needed at the early stage of treatment for erectile dysfunction (ED). We enrolled 180 patients with ED 1 : 1 to tadalafil 5 mg once daily or once-a-day tadalafil 5 mg combined with sildenafil 50 mg as needed. The efficacy measures included the 5-item version of the International Index of Erectile Function (IIEF-5) and the Sexual Encounter Profile (SEP). The safety was assessed by observing drug tolerability and adverse events. Total IIEF-5 scores of patients with severe ED in combined medication group were significantly higher than in tadalafil alone group. Question 2 scores of IIEF-5 of patients with moderate and severe ED in combined medication group were significantly higher than in tadalafil alone group. The significant improvement in question 3 scores of IIEF-5 existed only in patients with severe ED receiving combined medication. The percentage of 'yes' responses to SEP4, SEP5 and partner's SEP3 were improved significantly in combined medication group. There was no difference between two groups in the incidence of adverse events. Our results suggest that combined medication can better improve erectile function, especially for patients with severe ED. PMID:24387078

Cui, H; Liu, B; Song, Z; Fang, J; Deng, Y; Zhang, S; Wang, H; Wang, Z

2015-02-01

62

Long-term antidyskinetic efficacy of amantadine in Parkinson's disease.  

PubMed

Several randomized placebo-controlled trials have consistently shown antidyskinetic effects of amantadine in levodopa treated patients with advanced Parkinson's disease (PD). However, all of these were of short duration and there have been claims that the effect of amantadine on levodopa induced dyskinesias (LID's) wear off after about 9 months of treatment. This randomized placebo-controlled parallel-group study was performed to assess the long-term antidyskinetic effect of amantadine in 32 PD patients, who after having been on stable amantadine therapy for LID over at least one year- were switched in a double blind manner to amantadine or placebo and followed for 3 weeks. Dyskinesia duration and intensity were assessed by UPDRS IV items 32 and 33 as well as by patient's diaries. The primary outcome was the score change of UPDRS IV items 32 + 33 between baseline and 3 weeks after treatment as well as the between treatment group comparison of the score change of UPDRS IV items 32 + 33. There was a significant increase of UPDRS IV items 32 + 33 in patients treated with placebo from 3.06 (95% CI, 2.1-4.03) at baseline to 4.28 (95% CI, 3.1-5.4) at three-week follow-up (P = 0.02) compared with no significant change between baseline 3.2 (95% CI, 2.1-4.4) to follow-up 3.6 (95% CI, 2.3-4.8) in patients staying on amantadine. These findings argue for long-term antidyskinetic efficacy of amantadine in PD patients with LID's. PMID:20198649

Wolf, Elisabeth; Seppi, Klaus; Katzenschlager, Regina; Hochschorner, Guenter; Ransmayr, Gerhard; Schwingenschuh, Petra; Ott, Erwin; Kloiber, Iris; Haubenberger, Dietrich; Auff, Eduard; Poewe, Werner

2010-07-30

63

A 24-Week, Open-Label Extension Study to Investigate the Long-term Safety, Tolerability, and Efficacy of 13.3 mg/24 h Rivastigmine Patch in Patients With Severe Alzheimer Disease.  

PubMed

The long-term safety, tolerability, and efficacy of high-dose 13.3 mg/24 h rivastigmine patch in severe Alzheimer disease was evaluated in a 24-week, open-label extension to the double-blind ACTION study. Safety and tolerability, and efficacy on the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV), Severe Impairment Battery (SIB), and ADCS-Clinical Global Impression of Change (ADCS-CGIC) were assessed. Overall, 197 patients continued on 13.3 mg/24 h patch; 199 uptitrated from 4.6 mg/24 h to 13.3 mg/24 h patch. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar in patients who continued on, and patients who uptitrated to, 13.3 mg/24 h patch (AEs: 57.9% and 59.8%; serious AEs: 16.2% and 16.1%; discontinuations: 11.2% and 12.1%, respectively). Larger mean changes from double-blind baseline were observed in patients uptitrated on the ADCS-ADL-SIV (-4.6; SD=8.7) and SIB (-7.0; SD=16.6), than those who continued on 13.3 mg/24 h patch (-3.9; SD=8.0 and -4.7; SD=16.8, respectively). ADCS-CGIC scores were comparable. There were no clinically relevant between-group differences in safety and tolerability. Greater decline was observed in patients with delayed uptitration to high-dose 13.3 mg/24 h patch than patients who continued on high-dose patch. PMID:25437301

Farlow, Martin R; Grossberg, George T; Sadowsky, Carl H; Meng, Xiangyi; Velting, Drew M

2014-11-26

64

Long-Term (1-Year) Safety and Efficacy of a Single 6-mL Injection of Hylan G-F 20 in Indian Patients with Symptomatic Knee Osteoarthritis  

PubMed Central

Introduction: The prevalence of symptomatic knee osteoarthritis (OA) among Asians ?65 years is estimated to double by 2040. This study was designed to evaluate the safety and efficacy of a single, 6-mL intra-articular injection of hylan G-F 20 in Indian patients with knee OA at 26 weeks through to 52 weeks. Methods: This study was an open-label, multicentre, phase 4 clinical trial. Enrolled patients (N=394) were ?30 years old with Kellgren-Lawrence grade 1–3 OA; all patients received hylan G-F 20. WOMAC, SF-12, PTGA, and COGA scores, and OA medication use were evaluated at weeks 1, 4, 12, 26, 39, and 52 (initial treatment phase). At 26, 39, or 52 weeks, eligible patients could participate in a repeat treatment phase. McNemar-Bowkers, paired t-tests and ANOVA analyses were performed (alpha=0.05). Results: At 26 weeks, statistically significant changes from baseline were observed in all efficacy parameters, including the primary efficacy endpoint of WOMAC A1 (p<0.0001). Improvements continued for 52 weeks. No significant changes occurred in concomitant medication use. Eleven patients (2.8%) were re-injected at week 26 or 52. After repeat injection, statistically significant decreases were observed in WOMAC A1, WOMAC C and PTGA scores (p?0.028). Twenty-three (5.8%) patients reported 26 local target knee AEs. Conclusion: Among Indian patients within this study, a 6-mL hylan G-F 20 injection was well tolerated and effective in treating symptomatic knee OA with significant long-term (1 year) improvement of outcomes. When needed, repeat treatment was safe and efficacious for 4 weeks. Trial Registration: Clinical Trial Registry of India (CTRI/2010/091/000052) www.ctri.nic.in/Clinicaltrials/login.php. PMID:25328555

Pal, Sarvajeet; Thuppal, Sreedhar; Reddy, K.J; Avasthi, Sachin; Aggarwal, Anish; Bansal, Himanshu; Mohanasundaram, Senthilnathan; Bailleul, Francois

2014-01-01

65

Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years  

PubMed Central

Background: Teriflunomide, an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis (RMS), was well tolerated and effective in reducing magnetic resonance imaging (MRI) lesions in 179 RMS patients in a phase 2 36-week, placebo-controlled study. Methods: A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day. An interim analysis was performed at a cut-off on January 8 2010. Results: The mean and median duration of study treatment, including both the core and extension phase, from baseline to the interim cut-off, was 5.6 years (standard deviation: 2.7 years) and 7.1 years (range: 0.05–8.5 years), respectively. Of 147 patients, 62 (42.2%) discontinued (19% due to treatment-emergent adverse events (TEAEs)). The most common TEAEs were mild infections, fatigue, sensory disturbances and diarrhoea. No serious opportunistic infections occurred, with no discontinuations due to infection. Asymptomatic alanine aminotransferase increases (?3× upper limit of normal (ULN)) were common (7 mg, 64.2%; 14 mg, 62.1%); increases >3×ULN were similar across groups (7 mg, 12.3%; 14 mg, 12.1%). Mild decreases in neutrophil counts occurred; none led to discontinuation. The incidence of malignancies was comparable to that of the general population, and cases were not reminiscent of those observed in immunocompromised patients. Annualised relapse rates remained low, minimal disability progression was observed, with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters. Conclusion: Teriflunomide had a favourable safety profile for up to 8.5 years. PMID:22307384

Li, David K; Freedman, Mark S; Truffinet, Philippe; Benzerdjeb, Hadj; Wang, Dazhe; Bar-Or, Amit; Traboulsee, Anthony L; Reiman, Lucy E; O’Connor, Paul W

2012-01-01

66

The long-term safety of antiepileptic drugs.  

PubMed

Antiepileptic drugs (AEDs) are used by millions of people worldwide for the treatment of epilepsy, as well as in many other neurological and psychiatric conditions. They are frequently associated with adverse effects (AEs), which have an impact on the tolerability and success of treatment. Half the people who develop intolerable AEs discontinue treatment early on after initiation, while the majority of people will continue to be exposed to their effects for long periods of time. The long-term safety of AEDs reflects their potential for chronic, cumulative dose effects; rare, but potentially serious late idiosyncratic effects; late, dose-related effects; and delayed, teratogenic or neurodevelopmental effects. These AEs can affect every body system and are usually insidious. With the exception of delayed effects, most other late or chronic AEs are reversible. To date, there is no clear evidence of a carcinogenic effect of AEDs in humans. While physicians are aware of the long-term AEs of old AEDs (the traditional liver enzyme-inducing AEDs and valproate), information about AEs of new AEDs (such as lamotrigine, levetiracetam, oxcarbazepine, topiramate or zonisamide), particularly of their teratogenic effects, has emerged over the years. Sporadic publications have raised issues about AEs of the newer AEDs eslicarbazepine, retigabine, rufinamide, lacosamide and perampanel but their long-term safety profiles may take years to be fully appreciated. Physicians should not only be aware of the late and chronic AEs of AEDs but should systematically enquire and screen for these according to the individual AED AE profile. Care should be taken for individuals with comorbid conditions that may render them more susceptible to specific AEs. Prevention and appropriate management of long-term AED AEs is expected to improve adherence to treatment, quality of life and control of epilepsy. PMID:23673774

Gaitatzis, Athanasios; Sander, Josemir W

2013-06-01

67

Efficacy and Safety of Long-term Complementary Treatment with Standardised European Mistletoe Extract (Viscum album L.) in Addition to the Conventional Adjuvant Oncological Therapy in Patients with Primary Non-metastatic Breast Cancer Results of a multicentre, comparative, epidemiological cohort study in Germany and Switzerland  

Microsoft Academic Search

Summary Objectives: The purpose of the study was to evaluate the therapeutic efficacy and safety of long-term complementary the- rapy in primary, non-metastatic breast cancer patients in UICC stage I?III with a standardized European mistletoe ex- tract (Viscum album L., Iscador ? , \\

Paul R. Bock; Walter E. Friedel; Jürgen Hanisch; Marita Karasmann; Berthold Schneider

68

A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis.  

PubMed

Osteoporotic fractures are one of the major causes of increased morbidity and mortality in postmenopausal women and the overall aging population. One of the major issues in the management of postmenopausal osteoporosis is to find a safe and effective treatment in the long term (>3 years) to achieve and maintain a reduction in the risk of fracture. Strontium ranelate (PROTELOS(®)) is a relatively novel drug, currently approved in Europe for the treatment of postmenopausal osteoporosis. Strontium ranelate is the first agent of a new therapeutic class in osteoporosis, capable of both promoting bone formation and, to a lesser extent, inhibiting bone resorption. This uncoupling in bone turnover results in a net gain in bone mineral density (BMD), bone quality improvement and reduction in risk of vertebral and nonvertebral fractures, as initially demonstrated in the preplanned long-term registrative trials SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) at 5 years. Recently, open-label extensions of the SOTI and TROPOS trials up to 8 and, recently, 10 years have confirmed the sustained efficacy of strontium ranelate in increasing BMD, the long-term safety profile and the high compliance to treatment, independently from baseline BMD or other risk factors for osteoporotic fractures. Recent economic impact analyses have proved that long-term treatment with strontium ranelate is highly cost effective, especially in women older than 70 years of age. Histomorphometric analyses in animals and humans participating in the phase III trials have proved that the quality of mineralization is preserved in the long term and bone microarchitecture is ameliorated, with increased bone strength. Thus, strontium ranelate has been confirmed to be an effective compound for the long-term, chronic treatment of postmenopausal osteoporosis. PMID:23858336

Cianferotti, Luisella; D'Asta, Federica; Brandi, Maria Luisa

2013-06-01

69

The Impact of Methodological Approaches for Presenting Long-Term Clinical Data on Estimates of Efficacy in Psoriasis Illustrated by Three-Year Treatment Data on Infliximab  

Microsoft Academic Search

Background: Psoriasis affects about 2–3% of the Caucasian population. Biologics such as infliximab, etanercept, adalimumab and ustekinumab are efficacious treatments of plaque-type psoriasis. Critical to monitoring drug efficacy and safety is availability of long-term data. Despite the chronic nature of psoriasis, to date limited long-term clinical data have been available, as challenges are inherent in conducting a long-term analysis. With

M. Papoutsaki; M. Talamonti; A. Giunta; A. Costanzo; M. Ruzzetti; M. Teoli; S. Chimenti

2010-01-01

70

Long-term safety issues associated with mixer pump operation  

SciTech Connect

In this report, we examine several long-term issues: the effect of pump operation on future gas release events (GREs), uncontrolled chemical reactions, chronic toxic gas releases, foaming, and erosion and corrosion. Heat load in excess of the design limit, uncontrolled chemical reactions, chronic toxic gas releases, foaming, and erosion and corrosion have been shown not to be safety concerns. The effect of pump operation on future GREs could not be quantified. The problem with evaluating the long-term effects of pump operation on GREs is a lack of knowledge and uncertainty. In particular, the phenomena governing gas retention, particle size distribution, and settling are not well understood, nor are the interactions among these factors understood. There is a possibility that changes in these factors could increase the size of future GREs. Bounding estimates of the potential increase in size of GREs are not possible because of a lack of engineering data. Proper management of the hazards can reduce, but not eliminate, the possibility of undesirable changes. Maintaining temperature within the historical limits can reduce the possibility of undesirable changes. A monitoring program to detect changes in the gas composition and crust thickness will help detect slowly occurring changes. Because pump operation has be shown to eliminate GREs, continued pump operation can eliminate the hazards associated with future GREs.

Kubic, W.L. Jr.

1994-12-31

71

Efficacy of Lifestyle Modification for Long-Term Weight Control  

Microsoft Academic Search

A comprehensive program of lifestyle modification induces loss of ?10% of initial weight in 16 to 26 weeks, as revealed by a review of recent randomized controlled trials, including the Diabetes Prevention Program. Long-term weight control is facilitated by continued patient-therapist contact, whether provided in person or by telephone, mail, or e-mail. High levels of physical activity and the consumption

Thomas A. Wadden; Meghan L. Butryn; Kirstin J. Byrne

2004-01-01

72

Demonstrating the Safety of Long-Term Dry Storage - 13468  

SciTech Connect

Commercial nuclear plants in the United States were originally designed with the expectation that used nuclear fuel would be moved directly from the reactor pools and transported off site for either reprocessing or direct geologic disposal. However, Federal programs intended to meet this expectation were never able to develop the capability to remove used fuel from reactor sites - and these programs remain stalled to this day. Therefore, in the 1980's, with reactor pools reaching capacity limits, industry began developing dry cask storage technology to provide for additional on-site storage. Use of this technology has expanded significantly since then, and has today become a standard part of plant operations at most US nuclear sites. As this expansion was underway, Federal programs remained stalled, and it became evident that dry cask systems would be in use longer than originally envisioned. In response to this challenge, a strong technical basis supporting the long term dry storage safety has been developed. However, this is not a static situation. The technical basis must be able to address future challenges. Industry is responding to one such challenge - the increasing prevalence of high burnup (HBU) used fuel and the need to provide long term storage assurance for these fuels equivalent to that which has existed for lower burnup fuels over the past 25 years. This response includes a confirmatory demonstration program designed to address the aging characteristics of HBU fuel and set a precedent for a learning approach to aging management that will have broad applicability across the used fuel storage landscape. (authors)

McCullum, Rod [Nuclear Energy Institute, 1201 F St. NW, Washington, DC, 20004 (United States)] [Nuclear Energy Institute, 1201 F St. NW, Washington, DC, 20004 (United States); Brookmire, Tom [Dominion Energy, 5000 Dominion Boulevard Glen Allen, VA 23060 (United States)] [Dominion Energy, 5000 Dominion Boulevard Glen Allen, VA 23060 (United States); Kessler, John [Electric Power Research Institute, 1300 West W.T. Harris Boulevard, Charlotte, NC 28262 (United States)] [Electric Power Research Institute, 1300 West W.T. Harris Boulevard, Charlotte, NC 28262 (United States); Leblang, Suzanne [Entergy, 1340 Echelon Parkway, Jackson, MS 39211 (United States)] [Entergy, 1340 Echelon Parkway, Jackson, MS 39211 (United States); Levin, Adam [Exelon, 4300 Winfield Road, Warrenville, IL 60555 (United States)] [Exelon, 4300 Winfield Road, Warrenville, IL 60555 (United States); Martin, Zita [Tennessee Valley Authority, 1101 Market Street, Chattanooga, TN 37402 (United States)] [Tennessee Valley Authority, 1101 Market Street, Chattanooga, TN 37402 (United States); Nesbit, Steve [Duke Energy, 550 South Tryon Street, Charlotte, NC 28202 (United States)] [Duke Energy, 550 South Tryon Street, Charlotte, NC 28202 (United States); Nichol, Marc [Nuclear Energy Institute, 1201 F St. NW Washington DC, 2004 (United States)] [Nuclear Energy Institute, 1201 F St. NW Washington DC, 2004 (United States); Pickens, Terry [Xcel Energy, 414 Nicollet Mall, Minneapolis, MN 55401 (United States)] [Xcel Energy, 414 Nicollet Mall, Minneapolis, MN 55401 (United States)

2013-07-01

73

Long-term efficacy of latanoprost in primary congenital glaucoma  

PubMed Central

Purpose To investigate the success (glaucoma control) of latanoprost therapy of primary congenital glaucoma (PCG) and factors affecting the long-term outcome. Methods Patients with PCG treated with latanoprost were re-examined. At study visit and from clinical charts, we evaluated: intraocular pressure, length of glaucoma control with latanoprost, need of further medication or glaucoma surgery, systemic and topical side effects. Multivariate analysis was used to test factors related to the final outcome of the treatment. Results Eighty-one eyes of 44 patients with PCG, and 42 eyes of 29 patients with previous glaucoma surgery, had received latanoprost therapy. In the first group, a success (glaucoma control by latanoprost therapy) was found in 24 eyes (29.6%), whereas 57 eyes (70.4%) had received surgery (45 eyes (55.6%) in the first year); among the eyes with previous surgery, a success was found in 12 eyes (28.6%), 13 eyes (31%) required an additional therapy, and 17 eyes (40.5%) had received further glaucoma surgery. No patient discontinued the treatment because of side effects. Factors related to the failure of the latanoprost treatment were: the high score of severity of glaucoma (P=0.014) and low age at PCG presentation (P=0.042). Conclusions Long-term treatment with latanoprost is effective in about 30% of the eyes; factors related to failure were severe glaucomatous alterations, and young age at PCG presentation. PMID:24158022

Uva, M G; Avitabile, T; Reibaldi, M; Bucolo, C; Drago, F; Quaranta, L; Lionetti, E; Longo, A

2014-01-01

74

Assessment of Countermeasure Efficacy for Long-Term Space Missions  

NASA Technical Reports Server (NTRS)

One of the main functions of the upcoming International Space Station (ISS) will be to provide a venue for testing proposed countermeasures for their ability to protect humans from the debilitating effects of longterm space flight. However, several limiting factors preclude an evaluation process similar to that used in clinical trials which traditionally are implemented with large sample sizes of subjects, including control groups, and with blind or double-blind application of treatments according to factorial or other balanced experimental designs. In particular, only very limited numbers of human subjects will be available for actual field testing in the ISS With no more than 125 subjects planned to fly on all ISS missions over 10 years, it is not possible to test extensive combinations of some 15-20 proposed countermeasures. Furthermore because of safety concerns and operational considerations, it is unlikely that anything other than the current best guess at the most effective countermeasure package will ever be used on ISS. In particular, control or placebos will not be allowed. In view of these limitations, historical data and groundbased or animal studies will have to be used to compensate for small sample sizes and lack of controls in the field. As a result, statistical analysis methodology will have to be developed which allows for the integration of these disparate data types into a meaningful evaluation process. The process must be sequential, providing objective rules for deciding through time whether to reject or modify an ineffective countermeasure, or whether to certify one as effective. Additional output should include performance characteristics for all relevant physiological systems, including uncertainty analyses and estimates of accept/reject decision error rates.

Feiveson, Alan H.; Paloski, William H. (Technical Monitor)

2000-01-01

75

Long-term efficacy and safety of E/C/F/TDF vs EFV/FTC/TDF and ATV+RTV+FTC/TDF in HIV-1-infected treatment-naïve subjects ?50 years  

PubMed Central

Introduction In high-income countries, ?30% of HIV-infected patients are ?50 years (yrs) old (UNAIDS 2013). In two phases, three clinical trials (Studies 102 and 103) elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF; STB) had non-inferior efficacy and favourable safety vs efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF; ATR) or ritonavir-boosted atazanavir (ATV+RTV)+FTC/TDF (TVD) in HIV-infected, treatment-naïve subjects at Week 144. The efficacy and safety of STB in subjects < or ?50 yrs is described. Materials and Methods Post hoc analysis of efficacy, tolerability and safety in subjects < or ?50 yrs at Week 144. Results Subjects ?50 yrs in Study 102: STB: 14% (49/348), ATR: 16% (56/352); in Study 103: STB: 14% (48/353), ATV+RTV+TVD: 14% (48/355). Efficacy, safety and tolerability by age and study endpoint are shown in Table 1. Regardless of age, STB had robust efficacy at Week 144 with similar virologic outcomes vs ATR or ATV+RTV+TVD. Discontinuations (DC) due to AE on STB were similar to the comparators, most occurred by Week 48. Median changes in eGFR on STB were similar by age; DC with renal PRT was rare [STB: 4 (0.6%); ATV: 3 (0.8%); ATR: 0], 2 and 1 in ?50 yrs old strata, respectively. Conclusions STB compared to ATR or ATV+RTV+TVD, is an efficacious, well-tolerated and safe regimen for HIV-1-infected, treatment-naïve subjects

Gazzard, Brian; Marie Girard, Pierre; Di Perri, Giovanni; Gallant, Joel; Towner, William; Rogatto, Felipe; Demorin, Jennifer; McColl, Damian; Liu, Hui; Rhee, Martin; Szwarcberg, Javier; Piontkowsky, David

2014-01-01

76

Efficacy and long-term safety of dexibuprofen [S(+)-ibuprofen]: a short-term efficacy study in patients with osteoarthritis of the hip and a 1-year tolerability study in patients with rheumatic disorders.  

PubMed

The efficacy study was performed to prove the equivalent efficacy of dexibuprofen compared to the double dose of racemic ibuprofen and to show a clinical dose-response relationship of dexibuprofen. The 1-year tolerability study was carried out to investigate the tolerability of dexibuprofen. In the efficacy study 178 inpatients with osteoarthritis of the hip were assigned to 600 or 1200 mg of dexibuprofen or 2400 mg of racemic ibuprofen daily. The primary end-point was the improvement of the WOMAC OA index. A 1-year open tolerability study included 223 outpatients pooled from six studies. The main parameter was the incidence of clinical adverse events. In the efficacy study the evaluation of the improvement of the WOMAC OA index showed equivalence of dexibuprofen 400 mg t.i.d. compared to racemic ibuprofen 800 mg t.i.d., with dexibuprofen being borderline superior (P = 0.055). The comparison between the 400 mg t.i.d. and 200 mg t.i.d. doses confirmed a significant superior efficacy of dexibuprofen 400 mg (P = 0.023). In the tolerability study the overall incidence of clinical adverse events was 15.2% (GI tract 11.7%, CNS 1.3%, skin 1.3%, others 0.9%). The active enantiomer dexibuprofen proved to be an effective NSAID with a significant dose-response relationship. Compared to the double dose of racemic ibuprofen, dexibuprofen was at least equally efficient, with borderline superiority over dexibuprofen (P = 0.055). The tolerability study in 223 patients on dexibuprofen showed an incidence of clinical adverse events of 15.2% after 12 months. The results of the studies suggest that dexibuprofen is an effective NSAID with good tolerability. PMID:11771571

Mayrhofer, F

2001-11-01

77

Continuous effect with long-term safety in zoledronic acid therapy for polyostotic fibrous dysplasia with severe bone destruction.  

PubMed

Polyostotic fibrous dysplasia (PFD) is a rare non-inherited genetic disorder characterized by osteolytic lesions in multiple bones causing bone pain, deformity, and pathological fracture. As an anti-osteolytic agent, the new generation bisphosphonate zoledronic acid (ZOL) restricts lesion progression by inhibiting osteoclastic activity. Although ZOL is more effective than pamidronate, its efficacy and safety in long-term therapy in PFD is unknown. We report a case of PFD advanced to extensive bone destruction in the skull and ribs and evaluate the efficacy and long-term safety of early first-line ZOL in PFD with severe bone disease, recommending possible future treatments. The annual infusion of 5 mg ZOL was intravenously administered, cumulatively 20 mg over four courses, with oral supplementation of calcium, vitamin D, and potassium. No long-term use side effect was observed, and mild transient symptoms were easily resolved. Significant radiological improvement was seen in filling of destroyed bone and cortical thickening. ZOL decreased both serum collagen type 1 cross-linked C-telopeptide and type 1 procollagen N-terminal (P1NP) from extremely high baseline levels. An unexpected direct increase in P1NP after long-term therapy could indicate discontinuation of ZOL to observe its prolonged effect. Early first-line ZOL therapy is effective in PFD with severe bone destruction and is safe for long-term therapy. The use of bisphosphonates in FD remains off-label, and regular monitoring is highly advised. PMID:25230905

Wu, Di; Ma, Jie; Bao, Suqing; Guan, Haixia

2015-04-01

78

Long-Term Efficacy of Three Contraceptive Approaches for Population Control of Wild Horses  

Microsoft Academic Search

Controlling fertility of feral horses through the use of long-acting contraceptives or sterilization approaches has been championed as a reasonable and humane solution for addressing overpopulation problems in several western states. However, methods to accomplish long-term contraceptive efficacy of horses following a single treatment have been lacking. In fall 2002 and spring 2003, we initiated a study to compare the

Gary Killian; Nancy K. Diehl; Lowell Miller; Jack Rhyan

79

Long-term safety of aromatase inhibitors in the treatment of breast cancer  

PubMed Central

Following promising data for metastatic breast cancer in terms of efficacy and safety profile, third-generation aromatase inhibitors (AI), anastrozole, letrozole, and exemestane, underwent a full development in early setting. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting are still debated. Beyond the choice of clinical strategy, the long duration of exposure to AI in adjuvant setting required a full determination of the long-term toxicity profile of these agents. While all three AIs have either favorable (decreased incidence of hot flashes, gynecologic and thromboembolic side-effects) or unfavorable (skeletal complications, arthralgia, musculoskeletal pain, sexual dysfunction) class adverse events, some variability between AIs has been reported in side-effects as well as gastrointestinal, urogenital, neurologic, and visual disturbances, confirming the lack of interchangeability between the three AIs. The overall therapeutic index of AIs appears today superior to that of tamoxifen with proven improved efficacy and better toxicity profile. This review will explore the results from the available adjuvant AIs trials with a particular emphasis on safety profiles, quality of life, and therapeutic index, helping to define the present role of AIs in the adjuvant management of postmenopausal patients with breast cancer. PMID:18728707

Nabholtz, Jean-Marc A

2008-01-01

80

Open-Label, Long-Term Safety Study of Cevimeline in the Treatment of Postirradiation Xerostomia  

SciTech Connect

Purpose: To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. Methods and Materials: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). Results: Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). Conclusions: Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.

Chambers, Mark S. [Department of Head and Neck Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)], E-mail: mchamber@mdanderson.org; Jones, Christopher Uwe [Radiological Associates of Sacramento, Sacramento, CA (United States); Biel, Merrill A. [Ear, Nose and Throat Specialty Care of Minnesota, Minneapolis, MN (United States); Weber, Randal S. [Department of Head and Neck Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Hodge, Kenneth M. [Commonwealth Ear Nose and Throat, Louisville, KY (United States); Chen, Y. [Department of Radiation Oncology, University of Rochester Cancer Center, Rochester, NY (United States); Holland, John M. [Department of Radiation Oncology, Oregon Health and Science University, Portland, OR (United States); Ship, Jonathan [Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY (United States); Vitti, Robert; Armstrong, Ingrid [Daiichi Pharmaceutical Corporation, Montvale, NJ (United States); Garden, Adam S. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Haddad, Robert [Dana Farber Cancer Center, Harvard University, Boston, MA (United States)

2007-12-01

81

Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants  

Microsoft Academic Search

The long-term efficacy of hepatitis B vaccine, long-term effectiveness of hepatitis B immunisation programmes, immune memory induced by hepatitis B vaccine, current booster policies, and impact of hepatitis B virus mutants on immunisation programmes were reviewed at the Viral Hepatitis Prevention Board (VHPB) meeting in Sevilla, Spain, March 2004. The main focus was on universal vaccination programmes with data being

David FitzSimons; Guido François; Andrew Hall; Brian McMahon; André Meheus; Alessandro Zanetti; Bernard Duval; Wolfgang Jilg; Wulf Otto Böcher; Sheng-Nan Lu; Ulus Akarca; Daniel Lavanchy; Susan Goldstein; Jangu Banatvala; Pierre Van Damme

2005-01-01

82

Long-term efficacy of intensive cycle ergometer exercise training program for advanced COPD patients  

PubMed Central

Background Exercise training has been incorporated into the international guidelines for the treatment of chronic obstructive pulmonary disease (COPD). However, the long-term efficacy of the training program for patients with advanced COPD has never been evaluated in Thailand. Purpose To determine the long-term efficacy of intensive cycle ergometer exercise program on various clinical parameters of patients with advanced COPD. Materials and methods The patients with advanced COPD were separated into two groups: the intensive ergometer exercise program group and the control group. The clinical parameters of all the patients were assessed at baseline, every month for the first 3 months, and then every 3 months until they had completed the 24-month follow-up. Mann–Whitney U test was used to compare baseline mean differences between the groups. Repeated measure analysis was applied to determine the progress in all parameters during the entire follow-up period. Mean incase imputation method was applied to estimate the parameters of dropout cases. Results A total of 41 patients were enrolled: 27 in the intensive ergometer exercise program group and 14 in the control group. The intensive cycle ergometer exercise program group showed statistically significant improvements in muscle strength (from month 1 till the end of the study, month 24), endurance time (from month 1 till the end of measurement, month 12) and clinically significant improvements in 6-minute walk distance (from month 2 until month 9), dyspnea severity by transitional dyspnea index (from month 1 till the end of the study, month 24), and quality of life (from month 1 till the end of the study, month 24). There was no significant difference in survival rates between the groups. Conclusion The intensive ergometer exercise training program revealed meaningful long-term improvements in various clinical parameters for up to 2 years. These promising results should encourage health care professionals to promote exercise training for patients with advanced COPD who have limited daily activities despite optimal medication control. PMID:25624757

Pothirat, Chaicharn; Chaiwong, Warawut; Phetsuk, Nittaya; Liwsrisakun, Chalerm; Bumroongkit, Chaiwat; Deesomchok, Athavudh; Theerakittikul, Theerakorn; Limsukon, Atikun

2015-01-01

83

Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.  

PubMed

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results. PMID:21258801

Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

2012-05-01

84

Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA  

PubMed Central

Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of the specific glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation has a direct impact on cartilage and bone development, resulting in systemic skeletal dysplasia. There is no curative therapy for this skeletal dysplasia. This report describes long-term therapeutic efficacy in a 15-year-old boy with a severe form of MPS IVA who received successful allogeneic bone marrow transplantation (BMT) from his HLA-identical carrier sister. The level of the GALNS enzyme in the recipient’s lymphocytes reached almost half of normal level within two years after BMT. For the successive 9+ years post-BMT, GALNS activity in his lymphocytes maintained the same level as the donor’s, and the level of urinary uronic acid was reduced. Lumbar bone mineral density increased around 50% one year later post-BMT and was kept consistent. Radiographs showed that the figures of trochanter major and minor appeared, while the epiphyseal dysplasia in the femoral cap was almost unchanged. Loud snoring and apnea disappeared. Vital capacity increased to around 20% for the first two years and was maintained. Activity of daily life (ADL) was improved in work/study efficacy, respiratory status, sleep, joint pain, and frequency of infection. In conclusion, the long-term study of hematopoetic stem cell transplantation has shown clinical improvements in respiratory function, radiograph findings, ADL, and biochemical findings, suggesting that it is a potential therapeutic option for patients with MPS IVA. PMID:25593792

Chinen, Yasutsugu; Higa, Takeshi; Tomatsu, Shunji; Suzuki, Yasuyuki; Orii, Tadao; Hyakuna, Nobuyuki

2014-01-01

85

Continuing efficacy of milnacipran following long-term treatment in fibromyalgia: a randomized trial  

PubMed Central

Introduction Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to milnacipran (range, 17.9 to 54.4 months). Methods After completing a long-term, open-label, lead-in study of milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking milnacipran ?100 mg/day and reporting ?50% improvement from pre-milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to <30% reduction from pre-milnacipran exposure or worsening of fibromyalgia requiring alternative treatment. Adverse events and vital signs were also monitored. Results Time to LTR was shorter in patients randomized to placebo than in patients continuing milnacipran (P < 0.001). Median time to LTR was 56 days with placebo and was not calculable for milnacipran, because less than half of the latter group of patients lost therapeutic response by study end. Additionally, 81% of patients continuing on milnacipran maintained clinically meaningful pain response (?30% improvement from pre-milnacipran exposure), compared with 58% of patients switched to placebo (sensitivity analysis II; P < 0.001). The incidences of treatment-emergent adverse events were 58% and 47% for placebo and milnacipran, respectively. Mean decreases in blood pressure and heart rate were found in both groups, with greater decreases for patients switched to placebo. Conclusions Continuing efficacy of milnacipran was demonstrated by the loss of effect following withdrawal of treatment in patients who received an average of three years of milnacipran treatment. Trial registration ClinicalTrials.gov: NCT01014585 PMID:23953493

2013-01-01

86

Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging and Long-term Outcomes  

PubMed Central

Purpose To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials This study is Institutional Review Board approved and HIPPA compliant. 40 patients with hepatic neuroendocrine metastases were treated with 90Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria version 3.0. Response to therapy was assessed by size (WHO) and necrosis (EASL) guidelines. Time-to-response and overall survival was calculated using Kaplan-Meier method. Uni/multivariate analyses were performed. Results The median dose was 113 Gy (29 Gy-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); grade 3 and 4 bilirubin toxicities were experienced in 2 and 1 patient(s), respectively. Different responses were noted by WHO (CR: 1.2%, PR: 62.7%) and EASL (CR: 20.5%, PR: 43.4%). Median time-to-response was 4 and 4.9 months by lesion and subject, respectively. 1, 2 and 3-year overall survival rates were 72.5%, 62.5% and 45%, respectively. ECOG performance score 0 (p<0.0001), tumor burden ?25% (p=0.0019), albumin ?3.5 g/dL (p=0.017) and bilirubin ?1.2 mg/dL (p=0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin ?1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p=0.0001 and p=0.02). Conclusion 90Y therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival with low toxicity in line with published national guidelines recommending radioembolization as a potential option for unresectable hepatic neuroendocrine metastases. PMID:22137020

Memon, Khairuddin; Lewandowski, Robert J; Mulcahy, Mary F; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Gates, Vanessa L; Atassi, Bassel; Newman, Steven; Omary, Reed A; Benson, Al B; Salem, Riad

2011-01-01

87

Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD  

ERIC Educational Resources Information Center

Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

2009-01-01

88

Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants.  

PubMed

The long-term efficacy of hepatitis B vaccine, long-term effectiveness of hepatitis B immunisation programmes, immune memory induced by hepatitis B vaccine, current booster policies, and impact of hepatitis B virus mutants on immunisation programmes were reviewed at the Viral Hepatitis Prevention Board (VHPB) meeting in Sevilla, Spain, March 2004. The main focus was on universal vaccination programmes with data being presented from Italy, Saudi Arabia, Singapore, Spain, Taiwan, Thailand, The Gambia, and USA (Alaska). PMID:15964484

Fitzsimons, David; François, Guido; Hall, Andrew; McMahon, Brian; Meheus, André; Zanetti, Alessandro; Duval, Bernard; Jilg, Wolfgang; Böcher, Wulf Otto; Lu, Sheng-Nan; Akarca, Ulus; Lavanchy, Daniel; Goldstein, Susan; Banatvala, Jangu; Damme, Pierre Van

2005-07-14

89

Multicenter study of long-term (two-year) efficacy of lanthanum carbonate.  

PubMed

Long-term efficacy of lanthanum carbonate on hyperphosphatemia was examined in multicenter dialysis patients. Outcome and efficacy after 2 years was investigated in 101 patients who had undergone lanthanum carbonate administration. Thirty-three cases dropped out by the 2-year point; patients undergoing at least 2 years of administration totaled 68. Reasons for dropping out were as follows: improvement of hyperphosphatemia, nine cases; changing hospitals, seven cases; medical complications, five cases; digestive symptoms, four cases; poor compliance, four cases; parathyroidectomy, two cases; death, two cases. The mean dosage was increased from initial daily dosage of 744?mg to 1266?mg after 1 year, and to 1246?mg after 2 years. Serum phosphate concentration decreased significantly from the initial 6.15?mg to 5.57?mg/dL after 1 year, and to 5.45?mg/dL after 2 years. Although a lowering trend was observed in corrected calcium levels, the difference was not significant. Parathyroid hormone was unchanged. Achievement rate of Japanese Society for Dialysis Therapy (JSDT) management target values for both phosphorus and calcium improved from 32.7% to 50.0% after 1 year, and to 56.5% after 2 years. Lanthanum carbonate is useful as a therapeutic tool for hyperphosphatemia over long durations. PMID:23586506

Ando, Ryoichi; Kimura, Hitoshi; Sato, Hidehiko; Iwamoto, Shunsuke; Yoshizaki, Yuki; Chida, Yoshiko; Ishida, Yuji; Takayama, Masanobu; Yamada, Kouei; Tachibana, Ken; Ohtsuka, Masakazu; Kikuchi, Kan; Inoue, Atsushi

2013-04-01

90

Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex  

NASA Technical Reports Server (NTRS)

The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

Chen, W. R.; Lee, S.; Kato, K.; Spencer, D. D.; Shepherd, G. M.; Williamson, A.

1996-01-01

91

Long-term efficacy of denture cleansers in preventing Candida spp. biofilm recolonization on liner surface.  

PubMed

This study evaluated the long-term efficacy of denture cleansers against Candida spp. biofilm recolonization on liner surface. Specimens were fabricated of a poly(methyl methacrylate)-based denture liner and had their surface roughness evaluated at baseline and after cleansing treatments. C. albicans or C. glabrata biofilms were formed on liner surface for 48 h, and then the specimens were randomly assigned to one of cleaning treatments: two alkaline peroxides (soaking for 3 or 15 min), 0.5% sodium hypochlorite (10 min) or distilled water (control; 15 min). After the treatments, the specimens were sonicated to disrupt the biofilm, and residual cells were counted (cell/mL). Long-term effectiveness of the cleaning processes was determined by submitting a set of cleaned specimens to biofilm growth conditions for 48 h followed by estimation of cell counts. The topography of specimens after cleaning treatments was analyzed by SEM. Data were analyzed by ANOVA and Tukey's test (?; = 0.05). Results of cell count estimation showed significant differences in cleanliness among the treatments (p < 0.001), and it could be observed by SEM. However, no significant difference (p > 0.05) was observed among the Candida species regarding the recolonization condition. Alkaline denture cleansers showed similar cleaning performance and both differed from the control (p < 0.001). Sodium hypochlorite was the only treatment that removed biofilm efficiently, since no viable cells were found after its use. In conclusion, alkaline peroxide denture cleansers were not effective in removing Candida spp. biofilm from denture liner surfaces and preventing biofilm recolonization. PMID:20877973

Vieira, Ana Paula Coelho; Senna, Plínio Mendes; Silva, Wander José da; Del Bel Cury, Altair Antoninha

2010-01-01

92

Assessment of GE food safety using '-omics' techniques and long-term animal feeding studies.  

PubMed

Despite the fact that a thorough, lengthy and costly evaluation of genetically engineered (GE) crop plants (including compositional analysis and toxicological tests) is imposed before marketing some European citizens remain sceptical of the safety of GE food and feed. In this context, are additional tests necessary? If so, what can we learn from them? To address these questions, we examined data from 60 recent high-throughput '-omics' comparisons between GE and non-GE crop lines and 17 recent long-term animal feeding studies (longer than the classical 90-day subchronic toxicological tests), as well as 16 multigenerational studies on animals. The '-omics' comparisons revealed that the genetic modification has less impact on plant gene expression and composition than that of conventional plant breeding. Moreover, environmental factors (such as field location, sampling time, or agricultural practices) have a greater impact than transgenesis. None of these '-omics' profiling studies has raised new safety concerns about GE varieties; neither did the long-term and multigenerational studies on animals. Therefore, there is no need to perform such long-term studies in a case-by-case approach, unless reasonable doubt still exists after conducting a 90-day feeding test. In addition, plant compositional analysis and '-omics' profiling do not indicate that toxicological tests should be mandatory. We discuss what complementary fundamental studies should be performed and how to choose the most efficient experimental design to assess risks associated with new GE traits. The possible need to update the current regulatory framework is discussed. PMID:23253614

Ricroch, Agnès E

2013-05-25

93

Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature  

PubMed Central

Zonisamide (ZNS) efficacy and safety in epilepsy have been demonstrated in four double-blind, placebo-controlled studies. In the present article, we examined all long-term studies performed with this drug. Nine open-label studies, in which ZNS had been administered as an add-on or as monotherapy to epileptic patients for at least 6 months, were selected for our analysis. Four outcome measures were searched. Retention of this drug after 1 year varied between 45% and 65%. The percentages of patients achieving a ?50% seizure reduction, with respect to baseline, ranged between 37% and 65%. In patients with drug-resistant forms of epilepsy, the percentage of patients reaching a 6-month seizure freedom period was 9%. The percentages of patients who discontinued the experimental drug due to adverse effects ranged between 4% and 24%. Somnolence and dizziness were the most frequently reported adverse effects. Long-term studies demonstrate that ZNS has a good efficacy and tolerability profile, and support its use as adjunctive therapy for epileptic patients. PMID:19557119

Zaccara, Gaetano; Specchio, Luigi M

2009-01-01

94

Long term efficacy and patient satisfaction of microvascular decompression and gamma knife radiosurgery for trigeminal neuralgia.  

PubMed

The aim of our study was to evaluate the long term efficacy of microvascular decompression (MVD) and gamma knife radiosurgery (GKRS) with respect to pain relief and patient satisfaction. Both these modalities are accepted modalities of treatment for intractable trigeminal neuralgia. We excluded deceased patients, those who had a prior intervention and those requiring an additional intervention following initial treatment. A total of 69 patients were included in the study. Of these, 49 patients underwent treatment by GKRS and 20 by MVD. Pain status was assessed using the Barrow Neurological Institute (BNI) pain scale. The median follow up was 5.3years. There was no significant difference between the two groups with respect to initial pain relief (100% MVD, 84% GKRS; p=0.055). There was no significant difference in pain recurrence between the two groups (39% GKRS, 20% MVD; p=0.133). At last follow up, 85% of patients who underwent MVD had total pain relief (BNI scale I) compared to only 45% of GKRS patients (p=0.002). There was no significant difference in the patient satisfaction with respect to undergoing the same procedure again (90% MVD, 69% GKRS; p=0.1) and recommending it to family members (95% MVD, 84% GKRS; p=0.2). MVD offered total pain relief in a significantly higher number of patients than GKRS. There was no significant difference in the patient satisfaction rate between the two groups. PMID:25769254

Nanda, Anil; Javalkar, Vijayakumar; Zhang, Shihao; Ahmed, Osama

2015-05-01

95

Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes  

SciTech Connect

Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival with low toxicity, in line with published national guidelines recommending radioembolization as a potential option for unresectable hepatic neuroendocrine metastases.

Memon, Khairuddin; Lewandowski, Robert J. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Mulcahy, Mary F. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H.; Yaghmai, Vahid; Gates, Vanessa L.; Atassi, Bassel [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Newman, Steven [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Omary, Reed A. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Benson, Al B. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Salem, Riad, E-mail: r-salem@northwestern.edu [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States)

2012-07-01

96

Juxtaposing Math Self-Efficacy and Self-Concept as Predictors of Long-Term Achievement Outcomes  

ERIC Educational Resources Information Center

In this study, we tested the hypothesis that self-efficacy and self-concept reflect different underlying processes and both are critical to understanding long-term achievement outcomes. Although both types of self-belief are well established in educational psychology, research comparing and contrasting their relationship with achievement has been…

Parker, Philip David; Marsh, Herbert W.; Ciarrochi, Joseph; Marshall, Sarah; Abduljabbar, Adel Salah

2014-01-01

97

Long-term efficacy of NASHA Dx injection therapy for treatment of fecal incontinence  

PubMed Central

Background Injectable bulking treatment for fecal incontinence (FI) is intended to expand tissue in the anal canal and prevent fecal leakage. Use of injectable bulking agents is increasing because it can be performed in an outpatient setting and with low risk for morbidity. This study evaluated the long-term (36-month) clinical effectiveness and safety of injection of non-animal stabilized hyaluronic acid/dextranomer (NASHA Dx) on FI symptoms. Methods In a prospective multicenter trial, 136 patients with FI received the NASHA Dx bulking agent. Treatment success defined as a reduction in number of FI episodes by 50% or more compared with baseline (Responder50). Change from baseline in Cleveland Clinic Florida Fecal Incontinence Score (CCFIS) and Fecal Incontinence Quality of Life Scale (FIQL), and adverse events were also evaluated. Key Results Successful decrease in symptoms was achieved in 52% of patients at 6 months and this was sustained at 12 months (57%) and 36 months (52%). Mean CCFIS decreased from 14 at baseline to 11 at 36 months (p < 0.001). Quality-of-life scores for all four domains improved significantly between baseline and 36 months of follow-up. Severe adverse events were rare and most adverse events were transient and pertained to minor bleeding and pain or discomfort. Conclusions & Inferences Submucosal injection of NASHA Dx provided a significant improvement of FI symptoms in a majority of patients and this effect was stable during the course of the follow-up and maintained for 3 years. PMID:24837493

Mellgren, A; Matzel, K E; Pollack, J; Hull, T; Bernstein, M; Graf, W

2014-01-01

98

Improved spinal fusion efficacy by long-term delivery of bone morphogenetic protein-2 in a rabbit model  

PubMed Central

Background and purpose Various new delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2) have been introduced to improve its efficacy in osteogenesis. Of these, we have previously developed heparin-conjugated PLGA nanospheres (HCPN) as a long-term delivery system for BMP-2. In vitro studies have shown that the BMP-2 long-term delivery system enhances the level of bone formation. However, the long-term effects of BMP-2 on spinal fusion have not been assessed. Therefore, we now tested the hypothesis that the long-term delivery of BMP-2 using HCPN improves spinal fusion compared to short-term delivery in a rabbit fusion model. Methods 24 adult New Zealand White rabbits underwent posterolateral fusion (6 animals in 4 groups). The autograft group received an autologous iliac chip bone graft as a positive control. The BMP-2-PN group received rhBMP-2 (20 ?g per implant) and PLGA nanospheres (PN) suspended in fibrin gel, and served as a short-term release group. The HCPN group received HCPN suspended in fibrin gel without BMP-2 as a negative control. The BMP-2-HCPN group received rhBMP-2 (20 ?g per implant)-bound HCPN suspended in fibrin gel and served as a long-term release group. All animals were killed 12 weeks after surgery. Manual palpation, axial tensile tests, radiography, and histological evaluations were then performed. Results The spinal fusion rate and Young's modulus of the fusion mass were better in the BMP-2 long-term delivery group than in the short-term delivery group at an equivalent dose. However, the outcome of the long-term delivery was inferior to that of the autograft group. Interpretation The HCPN system showed potential as an effective carrier that might improve the osteogenic efficacy of BMP-2 for spinal fusion. PMID:22066556

2011-01-01

99

Long-Term Follow-up Observation of the Safety, Immunogenicity, and Effectiveness of Gardasil™ in Adult Women  

PubMed Central

Background Previous analyses from a randomized trial in women aged 24–45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN) and external genital lesions (EGL) related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women. Methods Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study [n?=?684]) or 29 to 50 years of age (in the original placebo group during the base study [n?=?651]). This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years) from both the original base study and the Colombian follow-up. Results There were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported. Conclusions Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24–45 year-old women. Trial Registration Clinicaltrials.gov NCT00090220 PMID:24391768

Luna, Joaquin; Plata, Manuel; Gonzalez, Mauricio; Correa, Alfonso; Maldonado, Ivete; Nossa, Claudia; Radley, David; Vuocolo, Scott; Haupt, Richard M.; Saah, Alfred

2013-01-01

100

Porous high-density polyethylene in functional rhinoplasty: Excellent long-term aesthetic results and safety  

PubMed Central

BACKGROUND: Experience with the use of porous high-density polyethylene (PHDPE) for reconstruction of the nasal framework has been limited. OBJECTIVE: To confirm the safety and utility of PHDPE by analyzing aesthetic outcomes and assessing the frequency of complication related to PHDPE in a large, population-based, long-term follow-up study. METHODS: A total of 151 patients who had undergone septoplasty and/or functional rhinoplasty using PHDPE were enrolled. PHDPE sheets were used for diverse purposes such as septal extension graft, spreader graft, columellar strut or dorsal augmentation graft. After a long-term follow-up period (mean [± SD] 39.5±27.8 months; range six to 101 months), postoperative aesthetic outcome was evaluated objectively (by independent surgeons) and subjectively (patient self-report). Complications related to PHDPE were estimated through review of medical records. RESULTS: The most common use of the PHDPE graft was for septal extension (n=80 [42.6%]) and spreader graft (n=58 [30.9%]). Results of aesthetic evaluation by surgeons were excellent in 61 cases (40.4%), good in 54 (35.8%) and fair in 34 (22.5%). According to patient self-report, 100 were ‘satisfied’ (66.2%) and 36 rated their new profile as ‘better than the preoperative profile’ (23.8%). Complications were reported in six cases (4.0% [five cases of extrusion and one case of infection]). All complications were resolved after the surgical removal of PHDPE sheets under local anesthesia. CONCLUSION: The present study demonstrated that PHDPE could be used in functional primary rhinoplasty with excellent long-term aesthetic results and safety. PMID:25152641

Kim, Young Hyo; Jang, Tae Young

2014-01-01

101

Long-term clinical trial safety experience with the inactivated split influenza vaccine, Vaxigrip.  

PubMed

Safety data on the inactivated split influenza vaccine, Vaxigrip, were compiled and analysed from 28 clinical trials (total: 4599 subjects aged 6 months to 99 years) to provide a robust estimate of the reactogenicity profile. The most frequent solicited reactions were non-severe injection site pain and erythema in children, adults, and elderly. Mild or moderate fever was the most frequent reaction in 6-36 months olds; few systemic reactions were reported in older groups. Reactogenicity was comparable in healthy and high-risk children. The long-term experience with the world's most widely used influenza vaccine, Vaxigrip, confirms its excellent tolerability, and supports its continued use in clinical practice worldwide. PMID:16271424

Delore, Valentine; Salamand, Camille; Marsh, Grenville; Arnoux, Sabine; Pepin, Stephanie; Saliou, Pierre

2006-03-01

102

Monitoring the Long-Term Safety Performance of a Repository for Used Nuclear Fuel - 12294  

SciTech Connect

The nuclear waste management programs of several nations include plans for the design, construction and operation of deep geological repositories. Some of these programs have initiated the licensing process for their repository designs. Monitoring strategies and systems are at different levels of development in each program and there is common ground with respect to the ultimate goal of the monitoring function. In this context, the primary functions of a monitoring system are considered to be the verification of safety performance and making available information that may be required for implementation of future decisions such as the timing of repository decommissioning and closure or the possible retrieval of waste containers. This study examines some of the relevant issues and outlines a conceptual monitoring system for further study and development during implementation of Adaptive Phased Management, the method selected by the Government of Canada for long-term management of used nuclear fuel. (author)

Villagran, J.E. [Nuclear Waste Management Organization, Toronto (Canada)

2012-07-01

103

Parametric Analysis of PWR Spent Fuel Depletion Parameters for Long-Term-Disposal Criticality Safety  

SciTech Connect

Utilization of burnup credit in criticality safety analysis for long-term disposal of spent nuclear fuel allows improved design efficiency and reduced cost due to the large mass of fissile material that will be present in the repository. Burnup-credit calculations are based on depletion calculations that provide a conservative estimate of spent fuel contents (in terms of criticality potential), followed by criticality calculations to assess the value of the effective neutron multiplication factor (k(sub)eff) for the a spent fuel cask or a fuel configuration under a variety of probabilistically derived events. In order to ensure that the depletion calculation is conservative, it is necessary to both qualify and quantify assumptions that can be made in depletion models.

DeHart, M.D.

1999-08-01

104

Safety of long-term dietary supplementation with L-arginine in pigs.  

PubMed

This study was conducted with a swine model to determine the safety of long-term dietary supplementation with L-arginine-HCl or L-arginine free base. Beginning at 30 days of age, pigs were fed a corn- and soybean meal-based diet (31.5 g/kg body weight/day) supplemented with 0, 1.21, 1.81 or 2.42 % L-arginine-HCl (Experiment 1) or with 0, 1, 1.5 or 2 % L-arginine (Experiment 2). The supplemental doses of 0, 1, 1.5, and 2 % L-arginine provided pigs with 0, 315, 473, and 630 mg L-arginine/kg body weight/day, respectively, which were equivalent to 0, 286, 430, and 573 mg L-arginine/kg body weight/day, respectively, in humans. At 121 days of age (91 days after initiation of supplementation), blood samples were obtained from the jugular vein of pigs at 1 and 4 h after feeding for hematological and clinical chemistry tests. Dietary supplementation with L-arginine increased plasma concentrations of arginine, ornithine, proline, albumin and reticulocytes, while reducing plasma concentrations of ammonia, free fatty acids, triglyceride, cholesterol, and neutrophils. L-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Other variables in standard hematology and clinical chemistry tests, serum concentrations of insulin, growth hormone and insulin-like growth factor-I did not differ among all the groups of pigs. These results indicate that dietary supplementation with L-arginine (up to 630 mg/kg body weight/day) is safe in pigs for at least 91 days. Our findings help guide clinical studies to determine the safety of long-term oral administration of L-arginine to humans. PMID:25655382

Hu, Shengdi; Li, Xilong; Rezaei, Reza; Meininger, Cynthia J; McNeal, Catherine J; Wu, Guoyao

2015-05-01

105

Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease  

Microsoft Academic Search

Hydroxyurea improves hematologic pa- rameters for children with sickle cell dis- ease (SCD), but its long-term efficacy at maximum tolerated dose (MTD) has not been determined. Between 1995 and 2002, hydroxyurea therapy was initiated for 122 pediatric patients with SCD including 106 with homozygous sickle cell anemia (HbSS), 7 with sickle hemoglobin C (HbSC), 7 with sickle\\/-thalassemia (HbS\\/ -thalassemia (6

Sherri A. Zimmerman; William H. Schultz; Jacqueline S. Davis; Chrisley V. Pickens; Nicole A. Mortier; Thad A. Howard; Russell E. Ware

2003-01-01

106

Long-term residual efficacy of commerical formulations of 16 pesticides to Typhlodromus pyri Scheuten (Acari: Phytoseiidae) inhabiting commerical vineyards  

Microsoft Academic Search

The long-term residual efficacy of 16 pesticides to the predatory phytoseiid mite,Typhlodromus pyri Scheuten, inhabiting commercial sprayed vineyards in South Moravia, Czchoslovakia, was evaluated in laboratory bioassays. Omethoate, chlorpyrifos-methyl and esfenvalerate were assessed as harmful and should not be sprayed. Mancozeb-efosite-Al mixture, diazinon, dicofol, bromopropylate, azinphos-ethyl and phosmet were assessed as moderately harmful. Fenitrothion, phosalone and mancozeb were assessed as

Miloslav Zacharda; Milan Hluchý

1991-01-01

107

Mathematical Analysis of the Long-Term Efficacy of Daily Home Hemodialysis Therapy with a Cold Dialysate Regeneration System  

Microsoft Academic Search

Background\\/Aim: We previously developed the cold dialysate regeneration system (CDRS) for use in daily home hemodialysis (HD). This study evaluates the long-term efficacy of the CDRS using a mathematical method. Method: HD with the CDRS was simulated using a method that integrates the mass-transfer model and the dialyzer solute kinetics model with a newly proposed model of CDRS function. Results:

Ki Moo Lim; Ji Hyun Kim; Eun Bo Shim

2010-01-01

108

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis  

PubMed Central

Background and objective Pirfenidone is an oral antifibrotic agent that is approved in several countries for the treatment of idiopathic pulmonary fibrosis (IPF). We performed a comprehensive analysis of safety across four clinical trials evaluating pirfenidone in patients with IPF. Methods All patients receiving pirfenidone 2403?mg/day in the Phase 3 CAPACITY studies (Studies 004 and 006) and all patients receiving at least one dose of pirfenidone in one of two ongoing open-label studies in patients with IPF (Studies 002 and 012) were selected for inclusion. Safety outcomes were evaluated from baseline until 28 days after the last dose of study drug. Results A total of 789 patients were included in the analysis. The median duration of exposure to pirfenidone was 2.6 years (range, 1 week–7.7 years), and the cumulative total exposure was 2059 person exposure years (PEY). Gastrointestinal and skin-related events were the most commonly reported adverse events; these were almost always mild to moderate in severity, and rarely led to treatment discontinuation. Elevations (>3× upper limit of normal) in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) occurred in 21/789 (2.7%) patients; the adjusted incidence of AST/ALT elevations was 1.7 per 100 PEY. Conclusions This comprehensive analysis of safety in a large cohort of IPF patients receiving pirfenidone for a total of 2059 PEY demonstrates that long-term treatment with pirfenidone is safe and generally well tolerated. PMID:24836849

Valeyre, Dominique; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; King, Talmadge E; Leff, Jonathan A; Noble, Paul W; Sahn, Steven A; du Bois, Roland M

2014-01-01

109

Quantitative Assessment of Countermeasure Efficacy for Long-Term Space Missions  

NASA Technical Reports Server (NTRS)

This slide presentation reviews the development of quantitative assessments of the effectiveness of countermeasures (CM) for the effects of space travel on humans for long term space missions. An example of bone mineral density (BMD) is examined to show specific quantitative measures for failure and success.

Feiveson, Alan H.

2000-01-01

110

The safety of etretinate as long-term therapy for psoriasis: Results of the Etretinate Follow-up Study  

Microsoft Academic Search

Background: Etretinate is an aromatic retinoid given orally to treat severe psoriasis, a chronic disease that often requires long-term therapy.Objective: We assessed the safety of long-term therapy with etretinate for psoriasis.Methods: This 5-year prospective study of a cohort of 956 patients with psoriasis treated with etretinate assessed the frequency of adverse events in relation to total use and in relation

Robert S Stern; Elizabeth Fitzgerald; Charles N Ellis; Nicholas Lowe; Michael T Goldfarb; Richard D Baughman

1995-01-01

111

Bronchial Thermoplasty – Long Term Safety and Effectiveness in Severe Persistent Asthma  

PubMed Central

Background Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. Objective To assess effectiveness and safety of BT in asthma patients 5 years post therapy. Methods BT-treated subjects from the Asthma Intervention Research 2 (AIR2) Trial (ClinicalTrials.gov NCT01350414) were evaluated annually for 5 years to assess long-term safety of BT and durability of treatment effect. Outcomes assessed post-BT included severe exacerbations, adverse events, healthcare utilization, spirometry data, and high resolution computed tomography (HRCT) scans. Results 162/190 BT-treated subjects (85.3%) from the AIR2 Trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and Emergency Room visits, and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months prior to BT treatment (average 5 year reduction in proportions: 44% for exacerbations and 78% for ER visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in Years 2 through 5 as compared to the first year after BT. Pre-BD FEV1 values remained stable between years 1 and 5 after BT, despite a 17% reduction in average daily inhaled corticosteroid dose. HRCT scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. Conclusions These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ER visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking ICS (inhaled corticosteroids) and LABA (long-acting-?2-agonists). PMID:23998657

Wechsler, Michael E.; Laviolette, Michel; Rubin, Adalberto S.; Fiterman, Jussara; Lapa e Silva, Jose R.; Shah, Pallav L.; Fiss, Elie; Olivenstein, Ronald; Thomson, Neil C.; Niven, Robert M.; Pavord, Ian D.; Simoff, Michael; Hales, Jeff B.; McEvoy, Charlene; Slebos, Dirk-Jan; Holmes, Mark; Phillips, Martin J.; Erzurum, Serpil C.; Hanania, Nicola A.; Sumino, Kaharu; Kraft, Monica; Cox, Gerard; Sterman, Daniel H.; Hogarth, Kyle; Kline, Joel N.; Mansur, Adel H.; Louie, Brian E.; Leeds, William M.; Barbers, Richard G.; Austin, John H.M.; Shargill, Narinder S.; Quiring, John; Armstrong, Brian; Castro, Mario

2014-01-01

112

Long-term efficacy of tiotropium in relation to smoking status in the UPLIFT trial.  

PubMed

UPLIFT (Understanding Potential Long-Term Improvements in Function with Tiotropium), a 4-yr trial of tiotropium in chronic obstructive pulmonary disease, allowed for assessment of smoking status on long-term responses to maintenance bronchodilator therapy. 5,993 patients were randomised (tiotropium/placebo). Lung function, St George's Respiratory Questionnaire, exacerbations and adverse events were followed. Patients were characterised as continuing smokers (CS), continuing ex-smokers (CE), or intermittent smokers (IS) based on self-reporting smoking behaviour. 60%, 14% and 26% of patients were CE, CS and IS, respectively. The rate of forced expiratory volume in 1 s (FEV(1)) decline for placebo patients was most rapid in CS (-52+/-4, -37+/2 and -23+/2 mL.yr(-1) in CS, IS, and CE, respectively). Tiotropium did not alter FEV(1) decline, but was associated with significant improvements in pre- and post-bronchodilator FEV(1) over placebo that persisted throughout the 4-yr trial for each smoking status (pre-bronchodilator: 127, 55 and 97 mL at 48 months in CS, IS and CE, respectively; p< or =0.0003). Tiotropium reduced exacerbation risk in CS (HR (95% CI) 0.80 (0.67-0.95)), in CE (0.85 (0.79-0.92)) and trended towards significance in IS (0.89 (0.79-1.00)). At 4 yrs, St George's Respiratory Questionnaire for tiotropium patients improved the most in CS (-4.63 units, p = 0.0006) and the least in IS (-0.60 units, p = 0.51), [corrected] compared with control. Tiotropium provided long-term benefits irrespective of smoking status, although differences among categories were observed. PMID:19717481

Tashkin, D P; Celli, B; Kesten, S; Lystig, T; Mehra, S; Decramer, M

2010-02-01

113

Long-term outcome and efficacy of endoscopic hemorrhoid ligation for symptomatic internal hemorrhoids  

PubMed Central

AIM: To assess the long-term outcome of endoscopic hemorrhoid ligation (EHL) for the treatment of symptomatic internal hemorrhoids. METHODS: A total of 759 consecutive patients (415 males and 344 females) were enrolled. Clinical presentations were rectal bleeding (593 patients) and mucosal prolapse (166 patients). All patients received EHL at outpatient clinics. Hemorrhoid severity was classified by Goligher’s grading. The mean follow-up period was 55.4 mo (range, 45-92 mo). RESULTS: The number of band ligations averaged 2.35 in the first session for bleeding and 2.69 for prolapsed patients. Bleeding was controlled in 587 (98.0%) patients, while prolapse was reduced in 137 (82.5%) patients. After treatment, 93 patients experienced anal pain and 48 patients had mild bleeding. Patient subjective satisfaction was 93.6%. Repeat treatment or surgery was performed if symptoms were not relieved in the first session. In the bleeding group, the recurrence rate was 3.7% (22 patients) at 1 year, and 6.6% and 13.0% at 2 and 5 years. In the prolapsed group, the recurrence rate was 3.0%, 9.6% and 16.9% at 1, 2 and 5 years, respectively. CONCLUSION: EHL is an easy and well-tolerated procedure for the treatment of symptomatic internal hemorrhoids, with good long-term results. PMID:21633644

Su, Ming-Yao; Chiu, Cheng-Tang; Lin, Wei-Pin; Hsu, Chen-Ming; Chen, Pang-Chi

2011-01-01

114

Multicenter study on the long-term (3-year) efficacy of lanthanum carbonate in dialysis patients.  

PubMed

We previously conducted a multicenter study enrolling 101 dialysis patients with hyperphosphatemia in which lanthanum carbonate (LC) was administered for 2 years. In this study, the administration has been continued for an additional year, and we have evaluated the long-term (a total of 3 years) effects of LC. The average serum phosphorus (P) level was 6.05 mg/dL at the start and decreased to 5.84 mg/dL after 3 years, but no significant differences were observed at both points. The average serum corrected calcium (Ca) level significantly reduced after 3 years (P < 0.001). As results of evaluating the achievement rates with the management target values of serum P, Ca and intact parathyroid hormone (PTH) stated in the Japanese guideline, the achievement rates increased after 3 years. From these results, LC is considered to be a useful P binder that can be used for long-term treatment of hyperphosphatemia, without causing a Ca load. PMID:24953759

Ando, Ryoichi; Yama, Satomi; Ohnishi, Tsuyoshi; Iwamoto, Shunsuke; Kimura, Hitoshi; Chida, Yoshiko; Ishida, Yuji; Yamada, Kouei; Inagaki, Yuichiro; Takayama, Masanobu; Tachibana, Ken; Kikuchi, Kan; Inoue, Atsushi; Ohtsuka, Masakazu

2014-06-01

115

Monitoring the Long-Term Effectiveness of Integrated Safety Management System (ISMS) Implementation Through Use of a Performance Dashboard Process  

SciTech Connect

This session will examine a method developed by Federal and Contractor personnel at the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) to examine long-term maintenance of DOE Integrated Safety Management System (ISMS) criteria, including safety culture attributes, as well as identification of process improvement opportunities. This process was initially developed in the summer of 2000 and has since been expanded to recognize the importance of safety culture attributes, and associated safety culture elements, as defined in DOE M 450.4-1, “Integrated Safety Management System Manual.” This process has proven to significantly enhance collective awareness of the importance of long-term ISMS implementation as well as support commitments by NNSA/NSO personnel to examine the continued effectiveness of ISMS processes.

Michael D. Kinney and William D. Barrick

2008-09-01

116

Long-Term Efficacy of Systemic Multiexon Skipping Targeting Dystrophin Exons 45–55 With a Cocktail of Vivo-Morpholinos in Mdx52 Mice  

PubMed Central

Antisense-mediated exon skipping, which can restore the reading frame, is a most promising therapeutic approach for Duchenne muscular dystrophy. Remaining challenges include the limited applicability to patients and unclear function of truncated dystrophin proteins. Multiexon skipping targeting exons 45–55 at the mutation hotspot of the dystrophin gene could overcome both of these challenges. Previously, we described the feasibility of exons 45–55 skipping with a cocktail of Vivo-Morpholinos in vivo; however, the long-term efficacy and safety of Vivo-Morpholinos remains to be determined. In this study, we examined the efficacy and toxicity of exons 45–55 skipping by intravenous injections of 6?mg/kg 10-Vivo-Morpholino cocktail (0.6?mg/kg each vPMO) every 2 weeks for 18 weeks to dystrophic exon-52 knockout (mdx52) mice. Systemic skipping of the entire exons 45–55 region was induced, and the Western blot analysis exhibited the restoration of 5–27% of normal levels of dystrophin protein in skeletal muscles, accompanied by improvements in histopathology and muscle strength. No obvious immune response and renal and hepatic toxicity were detected at the end-point of the treatment. We demonstrate our new regimen with the 10-Vivo-Morpholino cocktail is effective and safe for long-term repeated systemic administration in the dystrophic mouse model. PMID:25647512

Echigoya, Yusuke; Aoki, Yoshitsugu; Miskew, Bailey; Panesar, Dharminder; Touznik, Aleksander; Nagata, Tetsuya; Tanihata, Jun; Nakamura, Akinori; Nagaraju, Kanneboyina; Yokota, Toshifumi

2015-01-01

117

Long-term outcome and safety of transanal colonic irrigation for neurogenic bowel dysfunction  

Microsoft Academic Search

Study design:Long-term follow-up study.Objectives:Short-term results find transanal colonic irrigation (TAI) favourable in the treatment of neurogenic bowel dysfunction (NBD). Therefore, long-term results need to be described.Setting:Department of Surgery P, Aarhus University Hospital, Denmark.Methods:Between 1994 and 2007, 211 (115 female) patients with NBD (age: 7–81 years (median 49)) were introduced to TAI. One hundred and seventy-three patients had spinal cord injury

P M Faaborg; P Christensen; B Kvitsau; S Buntzen; S Laurberg; K Krogh

2009-01-01

118

Return-to-Work Self-Efficacy and Actual Return to Work Among Long-Term Sick-Listed Employees.  

PubMed

Objective Considering the costs incurred by sickness absence and the implications for the workers' quality of life, a fast return to work (RTW) is important. Self-efficacy (SE) seems to be an important predictor of RTW for employees with mental health problems. The predictive value of return-to-work self-efficacy (RTW-SE) has not been examined in employees on long-term sickness absence due to any cause. The aim of this study is to investigate whether RTW-SE is a predictor of time to RTW in long-term sick-listed employees with all-cause sickness absence. Furthermore, the relative contribution of RTW-SE in predicting RTW will be examined compared to health-related, job-related and personal factors. Methods In a longitudinal study, sick-listed employees who were currently on sick leave for more than 4 weeks filled out a self-report questionnaire. Demographics, health-related, personal, and job-related factors, and RTW-SE were measured. Employees were followed for 2 years to determine the duration until full RTW. Cox proportional hazards regression analyses were used to identify factors associated with time to RTW. Results Data were collected from 493 sick-listed employees. RTW-SE was a significant predictor of RTW. In a multivariate model, low RTW-SE, the thought of not being able to work while having symptoms (illness behaviour) and having chronic medical conditions were predictors of a longer duration until RTW. Conclusion When guiding long-term sick-listed employees, it is important to focus on factors such as SE and illness behaviour, instead of just focusing on the symptoms of the sick-listed employee. PMID:25354750

Volker, D; Zijlstra-Vlasveld, M C; Brouwers, E P M; van Lomwel, A G C; van der Feltz-Cornelis, C M

2014-10-30

119

The Association between Obstructive Sleep Apnea and Neurocognitive Performance—The Apnea Positive Pressure Long-term Efficacy Study (APPLES)  

PubMed Central

Study Objectives: To determine associations between obstructive sleep apnea (OSA) and neurocognitive performance in a large cohort of adults. Study Design: Cross-sectional analyses of polysomnographic and neurocognitive data from 1204 adult participants with a clinical diagnosis of obstructive sleep apnea (OSA) in the Apnea Positive Pressure Long-term Efficacy Study (APPLES), assessed at baseline before randomization to either continuous positive airway pressure (CPAP) or sham CPAP. Measurements: Sleep and respiratory indices obtained by laboratory polysomnography and several measures of neurocognitive performance. Results: Weak correlations were found for both the apnea hypopnea index (AHI) and several indices of oxygen desaturation and neurocognitive performance in unadjusted analyses. After adjustment for level of education, ethnicity, and gender, there was no association between the AHI and neurocognitive performance. However, severity of oxygen desaturation was weakly associated with worse neurocognitive performance on some measures of intelligence, attention, and processing speed. Conclusions: The impact of OSA on neurocognitive performance is small for many individuals with this condition and is most related to the severity of hypoxemia. Citation: Quan SF; Chan CS; Dement WC; Gevins A; Goodwin JL; Gottlieb DJ; Green S; Guilleminault C; Hirshkowitz M; Hype PR; Kay GG; Leary EB; Nichols DA; Schweitzer PK; Simon RD; Walsh JK; Kushida CA. The association between obstructive sleep apnea and neurocognitive performance—the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2011;34(3):303-314. PMID:21358847

Quan, Stuart F.; Chan, Cynthia S.; Dement, William C.; Gevins, Alan; Goodwin, James L.; Gottlieb, Daniel J.; Green, Sylvan; Guilleminault, Christian; Hirshkowitz, Max; Hyde, Pamela R.; Kay, Gary G.; Leary, Eileen B.; Nichols, Deborah A.; Schweitzer, Paula K.; Simon, Richard D.; Walsh, James K.; Kushida, Clete A.

2011-01-01

120

Intrathecal Ziconotide for Severe Chronic Pain: Safety and Tolerability Results of an Open-Label, Long-Term Trial  

Microsoft Academic Search

BACKGROUND: Ziconotide is a non-opioid drug indicated for management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted and who are intolerant of or refractory to other treatments. METHODS: Six-hundred and forty-four patients with severe chronic pain participated in this open-label, multicenter study. Ziconotide titration was followed by long-term infusion. Efficacy assessments included the Visual Analog

Mark S. Wallace; Richard Rauck; Robert Fisher; Steven G. Charapata; David Ellis; Sanjeeva Dissanayake

2008-01-01

121

Long-Term Efficacy and Patterns of Failure After Accelerated Partial Breast Irradiation: A Molecular Assay-Based Clonality Evaluation  

SciTech Connect

Purpose: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience. Methods and Materials: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for {>=}10 years. Results: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction-based loss of heterozygosity assay. Eighty-three percent of IBTRs (n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients. Conclusions: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction-based loss of heterozygosity assay, 83% of recurrences were classified as clonally related.

Vicini, Frank A. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)]. E-mail: fvicini@beaumont.edu; Antonucci, J. Vito [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Wallace, Michelle R.N. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Gilbert, Samuel [University of Michigan, Ann Arbor, MI (United States); Goldstein, Neal S. [Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI (United States); Kestin, Larry [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Chen, Peter [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Kunzman, Jonathan [Western Michigan University, Kalamazoo, MI (United States); Boike, Thomas [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Benitez, Pamela [Department of Surgery, William Beaumont Hospital, Royal Oak, MI (United States); Martinez, Alvaro [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

2007-06-01

122

Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID).  

PubMed

Adenosine deaminase (ADA)-deficient Severe Combined Immunodeficiency (ADA-deficient SCID) is characterized by impaired lymphocyte development and function resulting from the adenosine metabolism defect. Enzyme replacement therapy with polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) minimizes infectious complications of ADA-deficient patients who have not received bone marrow transplantation. In PEG-ADA therapy, enzymatically active ADA continuously circulates to act as a metabolic sink, detoxifying the adenosine and deoxyadenosine metabolites that accumulate to high levels in the absence of ADA. Studies have shown that upon the initiation of PEG-ADA therapy, the absolute numbers of circulating T and B lymphocytes and NK cells increase and protective immune function develops. However, the long-term efficacy is unknown. This retrospective study was designed to assess the long-term effectiveness of PEG-ADA treatment, based on evaluation of the immune function of nine ADA-deficient SCID patients (age 5-15) treated over the past decade. The results showed that the lymphocyte counts of all of the PEG-ADA treated patients were below the normal range at all times, despite initial improvements. A gradual decline of mitogenic proliferative responses occurred after a few years of treatment and normal antigenic response occurred less than expected. To this date, these low numbers and functions of lymphocytes had been adequate to provide protective immunity. These patients should be followed closely to detect a premature decline in immune function with aging in future decades of PEG-ADA therapy. PMID:16112907

Chan, Belinda; Wara, Diane; Bastian, John; Hershfield, Michael S; Bohnsack, John; Azen, Colleen G; Parkman, Robertson; Weinberg, Kenneth; Kohn, Donald B

2005-11-01

123

Patient Safety Policy in Long-Term Care: A Research Protocol to Assess Executive WalkRounds to Improve Management of Early Warning Signs for Patient Safety  

PubMed Central

Background At many hospitals and long-term care organizations (such as nursing homes), executive board members have a responsibility to manage patient safety. Executive WalkRounds offer an opportunity for boards to build a trusting relationship with professionals and seem useful as a leadership tool to pick up on soft signals, which are indirect signals or early warnings that something is wrong. Because the majority of the research on WalkRounds has been performed in hospitals, it is unknown how board members of long-term care organizations develop their patient safety policy. Also, it is not clear if these board members use soft signals as a leadership tool and, if so, how this influences their patient safety policies. Objective The objective of this study is to explore the added value and the feasibility of WalkRounds for patient safety management in long-term care. This study also aims to identify how executive board members of long-term care organizations manage patient safety and to describe the characteristics of boards. Methods An explorative before-and-after study was conducted between April 2012 and February 2014 in 13 long-term care organizations in the Netherlands. After implementing the intervention in 6 organizations, data from 72 WalkRounds were gathered by observation and a reporting form. Before and after the intervention period, data collection included interviews, questionnaires, and studying reports of the executive boards. A mixed-method analysis is performed using descriptive statistics, t tests, and content analysis. Results Results are expected to be ready in mid 2014. Conclusions It is a challenge to keep track of ongoing development and implementation of patient safety management tools in long-term care. By performing this study in cooperation with the participating long-term care organizations, insight into the potential added value and the feasibility of this method will increase. PMID:25048598

Hamers, Hub; van Achterberg, Theo; Schoonhoven, Lisette

2014-01-01

124

Long-term safety and tolerance of silicone and self-expandable airway stents: an experimental study  

Microsoft Academic Search

Background. A variety of respiratory stents are currently available, but the ideal airway prosthesis seems far from being recognized. The objective of this study was to verify safety and long-term effect on the bronchial wall of three different types of airway stents.Methods. Twelve healthy adult sheep were divided in three groups, scheduled to receive: (1) bare self-expandable metallic stents (Gianturco);

Francesco Puma; Raffaele Farabi; Moira Urbani; Stefano Santoprete; Niccolò Daddi; Antonio Di Meo; Rodolfo Gialletti; Adriano Tocchi; Giuliano Daddi

2000-01-01

125

Long-term antibacterial efficacy of air plasma-activated water  

NASA Astrophysics Data System (ADS)

Indirect air dielectric barrier discharge in close proximity to water creates an acidified, nitrogen-oxide containing solution known as plasma-activated water (PAW), which remains antibacterial for several days. Suspensions of E. coli were exposed to PAW for either 15 min or 3 h over a 7-day period after PAW generation. Both exposure times yielded initial antibacterial activity corresponding to a ~5-log reduction in cell viability, which decreased at differing rates over 7 days to negligible activity and a 2.4-log reduction for 15 min and 3 h exposures, respectively. The solution remained at pH ~2.7 for this period and initially included hydrogen peroxide, nitrate and nitrite anions. The solution composition varied significantly over this time, with hydrogen peroxide and nitrite diminishing within a few days, during which the antibacterial efficacy of 15 min exposures decreased significantly, while that of 3 h exposures produced a 5-log reduction or more. These results highlight the complexity of PAW solutions where multiple chemical components exert varying biological effects on differing time scales.

Traylor, Matthew J.; Pavlovich, Matthew J.; Karim, Sharmin; Hait, Pritha; Sakiyama, Yukinori; Clark, Douglas S.; Graves, David B.

2011-11-01

126

Intraoperative defibrillation threshold testing and postoperative long-term efficacy of cardioverter-defibrillator implantation  

PubMed Central

The aim of this study was to determine the defibrillation threshold (DFT) of implantable cardioverter-defibrillators (ICDs) and outcomes of treatment. Sixty-four patients received cardioverter-defibrillator implantation. During implantation, the DFT was determined by the defibrillation safety margin (DSM). All patients were followed up for 12–48 months after the implantation. The overall DFT was 14.27±2.56 J and the DSM was 18.40±1.89 J. Malignant ventricular arrhythmias occurred in 42 patients following cardioverter-defibrillator implantation including 500 episodes of non-sustained ventricular tachycardia (VT) and 289 episodes of persistent VT. VT was treated using antitachycardia pacing (ATP); 265 episodes were treated successfully by a single ATP treatment (91.69%) and 12 episodes were treated successfully by two ATP treatments (4.15%). Twelve episodes were converted by low-energy electrical cardioversion (4.15%). A total of 175 ventricular fibrillation (VF) episodes were identified, of which 18 episodes automatically terminated prior to treatment. In total, 146 episodes were converted by a single cardioversion with a defibrillation energy of 13.21±2.58 J and 11 episodes were converted by two cardioversions with a defibrillation energy of 16.19±2.48 J. It is safe and feasible to determine the DFT by DSM measurement during cardioverterdefibrillator implantation. PMID:23251292

GAN, TIANYI; CAO, XIAOZHI; YU, ZHANG; TANG, BAOPENG; LI, JINXIN; XU, GUOJUN; ZHOU, XIANHUI; ZHANG, YANYI; LI, YAODONG; ZHANG, JIANGHUA

2013-01-01

127

Long-Term Effects of Nucleus Accumbens Deep Brain Stimulation in Treatment-Resistant Depression: Evidence for Sustained Efficacy  

PubMed Central

Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated with antidepressant, anxiolytic, and procognitive effects in a small sample of patients suffering from treatment-resistant depression (TRD), followed over 1 year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients. Clinical effects, quality of life (QoL), cognition, and safety are reported. Eleven patients were stimulated with DBS bilateral to the NAcc. Main outcome measures were clinical effect (Hamilton Depression Rating Scale, Montgomery-Asperg Rating Scale of Depression, and Hamilton Anxiety Scale) QoL (SF-36), cognition and safety at baseline, 12 months (n=11), 24 months (n=10), and last follow-up (maximum 4 years, n=5). Analyses were performed in an intent-to-treat method with last observation carried forward, thus 11 patients contributed to each point in time. In all, 5 of 11 patients (45%) were classified as responders after 12 months and remained sustained responders without worsening of symptoms until last follow-up after 4 years. Both ratings of depression and anxiety were significantly reduced in the sample as a whole from first month of NAcc-DBS on. All patients improved in QoL measures. One non-responder committed suicide. No severe adverse events related to parameter change were reported. First-time, preliminary long-term data on NAcc-DBS have demonstrated a stable antidepressant and anxiolytic effect and an amelioration of QoL in this small sample of patients suffering from TRD. None of the responders of first year relapsed during the observational period (up to 4 years). PMID:22473055

Bewernick, Bettina H; Kayser, Sarah; Sturm, Volker; Schlaepfer, Thomas E

2012-01-01

128

Long-Term Stability and Safety of Transgenic Cultured Epidermal Stem Cells in Gene Therapy of Junctional Epidermolysis Bullosa  

PubMed Central

Summary We report a long-term follow-up (6.5 years) of a phase I/II clinical trial envisaging the use of autologous genetically modified cultured epidermal stem cells for gene therapy of junctional epidermolysis bullosa, a devastating genetic skin disease. The critical goals of the trial were to evaluate the safety and long-term persistence of genetically modified epidermis. A normal epidermal-dermal junction was restored and the regenerated transgenic epidermis was found to be fully functional and virtually indistinguishable from a normal control. The epidermis was sustained by a discrete number of long-lasting, self-renewing transgenic epidermal stem cells that maintained the memory of the donor site, whereas the vast majority of transduced transit-amplifying progenitors were lost within the first few months after grafting. These data pave the way for the safe use of epidermal stem cells in combined cell and gene therapy for genetic skin diseases. PMID:24511464

De Rosa, Laura; Carulli, Sonia; Cocchiarella, Fabienne; Quaglino, Daniela; Enzo, Elena; Franchini, Eleonora; Giannetti, Alberto; De Santis, Giorgio; Recchia, Alessandra; Pellegrini, Graziella; De Luca, Michele

2013-01-01

129

Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course.  

PubMed

In order to evaluate the efficacy, time-course of action and predictors of response to topical capsaicin, 39 patients with chronic post-herpetic neuralgia (PHN), median duration 24 months, were treated with 0.025% capsaicin cream for 8 weeks. During therapy the patients rated their pain on a visual analogue scale (VAS) and a verbal outcome scale. A follow-up investigation was performed 10-12 months after study onset on the patients who had improved. Nineteen patients (48.7%) substantially improved after the 8-week trial; 5 (12.8%) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations (4) or mastitis (1); 15 (38.5%) reported no benefit. The decrease in VAS ratings was significant after 2 weeks of continuous application. Of the responders 72.2% were still improved at the follow-up; only one-third of them had continued application irregularly. Treatment effect was not dependent on patient's age, duration or localization of PHN (trigeminal involvement was excluded), sensory disturbance or pain character. Treatment response was not correlated with the incidence, time-course or severity of capsaicin-induced burning. If confirmed in controlled trials, the long-term results of this open, non-randomized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes (perhaps degeneration) of nociceptive afferents. PMID:1779253

Peikert, A; Hentrich, M; Ochs, G

1991-12-01

130

Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement  

PubMed Central

Ustekinumab is a fully human monoclonal antibody targeting the common p40 subunit shared by interleukin (IL)-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 with their cell surface receptors, and thus blocks T helper (Th)-1 IL-12 and Th-17 IL-23 inflammatory pathways. Ustekinumab has been evaluated in the treatment of various chronic immune-mediated diseases including, psoriasis, psoriatic arthritis, Crohn’s disease, and multiple sclerosis. It led to a rapid and durable improvement in psoriasis area and severity index in patients with moderate to severe psoriasis. Ustekinumab also improved joint symptoms of psoriatic arthritis. Results in Crohn’s disease were more mitigated, albeit with a symptomatic improvement in patients refractory to tumor necrosis factor-? inhibitors. Ustekinumab did not reduce the number of magnetic resonance imaging brain lesions in multiple sclerosis. The most common adverse events to have been observed during clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headaches, and injection site reactions. A pooled analysis of clinical trial data indicated no specific patterns of infection or malignancy under long-term ustekinumab administration. Ustekinumab is easy to use, has a comfortable therapeutic regimen, improves quality of life in patients, and thus appears to be an attractive biological treatment that is adapted and accepted by patients with moderate to severe psoriasis. PMID:23641151

Toussirot, Éric; Michel, Fabrice; Béreau, Matthieu; Binda, Delphine

2013-01-01

131

Safety of Long-term Video-Electroencephalographic Monitoring for Evaluation of Epilepsy  

PubMed Central

OBJECTIVE: To determine the rate of medical complications from long-term video-electroencephalographic (EEG) monitoring for epilepsy. PATIENTS AND METHODS: We reviewed the medical records of 428 consecutive adult patients with epilepsy who were admitted for diagnostic scalp video-EEG monitoring at Mayo Clinic's site in Arizona from January 1, 2005, to December 31, 2006; 149 met inclusion criteria for the study. Seizure number and type as well as timing and presence of seizure-related adverse outcomes were noted. RESULTS: Of the 149 adult patients included in the study, seizure clusters occurred in 35 (23%); 752 seizures were recorded. The mean time to first seizure was 2 days, with a mean length of stay of 5 days. Among these patients, there was 1 episode of status epilepticus, 3 potentially serious electrocardiographic abnormalities, 2 cases of postictal psychosis, and 4 vertebral compression fractures during a generalized convulsion, representing 11% of patients with a recorded generalized tonic-clonic seizure. No deaths, transfers to the intensive care unit, falls, dental injuries, or pulmonary complications were recorded. An adverse event requiring intervention or interfering with normal activity occurred in 21% of these patients. Length of stay was not affected by occurrence of adverse events. CONCLUSION: Prolonged video-EEG monitoring is an acceptably safe procedure. Adverse events occur but need not result in substantial morbidity or increase length of hospitalization. Appropriate precautions must be in place to prevent falls and promptly detect and treat seizure clusters, status epilepticus, serious electrocardiographic abnormalities, psychosis, and fractures. PMID:19483165

Noe, Katherine H.; Drazkowski, Joseph F.

2009-01-01

132

Long-term clinical trial safety experience with the inactivated split influenza vaccine, Vaxigrip ®  

Microsoft Academic Search

Safety data on the inactivated split influenza vaccine, Vaxigrip®, were compiled and analysed from 28 clinical trials (total: 4599 subjects aged 6 months to 99 years) to provide a robust estimate of the reactogenicity profile. The most frequent solicited reactions were non-severe injection site pain and erythema in children, adults, and elderly. Mild or moderate fever was the most frequent

Valentine Delore; Camille Salamand; Grenville Marsh; Sabine Arnoux; Stephanie Pepin; Pierre Saliou

2006-01-01

133

Long-term Outcomes of the FRESH START Trial: Exploring the Role of Self-efficacy in Cancer Survivors’ Maintenance of Dietary Practices and Physical Activity  

PubMed Central

Objective This study examined whether changes in self-efficacy explain the effects of a mailed print intervention on long-term dietary practices of breast and prostate cancer survivors. The relationship between change in self-efficacy and long-term physical activity (PA) also was examined. Methods Breast and prostate cancer survivors (N=543) from 39 U.S. states and two Canadian provinces participated in the FRESH START intervention trial. Participants were randomly assigned to receive a 10-month program of mailed print materials on diet and PA available in the public domain or a 10-month program of tailored materials designed to increase fruit and vegetable (F&V) intake, decrease fat intake, and/or increase PA. Changes in self-efficacy for F&V intake and fat restriction were analyzed as potential mediators of the intervention’s effects on diet at 2-year follow-up. Because we previously found that change in self-efficacy for PA did not vary by group assignment, the relationship between change in self-efficacy and PA at 2-year follow-up was examined across study conditions. Results Results suggest that change in self-efficacy for fat restriction partially explained the intervention’s effect on fat intake (mean indirect effect=-.28), and change in self-efficacy for F&V consumption partially explained the intervention’s effect on daily F&V intake (mean indirect effect=.11). Change in self-efficacy for fat restriction partially accounted for the intervention’s impact on overall diet quality among men only (mean indirect effect=.60). Finally, change in self-efficacy for PA predicted PA at 2-year follow-up. Conclusions Findings suggest that self-efficacy may influence long-term maintenance of healthy lifestyle practices among cancer survivors. PMID:22544562

Mosher, Catherine E.; Lipkus, Isaac; Sloane, Richard; Snyder, Denise C.; Lobach, David F.; Demark-Wahnefried, Wendy

2012-01-01

134

Evaluating the Long-Term Safety of a Repository at Yucca Mountain   

SciTech Connect

Regulations require that the repository be evaluated for its health and safety effects for 10,000 years for the Site Recommendation process. Regulations also require potential impacts to be evaluated for up to a million years in an Environmental Impact Statement. The Yucca Mountain Project is in the midst of the Site Recommendation process. The Total System Performance Assessment (TSPA) that supports the Site Recommendation evaluated safety for these required periods of time. Results showed it likely that a repository at this site could meet the licensing requirements promulgated by the Nuclear Regulatory Commission. The TSPA is the tool that integrates the results of many years of scientific investigations with design information to allow evaluations of potential far-future impacts of building a Yucca Mountain repository. Knowledge created in several branches of physics is part of the scientific basis of the TSPA that supports the Site Recommendation process.

Abe Van Luik

2009-07-17

135

Long-term safety of nebivolol and valsartan combination therapy in patients with hypertension: an open-label, single-arm, multicenter study.  

PubMed

Long-term safety of a free-tablet combination of nebivolol and valsartan was assessed in a Phase III, open-label trial (NCT01415505). Adults with hypertension entered a 4-week placebo run-in phase, followed by a 52-week treatment phase. Initial dosage (Neb/Val 5/160 mg/d) was titrated up to 20/320 mg/d to achieve blood pressure (BP) goal (JNC7 criteria), with the addition of hydrochlorothiazide (up to 25 mg/d) if needed. Safety and tolerability parameters included adverse events. Efficacy assessments included baseline-to-endpoint change in diastolic BP and systolic BP and the percentage of patients who achieved BP goal. All analyses were performed using descriptive statistics. Study completion rate was 60.4% (489/810). The most frequent reason for discontinuation was insufficient therapeutic response (8.4%). Adverse events were experienced by 59.2% of patients, with the most common being headache (5.7%), nasopharyngitis (5.0%), and upper respiratory tract infection (4.6%). Three (0.4%) deaths occurred during the study; none was considered related to study medication. Mean ± standard deviation changes from baseline at week 52 (observed cases) were -25.5 ± 15.9 mm Hg (systolic BP) and -19.0 ± 8.7 mm Hg (diastolic BP). A total of 75.7% nebivolol/valsartan-treated and 57.8% nebivolol/valsartan/hydrochlorothiazide-treated completers achieved BP goal. Long-term treatment with nebivolol and valsartan in adults with hypertension was safe and well-tolerated. PMID:25492835

Neutel, Joel M; Giles, Thomas D; Punzi, Henry; Weiss, Robert J; Li, Huiling; Finck, Amy

2014-12-01

136

Safety and Long-Term Performance of Lithium-ion Pouch Cells  

NASA Technical Reports Server (NTRS)

Lithium-ion batteries have the highest energy density of the batteries available in the commercial market today. Although most lithium-ion cell designs use a metal can design, this has changed significantly in recent years. Cell designs are offered in the pouch format as they offer better volumetric and gravimetric energy densities and in some cases, higher tolerance to abuse or off-nominal conditions. In the past decade, several state-of-the-art lithium-ion pouch cell designs have been tested. The pouch cell designs have become more robust in the past two years but there are still a few issues that need to be looked into for optimization. The pouch cells seem to have a tendency to swell when left in storage under ambient conditions. The cells also swell under overvoltage and undervoltage conditions. A significant issue that has been observed is the swelling of the cells under a vacuum condition which could lead to deformation of the cell pouch after this exposure. This last factor would be very critical in the use of these cell designs for space applications as vacuum exposure is used to check for cell and battery leaks before it is flown into space. In rare cases, corrosion of the aluminum layer of the pouches has been observed in stored cells. Pouch material analysis has been carried out in an effort to understand the strength of the pouches and determine if this is a factor in the corrosion as well as unsafe condition of the cells as deformation of the inner layers of the pouch could occur when the cells swell under the various conditions described above. Pouch materials are typically aluminized plastic, made up of a layer of Al sandwiched between one or more layers of polymeric material. Deformations or cell manufacturing processes could lead to a compromise of the inner polymeric layer/s of the pouch leading to the corrosion of the Al layer in the aluminized pouch material. The safety of the pouch cell designs has been determined for cells from various manufacturers. The results are varied and in some cases, unexpected. This paper presents a summary of the tests carried out on a few li-ion pouch cell designs from various cell manufacturers. The data will include performance under different conditions specifically cycling under vacuum conditions with and without restraints as well as safety test data. The presentation will also include detailed analysis of the pouch material for the cells studied.

Jeevarajan, Judith

2012-01-01

137

Long-term analysis of the impact of longitudinal barriers on motorway safety.  

PubMed

The objective of this study was to assess the influence of longitudinal barriers located on the median strips and hard shoulders of toll motorways on crash severity in vehicles running off the roadway. The study was based on crashes involving injury and property damage only, recorded from 1996 to 2010 on a French toll motorway network of about 2000 km. In run-off from the roadway onto the hard shoulder, injury risk was halved by a longitudinal barrier. A specific one-sided W-beam guardrail ("GS4") appeared to be the best solution for cars, and even for LUVs and trucks. This does not affect the advisability of specific guardrails for bridges or of concrete barriers, when narrow working widths are required. In run-off onto median strips, a specific guardrail ("GS2") appeared to be the most efficient, followed by the three other metal guardrails currently installed. Concrete barriers, however, are much more effective in preventing complete crossing of the median, which is uncommon and mainly involves trucks, but often with very serious consequences. Longitudinal barriers make an important contribution to highway-user safety, providing a "forgiving" infrastructure in the event of a vehicle going off the road, provided that there are very few motorized two-wheel vehicles using the roadway. PMID:23911615

Martin, Jean-Louis; Mintsa-Eya, Colette; Goubel, Clément

2013-10-01

138

Effects of approach and services under differential response on long term child safety and welfare.  

PubMed

An outcome analysis was conducted based on an extended follow-up of the implementation of differential response program reforms in Child Protective Services offices in 10 counties in a Midwestern U.S. State. Random assignment was conducted of families that were first determined to be appropriate for family assessments. Experimental families (n=2,382) were each assigned to a non-forensic family assessment, and control families (n=2,247) each received a forensic investigation. Families were assigned continuously over a 15-month period and then tracked from 45 to 60 months from the date of assignment. Detailed information on services provided and family responses was obtained via two subsamples of experimental and control families. Measures of family engagement and service reception and utilization were utilized to determine instrumental outcomes introduced through family assessments. Improved family engagement and increased and broadened services were found to have occurred, and it was theorized that these changes mediated extended outcomes. Extended outcomes included reductions of rates of subsequent screened-in reports of child maltreatment, proportions of families that experienced child removals, and instances of new safety threats and problems in parenting. Differences in outcomes were found among the participating counties with 4 counties accounting for most outcome differences. The relationships between instrumental and extended outcomes were discussed with suggestions for further research. PMID:24957562

Loman, L Anthony; Siegel, Gary L

2015-01-01

139

Long-term safety and tolerability of donepezil 23?mg in patients with moderate to severe Alzheimer’s disease  

PubMed Central

Background Donepezil (23?mg/day) is approved by the US Food and Drug Administration for the treatment of patients with moderate to severe Alzheimer’s disease (AD). Approval was based on results from a 24-week, randomized, double-blind study of patients who were stable on donepezil 10?mg/day and randomized 2:1 to either increase their donepezil dose to 23?mg/day or continue taking 10?mg/day. The objective of this study was to assess the long-term safety and tolerability of donepezil 23?mg/day in patients with moderate to severe AD. Methods Patients who completed the double-blind study and were eligible could enroll into a 12-month extension study of open-label donepezil 23?mg/day. Clinic visits took place at open-label baseline and at months 3, 6, 9, and 12. Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs); changes in weight, electrocardiogram, vital signs, and laboratory parameters; and discontinuation due to AEs. Results 915 double-blind study completers were enrolled in the open-label extension study and 902 comprised the safety population. Mean treatment duration in this study was 10.3?±?3.5?months. In total, 674 patients (74.7%) reported at least one AE; in 320 of these patients (47.5%) at least one AE was considered to be possibly or probably study drug related. The majority of patients reporting AEs (81.9%) had AEs of mild or moderate severity. There were 268 patients (29.7%) who discontinued early, of which 123 (13.6%) were due to AEs. Patients increasing donepezil dose from 10?mg/day in the double-blind study to 23?mg/day in the extension study had slightly higher rates of AEs and SAEs than patients who were already receiving 23?mg (78.0% and 16.9% vs 72.8% and 14.0%, respectively). The incidence of new AEs declined rapidly after the first 2?weeks and remained low throughout the duration of the study. Conclusion This study shows that long-term treatment with donepezil 23?mg/day is associated with no new safety signals. The elevated incidence of AEs in patients increasing the dose of donepezil from 10?mg/day to 23?mg/day was limited to the initial weeks of the study. PMID:22681723

2012-01-01

140

Mathematical models as tools for probing long-term safety of CO2 storage  

SciTech Connect

Subsurface reservoirs being considered for storing CO{sub 2} include saline aquifers, oil and gas reservoirs, and unmineable coal seams (Baines and Worden, 2004; IPCC, 2005). By far the greatest storage capacity is in saline aquifers (Dooley et al., 2004), and our discussion will focus primarily on CO{sub 2} storage in saline formations. Most issues for safety and security of CO{sub 2} storage arise from the fact that, at typical temperature and pressure conditions encountered in terrestrial crust, CO{sub 2} is less dense than aqueous fluids. Accordingly, CO{sub 2} will experience an upward buoyancy force in most subsurface environments, and will tend to migrate upwards whenever (sub-)vertical permeable pathways are available, such as fracture zones, faults, or improperly abandoned wells (Bachu, 2008; Pruess, 2008a, b; Tsang et al., 2008). CO{sub 2} injection will increase fluid pressures in the target formation, thereby altering effective stress distributions, and potentially triggering movement along fractures and faults that could increase their permeability and reduce the effectiveness of a caprock in containing CO{sub 2} (Rutqvist et al., 2008; Chiaramonte et al., 2008). Induced seismicity as a consequence of fluid injection is also a concern (Healy et al., 1968; Raleigh et al., 1976; Majer et al., 2007). Dissolution of CO{sub 2} in the aqueous phase generates carbonic acid, which may induce chemical corrosion (dissolution) of minerals with associated increase in formation porosity and permeability, and may also mediate sequestration of CO{sub 2} as solid carbonate (Gaus et al., 2008). Chemical dissolution of caprock minerals could promote leakage of CO{sub 2} from a storage reservoir (Gherardi et al., 2007). Chemical dissolution and geomechanical effects could reinforce one another in compromising CO{sub 2} containment. Additional issues arise from the potential of CO{sub 2} to mobilize hazardous chemical species (Kharaka et al., 2006), and from migration of the large amounts of brine that would be mobilized by industrial-scale CO{sub 2} injection (Nicot et al., 2008; Birkholzer et al., 2008a, b).

Pruess, Karsten; Birkholzer, Jens; Zhou, Quanlin

2009-02-01

141

Efficacy of the Incredible Years Programme as an early intervention for children with conduct problems and ADHD: long-term follow-up  

Microsoft Academic Search

Background This study examined the long-term efficacy of the Incredible Years (IY) BASIC Parenting Programme delivered as a preventive intervention with parents of pre-school children who display signs of attention deficit hyperactivity disorder (ADHD) and conduct problems.Families were followed up after the completion of a controlled trial with 11 Sure Start areas in North and Mid-Wales and North West England.

K. Jones; D. Daley; J. Hutchings; T. Bywater; C. Eames

2008-01-01

142

Short and long-term efficacy of brief cognitive-behavioral therapy for patients with chronic temporomandibular disorder pain: A randomized, controlled trial  

Microsoft Academic Search

We evaluated the short- and long-term efficacy of a brief cognitive-behavioral therapy (CBT) for chronic temporomandibular disorder (TMD) pain in a randomized controlled trial. TMD clinic patients were assigned randomly to four sessions of either CBT (n=79) or an education\\/attention control condition (n=79). Participants completed outcome (pain, activity interference, jaw function, and depression) and process (pain beliefs, catastrophizing, and coping)

Judith A. Turner; Lloyd Mancl; Leslie A. Aaron

2006-01-01

143

Testing the Long-Term Efficacy of a Prevention Program for Improving Marital Conflict in Community Families  

ERIC Educational Resources Information Center

Family-focused prevention programs for community samples have potentially broad, clinically relevant implications but few studies have examined whether any program benefits continue to be observed over the long term. Although benefits of a marital conflict focused parent education program, the Happy Couples and Happy Kids (i.e., HCHK) program,…

Faircloth, W. Brad; Schermerhorn, Alice C.; Mitchell, Patricia M.; Cummings, Jennifer S.; Cummings, E. Mark

2011-01-01

144

Long-term safety of budesonide/formoterol for the treatment of elderly patients with bronchial asthma.  

PubMed

The long-term safety of budesonide/formoterol (BUD/FM) inhalation has not been fully evaluated, particularly in elderly patients with bronchial asthma. To evaluate the 12-month safety of BUD/FM inhalation for elderly asthmatic patients, the changes in serum potassium levels and pulse rate were examined. A retrospective chart review was conducted of consecutive patients who were treated with BUD/FM inhalation (two inhalations of 160/4.5 mg, twice daily; Symbicort Turbuhaler, AstraZeneca) at a hospital between February 2010 and January 2012. A total of 350 patients were treated with BUD/FM inhalation during the study period and were followed up over 12 months. The mean age of the patients was 60 years, and 19.4% and 21.4% of the patients were aged 65-74 years and ?75 years, respectively. One hundred and fourteen (32.6%) of the 350 patients continued the inhalation therapy for >12 months. Compared with the pretreatment data, reductions in serum potassium levels at 1, 6 and 12 months were not observed, even in the patients aged 65-74 and ?75 years. There was also no increase in the pulse rate at 1, 6 and 12 months, even in the patients aged 65-74 and ?75 years. The usual dosage of BUD/FM showed no adverse effects on the serum potassium levels and pulse rate in the adults, including the elderly with persistent asthma. PMID:24669267

Kagohashi, Katsunori; Satoh, Hiroaki; Ohara, Gen; Miyazaki, Kunihiko; Kawaguchi, Mio; Kurishima, Koichi; Hizawa, Nobuyuki

2014-04-01

145

Long-term safety of budesonide/formoterol for the treatment of elderly patients with bronchial asthma  

PubMed Central

The long-term safety of budesonide/formoterol (BUD/FM) inhalation has not been fully evaluated, particularly in elderly patients with bronchial asthma. To evaluate the 12-month safety of BUD/FM inhalation for elderly asthmatic patients, the changes in serum potassium levels and pulse rate were examined. A retrospective chart review was conducted of consecutive patients who were treated with BUD/FM inhalation (two inhalations of 160/4.5 mg, twice daily; Symbicort Turbuhaler, AstraZeneca) at a hospital between February 2010 and January 2012. A total of 350 patients were treated with BUD/FM inhalation during the study period and were followed up over 12 months. The mean age of the patients was 60 years, and 19.4% and 21.4% of the patients were aged 65–74 years and ?75 years, respectively. One hundred and fourteen (32.6%) of the 350 patients continued the inhalation therapy for >12 months. Compared with the pretreatment data, reductions in serum potassium levels at 1, 6 and 12 months were not observed, even in the patients aged 65–74 and ?75 years. There was also no increase in the pulse rate at 1, 6 and 12 months, even in the patients aged 65–74 and ?75 years. The usual dosage of BUD/FM showed no adverse effects on the serum potassium levels and pulse rate in the adults, including the elderly with persistent asthma. PMID:24669267

KAGOHASHI, KATSUNORI; SATOH, HIROAKI; OHARA, GEN; MIYAZAKI, KUNIHIKO; KAWAGUCHI, MIO; KURISHIMA, KOICHI; HIZAWA, NOBUYUKI

2014-01-01

146

Dapagliflozin efficacy and safety: a perspective review  

PubMed Central

Type 2 diabetes mellitus is a prevalent, progressive disease with a need for innovative therapeutic agents to continue to advance disease management. Dapagliflozin is the second agent in a new class of oral antihyperglycemic drugs: sodium-glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 is responsible for the majority of renal glucose reuptake; inhibition of the cotransporter allows for increased renal glucose excretion that consequently leads to reduced plasma glucose levels. Because this mechanism does not require the action of insulin, dapagliflozin rarely causes hypoglycemia and is effective in patients both early and late in the course of their disease. Studies of dapagliflozin have demonstrated efficacy both as monotherapy and in combination with oral antihyperglycemic agents and insulin. Dapagliflozin has been shown to decrease hemoglobin A1c (HbA1c) values 6 mmol/mol (0.5%) to 8 mmol/mol (0.7%). The most common adverse reactions observed with dapagliflozin in clinical trials were female genital mycotic infections, urinary tract infections, and nasopharyngitis. Dapagliflozin is a new oral agent for type 2 diabetes with short-term efficacy similar to dipeptidyl peptidase 4 inhibitors; its long-term safety and efficacy are unknown. PMID:25436106

2014-01-01

147

Green light laser efficacy in patients with prostatic hyperplasia on long-term treatment with 5-alpha reductase inhibitors  

Microsoft Academic Search

Introduction: High prevalence of BPH and gradual ageing of the population, combined with the existence of effective medical treatments for this condition, have led to an increasing use of surgery in patients on long-term treatment with 5-alpha reductase inhibitors (5-ARIs). Initially, patients treated with 5-ARIs were not considered good candidates for photoselective vaporization of the prostate with green laser. Objective:

Joaquín Ulises; Juan Escudero; Emilio López Alcina; Macarena Ramos de Campos; Francisco Ramada Benlloch; Francisco Sánchez Ballester; Emilio Marqués Vidal

2010-01-01

148

Long-Term Efficacy of Atenolol for Atrioventricular Reciprocating Tachycardia in Children Less Than 5 Years Old  

Microsoft Academic Search

Atrioventricular reciprocating tachycardia (AVRT) using an accessory pathway is the most common supraventricular tachycardia observed in infancy and childhood. There is a general agreement to treat children older than 5 years who are on a potentially long-term antiarrhythmic agent with radiofrequency catheter ablation. Atenolol, a relatively long-acting and cardioselective ß-adrenoceptor blocker, has been used to control the various types of

J. K. Ko; J. E. Ban; Y. H. Kim; I. S. Park

2004-01-01

149

A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain  

PubMed Central

Objective To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods This multicenter, open-label study started with a conversion/titration phase (?6 weeks) where subjects (n=638) were converted to individualized doses (range 20–300 mg) of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424). The primary objective (safety and tolerability) and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain) were monitored throughout the study. Results Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator’s discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%), nausea (10.7% and 9.9%), vomiting (4.1% and 9.7%), and somnolence (7.7% and 4.2%). Four deaths occurred during the study; all were considered unrelated to treatment. One subject died 13 months after the study ended. From the start to end of the conversion/titration phase, 84% of subjects had a clinically meaningful improvement in average pain score (?30% improvement), and the mean average pain scores remained stable through the maintenance phase. Conclusion This single-entity, extended-release formulation of hydrocodone was generally safe, well tolerated, and effective in reducing chronic pain for 48 weeks. This formulation provides a new option for patients experiencing chronic pain, especially those who are taking immediate-release hydrocodone and have concerns about liver toxicity due to acetaminophen. PMID:25473308

Nalamachu, Srinivas; Rauck, Richard L; Hale, Martin E; Florete, Orlando G; Robinson, Cynthia Y; Farr, Stephen J

2014-01-01

150

Long-Term Safety and Adverse Events of Risperidone in Children, Adolescents, and Adults with Pervasive Developmental Disorders  

ERIC Educational Resources Information Center

The objective of this study was to examine long-term adverse events of risperidone in 19 children, adolescents, and adults with Pervasive Developmental Disorders and intellectual disability, continuing risperidone for a mean of 186.5 weeks, following a 46-week risperidone study. Nineteen individuals continued long-term follow-up after our…

Hellings, Jessica A.; Cardona, Alicia M.; Schroeder, Stephen R.

2010-01-01

151

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia  

Microsoft Academic Search

ObjectivesTo summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important.

Franklin C Lowe; John D McConnell; Perry B Hudson; Nicholas A Romas; Rex Boake; Michael Lieber; Mostafa Elhilali; Jack Geller; Juliane Imperto-McGinely; Gerald L Andriole; Reginald C Bruskewitz; Patrick C Walsh; Georg Bartsch; John N Nacey; Sukrut Shah; Frances Pappas; Amy Ko; Thomas Cook; Elizabeth Stoner; Joanne Waldstreicher

2003-01-01

152

[Extracorporeal shockwave therapy (ESWT) in tendinosis calcarea of the rotator cuff. Long-term results and efficacy].  

PubMed

Calcifying tendinitis (TC) of the rotator cuff is a transient shoulder disease with a high rate of spontaneous resorption of the deposit. Therefore, primary treatment should be conservative. In cases of persistent pain despite conservative treatment, extracorporeal shock wave therapy (ESWT) can be performed as an alternative minimally invasive method. Various short-term studies have demonstrated the efficiency of ESWT for TC. To evaluate the short- and long-term results, complications, and the number of operations avoided by ESWT, a prospective study with 115 patients was performed over a period of 4 years. The patients had received high-energy ESWT once (group A: n = 56) or twice (group B: n = 59). Six months after therapy, 47% in group A and 77% in group B showed evidence of disappearance or disintegration of the calcium deposits. Pain relief was achieved in 45% of group A and 53% of group B. Four years after treatment, 20% of the patients had undergone surgery on the involved shoulder. Of the remaining patients, 59% (68 patients) were seen for follow-up. Subjectively, 78% of group A and 87% of group B judged the treatment to be successful. X-ray examination revealed complete or partial resorption of the calcium deposit in 93% in both groups. The Constant score increased from 45 before treatment to 88 in group A and 85 in group B after treatment. ESWT was successful for about 70% of the treated patients with no long-term complications seen. PMID:12219662

Daecke, W; Kusnierczak, D; Loew, M

2002-07-01

153

Perceived Risk and Self-Efficacy as Motivators: Understanding Individuals' Long-Term Use of Health Information.  

ERIC Educational Resources Information Center

Considers to what extent perceived risk and self-efficacy interact with each other to determine individuals' motivation to seek health information. Identifies 4 groups of individuals according to their perceived risk and self-efficacy; responsive, proactive, avoidance, and indifference. Attempts to resolve some of the outstanding issues with…

Rimal, Rajiv N.

2001-01-01

154

An Exploratory Study of Meanings of Risk Control for Long Term and Acute Effect Occupational Health and Safety Risks in Small Business Construction Firms  

Microsoft Academic Search

A qualitative study of employers' and employees' meanings of occupational health and safety (OHS) risk control was conducted among a sample of small businesses engaged in the Australian construction industry. Two OHS risks relevant to the construction industry were selected for study. One risk (falls from height) represented an immediate consequence, whereas the other (occupational skin disease) represented a long-term

Noni Holmes; Helen Lingard; Zeynep Yesilyurt; Fred De Munk

1999-01-01

155

An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain  

PubMed Central

Purpose Studies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4–17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure. Patients and methods This was a 53-week, multicenter, open-label trial of pregabalin (150–600 mg/day) in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke. Results A total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5). A majority of patients (87.4%) experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1%) or moderate (9.2%) in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS), and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ) and ten-item modified Brief Pain Inventory (mBPI-10) total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were ?20.1 and ?1.4, respectively. Conclusion These findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in patients with chronic central neuropathic pain. PMID:25114584

Onouchi, Kenji; Koga, Hiroaki; Yokoyama, Kazumasa; Yoshiyama, Tamotsu

2014-01-01

156

Long-Term Efficacy and Tolerability of Abdominal Once-Yearly Histrelin Acetate Subcutaneous Implants in Patients with Advanced Prostate Cancer  

PubMed Central

Objectives. Long-term assessment of the efficacy and tolerability of subcutaneous abdominal histrelin acetate implants that have been inserted for more than two years. Materials and Methods. Retrospective data collected over a six-year period at a single center from charts of 113 patients who received the subcutaneous abdominal histrelin acetate implant. Results. Following insertion of the first implant, 92.1% and 91.8% of patients had a serum testosterone level of ?30?ng/dL at 24 and 48 weeks, respectively. Serum testosterone levels remained at <30?ng/dL for 96% of patients at two years and for 100% of patients at 3, 4, and 5 years. The testosterone levels remained significantly less than baseline (P < 0.05). Six patients (5.3%) had androgen-independent progression when followed up on the long term, increasing the mean serum PSA at 3, 4, and 5 years to 35.0?µg/L (n = 22), 30.7?µg/L (n = 13), and 132.9?µg/L (n = 8), respectively. The mean serum PSA was significantly greater than baseline during these years (P < 0.05). Eight patients (7.1%) experienced minor, but not serious, adverse events from the histrelin acetate. Conclusion. Subcutaneous abdominal histrelin acetate implants are an effective long-term and well-tolerated administration method for treating patients with advanced prostate cancer. PMID:25548680

Woolen, Sean; Holzmeyer, Cameron; Nesbitt, Emily; Siami, Paul F.

2014-01-01

157

New treatment options for chronic constipation: Mechanisms, efficacy and safety  

PubMed Central

The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes. PMID:22114755

Camilleri, Michael

2011-01-01

158

Application of supercritical fluid extraction (SFE) to predict bioremediation efficacy of long-term composting of PAH-contaminated soil  

SciTech Connect

Supercritical fluid extraction (SFE) with pure carbon dioxide was used to obtain desorption curves of PAHs from four contaminated industrial soils. These were from a former gas works, a former tar processing plant, a former wood presentation plant, and a former gas-holder site. Total PAH concentrations ranged from 1495 to 2439 mg/kg. The desorption curves were fitted with a simple two-site model to determine the rapidly released fraction (F) representing bioavailability of PAHs. The F data obtained under various SFE pressures were compared with degradation results of a composting method applied on the soils. After composting and consequent long-term maturation, the residual PAH contaminations ranged from 4 to 36% of the original values. A possible explanation of the result variations is the different bioavailability of the pollutants. The best correlations between degradation results and F fraction were obtained applying 50{sup o}C and 300 bar. The F values gave very good agreement with degradation efficiencies and the total regression coefficients (r{sup 2}) ranged from 0.81 to 0.99. The degradation results together with bioavailable fractions appeared to be consistent with organic carbon contents in the soils and with volatile fractions of organics. The results indicate that SFE could be a rapid test to predict bioremediation results of composting of PAH-contaminated soils. 23 refs., 2 figs., 3 tabs.

Toma Cajthaml; Vaclav Sasek [Academy of Sciences of the Czech Republic, Prague (Czech Republic). Institute of Microbiology

2005-11-01

159

Efficacy of Coronary Angioplasty on Long-Term Outcome in Elderly Chinese Patients with ST Elevated Myocardial Infarction  

Microsoft Academic Search

The benefit and efficacy of interventional coronary therapies in elderly patients is still a controversial subject, especially\\u000a in parts of the world where traditional and conservative medicine is still mainstream. In China, the benefit of intervention\\u000a is still questionable, hence, this study investigated the prognostic significance of coronary angioplasty on outcomes of elderly\\u000a patients presenting with ST-segment elevated myocardial infarction

JieYan Shen; YongPing Du; Wei Song; JianPing Liu; ShuXuan Jin; Jun Bu; Ben He

2010-01-01

160

Safety, efficacy, and patient acceptability of rifaximin for hepatic encephalopathy.  

PubMed

Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production of ammonia by gut bacteria and, to some extent, other toxic derivatives from the gut. Clinical trials show that these effects improve episodes of hepatic encephalopathy. A large randomized trial found that rifaximin prevents recurrent episodes of hepatic encephalopathy. Most patients were treated concurrently with lactulose. Trials have varied greatly in design, outcomes, and duration of treatment regimes. Although a number of retrospective studies have indicated that long-term treatment with rifaximin is safe and possibly beneficial, high quality trials are needed to further clarify efficacy and safety of long-term treatment with rifaximin and evaluate effects of combination therapy with lactulose and branched-chain amino acids for patients with liver cirrhosis and hepatic encephalopathy. PMID:24672227

Kimer, Nina; Krag, Aleksander; Gluud, Lise L

2014-01-01

161

Prophylactic efficacy of fluoxetine, escitalopram, sertraline, paroxetine, and concomitant psychotherapy in major depressive disorder: Outcome after long-term follow-up.  

PubMed

The acute efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder (MDD) is well established; however their role in longer-term prevention of recurrence remains unconfirmed. This study aims at examining: the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up, the effect of concomitant cognitive behavioral therapy (CBT), and the predictors of outcome. In a prospective cohort study, 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine, escitalopram, sertraline and paroxetine-were followed up over several years. During an average follow-up period of 34.5 months, 76.5% of patients experienced MDD recurrence. Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant. The prophylactic efficacy for SSRI-only treatment was limited, with a recurrence rate of 82.0%, compared to 59.0% of patient recurrence rate in concomitant Cognitive Behavioral Therapy (CBT). The relatively small size of the CBT group and the lack of randomization may undermine the extrapolation of its findings to clinical practice. Nevertheless, the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence. PMID:25496869

Peselow, Eric D; Tobia, Gabriel; Karamians, Reneh; Pizano, Demetria; IsHak, Waguih William

2015-02-28

162

Long-Term Safety of Mometasone Furoate/Formoterol Combination for Treatment of Patients with Persistent Asthma  

PubMed Central

Objective: The combination of inhaled corticosteroid (ICS) and long-acting ?2-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS. Methods: This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged >12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 ?g) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 ?g). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC0–24h) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored. Results: The incidence of >1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 ?g, 77.3% [n = 109]; FP/S 250/50 ?g, 82.4% [n = 56]; MF/F 400/10 ?g, 79.2% [n = 103]; FP/S 500/50 ?g, 76.9% [n = 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 ?g, 28.4%; FP/S 250/50 ?g, 23.5%; MF/F 400/10 ?g, 23.1%; FP/S 500/50 ?g, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC0–24 h observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2–6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 ?g group; one for reduced visual acuity in the FP/S 250/50 ?g group) and no asthma-related deaths occurred. Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use. Conclusions: One-year treatment with the new combination therapies -twice-daily MF/F-MDI 200/10 and 400/10 ?g — is safe and well tolerated in patients with persistent asthma. PMID:20874458

Maspero, Jorge F; Nolte, Hendrik; Chérrez-Ojeda, Iván

2010-01-01

163

Effects of long-term zinc treatment in Japanese patients with Wilson disease: efficacy, stability, and copper metabolism.  

PubMed

Wilson disease is an autosomal recessive disorder with copper metabolism. In Japan, the standard treatment is the administration of copper chelating agents, such as D-penicillamine and trientine. In this study, the authors used zinc acetate to treat Japanese patients with Wilson disease and investigated its efficacy. The 37 patients that comprise this study were found to have Wilson disease using clinical and biochemical tests and were administrated zinc acetate for 48 weeks. The authors followed the clinical symptoms and laboratory findings of the patients by assessing their complete blood counts, biochemical findings, as well as the results of urinalysis and special laboratory tests for copper and zinc metabolism. We also examined side effects of the treatment. Zinc acetate did not aggravate the hepatic or neurological symptoms of any of the patients. Blood biochemical analysis also did not reveal elevation of alanine aminotransferase, aspartate aminotransferase, and ?-glutamyltranspeptidase levels. Zinc treatment did not aggravate the patients' clinical signs and/or laboratory findings. However, it did improve some clinical symptoms of the Wilson disease patients. Although this agent had some side effects, none of them were severe. The authors measured spot urinary copper excretion, which gave an indication of the efficacy of treatment and of the sufficient dosage of zinc. We recommend maintaining a spot urinary copper excretion less than 0.075-?g/mg creatinine. The authors conclude that zinc acetate is an effective and safe treatment for Japanese patients with Wilson disease. PMID:21078496

Shimizu, Norikazu; Fujiwara, Junko; Ohnishi, Shin; Sato, Mari; Kodama, Hiroko; Kohsaka, Takao; Inui, Ayano; Fujisawa, Tomoo; Tamai, Hiroshi; Ida, Shinobu; Itoh, Susumu; Ito, Michinori; Horiike, Norio; Harada, Masaru; Yoshino, Makoto; Aoki, Tsugutoshi

2010-12-01

164

Long-term safety and efficacy of tobramycin in the management of cystic fibrosis  

PubMed Central

Cystic fibrosis (CF) is a fatal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene whose mortality is conditioned by a progressive decline in lung function. Bacterial infections play a key role in this decline. Chronic bacterial infection in CF patients varies over time and the presence of Pseudomonas aeruginosa in sputum is a marker of poor prognosis. P. aeruginosa is eradicated from the airways using inhaled antibiotics administered in various formulations and devices. Antipseudomonal antibiotics have extended the survival of CF patients to 40 years. Tobramycin is a bactericidal aminoglycoside antibiotic with demonstrated activity against gram-negative microorganisms. Initially, the drug was administered as an inhaled parenteral solution. Subsequently, a specific tobramycin inhalation solution was developed. PulmoSphere™ technology enables dry tobramycin powder to be formulated for inhalation (tobramycin inhalation powder) using a small and portable capsule-based breath-activated device (T-326). Chronic colonization by P. aeruginosa is the main indication for aerosol antibiotic therapy. The American Cystic Fibrosis Foundation, European guidelines, and Spanish consensus guidelines provide different recommendations for eradication.

Vázquez-Espinosa, Emma; Girón, Rosa María; Gómez-Punter, Rosa Mar; García-Castillo, Elena; Valenzuela, Claudia; Cisneros, Carolina; Zamora, Enrique; García-Pérez, F Javier; Ancochea, Julio

2015-01-01

165

A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain.  

PubMed

Peripheral neuropathic pain (PNP) poses a significant clinical challenge. The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated in this 38-week open-label extension study. In total, 380 patients with PNP associated with diabetes or allodynia entered this study from two parent randomised, controlled trials. Patients received THC/CBD spray for a further 38 weeks in addition to their current analgesic therapy. Neuropathic pain severity was the primary efficacy measure using a pain 0-10 numerical rating scale (NRS). Additional efficacy, safety and tolerability outcomes were also investigated. In total, 234 patients completed the study (62 %). The pain NRS showed a decrease in score over time in patients from a mean of 6.9 points (baseline in the parent studies) to a mean of 4.2 points (end of open-label follow-up). The proportion of patients who reported at least a clinically relevant 30 % improvement in pain continued to increase with time (up to 9 months); at least half of all patients reported a 30 % improvement at all time points. Improvements were observed for all secondary efficacy outcomes, including sleep quality 0-10 NRS scores, neuropathic pain scale scores, subject global impression of change and EQ-5D questionnaire scores. THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use. In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia. PMID:25270679

Hoggart, B; Ratcliffe, S; Ehler, E; Simpson, K H; Hovorka, J; Lej?ko, J; Taylor, L; Lauder, H; Serpell, M

2015-01-01

166

Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease  

PubMed Central

Background As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited. Objective To analyse the long-term safety of adalimumab treatment. Methods This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data. Results The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population. Conclusions Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class. PMID:22562972

Burmester, Gerd R; Panaccione, Remo; Gordon, Kenneth B; McIlraith, Melissa J; Lacerda, Ana P M

2013-01-01

167

Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis.  

PubMed

Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common, but were mild and rarely required intervention. Other AEs were rare (?1 per cent in clinical trials; <10/million capsules sold). Hirsutism, gingival hyperplasia and hyperplastic dermatitis were rarely significant and resolved on dose reduction. Ciclosporin decreases staphylococcal and Malassezia infections in AD, and at the recommended dose is not a risk factor for other infections, neoplasia, renal failure or hypertension. The impact on glucose and calcium metabolism is not clinically significant for normal dogs. Concomitant treatment with most drugs is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate plasma ciclosporin concentrations, but short-term changes are not clinically significant. Monitoring of complete blood counts, urinalysis or ciclosporin levels is not justified except with higher than recommended doses and/or long-term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication for killed (including rabies) vaccines, but the licensed recommendation is that live vaccination is avoided during treatment. In conclusion, ciclosporin has a positive risk-benefit profile for the long-term management of canine AD. PMID:24682696

Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

2014-03-01

168

Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis  

PubMed Central

Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common, but were mild and rarely required intervention. Other AEs were rare (?1 per cent in clinical trials; <10/million capsules sold). Hirsutism, gingival hyperplasia and hyperplastic dermatitis were rarely significant and resolved on dose reduction. Ciclosporin decreases staphylococcal and Malassezia infections in AD, and at the recommended dose is not a risk factor for other infections, neoplasia, renal failure or hypertension. The impact on glucose and calcium metabolism is not clinically significant for normal dogs. Concomitant treatment with most drugs is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate plasma ciclosporin concentrations, but short-term changes are not clinically significant. Monitoring of complete blood counts, urinalysis or ciclosporin levels is not justified except with higher than recommended doses and/or long-term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication for killed (including rabies) vaccines, but the licensed recommendation is that live vaccination is avoided during treatment. In conclusion, ciclosporin has a positive risk-benefit profile for the long-term management of canine AD. PMID:24682696

Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

2014-01-01

169

Opioids in chronic non-cancer pain: systematic review of efficacy and safety  

Microsoft Academic Search

Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950–1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons

Eija Kalso; Jayne E. Edwards; R. Andrew Moore; Henry J. McQuay

2004-01-01

170

Associations of Dietary Intake and Physical Activity with Sleep Disordered Breathing in the Apnea Positive Pressure Long-term Efficacy Study (APPLES)  

PubMed Central

The purpose of this study was to examine whether dietary habits and physical activity patterns were independently associated with severity of sleep disordered breathing (SDB) in adults diagnosed with obstructive sleep apnea. Data collected from 320 adults participating in an ancillary study of The Apnea Positive Pressure Long-term Efficacy Study were analyzed as a cross-sectional assessment at study baseline. The respiratory disturbance index (RDI) was used as a measure of the severity of sleep disordered breathing. Separate linear regression models were fitted using RDI as the independent variable and various preselected components of dietary intake and physical activity as the dependent variables. The results indicated that even after adjusting for BMI, age, and daytime sleepiness, subjects with very severe and extremely severe SDB (RDI ? 50) consumed a diet that was higher in cholesterol, protein, total fat, and total saturated fatty acids. These findings were most evident among women. For all participants, those with RDI ? 50 in comparison to those < 50, on average consumed 88.16 more mg of cholesterol per day (95% CI: 44.45 to 131.86, p < 0.001). Among the women participants only, those with RDI ? 50 in comparison to those < 50, on average consumed 21.96 more grams of protein (95% CI: 2.64 to 41.29, p = 0.026), 27.75 more grams of total fat (95% CI: 3.38 to 52.11, p = 0.026), and 9.24 more grams of saturated fatty acids (95% CI: 0.67 to 17.80, p = 0.035). Furthermore, those with an RDI ? 50 had a 224.58 greater caloric expenditure than those with RDI < 50 from all activities including work and sleep (95% CI: 40.98 to 408.18, p = 0.017). Although significant results were seen in a reduction of physical activity from recreational activities, this finding was explained by the increase in BMI associated with higher levels of RDI. Citation: Vasquez MM; Goodwin JL; Drescher AA; Smith TW; Quan SF. Associations of dietary intake and physical activity with sleep disordered breathing in the apnea positive pressure long-term efficacy study (APPLES). J Clin Sleep Med 2008;4(5):411–418. PMID:18853696

Vasquez, Monica M.; Goodwin, James L.; Drescher, Amy A.; Smith, Terry W.; Quan, Stuart F.

2008-01-01

171

Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES)  

PubMed Central

Study Objective: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). Design, Setting, and Participants: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. Intervention: Active or sham CPAP Measurements: Three neurocognitive variables, each representing a neurocognitive domain: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) Results: The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. Conclusions: CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship. Clinical Trial Information: Registered at clinicaltrials.gov. Identifier: NCT00051363. Citation: Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602. PMID:23204602

Kushida, Clete A.; Nichols, Deborah A.; Holmes, Tyson H.; Quan, Stuart F.; Walsh, James K.; Gottlieb, Daniel J.; Simon, Richard D.; Guilleminault, Christian; White, David P.; Goodwin, James L.; Schweitzer, Paula K.; Leary, Eileen B.; Hyde, Pamela R.; Hirshkowitz, Max; Green, Sylvan; McEvoy, Linda K.; Chan, Cynthia; Gevins, Alan; Kay, Gary G.; Bloch, Daniel A.; Crabtree, Tami; Dement, William C.

2012-01-01

172

Long-Term Impact of Community-Based Information, Education and Communication Activities on Food Hygiene and Food Safety Behaviors in Vietnam: A Longitudinal Study  

PubMed Central

Background Ingestion of contaminated water or food is a major contributor to childhood diarrhea in developing countries. In Vietnam, the use of community-based information, education and communication (IEC) activities could be a sustainable strategy to improve food hygiene and food safety behaviors. This study thus examined the long-term impact of community-based IEC activities on food hygiene and food safety behaviors. Methods In this longitudinal study, we interviewed caregivers of children aged between six months and four years in suburban Hanoi. Baseline data were collected in January 2006 (n?=?125). After conducting IEC interventions, we collected a 1st set of evaluation data in January 2007 (n?=?132). To examine the long-term impact of the interventions, we then collected a 2nd set of evaluation data in January 2008 (n?=?185). Changes in childhood diarrhea prevalence, IEC coverage, and food hygiene and food safety behaviors were assessed over a two-year period using bivariate and logistic regression analyses. Effective IEC channels were determined through multiple linear regression analysis. Results Childhood diarrhea was significantly reduced from 21.6% at baseline to 7.6% at the 1st post-intervention evaluation (P?=?0.002), and to 5.9% at the 2nd evaluation. Among 17 food hygiene and food safety behaviors measured, a total of 11 behaviors were improved or maintained by the 2nd evaluation. Handwashing after toilet use was significantly improved at both evaluation points. Overall, 3 food safety behaviors and 7 food hygiene behaviors were found to have significantly improved at the 1st and at the 2nd evaluations, respectively. Flip chart communication administered by community groups was identified to be the most effective IEC channel for effecting behavior change (P?=?0.018). Conclusions Flip chart communication administered by community groups is effective for improving multiple food hygiene and food safety behaviors in sustainable ways, and should be included in water and health promotion programs. PMID:23950978

Takanashi, Kumiko; Quyen, Dao To; Le Hoa, Nguyen Thi; Khan, Nguyen Cong; Yasuoka, Junko; Jimba, Masamine

2013-01-01

173

Premarket Safety and Efficacy Studies for ADHD Medications in Children  

PubMed Central

Background Attention-deficit hyperactivity disorder (ADHD) is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing. Methods We identified all ADHD medications approved by the Food and Drug Administration (FDA) and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug’s clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials. Results A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419). Eleven drugs (55%) were approved after <100 participants were studied and 14 (70%) after <300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9), with 5 (38%) drugs approved after participants were studied <4 weeks and 10 (77%) after <6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed. Conclusions Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved. PMID:25007171

Bourgeois, Florence T.; Kim, Jeong Min; Mandl, Kenneth D.

2014-01-01

174

Key Performance Criteria Affecting the Most the Safety of a Nuclear Waste Long Term Storage : A Case Study Commissioned by CEA  

SciTech Connect

As part of the work scope set in the French law on high level long lived waste R&D passed in 1991, CEA is conducting a research program to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as centuries. This goal is a significant departure from the current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periods of time, the risk for Society of loosing oversight and control of such a facility is real, which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study (1) in which MUTADIS Consultants (2) and CEPN (3) were both involved. The case study looks into several past and actual human enterprises conducted over significant periods o f time, one of them dating back to the end of the 18th century, and all identified out of the nuclear field. Then-prevailing societal behavior and organizational structures are screened out to show how they were or are still able to cope with similar oversight and control goals. As a result, the study group formulated a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered as far as technical studies are concerned. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality.

Marvy, A.; Lioure, A; Heriard-Dubreuil, G.; Gadbois, S.; Schneider, T.; Schieber, C.

2003-02-24

175

Comparison of the efficacy and safety of nebulized beclometasone dipropionate and budesonide in severe persistent childhood asthma  

Microsoft Academic Search

Inhaled steroids are recommended for long-term control of asthma, but their use may be limited in young children because of difficulties in using the associated inhaler device. The use of nebulizers may help to overcome this issue, without compromising therapeutic efficacy or safety. This 14-week, multicentre, randomized, controlled, open-label, parallel-group study compared the efficacy and safety of nebulized corticosteroids in

C. Delacourt; G. Dutau; G. Lefrançois; P. Clerson

2003-01-01

176

Handling glacially induced faults in the assessment of the long term safety of a repository for spent nuclear fuel at Forsmark, Sweden  

NASA Astrophysics Data System (ADS)

Located deep into the Baltic shield, far from active plate boundaries and volcanism, Swedish bedrock is characterised by a low frequency of earthquakes of small magnitudes. Yet, faults, predominantly in the Lapland region, offsetting the quarternary regolith ten meters or more, reveal that Swedish bedrock suffered from substantial earthquake activity in connection to the retreat of the latest continental glacier, Weichsel. Storage of nuclear wastes, hazardous for hundreds of thousand years, requires, firstly, isolation of radionuclides and, secondly, retardation of the nuclides should the barriers fail. Swedish regulations require that safety is demonstrated for a period of a million years. Consequently, the repository must be designed to resist the impact of several continental glaciers. Large, glacially induced, earthquakes near the repository have the potential of triggering slip along fractures across the canisters containing the nuclear wastes, thereby simultaneously jeopardising isolation, retardation and, hence, long term safety. It has therefore been crucial to assess the impact of such intraplate earthquake upon the primary functions of the repository. We conclude that, by appropriate design of the repository, the negative impact of earthquakes on long term safety can be considerably lessened. We were, additionally, able to demonstrate compliance with Swedish regulations in our safety assessment, SR-Site, submitted to the authorities earlier this year. However, the assessment required a number of critical assumptions, e.g. concerning the strain rate and the fracture properties of the rock, many of which are subject of current research in the geoscientific community. By a conservative approach, though, we judge to have adequately propagated critical uncertainties through the assessment and bound the uncertainty space.

Munier, R.

2011-12-01

177

Long-term efficacy of tenofovir disoproxil fumarate therapy after multiple nucleos(t)ide analogue failure in chronic hepatitis B patients  

PubMed Central

Background/Aims The efficacy of tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B (CHB) patients following prior treatment failure with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in Asian populations. In this study we investigated the efficacy and safety of TDF rescue therapy in CHB patients after multiple NA treatment failure. Methods The study retrospectively analyzed 52 CHB patients who experienced failure with two or more NAs and who were switched to regimens containing TDF. The efficacy and safety assessments included hepatitis B virus (HBV) DNA undetectability, hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT) normalization and changes in serum creatinine and phosphorus levels. Results The mean HBV DNA level at baseline was 5.4 ± 1.76 log10 IU/mL. At a median duration of 34.5 months of TDF treatment, the cumulative probabilities of achieving complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12, 24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48 patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with elevated ALT at baseline. Lower levels of HBV DNA at baseline were significantly associated with increased CVR rates (p < 0.001). However, CVR rates did not differ between TDF monotherapy or combination therapy with other NAs, and were not affected by mutations associated with resistance to NAs. No significant adverse events were observed. Conclusions TDF is an efficient and safe rescue therapy for CHB patients after treatment failure with multiple NAs. PMID:25589833

Kim, Hyo Jin; Cho, Ju-Yeon; Kim, Yu Jin; Gwak, Geum-Youn; Paik, Yong-Han; Choi, Moon Seok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

2015-01-01

178

Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency  

PubMed Central

Objective The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Design Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Methods Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20–40?mg once daily and hydrocortisone 20–40?mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). Results In stage 1, patients had a median 1.5 (range, 1–9) intercurrent illness events with DR-HC and 1.0 (1–8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1–3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. Conclusions This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy. PMID:24944332

Nilsson, A G; Marelli, C; Fitts, D; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Edén Engström, B; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Lennernäs, H; Skrtic, S; Johannsson, G

2014-01-01

179

Long-Term Safety of Subcutaneous Abatacept in Rheumatoid Arthritis: Integrated Analysis of Clinical Trial Data Representing More Than Four Years of Treatment  

PubMed Central

Objective To investigate the safety of long-term subcutaneous (SC) abatacept treatment using integrated clinical trial data obtained in patients with rheumatoid arthritis refractory to traditional disease-modifying antirheumatic drugs. Methods Data from the double-blind and open-label phases of 5 clinical trials of SC abatacept were pooled. The overall and 6-month incidence rates were calculated as events per 100 patient-years of exposure. Results This analysis included 1,879 patients with 4,214.6 patient-years of exposure to SC abatacept. The mean ± SD length of exposure was 27.3 ± 9.1 months. The reported incidence rate of serious infections was 1.79 (95% confidence interval [95% CI] 1.42–2.24); the most frequent infections were pneumonia (incidence rate 0.36 [95% CI 0.22–0.59]), urinary tract infection (incidence rate 0.14 [95% CI 0.06–0.32]), and gastroenteritis (incidence rate 0.10 [95% CI 0.04–0.25]). Tuberculosis occurred rarely (incidence rate 0.09 [95% CI 0.04–0.25]). The reported incidence rate of malignancies was 1.32 (95% CI 1.01–1.72), and the most common was solid organ malignancy (incidence rate 0.69 [95% CI 0.48–0.99]). The incidence rate of autoimmune events was 1.37 (95% CI 1.06–1.78), and the most frequent events were psoriasis (incidence rate 0.33 [95% CI 0.20–0.56]) and Sjögren's syndrome (incidence rate 0.24 [95% CI 0.13–0.44]). The reported incidence rate of local injection site reactions was 1.72 (95% CI 1.36–2.17); these events occurred primarily during the first 6 months of treatment, and almost all were of mild or moderate intensity. The incidence rates of serious infections, malignancies, autoimmune events, and injection site reactions did not increase over time. Conclusion Long-term treatment with SC abatacept was associated with low incidence rates of serious infections, malignancies, and autoimmune events and was well tolerated, with infrequent injection site reactions. These findings are consistent with those related to treatment with intravenous abatacept. Long-term treatment with SC abatacept did not lead to new safety signals over time. PMID:24782324

Alten, Rieke; Kaine, Jeffrey; Keystone, Edward; Nash, Peter; Delaet, Ingrid; Genovese, Mark C

2014-01-01

180

Long Term Ecological Resources  

NSDL National Science Digital Library

Students analyze data on temperature and precipitation collected from 26 different Long Term Ecological Research sites and compare them with annual net primary productivity. The students then form an ecological rule to explain their results.

Scott Cooper

181

Long-term efficacy of psoriasis vulgaris treatments: analysis of treatment with topical corticosteroid and/or vitamin D3 analog, oral cyclosporin, etretinate and phototherapy over a 35-year period, 1975-2010.  

PubMed

Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side-effects and cost. It is necessary to evaluate the effect of long-term psoriasis treatment, but there have been no reports evaluating long-term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long-term treatment with a combination of topical corticosteroid and topical vitamin D3 analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant. PMID:23330814

Akasaka, Emiko; Mabuchi, Tomotaka; Manabe, Yasuaki; Yahagi, Eiichiro; Yamada-Hiruma, Azusa; Yamaoka, Hanako; Kojima, Tomoko; Kato, Masayuki; Ikoma, Norihiro; Ozawa, Akira; Haruki, Yasuo

2013-04-01

182

The long-term effects of a token economy on safety performance in open-pit mining.  

PubMed Central

A token economy that used trading stamps as tokens was instituted at two dangerous open-pit mines. Employees earned stamps for working without lost-time injuries, for being in work groups in which all other workers had no lost-time injuries, for not being involved in equipment-damaging accidents, for making adopted safety suggestions, and for unusual behavior which prevented an injury or accident. They lost stamp awards if they or other workers in their group were injured, caused equipment damage, or failed to report accidents or injuries. The stamps could be exchanged for a selection of thousands of items at redemption stores. Implementation of the token economy was followed by large reductions in the number of days lost from work because of injuries, the number of lost-time injuries, and the costs of accidents and injuries. The reductions in costs far exceeded the costs of operating the token economy. All improvements were maintained over several years. PMID:3667473

Fox, D K; Hopkins, B L; Anger, W K

1987-01-01

183

Long-Term Maintenance of Weight Loss: Current Status  

Microsoft Academic Search

Intervention strategies for promoting long-term weight loss are examined empirically and conceptually. Weight control research over the last 20 years has dramatically improved short-term treatment efficacy but has been less successful in improving long-term success. Interventions in preadolescent children show greater long-term efficacy than in adults. Extending treatment length and putting more emphasis on energy expenditure have modestly improved long-term

Robert W. Jeffery; Adam Drewnowski; Leonard H. Epstein; Albert J. Stunkard; G. Terence Wilson; Rena R. Wing; Dana Robin Hill

2000-01-01

184

Long-term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer  

PubMed Central

Purpose Tasquinimod (Active Biotech) is an oral immunomodulatory, anti-angiogenic, and anti-metastatic agent that delayed metastatic disease progression in a randomized placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). Here, we report long-term survival with biomarker correlates from this trial. Experimental Design Two hundred and one (134 tasquinimod and 67 placebo) men with mCRPC were evaluated. Forty-one men randomized to placebo crossed over to tasquinimod. Survival data were collected with a median follow-up time of 37 months. Exploratory biomarker studies at baseline and over time were collected to evaluate potential mechanism-based correlates with tasquinimod efficacy including progression-free survival (PFS) and overall survival (OS). Results With 111 mortality events, median OS was 33.4 months for tasquinimod versus 30.4 months for placebo overall, and 34.2 versus 27.1 months in men with bone metastases (n = 136), respectively. Multivariable analysis demonstrated an adjusted HR of 0.52 [95% confidence interval (CI), 0.35–0.78; P = 0.001] for PFS and 0.64 (95% CI, 0.42–0.97; P = 0.034) for OS, favoring tasquinimod. Time-to-symptomatic progression was improved with tasquinimod (P = 0.039, HR = 0.42). Toxicities tended to be mild in nature and improved over time. Biomarker analyses suggested a favorable impact on bone alkaline phosphatase and lactate dehydrogenase (LDH) over time and a transient induction of inflammatory biomarkers, VEGF-A, and thrombospondin-1 levels with tasquinimod. Baseline levels of thrombos-pondin-1 less than the median were predictive of treatment benefit. Conclusions The survival observed in this trial of men with minimally symptomatic mCRPC suggests that the prolongation in PFS with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable risk:benefit ratio. PMID:24255071

Armstrong, A.J.; Häggman, M.; Stadler, W.M.; Gingrich, J.R.; Assikis, V.; Polikoff, J.; Damber, J.E.; Belkoff, L.; Nordle, Ö.; Forsberg, G.; Carducci, M.A.; Pili, R.

2014-01-01

185

Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition.  

PubMed

Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin(+) undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells. PMID:25684226

Nori, Satoshi; Okada, Yohei; Nishimura, Soraya; Sasaki, Takashi; Itakura, Go; Kobayashi, Yoshiomi; Renault-Mihara, Francois; Shimizu, Atsushi; Koya, Ikuko; Yoshida, Rei; Kudoh, Jun; Koike, Masato; Uchiyama, Yasuo; Ikeda, Eiji; Toyama, Yoshiaki; Nakamura, Masaya; Okano, Hideyuki

2015-03-10

186

Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition  

PubMed Central

Summary Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin+ undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells. PMID:25684226

Nori, Satoshi; Okada, Yohei; Nishimura, Soraya; Sasaki, Takashi; Itakura, Go; Kobayashi, Yoshiomi; Renault-Mihara, Francois; Shimizu, Atsushi; Koya, Ikuko; Yoshida, Rei; Kudoh, Jun; Koike, Masato; Uchiyama, Yasuo; Ikeda, Eiji; Toyama, Yoshiaki; Nakamura, Masaya; Okano, Hideyuki

2015-01-01

187

Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance  

Microsoft Academic Search

Objective: We aimed to investigate the efficacy of pegvisomant in patients with acromegaly resistant to long-term ( ^ 24-month), high-dose treatment with octreotide-LAR (40mg\\/month) or lanreotide (120mg\\/month). Design: This was an open, prospective study. Subjects and Methods: We studied 16 patients with acromegaly (nine women; aged 28-61 years). The main outcome measures were IGF-I levels, blood pressure, glucose tolerance and

Annamaria Colao; Rosario Pivonello; Renata S Auriemma; Maria Cristina De Martino; Martin Bidlingmaier; Francesco Briganti; Fabio Tortora; Pia Burman; Ione A Kourides; Christian J Strasburger; Gaetano Lombardi

2006-01-01

188

Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials.  

PubMed

Papulopustular rosacea (PPR) is characterized by facial erythema and inflammatory lesions believed to be primarily caused by dysregulation of the innate immune system. More recent evidence also suggests that Demodex folliculorum mites may contribute to the etiology of PPR. Ivermectin (IVM) 1% cream is a novel topical treatment developed to treat PPR. Two phase 3 trials have demonstrated that IVM 1% cream was significantly better than vehicle at investigator global assessment (IGA) success rate and lesion reductions and that it was safe and well tolerated. Two 40-week extension studies of those trials were conducted to assess the long-term safety of IVM 1% cream vs azelaic acid (AzA) 15% gel. Subjects originally treated with IVM 1% continued on IVM 1% and those originally treated with vehicle switched to AzA 15% gel. IVM 1% cream was safe throughout the study with a lower incidence of related adverse events (AEs) compared to AzA 15% gel. No subjects in the IVM 1% cream group discontinued either study due to a related AE. IVM 1% also continued to be efficacious during the 40-week extension studies as the percentage of subjects with IGA scores of clear or almost clear was higher at the end of the study compared to baseline. The results of these 40-week extension studies support the use of IVM 1% cream as a long-term therapy for PPR as IVM 1% cream was shown to be safe and effective for up to 52 weeks of total treatment. PMID:25607706

Stein Gold, Linda; Kircik, Leon; Fowler, Joseph; Jackson, J Mark; Tan, Jerry; Draelos, Zoe; Fleischer, Alan; Appell, Melanie; Steinhoff, Martin; Lynde, Charles; Sugarman, Jeffrey; Liu, Hong; Jacovella, Jean

2014-11-01

189

Evaluation of the efficacy and safety of \\  

Microsoft Academic Search

Abstract Abstract Abstract Abstract Infantile irritant diaper dermatitis (IIDD) is an inflammation of the infantile skin covering the groin, lower stomach, upper thighs and buttocks. Infantile irritant diaper dermatitis may become difficult to treat, if the area becomes infected or the infant develops allergy to medications applied to the area. This study was conducted to evaluate the efficacy and safety

SUKANTA CHATTERJEE; NILANJANA PRAMANICK; SANTA CHATTOPADHYAY; KINKOR MUNIAN

190

Efficacy and Safety of Atomoxetine in the Treatment of Children and Adolescents with Attention Deficit Hyperactivity Disorder  

PubMed Central

Several non-stimulant medications have been used in the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine, was introduced in 2002. The safety and efficacy of atomoxetine in the treatment of ADHD for children, adolescents, and adults has been evaluated in over 4000 patients in randomized controlled studies and double blinded studies as well as in recent large longitudinal studies. This paper provides an updated summary of the literature on atomoxetine, particularly in relation to findings on the short- and long-term safety of atomoxetine in children and adolescents arising from recent large longitudinal cohort studies. Information is presented about the efficacy, safety, and tolerability of this medication. PMID:23641171

Kohn, Michael R.; Tsang, Tracey W.; Clarke, Simon D.

2012-01-01

191

Efficacy and safety of atomoxetine in the treatment of children and adolescents with attention deficit hyperactivity disorder.  

PubMed

Several non-stimulant medications have been used in the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine, was introduced in 2002. The safety and efficacy of atomoxetine in the treatment of ADHD for children, adolescents, and adults has been evaluated in over 4000 patients in randomized controlled studies and double blinded studies as well as in recent large longitudinal studies. This paper provides an updated summary of the literature on atomoxetine, particularly in relation to findings on the short- and long-term safety of atomoxetine in children and adolescents arising from recent large longitudinal cohort studies. Information is presented about the efficacy, safety, and tolerability of this medication. PMID:23641171

Kohn, Michael R; Tsang, Tracey W; Clarke, Simon D

2012-01-01

192

Long-Term Intrathecal Ziconotide for Chronic Pain: An Open-Label Study  

Microsoft Academic Search

This open-label multicenter study evaluated the long-term safety and efficacy of intrathecal ziconotide and included 78 patients with chronic pain who had completed one of two previous ziconotide clinical trials. Each patient's initial ziconotide dose was based on his or her dose from the study of origin and was adjusted as necessary on the basis of adverse events and analgesic

Lynn R. Webster; Robert Fisher; Steven Charapata; Mark S. Wallace

2009-01-01

193

Long-term follow-up of vertebral osteoporotic fractures treated by percutaneous vertebroplasty  

Microsoft Academic Search

The aim of this study was:to assess the long-term efficacy and safety of percutaneous vertebroplasty (PVP) for treating painful vertebral osteoporotic fractures, and to estimate the risk of vertebral fracture in the vicinity of a cemented vertebra. A prospective open study was conducted. PVP were carried out between July 1995 and September 2000 for 16 patients with symptomatic osteoporotic vertebral

Isabelle Legroux-Gérot; Christian Lormeau; Nathalie Boutry; Anne Cotten; Bernard Duquesnoy; Bernard Cortet

2004-01-01

194

Design and methods of a postmarketing pharmacoepidemiology study assessing long-term safety of Prolia® (denosumab) for the treatment of postmenopausal osteoporosis‡  

PubMed Central

Purpose To describe the rationale and methods for a prospective, open-cohort study assessing the long-term safety of Prolia® for treatment of postmenopausal osteoporosis (PMO) in postmarketing settings. Methods Data will be derived from United States Medicare, United Healthcare, and Nordic (Denmark, Sweden, Norway) national registries. Observation will begin on the date of first Prolia® regulatory approval (May 26, 2010) and continue for 10 years. Women with PMO will be identified by postmenopausal age, osteoporosis diagnosis, osteoporotic fracture, or osteoporosis treatment. Exposure to Prolia® and bisphosphonates will be updated during follow-up; exposure cohorts will be defined based on patient-years during which patients are on- or post-treatment. Nine adverse events (AEs) will be assessed based on diagnosis codes: osteonecrosis of the jaw (ONJ), atypical femoral fracture (AFF), fracture healing complications, hypocalcemia, infection, dermatologic AEs, acute pancreatitis, hypersensitivity, and new primary malignancy. Medical review will confirm selected potential cases of ONJ and AFF. Incidence rates (IRs) of AEs will be described overall and for exposure cohorts; multivariate Cox proportional hazard regression models will compare IRs of AEs across exposure cohorts. Utilization patterns of Prolia® for approved, and unapproved indications will be described. Conclusion This study is based on comprehensive preliminary research and considers methodological challenges specific to the study population. The integrated data systems used in this regulatory committed program can serve as a powerful data resource to assess diverse and rare AEs over time. © 2013 Amgen Inc. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:23857864

Xue, Fei; Ma, Haijun; Stehman-Breen, Catherine; Haller, Christine; Katz, Leonid; Wagman, Rachel B; Critchlow, Cathy W; Denosumab Global Safety Assessment Team

2013-01-01

195

Evaluating Aspects of Online Medication Safety in Long-Term Follow-Up of 136 Internet Pharmacies: Illegal Rogue Online Pharmacies Flourish and Are Long-Lived  

PubMed Central

Background A growing number of online pharmacies have been established worldwide. Among them are numerous illegal websites selling medicine without valid medical prescriptions or distributing substandard or counterfeit drugs. Only a limited number of studies have been published on Internet pharmacies with regard to patient safety, professionalism, long-term follow-up, and pharmaceutical legitimacy verification. Objective In this study, we selected, evaluated, and followed 136 Internet pharmacy websites aiming to identify indicators of professional online pharmacy service and online medication safety. Methods An Internet search was performed by simulating the needs of potential customers of online pharmacies. A total of 136 Internet pharmacy websites were assessed and followed for four years. According to the LegitScript database, relevant characteristics such as longevity, time of continuous operation, geographical location, displayed contact information, prescription requirement, medical information exchange, and pharmaceutical legitimacy verification were recorded and evaluated. Results The number of active Internet pharmacy websites decreased; 23 of 136 (16.9%) online pharmacies ceased operating within 12 months and only 67 monitored websites (49.3%) were accessible at the end of the four-year observation period. However, not all operated continuously, as about one-fifth (31/136) of all observed online pharmacy websites were inaccessible provisionally. Thus, only 56 (41.2%) Internet-based pharmacies were continuously operational. Thirty-one of the 136 online pharmacies (22.8%) had not provided any contact details, while only 59 (43.4%) displayed all necessary contact information on the website. We found that the declared physical location claims did not correspond to the area of domain registration (according to IP address) for most websites. Although the majority (120/136, 88.2%) of the examined Internet pharmacies distributed various prescription-only medicines, only 9 (6.6%) requested prior medical prescriptions before purchase. Medical information exchange was generally ineffective as 52 sites (38.2%) did not require any medical information from patients. The product information about the medicines was generally (126/136, 92.6%) not displayed adequately, and the contents of the patient information leaflet were incomplete in most cases (104/136, 76.5%). Numerous online operators (60/136, 44.1%) were defined as rogue Internet pharmacies, but no legitimate Internet-based pharmacies were among them. One site (0.7%) was yet unverified, 23 (16.9%) were unapproved, while the remaining (52/136, 38.2%) websites were not available in the LegitScript database. Contrary to our prior assumptions, prescription or medical information requirement, or the indication of contact information on the website, does not seem to correlate with “rogue pharmacy” status using the LegitScript online pharmacy verification standards. Instead, long-term continuous operation strongly correlated (P<.001) with explicit illegal activity. Conclusions Most Internet pharmacies in our study sample were illegal sites within the definition of “rogue” Internet pharmacy. These websites violate professional, legal, and ethical standards and endanger patient safety. This work shows evidence that online pharmacies that act illegally appear to have greater longevity than others, presumably because there is no compelling reason for frequent change in order to survive. We also found that one in five websites revived (closed down and reopened again within four years) and no-prescription sites with limited medicine and patient information are flourishing. PMID:24021777

2013-01-01

196

Comparison of antianginal efficacy of nifedipine and isosorbide dinitrate in chronic stable angina: a long-term, randomized, double-blind, crossover study  

SciTech Connect

Using a double-blind, crossover design, the comparative efficacy and safety of nifedipine and isosorbide dinitrate in the treatment of stable angina were studied in 34 patients. The study included a 2-week placebo washout period and two 6-week periods during which patients were randomized to either nifedipine or isosorbide dinitrate. The doses were titrated for each patient, and mean doses of the 2 drugs were comparable. A time-limited thallium treadmill test was performed at the end of each phase. Ischemic zone count rates were normalized to those of the nonischemic zone, and the change in this ratio with redistribution was calculated as reversible thallium defect. Two patients were discontinued from the study within 1 week after initiation of isosorbide dinitrate because of severe, intolerable headache. Two patients were withdrawn while receiving nifedipine: one had new congestive heart failure and the other had increasing angina. Of the remaining 30 patients who tolerated both drugs for at least 1 week, 4 patients from the isosorbide dinitrate group were either prematurely crossed over or discontinued from the study because of headache. One patient suffered headache from both drugs and was discontinued from the study. In the 30 patients, only nifedipine significantly reduced resting arterial pressure compared with baseline. Further, only nifedipine therapy resulted in significant decreases in the rate-pressure product and systolic pressure at a given workload. However, significant decreases in angina frequency, nitroglycerin consumption and exercise-induced maximum ST-segment depression and reversible thallium perfusion defect were produced by both nifedipine and isosorbide dinitrate.

Liang, C.S.; Coplin, B.; Wellington, K.

1985-05-17

197

Autologous stem cell transplantation with in vivo purged progenitor cells shows long-term efficacy in relapsed/refractory follicular lymphoma.  

PubMed

High-dose chemotherapy with autologous stem cell transplantation (ASCT) has been shown effective in the control of relapsed/refractory follicular lymphoma. We evaluate the long-term outcome of patients with relapsed or refractory follicular lymphoma treated with ASCT with in vivo purged progenitors cells. We report the long-term results of a prospective multicenter phase 2 trial on 124 relapsed/refractory follicular lymphoma patients treated with a program of anthracycline-based debulking chemotherapy, immunochemotherapy, mobilization of in vivo purged PBSC followed by ASCT. Median age was 52 years; 14% of patients had grade 3A histology. Debulking chemotherapy produced CR in 16% and PR in 71%, while 13% of patients progressed. After rituximab, cyclophosphamide, vincristine, prednisone (R-COP), CR was obtained in 60% and PR in 35%; 118 patients successfully mobilized PBSC and 117 proceeded to ASCT. The harvest in all the 32 molecularly informative patients was bcl-2 negative. TRM was 0%. The 5-year PFS was 54% and the 5-year OS was 83%. After a median f-up of 6.7 years (range 1.5-13.6), 54% are still in CR. These data show that prolonged PFS is achievable in relapsed/refractory patients with high dose autologous transplantation of in vivo purged progenitor cells. Am. J. Hematol. 90:230-234, 2015. © 2014 Wiley Periodicals, Inc. PMID:25502635

Arcaini, Luca; Morello, Lucia; Tucci, Alessandra; Rusconi, Chiara; Ladetto, Marco; Rattotti, Sara; Bonfichi, Maurizio; Bottelli, Chiara; Gabutti, Cristina; Bernasconi, Paolo; Varettoni, Marzia; Gotti, Manuel; Troletti, Daniela; Guerrera, Maria Luisa; Fiaccadori, Valeria; Sciarra, Roberta; Ferretti, Virginia Valeria; Alessandrino, Emilio Paolo; Rossi, Giuseppe; Morra, Enrica

2015-03-01

198

[Stapedectomy: long term results].  

PubMed

Stapedectomy, with its most innovatory variations, constitutes the treatment of choice for otoesclerosis. Short term results are spectacular, getting GAP closures of less than 5 dB approximatelly in 94% patients, variations depending on the authors. Long term follow up check results show a gradual auditory deterioration. The aim of this study is to audiometric evolution of patients operated of stapedectomy 7 to 10 years ago in our department and to correlate the results with those obtained by other authors, in an attempt to unify conclusions. PMID:12185900

Hernández Montero, E; Fraile Rodrigo, J; Marín Garrido, C; Sampériz, L Carmen; Llorente Arenas, E; Naya Gálvez, M J; Ortiz García, A

2002-04-01

199

Long-term conditions.  

PubMed

Technology enabled care services (TECS), which include technologies such as telehealth, telecare, telemedicine and self-care apps, are designed to help people manage long-term conditions and retain as much independence as possible. The NHS Commissioning Assembly has published TECS Resource for Commissioners, a toolkit that raises awareness of the range of TECS available and their benefits to patients and professionals, supports commissioners to collaborate with providers to implement TECS, and advises how to create a TECS strategy, oversee implementation plans and ensure effective evaluation. The publication is at tinyurl.com/khsebyr. PMID:25806457

2015-03-25

200

DNA vaccines: safety and efficacy issues  

Microsoft Academic Search

Summary  DNA technology has been harnessed to produce a variety of plasmid-based vaccines designed to prevent viral, bacterial and parasitic infections. The rapid adoption and implementation of this novel vaccine strategy carries with it important safety and efficacy concerns. This review will focus on whether DNA vaccines (1) are likely to induce systemic or organ-specific autoimmune disease, (2) have the potential

Dennis M. Klinman; Mitsuhiro Takeno; Motohide Ichino; Mili Gu; Galina Yamshchikov; Gil Mor; Jacqueline Conover

1997-01-01

201

Long-term efficacy of (90)Y ibritumomab tiuxetan therapy in follicular non-Hodgkin lymphoma and health-related quality of life.  

PubMed

The aim of this study was to analyze the outcomes of 37 follicular lymphoma (FL) patients treated with (90)ytrium ibritumomab tiuxetan (90Y-IT), outside of clinical trial, according to protocol ISCRTN36210045, after ?5 years follow-up to February 2014. Health-related quality of life (HRQoL) was evaluated with the SF-36, Spanish version, and compared with the general population of Spain. Patients had a mean age of 61.9 (range, 30-85) years and included 18 males. FLIPI, low: 25 (67.6 %), intermedium 9 (24.3 %), and low 3 (8.1 %). Previous therapy schedules >2: 48.6 % The median follow-up was 66 months, mean Time to Relapse (TTR) 71.3 months (58.8-83.8) median not reached. Thirty-four patients achieved complete response (91.8 %), and three no response. Mean overall survival: 82.3 months (71.6-92.9). Four patients presented with concomitant tumors (colon, breast, prostate, lung) after radioimmunotherapy, and three developed second primary neoplasms (esophagus, renal, and myelodysplastic syndrome in a relapsed patient who received fludarabine). Four of 10 deaths were related to lymphoma progression. Hematological toxicities were mild and easily managed. No patients required hospitalization. Negative scores were obtained in the physical and emotional roles items; however, the perception of general health and vitality were better than in the general population, with the best outcomes in non-relapsed patients. Radioimmunotherapy with 90Y-IT was safe and effective as long-term therapy in patients with FL. Early use of radioimmunotherapy could offer good, sustained responses with low toxicity over the long term and acceptable HRQoL. PMID:24985089

Andrade-Campos, Marcio Miguel; Montes-Limón, Anel E; Soro-Alcubierre, Gloria; Grasa, José María; Lopez-Gómez, Luis; Baringo, Teresa; Giraldo, Pilar

2014-12-01

202

Review of key Belotero Balance safety and efficacy trials.  

PubMed

Belotero Balance is a novel highly cross-linked hyaluronic acid that uses cohesive polydensified matrix technology to achieve cohesive gel; improved adaptation by the dermis; and a soft, smooth fill. Several studies have now compared Belotero Balance to bovine collagen and other hyaluronic acids. Two pivotal studies demonstrated the noninferiority and superiority of Belotero Balance to bovine collagen. In the first study, more than half of the patients maintained optimal correction at 6 months on the Belotero-treated side of the face. The second of those two studies followed patients to week 96 and demonstrated that the effects of Belotero Balance in this long-term, open-label study persisted in the majority of subjects without repeated treatment for at least one interval of 48 weeks. The filler was well tolerated, with only one of 34 total adverse events (injection-site bruising) considered to be related to the study device. A third study compared the safety and efficacy of other hyaluronic acids (i.e., Juvéderm and Restylane) with Belotero Balance. In this study, the safety profiles of all three hyaluronic acids were generally favorable, with site-specific adverse events mild to moderate and comparable across each hyaluronic acid. Aesthetic results were also similar, although Belotero Balance resulted in greater evenness than Restylane at 4 weeks by one indicator used in the study. Finally, a 5-year retrospective safety review of 317 patients treated with Belotero Balance over a 5-year period revealed no severe adverse events in any patients, including the absence of persistent nodules or granulomas. PMID:24077008

Lorenc, Z Paul; Fagien, Steven; Flynn, Timothy C; Waldorf, Heidi A

2013-10-01

203

Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials  

PubMed Central

Aims To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of anti-epileptic drugs (AEDs) for refractory epilepsy. Methods We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Group's specialized register, MEDLINE (1950 to March 2009), EMBASE (1980 to March 2009), and Current Contents Connect (1998 to March 2009) to conduct a systematic review of published studies, developed a treatment network and undertook a network meta-analysis. Results Forty-three eligible trials with 6346 patients and 12 interventions, including placebo, contributed to the analysis. Only three direct drug comparator trials were identified, the remaining 40 trials being placebo-controlled. Conventional random-effects meta-analysis indicated all drugs were superior in efficacy to placebo (overall odds ratio (OR] 3.78, 95% CI 3.14, 4.55) but did not permit firm distinction between drugs on the basis of the efficacy or tolerability. A Bayesian network meta-analysis prioritized oxcarbazepine, topiramate and pregabalin on the basis of short term efficacy. However, sodium valproate, levetiracetam, gabapentin and vigabatrin were prioritized on the basis of short-term efficacy and tolerability, with the caveat that vigabatrin is recognized as being associated with serious visual disturbance with chronic use. Conclusion Of the wide range of AEDs licensed for the treatment of refractory epilepsy, sodium valproate, levetiracetam and gabapentin demonstrated the best balance of efficacy and tolerability. Until regulators mandate greater use of active comparator trials with longer term follow-up, network meta-analysis provides the only available means to quantify these clinically important parameters. PMID:23351090

Bodalia, Pritesh N; Grosso, Anthony M; Sofat, Reecha; MacAllister, Raymond J; Smeeth, Liam; Dhillon, Soraya; Casas, Juan-Pablo; Wonderling, David; Hingorani, Aroon D

2013-01-01

204

Long-term efficacy of an imidacloprid 10 % / flumethrin 4.5 % polymer matrix collar (Seresto®, Bayer) against the Australian paralysis tick (Ixodes holocyclus) in dogs.  

PubMed

Two placebo-controlled pen studies were conducted to assess the efficacy of an imidacloprid 10 %/flumethrin 4.5 % polymer matrix collar (Seresto®, Bayer; Investigational Veterinary Product (IVP)) against the Australian paralysis tick (Ixodes holocyclus). Dogs assigned to the placebo (n = 8) or IVP (n ? 8) groups had collars (placebo or IVP) attached on Day 0 and were infested with 30 unfed, adult, female I. holocyclus at 14–28 day intervals over 227 days. Ticks were counted 24, 48 and 72 h post infestation to determine the acaricidal efficacy of the IVP. The acaricidal efficacy of the IVP 72 h post infestation exceeded 95 % on Days 17 (99.3 %), 59 (99.7 %), 73 (96.6 %), 87 (100.0 %), 101 (96.4 %), 115 (99.1 %) and 171 (95.8 %), but dropped on Days 45 (94.0 %) and 143 (77.8 %), and declined from Day 199 (79.9 %) to 227 (65.5 %). No adverse events related to treatment were observed. This study has demonstrated the excellent acaricidal efficacy (97.9 %) of the IVP collar against I. holocyclus 72 h post infestation over 16 weeks. PMID:23760870

Smith, Warwick M; Ahlstrom, Liisa A; Rees, Robert

2013-08-01

205

Examining the efficacy, safety, and patient acceptability of the combined contraceptive vaginal ring (NuvaRing®)  

PubMed Central

The contraceptive vaginal ring is a novel contraceptive method that offers unique advantages. Intravaginal delivery of both estrogen and progesterone allows continuous release of medication, resulting in lower systemic levels. The use of long-term combined hormonal contraception enables improved cycle control compared with progesterone-only methods. The indications and usage of the NuvaRing® are described along with the efficacy, tolerability, and safety. Overall, the contraceptive vaginal ring appears to be very effective, with a favorable side-effect profile, and is highly acceptable to most patients. PMID:21151688

Wieder, Devorah R; Pattimakiel, Lynn

2010-01-01

206

The risk of serious infection in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors decreased over time: a report from the registry of Japanese rheumatoid arthritis patients on biologics for long-term safety (REAL) database.  

PubMed

To investigate changes in the risk for serious infections (SIs) over time in Japanese rheumatoid arthritis (RA) patients treated with tumor necrosis factor inhibitors (TNFIs). This prospective cohort study included Japanese RA patients who began treatment with a TNFI from 2005 to 2007 (2005 group, n = 716, 634.2 patient years [PY]) and from 2008 to 2011 (2008 group, n = 352, 270.1 PY) at the time or after their enrollment in the registry of Japanese RA patients on biologics for long-term safety (REAL) database. Patients were observed for 12 months or until discontinuation of their initial TNFI in the REAL database. Drug discontinuation reasons and retention rates were analyzed. Incidence rates of serious adverse events (SAEs) were calculated with 95 % confidence intervals (CIs). The Cox proportional hazard model was applied to estimate the risk for SIs. The retention rate in the 2008 group was significantly lower than the 2005 group (p < 0.001). Discontinuation rates due to lack of efficacy or good control for the 2008 group were significantly higher than the 2005 group (p < 0.001). The crude incidence rate ratios comparing the 2008 group with the 2005 group for SAEs were 0.93 (95 % CI 0.65-1.34) and for SIs were 0.50 (0.24-1.03). The 2008 group had significantly lower risk for SIs than the 2005 group after adjusting for covariates (hazard ratio: 0.43 [0.20-0.93]). These results indicate significant decrease of the risk for SIs with TNFI treatment over time; this may be explained by evidence-based risk management of RA patients given TNFIs. PMID:24852650

Sakai, Ryoko; Cho, Soo-Kyung; Nanki, Toshihiro; Koike, Ryuji; Watanabe, Kaori; Yamazaki, Hayato; Nagasawa, Hayato; Amano, Koichi; Tanaka, Yoshiya; Sumida, Takayuki; Ihata, Atsushi; Yasuda, Shinsuke; Nakajima, Atsuo; Sugihara, Takahiko; Tamura, Naoto; Fujii, Takao; Dobashi, Hiroaki; Miura, Yasushi; Miyasaka, Nobuyuki; Harigai, Masayoshi

2014-12-01

207

Effectiveness and Safety of Spot Scanning Proton Radiation Therapy for Chordomas and Chondrosarcomas of the Skull Base: First Long-Term Report  

SciTech Connect

Purpose: To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. Methods and Materials: Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. Results: Mean follow-up period was 38 months (range, 14-92 months). Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. Conclusions: Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.

Ares, Carmen, E-mail: carmen.ares@psi.c [Center for Proton Radiation Therapy, Paul Scherrer Institute, Villigen (Switzerland); Hug, Eugen B.; Lomax, Antony J.; Bolsi, Alessandra; Timmermann, Beate; Rutz, Hans Peter [Center for Proton Radiation Therapy, Paul Scherrer Institute, Villigen (Switzerland); Schuller, Jan C. [Statistics Department, Swiss Group for Clinical Cancer Research, Bern (Switzerland); Pedroni, Eros; Goitein, Gudrun [Center for Proton Radiation Therapy, Paul Scherrer Institute, Villigen (Switzerland)

2009-11-15

208

Long-term testing  

NASA Astrophysics Data System (ADS)

Land-based gas turbines are significantly different from automotive gas turbines in that they are designed to operate for 50,000 h or greater (compared to 5,000-10,000 h). The primary goal of this research is to determine the long-term survivability of ceramic materials for industrial gas turbine applications. Research activities in this program focus on the evaluation of the static tensile creep and stress rupture (SR) behavior of three commercially available structural ceramics which have been identified by the gas turbine manufacturers as leading candidates for use in industrial gas turbines. For each material investigated, a minimum of three temperatures and four stresses will be used to establish the stress and temperature sensitivities of the creep and SR behavior. Because existing data for many candidate structural ceramics are limited to testing times less than 2,000 h, this program will focus on extending these data to times on the order of 10,000 h, which represents the lower limit of operating time anticipated for ceramic blades and vanes in gas turbine engines. A secondary goal of the program will be to investigate the possibility of enhancing life prediction estimates by combining interrupted tensile SR tests and tensile dynamic fatigue tests in which tensile strength is measured as a function of stressing rate. The third goal of this program will be to investigate the effects of water vapor upon the SR behavior of the three structural ceramics chosen for the static tensile studies by measuring the flexural strength as a function of stressing rate at three temperatures.

Ferber, M.; Graves, G. A., Jr.

209

Repeated Transradial Catheterization: Feasibility, Efficacy, and Safety  

PubMed Central

Transradial access is an alternative to the transfemoral approach in coronary interventions. It results in less access-site bleeding, shorter hospital stays, lower costs, and less pain for the patient. However, some authors have suggested that the transradial approach might lead to radial artery occlusion, which precludes repeated same-artery catheterizations. Using data from our center, we evaluated the feasibility, safety, and efficacy of repeated transradial catheterization. We reviewed the 3,006 transradial catheterizations performed at our center from 2006 through 2009. Patients who had undergone at least one repeated transradial catheterization were identified, their cases monitored through 2012, and their baseline characteristics and other factors, including procedural sequelae, were analyzed. Seventy-nine patients underwent repeated right radial artery catheterizations, for a total of 92 repeated procedures. Repeated access to the right radial artery was not achieved in 4 attempts (failure rate, 4.3%), because of poor pulses or the operator's inability to advance the wire. No major sequelae were noted. The average times between the 1st to 2nd, 2nd to 3rd, and 3rd to 4th catheterizations were 406, 595, and 401 days, respectively. Our procedural success rate of 95.7% in performing repeated transradial catheterizations with no major sequelae provides support for the efficacy and safety of such procedures. PMID:25593518

Constantinides, Savvas S.; Talias, Michael A.; Soteriades, Elpidoforos S.; Christou, Christos P.

2014-01-01

210

Tolerability and efficacy of long-term treatment with daptomycin, ceftazidime and colistin in a patient with a polymicrobial, multidrug-resistant prosthetic joint reinfection: a case report  

PubMed Central

Introduction Prosthetic joint infections are severe complications of joint implants. Further complications arise when polymicrobial and/or multidrug-resistant microorganisms are involved. Currently, there are limited data on the management of these infections and on the tolerability of long-term treatment with daptomycin, ceftazidime and colistin. Case presentation A 55-year-old Caucasian woman who had a right hip prosthesis removed 1 year prior because of infection was admitted for prosthesis reimplantation. On admission at our hospital, anamnesis regarding etiology and management of prosthesis infection was not available. On clinical, laboratory findings and imaging studies infection was not suspected. A hip prosthesis was reimplanted. At surgery, histopathological and microbiological investigations were not taken. Three weeks after reimplantation, surgical site infection due to Enterobacter cloacae was diagnosed and oral ciprofloxacin was prescribed. Four days later, a periprosthesis fluid collection was evidenced and a percutaneous needle aspirate grew Staphylococcus epidermidis and S. haemolyticus. Enterobacter genome was also detected from the same sample. Teicoplanin and meropenem were added to ciprofloxacin without clinical improvement. Moreover, acetabular cup dislocation was documented. She underwent prosthesis explantation, debridement, and positioning of an antimicrobial mixed spacer. From the intraoperatory cultures S. epidermidis and Acinetobacter baumannii were grown. Daptomycin, ceftazidime, colistin and rifampin were administered. Four days later, rifampin was stopped due to a suspected liver toxicity. While undergoing therapy she presented recurrent episodes of wound dehiscence and on the 22nd week of treatment a further surgical debridement was performed, upon which the spacer was removed. At this time, intraoperative cultures resulted negative. Three months later, after a total of 8 months, antimicrobials were interrupted. Subsequently, a femoral transcondylar traction was positioned, and 3 weeks later a new prosthesis was reimplanted. At over 1 year after reimplantation she is well. Conclusions Our findings suggest that microbiologic investigations are mandatory even when prosthetic joint infection is not suspected. Molecular methods for identification of microorganisms can be used in addition to conventional cultures especially when patients are under antibiotic treatment. Daptomycin, ceftazidime and colistin can be administered for several months without side effects. Guidelines specifically addressing the diagnosis and the management of polymicrobial, multidrug-resistant prosthetic joint infections need to be developed. PMID:24923703

2014-01-01

211

Efficacy of treatment and long-term follow-up of Batrachochytrium dendrobatidis PCR-positive anurans following itraconazole bath treatment.  

PubMed

All anuran specimens in the Wildlife Conservation Society's collections testing positive for Batrachochytrium dendrobatidis (Bd) were treated with itraconazole and then studied after treatment to assess the long-term effects of itraconazole and the drug's effectiveness in eliminating Bd carriers. Twenty-four individuals and eight colonies of 11 different species (75 total specimens) tested positive for Bd via polymerase chain reaction (PCR) on multicollection survey. All positive individuals and colonies were treated with a 0.01% itraconazole bath solution and retested for Bd via one of two PCR methodologies within 14 days of treatment completion, and all were negative for Bd. A total of 64 animals received secondary follow-up PCR testing at the time of death, 6-8 mo, or 12-15 mo post-treatment. Fourteen animals (14/64, 21.9%) were PCR positive for Bd on second follow-up. The highest percentage positive at second recheck were green-and-black poison dart frogs (Dendrobates auratus; 5/5 specimens, 100%), followed by red-eyed tree frogs (Agalychnis callidryas; 4/11, 36.4%), grey tree frogs (Hyla versicolor; 1/3, 33.3%), and green tree frogs (Hyla cinera; 3/11, 27.3%). Re-testing by PCR performed on 26/28 individuals that died during the study indicated 11/26 (42.3%) were positive (all via DNA extracted from formalin-fixed paraffin-embedded skin sections). However, there was no histologic evidence of chytridiomycosis in any of 27/28 individuals. The small number of deceased animals and effects of postmortem autolysis limited the ability to determine statistical trends in the pathology data, but none of the necropsied specimens showed evidence of itraconazole toxicity. Problems with itraconazole may be species dependent, and this report expands the list of species that can tolerate treatment. Although itraconazole is effective for clearance of most individuals infected with Bd, results of the study suggest that repeat itraconazole treatment and follow-up diagnostics may be required to ensure that subclinical infections are eliminated in amphibian collections. PMID:23805558

Georoff, Timothy A; Moore, Robert P; Rodriguez, Carlos; Pessier, Allan P; Newton, Alisa L; McAloose, Denise; Calle, Paul P

2013-06-01

212

Micromechanics-based prediction of creep failure of hard rock for long-term safety of high-level radioactive waste disposal system  

Microsoft Academic Search

A high-level radioactive waste disposal project is under way in Japan. Isolation of the radioactive waste in a rock formation at great depth is considered as one of the promising disposal methods. Before proceeding with the disposal project, however, assessment of the long-term stability of rock mass surrounding waste packages is necessary. This paper presents a micromechanics-based model for predicting

Kazuhiko Miura; Yoshiaki Okui; Hideyuki Horii

2003-01-01

213

Evaluation of efficacy and safety of finasteride 1 mg in 3177 Japanese men with androgenetic alopecia.  

PubMed

Before now, there has been no study of finasteride use exceeding 1 year in Japanese men with androgenetic alopecia (AGA) except the study subsequently conducted from the development phase. Since the launch of finasteride, no study in a larger population had been reported. Ethnic variation of the onset age, progressive nature and degree of hair loss of androgenetic alopecia are known. The therapeutic effect of oral finasteride (Propecia) was examined on androgenetic alopecia of Japanese men. The efficacy and safety of finasteride (1 mg tablet) was evaluated in Japanese men with AGA in the long term. The study enrolled 3177 men given finasteride 1 mg/day from January 2006 to June 2009 at our clinic. Efficacy was evaluated in 2561 men by the modified global photographic assessment; the photographs were assessed using the standardized 7-point rating scale. Safety data were assessed by interviews and laboratory tests in all men enrolled in the study. The overall effect of hair growth was seen in 2230 of 2561 men (87.1%), in whom hair greatly (11.1%), moderately (36.5%) and slightly (39.5%) increased. The response rate improved with increasing duration of treatment. Adverse reactions occurred in 0.7% (23/3177) of men; seven men discontinued treatment based on risk-benefit considerations. No specific safety problems associated with long-term use were observed. This study represents data collected at a single institution. Many patients did not receive follow-up examination. In Japanese men with AGA, oral finasteride used in the long-term study maintained progressive hair regrowth without recognized side-effect. PMID:21980923

Sato, Akio; Takeda, Akira

2012-01-01

214

The impact of focused, long-term, and collaborative professional development in math and science participants' self-efficacy, classroom practice, and student achievement  

NASA Astrophysics Data System (ADS)

The purpose of this study was to investigate the impact of a 2-year professional development model in math and science on the self-efficacy of the teacher and its effects on teacher practice and student outcomes. Further, this study sought to incorporate the instructional use of Inquiry-Based Learning methods of Problem-Based Learning, Japanese Lesson Study, and Action Research. Additionally, this study examined the impacts of these interventions on teacher efficacy and student outcomes. Thirty-eight collaborating participants were purposefully selected by the Math and Science Teacher Academy (MASTA) project grant co-directors because of their content-focused classrooms of mathematics and science. This quasi-experimental study included mathematics and science in-service teachers working on their masters in education. The 2-year, bi-monthly professional development model included collaborating Inquiry-Based Learning communities with in-depth focus on Japanese Lesson Study, Problem-Based Learning instruction, and Action Research. A chi-square analysis was conducted by grade on the difference in passing rate from the Texas Assessment of Knowledge and Skills mathematics and science tests between the MASTA participants and the state passing average. In mathematics there were significant v differences only at grades 3 and 7 where the state passing average was significantly higher than the MASTA students' passing rate. Only at grade 5 was the MASTA students' passing rate higher than the state, but the difference was not significantly different. The science passing rate received from three grade 5 MASTA participants was compared to the state average and a chi-squared was conducted. Although the passing rate for the grade 5 science test was 6% higher for MASTA student that the state, the difference was not statistically significant. However, after analyzing the qualitative participant responses from data gathered during the 2-year MASTA grant the data clearly reflected that teachers participating in the MASTA grant felt the professional development helped to improve their own teacher-efficacy and knowledge in their content areas.

Nottingham, Mary E.

215

The Long-Term Tolerability and Efficacy of Armodafinil in Patients with Excessive Sleepiness Associated with Treated Obstructive Sleep Apnea, Shift Work Disorder, or Narcolepsy: An Open-Label Extension Study  

PubMed Central

Study Objectives: Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in 12-week studies of patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. This study evaluated the tolerability and efficacy of armodafinil for ? 12 months. Methods: Patients with ES associated with treated OSA, SWD, or narcolepsy who completed one of four 12-week, double-blind studies were eligible for this multicenter, open-label study of ? 12 months' duration of treatment with armodafinil (50 to 250 mg/day). Adverse events and other criteria of tolerability were monitored throughout the study. Efficacy assessments included the Clinical Global Impression of Change (CGI-C), Brief Fatigue Inventory (BFI), and Epworth Sleepiness Scale (ESS). Results: Of 743 enrolled patients (474 with treated OSA, 113 with SWD, and 156 with narcolepsy), 57% of patients (420/743) completed 12 months or more of treatment. Discontinuations due to adverse events occurred in 13% of patients (95/743) during the initial 12-month period. Throughout the ? 12-month study, adverse events were generally of mild-to-moderate intensity; headache (25% [180/731]), nasopharyngitis (17% [123/731]), and insomnia (14% [99/731]) were the most common. Modest increases were observed in vital sign measurements (blood pressure [3.6/2.3 mm Hg], heart rate [6.7 beats per minute]) across all patient groups; most of the changes occurred by month 3. Improvements from baseline in efficacy assessments started at month 1 and were maintained throughout the study. Conclusions: Armodafinil remained effective and was generally well tolerated. Increased monitoring of blood pressure may be appropriate in patients on armodafinil. Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy. Citation: Black JE; Hull SG; Tiller J; Yang R; Harsh JR. The long-term tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder, or narcolepsy: an open-label extension study. J Clin Sleep Med 2010;6(5):458-466. PMID:20957846

Black, Jed E.; Hull, Steven G.; Tiller, Jane; Yang, Ronghua; Harsh, John R.

2010-01-01

216

Comparative long-term experience with immunoadsorption and dextran sulfate cellulose adsorption for extracorporeal elimination of low-density lipoproteins  

Microsoft Academic Search

Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to

W. Knisel; M. Pfohl; M. Müller; I. Besenthal; A. Nicuolo; W. Voelker; T. Risler; M. Eggstein

1994-01-01

217

Long-term safety of anti-TNF-? in PsA patients with concomitant HCV infection: a retrospective observational multicenter study on 15 patients.  

PubMed

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-?, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-? blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-? agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-? agents, accompanied by close monitoring, could be a therapeutic option. PMID:23975363

Costa, Luisa; Caso, Francesco; Atteno, Mariangela; Giannitti, Chiara; Spadaro, Antonio; Ramonda, Roberta; Vezzù, Maristella; Del Puente, Antonio; Morisco, Filomena; Fiocco, Ugo; Galeazzi, Mauro; Punzi, Leonardo; Scarpa, Raffaele

2014-02-01

218

Efficacy and long-term outcome of treatment for pure red cell aplasia after allogeneic stem cell transplantation from major ABO-incompatible donors.  

PubMed

No standard of care for pure red cell aplasia (PRCA) after major ABO-incompatible hematopoietic stem cell transplantation (HSCT) has been established. We conducted a retrospective cohort study to learn the efficacy and outcome of treatment for PRCA. One hundred forty-five recipients who showed delayed recovery of erythropoiesis and survived >100 days after transplantation without early disease progression were selected from 2846 records of major ABO-incompatible transplantation in the registry database in Japan, and detailed data of 46 recipients were collected. Treatment of PRCA, such as rapid tapering of calcineurin inhibitors, corticosteroids, or additional immunosuppressants, was given to 22 patients but not to the other 24 patients. The overall response rate of the treatment group was 54.5%. The number of days from diagnosis of PRCA to recovery of reticulocytes >1% and the cumulative number of red blood cell transfusions were not significantly different between the 2 groups. Infections accounted for the death of 7 of 11 patients in the treatment group. Univariate analysis identified 5 variables influencing survival, including graft-versus-host disease, disease progression, and treatment of PRCA; disease progression remained as the only factor negatively affecting survival by multivariate analysis. The present study could not provide supportive evidence for the beneficial effects of treatment for PRCA after major ABO-mismatched HSCT. PMID:23583828

Hirokawa, Makoto; Fukuda, Takahiro; Ohashi, Kazuteru; Hidaka, Michihiro; Ichinohe, Tatsuo; Iwato, Koji; Kanamori, Heiwa; Murata, Makoto; Sakura, Toru; Imamura, Masahiro; Adachi, Soichi; Suzuki, Ritsuro; Morishima, Yasuo; Sakamaki, Hisashi

2013-07-01

219

Efficacy of long-term milnacipran treatment in patients meeting different thresholds of clinically relevant pain relief: subgroup analysis of a randomized, double-blind, placebo-controlled withdrawal study  

PubMed Central

Background Fibromyalgia patients from a long-term, open-label study of milnacipran (50–200 mg/day) were eligible to participate in a 12-week, randomized, placebo-controlled withdrawal study. The withdrawal study evaluated loss of therapeutic response in patients who achieved ?50% pain improvements after receiving up to 3.25 years of milnacipran. This post-hoc analysis investigated whether patients who met lower thresholds of pain improvement also experienced worsening of fibromyalgia symptoms upon treatment withdrawal. Method Among patients who received milnacipran ?100 mg/day during the long-term study, three subgroups were identified based on percentage of pain reduction at randomization: ?50% (protocol-defined “responders”; n=150); ?30% to <50% (patients with clinically meaningful pain improvement; n=61); and <30% (n=110). Efficacy assessments included the visual analog scale (VAS) for pain, Fibromyalgia Impact Questionnaire-Revised (FIQR), 36-Item Short-Form Health Survey Physical Component Summary (SF-36 PCS), and Beck Depression Inventory (BDI). Results In the ?30 to <50% subgroup, significant worsening in pain was detected after treatment withdrawal. The difference between placebo and milnacipran in mean VAS score changes for this subgroup (+9.0, P<0.05) was similar to the difference in protocol-defined responders (+9.4, P<0.05). In the <30% subgroup, no worsening in pain was observed in either treatment arm. However, patients in this subgroup experienced significant worsening in FIQR scores after treatment withdrawal (placebo, +6.9; milnacipran, ?2.8; P<0.001), as well as worsening in SF-36 PCS and BDI scores. Conclusion Patients who experienced ?30% to <50% pain reduction with long-term milnacipran had significant worsening of fibromyalgia symptoms after treatment withdrawal. These results suggest that the conventional ?30% pain responder cutoff may be adequate to demonstrate efficacy in randomized withdrawal studies of fibromyalgia. Patients in the <30% pain reduction subgroup had worsening scores on the FIQR and other multidimensional measures after treatment withdrawal, indicating the importance of identifying and managing the multiple symptoms of fibromyalgia. PMID:25473309

Mease, Philip J; Clauw, Daniel J; Trugman, Joel M; Palmer, Robert H; Wang, Yong

2014-01-01

220

Safety and Efficacy of Modern Insulin Analogues  

PubMed Central

Background A1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. Methods Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. Results Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7±15.9 to 72.5±13.5) while the mean body weight was slightly increased (0.6±3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%±2.2%, 2.5±4.7 mmol/L, and 4.0±6.4 mmol/L, respectively. Conclusion The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes. PMID:23807921

Yoo, Hye Jin; Park, Keun Yong; Park, Kang Seo; Ahn, Kyu Jeung; Min, Kyung Wan; Park, Jeong Hyun; Chang, Sang Ah; Cha, Bong Soo; Kim, Dong-Jun; Kim, Yong Seong; Oh, Tae Keun; Chon, Suk; Nam-Goong, Il Seong; Kim, Mi Jin; Kim, Hye-Soon; Choi, Young Sik; Ahn, You Hern; Lee, Sora

2013-01-01

221

Topical Bromfenac Sodium for Long-Term Management of Vernal Keratoconjunctivitis  

Microsoft Academic Search

Background\\/Aims: We evaluated the efficacy and safety of long-term management of patients with vernal keratoconjunctivitis (VKC) with bromfenac sodium eye drops in combination with corticosteroids and anti-allergic eye drops. Methods: Twenty-two patients with VKC were randomly assigned to receive two test eye drops, either bromfenac sodium 0.1% (group A) or placebo eye drops (normal saline; group B) for a mean

Eiichi Uchio; Yuki Itoh; Kazuaki Kadonosono

2007-01-01

222

Long-term environmental stewardship.  

SciTech Connect

The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

Nagy, Michael David

2010-08-01

223

Presynaptic long-term plasticity  

PubMed Central

Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

Yang, Ying; Calakos, Nicole

2013-01-01

224

Long-Term Control with Etanercept (Enbrel®) of a Severe Acrodermatitis Continua of Hallopeau Refractory to Infliximab (Remicade®)  

Microsoft Academic Search

Hallopeau’s acrodermatitis is characterized by the presence of aseptic pustules on an inflammatory basis of the periungual or subungual region. The cyclic recurrences induce important physical and psychological morbidity. By analogy to the efficacy of TNF-? antagonists in the treatment of generalized pustular psoriasis, our patient illustrates the long-term efficacy and safety of etanercept (Enbrel®) in the treatment of Hallopeau’s

A.-M. Thielen; C. Barde; G. Marazza; J.-H. Saurat

2008-01-01

225

Current Antiviral Therapy of Chronic Hepatitis B: Efficacy and Safety  

Microsoft Academic Search

The treatment of chronic hepatitis B is in constant evolution. Interferon, the first agent licensed for chronic hepatitis\\u000a B treatment, has been superseded by the growing popularity of nucleoside\\/nucleotide analogues (NA). However, resistance to\\u000a these agents is a major challenge. Newer NAs, such as entecavir and tenofovir dipivoxil fumarate, have very low resistance\\u000a rates and favorable safety profiles. Long-term use

Yuk-Fai Lam; Man-Fung Yuen; Wai-Kay Seto; Ching-Lung Lai

226

Long-Term Use of Low-Molecular-Weight Heparin in Hemodialysis Patients: A 7Year Experience  

Microsoft Academic Search

Background: Low-molecular-weight-heparin (LMWH) is not routinely used as anticoagulant in hemodialysis (HD). The ideal dose and the safety of long-term use are not known. Methods: A prospective three-phase interventional study. Phase 1 involved dose titration, phase 2 safety and efficacy and phase 3 routine practice. Results: During 7 years of the use of the LMWH enoxaparin (EN), 236 patients were

B. Bernieh; Y. Boobes; M. R. Al Hakim; S. Abouchacra; H. Dastoor

2009-01-01

227

Basics (Long-Term Care)  

MedlinePLUS

... Term Care? Expand Long-term Care Considerations for LGBT Adults Expand Health Disparities Impacting LTC Expand Caregivers ... on Alzheimer's Disease Lesbian, Gay, Bisexual and Transgender (LGBT) community Home About Us Accessibility Disclaimer Privacy Contact ...

228

Medicare (Long-Term Care)  

MedlinePLUS

... term Care Services – Skilled Nursing Medicare does not pay the largest part of long-term care services ... 100 days . For the first 20 days, Medicare pays 100 percent of your costs. For days 21 ...

229

Prucalopride: safety, efficacy and potential applications  

PubMed Central

Chronic constipation is a very common functional gastrointestinal disorder which can be associated with significant impairments in quality of life for some people with the condition. Its management has, traditionally, been based on dietary and lifestyle changes and the use of a variety of laxative agents. The evidence base for the efficacy of the latter is, in many cases, slim. Not surprisingly, many patients remain dissatisfied with laxatives thus leading to the development of more pharmacological approaches. Among these approaches is the use of prokinetic agents; while prior molecules have been troubled by lack of selectivity and cardiac side effects, the new agent, prucalopride, appears to be highly selective for the serotonin 5-HT4 receptor and is, therefore, a potent stimulator of gut motility. In three large pivotal randomized controlled trials, prucalopride has been effective in relieving the cardinal symptoms of chronic constipation; these effects have been sustained in open-label follow up for as long as 18 months. The safety profile has been encouraging and, especially so, the absence of arrhythmogenic potential. Studies in men, in constipation-predominant irritable bowel syndrome and in other motor disorders are eagerly awaited. PMID:22282705

2012-01-01

230

Efficacy and Safety of Sitagliptin for the Treatment of New-Onset Diabetes after Renal Transplantation  

PubMed Central

New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5 ± 17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients. PMID:24817885

Boerner, Brian P.; Miles, Clifford D.

2014-01-01

231

Acute and long-term treatment of mania  

PubMed Central

The treatment of mania starts with a correct diagnosis and elementary measures to prevent risks for the patient, relatives, and others. Sometimes, compulsory admission and treatment may be required for a few days. Patients with psychotic or mixed mania may be more difficult to treat. At the present time, there is solid evidence supporting the use of lithium, the anticonvulsants valproate and carbamazepine, and the antipsychotics chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, combination therapy is the rule rather than the exception. The treatment of acute mania deserves a long-term view, and the evidence base for some treatments may be stronger than for others. When taking decisions about treatment, tolerabiliiy should also be a major concern, as differences in safety and tolerability may exceed differences in efficacy for most compounds, Psychoeducation of patients and caregivers is a povi/erful tool that should be used in combination with medication for optimal long-term outcome. Functional recovery should be the ultimate goal. PMID:18689287

Vieta, Eduard; Sanchez-Moreno, Jose

2008-01-01

232

Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme  

PubMed Central

Purpose The purpose of this study is to further evaluate the safety of the human papillomavirus (HPV)-16/18-AS04-adjuvanted vaccine (HPV-16/18-vaccine Cervarix®, GlaxoSmithKline, Belgium) through a pooled analysis of data from 42 completed/ongoing clinical studies. Methods Unsolicited adverse events (AEs) were reported for 30 days after each dose. Medically significant conditions, serious AEs (SAEs), potential immune-mediated diseases (pIMDs) and pregnancy outcomes were captured until study completion. Events leading to subject withdrawal were reviewed. Relative risks compared incidences of spontaneous abortion and pIMDs in controlled studies. Results Thirty one thousand one hundred seventy-three adolescent girls/women received HPV-16/18-vaccine alone (HPV group), 2166 received HPV-16/18-vaccine coadministered with another vaccine and 24 241 were controls. Mean follow-up was 39 months (range 0–113.3). Incidences of unsolicited AEs reported within 30 days after any dose were similar between HPV and Control groups (30.8%/29.7%). During the entire study period, reports of medically significant conditions (25.0%/28.3%) and SAEs (7.9%/9.3%) were also similarly distributed between groups. Deaths were rare: HPV (alone/coadministered) n = 25, controls n = 20 (n = 18 in blinded groups). pIMDs within 1 year were reported by 0.2% of HPV-16/18 vaccinees and controls. For each pIMD event category, no increased relative risks were reported for HPV-16/18 vaccinees versus controls. Coadministration did not change the overall safety profile. Pregnancy outcomes and withdrawal rates were similar between groups. Conclusions Analysis of safety data arising from 57 580 subjects and 96 704 HPV-16/18-vaccine doses shows that the incidences and distribution of AEs were similar among HPV-16/18-vaccine recipients and controls. No new safety signals were identified. The data confirm previous findings that HPV-16/18-vaccine has an acceptable benefit-risk profile in adolescent girls and adult women. PMID:24644063

Angelo, Maria-Genalin; David, Marie-Pierre; Zima, Julia; Baril, Laurence; Dubin, Gary; Arellano, Felix; Struyf, Frank

2014-01-01

233

Efficacy and safety of long acting injectable atypical antipsychotics: a review.  

PubMed

Schizophrenia is a chronic, severe and recurrent brain disorder that requires continuous, long-term treatment with antipsychotic medication to minimize relapse and provide clinical benefit to patients. For patients with schizophrenia, non-adherence to medication is a major risk factor for relapse and re-hospitalization. Long-acting injectable formulations of second-generation antipsychotics (SGAs-LAIs) provide constant medication delivery and the potential for improved adherence. Currently, three drugs are available for the treatment of schizophrenia, risperidone longacting injectable, olanzapine pamoate and paliperidone palmitate. Several studies have also demonstrated efficacy and safety of such drugs in patients with acute schizophrenia. In the present paper the literature on LAI atypical antipsychotics will be reviewed and practical advice will be given concerning the use of these drugs in the clinical practice. PMID:23343445

De Berardis, Domenico; Marini, Stefano; Carano, Alessandro; Lang, Antonella Padovan; Cavuto, Marilde; Piersanti, Monica; Fornaro, Michele; Perna, Giampaolo; Valchera, Alessandro; Mazza, Monica; Iasevoli, Felice; Martinotti, Giovanni; Di Giannantonio, Massimo

2013-08-01

234

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety  

Microsoft Academic Search

BACKGROUND: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking.

Alan G Wade; Ian Ford; Gordon Crawford; Alex McConnachie; Tali Nir; Moshe Laudon; Nava Zisapel

2010-01-01

235

Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: Results from phase III extension study 307  

PubMed Central

Objective To evaluate safety, tolerability, seizure frequency, and regional variations in treatment responses with the AMPA antagonist, perampanel, in a large extension study during up to 3 years of treatment. Methods Patients ?12 years old with partial-onset seizures despite treatment with 1–3 antiepileptic drugs at baseline completed a perampanel phase III trial and entered extension study 307 (NCT00735397). Patients were titrated to 12 mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open-label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [ECG], laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions. Results Among 1,216 patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in ?10% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only serious AEs reported in >1% of patients were epilepsy-related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or laboratory parameters were seen. After titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9 months (in 980 patients with ?9 months' exposure) and 58% and 60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). Median percentage reduction in frequency of secondarily generalized (SG) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance data ?1 year, 5.3% were seizure-free for the entire year. Significance No new safety signals emerged during up to 3 years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in SG seizures. PMID:24867391

Krauss, Gregory L; Perucca, Emilio; Ben-Menachem, Elinor; Kwan, Patrick; Shih, Jerry J; Clément, Jean-François; Wang, Xuefeng; Bagul, Makarand; Gee, Michelle; Zhu, Jin; Squillacote, David

2014-01-01

236

Safety self-efficacy and safety performance : Potential antecedents and the moderation effect of standardization  

Microsoft Academic Search

Purpose – The purpose of this paper is to suggest a new safety self-efficacy construct and to explore its antecedents and interaction with standardization to influence in-patient safety. Design\\/methodology\\/approach – The paper used a survey of 161 nurses using a self-administered questionnaire over a 14-day period in two large Israeli general hospitals. Nurses answered questions relating to four safety self-efficacy

Tal Katz-Navon; Eitan Naveh; Zvi Stern

2007-01-01

237

Long-Term Outcomes of Percutaneous Cryoablation for Patients with Hepatocellular Carcinoma within Milan Criteria  

PubMed Central

Background Accumulating evidences have suggested that percutaneous cryoablation could be a valuable alternative ablation therapy for HCC but there has been no large cohort-based analysis on its long-term outcomes. Methods A series of 866 patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who underwent percutaneous cryoablation was long-term followed. The safety, efficacy, 5-year survival, and prognostic factors of percutaneous cryoablation in the treatment of HCC were analyzed. Results A total of 1197 HCC lesions were ablated with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163 (97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but no treatment-related mortality. After a median of 30.9 months follow-up, 502 (60.3%) patients who achieved CR developed different types of recurrence. The cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent risk factors associated with local recurrence. The 5-year overall survival (OS) rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus DNA >106 copies/ml, and three HCC lesions were independently and significantly negative predictors to the post-cryoablation OS. Conclusions Percutaneous cryoablation is an effective therapy for patients with HCC within Milan criteria, with comparable efficacy, safety and long-term survival to the reported outcomes of radiofrequency ablation. PMID:25849963

Wang, Chunping; Lu, Yinying; Zeng, Zhen; Qu, Jianhui; Lou, Min; Wang, Hong; Gao, Xudong; Chang, Xiujuan; An, Linjing; Li, Hongyan; Chen, Yan; Hu, Ke-Qin; Yang, Yongping

2015-01-01

238

Risperidone Long-Acting Injection: Safety and Efficacy in Elderly Patients with Schizophrenia  

PubMed Central

Antipsychotic medication is considered the cornerstone of the treatment in elderly patients with schizophrenia. Long acting risperidone injection was the first antipsychotic available for use in this group of patients. Current scientific literature revealed that long-acting risperidone is effective in treating the positive and negative symptoms of schizophrenia and some improvements in cognition and functioning have also been found. In terms of efficacy, there is a paucity of randomized trials but the studies suggest that long-acting risperidone is efficient in the long-term management of schizophrenia, with a safety profile similar to that of oral risperidone. It seems that patient acceptance of treatment is greater when patients are switched from a traditional oral medication to depot risperidone and some improvements in cognition and functioning might be related. Further long-term comparisons with other oral and long-acting antipsychotic medications are needed. These studies should include cost-effectiveness data. Research into metabolic side effects is also needed. PMID:23861642

Catalán, Rosa; Penadés, Rafael

2011-01-01

239

Modeling the impact of climate change in Germany with biosphere models for long-term safety assessment of nuclear waste repositories.  

PubMed

Biosphere models are used to evaluate the exposure of populations to radionuclides from a deep geological repository. Since the time frame for assessments of long-time disposal safety is 1 million years, potential future climate changes need to be accounted for. Potential future climate conditions were defined for northern Germany according to model results from the BIOCLIM project. Nine present day reference climate regions were defined to cover those future climate conditions. A biosphere model was developed according to the BIOMASS methodology of the IAEA and model parameters were adjusted to the conditions at the reference climate regions. The model includes exposure pathways common to those reference climate regions in a stylized biosphere and relevant to the exposure of a hypothetical self-sustaining population at the site of potential radionuclide contamination from a deep geological repository. The end points of the model are Biosphere Dose Conversion factors (BDCF) for a range of radionuclides and scenarios normalized for a constant radionuclide concentration in near-surface groundwater. Model results suggest an increased exposure of in dry climate regions with a high impact of drinking water consumption rates and the amount of irrigation water used for agriculture. PMID:22742772

Staudt, C; Semiochkina, N; Kaiser, J C; Pröhl, G

2013-01-01

240

Long-term data archiving  

SciTech Connect

Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web Consortium, an independent standards body) as a new data interchange tool is being investigated and implemented. In order to facilitate data archiving, Raman data needs calibration as well as some other kinds of data treatment. Figure 1 illustrates schematically the present situation for Raman data calibration in the world-wide Raman spectroscopy community, and presents some of the terminology used.

Moore, David Steven [Los Alamos National Laboratory

2009-01-01

241

Performance considerations in long-term spaceflight  

NASA Technical Reports Server (NTRS)

Maintenance of skilled performance during extended space flight is of critical importance to both the health and safety of crew members and to the overall success of mission goals. An examination of long term effects and performance requirements is therefore a factor of immense importance to the planning of future missions. Factors that were investigated include: definition of performance categories to be investigated; methods for assessing and predicting performance levels; in-flight factors which can affect performance; and factors pertinent to the maintenance of skilled performance.

Akins, F. R.

1979-01-01

242

Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results  

PubMed Central

Background Clinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting. Objective To evaluate long-term safety of natalizumab and its impact on annualised relapse rate and Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting multiple sclerosis (RRMS). Methods The Tysabri (natalizumab) Observational Program (TOP) is an open-label, multinational, 10-year prospective study in clinical practice settings. Results In this 5-year interim analysis, 4821 patients were enrolled. Follow-up for at least 4?years from natalizumab commencement in 468 patients and at least 2?years in 2496 patients revealed no new safety signals. There were 18 cases of progressive multifocal leucoencephalopathy reported, following 11–44 natalizumab infusions. Mean annualised relapse rate decreased from 1.99 in the 12?months prior to baseline to 0.31 on natalizumab therapy (p<0.0001), remaining low at 5?years. Lower annualised relapse rates were observed in patients who used natalizumab as first MS therapy, in patients with lower baseline EDSS scores, and in patients with lower prenatalizumab relapse rates. Mean EDSS scores remained unchanged up to 5?years. Conclusions Interim TOP data confirm natalizumab's overall safety profile and the low relapse rate and stabilised disability levels in natalizumab-treated patients with RRMS in clinical practice. Trial registration number NCT00493298. PMID:24532785

Butzkueven, Helmut; Kappos, Ludwig; Pellegrini, Fabio; Trojano, Maria; Wiendl, Heinz; Patel, Radhika N; Zhang, Annie; Hotermans, Christophe; Belachew, Shibeshih

2014-01-01

243

Ice sheet sensitivity experiments as part of an assessment of long-term safety for a planned repository for spent nuclear fuel in Sweden  

NASA Astrophysics Data System (ADS)

An application to build a deep geological repository for spent nuclear fuel in Forsmark in south-central Sweden is currently under consideration by Swedish authorities. As part of the safety assessment, the response of the repository to an extensive glaciation over time scales of several hundred thousand years, in terms of ice thickness, bedrock depression and hydrostatic pressure, has to be evaluated. The most extensive glaciation over Eurasia recorded in geological proxies occurred during the MIS 6, at around 140 kyrs BP (Late Saalian glaciation). At this time, the few existing numerical ice-sheet reconstructions suggest that the Eurasian ice volume reached more than 70 m SLE, which is at least three times larger than during the Last Glacial Maximum (21 kyrs BP). The reconstruction of this ice sheet is complicated by the fact that the timing of the maximum ice volume may not have been coeval with the maximum eastern and southern extent of the Saalian ice sheet. In the present study, the maximum geographical extension of the Late Saalian glaciation serves as an extreme test case to assess the impact of ice thickness over the Forsmark repository site. We use the 3D-thermodynamical ice sheet-ice shelves and ice stream model GRISLI (Ritz et al. 2001) to simulate the Northern Hemisphere ice sheet topography of the Late Saalian glaciation. The model is forced by steady-state climatic fields (surface air temperature and precipitation) computed using the coupled atmosphere-ocean Community Earth System Model (CESM, NCAR) at ~1°x1° resolution, with boundary and forcing conditions representative for the MIS6 glacial maximum. Ice sheet simulations are run on a 20 km regular rectangular grid over the northern high latitudes and allow for floating ice. First, as part of the model validation, we show a numerical reconstruction of the MIS 6 Eurasian ice sheet using standard parameters for lapse rate, PDD coefficients and basal hydrology. Second, sensitivity experiments are presented, studying the impact of model parameters such as surface mass balance parameters and schemes of calving and basal hydrology on the ice thickness. With this approach we are able to provide reasonable upper and lower bounds of ice thickness for a possible extreme glaciation over the Forsmark area.

Wekerle, Claudia; Colleoni, Florence; Masina, Simona; Näslund, Jens-Ove; Brandefelt, Jenny

2014-05-01

244

The efficacy and safety of rituximab in treating childhood refractory nephrotic syndrome: A meta-analysis  

PubMed Central

Rituximab is considered to be a promising drug for treating childhood refractory nephrotic syndrome. However, the efficacy and safety of rituximab in treating childhood refractory nephrotic syndrome remain inconclusive. This meta-analysis aimed to investigate the efficacy and safety of rituximab treatment compared with other immunosuppressive agents in children with refractory nephrotic syndrome. Three randomized controlled trials and two comparative control studies were included in our analysis. The included studies were of moderately high quality. Compared with other immunotherapies, rituximab therapy significantly improved relapse-free survival (hazard ratio = 0.49, 95% confidence interval [CI], 0.26–0.92, P = 0.03). Rituximab also achieved a higher rate of complete remission (risk ratio,1.62; 95% CI, 0.92 to 2.84, P = 0.09) and reduced the occurrence of proteinuria (mean difference = ?0.25, 95% CI = ?0.29 to ?0.21, P < 0.00001); however, a more targeted rituximab treatment did not significantly increase serum albumin levels and did not significantly reduce adverse events. Rituximab might be a promising treatment for childhood refractory nephrotic syndrome; however, the long-term effects and cost-effectiveness of rituximab treatment were not fully assessed, and there were limited studies that evaluated the clinical benefits of a concurrent infusion of rituximab plus a steroid compared with an infusion of rituximab only. Additional studies are required to address these issues. PMID:25645999

Zhao, Zhihong; Liao, Guixiang; Li, Yongqiang; Zhou, Shulu; Zou, Hequn

2015-01-01

245

Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial  

PubMed Central

Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

2013-01-01

246

The efficacy and safety of rituximab in treating childhood refractory nephrotic syndrome: a meta-analysis.  

PubMed

Rituximab is considered to be a promising drug for treating childhood refractory nephrotic syndrome. However, the efficacy and safety of rituximab in treating childhood refractory nephrotic syndrome remain inconclusive. This meta-analysis aimed to investigate the efficacy and safety of rituximab treatment compared with other immunosuppressive agents in children with refractory nephrotic syndrome. Three randomized controlled trials and two comparative control studies were included in our analysis. The included studies were of moderately high quality. Compared with other immunotherapies, rituximab therapy significantly improved relapse-free survival (hazard ratio = 0.49, 95% confidence interval [CI], 0.26-0.92, P = 0.03). Rituximab also achieved a higher rate of complete remission (risk ratio,1.62; 95% CI, 0.92 to 2.84, P = 0.09) and reduced the occurrence of proteinuria (mean difference = -0.25, 95% CI = -0.29 to -0.21, P < 0.00001); however, a more targeted rituximab treatment did not significantly increase serum albumin levels and did not significantly reduce adverse events. Rituximab might be a promising treatment for childhood refractory nephrotic syndrome; however, the long-term effects and cost-effectiveness of rituximab treatment were not fully assessed, and there were limited studies that evaluated the clinical benefits of a concurrent infusion of rituximab plus a steroid compared with an infusion of rituximab only. Additional studies are required to address these issues. PMID:25645999

Zhao, Zhihong; Liao, Guixiang; Li, Yongqiang; Zhou, Shulu; Zou, Hequn

2015-01-01

247

Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability  

PubMed Central

?1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel ?1-adrenergic receptor antagonist whose affinity for the ?1A-adrenergic receptor is greater than that for the ?1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the ?1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society. PMID:25328864

Cho, Hee Ju; Yoo, Tag Keun

2014-01-01

248

The efficacy and safety of the quadrivalent human papillomavirus 6/11/16/18 vaccine gardasil.  

PubMed

Human papillomavirus (HPV) infection causes cervical cancer, a significant portion of anal, genital, and oropharyngeal cancers, genital warts, and recurrent respiratory papillomatosis. In June 2006, a quadrivalent HPV-6/11/16/18 vaccine (Gardasil/Silgard) was licensed in the United States, and subsequently in the European Union (September 2006). It has since been approved in 121 countries, with >74 million doses distributed globally as of March 2011. As the incidence of HPV infection peaks 5-10 years after the onset of sexual activity, preadolescents and adolescents represent an appropriate target group to implement HPV vaccination programs so as to achieve the maximal public health benefit. In this article, we provide an overview of the prophylactic efficacy of the vaccine in young women who were found to be negative to at least one of the four vaccine HPV types, thus approximating sexually naive adolescents. Because adolescents are also at high risk for other infections which are preventable by currently available vaccines, the development of concurrent immunization strategies may lead to better compliance, thereby contributing to the overall goal of protection against preventable diseases. We also summarize concomitant administration studies with meningococcal, diphtheria, tetanus, and pertussis vaccines, which were conducted in adolescents aged 9-15 years. Prophylactic efficacy in other populations (males aged 16-26 years) is also summarized along with long-term safety and efficacy studies. PMID:22018560

Haupt, Richard M; Sings, Heather L

2011-11-01

249

Omics Screening for Pharmaceutical Efficacy and Safety in Clinical Practice  

PubMed Central

As molecular techniques have improved, investigators have attempted to improve pharmaceutical efficacy and safety by making trait associations with genomic, epigenomic, transcriptomic, proteomic, and metabolomic polymorphisms. The ‘omics era has seen screening assays for pharmaceutical efficacy and safety translated into clinical practice. This manuscript will discuss each ‘omic field and the screening assays available to the clinician. While success has been demonstrated in each ‘omic field, many challenges remain. Assays need wider availability, predictive values remain low, and costs remain high. In order for clinicians to realize improved efficacy and safety due ‘omic screens, development of improved techniques, combining of ‘omic assays, and increased clinical utilization is necessary. This is an exciting time for investigators and clinicians that desire improved pharmaceutical therapy. PMID:23264882

Monte, Andrew A.; Vasiliou, Vasilis; Heard, Kennon J.

2012-01-01

250

A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes  

Microsoft Academic Search

Background: Gemifloxacin is an enhanced-affinity quinolone with potent activity against lower respiratory tract pathogens.Objective: The efficacy and safety of a 5-day course of gemifloxacin were compared with those of a standard 7-day regimen of clarithromycin in patients with an acute exacerbation of chronic bronchitis (AECB). The impact of treatment on the long-term (26 weeks) clinical outcome was also assessed.Methods: The

Robert Wilson; Jerome J Schentag; Peter Ball; Lionel Mandell

2002-01-01

251

Single infusion of rituximab for persistent steroid-dependent minimal-change nephrotic syndrome after long-term cyclosporine  

Microsoft Academic Search

Rituximab (RTX) has been successfully used as a rescue therapy in children with steroid-dependent nephrotic syndrome (SDNS).\\u000a However, little is known regarding maintenance therapy after a successful response to RTX in such patients. The efficacy and\\u000a safety of a single RTX infusion (375 mg\\/m2) were assessed in ten patients who had persistent SDNS associated with minimal-change disease (MCD) despite the long-term

Shuichiro Fujinaga; Daishi Hirano; Naoto Nishizaki; Koichi Kamei; Shuichi Ito; Yoshiyuki Ohtomo; Toshiaki Shimizu; Kazunari Kaneko

2010-01-01

252

Biologics in combination with nonbiologics: efficacy and safety.  

PubMed

The mechanisms of action of biologic therapies differ from the currently used systemic therapies by attacking specific steps in the pathogenesis pathway of psoriasis. Preliminary data show that combination therapy using biologics may allow for improved therapeutic efficacy with fewer side effects, including decreased risk of hepatotoxicity and nephrotoxicity commonly associated with the most widely used systemic agents, methotrexate, and cyclosporine. However, some concerns have been raised regarding the increased immunosuppression, increased risk of infection, potential for development of certain types of malignancy, as well as the significant increased cost of therapy. Both potential benefits and toxicities of combination therapy will be reviewed here. Long-term clinical studies are warranted to more accurately quantify the risks and benefits associated with combination therapy. The role of combination therapy will continue to be refined over the next few years to maximize its potential in the treatment of resistant psoriasis. PMID:15379778

Stebbins, William G; Lebwohl, Mark G

2004-01-01

253

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures  

PubMed Central

Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years. PMID:25616485

Bergey, Gregory K.; Mizrahi, Eli M.; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E.; Shields, Donald C.; Barkley, Gregory; Salanova, Vicenta; Olejniczak, Piotr; Cole, Andrew; Cash, Sydney S.; Noe, Katherine; Wharen, Robert; Worrell, Gregory; Murro, Anthony M.; Edwards, Jonathan; Duchowny, Michael; Spencer, David; Smith, Michael; Geller, Eric; Gwinn, Ryder; Skidmore, Christopher; Eisenschenk, Stephan; Berg, Michel; Heck, Christianne; Van Ness, Paul; Fountain, Nathan; Rutecki, Paul; Massey, Andrew; O'Donovan, Cormac; Labar, Douglas; Duckrow, Robert B.; Hirsch, Lawrence J.; Courtney, Tracy; Sun, Felice T.; Seale, Cairn G.

2015-01-01

254

Long-acting risperidone injection: efficacy, safety, and cost-effectiveness of the first long-acting atypical antipsychotic  

PubMed Central

Objective To review the pharmacokinetics, efficacy, safety, and cost-effectiveness of long-acting risperidone. Methods Studies published between January 2000 and October 2006 evaluating the pharmacokinetics, efficacy, safety, and cost-effectiveness of long-acting risperidone were reviewed, as identified from literature searches using Medline and EMBASE. Abstracts and posters on long-acting risperidone presented at key psychiatry congresses and available in the public domain during this time period were also reviewed. Results The unique pharmacokinetic profile of long-acting risperidone is derived from the encapsulation of risperidone in a glycolide/lactide matrix in the form of microspheres such that after a single intramuscular injection, significant plasma levels of the drug are achieved after week 3. Steady state, after repeated administration at 2-week intervals, is achieved after 3 injection cycles. Short- and long-term studies have demonstrated that long-acting risperidone (25, 37.5, or 50 mg) is both efficacious and well tolerated in a wide variety of patients with schizophrenia and related psychoses. Most patients can be switched from other oral and long-acting antipsychotic agents without compromising efficacy and safety. Long-acting risperidone may also reduce overall healthcare costs by decreasing rates of relapse and hospitalization. Conclusion The assured delivery of an atypical antipsychotic medication with long-acting risperidone has important implications for patient compliance, maintenance of stability, consistency of treatment, and improving patient outcomes including the achievement of remission. PMID:19300536

Chue, Pierre

2007-01-01

255

Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of ?-thalassemia and sickle cell disease.  

PubMed

A previously published clinical trial demonstrated the benefit of autologous CD34(+) cells transduced with a selfinactivating lentiviral vector (HPV569) containing an engineered ?-globin gene (?(A-T87Q)-globin) in a subject with ? thalassemia major. This vector has been modified to increase transduction efficacy without compromising safety. In vitro analyses indicated that the changes resulted in both increased vector titers (3 to 4 fold) and increased transduction efficacy (2 to 3 fold). An in vivo study in which 58 ?-thalassemic mice were transplanted with vector- or mock-transduced syngenic bone marrow cells indicated sustained therapeutic efficacy. Secondary transplantations involving 108 recipients were performed to evaluate long-term safety. The six month study showed no hematological or biochemical toxicity. Integration site (IS) profile revealed an oligo/polyclonal hematopoietic reconstitution in the primary transplants and reduced clonality in secondary transplants. Tumor cells were detected in the secondary transplant mice in all treatment groups (including the control group), without statistical differences in the tumor incidence. Immunohistochemistry and quantitative PCR demonstrated that tumor cells were not derived from transduced donor cells. This comprehensive efficacy and safety data provided the basis for initiating two clinical trials with this second generation vector (BB305) in Europe and in the USA in patients with ?-thalassemia major and sickle cell disease. PMID:25429463

Negre, Olivier; Bartholomae, Cynthia; Beuzard, Yves; Cavazzana, Marina; Christiansen, Lauryn; Courne, Céline; Deichmann, Annette; Denaro, Maria; de Dreuzy, Edouard; Finer, Mitchell; Fronza, Raffaele; Gillet-Legrand, Béatrix; Joubert, Christophe; Kutner, Robert; Leboulch, Philippe; Maouche, Leïla; Paulard, Anaïs; Pierciey, Francis J; Rothe, Michael; Ryu, Byoung; Schmidt, Manfred; von Kalle, Christof; Payen, Emmanuel; Veres, Gabor

2015-01-01

256

Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials.  

PubMed

Abstract Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA. PMID:24842477

Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Kawai, Shinichi; Sugiyama, Naonobu; Yuasa, Hirotoshi; Yamashita, Noriaki; Sugiyama, Noriko; Wagerle, Lorin Craig; Vlahos, Bonnie; Wajdula, Joseph

2015-03-01

257

Pediatric dyslipidemias: Prescription medication efficacy and safety  

Microsoft Academic Search

Pharmacologic treatment of patients with severe pediatric dyslipidemias remains problematic and is of significant concern for health care professionals treating these individuals. Issues include selection of appropriate treatment modalities, lack of pediatric indications for some therapies, duration of treatment, and possible adverse effects with early initiation of potentially life-long therapies. The objective of this review is to evaluate the safety

Barry Browne; Susie Vasquez

2008-01-01

258

Long-term effects of gonadotropin-releasing hormone analogs in girls with central precocious puberty  

PubMed Central

Gonadotropin-releasing hormone analogs (GnRHa) are widely used to treat central precocious puberty (CPP). The efficacy and safety of GnRHa treatment are known, but concerns regarding long-term complications are increasing. Follow-up observation results after GnRHa treatment cessation in female CPP patients up to adulthood showed that treatment (especially <6 years) was beneficial for final adult height relative to that of pretreated or untreated patients. Puberty was recovered within 1 year after GnRHa treatment discontinuation, and there were no abnormalities in reproductive function. CPP patients had a relatively high body mass index (BMI) at the time of CPP diagnosis, but BMI standard deviation score maintenance during GnRHa treatment seemed to prevent the aggravation of obesity in many cases. Bone mineral density decreases during GnRHa treatment but recovers to normal afterwards, and peak bone mass formation through bone mineral accretion during puberty is not affected. Recent studies reported a high prevalence of polycystic ovarian syndrome in CPP patients after GnRHa treatment, but it remains unclear whether the cause is the reproductive mechanism of CPP or GnRHa treatment itself. Studies of the psychosocial effects on CPP patients after GnRHa treatment are very limited. Some studies have reported decreases in psychosocial problems after GnRHa treatment. Overall, GnRHa seems effective and safe for CPP patients, based on long-term follow-up studies. There have been only a few long-term studies on GnRHa treatment in CPP patients in Korea; therefore, additional long-term follow-up investigations are needed to establish the efficacy and safety of GnRHa in the Korean population. PMID:25729392

2015-01-01

259

Safety and efficacy studies of liposomes in specific immunotherapy  

Microsoft Academic Search

Liposomes are lipid vesicles that have been extensively investigated because of their immunoadjuvant properties and their capacity to transport a variety of therapeutic agents. This article reports the results of 4 safety and efficacy studies of multilamellar liposomes used to incorporate an allergen extract in specific immunotherapy. The first study showed that cutaneous tolerance of encapsulated allergen extracts (5 grass

Sylvie Galvain; Claude André; Christine Vatrinet; Bertrand Villet

1999-01-01

260

Raspberry leaf and its effect on labour: Safety and efficacy  

Microsoft Academic Search

The purpose of this study was to examine the safety and efficacy of raspberry leaf products consumed by a group of mothers during their pregnancy, by comparison with a group of mothers who did not. A retrospective observational design was used. Subjects were women who birthed their babies at Westmead Hospital between January 1998–July 1998. The sample consisted of 108

Myra Parsons; Michele Simpson; Terri Ponton

1999-01-01

261

Human insulin: study of safety and efficacy in man  

Microsoft Academic Search

The safety and efficacy of a new highly purified neutral soluble human insulin produced by conversion of porcine insulin was compared with a highly purified neutral soluble porcine insulin in six normal men. The insulins were administered by subcutaneous injection at a dose of 0.075 U\\/kg body weight. Somatostatin was infused during the experiment to suppress endogenous insulin secretin. No

D R Owens; M K Jones; T M Hayes; L G Heding; K G Alberti; P D Home; J M Burrin; R G Newcombe

1981-01-01

262

Efficacy and safety of rituximab in type II mixed cryoglobulinemia  

Microsoft Academic Search

ready administered at the time of recruit- ment. All patients had active disease, poorly controlled or difficult to manage with previous treatments, including corti- costeroids in all. Efficacy and safety of rituximab therapy were evaluated in the following 6 months. The overall follow-up after rituximab treatment ranged from 9 to 31 months. Rituximab proved effective on skin vasculitis manifestations (ulcers,

Francesco Zaja; Salvatore De Vita; Cesare Mazzaro; Stefania Sacco; Daniela Damiani; Ginevra De Marchi; Angela Michelutti; Michele Baccarani; Renato Fanin; Gianfranco Ferraccioli

263

Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA patients  

PubMed Central

Objectives Evaluation of long-term safety of rituximab in rheumatoid arthritis (RA). Methods Pooled observed case analysis of data from patients with moderate-to-severe, active RA treated with rituximab in a global clinical trial programme. Results As of September 2010, 3194 patients had received up to 17 rituximab courses over 9.5?years (11?962 patient-years). Of these, 627 had >5 years’ follow-up (4418 patient-years). A pooled placebo population (n=818) (placebo+methotrexate (MTX)) was also analysed. Serious adverse event and infection rates generally remained stable over time and multiple courses. The overall serious infection event (SIE) rate was 3.94/100 patient-years (3.26/100 patient-years in patients observed for >5?years) and was comparable with placebo+MTX (3.79/100 patient-years). Serious opportunistic infections were rare. Overall, 22.4% (n=717) of rituximab-treated patients developed low immunoglobulin (Ig)M and 3.5% (n=112) low IgG levels for ?4?months after ?1 course. SIE rates were similar before and during/after development of low Ig levels; however, in patients with low IgG, rates were higher than in patients who never developed low IgG. Rates of myocardial infarction and stroke were consistent with rates in the general RA population. No increased risk of malignancy over time was observed. Conclusions This analysis demonstrates that rituximab remains generally well tolerated over time and multiple courses, with a safety profile consistent with published data and clinical trial experience. Overall, the findings indicate that there was no evidence of an increased safety risk or increased reporting rates of any types of adverse events with prolonged exposure to rituximab during the 9.5?years of observation. PMID:23136242

van Vollenhoven, Ronald F; Emery, Paul; Bingham, Clifton O; Keystone, Edward C; Fleischmann, Roy M; Furst, Daniel E; Tyson, Nicola; Collinson, Neil; Lehane, Patricia B

2013-01-01

264

The Long-Term Outcome of Medical Therapy for BPH  

Microsoft Academic Search

ObjectivesThe lack of cure with medical therapy implies life-long treatment emphasising the need for a thorough understanding of the long-term outcome. We review the natural history, markers for progression, placebo effect, efficacy, pharmacoeconomic aspects, and preventive measures.

Stephan Madersbacher; Martin Marszalek; Jakob Lackner; Peter Berger; Georg Schatzl

2007-01-01

265

Long-Term Effects of Peace Workshops in Protracted Conflicts  

ERIC Educational Resources Information Center

The current study evaluates the efficacy of an intensive four-day contact intervention (a peace workshop) organized in Sri Lanka and represents an initial step toward understanding the long-term impact of such interventions on attitudes and behaviors in the context of protracted ethnic conflict. Compared with two control groups, the participant…

Malhotra, Deepak; Liyanage, Sumanasiri

2005-01-01

266

Multimethod Behavioral Treatment of Long-Term Selective Mutism.  

ERIC Educational Resources Information Center

Conducted single-subject, experimental research to examine efficacy of treating severe, long-term selective mutism in nine-year-old male using shaping, multiple reinforcers, natural consequences, stimulus fading, and mild aversives. Implemented different treatment regimens in home and school environments. Home intervention resulted in increase in…

Watson, T. Steuart; Kramer, Jack J.

1992-01-01

267

Examining the efficacy and safety of squaric Acid therapy for treatment of recalcitrant warts in children.  

PubMed

The objective of the study was to determine the safety and efficacy of squaric acid dibutyl ester (SADBE) therapy on the treatment of recalcitrant warts in children. This retrospective chart review examined 72 patients treated using SADBE from July 2002 to December 2012. Patients were followed for 6 months to 11 years. Patients were treated at a pediatric dermatology outpatient clinic at the University of North Carolina at Chapel Hill. Seventy-two children with verrucae who failed initial treatment for warts were selected for the study. Full long-term follow-up was obtained in 48 patients. Four patients discontinued the use of SADBE because of adverse effects. The primary study outcome was efficacy of SADBE treatment. Adverse effects, dosages administered, type of wart, other cutaneous disease present, and level of immunosuppression were measured. Forty of 48 (83%) patients in whom treatment outcomes could be obtained reported complete resolution of their warts. Seventy percent of patients used a maximum concentration of 0.4% SADBE and 60% of patients reported no adverse effects. The majority of patients treated with SADBE reported complete resolution of warts. Most patients reported no adverse effects even while receiving doses as high as 2% daily. This study shows that SADBE is a safe and effective treatment for recalcitrant warts in children. PMID:25040421

Pandey, Shaily; Wilmer, Erin N; Morrell, Dean S

2015-01-01

268

Safety and efficacy of shilajit (mumie, moomiyo).  

PubMed

Shilajit (mumie; moomiyo, mummiyo) has been used for a wide variety of illnesses and conditions for many years. However, relatively few well-controlled human studies have been conducted on the effects of shiliajit, although a growing number of studies have been published in recent years involving animal and in vitro systems. The safety of shilajit is well documented based on animal and human studies. Various research studies indicate that shilajit exhibits antioxidant, anti-inflammatory, adaptogenic, immunomodulatory, and anti-dyslipidemic properties. Animal and human studies indicate that shilajit enhances spermatogenesis. Furthermore, animal and human data support its use as a 'revitalizer', enhancing physical performance and relieving fatigue with enhanced production of ATP. Key constituents in shilajit responsible for these effects appear to be dibenzo-?-pyrones and fulvic acid and their derivatives. Various mechanistic studies provide support for the above observed effects. Additional well-controlled human and animal studies involving the use of standardized products are needed. PMID:23733436

Stohs, Sidney J

2014-04-01

269

Antipsychotic agents: efficacy and safety in schizophrenia  

PubMed Central

Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA) and third generation antipsychotics (TGA), other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole) have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient. PMID:23236256

de Araújo, Arão Nogueira; de Sena, Eduardo Pondé; de Oliveira, Irismar Reis; Juruena, Mario F

2012-01-01

270

Long-Term Results of Targeted Intraoperative Radiotherapy (Targit) Boost During Breast-Conserving Surgery  

SciTech Connect

Purpose: We have previously shown that delivering targeted radiotherapy to the tumour bed intraoperatively is feasible and desirable. In this study, we report on the feasibility, safety, and long-term efficacy of TARGeted Intraoperative radioTherapy (Targit), using the Intrabeam system. Methods and Materials: A total of 300 cancers in 299 unselected patients underwent breast-conserving surgery and Targit as a boost to the tumor bed. After lumpectomy, a single dose of 20 Gy was delivered intraoperatively. Postoperative external beam whole-breast radiotherapy excluded the usual boost. We also performed a novel individualized case control (ICC) analysis that computed the expected recurrences for the cohort by estimating the risk of recurrence for each patient using their characteristics and follow-up period. Results: The treatment was well tolerated. The median follow up was 60.5 months (range, 10-122 months). Eight patients have had ipsilateral recurrence: 5-year Kaplan Meier estimate for ipsilateral recurrence is 1.73% (SE 0.77), which compares well with that seen in the boosted patients in the European Organization for Research and Treatment of Cancer study (4.3%) and the UK STAndardisation of breast RadioTherapy study (2.8%). In a novel ICC analysis of 242 of the patients, we estimated that there should be 11.4 recurrences; in this group, only 6 recurrences were observed. Conclusions: Lumpectomy and Targit boost combined with external beam radiotherapy results in a low local recurrence rate in a standard risk patient population. Accurate localization and the immediacy of the treatment that has a favorable effect on tumour microenvironment may contribute to this effect. These long-term data establish the long-term safety and efficacy of the Targit technique and generate the hypothesis that Targit boost might be superior to an external beam boost in its efficacy and justifies a randomized trial.

Vaidya, Jayant S., E-mail: jayant.vaidya@ucl.ac.uk [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Baum, Michael [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Tobias, Jeffrey S. [Department of Radiation Oncology, University College London Hospitals, London (United Kingdom); Wenz, Frederik [Radiation Oncology and Gynaecology, University Medical Centre of Mannheim (Germany); Massarut, Samuele [Surgery and Radiation Oncology, Centro di Riferimento Oncologico (CRO), Aviano (Italy); Keshtgar, Mohammed [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Hilaris, Basil [Radiation Oncology, Our Lady of Mercy, New York Medical College, New York (United States); Saunders, Christobel [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Williams, Norman R.; Brew-Graves, Chris [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Corica, Tammy [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Roncadin, Mario [Surgery and Radiation Oncology, Centro di Riferimento Oncologico (CRO), Aviano (Italy); Kraus-Tiefenbacher, Uta; Suetterlin, Marc [Radiation Oncology and Gynaecology, University Medical Centre of Mannheim (Germany); Bulsara, Max [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Joseph, David [Radiation Oncology, Sir Charles Gairdner Hospital and School of Surgery, University of Western Australia, Perth (Australia)

2011-11-15

271

Long-term control with etanercept (Enbrel) of a severe acrodermatitis continua of Hallopeau refractory to infliximab (Remicade).  

PubMed

Hallopeau's acrodermatitis is characterized by the presence of aseptic pustules on an inflammatory basis of the periungual or subungual region. The cyclic recurrences induce important physical and psychological morbidity. By analogy to the efficacy of TNF-alpha antagonists in the treatment of generalized pustular psoriasis, our patient illustrates the long-term efficacy and safety of etanercept (Enbrel) in the treatment of Hallopeau's acrodermatitis refractory to infliximab (Remicade). This treatment alternative should in consequence be considered in patients with a recalcitrant form of a potentially debilitating disease. PMID:18503258

Thielen, A-M; Barde, C; Marazza, G; Saurat, J-H

2008-01-01

272

Clinical efficacy and safety of statins in managing cardiovascular risk  

PubMed Central

Since their introduction in the 1980s, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have emerged as the one of the best-selling medication classes to date, with numerous trials demonstrating powerful efficacy in preventing cardiovascular outcomes. As our understanding of low-density lipoprotein cholesterol (LDL-C) and atherosclerosis continues to grow, the concept of ‘lower is better’ has corresponded with a ‘more is better’ approach to statin-based therapy. This review provides a detailed understanding of the clinical efficacy and safety of statins with a particular emphasis on the third generation drug, rosuvastatin. PMID:18561510

Kapur, Navin K; Musunuru, Kiran

2008-01-01

273

Efficacy, safety, and patient acceptability of the Essure™ procedure  

PubMed Central

The Essure™ system for permanent contraception was developed as a less invasive method of female sterilization. Placement of the Essure™ coil involves a hysteroscopic transcervical technique. This procedure can be done in a variety of settings and with a range of anesthetic options. More than eight years have passed since the US Food and Drug Administration approval of Essure™. Much research has been done to evaluate placement success, adverse outcomes, satisfaction, pain, and the contraceptive efficacy of the Essure™. The purpose of this review is to summarize the available literature regarding the efficacy, safety, and patient satisfaction with this new sterilization technique. PMID:21573052

Lessard, Collette R; Hopkins, Matthew R

2011-01-01

274

Efficacy, safety, and patient acceptability of the Essure™ procedure.  

PubMed

The Essure™ system for permanent contraception was developed as a less invasive method of female sterilization. Placement of the Essure™ coil involves a hysteroscopic transcervical technique. This procedure can be done in a variety of settings and with a range of anesthetic options. More than eight years have passed since the US Food and Drug Administration approval of Essure™. Much research has been done to evaluate placement success, adverse outcomes, satisfaction, pain, and the contraceptive efficacy of the Essure™. The purpose of this review is to summarize the available literature regarding the efficacy, safety, and patient satisfaction with this new sterilization technique. PMID:21573052

Lessard, Collette R; Hopkins, Matthew R

2011-01-01

275

Lessons from Long-term Studies  

E-print Network

Lessons from Long-term Studies Gordon Reeves U.S. Forest Service PNW Research Station Corvallis #12 #12;Lessons from Long-term Studies Habitat responds quickly Biological response variables · difficult;Long-term Studies of the Aquatic-Land Interaction Program, PNW Research Station, Corvallis Fish Creek

276

Long Term Surface Salinity Measurements  

NASA Technical Reports Server (NTRS)

Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

Schmitt, Raymond W.; Brown, Neil L.

2005-01-01

277

Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis  

PubMed Central

Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs (DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis (RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase (JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type?I?cytokine receptors family and ?-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb’s mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaLs (ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials. PMID:25232526

Lundquist, Lisa M; Cole, Sabrina W; Sikes, Martha L

2014-01-01

278

Sublingual Immunotherapy in Allergic Rhinitis: Efficacy, Safety, Adherence and Guidelines  

PubMed Central

Allergic rhinitis (AR) is a globally increasing health problem affecting the quality of life. Specific immunotherapy is an available causal treatment changing the basic allergic mechanisms of the disease. Over one hundred years, subcutaneous immunotherapy (SCIT) was developed and proved its efficacy but many adverse effects were recorded including anaphylaxis. In 1986, sublingual immunotherapy (SLIT) was introduced as an alternative solution to solve this problem. Our study aims to discuss SLIT from the points of efficacy, safety, adherence and guidelines developed. A literature search was conducted in Medline/PubMed and the Cochrane Library in January 2013 using the keywords "allergic rhinitis, sublingual immunotherapy, efficacy, safety, compliance, adherence, guidelines." All types of publications were included. We augmented our study by searching the reference lists of identified reviews. SLIT has been established in many guidelines as an evidence-based effective treatment in AR with safer profile than SCIT. The meta-analyses confirmed its efficacy and showed a significant reduction in both symptoms and medication scores. The most common recorded adverse effects were minor local effects in the mouth, gastrointestinal reactions with few cases of anaphylaxis and no fatality. Adherence is more favorable for SLIT mainly because it is safe, noninvasive and easily taken at home. We support the call to conduct large multi-centric studies to gain more statistical power and overcome the problem of heterogeneity observed in the meta-analyses. PMID:25436040

Elghanam, Karim Mohamed

2014-01-01

279

Sandostatin LAR in Acromegalic Patients: Long Term Treatment  

Microsoft Academic Search

We have evaluated the long term effects and safety of Sandostatin LAR, a long acting formulation of octreotide, during 18 subsequent injections given every fourth week to 14 octreotide-sensitive acrome- galic patients. The dosages (20, 30, or 40 mg) were adjusted according to GH response, side-effects, or symptom relief and assessed on day 28 after each injection. We found a

ANETTE KVISTBORG FLØGSTAD; JOHAN HALSE; SØREN BAKKE; IOANA LANCRANJAN; P. MARBACH; C. H. BRUNS; JAK JERVELL

280

Predictors of atypical femoral fractures during long term bisphosphonate therapy: A case series & review of literature  

PubMed Central

Background & objectives: Bisphosphonates (BPs) are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy. Methods: In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations. Results: Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison's disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of) cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) concentrations were within the reference range in all patients. Interpretation & conclusions: Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases. PMID:25222777

Bhadada, Sanjay Kumar; Sridhar, Subbiah; Muthukrishnan, Jeyaram; Mithal, Ambrish; Sharma, Dinesh C.; Bhansali, Anil; Dhiman, Vandana

2014-01-01

281

Efficacy and safety of febuxostat in elderly female patients  

PubMed Central

Background Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear. Objective The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients. Methods We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. Results We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups. Conclusion Our findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent. PMID:25214776

Mizuno, Tomohiro; Hayashi, Takahiro; Hikosaka, Sayo; Shimabukuro, Yuka; Murase, Maho; Takahashi, Kazuo; Hayashi, Hiroki; Yuzawa, Yukio; Nagamatsu, Tadashi; Yamada, Shigeki

2014-01-01

282

Comparison of the Efficacy of Different Long-term Interventions on Chronic Low Back Pain Using the Cross-sectional Area of the Multifidus Muscle and the Thickness of the Transversus Abdominis Muscle as Evaluation Indicators.  

PubMed

[Purpose] The purpose of this study was to examine the different effects of long-term intervention between proprioceptive neuromuscular facilitation (PNF) and neuromuscular joint facilitation (NJF) patterns for the pelvis on chronic low back pain as assessed by the cross-sectional area of the multifidus muscle and the thickness of the transversus abdominis muscle. [Subjects] The subjects were 12 young people (five males, seven females) who had experienced chronic low back pain on one side for more than 6 months. [Methods] The subjects were treated by resting, PNF or NJF therapy, and each treatment was administered for one month. Ultrasonography was used to measure the changes in the transversus abdominis muscle thickness and the multifidus muscle cross-sectional area. [Results] The thickness of the transversus abdominis muscle and the cross-sectional area of the multifidus muscle in the NJF group, after resting, increased significantly and were higher than those in the PNF group. [Conclusion] The results show that significantly better improvement can be obtained for chronic low back pain by applying long-term intervention of NJF patterns. PMID:25540480

Huang, Qiuchen; Li, Desheng; Zhang, Jing; Yang, Degang; Huo, Ming; Maruyama, Hitoshi

2014-12-01

283

Comparison of the Efficacy of Different Long-term Interventions on Chronic Low Back Pain Using the Cross-sectional Area of the Multifidus Muscle and the Thickness of the Transversus Abdominis Muscle as Evaluation Indicators  

PubMed Central

[Purpose] The purpose of this study was to examine the different effects of long-term intervention between proprioceptive neuromuscular facilitation (PNF) and neuromuscular joint facilitation (NJF) patterns for the pelvis on chronic low back pain as assessed by the cross-sectional area of the multifidus muscle and the thickness of the transversus abdominis muscle. [Subjects] The subjects were 12 young people (five males, seven females) who had experienced chronic low back pain on one side for more than 6 months. [Methods] The subjects were treated by resting, PNF or NJF therapy, and each treatment was administered for one month. Ultrasonography was used to measure the changes in the transversus abdominis muscle thickness and the multifidus muscle cross-sectional area. [Results] The thickness of the transversus abdominis muscle and the cross-sectional area of the multifidus muscle in the NJF group, after resting, increased significantly and were higher than those in the PNF group. [Conclusion] The results show that significantly better improvement can be obtained for chronic low back pain by applying long-term intervention of NJF patterns. PMID:25540480

Huang, Qiuchen; Li, Desheng; Zhang, Jing; Yang, Degang; Huo, Ming; Maruyama, Hitoshi

2014-01-01

284

Long-term pharmacological treatment of bipolar disorders.  

PubMed

Several lines of clinical, genetic, and pharmacological evidence point to an association between bipolar and psychotic disorders. The goals of maintenance and prophylactic treatment of bipolar disorder include the prevention of new episodes and the improvement of social, family, and occupational functioning. This goal can be mainly achieved by using long-term adequate pharmacological treatment that is tolerable to patients. Among mood-stabilizers, the main drugs used for such treatment, the role of atypical antipsychotics has greatly increased in recent years. Lithium still remains the drug that has produced the most convincing evidence of prophylactic action and has undergone the longest periods of observation. There has also been good confirmation for the maintenance efficacy of such anticonvulsant drugs as carbamazepine, valproate, and lamotrigine, the last having the strongest properties for prophylaxis of depressive episodes. The case for the usefulness of second-generation antipsychotic drugs in the long-term treatment of bipolar disorder has been rapidly accumulating. Based on controlled trials, the best evidence for maintenance efficacy exists for olanzapine. The vast majority of patients with bipolar illness experience inadequate response to monotherapy with mood-stabilizing drugs during long-term treatment. Some issues connected with polypharmacy targeting optimal maintenance results are discussed. In addition, the long-term management and the role of antidepressants in treatment of non-bipolar I illness is also briefly described. PMID:17262006

Rybakowski, Janusz

2007-02-01

285

Efficacy and safety of tiotropium Respimat® SMI in COPD in two 1-year randomized studies  

PubMed Central

Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 ?g versus placebo, inhaled via the Respimat® Soft Mist™ Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV1 response, Mahler Transition Dyspnea Index [TDI] and St George’s Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year). A total of 1990 patients with COPD participated (mean FEV1: 1.09 L). The mean trough FEV1 response of tiotropium 5 or 10 ?g relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 ?g (RR = 0.78; P = 0.002) and tiotropium 10 ?g (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001). Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 ?g), 2.7% (10 ?g), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat® SMI 5 ?g demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 ?g dose but with a lower frequency of anticholinergic adverse events. PMID:20714373

Bateman, Eric; Singh, Dave; Smith, David; Disse, Bernd; Towse, Lesley; Massey, Dan; Blatchford, Jon; Pavia, Demetri; Hodder, Rick

2010-01-01

286

Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy  

PubMed Central

Most psychotropic drugs used in the treatment of children and adolescents are applied "off label" with a direct risk of under- or overdosing and a delayed risk of long-term side effects. The selection of doses in paediatric psychiatric patients requires a consideration of pharmacokinetic parameters and the development of central nervous system, and warrants specific studies in children and adolescents. Because these are lacking for most of the psychotropic drugs applied in the Child and Adolescent and Psychiatry, therapeutic drug monitoring (TDM) is a valid tool to optimise pharmacotherapy and to enable to adjust the dosage of drugs according to the characteristics of the individual patient. Multi-centre TDM studies enable the identification of age- and development-dependent therapeutic ranges of blood concentrations and facilitate a highly qualified standardized documentation in the child and adolescent health care system. In addition, they will provide data for future research on psychopharmacological treatment in children and adolescents, as a baseline for example for clinically relevant interactions with various co-medications. Therefore, a German-Austrian-Swiss "Competence Network on Therapeutic Drug Monitoring in Child and Adolescent Psychiatry" was founded [1] introducing a comprehensive internet data base for the collection of demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents. PMID:19358696

Mehler-Wex, Claudia; Kölch, Michael; Kirchheiner, Julia; Antony, Gisela; Fegert, Jörg M; Gerlach, Manfred

2009-01-01

287

Non-calcium-containing phosphate binders: comparing efficacy, safety, and other clinical effects.  

PubMed

Phosphate-binder therapy for hyperphosphataemia is key to the treatment of patients with chronic kidney disease (CKD)-mineral and bone disorder (MBD). Calcium-free phosphate binders are increasingly favoured since calcium-based agents potentially cause harmful calcium overload and vascular calcification that confound the benefits of reducing serum phosphorus. Several calcium-free phosphate binders are available, including the non-absorbed agent sevelamer and the absorbed agents, e.g. lanthanum and magnesium salts. Randomised controlled studies consistently show that sevelamer and lanthanum carbonate offer equivalent lowering of serum phosphorus and often effectively achieve phosphorus targets versus calcium salts, with sevelamer having a positive effect on bone disease, vascular calcification, and patient-level outcomes in dialysis patients in several trials. There is also evidence that lanthanum carbonate can improve bone health, but data are limited to its effects to vascular calcification or patient-level outcomes. Magnesium salts have also been shown to reduce serum phosphorus levels, but clear evidence is lacking on bone, vascular, or clinical outcomes. It also remains to be established whether long-term systemic accumulation of lanthanum and magnesium, in tissues including bone, has clinically relevant toxic effects. This review summarises the evidence of efficacy and safety for newer calcium-free phosphate binders in CKD-MBD management. PMID:22555359

Frazão, João M; Adragão, Teresa

2012-01-01

288

JAK Inhibitors: Treatment Efficacy and Safety Profile in Patients with Psoriasis  

PubMed Central

Janus kinase (JAK) pathways are key mediators in the immunopathogenesis of psoriasis. Psoriasis treatment has evolved with the advent of targeted therapies, which inhibit specific components of the psoriasis proinflammatory cascade. JAK inhibitors have been studied in early phase trials for psoriasis patients, and the data are promising for these agents as potential treatment options. Tofacitinib, an oral or topically administered JAK1 and JAK3 inhibitor, and ruxolitinib, a topical JAK1 and JAK2 inhibitor, have been most extensively studied in psoriasis, and both improved clinical symptoms of psoriasis. Additional JAK1 or JAK3 inhibitors are being studied in clinical trials. In phase III trials for rheumatoid arthritis, tofacitinib was efficacious in patients with inadequate responses to tumor necrosis factor inhibitors, methotrexate monotherapy, or disease-modifying antirheumatic drugs. The results of phase III trials are pending for these therapies in psoriasis, and these agents may represent important alternatives for patients with inadequate responses to currently available agents. Further investigations with long-term clinical trials are necessary to verify their utility in psoriasis treatment and assess their safety in this patient population. PMID:24883332

Hsu, Leeyen; Armstrong, April W.

2014-01-01

289

Efficacy, safety, acceptability and affordability of cryotherapy: a review of current literature.  

PubMed

As a result of widespread screening and treatment programs, the incidence of cervical cancer has decreased by as much as 75% in the developed world. Commonly used treatment modalities for precancerous lesions include cone biopsy, the Loop Electrosurgical Excision Procedure (LEEP), laser ablation and cryotherapy. In recent years LEEP has replaced cryotherapy as a commonly provided outpatient procedure in many places; however increased awareness of the burden of cervical cancer in the developing world and increased awareness of long term consequences of LEEP ? such as cervical insufficiency ? have renewed interest in cryotherapy. We reviewed current literature addressing the technique, efficacy, safety and acceptability of cryotherapy, as well as special topics such as cost effectiveness, HIV, and low resource settings. Among studies we reviewed, cure rates ranged from 56.8-96.6% among prospective controlled trials and from 70-95.5% among observational studies. Cryotherapy has very low complication rates and serious complications requiring medical intervention or affecting future reproductive outcomes are extremely rare. Side effects including vaginal discharge and cramping are temporary, generally self-limited, and well tolerated after anticipatory patient counseling. When surveyed, women find cryotherapy highly acceptable. Compared to other treatment modalities, cryotherapy is very affordable and feasible to integrate into cervical cancer screening and treatment programs. PMID:22481625

McClung, E C; Blumenthal, P D

2012-04-01

290

Safety and efficacy of rosiglitazone in the elderly diabetic patient.  

PubMed

Diabetes is an important health condition for the aging population; at least 20% of patients over the age of 65 years have diabetes, and this number can be expected to grow rapidly in the coming decades. Rosiglitazone, a drug in the thiazolidinedione class which targets insulin resistance, was approved by drug regulatory bodies based on its ability to improve glycemic control nearly ten years ago. The greatest long-term risk in diabetes is cardiovascular disease with macrovascular disease being the cause of as much as 80% of mortality. More recently the cardiovascular safety of rosiglitazone was brought to center stage following several meta-analyses and the unplanned interim analysis of the RECORD trial. As opposed to pioglitazone, current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. A thiazolidinedione class effect however seems apparent with respect to the increased risk for fractures and congestive heart failure. Clinical trial evidence on rosiglitazone therapy in the elderly is limited. The available evidence is mainly related to observational cohort studies. Most of the trial evidence relates to a younger population and therefore these data can not be directly extrapolated to an older population. The effects of the thiazolidinedione drug class remain incompletely understood. PMID:19475776

Viljoen, Adie; Sinclair, Alan

2009-01-01

291

Animal Models for Microbicide Safety and Efficacy Testing  

PubMed Central

Purpose of review The first several human clinical trials for HIV prevention resulted in failure, sometimes with disastrous results, as both vaccines and microbicides have occasionally demonstrated the potential to increase rates of HIV infections in some recipients. Recently however, both vaccines and microbicides have finally achieved some level of success in phase 3 human trials, demonstrating that protection from HIV-1 infection is at least possible. Recent findings Recent studies have shown that topically applied vaginal gels, and oral pre-exposure prophylaxis (PrEP) using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans. Both the PrEP and topical efficacy results were predicted by nonhuman primate models, and several ongoing studies demonstrate both humanized mouse and NHP models of microbicide efficacy may reliably predict the success or failure of microbicide candidates in humans. Summary Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and hopefully use these models to better predict microbicide safety and efficacy in the future. Here we discuss the utility and relevance of animal models for safely and efficacy screening of microbicide candidates for advancing only the safest and most effective products to future human trials. PMID:23698560

Veazey, Ronald S.

2013-01-01

292

Transluminal Angioplasty of Transplanted Renal Artery Stenosis: A Review of the Literature for Its Safety and Efficacy  

PubMed Central

Transplant renal artery stenosis (TRAS) is a well-known cause of posttransplant hypertension accompanied by possible graft dysfunction and is potentially curable when is diagnosed early. Colour Doppler Ultrasonography (CDU) is the screening procedure of choice in most studies whereas some centers employ Magnetic Resonance Angiography (MRA), if available. Although both CDU and MRA can arouse suspicion of disease in less symptomatic cases, angiographic techniques are essential for confirmation of TRAS. Percutaneous Transluminal Angioplasty (PTA) is a good and widespread therapeutic approach for the treatment of TRAS due to its acceptable complication rate and high technical success rate. The purpose of this paper is to assess the safety and efficacy of PTA in the treatment of TRAS, to compare the long-term outcomes between different reports, and to examine the role of PTA with stenting in inhibiting recurrence of the disease. PMID:21559256

Leonardou, Polytimi; Gioldasi, Sofia; Pappas, Paris

2011-01-01

293

MP29-02 for the treatment of seasonal allergic rhinitis: a review of clinical pharmacology, efficacy and safety.  

PubMed

This review presents the pharmacology, clinical efficacy and safety of MP29-02 (Dymista®), a unique product for the treatment of allergic rhinitis. Allergic rhinitis is often thought of more as a nuisance than a meaningful medical condition, and the health impact of allergic rhinitis can easily be underestimated. As a result, allergic rhinitis can be undertreated, expectations for relief may not be met, and patients may be left dissatisfied and non-compliant with their medications. MP29-02 is the only currently available allergic rhinitis medication to provide potent early-phase histamine-receptor blocking and long-term anti-inflammatory effects in a single intranasal formulation and delivery system that represents an advance in the therapy of allergic rhinitis, in particular for patients with moderate-to-severe disease. PMID:24070043

Berger, William E

2013-09-01

294

Efficacy and safety of rufinamide in pediatric epilepsy  

PubMed Central

Rufinamide is a novel anticonvulsant medication approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of seizures associated with Lennox–Gastaut syndrome in patients 4 years of age and older, based upon clinical trials demonstrating clinical efficacy and tolerability. Rufinamide is especially effective for tonic–atonic seizures in Lennox–Gastaut syndrome, but is subsequently proving to be safe and effective in clinical practice for a broad patient population with refractory epilepsy. Although further research and clinical experience is needed, rufinamide holds the promise to positively impact the care of children with epilepsy. In this review, we review the use of rufinamide in pediatric epilepsy, with a focus on efficacy and safety. PMID:23634191

Hsieh, David T.

2013-01-01

295

The Long-Term Safety and Efficacy Follow-Up Study of Subjects Who Completed the Phase I Clinical Trial of Neurostem®-AD  

ClinicalTrials.gov

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Delirium, Dementia, Amnestic, Cognitive Disorders; Mental Disorders

2012-09-27

296

An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia  

ClinicalTrials.gov

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

2015-02-03

297

Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults with ADHD: Final Report of a 4-Year Study  

ERIC Educational Resources Information Center

Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial…

Adler, Lenard A.; Spencer, Thomas J.; Williams, David W.; Moore, Rodney J.; Michelson, David

2008-01-01

298

Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults With ADHDFinal Report of a 4Year Study  

Microsoft Academic Search

Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit\\/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial since the interim report), receiving up to 221 weeks of treatment.

Lenard A. Adler; Thomas J. Spencer; David W. Williams; Rodney J. Moore; David Michelson

2008-01-01

299

Long-term safety, tolerability, and efficacy of vismodegib in two patients with metastatic basal cell carcinoma and basal cell nevus syndrome.  

PubMed

Tumor responses in advanced basal cell carcinoma (BCC) have been observed in clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism is inhibition Hedgehog Signaling Pathway (HHSP) downstream target genes. HHSP inhibition has been shown to affect stem cells responsible for blood, mammary, and neural development. We report on our experience of treating two patients with advanced BCC participating. These two patients have had no new BCCs develop for at least 2.25 years. Both patients have been receiving ongoing daily treatment with vismodegib for greater than 2.75 years without experiencing any significant side effects. After prolonged continuous daily dosing with a SMO antagonist, we have not observed a significant alteration in hematologic parameters or physical abnormalities of the pectoral regions of two patients with advanced BCC. PMID:25386306

Weiss, Glen J; Tibes, Raoul; Blaydorn, Lisa; Jameson, Gayle; Downhour, Molly; White, Erica; Caro, Ivor; Von Hoff, Daniel D

2011-10-01

300

Long-term safety, tolerability, and efficacy of vismodegib in two patients with metastatic basal cell carcinoma and basal cell nevus syndrome  

PubMed Central

Tumor responses in advanced basal cell carcinoma (BCC) have been observed in clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism is inhibition Hedgehog Signaling Pathway (HHSP) downstream target genes. HHSP inhibition has been shown to affect stem cells responsible for blood, mammary, and neural development. We report on our experience of treating two patients with advanced BCC participating. These two patients have had no new BCCs develop for at least 2.25 years. Both patients have been receiving ongoing daily treatment with vismodegib for greater than 2.75 years without experiencing any significant side effects. After prolonged continuous daily dosing with a SMO antagonist, we have not observed a significant alteration in hematologic parameters or physical abnormalities of the pectoral regions of two patients with advanced BCC. PMID:25386306

Weiss, Glen J.; Tibes, Raoul; Blaydorn, Lisa; Jameson, Gayle; Downhour, Molly; White, Erica; Caro, Ivor; Von Hoff, Daniel D.

2011-01-01

301

Efficacy of optimal long-term management of multiple cardiovascular risk factors (CVD) on walking and quality of life in patients with peripheral artery disease (PAD): Protocol for randomized controlled trial  

PubMed Central

Peripheral artery disease (PAD) is an understudied chronic illness most prevalent in elderly individuals. PAD patients experience substantial walking impairment due to symptoms of limb ischemia that significantly diminishes quality of life (QOL). Cardiovascular disease (CVD) morbidity and mortality is increased in this population because of aggressive atherosclerosis resulting from untreated CVD risk factors. Despite current national guidelines recommending intensive CVD risk factor management for PAD patients, untreated CVD risk factors are common. Interventions that bridge this gap are imperative. The Vascular Insufficiency – Goals for Optimal Risk Reduction (VIGOR2) study is a randomized controlled trial (RCT) that examines the effectiveness of a long-term multifactor CVD risk reduction program on walking and quality of life in patients with PAD. The purpose of this article is to provide a detailed description of the design and methods of VIGOR2. PMID:22363015

Oka, Roberta K; Conte, Michael S; Owens, Christopher D; Rapp, Joseph; Fung, Gordon; Alley, Hugh F; Giacomini, John C; Myers, Jonathan; Mohler, Emile R

2012-01-01

302

Efficacy and safety of emerging immunotherapies in psoriasis.  

PubMed

Psoriasis is a common chronic inflammatory disease of the skin. Current biologic therapies are highly effective in the treatment of psoriasis, transforming the lives of patients with this significantly disabling disease. Advances in the understanding of the immunological pathogenesis of psoriasis have led to the development of new biologic therapies, targeting specific inflammatory cytokines upregulated in psoriasis. These include the IL-17 antagonists, secukinumab, brodalumab and ixekizumab; the IL-23 antagonists, guselkumab and tildrakizumab; and the oral small molecule therapies, tofacitinib and apremilast. Here, we review evidence for the efficacy and safety of these novel psoriasis therapies, providing clinicians with an overview of the next era in immunotherapy for psoriasis. PMID:25713988

Yiu, Zenas Zn; Warren, Richard B

2015-02-01

303

Retrolective, Comparative, Epidemiological Cohort Study with Parallel Groups Design for Evaluation of Efficacyand Safety of Drugs with ‘Well-Established Use’ Experience with the Long-Term Treatment Using the European Mistletoe Extract (Viscum album L.) in Addition to Conventional Oncological Therapy in Primary, Non-Metastatic Breast Carcinoma  

Microsoft Academic Search

SummaryThe randomized controlled clinical trial (RCT) is accepted as the ‘golden standard’ for the evaluation of efficacy and safety of new drugs. In contrast, to demonstrate efficacy and safety of drugs with ‘well-established use’ that have been on the European Community market for long time, observational comparative epidemiological studies can be used according to the European drug regulation directive. However,

P. R. Bock; W. E. Friedel; J. Hanisch; M. Karasmann; B. Schneider

2004-01-01

304

Managing the patient with dementia in long-term care.  

PubMed

The majority of residents in a nursing home have some degree of dementia. The prevalence is commonly from 70% to 80% of residents. This article covers the following topics on caring for patients with dementia in long-term care: (1) the efficacy of cholinesterase inhibitors and memantine, (2) the optimal environment for maintenance of function in moderate dementia, (3) the treatment of depression and agitation, and (4) the evaluation and management of eating problems. PMID:21641502

Rhodes-Kropf, Jennifer; Cheng, Huai; Castillo, Elizabeth Herskovits; Fulton, Ana Tuya

2011-05-01

305

Effect of treatment with divalproex sodium and lorazepam in residents of long-term-care facilities with dementia-related anxiety or agitation: retrospective chart review  

Microsoft Academic Search

Objective: The aim of this study was to compare the efficacy and safety of divalproex sodium with those of lorazepam in residents of long-term-care (LTC) facilities who had documented diagnoses of dementia with agitation or anxiety.Background: Anxiety and agitation are frequent behavioral complications of Alzheimer's disease that increase the costs and emotional stress associated with caring for these patients.Methods: LTC

I. Barton Frenchman; Christopher Capo; Heather Kass

2000-01-01

306

Long-Term Care Ombudsman Program  

MedlinePLUS

Long-Term Care Ombudsman Program (OAA, Title VII, Chapter 2, Sections 711/712) The Purpose of the Program and How it ... Services Provided to Persons Living in Long-Term Care Facilities Program data for FY 2013 indicate that ...

307

Group Benefits Long Term Disability Benefits  

E-print Network

­ not the specific job they were hired to do. Contracts that have an own occupation definition of disability usuallyGroup Benefits Long Term Disability Benefits #12;What are Long Term Disability (LTD) benefits? Long job to confirm whether you meet the definition of disability within your group benefits contract

308

Long-term preservation of Anammox bacteria  

Technology Transfer Automated Retrieval System (TEKTRAN)

Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass w...

309

Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease.  

PubMed

Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20?mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20?mg/kg/week or 40?mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n?=?4), infantile-onset (n?=?9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy. PMID:25617983

Case, Laura E; Bjartmar, Carl; Morgan, Claire; Casey, Robin; Charrow, Joel; Clancy, John P; Dasouki, Majed; DeArmey, Stephanie; Nedd, Khan; Nevins, Mary; Peters, Heidi; Phillips, Dawn; Spigelman, Zachary; Tifft, Cynthia; Kishnani, Priya S

2015-04-01

310

Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2).  

PubMed

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three-times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n = 172) versus CHEST-1 baseline (n = 237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n = 176) versus CHEST-1 baseline (n = 236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year. PMID:25395036

Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Hoeper, Marius M; Jansa, Pavel; Kim, Nick H; Wang, Chen; Wilkins, Martin; Fritsch, Arno; Davie, Neil; Colorado, Pablo; Mayer, Eckhard

2014-11-13

311

Efficacy and safety of deferoxamine conjugated to hydroxyethyl starch.  

PubMed

The efficacy and safety of deferoxamine conjugated to hydroxyethyl starch (HES-DFO) was evaluated in an in vitro rat cardiac membrane lipid peroxidation (CMLP) assay and in a swine model of regional myocardial ischemia/reperfusion injury in comparison to DFO. The rat CMLP results demonstrate that HES-DFO is at least as potent as DFO (IC50 = 10 and 13 microM, respectively). HES-DFO given intravenously (i.v.) at the equivalence of 25 mg/kg and 100 mg/kg DFO in a swine model of regional myocardial ischemia [20-min left anterior descending coronary artery (LAD) occlusion followed by 60-min reperfusion] showed no significant changes in hemodynamics as compared with DFO at 25 mg/kg i.v. In addition, HES-DFO was at least as potent as DFO with regard to recovery of regional segment shortening function (%SS). Furthermore, both HES-DFO and DFO significantly reduced tissue water content (edema) in the area at risk (AAR). We conclude that conjugation of DFO to HES improves the safety without any interference in the efficacy of DFO. PMID:1378124

Mousa, S A; Ritger, R C; Smith, R D

1992-03-01

312

Efficacy and safety of deferasirox in myelodysplastic syndromes.  

PubMed

Transfusion dependence in myelodysplastic syndrome (MDS) patients may lead to organ damage due to accumulation of non-transferrin-bound iron with consequent increased oxidative stress. Iron chelation has been reported in retrospective studies to improve overall survival in low-risk MDS patients, but this information needs to be validated in prospective trials. The oral iron chelator, deferasirox, has been shown to reduce serum ferritin levels in chelation naïve and pre-treated patients and to reduce labile plasma iron, independently from the efficacy on iron overload. Deferasirox is a potent NF-kB inhibitor, tested in vivo and on acute myeloid leukemia and MDS cell lines, and this effect may explain in part the phenomenon of hematological improvements reported in case reports and in different clinical trials. The drug has an acceptable safety profile, with the most common side effects reported being non-progressive change in serum creatinine level, gastrointestinal disturbances, and skin rash. In this review, we report the results of different studies testing safety and efficacy of deferasirox in MDS patients, side effects associated with the drug, and suggested management of iron overload. PMID:23417759

Breccia, Massimo; Alimena, Giuliana

2013-07-01

313

Mobilization of hematopoietic stem cells with lenograstim in healthy donors: efficacy and safety analysis according to donor age.  

PubMed

We reviewed and analyzed safety and efficacy data after mobilization with granulocyte colony-stimulating factor (G-CSF) according to healthy donor's (HDs) age as follows: <50 years (HDs-1, n = 161), aged 50 to 59 years (HDs-2, n = 62), and ?60 years or over (HDs-3, n = 23). Two hundred forty-six HDs were evaluated, and their characteristics were well balanced among age groups: most were male, siblings, and HLA matched. According to age group, the median numbers of CD34(+) cells in the peripheral blood for HDs-1, HDs-2, and HDs-3 were, respectively, 44.5, 34.5, and 26 (HDs-1 versus HDs-2, P = .002; HDs-1 versus HDs-3, P = .036; HDs-2 versus HDs-3, P = n.s.) at day 4 and 65.5, 58, and 46 (HDs-1 versus HDs-2, P = .039; HDs-1 versus HDs-3, P = .002; HDs-2 versus HDs-3, P = n.s.) at day 5. With a median apheresis session of 1, the number of CD34(+) cells/kg recipient body weight collected was not significantly different (6.4 in HDs-1, 6.0 in HDs-2, and 5.7 in HDs-3, P = n.s.). Short- and long-term safety did not differ among age groups. Bone pain was reported as the most frequent short-term adverse event (76.5%). After a median follow-up of 7.8 years, the observed rate of solid tumors, hematological malignancies, and cardiovascular and autoimmune events was similar to the expected incidence for these diseases in Western countries. These results show that G-CSF is effective in the mobilization of older HDs. Moreover, our data contribute to the growing body of evidence in support of the long-term safety of G-CSF for allogeneic donor stem cell mobilization also for elderly HDs. PMID:25636377

Martino, Massimo; Bonizzoni, Erminio; Moscato, Tiziana; Recchia, Anna Grazia; Fedele, Roberta; Gallo, Giuseppe Alberto; Console, Giuseppe; Messina, Giuseppe; Morabito, Fortunato

2015-05-01

314

Long-Term Follow-Up After Gene Therapy for Canavan Disease  

PubMed Central

Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetylaspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of psychomotor development. The goal of this prospective cohort study was to assess long-term safety and preliminary efficacy measures after gene therapy with an adeno-associated viral vector carrying the ASPA gene (AAV2-ASPA). Using noninvasive magnetic resonance imaging and standardized clinical rating scales, we observed Canavan disease in 28 patients, with a subset of 13 patients being treated with AAV2-ASPA. Each patient received 9 × 1011 vector genomes via intraparenchymal delivery at six brain infusion sites. Safety data collected over a minimum 5-year follow-up period showed a lack of long-term adverse events related to the AAV2 vector. Posttreatment effects were analyzed using a generalized linear mixed model, which showed changes in predefined surrogate markers of disease progression and clinical assessment subscores. AAV2-ASPA gene therapy resulted in a decrease in elevated NAA in the brain and slowed progression of brain atrophy, with some improvement in seizure frequency and with stabilization of overall clinical status. PMID:23253610

Leone, Paola; Shera, David; McPhee, Scott W.J.; Francis, Jeremy S.; Kolodny, Edwin H.; Bilaniuk, Larissa T.; Wang, Dah-Jyuu; Assadi, Mitra; Goldfarb, Olga; Goldman, H. Warren; Freese, Andrew; Young, Deborah; During, Matthew J.; Samulski, R. Jude; Janson, Christopher G.

2013-01-01

315

Long-Term Retrievability of IVC Filters: Should We Abandon Permanent Devices?  

SciTech Connect

Thromboembolic disease produces a considerable disease burden, with death from pulmonary embolism in the UK alone estimated at 30,000-40,000 per year. Whilst it is unproven whether filters actually improve longevity, the morbidity and mortality associated with thromboembolic disease in the presence of contraindications to anticoagulation is high. Thus complications associated with filter insertion, and whilst they remain in situ, must be balanced against the alternatives. Permanent filters remain in situ for the remainder of the patient's life and any complications from the filters are of significant concern. Filters that are not permanent are therefore attractive in these circumstances. Retrievable filters, to avoid or decrease long-term filter complications, appear to be a significant advance in the prevention of pulmonary embolism. In this review, we discuss the safety and effectiveness of both permanent and retrievable filters as well as the retrievability of retrievable inferior vena cava (IVC) filters, to explore whether the use of permanent IVC filters can be abandoned in favor of retrievable filters. Currently four types of retrievable filters are available: the Recovery filter (Bard Peripheral Vascular, Tempe, AZ, USA), the Guenther Tulip filter (Cook, Bloomington, IN, USA), the OptEase Filter (Cordis, Roden, The Netherlands), and the ALN filter (ALN Implants Chirurgicaux, Ghisonaccia, France). Efficacy and safety data for retrievable filters are as yet based on small series, with a total number of fewer than 1,000 insertions, and follow-up is mostly short term. Current long-term data are poor and insufficient to warrant the long-term implantation of these devices into humans. The case of fractured wire from a Recovery filter that migrated to the heart causing pericardial tamponade requiring open heart surgery is a reminder that any new endovascular device remaining in situ in the long term may produce unexpected problems. We should also bear in mind that the data on permanent filters are much more robust, with reports on over 9,500 cases with follow-up of up to 8 years. The original implantation time of 10-14 days has been extended to more than 100 days as the mean implantation time with some of the filter types. Follow-up (preferably prospective) is necessary for all retrievable filters, whether or not they are retrieved. Until these data become available we should restrict ourselves to the present indications of permanent and retrievable filters. If long-term follow-up data on larger numbers of cases confirm the initial data that retrievable filters are as safe and effective as permanent filters, the use of the retrievable filters is likely to expand.

Berczi, V., E-mail: berczi@hotmail.com; Bottomley, J. R.; Thomas, S. M.; Taneja, S.; Gaines, P. A.; Cleveland, T. J. [Northern General Hospital, Sheffield Vascular Institute (United Kingdom)

2007-09-15

316

Development/Plasticity/Repair Dopaminergic Control of Long-Term Depression/Long-Term  

E-print Network

Development/Plasticity/Repair Dopaminergic Control of Long-Term Depression/Long-Term Potentiation) 7102, University Pierre and Marie Curie, Paris 6, F-75005, Paris, France, and 2Unit of Psychopathology, U952, University Pierre and Marie Curie, Paris 6, F-75005, Paris, France Long-term memory

Arleo, Angelo

317

Long-term theranostic hydrogel system for solid tumors.  

PubMed

The long-term theranostic hydrogel system for solid tumors was prepared via simple physical mixing, which consisted of three major parts: the thermosensitive/biodegradable poly(organophosphazene) hydrogel, PEGylated cobalt ferrite nanoparticles, and paclitaxel (PTX). The PEGylated cobalt ferrite nanoparticles showed extremely low cytotoxicity due to the surface modification using PEG chains. The long-term theranostic hydrogel system showed adequate properties to be used for long-term MR theragnosis. In particular, the theranostic hydrogel gradually degraded over 28 days, and the PTX was sustainedly released out from the theranostic hydrogel over the same period in vitro. Furthermore, the in vivo efficacy of long-term MR theragnosis using the theranostic hydrogel system was estimated successfully over 3 weeks by using high field (4.7 T) animal MRI and solid tumor-bearing mice. Based on our results, we expect that this system can supply multiple data regarding a) the progress of therapy and b) the treatment processes via one- or two-time i.t. administration for cases in which surgical approaches are difficult to apply. Meanwhile, cancer patients can be free from the pain of multiple surgical treatments and have the advantage of therapy through a simple i.t. administration. PMID:22189146

Kim, Jang Il; Lee, Beom Suk; Chun, Changju; Cho, Jung-Kyo; Kim, Sang-Yoon; Song, Soo-Chang

2012-03-01

318

Laparoscopic nephrectomy for renal cell cancer: evaluation of efficacy and safety: a multicenter experience  

Microsoft Academic Search

Objectives. Although laparoscopic radical nephrectomy is a safe and minimally invasive alternative to open surgery, the long-term disease-free outcome of this procedure has not been reported. We evaluated our experience with the laparoscopic management of renal cell carcinoma to assess the clinical efficacy of this surgical modality.Methods. Between February 1991 and June 1997, 157 patients at five institutions were retrospectively

Jeffrey A Cadeddu; Yoshinari Ono; Ralph V Clayman; Peter H Barrett; Gunter Janetschek; Donald D Fentie; Elspeth M McDougall; Robert G Moore; Tsuneo Kinukawa; Abdelhamid M Elbahnasy; Joel B Nelson; Louis R Kavoussi

1998-01-01

319

Who Pays for Long-Term Care?  

MedlinePLUS

... Term Care? Expand Long-term Care Considerations for LGBT Adults Expand Health Disparities Impacting LTC Expand Caregivers ... on Alzheimer's Disease Lesbian, Gay, Bisexual and Transgender (LGBT) community Home About Us Accessibility Disclaimer Privacy Contact ...

320

Who Needs Care? (Long-Term Care)  

MedlinePLUS

... Term Care? Expand Long-term Care Considerations for LGBT Adults Expand Health Disparities Impacting LTC Expand Caregivers ... on Alzheimer's Disease Lesbian, Gay, Bisexual and Transgender (LGBT) community Home About Us Accessibility Disclaimer Privacy Contact ...

321

Transverse Myelitis: Long-Term Care  

MedlinePLUS

... at this stage. The long-term management of TM requires attention to a number of issues. These ... residual effects of any spinal cord injury, including TM. In addition to chronic medical problems, there are ...

322

Long-term, open-label study of once-daily ropinirole prolonged release in early Parkinson's disease.  

PubMed

Long-term safety and efficacy of once-daily ropinirole prolonged release (PR) were evaluated in subjects with early Parkinson's disease (PD). Subjects (n = 83) who completed one of two studies were enrolled in this open-label, multicenter, extension study, and followed for up to 78 months. Ropinirole PR was titrated/continued, and adjusted as appropriate during the maintenance phase (maximum 24 mg/day). L-dopa and other non-dopamine agonist PD medications were permitted. Safety outcomes included adverse events (AEs). Efficacy outcomes included Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores, and Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I) scores. The median duration of ropinirole PR exposure was 1,069 days. Most subjects (97.6%) reported at least one AE, most commonly (? 30%) nausea (42.2%), dizziness (41.0%), peripheral edema (38.6%), back pain (33.7%), and headache (31.3%). Seventeen (20.5%) subjects discontinued due to an AE. UPDRS and CGI scores indicated that the clinical status of subjects was maintained throughout the treatment period. In patients with early PD, long-term treatment with once-daily ropinirole PR was not associated with any new safety concerns, and was effective in maintaining clinical status. These results support the extended use of ropinirole PR for treatment of PD. PMID:21244307

Hauser, Robert A; Reichmann, Heinz; Lew, Mark; Asgharian, Afsaneh; Makumi, Clare; Shulman, Kenneth J

2011-05-01

323

Safety and efficacy assessment of carotid artery stenting in a high-risk population in a single-centre registry  

PubMed Central

Introduction Ischaemic stroke is the primary cause of long-term disability and the third most common cause of death. Internal carotid artery stenosis is an important risk factor for stroke and transient ischaemic attack (TIA). European Society of Cardiology (ESC) and American Heart Association (AHA) guidelines allow carotid artery stenting (CAS) as an alternative to endarterectomy in centres with low rates of death or stroke. Aim To assess the safety and efficacy of CAS in a single-centre observation. Material and methods We performed a retrospective analysis of all patients treated with CAS between March 2008 and July 2012. Clinical data and outcomes in both asymptomatic and symptomatic patients were analysed. Results A total of 214 consecutive patients were included in the registry. Symptomatic patients accounted for 57% of the study group and were more likely to have a history of stroke and/or TIA that occurred more than 6 months before the procedure (50% vs. 8%, p < 0.001). Asymptomatic patients were more likely to have a history of coronary artery disease (88% vs. 61%, p < 0.001), and the rates of previous acute coronary syndrome and revascularisation were also higher in this group (58% vs. 41% and 71% vs. 52%, respectively, both p < 0.05). The symptomatic group had higher incidence of stroke in periprocedural and 30-day observation (4% vs. 0%, p < 0.05). There was no difference in incidence of adverse events in long-term observation. Conclusions Carotid artery stenting is a safe and efficacious procedure. Every centre performing CAS should monitor the rate of periprocedural complications. PMID:25489319

Zimoch, Wojciech; Gwizdek, Tomasz; Konieczny, Rados?aw; Kübler, Piotr; Telichowski, Artur; Jankowska, Ewa A.; Reczuch, Krzysztof

2014-01-01

324

Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: two-year results including pharmacokinetics and concomitant hydroxyurea.  

PubMed

We report a prospective, randomized, Phase II study of deferasirox and deferoxamine (DFO) in sickle cell disease patients with transfusional iron overload, with all patients continuing on deferasirox after 24 weeks, for up to 2 years. The primary objective was to evaluate deferasirox safety compared with DFO; long-term efficacy and safety of deferasirox was also assessed. We also report, for the first time, the safety and pharmacokinetics of deferasirox in patients concomitantly receiving hydroxyurea. Deferasirox (n = 135) and DFO (n = 68) had comparable safety profiles over 24 weeks. Adverse events (AEs) secondary to drug administration were reported in 26.7% of patients in the deferasirox cohort and 28.6% in the DFO cohort. Gastrointestinal disorders were more common with deferasirox, including diarrhea (10.4% versus 3.6%) and nausea (5.2% versus 3.6%). The most common AE in the DFO group was injection-site pain irritation, which occurred in 7% of patients. Acute renal failure occurred in one patient on deferasirox who was continued on medication despite progressive impairment of renal function parameters. Serum ferritin levels were reduced in both treatment groups. Patients continuing on deferasirox for up to 2 years demonstrated an absolute median serum ferritin decrease of -614 ng/mL (n = 96). Increasing deferasirox dose was associated with improved response and a continued manageable safety profile. Concomitant hydroxyurea administration (n = 28) did not appear to influence the efficacy, safety (including liver and kidney function), and pharmacokinetic parameters of deferasirox. PMID:23946212

Vichinsky, Elliott; Torres, Marcela; Minniti, Caterina P; Barrette, Stephane; Habr, Dany; Zhang, Yiyun; Files, Beatrice

2013-12-01

325

Long Term Outcomes after Pediatric Liver Transplantation  

PubMed Central

Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

2013-01-01

326

Long-term surveillance plan for the Estes Gulch disposal site near Rifle, Colorado  

SciTech Connect

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy`s (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Estes Gulch disposal site near Rifle, Colorado. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Estes Gulch disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP.

NONE

1997-07-01

327

Interim long-term surveillance plan for the Cheney disposal site near, Grand Junction, Colorado  

SciTech Connect

This interim long-term surveillance plan (LTSP) describes the U.S. Department of Energy`s (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Cheney Disposal Site in Mesa County near Grand Junction, Colorado. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Cheney disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP.

NONE

1997-08-01

328

Long-term surveillance plan for the Mexican Hat disposal site Mexican Hat, Utah  

SciTech Connect

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy`s (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Mexican Hat, Utah, disposal site. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Mexican Hat disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP.

NONE

1997-06-01

329

Efficacy, pharmacology, and safety of amdinocillin in treatment of neonates.  

PubMed

One hundred and nine neonates with complications conducive to lethal infections were investigated to determine the efficacy, pharmacokinetics, and safety of amdinocillin. Of these 109 neonates, 70 were participants in the clinical study and 39 in the pharmacokinetic study. Amdinocillin (40 mg/kg per day) and penicillin (60,000 units/kg per day) were administered separately in divided doses by intramuscular injection at six-hourly intervals for five days. Amdinocillin/penicillin proved to be a safe and effective alternative to gentamicin/penicillin; no adverse reactions were noted nor did the regimen adversely affect renal or hepatic function. Throughout the treatment period, amdinocillin maintained high therapeutic serum levels. Resistance to amdinocillin did not develop during treatment. PMID:6310999

de Louvois, J; Mulhall, A

1983-08-29

330

Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial  

PubMed Central

Objective: To determine the long-term effect of adalimumab on patients with ankylosing spondylitis (AS) who participated in the Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS), a randomised, double-blind, placebo controlled, 24-week trial. Methods: Patients received adalimumab 40 mg every other week (eow) or placebo for 24 weeks in ATLAS. At week 24, patients were switched to open-label adalimumab 40 mg eow. Efficacy measures included 20% improvement in the Assessment in SpondyloArthritis International Society (ASAS) criteria (ASAS20), ASAS40 and ASAS partial remission responses and changes in individual components of the ASAS20 response evaluations, for example, Bath AS Functional Index (BASFI) and Bath AS Disease Activity Index (BASDAI). Two-year interim data were analysed based on the total duration of adalimumab exposure, irrespective of the treatment randomisation group. Results: At 2 years, 255 (82.0%) of the original 311 ATLAS patients continued receiving adalimumab treatment. Improvements in ASAS responses observed in ATLAS were sustained during long-term treatment; 64.5% (200/310) were ASAS20 responders, 50.6% (157/310) were ASAS40 responders and 33.5% (104/310) had maintained ASAS-defined partial remission. Changes in individual ASAS response components were sustained or improved during long-term adalimumab treatment. From ATLAS baseline to 2 years of adalimumab exposure, respectively, BASDAI improved from 6.3 (SD 1.7) to 2.4 (SD 2.3) and BASFI improved from 5.2 (SD 2.4) to 2.9 (SD 2.5). Adalimumab was well tolerated. No cases of tuberculosis, congestive heart failure, lupus-like symptoms, or demyelinating disease were reported. Conclusions: Adalimumab reduced the signs and symptoms of AS and induced partial remission for up to 2 years. The long-term safety profile was similar to the short-term safety profile. Trial registration information: NCT00085644 PMID:18701556

van der Heijde, D; Schiff, M H; Sieper, J; Kivitz, A J; Wong, R L; Kupper, H; Dijkmans, B A C; Mease, P J; Davis, J C

2009-01-01

331

Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation  

SciTech Connect

Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereas long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by which short-term memories are permanently stored, and b) a strong foundation for continued growth of an excellent undergraduate neuroscience program.

Calin-Jageman, Robert J

2009-09-12

332

Efficacy of 1.0% chlorhexidine-gluconate ethanol compared with 10% povidone-iodine for long-term central venous catheter care in hematology departments: a prospective study.  

PubMed

The efficacy of 1% chlorhexidine-gluconate ethanol and 10% povidone-iodine for skin antisepsis of central venous catheter (CVC) sites were compared among hematology patients. The CVC site colonization rates of those groups were 11.9% and 29.2%, respectively, and the catheter-associated blood stream infections were 0.75 and 3.62 per 1,000 catheter-days, respectively. One percent chlorhexidine-gluconate ethanol was superior to povidone-iodine to reduce skin colonizers at CVC sites even when catheters were used for long duration. PMID:24655901

Yamamoto, Natsuo; Kimura, Hideo; Misao, Hanako; Matsumoto, Hayato; Imafuku, Yuji; Watanabe, Akemi; Mori, Hiroko; Yoshida, Akiko; Miura, Saori; Abe, Yoshinobu; Toba, Mamoru; Suzuki, Hiromi; Ogawa, Kazuei; Kanemitsu, Keiji

2014-05-01

333

Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization.  

PubMed

At central synapses, activity-dependent synaptic plasticity has a crucial role in information processing, storage, learning, and memory under both physiological and pathological conditions. One widely accepted model of learning mechanism and information processing in the brain is Hebbian Plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are respectively activity-dependent enhancement and reduction in the efficacy of the synapses, which are rapid and synapse-specific processes. A number of recent studies have a strong focal point on the critical importance of another distinct form of synaptic plasticity, non-Hebbian plasticity. Non-Hebbian plasticity dynamically adjusts synaptic strength to maintain stability. This process may be very slow and occur cell-widely. By putting them all together, this mini review defines an important conceptual difference between Hebbian and non-Hebbian plasticity. PMID:25598658

Park, Joo Min; Jung, Sung-Cherl; Eun, Su-Yong

2014-12-01

334

Efficacy and safety of febuxostat in the treatment of hyperuricemia in stable kidney transplant recipients  

PubMed Central

Background Post-transplant hyperuricemia (PTHU), defined as serum uric acid concentration ?7.0 mg/dL or need for treatment with allopurinol or benzbromarone, reduces long-term allograft survival in kidney transplant recipients. Febuxostat, a new nonpurine selective xanthine oxidase inhibitor, is well tolerated in patients with moderate renal impairment. However, its efficacy and safety in kidney recipients with PTHU is unclear. We therefore assessed the efficacy and safety of febuxostat in stable kidney transplant recipients with PTHU. Methods Of 93 stable adult kidney transplant recipients, 51 were diagnosed with PTHU (PTHU group) and 42 were not (NPTHU group). Of the 51 patients with PTHU, 26 were treated with febuxostat (FX group) and 25 were not (NFX group), at the discretion of each attending physician. One-year changes in serum uric acid concentrations, rates of achievement of target uric acid (<6.0 mg/dL), estimated glomerular filtration rates in allografts, and adverse events were retrospectively analyzed in the FX, NFX, and NPTHU groups. Results The FX group showed significantly greater decreases in serum uric acid (?2.0±1.1 mg/dL versus 0.0±0.8 mg/dL per year, P<0.01) and tended to show a higher rate of achieving target uric acid levels (50% versus 24%; odds ratio 3.17 [95% confidence interval 0.96–10.5], P=0.08) than the NFX group. Although baseline allograft estimated glomerular filtration rates tended to be lower in the FX group than in the NFX group (40±14 mL/min/1.73 m2 versus 47±19 mL/min/1.73 m2), changes in allograft estimated glomerular filtration rate were similar (+1.0±4.9 mL/min/1.73 m2 versus ?0.2±6.9 mL/min/1.73 m2 per year, P=0.50). None of the patients in the FX group experienced any severe adverse effects, such as pancytopenia or attacks of gout, throughout the entire study period. Nephrologists were more likely than urologists to start febuxostat in kidney transplant recipients with PTHU (69% versus 8%). Conclusion Treatment with febuxostat sufficiently lowered uric acid levels without severe adverse effects in stable kidney transplant recipients with PTHU. PMID:24600205

Sofue, Tadashi; Inui, Masashi; Hara, Taiga; Nishijima, Yoko; Moriwaki, Kumiko; Hayashida, Yushi; Ueda, Nobufumi; Nishiyama, Akira; Kakehi, Yoshiyuki; Kohno, Masakazu

2014-01-01

335

Endovenous therapies of varicose veins: indications, procedures, efficacy and safety.  

PubMed

Venous insufficiency of the lower-extremity is common and the prevalence increases with age. Chronic venous insufficiency has a high impact on patients' health related quality of life (HRQOL) and is associated with considerable health care costs. In addition to classical symptoms, it may result in skin changes and venous ulcers. Since more than hundred years, surgical ligation of the junction with or without stripping has been the standard of care in the treatment of insufficient great and small saphenous veins. However, the recurrence rates are relatively high and surgery may be associated with serious adverse events, considerable down time and is cosmetically suboptimal. In the last decade several minimally invasive techniques have been introduced, to improve efficacy, patients' HRQOL and treatment satisfaction, and to reduce serious side effects, costs and postoperative pain. Dermatologists have played an important role in the development of minimal invasive therapies Ultrasound guided foam sclerotherapy, endovenous laser therapy and radiofrequency ablation are the most commonly used therapies, and challenge surgery as the gold standard of care in patients with varicose veins. The objective of this review is to inform clinicians about these three therapeutic options for saphenous varicose veins and to describe and compare the indications, procedures, efficacy and safety profile. PMID:20467390

Biemans, A A M; Van Den Bos, R R; Nijsten, T

2010-04-01

336

Exercise for Depression: Efficacy, Safety and Clinical Trial Implications  

PubMed Central

Exercise is gaining interest as a treatment for major depressive disorder (MDD).Though not yet fully established as an efficacious therapy for psychiatric disorders, exercise has well-established benefits for physcial health and overall well-being. However, there are potential health risks to exercise that need to be considered before recommending physical activity to a patient. We present the case of a 48 year-old woman who develolped significant elevations in creatine kinase and liver enzyme levels after three work-out sessions consisting of cardiovascular training on an elliptical machine and weightlifting. The elevations resolved with rest, then recurred when the patient again began exercising. These elevations occurred while the patient was participating in a double-blind, placebo-control phase II clinical trial of an experimental medication for MDD. This case highlights several aspects of the appropriate implementation of exercise recommendations in the psychiatric setting. Initiation of exercise regimens is not prohibited in clinical trials, and may be self-initiated by the depressed patient or recommended by the treating physician. This case also highlights that the value of placebo controls in clinical trials of experimental treatments applies to safety as well as efficacy factors. Exercise as a treatment for depression carries both potential benefit for depressive symptoms and risk for adverse events. The design of clinical trials would be strengthened by consideration of these effects of exercise in the future. PMID:19015630

Dunlop, Boadie W.; Self, Rachel L.

2015-01-01

337

Efficacy and safety of balloon kyphoplasty in the treatment of vertebral compression fractures: a systematic review  

Microsoft Academic Search

The aim of this study is to evaluate the efficacy and safety of balloon kyphoplasty (BK) in the management of vertebral compression fractures (VCFs). This study is based on a systematic review of the literature (until October 2004) and meta-analysis of clinical studies assessing the efficacy and safety of BK in the treatment of VCFs. Estimates of effect were based

Carmen Bouza; Teresa López; Angeles Magro; Lourdes Navalpotro; José María Amate

2006-01-01

338

Efficacy of a Food Safety Comic Book on Knowledge and Self-Reported Behavior for Persons Living with AIDS  

PubMed Central

Introduction Persons living with AIDS are highly vulnerable to foodborne enteric infections with the potential for substantial morbidity and mortality. Educational materials about foodborne enteric infections intended for this immunocompromised population have not been assessed for their efficacy in improving knowledge or encouraging behavior change. Methods/Results AIDS patients in four healthcare facilities in Chicago, New Orleans, and Puerto Rico were recruited using fliers and word of mouth to healthcare providers. Those who contacted research staff were interviewed to determine food safety knowledge gaps and risky behaviors. A food safety educational comic book that targeted knowledge gaps was created, piloted, and provided to these patients who were instructed to read it and return at least 2 weeks later for a follow-up interview. The overall food safety score was determined by the number of the 26 knowledge/belief/behavior questions from the survey answered correctly. Among 150 patients who participated in both the baseline and follow-up questionnaire, the intervention resulted in a substantial increase in the food safety score (baseline 59%, post-intervention 81%, p<0.001). The intervention produced a significant increase in all the food safety knowledge, belief, and behavior items that comprised the food safety score. Many of these increases were from baseline knowledge below 80 percent to well above 90%. Most (85%) of the patients stated they made a change to their behavior since receiving the educational booklet. Conclusion This comic book format intervention to educate persons living with AIDS was highly effective. Future studies should examine to what extent long-term behavioral changes result. PMID:24124447

Dworkin, Mark S.; Peterson, Caryn E.; Gao, Weihua; Mayor, Angel; Hunter, Robert; Negron, Edna; Fleury, Alison; Besch, C. Lynn

2013-01-01

339

Safety and efficacy of Bixa orellana (achiote, annatto) leaf extracts.  

PubMed

Bixa orellana leaf preparations have been used for many years by indigenous people for a variety of medicinal applications. Published research studies in animals indicate that various extracts of Bixa leaves exhibit antioxidant, broad antimicrobial (antibacterial and antifungal), anti-inflammatory, analgesic, hypoglycemic, and antidiarrheal activities. No studies have specifically assessed the ability of leaf extracts to inhibit urogenital infections although Bixa products have been used in folkloric medicine to treat gonorrhea and other infections. Few human studies have been conducted and published using Bixa leaf preparations. Many more studies have been conducted and published involving Bixa seed (annatto) extracts than with leaf extracts. No subchronic safety (toxicity) studies have been conducted in animals. A 6 month study in humans given 750 mg of leaf powder per day demonstrated no significant or serious adverse effects. Bixa leaf extracts appear to be safe when given under current conditions of use. However, additional human and animal controlled safety and efficacy studies are needed. In addition, detailed chemical analyses are required to establish structure-function relationships. PMID:24357022

Stohs, Sidney J

2014-07-01

340

The Efficacy, Safety, and Practicality of Treatments for Adolescents with Attention-Deficit\\/Hyperactivity Disorder (ADHD)  

Microsoft Academic Search

Studies examining interventions for adolescents diagnosed with attention-deficit\\/hyperactivity disorder (ADHD) were reviewed to evaluate their efficacy. These efficacy findings were supplemented with a preliminary system for judging safety and practicality. Results suggest that the stimulant drug methylphenidate (MPH) is safe and well-established empirically, but has some problems with inconvenience and noncompliance. Preliminary research supports the efficacy, safety, and practicality of

Bradley H. Smith; Daniel A. Waschbusch; Michael T. Willoughby; Steven Evans

2000-01-01

341

Extended safety and efficacy studies of a live attenuated double leucine and pantothenate auxotroph of Mycobacterium tuberculosis as a vaccine candidate  

PubMed Central

We have previously described the development of a live, fully attenuated Mycobacterium tuberculosis (Mtb) vaccine candidate strain with two independent attenuating auxotrophic mutations in leucine and pantothenate biosynthesis. In the present work, those studies have been extended to include testing for protective efficacy in a long-term guinea pig survival model and safety testing in the highly tuberculosis susceptible Rhesus macaque. To model the safety of the ?leuD ?panCD strain in HIV-infected human populations, a Simian Immunodeficiency Virus (SIV)-infected Rhesus macaque group was included. Immunization with the non-replicating ?leuD ?panCD conferred long-term protection against challenge with virulent M. tuberculosis equivalent to that afforded by BCG as measured by guinea pig survival. In safety studies, clinical, hematological and bacteriological monitoring of both SIV-positive and SIV-negative Rhesus macaques immunized with ?leuD ?panCD, revealed no vaccine-associated adverse effects. The results support the further development of the ?leuD ?panCD strain as a viable tuberculosis (TB) vaccine candidate. PMID:21549795

Sampson, Samantha L.; Mansfield, Keith G.; Carville, Angela; Magee, D. Mitchell; Quitugua, Teresa; Howerth, Elizabeth W.; Bloom, Barry R.; Hondalus, Mary K.

2011-01-01

342

Functional interpretation of metabolomics data as a new method for predicting long-term side effects: treatment of atopic dermatitis in infants.  

PubMed

Topical steroids are used for the treatment of primary atopic dermatitis (AD); however, their associated risk of serious complications is great due to the presence of vulnerable lesions in young children with AD. Topical calcineurin inhibitors (TCIs) are steroid-free, anti-inflammatory agents used for topical AD therapy. However, their use is prohibited in infants <2 years of age because of their carcinogenic potential. We conducted a randomized, double-blind trial to evaluate the efficacy of TCIs as a secondary AD treatment for children <2 years of age by comparing 1% pimecrolimus cream with 0.05% desonide cream. We performed urinary metabolomics to predict long-term side effects. The 1% pimecrolimus cream displayed similar efficacy and exceptional safety compared with the 0.05% desonide cream. Metabolomics-based long-term toxicity tests effectively predicted long-term side effects using short-term clinical models. This applicable method for the functional interpretation of metabolomics data sets the foundation for future studies involving the prediction of the toxicity and systemic reactions caused by long-term medication administration. PMID:25491116

Lee, Seul Ji; Woo, Sung-il; Ahn, Soo Hyun; Lim, Dong Kyu; Hong, Ji Yeon; Park, Jeong Hill; Lim, Johan; Kim, Mi-kyeong; Kwon, Sung Won

2014-01-01

343

The Risks and Benefits of Long-term Use of Hydroxyurea in Sickle Cell Anemia: A 17.5 Year Follow-Up  

PubMed Central

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at ? = 0.05 level (p-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. PMID:20513116

Steinberg, MH; McCarthy, WF; Castro, O; Ballas, SK; Armstrong, FD; Smith, W; Ataga, K; Swerdlow, P; Kutlar, A; DeCastro, L; Waclawiw, MA

2010-01-01

344

Long-Term Effects and Prognosis in Acute Heart Failure Treated with Tolvaptan: The AVCMA Trial  

PubMed Central

Background. Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. We previously reported the efficacy and safety of tolvaptan compared to carperitide in hospitalized patients with ADHF. There were some reports of cardio- and renal-protective effects in carperitide; therefore, the purpose of this study was to compare the long-term effects of tolvaptan and carperitide on cardiorenal function and prognosis. Methods and Results. One hundred and five ADHF patients treated with either tolvaptan or carperitide were followed after hospital discharge. Levels of plasma B-type natriuretic peptide, serum sodium, potassium, creatinine, and estimated glomerular filtration rate were measured before administration of tolvaptan or carperitide at baseline, the time of discharge, and one year after discharge. These data between tolvaptan and carperitide groups were not different one year after discharge. Kaplan-Meier survival curves demonstrated that the event-free rate regarding all events, cardiac events, all cause deaths, and rehospitalization due to worsening heart failure was not significantly different between tolvaptan and carperitide groups. Conclusions. We demonstrated that tolvaptan had similar effects on cardiac and renal function and led to a similar prognosis in the long term, compared to carperitide. PMID:25436213

Suzuki, Satoshi; Yoshihisa, Akiomi; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Abe, Yukihiko; Saito, Tomiyoshi; Ohwada, Takayuki; Suzuki, Hitoshi; Saitoh, Shu-ichi; Kubota, Isao; Takeishi, Yasuchika

2014-01-01

345

Long-term intrathecal ziconotide for chronic pain: an open-label study.  

PubMed

This open-label multicenter study evaluated the long-term safety and efficacy of intrathecal ziconotide and included 78 patients with chronic pain who had completed one of two previous ziconotide clinical trials. Each patient's initial ziconotide dose was based on his or her dose from the study of origin and was adjusted as necessary on the basis of adverse events and analgesic effect. The median ziconotide dose was 6.48 mcg/day (range, 0.00-120.00 mcg/day) at the Initial Visit and ranged from 5.52 to 7.20 mcg/day across all study visits. The most commonly reported new adverse events that were considered ziconotide related were memory impairment (11.3%); dizziness, nystagmus, and speech disorder (8.5% each); nervousness and somnolence (7.0% each); and abnormal gait (5.6%). There was no evidence of increased adverse event incidence at higher cumulative ziconotide doses. Elevations in creatine kinase were noted, but the proportion of patients with creatine kinase elevations did not change from the Initial Visit to the Termination Visit (4.1% each). Stable mean Visual Analog Scale of Pain Intensity scores during the three years of the study suggested no evidence of increased pain intensity with increased duration of ziconotide exposure. Long-term treatment with ziconotide appeared to be well tolerated and effective in patients whose response to ziconotide and ability to tolerate the drug had been previously demonstrated. PMID:18715748

Webster, Lynn R; Fisher, Robert; Charapata, Steven; Wallace, Mark S

2009-03-01

346

Prospective study on long-term treatment with oxcarbazepine in pediatric epilepsy.  

PubMed

Following a previous preliminary report on a group of children suffering from partial epilepsies, we present the final considerations on the same group in order to evaluate the long-term efficacy, tolerability and safety of oxcarbazepine (OXC). We enrolled 36 patients (mean age 8.5), between January 2003 and December 2004, with new diagnosis of partial epilepsy: 25 patients were affected by idiopathic partial epilepsy, eight by symptomatic epilepsy and three by cryptogenic epilepsy. Each patient was scheduled to attend the center four times after the initial examination: 3 months (T1), 12 months (T2), 24 (T3) months and 36 (T4) months after the beginning of OXC-monotherapy (T0). At the end of our study, 20 patients were seizure free (SF): nine stopped OXC because of SF for at least 2 years, 11 were still on therapy. One patient showed a reduction of seizure frequency >or=50%, three were non responders (but still on therapy), nine stopped OXC due to a non-responder condition during follow-up before T4 and one because of adverse effects. At the end of the study no EEG focal abnormalities became generalized because of treatment. Normalization of EEG was observed in ten patients. Our preliminary findings have been confirmed. OXC can be considered an effective and well tolerated first line drug for long-term monotherapy in children with epilepsy, both for idiopathic and symptomatic/cryptogenic forms. PMID:19597919

Franzoni, Emilio; Gentile, Valentina; Pellicciari, Alessandro; Garone, Caterina; Iero, Luisa; Gualandi, Stefano; Cordelli, Duccio Maria; Cecconi, Ilaria; Moscano, Filomena Caterina; Marchiani, Valentina; Errani, Alessandra

2009-09-01

347

The US Long Term Ecological Research Program  

NSDL National Science Digital Library

This peer-reviewed article from BioScience describes Long Term Ecological Research program in the US. The 24 projects of the National Science Foundation's Long Term Ecological Research Network, whose sites range from the poles to the Tropics, from rain forests to tundras and deserts, and from offshore marine to estuarine and freshwater habitats, address fundamental and applied ecological issues that can be understood only through a long-term approach. Each project addresses different ecological questions; even the scale of research differs across sites. Projects in the network are linked by the requirement for some research at each site on five core areas, including primary production, decomposition, and trophic dynamics, and by cross-site comparisons, which are aided by the universally available databases. Many species and environmental variables are studied, and a wide range of synthetic results have been generated.

JOHN E. HOBBIE, STEPHEN R. CARPENTER, NANCY B. GRIMM, JAMES R. GOSZ, and TIMOTHY R. SEASTEDT (; )

2003-01-01

348

[Long-term control of psoriasis is necessary].  

PubMed

Psoriasis is an immune mediated, inflammatory skin condition affecting approximately 1.43% of Spanish population. In clinical practice, physicians use PASI index to assess the severity. Psoriasis causes physical and mental disability comparable to other chronic diseases and affects seriously the patients quality of life. For treatment we have different options. Conventional systemic treatment such as methotrexate, cyclosporine and acitretin may be associated with relevant side effects, and organ toxicity that avoid long term therapy. Several psoriasis patients have other comorbid disorders like obesity, diabetes, dyslipemia, hypertension and an increased rate of cardiovascular disease and metabolic syndrome and these patients need safer treatments. The accumulating clinical experience with new therapies consistent on biological agents like efalizumab indicates that are effective therapies, with safety profile and no evidence of cumulative toxicity that allows a long term use. A better control of psoriasis improves patients quality of life. PMID:18341851

Sánchez Carazo, J L; Martínez Casimiro, L; Alegre de Miguel, V

2008-01-01

349

Advanced Diabetic Nephropathy with Nephrotic Range Proteinuria: A Pilot Study of the Long-Term Efficacy of Subcutaneous ACTH Gel on Proteinuria, Progression of CKD, and Urinary Levels of VEGF and MCP-1  

PubMed Central

Background and Objective. Adrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open-label pilot trial of ACTH gel in patients with advanced diabetic nephropathy. Study Design. Twenty-three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months. Outcome. The primary endpoint was the percentage of patients achieving a complete remission (<300?mg/24 hours) within 6 months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, and urinary cytokine markers. Results. After 6 months of ACTH gel therapy, 8 of 14 (57%) patients achieved a complete (n = 1) or partial (n = 7) remission. In the low-dose ACTH gel group (16 units), urinary protein fell from 6709 + 953 to 2224 + 489?mg/24 hrs (P < 0.001). In contrast, 2 of 6 patients in the 32-unit group achieved partial remission, but aggregate proteinuria (5324 + 751 to 5154 + 853?mg/24 hours) did not change. Urinary VEGF increased from 388 to 1346?pg/mg urinary creatinine (P < 0.02) in the low-dose group but remained unchanged in the high-dose group. Conclusion. ACTH gel stabilizes renal function and reduces urinary protein for up to 6 months after treatment. The ClinTrials.gov identifier is NCT01028287. PMID:24159603

Tumlin, J. A.; Galphin, C. M.; Rovin, B. H.

2013-01-01

350

Long-term Results of Endovascular Stent Graft Placement of Ureteroarterial Fistula  

SciTech Connect

PurposeTo evaluate the safety, efficacy, and long-term results of endovascular stent graft placement for ureteroarterial fistula (UAF).MethodsWe retrospectively analyzed stent graft placement for UAF performed at our institution from 2004 to 2012. Fistula location was assessed by contrast-enhanced computed tomography (CT) and angiography, and freedom from hematuria recurrence and mortality rates were estimated.ResultsStent graft placement for 11 UAFs was performed (4 men, mean age 72.8 {+-} 11.6 years). Some risk factors were present, including long-term ureteral stenting in 10 (91 %), pelvic surgery in 8 (73 %), and pelvic radiation in 5 (45 %). Contrast-enhanced CT and/or angiography revealed fistula or encasement of the artery in 6 cases (55 %). In the remaining 5 (45 %), angiography revealed no abnormality, and the suspected fistula site was at the crossing area between urinary tract and artery. All procedures were successful. However, one patient died of urosepsis 37 days after the procedure. At a mean follow-up of 548 (range 35-1,386) days, 4 patients (36 %) had recurrent hematuria, and two of them underwent additional treatment with secondary stent graft placement and surgical reconstruction. The hematuria recurrence-free rates at 1 and 2 years were 76.2 and 40.6 %, respectively. The freedom from UAF-related and overall mortality rates at 2 years were 85.7 and 54.9 %, respectively.ConclusionEndovascular stent graft placement for UAF is a safe and effective method to manage acute events. However, the hematuria recurrence rate remains high. A further study of long-term results in larger number of patients is necessary.

Okada, Takuya, E-mail: okabone@gmail.com; Yamaguchi, Masato, E-mail: masato03310402@yahoo.co.jp [Kobe University Hospital, Department of Radiology (Japan); Muradi, Akhmadu, E-mail: muradiakhmadu@gmail.com; Nomura, Yoshikatsu, E-mail: y_katsu1027@yahoo.co.jp [Kobe University Hospital, Center for Endovascular Therapy (Japan); Uotani, Kensuke, E-mail: uotani@tenriyorozu.jp [Tenri Hospital, Department of Radiology (Japan); Idoguchi, Koji, E-mail: idoguchi@ares.eonet.ne.jp [Kobe University Hospital, Center for Endovascular Therapy (Japan); Miyamoto, Naokazu, E-mail: naoka_zu@yahoo.co.jp; Kawasaki, Ryota, E-mail: kawaryo1999@yahoo.co.jp [Hyogo Brain and Heart Center at Himeji, Department of Radiology (Japan); Taniguchi, Takanori, E-mail: tan9523929@yahoo.co.jp [Tenri Hospital, Department of Radiology (Japan); Okita, Yutaka, E-mail: yokita@med.kobe-u.ac.jp [Kobe University Hospital, Department of Cardiovascular Surgery (Japan); Sugimoto, Koji, E-mail: kojirad@med.kobe-u.ac.jp [Kobe University Hospital, Department of Radiology (Japan)

2013-08-01

351

Safety and efficacy of etanercept in children with juvenile idiopathic arthritis below the age of 2 years.  

PubMed

Etanercept is approved for the treatment of patients with juvenile idiopathic arthritis (JIA) above the age of 2 years. Experience with younger children is limited. The aim of the present study was to evaluate the efficacy and safety of treatment with etanercept in children with JIA younger than 2 years. The prospective long-term observational BIKER registry documents baseline demographics, clinical characteristics, disease activity parameters and safety issues. Efficacy was determined using the PedACR response criteria, the JADAS-10 and the proposed criteria for inactive disease and remission after 3, 6, 12, 18 and 24 months. Safety assessments were based on adverse events (AE) and serious adverse events (SAEs) reports. Between January 2001 and June 2013, a total of 13 patients including four patients with systemic JIA (sJIA), four patients with extended oligoarthritis, one patient with persistent oligoarthritis and four patients with RF negative polyarthritis were treated with etanercept. Eleven patients with follow-up assessments were analysed in our study. Prior to etanercept, all patients have been exposed to methotrexate. At last observation, 6/11 patients reached a PedACR 70 response. Two patients with sJIA and 1 with nonsystemic JIA achieved inactive disease. Tolerability was good in most of the patients. Eight AE and one SAE occurred. One patient with sJIA was affected by Hodgkin's disease 18 months after discontinuation of etanercept. New onset uveitis occurred in two patients. Reasons for discontinuation were inefficacy in three (2 sJIA), intolerance in two, remission in three (2 sJIA) and the parents' request in one patient. Etanercept seems to improve JIA patients younger than 2 years including some of the patients with sJIA. Attention should be paid to the development of malignancies and autoimmune disorders. PMID:25208527

Windschall, D; Müller, T; Becker, I; Horneff, G

2015-04-01

352

Valuing a long-term care facility.  

PubMed

The business valuation industry generally uses at least one of three basic approaches to value a long-term care facility: the cost approach, sales comparison approach, or income approach. The approach that is chosen and the resulting weight that is applied to it depend largely on the circumstances involved. Because a long-term care facility is a business enterprise, more weight usually is given to the income approach which factors into the estimate of value both the tangible and intangible assets of the facility. PMID:10145686

Mellen, C M

1992-10-01

353

Safety and efficacy of peramivir for influenza treatment  

PubMed Central

Objective This report presents a review of the efficacy and safety of peramivir, a neuraminidase inhibitor that was granted Emergency Use Authorization by the US Food and Drug Administration (FDA) from October 23, 2009 to June 23, 2010 during the 2009 H1N1 pandemic. Methods Literature was accessed via PubMed (January 2000–April 2014) using several search terms: peramivir; BCX-1812; RWJ 270201; H1N1, influenza; antivirals; and neuraminidase inhibitors. The peramivir manufacturers, Shionogi and Co Ltd and BioCryst Pharmaceuticals, were contacted to obtain unpublished data and information presented at recent scientific meetings. Information was obtained from the Centers for Disease Control and Prevention (CDC) and from US FDA websites. English-language and Japanese-language reports in the literature were reviewed and selected based on relevance, along with information from the CDC, US FDA, and the drug manufacturers. Results We obtained eleven clinical trial reports of intravenous peramivir, two of which described comparisons with oseltamivir. Seven of nine other recently reported published studies was a dose–response study. Clinical reports of critically ill patients and pediatric patients infected with pandemic H1N1 described that early treatment significantly decreased mortality. Peramivir administered at 300 mg once daily in adult patients with influenza significantly reduces the time to alleviation of symptoms or fever compared to placebo. It is likely to be as effective as other neuraminidase inhibitors. Conclusion Although peramivir shows efficacy for the treatment of seasonal and pH1N1 influenza, it has not received US FDA approval. Peramivir is used safely and efficiently in hospitalized adult and pediatric patients with suspected or laboratory-confirmed influenza. Peramivir might be a beneficial alternative antiviral treatment for many patients, including those unable to receive inhaled or oral neuraminidase inhibitors, or those requiring nonintravenous drug delivery. PMID:25368514

Hata, Atsuko; Akashi-Ueda, Ryoko; Takamatsu, Kazufumi; Matsumura, Takuro

2014-01-01

354

Long-term use of adalimumab in the treatment of moderate to severe plaque psoriasis: a review of the literature  

PubMed Central

Psoriasis is a chronic T-cell-mediated inflammatory disease that primarily affects the skin and joints. Patients with moderate to severe psoriasis constitute about 30% of the psoriasis population. Treatment of this group is challenging due to the long-term side effects, toxicities and inconvenience of conventional treatments such as phototherapy, methotrexate and cyclosporine. However, recent advances in our understanding of the pathogenesis of psoriasis have led to the popular use of biologics, which offer a safer, more convenient and effective targeted therapy. Adalimumab was originally approved for treating rheumatoid arthritis. Currently, adalimumab is also approved for treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy or when other systemic therapies are medically less appropriate. Since the onset of the use of biologics, there have been concerns over safety and efficacy when used as long-term therapy. This paper reviews all publications, posters and abstracts reporting original data on the efficacy and/or safety of adalimumab in patients treated for chronic plaque psoriasis for more than 1 year. PMID:21437059

Moore, Angela Y; Richardson, Blakely S

2010-01-01

355

Chronic Hepatitis B: Integrating Long-Term Treatment Data and Strategies to Improve Outcomes in Clinical Practice  

PubMed Central

A number of agents can reduce viral replication in patients with chronic hepatitis B, but most patients do not undergo a curative response to these drugs and therefore require long-term therapy. Thus, recent studies have investigated the long-term safety, efficacy, and resistance profiles of several antiviral nucleotide/nucleoside agents: lamivudine, telbivudine, adefovir dipivoxil, entecavir, and tenofovir. The most recent data have revealed that lamivudine and telbivudine produce high rates of resistance when treatment is continued for 2–5 years; as a result, these agents are no longer preferred for first-line monotherapy. Entecavir and tenofovir, on the other hand, appear to have favorable safety and efficacy profiles when used as monotherapy, with very low rates of resistance over 5 years. In order to help clinicians incorporate these data into clinical practice, this monograph will review recently published data on hepatitis B antiviral medications, as well as explore when to consider cessation of therapy. The treatment of special patient populations and the need to screen patients for hepatocellular carcinoma will also be discussed. PMID:22557938

Afdhal, Nezam H.; Bacon, Bruce R.; Brown, Robert S.

2011-01-01

356

Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients  

PubMed Central

Background: Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities. PMID:25329968

Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Ulanski, Lawrence J.; Miller, Luke; Podella, Carla

2014-01-01

357

Cross-sectional survey and retrospective analysis of a large cohort of adults with type 1 diabetes with long-term continuous subcutaneous insulin infusion treatment.  

PubMed

Background. Continuous subcutaneous insulin infusion (CSII) is an established modality for intensive insulin treatment of type 1 diabetes (T1D), but long-term data concerning satisfaction, CSII function use, safety, and efficacy in real-life conditions are scarce. Methods. We analyzed a cohort of adult patients with T1D treated with CSII for more than 1 year in a single diabetes center. We performed a cross-sectional survey in 2010 (tolerance/satisfaction and behavior forms) and a retrospective analysis of medical records (including HbA1c level, hospitalization, and catheter infections). The primary objective was to assess long-term tolerance/satisfaction, and secondary objectives were safety and efficacy. Results. There were 295 patients analyzed. After a median duration of CSII use of 5 years, overall satisfaction was high for about 90% of patients. Mean CSII-related discomfort scores were low for work, recreation, and sleep and moderate for sport and sexual activity (2.5 ± 1.9, 2.6 ± 1.8, 2.6 ± 2.1, 3.4 ± 2.3, and 4.0 ± 2.9 of 10, respectively). Despite a high level of diabetes education, only one third of patients were using advanced CSII functions. During long-term follow-up, the safety of CSII treatment was good; the hospitalization rate was 0.18 patients/year, and catheter infections were scarce. The HbA1c level dropped about -0.5% independently from CSII duration (P < .05). Conclusions. In this adult cohort, satisfaction and tolerance, together with safety, of CSII were maintained at long-term follow up. The sole basic functions of CSII were currently used by patients. A 0.5% decrease in the HbA1c level was maintained during the study period. PMID:24876454

Joubert, Michael; Morera, Julia; Vicente, Angel; Rod, Anne; Parienti, Jean-Jacques; Reznik, Yves

2014-09-01

358

Ocular hypotensive efficacy and safety of once daily carteolol alginate  

PubMed Central

BACKGROUND/AIM—Carteolol is a ? adrenoceptor antagonist used topically to reduce intraocular pressure, typically twice daily. In an effort to provide a once daily dosing regimen, carteolol was formulated with 1% alginic acid. The objective of this study was to evaluate the efficacy and safety of carteolol alginate solution in comparison with standard carteolol solution.?METHODS—This was a double masked, parallel group, multicentre study. Patients with ocular hypertension or open angle glaucoma (n=235) were randomly assigned to receive either carteolol alginate four times daily or standard carteolol solution, twice daily. The masking was maintained through the use of a vehicle in the evening for the alginate group. Patients were evaluated at baseline, 15, 60, and 120 days.?RESULTS—At 0900 (presumed trough) on day 60, mean reductions in intraocular pressure (IOP) from baseline were 6.09 (SD 2.97) and 6.09 (3.18) mm Hg for the standard carteolol and alginate, respectively. At 1100 (presumed peak), mean reductions were 6.51 (2.53) and 6.47 (2.76) mm Hg, respectively. Results were similar at other times (day 15 and day 120). The most common side effect was transient stinging on instillation of drops, which did not differ significantly between groups. There were no differences of note in other ocular or systemic signs or symptoms.?CONCLUSION—The new alginate formulation of carteolol 2% given once daily was as effective as standard carteolol 2% given twice daily with no meaningful differences regarding safety.?? PMID:11466245

Demailly, P.; Allaire, C.; Trinquand, C.

2001-01-01

359

Efficacy and safety of methotrexate in alopecia areata*  

PubMed Central

BACKGROUND Alopecia areata is a chronic disorder of the hair follicles and nails, of unknown etiology, with clear autoimmune components and genetic factors. Several therapeutic options have been suggested; however, no treatment is able to modify the disease course. Methotrexate is an immunosuppressant used in various dermatoses and recently introduced as a therapeutic option for alopecia areata. OBJECTIVES To evaluate the efficacy and safety of methotrexate in alopecia areata. METHODS In a retrospective, non-controlled study, we evaluated 31 patients with alopecia areata in current or prior treatment with methotrexate to assess the therapeutic response according to sex, age, pattern of alopecia areata, disease duration, cumulative dose of methotrexate, use of systemic corticosteroids or other treatments, and drug safety. RESULTS Regrowth greater than 50% was observed in 67.7% of patients, with the best responses observed in those with <5 years of disease progression (79%), age over 40 years (73.3%), male patients (72.8%), cumulative dose of methotrexate 1000-1500 mg, and multifocal alopecia areata (93%). Among patients receiving systemic corticosteroids in combination with methotrexate, 77.3% had greater than 50% regrowth, compared with 44.4% in those who used methotrexate alone. The therapeutic dose ranged from 10-25 mg/week. No patient had serious adverse effects. Relapse was observed in 33.3% of patients with more than 50% regrowth. CONCLUSION Methotrexate appears to be a promising and safe medication for the treatment of severe alopecia areata when used alone or in combination with corticosteroids. PMID:25184911

Hammerschmidt, Mariana; Mulinari Brenner, Fabiane

2014-01-01

360

TOXIC MODELING SYSTEM LONG-TERM (TOXLT)  

EPA Science Inventory

The Toxic Modeling System Long-Term (TOXLT) is a personal-computer- based model that has been developed in conjunction with the release of the new version of the EPAs Industrial Source Complex (ISC2) Dispersion Models (EPA, 1992) and the promulgation of the EPAs A Tiered Modeling...

361

Evaluating Long-Term Disability Insurance Plans.  

ERIC Educational Resources Information Center

This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship between plan…

Powell, Jan

1992-01-01

362

Long-term treatment with recombinant  

E-print Network

Long-term treatment with recombinant nerve growth factor for HIV-associated sensory neuropathy and significantly im- proved pain symptoms. However, there was no improvement of neuropathy severity as assessed antiretroviral zal- citabine, didanosine, and stavudine is associated with a toxic neuropathy clinically similar

Steinbach, Joe Henry

363

Long-Term Stability of Social Participation  

ERIC Educational Resources Information Center

The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

2008-01-01

364

Long-Term Tracking Through Failure Cases  

Microsoft Academic Search

Long term tracking of an object, given only a single instance in an initial frame, remains an open problem. We propose a visual tracking algorithm, robust to many of the difficulties which often occur in real-world scenes. Correspondences of edge-based features are used, to overcome the reliance on the texture of the tracked object and improve invariance to lighting. Furthermore

Karel Lebeda; Simon Hadfield; Jiri Matas; Richard Bowden

2013-01-01

365

Long-term complications of chemotherapy  

Microsoft Academic Search

Patients with cancer are living longer and, therefore, are not only at risk for recurrence of the disease but also for long-term side effects of treatment. For patients treated with chemotherapy, secondary malignancies are a special concern, with acute nonlymphocytic leukemia being the most common. Although typically associated with alkylating agents, this complication is now being seen with use of

Mark A. Morgan; Stephen C. Rubin

1998-01-01

366

Long-Term Sequelae of Stroke  

PubMed Central

Scant attention has been paid to the long-term consequences and complications resulting from a stroke. Many stroke survivors go on to develop a variety of medical, musculoskeletal, and psychosocial complications, years after the acute stroke. The family physician is regularly called upon to deal with these problems, but is often hampered by a lack of resources. PMID:21221264

Teasell, Robert W.

1992-01-01

367

Truancy: Short and Long-Term Solutions.  

ERIC Educational Resources Information Center

This book offers guidance on dealing with the problem of truancy and non-attendance. It provides examples of the latest ways that schools, teachers, education welfare officers, and local education authorities in the United Kingdom have worked to overcome their attendance problems, identifying 120 short-term solutions and several long-term

Reid, Ken

368

Long-term cropping systems study  

Technology Transfer Automated Retrieval System (TEKTRAN)

This long-term study has been conducted on the Agronomy Farm at ARDC since the early 1970’s. In the beginning, the objectives were mainly related to crop production as affected by different cropping systems. The cropping systems included in the study are Continuous Corn, Soybean, and Sorghum; 2-year...

369

Long-term data storage in DNA  

Microsoft Academic Search

This article discusses how DNA might be used to store data. It is argued that, at present, DNA would be best employed as a long-term repository (thousands or millions of years). How data-containing DNA might be packaged and how the data might be encrypted, with particular attention to the encryption of written information, is also discussed. Various encryption issues are

Jonathan P. L Cox

2001-01-01

370

Long term perspectives in energy resources  

Microsoft Academic Search

Long term perspectives in global energy use patterns and energy resources are considered. The potential contributions of natural gas and coal, oil, nuclear energy, hydroelectric energy, and alternative energy resources (geothermal, wind, biomass, solar) are evaluated. It is concluded that fossile fuels will continue to provide the bulk of the world's energy through the upcoming decades. The political uncertainty of

C. Destival

1978-01-01

371

NATIONAL LONG TERM CARE SURVEY (NLTCS)  

EPA Science Inventory

National Long Term Care Surveys (NLTCS) are surveys of the entire aged population with a particular emphasis on the functionally impaired. Longitudinal study of the health and well-being of elderly Americans. Information about the population of chronically disabled elderly person...

372

LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)  

EPA Science Inventory

LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

373

Process synchronization without long-term interlock  

Microsoft Academic Search

A technique is presented for replacing long-term interlocking of shared data by the possible repetition of unprivileged code in case a version number (associated with the shared data) has been changed by another process. Four principles of operating system architecture (which have desirable effects on the intrinsic reliability of a system) are presented; implementation of a system adhering to these

William B. Easton

1971-01-01

374

Process synchronization without long-term interlock  

Microsoft Academic Search

A technique is presented for replacing long-term interlocking of shared data by the possible repetition of unprivileged code in case a version number (associated with the shared data) has been changed by another process. Four principles of operating system architecture (which have desirable effects on the intrinsic reliability of a system) are presented; implementation of a system adhering to these

William B. Easton

1972-01-01

375

Long-Term Recidivism of Child Molesters  

Microsoft Academic Search

We examined the long-term recidivism rates of 197 child molesters released from prison between 1958 and 1974. Overall, 42% of the total sample were reconvicted for sexual crimes, violent crimes, or both, with 10% of the total sample reconvicted 10–31 years after being released. Incest offenders were reconvicted at a slower rate than were offenders who selected only boys, with

R. Karl Hanson; Richard A. Steffy; Rene Gauthier

1993-01-01

376

Four Long-Term Fiscal Realities  

Microsoft Academic Search

The United States faces a long-run fiscal imbalance because of rapid projected growth in Social Security, Medicare, and Medicaid spending. The policy response to the imbalance will be shaped by four long-term fiscal realities. First, revenue will rise as a share of GDP. Second, entitlement spending will be reduced, relative to current policies. Third, the middle class, broadly defined, will

Alan D Viard

2009-01-01

377

Attachment style and long-term singlehood  

Microsoft Academic Search

This study examined how long-term single people satisfy their attachment and sexual needs. A community sample of single and coupled adults (N ¼ 142) located in the United States completed measures of attachment style, attachment figures, loneliness, depression, anxiety, quality of relationships with parents, and sexual behavior. In a structured interview, they answered questions about their childhoods and managing attachment,

DORY A. SCHACHNER; PHILLIP R. SHAVER; OMRI GILLATHc

2008-01-01

378

Clinical review: Long-term noninvasive ventilation  

Microsoft Academic Search

Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected

Dominique Robert; Laurent Argaud

2007-01-01

379

Long-term projection: Initializing sea level  

NASA Astrophysics Data System (ADS)

Long-term climate change and sea-level rise in model projections have been primarily determined by external forcing of climate conditions. Now, research shows that centennial projections of the dynamic sea level are also sensitive to the ocean's initial conditions.

Yin, Jianjun

2015-04-01

380

Safety and efficacy of LigaSure usage in pancreaticoduodenectomy  

PubMed Central

Background Over recent years, use of the LigaSure™ vessel sealing device has increased in major abdominal surgery to include pancreaticoduodenectomy (PD). LigaSure™ use during PD has expanded to include all steps of the procedure, including the division of the uncinate margin. This introduces the potential for thermal major vascular injury or margin positivity. The aim of the present study was to evaluate the safety and efficacy of LigaSure™ usage in PD in comparison to established dissection techniques. Methods One hundred and forty-eight patients who underwent PD from 2007 to 2012 at Robert Wood Johnson University Hospital were identified from a retrospective database. Two groups were recognized: those in which the LigaSure™ device was used (N = 114), and in those it was not (N = 34). Peri-operative outcomes were compared. Results Vascular intra-operative complications directly caused by thermal injury from LigaSure™ use occurred in 1.8% of patients. Overall vascular intra-operative complications, uncinate margin positivity, blood loss, length of stay, and complication severity were not significantly different between groups. The mean operative time was 77 min less (P < 0.010) in the LigaSure™ group. Savings per case where the LigaSure™ was used amounted to $1776.73. Conclusion LigaSure™ usage during PD is safe and effective. It is associated with decreased operative times, which may decrease operative costs in PD. PMID:23782268

Eng, Oliver S; Goswami, Julie; Moore, Dirk; Chen, Chunxia; Brumbaugh, Jennifer; Gannon, Christopher J; August, David A; Carpizo, Darren R

2013-01-01

381

Efficacy and Safety of Beating Heart Mitral Valve Replacement  

PubMed Central

Background: The interest in beating heart surgery is growing since better results can be obtained with this procedure compared to conventional myocardial protection techniques using cardioplegic solutions. This led us to consider mitral valve replacement with beating heart. Objectives: This study aimed to determine the safety and efficacy of beating heart mitral valve replacement without cross clamp. Methods: This prospective study was conducted on the patients with isolated mitral valve disease requiring mitral valve replacement according to ACC / AHA guidelines. In this study, 15 patients underwent mitral valve replacement using beating heart technique (Group A) and 15 ones underwent mitral valve replacement using arrested heart technique (Group B). The patients were randomized using block randomization. The data were analyzed using the SPSS statistical software. Results: Preoperative parameters were comparable in the two groups. Most of the patients in both study groups were in NYHA class III or IV. Postoperatively, however, most of the patients in the two groups were either in NYHA class I or II. No mortality occurred in the beating heart group, while one mortality occurred in the arrested heart group. The results showed a significant difference between the two groups regarding the mean bypass time, mean operating time, mean ICU stay, and mean length of hospital stay. Conclusions: Beating heart mitral valve replacement is equally safe as the arrested heart technique. Thus, it is recommended as an appropriate alternative to the arrested heart technique for mitral valve replacement. PMID:24936483

Wani, Mohd Lateef; Ahangar, Abdul Gani; Singh, Shyam; Irshad, Ifat; ul-Hassan, Nayeem; Wani, Shadab Nabi; Ahmad Ganie, Farooq; Bhat, Mohd Akbar

2014-01-01

382

Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications.  

PubMed

Ramelteon is a tricyclic synthetic analog of melatonin that acts specifically on MT1 and MT2 melatonin receptors. Ramelteon is the first melatonin receptor agonist approved by the Food and Drug Administration (FDA) for the treatment of insomnia characterized by sleep onset difficulties. Ramelteon is both a chronobiotic and a hypnotic that has been shown to promote sleep initiation and maintenance in various preclinical and in clinical trials. The efficacy and safety of ramelteon in patients with chronic insomnia was initially confirmed in short-term placebo-controlled trials. These showed little evidence of next-day residual effects, withdrawal symptoms or rebound insomnia. Other studies indicated that ramelteon lacked abuse potential and had a minimal risk of producing dependence or adverse effects on cognitive or psychomotor performance. A 6-month placebo-controlled international study and a 1-year open-label study in the USA demonstrated that ramelteon was effective and well tolerated. Other potential off-label uses of ramelteon include circadian rhythm sleep disorders such as shift-work and jet lag. At the present time the drug should be cautiously prescribed for short-term treatment only. PMID:23861638

Pandi-Perumal, Seithikurippu R; Spence, D Warren; Verster, Joris C; Srinivasan, Venkatramanujam; Brown, Gregory M; Cardinali, Daniel P; Hardeland, Rüdiger

2011-01-01

383

Long-term results of hysteroscopic myomectomy for abnormal uterine bleeding  

Microsoft Academic Search

Objective: To analyze the efficacy of transcervical resection of submucous myomas and to identify prognostic factors for long-term results.Methods: Two-hundred eighty-five women were treated with transcervical resection of submucous myomas without endometrial ablation. In case of incomplete resection a repeat procedure was offered. Long-term follow-up was obtained. Recurrence was defined as the need for further surgery. The relation of several

Mark H Emanuel; Kees Wamsteker; Augustinus A. M Hart; Godfried Metz; Frits B Lammes

1999-01-01

384

Biofeedback provides long term benefit for patients with intractable, slow and normal transit constipation  

Microsoft Academic Search

Background—Many patients with idiopathic constipation do not respond to conventional medical treatments. Recently biofeedback has been proposed as an alternative treatment but the long term results, and which patients benefit, are unknown. Treatment has usually been restricted to patients with normal colonic transit and impaired pelvic floor coordination on straining.Aims—To determine the efficacy and long term outcome of biofeedback treatment

E Chiotakakou-Faliakou; M A Kamm; A J Roy; J B Storrie; I C Turner

1998-01-01

385

Efficacy, safety and immunological actions of butanol-extracted FAHF-2 on peanut anaphylaxis  

PubMed Central

Background Therapies for peanut allergy (PNA) are urgently needed. Food Allergy Herbal Formula -2 (FAHF-2) has profound therapeutic effects in a murine peanut allergy model and is safe for food allergic adults in clinical trials. However the large FAHF-2 pill-load is not conducive to clinical studies in children. Thus refining FAHF-2 to decrease pill-load is essential for the inclusion of children in clinical trials and to facilitate studying FAHF-2 as a clinically useful botanical drug. Objectives Testing long term efficacy and safety of a butanol-purified extract of FAHF-2 (B-FAHF-2) in a murine model of PNA, and to explore its immunological mechanisms of action. Methods FAHF-2 was purified by butanol extraction. C3H/HeJ mice with established PNA received the 1st course of B-FAHF-2 at 6 mg, twice daily for 7 weeks (PNA/B-FAHF-2) or water (PNA/Sham) and were then challenged immediately after completing the treatment and 6 more times every 1–2 months post treatment up to week 50. Mice then received a second course of B-FAHF-2 treatment at week 52 and were challenged at week 65. In vivo and in vitro immunological effects on T, B and mast cells were also determined. Results Butanol purification reduced the volume of the effective dose ~5 fold. All PNA/B-FAHF-2 mice were completely protected from peanut anaphylaxis until the 5th challenge after the 1st course of treatment, as compared to PNA/sham mice. Partial protection persisted up to 50 weeks. A 2nd treatment course restored complete protection. B-FAHF-2 significantly suppressed Th2 cytokine, IgE and histamine levels in vivo, and showed direct inhibition of Th2, IgE-producing B cells and mast cell activation in vitro. B-FAHF-2 had a high margin of safety. Conclusion and clinical relevance B-FAHF-2 produced long-lasting protection against PN anaphylaxis for approximately half of the murine lifespan without side effects. B-FAHF-2 exhibited direct effects on multiple food allergy effector cells. PMID:21121976

Srivastava, Kamal; Yang, Nan; Chen, Yuming; Lopez-Exposito, Ivan; Song, Ying; Goldfarb, Joseph; Zhan, Jixun; Sampson, Hugh; Li, Xiu-Min

2010-01-01

386

Efficacy and Safety of Vorapaxar as Approved for Clinical Use in the United States  

PubMed Central

Background Vorapaxar is a protease?activated receptor?1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA). Methods and Results We examined the efficacy and safety of vorapaxar in the intended use population, considering 20 170 patients randomized in the multinational, double?blinded, placebo?controlled TRA 2°P?TIMI 50 trial. Of these, 16 897 qualified with a history of MI in the prior 2 weeks to 1 year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3 years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89; P<0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90; P<0.001), as well as the rate of CV death or MI (P<0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86, P<0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%, P=0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%; P=0.70. Conclusions In patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long?term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding. Clinical Trial Registration URL: clinicaltrials.gov Unique Identifier: NCT00526474. PMID:25792124

Magnani, Giulia; Bonaca, Marc P.; Braunwald, Eugene; Dalby, Anthony J.; Fox, Keith A. A.; Murphy, Sabina A.; Nicolau, José Carlos; Oude Ophuis, Ton; Scirica, Benjamin M.; Spinar, Jindrich; Theroux, Pierre; Morrow, David A.

2015-01-01

387

Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2–4 COPD: results from two replicate 48-week studies  

PubMed Central

Background Olodaterol is a long-acting ?2-agonist with a 24-hour bronchodilator profile. Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy. Methods Patients received olodaterol 5 ?g or 10 ?g or placebo once daily for 48 weeks. Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0–3) response (change from baseline), and trough FEV1 response at 12 weeks. Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks. Results Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively. In both studies, olodaterol 5 ?g and 10 ?g significantly improved the FEV1 AUC0–3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo. Secondary end points supported the efficacy of olodaterol. Conclusion These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 ?g and 10 ?g in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. PMID:24966672

Ferguson, Gary T; Feldman, Gregory J; Hofbauer, Peter; Hamilton, Alan; Allen, Lisa; Korducki, Lawrence; Sachs, Paul

2014-01-01