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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 efficacy and safety of etanercept in psoriasis].  

PubMed

There are many studies that have shown that etanercept is an effective and safe drug for the short-term treatment of moderate to severe psoriasis. However, psoriasis is a disease with a chronic or recurrent course associated to arthritis and comorbidities that diminish the patient's health and quality of life and that often requires either continuous or intermittent long-term treatment. The data available on the use of etanercept in the long-term treatment of psoriasis, even at high doses, have shown that it has a good efficacy and safety profile. Half of the patients obtained a 75% improvement on the Psoriasis Area and Severity Index (PASI-75 during prolonged treatments of up to 96 months. The PASI 75 response is higher in continuous regimes than in intermittent ones (with pauses). Most of the patients maintain the response at long-term, although a decrease in efficacy is observed in some of them, as occurs with other tumor necrosis factor inhibitors. Accumulated experience with etanercept in other chronic inflammatory diseases also supports this good safety profile. PMID:20492875

García-Patos Briones, V; Mollet Sánchez, J

2010-05-01

3

Long-term efficacy and safety of iloperidone: an update  

PubMed Central

Schizophrenia is a devastating neuropsychiatric disease with a worldwide prevalence of approximately 0.5%–1%. Since many patients do not achieve adequate symptom relief from available agents, alternate pharmacotherapeutic approaches are needed. In this context, iloperidone was recently approved by the US Food and Drug Administration for the treatment of schizophrenia. This paper first reviews its pharmacodynamic and pharmacokinetic profiles, emphasizing their clinical relevance. Next, it summarizes the literature on its acute and maintenance efficacy, safety, and tolerability. It then considers pharmacogenetic data which may help to predict response and risk of cardiac arrhythmias with this agent. Finally, it critically positions iloperidone relative to other first- and second-generation antipsychotics. PMID:24600226

Rado, Jeffrey T; Janicak, Philip G

2014-01-01

4

Long-term efficacy, safety and durability of Juvéderm® XC  

PubMed Central

Over the last decade, there has been increasing interest in minimally invasive cosmetic treatments, especially for facial rejuvenation. Next to botulinum toxin injection, the injection of soft tissue fillers is the second most frequent minimally invasive procedure performed in the USA. Hyaluronic acid (HA) is the most commonly used dermal filler. One of patients’ main concerns about filler injections pertains to pain and discomfort. Topical anesthetics, nerve blocks, and/or the incorporation of lidocaine to the filler have been applied in order to reduce distress and pain. Despite nerve blocks being an effective form of anesthesia, they may distort the area to be treated, as well as lengthen and complicate the procedure. Studies have shown that the incorporation of lidocaine to HA fillers significantly reduces pain and discomfort. Yet, one of the dilemmas about the addition of lidocaine solution to HA fillers is the possible alteration of the physical characteristics of the product by negatively impacting the efficacy and/or duration of the filler. The concern is that the addition of lidocaine could dilute the product, creating less correction per mL, changing the product’s viscosity and consequently the “lifting” ability. Also, this dilution could reduce the product’s duration. There may be a difference between a physician adding an aqueous solution into a lidocaine-free version of HA and the pre-incorporated lidocaine version of HA. An aqueous solution might dilute the product, while the pre-incorporated powder lidocaine appears to avoid this problem. Juvéderm® XC is manufactured with powder lidocaine 0.3%; it is associated with significantly less injection pain than Juvéderm® and other lidocaine-free versions of HA. Studies have shown that lidocaine enhances treatment comfort and optimizes the injection experience while maintaining a similar safety and effectiveness profile. Regarding the longevity, further study is necessary to determine if there is any difference in durability. PMID:23946665

Ballin, Annelyse C; Cazzaniga, Alex; Brandt, Fredric S

2013-01-01

5

Efficacy and safety of an extended-release niacin (niaspan): a long-term study  

Microsoft Academic Search

Crystalline nicotinic acid (immediate-release niacin) is effective therapy for lipoprotein regulation and cardiovascular risk reduction. However, inconvenient regimens and unpleasant side effects decrease compliance. Sustained-release formulations designed to circumvent these difficulties increase hepatotoxicity. Niaspan, a new US Food and Drug Administration (FDA)-approved, once-daily, extended-release form, has been found effective and safe in short-term trials. The long-term efficacy and safety of

David M Capuzzi; John R Guyton; John M Morgan; Anne C Goldberg; Robert A Kreisberg; O. A Brusco; Jerome Brody

1998-01-01

6

Long-Term Efficacy and Safety of Botulinum Toxin Injections in Dystonia  

PubMed Central

Local chemodenervation with botulinum toxin (BoNT) injections to relax abnormally contracting muscles has been shown to be an effective and well-tolerated treatment in a variety of movement disorders and other neurological and non-neurological disorders. Despite almost 30 years of therapeutic use, there are only few studies of patients treated with BoNT injections over long period of time. These published data clearly support the conclusion that BoNT not only provides safe and effective symptomatic relief of dystonia but also long-term benefit and possibly even favorably modifying the natural history of this disease. The adverse events associated with chronic, periodic exposure to BoNT injections are generally minor and self-limiting. With the chronic use of BoNT and an expanding list of therapeutic indications, there is a need to carefully examine the existing data on the long-term efficacy and safety of BoNT. In this review we will highlight some of the aspects of long-term effects of BoNT, including efficacy, safety, and immunogenicity. PMID:23381141

Ramirez-Castaneda, Juan; Jankovic, Joseph

2013-01-01

7

Long-term efficacy and safety of rosuvastatin 40 mg in patients with severe hypercholesterolemia.  

PubMed

Patients with elevated low-density lipoprotein (LDL) cholesteral levels are at high risk of cardiovascular events but are often undertreated and fail to achieve lipid goals. This open-label, noncomparative, multicenter study assessed efficacy and safety of rosuvastatin 40 mg for < or =96 weeks in 1,380 patients with severe hypercholesterolemia, including heterozygous familial hypercholesterolemia. Patients > or =18 years old with fasting LDL cholesterol > or =190 and < or =260 mg/dl and triglycerides <400 mg/dl entered a 6-week dietary lead-in, before receiving rosuvastatin 40 mg for 48 weeks. An optional additional 48-week treatment period followed. The initial period had 2 primary end points: percentage of patients achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III LDL cholesterol goals at 12 weeks, and long-term safety, assessed during 48 weeks by incidence and severity of adverse events (AEs) and abnormal laboratory values. Safety was the primary end point in the extension period. At 12 weeks, 83% of patients achieved NCEP ATP III LDL cholesterol goals, which were maintained during 48 and 96 weeks (81% and 84%, respectively). At 48 weeks, rosuvastatin 40 mg reduced LDL cholesterol from baseline by 52% and increased high-density lipoprotein (HDL) cholesterol by 11% (both p <0.0001). At 96 weeks, LDL cholesterol was reduced by 54% and HDL cholesterol increased by 13%. Rosuvastatin 40 mg was well tolerated during 96 weeks. The overall pattern and incidence of AEs and abnormal laboratory values were consistent with the published safety profile of rosuvastatin and higher doses of other statins. In conclusion, long-term treatment with rosuvastatin 40 mg is safe and effective in patients with severe hypercholesterolemia. PMID:17950795

Stein, Evan A; Amerena, John; Ballantyne, Christie M; Brice, Edmund; Farnier, Michel; Guthrie, Robert M; Harats, Dror; Ma, Patrick T S; Le Maulf, Florence; Melezínková, Helena; Gold, Alex; Sager, Philip

2007-11-01

8

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

9

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

10

Long-term efficacy and safety of eculizumab in Japanese patients with PNH: AEGIS trial.  

PubMed

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, progressive hematopoietic stem cell disorder characterized by chronic complement-mediated hemolysis leading to life-threatening complications and early mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal complement activation, reduces hemolysis, decreases the risk of thrombosis, and improves renal function and quality of life in PNH patients. The long-term efficacy and safety of eculizumab in Japanese patients were assessed in a 2-year extension to a 12-week, open-label study (AEGIS). Eculizumab treatment led to an immediate and sustained reduction in intravascular hemolysis (P < 0.001) and red blood cell transfusions (P = 0.0016) compared with baseline levels. There were no reports of thromboembolism during eculizumab treatment. The majority of patients had stable (56 %) or improved (41 %) renal function and an improved quality of life (P = 0.015), with sustained reductions in fatigue and dyspnea. Eculizumab was well tolerated; no deaths or serious hemolytic events were reported, and the rate of infections declined over time. There were no significant differences in the response to eculizumab in patients with or without bone marrow dysfunction. These results demonstrate that eculizumab is an effective, well-tolerated long-term treatment for Japanese PNH patients and leads to continued amelioration of some hemolytic complications. PMID:23934275

Kanakura, Yuzuru; Ohyashiki, Kazuma; Shichishima, Tsutomu; Okamoto, Shinichiro; Ando, Kiyoshi; Ninomiya, Haruhiko; Kawaguchi, Tatsuya; Nakao, Shinji; Nakakuma, Hideki; Nishimura, Jun-ichi; Kinoshita, Taroh; Bedrosian, Camille L; Ozawa, Keiya; Omine, Mitsuhiro

2013-10-01

11

Deferasirox: appraisal of safety and efficacy in long-term therapy  

PubMed Central

Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with ?-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy. PMID:23966805

Chaudhary, Preeti; Pullarkat, Vinod

2013-01-01

12

The long-term efficacy and safety of new biological therapies for psoriasis  

Microsoft Academic Search

Long-term therapy is often required for psoriasis. This article reviews the most recent long-term clinical data for biological agents that have been approved or for which late-stage development data have been released for the treatment of patients with moderate to severe plaque psoriasis. Efficacy data are available for up to five 12-week courses of alefacept (approximately 60 weeks of therapy), 36 months

Kim A. Papp

2006-01-01

13

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

PubMed

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

14

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

15

Long-term clinical safety and efficacy of NIROYAL vs. NIR intracoronary stent.  

PubMed

Research in vitro and in animal models suggested that gold electroplating of stents can attenuate neointimal hyperplasia and reduce thrombogenicity. The objective of this study was to evaluate the safety and efficacy of the gold-coated NIROYAL stent in the treatment of stenosed coronary arteries and bypass grafts. We retrospectively studied 181 consecutive patients undergoing deployment of NIR (n = 87) or NIROYAL (n = 94) coronary stents in a single tertiary referral center from July 1997 to December 1998. Mean follow-up duration for the NIR and NIROYAL patient groups were 11.6 and 11.4 (range, 3-12) months, respectively. Stent thrombosis rates were 3/87 (3%) in the NIR and 0/94 (0%) in the NIROYAL group (P = 0.07). The need for target lesion revascularization (TLR) in the NIR patient group was 8/87 (9%) compared to 11/94 (12%) in the NIROYAL patient group (P = 0.6). The overall MACE rates for the NIR and NIROYAL patient groups were 24/87 (28%) and 22/94 (23%), respectively (P = 0.5). The present study, hence, implies equivalence between the stainless steel NIR and the gold-plated NIROYAL stent with no significant difference in immediate and long-term clinical performance profiles. PMID:11590672

Harding, S A; McKenna, C J; Flapan, A D; Boon, N A

2001-10-01

16

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

17

Long-term safety and efficacy of topical cyclosporine in 156 children with vernal keratoconjunctivitis.  

PubMed

Vernal keratoconjunctivitis (VKC) is a chronic and potentially sight-threatening disease. Topical corticosteroids (Cs) seem to be the only effective treatment for this condition, although severe side effects may occur owing to their prolonged use. More recently, cyclosporine (Cyc) eye drops have been reported as a valid alternative, but so far such treatment has only been successfully experimented for a short time and in small numbers of patients. The aim of our study is to evaluate the long term safety and efficacy of topical cyclosporine eye drops in children suffering from VKC. Over a period of 7 years we followed a large group of children suffering from severe VKC. They were selected to start cyclosporine eye drop treatment, because of the prompt relapse of their disease as soon as they stopped topical corticosteroids administration. All patients were followed-up in an ambulatory care assessment. A total of 156 children with VKC were treated with topical cyclosporine eye drops over a period ranging from two to seven years [mean time 3.8 +/- 1.09 years] during the seasonal relapse [range 9-66 months; mean time 24.7+/-10.4 months]. Two formulations, at 1% and 2% (82% and 18%, respectively) concentrations, of cyclosporine eye drops were made. The dosage administered was one drop in each eye from two to four times a day, depending on the severity of the disease and the season. The ocular objective scores were determined and compared every year, at the beginning and at the end of each treatment period. Blood samples were collected once a year in order to check both kidney and liver functions, as well as cyclosporine serum levels. We enrolled 156 patients (mean age 8.31+/-2.79 years; 116 males and 40 females) who were followed-up over a period of 7 years [156 (100%) children during the first and the second year; 138 (88.5%) patients until the third year; 90 (57.7%) until the fourth year; 32 (20.5%) until the fifth year; 10 (6.4%) until the sixth year and 2 (1.3%) until the seventh year]. The ocular objective scores significantly improved (p less than 0.001) over the years when comparing them at the beginning and the end of each seasonal treatment period, except for the last year. Over the treatment period, non-significant changes were recorded in terms of kidney and liver enzymatic activities and also in terms of cyclosporine serum levels. Cyclosporine eye drops, either at 1% or 2% concentrations, resulted safe and effective for long-term treatment of VKC in 156 children. The lack of significance of the score results during the seventh year can be explained by the small number of subjects treated for such a long period. A systematic ocular examination and both liver and kidney functional investigations allowed us to exclude the possibility of local or systemic side effects due to cyclosporine. If either transient or long-lasting, the occurrence of burning was referred by some of the patients treated, but none of them required to discontinue the drug. In conclusion, this is the first study showing that topical cyclosporine is easily handled even by children, with safe and effective results even when it is used over a long period of time. Our findings, though encouraging, need to be confirmed by further studies. PMID:20943058

Pucci, N; Caputo, R; Mori, F; De Libero, C; Di Grande, L; Massai, C; Bernardini, R; Novembre, E

2010-01-01

18

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

PubMed Central

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

2012-01-01

19

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

20

The long-term safety and efficacy of opioids: A survey of 84 selected patients with intractable chronic noncancer pain  

PubMed Central

BACKGROUND: The use of opioids for chronic noncancer pain (CNCP) remains controversial. Despite a number of randomized controlled trials showing efficacy and safety in the short term, long-term data are limited. OBJECTIVE: To survey a selected cohort of patients with intractable CNCP with regard to long-term efficacy and safety of opioids. METHODS: The present study reports long-term results from a survey of 84 patients with CNCP. The majority of patients had neuropathic pain, were treated with opioids and were followed every three months for a median of 8.4 years. Outcomes examined were pain severity, adverse effects, pain relief, satisfaction, mood, problematic opioid use, tolerance, physical dependency, functional status, health-related quality of life, immune status, sexual function, morbidity and mortality. Measures included a numerical rating scale, the Hospital Anxiety and Depression Scale, Brief Pain Inventory interference scale, Pain Disability Index and Short-Form Health Survey 12, version 2. RESULTS AND CONCLUSIONS: Both long- and short-acting opioids were reported to be effective, with few significant long-term adverse effects in many subjects in the present selected cohort. The majority of patients reported at least 50% or greater pain relief and a moderate improvement in disability. Functional status and health-related quality of life scores were not severely affected. Problematic opioid use, tolerance and serious adverse effects, including constipation, were not major issues. The authors emphasize that the results obtained in the present selected group may not be generalizable to all CNCP patients in whom opioids are being initiated. PMID:20808965

Watson, C Peter N; Watt-Watson, Judy; Chipman, Mary

2010-01-01

21

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

22

Occipital nerve stimulation for chronic headache--long-term safety and efficacy.  

PubMed

The aim of this study was to examine the safety and efficacy of occipital nerve stimulation for medically intractable headache. Electrical stimulation of large sensory afferents has an antinociceptive effect. Occipital nerve stimulation may be effective for the treatment of medically intractable headache. Retrospective analysis was performed of 15 patients with medically refractory headache who underwent implantation of an occipital nerve stimulator. Pre- and postimplant data regarding headache frequency, severity, disability, depression and poststimulator complications were collected. Twelve patients were female and three male. Ages ranged from 21 to 52 years (mean 39 years). Eight patients had chronic migraine, three chronic cluster, two hemicrania continua and two had post-traumatic headache. Eight patients underwent bilateral and seven had unilateral lead placement. Patients were measured after 5-42 months (mean 19). All six mean headache measures improved significantly from baseline (P < 0.03). Headache frequency per 90 days improved by 25 days from a baseline of 89 days; headache severity (0-10) improved 2.4 points from a baseline of 7.1 points; MIDAS disability improved 70 points from a baseline of 179 points; HIT-6 scores improved 11 points from a baseline of 71 points; BDI-II improved eight points from a baseline of 20 points; and the mean subjective percent change in pain was 52%. Most patients (60%) required lead revision within 1 year. One patient required generator revision. Occipital nerve stimulation may be effective in some patients with intractable headache. Surgical revisions may be commonly required. Safety and efficacy results from prospective, randomized, sham-controlled studies in patients with medically refractory headache are needed. PMID:17257236

Schwedt, T J; Dodick, D W; Hentz, J; Trentman, T L; Zimmerman, R S

2007-02-01

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

Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome  

PubMed Central

Irritable bowel syndrome (IBS) is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes. Serotonin (5-hydroxytryptamine [5-HT]) plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous 5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity. Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with diarrhea-predominant IBS-D, once-daily 5 ?g and 10 ?g doses of ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 ?g dose of ramosetron-treated individuals compared to 27% of patients receiving placebo (P<0.001). Furthermore, the responder rate was increased in the oral administration of 5 ?g of ramosetron for at least 28 weeks (up to 52 weeks), and long-term efficacy for overall improvement of IBS symptoms was also demonstrated. The rate was further increased subsequently. Adverse events were reported by 7% in ramosetron treatment. No serious adverse events, eg, severe constipation or ischemic colitis, were reported for long-term treatment with ramosetron. In conclusion, further studies to evaluate the long-term efficacy and safety of ramosetron are warranted in the form of randomized controlled trials. PMID:23922505

Chiba, Toshimi; Yamamoto, Kazunari; Sato, Shoko; Suzuki, Kazuyuki

2013-01-01

25

The Long-Term Safety and Efficacy of Intrathecal Therapy Using Sufentanil in Chronic Intractable Non-Malignant Pain  

PubMed Central

This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome. PMID:25031819

Monsivais, Diane Burn

2014-01-01

26

Long-term safety and sustained efficacy of extended-release pramipexole in early and advanced Parkinson's disease  

PubMed Central

Background and purpose To assess the long-term safety and efficacy of pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). Methods In two double-blind (DB) studies of early PD and one of advanced PD, active-treatment arms received pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375–4.5 mg q.d.). Results Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ?10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ?10.0% were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to pramipexole introduction, at ?6.6 and ?6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of pramipexole (33 DB plus 80 OL) in early PD, and ?11.5 and ?9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. Conclusions These results support the long-term safety and efficacy of pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit. PMID:24834511

Hauser, R A; Schapira, A H V; Barone, P; Mizuno, Y; Rascol, O; Busse, M; Debieuvre, C; Fraessdorf, M; Poewe, W; Pramipexole ER Studies Group

2014-01-01

27

Efficacy, Safety, and Long-Term Follow-Up Results of EUS-Guided Transmural Drainage for Pancreatic Pseudocyst  

PubMed Central

Background and Aim. EUS-guided transmural drainage (EUS-GTD) is now considered a minimally invasive and effective alternative to surgery for drainage of symptomatic pancreatic pseudocysts. However, the technique is rather difficult, and sometimes serious complications occur to patients undergoing this procedure. We retrospectively evaluated efficacy, safety, and long-term follow-up results of EUS-GTD for pancreatic pseudocyst. Methods. Sixty-seven patients with pancreatic pseudocyst who underwent EUS-GTD from April 2000 to March 2011 were enrolled. We retrospectively evaluated (1) technical success, (2) clinical success, (3) adverse event of procedure, and (4) long-term follow-up results. Results. Total technical success rate was 88%. Ninety-one percent of external drainage, 79% of internal drainage, and 66% of puncture and aspiration only achieved clinical success. There was only one case with an adverse event, perforation (1.5%). The case required emergency operation. Total recurrence rate was 23.9%. Median follow-up period was 33.9 months. The recurrence rates in the cases of stent remaining, spontaneously dislodged, removed on schedule, external tube removal, and aspiration only were 10.0%, 12.5%, 42.9%, 50%, and 0%, respectively. Conclusion. EUS-GTD is a relatively safe and effective therapeutic method. However, further analysis should be done by larger series to determine the method of EUS-GTD for pancreatic pseudocyst. PMID:23554548

Kato, Shin; Katanuma, Akio; Maguchi, Hiroyuki; Takahashi, Kuniyuki; Osanai, Manabu; Yane, Kei; Kim, Toshifumi; Kaneko, Maki; Takaki, Ryo; Matsumoto, Kazuyuki; Matsumori, Tomoaki; Gon, Katsushige; Tomonari, Akiko

2013-01-01

28

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

29

Maintenance of remission with infliximab in inflammatory bowel disease: Efficacy and safety long-term follow-up  

PubMed Central

AIM: To evaluate the safety and efficacy of a long-term therapy with infliximab in Crohn’s disease (CD) and ulcerative colitis (UC) patients retrospectively. METHODS: The medical charts of 50 patients (40 CD and 10 UC), who received after a loading dose of 3 infliximab infusions scheduled re-treatments every 8 wk as a maintenance protocol, were reviewed. RESULTS: Median (range) duration of treatment was 27 (4-64) mo in CD patients and 24.5 (6-46) mo in UC patients. Overall, 32 (80%) CD and 9 (90%) UC patients showed a sustained clinical response or remission throughout the maintenance period. Three CD patients shortened the interval between infusions. Eight (20%) CD patients and 1 UC patient underwent surgery for flare up of disease. Nine out of 29 CD and 4 out of 9 UC patients, who discontinued infliximab scheduled treatment, are still relapse-free after a median of 16 (5-30) and 6.5 (4-16) mo following the last infusion, respectively. Ten CD patients (25%) and 1 UC patient required concomitant steroid therapy during maintenance period, compared to 30 (75%) and 9 (90%) patients at enrolment. Of the 50 patients, 16 (32%) experienced at least 1 adverse event and 3 patients (6%) were diagnosed with cancer during maintenance treatment. CONCLUSION: Scheduled infliximab strategy is effective in maintaining long-term clinical remission both in CD and UC and determines a marked steroid sparing effect. Long-lasting remission was observed following infliximab withdrawal. PMID:17876895

Caviglia, Renato; Ribolsi, Mentore; Rizzi, Marina; Emerenziani, Sara; Annunziata, Maria Laura; Cicala, Michele

2007-01-01

30

Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: A randomized, double-blind, placebo-controlled trial  

Microsoft Academic Search

Objective. To evaluate the safety and efficacy of long-term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA). Methods. In a randomized, double-blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The

Jean-Pierre Raynauld; Chris Buckland-Wright; Rupert Ward; Denis Choquette; Boulos Haraoui; Johanne Martel-Pelletier; Imad Uthman; Visithan Khy; Jean-Luc Tremblay; Carole Bertrand; Jean-Pierre Pelletier

2003-01-01

31

Long-term efficacy, safety, and side effect profile of botulinum toxin in dystonia: a 20-year follow-up.  

PubMed

Most long-term studies of the efficacy and safety profile of botulinum toxin (BoNT) in the treatment of dystonia are limited by lack of objective assessments, relatively small sample size, or short follow-up periods. We present one of the longest follow-up studies of BoNT treatment. This is a retrospective, longitudinal study that analyzes data on 89 patients treated with BoNT for dystonia at our Movement Disorders Clinic for up to 26 years (mean follow-up period of 18.5 years). The mean ages at the time of the first and last injections were 49 and 68 years old, respectively. The most common diagnoses were cervical dystonia (N = 51), blepharospasm (N = 34), and oromandibular dystonia (N = 26). The total number of onabotulinumtoxinA units received during the first injection was 140.3 as compared to 224.5 at the last injection (p < 0.0001). The global response effect was 3.18 after the first injection session and 3.57 after the last injection (p < 0.0001). The duration of response after the initial injection session and at the last injection was 16.33 weeks versus 19.42 weeks (p 0.0037), respectively. Adverse events, typically related to injection site, were reported in 19% of the visits. This series of dystonia patients with the longest reported treatment with BoNT provide evidence that in selected patients repeated chemodenervation is associated with sustained symptomatic benefit, decreased latency effect, and prolonged duration of therapeutic response. Despite the higher requirement of mean units per visit over time, only 19% of all treatment cycles are associated with adverse, but tolerable, side effects. PMID:25130293

Ramirez-Castaneda, Juan; Jankovic, Joseph

2014-11-01

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

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

34

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

35

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

36

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

37

Design of, and first data from, PATRO Children, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope® in children requiring growth hormone treatment  

PubMed Central

Objective: To describe the rationale, design and first data from PATRO Children, a postmarketing surveillance of the long-term efficacy and safety of somatropin (Omnitrope®) for the treatment of children requiring growth hormone treatment. Methods: PATRO Children is a multicentre, open, longitudinal, noninterventional study being conducted in children’s hospitals and specialised endocrinology clinics. The primary objective is to assess the long-term safety of Omnitrope® in routine clinical practice. Eligible patients are infants, children and adolescents (male or female) who are receiving treatment with Omnitrope® and who have provided informed consent. Patients who have been treated with another recombinant human growth hormone (rhGH) product before starting Omnitrope® are eligible for inclusion. All adverse events (AEs) are monitored and recorded, with particular emphasis on: long-term safety; the recording of malignancies; the occurrence and clinical impact of anti-hGH antibodies; the development of diabetes during Omnitrope® treatment in children short for gestational age (SGA); safety issues in patients with Prader–Willi syndrome (PWS). Efficacy assessments include auxological parameters, plus insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Results: As of September 2012, 1837 patients were enrolled in the study from 184 sites in 10 European countries. To date, efficacy data are reassuring and consistent with previous studies. In addition, there have been no confirmed cases of diabetes occurring under Omnitrope® treatment, no reports of malignancy and no safety issues in PWS patients. Conclusions: The efficacy and safety profile of Omnitrope® in the PATRO Children study so far are as expected. The ongoing study will extend the safety database for Omnitrope®, and rhGH products more generally, in paediatric indications. Of particular interest, PATRO Children will add important information on the diabetogenic potential of rhGH in children born SGA, the risk of malignancies in children receiving rhGH, and AEs with a possible causal relationship to rhGH treatment in children with PWS. PMID:23515245

Pfäffle, Roland; Schwab, Karl Otfried; Marginean, Otilia; Walczak, Mieczyslaw; Szalecki, Mieczyslaw; Schuck, Ellen; Zucchini, Stefano

2013-01-01

38

Safety and efficacy of long-term esomeprazole 20?mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs  

PubMed Central

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan. Methods This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20?mg once daily) in Japanese patients (aged ?20?years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive. Results A total of 130 patients (73.1% women, mean age 62.1?years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased ?-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1?year. Conclusion Long-term treatment with esomeprazole (20?mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer. Trial registration ClinicalTrials.gov identifier NCT00595517. PMID:23530709

2013-01-01

39

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

PubMed

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

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

Long-Term Efficacy and Safety of Atazanavir/Ritonavir Treatment in a Real-Life Cohort of Treatment-Experienced Patients with HIV Type 1 Infection  

PubMed Central

Abstract Atazanavir-based regimens have established efficacy and safety in both antiretroviral (ARV)-naive and -experienced patients. However, data evaluating effectiveness beyond 2 years is sparse. Therefore, we assessed the long-term outcomes of ritonavir-boosted atazanavir (ATV/r)-containing regimens in ARV-experienced patients in a clinical setting in a noncomparative, retrospective, observational study collecting data from three European HIV databases on ARV-experienced adults with HIV-1 infection starting an ATV/r-based regimen. Data were extracted every 6 months (maximum follow-up 5 years). Primary outcome was the proportion of patients remaining on ATV/r by baseline HIV-1 RNA (<500 or ?500?copies/ml). Secondary outcomes included time to virologic failure, reasons for discontinuation, and long-term safety profile. The duration of treatment and time to virologic failure were analyzed using the Kaplan–Meier method. Data were analyzed for 1,294 ARV-experienced patients (male 74%; mean ART exposure 5.7 years). After 3 years, 56% (95% CI: 52%, 60%) of patients with baseline HIV-1 RNA <500?copies/ml and 53% (95% CI: 49%, 58%) of those with HIV-1 RNA ?500?copies/ml remained on ATV/r. After 3 years, 75% (95% CI: 69%, 80%) of patients with baseline HIV-1 RNA <50?copies/ml remained suppressed and 51% (95% CI: 47%, 55%) of those with baseline HIV-1 RNA ?50?copies/ml achieved and maintained virologic suppression. Although adverse events (AEs) were the main known reason for discontinuation, no unexpected AEs were observed. In a real-life setting ATV/r-based regimens demonstrated sustained virologic suppression in ARV-experienced patients. After long-term therapy the majority of patients remained on treatment and no unexpected AEs were observed. PMID:23016535

Sönnerborg, Anders; Brockmeyer, Norbert; Thalme, Anders; Svedhem, Veronica; Dupke, Stephan; Eychenne, Jean-Luc; Nakonz, Tina; Jimenez-Exposito, Maria Jesus; Pugliese, Pascal

2013-01-01

42

Long-term safety, efficacy, and patient acceptability of teriparatide in the management of glucocorticoid-induced osteoporosis  

PubMed Central

Glucocorticoids are commonly prescribed medications to treat multiple diseases across many medical specialties. One of the most common yet largely unappreciated side effect of glucocorticoid use is increased risk of fracture. Many different therapies are indicated to prevent and treat this condition; many guidelines exist that suggest appropriate use of both glucocorticoids and the medications approved to prevent this common side effect of glucocorticoid therapy. Nevertheless, 30%–50% of patients on long-term glucocorticoid therapy sustain a fracture. Teriparatide, recombinant human parathyroid hormone (1–34), is a daily self-injectable therapy for 24 months approved for use in patients taking long-term glucocorticoids. Teriparatide has been shown to increase bone mineral density and reduce vertebral fracture risk in glucocorticoid-treated patients. Glucocorticoids have many adverse effects on bone that teriparatide has been shown to prevent or negate. Given the fact that preventive therapy for glucocorticoid-induced osteoporosis is often not prescribed, one wonders whether a daily self-injectable therapy for this condition would be prescribed by physicians and accepted by patients. This article reviews the epidemiology, pathophysiology, treatment, guidelines, and persistence data (when available) for patients with glucocorticoid-induced osteoporosis treated with teriparatide. PMID:23717037

Dore, Robin K

2013-01-01

43

Long-term efficacy, tolerability and safety of nalmefene as-needed in patients with alcohol dependence: A 1-year, randomised controlled study.  

PubMed

This study evaluated the long-term efficacy and safety of nalmefene treatment in reducing alcohol consumption. We randomised (1:3) 675 alcohol-dependent patients ? 18 years of age to 52 weeks of as-needed treatment with placebo or nalmefene 18 mg/day: A total of 112 patients (68%) in the placebo group and 310 (62%) in the nalmefene group completed the study. At month 6, the co-primary outcome variables showed no statistically-significant differences between the treatment groups; but at month 13, nalmefene was more effective than placebo, both in the reduction of the number of heavy drinking days (HDDs) (- 1.6 days/month (95% CI - 2.9; - 0.3); p = 0.017) and the reduction of total alcohol consumption (TAC) (- 6.5 g/day last month (95% CI - 12.5; - 0.4); p = 0.036). In a subgroup analysis of patients with high/very high drinking risk levels at screening and at randomisation (the target population), there was a significant effect in favour of nalmefene on TAC at month 6, and on both HDD and TAC at month 13. Improvements in Clinical Global Impression and liver enzymes were greater with nalmefene, compared to placebo. Most adverse events were mild or moderate, and transient; adverse events, including those leading to dropout, were more common with nalmefene. This study provides evidence for the long-term safety and efficacy of nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily, following a brief intervention. PMID:24671340

van den Brink, Wim; Sørensen, Per; Torup, Lars; Mann, Karl; Gual, Antoni

2014-03-26

44

Preclinical randomised safety, efficacy and physiologic study of the silicon dioxide inert-coated Axetis and bare metal stent: short-, mid- and long-term outcome.  

PubMed

Aims: To evaluate the short-, mid- and long-term safety, efficacy and vascular physiology of Axetis silicon dioxide (SiO2, abrading the micropores) inert-coated stent implantation in a randomised preclinical setting. Methods and results: Coronary arteries of domestic pigs were randomised to receive either Axetis or BMS (same design) stents with one-, three- and six-month follow-up (FUP), controlled by coronary angiography, optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histology (n=32). The time-dependent vasomotor reaction of coronary arteries to stenting was measured using modified myography (n=12). Complete endothelialisation of the Axetis stent was confirmed by OCT, IVUS and histology at one-month FUP. Histopathology revealed continuous healing of the vessel wall with a gradual reduction of inflammation and fibrin score during the six-month FUP in both stent types. Significantly smaller neointimal area and %area stenosis were measured in Axetis stents compared with BMS at each FUP time point. Vascular reactivity measurements showed significantly better endothelium-dependent vasodilation of stented arteries with Axetis implantation. Conclusions: Implantation of the Axetis SiO2-coated stent resulted in a significantly better safety, efficacy and vessel physiology profile compared with BMS of the same design with a continuous decrease in vessel inflammation during the six-month FUP. PMID:24769439

Pavo, Noemi; Syeda, Bonni; Bernhart, Andreas; Szentirmai, Eszter; Hemetsberger, Rayyan; Samaha, Eslam; Plass, Christian; Zlabinger, Katrin; Pavo, Imre J; Petrasi, Zsolt; Petnehazy, Ors; Hoerstrup, Simon P; Maurer, Gerald; Gyöngyösi, Mariann

2014-04-29

45

Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8years.  

PubMed

Long-term (up to 8years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ?50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained. PMID:25461210

Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

2014-12-01

46

An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain  

Microsoft Academic Search

BACKGROUND: Opioid analgesics have proven efficacy in the short-term management of chronic cancer pain, but data on their long-term use is more limited. OROS® hydromorphone is a controlled-release formulation of oral hydromorphone that may be particularly well suited to long-term management of chronic cancer pain because it provides stable plasma concentrations and consistent analgesia with convenient once-daily dosing. The objective

Magdi Hanna; Alberto Tuca; John Thipphawong

2009-01-01

47

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

48

A new antiresorptive approach to the treatment of fragility fractures: long-term efficacy and safety of denosumab.  

PubMed

An imbalance of the remodeling process for bone resorption leads to a loss of tissue with consequent microarchitectural damage, evident in conditions such as osteoporosis and related fragility fractures. Currently, pharmacological therapies are able to prevent or slow down bone resorption by inhibiting osteoclast activity. An innovative and targeted anti-resorptive approach is represented by the inhibition of RANK ligand (RANK-L), essential for the proliferation and activity of osteoclastic cells. The human monoclonal antibody against RANK-L (denosumab) has been approved for the treatment of osteoporosis. In clinical trials of patients with osteoporosis, inhibition of RANK-L has reduced bone loss and damage to the microarchitecture and was associated with an increase in mass and resistance at different skeletal sites, with most significant effects than those demonstrated by any other antiresorptive drugs. In addition, after 3 years of treatment, it showed a reduction in vertebral and non-vertebral fracture risk. Denosumab treatment also has not revealed any alteration in the physiological processes of fracture repair, showing no increase in the onset of complications 3 years after the fracture. The data show that denosumab offers an effective alternative therapeutic approach for the treatment of severe osteoporosis, with positive effects on BMD and reduction of fragility fractures risk. So, promising results in terms of therapeutic efficacy and reliability make desirable the wide clinical use of denosumab for the treatment of osteoporotic fractures in the near future. PMID:24046047

Tarantino, Umberto; Celi, Monica; Feola, Maurizio; Liuni, Federico Maria; Resmini, Giuseppina; Iolascon, Giovanni

2013-10-01

49

Central Venous Catheter Salvage in Home Parenteral Nutrition Catheter-Related Bloodstream Infections: Long-Term Safety and Efficacy Data.  

PubMed

Background: Catheter-related bloodstream infections (CRBSIs) are a serious complication in the provision of home parenteral nutrition (HPN). Antibiotic salvage of central venous catheters (CVCs) in CRBSI is recommended; however, this is based on limited reports. We assessed the efficacy of antibiotic salvage of CRBSIs in HPN patients. Materials and Methods: All confirmed CRBSIs occurring in patients receiving HPN in a national intestinal failure unit (IFU), between 1993 and 2011, were analyzed. A standardized protocol involving antibiotic and urokinase CVC locks and systemic antibiotics was used. Results: In total, 588 patients were identified with a total of 2134 HPN years, and 297 CRBSIs occurred in 137 patients (65 single and 72 multiple CRBSIs). The overall rate of CRBSI in all patients was 0.38 per 1000 catheter days. Most (87.9%) infections were attributable to a single microorganism. In total, 72.5% (180/248) of CRBSIs were salvaged when attempted (coagulase-negative staphylococcus, 79.8% [103/129], Staphylococcus aureus, 56.7% [17/30]; polymicrobial infections, 67.7% [21/30]; and miscellaneous, 66.1% [39/59]). CVC salvage was not attempted in 49 episodes because of life-threatening sepsis (n = 18), fungal infection (n = 7), catheter problems (n = 20), and CVC tunnel infection (n = 4). Overall, the CVC was removed in 33.7% (100/297) of cases. There were 5 deaths in patients admitted to the IFU for management of the CRBSI (2 severe sepsis at presentation, 3 metastatic infection). Conclusions: This is the largest reported series of catheter salvage in CRBSIs and demonstrates successful catheter salvage in most cases when using a standardized protocol. PMID:25224728

Dibb, Martyn J; Abraham, Arun; Chadwick, Paul R; Shaffer, Jon L; Teubner, Antje; Carlson, Gordon L; Lal, Simon

2014-09-15

50

Long term safety, efficacy, and patient acceptability of hyaluronic acid injection in patients with painful osteoarthritis of the knee  

PubMed Central

The increasing prevalence of painful knee osteoarthritis has created an additional demand for pharmacologic management to prevent or delay surgical management. Viscosupplementation, via intraarticular injection of hyaluronic acid (HA), aims to restore the favorable milieu present in the nonarthritic joint. The safety profile of intraarticular HA injections for painful knee osteoarthritis is well established, with the most common adverse effect being a self-limited reaction at the injection site. Although acceptance of the early literature has been limited by publication bias and poor study quality, more recent and rigorous meta-analysis suggests that intraarticular HA injection is superior to placebo injection for pain relief and matches, if not surpasses, the effect size of other nonoperative treatments, such as nonsteroidal anti-inflammatory medication. Intraarticular HA injection is effective in providing temporary pain relief in patients with painful knee osteoarthritis. Future investigations should focus on optimizing the composition and administration of HA agents to provide prolonged relief of painful osteoarthritis in the knee and other joints. PMID:23271899

McArthur, Benjamin A; Dy, Christopher J; Fabricant, Peter D; Valle, Alejandro Gonzalez Della

2012-01-01

51

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

PubMed

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 × 10(9)/L and 411 × 10(9)/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 × 10(9)/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600 × 10(9)/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

2014-04-01

52

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

53

Long-term efficacy and safety of statin treatment beyond six years: a meta-analysis of randomized controlled trials with extended follow-up.  

PubMed

Large-scale randomized controlled trials (RCTs) have well demonstrated the beneficial effects of cholesterol-lowering treatment with statins in patients at high risk of vascular disease. However, large statin RCTs were usually restricted to the typical 5-6 years. Moreover, non-cardiovascular events, especially the risk of cancer, probably failed to emerge within a restricted period of 6 years. The aim of this study was to evaluate the long-term efficacy and safety of statin treatment by performing a meta-analysis of statin RCTs with extended follow-up beyond 6 years. Six RCTs with post-trial follow-up were eligible for inclusion, involving 47,296 patients with total follow-up ranging from 6.7 to 14.7 years. During the post-trial period, all the surviving participants were advised to take a statin and the cholesterol level were almost identical between the original statin group and the original placebo group. Over the entire 6.7-14.7 years of follow-up, a significant reduction in the rates of all-cause mortality (relative risk 0.90, 95% confidence interval 0.85-0.96; P=0.0009), cardiovascular mortality (0.87, 0.81-0.93; P<0.0001) and major coronary events (0.79, 0.72-0.86; P<0.00001) was observed in favour of the original statin group. During 2-year post-trial period, further reduction in all-cause mortality (0.83, 0.74-0.93; P=0.001), cardiovascular mortality (0.81, 0.69-0.95; P=0.01) and major coronary events (0.77, 0.63-0.95; P=0.01) was observed among initially statin-treated patients. Over the entire follow-up period, statin treatment did not increase the incidence of cancers (0.99, 0.95-1.04; P=0.79), deaths from cancers (1.00, 0.93-1.07; P=0.98) and non-cardiovascular mortality (0.95, 0.90-1.00; P=0.07). In conclusion, statin treatment beyond 6 years is effective and safe in patients at high risk of vascular events. Moreover, earlier treatment with statin may not only preserve the initial benefit but also have further survival benefit for additional 2 years. Further studies are called for to explore the underlying mechanisms. PMID:24602799

Lv, Han-lu; Jin, Dong-mei; Liu, Mo; Liu, Ying-mei; Wang, Jing-feng; Geng, Deng-feng

2014-03-01

54

Long-Term Efficacy and Tolerability of Lanthanum Carbonate: Results from a 3Year Study  

Microsoft Academic Search

Background: Control of serum phosphate over the long term is essential in patients with end-stage renal disease. Six-month and 2-year extensions to a 6-month study evaluated the long-term safety, tolerability and efficacy of the new phosphate binder lanthanum carbonate. Methods: Patients who participated in a 6-month, randomized trial comparing lanthanum carbonate with calcium carbonate were eligible for a 24-week, open-label

Alastair J. Hutchison; Bart Maes; Johan Vanwalleghem; Gernot Asmus; Elfatih Mohamed; Roland Schmieder; Wolfgang Backs; Rene Jamar; Andre Vosskühler

2006-01-01

55

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

56

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

57

The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease  

PubMed Central

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20?years after motor onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the ‘NEST-UK’ consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients. This paper describes the long-term follow up over a 3–10-year postoperative period of the patients, grafted and non-grafted, recruited to this cohort using the ‘Core assessment program for intracerebral transplantations-HD’ assessment protocol. No significant differences were found over time between the patients, grafted and non-grafted, on any subscore of the Unified Huntington's Disease Rating Scale, nor on the Mini Mental State Examination. There was a trend towards a slowing of progression on some timed motor tasks in four of the five patients with transplants, but overall, the trial showed no significant benefit of striatal allografts in comparison with a reference cohort of patients without grafts. Importantly, no significant adverse or placebo effects were seen. Notably, the raclopride positron emission tomography (PET) signal in individuals with transplants, indicated that there was no obvious surviving striatal graft tissue. This study concludes that fetal striatal allografting in HD is safe. While no sustained functional benefit was seen, we conclude that this may relate to the small amount of tissue that was grafted in this safety study compared with other reports of more successful transplants in patients with HD. PMID:23345280

Barker, Roger A; Mason, Sarah L; Harrower, Timothy P; Swain, Rachel A; Ho, Aileen K; Sahakian, Barbara J; Mathur, Raj; Elneil, Sohier; Thornton, Steven; Hurrelbrink, Carrie; Armstrong, Richard J; Tyers, Pam; Smith, Emma; Carpenter, Adrian; Piccini, Paola; Tai, Yen F; Brooks, David J; Pavese, Nicola; Watts, Colin; Pickard, John D; Rosser, Anne E; Dunnett, Stephen B

2013-01-01

58

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

59

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

60

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

61

Long-term safety and efficacy of selective laser trabeculoplasty as primary therapy for the treatment of pseudoexfoliation glaucoma compared with primary open-angle glaucoma  

PubMed Central

Purpose To investigate the safety and efficacy of selective laser trabeculoplasty (SLT) to reduce intraocular pressure (IOP) in patients with pseudoexfoliation glaucoma (PXFG) compared with primary open-angle glaucoma (POAG). Design Non-randomized, prospective, clinical trial. Methods Nineteen eyes of 13 patients with POAG and 18 eyes of 13 patients with PXFG were treated with SLT. Patients were followed without antiglaucoma medications until additional medical, laser, or surgical intervention was initiated, at which time they were considered failures, had withdrawn from the study, or underwent a second SLT. Results The POAG and PXFG eyes showed similar reductions of IOP over the 49 months of follow-up. At 30 months of follow-up the POAG group showed a mean IOP of 17.6 ± 2.8 mmHg and a mean IOP reduction of 5.7 ± 2.1 mmHg; the PXFG group showed a mean IOP of 18.3 ± 4.7 and a mean IOP reduction of 5.3 ± 3.0 mmHg. Four eyes in the PXFG group and three eyes in the POAG group failed by 30 months. The cumulative probability of success was 74% for the PXFG group and 77% for the POAG group. Four PXFG eyes underwent a second SLT after 30 months of follow-up with a final IOP of 17.6 ± 2.8 mmHg. There were no serious adverse events. Conclusion SLT is a safe and effective method to lower IOP in patients with PXFG as initial glaucoma therapy. Both groups showed similar IOP reductions and failure rates. PMID:21311650

Shazly, Tarek A; Smith, Jan; Latina, Mark A

2011-01-01

62

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

63

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

64

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

65

Clinical efficacy, radiographic and safety findings through 2?years of golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of the randomised, placebo-controlled GO-REVEAL study  

PubMed Central

Objectives To assess long-term golimumab efficacy/safety in patients with active psoriatic arthritis (PsA). Methods Adult PsA patients (?3 swollen, ?3 tender joints, active psoriasis) were randomly assigned to subcutaneous injections of placebo, golimumab 50?mg or 100?mg every 4?weeks (q4wks) through week 20. All patients received golimumab 50 or 100?mg beginning week 24. Findings through 2?years are reported. Efficacy evaluations included ?20% improvement in American College of Rheumatology (ACR20) response, good/moderate response in Disease Activity Scores incorporating 28 joints and C-reactive protein (DAS28-CRP), ?75% improvement in Psoriasis Area and Severity Index (PASI75) and changes in PsA-modified Sharp/van der Heijde scores (SHS). Results Golimumab treatment through 2?years was effective in maintaining clinical response (response rates: ACR20 63%–70%, DAS28-CRP 77%–86%, PASI75 56%–72%) and inhibiting radiographic progression (mean change in PsA-modified SHS in golimumab-treated patients: ?0.36), with no clear difference between doses. No new safety signals were identified through 2?years. With the study's tuberculosis screening and prophylactic measures, no patient developed active tuberculosis through 2?years. Conclusions Golimumab 50 and 100?mg for up to 2?years yielded sustained clinical and radiographic efficacy when administered to patients with active PsA. Increasing the golimumab dose from 50 to 100?mg q4wks added limited benefit. Golimumab safety through up to 2?years was consistent with other antitumour necrosis factor ? agents used to treat PsA. Treatment of patients with latent tuberculosis identified at baseline appeared to be effective in inhibiting the development of active tuberculosis. PMID:23161902

Kavanaugh, Arthur; McInnes, Iain B; Mease, Philip J; Krueger, Gerald G; Gladman, Dafna D; van der Heijde, Désirée; Mudivarthy, Surekha; Xu, Weichun; Mack, Michael; Xu, Zhenhua; Beutler, Anna

2013-01-01

66

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

67

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

68

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

69

Efficacy of long term weekly ACTH therapy for intractable epilepsy.  

PubMed

Background: Adrenocorticotropic hormone (ACTH) therapy is the first-line therapy for infantile spasms, and is effective for many other intractable epilepsies. While spasms may respond to ACTH for weeks, a substantial proportion of patients develop recurrent seizures over a yearly period. To maintain efficacy, we treated two children with intractable epilepsy with weekly ACTH therapy for 1year and described the changes in clinical seizures, electroencephalograms, developmental assessments and side effects. Subjects and methods: A girl with infantile spasms due to lissencephaly and a boy with atypical absence seizures were studied. In both cases, seizures were frequent and resistant to antiepileptic drugs; electroencephalograms showed continuous epileptiform activities, and the patients' development was delayed and stagnant prior to ACTH treatment. The initial ACTH therapy (daily 0.015mg/kg for 2weeks, 0.015mg/kg every 2days for 1week, 0.0075mg/kg every 2days for 1week), was transiently effective in both cases. The second-round ACTH therapy consisted of the initial ACTH therapy protocol followed by weekly ACTH injections (0.015mg/kg or 0.0075mg/kg) for 1year. Both cases were followed for at least 1year after therapy. Results: In both patients, clinical seizures were completely controlled during and 1year after the second-round AHCH therapy. Continuous epileptiform discharges disappeared, while intermittent interictal epileptiform discharges remained. Both patients showed some developmental gains after achieving seizure control. No serious side effects were recorded. Conclusion: Further studies are warranted to determine if a long-term weekly ACTH is a safe and effective treatment for intractable epilepsy. PMID:25149137

Inui, Takehiko; Kobayashi, Tomoko; Kobayashi, Satoru; Sato, Ryo; Endo, Wakaba; Kikuchi, Atsuo; Nakayama, Tojo; Uematsu, Mitsugu; Takayanagi, Masaru; Kato, Mitsuhiro; Saitsu, Hirotomo; Matsumoto, Naomichi; Kure, Shigeo; Haginoya, Kazuhiro

2014-08-19

70

Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment  

Microsoft Academic Search

Purpose  To investigate the efficacy and safety of dienogest as a long-term treatment in endometriosis, with follow-up after treatment\\u000a discontinuation. The study included women with endometriosis, who had previously completed a 12-week, placebo-controlled study\\u000a of dienogest, who participated in an open-label extension study for up to 53 weeks. Thereafter, a patient subgroup was evaluated\\u000a in a 24-week follow-up after treatment discontinuation.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A

Felice Petraglia; Daniela Hornung; Christian Seitz; Thomas Faustmann; Christoph Gerlinger; Stefano Luisi; Lucia Lazzeri; Thomas Strowitzki

71

Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis.  

PubMed

Myasthenia gravis (MG) is a chronic autoimmune disorder with a fluctuating clinical course. The aim of immunotherapy is to bring about long-term remission. We evaluated the safety and efficacy of cyclophosphamide in generalized MG. We also highlight the limitations of cyclophosphamide therapy in inducing long-term remission. Data from 22 patients with generalized MG who received cyclophosphamide therapy were analyzed in terms of its safety and outcome. Twelve patients completed at least six pulses of intravenous cyclophosphamide therapy, and all improved symptomatically at 6 months. At 1 year, only seven patients reported sustained benefit and five had discontinued oral pyridostigmine. During a follow-up period of 56.67 months, all but one patient relapsed and required alternative immunomodulatory therapy. The average time to remission after the initiation of intravenous pulse cyclophosphamide (n=12) was 3.6 months (standard deviation [SD] 1.6 months, range 1-6 months), while the mean duration of remission was 20.3 months (SD 8.8 months, range 12-39 months). Forty-six adverse events were documented in 11 patients over 127 cyclophosphamide pulses. Most of the adverse events were managed symptomatically. In four patients, cyclophosphamide had to be discontinued due to adverse events. Intravenous pulse cyclophosphamide is effective in the management of MG; however remission may be short, necessitating long-term follow-up and alternative immunomodulation. Careful monitoring for adverse events should be mandatory. PMID:25043165

Nagappa, M; Netravathi, M; Taly, A B; Sinha, S; Bindu, P S; Mahadevan, A

2014-11-01

72

Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo (Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study  

PubMed Central

Hochu-ekki-to is a traditional herbal (Kampo) medicine that has been shown to be effective for patients with Kikyo (delicate, easily fatigable, or hypersensitive) constitution. Previous case reports have suggested that this herbal drug was effective for a certain subgroup of patients with atopic dermatitis (AD). We aimed to evaluate the efficacy and safety of Hochu-ekki-to in the long-term management of Kikyo patients with AD. In this multicenter, double blind, randomized, placebo-controlled study, 91 Kikyo patients with AD were enrolled. Kikyo condition was evaluated by a questionnaire scoring system. All patients continued their ordinary treatments (topical steroids, topical tacrolimus, emollients or oral antihistamines) before and after their protocol entry. Hochu-ekki-to or placebo was orally administered twice daily for 24 weeks. The skin severity scores, total equivalent amount (TEA) of topical agents used for AD treatment, prominent efficacy (cases with skin severity score = 0 at the end of the study) rate and aggravated rate (more than 50% increase of TEA of topical agents from the beginning of the study) were monitored and evaluated. Seventy-seven out of 91 enrolled patients completed the 24-week treatment course (Hochu-ekki-to: n = 37, placebo: n = 40). The TEA of topical agents (steroids and/or tacrolimus) was significantly (P < 0.05) lower in the Hochu-ekki-to group than in the placebo group, although the overall skin severity scores were not statistically different. The prominent efficacy rate was 19% (7 of 37) in the Hochu-ekki-to group and 5% (2 of 40) in the placebo group (P = 0.06). The aggravated rate was significantly (P < 0.05) lower in the Hochu-ekki-to group (3%; 1 of 37) than in the placebo group (18%; 7 of 39). Only mild adverse events such as nausea and diarrhea were noted in both groups without statistical difference. This placebo-controlled study demonstrates that Hochu-ekki-to is a useful adjunct to conventional treatments for AD patients with Kikyo constitution. Use of Hochu-ekki-to significantly reduces the dose of topical steroids and/or tacrolimus used for AD treatment without aggravating AD. PMID:18955318

Ishii, Masamitsu; Takeuchi, Satoshi; Tanaka, Yoichi; Shintani, Takahiro; Yamatodani, Atsushi; Kusunoki, Tadashi; Furue, Masutaka

2010-01-01

73

Long-term safety and efficacy of a once-daily niacin\\/ lovastatin formulation for patients with dyslipidemia * * A complete list of participants in the Research Group and Publication Committee appears in the Appendix  

Microsoft Academic Search

Combination therapy is increasingly recommended for patients with multiple lipid disorders, especially those at high risk for coronary events. We investigated the long-term safety and effectiveness of a new drug formulation containing once-daily extended-release niacin and lovastatin. A total of 814 men and women (mean age 59 years) with dyslipidemia were enrolled in a 52-week multicenter, open-label study. We used

Moti L Kashyap; Mark E McGovern; Kathleen Berra; John R Guyton; Peter O Kwiterovich; Wayne L Harper; Phillip D Toth; Laurence K Favrot; Boris Kerzner; Stephen D Nash; Harold E Bays; Phillip D Simmons

2002-01-01

74

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

75

Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia  

Microsoft Academic Search

Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia and premature coronary heart disease (CHD). The lower the plasma cholesterol level, the more likely it is that CHD can be prevented or retarded; aggressive cholesterol-lowering therapies may be indicated for FH patients with CHD. This study describes the long-term (6 years) safety and efficacy of intensive cholesterol-lowering therapies with low-density lipoprotein

Hiroshi Mabuchi; Junji Koizumi; Masami Shimizu; Kouji Kajinami; Susumu Miyamoto; Kousei Ueda; Tadayoshi Takegoshi

1998-01-01

76

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

77

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

78

Long-Term Efficacy of Intracoronary Irradiation in Inhibiting In-Stent Restenosis  

E-print Network

Long-Term Efficacy of Intracoronary Irradiation in Inhibiting In-Stent Restenosis David J. Brenner for inhibition of in-stent restenosis. Results of randomized clinical trials at 6 months after gamma ray promising modality for significantly delaying, although probably not preventing, in-stent restenosis

Brenner, David Jonathan

79

Long-term efficacy of miglustat in paediatric patients with Niemann-Pick disease type C.  

PubMed

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease characterized by progressive neurological manifestations. Oral miglustat was first approved for the treatment of children and adults with NP-C in Europe in 2009. There are still relatively few published data on the long-term efficacy and safety of miglustat in patients with NP-C in clinical practice. We report the effects of up to 6 years of treatment with miglustat 100 mg t.i.d. in five children. Overall, 3/5 patients displayed progressive dysphagia before starting miglustat, and 4/5 showed marked cognitive and/or motor impairment. The mean age at treatment start was 11.6 years, and the median (range) duration of therapy so far is 4 (4.1 to 6.1) years. No treatment dose alterations were required, but therapy was interrupted for 1-3 months at least once in all patients due to supply issues. Swallowing function was stabilised during miglustat therapy, with no significant increase in Han dysphagia scale or aspiration-penetration index scores among four evaluable patients (p > 0.05). Scores on the mini-mental state examination indicated an improvement in cognitive function during the first 3-6 months of miglustat therapy, followed by stabilisation up to 5 years. Ambulatory function remained stable for at least the first 2 years of treatment in most patients, but there was a trend towards deterioration thereafter, possibly related to treatment interruptions. The safety/tolerability profile of miglustat was similar to previous clinical studies, although reports of gastrointestinal disturbances were rare. Overall, miglustat appeared to stabilise key parameters of neurological disease progression. PMID:22476655

Chien, Y H; Peng, S F; Yang, C C; Lee, N C; Tsai, L K; Huang, A C; Su, S C; Tseng, C C; Hwu, W L

2013-01-01

80

Serum cholesterol levels modulate long-term efficacy of cholinesterase inhibitors in Alzheimer disease  

Microsoft Academic Search

The clinical, genetic or biological variables which regulate long-term efficacy of cholinesterase inhibitors (ChEIs) in Alzheimer disease (AD) are still unknown and it is not possible to predict who will benefit from the treatment. In this study we showed that high cholesterol levels correlated with faster decline at 1-year follow-up in AD patients on ChEIs. These findings suggest that serum

Barbara Borroni; Carla Pettenati; Tania Bordonali; Nabil Akkawi; Monica Di Luca; Alessandro Padovani

2003-01-01

81

Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration.  

PubMed

The aim of this study was to evaluate the long-term efficacy of haloperidol in autistic children and to determine whether discontinuous drug administration was as effective as continuous drug administration. Sixty children, 48 males and 12 females, ages 2.3 to 7.9 years (X 5.1) completed the study. They received haloperidol over a period of 6 months followed by a 4-week drug withdrawal/placebo period. Haloperidol remained effective, and the discontinuous treatment schedule did not diminish its efficacy. Children with prominent symptoms of irritability, angry and labile affect, and uncooperativeness were the best responders to haloperidol. PMID:2914841

Perry, R; Campbell, M; Adams, P; Lynch, N; Spencer, E K; Curren, E L; Overall, J E

1989-01-01

82

Long-term safety of dichloroacetate in congenital lactic acidosis.  

PubMed

We followed 8 patients (4 males) with biochemically and/or molecular genetically proven deficiencies of the E1? subunit of the pyruvate dehydrogenase complex (PDC; 3 patients) or respiratory chain complexes I (1 patient), IV (3 patients) or I+IV (1 patient) who received oral dichloroacetate (DCA; 12.5 mg/kg/12 h) for 9.7 to 16.5 years. All subjects originally participated in randomized controlled trials of DCA and were continued on an open-label chronic safety study. Patients (1 adult) ranged in age from 3.5 to 40.2 years at the start of DCA administration and are currently aged 16.9 to 49.9 years (mean ± SD: 23.5 ± 10.9 years). Subjects were either normal or below normal body weight for age and gender. The 3 PDC deficient patients did not consume high fat (ketogenic) diets. DCA maintained normal blood lactate concentrations, even in PDC deficient children on essentially unrestricted diets. Hematological, electrolyte, renal and hepatic status remained stable. Nerve conduction either did not change or decreased modestly and led to reduction or temporary discontinuation of DCA in 3 patients, although symptomatic worsening of peripheral neuropathy did not occur. We conclude that chronic DCA administration is generally well-tolerated in patients with congenital causes of lactic acidosis and is effective in maintaining normal blood lactate levels, even in PDC-deficient children not consuming strict ketogenic diets. PMID:23611579

Abdelmalak, Monica; Lew, Alicia; Ramezani, Ryan; Shroads, Albert L; Coats, Bonnie S; Langaee, Taimour; Shankar, Meena N; Neiberger, Richard E; Subramony, S H; Stacpoole, Peter W

2013-06-01

83

Long-term safety of India ink tattoos in the colon  

Microsoft Academic Search

Background: When the India ink tattoo is used as a guide for follow-up examinations, the tattoo may remain in the colon for the remainder of that patient's life. This raises the question of the long-term safety of India ink tattoos. The long-term clinical and histologic consequences of the tattoo have not been studied in a large group of patients. Methods:

Burton A. Shatz; Leonard B. Weinstock; Paul E. Swanson; Erik P. Thyssen

1997-01-01

84

Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02D malaria vaccine in infants living in a malaria-endemic region  

PubMed Central

Background The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02D vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20?months of follow up. Methods This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02D or hepatitis B vaccine at 8, 12, and 16?weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. Results From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02D (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18?months after completion of vaccination, 71.8% of recipients of RTS,S/AS02D and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02D and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02D group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p?=?0.072) and 26.7% (95% CI: -33.1 to 59.6, p?=?0.307) over 12 and 18?months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p?=?0.545). Conclusions The acceptable safety profile and good tolerability of RTS,S/AS02D in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20?month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02D group remained significantly higher compared to control for the study duration. Over 18?months follow up, RTS,S/AS02D prevented approximately a quarter of malaria cases in the study population. Clinical trials Gov identifier: NCT00289185 PMID:23297680

2013-01-01

85

Transplantation of Purified Autologous Leukapheresis-Derived CD34(+) and CD133(+) Stem Cells for Patients With Chronic Spinal Cord Injuries: Long-Term Evaluation of Safety and Efficacy.  

PubMed

This study is aimed at describing a novel method for treating patients with chronic complete spinal cord injuries (SCIs) by utilizing autologous, purified CD34(+) and CD133(+) stem cells (SCs). The study focuses on the safety and efficacy of transplanting unmanipulated, autologous, purified stem cells in treated patients during a 5-year follow-up period. In this report, 19 patients were included (16 males and 3 females) who presented with a complete SCI (ASIA-A) in the thoracic region. The patients' endogenous cells were mobilized with subcutaneous granulocyte-colony-stimulating factor (G-CSF) for 5 days. We utilized the CliniMACS magnetic separation system to purify leukapheresis-derived CD34(+) and CD133(+) SCs. Purified SCs were directly transplanted into the SCI site. Patients were then monitored and followed for up to 5 years. On average, 76?×?10(6) purified SCs were obtained from each patient, with 95.2% purity and >98% viability. SC transplantation into the cyst cavity or the subarachnoid space was successful and well tolerated in all 19 patients and did not cause any allergic or inflammatory reactions within the CNS in the early or late periods after transplantation. Ten patients (53%) showed no improvement after 42-60 months (ASIA-A), while seven patients (37%) demonstrated segmental sensory improvement (ASIA-B), and the remaining two patients (10%) had motor improvement (ASIA-C). This study presents a safe method for transplanting specific populations of purified autologous SCs that can be used to treat SCIs in a clinical setting. The results may be utilized as a stepping-stone for future investigations in the field of regenerative medicine for treatment of SCIs and other neurological diseases. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation. PMID:25372344

Al-Zoubi, Adeeb; Jafar, Emad; Jamous, Mohammad; Al-Twal, Feras; Al-Bakheet, Sameh; Zalloum, Mahasen; Khalifeh, Farah; Radi, Samer Abu; El-Khateeb, Mohammed; Al-Zoubi, Ziad

2014-01-01

86

Long-term carbimazole pretreatment reduces the efficacy of radioiodine therapy  

PubMed Central

Introduction: Data from several studies suggest that pretreatment with antithyroid drugs (ATD) before 131I increases the risk of treatment failure. This effect has been demonstrated more consistently with propylthiouracil than with carbimazole (CMZ) or methimazole (MMI). Men with Graves’ disease (GD) have a lower rate of remission with 131I compared to women and the impact of long-term ATD pretreatment on the success of 131I is unknown. The objective of our study was to compare the efficacy of fixed doses of radioiodine between patients with and without long-term CMZ pretreatment. Materials and Methods: We performed a retrospective study on 335 male patients with GD treated with 131I from 1998 to 2008. 148 patients had been pretreated with CMZ, and the remaining 187 patients received 131I without pretreatment. We compared the success rate of a single dose of 131I, between patients with and without long-term CMZ pretreatment. Results: The success rate of a single dose of 131I was significantly higher in patients without pretreatment than in patients who were pretreated with CMZ (91.4% vs. 82.3%, P = 0.01). The rate of hypothyroidism in the first 6 months after 131I therapy was significantly higher in patients without pretreatment (55.1% vs. 44.6%, P = 0.05). There was also a trend for higher cumulative rate of hypothyroidism at last follow-up in nonpretreated patients (78.1% vs. 69.7%). Conclusion: Male patients with Graves’ hyperthyroidism pretreated with CMZ have lower efficacy with 131I therapy compared to nonpretreated patients. CMZ pretreatment given for a prolonged period reduces the efficacy of 131I therapy. PMID:25593832

Shivaprasad, C.; Prasanna Kumar, K. M.

2015-01-01

87

ATO/ATRA/Anthracycline-Chemotherapy Sequential Consolidation Achieves Long-Term Efficacy in Primary Acute Promyelocytic Leukemia  

PubMed Central

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse-free survival (RFS) were 94.4%±3.9% and 94.6±3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL. PMID:25122165

Li, Xu-Dong; He, Yi; Xiao, Ruo-Zhi; Fang, Zhi-Gang; Wang, Dong-Ning; Liu, Jia-Jun; Yan, Jin-Song; Huang, Ren-Wei; Lin, Dong-Jun; Liu, Quentin

2014-01-01

88

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

89

The Efficacy and Long-Term Outcome of Microcoil Embolotherapy for Acute Lower Gastrointestinal Bleeding  

PubMed Central

Objective To evaluate the clinical efficacy as well as long-term clinical outcomes of superselective microcoil embolization for lower gastrointestinal bleeding (LGIB). Materials and Methods Between 1997 and 2009, 26 patients with intended transcatheter embolotherapy for LGIB were retrospectively reviewed. Embolization was performed only when the catheter could be advanced to or distal to the mesenteric border of the bowel. The main purpose of our study was to assess technical success, recurrent bleeding rate and complications. We also evaluated the long-term clinical outcome, including late recurrent LGIB, bowel ischemia and the survival rate. Results Twenty-two bleeding sources were in the territory of superior mesenteric artery and four in the inferior mesenteric artery. Technical success was achieved in 22 patients (84.6%). The target vessel of embolization was vasa recta in seventeen patients and marginal artery in the remaining five patients. Early rebleeding occurred in two patients (7.7%) and bowel ischemia in two patients, of whom the embolized points were both at the marginal artery. Delayed recurrent bleeding (> 30 days) occurred in two angiodysplasia patients. Five patients (19.2%) died within the first 30 days of intervention. Long-term follow-up depicted estimated survival rates of 58.2 and 43.1% after one, and five years, respectively. Conclusion Transcatheter embolotherapy to treat LGIB is effective with low rebleeding and ischemic complications. Considering the advanced age and complex medical problems of these patients, the minimal invasive embolotherapy may be used as both a primary and potentially definitive treatment of LGIB. PMID:23483780

Teng, Hui-Chung; Lin, Yih-Huie; Huang, Jer-Shyung; Chen, Chiung-Yu; Lee, Shang-Chieh; Pan, Huay-Ben

2013-01-01

90

LONG TERM EFFICACY OF BIOFEEDBACK THERAPY FOR DYSSYNERGIA -RANDOMIZED CONTROLLED TRIAL  

PubMed Central

Objectives Although biofeedback therapy is effective in the short term management of dyssynergic defecation, its long term efficacy is unknown. Our aim was to compare the one year outcome of biofeedback (manometric- assisted pelvic relaxation, and simulated defecation training), with standard therapy (diet, exercise, laxatives) in patients who completed 3 months of either therapy. Methods Stool diaries, visual analog scales (VAS), colonic transit, anorectal manometry, and balloon expulsion time were assessed at baseline, and at one year after each treatment. All subjects were seen at 3 month intervals and received reinforcement. Primary outcome measure (ITT analysis) was a change in the number of complete spontaneous bowel movements (CSBM) per week. Secondary outcome measures included bowel symptoms, changes in dyssynergia and anorectal function. Results Of 44 eligible patients with dyssynergic defecation, 26 agreed to participate in the long term study. All 13 subjects who received biofeedback, and 7 of 13 who received standard therapy completed one year; 6 failed standard therapy. The number of CSBMs/week increased significantly (p<0.001) in the biofeedback but not in the standard group. Dyssynergia pattern normalized (p<0.001), balloon expulsion time improved (p=0.0009), defecation index increased (p<0.001) and colonic transit time normalized (p=0.01) only in the biofeedback group. Conclusions Biofeedback therapy provided sustained improvement of bowel symptoms and anorectal function in constipated subjects with dyssynergic defecation while standard therapy was largely ineffective. PMID:20179692

Rao, Satish SC; Valestin, Jessica; Brown, C Kice; Zimmerman, Bridget; Schulze, Konrad

2013-01-01

91

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.

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

2014-01-01

92

Long-Term Safety of Oral Transmucosal Fentanyl Citrate for Breakthrough Cancer Pain  

Microsoft Academic Search

This open-label study evaluated the long-term safety and tolerability of oral transmucosal fentanyl citrate (OTFC) in ambulatory cancer patients with breakthrough pain undergoing cancer care at 32 university- or community-based practices. Patients had participated in a previous short-term titration trial of OTFC, were experiencing at least one episode per day of breakthrough pain, and had achieved relief of their breakthrough

Richard Payne; Paul Coluzzi; Lowell Hart; Mary Simmonds; Alan Lyss; Richard Rauck; Robert Berris; Michael A Busch; Earl Nordbrook; Diane B Loseth; Russell K Portenoy

2001-01-01

93

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

94

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

95

Long-term therapeutic efficacy of photo-selective vaporization of prostate  

NASA Astrophysics Data System (ADS)

OBJECTIVES: We evaluated the long term therapeutic efficacy of 80 watt photo-selective vaporization of the prostate (PVP) in patients suffering from lower urinary tract symptoms (LUTS) secondary to prostatic obstruction. MATERIAL & METHODS: 150 unselected patients at the average age 73 (range 51-92) and a mean American Society of Anesthesiologists score of 2.4 (median 2.0), of whom 33% were medicated with acetylsalicylic acid and 5% were anticoagulated with warfarin. Inclusion/exclusion criteria were the same as for TUR-P at our institution. First patient was operated March 2004 and yearly follow-up of all patients has been attempted for 5 years. Follow-up variables have included yearly creatinine, PSA, IPSS, ØOL, post-void residual urin and maximum/average urine flow rate. RESULTS: At 12 and 24 months postoperatively, the following parameters were significantly (p<0.001) improved: trans-rectal ultrasound, international prostate symptom score, quality of life score, post-void residual urine volume, flow max/average, opening pressure, pressure @ flow-max, and micturition resistance. At 48 and 60 months creatinine, PSA, IPSS, ØOL, post-void residual urin and maximum/average urine flow rates were still significantly (p<0.001) improved compared to pre-operative values. CONCLUSION: Up to 5 year follow-up reveals that 80 watt PVP provides significant and stable symptom relief as well as objective improvement in residual urine and flowmetric outcomes.

Arum, Carl-Jørgen; Muller, Camilla; Romundstad, Pal; Stokkan, Inger; Mjønes, Jan

2010-02-01

96

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

97

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

98

Safety features of budesonide inhalation suspension in the long-term treatment of asthma in young children  

Microsoft Academic Search

Early inhaled corticosteroid treatment improves symptom control and pulmonary function in children with asthma; however, long-term\\u000a safety data are limited in infants and young children. This study assessed the long-term safety of budesonide inhalation suspension\\u000a (BIS) in young children with persistent asthma. To continue to provide BIS to children who needed it—prior to US Food and\\u000a Drug Administration approval—children 8

Jeffrey G. Leflein; James W. Baker; Howard Eigen; Ewa Lyzell; Lawrence McDermott

2005-01-01

99

Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone  

Microsoft Academic Search

The identification of a safe, orally active iron chelator is critically important for the prevention of morbidity and early death in patients receiving regular red cell transfu- sions. Based on our findings in a 1-year multicenter, prospective study of the safety and efficacy of deferiprone in pa- tients with thalassemia major, we have extended the treatment period to 4 years.

Alan R. Cohen; Renzo Galanello; Antonio Piga; Vincenzo De Sanctis; Fernando Tricta

2003-01-01

100

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

101

Bioresorbable scaffolds: focus on vascular response and long-term safety.  

PubMed

Bioresorbable vascular scaffolds (BVS) are considered the fourth revolution in Interventional Cardiology, thus promising to address some of the pending issues with current-generation drug eluting stents (DES). Notably, most of the potential advantages of BVS over other current devices are due to a peculiar vascular response, called "vascular restoration therapy". The emerging data from real-world expanded use registries suggest that BVS use is feasible in a wide variety of patients (from low- to high- risk), and lesions (from simplex to complex). However, few safety concerns with currently available BVS have arised from initial experiences all over the word. Data from ongoing large-scale randomized controlled trials will be able to demonstrate whether BVS improve patient early and long-term outcomes compared to best-in-class DES. PMID:25373397

Scalone, G; Brugaletta, S; Gomez, O; Otsuki, S; Sabate, M

2015-03-01

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

Low long-term efficacy and tolerability of add-on rufinamide in patients with Dravet syndrome.  

PubMed

In this retrospective European multicenter study we evaluated the efficacy and tolerability of rufinamide in patients with Dravet syndrome and refractory seizures. Twenty patients were included; in 16 patients a SCN1A mutation was detected. The responder rate after 6 months was 20%, and after 34 months, 5%. The retention rate was 45% after 6 months and 5% after 34 months. Rufinamide treatment was stopped because of aggravation of seizures (30%), no effect (45%), and side effects (10%). The efficacy and long-term retention rate were low in our patients with Dravet syndrome and refractory seizures, far lower than in patients with Lennox-Gastaut syndrome; one-third of our patients experienced seizure aggravation. Therefore, rufinamide does not seem to be a suitable option for long-term treatment in patients with Dravet syndrome. PMID:21620771

Mueller, A; Boor, R; Coppola, G; Striano, P; Dahlin, M; von Stuelpnagel, C; Lotte, J; Staudt, M; Kluger, G

2011-07-01

104

Efficacy of adjuvant CYVADIC chemotherapy in early-stage uterine sarcomas: results of long-term follow-up  

Microsoft Academic Search

Odunsi K, Moneke V, Tammela J, Ghamande S, Seago P, Driscoll D, Marchetti D, Baker T, Lele S. Efficacy of adjuvant CYVADIC chemotherapy in early-stage uterine sarcomas: results of long-term follow-up. Int J Gynecol Cancer 2004;14:659—664. Data on adjuvant chemotherapy in early-stage uterine sarcomas are conflicting and most often based on small patient groups with relatively short duration of follow-up.

K. Odunsi; V. Moneke; J. Tammela; S. Ghamande; P. Seago; D. Driscoll; D. Marchetti; T. Baker; S. Lele

2004-01-01

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

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

107

Efficacy of Long-Term 4.0 g/Day Mesalazine (Pentasa) for Maintenance Therapy in Ulcerative Colitis  

PubMed Central

Background High-dose (4.0 g/day) mesalazine is typically used for induction therapy, but its efficacy as maintenance therapy remains to be determined. We conducted a multicenter retrospective study to investigate the efficacy of continuous treatment with 4.0 g/day of mesalazine. Material/Methods Japanese ulcerative colitis (UC) patients receiving acute induction therapy with 4.0 g/day mesalazine were enrolled and followed. Those who clinically improved or who achieved clinical remission were categorized into 2 sub-groups according to the median duration of treatment with 4.0 g/day of mesalazine. The clinical relapse frequency and the time to relapse were analyzed. Results We enrolled 180 patients with active UC, and then 115 patients who clinically improved or who achieved clinical remission after treatment with 4.0 g/day mesalazine were categorized into 2 sub-groups according to the median of treatment duration: a short-term treatment group (?105 days, n=58) and a long-term treatment group (>105 days, n=57). Overall, 45 (39.1%) patients relapsed: 28 (48.3%) in the short-term treatment group and 17 (29.8%) in the long-term treatment group. This difference was statistically significant (p<0.05). The relapse-free rate in the long-term treatment group was significantly higher than that in the short-term treatment group (p<0.05). The mean time to relapse in the long-term treatment group was significantly longer than that in the short-term treatment group (425.6±243.8 days vs. 277.4±224.5 days; p<0.05). Conclusions Long-term continuous treatment with high-dose mesalazine (4.0 g/day) may be more effective than short-term treatment for maintenance of remission in UC patients. PMID:25064629

Takeshima, Fuminao; Matsumura, Masato; Makiyama, Kazuya; Ohba, Kazuo; Yamakawa, Masaki; Nishiyama, Hitoshi; Yamao, Takuji; Akazawa, Yuko; Yamaguchi, Naoyuki; Ohnita, Ken; Ichikawa, Tatsuki; Isomoto, Hajime; Nakao, Kazuhiko

2014-01-01

108

Ziprasidone in Adolescents with Schizophrenia: Results from a Placebo-Controlled Efficacy and Long-Term Open-Extension Study  

PubMed Central

Abstract Objective The purpose of this study was to evaluate the short- and long-term efficacy, safety, and tolerability of ziprasidone in adolescents with schizophrenia. Methods Subjects ages 13–17 years with schizophrenia (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM-IV]) were enrolled in a 6 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE). Subjects were randomized in a 2:1 ratio to flexible-dose oral ziprasidone (40–160?mg/day, based on weight) or placebo. Primary end-point was change from baseline in Brief Psychiatric Rating Scale–Anchored (BPRS-A) total score. Safety assessments included adverse events, vital signs, laboratory measures, electrocardiograms, weight and body mass index, and movement disorder ratings. Results Planned interim analysis for the primary end-point in the RCT resulted in early termination of both studies because of futility. In the RCT, 283 subjects received ziprasidone (n=193) or placebo (n=90). In the intent-to-treat analysis population, the least squares mean (SE) BPRS–A score decrease from baseline at week 6 was not significantly different (p=0.15; ?14.16 [0.78] for ziprasidone and ?12.35 [1.05] for placebo). Per-protocol analysis was significant (p=0.02). In the OLE, 221 subjects entered the OLE and received ziprasidone for a median of 99 days. The mean (SD) change in BPRS-A score from end of RCT to end of OLE (last observation carried forward) was ?6.9 (8.9). The most common treatment-emergent adverse events (?10%) for all causalities during the RCT were somnolence and extrapyramidal disorders, and during OLE was somnolence only. No subjects had Fridericia's corrected QT (QTcF) ?500?ms in the RCT or OLE phases. One completed suicide occurred during the OLE phase. For RCT and OLE, no clinically significant changes were reported in metabolic indices and laboratory measures. Conclusions Ziprasidone failed to separate from placebo in treatment of schizophrenia in adolescents. Ziprasidone was generally well tolerated with an overall neutral weight and metabolic profile. Clinical Trials Registry NCT00257192 and NCT00265382 at ClinicalTrials.gov. PMID:24111983

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

2013-01-01

109

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

110

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

111

[Long-term efficacy of endovascular embolization with silk particles and their effects on surrounding tissues in rabbits].  

PubMed

Long-term efficacy of therapeutic embolization with silk particles in rabbits was observed. The effectiveness of embolization and their histotoxicity on surrounding tissues were compared with dry dura mater particles, polyvinyl alcohol foam (i.e. Ivalon) and isobutyl 1-2-cyanoacrylate (IBCA). The results showed that the endovascular embolization with silk particles was almost as effective as that with IBCA and superior to dry dura mater particles or Ivalon. The toxicity of silk particles was similar to Ivaion, but less than IBCA and dry dura mater particles. The authors considered that silk particles are a good embolic agent at present. PMID:8404339

Wu, Z Q

1993-01-01

112

Long-Term Efficacy and Rotational Stability of AcrySof Toric Intraocular Lens Implantation in Cataract Surgery  

PubMed Central

Purpose To evaluate the long-term efficacy and rotational stability of the AcrySof toric intraocular lens (IOL) in correcting preoperative astigmatism in cataract patients. Methods This prospective observational study included 30 eyes from 24 consecutive patients who underwent implantation of an AcrySof toric IOL with micro-coaxial cataract surgery between May 2008 and September 2008. Outcomes of visual acuity, refractive and keratometric astigmatism, and IOL rotation after 1 day, 1 month, 3 months, and long-term (mean, 13.3±5.0 months) follow-up were evaluated. Results At final follow-up, 73.3% of eyes showed an uncorrected visual acuity of 20/25 or better. The postoperative keratometric value was not different from the preoperative value; mean refractive astigmatism was reduced to -0.28±0.38 diopter (D) from -1.28±0.48 D. The mean rotation of the toric IOL was 3.45±3.39 degrees at final follow-up. One eye (3.3%) exhibited IOL rotation of 10.3 degrees, the remaining eyes (96.7%) had IOL rotation of less than 10 degrees. Conclusions Early postoperative and long-term follow-up showed that implantation of the AcrySof toric IOL is an effective, safe, and predictable method for managing corneal astigmatism in cataract patients. PMID:20714383

Kim, Myung Hun; Chung, Tae-Young

2010-01-01

113

Long-term efficacy of systemic multiexon skipping targeting dystrophin exons 45-55 with a cocktail of vivo-morpholinos in mdx52 mice.  

PubMed

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

114

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

Microsoft Academic Search

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

William D. Barrick; Michael D. Kinney

2008-01-01

115

Long-term safety of pulsed irrigation evacuation (PIE) use with chronic bowel conditions.  

PubMed

We wanted to determine the long-term effects of pulsed irrigation evacuation on the colon. Sigmoidoscopy/colonoscopy was performed on four patients with spinal cord injuries who have used this procedure an average of 3.5 times weekly, for an average of 6.7 years. No gross or microscopic abnormalities were identified in any of these individuals. Impactions as well as other complaints were markedly diminished or absent following the initiation of this therapy. Pulsed irrigation evacuation is a safe and effective method for long-term treatment of chronic neurogenic bowel. PMID:9724176

Gramlich, T; Puet, T

1998-08-01

116

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

117

Long term therapeutic efficacy of a soft monobloc mandibular advancement device in adults with obstructive sleep apnea.  

PubMed

Aim. To evaluate the long term (48 months) therapeutic efficacy of a soft monobloc mandibular advancement device in adult patients with mild or moderate obstructive sleep apnea. Methods. The study population comprised 28 patients (6 female and 22 male, mean age 52.2 ± 6.8 years) affected by obstructive sleep apnea. After a baseline medical and somnographic examination, a functional examination of the stomatognathic system, and a questionnaire focused on sleep-related qualities and a daytime somnolence, each patient received an individual device. Two follow-ups were made 6 months (T1) and 48 months (T2) after soft monobloc mandibular advancement device treatment had been initiated, and all initial examinations were repeated. Results. The statistical analysis showed a significant decrease in body mass index value between T1 and T2 (? = 0,012), an increase of Epworth sleepiness scale value between T1 and T2 (? = 0,012), and a significant improvement and decrease of apnea/hypopnea index between T0 and T1 (? = 0,010) and between T0 and T2 (? = 0,013). Conclusion. Treatment with the soft monobloc mandibular advancement device is a therapeutic solution with long term and stable effects (48 months) for patients suffering from mild or moderate obstructive sleep apnea. PMID:25642453

Ballanti, Fabiana; Ranieri, Salvatore; Baldini, Alberto; Cozza, Paola

2015-01-01

118

Long Term Therapeutic Efficacy of a Soft Monobloc Mandibular Advancement Device in Adults with Obstructive Sleep Apnea  

PubMed Central

Aim. To evaluate the long term (48 months) therapeutic efficacy of a soft monobloc mandibular advancement device in adult patients with mild or moderate obstructive sleep apnea. Methods. The study population comprised 28 patients (6 female and 22 male, mean age 52.2 ± 6.8 years) affected by obstructive sleep apnea. After a baseline medical and somnographic examination, a functional examination of the stomatognathic system, and a questionnaire focused on sleep-related qualities and a daytime somnolence, each patient received an individual device. Two follow-ups were made 6 months (T1) and 48 months (T2) after soft monobloc mandibular advancement device treatment had been initiated, and all initial examinations were repeated. Results. The statistical analysis showed a significant decrease in body mass index value between T1 and T2 (? = 0,012), an increase of Epworth sleepiness scale value between T1 and T2 (? = 0,012), and a significant improvement and decrease of apnea/hypopnea index between T0 and T1 (? = 0,010) and between T0 and T2 (? = 0,013). Conclusion. Treatment with the soft monobloc mandibular advancement device is a therapeutic solution with long term and stable effects (48 months) for patients suffering from mild or moderate obstructive sleep apnea. PMID:25642453

Ballanti, Fabiana; Ranieri, Salvatore; Cozza, Paola

2015-01-01

119

Long-term efficacy of deep sclerectomy in Posner-Schlossman syndrome.  

PubMed

The Posner-Schlossman syndrome (PSS) is an elusive disease that can lead to serious consequences such as glaucomatous damage. Deep sclerectomy has been proven thus far to be the most effective surgical intervention to keep intraocular pressure (IOP) elevation under control compared with other surgical techniques, because it presents the least amount of postoperative complications. The aim of this case report is to demonstrate the efficacy of deep sclerectomy with T-Flux and the long-lasting effects that persist after 7?years in an eye affected by PSS. This case report demonstrates that an intervention of deep sclerectomy can lead to excellent results in terms of visual acuity as well as IOP lowering early in the history of the patient affected by PSS so that it can preclude establishment of glaucomatous damage. PMID:25616652

Campana, Fiamma; Caramello, Guido; Dallorto, Laura; Rolle, Teresa

2015-01-01

120

Long-term effectiveness and safety of GnRH agonist plus raloxifene administration in women with uterine leiomyomas  

Microsoft Academic Search

BACKGROUND: Our aim was to evaluate the long-term effectiveness and safety of GnRH agonist plus raloxifene administration in women with symptomatic uterine leiomyomas. METHODS: Fifty pre-menopausal women with uterine leiomyomas were treated with leuprolide acetate depot at dose of 3.75 mg\\/28 days and raloxifene hydro- chloride at 60 mg\\/day for 18 cycles. At admission and after each six cycles of

Stefano Palomba; Francesco Orio Jr; Tiziana Russo; Angela Falbo; Teresa Cascella; Patrizia Doldo; Carmine Nappi; Gaetano Lombardi; Pasquale Mastrantonio; Fulvio Zullo

121

Short- and Long-Term Safety of Weekly High-Dose Vitamin D3 Supplementation in School Children  

PubMed Central

Background: Hypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group. We assessed the safety of high doses of vitamin D3 administered to apparently healthy schoolchildren. Methods: To assess short-term safety, 25 subjects randomly received placebo or vitamin D3 at doses of 14,000 IU/wk for 8 wk. To assess long-term safety, 340 subjects randomly received placebo, vitamin D3 as 1,400 IU/wk or 14,000 IU/wk for 1 yr. Biochemical variables were monitored at 0, 2, 4, 6, and 8 wk and 8 wk off therapy in the short-term study and at 0, 6, and 12 months in the long-term study. Results: In both the short- and long-term studies, mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group. In the short-term study, mean 25-hydroxyvitamin concentrations increased from 44 (± 11) to 54 (± 19) ng/ml in the treated groups (P = 0.033). In the long-term study, mean 25-hydroxyvitamin D levels increased from 15 ± 8 to 19 ± 7 ng/ml (P < 0.0001) in subjects receiving 1,400 IU/wk and from 15 ± 7 to 36 ± 22 ng/ml (P < 0.0001) in the group receiving 14,000 IU/wk. No subject developed vitamin D intoxication. Conclusion: Vitamin D3 at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels. PMID:18445674

Maalouf, Joyce; Nabulsi, Mona; Vieth, Reinhold; Kimball, Samantha; El-Rassi, Rola; Mahfoud, Ziyad; El-Hajj Fuleihan, Ghada

2008-01-01

122

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

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 of Pulsed Irrigation Evacuation (PIE) Use with Chronic Bowel Conditions  

Microsoft Academic Search

We wanted to determine the long-term effects ofpulsed irrigation evacuation on the colon.Sigmoidoscopy\\/colonoscopy was performed on four patientswith spinal cord injuries who have used this procedure an average of 3.5 times weekly, for an averageof 6.7 years. No gross or microscopic abnormalities wereidentified in any of these individuals. Impactions aswell as other complaints were markedly diminished or absent following the

Terry Gramlich; Terry Puet

1998-01-01

125

Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters  

PubMed Central

Andes virus (ANDV) is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV)-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G). This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure), and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025), but animals were not significantly protected following 1 year of vaccination (p = 0.090). The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity. PMID:24492621

Prescott, Joseph; DeBuysscher, Blair L.; Brown, Kyle S.; Feldmann, Heinz

2014-01-01

126

Efficacy of combined interferon alpha and long-term lamivudine therapy in children with chronic hepatitis B.  

PubMed

The aim of this study was to evaluate the efficacy of interferon alpha (IFN-alpha) and long-term lamivudine therapy in children with chronic hepatitis B and to determine the optimal duration of lamivudine therapy. Thirty-eight HBeAg-positive children simultaneously received IFN-alpha2a 5 MU/m2 to 10 MU/m2 for six months and lamivudine (4 mg/kg/day). Lamivudine was administered until anti-HBe seroconversion and was continued for six months in responders. During the five-year study period, we evaluated the efficacy of treatment, occurrence of YMDD mutants and adverse effects. During the study period, alanine aminotransferase (ALT) normalization, clearance of hepatitis B virus (HBV) DNA, HBeAg/anti-HBeAb, HBsAg/anti-HBsAb seroconversion, and histological response were noted in 27 (71.1%), 14 (36.8%), 13 (34.2%), 2 (5.2%) and 10 (47.9%) patients, respectively. Complete response was determined in 34.2% (13/38), and in 69.2% of these responders, response was achieved within 18 months. Breakthrough and YMDD mutant rates were 65.8% and 55.2%, respectively. Breakthrough time was a median 24 months and was associated with low baseline ALT level (p < 0.01). In conclusion, although lamivudine was used for a longer period, the response rate was not higher than in previous reports. We suggest that 18 months' duration of lamivudine treatment is sufficient for combination therapy. PMID:21434529

Kulo?lu, Zarife; Kansu, Aydan; Erden, Esra; Girgin, Nurten

2010-01-01

127

‘Taking Care of Myself’Efficacy of an intervention programme for caregivers of a relative with dementia living in a long-term care setting  

Microsoft Academic Search

The purpose of this randomized study was to test the efficacy of an intervention programme entitled ‘Taking Care of Myself’ on selected indicators of mental health of daughter caregivers of elderly parents with dementia living in a long-term care setting. The programme is based on an empowerment perspective and on a stress and coping theoretical framework. Three groups of caregivers

Francine Ducharme; Louise Lévesque; Lise Lachance; Francine Giroux; Alain Legault; Michel Préville

2005-01-01

128

Long-Term Efficacy of Endoscopic Submucosal Dissection Compared with Surgery for Early Gastric Cancer: A Retrospective Cohort Study  

PubMed Central

Background/Aims This study aimed to compare the outcomes of endoscopic submucosal dissection (ESD) and gastrectomy based on the two sets of indications for ESD, namely guideline criteria (GC) and expanded criteria (EC). Methods Between January 2004 and July 2007, 213 early gastric cancer (EGC) patients were enrolled in this study. Of these patients, 142 underwent ESD, and 71 underwent gastrectomy. We evaluated the clinical outcomes of these patients according to the criteria. Results The complication rates in the ESD and gastrectomy groups were 8.5% and 28.2%, respectively. The duration of hospital stay was significantly shorter in the ESD group than the gastrectomy group according to the GC and EC (p<0.001 and p<0.001, respectively). There was no recurrence in the ESD and gastrectomy groups according to the GC, and the recurrence rates in the ESD and gastrectomy groups were 4.7% and 0.0% according to the EC, respectively (p=0.279). The occurrence rates of metachronous cancer in the ESD and gastrectomy groups were 5.7% and 5.0% according to the GC (p=1.000) and 7.5% and 0.0% according to the EC (p=0.055), respectively. Conclusions Based on safety, duration of hospital stay, and long-term outcomes, ESD may be an effective and safe first-line treatment for EGC according to the EC and GC. PMID:25228976

Kim, Dae Yong; Hong, Su Jin; Cho, Gyu Seok; Jeong, Gui Ae; Kim, Hee Kyung; Han, Jae Pil; Lee, Yun Nah; Ko, Bong Min; Lee, Moon Sung

2014-01-01

129

Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report.  

PubMed

There is presently a great interest in the therapeutic potential of agmatine, decarboxylated arginine, for various diseases. Recent clinical studies have already shown that oral agmatine sulfate given for up to 3 weeks provides a safe and, as compared with current therapeutics, more effective treatment for neuropathic pain. These studies have ushered in the use of dietary agmatine as a nutraceutical. However, in view of information paucity, assessment of long-term safety of oral agmatine treatment is now clearly required. The authors of this report undertook to assess their own health status during ongoing consumption of a high daily dosage of oral agmatine over a period of 4-5 years. A daily dose of 2.67 g agmatine sulfate was encapsulated in gelatin capsules; the regimen consists of six capsules daily, each containing 445 mg, three in the morning and three in the evening after meals. Clinical follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All measurements thus far remain within normal values and good general health status is sustained throughout the study period, up to 5 years. This case study shows for the first time that the recommended high dosage of agmatine may be consumed for at least 5 years without evidence of any adverse effects. These initial findings are highly important as they provide significant evidence for the extended long-term safety of a high daily dosage of dietary agmatine--a cardinal advantage for its utility as a nutraceutical. PMID:25247837

Gilad, Gad M; Gilad, Varda H

2014-11-01

130

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

131

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

132

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

133

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

134

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

135

Safety and Feasibility of Long-term Intravenous Sodium Nitrite Infusion in Healthy Volunteers  

PubMed Central

Background Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO) for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. Methodology Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075) between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21–56 years)) were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr). Clinical, physiologic and laboratory data before, during and after infusion were analyzed. Findings The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg) and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. Conclusion Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. Clinical Trial Registration Information http://www.clinicaltrials.gov; NCT00103025 PMID:21249218

Pluta, Ryszard M.; Oldfield, Edward H.; Bakhtian, Kamran D.; Fathi, Ali Reza; Smith, René K.; DeVroom, Hetty L.; Nahavandi, Masoud; Woo, Sukyung; Figg, William D.; Lonser, Russell R.

2011-01-01

136

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

137

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

138

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

139

Sun Protection Intervention for Highway Workers: Long-Term Efficacy of UV Photography and Skin Cancer Information on Men’s Protective Cognitions and Behavior  

Microsoft Academic Search

Background  The risk for skin cancer is increased among older males and outdoor workers who have high levels of ultraviolet (UV) exposure.\\u000a \\u000a \\u000a \\u000a Purpose  This study was designed to examine the long-term efficacy of UV photography interventions on male outdoor workers, the potential\\u000a mediators of its impact, and the efficacy of UV photography and skin cancer vs. aging information with this population.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  One

Michelle L. Stock; Meg Gerrard; Frederick X. Gibbons; Jennifer L. Dykstra; Heike I. M. Mahler; Laura A. Walsh; James A. Kulik

2009-01-01

140

Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience.  

PubMed

To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4-5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n = 4, 5.33%), chest pain (n = 28, 38.7%), reflux (n = 15, 20%), and bleeding (n = 9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1-3, 3-5, 5-8, 8-10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 +/- 0.28 years (95% CI: 2.25-3.35) and 4.28 +/- 0.40 years (95% CI: 3.51-5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate. PMID:19296113

Zhao, Jun-Gong; Li, Yong-Dong; Cheng, Ying-Sheng; Li, Ming-Hua; Chen, Ni-Wei; Chen, Wei-Xiong; Shang, Ke-Zhong

2009-08-01

141

Safety and tolerability of long-term propafenone therapy for supraventricular tachyarrhythmias. The Propafenone Multicenter Study Group.  

PubMed

An important issue regarding the long-term use of antiarrhythmic drugs concerns the safety of these agents, particularly with regard to cardiac toxicity. Propafenone is an effective drug for preventing supraventricular tachyarrhythmia, but the incidence of side effects during longterm therapy in patients with such arrhythmias has not been adequately reported. A total of 480 patients received oral propafenone as therapy for symptomatic atrial fibrillation, atrial flutter, or supraventricular tachycardia. During the follow-up (mean 14.4 months), 290 patients (60%) discontinued propafenone therapy, but in only 70 patients (15%) was the reason for discontinuation an adverse drug reaction. Overall, 284 patients (59%) experienced at least 1 adverse reaction, and the incidence was related to dose and age >65 years. The overall incidence of side effects was not related to structural heart disease; however, cardiovascular toxicity including arrhythmia aggravation, congestive heart failure, and serious conduction disturbances occurred more often in those with heart disease (20% vs 13%). Sixteen patients died during drug therapy, but in only 1 case was the drug considered contributory. For patients with a supraventricular arrhythmia, propafenone was well tolerated and was infrequently discontinued because of side effects. The incidence of serious cardiac toxicity when propafenone was used to treat supraventricular arrhythmia was low, and these side effects were more frequent in patients with structural heart disease. PMID:8752188

Podrid, P J; Anderson, J L

1996-08-15

142

Dapagliflozin efficacy and safety: a perspective review.  

PubMed

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

Anderson, Sarah L

2014-12-01

143

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

144

Randomized Controlled Trial to Determine the Efficacy of Long-Term Growth Hormone Treatment in Severely Burned Children  

PubMed Central

Background Recovery from a massive burn is characterized by catabolic and hypermetabolic responses that persist up to 2 years and impair rehabilitation and reintegration. The objective of this study was to determine the effects of long-term treatment with recombinant human growth hormone (rhGH) on growth, hypermetabolism, body composition, bone metabolism, cardiac work, and scarring in a large prospective randomized single-center controlled clinical trial in pediatric patients with massive burns. Patients and Methods A total of 205 pediatric patients with massive burns over 40% total body surface area were prospectively enrolled between 1998 and 2007 (clinicaltrials.gov ID NCT00675714). Patients were randomized to receive either placebo (n = 94) or long-term rhGH at 0.05, 0.1, or 0.2 mg/kg/d (n = 101). Changes in weight, body composition, bone metabolism, cardiac output, resting energy expenditure, hormones, and scar development were measured at patient discharge and at 6, 9, 12, 18, and 24 months postburn. Statistical analysis used Tukey t test or ANOVA followed by Bonferroni correction. Significance was accepted at P < 0.05. Results RhGH administration markedly improved growth and lean body mass, whereas hypermetabolism was significantly attenuated. Serum growth hormone, insulin-like growth factor-I, and IGFBP-3 was significantly increased, whereas percent body fat content significantly decreased when compared with placebo, P < 0.05. A subset analysis revealed most lean body mass gain in the 0.2 mg/kg group, P < 0.05. Bone mineral content showed an unexpected decrease in the 0.2 mg/kg group, along with a decrease in PTH and increase in osteocalcin levels, P < 0.05. Resting energy expenditure improved with rhGH administration, most markedly in the 0.1 mg/kg/d rhGH group, P < 0.05. Cardiac output was decreased at 12 and 18 months postburn in the rhGH group. Long-term administration of 0.1 and 0.2 mg/kg/d rhGH significantly improved scarring at 12 months postburn, P < 0.05. Conclusion This large prospective clinical trial showed that long-term treatment with rhGH effectively enhances recovery of severely burned pediatric patients. PMID:19734776

Branski, Ludwik K.; Herndon, David N.; Barrow, Robert E.; Kulp, Gabriela A.; Klein, Gordon L.; Suman, Oscar E.; Przkora, Rene; Meyer, Walter; Huang, Ted; Lee, Jong O.; Chinkes, David L.; Mlcak, Ronald P.; Jeschke, Marc G.

2014-01-01

145

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

146

Open label, long-term, pragmatic study on levetiracetam in the treatment of juvenile myoclonic epilepsy  

Microsoft Academic Search

PurposePatients with juvenile myoclonic epilepsy (JME) may be resistant or show adverse effects to valproate. We present a multicenter, prospective, long-term, open-label study evaluating the efficacy and safety of levetiracetam in JME.

Luigi Maria Specchio; Antonio Gambardella; Anna Teresa Giallonardo; Roberto Michelucci; Nicola Specchio; Giovanni Boero; Angela La Neve

2006-01-01

147

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

148

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

149

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

150

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.

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

2014-01-01

151

[Long-term efficacy of naftopidil for treatment of lower urinary tract symptoms with benign prostatic hyperplasia].  

PubMed

Naftopidil was administered to 67 patients with benign prostatic hyperplasia (BPH) for 12 months. Changes in total/each International Prostate Symptom Score (IPSS) for irritative and obstructive symptoms, nocturia, and residual urine volume were compared before and after its administration. As a result, a significant decrease of score was found in total-IPSS, obstructive and irritative symptoms, which also showed a tendency to decrease at the end of the first month. Nocturia and residual urine volume also significantly decreased after its administration. Naftopidil is considered to be effective in the treatment of BPH, especially irritative symptoms including nocturia in treatments for BPH, because both irritative and obstructive symptoms (IPSS subjective endpoints) and residual urine volume (objective endpoint) were improved after its long-term administration. PMID:12784711

Akasaka, Toshiyuki; Funaki, Hiroyoshi; Hirano, Shigeru; Ohinata, Mitsuru; Fujishima, Mikihiko; Kudou, Takuji; Suzuki, Akira; Iinuma, Masahiro

2003-04-01

152

Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs  

PubMed Central

Objectives To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs. Methods This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies received a weight-tiered dosing equivalent of 10 mg/kg abatacept, with MTX at doses up to 8 mg/week; newly enrolled patients received weight-tiered 10 mg/kg abatacept monotherapy. Safety and efficacy were assessed. Results A total of 217 patients (Phase I, n = 13; Phase II, n = 178; newly enrolled, n = 26) were treated with IV abatacept for a mean of 3 years. Serious adverse events occurred in 67/217 (30.9%) patients. Most adverse events were mild or moderate. For all cohorts combined, American College of Rheumatology 20% response rates ranged from 61.3 to 81.8% for as-observed and last observation carried forward analyses over 192 weeks. Following initial response, clinical and functional outcomes were maintained for up to 3 years. Conclusions In Japanese patients with RA, IV abatacept with and without background MTX showed tolerable safety and sustained efficacy over 3 years. PMID:24754273

Matsubara, Tsukasa; Urata, Yukitomo; Suematsu, Eiichi; Ohta, Shuji; Honjo, Shigeru; Abe, Tohru; Yamamoto, Ami; Miyasaka, Nobuyuki

2014-01-01

153

The Chemopreventive Efficacies of Nonsteroidal Anti-inflammatory Drugs: the Relationship of Short-term Biomarkers to Long-term Skin Tumor Outcome  

PubMed Central

The UVB component of sunlight, which causes DNA damage and inflammation, is the major cause of nonmelanoma skin cancer (NMSC), the most prevalent of all cancers. Nonsteroidal anti-inflammatory drugs (NSAIDs) and coxibs have been shown to be effective chemoprevention agents in multiple preclinical trials, including NMSC, colon and urinary bladder cancer. NSAIDs, however, cause gastrointestinal irritation, which led to the recent development of nitric oxide (NO) derivatives that may partially ameliorate this toxicity. This study compared the efficacy of several NSAIDs and NO-NSAIDs on UV-induced NMSC in SKH-1 hairless mice and determined whether various short-term biomarkers were predictive of long-term tumor outcome with these agents. Naproxen at 100 (p>.05) and 400 ppm (p<.01) in the diet reduced tumor multiplicity by 26 and 63% respectively. The NO-naproxen at slightly lower molar doses shows similar activities. Aspirin at 60 or 750 ppm in the diet reduced tumor multiplicity by 19 and 50%; while the equivalent doses (108 and 1350 ppm) were slightly less effective. Sulindac at 25 and 150 ppm in the diet doses far below the Human Equivalent Dose, was the most potent NSAID with reductions of 50 and 94% respectively. In testing short-term biomarkers we found that agents that reduce UV-induced prostaglandin E2 synthesis and/or inhibit UV-induced keratinocyte proliferation yielded long-term tumor efficacy. PMID:23682071

Mikulec, Carol; Rundhaug, Joyce E.; Simper, Melissa S.; Lubet, Ronald A.; Fischer, Susan M.

2013-01-01

154

Efficacy of OK-432 sclerotherapy in treatment of lymphatic malformations: long-term follow-up results.  

PubMed

Lymphatic malformations (LMs) are rare congenital tumors of the lymphatic system often affecting the head and neck area. Because of cosmetic and functional symptoms most patients need to be treated. Traditionally surgical treatment has been considered to be the first-line treatment for LM. However, it is challenging because of the need for complete excision. The risk of poor cosmetic result and damage to surrounding structures is high. Since Ogita presented OK-432 as a treatment for LM in 1987, it has been widely used as the primary treatment. Many papers have been published on this topic but with relatively short follow-up times. We present a material of 36 LMs treated with OK-432 during the period of 1999-2009 and with an average follow-up time of 6 years. Immediate post-treatment results were compared with the late follow-up findings. Primary and late response to therapy was evaluated with an MRI scan by measuring the change in lesion size. At the follow-up visit, all patients were clinically examined and they answered a symptom questionnaire. Later 26/36 patients were also available for a quality of life questionnaire. Primarily 67% demonstrated a complete or marked response. At the follow-up 64% showed a complete or marked response, in 11% the final response was better than the initially observed and only 2 patients had relapsed. The initial response predicted the long-term outcome accurately and the effect of OK-432 sclerotherapy seems to be long lasting. According to the MRI evaluation 80% and subjectively 94% of the patients benefitted from the treatment. Quality of life questionnaire showed high post-treatment satisfaction. We found OK-432 sclerotherapy to be a safe and effective treatment with a long lasting effect in the management of macrocystic LMs. PMID:23649509

Weitz-Tuoretmaa, Annamaria; Rautio, Riitta; Valkila, Jan; Keski-Säntti, Harri; Keski-Nisula, Leo; Laranne, Jussi

2014-02-01

155

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

156

PGE(1) treatment of severe intermittent claudication (short-term versus long-term, associated with exercise)--efficacy and costs in a 20-week, randomized trial.  

PubMed

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 980 patients (883 completed the study) with an average total walking distance of 85.5 +/-10 m (range 22-119). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in 2 days by a 2-hour infusion (first day: morning 20 microg, afternoon 40 microg; second day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate tolerability or side effects. Full dosage (60 microg bid) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks and at 20 weeks in the STP more than in the LTP group. At 4 weeks the variation (increase) in pain-free walking (PFWD) was 167.8% (of the initial value) in the LTP group and 185% in the STP group (p<0.05). At 4 weeks the variation (increase) in total walking distance (TWD) was 227.6% of the initial value in the LTP group and 289% in the STP group (p<0.05). At 20 weeks the increase in PFWD was 496% of the initial value in the LTP group vs 643% in the STP group (147% difference; p<0.02). The increase in TWD was 368% in the LTP group and 529% in the STP group (161% difference; p<0.02). In both groups there was a significant increase in PFWD and TWD at 4 and 20 weeks, but results obtained with STP are better considering both walking distances. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 6.3% of the treated subjects in the LTP and 3% in the STP. Average cost of LTP was 6,664 Euro; for STP the average costs was approximately 1,820 E. The cost to achieve an improvement in walking distance of 1 m was 45.8 E with the LTP and 8.5 E with the STP (18% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,989 E vs. 421 E with STP (p<0.02). Between-group analysis favors STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE, treatment. With STP less time is spent in infusion and more in the exercise program. STP reduces costs, speeds rehabilitation, and may be easily used in a larger number of nonspecialized units. PMID:10959507

Belcaro, G; Nicolaides, A N; Agus, G; Cesarone, M R; Geroulakos, G; Pellegrini, L; De Sanctis, M T; Incandela, L; Ricci, A; Mondani, P; De Angelis, R; Ippolito, E; Barsotti, A; Vasdekis, S; Ledda, A; Christopoulos, D; Errichi, B M; Helmis, H; Cornelli, U; Ramaswami, G; Dugall, M; Bucci, M; Martines, G; Ferrari, P G; Corsi, M; Di Francescantonio, D

2000-08-01

157

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

158

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

PubMed Central

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

159

The effectiveness of a long-term professional development program on teachers' self-efficacy, attitudes, skills, and knowledge using a thematic learning approach  

NASA Astrophysics Data System (ADS)

The purpose of this research study was to determine the effectiveness of a long-term professional development program on self-efficacy beliefs, science attitudes, skills, and knowledge of elementary teachers. The target school was located in the Lower Rio Grande Valley of Texas. Major elements of the study included the use of thematic science strands, use of the 5E constructivist-oriented instructional model, a focus on the interdisciplinary nature of the science process skills, and guided, inquiry-based learning experiences. These elements mirror the principles identified as being essential components of effective professional development for mathematics, and science education (Fullan, 1985; Sparks & Loucks-Horsley, 1990; Loucks-Horsley, 1997). The research team was actively involved with the participants for a total of 30 days at their school over the 24 months of the study. During each training, the research team modeled the 5E constructivist-oriented instructional strategy, and the interdisciplinary nature of the science process skills, set up a wide variety of activity centers, and provided the teachers with opportunities to improve their attitudes, skills, and knowledge of the science content, and teaching strategies. The 15 participants completed pre-, post-, and post-post-Leadership Team Surreys. Quantitative data analyses of gain scores measuring level of confidence to teach Marine and Earth Science, content knowledge, and teaching strategies were significant, p < .001. The participants' efficacy-beliefs and outcome expectancy were assessed with a pre- and posttest Science Teacher Self-Efficacy Beliefs Instrument that measures both elements. Self-efficacy beliefs were significant at p < .001. Outcome expectancies were not significant, p > .05. Qualitative analysis of reflective journal comments, classroom observations, and the participants understanding, and use of science process skills across the curriculum supported the quantitative data results. The data demonstrate significant improvement in the self-efficacy beliefs, attitudes, skills, and knowledge toward teaching science of the Pre-Kindergarten--2nd -grade teachers who participated in this long-term professional development study.

Tinnin, Richard Kinna

160

Acute and long-term efficacy of antituberculous treatment in HIV-seropositive patients with tuberculosis: a study of 36 cases.  

PubMed

Thirty-six consecutively observed HIV-seropositive patients with tuberculosis, including 31 patients with AIDS, who received antituberculous treatment, were followed up to evaluate its efficacy. Treatment with standard antituberculous regimens was intended except when an individual's condition required a modified therapeutic approach. Therapeutic failure occurred in five patients (14%) while on treatment, one also had a post-treatment relapse. Treatment failure was associated with drug resistance and non-compliance in three patients and in another two, both of whom died early in the course of their disease, with HIV-related conditions other than tuberculosis. The median relapse-free post-treatment follow-up time in 24 patients in whom treatment did not fail was 13 months (range 4-67). Standard antituberculous treatment is highly effective in the immediate and long-term treatment of HIV-related tuberculosis provided that drug susceptibility and treatment compliance are confirmed. PMID:8454888

Schürmann, D; Bergmann, F; Jautzke, G; Fehrenbach, J; Mauch, H; Ruf, B

1993-01-01

161

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

162

Prazosin versus quetiapine for nighttime posttraumatic stress disorder symptoms in veterans: an assessment of long-term comparative effectiveness and safety.  

PubMed

Posttraumatic stress disorder (PTSD) is an anxiety disorder experienced by combat veterans. Nighttime symptoms are often unrelieved by selective serotonin reuptake inhibitor therapy, and increased use of prazosin or quetiapine for treatment is seen. The purpose of this study was to determine the short- and long-term effectiveness and safety of prazosin versus quetiapine for treating nighttime symptoms in veteran PTSD patients. This is a historical prospective cohort study using retrospective chart review. Three hundred twenty-four patients with a diagnosis of PTSD, based on International Classification of Diseases, Ninth Revision coding, who were initially prescribed prazosin or quetiapine for nighttime symptoms were screened for inclusion. Short-term effectiveness was determined by documentation of symptomatic improvement within 6 months, and long-term effectiveness if patients continued therapy to study end date. Safety was assessed by comparing incidence of adverse drug effects causing discontinuation of either study drug. This study included 237 patients: 62 received prazosin, and 175 received quetiapine. Short-term effectiveness was similar for prazosin (61.3%) and quetiapine (61.7%; P = 0.54). However, patients prescribed prazosin were significantly more likely to continue their therapy to study end date compared with quetiapine (48.4% vs 24%; P < 0.001; odds ratio, 3.0; 95% confidence interval, 1.62-5.45), thus achieving long-term effectiveness. Alternatively, patients in the quetiapine group were more likely to discontinue therapy because of adverse effects compared with the prazosin group (34.9% vs 17.7%; P = 0.008). Because of similar rate of short-term effectiveness, superior long-term effectiveness, and lower incidence of events leading to discontinuation, compared with quetiapine, prazosin should be used first-line for treating nighttime PTSD symptoms in a veteran population. PMID:20473055

Byers, Melanie G; Allison, Kristen M; Wendel, Christopher S; Lee, Jeannie K

2010-06-01

163

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

164

Diltiazem treatment for the management of ischaemia in patients with poor left ventricular function: safety of long term administration.  

PubMed Central

The tendency of oral diltiazem (a calcium entry blocking agent and a negative inotrope) to induce or exacerbate congestive heart failure when used for the long term management of myocardial ischaemia in patients with poor left ventricular function has not been investigated before. Twenty two patients (aged 42-73 years) with pretreatment left ventricular ejection fraction ranging from 0.11 to 0.39 were given open label oral diltiazem (120-360 mg/24 h (mean 254 mg)) for two weeks to 16 months (mean 7.5 months, median 6.2 months). There was a weight change of greater than 3 lb (1.35 kg) in nine patients--five gained weight and four lost it. Diltiazem treatment did not alter the mean (SD) cardiothoracic ratio on chest x ray (0.47 (0.06) before vs 0.48 (0.05) after) or the left ventricular ejection fraction at rest (0.28 (0.09) before vs 0.26 (0.08) after). Diltiazem was discontinued in one patient because of symptoms indicative of worsening congestive heart failure. No patient required admission to hospital for treatment of symptoms resulting from further left ventricular decompensation. Diltiazem was discontinued in six other patients for other reasons. Long term administration of oral diltiazem was not regularly associated with a deterioration in clinical, radiographic, or radionuclide ventriculographic estimates of left ventricular function, even in patients with poor baseline left ventricular systolic performance. PMID:3676040

Zema, M J; Perlmutter, S; Mankes, S; Nikitopoulos, C

1987-01-01

165

The long-term efficacy and tolerability of hyaluronic acid in adult patients with Kashin-Beck disease of the knee.  

PubMed

The aim of this study was to prospectively evaluate the long-term efficacy and tolerability of hyaluronic acid (HA) for the treatment of knee pain due to Kashin-Beck disease (KBD). A total of 113 patients with KBD-based knee pain were treated with a 3-week course of HA. Clinical assessments were performed for each patient at 0 (baseline), 1, 2, 4, 8, 12, 24, and 52 weeks. The primary efficacy measure was the visual analog scale (VAS) pain score. The secondary efficacy measures included the WOMAC A (pain), B (stiffness), and C (function) scores; the total WOMAC score; and the global assessments by patients and physicians. Tolerability was evaluated based on adverse events (AEs) and physician reporting. The VAS was significantly reduced within the first 4 weeks of treatment, and the reduction was maintained over 52 weeks (p?

Tang, Xin; Zhou, Zong-Ke; Liu, Gang; Shen, Bin; Kang, Peng-De; Li, Jian; Li, Qi; Pei, Fu-Xing

2015-01-01

166

Long-term safety of the aminobisphosphonate alendronate in adult dogs. II. Histomorphometric analysis of the L5 vertebrae.  

PubMed

Osteoporosis is a major health problem. Bisphosphonates are synthetic compounds that are taken up preferentially by the skeleton and suppress osteoclast-mediated bone resorption. Alendronate (ALN) is an aminobisphosphonate used in the treatment of diseases characterized by increased bone resorption including osteoporosis. The purpose of this study was to rule out possible adverse effects of the chronic administration of ALN on the quality of bone. Thirty-one 20- to 21-month-old beagles (n = 7-8 per group, females and males) were treated p.o. for 157 weeks with ALN at 0.00, 0.25, 0.5 or 1.00 mg/kg/day and labeled in vivo with oxytetracycline and calcein. Undecalcified bone sections obtained from the fifth lumbar vertebra were evaluated by static and dynamic histomorphometry. Cortical or cancellous bone volume and indices of architecture were not affected by treatment. Osteoid thickness and mineralization lag time were not changed by treatment. Tissue level bone turnover was inhibited in a dose-dependent manner in males. The results indicate that long-term ALN administration at up to 5 times the dose used for treatment of osteoporosis in clinical trials causes no abnormalities in bone remodeling or bone structure. PMID:8558443

Balena, R; Markatos, A; Seedor, J G; Gentile, M; Stark, C; Peter, C P; Rodan, G A

1996-01-01

167

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs  

PubMed Central

Duchenne muscular dystrophy (DMD) is a genetic progressive muscle disease resulting from the lack of dystrophin and without effective treatment. Adult stem cell populations have given new impetus to cell-based therapy of neuromuscular diseases. One of them, muscle-derived stem cells, isolated based on delayed adhesion properties, contributes to injured muscle repair. However, these data were collected in dystrophic mice that exhibit a relatively mild tissue phenotype and clinical features of DMD patients. Here, we characterized canine delayed adherent stem cells and investigated the efficacy of their systemic delivery in the clinically relevant DMD animal model to assess potential therapeutic application in humans. Delayed adherent stem cells, named MuStem cells (muscle stem cells), were isolated from healthy dog muscle using a preplating technique. In vitro, MuStem cells displayed a large expansion capacity, an ability to proliferate in suspension, and a multilineage differentiation potential. Phenotypically, they corresponded to early myogenic progenitors and uncommitted cells. When injected in immunosuppressed dystrophic dogs, they contributed to myofiber regeneration, satellite cell replenishment, and dystrophin expression. Importantly, their systemic delivery resulted in long-term dystrophin expression, muscle damage course limitation with an increased regeneration activity and an interstitial expansion restriction, and persisting stabilization of the dog's clinical status. These results demonstrate that MuStem cells could provide an attractive therapeutic avenue for DMD patients. PMID:21924229

Rouger, Karl; Larcher, Thibaut; Dubreil, Laurence; Deschamps, Jack-Yves; Le Guiner, Caroline; Jouvion, Gregory; Delorme, Bruno; Lieubeau, Blandine; Carlus, Marine; Fornasari, Benoît; Theret, Marine; Orlando, Priscilla; Ledevin, Mireille; Zuber, Céline; Leroux, Isabelle; Deleau, Stéphane; Guigand, Lydie; Testault, Isabelle; Le Rumeur, Elisabeth; Fiszman, Marc; Chérel, Yan

2011-01-01

168

Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.  

PubMed

Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia. PMID:21654821

Crane, B; Luo, X; Demaster, A; Williams, K D; Kozink, D M; Zhang, P; Brown, T T; Pinto, C R; Oka, K; Sun, F; Jackson, M W; Chan, L; Koeberl, D D

2012-04-01

169

Long-term atropine treatment lowers the efficacy of carbachol to stimulate phosphatidylinositol breakdown in the cerebral cortex and hippocampus of rats.  

PubMed Central

The effect of long-term treatment with atropine, a muscarinic antagonist, known to cause up-regulation of receptor numbers, was examined on the muscarinic-receptor-mediated stimulation of phosphoinositide breakdown in the rat cerebral cortex and hippocampus. Although the numbers of both M1 muscarinic receptors, as measured by [3H]pirenzepine binding, and M1 and M2 receptors increased in both brain regions, the maximal breakdown of myo-[3H]inositol-labelled phosphoinositides was unaltered in the presence of carbachol at a saturating concentration (10(-2) M). In fact the efficacy of carbachol was decreased in slices from atropine-treated cerebral cortex [EC50 (concentration producing half-maximal effect) = 93 microM] as compared with the saline-treated control (EC50 = 23 microM)(P less than 0.005). Similarly the EC50 value (23 microM) in hippocampal slices from saline-treated rats increased in atropine-treated rats to 126 microM (P less than 0.005). This lowered efficacy of muscarinic stimulation could not be explained in terms of residual atropine in the tissue from treated rats. The noradrenaline- or serotonin (5-hydroxytryptamine)-stimulated breakdown or the K+ potentiation of the muscarinic-receptor-stimulated breakdown of [3H]phosphoinositides was not affected by the atropine treatment. Chromatography of the released [3H]inositol phosphates shows that atropine treatment did not cause any qualitative change in the pattern of [3H]inositol phosphates released by carbachol stimulation. PMID:3390140

Goobar, L; Bartfai, T

1988-01-01

170

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

171

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.

Cooper, Scott

172

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

173

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

174

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

175

Clinical use of intravenous iron: administration, efficacy, and safety.  

PubMed

This section reviews the history, pharmacology, administration, efficacy, and toxicity of intravenous iron. Intravenous iron offers advantages over oral iron for the treatment of iron deficiency anemia across a wide range of disease states associated with absolute and functional iron deficiency. However, there remain concerns about the acute safety profiles of the available preparations and the potential for long-term toxicity with their repeated administration. Seven intravenous iron formulations are available. Confusion concerning the relative toxicities of the different formulations abounds. The similarities and differences are discussed. Iron repletion has been associated with adverse outcomes in infections. The relationship, if any, between intravenous iron administration and infections is reviewed. The potential advantages of total dose infusion (TDI), complete repletion in a single setting, are highlighted. A new paradigm for iron replacement therapy in iron deficiency anemia is presented. PMID:21239816

Auerbach, Michael; Ballard, Harold

2010-01-01

176

Safety and efficacy of video-assisted thoracic surgical techniques for the treatment of spontaneous pneumothorax  

Microsoft Academic Search

Video-assisted thoracic surgery has been widely used in the treatment of spontaneous pneumothorax despite a paucity of data regarding the relative safety and long-term efficacy for this procedure. We reviewed 113 consecutive patients (68 male and 45 female patients, aged 15 to 92 years, mean 35.1) who underwent 121 video-assisted thoracic surgical procedures during 119 hospitalizations from 1991 through 1993.

Keith S. Naunheim; Michael J. Mack; Steven R. Hazelrigg; Mark K. Ferguson; Peter F. Ferson; Theresa M. Boley; Rodney J. Landreneau

1995-01-01

177

Long-Term (Postnatal Day 70) Outcome and Safety of Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Neonatal Hyperoxic Lung Injury  

PubMed Central

Purpose This study was performed to evaluate the long-term effects and safety of intratracheal (IT) transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in neonatal hyperoxic lung injury at postnatal day (P)70 in a rat model. Materials and Methods Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (90% oxygen) within 10 hours after birth and allowed to recover at room air until sacrificed at P70. In the transplantation groups, hUCB-MSCs (5×105) were administered intratracheally at P5. At P70, various organs including the heart, lung, liver, and spleen were histologically examined, and the harvested lungs were assessed for morphometric analyses of alveolarization. ED-1, von Willebrand factor, and human-specific nuclear mitotic apparatus protein (NuMA) staining in the lungs and the hematologic profile of blood were evaluated. Results Impaired alveolar and vascular growth, which evidenced by an increased mean linear intercept and decreased amount of von Willebrand factor, respectively, and the hyperoxia-induced inflammatory responses, as evidenced by inflammatory foci and ED-1 positive alveolar macrophages, were attenuated in the P70 rat lungs by IT transplantation of hUCB-MSCs. Although rare, donor cells with human specific NuMA staining were persistently present in the P70 rat lungs. There were no gross or microscopic abnormal findings in the heart, liver, or spleen, related to the MSCs transplantation. Conclusion The protective and beneficial effects of IT transplantation of hUCB-MSCs in neonatal hyperoxic lung injuries were sustained for a prolonged recovery period without any long-term adverse effects up to P70. PMID:23364976

Ahn, So Yoon; Chang, Yun Sil; Kim, Soo Yoon; Sung, Dong Kyung; Kim, Eun Sun; Rime, So Yub; Yu, Wook Joon; Choi, Soo Jin; Oh, Won Il

2013-01-01

178

Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience ? ? This study was sponsored by Procter & Gamble Pharmaceuticals, Cincinnati, Ohio, and Aventis Pharma, Bridgewater, New Jersey  

Microsoft Academic Search

Limited placebo-controlled data are available to assess the long-term fracture efficacy of bisphosphonates. In order to determine the effects of 5 years of risedronate treatment, we extended a 3-year, placebo-controlled vertebral fracture study in osteoporotic women for an additional 2 years; women who entered the extension study continued to receive 5 mg risedronate or placebo according to the original randomization,

O. H Sorensen; G. M Crawford; H Mulder; D. J Hosking; C Gennari; D Mellstrom; S Pack; D Wenderoth; C Cooper; J.-Y Reginster

2003-01-01

179

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.

J Drugs Dermatol. 2014;13(11):1380-1386. 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

180

Long-term remission in an aggressive Crooke cell adenoma of the pituitary, 18 months after discontinuation of treatment with temozolomide  

PubMed Central

Key Clinical Message The clinical course of our patient, who sustained remission status for at least 18 months highlights the chance of long-term hormonal and tumor remission and demonstrates the efficacy and safety of discontinuation of temozolomide therapy. Prospective studies are required in order to define predictors of long-term remission of this promising therapeutic modality. PMID:25356225

Asimakopoulou, Athina; Tzanela, Marinela; Koletti, Ageliki; Kontogeorgos, George; Tsagarakis, Stylianos

2014-01-01

181

Long-term control of cystoid macular oedema in noninfectious uveitis with Mycophenolate Mofetil  

Microsoft Academic Search

Purpose To evaluate the long-term safety and efficacy of Mycophenolate Mofetil (MMF) for the control of cystoid macular oedema (CMO) secondary to noninfectious uveitis (NU). Methods The medical records of 19 consecutive patients with inflammatory CMO treated with MMF were retrospectively reviewed. Patient demographics, best corrected visual acuity (BCVA), fluorescein angiography (FA), and optical coherence tomography (OCT) findings were evaluated.

Piergiorgio Neri; Cesare Mariotti; Luca Cimino; Lucia Mercanti; Alfonso Giovannini

2009-01-01

182

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

183

Meloxicam: a reappraisal of pharmacokinetics, efficacy and safety.  

PubMed

The discovery of two distinct isoenzymes of COX has led to the development and clinical introduction of COX-2 inhibitors with increased selectivity onto the market. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class, and is a preferential inhibitor of COX-2, demonstrating effectiveness with anti-inflammatory, analgesic and antipyretic activity. Meloxicam is therapeutically utilised in the management of osteoarthritis and rheumatoid arthritis. Trials have examined the risk of gastrointestinal ulceration of meloxicam when compared with traditional non-specific COX-inhibiting NSAIDs with mixed results; meloxicam seems to have a greater gastrointestinal risk than the highly specific COX-2 NSAIDs. Meloxicam has a plasma half-life of approximately 20 h and is convenient for once daily administration. Neither moderate renal nor hepatic insufficiency significantly alters the pharmacokinetics of meloxicam in short-term studies. Furthermore, dose adjustment is not required in the elderly. Recent drug-drug interaction studies have demonstrated that meloxicam interacts with some medications, including cholestyramine, lithium and some inhibitors of cytochrome P450 -2C9 and -3A4. Consequently, increased clinical vigilance should be maintained when coprescribing some medications with meloxicam. Concentration-dependent therapeutic and toxicological effects have yet to be extensively elucidated for meloxicam. Long-term safety in various organ systems, especially in the heart and vascular system and with concomitant drug administration, remains to be proven. The pharmacokinetics of meloxicam enables once daily application, which increases compliance compared with some shorter acting NSAIDs; however, long-term clinical data clearly demonstrating safety and efficacy advantages are lacking. PMID:16197363

Gates, Brian J; Nguyen, Trang T; Setter, Stephen M; Davies, Neal M

2005-10-01

184

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

185

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

186

Multiple use of dialyzers: Safety and efficacy  

Microsoft Academic Search

Multiple use of dialyzers: Safety and efficacy. The practice of multiple use of dialyzers was examined over a 15-month period on all 104 patients in a chronic maintenance hemodialysis facility. A computerized medical information system permitted analysis of the incidence of events in over 10,000 successive hemodialyses. It also allowed analysis of the events in 27 patients dialyzed for a

Kotagal S Kant; Victor E Pollak; Margaret Cathey; Dan Goetz; Rebecca Berlin; David F Eydel; Judy Tessel; Roberta Hall

1981-01-01

187

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

188

Long-term outcome of patients with drug-refractory atrial flutter and fibrillation after single- and dual-site right atrial pacing for arrhythmia prevention  

Microsoft Academic Search

Objectives. An initial crossover study comparing dual- and single-site right atrial pacing was performed followed by a long-term efficacy and safety evaluation of dual-site right atrial pacing in patients with drug-refractory atrial fibrillation (AF). Also examined was the efficacy of two single-site right atrial pacing modes (high right atrium and coronary sinus ostium) and the long-term need for cardioversion, antithrombotic

Philippe Delfaut; Sanjeev Saksena; Atul Prakash; Ryszard B. Krol

1998-01-01

189

Long-term safety of statin-fibrate combination treatment in the management of hypercholesterolaemia in patients with coronary artery disease.  

PubMed Central

OBJECTIVE--To evaluate the long-term safety profile of treatment with a statin-fibrate combination in a cohort of patients with documented coronary artery disease. DESIGN--Retrospective cohort analytical study. SETTING--District general hospital. PATIENTS--102 (81 male and 21 female) hypercholesterolaemic (total cholesterol concentration > 6.5 mmol/l) patients with documented coronary artery disease and who had been treated with a statin-fibrate combination for over 1 year. Coronary artery disease was confirmed by angiography in 93 patients and by a positive (Bruce protocol) exercise test in the remainder. Fifty eight patients had a history of previous coronary bypass graft surgery. INTERVENTIONS--Twice daily lipid lowering treatment was given, with the fibrate administered in the morning (either bezafibrate 400 mg (n = 101) or fenofibrate 200 mg (n = 1)) and the statin in the evening (either simvastatin 10 mg (n = 23), 20 mg (n = 72), or 40 mg (n = 2) or pravastatin 10 mg (n = 1) or 20 mg (n = 4)). Treatment continued for 1 (n = 9), 2 (n = 58), or 3 (n = 35) years. MAIN OUTCOME MEASURES--Selected laboratory variables (total cholesterol concentration and liver (aspartate transaminase (AST)) and muscle enzyme (creatine kinase (CK)) activities) and documented symptomatology. RESULTS--A mean (SD) total cholesterol concentration of 5.2 (0.8) mmol/l was achieved after combined treatment for 1 year which was maintained at annual follow up. Over a maximum 3 year follow up no patient reported myalgic symptoms and none had a measured CK activity > 10 times above nomal. Four men on a simvastatin-bezafibrate combination had a CK activity rise to less than three times normal. Fourteen patients with a negative history of alcohol excess (consumption < 21 units/week) had borderline raised AST values. CONCLUSIONS--Statin-fibrate combination treatment for up to 3 years in a cohort of patients with coronary artery disease was not associated with serious disturbances in biochemical markers of muscle or liver function. PMID:7662446

Feher, M. D.; Foxton, J.; Banks, D.; Lant, A. F.; Wray, R.

1995-01-01

190

Efficacy of ursodeoxycholic acid in combination with interferon-alpha in treating chronic hepatitis C: results of a long-term follow-up trial.  

PubMed

Ursodeoxycholic acid (UDCA) has recently been combined with interferon (IFN) in the treatment of individuals with chronic hepatitis C. However, whether its addition results in a long-term favourable response to IFN remains unclear. A prospective randomized trial of IFN alone versus IFN plus UDCA was therefore undertaken in 52 patients with chronic hepatitis C. All patients received a 24 week course of IFN-alpha (6 x 10(6) U/day for 2 weeks and then three times a week for 22 weeks) and half also received UDCA (600 mg/day) with IFN and then alone for 48 additional weeks. Normalization of serum alanine transaminase (ALT) concentrations at 0, 24 and 48 weeks after cessation of IFN therapy was apparent in 77, 42 and 42% of patients in the IFN-alone group and in 77, 54 and 42% of patients in the IFN plus UDCA group, respectively. There was no significant difference between the two groups with regard to response rate to IFN and the addition of UDCA to IFN treatment had no significant effect on hepatitis C virus (HCV) viraemia. During the follow-up period, 10 of 20 patients with normal serum ALT at the end of IFN treatment relapsed in the IFN-alone group compared with 11 of 20 patients in the IFN plus UDCA group. Among these relapsed patients, serum ALT concentration was significantly lower in the IFN plus UDCA group than in the IFN-alone group during the follow-up period. Twenty-four weeks after cessation of IFN therapy, the percentage of patients with HCV-RNA in their serum who showed a normalization of serum ALT concentrations was significantly higher in the IFN plus UDCA group than in the IFN-alone group (44 vs 6%). Thus, although the addition of UDCA was not associated with a favourable long-term response to HCV viraemia, it did reduce the risk and the severity of relapse following the cessation of IFN therapy. PMID:9034935

Tanaka, K; Kondo, M; Sakaguchi, T; Saito, S; Arata, S; Ikeda, M; Kitamura, T; Morimoto, M; Sekihara, H

1996-12-01

191

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

192

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

193

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.

194

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

195

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

196

Efficacy of Long-Term Daily Dosage of Alfuzosin 10 mg upon Sexual Function of Benign Prostatic Hypertrophy Patients: Two-Year Prospective Observational Study  

PubMed Central

Purpose To identify sexual function improvement associated with alfuzosin (10 mg daily for 2 years). Materials and Methods We enrolled 30 men with lower urinary tract symptom (LUTS) who visited Gyeongsang National University Hospital between 2010 and 2012. At first visit, urinalysis, prostate specific antigen, transrectal ultrasound, and uroflowmetry were performed. The nternational Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF), and Male Sexual Health Questionnaire Ejaculation Function Domain (MSHQ-EjFD) questionnaires were administered, and the subjects answered the same questionnaires at 1 month, 6 months, 1 year, and 2 years of follow-up. Results Twelve men completed of the entire study. After administration of alfuzosin, the median IPSS at first visit, 1 month, 6 months, 1 year, and 2 years was 18.00 (interquatile range [IQR]: 14.00~29.75), 20.00 (IQR: 11.50~30.00), 15.50 (IQR: 8.50~25.25), 14.50 (IQR: 9.25~19.50), and 11.50 (IQR: 5.00~17.75), respectively, which showed an improvement. The median QoL at the same times was 4.50 (IQR: 4.00~5.00), 4.50 (IQR: 4.00~5.00), 3.00 (IQR: 2.00~4.00), 3.50 (IQR: 2.25~4.00), and 3.00 (IQR: 1.00~3.00), respectively, and also showed improvement. Likewise, the median IIEF was 36.50 (IQR: 24.50~46.75), 37.50 (IQR: 26.75~47.25), 45.50 (IQR: 35.00~59.75), 48.50 (IQR: 34.75~62.75), and 47.50 (IQR: 43.25~61.00), while the median MSHQ-EjFD was 19.00 (IQR: 12.0~24.75), 19.50 (IQR: 13.50~27.75), 23.00 (IQR: 19.25~32.25), 26.50 (IQR: 18.25~34.50), 27.00 (IQR: 21.50~32.50), respectively, with both showing improvement. Conclusions After administration of alfuzosin (10 mg daily for 2 years), the IPSS, QoL, IIEF, and MSHQ-EjFD all improved significantly. This means long-term administration of 10 mg of alfuzosin daily would be effective not only for LUTS but also erectile function and ejaculation. PMID:25606561

Yoon, Sol; Choi, Jae Hwi; Lee, Seung Hyun; Choi, See Min; Jeh, Seong Uk; Kam, Sung Chul; Hwa, Jeong Seok; Chung, Ky Hyun

2014-01-01

197

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

198

Treatment of severe intermittent claudication with PGE1--a short-term vs a long-term infusion plan--a 20 week, European randomized trial--analysis of efficacy and costs.  

PubMed

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied by comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 109 patients (96 completed the study) with an average total walking distance of 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks). In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP, phase 2 treatment was performed in 2 days by a 2-hour infusion (1st day: morning 20 microg, afternoon 40 microg; 2nd day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate reduced tolerability or side effects. Full dosage (60 microg b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of the 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% STP vs 107.3% LTP), and at 20 weeks (351% STP vs 242% LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. Average cost of LTP was approximately 6,588 ECU; for STP the average cost was approximately 1,881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,937 ECU vs 550 ECU with STP (p<0.02). The cost of PGE1 (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP). In summary, between-group-analysis favors STP, in terms of walking distance and costs. Results indicate good efficacy and tolerability of PGE1 treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation, and may be used in a larger number of nonspecialized units available to follow the protocol. PMID:9822044

Belcaro, G; Laurora, G; Nicolaides, A N; Agus, G; Cesarone, M R; DeSanctis, M T; Incandela, L; Ricci, A; Cazaubon, M; Ippolito, E; Barsotti, A; Vasdekis, S; Ledda, A; Iacobitti, P; Christopoulos, D; Errichi, B M; Helmis, H; Cornelli, U; Ramaswami, G; Bucci, M; Ferrari, P G; Corsi, M; Pomante, P; Mezzanotte, L; Geroulakos, G

1998-11-01

199

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.

200

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

201

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

202

Repeated transradial catheterization: feasibility, efficacy, and safety.  

PubMed

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

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

2014-12-01

203

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

204

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

205

CAPD with an amino acid dialysis solution: A long-term, cross-over study  

Microsoft Academic Search

CAPD with an amino acid dialysis solution: A long-term, cross-over study. This prospective cross-over study was undertaken to evaluate the safety and efficacy of a 1% amino acid dialysis solution on the nutritional and metabolic changes, plasma amino acid profiles and peritoneal membrane function of patients on CAPD. Six CAPD patients had one exchange a day with two liters of

Michele Bruno; Cristiana Bagnis; Martino Marangella; Lidia Rovera; Alberto Cantaluppi; Franco Linari

1989-01-01

206

A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease  

Microsoft Academic Search

Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2¡8.7 yrs (mean¡SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 mg or placebo

R. Casaburi; D. A. Mahler; P. W. Jones; A. Wannerz; G. San Pedro; S. S. Menjoge; C. W. Serby; T. Witek Jr

2002-01-01

207

Efficacy, safety and risk of augmentation of rotigotine for treating restless legs syndrome.  

PubMed

The present study aimed to examine the long-term efficacy and safety of rotigotine treatment for restless legs syndrome (RLS), as well as the rate of clinically significant augmentation, in a 1-year open-label study of Japanese subjects. Japanese patients with RLS who had been treated with rotigotine or placebo in a double-blind trial were enrolled in a 1-year, open-label, uncontrolled extension study and treated with rotigotine at a dose of up to 3 mg/24 h after an 8-week titration phase. Outcomes included International Restless Legs Syndrome Study Group rating scale (IRLS scale), Pittsburgh Sleep Quality Index (PSQI), safety, and investigator-/expert panel-assessed augmentation (including Augmentation Severity Rating Scale). Overall, 185 patients entered the open-label study and 133 completed the study. IRLS and PSQI total scores improved throughout the 52-week treatment period (IRLS, from 23.2±5.1 to 7.8±7.6 and PSQI, from 8.0±3.1 to 5.0±2.9). Treatment-emergent adverse events were mild to moderate in severity, and included application site reactions (52.4%) and nausea (28.6%). Clinically significant augmentation occurred in five patients (2.7%). These results indicate a good long-term efficacy of rotigotine for treating RLS, with a relatively low risk of clinically significant augmentation. PMID:23103551

Inoue, Yuichi; Hirata, Koichi; Hayashida, Kenichi; Hattori, Nobutaka; Tomida, Takayuki; Garcia-Borreguero, Diego

2013-01-10

208

Long-term safety of anti-TNF adalimumab in HBc antibody-positive psoriatic arthritis patients: a retrospective case series of 8 patients.  

PubMed

Immunosuppressive drugs commonly used in the treatment of psoriatic arthritis make patients more susceptible to viral, bacterial, and fungal infections because of their mechanism of action. They not only increase the risk of new infections but also act altering the natural course of preexisting infections. While numerous data regarding the reactivation of tuberculosis infection are available in the literature, poor information about the risk of reactivation or exacerbation of hepatitis viruses B and C infections during treatment with biologics has been reported. Furthermore, reported series with biological therapy included short periods of followup, and therefore, they are not adequate to verify the risk of reactivation in the long-term treatment. Our study evaluated patients with a history of hepatitis B and psoriatic arthritis treated with adalimumab and monitored up to six years. During the observation period, treatment was effective and well tolerated in all patients, and liver function tests and viral load levels remained unchanged. PMID:23606869

Laurenti, R; Giovannangeli, F; Gubinelli, E; Viviano, M T; Errico, A; Leoni, L; Ballanti, E; Migliore, A

2013-01-01

209

Long-Term Safety of Anti-TNF Adalimumab in HBc Antibody-Positive Psoriatic Arthritis Patients: A Retrospective Case Series of 8 Patients  

PubMed Central

Immunosuppressive drugs commonly used in the treatment of psoriatic arthritis make patients more susceptible to viral, bacterial, and fungal infections because of their mechanism of action. They not only increase the risk of new infections but also act altering the natural course of preexisting infections. While numerous data regarding the reactivation of tuberculosis infection are available in the literature, poor information about the risk of reactivation or exacerbation of hepatitis viruses B and C infections during treatment with biologics has been reported. Furthermore, reported series with biological therapy included short periods of followup, and therefore, they are not adequate to verify the risk of reactivation in the long-term treatment. Our study evaluated patients with a history of hepatitis B and psoriatic arthritis treated with adalimumab and monitored up to six years. During the observation period, treatment was effective and well tolerated in all patients, and liver function tests and viral load levels remained unchanged. PMID:23606869

Laurenti, R.; Giovannangeli, F.; Gubinelli, E.; Viviano, M. T.; Errico, A.; Leoni, L.; Ballanti, E.; Migliore, A.

2013-01-01

210

Long-term outcomes five years after selective dorsal rhizotomy  

Microsoft Academic Search

BACKGROUND: Selective dorsal rhizotomy (SDR) is a well accepted neurosurgical procedure performed for the relief of spasticity interfering with motor function in children with spastic cerebral palsy (CP). The goal is to improve function, but long-term outcome studies are rare. The aims of this study were to evaluate long-term functional outcomes, safety and side effects during five postoperative years in

Eva Nordmark; Annika Lundkvist Josenby; Jan Lagergren; Gert Andersson; Lars-Göran Strömblad; Lena Westbom

2008-01-01

211

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

212

Long-term risks of bisphosphonate therapy.  

PubMed

The objective this study was to summarize long-term risks associated with bisphosphonate therapy. Search of relevant medical publications for data from clinical trials, trial extensions, observational studies and post-marketing reports. Trial extensions and modifications did not reveal significant long-term safety issues. Observational data suggest at least as many benefits as risks. Post-marketing reports of musculoskeletal pain, osteonecrosis of the jaw and atypical femur fractures have been widely circulated in the lay press. Most focus on long-terms risks has been on osteonecrosis of the jaw and atypical femur fractures which occur in patients who have not received bisphosphonate therapy but may be more frequent (though still uncommon) in patients who have been on treatment for 5 years or longer. Lower-risk patients may be able to stop treatment after 3-5 years for a "drug holiday," which mitigates these long-term risks; for higher risk patients, therapy through 6-10 years appears to be advisable and offers more benefits than risks. PMID:25166043

Watts, Nelson B

2014-07-01

213

Loteprednol etabonate ophthalmic suspension 0.5 %: efficacy and safety for postoperative anti-inflammatory use.  

PubMed

Topical corticosteroids are routinely used as postoperative ocular anti-inflammatory drugs; however, adverse effects such as increased intraocular pressure (IOP) are observed with their use. While older corticosteroids such as dexamethasone and prednisolone acetate offer good anti-inflammatory efficacy, clinically significant increases in IOP (?10 mmHg) are often associated with their use. Loteprednol etabonate, a novel C-20 ester-based corticosteroid, was retrometabolically designed to offer potent anti-inflammatory efficacy but with decreased impact on IOP. After exerting its therapeutic effects on the site of action, loteprednol etabonate is rapidly converted to inactive metabolites, resulting in fewer adverse effects. Randomized controlled studies have demonstrated the clinical efficacy and safety of loteprednol etabonate ophthalmic suspension 0.5 % for the treatment of postoperative inflammation in post-cataract patients with few patients, if any, exhibiting clinically significant increases (?10 mmHg) in IOP. Furthermore, safety studies demonstrated a minimal effect of loteprednol etabonate on IOP with long-term use or in steroid responders with a much lower propensity to increase IOP relative to prednisolone acetate or dexamethasone. The anti-inflammatory treatment effect of loteprednol etabonate appears to be similar to that of rimexolone and difluprednate with less impact on IOP compared to difluprednate, although confirmatory comparative studies are needed. The available clinical data suggest that loteprednol etabonate is an efficacious and safe corticosteroid for the treatment of postoperative inflammation. PMID:22707339

Amon, Michael; Busin, Massimo

2012-10-01

214

Long-term potentiation in the hippocampus.  

PubMed

Long-term potentiation of field and single neuronal responses recorded in various hippocampal fields is described on the basis of author's and literary data. Most of intrahippocampal and extrinsic connections in both in vivo and in vitro hippocampal preparations show this phenomenon after one or several conditioning trains of comparatively short duration (20 s or less) at various frequencies (from 10 to 400 Hz). Properties of hippocampal potentiation are described. The properties include long term persistence (hours and days) of the potentiated response, its low frequency depression, self-restoration after the depression, specificity of the potentiation for the tetanized pathway, necessity of activation of a sufficient number of neuronal elements ('cooperativity') to produce the potentiation, possible involvement of 'reinforcing' brain structures during conditioning tetanization. These properties are distinct from those of 'usual' short-term post-tetanic potentiation and lead to the suggestion that the neuronal mechanisms underlying long-term post-tetanic are similar to those underlying memory and behavioral-conditioned reflex. Neurophysiological mechanisms of long-term potentiation are discussed. The main mechanism consists in an increase in efficacy of excitatory synapses as shown by various methods including intracellular recording and quantal analysis. The latter favours presynaptic localization of changes of synaptic efficacy showing increase in the number of transmitter quanta released per presynaptic impulse. However, changes in the number of subsynaptic receptors or localized changes in dendritic postsynaptic membrane are not excluded. Biochemical studies indicate the increase in transmitter release and calcium-dependent phosphorylation of pyruvate dehydrogenase after tetanization. Instances of persistent response facilitations at other levels of the vertebrate central nervous system (especially at neocortical level) are considered and compared with hippocampal long-term potentiation. It is suggested that modifiable excitatory synapses necessary for learning have been identified in studies of long-term potentiation. These synapses are presumably modified as a result of close sequential activation of the following three structures: excitatory presynaptic fibers, the postsynaptic neuron and a 'reinforcing' brain system. PMID:6141538

Voronin, L L

1983-12-01

215

Feasibility and Safety of Laparoscopic Surgery for Obese Korean Women with Endometrial Cancer: Long-Term Results at a Single Institution  

PubMed Central

The purpose of this study was to evaluate the surgical feasibility of and survival outcome after laparoscopy in obese Korean women with endometrial cancer which has recently been increasing. We reviewed the medical records of the patients treated at our medical institution between 1999 and 2012. The patients were divided into three groups, non-obese (Body Mass Index [BMI]<25.0), overweight (BMI 25-27.99), and obese (BMI?28.0). These patient groups were compared in terms of their clinical characteristics, treatment methods, as well as surgical and survival outcomes. In total, 55 of the 278 eligible patients were obese women. There were no differences in the three groups in terms of the proportion of patients who underwent lymphadenectomy, their cancer stage, histologic type, type of adjuvant treatment administered, intra-, post-operative, and long-term complications, operative time, number of removed lymph nodes, blood loss, and duration of hospitalization (P=0.067, 0.435, 0.757, 0.739, 0.458, 0.173, 0.076, 0.124, 0.770, 0.739, and 0.831, respectively). The Disease-Free Survival (DFS) times were 139.1 vs. 121.6 vs. 135.5 months (P=0.313), and the Overall Survival (OS) times were 145.2 vs. 124.8 vs. 139.5 months (P=0.436) for each group, respectively. Obese women with endometrial cancer can, therefore, be as safely managed using laparoscopy as women with normal BMIs. PMID:25408586

Lee, Shin-Wha; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun

2014-01-01

216

Prucalopride: safety, efficacy and potential applications.  

PubMed

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

Quigley, Eamonn M M

2012-01-01

217

St. Louis Sites Fact Sheet LONG-TERM STEWARDSHIP  

E-print Network

of prohibitive costs, and worker safety issues. Long-term stewardship will be required to ensure that remedies, HISS). These sites contain soils contaminated with radium, thorium, and uranium as a result

US Army Corps of Engineers

218

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

Microsoft Academic Search

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)

Carmen Ares; Eugen B. Hug; Antony J. Lomax; Alessandra Bolsi; Beate Timmermann; Hans Peter Rutz; Jan C. Schuller; Eros Pedroni; Gudrun Goitein

2009-01-01

219

Long-term treatment goals: enhancing healthy outcomes.  

PubMed

The long-term management of schizophrenia with a goal of functional rehabilitation remains an enormous challenge to clinicians despite improvements in drug therapy, psychosocial treatments, and family and community interventions. The goals of long-term therapy are to preserve the gains made during acute treatment, prevent symptom exacerbation, enhance psychosocial functioning, and improve quality of life. Schizophrenia is an illness that disrupts broad areas of mental function, including thought, cognition, affect, and motor performance. The new antipsychotics should aid physicians in meeting higher treatment goals for persons with schizophrenia. These agents combine high efficacy with improved tolerability, mainly through a low liability for extrapyramidal symptoms and probably improve cognitive affect. Recent studies have demonstrated efficacy of these new antipsychotics in improving psychopathology and symptoms and in preventing relapse during long-term use. These drugs are likely to provide physicians with an increasingly viable option in the long-term treatment and rehabilitation of patients with schizophrenia. PMID:14978456

Casey, Daniel E

2003-11-01

220

Dexmedetomidine hydrochloride as a long-term sedative.  

PubMed

Dexmedetomidine undoubtedly is a useful sedative in the intensive care setting because it has a minimal effect on the respiratory system. Dexmedetomidine infusions lasting more than 24 hours have not been approved since the first approval was acquired in the US in 1999. However, in 2008, dexmedetomidine infusions for prolonged use were approved in Colombia and in the Dominican Republic, and the number of countries that have granted approval for prolonged use has been increasing every year. This review discusses the literature examining prolonged use of dexmedetomidine and confirms the efficacy and safety of dexmedetomidine when it is used for more than 24 hours. Dexmedetomidine was administered at varying doses (0.1-2.5 ?g/kg/hour) and durations up to 30 days. Dexmedetomidine seems to be an alternative to benzodiazepines or propofol for achieving sedation in adults because the incidences of delirium and coma associated with dexmedetomidine are lower than the corresponding incidences associated with benzodiazepines and propofol, although dexmedetomidine administration can cause mild adverse effects such as bradycardia. Controlled comparative studies on the efficacy and safety of dexmedetomidine and other sedatives in pediatric patients have not been reported. However, dexmedetomidine seems to be effective in managing extubation, reducing the use of conventional sedatives, and as an alternative for inducing sedation in patients for whom traditional sedatives induce inadequate sedation. Prolonged dexmedetomidine infusion has not been reported to have any serious adverse effects. Dexmedetomidine appears to be an alternative long-term sedative, but further studies are needed to establish its efficacy and safety. PMID:21845052

Kunisawa, Takayuki

2011-01-01

221

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

222

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

223

Long-Term Doxycycline-Controlled Expression of Human Tyrosine Hydroxylase after Direct Adenovirus-Mediated Gene Transfer to a Rat Model of Parkinson's Disease  

Microsoft Academic Search

Developments of technologies for delivery of foreign genes to the central nervous system are opening the field to promising treatments for human neurodegenerative diseases. Gene delivery vectors need to fulfill several criteria of efficacy and safety before being applied to humans. The ability to drive expression of a therapeutic gene in an adequate number of cells, to maintain long-term expression,

Olga Corti; Amelia Sanchez-Capelo; Philippe Colin; Naima Hanoun; Michel Hamon; Jacques Mallet

1999-01-01

224

Ospemifene 12-month safety and efficacy in postmenopausal women with vulvar and vaginal atrophy  

PubMed Central

Objective Assessment of 12-month safety of ospemifene 60 mg/day for treatment of postmenopausal women with vulvar and vaginal atrophy (VVA). Methods In this 52-week, randomized, double-blind, placebo-controlled, parallel-group study, women 40–80 years with VVA and an intact uterus were randomized 6 : 1 to ospemifene 60 mg/day or placebo. The primary objective was 12-month safety, particularly endometrial; 12-week efficacy was assessed. Safety assessments included endometrial histology and thickness, and breast and gynecological examinations. Efficacy evaluations included changes from baseline to week 12 in percentage of superficial and parabasal cells and vaginal pH. Results Of 426 randomized subjects, 81.9% (n = 349) completed the study with adverse events the most common reason for discontinuation (ospemifene 9.5%; placebo 3.9%). Most (88%) treatment-emergent adverse events with ospemifene were considered mild or moderate. Three cases (1.0%) of active proliferation were observed in the ospemifene group. For one, active proliferation was seen at end of study week 52, and diagnosed as simple hyperplasia without atypia on follow-up biopsy 3 months after the last dose. This subsequently resolved with progestogen treatment and dilatation and curettage. In six subjects (five ospemifene (1.4%), one placebo (1.6%)) endometrial polyps were found (histopathology); however, only one (ospemifene) was confirmed as a true polyp during additional expert review. Endometrial histology showed no evidence of carcinoma. Statistically significant improvements were seen for all primary and secondary efficacy measures and were sustained through week 52 with ospemifene vs. placebo. Conclusions The findings of this 52-week study confirm the tolerance and efficacy of oral ospemifene previously reported in short- and long-term studies. PMID:23984673

2014-01-01

225

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

226

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

227

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

228

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

229

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

230

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

231

Evaluation of the efficacy, toxicity and safety of vinorelbine incorporated in a lipid emulsion.  

PubMed

To reduce the severe adverse effects of vinorelbine (VRB) with the aim of improving patient compliance, a parenteral vinorelbine-loaded lipid emulsion (VLE) has been developed. The objective of the present study was to get insight into the preclinical antitumor efficacy, toxicity and safety of VLE, and compare this with that of the commercial product, Navelbine(®) i.v. (VS). Comparable antitumor efficacy of VLE and VS was observed in tumor-bearing nude mouse models inoculated with A549 human lung cancer, hepatoma solidity (Heps) G2 cancer and BCAP-37 human breast cancer cells. The median lethal dose (LD(50)) in mice was 29.3mg/kg (male) and 32.1mg/kg (female) for VLE, while the corresponding value was 30.5mg/kg (male and female) for VS. In the long-term toxicity study, VLE significantly reduced the decreases in RBC, HC, WBC and WBC differential count (DC) levels. Lesions in spleen, thymus, lymph nodes, bone marrow, testis, ovary and injection site induced by VS were much more severe compared with VLE. VLE also exhibited less local venous irritation than VS, as well as no hemolysis or hypersensitivity. Consequently, these observations clearly indicate that the lipid emulsion could be a useful potential parenteral carrier for VRB with equivalent efficacy and lower toxicity. PMID:21421039

Su, Min; Zhao, Mingming; Luo, Yanfei; Lin, Xia; Xu, Lishuang; He, Haibing; Xu, Hui; Tang, Xing

2011-06-15

232

Efficacy and safety of topical tacrolimus for the treatment of face and neck vitiligo.  

PubMed

Vitiligo is a common acquired idiopathic hypomelanotic disorder characterized by circumscribed depigmented maculae. The conventional treatments are limited by their inconsistent and incomplete responses, relapse rate, inconvenience to apply, side-effects and especially long-term effects. The aim of the present study was to determine the efficacy and safety of topical tacrolimus as monotherapy for the treatment of face/neck vitiligo in Taiwan. This was a multicenter, open-label, non-comparative study. Patients were at least 16 years old and had vitiligo lesions with Vitiligo Index of Disease Activity score +1 or more on face or neck. Patients received a monotherapy with 0.1% of tacrolimus ointment twice daily for 12 weeks. The efficacy was measured by the percentage of repigmentation of target lesion, which was graded as minimal (1-25%), mild (26-50%), moderate (51-75%) or excellent (76-100%). Patients who had at least mild repigmentation were defined as responders. A total of 61 patients were enrolled in this investigation. Most of the patients showed repigmentation at week 4. At the end of treatment, all patients showed repigmentation and 45.9% of patients were responders. During the study, 15 adverse events related to the ointment were reported. All the reported adverse events were mild and similar to the well-known adverse effect of tacrolimus in the treatment of atopic dermatitis. Tacrolimus ointment is effective and well tolerated for the treatment of patients with vitiligo in Taiwan. It will be another drug of choice for persons with vitiligo who are unable to receive regular phototherapy and fear the side-effects of topical steroid in long-term use. PMID:20175845

Lo, Yuan-Hsin; Cheng, Gwo-Shing; Huang, Chieh-Chen; Chang, Wen-Yu; Wu, Chieh-Shan

2010-02-01

233

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, Celine; Deichmann, Annette; Denaro, Maria; Dreuzy, Edouard de; Finer, Mitchell; Fronza, Raffaele; Gillet-Legrand, Beatrix; Joubert, Christophe; Kutner, Robert; Leboulch, Philippe; Maouche, Leila; Paulard, Anais; Pierciey, Francis J; Rothe, Michael; Ryu, Byoung; Schmidt, Manfred; Kalle, Christof von; Payen, Emmanuel; Veres, Gabor

2015-01-01

234

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

235

Long-term oxygen therapy.  

PubMed

This article provides an overview of the status of long-term oxygen therapy (LTOT). In the United States, payment cutbacks are occurring as a result of congressionally mandated competitive bidding and capped rental programs. These Medicare programs are discussed. These legislative and regulatory changes may result in reduced patient access to appropriate oxygen-delivery systems that meet medical needs, including optimal ambulation. Prescribing LTOT is addressed in this article, as is the need for adequate patient education. The importance of appropriate monitoring and reassessment is presented. The use of an LTOT collaborative care model is discussed. Although the new intermittent flow oxygen-delivery systems have potential benefits, there is consensus that each patient should be tested on the specific device because of variability in delivery and patient response. Feasible locations for patient education and monitoring are identified. PMID:21285057

Christopher, Kent L; Porte, Phillip

2011-02-01

236

The Efficacy of Material Safety Data Sheets and Worker Acceptability  

Microsoft Academic Search

This study quantified how well the Material Safety Data Sheet (MSDS) diffused information to workers, compared the efficacy of an OSHA type form with the Chemical Manufacturer’s Association\\/American National Standards Institute (CMA\\/ANSI Z400.1) structure and the International Chemical Safety Card (ICSC), and determined worker acceptability and understanding of MSDSs at a large national laboratory. An inventory questionnaire and quantitative testing

Charles C Phillips; Bill C Wallace; Charles B Hamilton; Robert T Pursley; Gregory C Petty; Charles K Bayne

1999-01-01

237

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

238

Long-term Improvement in Functional Dyspepsia Using Hypnotherapy  

Microsoft Academic Search

See editorial on page 2132. Background & Aims: We have shown hypnotherapy (HT) to be effective in irritable bowel syndrome, with long- term improvements in symptomatology andquality of life (QOL). This study aimed to assess the efficacy of HT in functional dyspepsia (FD). Methods: A total of 126 FD patients were randomized to HT, supportive therapy plus placebo medication, or

EMMA LOUISE CALVERT; LESLEY ANNE HOUGHTON; PATRICIA COOPER; JULIE MORRIS; PETER JAMES WHORWELL

2002-01-01

239

Long-term improvement in functional dyspepsia using hypnotherapy  

Microsoft Academic Search

Background & Aims: We have shown hypnotherapy (HT) to be effective in irritable bowel syndrome, with long-term improvements in symptomatology and quality of life (QOL). This study aimed to assess the efficacy of HT in functional dyspepsia (FD). Methods: A total of 126 FD patients were randomized to HT, supportive therapy plus placebo medication, or medical treatment for 16 weeks.

Emma Louise Calvert; Lesley Anne Houghton; Patricia Cooper; Julie Morris; Peter James Whorwell

2002-01-01

240

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

241

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

242

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

243

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

244

Long-term, intermittent treatment of chronic hand eczema with mometasone furoate.  

PubMed

Chronic hand eczema can be incapacitating, and there is little knowledge of the efficacy and safety of long-term treatment with topical corticosteroids. We compared the efficacy and safety of two different schedules for the treatment of chronic hand eczema with a potent topical corticosteroid, mometasone furoate. In a prospective, open, randomized trial, 120 patients with chronic hand eczema were treated daily with mometasone furoate fatty cream until the dermatitis cleared or for a maximum of 9 weeks. Those who cleared were randomized to treatment for up to 36 weeks with mometasone furoate on Sunday, Tuesday and Thursday (group A), mometasone furoate on Saturday and Sunday (group B) or no further corticosteroid treatment (group C). In the event of relapse, patients were permitted daily treatment with mometasone furoate for 3 weeks on two separate occasions. For 50 of 106 randomized patients, daily treatment for 3 weeks controlled their dermatitis; 29 needed 6 weeks and 27 needed 9 weeks of treatment. During the maintenance phase, 29 of 35 (83%) in group A, 25 of 37 (68%) in group B and nine of 34 (26%) in group C had no recurrences (P = 0.001, chi2-test). Side-effects were minimal. It is concluded that long-term, intermittent treatment of chronic hand eczema with mometasone furoate fatty cream is effective and safe. PMID:10354026

Veien, N K; Olholm Larsen, P; Thestrup-Pedersen, K; Schou, G

1999-05-01

245

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

246

Viability of Long-Term Gene Therapy in the Cochlea  

PubMed Central

Gene therapy has been investigated as a way to introduce a variety of genes to treat neurological disorders. An important clinical consideration is its long-term effectiveness. This research aims to study the long-term expression and effectiveness of gene therapy in promoting spiral ganglion neuron survival after deafness. Adenoviral vectors modified to express brain derived neurotrophic factor or neurotrophin-3 were unilaterally injected into the guinea pig cochlea one week post ototoxic deafening. After six months, persistence of gene expression and significantly greater neuronal survival in neurotrophin-treated cochleae compared to the contralateral cochleae were observed. The long-term gene expression observed indicates that gene therapy is potentially viable; however the degeneration of the transduced cells as a result of the original ototoxic insult may limit clinical effectiveness. With further research aimed at transducing stable cochlear cells, gene therapy may be an efficacious way to introduce neurotrophins to promote neuronal survival after hearing loss. PMID:24751795

Atkinson, Patrick J.; Wise, Andrew K.; Flynn, Brianna O.; Nayagam, Bryony A.; Richardson, Rachael T.

2014-01-01

247

Transuranic waste: long-term planning  

SciTech Connect

Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig.

Young, K.C.

1985-07-01

248

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

249

Topical retinoids in acne vulgaris: update on efficacy and safety.  

PubMed

Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe. Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy. PMID:18973403

Thielitz, Anja; Gollnick, Harald

2008-01-01

250

New Devices Designed to Improve the Long-Term Results of Endovascular Treatment of Intracranial Aneurysms  

PubMed Central

Summary Endovascular coiling can improve the outcome of patients with ruptured intracranial aneurysms, but angiographic recurrences are frequent compared to surgical clipping. New coils or devices have been introduced to improve long-term results of endovascular treatment but none have been the object of a valid clinical trial. We have proposed a multicentric randomized double-blind study comparing radioactive and standard coil occlusion of aneurysms. The purpose of this article is to review issues that are specific to the design of clinical trials to assess embolic agents that could improve the long-term efficacy of endovascular treatment of intracranial aneurysms. The proposed trial is a randomized, multi-center, prospective, controlled trial comparing the new generation coils to standard platinum coils. Blinding, if at all possible, is preferable to minimize bias, at least for follow-up angiographic studies that should cover a period of 18 months. All patients with an intracranial aneurysm eligible for endovascular treatment would be proposed to participate. The study would enrol approximately 500 patients equally divided between the two groups, recruited within two years, to demonstrate a decrease in the recurrence rate, the primary outcome measure, from 20% to 10%. Secondary outcome measures should assure that complications, initial clinical and angiographic results remain unchanged. Independent data safety and monitoring committees are crucial to the credibility of trials and to ensure scientific rigor and objectivity. The scientific demonstration of an improved long-term efficacy, without significant compromise regarding safety, is mandatory before considering the widespread use of a new embolic device for the endovascular treatment of aneurysms. PMID:20587221

Raymond, J.; Leblanc, P.; Chagnon, M.; Gévry, G.; Collet, J.-P.; Guilbert, F.; Weill, A.; Roy, D.

2004-01-01

251

Long-term monitoring FBG-based cable load sensor  

Microsoft Academic Search

Stay cables are the main load-bearing components of stayed-cable bridges. The cables stress status is an important factor to the stayed-cable bridge structure safety evaluation. So it's very important not only to the bridge construction, but also to the long-term safety evaluation for the bridge structure in-service. The accurate measurement for cable load depends on an effective sensor, especially to

Zhichun Zhang; Zhi Zhou; Chuan Wang; Jinping Ou

2006-01-01

252

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

253

Sublingual immunotherapy in allergic rhinitis: efficacy, safety, adherence and guidelines.  

PubMed

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

Aboshady, Omar Ali; Elghanam, Karim Mohamed

2014-12-01

254

Long-term solar-terrestrial observations  

NASA Technical Reports Server (NTRS)

The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

1988-01-01

255

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.

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

2014-01-01

256

Quality, efficacy and safety of complementary medicines: fashions, facts and the future. Part II: Efficacy and safety  

PubMed Central

This is the second of two papers which review issues concerning complementary medicines. The first reviewed the extent of use of complementary medicines, and issues related to the regulation and pharmaceutical quality of these products; the second considers evidence for the efficacy of several well-known complementary medicines, and discusses complementary-medicines pharmacovigilance. The term complementary medicines describes a range of pharmaceutical-type preparations, including herbal medicines, homoeopathic remedies, essential oils and dietary supplements, which mainly sit outside conventional medicine. The use of complementary medicines is a popular healthcare approach in the UK, and there are signs that the use of such products is continuing to increase. Patients and the public use complementary medicines for health maintenance, for the treatment or prevention of minor ailments, and also for serious, chronic illnesses. There is a growing body of evidence from randomized controlled trials and systematic reviews to support the efficacy of certain herbal extracts and dietary supplements in particular conditions. However, many other preparations remain untested. Strictly speaking, evidence of efficacy (and safety) for herbal medicines should be considered to be extract specific. Pharmacovigilance for complementary medicines is in its infancy. Data are lacking in several areas relevant to safety. Standard pharmacovigilance tools have additional limitations when applied to investigating safety concerns with complementary medicines. PMID:12680880

Barnes, Joanne

2003-01-01

257

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

258

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

259

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

260

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

2014-09-24

261

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

262

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

263

Virtual Models of Long-Term Care  

ERIC Educational Resources Information Center

Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

Phenice, Lillian A.; Griffore, Robert J.

2012-01-01

264

Long Term TOA - M Data and Information  

Atmospheric Science Data Center

A Long-Term TOA and Constrained Surface Radiation Budget Project ... (TOA) and surface is a fundamental quantity governing climate variability and, for that reason, NASA has been making concerted ... utilizes knowledge gained in the last 10 years through CERES data analyses and apply the knowledge to existing data to develop long-term ...

2014-08-06

265

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 ...

266

Long-term combination antipsychotic treatment in VA patients with schizophrenia.  

PubMed

Treatment guidelines consider antipsychotic monotherapy the standard of care for patients with schizophrenia. However, previous studies have reported widely varying, and sometimes high, rates of antipsychotic polypharmacy. We identified 61,257 VA patients with schizophrenia in fiscal year 2000 who had >or=90 non-institutionalized days and one or more fills of antipsychotic medications. We used criteria of increasing stringency (>or=30, >or=60, or >or=90 overlapping days' supply of antipsychotic medications) and several cross-sectional criteria from previous studies to compare the prevalence of antipsychotic polypharmacy using these definitions. We also describe specific treatment combinations among patients receiving long-term polypharmacy. The prevalence of antipsychotic polypharmacy was 20.0%, 13.1%, and 9.5% when defined by a >or=30, >or=60, or >or=90-day overlap, respectively. Cross-sectional definitions used in previous studies did not identify 32-89% of patients receiving long-term polypharmacy (>or=90 days). In addition, approximately half of patients identified by cross-sectional criteria had only short-term overlaps of antipsychotic medications. Among patients receiving long-term polypharmacy, 74% received a first- and a second-generation agent, 18% received two second-generation agents, and 6% received two first-generation agents. Definitions of polypharmacy that rely on cross-sectional data or narrow observation periods do not accurately identify patients receiving long-term treatment; in this study, only 10% of patients with schizophrenia received combination treatments for >or=90 days. The most commonly used antipsychotic combinations have little support for safety or efficacy. Further research is needed to understand the impact of these treatments on symptoms, side effects, and costs. PMID:16631354

Kreyenbuhl, Julie; Valenstein, Marcia; McCarthy, John F; Ganoczy, Dara; Blow, Frederic C

2006-05-01

267

Transdermal application of methimazole in hyperthyroid cats: a long-term follow-up study.  

PubMed

Transdermal methimazole is suggested as an alternative to oral therapy for hyperthyroid cats that are difficult to pill. However, no information on long-term management with this treatment is available. Our objective was therefore to retrospectively evaluate the efficacy and safety of long-term transdermal methimazole treatment in hyperthyroid cats. Sixty cats with newly diagnosed hyperthyroidism and available long-term follow-up information were included. Methimazole was formulated in a pluronic lecithin organogel-based vehicle and was applied to the pinna of the inner ear. Cats were re-evaluated at regular intervals. Median (range) follow-up was 22.6 months (3.6-88.4 months). Clinical improvement was observed in all cats and side effects were rare (mild transient gastrointestinal signs: n = 3; erythema of the pinna: n = 2, necessitating a switch to oral medication). Despite a significant decrease, with median T4 concentrations within the reference interval during the follow-up period, several cats repeatedly had T4 concentrations in the thyrotoxic and hypothyroid range. Maximal and minimal daily doses during the follow-up period were 15.0 and 1.0 mg, respectively; they were significantly higher than the starting dose after 24-36 months of therapy. Although the majority of owners were highly satisfied with the treatment, several admitted not treating their cat regularly. Transdermal methimazole is a safe option for the long-term management of feline hyperthyroidism. However, it seems difficult to keep the T4 concentrations constantly within the reference interval. Higher doses can be expected after prolonged treatment and, despite the convenience of transdermal application, owner compliance should be assessed regularly. PMID:24174499

Boretti, Felicitas S; Sieber-Ruckstuhl, Nadja S; Schäfer, Sandra; Gerber, Bernhard; Baumgartner, Claudia; Riond, Barbara; Hofmann-Lehmann, Regina; Reusch, Claudia E

2014-06-01

268

Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis  

Microsoft Academic Search

The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales

D T Wade; P M Makela; H House; C Bateman; P Robson

2006-01-01

269

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

270

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

271

Efficacy and safety of rufinamide in pediatric epilepsy.  

PubMed

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; Thiele, Elizabeth A

2013-05-01

272

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

273

Long-term treatment of benign prostatic hyperplasia with alfuzosin: a 12-18 month assessment. BPHALF Group.  

PubMed

In order to assess the efficacy and safety of alfuzosin, an alpha-1 blocker, in symptomatic patients with benign prostatic hyperplasia (BPH), 131 patients who had completed a 6-month placebo-controlled trial conducted on parallel groups entered a 12-month open study; 122 patients were treated with alfuzosin for 12 months and 56 patients for 18 months. After 12 months, all obstructive and irritative symptoms assessed according to the Boyarsky scale were significantly improved, as were peak flow rates in obstructed patients and mean flow rates and residual urine in the whole population. Voiding symptoms showed sustained improvement after treatment for 12 to 18 months. Only 5.3% of patients experienced vasodilatory side effects, none of which led to withdrawal from the study. No side effect related to long-term administration was reported. Alfuzosin has a beneficial effect on voiding symptoms in patients with BPH and can be safely used in long-term administration. PMID:10071548

Jardin, A; Bensadoun, H; Delauche-Cavallier, M C; Attali, P

1993-11-01

274

Long-term care in North Carolina.  

PubMed

Much of long-term care is not considered health care, as it is custodial, social, and supportive. But excellent long-term care is also preventive, timely, and accessible, and it provides space for long-term care recipients to find joy and meaning in their lives. This issue of the NCMJ provides abroad overview of long-term care, practical information about programs in our state, and tips for how to make use of these programs. Commentaries and sidebars in this issue also highlight new ideas, innovation, and transformation. This issue brief sets the stage by describing major events that have shaped the current framework of long-term care services and supports. It also discusses current trends that are influencing long-term care, including the emphasis on quality improvement methods, culture change, health care reform, the influence of geriatrics in primary care, and the desire for home-based care. Although we are not yet where we want to be in North Carolina, we are moving toward a long-term care system that will serve all North Carolinians well. PMID:25237870

White, Heidi K

2014-01-01

275

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

276

Long-term follow-up after gene therapy for canavan disease.  

PubMed

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-acetyl-aspartate (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 × 10(11) 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

2012-12-19

277

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

278

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

279

Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER)  

PubMed Central

Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (<1-45 years of age, 21 female). Severest phenotypes (central nervous system, gastrointestinal, joint bleeding episodes) were highly prevalent. Twenty-one patients received recombinant activated factor VII (24 courses), four received plasma-derived factor VII, and ten received freshfrozen plasma. Prophylactic schedules clustered into “frequent” courses (three times weekly, n=23) and “infrequent” courses (?2 times weekly, n=15). Excluding courses for menorrhagia, “frequent” and “infrequent” courses produced 18/23 (78%) and 5/12 (41%) “excellent” outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on “frequent” administrations (three times weekly) and a 90 ?g/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency (clinicaltrials.gov: NCT01269138). PMID:23403322

Napolitano, Mariasanta; Giansily-Blaizot, Muriel; Dolce, Alberto; Schved, Jean F.; Auerswald, Guenter; Ingerslev, Jørgen; Bjerre, Jens; Altisent, Carmen; Charoenkwan, Pimlak; Michaels, Lisa; Chuansumrit, Ampaiwan; Di Minno, Giovanni; Caliskan, Ümran; Mariani, Guglielmo

2013-01-01

280

Safety and efficacy of encainide for malignant ventricular arrhythmias.  

PubMed

The antiarrhythmic effect of encainide was evaluated in 140 patients with documented symptomatic ventricular tachycardia or ventricular fibrillation refractory to conventional agents. In 102 patients with reproducible spontaneous arrhythmia, noninvasive methods, including ambulatory monitoring and exercise testing, were used to evaluate drug efficacy, while in the remaining 38 patients electrophysiologic testing was performed. Side effects necessitated drug discontinuation in 10 patients before noninvasive evaluation. Of the remaining 92 patients 44 (48%) responded to encainide. Of the 38 patients who underwent electrophysiologic study, 1 discontinued encainide because of side effects and in 4 patients the spontaneous occurrence of sustained ventricular tachycardia precluded repeat study. Of the remaining 33 patients, 10 (30%) were rendered noninducible with encainide. The drug was more effective in those with a left ventricular ejection fraction greater than 35% (p less than 0.03) and in those presenting with nonsustained ventricular tachycardia. Side effects were reported in 53 of 140 patients (38%) and were primarily nausea, vomiting, headaches and tremors. Aggravation of arrhythmia occurred in 4% of patients with a history of nonsustained arrhythmia and in 25% of those with a history of sustained ventricular tachycardia or ventricular fibrillation. Worsening of arrhythmia was not related to mean dose of drug, mean blood level or electrocardiographic changes; it was more likely to occur in patients with a markedly reduced left ventricular ejection fraction (average 32%) and in those with a history of sustained ventricular tachyarrhythmia (p less than 0.05). Long-term encainide therapy was continued in 48 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3092625

Tordjman, T; Podrid, P J; Raeder, E; Lown, B

1986-08-29

281

An update on the safety and efficacy of topical retinoids.  

PubMed

Adapalene, tazarotene, and tretinoin are topical retinoids that are approved by the US Food and Drug Administration (FDA) and have overall favorable safety profiles. These agents are effective in a variety of skin disorders. Local adverse events, seen especially during the early course of treatment, include peeling, erythema, dryness, burning, and itching. The degree of local skin intolerance varies among patients and may relate to the vehicle formulation used. These local effects can be minimized by decreasing exposure to sunlight, avoiding extreme temperatures, and using moisturizers. Use of these agents has been found to be advantageous over current systemic retinoids from a toxicologic perspective. This article reviews the safety, efficacy, and photostability of the available topical retinoids. PMID:15773539

Phillips, Tania J

2005-02-01

282

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With  

E-print Network

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated

Napp, Nils

283

Lessons from Long-term Studies  

E-print Network

Lessons from Long-term Studies Gordon Reeves U.S. Forest Service PNW Research Station Corvallis #12 for a watershed and reaches to produce fish depends on inherent features #12;#12;Elk River Chinook Salmon Numbers

284

State Medicaid Programs (Long-Term Care)  

MedlinePLUS

... your family by thinking ahead and making your decisions known. Costs & How to Pay Long-term care is expensive, but there are several ways ... is a joint federal and state government program that helps people with low income and ...

285

Long Term Effects of Food Poisoning  

MedlinePLUS

... develop chronic arthritis. Brain and nerve damage A Listeria infection can lead to meningitis, an inflammation of ... brain. If a newborn infant is infected with Listeria , long-term consequences may include mental retardation, seizures, ...

286

Powell Lawton's Contributions to Long-Term Care Settings  

Microsoft Academic Search

The design of long-term care facilities has changed radically over the past three decades, due in large part to the pioneering work of Powell Lawton. His early conceptualizations of key principles for people with dementia-orientation, negotiability, personalization, social interaction and safety-were considered somewhat radical when first applied in the Weiss Institute. Now, several decades later, many of the design implications

Margaret P. Calkins

2003-01-01

287

Who Should Buy Long-Term Bonds?  

Microsoft Academic Search

According to conventional wisdom, long-term bonds are appropriate for conservative long-term investors. This paper develops a model of optimal consumption and portfolio choice for infinite-lived investors with recursive utility who face stochastic interest rates, solves the model using an approximate analytical method, and evaluates conventional wisdom. As risk aversion increases, the myopic component of risky asset demand disappears but the

John Y. Campbell; Luis M. Viceira

2001-01-01

288

Long-term solar activity predictions  

NASA Technical Reports Server (NTRS)

The need for long term solar activity predictions is addressed. The spatial organization of solar activity is described including applications for predictions, and ancient evidence for solar variability. Methods of predicting sunspot numbers are discussed. The inherent accuracy of the methods varies considerably, but a typical error bar 20%. The accuracy of sunspot cycle predictions is considered along with long term predictions of great solar events.

Mcintosh, P. S.; Brown, G. M.; Buhmann, R.; Clark, T.; Fougere, P. F.; Hunter, H.; Lincoln, J. V.; Sargent, H. H., III; Timothy, J. G.; Lin, Y. Z.

1979-01-01

289

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

290

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

291

Long-term surveillance plan for the Cheney disposal site near Grand Junction, 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 Cheney Disposal Site 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

1997-07-01

292

Long-term surveillance plan for the South Clive disposal site Clive, 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 South Clive disposal site in Clive, Utah. This LSTP describes the long-term surveillance program the DOE will implement to ensure the South Clive 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

1997-09-01

293

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

294

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

295

Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization  

PubMed Central

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.

Jung, Sung-Cherl; Eun, Su-Yong

2014-01-01

296

Efficacy and safety of lenalidomide for refractory cutaneous lupus erythematosus  

PubMed Central

Introduction Cutaneous lupus erythematosus (CLE) is a chronic disease characterized by disfigurement and a relapsing course. Thalidomide has proven its efficacy in refractory cutaneous lupus disease, although it is not exempt from significant side effects and frequent relapses after withdrawal. New thalidomide analogues have been developed but lack clinical experience. The aim of this preliminary phase II study was to evaluate the efficacy and safety of lenalidomide in patients with refractory CLE. Methods Fifteen patients with refractory cutaneous lupus disease were enrolled in this single-center, open-label, non-comparative pilot trial between January 2009 and December 2010. Oral lenalidomide (5 to 10 mg/day) was administered and tapered according to clinical response. Patients were followed up for a mean of 15 months (range: 7 to 30). Primary efficacy endpoint was the proportion of patients achieving complete response, defined by a Cutaneous Lupus Erythematosus Disease Area and Severity index (CLASI) activity score of 0. Other secondary endpoints included development of side effects, evaluation of cutaneous and systemic flares, and impact on the immunological parameters. Results One patient discontinued treatment due to side effects. All remaining patients saw clinical improvement and this was already noticeable after 2 weeks of treatment. Twelve of those patients (86%) achieved complete response but clinical relapse was frequent (75%), usually occurring 2 to 8 weeks after lenalidomide's withdrawal. No influence on systemic disease, immunological parameters or CLASI damage score was observed. Side effects including insomnia, grade 2 neutropenia and gastrointestinal symptoms, were minor (13%). These resolved after withdrawing medication. Neither polyneuropathy nor thrombosis was observed. Conclusion Lenalidomide appears to be efficacious and safe in patients with refractory CLE, but clinical relapse is frequent after its withdrawal. Trial registration ClinicalTrials.gov: NCT01408199. PMID:23217273

2012-01-01

297

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

298

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

299

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

300

Long-term outcomes after severe shock.  

PubMed

Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ?1 ?g/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below US population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely critically ill patients have similar outcomes to general intensive care unit survivor populations. PMID:25394248

Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

2015-02-01

301

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

302

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

303

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

304

Long-term data in the treatment of psoriasis.  

PubMed

Moderate-to-severe plaque psoriasis is associated with a considerable disease burden and treatment needs are often unmet. Several conventional systemic drugs are available as treatments, including methotrexate, cyclosporin, retinoids and psoralen ultraviolet A, which, although effective, are associated with considerable toxicity that limits their long-term use. Recent developments in more targeted therapies involving biological agents, such as anti-T-cell agents and inhibitors of tumour necrosis factor-alpha, offer an alternative treatment approach with the possibility of longer continuous therapy, which may translate into disease control and improved quality of life. Although the majority of data supporting the use of biological agents have been obtained in short-term studies of 3-6 months' duration, some agents have been evaluated for longer periods of continuous administration. Comparison of efficacy among these agents may better define their role as long-term therapy. This article discusses the data currently available on both conventional and biological systemic therapies for psoriasis, in terms of short-term and long-term use. PMID:18700911

Thaçi, D

2008-08-01

305

Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease  

PubMed Central

Background The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 ?g or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ?70% and FEV1 <80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation. Results At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001). More patients had a SGRQ improvement ?4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p = 0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9). Adverse events were minor in both studies. Conclusion Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II). PMID:21518460

2011-01-01

306

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

307

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

308

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

309

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

310

Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program  

Microsoft Academic Search

The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine,

J. Gosz

2001-01-01

311

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

312

Long-Term Impacts of Educational Interventions  

ERIC Educational Resources Information Center

The school accountability movement has led to a marked increase in the use of standardized test scores to measure school and teacher productivity, yet little is known about the correlation between test score gains and improvements in long-term outcomes. In the first chapter of my dissertation, I study the impact of a school choice policy in…

Deming, David James

2010-01-01

313

Professionalism in Long-Term Care Settings  

ERIC Educational Resources Information Center

Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

Lubinski, Rosemary

2006-01-01

314

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

315

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

316

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

317

Cigarette smoking in long-term schizophrenia  

Microsoft Academic Search

Purpose. – Cigarette smoking is a great health problem and prevalent among subjects with schizophrenia. Our aim was to investigate the prevalence and associations of cigarette smoking in patients with long-term schizophrenia.Methods. – Seven hundred and sixty schizophrenia patients were interviewed and their cigarette smoking was recorded.Results. – Smoking was more prevalent men than in women patients. In logistic regression

R. K. R. Salokangas; T. Honkonen; E. Stengård; A.-M. Koivisto; J. Hietala

2006-01-01

318

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...

319

Robotics for Long-Term Monitoring  

Microsoft Academic Search

While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of

Sarkis Shahin; Celso Duran

2002-01-01

320

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

321

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

322

Long-Term Opioid Therapy Reconsidered  

PubMed Central

In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment. PMID:21893626

Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A.; Chou, Roger

2012-01-01

323

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

324

Efficacy and safety of duloxetine 60 mg once daily in major depressive disorder: a review with expert commentary  

PubMed Central

Objective: Major depressive disorder (MDD) is a significant public health concern and challenges health care providers to intervene with appropriate treatment. This article provides an overview of efficacy and safety information for duloxetine 60 mg/day in the treatment of MDD, including its effect on painful physical symptoms (PPS). Design: A literature search was conducted for articles and pooled analyses reporting information regarding the use of duloxetine 60 mg/day in placebo-controlled trials. Setting: Placebo-controlled, active-comparator, short- and long-term studies were reviewed. Participants: Adult (?18 years) patients with MDD. Measurements: Effect sizes for continuous outcome (change from baseline to endpoint) and categorical outcome (response and remission rates) were calculated using the primary measures of 17-item Hamilton Rating Scale for Depression (HAMD-17) or Montgomery–Åsberg Depression Rating Scale (MADRS) total score. The Brief Pain Inventory and Visual Analogue Scales were used to assess improvements in PPS. Glass estimation method was used to calculate effect sizes, and numbers needed to treat (NNT) were calculated based on HAMD-17 and MADRS total scores for remission and response rates. Safety data were examined via the incidence of treatment-emergent adverse events and by mean changes in vital-sign measures. Results: Treatment with duloxetine was associated with small-to-moderate effect sizes in the range of 0.12 to 0.72 for response rate and 0.07 to 0.65 for remission rate. NNTs were in the range of 3 to 16 for response and 3 to 29 for remission. Statistically significant improvements (p?0.05) were observed in duloxetine-treated patients compared to placebo-treated patients in PPS and quality of life. The safety profile of the 60-mg dose was consistent with duloxetine labeling, with the most commonly observed significant adverse events being nausea, dry mouth, diarrhea, dizziness, constipation, fatigue, and decreased appetite. Conclusion: These results reinforce the efficacy and tolerability of duloxetine 60 mg/day as an effective short- and long-term treatment for adults with MDD. The evidence of the independent analgesic effect of duloxetine 60 mg/day supports its use as a treatment for patients with PPS associated with depression. This review is limited by the fact that it included randomized clinical trials with different study designs. Furthermore, data from randomized controlled trials may not generalize well to real clinical practice. PMID:24432034

Ball, Susan G; Desaiah, Durisala; Zhang, Qi; Thase, Michael E; Perahia, David G S

2013-01-01

325

Long-term biological investigations in space.  

PubMed

Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight. PMID:11841093

Lotz, R G; Fuchs, H; Bertsche, U

1975-01-01

326

Safety and Efficacy of Biodegradable Drug-Eluting vs. Bare Metal Stents: A Meta-Analysis from Randomized Trials  

PubMed Central

Background Biodegradable polymeric coatings have been proposed as a promising strategy to enhance biocompatibility and improve the delayed healing in the vessel. However, the efficacy and safety of biodegradable polymer drug-eluting stents (BP-DES) vs. bare metal stents (BMS) are unknown. The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing the outcomes of BP-DES vs. BMS. Methods and Results PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until December 2013, that compared any of approved BP-DES and BMS. Efficacy endpoints were target-vessel revascularization (TVR), target-lesion revascularization (TLR) and in-stent late loss (ISLL). Safety endpoints were death, myocardial infarction (MI), definite stent thrombosis (DST). The meta-analysis included 7 RCTs with 2,409 patients. As compared with BMS, there was a significantly reduced TVR (OR [95% CI]?=?0.37 [0.28–0.50]), ISLL (OR [95% CI]?=??0.41 [?0.48–0.34]) and TLR (OR [95% CI]?=?0.38 [0.27–0.52]) in BP-DES patients. However, there were no difference for safety outcomes between BP-DES and BMS. Conclusions BP-DES is more effective in reducing ISLL, TVR and TLR, as safe as standard BMS with regard to death, ST and MI. Further large RCTs with long-term follow-up are warranted to better define the relative merits of BP-DES. PMID:24945816

Zhao, Xiaohui

2014-01-01

327

Long-term impact of treatment in women diagnosed with bulimia nervosa  

Microsoft Academic Search

Objective: Both cognitive-behavioral therapy (CBT) and antidepressant medication have demonstrated efficacy in the treatment of bulimia nervosa. However, data concerning the long-term impact of such treatments have been limited. This study sought to determine if treatment with CBT and antidepressant medication was associated with better long-term outcome among women diagnosed with bulimia nervosa. Method: Women (N = 101) who completed

Pamela K. Keel; James E. Mitchell; Traci L. Davis; Scott J. Crow

2002-01-01

328

Nephrotoxicity of immunosuppressive drugs: Long-term consequences and challenges for the future  

Microsoft Academic Search

The calcineurin inhibitors cyclosporin A (CsA) and tacrolimus (FK506) are associated with dose- and efficacy-limiting adverse events, including nephrotoxicity, which may diminish their overall benefits for long-term graft survival. Nephrotoxicity is difficult to distinguish from chronic allograft rejection and is a particular problem in the setting of renal transplantation. Minimizing immunosuppressant-induced nephrotoxicity could improve long-term renal allograft survival. However, to

Angelo M. de Mattos; Ali J. Olyaei; William M. Bennett

2000-01-01

329

Does Long-Term Treatment of Schizophrenia With Antipsychotic Medications Facilitate Recovery?  

PubMed Central

Antipsychotic medications are viewed as cornerstones for both the short-term and long-term treatment of schizophrenia. However, evidence on long-term (10 or more years) efficacy of antipsychotics is mixed. Double-blind discontinuation studies indicate significantly more relapses in unmedicated schizophrenia patients in the first 6-10 months, but also present some potentially paradoxical features. These issues are discussed. PMID:23512950

Harrow, Martin

2013-01-01

330

Long-Term Outcome of Pneumatic Dilation in the Treatment of Achalasia  

Microsoft Academic Search

OBJECTIVE:Achalasia is a well-defined esophageal motor disorder for which pneumatic dilation is an established therapeutic method. Even though it has been used for several years, there are limited data on the long-term outcomes of patients treated with this procedure. Hence, we aimed to evaluate the long-term efficacy of pneumatic dilation to control the symptoms of achalasia.METHODS:The medical records of all

Georgios Karamanolis; Spiros Sgouros; Georgios Karatzias; Efthimia Papadopoulou; Konstantinos Vasiliadis; Gerasimos Stefanidis; Apostolos Mantides

2005-01-01

331

Evaluation of long-term entecavir treatment in stable chronic hepatitis B patients switched from lamivudine therapy  

PubMed Central

Purpose Current Japanese guidelines recommend that patients should be switched from lamivudine to entecavir when they meet certain criteria. This analysis examines the efficacy and safety of long-term entecavir therapy in patients who were switched to entecavir after 24 weeks’ lamivudine therapy in Japanese studies ETV-047 and ETV-060. Methods The Phase II Japanese study ETV-047 assessed the efficacy of different entecavir doses when compared with lamivudine. A total of 33 Japanese patients who received lamivudine 100 mg daily in ETV-047 entered the open-label rollover study ETV-060 and subsequently received treatment with entecavir 0.5 mg daily. Hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroconversion, and resistance were evaluated among patients with available samples for up to 96 weeks. Safety was assessed throughout the treatment period. Results After 96 weeks of entecavir therapy in ETV-060, 90% of patients achieved HBV DNA <400 copies/mL as compared to 21% of patients who completed 24 weeks of lamivudine therapy in ETV-047. Increasing proportions of patients achieved ALT normalization and HBeAg seroconversion following long-term entecavir treatment. No patients experienced virologic breakthrough, and substitutions associated with entecavir resistance were not observed in patients with detectable HBV DNA. Entecavir was well tolerated during long-term treatment. Conclusions Switching lamivudine-treated patients with chronic hepatitis B to entecavir results in increased virologic suppression with no evidence of resistance through 2 years of entecavir therapy. These findings support recommendations in the current Japanese treatment guidelines that stable lamivudine patients should be switched to entecavir. PMID:21063482

Sata, Michio; Chayama, Kazuaki; Shindo, Michiko; Toyota, Joji; Mochida, Satoshi; Tomita, Eiichi; Kumada, Hiromitsu; Yamada, Gotaro; Yatsuhashi, Hiroshi; Hayashi, Norio; Ishikawa, Hiroki; Seriu, Taku; Omata, Masao

2010-01-01

332

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

333

Development of novel combined anticalcification protocols including immunologic modification for prolonged durability of cardiac xenograft: preclinical study using large-animal long-term circulatory models.  

PubMed

Cardiac xenografts are conventionally cross-linked with glutaraldehyde (GA) to impart tissue stability, reduce antigenicity, and maintain tissue sterility. However, GA-fixed xenografts are prone to calcification after long-term implantation in humans, because of phospholipids, free aldehyde groups, and residual antigenicity. We evaluated preclinical safety and efficacy using large-animal long-term circulatory models for our novel combined anticalcification protocol including immunological modification, which had been proven effective in small animal experiments. Bovine/porcine xenografts were treated with decellularization, immunological modification with ?-galactosidase, GA fixation with organic solvent, and detoxification with glycine. Valve conduits made of these xenografts were transplanted into the pulmonary root of goats, and hemodynamic, radiological, immunohistopathological, and biochemical results were obtained for 12 months after implantation. Evaluation of echocardiography and cardiac catheterization demonstrated good hemodynamic status and function of the pulmonary xenograft valves. Durability of the xenografts was well preserved without calcification by specimen radiography and immunohistopathological examination. The calcium concentrations of the explanted xenografts were lower than the control xenografts. This preclinical study using large-animal long-term circulatory models demonstrated that our synergistic and simultaneous employment of multiple anticalcification therapies and novel tissue treatments, including immunological modifications, have promising safety and efficacy and should be examined further in future clinical studies. PMID:25303800

Lim, Hong-Gook; Jeong, Saeromi; Shin, Jun-Seop; Park, Chung-Gyu; Kim, Yong Jin

2015-01-01

334

Clinical safety and efficacy of probiotic administration following burn injury.  

PubMed

Provision of probiotics has been limited postburn by questionable potential for bacterial translocation and risk of infection in an immune-compromised population. The purpose of this study was to evaluate the safety of probiotic administration in acutely burned, pediatric patients. Subjects were randomized to receive probiotic (n = 10) vs placebo (n = 10) twice daily. The investigational product was initiated within 10 days of burn, and daily supplementation continued until wound closure. Nursing staff was provided education regarding optimal procedures to minimize potential for study product cross contamination. Clinical outcomes (infection, antibiotic, antifungal, and operative days, tolerance, and mortality) were recorded. Length of stay was modified for burn size. Student's t-test, ? test, and nonparametric Wilcoxon's rank-sum test were used for comparative analysis. No differences were noted (probiotic; placebo) for age (7.1 ± 2.2; 6.9 ± 1.7), burn size (38.0 ± 5.9; 45.5 ± 4.45), full thickness (24.6 ± 5.6; 32.1 ± 5.4), postburn day admit (0.8 ± 0.4; 1.1 ± 0.4), or inhalation injury (10%; 20%). Infection days, antibiotic use, constipation, and emesis were similar between groups. Trends toward increased antifungal and laxative use as well as diarrhea incidence were evident in the controls (P < .30). Flatulence was statistically higher with probiotics. The control group trended toward higher requirement for excision/graft procedure. Medical length of stay was not significantly different between groups; however, time required to complete wound healing was shortened with probiotics. This study documents safety and provides preliminary efficacy data relative to probiotic supplementation postburn. PMID:25559730

Mayes, Theresa; Gottschlich, Michele M; James, Laura E; Allgeier, Chris; Weitz, Julie; Kagan, Richard J

2015-01-01

335

Drug Safety in the Treatment of Crohn’s Disease  

Microsoft Academic Search

The management of Crohn’s disease usually consists of a succession of short-term acute phase treatments followed by long-term maintenance therapy. The disease affects young patients and for this reason the long-term safety of the drugs needs to be especially taken into consideration. The safety, dose, duration for optimal efficacy and the most frequent adverse events will be described in this

Pascal Juillerat; Christian Felley; Christian Mottet; Florian Froehlich; John-Paul Vader; Bernard Burnand; Jean-Jacques Gonvers; Pierre Michetti

2005-01-01

336

Breakthroughs in long term care design.  

PubMed

In summary, here is what design is trying to accomplish in long term care facilities: Functional access; Privacy as entitlement; Sensory optimization to improve vision and hearing; Reduced walking and wheeling distances that still allow people to be mobile; Effective or functional placement of space and equipment; The option of smaller scale, so neither residents nor staff feel like they are hanging out with a unit full of, perhaps 68, people all the time; Flexibility and adaptability PMID:10130697

Hiatt, L

1991-01-01

337

Long-Term Morbidity of PCOS  

Microsoft Academic Search

Polycystic ovary syndrome, economic burden, healthcare cost, diabetes mellitus, cardiovascular disease, dyslipidemia, metabolic\\u000a syndrome, endometrial cancer The polycystic ovary syndrome (PCOS) results in a number of immediate and long-term morbidities\\u000a that are associated with a significant impact on quality of life and on economic costs. Immediate morbidities include menstrual\\u000a dysfunction and abnormal uterine bleeding, subfertility and infertility, and androgen excess-related

Ricardo Azziz

338

Emotional behavior in long-term marriage  

Microsoft Academic Search

In exploring the emotional climate of long-term marriages, this study used an observational coding system to identify specific emotional behaviors expressed by middle-aged and older spouses during discussions of a marital problem. One hundred and fifty-six couples differing in age and marital satisfaction were studied. Emotional behaviors expressed by couples differed as a function of age, gender, and marital satisfaction.

Laura L. Carstensen; John M. Gottman; Robert W. Levenson

1995-01-01

339

Synaptic tagging and long-term potentiation  

Microsoft Academic Search

Repeated stimulation of hippocampal neurons can induce an immediate and prolonged increase in synaptic strength that is called long-term potentiation (LTP)-the primary cellular model of memory in the mammalian brain1. An early phase of LTP (lasting less than three hours) can be dissociated from late-phase LTP by using inhibitors of transcription and translation2-8. Because protein synthesis occurs mainly in the

Uwe Frey; Richard G. M. Morris

1997-01-01

340

Electrodes for long-term esophageal electrocardiography.  

PubMed

The emerging application of long-term and high-quality ECG recording requires alternative electrodes to improve the signal quality and recording capability of surface skin electrodes. The esophageal ECG has the potential to overcome these limitations but necessitates novel recorder and lead designs. The electrode material is of particular interest, since the material has to ensure conflicting requirements like excellent biopotential recording properties and inertness. To this end, novel electrode materials like PEDOT and silver-PDMS as well as established electrode materials such as stainless steel, platinum, gold, iridium oxide, titanium nitride, and glassy carbon were investigated by long-term electrochemical impedance spectroscopy and model-based signal analysis using the derived in vitro interfacial properties in conjunction with a dedicated ECG amplifier. The results of this novel approach show that titanium nitride and iridium oxide featuring microstructured surfaces did not degrade when exposed to artificial acidic saliva. These materials provide low electrode potential drifts and insignificant signal distortion superior to surface skin electrodes making them compatible with accepted standards for ambulatory ECG. They are superior to the noble and polarizable metals such as platinum, silver, and gold that induced more signal distortions and are superior to esophageal stainless steel electrodes that corrode in artificial saliva. The study provides rigorous criteria for the selection of electrode materials for prolonged ECG recording by combining long-term in vitro electrode material properties with ECG signal quality assessment. PMID:23649132

Niederhauser, Thomas; Haeberlin, Andreas; Marisa, Thanks; Jungo, Michael; Goette, Josef; Jacomet, Marcel; Abacherli, Roger; Vogel, Rolf

2013-09-01

341

Long-term mexiletine for ventricular arrhythmia.  

PubMed

Use of mexiletine was evaluated in 313 patients with ventricular tachyarrhythmias refractory to conventional antiarrhythmic drugs. Therapy with mexiletine was continued long term in 107 patients who responded to the drug and were free of side effects during a short-term evaluation in hospital. During an average follow-up of 22.8 months (0.1 to 70 months), 19 patients died (17.8%). Eleven patients had sudden death (3.6% per year), while six patients died of progressive congestive heart failure and two of noncardiac causes. Nonfatal ventricular arrhythmia recurred in 14 patients (4.9% per year). Overall, 25 patients had recurrent arrhythmia (incidence of 5.5% per year). Side effects occurred in 13 patients after an average of 5.1 months and were primarily gastrointestinal and neurologic. Sixty-one patients (57%) have continued on mexiletine therapy for an average of 32.2 months (1 to 70 months). Outcome during long-term therapy was not related to drug dose, blood level, or presenting arrhythmia. We conclude that if therapy with mexiletine is carefully evaluated and individualized, the drug is effective and well tolerated during long-term use. PMID:6720534

Stein, J; Podrid, P J; Lampert, S; Hirsowitz, G; Lown, B

1984-05-01

342

Potential benefit of dolutegravir once daily: efficacy and safety  

PubMed Central

The viral integrase enzyme has recently emerged as a primary alternative target to block HIV-1 replication, and integrase inhibitors are considered a pivotal new class of antiretroviral drugs. Dolutegravir is an investigational next-generation integrase inhibitor showing some novel and intriguing characteristics, ie, it has a favorable pharmacokinetic profile with a prolonged intracellular half-life, rendering feasible once-daily dosing without the need for ritonavir boosting and without regard to meals. Moreover, dolutegravir is primarily metabolized via uridine diphosphate glucuronosyltranferase 1A1, with a minor component of the cytochrome P450 3A4 isoform, thereby limiting drug–drug interactions. Furthermore, its metabolic profile enables coadministration with most of the other available antiretroviral agents without dose adjustment. Recent findings also demonstrate that dolutegravir has significant activity against HIV-1 isolates with resistance mutations associated with raltegravir and/or elvitegravir. The attributes of once-daily administration and the potential to treat integrase inhibitor-resistant viruses make dolutegravir an interesting and promising investigational drug. In this review, the main concerns about the efficacy and safety of dolutegravir as well as its resistance profile are explored by analysis of currently available data from preclinical and clinical studies. PMID:23413040

Fantauzzi, Alessandra; Turriziani, Ombretta; Mezzaroma, Ivano

2013-01-01

343

Rufinamide in children with refractory epilepsy: pharmacokinetics, efficacy, and safety.  

PubMed

We examined the influence of age and type of concomitant antiepileptic drugs (AEDs) on the pharmacokinetics of rufinamide (RUF) as well as its efficacy and safety in 51 children with refractory epilepsy. In a retrospective noninterventional survey, dose-to-concentration ratios of RUF and concomitant AEDs were calculated: the weight-normalized dose (mg/kg/d) divided by the steady-state trough plasma drug level, which was used as a measure of clearance. During treatment with RUF concomitantly with valproic acid (VPA) young children, aged 0 to 4.9 years, had a low clearance of RUF, which did not differ from older children. If not on VPA but on enzyme inducers, young children had a threefold higher clearance of RUF than the older ones. In young children not on VPA, those on enzyme inducers had 1.7-fold higher clearance than those on nonenzyme inducers. In children neither on VPA nor on enzyme inducers, RUF clearance was age-dependent with higher clearance in younger children. Adding RUF did not change the pharmacokinetics of concomitantly used AEDs. Seizure response after 2 to 3 months on RUF treatment was found in 12 of 51 children (23.5%), at mean plasma level of 36.9?±?22.0 µmol/L. Adverse events were reported in 41% of the patients of which fatigue was most frequent (24%). PMID:22941776

Dahlin, Maria G; Ohman, Inger

2012-10-01

344

Efficacy and safety of ruxolitinib in Asian patients with myelofibrosis.  

PubMed

Myelofibrosis is characterized by progressive cytopenias, bone marrow fibrosis, splenomegaly and severe constitutional symptoms. In the phase 3 Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies, ruxolitinib, a potent Janus kinase 1 (JAK1)/JAK2 inhibitor, provided substantial improvements in splenomegaly, symptoms, quality-of-life measures and overall survival compared with placebo or best available therapy. No assessments of the efficacy and safety of ruxolitinib have been conducted in Asian patients. Here, we describe results from an open-label, single-arm, phase 2 trial evaluating ruxolitinib in Asian patients with myelofibrosis (n = 120). The primary endpoint was met, with 31.7% of patients achieving a ? 35% reduction from baseline spleen volume at week 24. As measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0, 49% of patients achieved a ? 50% reduction from baseline in total symptom score. Adverse events were consistent with those seen in the COMFORT studies. Ruxolitinib was well tolerated in Asian patients with myelofibrosis and provided substantial reductions in splenomegaly and improvements in symptoms. PMID:25315076

Jung, Chul Won; Shih, Lee-Yung; Xiao, Zhijian; Jie, Jin; Hou, Hsin-An; Du, Xin; Wang, Ming-Chung; Park, Seonyang; Eom, Ki-Seong; Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Kim, Jin Seok; Zhou, Daobin; Saito, Shigeki; Li, Junmin; Handa, Hiroshi; Jianyong, Li; Ohishi, Kohshi; Hou, Ming; Depei, Wu; Takenaka, Katsuto; Liu, Ting; Hu, Yu; Amagasaki, Taro; Ito, Kazuo; Gopalakrishna, Prashanth; Akashi, Koichi

2014-11-20

345

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

346

Long-term Drug Treatment for Obesity: A Systematic and Clinical Review  

PubMed Central

Importance Thirty-six percent of US adults are obese and many cannot lose sufficient weight to improve health with lifestyle interventions alone. Objective Conduct a systematic review of medications currently approved in the US for obesity treatment in adults. We also discuss off-label use of medications studied for obesity and provide considerations for obesity medication use in clinical practice. Evidence Acquisition A PubMed search from inception through September, 2013 was performed to find meta-analyses, systematic reviews, and randomized, placebo-controlled trials for currently-approved obesity medications lasting ?1y, that had a primary or secondary outcome of body weight, included ?50 participants per group, reported ?50% retention, and reported results on an intention-to-treat basis. Studies of medications approved for other purposes but tested for obesity treatment were also reviewed. Results Obesity medications approved for long-term use, when prescribed with lifestyle interventions, produce additional weight loss relative to placebo ranging from approximately 3% of initial weight for orlistat and lorcaserin to 9% for top-dose (15/92mg) phentermine/topiramate-ER at 1y. The proportion of patients achieving clinically-meaningful (?5%) weight loss ranges from 37–47% for lorcaserin, 35–73% for orlistat, and 67–70% for top-dose phentermine/topiramate-ER. All three produce greater improvements in many cardiometabolic risk factors than placebo, but no obesity medication has been shown to reduce cardiovascular morbidity or mortality. Most prescriptions are for noradrenergic medications, despite their approval only for short-term use and limited data for their long-term safety and efficacy. Conclusions/Relevance Medications approved for long-term obesity treatment, when used as an adjunct to lifestyle intervention, lead to greater mean weight loss and an increased likelihood of achieving clinically-meaningful 1-year weight loss relative to placebo. By discontinuing medication in patients who do not respond with weight loss ?5%, clinicians can decrease their patients' exposure to the risks and costs of drug treatment when there is little prospect of long-term benefit. PMID:24231879

Yanovski, Susan Z.; Yanovski, Jack A.

2014-01-01

347

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

348

Long-term cholinesterase inhibitor therapy for Alzheimer's disease: Implications for long-term care  

Microsoft Academic Search

As the population ages and Alzheimer's disease (AD) becomes more prevalent, nursing facilities will be faced with managing more AD patients than in previous decades. Managing this population will pose a significant challenge for the resources of long-term care facilities. In short-and long-term studies, cholinesterase (ChE) inhibitor treatment has been shown to benefit the symptoms of mild to moderate AD.

Sharon A. Brangman

2003-01-01

349

Efficacy, safety and quality-of-life associated with lenalidomide plus dexamethasone for the treatment of relapsed or refractory multiple myeloma: the Spanish experience.  

PubMed

Here we report the efficacy, safety and health-related quality-of-life (HRQoL) associated with long-term lenalidomide and dexamethasone (Len + Dex) treatment in patients with relapsed or refractory multiple myeloma (RRMM) enrolled in the Spanish cohort of the MM-018 study. In this open-label, multicenter, single-arm expanded access study, 63 patients received Len + Dex until disease progression. The overall response rate was 78%, with 21% of the patients achieving a complete response. The quality of response improved with continuous treatment. The median duration of response was 18.4 months. Median time-to-progression and progression-free survival was 13.3 months for both; median overall survival was not reached. Len + Dex had a manageable safety profile consistent with previously reported phase III studies. HRQoL assessments (n = 42) at baseline and 6 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ MY-20 questionnaires revealed that patients with RRMM treated with long-term lenalidomide reported clinically relevant improvements in certain QoL and symptoms scores regardless of treatment response (ClinicalTrials.gov: NCT00420849). PMID:22292853

Alegre, Adrian; Oriol-Rocafiguera, Albert; Garcia-Larana, Jose; Mateos, Maria-Victoria; Sureda, Anna; Martinez-Chamorro, Carmen; Cibeira, Maria Teresa; Aguado, Beatriz; Knight, Robert; Rosettani, Barbara

2012-09-01

350

Long-Term Efficacy of Postpartum Intravenous Iron Therapy  

PubMed Central

Background. The potential benefits of administering a dose of intravenous iron in patients with moderate postpartum anaemia rather than oral iron alone remains unproven. Aims. To determine whether a single injection of intravenous iron followed by a 6-week course of oral iron is as effective over 6 months in restoring normal haemoglobin levels and replenishing iron stores in women with moderate postpartum anaemia as a course of oral iron alone in women with mild postpartum anaemia. Materials and Methods. Retrospective two-arm cohort study in women with mild postpartum anaemia (haemoglobin 9.6–10.5?g/dL) prescribed iron daily for 6 weeks (N = 150) and women with moderate postpartum anaemia (haemoglobin 8.5–9.5?g/dL), given a single 500?mg injection of intravenous iron followed by iron daily for 6 weeks (N = 75). Haemoglobin and ferritin were measured 6 months postpartum. Results. Haemoglobin returned to similar mean levels in both groups. Ferritin levels were statistically significantly higher in the intravenous + oral group (57.7 ± 49.3??g/L versus 32.9 ± 20.1??g/L). Conclusions. Despite lower baseline haemoglobin, intravenous iron carboxymaltose was superior to oral iron alone in replenishing iron stores in moderate postpartum anaemia and may prove similarly beneficial in mild postpartum anaemia. PMID:25431768

Zimmermann, Roland

2014-01-01

351

Review of the safety, efficacy and patient acceptability of the levonorgestrel-releasing intrauterine system  

PubMed Central

The levonorgestrel-containing intrauterine system is an extremely effective, reversible and safe form of long-term yet reversible birth control. In view of its efficacy, it is a safer alternative to permanent contraceptive methods such as sterilization. It is especially useful in situations where use of estrogen-containing contraceptives is contraindicated. While menstrual disturbances are a common side effect, proper counseling improves compliance. In addition to its contraceptive effect, the levonorgestrel intrauterine system offers potential therapeutic benefits in other clinical contexts, including menorrhagia, symptomatic fibroids, endometriosis, and endometrial protection. PMID:19920976

Kailasam, Chandra; Cahill, David

2008-01-01

352

Efficacy and safety of steroid injections for shoulder and elbow tendonitis: a meta-analysis of randomised controlled trials  

PubMed Central

Objectives: To assess the efficacy and safety of steroid injections for patients with tendonitis of the shoulder or elbow. Methods: A systematic review of the literature using PubMed, EMBASE, the Cochrane library and manual searches was performed until April 2008. All randomised controlled trials (RCTs) reporting the efficacy on pain or functional disability, and/or the safety of steroid injections, versus placebo, non-steroidal anti-inflammatory drugs (NSAIDs) or physiotherapy in patients with tendonitis were selected. Pooled effect size (ES) was calculated by meta-analysis using the Mantel–Haenszel method. Results: In all, 20 RCTs were analysed (744 patients treated by injections and 987 patients treated by controls; 618 shoulders and 1113 elbows). The pooled analysis indicated only short-term effectiveness of steroids versus the pooled controls for pain and function (eg, pain at week 1–3 ES?=?1.18 (95% CI 0.27 to 2.09), pain at week 4–8 ES?=?1.30 (95% CI 0.55 to 2.04), pain at week 12–24 ES?=??0.38 (95% CI ?0.85 to 0.08) and pain at week 48 ES?=?0.07 (95% CI ?0.60 to 0.75)). Sensitivity analyses indicated similar results whatever the localisation, type of steroid and type of comparator except for NSAIDs: steroid injections were not significantly better than NSAIDs in the short-term. Steroid injections appeared more effective than pooled other treatments in acute or subacute tendonitis. The main side effects were transient pain after injection (10.7% of corticosteroid injections) and skin modification (4.0%). Conclusions: Steroid injections are well tolerated and more effective for tendonitis in the short-term than pooled other treatments, though similar to NSAIDs. No long-term benefit was shown. PMID:19054817

Gaujoux-Viala, C; Dougados, M; Gossec, L

2009-01-01

353

Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature.  

PubMed

Growth hormone (GH) is the most frequently used treatment in children with idiopathic short stature (ISS). Aromatase inhibitor (AI) therapy is still in an experimental state, and both final height (FH) and long-term efficacy data in ISS have not been published. We present a 14.5-year-old boy with ISS and a height of 142.7 cm [standard deviation score (SDS) -2.79]. Based on the baseline bone age (BA) of 13.5-14 years, his predicted adult height (PAH) by Bayley/Pinneau was 154 cm (SDS -3.77)-158.2 (SDS -3.15). After a 5-year letrozole monotherapy, FH was 169 cm (SDS -1.57) showing a height difference between PAH and FH from 10.8 to 15 cm. No permanent side effects of the medication have been observed. Both a transient occurrence and a spontaneous recovery of decreased bone mineral apparent density were seen, verified by dual-energy X-ray absorptiometry. Spinal magnetic resonance imaging revealed no vertebral abnormalities. All therapy might be an effective and low-cost alternative to the use of GH. Further controlled trials should prove efficacy and safety of long-term AI therapy in boys with ISS. PMID:22876562

Krebs, Andreas; Moske-Eick, Olaf; Doerfer, Jürgen; Roemer-Pergher, Cordula; van der Werf-Grohmann, Natascha; Schwab, Karl Otfried

2012-01-01

354

Long-term creatine supplementation does not significantly affect clinical markers of health in athletes  

Microsoft Academic Search

Creatine has been reported to be an effective ergogenic aid for athletes. However, concerns have been raised regarding the long-term safety of creatine supplementation. This study examined the effects of long-term creatine supplementation on a 69-item panel of serum, whole blood, and urinary markers of clinical health status in athletes. Over a 21-month period, 98 Division IA college football players

Richard B. Kreider; Charles Melton; Christopher J. Rasmussen; Michael Greenwood; Stacy Lancaster; Edward C. Cantler; Pervis Milnor; Anthony L. Almada

2003-01-01

355

Long-term monitoring FBG-based cable load sensor  

NASA Astrophysics Data System (ADS)

Stay cables are the main load-bearing components of stayed-cable bridges. The cables stress status is an important factor to the stayed-cable bridge structure safety evaluation. So it's very important not only to the bridge construction, but also to the long-term safety evaluation for the bridge structure in-service. The accurate measurement for cable load depends on an effective sensor, especially to meet the long time durability and measurement demand. FBG, for its great advantage of corrosion resistance, absolute measurement, high accuracy, electro-magnetic resistance, quasi-distribution sensing, absolute measurement and so on, is the most promising sensor, which can cater for the cable force monitoring. In this paper, a load sensor has been developed, which is made up of a bushing elastic supporting body, 4 FBGs uniformly-spaced attached outside of the bushing supporting body, and a temperature compensation FBG for other four FBGs, moreover a cover for protection of FBGs. Firstly, the sensor measuring principle is analyzed, and relationship equation of FBG wavelength shifts and extrinsic load has also been gotten. And then the sensor calibration experiments of a steel cable stretching test with the FBG load sensor and a reference electric pressure sensor is finished, and the results shows excellent linearity of extrinsic load and FBG wavelength shifts, and good repeatability, which indicates that such kind of FBG-based load sensor is suitable for load measurement, especially for long-term, real time monitoring of stay-cables.

Zhang, Zhichun; Zhou, Zhi; Wang, Chuan; Ou, Jinping

2006-03-01

356

The assessment and treatment of long-term, non-specific spinal pain : behavioural medicine, a cognitive-behavioural perspective.  

E-print Network

??Background: Matching treatment specifically to the needs of long-term, non-specific spinal pain (LTSP) patients might greatly enhance treatment efficacy, but the heterogeneity of patients has… (more)

Bergström, Gunnar

2000-01-01

357

The Safety, Pharmacokinetics, and Efficacy of Intraocular Celecoxib  

PubMed Central

Purpose. To determine safety, pharmacokinetics, and anti-inflammatory effects of intraocular celecoxib. Methods. The right eye of animals was injected with 1.5, 3, or 6 mg celecoxib prepared in dimethyl sulfoxide (DMSO). Left eyes served as controls and received 0.1 mL DMSO. Electroretinograms (ERG) were obtained at baseline and at 1, 4, and 12 weeks, and eyes were enucleated afterward for histopathologic analysis. For pharmacokinetics, 3 mg celecoxib was injected, and vitreous and retina/choroid drug levels were then analyzed at specific time points. For efficacy, 1 ?g lipopolysaccharide was injected to induce inflammation; the right eye was then injected with 3 mg celecoxib (six eyes) or 2 mg triamcinolone acetonide (six eyes) and the left eye with saline. Twenty-four hours later, aqueous fluid was removed, and total leukocyte concentration and prostaglandin E2 (PGE2) concentration were determined. Results. Histologic and ERG studies demonstrated no signs of retinal or optic nerve toxicity. After a single 3-mg injection, vitreous (0.06 ?g/mL) and retina/choroid (132.31 ?g/g) celecoxib concentrations at 8 weeks exceeded median inhibitory concentration. Treatment with celecoxib and triamcinolone significantly reduced total leukocyte count by 40% (P = 0.02) and 31% (P = 0.01), respectively. Reduction in PGE2 levels paralleled reduction in leukocyte counts (P < 0.05). There was no increase in intraocular pressure, but cataract formation was observed at higher concentrations. Conclusions. Intraocular injection of celecoxib appeared to be nontoxic and demonstrated excellent penetration into the retina/choroid and sustained drug levels out to 8 weeks. Celecoxib demonstrated potent anti-inflammatory effects, but there was an association with cataract formation at higher doses. PMID:24458149

Kim, Stephen J.; Toma, Hassanain; Shah, Rohan; Kompella, Uday B.; Vooturi, Sunil K.; Sheng, Jinsong

2014-01-01

358

Safety and Efficacy of Melatonin in Pediatric Migraine Prophylaxis.  

PubMed

Objective: Preventive therapy in migraine must be started in children with frequent or disabling headaches and up to now, no drugs have been approved for migraine preventive therapy in children. The aim of the present research was to investigate safety and efficacy of melatonin in pediatric migraine prophylaxis. Methods: In a quasi- experimental study, monthly frequency, severity and duration of headache, migraine disability and clinical side effects of sixty migraineurs children whom were referred to Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd, Iran from January to June 2013 and were treated with single dose of 0.3 mg/kg melatonin for three months, were evaluated. Results: Thirty two (53.3%) girls and 28(46.7%) boys with mean age of 10.31 ± 2.39 years were evaluated 38 of whom (63.3%) had migraine without aura. Clinical adverse events were seen in 23.3% (N=14) of children including sleepiness in seven, vomiting in four, mild hypotension in two and constipation in one child. Excessive daytime sleepiness as a serious side effect was seen in three children which caused the drug use to be stopped. Monthly frequency, severity and duration of headache reduced from 15.63±7.64 to 7.07±4.42 attacks, from 6.20±1.67 to 3.55± 2.11, and from 2.26±1.34 to 1.11±0.55 hours, respectively. Pediatric Migraine Disability Assessment score decreased from 31.72 ±8.82 to 17.78 ±10.64. (All p < 0.05) Conclusion: Melatonin might be considered as an effective and without life-threatening side effects drug in prophylaxis of migraine in children. PMID:24909684

Fallah, Razieh; Shoroki, Fatemeh Fazeli; Ferdosian, Farzad

2014-06-01

359

The Safety and Efficacy of Day Care Cataract Surgery  

PubMed Central

ABSTRACT Purpose: To evaluate safety and efficacy of day care cataract surgery in developing country. Patients and Methods: This prospective study included 200 patients planned for cataract surgery during October and November 2012 divided in to two groups, day care cataract surgery (DCCS) and inpatient cataract surgery (ICS), with same number of male and female patients right and left eyes. All patients had same operative conditions and postoperative follow up. Results: The average age of patients in this study was 68.4 ± 7.47 years. Visual acuity before cataract extraction was 0.1754 where 44.5% of patients had severe visual impairment and another 23% had complicated cataract. Posterior capsule rupture was noted in 4.5% of cases. The main risk factors in both groups were: higher age, female gender, left side, complicated cataract, higher dioptric power of IOL and ECCE. Regular control opthalmologic examinations 30, 90 and 180 days after the cataract extraction did not reveal signs bullous keratopathy, wound dehiscence, cystoid macular edema and endophtalmitis in any of patients. Postoperative visual acuity 180 days after the operation in DCCS was 0.920 ± 0.154 and 0.928 ± 0.144 in ICS. Visual acuity less than 0.5 was noted in 4.5% due to posterior eye segment changes. Patients in DCCS group had 30 control examinations more and 95 days of hospitalization less than ICS with 16.5% cost reduction. Conclusion: The concept of day care cataract surgery is equally safe and more cost effective than inpatient cataract surgery. PMID:24937936

Cabric, Emir; Zvornicanin, Jasmin; Jusufovic, Vahid

2014-01-01

360

Long-Term Wind Power Variability  

SciTech Connect

The National Renewable Energy Laboratory started collecting wind power data from large commercial wind power plants (WPPs) in southwest Minnesota with dedicated dataloggers and communication links in the spring of 2000. Over the years, additional WPPs in other areas were added to and removed from the data collection effort. The longest data stream of actual wind plant output is more than 10 years. The resulting data have been used to analyze wind power fluctuations, frequency distribution of changes, the effects of spatial diversity, and wind power ancillary services. This report uses the multi-year wind power data to examine long-term wind power variability.

Wan, Y. H.

2012-01-01

361

Long-term space flights - personal impressions  

NASA Astrophysics Data System (ADS)

During a final 4-month stage of a 1-year space flight of cosmonauts Titov and Manarov, a physician, Valery Polyakov was included on a crew for the purpose of evaluating their health, correcting physical status to prepare for the spacecraft reentry and landing operations. The complex program of scientific investigations and experiments performed by the physician included an evaluation of adaptation reactions of the human body at different stages of space mission using clinicophysiological and biochemical methods; testing of alternative regimes of exercise and new countermeasures to prevent an unfavourable effect of long-term weightlessness.

Polyakov, V. V.

362

A long-term climatology of medicanes  

NASA Astrophysics Data System (ADS)

Medicanes, intense and destructive mesoscale cyclones exhibiting several similarities with tropical hurricanes, are known to struck occasionally the Mediterranean Sea. Thanks to a high-resolution dynamical downscaling effort, we are able to study for the first time the long-term climatology of those rare storms in a systematic way. The distribution of medicanes frequency in space and time is discussed, and the environmental factors responsible for their formation are investigated. We find that medicanes develop in those areas of the Mediterranean region where intrusions of cold air in the upper troposphere can produce configurations of thermodynamical disequilibrium of the atmosphere similar to those associated with the formation of tropical cyclones.

Cavicchia, Leone; von Storch, Hans; Gualdi, Silvio

2014-09-01

363

[Long term prognosis after circulatory arrest].  

PubMed

24 PATIENTS HAVING SURVIVED MORE THAN 18 MONTHS AFTER AN EPISODE OF CIRCULATORY ARREST WERE EXAMINED WITH THE AIM OF ASSESSING THE PSYCHOLOGICAL REACTIONS TO SUCH AN INCIDENT. The results obtained were encouraging, since immediately after the circulatory arrest there were only monor troubles reflecting the simple bringing into action of defence mechanisms. Long term adaptation was deemed excellent in 80 p.cent of cases which should, nevertheless, lead to any underestimation of those sequelae which, though happily rare, are highly incapacitating. PMID:1153308

Nicolas, G; Besancon, G; Bouhour, J B; Godin, J F; Vincent, J P

1975-05-10

364

Long term thermoelectric module testing system  

NASA Astrophysics Data System (ADS)

Thermoelectric generators can be used for converting waste heat into electric power. Significant interest in developing new materials in recent years has led to the discovery of several promising thermoelectrics, however, there can be considerable challenges in developing the materials into working devices. Testing and feedback is needed at each step to gain valuable information for identification of difficulties, quality of the materials and modules, repeatability in fabrication, and longevity of the devices. This paper describes a long-term module testing system for monitoring the output power of a module over extended testing times. To evaluate the system, we have tested commercially available thermoelectric modules over a one month time period.

D'Angelo, Jonathan; Hogan, Timothy

2009-10-01

365

Efficacy and safety of budesonide\\/formoterol in the management of chronic obstructive pulmonary disease  

Microsoft Academic Search

Efficacy and safety of budesonide\\/formoterol in the management of chronic obstructive pulmonary disease. W. Szafranski, A. Cukier, A. Ramirez, G. Menga, R. Sansores, S. Nahabedian, S. Peterson, H. Olsson. #ERS Journals Ltd 2003. ABSTRACT: The efficacy and safety of budesonide\\/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease

W. Szafranski; A. Cukier; A. Ramirez; G. Mengaz; R. Sansores; S. Nahabedian; S. Peterson; H. Olsson

2003-01-01

366

Safety and efficacy of elective carotid artery stenting in high-risk patients  

Microsoft Academic Search

OBJECTIVESWe sought to evaluate the safety and efficacy of carotid artery stenting (CAS) in high risk patients.BACKGROUNDCarotid endarterectomy (CE) has been shown to be more effective than medical therapy, but it has limitations. Carotid artery stenting may be a reasonable alternative, particularly in high-risk patients.METHODSWe prospectively evaluated the safety and efficacy of CAS in 170 consecutive patients who underwent the

Fayaz Shawl; Waleed Kadro; Michael J Domanski; Fernando L Lapetina; Aleem A Iqbal; Kathy G Dougherty; David D Weisher; Jaime F Marquez; S. Tariq Shahab

2000-01-01

367

Prescribers' responses to alerts during medication ordering in the long term care setting  

Microsoft Academic Search

OBJECTIVE: Computerized physician order entry with clinical decision support has been shown to improve medication safety in adult inpatients, but few data are available regarding its usefulness in the long-term care setting. The objective of this study was to examine opportunities for improving medication safety in that clinical setting by determining the proportion of medication orders that would generate a

Terry S. Field; Martin DeFlorio; Jane Laprino; Jill C. Auger; Paula A. Rochon; David W. Bates; Jerry H. Gurwitz

2006-01-01

368

Research Paper: Prescribers' Responses to Alerts During Medication Ordering in the Long Term Care Setting  

Microsoft Academic Search

ObjectiveComputerized physician order entry with clinical decision support has been shown to improve medication safety in adult inpatients, but few data are available regarding its usefulness in the long-term care setting. The objective of this study was to examine opportunities for improving medication safety in that clinical setting by determining the proportion of medication orders that would generate a warning

James Judge; Terry S. Field; Martin DeFlorio; Jane Laprino; Jill Auger; Paula Rochon; David W. Bates; Jerry H. Gurwitz

2006-01-01

369

Comparison of Efficacy and Safety of Tenofovir and Entecavir in Chronic Hepatitis B Virus Infection: A Systematic Review and Meta-Analysis  

PubMed Central

Objective Tenofovir (TDF) and entecavir (ETV) are both potent antiviral agents for the treatment of chronic hepatitis B virus (HBV) infection. Multiple studies have compared efficacy and safety of these two agents, but yielded inconsistent results. Hence, we conducted a meta-analysis to discern comparative efficacy and safety. Methods Published data relevant to a comparison of TDF and ETV used in HBV were included. HBV DNA suppression rate, ALT normalization rate, and HBeAg seroconversion rate at 24 weeks and 48 weeks were reviewed. Drug safety profiles and resistance were also discussed. Results Seven articles met entry criteria. Four and six articles included data for 24 and 48-week HBV DNA suppression rates, respectively, and no significant differences for the rates between the two drugs were found in chronic HBV patients (TDF vs. ETV: relative risk [RR]?=?1.10, 95% CI?=?0.91–1.33 and RR?=?1.07, 95% CI?=?0.99–1.17 for 24 weeks and 48 weeks, respectively). For the ALT normalization rate (three studies for 24 weeks, four articles for 48 weeks) and HBeAg seroconversion rate (two and four studies for 24 weeks and 48 weeks, respectively), no difference was observed between TDF and ETV. Additionally, no significant distinction in short term safety was found for CHB patients. Conclusions TDF and ETV are similarly effective and safe in chronic HBV patients after 24 weeks and 48 weeks of anti-viral therapy. Nevertheless, the long-term efficacy and safety of TDF and ETV should be monitored in prolonged therapy. PMID:24905092

Zhang, Chi; Ye, Xiaohua; Gao, Yanhui; Zhou, Shudong; Yang, Yi

2014-01-01

370

Long-term anticoagulation. Indications and management.  

PubMed Central

Each year half a million persons in the United States receive long-term anticoagulant therapy to prevent venous and arterial thromboembolism. Unfortunately, the relative benefits and risks of anticoagulant therapy have not been adequately quantified for many thromboembolic disorders, and the decisions as to whether, for how long, and how intensely to administer anticoagulation are often complex and controversial. Several expert panels have published recommendations for anticoagulant therapy for different thromboembolic disorders; the primary area of disagreement among these panels concerns the optimal intensity of anticoagulation. Recent research and analytic reviews have helped to clarify both the risk factors for and the appropriate diagnostic evaluation of anticoagulant-induced hemorrhage. Clinicians must be aware of the nonhemorrhagic complications of anticoagulant therapy, particularly during pregnancy. The administration of anticoagulants is difficult both in relation to dosing and long-term monitoring. Knowledge of the pharmacology of the anticoagulants, an organized approach to ongoing monitoring, and thorough patient education may facilitate the safe and effective use of these drugs. PMID:2686173

Stults, B M; Dere, W H; Caine, T H

1989-01-01

371

Long-term evolution of transposable elements  

PubMed Central

Transposable elements are often considered parasitic DNA sequences, able to invade the genome of their host thanks to their self-replicating ability. This colonization process has been extensively studied, both theoretically and experimentally, but their long-term coevolution with the genomes is still poorly understood. In this work, we aim to challenge previous population genetics models by considering features of transposable elements as quantitative, rather than discrete, variables. We also describe more realistic transposable element dynamics by accounting for the variability of the insertion effect, from deleterious to adaptive, as well as mutations leading to a loss of transposition activity and to nonautonomous copies. Individual-based simulations of the behavior of a transposable-element family over several thousand generations show different ways in which active or inactive copies can be maintained for a very long time. Results reveal an unexpected impact of genetic drift on the “junk DNA” content of the genome and strongly question the likelihood of the sustainable long-term stable transposition-selection equilibrium on which numerous previous works were based. PMID:18040048

Le Rouzic, Arnaud; Boutin, Thibaud S.; Capy, Pierre

2007-01-01

372

Impact of safety monitoring on error probabilities of binary efficacy outcome analyses in large phase III group sequential trials  

PubMed Central

In phase III clinical trials, some adverse events may not be rare or unexpected and can be considered as a primary measure for safety, particularly in trials of life-threatening conditions, such as stroke or traumatic brain injury. In some clinical areas, efficacy endpoints may be highly correlated with safety endpoints, yet the interim efficacy analyses under group sequential designs usually do not consider safety measures formally in the analyses. Furthermore, safety is often statistically monitored more frequently than efficacy measures. Since early termination of a trial in this situation can be triggered by either efficacy or safety, the impact of safety monitoring on the error probabilities of efficacy analyses may be non-trivial if the original design does not take the multiplicity effect into account. We estimate the actual error probabilities for a bivariate binary efficacy-safety response in large confirmatory group sequential trials. The estimated probabilities are verified by Monte Carlo simulation. Our findings suggest that type I error for efficacy analyses decreases as efficacy-safety correlation or between-group difference in the safety event rate increases. In addition, while power for efficacy is robust to misspecification of the efficacy-safety correlation, it decreases dramatically as between-group difference in the safety event rate increases. PMID:22589042

Weng, Yanqiu; Zhao, Wenle; Palesch, Yuko

2015-01-01

373

Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.  

PubMed

Sativex is an endocannabinoid system modulator principally containing ?(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised controlled trial, Sativex had a clinically relevant effect on spasticity associated with multiple sclerosis (MS). Patients self-titrated oromucosal Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to evaluate the safety and tolerability of long-term treatment by recording the incidence and severity of adverse events (AEs). Secondary outcomes were to determine evidence of developing tolerance and to assess the long-term dosing profile of Sativex. A validated 11-point Numerical Rating Scale of spasticity severity was used to assess efficacy. A total of 146 patients elected to enter this open-label follow-up safety trial. Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10 %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with two psychiatric events reported by one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred following abrupt cessation of treatment. Baseline symptoms including spasticity did not deteriorate but were maintained to study completion in those patients who did not withdraw. No new safety concerns were identified with chronic Sativex treatment, and serious AEs were uncommon. There was no evidence of tolerance developing, and patients who remained in the study reported continued benefit. PMID:22878432

Serpell, Michael G; Notcutt, William; Collin, Christine

2013-01-01

374

Tolerance to inhaled Duovent. A long-term study.  

PubMed

Fenoterol with ipratropium bromide (Duovent) is a recently used combination between an anticholinergic and a beta-adrenergic drug useful in obtaining a more effective bronchodilatation and/or reducing the single drug doses. It has been suggested that, as in the case of beta-agonists, its clinical efficacy may be limited by the development of tolerance. We studied the effects of inhaled Duovent in 15 asthmatic patients for 3 months, using a rigidly controlled protocol. Appropriate serial physiological measurements were made at regular intervals during the 90-day study. In all instances the day-one bronchodilator response was significant, prompt and sustained: at 1, 4, 8 and 12 weeks the response was statistically the same as on day 1. It is concluded that, when the important variables are properly controlled, no evidence of tolerance to long-term therapy with Duovent is demonstrable. PMID:2951809

Carlone, S; Angelici, E; Palange, P; Shaqadan, W; Luciani, G; Serra, P

1986-01-01

375

Long-Term Expression and Safety of Administration of AAVrh.10hCLN2 to the Brain of Rats and Nonhuman Primates for the Treatment of Late Infantile Neuronal Ceroid Lipofuscinosis  

PubMed Central

Abstract Late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal, lysosomal storage disorder caused by mutations in the CLN2 gene, results in a deficiency of tripeptidyl-peptidase I (TPP-I) activity in neurons. Our prior studies showed that delivery of the human CLN2 cDNA directly to the CNS, using an adeno-associated virus serotype 2 (AAV2) vector, is safe in children with LINCL. As a second-generation strategy, we have demonstrated that AAVrh.10hCLN2, a rhesus-derived AAV vector, mediates wide distribution of TPP-I through the CNS in a murine model. This study tests the hypothesis that direct administration of AAVrh.10hCLN2 to the CNS of rats and nonhuman primates at doses scalable to humans has an acceptable safety profile and mediates significant CLN2 expression in the CNS. A dose of 1011 genome copies (GC) was administered bilaterally to the striatum of Sprague Dawley rats with sacrifice at 7 and 90 days with no significant impact except for mild vector-related histopathological changes at the site of vector administration. A dose of 1.8×1012 GC of AAVrh.10hCLN2 was administered to the CNS of 8 African green monkeys. The vector-treated monkeys did not differ from controls in any safety parameter except for mild to moderate white matter edema and inflammation localized to the administration sites of the vector. There were no clinical sequelae to these localized findings. TPP-I activity was >2 SD over background in 31.7±8.1% of brain at 90 days. These findings establish the dose and safety profile for human clinical studies for the treatment of LINCL with AAVrh.10hCLN2. PMID:23131032

Sondhi, Dolan; Johnson, Linda; Purpura, Keith; Monette, Sebastien; Souweidane, Mark M.; Kaplitt, Michael G.; Kosofsky, Barry; Yohay, Kaleb; Ballon, Douglas; Dyke, Jonathan; Kaminksy, Stephen M.; Hackett, Neil R.

2012-01-01

376

Safety and efficacy of outpatient bronchoscopy in lung transplant recipients - a single centre analysis of 3,197 procedures  

PubMed Central

Background Bronchoscopy represents an important diagnostic and therapeutic tool in the management of lung transplant (LTx) recipients. Outpatient bronchoscopy reduces health costs and may improve quality of life amongst these patients. This retrospective study assessed the safety and efficacy of outpatient bronchoscopy including trans-bronchial biopsy. Methods All outpatient bronchoscopies performed on lung transplant recipients between 1 August 2008 and 31 January 2011 were reviewed. Sample quality, duration and complications were recorded. Cost analysis was performed from local trust financial data. Results A total of 3,197 bronchoscopies were performed on 571 LTx recipients under topical anaesthesia. Fourteen percent of examinations required intravenous sedation. In 79.8% of examinations no complications were observed. Most complications were minor (17.9%) including cough (5.3%) and minimal bleeding after trans-bronchial biopsy (7.8%). Major complications (2.3%) were pneumothorax, severe bleeding and severe desaturation. No attributable deaths were recorded during the observation period. Quality of examination based on bronchoalveolar lavage recovery median (>50%) and biopsy results was adequate at 75% and 77.4%, respectively. Independent risk factors associated with complication were long-term oxygen therapy, sedation before examination, balloon dilatation and transbronchial biopsy. After excluding high-risk procedures annual savings per patient (2.2 bronchoscopies per year) were 2140€. Conclusions Outpatient bronchoscopy after LTx is safe. The low complication rate could be attributed to withholding of intravenous sedation. Furthermore, it reduces health community costs. PMID:24917927

2014-01-01

377

Immediate and long term outcome after infrathalamic and thalamic lesioning for intractable Tourette's syndrome  

PubMed Central

OBJECTIVE—The surgical treatment of intractable Tourette's syndrome is controversial. Experience with 17 consecutive patients treated between 1970 and 1998 is reviewed and the efficacy and safety of surgical treatment is assessed.?METHODS—These patients were retrospectively reclassified into subtypes according to the protocol of the Tourette's Syndrome Study Group. One patient was excluded from the study. Ventriculography based stereotactic zona incerta (ZI) and ventrolateral/ lamella medialis thalamotomy (VL/LM) were performed on all patients. The preoperative, postoperative, and late tic severities were assessed by the tic severity rating scale. The median follow up of 11 patients (65%) was 7 years (range 3.5-17 years) and six patients were lost to long term follow up.?RESULTS—Median age was 23 years (range 11-40) at the time of surgery. Median duration of illness was 14 years (range 3-33). The mean preoperative motor and vocal tic severities were estimated to be 4.44 (SD 0.63) and 3.81 (SD 0.66), respectively. Unilateral ZI lesioning and VL/LM lesioning selected by asymmetry of symptoms provide an effective control of tic severity (p motor and vocal<0.001). In attenuation of contralateral symptoms, a second surgical intervention in the relevant side could reduce tic severity sufficiently (p motor<0.01; p vocal<0.005). Transient complications occurred in 68% of patients. Only one permanent complication was registered in six patients followed up after unilateral surgery. Two out of five patients followed up after bilateral surgery had disabling side effects of surgery.?CONCLUSIONS—ZI and VL/LM lesioning provide a significant long term reduction of tic severity in intractable Tourette's syndrome. Adequate selection of the side of first intervention might prevent the patient from increased risk of bilateral surgery.?? PMID:11309463

Babel, T; Warnke, P; Ostertag, C

2001-01-01

378

Development of accident management measures for RBMK-1500 in the case of loss of long-term core cooling  

Microsoft Academic Search

Results of the Level 1 Probabilistic Safety Assessment of the Ignalina Nuclear Power Plant have shown that in the risk topography transients are dominating. Analysis has shown that failure of the long-term core cooling is the main contributor to the core damage frequency. However, the reactor core damage in the long-term indicates the potential opportunities for the accident management. The

E. Uspuras; A. Kaliatka; V. Vileiniskis

2006-01-01

379

[Enteral nutrition through long-term jejunostomy].  

PubMed

We present the case of a female patient suffering a peritonitis episode after subtotal gastrectomy due to gastric neoplasm in relation to lesser curvature necrosis extending to the anterior esophageal wall. This an uncommon andsevere complication that made mandatory further aggressive surgery: transection of the abdominal esophagus, transection of the gastric stump, and cervical esophagostomy with creation of a jejunostomy with a needle catheter for feeding. This digestive tube access technique is generally used during major abdominal post-surgery until oral intake is reestablished. Our patient has been 187 days with this therapy since reconstruction of the GI tract was ruled out due to tumoral infiltration of the colon and tumor recurrence at the gastrohepatic omentum. To date, there has been no complication from permanence and/or long-term use of this technique. PMID:18372950

Fernández, T; Neira, P; Enríquez, C

2008-01-01

380

Long-term control of root growth  

SciTech Connect

A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin. 7 figs.

Burton, F.G.; Cataldo, D.A.; Cline, J.F.; Skiens, W.E.

1992-05-26

381

Long-term sequelae to foodborne disease.  

PubMed

Most of the concern about foodborne disease has been focused on the immediate effects of acute infection. Recent information has shown that many of these foodborne infections also have long-term sequelae with serious health effects and a significant economic impact. To increase the awareness of animal health professionals to these sequelae, the authors discuss two groups of sequelae which are strongly associated with preceding infection (reactive arthritides, including Reiter's syndrome, and the Guillain-Barré syndrome) as well as the possible association between Crohn's disease and Mycobacterium paratuberculosis. The discussion includes a description of the disease syndromes along with epidemiological and economic information. More reliable epidemiologial and economic data on chronic sequelae to foodborne disease will be needed for future evaluation of the cost-effectiveness of mitigation strategies to reduce the occurrence of foodborne pathogens. PMID:9501346

McDowell, R M; McElvaine, M D

1997-08-01

382

Long-term control of root growth  

DOEpatents

A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin.

Burton, Frederick G. (West Richland, WA); Cataldo, Dominic A. (Kennewick, WA); Cline, John F. (Prosser, WA); Skiens, W. Eugene (Richland, WA)

1992-05-26

383

Kentucky Long-Term Policy Research Center  

NSDL National Science Digital Library

Created in 1992 by the Kentucky General Assembly, the Kentucky Long-Term Policy Research Center is dedicated to helping the Bluegrass State "act as a catalyst to change the way decisions are made in government." Their research has proved seminal to the state's advancement, and interested parties can learn about their publications, conferences, and other work on this site. First-time visitors should start by looking over some of their work in the "Publications" area. Here they will find full-length reports, their "Policy Notes" series, and PowerPoint presentations created by staff members. There are several hundred publications here, which can be viewed by topics, which range from "aging population" to "workforce development". The "Videos" section is quite good as well, and it features talks with 43 persons of interest from across the state, including journalist Betty Winston Baye and the mayor of Madisonville, Karen Cunningham.

384

Managing Records for the Long Term - 12363  

SciTech Connect

The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the Office of Legacy Management will keep records management as a high priority. (authors)

Montgomery, John V. [U.S. Department of Energy, Office of Legacy Management, Morgantown, West Virginia (United States); Gueretta, Jeanie [U.S. Department of Energy, Office of Legacy Management, Grand Junction, Colorado (United States)

2012-07-01

385

Sertindole in the long-term treatment of schizophrenia.  

PubMed

This study assessed the safety and tolerability of sertindole in the long-term treatment of schizophrenia. An open-label, noncomparative, flexible-dose study was carried out in 11 European countries. Upon completion of an 8-week, haloperidol-referenced randomized clinical trial with sertindole, patients were offered sertindole maintenance treatment up to 18 months. In total, 294 patients were enrolled, of whom 237 (81%) had received sertindole and 57 (19%) had received haloperidol in the lead-in trial. The modal dose during the maintenance period was 16 mg/day. Patients showed therapeutic improvement indicated by significant decreases in the Positive And Negative Syndrome Scale and Clinical Global Impression 'severity-of-illness' scores. An adverse event was the primary reason for withdrawal in 13% of patients. The most common adverse events were fatigue and weight gain, both with incidences of 14%. The incidence of extrapyramidal symptoms was 18%, and 11% of the patients required anticholinergic medication. No statistically significant changes were observed in laboratory values or vital signs, but the mean serum prolactin levels decreased. The mean change in weight from baseline to the last assessment was 2.7 kg. The largest weight increase was observed in patients who were underweight at baseline. Long-term treatment with sertindole was safe and well tolerated, and patients showed clinical improvement beyond acute treatment. PMID:22609816

Hale, Anthony S; Azorin, Jean M; Lemming, Ole M; Mæhlum, Eli

2012-07-01

386

A clinical appraisal of patients following long-term contraception.  

PubMed

This study presents a clinical evaluation of private patients between the ages of 16 and 40 who have used contraceptive measures from January 1, 1961, through December 31, 1973. The clinical evaluation involves 3,746 private patients. The contraceptive methods of 641 patients (17 per cent) who have been bollowed for a total of 99,996 months (13 years each) are presented and analyzed. The patients are evaluated as to weight, blood pressure, pregnancy, pap smears. laboratory changes, pelvic surgery, breast surgery, incidence of cancer, contraceptive failures and changes in contraceptive practices over this span of time. This paper evaluates the role of such sociologic factors as education, religion, economic level, occupation, working status, changing marital status, age at the time of contraceptive choice, and the attitude of the husband with regard to long-term contraceptive therapy. Side effects have been well publicized. Safety has been questioned but essentially proved for the vast majority of the patients. Collected data enable some insight into the life style and motivation of the long-term contraceptive users. PMID:1146899

Keifer, W S; Scott, J C

1975-06-15

387

Long-Term Effects of Risperidone in Children with Autism Spectrum Disorders: A Placebo Discontinuation Study  

ERIC Educational Resources Information Center

Objective: The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. Method: Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe…

Troost, Pieter W.; Lahuis, Bertine E.; Steenhuis, Mark-Peter; Ketelaars, Cees E. J.; Buitelaar, Jan K.; van Engeland, Herman; Scahill, Lawrence; Minderaa, Ruud B.; Hoekstra, Pieter J.