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1

Long-term safety and efficacy of continuous intrathecal baclofen.  

PubMed

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

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

2002-10-01

2

The long-term efficacy and safety profile of barnidipine.  

PubMed

Two multicentre trials have investigated the efficacy and tolerability of treatment with once-daily barnidipine, in patients with mild to moderate essential hypertension. The long-term efficacy and safety of barnidipine were demonstrated in a long-term, multicentre, open-label study. In total, 106, 79 and 32 patients were followed for the first, second and third year, respectively. Patients received barnidipine at a dose titrated to achieve a sitting DBP > or = 90 mmHg or a decrease in sitting BDP > or = 10 mmHg. If necessary, another antihypertensive agent was added to achieve normalisation of blood pressure. In the first year, normalisation of blood pressure was achieved in 91% of patients. This was maintained in 91% and 81% of patients in the second and third years, respectively. At the end of treatment in both years, over 60% of patients remained on barnidipine monotherapy (10 or 20 mg/day). A low incidence of adverse events possibly or probably related to barnidipine (10 or 20 mg/day) monotherapy was reported in the first and second years with headache, peripheral oedema and palpitations the most commonly reported. In the third year of follow-up, only one adverse event, an ECG abnormality, was considered to be possibly related to the study medication. The effective 24 hour control of blood pressure with barnidipine monotherapy was confirmed in a randomised, double-blind, placebo-controlled, cross-over study of 20 patients. These patients were given 6 week regimens of both barnidipine (20 mg/day) and placebo. Office and 24 hour ambulatory blood pressures were recorded at the end of each treatment phase. Barnidipine lowered blood pressure to a significantly greater extent than placebo both at night and during the day. Adverse events were classified as mild or moderate and fewer adverse events were reported with barnidipine treatment compared with placebo. Barnidipine monotherapy (20 mg/day) is safe and effective in providing 24 hour control of blood pressure. Furthermore, the efficacy and tolerability of barnidipine monotherapy (10 or 20 mg/day) are maintained for at least 2 years. PMID:11221291

Smilde, J G

2000-11-01

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.

Rado, Jeffrey T; Janicak, Philip G

2014-01-01

4

The long-term efficacy and safety of two different corticosteroids in chronic sarcoidosis  

Microsoft Academic Search

Deflazacort (DFZ) is claimed to have fewer adverse bone effects than prednisone (PDN) at doses with equivalent anti-inflammatory activity (5 mg PDN=6 mg DFZ). However, its safety over the long-term has never been tested in a controlled trial.The aim of the present study was to assess prospectively the safety and efficacy of DFZ compared with PDN in previously untreated patients

G. Rizzato; A. Riboldi; B. Imbimbo; A. Torresin; S. Milani

1997-01-01

5

Efficacy and safety of risperidone in the long-term treatment of patients with schizophrenia  

Microsoft Academic Search

The long-term efficacy and safety of risperidone were evaluated in patients with chronic schizophrenia in an open-label study. Thirty-two patients received risperidone for 1 year and 19 of the 32 received risperidone for 2 years. The mean dose of risperidone was 9.4 mg\\/d in the 1-year follow-up and 8 mg\\/d in the 2-year follow-up. At the end of 1 and

Eva Lindström; Bo Eriksson; Anders Hellgren; Lars von Knorring; Göran Eberhard

1995-01-01

6

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

7

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

PubMed

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

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

2014-07-01

8

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.

Ramirez-Castaneda, Juan; Jankovic, Joseph

2013-01-01

9

Long-term outpatient dalteparin (fragmin) therapy for arterial and venous thrombosis: efficacy and safety--a preliminary report.  

PubMed

The availability of low molecular weight heparin (LMWH), with associated ease of home delivery and enhanced efficacy and safety, has rendered the long-term outpatient use of LMWH feasible. Although warfarin is usually used for long-term secondary prevention, it is not the drug of choice for a variety of conditions such as antiphospholipid thrombosis syndrome, sticky platelet syndrome, and patients with malignancy and other medical conditions who have failed adequate warfarin doses. We assessed the long-term efficacy and safety of outpatient dalteparin in a series of patients with conditions associated with prior warfarin failure or potential to warfarin therapy (antiphospholipid syndrome). The results of this study, detailed herein, demonstrate that long-term dalteparin is highly effective and safe when used as long-term therapy for secondary prevention in selected prothrombotic disorders. PMID:10726039

Bick, R L; Rice, J

1999-10-01

10

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

11

Long-term, Multicenter Study of the Safety and Efficacy of Topical Alprostadil Cream in Male Patients with Erectile Dysfunction  

Microsoft Academic Search

Introduction. Alprostadil is approved for treatment of male erectile dysfunction (ED) by injection or urethral insertion. Topical delivery of alprostadil offers an improved alternative. Aim. To evaluate the long-term safety and efficacy of topical alprostadil cream. Methods. This was a multicenter, open-label, long-term study in 1,161 patients (998 double-blind rollover; 163 naïve) with ED. For the first 4 weeks, patients

Michael Rooney; William Pfister; Mary Mahoney; Melissa Nelson; James Yeager; Christopher Steidle

2009-01-01

12

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.

Kivelevitch, Dario; Mansouri, Bobbak; Menter, Alan

2014-01-01

13

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.

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

2013-01-01

14

Long-term Efficacy and Safety of Piracetam in the Treatment of Progressive Myoclonus Epilepsy  

Microsoft Academic Search

Background: Piracetam has been proven to be effec- tive and well tolerated in the treatment of myoclonus in short-term studies. Objective: To assess its long-term clinical efficacy, 11 patients with disabling myoclonus due to progressive my- oclonus epilepsy were treated with piracetam in an open- label study. Methods: Neurologic outcome (at the 1st, 6th, 12th, and 18th month of treatment)

Marco Fedi; David Reutens; Francois Dubeau; Eva Andermann; Daniela D'Agostino; Frederick Andermann

2001-01-01

15

Long-term efficacy and safety of modafinil (PROVIGIL ®) for the treatment of excessive daytime sleepiness associated with narcolepsy  

Microsoft Academic Search

Objectives: To assess the long-term efficacy and safety of modafinil in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.Background: Modafinil has been shown to be effective and well tolerated for treating EDS associated with narcolepsy in two large-scale, well-controlled, 9-week clinical trials.Methods: Four hundred and seventy eight adult patients with a diagnosis of narcolepsy who had completed one of

Merrill M Mitler; John Harsh; Max Hirshkowitz; Christian Guilleminault

2000-01-01

16

Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension  

Microsoft Academic Search

Background: Even within the normal range, aldosterone levels are linked to end-organ toxicity and mortality in patients with hypertension. Treatment with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers does not sufficiently reduce plasma aldosterone levels.Objective: This study was conducted to assess the long-term safety profile and efficacy of the selective aldosterone blocker eplerenone.Methods: This was a multicenter, open-label, uncontrolled trial in

Ellen D. Burgess; Yves Lacourciére; Luis M. Ruilope-Urioste; Suzanne Oparil; Jay H. Kleiman; Scott Krause; Barbara Roniker; Clement Maurath

2003-01-01

17

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

Microsoft Academic Search

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

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

2000-01-01

18

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

PubMed

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

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

2013-11-01

19

On-line haemodiafiltration. Safety and efficacy in long-term clinical practice  

Microsoft Academic Search

with on-line HDF. The study covers two aspects: first,0.5±0.4 ml\\/min in the remaining patients. analysis of the population treated, and second evalu- ation of the microbiological safety and efficacy of high-flux HDF used routinely. On-line HDF, treatment schedule and operational conditions The treatment schedule was based on three HDF sessions\\/week for all patients with a session lasting 3-4 h. On-line

B. Canaud; J. Y. Bosc; H. Leray-Moragues; F. Stec; A. Argiles; M. Leblanc; C. Mion

20

Long-term efficacy, safety, and tolerability of Hizentra® for treatment of primary immunodeficiency disease.  

PubMed

Hizentra(®) (20% subcutaneous immunoglobulin [SCIG]) was administered to subjects with primary immunodeficiency disease in two extension studies in the EU and US to assess long-term efficacy and tolerability. Subjects (aged 4-69 years) were treated for 148 weeks in the EU (N = 40; 5405 infusions) and 87 weeks in the US (N = 21; 1735 infusions). Weekly doses were 116.0 mg/kg (EU) and 193.2 mg/kg (US); IgG levels were 7.97 g/L (EU) and 11.98 g/L (US). Annualized rates of serious bacterial infections were 0.05 infections/subject/year (EU) and 0.06 infections/subject/year (US). Rates of any infection were 3.33 infections/subject/year (EU) and 2.38 infections/subject/year (US). The rate of bronchopulmonary infections was higher in the EU study. No treatment-related serious AEs occurred; no subject discontinued because of treatment-related AEs. Self-administered Hizentra afforded sustained effective protection from infections and favorable tolerability during an extended treatment period of up to 3 years. PMID:24412910

Jolles, Stephen; Borte, Michael; Nelson, Robert P; Rojavin, Mikhail; Bexon, Martin; Lawo, John-Philip; Wasserman, Richard L

2014-02-01

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.

Senabre-Gallego, Jose Miguel; Santos-Ramirez, Carlos; Santos-Soler, Gregorio; Salas-Heredia, Esteban; Sanchez-Barrioluengo, Mabel; Barber, Xavier; Rosas, Jose

2013-01-01

22

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

PubMed Central

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

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

2013-01-01

23

Long-term efficacy, safety and durability of Juv?derm(R) 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.

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

2013-01-01

24

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.

Monsivais, Diane Burn

2014-01-01

25

The long-term safety and efficacy of intrathecal therapy using sufentanil in chronic intractable non-malignant pain.  

PubMed

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, Jose Jesus; Monsivais, Diane Burn

2014-07-01

26

Long-term efficacy and safety of polyalkylimide gel for the treatment of HIV-associated lipoatrophy.  

PubMed

The long-term safety and efficacy of products used in the correction of HIV-associated facial lipoatrophy (FLA) are largely unknown. The purpose of this study was to describe the long-term efficacy and safety of polyalkylimide gel (PAIG) in the treatment of HIV-associated FLA. In this open-label, randomized, single-center study, 31 HIV-positive individuals (median age 48 years (interquartile ranges (IQR) 45, 55, 97% male) with FLA were randomized to immediate (week 0 and six) or delayed (week 12 and 18) PAIG injections. Week 96 endpoints included change in FLA severity scores (FLSS) (five-point scale), proportion of patients with adverse events, and changes in quality of life, depression and anxiety using validated surveys. Results at week 96 were available for 28 patients. Adverse events, including swelling, redness, bruising and pain, were mild, and resolved after a median of three days following the injection. At week 96, median changes in physician and patient FLSS scores were -2 (IQR -3, -1; p<0.001 vs. baseline) and -2 (IQR -2, -1; p<0.001 vs. baseline), respectively. Physician and patient FLSS scores were not significantly different between the groups at week 96. Significant improvements in patient's anxiety (p<0.001), depression (p<0.001) and mental health (p=0.01) were observed from baseline to week 96. In conclusion, treatment with PAIG was associated with sustained improvements in both the physical and psychological components of FLA through 96 weeks of follow-up. PMID:20024700

Antoniou, Tony; Raboud, Janet M; Kovacs, Colin; Diong, Christina; Brunetta, Jason; Smith, Graham; Halpenny, Roberta; Beninger, Francis; Loutfy, Mona R

2009-10-01

27

A randomized trial of the long-term, continued efficacy and safety of modafinil in narcolepsy  

Microsoft Academic Search

Objective: To assess the continued efficacy of modafinil in the treatment of excessive daytime somnolence (EDS) of narcolepsy.Background: Modafinil has been shown to be a safe and effective treatment for the EDS presented by patients with narcolepsy. However, the duration of treatment has been relatively brief, particularly considering the chronic nature of the disease.Methods: Sixty-nine patients with narcolepsy, who completed

H Moldofsky; R. J Broughton; J. D Hill

2000-01-01

28

Long-Term Efficacy and Safety of Linagliptin in Patients With Type 2 Diabetes and Severe Renal Impairment  

PubMed Central

OBJECTIVE This placebo-controlled study assessed long-term efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes and severe renal impairment (RI). RESEARCH DESIGN AND METHODS In this 1-year, double-blind study, 133 patients with type 2 diabetes (HbA1c 7.0–10.0%) and severe RI (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) at screening were randomized to linagliptin 5 mg (n = 68) or placebo (n = 65) once daily, added to existing background therapy. The primary efficacy end point was HbA1c change from baseline to week 12. Efficacy and safety end points were assessed after 1 year. RESULTS At week 12, adjusted mean HbA1c decreased by ?0.76% with linagliptin and ?0.15% with placebo (treatment difference, ?0.60%; 95% CI ?0.89 to ?0.31; P < 0.0001). HbA1c improvements were sustained with linagliptin (?0.71%) over placebo (0.01%) at 1 year (treatment difference ?0.72%, ?1.03 to ?0.41; P < 0.0001). Mean insulin doses decreased by ?6.2 units with linagliptin and ?0.3 units with placebo. Overall adverse event incidence was similar over 1 year (94.1 vs. 92.3%). Incidence of severe hypoglycemia with linagliptin and placebo was comparably low (three patients per group). Linagliptin and placebo had little effect on renal function (median change in eGFR, ?0.8 vs. ?2.2 mL/min/1.73 m2), and no drug-related renal failure occurred. CONCLUSIONS In patients with type 2 diabetes and severe RI, linagliptin provided clinically meaningful improvements in glycemic control with very low risk of severe hypoglycemia, stable body weight, and no cases of drug-related renal failure. The potential for linagliptin to spare insulin and provide long-term renal safety warrants further investigations.

McGill, Janet B.; Sloan, Lance; Newman, Jennifer; Patel, Sanjay; Sauce, Christophe; von Eynatten, Maximilian; Woerle, Hans-Juergen

2013-01-01

29

Efficacy and safety of long term entecavir in chronic hepatitis B treatment naïve patients in clinical practice.  

PubMed

Background and aims. Entecavir (ETV) is effective and safe in patients with chronic hepatitis B in the short term, but its long term efficacy and safety has not been established. Material and methods. We evaluated HBV DNA clearance, HBeAg/antiHBe and HBsAg/antiHBs seroconversion rates in HBeAg-positive and negative NUC naïve HBV patients treated with ETV for more than 6 months, and predictors of response. Results. A hundred and sixty nine consecutive patients were treated with ETV for a median of 181 weeks. 61% were HBeAg positive, 23% were cirrhotics, and mean HBV-DNA levels were 6,88 ± 1,74 log10 IU/mL. Overall, 156 (92%) patients became HBV DNA undetectable, 92 (88%) HBeAg positive and 64 (98%) HBeAg negative patients. Seventy four (71%) patients cleared HBeAg after a median of 48 weeks of treatment, 23 (14%) patients cleared HBsAg (19 HBeAg positive and 4 HBeAg negative, p 0.025) after a median of 96 weeks of treatment, and 22 (13%) patients developed protective titers of anti-HBs. At the end of the study, 35 (20%) patients had discontinued therapy: 33 HBeAg positive and 2 HBeAg negative; 9 of them (26%) developed virological relapse after a median of 48 weeks of stopping treatment. None of the patients had primary non response and one patient developed breakthrough. Two patients developed HCC, three underwent liver transplantation and 3 deaths were attributable to liver-related events. No serious adverse events were reported. Conclusion. Long term ETV treatment showed high virological response rates, and a favorable safety profile for NUC-naive HBeAg-positive and negative patients treated in clinical practice. PMID:24756007

Ridruejo, Ezequiel; Marciano, Sebastián; Galdame, Omar; Reggiardo, María V; Muñoz, Alberto E; Adrover, Raúl; Cocozzella, Daniel; Fernandez, Nora; Estepo, Claudio; Mendizabal, Manuel; Romero, Gustavo A; Levi, Diana; Schroder, Teresa; Paz, Silvia; Fainboim, Hugo; Mandó, Oscar G; Gadano, Adrián C; Silva, Marcelo O

2014-01-01

30

Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab  

PubMed Central

Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-?B ligand (RANKL), a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. Denosumab treatment is associated with a rapid, sustained, and reversible reduction in bone turnover markers, a continuous marked increase in bone mineral density at all sites, and a marked decrease in the risk of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis. Therefore, it could be considered as an effective alternative to previous bisphosphonate treatment as well as first-line treatment of severe osteoporosis. Cost-effectiveness studies support this suggestion. In addition, denosumab seems to be the safest treatment option in patients with impaired renal function. Denosumab is characterized by reversibility of its effect after treatment discontinuation, in contrast with bisphosphonates. Large-scale clinical trials, including the extension of FREEDOM trial for up to 5 years, are reassuring for its safety. However, given its brief post-market period, vigilance regarding adverse events related to putative RANKL inhibition in tissues other than bone, as well as those related to bone turnover oversuppression, is advised.

Anastasilakis, Athanasios D; Toulis, Konstantinos A; Polyzos, Stergios A; Anastasilakis, Chrysostomos D; Makras, Polyzois

2012-01-01

31

Long-term safety, efficacy and palatability of oral meloxicam at 0.01–0.03 mg\\/kg for treatment of osteoarthritic pain in cats  

Microsoft Academic Search

Osteoarthritis is a chronic, painful condition that is now recognised as affecting a large proportion of cats. Non-steroidal anti-inflammatory drugs (NSAIDs) have proven efficacy in dogs and humans but there are limited published data on the use of NSAIDs in the long-term management of this condition in cats. This prospective study aimed to assess the long-term safety and palatability of

Marcus N. Gunew; Victor H. Menrath; Rhett D. Marshall

2008-01-01

32

The efficacy and safety of long-term Norditropin® treatment in children with Prader-Willi syndrome.  

PubMed

Prader-Willi syndrome is a genetic disorder that is associated with short stature, partial growth hormone deficiency, small hands and feet, learning and behavioural problems, and hyperphagia leading to severe, often morbid, obesity. Growth hormone therapy is associated with an improvement in height and body composition. We evaluated the efficacy and safety of long-term growth hormone treatment in a retrospective observational multinational study of 41 prepubertal children (mean age 3.8±3.0 years) with genetically diagnosed Prader-Willi syndrome treated with growth hormone (0.03-0.06 mg/kg/day) for >12 months [mean duration 4.1 (range 0.9-9.5) years]. Height, weight, and body composition measurements were recorded at baseline and at 6 month intervals until last observation. Mean (SD) gain in height at 12 months was 0.9 (0.2) SD score (p<0.0001). At last observation (after approximately 6 years) mean gain in height was 1.3 (0.3) (p=0.0001) with 85% of children achieving height>- 2 SD score. Body composition improved during treatment with an estimated 9.1% increase in lean body mass and 9.1% decrease in fat mass at last observation (p=0.019). Scoliosis was reported in 3 patients at baseline and 8 patients at last observation. Sleep apnoea was recorded in 3 (7.3%) patients. There were no other severe adverse events reported. Long-term growth hormone treatment of prepubertal children with Prader-Willi syndrome was associated with significant improvements in height and body composition. Treatment was well tolerated. The development of scoliosis warrants monitoring by an orthopaedic specialist. PMID:23632904

Meinhardt, U; Christiansen, J S; Farholt, S; Lämmer, C; Ostergaard, J R; Schmidt, F; Kappelgaard, A-M; Eiholzer, U

2013-07-01

33

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

34

An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia  

PubMed Central

Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE) monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7%) subjects completed this study: 209 of the 279 subjects (75%) in the 6-month group and 55 of the 111 subjects (50%) in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (?10% of subjects) were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs) were reported by 36 (9%) subjects. The AE profile in this study was qualitatively similar to those of other studies in adult subjects with schizophrenia and in other psychiatric studies of risperidone in pediatric populations. Conclusions Risperidone maintenance treatment in adolescents over 6 to 12 months was well tolerated, consistent with related studies in this clinical population, and associated with continued efficacy. Clinical trials ClinicalTrials.gov registration number: NCT00246285 http://clinicaltrials.gov/ct2/show/NCT00246285?term=NCT00246285&rank=1

2012-01-01

35

Long-term efficacy and safety of anastrozole for adjuvant treatment of early breast cancer in postmenopausal women  

PubMed Central

For more than 20 years, tamoxifen has been the gold standard for the adjuvant treatment of postmenopausal women with hormone-responsive early breast cancer. However, recent randomized trials have shown efficacy and tolerability benefits with the third-generation aromatase inhibitor anastrozole, resulting in an increased use of this agent in the adjuvant setting. Data on anastrozole’s long-term efficacy and tolerability are therefore of interest in clinical practice and will be reviewed here, especially in the light of the 100-month analysis of the ATAC (Anastrozole, Tamoxifen Alone or in Combination) trial.

Gangadhara, Sharath; Bertelli, Gianfilippo

2009-01-01

36

Long-Term Safety and Efficacy of Nevirapine-Based Approaches in HIV Type 1Infected Patients  

Microsoft Academic Search

Using a multicenter, cross-sectional, observation study, the long-term safety, metabolic profile, and viral ef- ficacy of nevirapine (NVP)-based approaches in HIV-1-infected patients treated for at least 2 years were as- sessed. For 4 months, all consecutive HIV-1-infected patients who had been receiving an NVP-containing reg- imen for at least 2 years were recruited. A total of 613 patients were included

Anna Bonjoch; Roger Paredes; Pere Domingo; Manel Cervantes; Enric Pedrol; Esteve Ribera; Lluis Force; Josep M. Llibre; Josep Vilaro; David Dalmau; Josep Cucurull; Jaume Mascaro; Angels Masabeu; Nuria Perez-Alvarez; Jordi Puig; Denise Cinquegrana; Bonaventura Clotet

2006-01-01

37

Immediate and long-term efficacy and safety of photodynamic therapy with Photolon (Fotolon): a seven-year clinical experience  

NASA Astrophysics Data System (ADS)

The purpose of the present study was to summarize data on the long-term efficacy of photodynamic therapy (PDT) with Photolon in patients with malignant tumors of various types and localizations. The data obtained show that PDT with Photolon is a highly effective therapeutic modality for the treatment of skin tumors, cervical intraepithelial neoplasias, lung cancers, disseminated forms of melanoma, primary and metastatic brain tumors, several ophthalmologic diseases. This paper provides a review of most illustrative studies of the application of PDT with Photolon for the treatment of different oncological and non-oncological diseases performed in leading clinical centers of the Republic of Belarus and Russia.

Istomin, Yuri P.; Kaplan, Michael A.; Shliakhtsin, Siarhei V.; Lapzevich, Tatsiana P.; Cerkovsky, Dmitriy A.; Marchanka, Ludmila N.; Fedulov, Alexander S.; Trukhachova, Tatsiana V.

2009-06-01

38

Long-term opioid therapy for chronic noncancer pain: a systematic review and meta-analysis of efficacy and safety.  

PubMed

Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term efficacy and adverse events (including addiction). We systematically reviewed the clinical evidence on patients treated with opioids for CNCP for at least six months. Of 115 studies identified by our search of eleven databases (through April 7, 2007), 17 studies (patients [n]=3,079) met inclusion criteria. Studies evaluated oral (studies [k]=7; n=1,504), transdermal (k=3; n=1, 993), and/or intrathecal (k=8; n=177) opioids. Many patients withdrew from the clinical trials due to adverse effects (oral: 32.5% [95% confidence interval (CI), 26.1%-39.6%]; intrathecal: 6.3% [95% CI, 2.9%-13.1%]; transdermal: 17.5% [95% CI, 6.5%-39.0%]), or due to insufficient pain relief (oral: 11.9% [95% CI, 7.8%-17.7%]; intrathecal: 10.5% [95% CI, 3.5%-27.4%]; transdermal: 5.8% [95% CI, 4.2%-7.3%]). Signs of opioid addiction were reported in only 0.05% (1/2,042) of patients and abuse in only 0.43% (3/685). There was an insufficient amount of data on transdermal opioids to quantify pain relief. For patients able to remain on oral or intrathecal opioids for at least six months, pain scores were reduced long-term (oral: standardized mean difference [SMD] 1.99, 95% CI, 1.17-2.80; intrathecal: SMD 1.33, 95% CI, 0.97-1.69). We conclude that many patients discontinue long-term opioid therapy due to adverse events or insufficient pain relief; however, weak evidence suggests that oral and intrathecal opioids reduce pain long-term in the relatively small proportion of individuals with CNCP who continue treatment. PMID:18178367

Noble, Meredith; Tregear, Stephen J; Treadwell, Jonathan R; Schoelles, Karen

2008-02-01

39

Long-term Safety and Efficacy Results of Once-Daily Emtricitabine-Based Highly Active Antiretroviral Therapy Regimens in Human Immunodeficiency Virus-Infected Pediatric Subjects  

Microsoft Academic Search

OBJECTIVES.The purpose of this work was to obtain long-term safety and efficacy data for antiretroviral regimens containing emtricitabine in HIV-infected pediatric sub- jects and confirm that a pediatric dose of 6 mg\\/kg once daily would provide steady- state emtricitabine concentrations comparable to those observed in adults given 200 mg of emtricitabine once daily. PATIENTS AND METHODS.HIV-infected subjects between 3 months

Xavier Saez-Llorens; Avy Violari; Ram Yogev; Andrew Wiznia; Greg Chittick; John Hinkle; M. Robert Blum; Nathalie Adda; Franck Rousseau; Federico Gomez

2008-01-01

40

Long-term efficacy and safety of oral Viagra® (sildenafil citrate) in men with erectile dysfunction and the effect of randomised treatment withdrawal  

Microsoft Academic Search

The long-term efficacy and safety of oral Viagra® (sildenafil citrate), a selective phosphodiesterase 5 inhibitor, and the effect of withdrawing treatment were evaluated in men with erectile dysfunction (ED). In 233 men with ED of psychogenic or mixed organic\\/psychogenic aetiology, 16 weeks of open-label, flexible-dose sildenafil treatment (10–100 mg) was followed by eight weeks of double-blind, fixed-dose, randomised withdrawal to

E Christiansen; WR Guirguis; D Cox; IH Osterloh

2000-01-01

41

A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects  

Microsoft Academic Search

BACKGROUND: Treatment of obese subjects with topiramate has recently been associated with significant weight loss in a 6-month dose-ranging study.OBJECTIVE: To investigate the long-term efficacy and safety of topiramate in obese subjects.DESIGN: Randomised, double-blind, placebo-controlled study investigating three doses of topiramate: 96, 192, and 256 mg\\/day. All subjects also participated in a nonpharmacological weight-loss programme.SUBJECTS: The study included 1289 subjects

J Wilding; L Van Gaal; A Rissanen; F Vercruysse; M Fitchet

2004-01-01

42

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.

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

2013-01-01

43

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.

Triantafillidis, John K; Malgarinos, George

2014-01-01

44

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

PubMed

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

45

Long-term safety, efficacy and palatability of oral meloxicam at 0.01-0.03 mg/kg for treatment of osteoarthritic pain in cats.  

PubMed

Osteoarthritis is a chronic, painful condition that is now recognised as affecting a large proportion of cats. Non-steroidal anti-inflammatory drugs (NSAIDs) have proven efficacy in dogs and humans but there are limited published data on the use of NSAIDs in the long-term management of this condition in cats. This prospective study aimed to assess the long-term safety and palatability of oral meloxicam and its efficacy in treating osteoarthritic pain in cats when given at a dose of 0.01-0.03 mg/kg once daily. Forty cats diagnosed with osteoarthritis completed the trial with a mean treatment duration of 5.8 months. Gastrointestinal upset in 2/46 (4%) cats was the only adverse effect noted. No deleterious effect on renal function was detected in cats studied. Owners subjectively assessed treatment efficacy as good or excellent in 34/40 (85%) of cases. The results of this study showed oral meloxicam to be safe and palatable long-term treatment for osteoarthritis in cats when given with food at a dose of 0.01-0.03 mg/kg. PMID:18440263

Gunew, Marcus N; Menrath, Victor H; Marshall, Rhett D

2008-07-01

46

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

47

Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: a review of controlled and naturalistic studies.  

PubMed

Attention-deficit/hyperactivity disorder (ADHD) is a common disorder of childhood that often persists into adulthood. Although stimulant medications are recommended as the first-line treatment for ADHD because of their documented short-term effects in children and adults, less is known about their effects on long-term outcome in adults. Here we review the long-term efficacy and safety of the stimulant drugs methylphenidate and amphetamine, as well as the related compound atomoxetine. We performed a systematic review to identify direct and indirect effects of stimulant therapy on long-term outcome in adults. Five randomized controlled trials (RCTs), and 10 open-label extension studies of initial short-term RCTs, with total follow-up of at least 24weeks, were identified. All these RCTs found that medication was significantly more efficacious than placebo in treating ADHD in adults, and the extension studies showed that this favorable effect of medication was maintained during the open-label follow-up period. However, since the maximum duration of these pharmacological trials was 4years, we also reviewed 18 defined naturalistic longitudinal and cross-sectional studies, to provide more information about longer term functional outcomes, side effects and complications. These observational studies also showed positive correlations between early recognition of the disorder, stimulant treatment during childhood and favorable long-term outcome in adult ADHD patients. In conclusion, stimulant therapy of ADHD has long-term beneficial effects and is well tolerated. However, more longitudinal studies of long duration should be performed. In addition, the ethical issues involved in performing double blind RCTs of many years duration should be further explored. PMID:22917983

Fredriksen, Mats; Halmøy, Anne; Faraone, Stephen V; Haavik, Jan

2013-06-01

48

Long-Term Efficacy and Safety Profile of Lanthanum Carbonate: Results for up to 6 Years of Treatment  

PubMed Central

Background/Aims Lanthanum carbonate (LC, FOSRENOL®) is an effective phosphate binder for which tolerability and a safety profile have been reported in haemodialysis patients. Patients from previous studies entered a 2-year extension, enabling assessment of efficacy and safety for up to 6 years of LC monotherapy. Methods Patients from four previous trials entered this study. Results Ninety-three patients started the extension, with 22 entering a sixth year of LC treatment. Two-thirds of all patients received LC doses of 2,250 or 3,000 mg/day. Reductions in serum phosphate and calcium × phosphate product were maintained for up to 6 years. There were no new or unexpected adverse events (AEs), and no increase in the incidence of events with increasing treatment exposure. Over the complete duration of therapy, treatment-related AEs occurred in 25.8% of patients and were primarily gastrointestinal in nature. No clinically relevant changes in liver function tests were observed and there was no evidence of adverse effects on the liver, bone or the central nervous system. Conclusions LC monotherapy was effective and well tolerated for up to 6 years with no evidence of safety concerns or increased frequency of AEs.

Hutchison, Alastair J.; Barnett, M. Edwina; Krause, Rolfdieter; Kwan, Jonathan T.C.; Siami, Ghodrat A.

2008-01-01

49

Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia  

PubMed Central

All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) combination-based therapy has benefitted newly diagnosed acute promyelocytic leukemia (APL) in short-term studies, but the long-term efficacy and safety remained unclear. From April 2001, we have followed 85 patients administrated ATRA/ATO with a median follow-up of 70 months. Eighty patients (94.1%) entered complete remission (CR). Kaplan–Meier estimates of the 5-year event-free survival (EFS) and overall survival (OS) for all patients were 89.2% ± 3.4% and 91.7% ± 3.0%, respectively, and the 5-year relapse-free survival (RFS) and OS for patients who achieved CR (n = 80) were 94.8% ± 2.5% and 97.4% ± 1.8%, respectively. Upon ATRA/ATO, prognosis was not influenced by initial white blood cell count, distinct PML-RAR? types, or FLT3 mutations. The toxicity profile was mild and reversible. No secondary carcinoma was observed, and 24 months after the last dose of ATRA/ATO, patients had urine arsenic concentrations well below the safety limit. These results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for de novo APL.

Hu, Jiong; Liu, Yuan-Fang; Wu, Chuan-Feng; Xu, Fang; Shen, Zhi-Xiang; Zhu, Yong-Mei; Li, Jun-Min; Tang, Wei; Zhao, Wei-Li; Wu, Wen; Sun, Hui-Ping; Chen, Qiu-Sheng; Chen, Bing; Zhou, Guang-Biao; Zelent, Arthur; Waxman, Samuel; Wang, Zhen-Yi; Chen, Sai-Juan; Chen, Zhu

2009-01-01

50

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

PubMed Central

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

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

2011-01-01

51

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.

2013-01-01

52

Long-term safety, efficacy, and tolerability of imidafenacin in the treatment of overactive bladder: a review of the Japanese literature  

PubMed Central

Imidafenacin is an antimuscarinic agent with high affinity for the M3 and M1 muscarinic receptor subtypes and low affinity for the M2 subtype, and is used to treat overactive bladder. Several animal studies have demonstrated that imidafenacin has organ selectivity for the bladder over the salivary glands, colon, heart, and brain. In Phase I studies in humans, the approximately 2.9-hour elimination half-life of imidafenacin was shorter than that of other antimuscarinics such as tolterodine and solifenacin. Imidafenacin was approved for clinical use in overactive bladder in Japan in 2007 after a randomized, double-blind, placebo-controlled Phase II study and a propiverine-controlled Phase III study conducted in Japanese patients demonstrated that imidafenacin 0.1 mg twice daily was clinically effective for treating overactive bladder and was not inferior to propiverine for reduction of episodes of incontinence, with a better safety profile than propiverine. Several short-term clinical studies have demonstrated that imidafenacin also improves sleep disorders, nocturia, and nocturia-related quality of life. In addition, it is speculated that addon therapy with imidafenacin is beneficial for men with benign prostatic hyperplasia whose overactive bladder symptoms are not controlled by alpha-1 adrenoceptor antagonists. No cognitive impairment or influence of imidafenacin on the QTc interval has been observed. Although there have been very few relevant long-term clinical studies, the available information suggests the long-term efficacy, safety, and tolerability of imidafenacin, with less frequent severe adverse events, such as dry mouth and constipation. In addition, imidafenacin can be used safely for a long time even for cognitively vulnerable elderly patients with symptoms of overactive bladder. Thus, it is highly likely that imidafenacin is safe, efficacious, and tolerable to control symptoms of overactive bladder even over the long term. However, it remains unknown if the practical effectiveness of imidafenacin is applicable to ethnic groups other than Japanese.

Masumori, Naoya

2013-01-01

53

Long-term safety, efficacy, and tolerability of imidafenacin in the treatment of overactive bladder: a review of the Japanese literature.  

PubMed

Imidafenacin is an antimuscarinic agent with high affinity for the M(3) and M(1) muscarinic receptor subtypes and low affinity for the M(2) subtype, and is used to treat overactive bladder. Several animal studies have demonstrated that imidafenacin has organ selectivity for the bladder over the salivary glands, colon, heart, and brain. In Phase I studies in humans, the approximately 2.9-hour elimination half-life of imidafenacin was shorter than that of other antimuscarinics such as tolterodine and solifenacin. Imidafenacin was approved for clinical use in overactive bladder in Japan in 2007 after a randomized, double-blind, placebo-controlled Phase II study and a propiverine-controlled Phase III study conducted in Japanese patients demonstrated that imidafenacin 0.1 mg twice daily was clinically effective for treating overactive bladder and was not inferior to propiverine for reduction of episodes of incontinence, with a better safety profile than propiverine. Several short-term clinical studies have demonstrated that imidafenacin also improves sleep disorders, nocturia, and nocturia-related quality of life. In addition, it is speculated that addon therapy with imidafenacin is beneficial for men with benign prostatic hyperplasia whose overactive bladder symptoms are not controlled by alpha-1 adrenoceptor antagonists. No cognitive impairment or influence of imidafenacin on the QTc interval has been observed. Although there have been very few relevant long-term clinical studies, the available information suggests the long-term efficacy, safety, and tolerability of imidafenacin, with less frequent severe adverse events, such as dry mouth and constipation. In addition, imidafenacin can be used safely for a long time even for cognitively vulnerable elderly patients with symptoms of overactive bladder. Thus, it is highly likely that imidafenacin is safe, efficacious, and tolerable to control symptoms of overactive bladder even over the long term. However, it remains unknown if the practical effectiveness of imidafenacin is applicable to ethnic groups other than Japanese. PMID:23390360

Masumori, Naoya

2013-01-01

54

Safety and Efficacy of Tetrabenazine and Use of Concomitant Medications During Long-Term, Open-Label Treatment of Chorea Associated with Huntington's and Other Diseases  

PubMed Central

Background Although tetrabenazine, a drug that depletes presynaptic dopamine by inhibiting vesicular monoamine transporter 2 (VMAT2), was approved by the U.S. Food and Drug Administration in 2008 for the treatment of chorea associated with Huntington’s disease (HD), there is a paucity of data on its long-term efficacy and safety. Methods Approximately 2,000 patients with a variety of hyperkinetic movement disorders had been treated with open-label tetrabenazine at the Movement Disorders Clinic, Baylor College of Medicine, since 1979. Tetrabenazine was usually started at 12.5?mg/day, and the dosage was gradually increased (up to 300?mg/day). Responses were rated by the investigator 1–5, with 1 ?=? marked chorea reduction, excellent improvement in function; 2 ?=? moderate chorea reduction, very good improvement in function; 3 ?=? fair chorea improvement, only mild improvement in function; 4 ?=? poor or no response for chorea and function; and 5 ?=? worsening chorea, some functional deterioration. Efficacy and safety were analyzed retrospectively. Results By 2004, 98 HD chorea patients had received tetrabenazine for a mean of 3.1 years (range ?1–11.4 years). Of those with valid ratings, 75% had either marked or very good responses (rating 1 or 2) at their optimal dosages. The most common adverse events occurring in ?5% of the patients were somnolence (39%), insomnia (33%), depression (31%), accidental injury (26%), and dysphagia (19%). Efficacy and safety were comparable to results for non-HD chorea patients. Discussion Tetrabenazine treatment was associated with long-term improvement in chorea. Adverse event rates were comparable to those reported from controlled trials.

Shen, Vivienne; Clarence-Smith, Kathleen; Hunter, Christine; Jankovic, Joseph

2013-01-01

55

Assessing efficacy/effectiveness and safety/tolerability profiles of adjunctive pramipexole in bipolar depression: acute versus long-term data.  

PubMed

Bipolar depression represents the most difficult-to-treat phase of bipolar disorder, mood-stabilizing compounds and second-generation antipsychotics being only partially effective, whereas the use of antidepressants is highly controversial because of risks of inefficacy, switching, rapid cycling, and increased suicidality. Among various augmentative pharmacological treatments, compounds with dopamine-enhancing activity have been shown to be variably beneficial in the treatment of bipolar depression with drug-resistance features. In particular, pramipexole - a dopamine D2/D3 receptor agonist - showed antidepressant properties in bipolar depressed patients in both randomized-controlled trials and open acute and follow-up reports. The present review aims to provide an updated perspective on the use of adjunctive pramipexole in bipolar depression, taking into account randomized-controlled trials, as well as open naturalistic studies, with a specific focus on the evaluation of acute versus long-term data in terms of effectiveness and tolerability. Despite methodological differences, short-term studies support the acute efficacy and tolerability/safety of adjunctive pramipexole, whereas open extended observations seem to confirm the effectiveness of the compound, with some additional concern in terms of safety and tolerability issues. Adjunctive pramipexole may be a valid option in both the acute and the long-term treatment of drug-resistant bipolar depression, with possible superior tolerability in the short term. PMID:24081199

Dell'Osso, Bernardo; Ketter, Terence A

2013-11-01

56

Efficacy of ibandronate: a long term confirmation  

PubMed Central

Data deriving from randomized clinical trials, observational studies and meta-analyses, including treatment regimens unlicensed for use in clinical practice, clearly support that 150 mg once-monthly oral and 3 mg quarterly i.v. doses of ibandronate are associated with efficacy, safety and tolerability; notably both these marketed regimens, which largely correspond to ACE ?10.8 mg, may in addition provide a significant efficacy on non-vertebral and clinical fracture (Fx) efficacy. The MOBILE and the DIVA LTE studies confirmed a sustained efficacy of monthly oral and quarterly i.v. regimens respectively, over 5 years. Furthermore, improved adherence rates with monthly ibandronate, deriving from studies evaluating large prescription databases, promise to enhance fracture protection and decrease the social and economic burden of postmenopausal osteoporosis.

Di Munno, Ombretta; Delle Sedie, Andrea

2010-01-01

57

Treatment of postrenal transplant erythrocytosis. Long-term efficacy and safety of angiotensin-converting enzyme inhibitors.  

PubMed

Fifty-two patients with postrenal transplant erythrocytosis were treated with an angiotensin-converting enzyme inhibitor (lisinopril or enalapril) for a median of 13 months (range 0-44). A significant fall in haemoglobin of 1.8 +/- 1.6 g dl-1 (range - 0.8 to 6.6) occurred over the first 3 months (p < 0.0001). The haemoglobin then remained stable for as long as 3 years. Both enalapril and lisinopril were equally effective. Therapy was withdrawn in 16 patients (31%) because of decline in renal function (6), anaemia (5), hypotension (3), hyperkalaemia (1) or erectile impotence (1) - complications which were all reversible. Angiotensin-converting enzyme inhibitors in low dose are a safe and effective long-term therapy for postrenal transplant erythrocytosis. PMID:8938674

MacGregor, M S; Rowe, P A; Watson, M A; Rodger, R S; Junor, B J; Briggs, J D

1996-01-01

58

A long term treatment with a venotropic drug. Results on efficacy and safety of Daflon 500 mg in chronic venous insufficiency.  

PubMed

Drugs for long term administration have to prove their efficacy and safety. Previously published double blind controlled studies (from single dose to two months treatment) have already demonstrated the phlebotropic activity of Daflon 500 mg in chronic venous insufficiency (CVI). The aim of the study was to investigate the safety of this agent during one year of continuous administration. Two-hundred and fifteen out-patients suffering from CVI received Daflon 500 mg, 2 tablets per day. Therapeutic activity was evaluated every 2 months on: 1) venous symptoms (functional discomfort, cramps, evening oedema) assessed by a 0 to 4 scale; 2) supramalleolar and calf circumferences; 3) overall assessment of efficacy (excellent, useful, nil). Acceptability was assessed by recording the side effects and measuring laboratory parameters. Results: 170 patients completed the study. Functional symptoms were statistically significantly improved as shown by the following: functional discomfort: 0.55 +/- 0.06 vs 2.63 +/- 0.06, supra-malleolar circumference in cm: 22.5 +/- 0.2 vs 23.1 +/- 0.2, and calf circumference in cm: 34.7 +/- 0.3 vs 35.2 +/- 0.3. This improvement in the symptoms quickly appeared from the first control (M2) and reached about 50% of the total decrease. Overall assessment of efficacy was evaluated as follows: excellent = 58%, useful = 33%, nil = 9% of the cases. Laboratory parameters remained constant during the 12 months. Side effects were essentially gastralgia (n = 7). According to these results, it appears the efficacy and safety of Daflon 500 mg are corroborated even after a one year administration. PMID:2632651

Guillot, B; Guilhou, J J; de Champvallins, M; Mallet, C; Moccatti, D; Pointel, J P

1989-01-01

59

Long-term efficacy and safety outcomes after unrestricted use of drug-eluting stents in patients with acute coronary syndrome.  

PubMed

Background: Recent randomized clinical trials have reported favorable clinical outcomes after the use of drug-eluting stents (DES) in patients with acute coronary syndrome (ACS). However, the long-term efficacy and safety outcomes, bleeding outcome in particular, after DES implantation in ACS patients have not been thoroughly evaluated in a real-world population. Methods?and?Results: We evaluated long-term clinical outcomes in 565 consecutive ACS patients who underwent DES implantation in an emergency setting between 2004 and 2011 (ST-segment elevation acute myocardial infarction [STEMI]: n=269, non-STEMI/unstable angina pectoris: n=296). Mean clinical follow-up period in this study was 4.6±2.0 years. The cumulative incidence of all-cause death, cardiac death, myocardial infarction, stent thrombosis and target-lesion revascularization was 6.9%, 4.0%, 2.2%, 1.3% and 8.4% at 1 year, and 19.6%, 6.7%, 5.6%, 3.0% and 13.9% at 5 years, respectively. The cumulative 5-year incidence of major bleeding events was 8.4% (n=42). Fatal bleeding events, however, occurred in only 4 patients, even including 2 patients who required resuscitation upon arrival at the hospital. Of the 42 patients with major bleeding events, 39 were taking dual antiplatelet therapy (DAPT) at the time of bleeding. Conclusions: DES implantation provided favorable long-term clinical outcomes with an acceptably low incidence of fatal bleeding in a real-world population of ACS patients. However, prolonged DAPT seems to be associated with major bleeding after DES implantation. (Circ J 2014; 78: 1628-1635). PMID:24828916

Kawaji, Tetsuma; Shiomi, Hiroki; Morimoto, Takeshi; Tamura, Toshihiro; Nishikawa, Ryusuke; Yano, Mariko; Tazaki, Junichi; Imai, Masao; Saito, Naritatsu; Makiyama, Takeru; Shizuta, Satoshi; Ono, Koh; Kimura, Takeshi

2014-06-25

60

Patient Self-Management of Oral Anticoagulation with Vitamin K Antagonists in Everyday Practice: Efficacy and Safety in a Nationwide Long-Term Prospective Cohort Study  

PubMed Central

Patient self-management (PSM) of oral anticoagulation is under discussion, because evidence from real-life settings is missing. Using data from a nationwide, prospective cohort study in Switzerland, we assessed overall long-term efficacy and safety of PSM and examined subgroups. Data of 1140 patients (5818.9 patient-years) were analysed and no patient were lost to follow-up. Median follow-up was 4.3 years (range 0.2–12.8 years). Median age at the time of training was 54.2 years (range 18.2–85.2) and 34.6% were women. All-cause mortality was 1.4 per 100 patient-years (95% CI 1.1–1.7) with a higher rate in patients with atrial fibrillation (2.5; 1.6–3.7; p<0.001), patients>50 years of age (2.0; 1.6–2.6; p<0.001), and men (1.6; 1.2–2.1; p?=?0.036). The rate of thromboembolic events was 0.4 (0.2–0.6) and independent from indications, sex and age. Major bleeding were observed in 1.1 (0.9–1.5) per 100 patient-years. Efficacy was comparable to standard care and new oral anticoagulants in a network meta-analysis. PSM of properly trained patients is effective and safe in a long-term real-life setting and robust across clinical subgroups. Adoption in various clinical settings, including those with limited access to medical care or rural areas is warranted.

Nagler, Michael; Bachmann, Lucas M.; Schmid, Pirmin; Raddatz Muller, Pascale; Wuillemin, Walter A.

2014-01-01

61

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.

Nakajima, Masayuki; Iwasaki, Naoki; Adachi, Masaki

2014-01-01

62

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.

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

2012-01-01

63

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

PubMed Central

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

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

2010-01-01

64

Efficacy and Safety of Long-Term Fluoxetine Versus Lithium Monotherapy of Bipolar II Disorder: A Randomized, Double-Blind, Placebo-Substitution Study  

PubMed Central

Objective The authors examined the safety and efficacy of long-term fluoxetine monotherapy, lithium monotherapy, and placebo therapy in preventing relapse and recurrence of bipolar type II major depressive episode. The authors hypothesized that fluoxetine monotherapy would be superior to lithium monotherapy with a similar hypomanic mood conversion rate. Method Patients at least 18 years old who recovered from their major depressive episode during initial open-label fluoxetine monotherapy were randomly assigned to receive 50 weeks of double-blind monotherapy with fluoxetine at 10–40 mg/day, lithium at 300–1200 mg/day, or placebo. The primary outcome measure was time to relapse or recurrence. Secondary outcome measures included the proportion of patients remaining well and the frequency of hypomanic symptoms. Results There were no significant differences in clinical or demographic characteristics among the fluoxetine (N=28), lithium (N=26), and placebo (N=27) groups. The mean time to relapse was 249.9 days for the fluoxetine group, 156.4 days for the lithium group, and 186.9 days for the placebo group. The hazard of relapse was significantly lower with fluoxetine compared with lithium, and the estimated hazard of relapse with lithium was 2.5 times greater than with fluoxetine. There were no statistically significant or clinically meaningful differences in hypomanic symptoms among treatment groups over time. One patient taking fluoxetine and one patient taking placebo discontinued treatment because of hypomania. Conclusion These findings suggest that long-term fluoxetine monotherapy may provide superior relapse-prevention benefit relative to lithium monotherapy after recovery from bipolar II major depressive episode without an increase in hypomanic mood conversion episodes.

Amsterdam, Jay D.; Shults, Justine

2010-01-01

65

HANGING BY A THREAD: THE LONG-TERM EFFICACY AND SAFETY OF TRANSSCLERAL SUTURED INTRAOCULAR LENSES IN CHILDREN (AN AMERICAN OPHTHALMOLOGICAL SOCIETY THESIS)  

PubMed Central

Purpose To evaluate the long-term efficacy, safety, and advisability of using transscleral sutured posterior chamber intraocular lenses (IOLs) in pediatric patients with no capsular support and to determine whether 10-0 polypropylene suture should be used for this purpose. Methods A long-term retrospective interventional case series review of 33 eyes of 26 patients who had a sutured IOL at Duke University Eye Center were evaluated for the intraoperative surgical risks, postoperative visual and refractive outcomes, and the number, type, and severity of the postoperative complications. In addition, a survey of pediatric ophthalmologists’ experience with suture breakage was performed. Results Postoperative visual acuity was significantly improved after surgery (P < .001). Predicted vs actual refraction was not significantly different (P = .10) and was within 1.50 diopters of predicted in 66% of patients. A refractive myopic shift occurred over time and was age-dependent. Intraoperative and immediate postoperative complications were minimal and not sight-threatening. Three patients developed subluxation of the IOL secondary to spontaneous 10-0 polypropylene suture breakage at 3.5, 8, and 9 years after surgery. A survey of pediatric ophthalmologists revealed 10 similar cases (mean, 5 years after surgery). Conclusion Transscleral fixation of an IOL in a child appears to be a safe and effective procedure provided that the suture material used is stable enough to resist significant degradation over time. Caution should be exercised in the use of 10-0 polypropylene suture to fixate an IOL to the sclera in children, and an alternative material or size should be considered.

Buckley, Edward G.

2007-01-01

66

Long-term efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of non-cancer chronic pain  

PubMed Central

Objective: The aim of this study was to assess safety and efficacy of fixed combination oxycodone prolonged release (PR)/naloxone PR in terms of both analgesia and improving opioid-induced bowel dysfunction (OIBD) and associated symptoms, such as opioid-induced constipation (OIC), in adults with chronic non-cancer pain. Study design: These were open-label extension studies in which patients who had previously completed a 12-week, double-blind study received oxycodone PR/naloxone PR for up to 52 weeks. The analgesia study assessed pain using the modified Brief Pain Inventory-Short Form (BPI-SF). The bowel function study assessed improvements in constipation using the Bowel Function Index (BFI). Results: At open-label baseline in the analgesia study (n = 379), mean score [± standard deviation (SD)] for the BPI-SF item ‘average pain over the last 24 h’ was 3.9 ± 1.52, and this remained low at 6 months (3.7 ± 1.59) and 12 months (3.8 ± 1.72). Mean scores for BPI-SF item ‘sleep interference’, and the BPI-SF ‘pain’ and ‘interference with activities’ subscales also remained low throughout the 52-week study. In the bowel function study (n = 258), mean BFI score (± SD) decreased from 35.6 ± 27.74 at the start of the extension study to 20.6 ± 24.01 after 12 months of treatment with oxycodone PR/naloxone PR. Pain scores also remained low and stable during this study. Adverse events in both extension phases were consistent with those associated with opioid therapy; no additional safety concerns were observed. Conclusion: Results from these two open-label extension studies demonstrate the long-term efficacy and tolerability of fixed combination oxycodone PR/naloxone PR in the treatment of chronic pain. Patients experienced clinically relevant improvements in OIBD while receiving effective analgesic therapy.

Sandner-Kiesling, A; Leyendecker, P; Hopp, M; Tarau, L; Lejcko, J; Meissner, W; Sevcik, P; Hakl, M; Hrib, R; Uhl, R; Durr, H; Reimer, K

2010-01-01

67

Long-term Safety and Efficacy of Human-Induced Pluripotent Stem Cell (iPS) Grafts in a Preclinical Model of Retinitis Pigmentosa  

PubMed Central

The U.S. Food and Drug Administration recently approved phase I/II clinical trials for embryonic stem (ES) cell–based retinal pigmented epithelium (RPE) transplantation, but this allograft transplantation requires lifelong immunosuppressive therapy. Autografts from patient-specific induced pluripotent stem (iPS) cells offer an alternative solution to this problem. However, more data are required to establish the safety and efficacy of iPS transplantation in animal models before moving iPS therapy into clinical trials. This study examines the efficacy of iPS transplantation in restoring functional vision in Rpe65rd12/Rpe65rd12 mice, a clinically relevant model of retinitis pigmentosa (RP). Human iPS cells were differentiated into morphologically and functionally RPE-like tissue. Quantitative real-time polymerase chain reaction (RT-PCR) and immunoblots confirmed RPE fate. The iPS-derived RPE cells were injected into the subretinal space of Rpe65rd12/Rpe65rd12 mice at 2 d postnatally. After transplantation, the long-term surviving iPS-derived RPE graft colocalized with the host native RPE cells and assimilated into the host retina without disruption. None of the mice receiving transplants developed tumors over their lifetimes. Furthermore, electroretinogram, a standard method for measuring efficacy in human trials, demonstrated improved visual function in recipients over the lifetime of this RP mouse model. Our study provides the first direct evidence of functional recovery in a clinically relevant model of retinal degeneration using iPS transplantation and supports the feasibility of autologous iPS cell transplantation for retinal and macular degenerations featuring significant RPE loss.

Li, Yao; Tsai, Yi-Ting; Hsu, Chun-Wei; Erol, Deniz; Yang, Jin; Wu, Wen-Hsuan; Davis, Richard J; Egli, Dieter; Tsang, Stephen H

2012-01-01

68

Long-term safety and efficacy of human-induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa.  

PubMed

The U.S. Food and Drug Administration recently approved phase I/II clinical trials for embryonic stem (ES) cell-based retinal pigmented epithelium (RPE) transplantation, but this allograft transplantation requires lifelong immunosuppressive therapy. Autografts from patient-specific induced pluripotent stem (iPS) cells offer an alternative solution to this problem. However, more data are required to establish the safety and efficacy of iPS transplantation in animal models before moving iPS therapy into clinical trials. This study examines the efficacy of iPS transplantation in restoring functional vision in Rpe65(rd12)/Rpe65(rd12) mice, a clinically relevant model of retinitis pigmentosa (RP). Human iPS cells were differentiated into morphologically and functionally RPE-like tissue. Quantitative real-time polymerase chain reaction (RT-PCR) and immunoblots confirmed RPE fate. The iPS-derived RPE cells were injected into the subretinal space of Rpe65(rd12)/Rpe65(rd12) mice at 2 d postnatally. After transplantation, the long-term surviving iPS-derived RPE graft colocalized with the host native RPE cells and assimilated into the host retina without disruption. None of the mice receiving transplants developed tumors over their lifetimes. Furthermore, electroretinogram, a standard method for measuring efficacy in human trials, demonstrated improved visual function in recipients over the lifetime of this RP mouse model. Our study provides the first direct evidence of functional recovery in a clinically relevant model of retinal degeneration using iPS transplantation and supports the feasibility of autologous iPS cell transplantation for retinal and macular degenerations featuring significant RPE loss. PMID:22895806

Li, Yao; Tsai, Yi-Ting; Hsu, Chun-Wei; Erol, Deniz; Yang, Jin; Wu, Wen-Hsuan; Davis, Richard J; Egli, Dieter; Tsang, Stephen H

2012-01-01

69

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)

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

2014-01-01

70

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

71

Long-term efficacy of biologics in dermatology  

PubMed Central

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

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

2010-01-01

72

Rationale and design of PATRO Adults, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope® for the treatment of adult patients with growth hormone deficiency  

PubMed Central

Objective: To describe the rationale and design of PATRO Adults, a postmarketing surveillance study of the long-term efficacy and safety of somatropin (Omnitrope®) for the treatment of adult patients with growth hormone deficiency (GHD). Methods: PATRO Adults is an observational, multicentre, open, longitudinal, noninterventional study being conducted in hospitals and specialized endocrinology clinics across several European countries. The primary objective is to assess the safety and efficacy of Omnitrope® in adults treated in routine clinical practice. Eligible patients are male or female adults who are receiving treatment with Omnitrope® and who have provided informed consent. Patients who have been treated with another human growth hormone (hGH) product before starting Omnitrope® therapy will also be eligible for inclusion. Efficacy assessments will be based on the analysis of the following: insulin-like growth factor-1 levels within age- and gender-adjusted normal ranges; anthropometric measures (weight, waist circumference, total fat mass, lean body mass, total body water); bone mineral density; lipids; effects on cardiovascular risk factors such as glucose metabolism, blood pressure and inflammatory markers (e.g. C-reactive protein); and quality of life. All adverse events will be monitored and recorded. Particular emphasis will be placed on long-term safety, the recording of malignancies, the occurrence and clinical impact of antirecombinant hGH antibodies, the incidence, severity and duration of hyperglycaemia, and the development of diabetes during treatment with Omnitrope®. Conclusions: PATRO Adults is a large, long-term, postmarketing surveillance study that will extend the safety database for Omnitrope®, as well as contributing to the available data for all recombinant hGH products. Of particular interest, the study will provide important data on the impact of long-term GH replacement therapy on the development of diabetes mellitus, the recurrence/regrowth of hypothalamic–pituitary tumours, and de novo malignancy or recurrence of other (non-hypothalamic–pituitary) tumours.

Beck-Peccoz, Paolo; Minuto, Francesco; Leal-Cerro, Alfonso; Stalla, Gunter

2012-01-01

73

Safety of long-term PPI therapy.  

PubMed

Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published in the past decade and are critically reviewed in this article and the existing evidence is evaluated and translated into possible clinical consequences. Based on the existing evidence the benefits of PPI treatment seem to outweigh potential risks in the large majority of patients especially if PPI use is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead to a careful evaluation of the indication for PPI treatment. PMID:23998981

Reimer, Christina

2013-06-01

74

Long-Term Efficacy of Dynamic Graciloplasty for Fecal Incontinence  

Microsoft Academic Search

PURPOSE: Patients with end-stage fecal incontinence in whom all standard medical and surgical treatment has failed or is not expected to be effective can be treated by dynamic graciloplasty. The aim of this study was to review the long-term efficacy data. METHODS: Success was defined as a greater than 50 percent decrease in the frequency of incontinent episodes. Measured physiologic

Steven D. Wexner; Cor Baeten; Randolph Bailey; Arne Bakka; Bruce Belin; Paul Belliveau; Eugen Berg; W. Donald Buie; Marcus Burnstein; John Christiansen; John Coller; Susan Galandiuk; J. Lange; Robert Madoff; Klaus E. Matzel; Lars Påhlman; Rolland Parc; John Reilly; Massimo Seccia; Alan G. Thorson; Anthony M. Vernava III

2002-01-01

75

Long-term efficacy of pregabalin in generalized anxiety disorder.  

PubMed

A multicenter, randomized, placebo-controlled, double-blind study was conducted to evaluate the efficacy of pregabalin in preventing relapse of generalized anxiety disorder (GAD) after response to short-term treatment. Outpatients (n=624) with GAD for > or =1 year received open-label pregabalin (450 mg/day) for 8 weeks and, if a clinical response was observed, were randomized to receive either pregabalin (450 mg/day; n=168) or placebo (n=170) for 24 weeks. The primary efficacy parameter was time to relapse. Among responders to open-label acute treatment with pregabalin, time to relapse of GAD was significantly longer for patients treated with pregabalin compared with placebo (P<0.0001). Fifty per cent of the placebo group had relapsed by day 23, and at study endpoint, 65% had relapsed. In the pregabalin group, only 42% had relapsed by study end. Total attrition during double-blind treatment was somewhat higher on pregabalin compared with placebo (21.4 vs. 15.3%); attrition owing to adverse events (AEs) was also somewhat higher on pregabalin (6.0 vs. 2.4%). AEs were relatively low in the double-blind phase; only three AEs occurred with an incidence of more than 5% on pregabalin and placebo, respectively: infection (14.9 vs. 11.2%), headache (10.1 vs. 11.2%), and somnolence (6.0 vs. 0%). No safety concerns were identified with long-term treatment. The study indicates that pregabalin is an effective treatment for the prevention of relapse in patients with GAD. PMID:18090504

Feltner, Douglas; Wittchen, Hans-Ulrich; Kavoussi, Richard; Brock, Jerri; Baldinetti, Francesca; Pande, Atul C

2008-01-01

76

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

2014-01-01

77

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

78

Long-term Safety and Efficacy Following Systemic Administration of a Self-complementary AAV Vector Encoding Human FIX Pseudotyped With Serotype 5 and 8 Capsid Proteins  

PubMed Central

Adeno-associated virus vectors (AAV) show promise for liver-targeted gene therapy. In this study, we examined the long-term consequences of a single intravenous administration of a self-complementary AAV vector (scAAV2/ 8-LP1-hFIXco) encoding a codon optimized human factor IX (hFIX) gene in 24 nonhuman primates (NHPs). A dose–response relationship between vector titer and transgene expression was observed. Peak hFIX expression following the highest dose of vector (2 × 1012 pcr-vector genomes (vg)/kg) was 21 ± 3 µg/ml (~420% of normal). Fluorescent in-situ hybridization demonstrated scAAV provirus in almost 100% of hepatocytes at that dose. No perturbations of clinical or laboratory parameters were noted and vector genomes were cleared from bodily fluids by 10 days. Macaques transduced with 2 × 1011 pcr-vg/kg were followed for the longest period (~5 years), during which time expression of hFIX remained >10% of normal level, despite a gradual decline in transgene copy number and the proportion of transduced hepatocytes. All macaques developed serotype-specific antibodies but no capsid-specific cytotoxic T lymphocytes were detected. The liver was preferentially transduced with 300-fold more proviral copies than extrahepatic tissues. Long-term biochemical, ultrasound imaging, and histologic follow-up of this large cohort of NHP revealed no toxicity. These data support further evaluation of this vector in hemophilia B patients.

Nathwani, Amit C; Rosales, Cecilia; McIntosh, Jenny; Rastegarlari, Ghasem; Nathwani, Devhrut; Raj, Deepak; Nawathe, Sushmita; Waddington, Simon N; Bronson, Roderick; Jackson, Scott; Donahue, Robert E; High, Katherine A; Mingozzi, Federico; Ng, Catherine YC; Zhou, Junfang; Spence, Yunyu; McCarville, M Beth; Valentine, Marc; Allay, James; Coleman, John; Sleep, Susan; Gray, John T; Nienhuis, Arthur W; Davidoff, Andrew M

2011-01-01

79

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.

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

2011-01-01

80

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.

2012-01-01

81

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.

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

2013-01-01

82

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

83

Long-term efficacy of human papillomavirus vaccination  

Microsoft Academic Search

Achieving long-term protection following vaccination is crucial to ensuring that high levels of immunity are maintained within a population while eliminating the need to introduce booster vaccinations. Based on an analysis of the hepatitis B virus vaccine, several factors have been shown to contribute to long-term protection, namely: specific lymphoproliferation, the in vivo humoral response, and immune memory. To ensure

Kevin A. Ault

84

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

PubMed Central

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

Cianferotti, Luisella; D'Asta, Federica

2013-01-01

85

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

Microsoft Academic Search

Purpose: To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. Methods and Materials: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction

Mark S. Chambers; Christopher Uwe Jones; Merrill A. Biel; Randal S. Weber; Kenneth M. Hodge; Y. Chen; John M. Holland; Jonathan A. Ship; Robert Vitti; Ingrid Armstrong; Adam S. Garden; Robert Haddad

2007-01-01

86

Efficacy of Lifestyle Modification for Long-Term Weight Control  

Microsoft Academic Search

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

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

2004-01-01

87

Clinical safety surveillance study of the safety and efficacy of long-term home treatment with ReFacto utilizing a computer-aided diary: a Nordic multicentre study.  

PubMed

A Nordic multicentre, open-label, non-interventional postmarketing surveillance study was carried out during a period of 24 months evaluating safety and efficacy of ReFacto as prophylactic or on-demand replacement therapy in patients with haemophilia A treated by self-medication. Fifty-seven patients were enrolled and studied for safety; efficacy was evaluated in 39 patients who received ReFacto for 24 months and recorded sufficient diary data on a hand-held computer. The compliance of using the device was good in small children, variable in adults and poor in teenagers. The fact that the overall compliance was low constituted a limitation of the number of patients with reliable diary data. Overall safety was rated as excellent or good by the clinicians for all patients at all visits and overall efficacy at 24 months evaluated to be excellent (74%) or good (26%). It was noticed that >/=50% of patients/parents reported no absences from school or work owing to bleeding episodes during the study period. Among patients on regular prophylaxis, 6 of the 30 patients (20%) receiving ReFacto experienced no bleeding episodes. A median of four bleeding episodes occurred during the 24-month study period, and 93% of the episodes were resolved with safety and efficacy in prophylaxis as well as treatment of bleeding episodes. PMID:18752534

Petrini, P; Rylander, C

2009-01-01

88

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

89

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

90

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

91

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

92

Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms--long-term follow-up of a placebo-controlled, double-blind, multicenter trial.  

PubMed

In an open-label extension of a randomized, double-blind clinical trial, the long-term efficacy and tolerability of a fixed combination of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule (PRO 160/120) were investigated in elderly men with moderate or severe lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Two hundred and fifty-seven patients were randomly treated with 2 x 1 capsule/day PRO 160/120 or placebo for 24 weeks, followed by a 24-week control period and a 48-week follow-up period in which all patients received PRO 160/120. Efficacy measures included the assessment of LUTS [International Prostate Symptom Score ((I-PSS) self-rating questionnaire] and uroflow and sonographic parameters. Two hundred and nineteen subjects participated in the follow-up. Between baseline and end of observation (week 96) the I-PSS total score was reduced by 53% (P < 0.001), peak and average urinary flow increased by 19% (P < 0.001), and residual urine volume decreased by 44% (P = 0.03). The incidence of adverse events during follow-up was one in 1,181 treatment days; in only one event a causal relationship with intake of PRO 160/120 could not be excluded. Treatment with PRO 160/120 thus provides a clinically relevant benefit over a period of 96 weeks. PMID:18038253

Lopatkin, Nikolai; Sivkov, Andrey; Schläfke, Sandra; Funk, Petra; Medvedev, Alexander; Engelmann, Udo

2007-01-01

93

Tamsulosin: 3Year Long-Term Efficacy and Safety in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Obstruction: Analysis of a European, Multinational, Multicenter, Open-Label Study  

Microsoft Academic Search

Objective: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) treated for up to 3 years. Methods: Patients were enrolled from two European, 12-week, placebo-controlled trials. This analysis reports on 355 patients randomized originally to

C. C. Schulman; J. Cortvriend; U. Jonas; T. M. T. W. Lock; S. Vaage; M. J. Speakman

1999-01-01

94

Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes  

PubMed Central

Background Hypereosinophilic syndromes (HES) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid-refractory or develop corticosteroid toxicity. Mepolizumab, a humanised monoclonal anti-interleukin-5 antibody, demonstrated corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HES. Objective To evaluate long-term safety and efficacy of mepolizumab (750 mg) in HES. Methods MHE100901 is an open-label extension study. The primary endpoint was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of anti-mepolizumab antibodies were also explored. Results Seventy-eight subjects received 1–66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range 4–302). The most common dosing interval was 9–12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including one death, were reported by the investigator as possibly due to mepolizumab in three subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone-free without other HES medications for ?12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew prior to study completion for death (n=4), lack of efficacy (n=6), or other reasons. Conclusion Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES.

Roufosse, Florence E; Kahn, Jean-Emmanuel; Gleich, Gerald J; Schwartz, Lawrence B; Singh, Anish D; Rosenwasser, Lanny J; Denburg, Judah A; Ring, Johannes; Rothenberg, Marc E; Sheikh, Javed; Haig, Ann E; Mallett, Stephen A; Templeton, Deborah N; Ortega, Hector G; Klion, Amy D

2012-01-01

95

Assessing Long Term Drug Safety: Lessons (Re) Learned from Raptiva  

PubMed Central

Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in approximately 2,700 patients of whom only 218 were exposed to the drug for more than one year. In 2009, after over 46,000 patients were exposed to efalizumab, the drug was withdrawn from the market after 3 confirmed and one suspected case of progressive multifocal leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is extremely unlikely that the four reported cases were due to chance and given that PML occurs primarily in patients who are immunosuppressed, the association is likely causal. The identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the strengths and weaknesses of the current drug approval and pharmacovigilance processes for fully measuring the safety of a drug. Patients and clinicians need to be aware of the relative completeness and limitations of existing safety data of a drug when selecting a treatment.

Seminara, Nicole; Gelfand, Joel M

2010-01-01

96

Short-term Cognitive-Behavioral Therapy for Binge Eating Disorder: Long-term efficacy and predictors of long-term treatment success.  

PubMed

The present study evaluates the long-term efficacy (four years after treatment) of a short-term Cognitive-Behavioral Treatment (CBT) of Binge Eating Disorder (BED). We examined patient characteristics, mostly measured at the end of treatment, for their predictive value of long-term success. Forty-one BED-patients between 18 and 70 years took part in a randomized controlled trial (RCT) for a short-term treatment and were evaluated until 4 years after treatment. Assessments comprised structured interviews on comorbid mental disorder/eating disorder pathology and questionnaires on eating disorder pathology/general psychopathology. BED core symptoms and associated psychopathology improved substantially during treatment phase and further improved or at least remained stable during the follow-up period. End of treatment predictors for long term success were elevated weight and eating concern and higher frequency of objective binges. Tailoring additional interventions to patients' individual needs could further improve treatment efficacy. PMID:24929926

Fischer, Sophia; Meyer, Andrea H; Dremmel, Daniela; Schlup, Barbara; Munsch, Simone

2014-07-01

97

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

PubMed Central

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

Nabholtz, Jean-Marc A

2008-01-01

98

Long-term Safety of Dichloroacetate in Congenital Lactic Acidosis  

PubMed Central

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 hours) 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.

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.

2013-01-01

99

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

100

Efficacy and Safety of Up to 8 Years of Long-term Growth Hormone Treatment in Short Children Born Small for Gestational Age in Japan: Analysis of the Subpopulation According to the Japanese Guideline  

PubMed Central

The efficacy and safety of 8 yr of GH treatment was assessed in 44 Japanese children with small for gestational age (SGA) short stature who met the criteria for GH treatment initiation (height SD score (SDS) <–2.5 SD) of the Japanese guidelines. Height SDS in subjects improved throughout the study period, and average height SDS improved from –3.5 to –1.6 and from –3.4 to –1.9 in the 0.033/0.067 mg and 0.067/0.067 mg groups, respectively, after 8 yr of GH treatment. Delta height SD was approximately +2 after 4 yr of treatment, and ? IGF-1 showed a significant positive correlation with ? height SD after both 1 and 2 yr (r = 0.415 and 0.488, respectively) of treatment. There was no correlation between the age at the start of treatment and age at onset of puberty, and the median age at the onset of puberty in the subjects was almost the same as that in healthy children. In conclusion, clinically significant improvements in the height SDS was confirmed in short children born SGA after 8 yr of GH treatment without any safety problems.

Tanaka, Toshiaki; Yokoya, Susumu; Fujieda, Kenji; Seino, Yoshiki; Tada, Hiroshi; Mishina, Jun; Saito, Susumu; Takata, Ami; Ohki, Nobuhiko

2012-01-01

101

Efficacy of long-term anticoagulant treatment in subgroups of patients after myocardial infarction  

Microsoft Academic Search

OBJECTIVE--To investigate the efficacy of long term oral anticoagulant treatment in subgroups of patients after myocardial infarction. DESIGN--Analysis of the effect of anticoagulant treatment in subgroups of hospital survivors of myocardial infarction based upon age, gender, history of hypertension, previous myocardial infarction, smoking habits, diabetes mellitus, Killip class, anterior location of infarction, thrombolytic therapy, and use of beta blockers. SUBJECTS--Participants

P. F. van Bergen; J. W. Deckers; J. J. Jonker; R. T. van Domburg; A. J. Azar; A. Hofman

1995-01-01

102

Tolerability and Efficacy of Almotriptan in the Long-Term Treatment of Migraine  

Microsoft Academic Search

Background: Almotriptan is a highly specific 5-HT1B\\/1D receptor agonist, which acts selectively on blood vessels of the brain. Short-term studies have demonstrated that almotriptan provides rapid, effective and reliable relief of migraine attacks, while offering excellent tolerability. Purpose: To assess the long-term tolerability and efficacy of oral almotriptan 12.5 mg administered for every migraine attack over a 1-year period. Methods:

J. Pascual; R. Falk; R. Docekal; A. Prusinski; J. Jelencsik; X. Cabarrocas; X. Segarra; X. Luria; P. Ferrer

2001-01-01

103

HYDROGEOLOGICAL MODELLING, A PREREQUISITE IN LONG-TERM SAFETY ASSESSMENT FOR UNDERGROUND WASTE DISPOSAL  

Microsoft Academic Search

The disposal of heat generating and long-lived radioactive waste in deep geological formations is a technically and scientifically challenging problem. Due to the fact that long-term impact on the environment and man can not be ruled out from the outset the characterisation of the hydrogeological conditions of such repositories or waste disposal sites forms the basis for any long-term safety

Wernt Brewitz; Eckhard Fein; Christine Fahrenholz

104

Validity testing of the Long-Term Medication Behavior Self-Efficacy Scale.  

PubMed

Self-efficacy is an important determinant of health behavior that can be targeted for intervention. Little effort has been given to the development of valid measures for self-efficacy with medication taking for adherence research. The purpose of this study was to determine the criterion validity of the Long-Term Medication Behavior Self-Efficacy Scale (LTMBSES). Individual patient data from 6 existing adherence studies in transplant, hyperlipidemia, and AIDS/HIV patients (n = 1021) were pooled. Validity was determined by assessing the relation between the LTMBSES score and medication adherence--both self-reported and electronically monitored. A weak relationship was found between the LTMBSES score and adherence, which can possibly be attributed to a ceiling effect, caused by a too homogeneous population and/or a failure of the scale to challenge patients. Generalized Estimating Equations revealed that the total average self-efficacy score predicted reported medication adherence (p < .0001). The Receiver Operating Characteristic curve revealed the area under the curve was 0.67, indicating a significant (p < .0001), but poor predictive capability. Evidence for criterion validity of the Long-Term Medication Behavior Self-Efficacy Scale is not yet convincing. Future research should focus on: (1) validation in a population with a more heterogenous level of adherence, and (2) making the scale more challenging by referring to "always taking the medication without exception." PMID:15633781

Denhaerynck, Kris; Abraham, Ivo; Gourley, Greta; Drent, Gerda; De Vleeschouwer, Peter; Papajcik, Doreen; Lince, Elaine; De Geest, Sabina

2003-01-01

105

Long-term Safety and Efficacy of a Once-Daily Regimen of Emtricitabine, Didanosine, and Efavirenz in HIV-Infected, Therapy-Naive Children and Adolescents: Pediatric AIDS Clinical Trials Group Protocol P1021  

Microsoft Academic Search

BACKGROUND. Compliance with complex antiretroviral therapy regimens is a problem for HIV-1-infected children and their families. Simple, safe, and effective regimens are important for long-term therapeutic success. METHODS. A novel, once-daily dosing regimen of 3 antiretroviral drugs, emtricitab- ine, didanosine, and efavirenz, was tested in 37 therapy-naive HIV-infected chil- dren and adolescents between 3 and 21 years of age (inclusive).

Ross E. McKinney; John Rodman; Chengcheng Hu; Paula Britto; Michael Hughes; Mary Elizabeth Smith; Leslie K. Serchuck; Joyce Kraimer; Alberto A. Ortiz; Patricia Flynn; Ram Yogev; Stephen Spector; Linda Draper; Paul Tran; Melissa Scites; Ruth Dickover; Adriana Weinberg; Coleen Cunningham; Elaine Abrams; M. Robert Blum; Gregory E. Chittick; Laurie Reynolds; Mobeen Rathore

106

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

SciTech Connect

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

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

2007-12-01

107

Efficacy of Anal Fistula Plug in Closure of Cryptoglandular Fistulas: Long-Term Follow-Up  

Microsoft Academic Search

Purpose  The long-term efficacy of Surgisis anal fistula plug in closure of cryptoglandular anorectal fistulas was studied.\\u000a \\u000a \\u000a \\u000a Methods  Patients with high cryptoglandular anorectal fistulas were prospectively studied. Additional variables recorded were: number\\u000a of fistula tracts, and presence of setons. Under general anesthesia and in prone jackknife position, patients underwent irrigation\\u000a of the fistula tract by using hydrogen peroxide. Each primary opening was

Bradley J. Champagne; Lynn M. O’Connor; Martha Ferguson; Guy R. Orangio; Marion E. Schertzer; David N. Armstrong

2006-01-01

108

Long-term efficacy of infliximab for refractory ulcerative colitis: results from a single center experience  

PubMed Central

Background The long-term efficacy of infliximab (IFX) for patients with refractory ulcerative colitis (UC) is unclear. The aim of this study was to assess the long-term outcomes of IFX treatment in patients with refractory UC. Methods Thirty-three patients with refractory UC who received IFX treatment at Kyoto University Hospital between 2003 and 2013 were retrospectively evaluated. IFX intensification was defined as a dose escalation (up to 10 mg/kg) and/or shorter intervals between infusions (every 4–6 weeks). Results Of the 33 patients who received scheduled infusions of IFX, 24 (72.7%) achieved clinical remission within 8 weeks after initiating IFX treatment. Of these 24 responders, 17 (70.8%) experienced a relapse of UC and required IFX intensification, and 16 (66.7%) eventually maintained clinical remission with IFX treatment, including IFX intensification. Of the 33 patients, 6 (18.2%) underwent colectomy during IFX treatment. Multivariate regression analysis showed that a serum C-reactive protein (CRP) concentration <5 mg/L two weeks after starting IFX was a predictor of a positive clinical response to IFX induction therapy. No severe adverse events occurred in UC patients treated with IFX. Conclusion IFX intensification was necessary for long-term maintenance of remission and to prevent colectomy in patients with refractory UC.

2014-01-01

109

Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials.  

PubMed

BENCHMRK-1 and -2 are ongoing double-blind phase III studies of raltegravir in patients experiencing failure of antiretroviral therapy with triple-class drug-resistant human immunodeficiency virus infection. At week 96 (combined data), raltegravir (400 mg twice daily) plus optimized background therapy was generally well tolerated, with superior and durable antiretroviral and immunological efficacy, compared with optimized background therapy alone. PMID:20085491

Steigbigel, Roy T; Cooper, David A; Teppler, Hedy; Eron, Joseph J; Gatell, Jose M; Kumar, Princy N; Rockstroh, Jurgen K; Schechter, Mauro; Katlama, Christine; Markowitz, Martin; Yeni, Patrick; Loutfy, Mona R; Lazzarin, Adriano; Lennox, Jeffrey L; Clotet, Bonaventura; Zhao, Jing; Wan, Hong; Rhodes, Rand R; Strohmaier, Kim M; Barnard, Richard J; Isaacs, Robin D; Nguyen, Bach-Yen T

2010-02-15

110

Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial.  

PubMed

The efficacy and tolerability of a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) was investigated in elderly, male patients suffering from lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia in a prospective multicenter trial. A total of 257 patients (129 and 128, respectively) were randomized to treatment with PRO 160/120 or placebo (127 and 126 were evaluable for efficacy). Following a single-blind placebo run-in phase of 2 weeks, the patients received 2 x 1 capsule/day of the study medication under double-blind conditions over a period of 24 weeks. Double-blind treatment was followed by an open control period of 24 weeks during which all patients were administered PRO 160/120. Outcome measures for treatment efficacy included the assessment of the patients' LUTS by means of the I-PSS self-rating questionnaire and a quality of life index as well as uroflow and sonographic parameters. Using the International Prostate Symptom Score (I-PSS), patients treated with PRO 160/120 exhibited a substantially higher total score reduction after 24 weeks of double-blind treatment than patients of the placebo group (6 points vs 4 points; P=0.003, one tailed) with a tendency in the same direction after 16 weeks. This applied to obstructive as well as to irritative symptoms, and to patients with moderate or severe symptoms at baseline. Patients randomized to placebo showed a marked improvement in LUTS (as measured by the I-PSS) after being switched to PRO 160/120 during the control period (P=0.01, one tailed, in comparison to those who had been treated with PRO 160/120 in the double-blind phase). The tolerability of PRO 160/120 was comparable to the placebo. In conclusion, PRO 160/120 was clearly superior to the placebo for the amelioration of LUTS as measured by the I-PSS. PRO 160/120 is advantageous in obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms. The tolerability of the herbal extract was excellent. PMID:15928959

Lopatkin, N; Sivkov, A; Walther, C; Schläfke, S; Medvedev, A; Avdeichuk, J; Golubev, G; Melnik, K; Elenberger, N; Engelmann, U

2005-06-01

111

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.

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

2013-01-01

112

Long-Term Safety and Tolerability of Tadalafil in the Treatment of Erectile Dysfunction  

Microsoft Academic Search

Objective: To assess the long-term safety and tolerability of tadalafil for patients with erectile dysfunction (ED).Patients and Methods: This was a multicentre, open-label, 24-month extension trial involving 1173 men with ED. The mean age was 57 (range 23–83) years and 74.8% of patients were taking concomitant medications for comorbid conditions, including diabetes mellitus in 30.5% of men and hypertension in

F. Montorsi; B. Verheyden; E. J. H. Meuleman; K.-P Jünemann; I. Moncada; L. Valiquette; A. Casabe; C. Pacheco; J. Denne; J. Knight; S. Segal; V. S. Watkins

2004-01-01

113

Long-term safety of lamivudine treatment in patients with chronic hepatitis B  

Microsoft Academic Search

Background & aims: Data on thelong-term safety of lamivudine are limited. The aim of this analysis was to determine the incidence of hepatitis flares, hepatic decompensation, and liver-disease-related (LDR) serious adverse events (SAE) during long-term lamivudine treatment. Methods: We reviewed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years (median, 4

Anna S. F Lok; Ching-Lung Lai; Nancy Leung; Guang-Bi Yao; Zhen-Yu Cui; Eugene R Schiff; Jules L Dienstag; E. Jenny Heathcote; Nancy R Little; Dorothea A Griffiths; Stephen D Gardner; Mary Castiglia

2003-01-01

114

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

115

Long-term tolerability and efficacy of lamotrigine in pediatric patients with epilepsy.  

PubMed

Accumulating data suggest that the antiepilepsy drug lamotrigine, which has been available for adult use for more than a decade, also confers broad-spectrum, well-tolerated control of epilepsy in children. The current study--the open-label continuation phase of several short-term clinical trials--was conducted to assess the long-term tolerability and efficacy of lamotrigine as open-label adjunctive therapy or monotherapy in pediatric patients for a variety of seizure types and syndromes including partial seizures, absence seizures, and Lennox-Gastaut syndrome. Clinic visits occurred every 24 weeks throughout the treatment period. A total of 252 patients under 16 years of age were enrolled in the study. The numbers of patients exposed to at least 48 weeks, 96 weeks, and 144 weeks of treatment with lamotrigine were 185 (73.4%), 119 (47.2%), and 60 (23.8%), respectively, for an average duration of exposure of 96.7 weeks. The most common adverse events considered by the investigator to be drug related were dizziness (9.1%), somnolence (7.9%), nausea (6.3%), vomiting (5.2%), and headache (5.2%). The most common serious adverse events (regardless of suspected cause) included pneumonia (3.0%) and infection (1.9%). Investigators judged that the overall clinical status of three-fourths of the patients had improved at treatment weeks 48 and 96 relative to prelamotrigine clinical status. Lamotrigine administered as monotherapy or adjunctive therapy for an average of 2 years (96.7 weeks) was well tolerated and effective in pediatric patients with partial or generalized epilepsy. These results complement and extend the large body of data demonstrating the tolerability and efficacy of lamotrigine with short- and long-term use in adults. PMID:12088084

Duchowny, Michael; Gilman, Jamie; Messenheimer, John; Womble, Gilda; Risner, Marcus

2002-04-01

116

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

PubMed Central

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

2013-01-01

117

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

PubMed

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

Ricroch, Agnès E

2013-05-25

118

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

PubMed

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

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

2013-04-01

119

Long-term safety of living kidney donors aged 60 and older.  

PubMed

In Japan, kidney transplantation procedures are usually dependent upon live donors. As the recipient ages have been increasing, so has there been a corollary increase in the age of the live donors. Despite this being controversial, the use of older donors is becoming increasingly common. The purpose of our study was to evaluate the long-term safety of accepting older living kidney donors and graft survival rates. We retrospectively analyzed long-term donor outcomes for consecutive patients at our institution between January 1990 and December 2011. Older live kidney donors were defined as ? 60 years and younger live kidney donors were defined as <60 years old. Thirty-three were ? 60 years and 55 donors were <60 years. The mean follow-up term was 7 years and 4 months. Predonation, older donors had a lower estimated glomerular filtration rate (eGFR) level (77.1 ± 9.5 mL/min/1.73 m(2)) than younger donors (85.8 ± 14.6 mL/min/1.73 m(2); P < .01). More older donors had a history of hypertension (42.4% vs 9.1%; P < .01). In both groups, eGFR levels decreased about 40% immediately after nephrectomy. Residual renal function though was stable on long-term follow-up. The incidence of de novo hypertension and proteinuria after nephrectomy was not different between the 2 groups. In older donors, there were no perioperative complications that required extended hospital stays. Graft survival over a period of 10 years was similar in both groups. In our study, donor age had no influence on the deterioration of renal function after nephrectomy. Regardless of age, careful evaluation and follow-up are important for the donor's long-term safety after donation. PMID:24655952

Toyoda, M; Yamanaga, S; Kawabata, C; Hidaka, Y; Inadome, A; Arakane, F; Uekihara, S; Seishi, I

2014-03-01

120

Antiviral Therapy: Analysis of Long-term Efficacy and Safety  

Microsoft Academic Search

Despite the adoption of universal vaccination in many countries, chronic hepatitis B virus (HBV) infection continues to be\\u000a a global problem. Morbidity and mortality from this infection, although possibly declining, remains significant. Fortunately,\\u000a our treatment armamentarium has expanded exponentially in the past decade. Newer antiviral agents are not only effective against\\u000a HBV infection, but they also confer a lower risk

Helen S. Te

2010-01-01

121

Effectiveness and safety of antipsychotics in early onset psychoses: a long-term comparison.  

PubMed

The effectiveness and safety of various antipsychotics was evaluated in a long-term study on 47 patients, 29 with schizophrenia and 18 with schizoaffective disorder, aged 10 to 17 years (mean 15.5) at onset. Follow-up ranged from 3 years (all 47 patients) to 11 years (19 patients). Data were collected on the following antipsychotics: haloperidol, risperidone, olanzapine, quetiapine, aripiprazole and clozapine. Cases with positive response were significantly more frequent with clozapine as compared to haloperidol, risperidone and olanzapine. Risperidone was significantly better than haloperidol at the 3-year follow-up. A comparison of the degree of clinical improvement evaluated with PANSS and CGI in patients treated with drugs in subsequent periods showed clozapine led to significantly greater improvement as compared to haloperidol, risperidone and olanzapine, and risperidone as compared to haloperidol. Data on long-term functioning significantly favored clozapine as compared to all the other drugs. Discontinuation due to side effects involved 20% patients with clozapine, lower percentage with the other drugs. The results of this study on early-onset schizophrenic and schizoaffective disorders confirm that even in the long-term, clozapine is more effective than haloperidol, risperidone and olanzapine. Despite a relevant incidence of adverse effects, clozapine seems to have unique effectiveness in treating children and adolescents with early-onset schizophrenic disorders. PMID:21570128

Cianchetti, Carlo; Ledda, Maria Giuseppina

2011-10-30

122

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

123

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

124

Estimation of underground cavities stability for long-term safety of nuclear waste repository  

NASA Astrophysics Data System (ADS)

There is the increased interest to a problem of storages of radioactive waste creation in geological structures in present. Such projects are developed and the construction of these objects is conducted in many countries. This is caused by real, safety and economically acceptable character of radioactive waste underground isolation from human environment. Exploitation term of this objects is tens, hundreds and more years. The rock massif is the long acting natural barrier on a way of radionuclides distribution so the problem of ecological safety is long-term stability of storages and surrounding rock. Therefore one of the main problems is the development of evaluation and forecasting methods of underground structures supporting constructions long stability. The regularities of roof of cameras and pillars deformation and failure in time, depending on its geometric sizes, physical-mechanical properties of rocks, stress state and massif structure are obtained as result of mine research. On basis of kinetic theory of rock failure, creep theory and statistical analysis of experimental datas, which was obtained in mine conditions, the model of supporting constructions long-term strength is developed. This model allows to make an estimation and forecasting of underground structures current state evolution in time.

Rogojnikov, O.; Mansurov, V.

2003-04-01

125

The Cox maze III procedure for atrial fibrillation: long-term efficacy in patients undergoing lone versus concomitant procedures  

Microsoft Academic Search

BackgroundFor the last decade, the Cox maze III procedure has been available for the treatment of atrial fibrillation. It is unknown whether the operation has similar efficacy in patients with lone atrial fibrillation compared with that in patients with atrial fibrillation associated with coronary, valve, or congenital heart disease. This study examined the long-term outcome of patients who underwent this

Sunil M Prasad; Hersh S Maniar; Cindy J Camillo; Richard B Schuessler; John P Boineau; Thoralf M Sundt; James L Cox; Ralph J Damiano

2003-01-01

126

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

PubMed Central

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

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

2013-01-01

127

Long-Term Safety and Effectiveness of the 'OptEase' Vena Cava Filter  

SciTech Connect

Purpose: To assess the long-term safety and effectiveness of the OptEase inferior vena cava (IVC) filter. Materials and Methods: In this Institutional Review Board-approved, retrospective study, we reviewed data of 71 patients who received an OptEase filter at our institution from 2002 to 2007. Thirty-nine (55%) patients had symptoms of venous thromboembolism before filter placement. The indications for filter included contraindication to anticoagulation in 31 (44%) patients, prophylaxis against pulmonary embolism (PE) in 29 (41%) patients, and failure of anticoagulation in 11 (15%) patients. Procedure-related complications, such as symptomatic post-filter PE, deep venous thrombosis (DVT), IVC occlusion, and incidental imaging-evident filter-related complications, were recorded. Safety was assessed by the occurrence of filter-related complications during placement and follow-up. Effectiveness was assessed by the occurrence of post-filter PE. Results: Sixty-five (92%) filters were placed under fluoroscopy, and 6 (8%) were placed using intravascular ultrasound guidance. Seventy (99%) filters were placed successfully. Seven (10%) filters were placed in the suprarenal cava. Retrieval was attempted in 14 (20%) patients, and 12 filters were successfully retrieved. Clinical follow-up was available for 20 {+-} 21 months. Symptoms of postfilter PE and DVT occurred in 15% (n = 11) and 10% (n = 7) patients, respectively. None of these patients had computed tomography (CT)-proven PE, and only one had ultrasound-proven new DVT. One patient had symptomatic IVC occlusion. Follow-up abdominal CT in 20 patients showed thrombus in the filter in two of them. There were no instances of filter migration, filter tilt, or caval wall penetration. Conclusion: The OptEase filter appears to have an acceptable long-term safety profile. The filter was effective against PE.

Kalva, Sanjeeva P., E-mail: skalva@partners.org [Massachusetts General Hospital, Department of Radiology (United States); Marentis, Theodore C. [Harvard Medical School Boston, Department of Radiology (United States); Yeddula, Kalpana; Somarouthu, Bhanusupriya; Wicky, Stephan [Massachusetts General Hospital, Department of Radiology (United States); Stecker, Michael S. [Brigham's Women's Hospital, Department of Radiology (United States)

2011-04-15

128

Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.  

PubMed

In a 'blinded' trial (in Sri Lanka, 1996-98) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 micrograms/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg. Treated subjects were followed-up for 24 months. This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis. All subjects had pre-treatment microfilaria (mf) counts over 100/mL. All 3 treatments significantly reduced mf counts, with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment. Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti; albendazole-DEC combination had the greatest activity according to this test, with antigen levels decreasing to 30.5% of pre-treatment antigen levels, 24 months after therapy. All 3 treatments were clinically safe and well tolerated. These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic populations. PMID:11491010

Ismail, M M; Jayakody, R L; Weil, G J; Fernando, D; De Silva, M S; De Silva, G A; Balasooriya, W K

2001-01-01

129

Criticality safety evaluation for long term storage of FFTF fuel in interim storage casks  

SciTech Connect

It has been postulated that a degradation phenomenon, referred to as ``hot cell rot``, may affect irradiated FFTF mixed plutonium-uranium oxide (MOX) fuel during dry interim storage. ``Hot cell rot`` refers to a variety of phenomena that degrade fuel pin cladding during exposure to air and inert gas environments. It is thought to be a form of caustic stress corrosion cracking or environmentally assisted cracking. Here, a criticality safety analysis was performed to address the effect of the ``hot cell rot`` phenomenon on the long term storage of irradiated FFTF fuel in core component containers. The results show that seven FFTF fuel assemblies or six Ident-69 pin containers stored in core component containers within interim storage casks will remain safely subcritical.

Richard, R.F.

1995-05-11

130

Safety and effectiveness profile of raloxifene in long-term, prospective, postmarketing surveillance.  

PubMed

This large-scale postmarketing surveillance of raloxifene (60 mg/day) was conducted to assess the safety and effectiveness of raloxifene for long-term use in postmenopausal Japanese women with osteoporosis. The baseline examination included 6,967 women (mean age, 70.4 years). Participants completed observation after 6, 12, 24, and 36 months of therapy. Adverse drug reactions (ADR) were reported in 776 participants (11.14 %), with a total of 87 serious ADR cases occurring in 76 participants (1.09 %). The most frequently reported ADRs were edema peripheral (45/6,967, 0.65 %) and venous thromboembolism (11/6,967, 0.16 %). Of the 6,967 participants, 2,784 were included in the effectiveness analysis. Lumbar spine bone mineral density (BMD) increased significantly (p < 0.001, paired t test) compared with baseline at 6, 12, 24, and 36 months (2.51 %, 2.85 %, 4.76 %, and 3.51 %, respectively). Significant decreases in serum and urinary cross-linked amino-terminal telopeptide of type I collagen (NTX) and urinary deoxypyridinoline levels from baseline were observed at 3 months, followed by a significant decrease of serum bone alkaline phosphatase at 6 months [p < 0.001 for all comparisons except serum NTX (p = 0.011), Wilcoxon signed-rank test]. Early reductions in the biochemical markers of bone turnover (BTM) observed at 3 months with raloxifene treatment correlated negatively with subsequent increases in lumbar spine BMD at 1 year (r = -0.347, p = 0.008). The incidence of any new clinical fractures within 3 years was 1.18 % (82/6,967 participants). In summary, no new signals in safety were observed in the daily use of raloxifene. Moreover, the effectiveness profile of raloxifene was confirmed in practical use by this large-scale, long-term, postmarketing surveillance. PMID:22752125

Iikuni, Noriko; Hamaya, Etsuro; Nihojima, Shigeru; Yokoyama, Shunji; Goto, Wakana; Taketsuna, Masanori; Miyauchi, Akimitsu; Sowa, Hideaki

2012-11-01

131

An inventory of European data sources for the long-term safety evaluation of methylphenidate.  

PubMed

To compile an inventory of European healthcare databases with potential to study long-term effects of methylphenidate (MPH) in patients with attention deficit hyperactivity disorder (ADHD). Potential databases were identified through expert opinion, the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, and literature search. An online survey was conducted among database providers/coordinators to ascertain the databases' appropriateness for inclusion into the inventory. It included questions about database characteristics, sample size, availability of information on drug exposure, clinical data and accessibility. Forty-two databases from 11 countries were identified and their coordinators invited to participate; responses were obtained for 22 (52.4 %) databases of which 15 record ADHD diagnoses. Eleven had sufficient data on ADHD diagnosis, drug exposure, and at least one type of outcome information (symptoms/clinical events, weight, height, blood pressure, heart rate) to assess MPH safety. These were Aarhus University Prescription Database, Danish National Birth Cohort (Denmark); German Health Interview and Examination Survey for Children and Adolescents; Health Search Database Thales, Italian ADHD Register, Lombardy Region ADHD Database (Italy); Avon Longitudinal Study of Parents and Children, General Practice Research Database, The Health Improvement Network, QResearch (UK) and IMS Disease Analyzer (UK, Germany, France). Of the 20 databases with no responses, information on seven from publications and/or websites was obtained; Pedianet and the Integrated Primary Care Information database were considered suitable. Many European healthcare databases can be used for multinational long-term safety studies of MPH. Methodological research is underway to investigate the feasibility of their pooling and analysis. PMID:23508655

Murray, Macey L; Insuk, Suppachai; Banaschewski, Tobias; Neubert, Antje C; McCarthy, Suzanne; Buitelaar, Jan K; Coghill, David; Dittmann, Ralf W; Konrad, Kerstin; Panei, Pietro; Rosenthal, Eric; Sonuga-Barke, Edmund J; Wong, Ian C K

2013-10-01

132

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

PubMed

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 and 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

133

Long-term Efficacy of Bromocriptine in Macroprolactinomas and Giant prolactinomas in Men  

Microsoft Academic Search

We prospectively analyzed presentations and long-term therapeutic responses to bromocriptine (BRC) in 29 newly diagnosed men\\u000a with macroprolactinomas including 14 patients with 'giant prolactinoma'. Clinical symptoms, prolactin (PRL) levels and tumor\\u000a size on MRI were measured before BRC and sequentially thereafter. The duration of follow-up were 6 to 96 (30.7 ± 14.4) months.\\u000a Pretreatment PRL ranged between 124 and 29200 ng\\/mL

Arijit Chattopadhyay; Anil Bhansali; Shariq R Masoodi

2005-01-01

134

Long-term Safety and Tolerability of Colesevelam HCl in Subjects with Type 2 Diabetes.  

PubMed

The bile acid sequestrant, colesevelam hydrochloride, is approved for glycemic control in adults with type 2 diabetes. In three double-masked, placebo-controlled studies, colesevelam hydrochloride 3.75 g/day demonstrated its glycemic-lowering properties when added to existing metformin-, insulin-, or sulfonylurea-based therapy in adults with inadequately controlled type 2 diabetes. This was a 52-week open-label extension study conducted at 63 sites in the United States and one site in Mexico to further evaluate the safety and tolerability of colesevelam hydrochloride in subjects with type 2 diabetes. All subjects who completed the three double-masked, placebo-controlled studies were eligible to enroll in this open-label extension. In total, 509 subjects enrolled and received open-label colesevelam hydrochloride 3.75 g/day for 52 weeks. Safety and tolerability of colesevelam hydrochloride was evaluated by the incidence and severity of adverse events. In total, 360 subjects (70.7%) completed the extension. Of the safety population, 361 subjects (70.9%) experienced an adverse event, most (88.1%) being mild or moderate in severity. Fifty-six adverse events (11.0%) were drug-related; the most frequent drug-related adverse events were constipation and dyspepsia. Thirty-five subjects (6.9%) discontinued due to an adverse event. Fifty-four subjects (10.6%) experienced a serious adverse event; only one was considered drug-related (diverticulitis). Seventeen subjects (3.3%) experienced hypoglycemia; most episodes were mild or moderate in severity. Glycemic improvements with colesevelam hydrochloride were seen without change in weight over 52 weeks (0.2 kg mean reduction from baseline). Colesevelam hydrochloride was safe and well-tolerated as long-term therapy for patients with type 2 diabetes. PMID:19862667

Goldfine, A B; Fonseca, V A; Jones, M R; Wang, A C; Ford, D M; Truitt, K E

2010-01-01

135

Long-term safety study of iguratimod in patients with rheumatoid arthritis.  

PubMed

We conducted a 52-week clinical study of iguratimod in 394 Japanese patients with rheumatoid arthritis to evaluate the long-term safety of the drug. Iguratimod was administered orally at a daily dose of 25 mg for the first 4 weeks and 50 mg for the subsequent 48 weeks. Some of the patients continued the treatment for 100 weeks for their benefit. The cumulative incidence of adverse events for 100 weeks was 97.6%. The cumulative incidence of adverse reactions was 65.3%; unfavorable symptoms and signs (excluding abnormal laboratory data changes) accounted for 33.2% of the reactions, and abnormal laboratory data changes accounted for 50.4%. The continued treatment rate was 66.8% at week 28 and 53.6% at week 52. For reference, the American College of Rheumatology (ACR) 20 response rate was calculated for the patients who had assessable disease activity, who did not violate the study protocol, and who continued the study treatment at weeks 28 and 52. The rate was 46.9% at week 28 and 41.0% at week 52. To use iguratimod safely for a long time, patients should be observed closely for adverse reactions such as increased hepatic enzymes. PMID:17278016

Hara, Masako; Abe, Tohru; Sugawara, Sachiko; Mizushima, Yutaka; Hoshi, Keiko; Irimajiri, Shoichiro; Hashimoto, Hiroshi; Yoshino, Shinichi; Matsui, Nobuo; Nobunaga, Masashi

2007-01-01

136

Short and Long-Term Safety of the 2009 AS03-Adjuvanted Pandemic Vaccine  

PubMed Central

Background This study assessed the short and the long term safety of the 2009 AS03 adjuvanted monovalent pandemic vaccine through an active web-based electronic surveillance. We compared its safety profile to that of the seasonal trivalent inactivated influenza vaccine (TIV) for 2010–2011. Methodology/Principal Findings Health care workers (HCW) vaccinated in 2009 with the pandemic vaccine (Arepanrix ® from GSK) or HCW vaccinated in 2010 with the 2010–2011 TIV were invited to participate in a web-based active surveillance of vaccine safety. They completed two surveys the day-8 survey covered the first 7 days post-vaccination and the day-29 survey covered events occurring 8 to 28 days after vaccination. Those who reported a problem were called by a nurse to obtain details. The main outcome was the occurrence of a new health problem or the worsening of an existing health condition that resulted in a medical consultation or work absenteeism. For the pandemic vaccine, a six-month follow-up for the occurrence of serious adverse events (SAE) was conducted. Among the 6242 HCW who received the pandemic vaccine, 440 (7%) reported 468 events compared to 328 of the 7645 HCW (4.3%) who reported 339 events after the seasonal vaccine. The 2009 pandemic vaccine was associated with significantly more local reactions than the 2010–2011 seasonal vaccine (1% vs. 0.03%, p<0.001). Paresthesia was reported by 7 HCW (0.1%) after the pandemic vaccine but by none after the seasonal vaccine. For the pandemic vaccine, no clustering of SAE was found in the 6 month follow-up. Conclusion The 2009 pandemic vaccine seems to have a good safety profile, similar to the 2010–2011 TIV, with the exception of local reactions. This surveillance was adequately powered to identify AE associated with an excess risk ?1 per 1000 vaccinations but is insufficient to detect rare AE. Trial Registration ClinicalTrials.gov NCT01289418, NCT01318876

De Serres, Gaston; Gariepy, Marie-Claude; Coleman, Brenda; Rouleau, Isabelle; McNeil, Shelly; Benoit, Melanie; McGeer, Allison; Ambrose, Ardith; Needham, Judy; Bergeron, Chantal; Grenier, Cynthia; Sleigh, Kenna; Kallos, Arlene; Ouakki, Manale; Ouhoummane, Najwa; Stiver, Grant; Valiquette, Louis; McCarthy, Anne; Bettinger, Julie

2012-01-01

137

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?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

138

Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety1-3  

Microsoft Academic Search

Background: Nonpathogenic live bacteria are consumed as food by many children, particularly in the form of yogurt. The tolerance and safety of long-term consumption of specific types and strains of probiotic bacteria are not well documented. Objective: The goal was to evaluate tolerance to formulas con- taining 2 levels of probiotic supplementation and effects on growth, general clinical status, and

Jose M Saavedra; Adel Abi-Hanna; Nancy Moore; Robert H Yolken

139

Long-term efficacy of leptin replacement in patients with Dunnigan-type familial partial lipodystrophy  

PubMed Central

The Dunnigan-type familial partial lipodystrophy (FPLD) is characterized by a variable loss of fat from the extremities and trunk and excess subcutaneous fat in the chin and supraclavicular area. Associated metabolic abnormalities include hypoleptinemia, insulin resistance, and dyslipidemia. Our goal was to observe changes in metabolic parameters for patients with FPLD on long-term leptin replacement and to compare the metabolic characteristics seen in FPLD with those seen in generalized lipodystrophy (GL) from our previous studies. This was an open-label study of 6 patients with FPLD receiving maximal doses of oral antidiabetic and lipid-lowering medications at baseline. Recombinant leptin was given through twice-daily subcutaneous injections at a maximal dose of 0.08 mg/kg per day over 12 months to simulate normal to high normal physiologic levels. Triglycerides were reduced by 65% at 4 months (749 ± 331 to 260 ± 58 mg/dL) and significantly reduced at 12 months for 5 patients (433 ± 125 to 247 ± 69 mg/dL; P = .03). Total cholesterol also decreased (280 ± 49 to 231 ± 41 mg/dL; P = .01). Insulin sensitivity and fasting glucose levels (190 ± 26 to 151 ± 15 mg/dL; P < .01) improved. Glucose tolerance and glycosylated hemoglobin levels (8.4% ± 0.6% to 8.0% ± 0.4%; P = .07) did not change. As shown in patients with GL, patients with FPLD have improvement in triglycerides, fasting glucose, and insulin sensitivity with leptin replacement. In contrast to the patients with GL, the patients with FPLD are older, have higher leptin levels, and notably lower insulin secretion for a similar degree of hyperglycemia. Low-dose recombinant methionyl human leptin for patients with FPLD has an important role in improving triglycerides, beyond that of available lipid-lowering agents. In improving glycemic control, normalization of glucose tolerance in hypoinsulinemic patients with FPLD requires insulin and leptin therapy. This is the first study to examine the effects of long-term leptin replacement in patients with FPLD.

Park, Jean Y.; Javor, Edward D.; Cochran, Elaine K.; DePaoli, Alex M.; Gorden, Phillip

2008-01-01

140

Safety of the long-term use of proton pump inhibitors  

PubMed Central

The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaffin-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-term use of PPIs. Long-term use of PPIs does not lead to vitamin B12 deficiencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use long-term in persons in whom there is a clear need for the maintenance of extensive acid inhibition.

Thomson, Alan BR; Sauve, Michel D; Kassam, Narmin; Kamitakahara, Holly

2010-01-01

141

Long-term efficacy of medium-dose UVA1 phototherapy in atopic dermatitis  

Microsoft Academic Search

Background: UVA1 (340–400 nm) therapy proved to be highly effective in patients with severe atopic dermatitis. The optimal dose regarding therapeutic efficacy and possible side effects is still to be evaluated. In vitro cell culture as well as in vivo animal studies recently indicated that a correlation between UVA irradiation and photoaging, skin carcinogenesis, or melanoma induction may exist. Therefore

Dietrich Abeck; Tanja Schmidt; Heike Fesqd; Kerstin Strom; Martin Mempel; Knut Brockow; Johannes Ring

2000-01-01

142

Long-term efficacy of medium-dose UVA1 phototherapy in atopic dermatitis  

Microsoft Academic Search

Background: UVA1 (340-400 nm) therapy proved to be highly effective in patients with severe atopic dermatitis. The optimal dose regarding therapeutic efficacy and possible side effects is still to be evaluated. In vitro cell culture as well as in vivo animal studies recently indicated that a correlation between UVA irradiation and photoaging, skin carcinogenesis, or melanoma induction may exist. Therefore

Dietrich Abeck; Tanja Schmidt; Heike Fesq; Kerstin Strom; Martin Mempel; Knut Brockow; Johannes Ring

2000-01-01

143

Efficacy of statins in familial hypercholesterolaemia: a long term cohort study  

Microsoft Academic Search

Objective To determine the efficacy of statin treatment on risk of coronary heart disease in patients with familial hypercholesterolaemia.Design Cohort study with a mean follow-up of 8.5 years.Setting 27 outpatient lipid clinics.Subjects 2146 patients with familial hypercholesterolaemia without prevalent coronary heart disease before 1 January 1990.Main outcome measures Risk of coronary heart disease in treated and “untreated” (delay in starting

Jorie Versmissen; Daniëlla M Oosterveer; Mojgan Yazdanpanah; Joep C Defesche; Dick C G Basart; Anho H Liem; Jan Heeringa; Jacqueline C Witteman; Peter J Lansberg; John J P Kastelein; Eric J G Sijbrands

2008-01-01

144

Efficacy of long term cyclic administration of the poorly absorbed antibiotic Rifaximin in symptomatic, uncomplicated colonic diverticular disease  

PubMed Central

AIM: To comparatively evaluate the long term efficacy of Rifaximin and dietary fibers in reducing symptoms and/or complication frequency in symptomatic, uncomplicated diverticular disease. METHODS: 307 patients (118 males, 189 females, age range: 40-80 years) were enrolled in the study and randomly assigned to: Rifaximin (400 mg bid for 7 d every month) plus dietary fiber supplementation (at least 20 gr/d) or dietary fiber supplementation alone. The study duration was 24 mo; both clinical examination and symptoms’ questionnaire were performed every two months. RESULTS: Both treatments reduced symptom frequency, but Rifaximin at a greater extent, when compared to basal values. Symptomatic score declined during both treatments, but a greater reduction was evident in the Rifaximin group (6.4 ± 2.8 and 6.2 ± 2.6 at enrollment, p = NS, 1.0 ± 0.7 and 2.4 ± 1.7 after 24 mo, p < 0.001, respectively). Probability of symptom reduction was higher and complication frequency lower (Kaplan-Meyer method) in the Rifaximin group (p < 0.0001 and 0.028, respectively). CONCLUSION: In patients with symptomatic, uncomplicated diverticular disease, cyclic administration of Rifaximin plus dietary fiber supplementation is more effective in reducing both symptom and complication frequency than simple dietary fiber supplementation. Long term administration of the poorly absorbed antibiotic Rifaximin is safe and well tolerated by the patients, confirming the usefulness of this therapeutic strategy in the overall management of diverticular disease.

Colecchia, Antonio; Vestito, Amanda; Pasqui, Francesca; Mazzella, Giuseppe; Roda, Enrico; Pistoia, Francesca; Brandimarte, Giovanni; Festi, Davide

2007-01-01

145

Tracking the extramedullary PML-RAR?-positive cell reservoirs in a preclinical model: biomarker of long-term drug efficacy.  

PubMed

Using an acute promyelocytic leukemia (APL) preclinical model, we show that oncogene-specific PCR (Polymerase Chain Reaction)-based assays allow to evaluate the efficacy of immunotherapy combining all-trans retinoic acid (ATRA) and a DNA-based vaccine targeting the promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR?) oncogene. Kaplan-Meier survival analysis according to the peripheral blood PML-RAR? normalized copy number (NCN) clearly shows that ATRA + DNA-treated mice with an NCN lower than 10 (43%) formed the group with a highly significant (p < 0.0001) survival advantage. Furthermore, a PCR assay was used to assess various tissues and organs for the presence of PML-RAR?-positive cells in long-term survivors (n = 15). As expected, the majority of mice (n = 10) had no measurable tissue level of PML-RAR?. However, five mice showed a weak positive signal in both the brain and spleen (n = 2), in the brain only (n = 2) and in the spleen only (n = 1). Thus tracking the oncogene-positive cells in long-term survivors reveals for the first time that extramedullary PML-RAR?-positive cell reservoirs such as the brain may persist and be involved in relapses. PMID:22906630

Pokorna, Katerina; Le Pogam, Carole; Chopin, Martine; Balitrand, Nicole; Reboul, Murielle; Cassinat, Bruno; Chomienne, Christine; Padua, Rose Ann; Pla, Marika

2013-02-01

146

Long-term antibacterial efficacy of air plasma-activated water  

NASA Astrophysics Data System (ADS)

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

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

2011-11-01

147

Short- and Long-Term Efficacy of Hexadecylphosphocholine against Established Leishmania infantum Infection in BALB/c Mice  

PubMed Central

In the immunocompetent host, visceral leishmaniasis (VL) is a fatal disease if untreated. In immunosuppressed patients, VL is an opportunistic infection for which there is no effective treatment for relapses. Here we report on the long-term activity of orally administered hexadecylphosphocholine (HDPC) against established Leishmania infantum infection in BALB/c mice. HDPC is a synthetic phospholipid with antiproliferative properties that has been extensively studied for its cancerostatic activity. Its short-term leishmanicidal effects in mice recently infected with viscerotropic Leishmania species have been previously reported. First, we show that 5 days of oral therapy with HDPC (20 mg/kg of body weight/day) led to amastigote suppression in the liver and the spleen of 94 and 78%, respectively (versus 85 and 55% suppression by meglumine antimonate in the liver and spleen, respectively), in mice infected 6 weeks before treatment and examined 3 days after the end of treatment. These results demonstrate the short-term efficacy of HDPC against an established Leishmania infection. Next, the long-term efficacy of HDPC was examined. In HDPC-treated mice both the hepatic and splenic amastigote loads were significantly reduced (at least 89%) 10, 31, and 52 days after the end of the treatment. In the treated mice, the increase of the splenic load was significantly slower than that in the untreated mice, demonstrating that the HDPC-exerted inhibition of Leishmania growth persisted for at least 7 to 8 weeks. Orally administered HDPC—the safe doses and side effects of which are at least partially known—appears to be a promising candidate for the treatment of VL.

Le Fichoux, Yves; Rousseau, Deborah; Ferrua, Bernard; Ruette, Sandrine; Lelievre, Alain; Grousson, Dominique; Kubar, Joanna

1998-01-01

148

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

PubMed Central

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

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

2013-01-01

149

Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa.  

PubMed

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

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

2014-01-14

150

Long-Term Benefits of Prompts to Use Safety Belts among Drivers Exiting Senior Communities  

ERIC Educational Resources Information Center

Senior drivers are vulnerable to automobile crashes and subsequent injury and death. Safety belts reduce health risks associated with auto crashes. Therefore, it is important to encourage senior drivers to wear safety belts while driving. Using a repeated baseline design (AAB), we previously reported that motivating signs boosted safety belt usage…

Cox, Cory D.; Cox, Brian S.; Cox, Daniel J.

2005-01-01

151

Long-term Benefits of Prompts to Use Safety Belts among Drivers Exiting Senior Communities  

Microsoft Academic Search

Senior drivers are vulnerable to automobile crashes and subsequent injury and death. Safety belts reduce health risks associated with auto crashes. Therefore, it is important to encourage senior drivers to wear safety belts while driving. Using a repeated baseline design (AAB), we previously reported that motivating signs boosted safety belt usage by drivers exiting senior communities from baseline (72% and

CORY D. COX; BRIAN S. COX; Daniel J Cox

2005-01-01

152

Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis  

Microsoft Academic Search

In a ‘blinded’ trial (in Sri Lanka, 1996–1998) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 ?g\\/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg\\/kg or albendazole 600 mg with ivermectin 400 ?g\\/kg. Treated subjects were followed-up for

M. M. Ismail; R. L. Jayakody; G. J. Weil; Deepika Fernando; M. S. G. De Silva; G. A. C. De Silva; W. K. Balasooriya

2001-01-01

153

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

PubMed

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

Peikert, A; Hentrich, M; Ochs, G

1991-12-01

154

Long-term benefits of prompts to use safety belts among drivers exiting senior communities.  

PubMed

Senior drivers are vulnerable to automobile crashes and subsequent injury and death. Safety belts reduce health risks associated with auto crashes. Therefore, it is important to encourage senior drivers to wear safety belts while driving. Using a repeated baseline design (AAB), we previously reported that motivating signs boosted safety belt usage by drivers exiting senior communities from baseline (72% and 68% usage), to postinstallation of signs (94%), to 6 months follow-up (80%). The current study was a 4-year follow-up in which six senior communities, with seat belt signs, were compared to six matched control senior communities with no signs. Safety belt usage was stable, across 4 years, at approximately 80% for both male and female drivers and front seat passengers for the six communities with signs, and was approximately 55% for control sites. These finding suggest that the simple and low-cost intervention of erecting signs to prompt safety belt use has persistent benefits that affect driver and passenger behavior alike. PMID:16463533

Cox, Cory D; Cox, Brian S; Cox, Daniel J

2005-01-01

155

Peer Tutoring to Prevent Firearm Play: Acquisition, Generalization, and Long-term Maintenance of Safety Skills  

PubMed Central

Hundreds of accidental injuries and deaths to children occur annually in the United States as a result of firearm play. Behavioral skills training (BST) and in situ training have been found to be effective in teaching children the skills to use if they find a firearm, but training requires substantial time and effort. The current study examined the use of peers as tutors as a potential way to decrease the time and resources needed to teach these safety skills to youngsters. Peer trainers conducted BST and in situ training with other children. Children taught by the peer trainers acquired the safety skills and demonstrated them in naturalistic situations in which the skills were needed. Furthermore, all of the peer trainers acquired and maintained the skills. These results support the use of peer tutoring for teaching safety skills to other children.

Jostad, Candice M; Miltenberger, Raymond G; Kelso, Pamela; Knudson, Peter

2008-01-01

156

Long-term efficacy of a printed or a Web-based tailored physical activity intervention among older adults  

PubMed Central

Background This study provides insight into the long-term efficacy (i.e. 12 month results) of the Web-based or print-delivered tailored Active Plus intervention (with and without environmental approach) to promote physical activity (PA) among the over-fifties. Differences in effect among subgroups are studied as well. Methods Intervention groups (i.e. print-delivered basic (PB; N = 439), print-delivered environmental (PE; N = 435), Web-based basic (WB; N = 423), Web-based environmental (WE; N = 432)) and a waiting list control group (N = 411) were studied in a clustered randomized controlled trial. Intervention participants received tailored advice three times within 4 months. Long-term effects (12 months after the intervention has started, i.e. 8 months after the intervention was completed) on PA (i.e. self-reported weekly minutes and days of sufficient PA) were tested using multilevel linear regression analyses. Participants’ age, gender, BMI, educational level, PA intention and the presence of a chronic physical limitation were considered to be potential moderators of the effect. Results Overall, the Active Plus intervention was effective in increasing weekly days of sufficient PA (B=0.49; p=.005), but ineffective in increasing weekly minutes of PA (B=84.59; p=.071). Per intervention condition analysis showed that the PB-intervention (Bdays=0.64; p=.002; Bmin=111.36; p=.017) and the PE-intervention (Bdays=0.70; p=.001; Bmin=157.41; p=.001) were effective in increasing days and minutes of PA. Neither Web-based conditions significantly increased PA, while the control group decreased their PA. In contrast to the intervention effect on minutes of PA, the effect on weekly days of PA was significantly moderated by the participants’ baseline intention to be sufficiently physically active. Conclusions In general, after 12 months the print-delivered interventions resulted in stronger effects than the Web-based interventions. The participants’ baseline intention was the only significant moderator of the intervention effect. All other assessed user characteristics did not significantly moderate the effect of the intervention, which might indicate that the intervention is sufficiently tailored to the different participant characteristics. Additional efforts should be taken to increase the sustainability of Web-based interventions. Trial registration Dutch Trial Register: NTR2297.

2013-01-01

157

Long-term treatment of venous thromboembolism.  

PubMed

Long term treatment of venous thromboembolism is essential to complete therapy of the index episode and to reduce recurrences. Vitamin K antagonists are the mainstay for the long term treatment of venous thromboembolism for the majority of the patients as they allow oral administration. Low-molecular weight heparins are recommended for the long term treatment of cancer patients. The duration of long term anticoagulation depends on the features of the index venous thromboembolism and on the presence of associated risk factors. Patients at high risk for recurrence - mainly those who suffered unprovoked venous thromboembolism and those with cancer - should be evaluated for extended anticoagulation. The risk for major bleeding complications and the inconvenience for monitoring, dose adjustment and drug-food interactions are the main constraints for indefinite anticoagulant treatment. New anticoagulants with more favourable efficacy- safety profile and reduced need for monitoring could improve the feasibility of extended anticoagulation. PMID:24846227

Becattini, Cecilia; Manina, Giorgia

2014-05-01

158

Use of survivorship and contact stress analyses to predict the long-term efficacy of new generation joint replacement designs. A model for FDA device evaluation.  

PubMed

Long-term investigational device exemption (IDE) clinical trial evaluation, as currently monitored by the Food and Drug Administration (FDA) regulatory process, is time-consuming, burdensome, and extremely costly to the product developers and ultimately to the consumer. Thus, almost all devices introduced in the past decade have not been clinically tested; they have been introduced under a "510k" grandfather provision that does not address the safety and efficacy of the product. As a result, joint replacement devices have been sold and used with serious failure consequences for the consumer. When 10-year survivorship studies are available for specific joints that demonstrate strong evidence of favorable clinical performance with suitable supporting analysis, they can be used as a standard for comparison with newer, similar designs. Additionally, contact stress analysis of the bearing surfaces of these joint replacements can be used to determine their long-term wear characteristics under normal loading conditions and compared to retrieved devices used for 10 years or more. Devices that demonstrate a 90% survivorship over a 10-year interval and have low enough contact stresses to minimize wear failure during the same period can be used as "standard designs" to which newer designs should be compared. Using this methodology, the developers of any new device should cite the standard design that they have improved on and document an improvement in early (1 to 3 years) survivorship studies with a contact stress analysis demonstrating bearing contact stresses equal to or lower than the standard design. Any device that fails more often or wears out faster than a standard design should not be released until design modifications have proved it superior or equal to the standard designs. PMID:1997955

Buechel, F F; Pappas, M J; Greenwald, A S

1991-01-01

159

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

ScienceCinema

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.

160

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

Microsoft Academic Search

BackgroundInfusion 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.MethodologyHealthy 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

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

2011-01-01

161

Sodium ferric gluconate complex in haemodialysis patients: a prospective evaluation of long-term safety  

Microsoft Academic Search

Background. A previous single dose placebo- controlled double-blinded trial showed an extremely low (0.4%) intolerance rate of sodium ferric gluconate complex (SFGC) in SFGC-naive haemodialysis patients. No large prospective trials have assessed the safety of SFGC during repeated exposure in the outpatient haemodialysis setting. Methods. Chronic haemodialysis patients complet- ing the single-dose trial of SFGC were eligible to participate in

Beckie Michael; Daniel W. Coyne; Vaughn W. Folkert; Naomi V. Dahl; David G. Warnock

162

Long-term safety of abatacept in patients with rheumatoid arthritis.  

PubMed

Abatacept is a selective T cell co-stimulation modulator that was first approved by the Italian Medicines Agency and reimbursed by the Italian National Health Service when used to treat active rheumatoid arthritis "not sufficiently responsive to other disease-modifying anti-rheumatic drugs (DMARDs) including at least one TNF inhibitor", and is now also approved as a first line biological agent. The aim of this review is to summarise the safety data collected in clinical trials and observational studies. PMID:23800448

Atzeni, Fabiola; Sarzi-Puttini, Piercarlo; Mutti, Alessandra; Bugatti, Serena; Cavagna, Lorenzo; Caporali, Roberto

2013-10-01

163

Long-term efficacy of routine access to antiretroviral-resistance testing in HIV type 1-infected patients: results of the clinical efficacy of resistance testing trial.  

PubMed

The long-term efficacy of making resistance testing routinely available to clinicians has not been established. We conducted a clinical trial at 6 US military hospitals in which volunteers infected with human immunodeficiency virus type-1 were randomized to have routine access to phenotype resistance testing (PT arm), access to genotype resistance testing (GT arm), or no access to either test (VB arm). The primary outcome measure was time to persistent treatment failure despite change(s) in antiretroviral therapy (ART) regimen. Overall, routine access to resistance testing did not significantly increase the time to end point. Time to end point was significantly prolonged in the PT arm for subjects with a history of treatment with > or =4 different ART regimens or a history of treatment with nonnucleoside reverse-transcriptase inhibitors before the study, compared with that in the VB arm. These results suggest that routine access to resistance testing can improve long-term virologic outcomes in HIV-infected patients who are treatment experienced but may not impact outcome in patients who are naive to or have had limited experience with ART. PMID:14986258

Wegner, Scott A; Wallace, Mark R; Aronson, Naomi E; Tasker, Sybil A; Blazes, David L; Tamminga, Cindy; Fraser, Susan; Dolan, Matthew J; Stephan, Kevin T; Michael, Nelson L; Jagodzinski, Linda L; Vahey, Maryanne T; Gilcrest, Joyce L; Tracy, LaRee; Milazzo, Mark J; Murphy, Daniel J; McKenna, Paula; Hertogs, Kurt; Rinehart, Alex; Larder, Brendan; Birx, Deborah L

2004-03-01

164

Long term outcomes reporting the safety of breast conserving therapy compared to mastectomy: 20-year results of EORTC 10801  

PubMed Central

Large multicenter clinical trials have demonstrated the safety of breast conserving surgery and radiation (BCT) compared to modified radical mastectomy (MRM). At 20 years follow-up, the European Organization of Research and Treatment of Cancer (EORTC) 10801 trial reports the outcomes of distant metastasis (DM) and overall survival (OS) for stage 1 and 2 breast cancers treated from 1980-1986. Even though BCT had a higher 10 years local-regional recurrence (LRR) at 20% compared to MRM (12%), no significant difference was identified in long term OS (44% in the BCT group and 39% in the MRM group) or time to DM. Factors associated with increased LRR were dependent on biologic characteristics including larger tumor size, lymph node metastasis, and receptor subtype. BCT should be offered in appropriate patients when complete resection can be achieved. Continued research evaluating the heterogeneity of breast cancer subtypes will help further guide local-regional therapy for continued improvement in LRR, DM, and OS.

Black, Dalliah M.; Hunt, Kelly K.

2013-01-01

165

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

166

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.

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

2012-01-01

167

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

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

2011-01-01

168

A long-term follow-up evaluation of electronic health record prescribing safety  

PubMed Central

Objective To be eligible for incentives through the Electronic Health Record (EHR) Incentive Program, many providers using older or locally developed EHRs will be transitioning to new, commercial EHRs. We previously evaluated prescribing errors made by providers in the first year following transition from a locally developed EHR with minimal prescribing clinical decision support (CDS) to a commercial EHR with robust CDS. Following system refinements, we conducted this study to assess the rates and types of errors 2?years after transition and determine the evolution of errors. Materials and methods We conducted a mixed methods cross-sectional case study of 16 physicians at an academic-affiliated ambulatory clinic from April to June 2010. We utilized standardized prescription and chart review to identify errors. Fourteen providers also participated in interviews. Results We analyzed 1905 prescriptions. The overall prescribing error rate was 3.8 per 100 prescriptions (95% CI 2.8 to 5.1). Error rates were significantly lower 2?years after transition (p<0.001 compared to pre-implementation, 12?weeks and 1?year after transition). Rates of near misses remained unchanged. Providers positively appreciated most system refinements, particularly reduced alert firing. Discussion Our study suggests that over time and with system refinements, use of a commercial EHR with advanced CDS can lead to low prescribing error rates, although more serious errors may require targeted interventions to eliminate them. Reducing alert firing frequency appears particularly important. Our results provide support for federal efforts promoting meaningful use of EHRs. Conclusions Ongoing error monitoring can allow CDS to be optimally tailored and help achieve maximal safety benefits. Clinical Trials Registration ClinicalTrials.gov, Identifier: NCT00603070.

Abramson, Erika L; Malhotra, Sameer; Osorio, S Nena; Edwards, Alison; Cheriff, Adam; Cole, Curtis; Kaushal, Rainu

2013-01-01

169

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

PubMed Central

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

2012-01-01

170

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

Microsoft Academic Search

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

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

2006-01-01

171

Clinical Efficacy and Toxicity Profile of Tacrolimus and Mycophenolic Acid in Relation to Combined Long-term Pharmacokinetics in de Novo Renal Allograft Recipients  

Microsoft Academic Search

Introduction: Tacrolimus and mycophenolate mofetil are effective drugs characterized by specific toxicity profiles that may compromise their long-term use in renal transplant recipients. Clinicians, therefore, need reliable drug monitoring tools for relating efficacy and toxicity to drug exposure.Study design: We conducted a prospective 12-month pharmacokinetic study of tacrolimus and mycophenolic acid in 100 de novo recipients. The aim was to

Dirk R. J. Kuypers; Kathleen Claes; Pieter Evenepoel; Bart Maes; Yves Vanrenterghem

2004-01-01

172

Evaluation of long-term efficacy of interferon alpha-2b and ribavirin in combination in naive patients with chronic hepatitis C: an Italian multicenter experience  

Microsoft Academic Search

Background\\/Aims: A combination of interferon alpha and ribavirin has been suggested to reach a higher rate of sustained virological response in patients with chronic hepatitis C than monotherapy. In this study we assessed the long-term efficacy of this combination therapy in the treatment of selected Italian naive chronic hepatitis C patients compared to interferon alpha monotherapy.Methods: We enrolled 428 naive

Giuseppe Barbaro; Gabriella Di Lorenzo; Maurizio Soldini; Giuseppe Giancaspro; Adriano Pellicelli; Benvenuto Grisorio; Giorgio Barbarini

2000-01-01

173

Long-term efficacy of nucleoside monotherapy in preventing HBV infection in HBsAg-negative recipients of anti-HBc-positive donor livers  

Microsoft Academic Search

Background and aim  Transmission of hepatitis B virus (HBV) infection occurs in up to 87.5% of HBsAg-negative recipients of anti-HBc-positive\\u000a donor livers in the absence of HBV prophylaxis. There is no standardized prophylactic regimen to prevent HBV infection in\\u000a this setting. The aim of this study was to determine the long-term efficacy of nucleoside analogue to prevent HBV infection\\u000a in this

Watcharasak Chotiyaputta; Shawn J. Pelletier; Robert J. Fontana; Anna S. F. Lok

2010-01-01

174

Nurse-Physician Communication in the Long-Term Care Setting: Perceived Barriers and Impact on Patient Safety  

PubMed Central

Purpose Clear and complete communication between health care providers is a prerequisite for safe patient management and is a major priority of the Joint Commission's 2008 National Patient Safety Goals. The goal of this study was to describe nurses' perceptions of nurse-physician communication in the long-term care (LTC) setting. Methods Mixed-method study including a self-administered questionnaire and qualitative semi-structured telephone interviews of licensed nurses from 26 LTC facilities in Connecticut. The questionnaire measured perceived openness to communication, mutual understanding, language comprehension, frustration, professional respect, nurse preparedness, time burden and logistical barriers. Qualitative interviews focused on identifying barriers to effective nurse-physician communication that may not have previously been considered and eliciting nurses' recommendations for overcoming those barriers. Results Three-hundred seventy-five (375) nurses completed the questionnaire and 21 nurses completed qualitative interviews. Nurses identified several barriers to effective nurse-physician communication: lack of physician openness to communication, logistic challenges, lack of professionalism, and language barriers. Feeling hurried by the physician was the most frequent barrier (28%), followed by finding a quiet place to call (25%) and difficulty reaching the physician (21%). In qualitative interviews, there was consensus that nurses needed to be brief and prepared with relevant clinical information when communicating with physicians and that physicians needed to be more open to listening. Conclusions A combination of nurse and physician behaviors contributes to ineffective communication in the LTC setting. These findings have important implications for patient safety and support the development of structured communication interventions to improve quality of nurse-physician communication.

Tjia, Jennifer; Mazor, Kathleen M.; Field, Terry; Meterko, Vanessa; Spenard, Ann; Gurwitz, Jerry H.

2009-01-01

175

Long-term safety and efficacy of percutaneous coronary intervention with stenting and coronary artery bypass surgery for multivessel coronary artery disease: A meta-analysis with 5-year patient-level data from the ARTS, ERACI-II, MASS-II, and SoS trials  

Microsoft Academic Search

Background - Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups. Methods and

J. Daemen; H. Boersma; M. Flather; J. Booth; R. H. Stables; A. Rodriguez; G. A. Rodriguez-Granillo; W. A. Hueb; P. A. Lemos; P. W. J. C. Serruys

2008-01-01

176

Long-Term Safety and Efficacy of Percutaneous Coronary Intervention With Stenting and Coronary Artery Bypass Surgery for Multivessel Coronary Artery Disease A Meta-Analysis With 5Year Patient-Level Data From the ARTS, ERACI-II, MASS-II, and SoS Trials  

Microsoft Academic Search

Background—Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups. Methods and Results—We performed

Joost Daemen; Eric Boersma; Marcus Flather; Jean Booth; Rod Stables; Alfredo Rodriguez; Gaston Rodriguez-Granillo; Whady A. Hueb; Pedro A. Lemos; Patrick W. Serruys

2011-01-01

177

Efficacy, safety, and cost-effectiveness of glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis  

PubMed Central

The current Multiple Sclerosis (MS) therapeutic landscape is rapidly growing. Glatiramer acetate (GA) remains unique given its non-immunosuppressive mechanism of action as well as its superior long-term safety and sustained efficacy data. In this review, we discuss proposed mechanisms of action of GA. Then we review efficacy data for reduction of relapses and slowing disability as well as long term safety data. Finally we discuss possible future directions of this unique polymer in the treatment of MS.

Boster, Aaron; Bartoszek, Mary Pat; O'Connell, Colleen; Pitt, David; Racke, Michael

2011-01-01

178

Clozapine: Efficacy and Safety  

Microsoft Academic Search

Clozapine (Clozaril) represents the first major advance in the pharmacological treatment of schizophrenia since the introduction of antipsychotics into clinical practice in the 1950s. Studies consistently support its efficacy for reducing positive symptoms in acutely psychotic patients and in treatment-resistant patients, for preventing positive symptom exacerbations as a maintenance treatment, and for reducing symptoms of hostility and violence. There is

Robert W. Buchanan

1995-01-01

179

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

180

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

181

Long term efficacy of a controlled-release formulation of isosorbide 5-mononitrate (Imdur) in angina patients receiving beta-blockers.  

PubMed

In a multicentre double-blind crossover study the clinical efficacy and tolerability of a controlled-release formulation, Durules, of isosorbide 5-mononitrate (Imdur) 60mg once daily was compared with placebo over 2 weeks in 70 patients with stable exercise-induced angina pectoris who were receiving concomitant long term beta-blockade. Isosorbide 5-mononitrate significantly improved exercise capacity and signs of myocardial ischaemia, while reducing the number of anginal attacks and consumption of short-acting glyceryl trinitrate tablets compared with beta-blocker therapy alone. During an open follow-up period of 1 year, there was no attenuation of the antianginal efficacy of isosorbide 5-mononitrate. The drug was well tolerated during both phases of the study, and the only significant adverse effect was headache, which rapidly disappeared during continued treatment. PMID:2887418

Uusitalo, A

1987-01-01

182

Coping Self-Efficacy Perceptions as a Mediator Between Acute Stress Response and Long-Term Distress Following Natural Disasters  

Microsoft Academic Search

The mediating effect of coping self-efficacy (CSE) perceptions between acute stress responses (ASR) and 1-year distress following two disasters was tested. Between 3 and 8 weeks after the second disaster and again at 1 year, 46 residents completed questionnaires. Posttraumatic Stress Disorder (PTSD) symptoms and global distress served as outcomes. Multiple regression demonstrated that ASR and Time 1 CSE were

Charles C. Benight; Michelle L. Harper

2002-01-01

183

Effect of Contralateral Occlusion on Long-Term Efficacy of Endarterectomy in the Asymptomatic Carotid Atherosclerosis Study (ACAS)  

Microsoft Academic Search

Background and Purpose—The Asymptomatic Carotid Atherosclerosis Study (ACAS) established the effectiveness of prophylactic carotid endarterectomy, for patients in good health who had stenosis $60%, if conducted by surgeons with a surgical morbidity and mortality of ,3%. This secondary analysis was performed to determine whether the presence of contralateral cervical carotid occlusion alters the efficacy of asymptomatic ipsilateral carotid endarterectomy. Methods—One

William H. Baker; Virginia J. Howard; George Howard; James F. Toole

184

Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting  

Microsoft Academic Search

Background. Fabry disease is an X-linked disorder of glycosphingolipid catabolism that is the result of an intracellular deficiency in the lysosomal enzyme a-galactosidase A (a-Gal A). This enzymatic defect results in the accumulation of globotriaosylceramide (Gb3) within cells and causes progressive neurological, cardiovascular and renal dysfunction. Our objective is to describe the safety and renal effects of long-term enzyme replacement

Raphael Schiffmann; Markus Ries; Margaret Timmons; John T. Flaherty; Roscoe O. Brady

2006-01-01

185

Long-term safety of extended-release oxybutynin chloride in a community-dwelling population of participants with overactive bladder: A one-year study  

Microsoft Academic Search

In this multicenter, open-label study of extended- and immediate-release oxybutynin chloride, community-dwelling participants were studied for up to 12 months to evaluate the long-term safety profile of extended-release oxybutynin. Quality-of-life assessments designed to measure the impact of incontinence and evaluate treatment outcome were used to study subjective improvement.A total of 904 women and 163 men (mean age 64 years, range

Ananias Diokno; Peter Sand; Richard Labasky; Paul Sieber; Joseph Antoci; Gary Leach; Linda Atkinson; Detlef Albrecht

2002-01-01

186

Long-term, tunneled, noncuffed central venous catheter in cancer patients (Vygon): safety, efficacy, and complications  

Microsoft Academic Search

Background  Totally implantable or partially cuffed central venous catheters (CVC) are commonly used in cancer patients, but they are often expensive and may produce complications. To minimize costs, we have been using a low-cost, partially tunneled, silicone elastomer catheter with no Dacron cuff or antireflux valve (Vygon) since 2001. This study is a retrospective investigation of our experience using the Vygon

Giovanna Masci; Massimo Magagnoli; Vittorio Pedicini; Dario Poretti; Luca Castagna; Carlo Carnaghi; Emanuela Morenghi; Antonietta Del Vecchio; Rita Finotto; Giorgio Brambilla; Armando Santoro

2006-01-01

187

Long-term efficacy and safety of firocoxib in the treatment of dogs with osteoarthritis.  

PubMed

Thirty-nine client-owned dogs with osteoarthritis were treated with 5 mg/kg firocoxib administered orally, once a day for 52 weeks. Veterinary examinations were performed on approximately days 0, 15, 90, 180, 270 and 360. Twenty-five dogs completed the study. The withdrawal rate associated with gastrointestinal side effects was low (5.1 per cent of dogs). Based on the owners' assessment, 82 per cent of the dogs had improved at day 15, 84 per cent of the 32 remaining dogs had improved at day 90, and 96 per cent of the 25 dogs that completed the trial had improved at day 360. During this trial, 12 (48 per cent) of the 25 remaining dogs showed an improvement in their lameness from day 90 to day 360 (P<0.05). PMID:21642297

Autefage, A; Palissier, F M; Asimus, E; Pepin-Richard, C

2011-06-11

188

Long Term Care Study.  

National Technical Information Service (NTIS)

Long-term care needs and facilities in Saginaw, Mich., and alternatives to institutionalization were investigated. The instrument for the study was designed by the East Central Michigan Health Systems Agency. Long-term care facilities in Saginaw were surv...

1978-01-01

189

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

PubMed Central

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

Camilleri, Michael

2011-01-01

190

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

PubMed Central

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

Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

2014-01-01

191

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

192

Reporting of long-term extension studies: lack of consistency calls for consensus  

Microsoft Academic Search

Double-blind, randomised controlled studies represent the gold-standard approach to determine the safety and efficacy of therapeutic interventions. In chronic conditions such as rheumatoid arthritis (RA), long-term data are vital to confirm maintenance of effect and identify potential safety signals. The recent introduction of numerous biological therapies for RA has been followed by various long-term extension (LTE) studies. Although useful, the

Maya H Buch; Daniel Aletaha; Paul Emery; Josef S Smolen

2011-01-01

193

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

SciTech Connect

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

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

2003-02-24

194

Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene.  

PubMed

Adoptive transfer of donor-derived T lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT) without the risk for uncontrolled graft versus host disease (GvHD). Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. We now report the long-term follow-up of 10 patients infused with such safety switch-modified T cells. We find long-term persistence of iC9-modified (iC9-T) T cells in vivo in the absence of emerging oligoclonality and a robust immunologic benefit, mediated initially by the infused cells themselves and subsequently by an apparently accelerated reconstitution of endogenous naive T lymphocytes. As a consequence, these patients have immediate and sustained protection from major pathogens, including cytomegalovirus, adenovirus, BK virus, and Epstein-Barr virus in the absence of acute or chronic GvHD, supporting the beneficial effects of this approach to immune reconstitution after haplo-HSCT. This study was registered at www.clinicaltrials.gov as #NCT00710892. PMID:24753538

Zhou, Xiaoou; Di Stasi, Antonio; Tey, Siok-Keen; Krance, Robert A; Martinez, Caridad; Leung, Kathryn S; Durett, April G; Wu, Meng-Fen; Liu, Hao; Leen, Ann M; Savoldo, Barbara; Lin, Yu-Feng; Grilley, Bambi J; Gee, Adrian P; Spencer, David M; Rooney, Cliona M; Heslop, Helen E; Brenner, Malcolm K; Dotti, Gianpietro

2014-06-19

195

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.

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

2011-01-01

196

Long-term administration and efficacy of oxaliplatin with no neurotoxicity in a patient with rectal cancer: Association between neurotoxicity and the GSTP1 polymorphism  

PubMed Central

Neurotoxicity is one of the most frequent side-effects of oxaliplatin. Oxaliplatin-induced cumulative and dose-limiting neurotoxicity either results in dose reduction or decreases the patients’ quality of life. However, the symptoms of neurotoxicity often vary among patients. The current study presents the case of a male with rectal cancer, who was administered a cumulative oxaliplatin dose of >5,000 mg/m2 without developing neurotoxicity or allergic reactions. Consequently, this patient continued therapy with modified 5-fluorouracil, leucovorin and oxaliplatin treatment for four years, with stabilization of the disease. This case indicates that if oxaliplatin-containing chemotherapy shows efficacy with no toxicity, the long-term administration of oxaliplatin would be effective and tolerable. Previously, the analysis of genomic polymorphisms in drug target genes has been important for explaining interindividual variations in the efficacy and toxicity of anti-cancer drugs. In the present patient, the glutathione S-transferase P1 (GSTP1) gene polymorphism, which is involved in the detoxification of platinum drugs, was analyzed. The genotype of the present case has been revealed as wild type (Ile/Ile) genotype. In addition, the associations between oxaliplatin-induced neurotoxicity and the GSTP1 polymorphism were also assessed. Certain studies have demonstrated that oxaliplatin-induced neurotoxicity occurs more frequently in patients with the Ile/Ile genotype, while others have demonstrated that those patients with the Val/Val or Ile/Val genotypes are more likely to develop neurotoxicity. Therefore, correlation between the GSTP1 polymorphism and oxaliplatin-induced neurotoxicity remains controversial. Overall, further development of individualized chemotherapy with an analysis of genomic polymorphisms in the drug target genes is required for the prophylaxis oxaliplatin-induced neurotoxicity.

KITADE, HIRONORI; SHIMASAKI, TAKEO; IGARASHI, SAYA; SAKUMA, HIROSHI; MORI, MITSUE; TOMOSUGI, NAOHISA; NAKAI, MASUO

2014-01-01

197

Sustainable development and next generation's health: a long-term perspective about the consequences of today's activities for food safety  

Microsoft Academic Search

clInIcAl experIence Summary. Development is defined sustainable when it meets the needs of the present without compro- mising the ability of future generations to meet their own needs. Pivoting on social, environmental and economic aspects of food chain sustainability, this paper presents the concept of sustainable food safety based on the prevention of risks and burden of poor health for

Chiara Frazzoli; Carlo Petrini; Alberto Mantovani

2009-01-01

198

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

PubMed Central

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

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

1987-01-01

199

An approach to quantitative assessment of crew well-being for providing safety of long-term space missions  

NASA Astrophysics Data System (ADS)

The main destination of Life Support Systems - to support life and provide crew safety - put the problem of the most effective providing this function. In the scope of the whole mission the safety of crew depends on many interrelating features of space ship, LSS, and scenario of given mission itself. Effective risk mitigation needs optimal minimizing of all risk factors. Effective minimization presumes quantitative presentation of these factors. In the paper an approach to quantitative assessment of quality of life in the scope of previously introduced integrated coefficient of maximum reliability. One of the most significant risk factors is crew fatal mistake. There is always other-than-zero probability of a fatal human mistake in controlling the vehicle, landing module, nuclear reactor or other vital device. It is difficult to estimate the probability of such a mistake, but it is apparent that this probability increases with impaired human health. Under closed air cycling such a condition is highly probable as demonstrated by the Sick Building Syndrome (SBS) in highly sealed, so-called "energy efficient" buildings. Seemingly, the cause of SBS is a set of not completely identified factors, yet, it should be noted that in spite of complete pressurization the crew of Bios-3 did not have complaints typical for SBS. It cannot be ruled out that the higher plants may be the most realistic remedy to reduce the probability of the crew's fatal mistakes. All this gives the way to convert so difficultly formalizable parameter as quality of life into probability of accident. A simple monotonous dependence of deterioration of crew health and probability of a fatal mistake on mission time is discussed. Possible medical-biological experiments for more detailed estimations of this dependency are considered.

Bartsev, S. I.; Mezhevikin, V. V.; Okhonin, V. A.

200

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

201

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

PubMed

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

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

1987-01-01

202

Five year follow-up after a first booster vaccination against tick-borne encephalitis following different primary vaccination schedules demonstrates long-term antibody persistence and safety.  

PubMed

Long-term vaccination programs are recommended for individuals living in regions endemic for tick-borne encephalitis (TBE). Current recommendations suggest a first booster vaccine be administered 3 years after a conventional regimen or 12-18 months after a rapid regimen. However, the research supporting subsequent booster intervals is limited. The aim of this study was thus to evaluate the long-term persistence of TBE antibodies in adults and adolescents after a first booster dose with Encepur(®). A total of 323 subjects aged 15 years and over, who had received one of four different primary TBE vaccination series in a parent study, participated in this follow-up Phase IV trial. Immunogenicity and safety were assessed for up to five years after a first booster dose, which was administered three years after completion of the primary series. One subset of subjects was excluded from the booster vaccination since they had already received their booster prior to enrolment. For comparison, immune responses were still recorded for these subjects on Day 0 and on an annual basis until Year 5, but safety information was not collected. Following a booster vaccination, high antibody titers were recorded in all groups throughout the study. Neutralization test (NT) titers of ?10 were noted in at least 94% of subjects at every time point post-booster (on Day 21 and through Years 1-5). These results demonstrated that a first booster vaccination following any primary immunization schedule results in high and long-lasting (>5 years) immune responses. These data lend support to the current belief that subsequent TBE booster intervals could be extended from the current recommendation. NCT00387634. PMID:24950352

Beran, Ji?í; Xie, Fang; Zent, Olaf

2014-07-23

203

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.

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

2014-01-01

204

Establishing Long-Term Efficacy in Chronic Disease: Use of Recursive Partitioning and Propensity Score Adjustment to Estimate Outcome in MS  

PubMed Central

Context Establishing the long-term benefit of therapy in chronic diseases has been challenging. Long-term studies require non-randomized designs and, thus, are often confounded by biases. For example, although disease-modifying therapy in MS has a convincing benefit on several short-term outcome-measures in randomized trials, its impact on long-term function remains uncertain. Objective Data from the 16-year Long-Term Follow-up study of interferon-beta-1b is used to assess the relationship between drug-exposure and long-term disability in MS patients. Design/Setting To mitigate the bias of outcome-dependent exposure variation in non-randomized long-term studies, drug-exposure was measured as the medication-possession-ratio, adjusted up or down according to multiple different weighting-schemes based on MS severity and MS duration at treatment initiation. A recursive-partitioning algorithm assessed whether exposure (using any weighing scheme) affected long-term outcome. The optimal cut-point that was used to define “high” or “low” exposure-groups was chosen by the algorithm. Subsequent to verification of an exposure-impact that included all predictor variables, the two groups were compared using a weighted propensity-stratified analysis in order to mitigate any treatment-selection bias that may have been present. Finally, multiple sensitivity-analyses were undertaken using different definitions of long-term outcome and different assumptions about the data. Main Outcome Measure Long-Term Disability. Results In these analyses, the same weighting-scheme was consistently selected by the recursive-partitioning algorithm. This scheme reduced (down-weighted) the effectiveness of drug exposure as either disease duration or disability at treatment-onset increased. Applying this scheme and using propensity-stratification to further mitigate bias, high-exposure had a consistently better clinical outcome compared to low-exposure (Cox proportional hazard ratio?=?0.30–0.42; p<0.0001). Conclusions Early initiation and sustained use of interferon-beta-1b has a beneficial impact on long-term outcome in MS. Our analysis strategy provides a methodological framework for bias-mitigation in the analysis of non-randomized clinical data. Trial Registration Clinicaltrials.gov NCT00206635

Goodin, Douglas S.; Jones, Jason; Li, David; Traboulsee, Anthony; Reder, Anthony T.; Beckmann, Karola; Konieczny, Andreas; Knappertz, Volker

2011-01-01

205

Progress in the treatment of chronic hepatitis B: long-term experience with adefovir dipivoxil  

Microsoft Academic Search

Most chronic hepatitis B patients do not undergo a curative response to interferon-a or nucleoside\\/ nucleotide-based regimens and require long-term therapy. Long-term safety, efficacy and resistance profiles of hepatitis B virus (HBV) drugs are therefore crucial issues for patient management. Adefovir dipivoxil is a nucleotide prodrug indicated for the treatment of patients with hepatitis B e antigen positive or hepatitis

William E. Delaney

2007-01-01

206

Long-Term Maintenance of Weight Loss: Current Status  

Microsoft Academic Search

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

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

2000-01-01

207

Long term treatment of rheumatoid arthritis with rituximab.  

PubMed

B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). Rituximab is a chimeric monoclonal antibody that depletes B-cells by binding to the CD20 surface antigen that has been approved for the treatment of RA. Its efficacy has been clearly demonstrated by different clinical trials and, recently, in long-term observational studies. The use of rituximab in clinical practice has highlighted its efficacy and safety over more than 5 years of treatment, as well as to try to understand the timing for retreatment of patients relapsing after a good initial response. PMID:19393205

Caporali, Roberto; Caprioli, Marta; Bobbio-Pallavicini, Francesca; Bugatti, Serena; Montecucco, Carlomaurizio

2009-06-01

208

Long-term mizoribine intermittent pulse therapy for young patients with flare of lupus nephritis  

Microsoft Academic Search

Mizoribine (MZR) is a novel purine synthesis inhibitor that was developed in Japan. We previously reported the efficacy and\\u000a safety of oral MZR intermittent pulse therapy, which is associated with elevated peak serum MZR levels, in selected patients\\u000a with lupus nephritis. However, the efficacy and safety of long-term MZR intermittent pulse therapy (administered for over\\u000a 24 months) in lupus nephritis patients

Hiroshi Tanaka; Koji Tsugawa; Koichi Suzuki; Tohru Nakahata; Etsuro Ito

2006-01-01

209

Long-term benefit of hepatitis C therapy in a safety net hospital system: a cross-sectional study with median 5-year follow-up  

PubMed Central

Objectives To demonstrate the survival benefit from sustained virological response (SVR) in a safety net hospital population with limited resources for hepatitis C virus (HCV) therapy. Design and setting We conducted a retrospective study at an urban safety net hospital in the USA. Participants and intervention 242 patients receiving standard HCV therapy between 2001 and 2006. Primary and secondary outcome measures Response rates, including SVR, were recorded for each patient. Univariate and multivariate analyses were performed to identify predictors of SVR and 5-year survival. Results A total of 242 eligible patients were treated. Treatment was completed in 197 (81%) patients, with 43 patients discontinuing therapy early—32 due to adverse events and 11 due to non-compliance. Complications on treatment were frequent, including three deaths. SVR was achieved in 83 patients (34%). On multivariate analysis, independent predictors of a decreased likelihood of achieving SVR included African–American race (OR 0.20, 95% CI 0.07 to 0.54), genotype 1 HCV infection (OR 0.25, 95% CI 0.13 to 0.50) and the presence of cirrhosis (OR 0.26, 95% CI 0.12 to 0.58). Survival was 98% in those achieving SVR (median follow-up 72?months) and 71% in non-responders and those discontinuing therapy (n=91, median known follow-up 65 and 36?months, respectively). On multivariate analysis, the only independent predictor of improved survival was SVR (HR 0.12, 95% CI 0.03 to 0.52). Both cirrhosis and hypoalbuminaemia were independent predictors of increased mortality. Conclusions Treatment before histological cirrhosis develops, in combination with careful selection, may improve long-term outcomes without compromising other healthcare endeavours in safety net hospitals and areas with financial limitations.

Singal, Amit G; Dharia, Tushar D; Malet, Peter F; Alqahtani, Saleh; Zhang, Song; Cuthbert, Jennifer A

2013-01-01

210

Long-term safety of a non-chlorofluorocarbon-containing triamcinolone acetonide inhalation aerosol in patients with asthma. Azmacort HFA Study Group.  

PubMed

In response to environmental concerns regarding chlorofluorocarbon (CFC), two new triamcinolone acetonide (TAA) inhalation aerosol (Azmacort Inhalation Aerosol) formulations have been developed using a more environmentally favorable propellant, HFA-134a (1,1,1,2-tetrafluoroethane). This multicenter, open-label study evaluated the safety of switching asthma patients from TAA-CFC to one of two TAA-HFA formulations. After a 2- or 4-week baseline period during which patients received only CFC-containing TAA Inhaler, 552 patients were randomized to receive TAA-HFA 75 or 225 microg for 6 or 12 months. A total of 493 patients completed treatment. Seven patients discontinued because of adverse events and two because of ineffective asthma control. The incidence of adverse events was similar in the two treatment groups, and most events were mild to moderate in severity and were not considered related to study medication. No clinically relevant suppression of the hypophyseal-pituitary-adrenal (HPA) axis was observed. Pulmonary function tests were not adversely affected by use of either study medication, and improvements were noted in forced expiratory volume in 1 sec (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25%-75%) throughout the course of treatment. This study confirms that TAA-HFA provides effective, long-term asthma control and can safely be substituted for the currently marketed CFC-containing TAA product. PMID:10805203

Nelson, H S; Kane, R E; Petillo, J; Banerji, D

2000-04-01

211

Long-Term Safety and Tolerability of Rivastigmine in Patients With Alzheimer's Disease Switched From Donepezil: An Open-Label Extension Study  

PubMed Central

Objectives: The objective of this article is to present safety and tolerability data from the long-term extension phase of a core study conducted in patients with Alzheimer's disease (AD) who were immediately switched to rivastigmine. Method: This was a 26-week open-label extension (OLE) of a prospective, 26-week, open-label, single-arm, multicenter study conducted in the United States from October 2003 to January 2005. Patients had a diagnosis of Alzheimer's disease according to DSM-IV-TR and National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. Safety and tolerability of rivastigmine were monitored through monthly telephone contacts. At week 52, patients or caregivers were contacted by telephone to evaluate the patient's well-being. Results: 146 patients (approximately 79% of patients who completed the core phase) entered this OLE. Most patients (N = 115, 78.8%) completed the full 26 weeks of the extension phase, during which time they received a mean rivastigmine dosage of 10.5 mg/day. The number of patients reporting newly occurring or worsening adverse events decreased considerably during the OLE (N = 84, 57.5%) compared with the core phase (the first 26 weeks; N = 116, 79.5%). Most patients reported adverse events that were mild or moderate in severity. At the end of the OLE, the majority of patients (128/146; 87.7%) were still receiving treatment with rivastigmine. At week 52, most caregivers expressed satisfaction with rivastigmine treatment (77.4%) and with the changes observed in the patient's behavior during the study (71.9%). Conclusions: For patients not tolerating or not responding to donepezil, treatment with rivastigmine was safe and well tolerated for at least 52 weeks.

Figiel, Gary S.; Koumaras, Barbara; Meng, Xiangyi; Strigas, John; Gunay, Ibrahim

2008-01-01

212

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

213

Efficacy and safety of adding a second antihypertensive agent to eplerenone in patients with essential hypertension  

Microsoft Academic Search

Aldosterone is a mineralocorticoid that plays an important, independent role in the pathophysiology of hypertension. Hypertension treatment often requires combination therapy; standard therapies, including ACEIs and ARBs, do not provide sustained reductions in aldosterone. This 14-month open-label, titration-to-effect study examined the efficacy and long-term safety of eplerenone (EPL), a selective aldosterone blocker, in 582 patients with mild-to-moderate hypertension. The dose

E. Burgess; L. M. Ruilope; E. Francischetti; F. Martinez; M. Gatlin; K. Feaheny; S. Krause

2003-01-01

214

Safety pharmacology in 2010 and beyond: survey of significant events of the past 10 years and a roadmap to the immediate-, intermediate- and long-term future in recognition of the tenth anniversary of the Safety Pharmacology Society.  

PubMed

In recognition of the tenth anniversary of the Safety Pharmacology Society (SPS), this review summarizes the significant events of the past 10years that have led to the birth, growth and evolution the SPS and presents a roadmap to the immediate-, intermediate- and long-term future of the SPS. The review discusses (i) the rationale for an optimal non-clinical Safety Pharmacology testing, (ii) the evolution of Safety Pharmacology over the last decade, (iii) its impact on drug discovery and development, (iv) the merits of adopting an integrated risk assessment approach, (v) the translation of non-clinical findings to humans and finally (vi) the future challenges and opportunities facing this discipline. Such challenges include the emergence of new molecular targets and new approaches to treat diseases, the rapid development of science and technologies, the growing regulatory concerns and associated number of guidance documents, and the need to train and educate the next generation of safety pharmacologist. PMID:21689769

Bass, Alan S; Vargas, Hugo M; Valentin, Jean-Pierre; Kinter, Lewis B; Hammond, Tim; Wallis, Rob; Siegl, Peter K S; Yamamoto, Keiji

2011-01-01

215

Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine  

Microsoft Academic Search

BACKGROUND: Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits.PATIENTS AND METHODS: Eligible patients had a body-mass index greater than 30 kg\\/m2; those who lost 6 kg

Marian Apfelbaum; Philippe Vague; Olivier Ziegler; Corinne Hanotin; Florence Thomas; Eric Leutenegger

1999-01-01

216

Vagus nerve stimulation for treatment of medically intractable seizures. Evaluation of long-term outcome  

Microsoft Academic Search

Vagus nerve stimulation (VNS) constitutes an adjunctive, modern management of medically intractable seizures, especially when surgery is inadvisable. Objective: To evaluate the long-term results as regards efficacy, safety and tolerability of VNS in epileptic subjects, with focal and\\/or generalised seizures, refractory to old and new AEDs, without indication for resective surgery. Patients: 51 epileptic subjects (30 males, 21 females), aged

Paolo Tanganelli; Sergio Ferrero; Patrizio Colotto; Giovanni Regesta

2002-01-01

217

Impact of stent deployment procedural factors on long-term effectiveness and safety of sirolimus-eluting stents (final results of the multicenter prospective STLLR trial).  

PubMed

Drug-eluting stent failures were associated with various clinical factors. However, the clinical impact of stent deployment technique was unknown. This study was designed to evaluate the frequency and impact of suboptimal percutaneous coronary intervention on long-term outcomes of 1,557 patients treated with sirolimus-eluting stents (SESs) in 41 US hospitals. All steps of the interventional procedure were scrutinized by an independent core laboratory to determine the occurrence of geographic miss (GM). GM included longitudinal (LGM; injured or diseased segment not covered by SES) or axial GM (balloon-artery size ratio <0.9 or >1.3) mismatches. Patients with and without GM were stratified (GM vs no-GM group). Patients, investigators, and the independent clinical event adjudication committee were blind to study group assignments. The primary end point was 1-year target-vessel revascularization (TVR) rate. Incidences and predictors of GM and safety outcomes were secondary end points. GM occurred in 943 patients (66.5%): 47.6% had LGM, 35.2% had axial GM, and 16.5% had both. One-year TVR rates were 5.1% in the GM group versus 2.5% in the no-GM group (p=0.025). TVR was 6.1% in the LGM versus 2.6% in the no-LGM subgroups (p=0.001). The association of GM with 1-year TVR was independent of clinical or anatomic factors (hazard ratio 2.0, 95% confidence interval 1.0 to 4.02, p=0.05). There was a 3-fold increase in myocardial infarction rates associated with GM (2.4% vs 0.8%; p=0.04). In conclusion, GM occurred frequently during SES implantation and was associated with increased risk of TVR and myocardial infarction at 1 year. These results emphasized the need for improvement in contemporary percutaneous coronary intervention practices and technologies. PMID:18549844

Costa, Marco A; Angiolillo, Dominick J; Tannenbaum, Mark; Driesman, Mitchell; Chu, Alan; Patterson, John; Kuehl, William; Battaglia, Joseph; Dabbons, Samir; Shamoon, Fayez; Flieshman, Bruce; Niederman, Alan; Bass, Theodore A

2008-06-15

218

A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia  

PubMed Central

Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n?=?130) or SOC (n?=?131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P?=?.184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P?=?.044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P?=?.505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P?=?.011) and akathisia (P?=?.029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was significantly greater in the SOC group at 24-week endpoint (P?=?.004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P?=?.444). Conclusion These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics. Trials registration A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia ClinicalTrials.gov identifier: NCT00845026.

2013-01-01

219

Zonisamide: its pharmacology, efficacy and safety in clinical trials.  

PubMed

Zonisamide is a benzisoxazole derivative, chemically unrelated to other antiepileptic drugs, that appears to have multiple mechanisms of action, including inhibition of Na(+) channels and reduction of T-type Ca(2+) currents. It is currently licensed in Europe and the USA for adjunctive treatment of partial seizures in adults, and in Europe as monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy. Zonisamide displays predictable, dose-dependent pharmacokinetics and has a half-life of ~60 h, allowing once- or twice-daily administration. It has a low potential for interactions with other medications, including oral contraceptives. The clinical efficacy of adjunctive zonisamide therapy has been established in four pivotal, phase III, randomized, double-blind, placebo-controlled trials, which together included approximately 850 patients, aged 12-77 years, with refractory partial epilepsy. In all four trials, zonisamide 300-600 mg/day resulted in significant reductions in median total seizure rates vs placebo, and zonisamide was generally well tolerated; the most frequently reported adverse events being somnolence, dizziness and anorexia/weight loss. Subanalysis of the primary European trial indicated that zonisamide was effective when administered as first-line adjunctive treatment, and a long-term extension to the same trial demonstrated that the efficacy and safety/tolerability of adjunctive zonisamide was sustained for up to 36 months. Once-daily monotherapy with zonisamide (200-500 mg/day) has been shown to be non-inferior to, and as well tolerated as, twice-daily monotherapy with controlled-release carbamazepine (400-1200 mg/day) in adults with newly diagnosed partial epilepsy. Zonisamide has also been shown to have favourable long-term retention rates, an important indication of its overall effectiveness. PMID:23106522

Brodie, M J; Ben-Menachem, E; Chouette, I; Giorgi, L

2012-01-01

220

Lack of bone neoplasms and persistence of bone efficacy in cynomolgus macaques after long-term treatment with teriparatide [rhPTH(1-34)].  

PubMed

In rats, teriparatide [rhPTH(1-34)] causes marked increases in bone mass and osteosarcoma. In primates, teriparatide causes lesser increases in bone mass, and osteosarcomas have not been reported. Previous studies in primates were not designed to detect bone tumors and did not include a prolonged post-treatment observation period to determine whether tumors would arise after cessation of treatment. Ovariectomized (OVX), skeletally mature, cynomolgus monkeys (n = 30 per group) were given teriparatide for 18 mo at either 0 or 5 microg/kg/d subcutaneously. After 18 mo of treatment, subgroups of six monkeys from both groups were killed and evaluated, whereas all remaining monkeys entered a 3-yr observation period in which they did not receive teriparatide. Surveillance for bone tumors was accomplished with plain film radiographs, visual examination of the skeleton at necropsy, and histologic evaluation of multiple skeletal sites. Quantitative assessments of bone mass, architecture, and strength were also performed. After the 18-mo treatment period, vertebral BMD, BMC, and strength (ultimate load) were increased by 29%, 36%, and 52%, respectively, compared with OVX controls. Proximal femur BMD, BMC, and strength were also increased by 15%, 28% and 33%, respectively. After 3 yr without treatment, no differences in bone mass or strength at the vertebra were observed relative to OVX controls; however, the femoral neck showed significant persistence in stiffness (20%), BMC (14%), and trabecular BV/TV (53%), indicating a retention of teriparatide efficacy at the hip. Radiographs and histology did not identify any bone proliferative lesions or microscopic lesions of osteosarcoma at the end of the treatment or observation period. These data indicate that teriparatide did not induce bone proliferative lesions over a 4.5-yr interval of observation, including 18 mo of treatment and 3 yr of follow-up observation. Bone analyses confirmed that teriparatide caused increases in bone mass and strength, consistent with previous studies. During the withdrawal phase, beneficial effects of teriparatide treatment on the vertebra were lost; however, some of the beneficial effects on the proximal femur persisted for 3 yr after cessation of treatment. Although the lack of bone tumors in this study provides some additional reassurance regarding the safety of teriparatide for the primate skeleton, the small group size and other limitations of this, or any other animal study, limit the ability to draw definitive conclusions regarding the risk of bone tumor developments in patients. PMID:18684088

Vahle, John L; Zuehlke, Ulrich; Schmidt, Allen; Westmore, Michael; Chen, Peiqi; Sato, Masahiko

2008-12-01

221

Ibuprofen: pharmacology, efficacy and safety  

Microsoft Academic Search

Objectives  This review attempts to bring together information from a large number of recent studies on the clinical uses, safety and\\u000a pharmacological properties of ibuprofen. Ibuprofen is widely used in many countries for the relief of symptoms of pain, inflammation\\u000a and fever. The evidence for modes of action of ibuprofen are considered in relation to its actions in controlling inflammation,\\u000a pain

K. D. Rainsford

2009-01-01

222

Self-assemblies of pH-activatable PEGylated multiarm poly(lactic acid-co-glycolic acid)-doxorubicin prodrugs with improved long-term antitumor efficacies.  

PubMed

Two pH-activatable star-shaped prodrugs are synthesized through the condensation reaction between Y- or dumbbell-shaped poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PEG-PLGA) copolymer and acid-sensitive cis-aconityl-doxorubicin. The prodrugs self-assemble into micelles with favorable hydrodynamic radii and relatively low critical micelle concentrations. In vitro DOX release from prodrug micelles is accelerated by the decrease of the PLGA content or at the late endosomal pH. The efficient cellular uptake and intracellular DOX release of the prodrug micelles are confirmed and the improved long-term anti-proliferative activities of prodrug micelles are revealed. These features suggest that the prodrugs provide a favorable approach to construct effective polymeric drug delivery systems for malignancy therapy. PMID:23852836

Ding, Jianxun; Li, Di; Zhuang, Xiuli; Chen, Xuesi

2013-10-01

223

[Efficacy and tolerability of long-term using of glatimer acetate (copaxone): a 10 year-study in the Moscow Municipal Multiple Sclerosis center].  

PubMed

Experience of 10-year administration of glatimer acetate (copaxone) in 74 patients with active remitting multiple sclerosis is summarized. The significant decrease in the frequency of exacerbations was seen over these ten years. Disease severity on the EDSS was stable and decreased only to the end of the 10-year period. The positive stable clinical dynamics did not depend on the disease severity at baseline. The drug was well-tolerated that allowed to control the course of multiple sclerosis: 64.8% of patients had no more than one exacerbation over 10 years and in 71.6% patients, the disease progression was absent or minimal (less than one score on EDSS). It has been concluded, that the long-term 10-year treatment with copaxone enables to control the development of disease in many patients. PMID:22677683

Bo?ko, A N; Davydovskaia, M V; Demina, T L; Lashch, N Iu; Ovcharov, V V; Popova, E V; Popova, N F; Romashkin, A V; Bo?ko, O V; Khachanova, N V; Sharanova, S N; Shchur, S G; Gusev, E I

2012-01-01

224

Efficacy of the Disappearance of Lateral Spread Response before and after Microvascular Decompression for Predicting the Long-Term Results of Hemifacial Spasm Over Two Years  

PubMed Central

Objective The purpose of this large prospective study is to assess the association between the disappearance of the lateral spread response (LSR) before and after microvascular decompression (MVD) and clinical long term results over two years following hemifacial spasm (HFS) treatment. Methods Continuous intra-operative monitoring during MVD was performed in 244 consecutive patients with HFS. Patients with persistent LSR after decompression (n=22, 9.0%), without LSR from the start of the surgery (n=4, 1.7%), and with re-operation (n=15, 6.1%) and follow-up loss (n=4, 1.7%) were excluded. For the statistical analysis, patients were categorized into two groups according to the disappearance of their LSR before or after MVD. Results Intra-operatively, the LSR was checked during facial electromyogram monitoring in 199 (81.5%) of the 244 patients. The mean follow-up duration was 40.9±6.9 months (range 25-51 months) in all the patients. Among them, the LSR disappeared after the decompression (Group A) in 128 (64.3%) patients; but in the remaining 71 (35.6%) patients, the LSR disappeared before the decompression (Group B). In the post-operative follow-up visits over more than one year, there were significant differences between the clinical outcomes of the two groups (p<0.05). Conclusion It was observed that the long-term clinical outcomes of the intra-operative LSR disappearance before and after MVD were correlated. Thus, this factor may be considered a prognostic factor of HFS after MVD.

Kang, Min-Cheol; Choi, Yu-Seok; Choi, Hak-Ki; Lee, Sang-Hoon; Ghang, Chang-Gu

2012-01-01

225

Early surgical abortion: Efficacy and safety  

Microsoft Academic Search

Objective: Because of concern over the higher rates of failed abortion, many clinicians defer surgical abortion until 7 menstrual weeks or later. We conducted this study to evaluate the efficacy and safety of early surgical abortions that are performed by numerous physicians in a community-based setting. Study Design: We prospectively gathered data on all eligible patients who had surgical abortions

Maureen E. Paul; Caroline M. Mitchell; Angela J. Rogers; Michelle C. Fox; Elyse G. Lackie

2002-01-01

226

Safety and Efficacy of Neonatal Vaccination  

PubMed Central

Newborns have an immature immune system that renders them at high risk for infection while simultaneously reducing responses to most vaccines, thereby posing challenges in protecting this vulnerable population. Nevertheless, certain vaccines, such as Bacillus Calmette Guérin (BCG) and Hepatitis B vaccine (HBV), do demonstrate safety and some efficacy at birth, providing proof of principal that certain antigen-adjuvant combinations are able to elicit protective neonatal responses. Moreover, birth is a major point of healthcare contact globally meaning that effective neonatal vaccines achieve high population penetration. Given the potentially significant benefit of vaccinating at birth, availability of a broader range of more effective neonatal vaccines is an unmet medical need and a public health priority. This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination.

Demirjian, Alicia; Levy, Ofer

2009-01-01

227

Experience in the long-term treatment of patients with hirsutism and/or acne with cyproterone acetate-containing preparations: efficacy, metabolic and endocrine effects.  

PubMed

The effects and side effects of long-term treatment with cyproterone acetate (CPA) are described. Hammerstein's reverse sequential regimen (10 days 100 mg CPA, 21 days 50 micrograms ethinylestradiol (EE)) was used in most cases, although postmenopausal and hysterectomized women received 50 mg CPA/day continuously as monotherapy. The degree of androgenization was assessed in 143 of a total group of 188 women treated from 1968 to the present. The results of the treatment were good or very good in about 75% of hirsutism patients and in more than 90% of acne patients. Adverse events were recorded in 23% of cases. Most were mild and transient, and caused discontinuation of the therapy in only 9% of patients. From this population representing all cases treated and analysed retrospectively, a subgroup of patients was selected for a prospective investigation. Thirty-five patients with good response to CPA and longlasting therapy were included into this 2-year follow-up study; of these, 24 had previously received CPA for 5 or more years, 9 for more than 10 years and 2 for more than 15 years. Treatment in these patients consisted of 5 different regimens of various doses of CPA combined with EE and CPA alone in order to evaluate possible effects of concomitant estrogen treatment as well as a possible dose- or time-dependency of potential side effects. Clinicochemical, metabolic and endocrine parameters were determined at the start and end of the study. The hematological and clinicochemical parameters were within the normal ranges. There was a slight decrease of glucose tolerance and a moderate increase of insulin and C peptide after oral glucose loading. The effects of CPA and EE on lipometabolism were slight and apparently dependent on the dose of CPA and the therapeutic regimen. No suppression of adrenal function or of responsiveness to ACTH was seen. Fasting prolactin levels and serum prolactin concentrations after provocation with metoclopramide did not show any gross deviations. Sonography of the breast and liver did not show any abnormalities apart from adenofibrosis or mastopathy in 2 patients. In conclusion, CPA with or without EE was in our hands an effective and safe method of long-term treatment of hirsutism and/or acne in women. PMID:7584530

van Wayjen, R G; van den Ende, A

1995-01-01

228

Long-term testing  

SciTech Connect

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.

1994-12-31

229

Is there sufficient evidence to support the long-term efficacy of mineral trioxide aggregate (MTA) for endodontic therapy in primary teeth?  

PubMed

Several papers have been published to illustrate the effectiveness of mineral trioxide aggregate (MTA) as a pulpotomy medicament. Most of these reports do not offer a critical assessment on the data quality. Therefore, this review evaluated whether the currently available evidence is of an appropriate quality to support the long-term effectiveness of MTA as a pulpotomy medicament in primary molars using a standardized assessment criterion. A comprehensive literature search of human clinical outcome studies, which employed MTA as a pulpotomy medicament in primary teeth, was conducted using the MEDLINE database. Two independent observers rated these articles using the standardized assessment criteria. Furthermore, based on the initial sample mentioned in the individual studies and the sample included for the final analysis, the drop-out rates were calculated. Twenty-two studies were included for quality assessment with an excellent interobserver agreement. None of the 22 studies obtained grade A, four studies attained grade B1, five were graded B2 and 13 received grade C. Based on the assessment criteria employed, there was no evidence that MTA was better than present materials and techniques as a pulpotomy medicament. Furthermore, given the low quality of data, it is highly desirable to establish standard requisites for conducting and reporting on pulp therapy studies in primary teeth so as to benefit both researchers and clinicians to produce high-quality studies that are comparable and to prevent the misuse of clinical material and resources. PMID:23136828

Anthonappa, R P; King, N M; Martens, L C

2013-03-01

230

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

231

Perfusion SPECT Changes After Acute and Chronic Vagus Nerve Stimulation in Relation to Prestimulus Condition and Long-Term Clinical Efficacy  

Microsoft Academic Search

Left-sided vagus nerve stimulation (VNS) is an efficacious treat- ment for patients with refractory epilepsy. Previous studies have implicated thalamic and mesial temporal involvement in acute stimulation. In this study, acute and chronic effects of VNS in patients with refractory complex partial seizures with or without secondary generalization (CPS SG) were evaluated with re- spect to the prestimulus condition and

Koenraad Van Laere; Kristl Vonck; Paul Boon; Jan Versijpt; Rudi Dierckx

232

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

PubMed

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

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

2013-08-01

233

Long-term safety of Mometasone Furoate administered via a dry powder inhaler in children: Results of an open-label study comparing Mometasone Furoate with Beclomethasone Dipropionate in children with persistent asthma  

Microsoft Academic Search

BACKGROUND: To assess the long-term pediatric safety of 2 doses of mometasone furoate administered via a dry powder inhaler (MF-DPI) for mild-to-moderate persistent asthma and compare them with that of beclomethasone dipropionate administered via a metered dose inhaler (BDP-MDI) in the treatment of persistent asthma. Both MF-DPI doses tested are twice the approved pediatric dosage of 100 ?g once-daily (QD)

Michael Noonan; Jeffrey Leflein; Jonathan Corren; Heribert Staudinger

2009-01-01

234

Isolation and transplantation of highly purified autologous peripheral CD34+ progenitor cells: purging efficacy, hematopoietic reconstitution and long-term outcome in children with high-risk neuroblastoma  

Microsoft Academic Search

We have investigated the purging efficacy of positive selection of autologous mobilized CD34+ peripheral stem cells in 22 children with high-risk neuroblastoma. CD34+ cell selection was performed using the method of magnetic-activated cell sorting (MACS). The median purity of the CD34+ cells post selection was 97.6% (range 81.7–99.7). For detection of contaminating neuroblastoma cells before and after CD34+ selection, the

R Handgretinger; P Lang; K Ihm; M Schumm; A Geiselhart; E Koscielniak; B Hero; T Klingebiel; D Niethammer

2002-01-01

235

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.

2014-01-01

236

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

PubMed

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

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

2014-02-01

237

Safety, long-term results, and predictors of recurrence after complete endocardial ventricular tachycardia substrate ablation in patients with previous myocardial infarction.  

PubMed

Conduction channels and electrograms with isolated component/late potentials are sensitive markers of the substrate of post-myocardial infarction sustained monomorphic ventricular tachycardia (VT). Ablation of all conduction channels and isolated component/late potentials (complete endocardial VT substrate ablation [CEVTSA]) during sinus rhythm could simplify and facilitate the ablation procedure, mainly in patients without references for clinical VT substrate identification. The aim of this study was to assess the safety, efficacy, and predictors of VT recurrence after CEVTSA. Electroanatomic mapping and CEVTSA were performed in 59 post-myocardial infarction patients (mean age 67 ± 9 years, mean left ventricular ejection fraction 30 ± 11%), 24 of whom did not have clinical VT substrate references. The mean areas of scar (?1.5 mV) and dense scar (?0.5 mV) were 76 ± 42 and 34 ± 24 cm(2), respectively; isolated component/late potentials and conduction channels were identified and ablated in 97% and 83% of patients (mean ablation area 14 ± 10 cm(2)). No life-threatening complications occurred during the procedure. After 1 year and at the end of follow-up (mean 39 ± 21 months), 81% and 58% of patients were free of VT. No differences were observed between patients with and without specific clinical VT substrate identification. Univariate analysis identified the left ventricular ejection fraction, VT cycle length (VTCL), infarct location (inferior vs anterior), and dense scar area as predictors of VT recurrence, and Cox analysis identified VTCL (hazard ratio 0.42, p <0.001) and dense scar area (hazard ratio 2.65, p <0.0006) as independent predictors. No patients with dense scar area ?25 cm(2) and VTCL >350 ms had recurrences. In conclusion, CEVTSA is safe and effective, even in patients without clinical VT substrate identification. Scar area and VTCL are valuable predictors of VT recurrence. PMID:23228925

Arenal, Ángel; Hernández, Jesús; Calvo, David; Ceballos, Cecilia; Atéa, Leonardo; Datino, Tomás; Atienza, Felipe; González-Torrecilla, Esteban; Eídelman, Gabriél; Miracle, Ángel; Avila, Pablo; Bermejo, Javier; Fernández-Avilés, Francisco

2013-02-15

238

The value of information generated by long-term toxicity studies in the dog for the nonclinical safety assessment of pharmaceutical compounds.  

PubMed

Data on 117 pharmaceutical compounds in the CMR toxicology database have been analyzed to determine what new toxicological information was provided by the dog in chronic (6 months or longer) toxicity testing. For more than half of the 117 compounds, all salient effects in the dog were seen for the first time within 3 months. For just under one-third of the compounds, any effects that occurred for the first time beyond 3 months in the dog were also seen in studies in the rat. Only 13 of the 117 compounds showed new and possibly important effects in the chronic study. No particular therapeutic class nor any other single circumstance was implicated in these 13 cases. Types of late-onset findings in the dog occurring with more than 1 compound included nonspecific effects or hypertrophic/hyperplastic changes. There may be several reasons, pragmatic as well as scientific, why it can sometimes be desirable to carry out chronic repeat-dose studies of 6 months or longer in the dog. However, the results of this retrospective evaluation have demonstrated that in the large majority of cases analyzed, long-term toxicity studies in the dog provide relatively little qualitatively new toxicological information not already gained from a short-term (3 month) study in the dog in conjunction with short- and long-term studies in the rat. PMID:7601320

Parkinson, C; Lumley, C E; Walker, S R

1995-04-01

239

Presynaptic long-term plasticity  

PubMed Central

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

Yang, Ying; Calakos, Nicole

2013-01-01

240

Long-Term Efficacy Following Readministration of an Adeno-Associated Virus Vector in Dogs with Glycogen Storage Disease Type Ia  

PubMed Central

Abstract Glycogen storage disease type Ia (GSD-Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), primarily found in liver and kidney, which causes life-threatening hypoglycemia. Dogs with GSD-Ia were treated with double-stranded adeno-associated virus (AAV) vectors encoding human G6Pase. Administration of an AAV9 pseudotyped (AAV2/9) vector to seven consecutive GSD-Ia neonates prevented hypoglycemia during fasting for up to 8?hr; however, efficacy eventually waned between 2 and 30 months of age, and readministration of a new pseudotype was eventually required to maintain control of hypoglycemia. Three of these dogs succumbed to acute hypoglycemia between 7 and 9 weeks of age; however, this demise could have been prevented by earlier readministration an AAV vector, as demonstrated by successful prevention of mortality of three dogs treated earlier in life. Over the course of this study, six out of nine dogs survived after readministration of an AAV vector. Of these, each dog required readministration on average every 9 months. However, two were not retreated until >34 months of age, while one with preexisting antibodies was re-treated three times in 10 months. Glycogen content was normalized in the liver following vector administration, and G6Pase activity was increased in the liver of vector-treated dogs in comparison with GSD-Ia dogs that received only with dietary treatment. G6Pase activity reached approximately 40% of normal in two female dogs following AAV2/9 vector administration. Elevated aspartate transaminase in absence of inflammation indicated that hepatocellular turnover in the liver might drive the loss of vector genomes. Survival was prolonged for up to 60 months in dogs treated by readministration, and all dogs treated by readministration continue to thrive despite the demonstrated risk for recurrent hypoglycemia and mortality from waning efficacy of the AAV2/9 vector. These preclinical data support the further translation of AAV vector–mediated gene therapy in GSD-Ia.

Demaster, Amanda; Luo, Xiaoyan; Curtis, Sarah; Williams, Kyha D.; Landau, Dustin J.; Drake, Elizabeth J.; Kozink, Daniel M.; Bird, Andrew; Crane, Bayley; Sun, Francis; Pinto, Carlos R.; Brown, Talmage T.; Kemper, Alex R.

2012-01-01

241

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.

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

2010-01-01

242

Safety and efficacy of saphenectomy in elderly patients  

PubMed Central

Summary Aim The aim of this study is to evaluate safety and efficacy of saphenactomy in elderly patients. Patients and methods A total of 358 patients with varicose veins of the lower limbs treated between January 2001 and December 2011. 213 of these were patients under 65 years old and 145 patients were over this age. We have evaluated short- and long-term complications to compare the results among young and elderly patients. Results Postoperative complications that occurred were: infection, haematoma, nerve injury (paresthesia and pain) and deep vein thrombosis. Although a trend towards better results was observed among the young patients, no significant differences were shown in our experience. Conclusion Elective saphenectomy has a good outcome also in the elderly patients. The slightly higher rate of complications that occurred in older patients is not significant and does not support advising against the use of this surgical approach in the elderly. So in our opinion saphenectomy is quite safe and feasible also in patients over 65 years.

MILONE, M.; MAIETTA, P.; BIANCO, P.; PISAPIA, A.; SHATALOVA, O.; TAFFURI, C.; SALVATORE, G.; MUSELLA, M.; MILONE, F.

2013-01-01

243

Herbal ephedra\\/caffeine for weight loss: a 6-month randomized safety and efficacy trial  

Microsoft Academic Search

Objective: To examine long-term safety and efficacy for weight loss of an herbal Ma Huang and Kola nut supplement (90\\/192 mg\\/day ephedrine alkaloids\\/caffeine).Design: Six-month randomized, double-blind placebo controlled trial.Subjects: A total of 167 subjects (body mass index (BMI) 31.8±4.1 kg\\/m2) randomized to placebo (n=84) or herbal treatment (n=83) at two outpatient weight control research units.Measurements: Primary outcome measurements were changes

CN Boozer; PA Daly; P Homel; JL Solomon; D Blanchard; JA Nasser; R Strauss; T Meredith

2002-01-01

244

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

PubMed Central

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

Wieder, Devorah R; Pattimakiel, Lynn

2010-01-01

245

Long-term efficacy of low-dose all-trans retinoic acid plus minimal chemotherapy induction followed by the addition of intravenous arsenic trioxide post-remission therapy in newly diagnosed acute promyelocytic leukaemia.  

PubMed

We evaluated the efficacy of low-dose all-trans retinoic acid (ATRA) plus minimal chemotherapy for induction in newly diagnosed acute promyelocytic leukaemia (APL). Furthermore, we compared its long-term outcome with or without the addition of intravenous arsenic trioxide (ATO) in post-remission therapy. From January 2004 to September 2011, a total of 109 patients with a median age of 41?years (range 14-73) were enrolled in the study. Two arms were assigned according to post-remission protocols: ATO group cases were subsequently treated with intravenous ATO, standard chemotherapy, and ATRA. No-ATO group cases were subsequently treated with chemotherapy and ATRA only. Patients were monitored of minimal residual disease (MRD) by reverse-transcriptase polymerase chain reaction. The haematologic complete remission (CR) rate was 96.3%. The early death rate was 0.9%. At a median follow-up of 49?months (range 8-102?months), the Kaplan-Meier estimates of 5-year relapse-free survival were significantly better for patients in the ATO group than in the no-ATO group, 94.4% vs 54.8% (p?=?0.0001), and the 5-year overall survival rate was 95.7% vs 64.1%, in the two groups (p?=?0.003). Our data show that low-dose ATRA plus minimal chemotherapy exhibits efficacy in induction therapy for untreated APL and suggest that the addition of ATO to post-remission therapy significantly improves the long-term outcome. PMID:23963734

Lou, Yinjun; Qian, Wenbin; Meng, Haitao; Mai, Wenyuan; Tong, Hongyan; Tong, Yin; Huang, Jian; Jin, Jie

2014-03-01

246

Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus  

Microsoft Academic Search

Background. Switching from calcineurin inhibitors (CNIs) to sirolimus might improve renal function in chronic renal transplant patients. Methods. In a prospective study, we assessed long- term efficacy and safety parameters in 43 renal transplant recipients who were switched from a CNI (cyclosporin A, 65%; and tacrolimus, 35%) to sirolimus for either chronic allograft dysfunction (n ¼ 38) or recurrent cutaneous

Viorica Bumbea; Nassim Kamar; David Ribes; Laure Esposito; Anne Modesto; Joelle Guitard; Ghassan Nasou; Dominique Durand; Lionel Rostaing

247

[Liposomal-amphotericin B efficacy and safety].  

PubMed

Liposomal amphotericin B (L-AMB), a lipid-based amphotericin B formulation, has been used in Japan since June 2006 to treat fungal infection. In the 3 years since L-AMB was launched, few reports have been made on its status. To ensure its appropriate use, we restrospectively reviewed its efficacy and safety in treating fungal infections. 25 subjects with fungal infection treated with L-AMB from April 2007 until February 2008. Of those, 16 showed clinical improvement. Elevated serum creatinine occurred in 1 and decreased serum potassium in 6. We found a positive relationship between the serum potassium decrease and L-AMB dose. Logistic regression analysis of this relationship showed that serum potassium tended to fall on day 5 to 6 of L-AMB administration. While L-AMB appears highly effective in fungal infection, it requires serum potassium monitoring to ensure patient safety. PMID:20420165

Hamada, Yukihiro; Komatsu, Toshiaki; Seto, Yoshinori; Matsubara, Hajime; Kume, Hikaru; Sunakawa, Keisuke; Yago, Kazuo

2010-03-01

248

Basics (Long-Term Care)  

MedlinePLUS

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

249

BHT, Long-Term Toxicity.  

National Technical Information Service (NTIS)

The Chemical Manufacturers Association (CMA) recently received preliminary results of a long-term toxicity study on butylated hydroxytoluene (BHT) in rats. The study was conducted by the Institute of Toxicology, National Food Institute of Denmark. Prelimi...

1983-01-01

250

Topical 5% Imiquimod Long-Term Treatment of Cutaneous Warts Resistant to Standard Therapy Modalities  

Microsoft Academic Search

Background: Long-lasting cutaneous warts may represent an unbearable stigma to patients and therefore pose a singular challenge for the physician. Generally, these warts are induced by human papillomavirus (HPV) 2, HPV-27 or HPV-57. Objectives: The present study was conducted to evaluate the efficacy and safety of long-term treatment with imiquimod 5% cream applied to long-lasting (mean duration 6.3 years) common

E.-I. Grussendorf-Conen; S. Jacobs; A. Rübben; U. Dethlefsen

2002-01-01

251

Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk  

Microsoft Academic Search

OBJECTIVE: Recent reports warn that the worldwide cell culture capacity is\\u000a insufficient to fulfill the increasing demand for human protein drugs.\\u000a Production in milk of transgenic animals is an attractive alternative.\\u000a Kilogram quantities of product per year can be obtained at relatively low\\u000a costs, even in small animals such as rabbits. We tested the long-term\\u000a safety and efficacy of recombinant

Hout van den J. M. P; Joep H. J. Kamphoven; J. P. Brakenhoff; A. H. Cromme-Dijkhuis; N. Weisglas-Kuperus; A. J. J. Reuser; A. G. Vulto; W. C. J. Hop; Corven van E. J; O. P. van Diggelen; Ploeg van der A. T; P. A. van Doorn; E. I. van der Voort; Doorn van P. A; E. J. van Corven; J. L. van Hove; J. A. M. Smeitink; G. de Jong; L. P. F. Winkel; A. T. van der Ploeg

2004-01-01

252

Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis  

Microsoft Academic Search

BACKGROUND: The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA). As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily

Roy Fleischmann; Hyman Tannenbaum; Neha P Patel; Marianne Notter; Peter Sallstig; Jean-Yves Reginster

2008-01-01

253

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

254

Efficacy and safety of intrauterine insemination in patients with moderate-to-severe endometriosis.  

PubMed

Performing intrauterine insemination (IUI) in moderate-to-severe endometriosis patients is not implemented in international guidelines, as only limited data exist on treatment efficacy and safety. This retrospective study examined the efficacy and safety of two IUI treatment strategies performed between January 2007 and July 2012 in moderate-to-severe endometriosis patients. Eight (40.0%) versus seven (15.6%) ongoing pregnancies were accomplished in patients undergoing IUI with ovarian stimulation (n=20, 61 cycles) versus IUI without ovarian stimulation in the first three cycles followed by IUI with ovarian stimulation (IUI with natural/ovarian stimulation; n=45, 184 cycles). Preceding long-term pituitary down-regulation tended to result in a higher ongoing pregnancy rate (adjusted HR 1.8) and a higher chance of endometriosis recurrence (adjusted HR 2.3). Eight (40.0%) versus 16 (35.6%) recurrences of endometriosis complaints were reported in patients receiving IUI with ovarian stimulation versus IUI with natural/ovarian stimulation. IUI might be a valuable treatment in moderate-to-severe endometriosis patients and IUI with ovarian stimulation should be offered over IUI with natural/ovarian stimulation. Preceding long-term pituitary down-regulation might positively influence the ongoing pregnancy rate and can be considered. Whether this treatment strategy can be structurally offered prior to IVF must be investigated in a randomized controlled trial. PMID:24656562

van der Houwen, Lisette E E; Schreurs, Anneke M F; Schats, Roel; Heymans, Martijn W; Lambalk, Cornelis B; Hompes, Peter G A; Mijatovic, Velja

2014-05-01

255

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

256

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

257

Current Antiviral Therapy of Chronic Hepatitis B: Efficacy and Safety  

Microsoft Academic Search

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

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

258

Opioid-Induced Constipation in Advanced Illness: Safety and Efficacy of Methylnaltrexone Bromide  

PubMed Central

Constipation, one of the major side effects of opiates used in palliative care, can impair patients’ quality of life to a point where it prevents sufficient pain control. Methylnaltrexone is a novel ?-receptor antagonist, which does not pass the blood brain barrier. It is licensed to treat opiate induced constipation for patients with advanced diseases. This review article presents an overview of pharmacology and safety of its application, evidence of its efficacy and economic aspects of its use in clinical practice. Available data are limited but strongly suggest that methylnaltrexone causes laxation in less than 24 hours for at least half of those patients over the first two weeks of usage without impairing pain control or causing serious adverse effects. To avoid danger of gastrointestinal perforation it is contraindicated for patients at risk for that complication. More research is needed to evaluate its long-term efficacy and economic impact.

Bader, S.; Jaroslawski, K.; Blum, H.E.; Becker, G.

2011-01-01

259

Modeling of Long Term Care.  

National Technical Information Service (NTIS)

Long-term care (LTC) refers to services for those who are chronically ill with physical or mental disabilities. This monograph focuses on those people who require government assistance in obtaining such care. It explores the use of modeling and simulation...

M. Katzper

1981-01-01

260

Long Term Illness and Wages  

ERIC Educational Resources Information Center

Long-term illness (LTI) is a more prevalent workplace risk than fatal accidents but there is virtually no evidence for compensating differentials for a broad measure of LTI. In 1990 almost 3.4 percent of the U.K. adult population suffered from a LTI caused solely by their working conditions. This paper provides the first estimates of compensating…

Sandy, Robert; Elliott, Robert R.

2005-01-01

261

Long-term treatment of lupus nephritis with cyclosporin A.  

PubMed

We evaluated the efficacy and safety of long-term treatment with cyclosporin A (CSA) in type IV lupus nephritis. Seventeen patients with biopsy-proven WHO type IV lupus nephritis were enrolled in a prospective, open study. Twelve of the 17 completed 48 months of treatment with CSA and prednisolone. Three patients required the addition of azathioprine, at 12, 38 and 47 months, respectively, for cutaneous disease flare with refractory rashes. One patient was lost to follow-up at 40 months. The mean +/- SD duration of treatment was 43.2 +/- 10.1 months (range 15.7-48 months). A significant reduction of proteinuria and a significant rise in serum albumin were noted 1 month after initiation of treatment. Improvement was maintained throughout the study except for three patients who relapsed with recurrence of nephrotic syndrome. There were no significant changes in serum creatinine level or creatinine clearances throughout the study. Repeat renal biopsy at 12 months following treatment with CSA showed histological improvement, with WHO type II changes in all 17 patients accompanying significant reduction in activity indices. Patients with baseline haemoglobin (Hgb) levels < 12 g/dl showed significant improvement. Serum C3 and C4 levels were not changed significantly. Corticosteroid-sparing effects were noted. Side-effects included hypertension, gum hypertrophy and mild hirsuitism, but were not serious. Combination therapy using CSA and prednisone is effective and safe for long-term treatment in lupus patients with WHO type IV nephritis. PMID:9893761

Tam, L S; Li, E K; Leung, C B; Wong, K C; Lai, F M; Wang, A; Szeto, C C; Lui, S F

1998-08-01

262

[Prenatal corticosteroids: short-term and long-term effects of multiple courses. A literature review].  

PubMed

Prenatal corticosteroids administration is one of the major advances in obstetrics and neonatology for the prevention of preterm-birth related complications. However, concerns have been raised about its safety regarding neonatal growth and children development. Therefore, some obstetricians have restricted the use of corticosteroids to precisely defined indications. It remains some uncertainty regarding the choice of antenatal corticosteroids, the interval between injections, the timing of effectiveness and the maximum number of courses per pregnancy that is acceptable without causing complications among children. Thus, we performed a current literature review in 2013 regarding short- and long-term efficacy and safety in order to give clear recommendations to practitioners. PMID:24529761

Fuchs, F; Audibert, F; Senat, M-V

2014-03-01

263

Long term stability in RHIC  

SciTech Connect

This study of long term stability in RHIC appears to indicate that the dynamic aperture depends on the number of turns the particles are required to survive. The dynamic aperture will decrease as the number of turns is increased. This effect is a non-linear orbit effect, and is present in the absence of synchrotron oscillations or tune ripples, although the presence of synchrotron oscillations or tune ripple may make the effect worse. The effect appears to depend on the choice of {beta}*. It is an appreciable effect for {beta}* = 2 and barely noticeable for {beta}* = 6 in RHIC. Thus, the long term stability effects can be reduced by increasing {beta}*, and accepting the associated loss in luminosity. So far, this study does not include synchrotron oscillations, which may change the results reported here. 2 refs., 16 figs.

Parzen, G.

1991-03-01

264

Issues in long term care.  

PubMed

Chaplaincy in a long term care facility requires attention to specialized concerns related to the extended length of stay. This article argues the need to (1) retain or restore resident's home church tie; (2) be sensitive to resident/family communications; (3) participate in an interdisciplinary team; (4) understand when to maintain confidentiality and when to speak; (5) know who needs spiritual nourishment. PMID:10312727

Kratz, D G

1988-01-01

265

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

PubMed Central

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

Boerner, Brian P.; Miles, Clifford D.

2014-01-01

266

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

267

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

268

Long-term potentiation and long-term depression: a clinical perspective  

PubMed Central

Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

Bliss, Timothy V.P.; Cooke, Sam F

2011-01-01

269

Efficacy and safety of bevacizumab in glioblastomas.  

PubMed

Glioblastoma multiforme (GBM) is a common and malignant primary brain tumor arising from glial precursors the survival of which is estimated to be about 14 months after diagnosis despite current standard care with radiotherapy, surgery, and chemotherapies. Therapeutic approaches were greatly improved in the last years; however, GBM still represents the most lethal subtype of glioma. Actually, it has been estimated that only about 3.4% of patients will survive at the most five years when obtaining the best outcome from treatment; however, this depends on tumor resistance, which is generally related to repairing radiation injury, and self- improving cell growth repair and survival. All GBMs recur after initial therapy, limiting patients ? survival at 20-25% within 1 year after diagnosis of recurrent disease. Moreover, for recurrent GBM response rates are less than 10% (ranging from 5% to 9%), and progression free survival at 6-month (PFS-6) rates ranges between 9% and 28% (median 15%). The development of targeted therapy based on tumor vascular blockade led to the approval of bevacizumab for recurrent or progressive glioblastoma, since it was proven that this offers a new opportunity for patients suffering from this malignancy. Bevacizumab is a recombinant antivascular monoclonal antibody binding to circulating Vascular Endothelial Growth Factor (VEGF) preventing this cytokine from reaching its receptors (VEGFR1 and VEGFR2) on endothelium, resulting in an inhibition of cells proliferation and vessels sprouting. The aim of this review is to address bevacizumab mode of action in malignant gliomas and provide a summary on currently available data on efficacy and safety. PMID:22214463

De Fazio, S; Russo, E; Ammendola, M; Donato Di Paola, E; De Sarro, G

2012-01-01

270

The safety of specific immunotherapy for patients allergic to house-dust mites and pollen in relation to the development of neoplasia and autoimmune disease: a long-term, observational case-control study.  

PubMed

Background: Specific immunotherapy (SIT) safety has been well documented. However, the prolonged late side effects in patients who terminated SIT several years previously have been reported on in only a limited number of studies. The aim of this study was to perform a 20-year post-SIT observational evaluation for the assessment of any manifestation of serious immunological disease. Materials and Methods: In total, 1,144 patients (521 women and 623 men), with a mean age of 22.8 ± 16.9 years (at the moment of SIT completion) and who had atopic bronchial asthma and/or allergic rhinitis, were observed 20 years after immunotherapy. New neoplastic and autoimmune disease cases were monitored. The SIT group was compared to a control group consisting of 1,154 allergic patients who had never received SIT and had only had symptomatic treatment. Results: There was an inverse association between SIT treatment and the prevalence of new chronic myeloid leukemia and chronic lymphoblastic leukemia cases (OR 0.32, 95% CI 0.18-0.81 and OR 0.58, CI 0.44-0.78, respectively). In other neoplastic diseases, however, prevalences similar to those observed in the control group were confirmed. There were also no significant differences in the autoimmune disease prevalence between the analyzed groups. Conclusion: The results of this long-term observational study indicate a lack of a significant prevalence for new instances of neoplastic and autoimmune diseases, which suggests that SIT in the long term is indeed safe. © 2014 S. Karger AG, Basel. PMID:24776522

Bozek, Andrzej; Koz?owska, Renata; Jarzab, Jerzy

2014-01-01

271

Long-term safety of Mometasone Furoate administered via a dry powder inhaler in children: Results of an open-label study comparing Mometasone Furoate with Beclomethasone Dipropionate in children with persistent asthma  

PubMed Central

Background To assess the long-term pediatric safety of 2 doses of mometasone furoate administered via a dry powder inhaler (MF-DPI) for mild-to-moderate persistent asthma and compare them with that of beclomethasone dipropionate administered via a metered dose inhaler (BDP-MDI) in the treatment of persistent asthma. Both MF-DPI doses tested are twice the approved pediatric dosage of 100 ?g once-daily (QD) for children aged 4–11 years. Methods Children (N = 233) aged 4–11 years were randomized to 52 weeks of treatment with MF-DPI 200 ?g QD AM, MF-DPI 100 ?g twice daily (BID), or BDP-MDI 168 ?g BID. Patients had used inhaled corticosteroids (ICSs) daily for ? 30 days before the screening visit and were on stable ICS doses for ? 2 weeks before screening. The primary safety variable was the incidence of adverse events. Secondary safety variables were laboratory tests (including cortisol concentrations), vital signs, and physical examination. Results The incidence of adverse events was similar in all 3 treatment groups. The most frequently reported adverse event was upper respiratory tract infection, reported by 47%–49% of the MF-DPI-treated patients and 51% of the BPD-treated patients. Most adverse events were considered unrelated to study drug. The most frequently reported related adverse events were headache (MF-DPI 200 ?g QD AM, 8%; MF-DPI 100 ?g BID, 4%; BDP-MDI 168 ?g BID, 2%) and oral candidiasis (4% in each treatment group). No clinically relevant changes in laboratory values, including plasma cortisol, vital signs, or physical examinations were noted in any treatment group. Conclusion Both MF-DPI doses were well tolerated, with no unusual or unexpected adverse events or safety concerns, and had a similar adverse event profile to that of BDP-MDI 168 ?g BID.

Noonan, Michael; Leflein, Jeffrey; Corren, Jonathan; Staudinger, Heribert

2009-01-01

272

Efficacy and Safety of Caspofungin in Solid Organ Transplant Recipients  

Microsoft Academic Search

Efficacy and safety data for the echinocandins in solid organ transplant (SOT) recipients are limited. We reviewed data from three clinical trials that enrolled SOT patients receiving caspofungin therapy for an invasive fungal infection (IFI). Caspofungin was administered at doses ranging from 50 to 100 mg\\/day. Efficacy was assessed in all patients at the end of caspofungin therapy (EOT). Adverse

J. Petrovic; A. Ngai; S. Bradshaw; A. Williams-Diaz; A. Taylor; C. Sable; S. Vuocolo; N. Kartsonis

2007-01-01

273

Comparative safety and efficacy of proton pump inhibitors in paediatric gastroesophageal reflux disease.  

PubMed

Gastroesophageal reflux is one of the most common reasons for referrals to paediatricians or paediatric gastroenterologists. Gastric acid-buffering agents, mucosal surface barriers and gastric anti-secretory agents are the main groups of medications currently used for treating gastroesophageal reflux disease (GERD) in children. Recently, the use of proton pump inhibitors (PPIs) for the treatment of GERD in children has increased considerably. Their effectiveness in healing erosive oesophagitis in paediatric subjects and in improving GERD symptoms has been established in many studies. However, the effectiveness in other clinical conditions and the long-term safety of PPIs for paediatric GERD have not been fully established yet and thus are still under debate. Therefore, the aim of this article is to provide a comparative review of the efficacy, safety and tolerability of PPIs in paediatric GERD. The available data suggest that short-term use of PPIs is well tolerated. Adverse events tend to be of a mild-to-moderate nature, with headache being the most frequently reported treatment-related adverse event. However, further well-designed trials and observational studies are still needed to clarify the efficacy and safety of PPIs in the paediatric population, especially in infants under the age of 12 months. PMID:24706290

Kierkus, Jaroslaw; Oracz, Grzegorz; Korczowski, Bartosz; Szymanska, Edyta; Wiernicka, Anna; Woynarowski, Marek

2014-05-01

274

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

PubMed

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

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

2013-08-01

275

Evolving trends in the long-term treatment of bipolar disorder.  

PubMed

The episodic and chronic nature of bipolar disorder usually requires long-term treatment in all patients, yet there is an unmet need for well-tolerated and clinically effective maintenance therapy with enhanced patient adherence. Few well-tolerated treatment options are currently available that are both effective in all phases of bipolar disorder and prevent recurrence of episodes. Lithium has well-established efficacy in the prevention of further manic episodes and may also be effective in the prevention of depression and suicide, but safety is a concern due to narrow therapeutic window. For valproate and carbamazepine, data appear much less compelling. Lamotrigine has shown to be effective for long-term prevention of depressive episodes. Controlled studies suggest that atypical antipsychotics may also have mood-stabilizing properties and might become standard for long-term therapy in the new future. The role of psychoeducation in improving adherence to medication in long-term treatment and overall patient outcomes is also crucial. PMID:17366344

Vieta, Eduard; Rosa, Adriane R

2007-01-01

276

How long should long be? Long-term trials in rheumatic diseases.  

PubMed Central

In the interests of the safety of patients it is necessary to collect long-term clinical data. It is often assumed that the longer the trial the better. However, the longer the trial the more scientific compromises are necessary if it is to be carried out in a practical way. Because the therapeutic efficacy of and tolerance to the nonsteroidal anti-inflammatory drug diclofenac was established after 6 months' trial the optimal duration for a comparative long-term trial of this preparation is 6 months. The small amount of information gained from trials of diclofenac longer than this did not justify the reduction in quality of trial design and performance that they required. Thus it would appear that at least for 1 antirheumatic drug the assumption that 'the longer the trial the better' is not true.

Ciccolunghi, S N; Chaudri, H A; Schubiger, B I

1979-01-01

277

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.

2014-01-01

278

Long-Term Care Ombudsman Program  

MedlinePLUS

... shortly. Unable to Share This Page Long-Term Care Ombudsman Program (OAA, Title VII, Chapter 2, Sections ... Services Provided to Persons Living in Long-Term Care Facilities Program data for FY 2011 indicate that ...

279

Pricing and hedging long-term options  

Microsoft Academic Search

Do long-term and short-term options contain differential information? If so, can long-term options better differentiate among alternative models? To answer these questions, we first demonstrate analytically that differences among alternative models usually may not surface when applied to short-term options, but do so when applied to long-term contracts. Using S&P 500 options and LEAPS, we find that short- and long-term

Gurdip Bakshi; Charles Cao; Zhiwu Chen

2000-01-01

280

Long-Term Planning in Higher Education.  

ERIC Educational Resources Information Center

This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

281

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

282

Long-Term Effects of Peace Workshops in Protracted Conflicts  

ERIC Educational Resources Information Center

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

Malhotra, Deepak; Liyanage, Sumanasiri

2005-01-01

283

Long Term Surface Salinity Measurements  

NASA Technical Reports Server (NTRS)

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

Schmitt, Raymond W.; Brown, Neil L.

2005-01-01

284

Long-term competence restoration.  

PubMed

While the United States Supreme Court's Jackson v. Indiana decision and most state statutes mandate determinations of incompetent defendants' restoration probabilities, courts and forensic clinicians continue to lack empirical evidence to guide these determinations and do not yet have a consensus regarding whether and under what circumstances incompetent defendants are restorable. The evidence base concerning the restoration likelihood of those defendants who fail initial restoration efforts is even further diminished and has largely gone unstudied. In this study, we examined the disposition of a cohort of defendants who underwent long-term competence restoration efforts (greater than six months) and identified factors related to whether these defendants were able to attain restoration and adjudicative success. Approximately two-thirds (n = 52) of the 81 individuals undergoing extended restoration efforts were eventually deemed restored to competence. Lengths of hospitalization until successful restoration are presented with implications for the reasonable length of time that restoration efforts should persist. Older individuals were less likely to be restored and successfully adjudicated, and individuals with more severe charges and greater factual legal understanding were more likely to be restored and adjudicated. The significance of these findings for courts and forensic clinicians is discussed. PMID:24618523

Morris, Douglas R; DeYoung, Nathaniel J

2014-01-01

285

Long-term stellar variability  

NASA Astrophysics Data System (ADS)

Stars with significant subsurface convection zones develop magnetic loop structures that, arising from the surface upward to the external atmospheres, cause flux variability detectable throughout the whole electromagnetic spectrum. In fact, diagnostics of magnetic activity are in radio wavelengths, where gyrosincrotron radiation arises from the quiescent and flaring corona; in the optical region, where important signatures are the Balmer lines, the Ca ii IRT and H&K lines; in the UV and X ray domains, the latter mainly due to coronal thermal plasma. The zoo of different magnetic features observed for the Sun - spots, faculae, flares, CMEs - are characterized by different temporal evolution and energetics, both in quantity and quality. As a consequence, the time scale of variability, the amount of involved energy and the quality of the involved photons are used as fingerprints in interpreting the observed stellar variability in the framework of the solar-stellar analogy. Here I review main results from long-term multiwavelength observations of cool star atmospheres, with emphasis to similarities and differences with the solar case.

Pagano, Isabella

2010-02-01

286

Systematic review of efficacy and safety of pemetrexed in non-small-cell-lung cancer.  

PubMed

Introduction Lung cancer accounts for 20 % of cancer deaths in Spain. The most frequent subtype (87 %) is non-small cell lung cancer (NSCLC). Pemetrexed is a recently marketed drug added to NSCLC therapeutic arsenal. It seems to have become one of the most used options for the treatment of this condition over the last 3 years. Aim of the review To evaluate the efficacy and safety of pemetrexed in NSCLC, in the different therapy lines. Method A systematic search of published literature was conducted using the main databases (MEDLINE, EMBASE, the Cochrane Library and the Center for Reviews and Dissemination) and subsequently a search of referenced literature was performed. We included clinical trials, meta-analyses and systematic reviews. The evaluation of the quality of the articles was performed by pairs using specific assessment scales, Critical Appraisal Skills Program (CASP) adapted for CASP Spain. Then we extracted data on efficacy and safety according to the treatment line assessed. Results We identified 277 references. Finally, nine clinical trials and a meta-analysis complied with inclusion criteria. In first-line induction, treatment with pemetrexed associated with a platinum was similar in terms of efficacy to other alternative chemotherapy regimens, except in patients with non-squamous histology, in whom survival was higher in the experimental group. In maintenance treatment, greater efficacy was seen with pemetrexed in patients with non-squamous histology. In second-line treatment, there were no significant differences in terms of efficacy and safety for pemetrexed treatment versus other chemotherapy options. The most frequent adverse reactions were: hematological, gastrointestinal and neurological. All were significantly less frequent with pemetrexed versus other alternative therapies, except for liver toxicity. Conclusions Due to the high degree of uncertainty as to its efficacy in certain subgroups of patients, including conflicting data; to its recent incorporation, and therefore lack of safety data in the medium and long term, and the high budgetary impact of its incorporation into health systems, it seems reasonable to optimize its use, identifying those patients who may benefit most. PMID:24590919

Pérez-Moreno, Maria Antonia; Galván-Banqueri, Mercedes; Flores-Moreno, Sandra; Villalba-Moreno, Angela; Cotrina-Luque, Jesús; Bautista-Paloma, Francisco Javier

2014-06-01

287

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

288

Pediatric dyslipidemias: Prescription medication efficacy and safety  

Microsoft Academic Search

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

Barry Browne; Susie Vasquez

2008-01-01

289

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

Microsoft Academic Search

Purpose  Current Japanese guidelines recommend that patients should be switched from lamivudine to entecavir when they meet certain\\u000a criteria. This analysis examines the efficacy and safety of long-term entecavir therapy in patients who were switched to entecavir\\u000a after 24 weeks’ lamivudine therapy in Japanese studies ETV-047 and ETV-060.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The Phase II Japanese study ETV-047 assessed the efficacy of different entecavir doses when

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

2010-01-01

290

Long-term results of sleeve lobectomy for lung cancer  

Microsoft Academic Search

Objective: Sleeve lobectomy is a lung saving procedure indicated for central tumors for which the alternative is a pneumonectomy. Current controversies relate to the safety of the procedure and adequacy as a cancer operation. The aim of the study is to analyze long-term survival after sleeve lobectomy, particularly in relation with nodal status and histological type. The incidence and patterns

François Tronc; Jocelyn Grégoire; Jacques Rouleau; Jean Deslauriers

2000-01-01

291

Long-term plutonium storage: Design concepts  

SciTech Connect

An important part of the Department of Energy (DOE) Weapons Complex Reconfiguration (WCR) Program is the development of facilities for long-term storage of plutonium. The WCR design goals are to provide storage for metals, oxides, pits, and fuel-grade plutonium, including material being held as part of the Strategic Reserve and excess material. Major activities associated with plutonium storage are sorting the plutonium inventory, material handling and storage support, shipping and receiving, and surveillance of material in storage for both safety evaluations and safeguards and security. A variety of methods for plutonium storage have been used, both within the DOE weapons complex and by external organizations. This paper discusses the advantages and disadvantages of proposed storage concepts based upon functional criteria. The concepts discussed include floor wells, vertical and horizontal sleeves, warehouse storage on vertical racks, and modular storage units. Issues/factors considered in determining a preferred design include operational efficiency, maintenance and repair, environmental impact, radiation and criticality safety, safeguards and security, heat removal, waste minimization, international inspection requirements, and construction and operational costs.

Wilkey, D.D.; Wood, W.T. [Los Alamos National Lab., NM (United States); Guenther, C.D. [Fluor Daniel, Inc., Irvine, CA (United States)

1994-08-01

292

Viability of long-term gene therapy in the cochlea.  

PubMed

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

293

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.

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

2014-01-01

294

Sildenafil: Efficacy and Safety in Daily Clinical Experience  

Microsoft Academic Search

Objectives: Sildenafil citrate (Viagra™) is a potent selective inhibitor of phosphodiesterase type 5 proposed for the oral treatment of erectile dysfunction (ED). The aim of this study was to evaluate its efficacy and safety when used in daily practice in patients with ED of various aetiology.Patients and Methods: From September 1998 to April 1999, 380 patients chose sildenafil as treatment

Fabrizio Palumbo; Carlo Bettocchi; Francesco P. Selvaggi; John P. Pryor; David J. Ralph

2001-01-01

295

A Study of Cardiac Monitor Safety and Efficacy.  

National Technical Information Service (NTIS)

The objective of this study was to investigate the safety and efficacy of cardiac monitors and to identify those parameters which should be included in a standard. The primary focus of the study was on ECG monitors with their associated QRS detectors, hea...

A. A. Schoenberg

1977-01-01

296

In vitro efficacy and safety of poly-herbal formulations  

Microsoft Academic Search

Indigenous plants are used as a traditional source of raw materials for the manufacture of medicines. Modernizing the ancient art of herbal medicine bequeathed from generations entails addressing two interrelated issues i.e. efficacy, and safety prior to their acceptance and use worldwide. The present study was designed to investigate three of our veterinary poly-herbal formulations – Phytocee™ an antistressor; Zigbir®

C. V. Chandrasekaran; K. Sundarajan; Kripalini David; Amit Agarwal

2010-01-01

297

Efficacy and safety of rituximab in type II mixed cryoglobulinemia  

Microsoft Academic Search

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

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

298

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

299

Financing Reform for Long-Term Care  

Microsoft Academic Search

The way the nation provides for the financing and delivery of long-term care is badly in need of reform. The principal options for change are private insurance, altering Medicaid, and 110 FROM NURSJNG HOMES TO HOME CARE public long-term care insurance. This article uses the Brookings-ICE Long-Term Care Financing Model to evaluate each of these options in terms of affordability,

Joshua M. Wiener

1996-01-01

300

Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema  

PubMed Central

Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed.

Fong, Angie HC; Lai, Timothy YY

2013-01-01

301

Long-Term Outcomes of Prophylactic Endoscopic Histoacryl Injection for Gastric Varices with a High Risk of Bleeding  

Microsoft Academic Search

Purpose  Endoscopic histoacryl injection (EHI) is reported to be an effective treatment modality for bleeding gastric varices (GVs)\\u000a but controversial as a prophylactic treatment for non-bleeding GVs because efficacy and safety have yet to be determined.\\u000a The aim of this study was to evaluate safety and long-term outcomes of prophylactic EHI for non-bleeding GVs with a high risk\\u000a of bleeding.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Thirty-three

Yun Jung Chang; Jong-Jae Park; Moon Kyung Joo; Beom Jae Lee; Jae-Won Yun; Dae-Woong Yoon; Ji Hoon Kim; Jong Eun Yeon; Jae Seon Kim; Kwan Soo Byun; Young-Tae Bak

2010-01-01

302

Long-term correlations in earth sciences  

NASA Astrophysics Data System (ADS)

In this article we review the occurrence and consequences of long-term memory in geophysical records like climate and seismic records, and describe similarities with financial data sets. We review several methods to detect linear and nonlinear long-term correlations, also in the presence of external trends, and show how external trends can be detected in data with long-term memory. We show as well that long-term correlations lead to a natural clustering of extreme events and discuss the implications for several geophysical data sets.

Bunde, Armin; Lennartz, Sabine

2012-06-01

303

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

304

The clinical efficacy and safety of a fluoroquinolone-containing regimen for pulmonary MAC disease.  

PubMed

Despite recent advances in chemotherapy, the treatment of pulmonary Mycobacterium avium complex (MAC) disease remains unsatisfactory. Judging from its MIC, fluoroquinolones including gatifloxacin (GFLX) are expected to demonstrate efficacy against MAC disease. However, there have been few clinical studies using fluoroquinolones. Therefore, a prospective study to evaluate the clinical efficacy and safety of a fluoroquinolone-containing regimen for the treatment of pulmonary MAC disease was conducted. In this trial, patients with pulmonary MAC disease received protocol-guided combined chemotherapy with rifampin (RFP) and ethambutol (EB) plus either GFLX or clarithromycin (CAM). Adult patients who fulfilled the criteria of the ATS definition of pulmonary MAC disease were enrolled in this study. The patients provided their informed consent, and treatments were administered for 1 year. Of 27 patients enrolled from three facilities, 14 patients were treated with the CAM-containing regimen and 13 patients were treated with the GFLX-containing regime. Four patients did not complete the 1-year treatment because of adverse events. Nine patients (64.3%) in the CAM group and 11 patients (84.6%) in the GFLX group achieved eradication of pathogens. Adverse events were observed more frequently in the GFLX group than in the CAM group. However, there were no severe adverse events in either group. The long-term results showed a similar relapse rate between the CAM and GFLX groups. The fluoroquinolone-containing regimen demonstrated both high efficacy and relative safety for pulmonary MAC disease that was similar to that of the CAM-containing regimen, which is considered to be the standard regimen. PMID:21927844

Fujita, Masaki; Kajiki, Akira; Tao, Yoshiaki; Miyazaki, Masayuki; Ouchi, Hiroshi; Harada, Eiji; Ikegame, Satoshi; Matsumoto, Takemasa; Uchino, Junji; Watanabe, Kentaro; Nakanishi, Yoichi

2012-04-01

305

TNF? blockade in human diseases: An overview of efficacy and safety  

PubMed Central

Tumor necrosis factor-alpha (TNF?) antagonists including antibodies and soluble receptors have shown remarkable efficacy in various immune-mediated inflammatory diseases (IMID). As experience with these agents has matured, there is an emerging need to integrate and critically assess the utility of these agents across disease states and clinical sub-specialties. Their remarkable efficacy in reducing chronic damage in Crohn’s disease and rheumatoid arthritis has led many investigators to propose a new, ‘top down’ paradigm for treating patients initially with aggressive regimens to quickly control disease. Intriguingly, in diseases such as rheumatoid arthritis and asthma, anti-TNF? agents appear to more profoundly benefit patients with more chronic stages of disease but have a relatively weaker or little effect in early disease. While the spectrum of therapeutic efficacy of TNF? antagonists widens to include diseases such as recalcitrant uveitis and vasculitis, these agents have failed or even exacerbated diseases such as heart failure and multiple sclerosis. Increasing use of these agents has also led to recognition of new toxicities as well as to understanding of their excellent long-term tolerability. Disconcertingly, new cases of active tuberculosis still occur in patients treated with all TNF? antagonists due to lack of compliance with recommendations to prevent reactivation of latent tuberculosis infection. These safety issues as well as guidelines to prevent treatment-associated complications are reviewed in detail in this article. New data on mechanisms of action and development of newer TNF? antagonists are discussed in a subsequent article in the Journal. It is hoped that these two review articles will stimulate a fresh assessment of the priorities for research and clinical innovation to improve and extend therapeutic use and safety of TNF? antagonism.

Lin, Jan; Ziring, David; Desai, Sheetal; Kim, Sungjin; Wong, Maida; Korin, Yael; Braun, Jonathan; Reed, Elaine; Gjertson, David; Singh, Ram Raj

2008-01-01

306

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

307

Efficacy and safety of etanercept in chronic immune-mediated disease.  

PubMed

Introduction: TNF-? inhibitors have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying antirheumatic drugs in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a fusion protein that acts as a 'decoy receptor' for TNF-?. Areas covered: This paper evaluates the efficacy and safety of etanercept in patients with chronic inflammatory immune-mediated diseases. Expert opinion: Etanercept was first approved for the treatment of rheumatoid arthritis (RA) and subsequently of chronic plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and juvenile RA. Etanercept as other TNF-? inhibitors, particularly infliximab, may be administered off-label to treat other chronic inflammatory immune-mediated diseases such as systemic sclerosis, Behcet disease, systemic lupus erythematosus, polymyositis, dermatomyositis and mixed connective tissue disease. Early etanercept treatment prevents joint damage and helps to avoid long-term disability in arthritis. Etanercept administered at a dose of 50 mg once weekly is effective in inducing an earlier remission of RA, and etanercept 50 mg twice weekly may favor a more rapid improvement of psoriasis and psoriatic arthritis. Etanercept and adalimumab may exert beneficial effects on lipid profile and improve endothelial dysfunction. Appropriate screening tests for latent tuberculosis, hepatitis B virus and hepatitis C virus should be performed before starting etanercept. TNF-? inhibitors including etanercept are contraindicated in patients with demyelinating diseases. PMID:24654562

Murdaca, Giuseppe; Spanò, Francesca; Contatore, Miriam; Guastalla, Andrea; Magnani, Ottavia; Puppo, Francesco

2014-05-01

308

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.

de Araujo, Arao Nogueira; de Sena, Eduardo Ponde; de Oliveira, Irismar Reis; Juruena, Mario F

2012-01-01

309

The magnetic navigation system allows safety and high efficacy for ablation of arrhythmias  

PubMed Central

Aims We aimed to evaluate the safety and long-term efficacy of the magnetic navigation system (MNS) in a large number of patients. The MNS has the potential for improving safety and efficacy based on atraumatic catheter design and superior navigation capabilities. Methods and results In this study, 610 consecutive patients underwent ablation. Patients were divided into two age- and sex-matched groups. Ablations were performed either using MNS (group MNS, 292) or conventional manual ablation [group manual navigation (MAN), 318]. The following parameters were analysed: acute success rate, fluoroscopy time, procedure time, complications [major: pericardial tamponade, permanent atrioventricular (AV) block, major bleeding, and death; minor: minor bleeding and temporary AV block]. Recurrence rate was assessed during follow-up (15 ± 9.5 months). Subgroup analysis was performed for the following groups: atrial fibrillation, isthmus dependent and atypical atrial flutter, atrial tachycardia, AV nodal re-entrant tachycardia, circus movement tachycardia, and ventricular tachycardia (VT). Magnetic navigation system was associated with less major complications (0.34 vs. 3.2%, P = 0.01). The total numbers of complications were lower in group MNS (4.5 vs. 10%, P = 0.005). Magnetic navigation system was equally effective as MAN in acute success rate for overall groups (92 vs. 94%, P = ns). Magnetic navigation system was more successful for VTs (93 vs. 72%, P < 0.05). Less fluoroscopy was used in group MNS (30 ± 20 vs. 35 ± 25 min, P < 0.01). There were no differences in procedure times and recurrence rates for the overall groups (168 ± 67 vs. 159 ± 75 min, P = ns; 14 vs. 11%, P = ns; respectively). Conclusions Our data suggest that the use of MNS improves safety without compromising efficiency of ablations. Magnetic navigation system is more effective than manual ablation for VTs.

Bauernfeind, Tamas; Akca, Ferdi; Schwagten, Bruno; de Groot, Natasja; Van Belle, Yves; Valk, Suzanne; Ujvari, Barbara; Jordaens, Luc; Szili-Torok, Tamas

2011-01-01

310

Adverse effects of long-term proton pump inhibitor therapy.  

PubMed

Proton pump inhibitors have an excellent safety profile and have become one of the most commonly prescribed class of drugs in primary and specialty care. Long-term, sometimes lifetime, use is becoming increasingly common, often without appropriate indications. This paper is a detailed review of the current evidence on this important topic, focusing on the potential adverse effects of long-term proton pump inhibitor use that have generated the greatest concern: B12 deficiency; iron deficiency; hypomagnesemia; increased susceptibility to pneumonia, enteric infections, and fractures; hypergastrinemia and cancer; drug interactions; and birth defects. We explain the pathophysiological mechanisms that may underlie each of these relationships, review the existing evidence, and discuss implications for clinical management. The benefits of proton pump inhibitor use outweigh its risks in most patients. Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from long-term therapy. PMID:21365243

Sheen, Edward; Triadafilopoulos, George

2011-04-01

311

Efficacy and safety of maraviroc vs. efavirenz in treatment-naive patients with HIV-1: 5-year findings  

PubMed Central

Objective: Maraviroc, a chemokine co-receptor type 5 (CCR5) antagonist, has demonstrated comparable efficacy and safety to efavirenz, each in combination with zidovudine/lamivudine, over 96 weeks in the Maraviroc vs. Efavirenz Regimens as Initial Therapy (MERIT) study. Here we report 5-year findings. Design: A randomized, double-blind, multicenter phase IIb/III study with an open-label extension phase. Methods: Treatment-naive patients with CCR5-tropic HIV-1 infection (Trofile) received maraviroc 300?mg twice daily or efavirenz 600?mg once daily, and zidovudine/lamivudine 300?mg/150?mg twice daily. After the last patient's week 96 visit, the study was unblinded and patients could enter a nominal 3-year open-label phase. Endpoints at the 5-year nominal visit (week 240) included proportion of patients (CCR5 tropism re-confirmed by enhanced sensitivity Trofile) with viral load (plasma HIV-1 RNA) below 50 and 400?copies/ml, and change from baseline in CD4+ cell count, as well as safety. Results: The proportion of patients maintaining viral load below 50?copies/ml was similar between treatment arms throughout the study and at week 240 (maraviroc 50.8% vs. efavirenz 45.9%). Maraviroc-treated patients had a greater increase from baseline in mean CD4+ cell count than efavirenz-treated patients at week 240 (293 vs. 271?cells/?l, respectively). Fewer patients on maraviroc vs. efavirenz experienced treatment-related adverse events (68.9 vs. 81.7%) and discontinued as a result of any adverse event (10.6 vs. 21.3%). Conclusion: Maraviroc maintained similar long-term antiviral efficacy to efavirenz over 5 years in treatment-naive patients with CCR5-tropic HIV-1. Maraviroc was generally well tolerated with no unexpected safety findings or evidence of long-term safety concerns.

Cooper, David A.; Heera, Jayvant; Ive, Prudence; Botes, Mariette; Dejesus, Edwin; Burnside, Robert; Clumeck, Nathan; Walmsley, Sharon; Lazzarin, Adriano; Mukwaya, Geoffrey; Saag, Michael; van Der Ryst, Elna

2014-01-01

312

Foreign Currency for Long-Term Investors  

Microsoft Academic Search

Conventional wisdom holds that conservative investors should avoid exposure to foreign currency risk. Even if they hold foreign equities, they should hedge the currency exposure of these positions and hold only domestic Treasury bills. This paper argues that the conventional wisdom may be wrong for long-term investors. Domestic bills are risky for long-term investors, because real interest rates vary over

John Y. Campbell; Luis M. Viceira; Joshua S. White

2003-01-01

313

Buying Long-Term Care Insurance  

MedlinePLUS

... you can afford the long-term care insurance policy over time, as your monthly income may change Research and consider different options and talk with a professional before finalizing your decision Don’t feel pressured into making a decision LTC PathFinder Long-term care is ...

314

Long Term Preservation of Digital Information.  

ERIC Educational Resources Information Center

The preservation of digital data for the long term presents a variety of challenges from technical to social and organizational. The technical challenge is to ensure that the information, generated today, can survive long term changes in storage media, devices, and data formats. This paper presents a novel approach to the problem. It distinguishes…

Lorie, Raymond A.

315

Conditions for Gaussian long term manufacturing processes  

Microsoft Academic Search

The manufacturing community defines capability indices for manufacturing processes applicable time-wise for both long term and short term processes. The long term process distribution can be constructed from the consolidation of the data sets that was used to estimate the multiple short term distributions. There is a tendency for Gaussian distributed short-term processes to exhibit time sensitive random variation in

R. J. Pieper; Nikhil T. Satyala

2009-01-01

316

Topical nonsteroidal anti-inflammatory drugs for management of osteoarthritis in long-term care patients.  

PubMed

Osteoarthritis is common in patients ?65 years of age. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed for osteoarthritis pain, they pose age-related cardiovascular, renal, and gastrointestinal risks. Two topical NSAIDs, diclofenac sodium 1% gel (DSG) and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution (D-DMSO), are approved in the US for the treatment of osteoarthritis pain. Topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO) and hand (DSG) osteoarthritis. Analyses of data from randomized controlled trials of DSG in hand and knee osteoarthritis demonstrate significant improvement of pain and function in both younger patients (<65 years) and older patients (?65 years) and suggest good safety and tolerability. However, long-term safety data in older patients are limited. Topical NSAIDs can ease medication administration and help address barriers to pain management in older patients, such as taking multiple medications and inability to swallow, and are a valuable option for long-term care providers. PMID:22076115

Argoff, Charles E; Gloth, F Michael

2011-01-01

317

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

PubMed

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

Lessard, Collette R; Hopkins, Matthew R

2011-01-01

318

Clinical efficacy and safety of statins in managing cardiovascular risk  

PubMed Central

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

Kapur, Navin K; Musunuru, Kiran

2008-01-01

319

Safety and efficacy of azacitidine in myelodysplastic syndromes  

PubMed Central

Purpose: The clinical efficacy, different dosages, treatment schedules, and safety of azacitidine are reviewed. Summary: Azacitidine is the first drug FDA-approved for the treatment of myelodysplastic syndromes that has demonstrated improvements in overall survival and delaying time to progression to acute myelogenous leukemia. The recommended dosage of azacitidine is 75 mg/m2 daily for 7 days, with different treatment schedules validated. It appears to be well tolerated, with the most common adverse effects being myelosuppression. Several other off-label recommendations were also analyzed. Conclusion: Azacitidine is the first DNA hypomethylating agent approved by FDA for the treatment of myelodysplastic syndromes with demonstrated efficacy.

Vigil, Carlos E; Martin-Santos, Taida; Garcia-Manero, Guillermo

2010-01-01

320

Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus.  

PubMed

To assess the long-term efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus inadequately controlled with thiazolidinedione monotherapy, 565 patients were randomised to saxagliptin (2.5 mg or 5 mg) or placebo added to thiazolidinedione over 76 weeks (24-week short-term + 52-week long-term extension period) in this phase 3, double-blind, placebo-controlled trial; 360 patients completed the study. At 76 weeks, adjusted mean changes from baseline HbA(1C) (repeated measures model; 95% CI) for saxagliptin 2.5 mg, 5 mg, and placebo were -0.59% (-0.75, -0.43), -1.09% (-1.26, -0.93), and -0.20% (-0.39, -0.01), respectively (post hoc and nominal p=0.0019 and p<0.0001 for saxagliptin 2.5 mg and 5 mg vs. placebo, respectively). Adverse event frequency was similar between groups. Confirmed hypoglycaemic events were 1.0% and 0% vs. 0.5% for saxagliptin 2.5 mg and 5 mg vs. placebo, respectively. Results should be interpreted with caution given the proportion of patients who discontinued or required glycaemic rescue therapy during the 76-week course of study. Saxagliptin added to thiazolidinedione provided sustained incremental efficacy vs. placebo with little hypoglycaemia for up to 76 weeks and was generally well tolerated. PMID:21562064

Hollander, Priscilla L; Li, Jia; Frederich, Robert; Allen, Elsie; Chen, Roland

2011-04-01

321

Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study.  

PubMed

In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase II] or OV-1012 [Phase III]) are receiving clobazam at dosages ?2.0 mg/kg/day (?80 mg/day). Of 306 eligible patients from OV-1002 or OV-1012, 267 entered the open-label extension. As of the interim date, July 1, 2010, 213 patients (79.8%) had remained in the trial, and 189 had received clobazam for ?12 months, 128 for ?18 months, and 94 for ?24 months. Median percentage decreases in average weekly rates of drop seizures were 71.1% and 91.6% at Months 3 and 24. Mean modal and mean maximum daily dosages were 0.94 mg/kg and 1.22 mg/kg for those who had received clobazam for ?1 year. The 4 most common adverse events were upper respiratory tract infection (18.4%), fall (14.2%), pneumonia (13.9%), and somnolence (12.7%). Clobazam's adverse event profile was consistent with its profile in controlled trials. PMID:23141144

Ng, Yu-Tze; Conry, Joan; Paolicchi, Juliann; Kernitsky, Lydia; Mitchell, Wendy; Drummond, Rebecca; Isojarvi, Jouko; Lee, Deborah; Owen, Randall

2012-12-01

322

Observation of time-dependent adverse events and the influence of drop-out thereon in long-term safety studies--simulation study under the current practice of post-marketing safety evaluation in Japan.  

PubMed

Safety assessment of a new drug should be continuously carried out in the premarketing phase as well as in the postmarketing phase. Considering the actual conditions and problems of postmarketing safety studies in Japan, i.e., the lack of attention to the extent of patients' exposure to the drug (duration and the number of patients), we simulated the number of adverse events to be observed after specified intervals of exposure. This was done by applying different sets of hazard functions for a Weibull distribution under the circumstances that a certain number of patients has dropped out, focusing on rare and delayed adverse events associated with chronically used drugs. By using the result of these simulations, we point out potential problems of underestimating adverse event rates in situations where the hazard rate of the event escalates over time. Patients drop-out from the study also deteriorates the ability to observe such time-dependent adverse events. The simulation can also serve as a useful tool to examine the necessary sample size and the duration of exposure in order to observe and characterize potentially expected adverse events. It is important to take the two key factors into consideration: the change of hazard function over time and the effect of drop-out in designing, analyzing, and evaluating safety studies for new drugs. PMID:15206536

Narukawa, Mamoru; Yafune, Akifumi; Takeuchi, Masahiro

2004-05-01

323

A multicentre open-label safety and efficacy study of tetrodotoxin for cancer pain  

PubMed Central

Background Cancer pain is highly prevalent, and existing treatments are often insufficient to provide adequate relief. Objectives We assessed the long-term safety and efficacy of subcutaneous tetrodotoxin treatment in reducing the intensity of chronic cancer-related pain. Methods In this multicentre open-label longitudinal trial, 30 ?g tetrodotoxin was administered subcutaneously twice daily for 4 days in a heterogeneous cohort of patients with persistent pain despite opioids and other analgesics. “Responder” was defined as a mean reduction of 30% or more in pain intensity from baseline; and “clinical responder” as some pain reduction, but less than 30%, plus agreement on the part of both the patient and the physician that a meaningful analgesic response to treatment had occurred. Results Of 45 patients who entered the longitudinal trial, 41 had sufficient data for analysis. Of all 45 patients, 21 (47%) met the criteria for “responder” [16 patients (36%)] or “clinical responder” [5 patients (11%)]. Onset of pain relief was typically cumulative over days, and after administration ended, the analgesic effect subsided over the course of a few weeks. No evidence of loss of analgesic effect was observed during subsequent treatments (2526 patient–days in total and a maximum of 400 days in 1 patient). One patient withdrew from the study because of adverse events. Toxicity was usually mild (82%) or moderate (13%), and remained so through subsequent treatment cycles, with no evidence of cumulative toxicity or tolerance. Conclusions Long-term treatment with tetrodotoxin is associated with acceptable toxicity and, in a substantial minority of patients, resulted in a sustained analgesic effect. Further study of tetrodotoxin for moderate-to-severe cancer pain is warranted.

Hagen, N.A.; Lapointe, B.; Ong-Lam, M.; Dubuc, B.; Walde, D.; Gagnon, B.; Love, R.; Goel, R.; Hawley, P.; Ngoc, A. Ho; du Souich, P.

2011-01-01

324

Managing the patient with dementia in long-term care.  

PubMed

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

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

2011-05-01

325

Long term treatment of rheumatoid arthritis with rituximab  

Microsoft Academic Search

B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). Rituximab is a chimeric monoclonal antibody that depletes B-cells by binding to the CD20 surface antigen that has been approved for the treatment of RA. Its efficacy has been clearly demonstrated by different clinical trials and, recently, in long-term observational studies. The use of rituximab in clinical

Roberto Caporali; Marta Caprioli; Francesca Bobbio-Pallavicini; Serena Bugatti; Carlomaurizio Montecucco

2009-01-01

326

Efficacy and safety of deep sclerectomy in uveitic glaucoma  

Microsoft Academic Search

Purpose To evaluate the safety and efficacy of deep sclerectomy with implant and mitomycin C in uveitic glaucoma. Design Prospective, noncomparative case study. Patients and methods Nine patients (13 eyes) with uncontrolled uveitic glaucoma underwent deep sclerectomy with implant from 2002 to 2006. All\\u000a patients had their uveitis controlled before and after surgery with anti-inflammatory therapy. Main outcome measures Control

Saleh A. Al Obeidan; Essam A. Osman; Abdulrahman M. Al-Muammar; Ahmed M. Abu El-Asrar

2009-01-01

327

Lessons Learned from an Osteoporosis Clinical Trial in Frail Long Term Care Residents  

PubMed Central

Background Although osteoporosis affects women of all ages, the impact is most pronounced in frail residents in long term care. Nevertheless, few interventional trials have been performed in this population and few data on therapeutic alternatives are available in this cohort. Purpose We describe the challenges and lessons learned in developing and carrying out a trial in frail long term care residents. Methods The ZEST (Zoledronic acid in frail Elders to STrengthen bone) study was designed to examine the safety and efficacy of a single-dose therapy for osteoporosis in frail residents in long term care in the Pittsburgh area. Women with osteoporosis who were 65 years of age and older and currently not on therapy, were randomized in a blinded fashion to intravenous zoledronic acid or placebo. Follow-up of each participant was planned for 2 years. All participants received appropriate calcium and vitamin D supplementation. Results Seven hundred and thirty-three contacts were made with long term care residents of 9 participating facilities. Of 252 women screened, 181 women were eligible, enrolled, and were randomized. Multiple barriers to research in long term care facilities were encountered but overcome with direct communication, information sessions, in-service trainings and social events. Lessons learned included designing the study in a manner that avoided placing an additional burden on an already overcommitted facility staff, a two-stage consent process to separate screening from randomization, and a flexible examination schedule to accommodate residents while obtaining the necessary outcome measurements. Furthermore, a mobile unit accessible to participants containing state-of-the-art dual x-ray absorptiometry, assessment for vertebral fractures, and phlebotomy equipment allows all assessments to be performed on-site at each facility. Serious adverse events are collected from affiliated hospitals in real time with a novel electronic surveillance system. Limitations The major limitation is selection of outcomes that can be assessed at participating facilities and do not require transport of participants to hospitals or clinics. Conclusions Clinical research for osteoporosis can be successfully and safely performed with frail residents in long term care facilities. Lessons learned from this study may inform future investigations among frail elderly residents of these facilities.

Greenspan, S.L.; Nace, D.; Perera, S.; Ferchak, M.; Fiorito, G.; Medich, D.; Zukowski, K.; Adams, D.; Lee, C.; Saul, M.; Resnick, N.M.

2013-01-01

328

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

329

What Is Long-Term Care?  

MedlinePLUS

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

330

Who Needs Care? (Long-Term Care)  

MedlinePLUS

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

331

Administration in Long Term Care Facilities.  

National Technical Information Service (NTIS)

The proceedings of a seminar on strategies for improving long-term care facilities through better management are reported. Forms for use in the identification of goals, problem areas, and management practices are included. An intersystem approach to long-...

1976-01-01

332

Long Term Cryopreservation of Dog Granulocytes.  

National Technical Information Service (NTIS)

Granulocytes isolated by counterflow centrifugation eluriation (CCE) from leukapheresed dog blood, frozen in liquid nitrogen at -196 C, were studied. The effects of long term cryopreservation on cell recovery and in vitro function were determined. In eigh...

F. J. Lionetti F. W. Luscinskas C. R. Valeri A. J. Melaragno

1981-01-01

333

Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV1-infected patients. Data from a double-blind randomized active-controlled multicentre study  

Microsoft Academic Search

Background. Tenofovir disoproxil fumarate (TDF) was developed for the treatment of human immuno- deficiency virus (HIV) infection. However, controlled data are sparse on the long-term renal tolerability of TDF at the currently approved daily dose of 300 mg in treatment-naive HIV-infected patients. Methods. Over 144 weeks, this 600 patient, multicentre randomized, placebo-controlled, double-blind trial compared stavudine (301 patients) and TDF

Hassane Izzedine; Jean Sebastien Hulot; Daniel Vittecoq; Joel E. Gallant; Schlomo Staszewski; Vincent Launay-Vacher; Andrew Cheng; Gilbert Deray

334

Evaluation of Adverse Reactions in Hemophiliacs from Long-Term Exposure to Blood and Blood Products.  

National Technical Information Service (NTIS)

This study assesses current therapeutic efficacy and adverse reactions in hemophiliacs. Approximately 50 percent of hemophiliacs showed long term (greater than 6 months) abnormalities of liver function. A significant increase in diastolic blood pressure w...

S. S. Shapiro

1976-01-01

335

Long-Term Use of Benzodiazepines  

PubMed Central

Problems associated with physical dependence and abuse of benzodiazepines by a small percentage of patients have reduced their popularity from the most commonly prescribed psychoactive drug in the 1970s to being prescribed for mainly short periods. Patients who benefit from long-term benzodiazepine use are nearly ignored by the medical community as a whole. This article details what patient population can improve from long-term benzodiazepine therapy, the risks and benefits of treatment, and how to select appropriate candidates.

Potts, Nicholas L.S.; Krishnan, K. Ranga R.

1992-01-01

336

Evidence-based long term care design.  

PubMed

Research on the impact of the built environment in long-term care settings continues to grow. This article focuses on work conducted and published since 2000, when an earlier review on research on dementia and design was published. The vast majority of research that addressed neurological conditions in residents in long-term care settings (assisted living and nursing homes) relates to Alzheimer's disease and related dementias. PMID:19893184

Calkins, Margaret P

2009-01-01

337

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

338

Preceptors in long-term care  

Microsoft Academic Search

A preceptor is an experienced and competent staff member who serves as a clinical role model and resource person to newly employed nursing personnel. Although this concept has been prominent since the late 1970s in acute health care settings, preceptors rarely are used in long-term care facilities. This article describes the overall effectiveness of the first long-term care preceptor program

Cindy A Shemansky

1998-01-01

339

Classification of Long-Term EEG Recordings  

Microsoft Academic Search

\\u000a Computer assisted processing of long-term EEG recordings is gaining a growing importance. To simplify the work of a physician,\\u000a that must visually evaluate long recordings, we present a method for automatic processing of EEG based on learning classifier.\\u000a This method supports the automatic search of long-term EEG recording and detection of graphoelements – signal parts with characteristic\\u000a shape and defined

Karel Kosar; Lenka Lhotská; Vladimir Krajca

2004-01-01

340

Long-Term Property Insurance 1  

Microsoft Academic Search

This paper proposes long-term insurance (LTI) as an alternative to the standard annual property insurance policy. LTI offers significant benefits to many stakeholders by reducing insurers' administrative costs, lowering search costs, providing stability to consumers and incentivizing property owners to invest in risk-reducing measures. A simple two-period model illustrates situations that would make a long-term contract attractive to both insurers

Dwight Jaffee; Howard Kunreuther; Erwann Michel-Kerjan

341

Balancing the Efficacy and Safety of Vaccines in the Elderly  

PubMed Central

With advances in global health care, ageing populations are expected to grow worldwide throughout the 21st century. Increased lifespan is a testament to modern medical and social practices, but also presents a growing challenge to a system with limited resources. Elderly populations present specific concerns related to preventative health practices, especially vaccination. Although the power of vaccination is unquestionable in controlling infectious disease, immunosenescence can lead to reduced immune responses following immunization in the elderly, and increased morbidity and mortality. Further complicating this issue, some vaccines themselves may pose a substantial safety risk in the elderly when compared to younger counterparts. Though any health care intervention must balance risk and reward, safety and immunogenicity are often poorly characterized in older populations. This review explores several domestic and travel vaccines, examining what is known concerning efficacy and safety in the elderly, and considers future alternatives.

Amanna, Ian J.

2012-01-01

342

On-Demand Therapy with Pantoprazole 20 mg as Effective Long-Term Management of Reflux Disease in Patients with Mild GERD: The ORION Trial  

Microsoft Academic Search

Aims: To compare safety and efficacy of on-demand pantoprazole 20 mg\\/40 mg versus placebo in the long-term management of patients with mild gastroesophageal reflux disease (GERD) after heartburn relief. Methods: A total of 634 patients with endoscopically confirmed GERD grade 0\\/I and heartburn were included. During the acute phase, patients were treated with pantoprazole 20 mg once daily for 4

T. Scholten; C. P. M. Dekkers; K. Schütze; T. Körner; M. Bohuschke; G. Gatz

2005-01-01

343

Long-term treatment with pitavastatin (NK104), a new HMG-CoA reductase inhibitor, of patients with heterozygous familial hypercholesterolemia  

Microsoft Academic Search

The clinical efficacy and safety of pitavastatin (NK-104), a novel HMG-CoA reductase inhibitor, during long-term treatment, were examined in 25 patients (male\\/female=11\\/14, mean age=53±13 (mean±SD) years) with heterozygous familial hypercholesterolemia (FH). After a period on placebo of >4 weeks, 2 mg\\/day of pitavastatin was administered for 8 weeks, and the dose was increased to 4 mg\\/day for up to 104

Yoshihiro Noji; Toshinori Higashikata; Akihiro Inazu; Atsushi Nohara; Kosei Ueda; Susumu Miyamoto; Kouji Kajinami; Tadayoshi Takegoshi; Junji Koizumi; Hiroshi Mabuchi

2002-01-01

344

Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients  

Microsoft Academic Search

T-cell immunotherapy that takes advan- tage of Epstein-Barr virus (EBV)- stimulated immunity has the potential to fill an important niche in targeted therapy for EBV-related cancers. To address ques- tions of long-term efficacy, safety, and practicality, we studied 114 patients who had received infusions of EBV-specific cytotoxic T lymphocytes (CTLs) at 3 differ- ent centers to prevent or treat EBV

Helen E. Heslop; Karen S. Slobod; Martin A. Pule; Gregory A. Hale; Alexandra Rousseau; Colton A. Smith; Catherine M. Bollard; Hao Liu; Meng-Fen Wu; Richard J. Rochester; Persis J. Amrolia; Julia L. Hurwitz; Malcolm K. Brenner; Cliona M. Rooney

345

Long-term ribavirin therapy in hepatitis C virus-positive renal transplant patients: effects on renal function and liver histology  

Microsoft Academic Search

Background:Long-term renal transplant (RT) recipient mortality and graft loss increase significantly in hepatitis C virus positive (HCV-[+]ve) patients. Treatment with ?-interferon in this population is associated with a high rate of acute rejection. The aims of this study were the evaluation of the efficacy and the safety of ribavirin monotherapy in 16 HCV-(+) RT patients (group A) matched to 32

Nassim Kamar; Karine Sandres-Saune; Janick Selves; David Ribes; Olivier Cointault; Dominique Durand; Jacques Izopet; Lionel Rostaing

2003-01-01

346

Long-term Therapy With Tenofovir Is Effective for Patients Co-Infected With Human Immunodeficiency Virus and Hepatitis B Virus  

Microsoft Academic Search

BACKGROUND & AIMS: We investigated the long-term efficacy and renal safety of tenofovir disoproxil fumarate (TDF), administered to patients co-infected with human immunodeficiency virus and hepatitis B virus (HBV) as part of an antiretroviral therapy. METHODS: We performed a multicenter, prospective cohort study of 102 patients co-infected with human immunodeficiency virus and HBV who were treated with TDF. RESULTS: At

Jurriën G. P. Reijnders; Bettina E. Hansen; Hans L. Zaaijer; Jan M. Prins; Suzan D. Pas; Martin Schutten; Andy I. M. Hoepelman; Clemens Richter; Jan W. Mulder; Rob A. de Man; Harry L. A. Janssen; Marchina E. van der Ende

2010-01-01

347

Long-term treatment of hyperphosphatemia with bixalomer in Japanese hemodialysis patients.  

PubMed

Bixalomer is a nonabsorbable polymer that binds phosphate in the gastrointestinal tract and lowers the serum phosphate level by inhibiting phosphate absorption. The safety and efficacy of long-term bixalomer treatment were assessed in Japanese hemodialysis patients with hyperphosphatemia. This was a multicenter open-label study with a 48-week treatment period. The main efficacy endpoints were the serum phosphate level and rate of achieving the target serum phosphate range (3.5-6.0 mg/dL). Bixalomer was initiated at a dose of 1.5 g/day, which was increased to a maximum of 7.5 g/day depending on the serum phosphate response. Of 248 subjects who started treatment, 179 completed the study. The mean serum phosphate level decreased over time and remained around 5.5 mg/dL from weeks 16 to 48. The target serum phosphate level was reached in >50% of subjects by week 7 and was maintained in 65.2% to 75.9% until week 48. The incidence of adverse events and adverse drug reactions was 94.4% and 29.4%, respectively. There was a potential relationship with the study drug for four serious adverse events (ischemic colitis, hemorrhagic intestinal diverticulum, esophageal ulcer, and acute cholecystitis), which occurred in one patient each. Constipation was the most common adverse drug reaction (21.0%). Most adverse events and adverse drug reactions occurred soon after starting administration, and their incidence did not increase during long-term treatment. Bixalomer did not reduce the bicarbonate level or promote metabolic acidosis. Bixalomer is clinically useful for the long-term treatment of hyperphosphatemia. PMID:24330556

Akizawa, Tadao; Kameoka, Chisato; Kaneko, Yuichiro; Kawasaki, Shigenori

2013-12-01

348

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.

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

349

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

350

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

PubMed Central

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

Mehler-Wex, Claudia; Kolch, Michael; Kirchheiner, Julia; Antony, Gisela; Fegert, Jorg M; Gerlach, Manfred

2009-01-01

351

Safety and efficacy of silodosin for the treatment of benign prostatic hyperplasia  

PubMed Central

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the ?1-adrenergic receptor antagonists. Silodosin is a new ?1-adrenergic receptor antagonist that is selective for the ?1A-adrenergic receptor. By antagonizing ?1A-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the ?1A-adrenergic receptor than for the ?1B-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by ?1B-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective ?1A-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH.

Yoshida, Masaki; Kudoh, Junzo; Homma, Yukio; Kawabe, Kazuki

2011-01-01

352

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

PubMed Central

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

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

2010-01-01

353

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

PubMed

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

Frazão, João M; Adragão, Teresa

2012-01-01

354

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

PubMed Central

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

Hsu, Leeyen; Armstrong, April W.

2014-01-01

355

Profile of vildagliptin in type 2 diabetes: efficacy, safety, and patient acceptability  

PubMed Central

Vildagliptin is a selective and potent dipeptidyl peptidase-4 inhibitor that improves glycemic control by inhibiting the degradation of both endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. This article is a comprehensive review of the safety and efficacy of vildagliptin in patients with type 2 diabetes. Clinical evidence has proven that it effectively decreases hemoglobin A1c with a low risk of hypoglycemia and is weight neutral. The addition of vildagliptin to metformin improves glucose control and significantly reduces gastrointestinal adverse events, particularly in patients inadequately controlled with metformin monotherapy. Its long-term advantages include preservation of ?-cell function, reduction in total cholesterol, decrease in fasting lipolysis in adipose tissue, and triglyceride storage in non-fat tissues. Vildagliptin is well tolerated with a low incidence of AEs, and it does not increase the risk of cardiovascular/cerebrovascular (CCV) events. It can be taken before or after meals, and has little drug interaction, thus it will be well accepted.

Pan, CY; Wang, XL

2013-01-01

356

JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis.  

PubMed

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

Hsu, Leeyen; Armstrong, April W

2014-01-01

357

Conducting a hazardous vulnerability assessment for a long term care facility.  

PubMed

The article and outline of an all hazards emergency management plan which follows are excerpted from the "IAHSS Long Term Care Safety and Security Guide," prepared by the IAHSS Long Term Security Task Force. The complete guide is available to members in the Educational Materials section of the IAHSS web page. PMID:24020328

2013-01-01

358

A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor.  

PubMed

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder caused by gain-of-function mutations in the G protein-coupled chemokine receptor CXCR4. The CXCR4 antagonist plerixafor, which is approved by the US Food and Drug Administration (FDA) for stem cell mobilization in cancer and administered for that indication at 0.24 mg/kg, has been shown in short-term (1- to 2-week) phase 1 dose-escalation studies to correct neutropenia and other cytopenias in WHIM syndrome. However, long-term safety and long-term hematologic and clinical efficacy data are lacking. Here we report results from the first long-term clinical trial of plerixafor in any disease, in which 3 adults with WHIM syndrome self-injected 0.01 to 0.02 mg/kg (4% to 8% of the FDA-approved dose) subcutaneously twice daily for 6 months. Circulating leukocytes were durably increased throughout the trial in all patients, and this was associated with fewer infections and improvement in warts in combination with imiquimod; however, immunoglobulin levels and specific vaccine responses were not fully restored. No drug-associated side effects were observed. These results provide preliminary evidence for the safety and clinical efficacy of long-term, low-dose plerixafor in WHIM syndrome and support its continued study as mechanism-based therapy in this disease. The ClinicalTrials.gov identifier for this study is NCT00967785. PMID:24523241

McDermott, David H; Liu, Qian; Velez, Daniel; Lopez, Lizbeeth; Anaya-O'Brien, Sandra; Ulrick, Jean; Kwatemaa, Nana; Starling, Judy; Fleisher, Thomas A; Priel, Debra A Long; Merideth, Melissa A; Giuntoli, Robert L; Evbuomwan, Moses O; Littel, Patricia; Marquesen, Martha M; Hilligoss, Dianne; Decastro, Rosamma; Grimes, George J; Hwang, Samuel T; Pittaluga, Stefania; Calvo, Katherine R; Stratton, Pamela; Cowen, Edward W; Kuhns, Douglas B; Malech, Harry L; Murphy, Philip M

2014-04-10

359

Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy  

PubMed Central

OBJECTIVE To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks.

Ziegler, Dan; Hidvegi, Tibor; Gurieva, Irina; Bongardt, Sabine; Freynhagen, Rainer; Sen, David; Sommerville, Kenneth

2010-01-01

360

Long-term efficacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United States-People's Republic of China Study Group on Hepatitis B.  

PubMed

Perinatal transmission of hepatitis B virus (HBV) contributes to the high prevalence of chronic infection in China and many other countries. In a placebo-controlled trial among 166 infants, the 12-month efficacy of active postexposure prophylaxis to prevent chronic perinatal HBV infection varied by vaccine (range, 45%-89%). In a 5-year follow-up study, 2 additional infants became chronically infected with HBV, and the efficacy of active prophylaxis was estimated to be 38% and 72% for the two vaccines at 5 years. In addition, 80% of immunized infants continued to have protective levels of antibody at the end of 5 years. However, among 27 infants who received passive-active immunoprophylaxis with high-dose hepatitis B immune globulin, only 60% (11/19) had protective antibody levels. These data indicate that active postexposure immunization initiated soon after birth continues to provide protection during early childhood when there is a high risk of chronic HBV infection. PMID:7798683

Xu, Z Y; Duan, S C; Margolis, H S; Purcell, R H; Ou-Yang, P Y; Coleman, P J; Zhuang, Y L; Xu, H F; Qian, S G; Zhu, Q R

1995-01-01

361

Androgens and male aging: current evidence of safety and efficacy  

PubMed Central

Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone and muscle strength, bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens, and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence, the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism, in the best case reversed by testosterone treatment, has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome, bone mineral density, of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry: double-blind, placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment.

Gooren, Louis J.

2010-01-01

362

[Analysis of efficacy and safety of administration of moxonidine in patients with arterial hypertension and hypertensive crises].  

PubMed

In the review we present detailed analysis of antihypertensive action of 3-nd generation sympatholytic moxonidine. Due to selective interaction with imidazoline I1-receptors moxonidine diminishes sympathetic activity causing lowering of peripheral vascular resistance. This leads to significant lowering of systolic and diastolic arterial pressure. Efficacy and safety of the drug has been shown both for the management of uncomplicated hypertensive crises and long term treatment of arterial hypertension (AH). Appropriateness of the use of moxonidine in patients with AH combined with diabetes mellitus, metabolic syndrome, chronic obstructive pulmonary disease has been confirmed. Moxonidine is well tolerated; its bioavailability after oral intake reaches 90%. The drug produces neither hypotensive "first dose" nor rebound effects. PMID:21878076

Gaponova, N I; Abdrakhmanov, V R; Baratashvili, V L; Tereshchenko, S N

2011-01-01

363

Efficacy of pyrethroid-treated nets against malaria vectors and nuisance-biting mosquitoes in Tanzania in areas with long-term insecticide-treated net use: Pyrethroid-treated nets against malaria vectors and nuisance-biting mosquitoes  

Microsoft Academic Search

treatment. methods Anopheles gambiae Giles s.l., An. funestus Giles s.l. and Culex quinquefasciatus Say were collected during three national surveys and two insecticide-treated net (ITN) studies in Tanzania. Knockdown effect and mortality were measured in standard WHO susceptibility tests and ball-frame bio-efficacy tests. Test results from 1999 to 2004 were compared to determine trends in resistance development. results Anopheles gambiae

Manisha A. Kulkarni; Robert Malima; Frank W. Mosha; Shandala Msangi; Ezra Mrema; Bilali Kabula; Boniface Lawrence; Safari Kinung’hi; John Swilla; William Kisinza; Manfred E. Rau; Jane E. Miller; Joanna Armstrong Schellenberg; Caroline Maxwell; Mark Rowland; Stephen Magesa; Chris Drakeley

2007-01-01

364

Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation  

SciTech Connect

Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereas long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by which short-term memories are permanently stored, and b) a strong foundation for continued growth of an excellent undergraduate neuroscience program.

Calin-Jageman, Robert J

2009-09-12

365

Long-term surveillance plan for the Estes Gulch disposal site near Rifle, Colorado  

SciTech Connect

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy`s (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Estes Gulch disposal site near Rifle, Colorado. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Estes Gulch disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP.

NONE

1997-07-01

366

Animal Models for Microbicide Safety and Efficacy Testing  

PubMed Central

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

Veazey, Ronald S.

2013-01-01

367

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.

Hsieh, David T.

2013-01-01

368

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

369

Efficacy and safety of latanoprost in eyes with uveitic glaucoma  

Microsoft Academic Search

Background  To compare the efficacy and safety of latanoprost against a fixed combination of dorzolamide and timolol in eyes with elevated\\u000a intraocular pressure (IOP) or glaucoma and anterior or intermediate uveitis.\\u000a \\u000a \\u000a \\u000a Methods  Fifty-eight patients with anterior or intermediate uveitis and elevated IOP or glaucoma presented or followed up in the Ocular\\u000a Inflammation and Immunology Service of General Hospital of Athens were randomly

Nikos N. Markomichelakis; Agori Kostakou; Ioannis Halkiadakis; Sonia Chalkidou; Dimitrios Papakonstantinou; Gerasimos Georgopoulos

2009-01-01

370

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).

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

2013-01-01

371

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

PubMed

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 fresh frozen 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. 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, Umran; Mariani, Guglielmo

2013-04-01

372

The long-term ecological research program  

NASA Astrophysics Data System (ADS)

Major developments have emerged in the field of ecology as a result of taking a long-term approach to both basic and applied research [Strayer, 1986]. In recognition of both the advantages of long-term research programs and the historical difficulty of sustaining such research efforts, the National Science Foundation (NSF) instituted its Long-Term Ecological Research (LTER) Program in 1980 [Callahan, 1984]. The LTER Program has a number of important links with the geosciences and is likely to play a significant role in work on terrestrial, freshwater, and estuarine ecosystems within the International Geosphere-Biosphere Program (IBGP); it is thus a good time for us to begin communicating with geoscientists who are helping to shape IGBP.

Swanson, Frederick J.; Franklin, J. F.

373

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

374

Nexplanon: the new implant for long-term contraception. A comprehensive descriptive review.  

PubMed

Nexplanon(®) is a new long-term reversible contraception method. The current review is aimed to analyze the published data concerning the contraceptive effectiveness of Nexplanon(®) and its effects on reproductive function. Pharmacological properties and technical procedures of insertion and removal, as well as the efficacy and safety data available, were discussed. Possible strategies for treating Nexplanon(®)-related bleeding were also described. With regard to the future research and the future scientific developments of contraceptive implants, the possible use of Nexplanon(®) wide-ranging for the symptomatic treatment of endometriosis and premenstrual syndrome (PMS) were considered. Finally, it was defined in which women the use of Nexplanon(®) is indicated and in which it is contra-indicated. PMID:22339096

Palomba, Stefano; Falbo, Angela; Di Cello, Annalisa; Materazzo, Caterina; Zullo, Fulvio

2012-09-01

375

Linagliptin: farmacology, efficacy and safety in type 2 diabetes treatment  

PubMed Central

Type 2 diabetes mellitus (T2DM) has a high prevalence and incidence around the world. The complex pathophysiology mechanism is among the barriers for diabetes treatment. Type 2 diabetes patients have dysfunction in incretin hormones (as glucagon-like peptide-1 or GLP-1, and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level reduction in a glucose-dependent manner. Linagliptin is a highly specific and potent inhibitor of DPP-4 that is currently indicated for the treatment of type 2 diabetes. Clinical studies with linagliptin demonstrated efficacy in reducing glycated hemoglobin (HbA1c) levels in type 2 diabetes patients, while maintaining a placebo-like safety and tolerability profile. Linagliptin has an interesting pharmacokinetic profile in terms of its predominantly non-renal elimination and the main implication of this characteristic is that no dose adjustment is necessary in patients with renal disease. Also, no dose adjustment is required in patients with hepatic insufficiency, as well in elderly or obese patients. This article will review the pharmacokinetic profile, efficacy data and safety aspects of linagliptin in type 2 diabetes patients.

2013-01-01

376

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

377

Long-term Outcomes of Drug-eluting versus Bare-metal stent for ST-elevation Myocardial Infarction  

PubMed Central

Background Long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain uncertain. Objective To investigate long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). Methods We performed search of MEDLINE, EMBASE, the Cochrane library, and ISI Web of Science (until February 2013) for randomized trials comparing more than 12-month efficacy or safety of DES with BMS in patients with STEMI. Pooled estimate was presented with risk ratio (RR) and its 95% confidence interval (CI) using random-effects model. Results Ten trials with 7,592 participants with STEMI were included. The overall results showed that there was no significant difference in the incidence of all-cause death and definite/probable stent thrombosis between DES and BMS at long-term follow-up. Patients receiving DES implantation appeared to have a lower 1-year incidence of recurrent myocardial infarction than those receiving BMS (RR = 0.75, 95% CI 0.56 to 1.00, p= 0.05). Moreover, the risk of target vessel revascularization (TVR) after receiving DES was consistently lowered during long-term observation (all p< 0.01). In subgroup analysis, the use of everolimus-eluting stents (EES) was associated with reduced risk of stent thrombosis in STEMI patients (RR = 0.37, p=0.02). Conclusions DES did not increase the risk of stent thrombosis in patients with STEMI compared with BMS. Moreover, the use of DES did lower long-term risk of repeat revascularization and might decrease the occurrence of reinfarction.

Wang, Liping; Wang, Hongyun; Dong, Pingshuan; Li, Zhuanzhen; Wang, Yanyu; Duan, Nana; Zhao, Yuwei; Wang, Shaoxin

2014-01-01

378

Long-term Outcomes of Drug-eluting versus Bare-metal stent for ST-elevation Myocardial Infarction.  

PubMed

Background: Long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain uncertain. Objective: To investigate long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). Methods: We performed search of MEDLINE, EMBASE, the Cochrane library, and ISI Web of Science (until February 2013) for randomized trials comparing more than 12-month efficacy or safety of DES with BMS in patients with STEMI. Pooled estimate was presented with risk ratio (RR) and its 95% confidence interval (CI) using random-effects model. Results: Ten trials with 7,592 participants with STEMI were included. The overall results showed that there was no significant difference in the incidence of all-cause death and definite/probable stent thrombosis between DES and BMS at long-term follow-up. Patients receiving DES implantation appeared to have a lower 1-year incidence of recurrent myocardial infarction than those receiving BMS (RR = 0.75, 95% CI 0.56 to 1.00, p= 0.05). Moreover, the risk of target vessel revascularization (TVR) after receiving DES was consistently lowered during long-term observation (all p< 0.01). In subgroup analysis, the use of everolimus-eluting stents (EES) was associated with reduced risk of stent thrombosis in STEMI patients (RR = 0.37, p=0.02). Conclusions: DES did not increase the risk of stent thrombosis in patients with STEMI compared with BMS. Moreover, the use of DES did lower long-term risk of repeat revascularization and might decrease the occurrence of reinfarction. PMID:25004414

Wang, Liping; Wang, Hongyun; Dong, Pingshuan; Li, Zhuanzhen; Wang, Yanyu; Duan, Nana; Zhao, Yuwei; Wang, Shaoxin

2014-07-01

379

Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.  

PubMed

Tafamidis, a transthyretin (TTR) kinetic stabilizer, delayed neuropathic progression in patients with Val30Met TTR familial amyloid polyneuropathy (TTR-FAP) in an 18-month randomized controlled trial (study Fx-005). This 12-month, open-label extension study evaluated the long-term safety, tolerability, and efficacy of tafamidis 20 mg once daily in 86 patients who earlier received blinded treatment with tafamidis or placebo. Efficacy measures included the Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy total quality of life (TQOL) score, and changes in neurologic function and nutritional status. We quantified the monthly rates of change in efficacy measures, and TTR stabilization, and monitored adverse events (AEs). Patients who continued on tafamidis had stable rates of change in NIS-LL (from 0.08 to 0.11/month; p = 0.60) and TQOL (from -0.03 to 0.25; p = 0.16). In patients switched from placebo, the monthly rate of change in NIS-LL declined (from 0.34 to 0.16/month; p = 0.01), as did TQOL score (from 0.61 to -0.16; p < 0.001). Patients treated with tafamidis for 30 months had 55.9 % greater preservation of neurologic function as measured by the NIS-LL than patients in whom tafamidis was initiated later. Plasma TTR was stabilized in 94.1 % of patients treated with tafamidis for 30 months. AEs were similar between groups; no patients discontinued because of an AE. Long-term tafamidis was well tolerated, with the reduced rate of neurologic deterioration sustained over 30 months. Tafamidis also slowed neurologic impairment in patients previously given placebo, but treatment benefits were greater when tafamidis was begun earlier. PMID:23974642

Coelho, Teresa; Maia, Luis F; da Silva, Ana Martins; Cruz, Márcia W; Planté-Bordeneuve, Violaine; Suhr, Ole B; Conceiçao, Isabel; Schmidt, Hartmut H-J; Trigo, Pedro; Kelly, Jeffery W; Labaudinière, Richard; Chan, Jason; Packman, Jeff; Grogan, Donna R

2013-11-01

380

Bidding for Long-Term Care Patients.  

National Technical Information Service (NTIS)

This document outlines options for a long-term care system in which competitive bidding is used to establish the price of care. The design of the competitive bidding mechanism is examined along with the interaction and cross-impact of competitive bidding ...

A. J. Hogan C. V. Getts

1982-01-01

381

Long-Term Recidivism of Child Molesters  

Microsoft Academic Search

We examined the long-term recidivism rates of 197 child molesters released from prison between 1958 and 1974. Overall, 42% of the total sample were reconvicted for sexual crimes, violent crimes, or both, with 10% of the total sample reconvicted 10–31 years after being released. Incest offenders were reconvicted at a slower rate than were offenders who selected only boys, with

R. Karl Hanson; Richard A. Steffy; Rene Gauthier

1993-01-01

382

LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)  

EPA Science Inventory

LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

383

Long-Term Monitoring of Polars  

NASA Astrophysics Data System (ADS)

We present long-term observations of magnetic cataclysmic variables AM Her, AN UMa, AR UMa, DP Leo, and V1309 Ori obtained with the ROTSEIIId telescope. All data have been analysed and preliminary results indicate periods of 170 days, 217 days, and 180 days for AM Her, AN UMa, and AR UMa, respectively.

Kalomeni, B.

2012-04-01

384

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

385

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

386

Long-Term Care Research and Policy  

ERIC Educational Resources Information Center

This article provides a framework for understanding how long-term care (LTC) research contributes to policy, develops a typology of research contributions to policy with examples of each type, and suggests ways to ensure that contributions continue in the future. The article draws on in-depth interviews with LTC experts working at the interface…

Kemper, Peter

2003-01-01

387

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

388

Long-term opioid therapy reconsidered.  

PubMed

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

2011-09-01

389

Long-term studies of dopamine agonists.  

PubMed

Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy. PMID:11909984

Hubble, Jean P

2002-02-26

390

TOXIC MODELING SYSTEM LONG-TERM (TOXLT)  

EPA Science Inventory

The Toxic Modeling System Long-Term (TOXLT) is a personal-computer- based model that has been developed in conjunction with the release of the new version of the EPAs Industrial Source Complex (ISC2) Dispersion Models (EPA, 1992) and the promulgation of the EPAs A Tiered Modeling...

391

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.

Teasell, Robert W.

1992-01-01

392

Foundation work in long-term care.  

PubMed

Health foundations have invested in services, research, and advocacy to improve the financing and delivery of long-term services and supports. This article describes some of the broad array of approaches they have taken--in such areas as aging in place, assisted living, "culture change" in nursing homes, quality improvement, augmenting the workforce, and paying for care. PMID:20048379

LeRoy, Lauren; Treanor, Katherine; Art, Emily

2010-01-01

393

LONG-TERM PERITONEAL DIALYSIS IN INFANTS  

Microsoft Academic Search

Although the numbers of infants requiring dialysis are small, management of these patients presents many chal- lenges. Mortality is high in infants with comorbidities, com- plications of dialysis are common, and most of these infants need enteral feeding. However, the long-term outcome for otherwise healthy infants is comparable to that for older children.

Lesley Rees

394

Long Term Capability Requirements as derived from the Long Term Requirements Study  

Microsoft Academic Search

Of the 38 Long Term Capability Requirements indentified by NATO in the 2009 Long Term Requirements Study, at least four can be directly applied to waterside security research and technology. First, Area Access Control, the capability of controlling access to designated unattended areas and borders, denying or allowing access to appropriate personnel and equipment. It must be capable of monitoring

J. Brownlee

2010-01-01

395

Long Term Care. Survey and Plan for Long Term Care in East Central Michigan.  

National Technical Information Service (NTIS)

A plan for development of facilities for long-term care in East Central Michigan is presented by East Central Michigan Comprehensive Health Planning Council (ECMCHPC) which is based on the findings of a survey of long-term care facilities. General plannin...

1975-01-01

396

A randomized prospective study comparing the efficacy of on-demand therapy versus continuous therapy for 6 months for long-term maintenance with omeprazole 20 mg in patients with gastroesophageal reflux disease in Japan  

PubMed Central

Aim To assess the efficacy of continuous therapy (cont) and on-demand therapy (on-demand) as maintenance therapy for gastroesophageal reflux disease (GERD). Methods Patients with upper GI endoscopy (EGD)-proven GERD who completed 8 weeks of initial therapy were randomized to cont (omeprazole 20 mg od) or on-demand (omeprazole 20 mg on-demand) group. Assessments by the Global Overall Symptom (GOS) scale at baseline (at the start of maintenance therapy) and at 8-week, 16–week, and 24-week visits were made and EGD was performed at 24 weeks. Symptom relief was defined as percentages of patients whose GOS score of 1 or 2. Results Of the 117 enrolled patients, cont/on-demand was 59/58 and nonerosive reflux disease (NERD)/reflux esophagitis (RE) before the initial therapy was 35/82. Symptom relief in cont/on-demand were 57.6%/48.3% at baseline (n.s.), 66.7%/54.7% at 8 week (n.s.), 64.6%/54.7% at 16 weeks (n.s.), and 66.7%/74.0% at 24 weeks (n.s.). When subjects were divided into NERD and RE, symptom relief in cont/on-demand were 33.3%/41.2% at baseline (n.s.), 43.8%/64.3% at 8 weeks (n.s.), 50.0%/42.9% at 16 weeks (n.s.), and 50.0%/69.2% at 24 weeks (n.s.) in NERD, while those were 68.3%/51.2% at baseline (n.s.), 76.3%/51.3% at 8 weeks (p < 0.05), 70.6%/59.0% at 16 weeks (n.s.), and 72.7%/75.7% at 24 weeks (n.s.) in RE, respectively. At 24-week EGD, all patients in NERD remained as NERD but number of healed patients was significantly higher in cont (85.3%) than in on-demand (44.4%) (p < 0.01) in RE. Conclusions Since NERD is defined by symptoms, as a result of the limited efficacy of continuous therapy, on-demand therapy would be sufficient as maintenance therapy in NERD patients. Regarding RE, continuous therapy would be recommended in terms of reduced symptoms and maintaining mucosal healing.

Hojo, Mariko; Asaoka, Daisuke; Sasaki, Hitoshi; Watanabe, Sumio

2014-01-01

397

Long-term results after pancreas transplantation.  

PubMed

With the advances in technique and immunosupression, not only the short- but the long-term outcomes of pancreas transplantation have improved significantly. This retrospective study describes the long-term outcomes of simultaneous pancreas and kidney (SPK) transplants, pancreas after kidney (PAK), and pancreas transplants alone (PTA). An overall analysis was performed for all deceased donor (DD) primary pancreas transplants performed in the United States between 1988 and 1999. In addition, the long-term outcome for pancreas transplants performed at the University of Minnesota (UM) was analyzed. For SPK transplants performed in the United States between 1998 and 1999, the half-life of the pancreas was almost 12 years, and was 12.5 years for kidneys. For SPK cases where the pancreas was functioning at 1 year, the half-lives of both the pancreas and the kidney grafts extended more than 14 years. The half-lives of solitary pancreas transplants were between 7 years for PAK and 9 years for PTA cases. For US solitary transplants with at least 1 year of graft function, the half-lives extended to almost 9 years. Pancreas transplants performed at the UM showed the same significant improvements over time. Of special interest is the excellent long-term graft function of pancreas transplants from a living donor, which in the early years clearly surpassed that of solitary DD pancreas transplants. A multivariate analysis showed that the factor with the highest impact on long-term graft function in all three transplant categories was the use of a young donor. In SPK cases, the most frequent reason for late graft loss was death with a functioning graft. In solitary pancreas transplants, most late graft losses were still due to immunological reasons. PMID:17889177

Sutherland, D E R; Gruessner, A C

2007-09-01

398

Long-term consequences of severe infections.  

PubMed

There are convincing data to show that the consequences of a severe infection extend well beyond the first month following it. During the first year after severe sepsis or infection, the survival of sepsis patients is guarded compared with matched control groups. Their quality of life is impaired, and they suffer from rapid degradation in cognition and functional capacity. We could postulate three explanations for the long-term bad outcomes of severe infections and sepsis (or a combination of the three): (i) sepsis usually happens in the elderly and sick, and it causes deterioration in life expectancy and functional status as an acute, non-specific event; (ii) an interaction between specific mechanisms of sepsis and underlying disorders; or (iii) long-term complications directly related to infection. If the second or third explanations are true, then management of the original infection/sepsis might have an influence on long-term outcomes. Elderly survivors of severe infections should be carefully assessed for whether they need intermediate care for recuperation and re-conditioning when leaving hospital. We need prospective, observational studies to define which are the factors that most influence long-term outcomes, and especially management of the acute infection. The investigation of long-term outcomes in trials of treatment modalities for sepsis or severe infections should be encouraged. The true answer for whether one treatment is better than another in severe infections or sepsis lies in the people trajectory in the year following the infection, and not only on 4-6 weeks outcome. PMID:23397980

Leibovici, L

2013-06-01

399

Urinary bag decontamination for long-term use: a systematic review.  

PubMed

A systematic review of research on urinary drainage bag decontamination methods was conducted to evaluate existing evidence for practice related to long-term urinary catheter users. Six trials were found that met inclusion criteria. In addition, 9 clinical practice guidelines about urinary catheter care from 3 English-speaking countries were examined. Two studies were of modest quality; they included a randomized trial of 54 persons in a rehabilitation hospital and a laboratory comparison of 5 decontamination products. Three other articles included in the review were case series. All were published between 1985 and 1994. Bleach (NaClO) solutions of varying concentrations (0.06%-1%) were most often tested, and results were similar in controlling microbial contamination in the drainage bags. However, the studies often lacked definitions or standardization of key outcome measures such as safety and ease of the procedure and integrity of the drainage bag. The clinical practice guidelines differed in advice on bag decontamination, and some did not address it. Further research is recommended to evaluate the efficacy of decontamination procedures in patients with long-term indwelling catheters and drainage bags. PMID:23652701

Wilde, Mary H; Fader, Mandy; Ostaszkiewicz, Joan; Prieto, Jacqui; Moore, Katherine

2013-01-01

400

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, alth