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Sample records for long-term safety efficacy

  1. Long-term efficacy and safety of human papillomavirus vaccination

    PubMed Central

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

    2014-01-01

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

  2. Long-term safety and efficacy of teriflunomide

    PubMed Central

    Comi, Giancarlo; Freedman, Mark S.; Miller, Aaron E.; Kappos, Ludwig; Bouchard, Jean-Pierre; Lebrun-Frenay, Christine; Mares, Jan; Benamor, Myriam; Thangavelu, Karthinathan; Liang, Jinjun; Truffinet, Philippe; Lawson, Victoria J.; Wolinsky, Jerry S.

    2016-01-01

    Objective: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563). Methods: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg. Results: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score ≤2.5; probability of 12-week disability progression ≤0.48). Conclusions: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide. Classification of evidence: This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term. PMID:26865517

  3. Long-term safety and efficacy of infliximab for the treatment of ankylosing spondylitis

    PubMed Central

    Elalouf, Ofir; Elkayam, Ori

    2015-01-01

    The introduction of TNFα blockers has revolutionized the treatment of ankylosing spondylitis (AS). The objectives of this review are to summarize the most up-to-date data on long-term efficacy and safety of infliximab in AS, with special emphasis on axial and extra-articular disease, predictors of response, and radiological response. The general consensus of this literature search was that infliximab is highly efficacious in the treatment of AS. Most studies have demonstrated good clinical outcomes after 3 years of treatment, as measured by Spondyloarthritis International Society response in 75%–85% of treated AS patients. Reports on the long-term effects of infliximab as documented by radiological findings, however, are controversial. While some studies reported a similar progression rate as that of the historical OASIS cohort, others have suggested that infliximab may halt new bone formation. The long-term safety of infliximab is well known, mainly from data stored in national registries. While it has been suggested that side effects of infliximab may be fewer in AS compared to rheumatoid arthritis, data on this issue are sparse, with most of the information on long-term safety pertaining to rheumatoid arthritis. It can however be concluded that the long-term efficacy of infliximab is apparently maintained in AS and with an acceptable safety profile. PMID:26640380

  4. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy

    PubMed Central

    Witt, Thomas; Worth, Robert; Henry, Thomas R.; Gross, Robert E.; Nazzaro, Jules M.; Labar, Douglas; Sperling, Michael R.; Sharan, Ashwini; Sandok, Evan; Handforth, Adrian; Stern, John M.; Chung, Steve; Henderson, Jaimie M.; French, Jacqueline; Baltuch, Gordon; Rosenfeld, William E.; Garcia, Paul; Barbaro, Nicholas M.; Fountain, Nathan B.; Elias, W. Jeffrey; Goodman, Robert R.; Pollard, John R.; Tröster, Alexander I.; Irwin, Christopher P.; Lambrecht, Kristin; Graves, Nina; Fisher, Robert

    2015-01-01

    Objective: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy. Methods: This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators' discretion. Seizure frequency was determined using daily seizure diaries. Results: The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p < 0.001). Conclusion: Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population. Classification of evidence: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years. PMID:25663221

  5. Efficacy and safety of long-term botulinum toxin treatment in craniocervical dystonia: a systematic review.

    PubMed

    Colosimo, Carlo; Tiple, Dorina; Berardelli, Alfredo

    2012-11-01

    Botulinum neurotoxins have been shown to be a safe and effective therapeutic option for most forms of focal dystonia, and are now considered to provide the best symptomatic treatment in these disorders. However, only a few papers addressed the long-term efficacy and safety of repeated treatments with this drug. This article reviews the data from clinical trials that have assessed the long-term results of botulinum neurotoxin type A (BoNT-A) and type B in the treatment of the different forms of focal craniocervical dystonia, cervical dystonia (CD), blepharospasm, oromandibular, and laryngeal dystonia. Studies on the long-term effects of BoNT-A therapy have demonstrated that the majority of patients comply with this repeated treatment because they experience a positive and stable effect over time. It is still unclear whether in patients with focal dystonia the mean dose of BoNT-A changes over time. In spite of the wide spectrum of side effects reported to be associated with BoNT-A treatment, there is no evidence of specific side effects due exclusively to the long-term use of such drugs. The only exception to these positive long-term findings is the occurrence of a subgroup of patients with CD who fail to maintain a sustained response after the first or second effective treatment, partly owing to the development of neutralizing antibodies against the toxin. Longitudinal studies aimed at defining the risk factors for this abnormal pattern of response to botulinum toxin treatment are currently being conducted. PMID:22359151

  6. Long-term safety and efficacy of sapropterin: the PKUDOS registry experience.

    PubMed

    Longo, Nicola; Arnold, Georgianne L; Pridjian, Gabriella; Enns, Gregory M; Ficicioglu, Can; Parker, Susan; Cohen-Pfeffer, Jessica L

    2015-04-01

    The Phenylketonuria (PKU) Demographics, Outcomes and Safety (PKUDOS) registry is designed to provide longitudinal safety and efficacy data on subjects with PKU who are (or have been) treated with sapropterin dihydrochloride. The PKUDOS population consists of 1189 subjects with PKU: N = 504 who were continuously exposed to sapropterin from date of registry enrollment, N = 211 who had intermittent exposure to the drug, and N = 474 with some other duration of exposure. Subjects continuously exposed to sapropterin showed an average 34% decrease in blood phenylalanine (Phe)--from 591 382 ?mol/L at baseline to 392 239 ?mol/L (p = 0.0009) after 5 years. This drop in blood Phe was associated with an increase in dietary Phe tolerance [from 1000 959 mg/day (pre-sapropterin baseline) to 1539 840 mg/day after 6 years]. Drug-related adverse events (AEs) were reported in 6% of subjects, were mostly considered non-serious, and were identified in the gastrointestinal, respiratory, and nervous systems. Serious drug-related AEs were reported in ? 1% of subjects. Similar safety and efficacy data were observed for children<4 years. Long-term data from the PKUDOS registry suggest that sapropterin has a tolerable safety profile and that continuous use is associated with a significant and persistent decrease in blood Phe and improvements in dietary Phe tolerance. PMID:25724073

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

    PubMed Central

    Chaudhary, Preeti; Pullarkat, Vinod

    2013-01-01

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

  8. Tocilizumab in refractory rheumatoid arthritis: long-term efficacy, safety, and tolerability beyond 2 years

    PubMed Central

    Farah, Ziad; Ali, Sabreen; Price-Kuehne, Fiona; Mackworth-Young, Charles G

    2016-01-01

    Objectives To evaluate the long-term efficacy and safety of tocilizumab (TCZ) in clinical patients with rheumatoid arthritis (RA) refractory to synthetic disease-modifying antirheumatic drugs, anti-tumor necrosis factor agents, and B-cell depletion therapy with rituximab (RTX). Methods We conducted a single-center retrospective study of 22 patients with RA treated with TCZ. We collected data including demographics and medication histories. We recorded clinical parameters including tender joint counts and swollen joint counts, and laboratory parameters including inflammatory makers and lipid profiles over regular intervals of TCZ treatment. Results In all, 22 patients with RA were included, 20 of whom were female. The median age at the first dose of TCZ was 62 years (range: 35–75 years). The mean duration of the disease from diagnosis with RA to May 2015 was 15.7 years (range: 6–30 years). A total of 15 out of 22 patients remained on TCZ at the end of the study, and in all, there was an improvement in markers of disease activity following initiating TCZ. The effect was sustained for a mean of 35 months (SD±15.5 months, range: 9–72 months). Of the 17 patients who failed to respond to RTX previously, 12 patients remained on TCZ. In all, eight out of 22 patients developed adverse events, five of whom discontinued TCZ. In contrast to previously documented short-term data, TCZ did not result in a statistically significant (P<0.05) long-term deterioration in lipid profile for any of the lipid parameters measured in our cohort (mean ± SD at initiation of TCZ to most recent follow-up: total cholesterol 5.25±1.05 to 5.28±0.77 mmol/L, high-density lipoprotein 1.72±0.54 to 1.67±0.43 mmol/L, low-density lipoprotein 3.05±0.98 to 2.98±0.81 mmol/L, and cholesterol to high-density lipoprotein ratio 3.41±1.23 to 3.40±1.22). Conclusion The efficacy of TCZ in patients with RA refractory to disease-modifying drugs, including anti-tumor necrosis factor blockade and RTX, is sustained over 3 years. TCZ confers a good safety profile in the long term even in patients who previously developed adverse events to other rheumatic drugs. In the long run, there is no statistically significant deterioration in lipid profile during treatment with TCZ. PMID:27069354

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2001-10-01

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

  11. Long-term efficacy and safety of raltegravir in the management of HIV infection.

    PubMed

    Liedtke, Michelle D; Tomlin, C Ryan; Lockhart, Staci M; Miller, Misty M; Rathbun, R Chris

    2014-01-01

    Raltegravir is an integrase strand-transfer inhibitor approved for the treatment of HIV infection. It was the first medication in a novel class of antiretroviral agents to be approved for use in the United States in 2007. Raltegravir exhibits potent activity against wild-type HIV-1, but resistance development has been noted through three different pathways. It is metabolized primarily through uridine diphosphate glucuronosyltransferase 1A1 and has a single inactive glucuronide metabolite. Raltegravir is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes and exhibits low potential for drug-drug interactions; however, strong uridine diphosphate glucuronosyltransferase 1A1 inhibitors or inducers can alter the pharmacokinetics of raltegravir. It is well tolerated, and the most commonly reported adverse effects include headache, nausea, and diarrhea. Serious adverse effects with raltegravir are rare but include rhabdomyolysis and severe skin and hypersensitivity reactions. It has been approved for use in both treatment-naïve and treatment-experienced patients and is a preferred first-line agent in both United States and European HIV treatment guidelines. Although initial approval was granted on 48-week data, 5-year clinical data have recently been published. This article reviews the data supporting long-term efficacy and safety of raltegravir in the treatment of HIV infection. PMID:24672249

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

    PubMed Central

    Kivelevitch, Dario; Mansouri, Bobbak; Menter, Alan

    2014-01-01

    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)-α 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-α agents are currently considered as first line biological therapies for the treatment of moderate to severe psoriasis and psoriatic arthritis. Currently approved anti-TNF-α agents include etanercept, adalimumab, and infliximab for psoriasis and psoriatic arthritis as well as golimumab and certolizumab for psoriatic arthritis. In this article, we aim to evaluate the long term safety and efficacy of etanercept in psoriasis and psoriatic arthritis. PMID:24790410

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

    PubMed Central

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

    2013-01-01

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

  14. [Long-term efficacy and safety of lurasidone in the treatment of schizophrenia].

    PubMed

    Samalin, L; Honciuc, M; Llorca, P-M

    2015-12-01

    Lurasidone is a new second-generation antipsychotic approved in March 2014 by the European Medicines Agency for the treatment of schizophrenia. Lurasidone has demonstrated its efficacy in long-term studies. It has been shown to reduce significantly the risk of relapse in comparison with placebo in patients with schizophrenia. In comparator study, lurasidone was noninferior to quetiapine XR in risk for relapse. In open-label studies, lurasidone was associated with sustained improvement in efficacy measures observed and well-tolerated inpatients with schizophrenia who had switched to lurasidone from another antipsychotic. Available evidence showed also that lurasidone might be involved in the long-term improvement of cognitive performance in schizophrenic patients. Lurasidone differs from the other second-generation antipsychotics by a good tolerability profile, in particular in terms of metabolic and cardiovascular profiles. Lurasidone seems to have a moderate link with the occurrence of akathisia and extrapyramidal symptoms. Although lurasidone long-acting formulation is lacking, the long-term profile of lurasidone appears compatible with a good acceptability and consequently a good compliance to treatment of patients with schizophrenia. PMID:26603973

  15. Long-term efficacy and safety of incobotulinumtoxinA injections in patients with cervical dystonia

    PubMed Central

    Dressler, Dirk; Paus, Sebastian; Seitzinger, Andrea; Gebhardt, Bernd; Kupsch, Andreas

    2013-01-01

    Introduction Previously, controlled trials have demonstrated the efficacy and tolerability of fixed doses of incobotulinumtoxinA (Xeomin, NT 201, botulinum toxin type A free from complexing proteins) to treat cervical dystonia (CD). To explore the clinical relevance of these findings, this study evaluated long-term use of flexible dosing regimens of incobotulinumtoxinA in a setting close to real-life clinical practice. Methods Patients with CD received five injection sessions of incobotulinumtoxinA using flexible intervals (10–24 weeks) and dosing (≤300 Units) based on patients’ needs. Outcome measures included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Dystonia Discomfort Scale (DDS), Investigator Global Assessment of Efficacy (IGAE) and Patient Evaluation of Global Response (PEGR). Results Of 76 patients enrolled (men: 34%; naïve to botulinum toxin: 25%), 64 completed the study, receiving treatment over a duration of 49.3–114.1 weeks (total maximum duration: 121 weeks). Mean TWSTRS-Total and DDS scores significantly improved from study baseline to 4 weeks after each injection session (ranges of improvement: TWSTRS-Total: −11.7 to −14.3; DDS: −20.2 to −23.0). Up to 81.6% of investigators rated the efficacy as ‘good’ or ‘very good’ (IGAE) and up to 78.9% of patients rated the treatment response as ‘improved’ (PEGR). The most common adverse events were dysphagia, nasopharyngitis and headache. Conclusions In this long-term study, incobotulinumtoxinA was administered using more flexible dosing regimens than those permitted in previous controlled trials. Repeated injections of highly purified incobotulinumtoxinA are effective and well tolerated for the treatment of CD in a setting close to real-life clinical practice. PMID:23687362

  16. Long-term safety and efficacy of insulin degludec in the management of type 2 diabetes

    PubMed Central

    Thuillier, Philippe; Alavi, Zarrin; Kerlan, Véronique

    2015-01-01

    Insulin degludec (IDeg) is a novel antiglycemic agent belonging to the therapeutic class of ultra-long duration basal insulin analogs. Its half-life and duration of action are 25 hours and 42 hours, respectively. This pharmacodynamic profile leads to a strict dosing schedule, ie, IDeg is injected at the same time each day to ensure optimal biological action and consistent glycemic control. According to the literature, IDeg provides glycemic control and nocturnal hypoglycemia reduction comparable with other long-acting analogs in type 2 diabetes mellitus. The risk of severe hypoglycemic episodes seems also to be reduced when using IDeg therapy; however, long-term follow-up is warranted for monitoring of possible but relatively infrequent adverse events. IDeg is also available in combination with aspart insulin and with liraglutide. The above preparations have been approved by the European Medicines Agency and other national health authorities. In 2012, the US Food and Drug Administration asked for a complementary study on IDeg-associated cardiovascular risk. Future prospective evaluation of large cohorts of patients with type 2 diabetes mellitus treated with IDeg, with long-term follow-up, can provide further relevant information on the safety of IDeg therapy. PMID:26457056

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

    PubMed Central

    Kissin, Igor

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-03-01

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

  20. Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia.

    PubMed

    Beal, J E; Olson, R; Lefkowitz, L; Laubenstein, L; Bellman, P; Yangco, B; Morales, J O; Murphy, R; Powderly, W; Plasse, T F; Mosdell, K W; Shepard, K V

    1997-07-01

    We studied the effects of long-term (12 months) dronabinol in 94 late-stage acquired immunodeficiency syndrome (AIDS) patients (mean CD4 count of 45/mm3) who previously participated in a 6-week study (placebo versus dronabinol). All patients received dronabinol orally-2.5 mg twice daily (90%) or 2.5 mg once daily (10%). Appetite was measured using a visual analogue scale for hunger (VASH). Dronabinol was associated with consistent improvement in mean appetite. Patients previously treated with dronabinol continued to show improvement in VASH (percent change from baseline of 6-week trial: 48.6-76.1% at each month), whereas those previously treated with placebo exhibited substantial improvement in mean appetite, particularly during the initial 4 months of treatment (48.5-69.9%). Thereafter, dronabinol was associated with a VASH change at least twice baseline. Patients tended toward stable body weight for at least 7 months. Adverse events were primarily related to known central nervous system effects of dronabinol. These data support long-term, safe use of dronabinol for anorexia associated with weight loss in patients with AIDS. PMID:9223837

  1. Long-term efficacy and safety of tocilizumab in giant cell arteritis and large vessel vasculitis

    PubMed Central

    Evans, Jobie; Steel, Lauren; Borg, Frances; Dasgupta, Bhaskar

    2016-01-01

    Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GCA. Tocilizumab (TCZ), a humanised antihuman IL-6 receptor antibody, has been used successfully in several reports as a treatment for GCA and LVV. We report the potentially long-term successful use of TCZ in 8 cases of refractory LVV. All of our patients achieved a good clinical response to TCZ and C reactive protein reduced from an average of 70.3 to 2.5. In all cases, the glucocorticoid dose was reduced, from an average of 24.6?mg prednisolone prior to TCZ treatment to 4.7?mg, indicating that TCZ may enable a reduction in glucocorticoid-associated adverse events. However, regular TCZ administration was needed for disease control in most cases. TCZ was discontinued in one case due to the development of an empyema indicating the need for careful monitoring of infection when using this treatment. PMID:26819753

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

    PubMed Central

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

    2014-01-01

    Background and purpose To assess the long-term safety and efficacy of pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). Methods In two double-blind (DB) studies of early PD and one of advanced PD, active-treatment arms received pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.3754.5 mg q.d.). Results Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ?10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ?10.0% were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to pramipexole introduction, at ?6.6 and ?6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of pramipexole (33 DB plus 80 OL) in early PD, and ?11.5 and ?9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. Conclusions These results support the long-term safety and efficacy of pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit. PMID:24834511

  3. Risperidone long-acting injection: a review of its long term safety and efficacy

    PubMed Central

    Rainer, Michael K

    2008-01-01

    A long-acting form of the second-generation antipsychotic drug risperidone is now broadly available for the treatment of schizophrenia and closely related psychiatric conditions. It combines the advantage of previously available depot formulations for first-generation drugs with the favorable characteristics of the modern “atypical” antipsychotics, namely higher efficacy in the treatment of the negative symptoms of schizophrenia and reduced motor disturbances. Published clinical studies show an objective clinical efficacy (as per psychiatric symptom scores and relapse data) that exceeds that of oral atypical antipsychotics when patients are switched to the long-acting injectable form, a low incidence of treatment-emergent extrapyramidal side effects, and very good acceptance by patients. Available data for maintenance treatment of bipolar disorder show equivalence with the oral form instead of superiority, but are still limited. As it seems likely that efficacy benefits are mostly due to the fact that the injectable form reduces the demand for patient compliance to one physician visit every 2 weeks instead of self-administration on a daily or twice-daily basis, additional potential could exist in other psychiatric disorders where atypical antipsychotic drugs are of benefit but where patient adherence to treatment schedules is typically low. PMID:19183782

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

    PubMed Central

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

    2011-01-01

    Background Prolonged-release melatonin (PRM) 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 1880 and lack of withdrawal and rebound symptoms upon discontinuation. Objective To investigate the efficacy, safety, and withdrawal phenomena associated with 612 months PRM treatment. Methods Data from a prospective 612-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary), adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]). Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM. Results Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as good or very good was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production. Conclusion Results support the efficacy and safety of PRM in primary insomnia patients aged 2080 throughout 612 months of continuous therapy. PRM discontinuation even after 12 months was not associated with adverse events, withdrawal symptoms, or suppression of endogenous melatonin production. PMID:21845053

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

    PubMed Central

    Planas, Raquel; Martin, Roland; Sospedra, Mireia

    2014-01-01

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

  6. Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update

    PubMed Central

    Messalli, Enrico M; Scaffa, Cono

    2010-01-01

    The integrity of bone tissue and its remodeling that occurs throughout life requires a coordinated activity of osteoblasts and osteoclasts. The decreased estrogen circulating level during postmenopausal transition, with a prevalence of osteoclastic activity over osteoblastic activity, represents the main cause of bone loss and osteoporosis. Osteoporosis is a chronic disease requiring long-term therapy and it is important to evaluate the efficacy and safety of treatments over several years, as the fear of health risks is a common reason for discontinuing therapy. Raloxifene is a selective estrogen receptor modulator (SERM) leading to estrogen-agonist effects in some tissues and estrogen-antagonist effects in others. Raloxifene is effective to prevent and treat postmenopausal vertebral osteoporosis, with reduction of spine fractures and, in post-hoc analyses, non-spine fractures in high-risk subjects. Moreover, raloxifene reduces the risk of invasive breast cancer and improves the levels of serum lipoprotein but with an increased risk of venous thromboembolism and fatal stroke, without significant change in the incidence of coronary events. For these reasons the overall risk-benefit profile is favorable. Therefore, when considering the use of raloxifene in a postmenopausal woman, we should take into account the osteoporosis-related individual risk and weigh the potential benefits, skeletal and extra-skeletal, against the health risks. PMID:21072271

  7. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results.

    PubMed

    Wang, Michael L; Blum, Kristie A; Martin, Peter; Goy, Andre; Auer, Rebecca; Kahl, Brad S; Jurczak, Wojciech; Advani, Ranjana H; Romaguera, Jorge E; Williams, Michael E; Barrientos, Jacqueline C; Chmielowska, Ewa; Radford, John; Stilgenbauer, Stephan; Dreyling, Martin; Jedrzejczak, Wieslaw Wiktor; Johnson, Peter; Spurgeon, Stephen E; Zhang, Liang; Baher, Linda; Cheng, Mei; Lee, Dana; Beaupre, Darrin M; Rule, Simon

    2015-08-01

    Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 months; 46% of patients were treated for >12 months, and 22% were treated for ≥2 years. The ORR was 67% (23% complete response), with a median duration of response of 17.5 months. The 24-month progression-free survival and overall survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). The most frequent grade ≥3 infections included pneumonia (8%), urinary tract infection (4%), and cellulitis (3%). Grade ≥3 bleeding events in ≥2% of patients were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence of infection, diarrhea, and bleeding was highest for the first 6 months of therapy and less thereafter. With longer follow-up, ibrutinib continues to demonstrate durable responses and favorable safety in relapsed/refractory MCL. The trial is registered to www.ClinicalTrials.gov as #NCT01236391. PMID:26059948

  8. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results

    PubMed Central

    Blum, Kristie A.; Martin, Peter; Goy, Andre; Auer, Rebecca; Kahl, Brad S.; Jurczak, Wojciech; Advani, Ranjana H.; Romaguera, Jorge E.; Williams, Michael E.; Barrientos, Jacqueline C.; Chmielowska, Ewa; Radford, John; Stilgenbauer, Stephan; Dreyling, Martin; Jedrzejczak, Wieslaw Wiktor; Johnson, Peter; Spurgeon, Stephen E.; Zhang, Liang; Baher, Linda; Cheng, Mei; Lee, Dana; Beaupre, Darrin M.; Rule, Simon

    2015-01-01

    Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 months; 46% of patients were treated for >12 months, and 22% were treated for ≥2 years. The ORR was 67% (23% complete response), with a median duration of response of 17.5 months. The 24-month progression-free survival and overall survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). The most frequent grade ≥3 infections included pneumonia (8%), urinary tract infection (4%), and cellulitis (3%). Grade ≥3 bleeding events in ≥2% of patients were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence of infection, diarrhea, and bleeding was highest for the first 6 months of therapy and less thereafter. With longer follow-up, ibrutinib continues to demonstrate durable responses and favorable safety in relapsed/refractory MCL. The trial is registered to www.ClinicalTrials.gov as #NCT01236391. PMID:26059948

  9. Long-term safety and efficacy of Gamma Knife surgery in classical trigeminal neuralgia: a 497-patient historical cohort study.

    PubMed

    Régis, Jean; Tuleasca, Constantin; Resseguier, Noémie; Carron, Romain; Donnet, Anne; Gaudart, Jean; Levivier, Marc

    2016-04-01

    OBJECT Gamma Knife surgery (GKS) is one of the surgical alternatives for the treatment of drug-resistant trigeminal neuralgia (TN). This study aims to evaluate the safety and efficacy of GKS in a large population of patients with TN with very long-term clinical follow-up. METHODS Between July 1992 and November 2010, 737 patients presenting with TN were treated using GKS. Data were collected prospectively and were further retrospectively evaluated at Timone University Hospital. The frequency and severity of pain, as well as trigeminal nerve function, were evaluated before GKS and regularly thereafter. Radiosurgery using the Gamma Knife (model B, C, 4C, or Perfexion) was performed with the help of both MR and CT targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4-14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90 Gy) was prescribed. RESULTS The safety and efficacy are reported for 497 patients with medically refractory classical TN who were never previously treated by GKS and had a follow-up of at least 1 year. The median age in this series was 68.3 years (range 28.1-93.2 years). The median follow-up period was 43.8 months (range 12-174.4 months). Overall, 456 patients (91.75%) were initially pain free in a median time of 10 days (range 1-180 days). Their actuarial probabilities of remaining pain free without medication at 3, 5, 7, and 10 years were 71.8%, 64.9%, 59.7%, and 45.3%, respectively. One hundred fifty-seven patients (34.4%) who were initially pain free experienced at least 1 recurrence, with a median delay of onset of 24 months (range 0.6-150.1 months). However, the actuarial rate of maintaining pain relief without further surgery was 67.8% at 10 years. The hypesthesia actuarial rate at 5 years was 20.4% and at 7 years reached 21.1%, but remained stable until 14 years with a median delay of onset of 12 months (range 1-65 months). Very bothersome facial hypesthesia was reported in only 3 patients (0.6%). CONCLUSIONS Retrogasserian GKS proved to be safe and effective in the long term and in a very large number of patients. Even if the probability of long-lasting effects may be modest compared with microvascular decompression, the rarity of complications prompts discussion of using GKS as the pragmatic surgical first- or second-intention alternative for classical TN. However, a randomized trial, or at least a case-matched control study, would be required to compare with microvascular decompression. PMID:26339857

  10. Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia.

    PubMed

    Hudgins, Lisa C; Kleinman, Bryan; Scheuer, Abby; White, Sharon; Gordon, Bruce R

    2008-11-01

    Untreated pediatric patients with homozygous familial hypercholesterolemia usually have myocardial infarctions, heart failure, or death by the teenage years. Low-density lipoprotein (LDL) apheresis effectively lowers LDL cholesterol in the short term, but there is little published information on the long-term safety and efficacy of this treatment in children. An analysis was performed of a registry of all 29 patients who began LDL apheresis before 18 years of age at 15 sites during the 11 years since approval by the United States Food and Drug Administration. A chart review of 9 patients treated at The Rogosin Institute was also performed to obtain additional details about lipid lowering, adverse events, and cardiovascular status. Of the 29 patients, 20 are currently treated, with a mean age at the start of treatment of 9 +/- 4 years (range 3 to 15) and a mean treatment duration of 6 +/- 4 years (range 2 to 21). The baseline LDL cholesterol (521 +/- 126 mg/dl) is acutely lowered by 75% and chronically lowered by 48% with biweekly sessions. Systemic adverse events have been uncommon. Atherosclerotic disease of the coronary arteries and/or aorta or aortic valve was evident by angiography and/or echocardiography in 12 patients (60%) at baseline and progressed to more severe, symptomatic disease in 6 (30%). In conclusion, LDL apheresis is well tolerated for decades by even very young pediatric patients with homozygous familial hypercholesterolemia. It effectively lowers LDL cholesterol, but target LDL levels are not achieved, and some patients will show progression of cardiovascular disease. PMID:18940291

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

    PubMed

    Böhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

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

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

    PubMed Central

    Bhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

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

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

    PubMed Central

    Triantafillidis, John K; Malgarinos, George

    2014-01-01

    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

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

    PubMed Central

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

    2008-01-01

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

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

    SciTech Connect

    Yankee, Thomas M. Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-05

    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.

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

    PubMed

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

    2013-06-01

    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

  17. Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up

    PubMed Central

    Okada, Kenya; Sudo, Yohei; Itoh, Hiromichi; Yoshida, Hisao; Kuroda, Tatsuhiko

    2014-01-01

    Objective: To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. Methods: Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. Results: Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7%) of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%). No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. Conclusion: The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy. PMID:26770729

  18. Rituximab in previously treated primary immune thrombocytopenia patients: evaluation of short- and long-term efficacy and safety.

    PubMed

    Santoro, Cristina; Biondo, Francesca; Baldacci, Erminia; De Propris, Maria Stefania; Guarini, Anna; Paoloni, Francesca; Fo, Roberto; Mazzucconi, Maria Gabriella

    2014-01-01

    The anti-CD20 chimeric monoclonal antibody rituximab has been effectively used in the treatment of patients with primary immune thrombocytopenia (pITP). We retrospectively evaluated 19 patients affected by pITP resistant to 2 or more lines of therapy who were treated with rituximab. Nine of the 19 patients showed an initial response (47.4%). The sustained response rate was 31.6% (6/19). The median follow-up of the patients was 53.2 months (range 9.2-92.9). Disease-free survival at 48 months was 62.2%. Following rituximab treatment, a proportion of patients (42%) recovered a normal B lymphocyte number. During the follow-up, no opportunistic or severe infectious complications were observed. These data confirm, over a long period of observation, the efficacy and safety of rituximab treatment in the management of patients with resistant pITP. PMID:24356282

  19. Comparison of Long-Term Safety and Efficacy Outcomes after Drug-Eluting and Bare-Metal Stent Use across Racial Groups: insights from NHLBI Dynamic Registry

    PubMed Central

    Olafiranye, Oladipupo; Vlachos, Helen; Mulukutla, Suresh R.; Marroquin, Oscar; Selzer, Faith; Kelsey, Sheryl F.; Williams, David O.; Strollo, Patrick J.; Reis, Steven E.; Lee, Joon S.; Smith, AJ. Conrad

    2015-01-01

    Background Long-term data on outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and bare-metal stent (BMS) across racial groups are limited, and minorities are under-represented in existing clinical trials. Whether DES has better long-term clinical outcomes compared to BMS across racial groups remains to be established. Accordingly, we assessed whether longer-term clinical outcomes are better with DES compared to BMS across racial groups. Methods Using the multicenter National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry, 2-year safety (death, MI) and efficacy (repeat revascularization) outcomes of 3,326 patients who underwent PCI with DES versus BMS were evaluated. Results With propensity-score adjusted analysis, the use of DES, compared to BMS, was associated with a lower risk for death or MI at 2 years for both blacks (adjusted Hazard Ratio (aHR)=0.41, 95% CI 0.25–0.69, p<0.001) and whites (aHR=0.67, 95% CI 0.51–0.90, p=0.007). DES use was associated with a significant 24% lower risk of repeat revascularization in whites (aHR=0.76, 95% CI 0.60–0.97, p=0.03) and with nominal 34% lower risk in blacks (aHR=0.66, 95% CI 0.39–1.13, p=0.13). Conclusion Use of DES in PCI was associated with better long-term safety outcomes across racial groups. Compared to BMS, DES was more effective in reducing repeat revascularization in whites and blacks, but this benefit was attenuated after statistical adjustment in blacks. These findings indicate that DES is superior to BMS in all patients regardless of race. Further studies are needed to determine long-term outcomes across racial groups with newer generation stents. PMID:25697874

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

    PubMed Central

    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

    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-RARα 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. PMID:19225113

  1. Long-term results of BVS implantation: a focus on safety and efficacy of the bioresorbable technology.

    PubMed

    DEN Dekker, Wijnand K; VAN Geuns, Robert J; Diletti, Roberto

    2016-08-01

    The everolimus eluting bioresorbable vascular scaffold (BVS) represents a novel technology and a novel paradigm for treatment of coronary artery disease, with the potential of improving the long-term clinical outcomes after complete bioresorption. The increasing amount of clinical data is adding in a gradual understanding of the appropriate implantation technique, but long-term results after BVS implantation are sparse. In addition, concern related to a possible increased rate of scaffold thrombosis has recently risen. The present article reviews the current status of knowledge on bioresorbable vascular scaffold from the preclinical phase and the first-in-man experience to the recently reported large randomized trials. Challenging subsets are discussed as well as possible factors impacting on the occurrence of thrombotic events, particularly focusing on clinical outcomes reported in the longest follow-ups currently available. PMID:27175976

  2. Long-term safety and efficacy of high-dose controlled-release nifedipine (80 mg per day) in Japanese patients with essential hypertension

    PubMed Central

    Shimamoto, Kazuaki; Kimoto, Masafumi; Matsuda, Yoshimi; Asano, Kozue; Kajikawa, Mariko

    2015-01-01

    High-dose calcium channel blocker (CCB) shows strong blood pressure (BP) lowering effect. Currently available of controlled-release (CR) nifedipine 80 mg per day clinical data are limited to monotherapy and short-term or long-term retrospective studies. We report the safety and efficacy results of a 52-week, prospective open-label study, in which Japanese patients with essential hypertension were treated with CR nifedipine [80 mg per day; 40 mg bis in die (BID; twice daily)] in combination with other antihypertensive drugs. The patients with inadequate BP control despite treatment with CR nifedipine (40 mg once daily) in combination with other antihypertensive drugs were enrolled. The primary objective of this study was to assess the long-term safety of CR nifedipine (80 mg per day). Efficacy variables included changes in the mean sitting BP, the target BP achievement rate and the BP response rate. CR nifedipine (80 mg per day) was generally well tolerated, with the most common drug-related treatment-emergent adverse event being tachycardia (6.9% of patients). Serious treatment-emergent adverse events were reported in three (4.2%) patients. By week 52, the mean reductions in sitting systolic and diastolic BP were 19.4 and 13.6 mm Hg, respectively. The target BP achievement and BP response rates after 52 weeks of treatment were 32.4 and 63.4%, respectively. Based on these findings, long-term treatment with CR nifedipine at 40 mg BID in combination with antihypertensive drugs was well tolerated and effective in Japanese patients with essential hypertension. PMID:25876832

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

    PubMed

    Masumori, Naoya

    2013-01-01

    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

  4. Update on long-term efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus

    PubMed Central

    Liakos, Aris; Karagiannis, Thomas; Bekiari, Eleni; Boura, Panagiota

    2015-01-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycaemic agents with an insulin-independent mode of action. Dapagliflozin is a member of the SGLT2 inhibitors class that has received marketing authorization in Europe and the US for use in patients with type 2 diabetes. This review summarizes current evidence from clinical trials assessing the clinical efficacy and safety of dapagliflozin, and presents data regarding its cost-effectiveness. Treatment with dapagliflozin results in similar reduction in haemoglobin A1c with other oral antihyperglycaemic drugs, which is preserved over 4 years of treatment. However, compared with most antidiabetic agents, dapagliflozin provides additional clinical benefits including body weight loss and blood pressure reduction. Moreover, treatment with dapagliflozin does not increase risk for hypoglycaemia, but is associated with increased incidence of mild to moderate urinary and genital tract infections. A pivotal outcomes trial of dapagliflozin is expected to clarify its effect on cardiovascular endpoints, whilst a causative relationship between dapagliflozin and select malignancies is unlikely. Finally, based on recent economic evaluations dapagliflozin seems to be a cost-effective option for type 2 diabetes in some settings. PMID:25941564

  5. Update on long-term efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus.

    PubMed

    Liakos, Aris; Karagiannis, Thomas; Bekiari, Eleni; Boura, Panagiota; Tsapas, Apostolos

    2015-04-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycaemic agents with an insulin-independent mode of action. Dapagliflozin is a member of the SGLT2 inhibitors class that has received marketing authorization in Europe and the US for use in patients with type 2 diabetes. This review summarizes current evidence from clinical trials assessing the clinical efficacy and safety of dapagliflozin, and presents data regarding its cost-effectiveness. Treatment with dapagliflozin results in similar reduction in haemoglobin A1c with other oral antihyperglycaemic drugs, which is preserved over 4 years of treatment. However, compared with most antidiabetic agents, dapagliflozin provides additional clinical benefits including body weight loss and blood pressure reduction. Moreover, treatment with dapagliflozin does not increase risk for hypoglycaemia, but is associated with increased incidence of mild to moderate urinary and genital tract infections. A pivotal outcomes trial of dapagliflozin is expected to clarify its effect on cardiovascular endpoints, whilst a causative relationship between dapagliflozin and select malignancies is unlikely. Finally, based on recent economic evaluations dapagliflozin seems to be a cost-effective option for type 2 diabetes in some settings. PMID:25941564

  6. 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

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

    2013-01-01

    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. PMID:24255799

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

    PubMed Central

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

    2013-01-01

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

  8. Profile of paliperidone palmitate once-monthly long-acting injectable in the management of schizophrenia: long-term safety, efficacy, and patient acceptability – a review

    PubMed Central

    González-Rodríguez, Alexandre; Catalán, Rosa; Penadés, Rafael; Garcia-Rizo, Clemente; Bioque, Miquel; Parellada, Eduard; Bernardo, Miquel

    2015-01-01

    Background and objectives Short-term studies focused on once-monthly paliperidone palmitate (PP) at doses of 25 mg eq, 50 mg eq, 75 mg eq, 100 mg eq, or 150 mg eq have shown its efficacy and tolerability in the treatment of schizophrenia patients. However, few open-label and long-term studies are available regarding this new pharmacological formulation. Thus, our main aim was to review the scientific evidence on efficacy, safety, tolerability, and preference of PP in these populations. Method Electronic searches were conducted by using PubMed and ISI Web of Knowledge databases. All relevant studies published from 2009 until January 2015 were included without any language restriction if patients met diagnostic criteria for schizophrenia, and adequate information on efficacy, safety, and tolerability of once-monthly PP was available. Results Nineteen studies were identified irrespective of the study design and duration of the follow-up period. Randomized, double-blind, placebo-controlled trials found that schizophrenia patients receiving PP showed a significant improvement in psychotic symptoms and similar adverse events compared to placebo and suggested that all doses of PP were efficacious and well tolerated. Other studies demonstrated noninferiority of PP compared to risperidone long-acting injectable in recently diagnosed schizophrenia patients, chronically ill patients, as well as in acute and nonacute symptomatic schizophrenia patients, and a similar proportion of treatment-emergent adverse events between both groups were also noted. Conclusion Several studies have demonstrated that schizophrenia patients treated with PP show higher rates of improvement of psychotic symptoms compared to placebo, and similar efficacy and tolerability outcomes were noted when comparing PP to risperidone long-acting injectable or oral, paliperidone extended release. PMID:26082620

  9. Long-Term Efficacy and Safety of Repeated Intravescial OnabotulinumtoxinA Injections Plus Hydrodistention in the Treatment of Interstitial Cystitis/Bladder Pain Syndrome.

    PubMed

    Lee, Cheng-Ling; Kuo, Hann-Chorng

    2015-10-01

    Intravesical onabotulinumtoxinA (BoNT-A) injection can relieve symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks sustainability. Repeated injections have been shown to provide a superior outcome to a single injection, but data on long-term efficacy and safety is limited. In this prospective study, we enrolled patients with refractory IC/BPS, and treated them with 100 U of BoNT-A injection plus hydrodistention followed by repeated injections every six months for up to two years or until the patient wished to discontinue. A "top-up" dose was offered after the fourth injection. Of these 104 participants, 56.7% completed four BoNT-A injections and 34% voluntarily received the fifth injection due to exacerbated IC symptoms. With a follow-up period of up to 79 months, O'Leary-Sant symptom and problem indexes (ICSI, ICPI, OSS), pain visual analogue scale (VAS) functional bladder capacity, frequency episodes, and global response assessment (GRA) all showed significant improvement (p < 0.0001). Those who received repeated injections had a better success rate during the long-term follow-up period. The incidence of adverse events did not rise with the increasing number of BoNT-A injections. A higher pre-treatment ICSI and ICPI score was predictive for successful response to repeated intravesical BoNT-A injections plus hydrodistention. PMID:26506388

  10. Long-Term Efficacy and Safety of Repeated Intravescial OnabotulinumtoxinA Injections Plus Hydrodistention in the Treatment of Interstitial Cystitis/Bladder Pain Syndrome

    PubMed Central

    Lee, Cheng-Ling; Kuo, Hann-Chorng

    2015-01-01

    Intravesical onabotulinumtoxinA (BoNT-A) injection can relieve symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks sustainability. Repeated injections have been shown to provide a superior outcome to a single injection, but data on long-term efficacy and safety is limited. In this prospective study, we enrolled patients with refractory IC/BPS, and treated them with 100 U of BoNT-A injection plus hydrodistention followed by repeated injections every six months for up to two years or until the patient wished to discontinue. A “top-up” dose was offered after the fourth injection. Of these 104 participants, 56.7% completed four BoNT-A injections and 34% voluntarily received the fifth injection due to exacerbated IC symptoms. With a follow-up period of up to 79 months, O’Leary-Sant symptom and problem indexes (ICSI, ICPI, OSS), pain visual analogue scale (VAS) functional bladder capacity, frequency episodes, and global response assessment (GRA) all showed significant improvement (p < 0.0001). Those who received repeated injections had a better success rate during the long-term follow-up period. The incidence of adverse events did not rise with the increasing number of BoNT-A injections. A higher pre-treatment ICSI and ICPI score was predictive for successful response to repeated intravesical BoNT-A injections plus hydrodistention. PMID:26506388

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

    PubMed Central

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

    2015-01-01

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

  12. Long-term safety, efficacy, and patient acceptability of the intrauterine Copper T-380A contraceptive device

    PubMed Central

    Kaneshiro, Bliss; Aeby, Tod

    2010-01-01

    The intrauterine device (IUD), primarily in the form of the copper IUD, is used by more than 150 million women around the world, making it the most widely used reversible method of contraception. With a remarkably low failure rate of less than 1 per 100 women in the first year of use, the Copper T-380A is in the top tier of contraceptives in terms of efficacy. Risks of utilization include perforation and an increased risk of infection in the first 20 days following insertion. Overall, the number of adverse events is low, making the Copper T-380A a very safe contraceptive method. The most common reasons for the discontinuation of this method are menstrual bleeding and dysmenorrhea. However, cumulative discontinuation rates of Copper T-380A are lower than that have been reported for other methods, indicating that the Copper T-380A is highly acceptable to women. After 5 years, approximately 50% of all women, who have a Copper T-380A inserted, will continue to use this highly effective contraceptive method. PMID:21072313

  13. 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

    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

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

  14. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

    PubMed Central

    Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

    2015-01-01

    Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

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

    PubMed Central

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

    2014-01-01

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

  16. Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors.

    PubMed

    Gambacorti-Passerini, Carlo; Kantarjian, Hagop M; Kim, Dong-Wook; Khoury, Hanna J; Turkina, Anna G; Brümmendorf, Tim H; Matczak, Ewa; Bardy-Bouxin, Nathalie; Shapiro, Mark; Turnbull, Kathleen; Leip, Eric; Cortes, Jorge E

    2015-09-01

    Long-term efficacy and safety of bosutinib (≥4 years follow-up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated-phase [AP, n = 79] chronic myeloid leukemia [CML], blast-phase [BP, n = 64] CML, acute lymphoblastic leukemia [ALL, n = 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1-88.6), 2.8 (0.03-55.9), 0.97 (0.3-89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan-Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (n = 9) for AP and pyrexia (n = 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib-related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge-to-transplant role in BP patients); toxicity was manageable. PMID:26040495

  17. Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

    PubMed Central

    Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Shoji, Toshiharu; Miyasaka, Nobuyuki; Koike, Takao

    2014-01-01

    Abstract Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules. PMID:24593170

  18. Long-term safety and efficacy of sirolimus-eluting stents versus bare-metal stents in real world clinical practice in Japan.

    PubMed

    Kimura, Takeshi; Morimoto, Takeshi; Furukawa, Yutaka; Nakagawa, Yoshihisa; Kadota, Kazushige; Iwabuchi, Masashi; Shizuta, Satoshi; Shiomi, Hiroki; Tada, Tomohisa; Tazaki, Junichi; Kato, Yoshihiro; Hayano, Mamoru; Abe, Mitsuru; Tamura, Takashi; Shirotani, Manabu; Miki, Shinji; Matsuda, Mitsuo; Takahashi, Mamoru; Ishii, Katsuhisa; Tanaka, Masaru; Aoyama, Takeshi; Doi, Osamu; Hattori, Ryuichi; Tatami, Ryozo; Suwa, Satoru; Takizawa, Akinori; Takatsu, Yoshiki; Takahashi, Masaaki; Kato, Hiroshi; Takeda, Teruki; Lee, Jong-Dae; Nohara, Ryuji; Ogawa, Hisao; Tei, Chuwa; Horie, Minoru; Kambara, Hirofumi; Fujiwara, Hisayoshi; Mitsudo, Kazuaki; Nobuyoshi, Masakiyo; Kita, Toru

    2011-09-01

    Long-term safety and efficacy of drug-eluting stents remains controversial. The CREDO-Kyoto registry cohort-2 is a physician-initiated non-company sponsored multi-center registry enrolling consecutive patients undergoing first coronary revascularization in 26 centers in Japan. We compared 3-year outcome between patients treated with sirolimus-eluting stent (SES) only (5092 patients) and bare-metal stent (BMS) only (5405 patients). SES-use as compared with BMS-use was associated with significantly lower adjusted risk for all-cause death [hazard ratio (HR) [95% confidence interval (CI)] 0.72 (0.59-0.87), P = 0.0007], which was mainly driven by the reduction in non-cardiac death [HR (95% CI) 0.64 (0.48-0.85), P = 0.002]. The risk of cardiac death [HR (95% CI) 0.82 (0.63-1.07), P = 0.15], myocardial infarction [HR (95% CI) 0.73 (0.51-1.03), P = 0.07] and definite stent thrombosis [HR (95% CI) 0.62 (0.35-1.09), P = 0.1] was not different between the two groups. Despite longer duration of thienopyridine administration, SES-use was associated with significantly lower risk for bleeding [HR (95% CI) 0.75 (0.6-0.95), P = 0.02] and similar risk for stroke [HR (95% CI) 1.0 (0.75-1.34), P = 1.0]. The risk for target-lesion revascularization (TLR) was markedly lower in the SES group [HR (95% CI) 0.42 (0.36-0.48), P < 0.0001]. The direction and magnitude of the effect of SES relative to BMS in patients presenting acute myocardial infarction (AMI) were similar to those in patients presenting otherwise. In conclusion, SES-use as compared with BMS-use was associated with marked reduction of TLR without any increases in death, myocardial infarction, stent thrombosis, stroke and bleeding in real world clinical practice regardless of clinical presentation including AMI. PMID:24122590

  19. A security/safety survey of long term care facilities.

    PubMed

    Acorn, Jonathan R

    2010-01-01

    What are the major security/safety problems of long term care facilities? What steps are being taken by some facilities to mitigate such problems? Answers to these questions can be found in a survey of IAHSS members involved in long term care security conducted for the IAHSS Long Term Care Security Task Force. The survey, the author points out, focuses primarily on long term care facilities operated by hospitals and health systems. However, he believes, it does accurately reflect the security problems most long term facilities face, and presents valuable information on security systems and practices which should be also considered by independent and chain operated facilities. PMID:20873497

  20. Long-term efficacy and safety of rabeprazole in patients taking low-dose aspirin with a history of peptic ulcers: a phase 2/3, randomized, parallel-group, multicenter, extension clinical trial

    PubMed Central

    Fujishiro, Mitsuhiro; Higuchi, Kazuhide; Kato, Mototsugu; Kinoshita, Yoshikazu; Iwakiri, Ryuichi; Watanabe, Toshio; Takeuchi, Toshihisa; Sugisaki, Nobuyuki; Okada, Yasushi; Ogawa, Hisao; Arakawa, Tetsuo; Fujimoto, Kazuma

    2015-01-01

    A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated. PMID:26060354

  1. Long-Term Safety and Efficacy of Atazanavir-Based Therapy in HIV-Infected Infants, Children and Adolescents: The Pediatric AIDS Clinical Trials Group Protocol 1020A

    PubMed Central

    Rutstein, Richard M.; Samson, Pearl; Fenton, Terry; Fletcher, Courtney V.; Kiser, Jennifer J.; Mofenson, Lynne M.; Smith, Elizabeth; Graham, Bobbie; Mathew, Marina; Aldrovani, Grace

    2014-01-01

    Background Atazanavir is an attractive option for the treatment of Pediatric HIV infection, based on once daily dosing and the availability of a formulation appropriate for younger children. PACTG 1020A was a phase I/II open label study of atazanavir (ATV) (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses. Methods Antiretroviral-naïve and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA >5000 copies/ml (cpm) were enrolled at sites in the United States and South Africa. Results Of 195 children enrolled 142 (73%) subjects received ATV-based regimens at the final protocol recommended dose. 58% were treatment naive. Overall, at week 24, 84/139 subjects (60.4%) and at week 48, 83/142 (58.5%), had HIV RNA ≤400 cpm. At week 48, 69.5% of naïve and 43.3% of experienced subjects had HIV RNA ≤400 cpm; median CD4 increase was 196.5 cells/mm3. The primary adverse event was increased serum bilirubin; 9% of subjects had levels > 5.1 times upper limit of normal and 1.4% noted jaundice. 3% of subjects experienced Grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15% increase in total cholesterol (TC), with TC >199 mg/dL increasing from 1% at baseline to 5.7%. Conclusions Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary adverse event, as expected, was an increase in bilirubin levels. PMID:25232777

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

    PubMed

    McDonnell, David P; Landry, John; Detke, Holland C

    2014-11-01

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

  3. 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

    2014-01-01

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

  4. 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

    2013-01-01

    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 γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year. Conclusion Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer. Trial registration ClinicalTrials.gov identifier NCT00595517. PMID:23530709

  5. Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short-term and long-term efficacy and safety results.

    PubMed

    Barge-Caballero, Gonzalo; Barge-Caballero, Eduardo; Marzoa-Rivas, Raquel; Paniagua-Martín, María J; Barrio-Rodríguez, Alfredo; Naya-Leira, Carmen; Blanco-Canosa, Paula; Grille-Cancela, Zulaika; Vázquez-Rodríguez, José Manuel; Crespo-Leiro, María G

    2015-09-01

    We conducted an observational study of 30 heart transplant recipients with serum low-density lipoprotein cholesterol (LDL-c) >100 mg/dl despite previous statin therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long-term rosuvastatin therapy beyond this 12-week period were reviewed in February 2015. Over the 12-week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL-c and the ratio TC/high-density lipoprotein cholesterol (HDL-c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were -48.7 mg/dl, -46.6 mg/dl, and -0.9, respectively. Seventeen (57%) achieved a serum LDL-c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL-c, hepatic enzymes, bilirubin, or CPK. Twenty-seven (90%) patients continued on long-term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens. PMID:25864881

  6. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan.

    PubMed

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Itamura, Rio; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75-225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (-10.76; P=0.031), but not in the flexible-dose (-10.37; P=0.106) group compared with placebo (-9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan. PMID:26513202

  7. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan

    PubMed Central

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75–225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (−10.76; P=0.031), but not in the flexible-dose (−10.37; P=0.106) group compared with placebo (−9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan. PMID:26513202

  8. Long-term efficacy and safety of etravirine-containing regimens in a real-life cohort of treatment-experienced HIV-1-infected patients.

    PubMed

    Allavena, Clotilde; Katlama, Christine; Cotte, Laurent; Roger, Pierre Marie; Delobel, Pierre; Cheret, Antoine; Duvivier, Claudine; Poizot-Martin, Isabelle; Hoen, Bruno; Cabie, André; Cheret, Arnaud; Lahoulou, Rima; Raffi, François; Pugliese, Pascal

    2016-05-01

    Objectives Etravirine (ETR) was approved in France in September 2008 and is used in combination with a boosted protease inhibitor (bPI) and other anti-retrovirals (ART) in HIV-infected pre-treated patients. This study aimed to report in a real-life setting the efficacy and tolerability of ETR-based regimens and factors associated with virological response. Methods The study population included all treatment-experienced patients who initiated an ETR-based regimen between September 2008 and July 2013 from the French Dat'AIDS cohort. Analyses were performed in ART-experienced patients starting ETR after virological failure (VF) or as a maintenance therapy (MT), with or without bPI. Results A total of 2006 patients (VF, n = 1014 (51%); MT, n = 992 (49%)) were included. At M12, the proportion of patients with HIV RNA < 50 copies/ml was 71.7% (72.0% and 71.1% with or without bPI) in the VF group and 90.5% (85.0% and 92.3% with or without bPI) in the MT group, without significant differences regarding the use of bPI. ETR was discontinued in 8.8% of patients for adverse events in 23.9% of cases (21.5% in VF, 29.5% in MT), treatment failure in 15.2% (16.2% in VF, 7.4% in MT) or simplification in 5.4% (4.6% in VF, 7.4% in MT). In the VF group, factors associated with virological response were a longer duration of HIV infection (OR = 2.7; p < 0.001) and baseline HIV RNA < 5 log10 copies/mL (OR = 2.1; p = 0.002). Conclusion This study shows that in ART-experienced patients ETR is well tolerated with a high efficacy when combined with other active drugs, even when the regimen does not include a bPI. PMID:26757613

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

    PubMed Central

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

    2012-01-01

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

  10. Bariatric/metabolic surgery: short- and long-term safety.

    PubMed

    Kim, Jong-Han; Wolfe, Bruce

    2012-12-01

    The increasing incidence of bariatric/metabolic surgery has brought concerns about the short- and long-term safety of this definitive treatment option. Many multicenter, large cohort studies of outcomes after bariatric surgery have been performed worldwide. Due to innovation in surgical methods and postoperative management programs in this field, there is a continuous improvement of outcomes related to safety. Many systemic and surgical complications after bariatric surgery have been reported, and late complications after gastric banding procedure are becoming issues as long-term follow-up studies are being performed. These databases utilize both clinical and administrative data methods. They may report in hospital only 30 or 90 day complication rates. Perioperative mortality in the past has been reported in as many as 1.5 to 2 % of bariatric surgical cases. Most recently this mortality has been reduced to 0.04-0.3 % from registries involving many thousands of patients. Complications are defined variably. Serious complications reportedly occur in 1-4 % of patients. In malabsorptive procedures, nutritional and micronutrient support is important because they frequently cause nutritional and metabolic problems long after surgery. Also, procedure-related complications such as intestinal obstruction and anastomotic stricture should be monitored after gastric bypass. This review refers to such adverse events which can threaten patient safety after bariatric surgery. PMID:23054663

  11. Long-term safety issues associated with mixer pump operation

    SciTech Connect

    Kubic, W.L. Jr.

    1994-12-31

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

  12. The efficacy and safety of reinstitution of tocilizumab in patients with relapsed active rheumatoid arthritis after long-term withdrawal of tocilizumab: retreatment of patients with rheumatoid arthritis with novel anti-IL-6 receptor antibody after a long-term interval following SAMURAI: the RONIN study.

    PubMed

    Sagawa, Akira

    2011-08-01

    We have evaluated the efficacy and safety of tocilizumab (TCZ) re-administration in patients with active rheumatoid arthritis (RA) who had previously received TCZ treatment for about 31 months. Four patients whose RA had been well-controlled with 8 mg/kg TCZ treatment every 4 weeks and had withdrawn from the treatment were enrolled. They resumed TCZ treatment after TCZ was authorized for RA treatment in Japan. Disease activity was assessed by the Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR), and synovitis in the wrists and elbows was measured by ultrasonography at baseline and during follow-up. The mean DAS28-ESR was 6.32 before the first TCZ infusion. After fewer than 20 months of initial TCZ treatment, the mean DAS28-ESR decreased to 1.87. However, after withdrawal of TCZ treatment, the disease activity could not be sufficiently controlled with conventional disease-modifying antirheumatic drugs or biologic agents. The maximum interval between TCZ treatments was approximately 34 months. Following reinstatement of the TCZ treatment, within 12 months the mean DAS28-ESR improved from 5.21 to 2.87, with the synovitis in the wrists and elbow joints also showing great improvement. These findings demonstrate that TCZ retreatment in active RA patients who had relapsed after long-term discontinuation of TCZ treatment led to an improvement in the signs and symptoms of RA and in synovitis without any severe adverse events. PMID:21347804

  13. Efficacy, safety, and tolerability of long-term lipoprotein apheresis in patients with LDL- or Lp(a) hyperlipoproteinemia: Findings gathered from more than 36,000 treatments at one center in Germany.

    PubMed

    Heigl, Franz; Hettich, Reinhard; Lotz, Norbert; Reeg, Harduin; Pflederer, Tobias; Osterkorn, Dirk; Osterkorn, Klaus; Klingel, Reinhard

    2015-05-01

    LDL cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are main risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 36,745 LA treatments of 118 patients with CVD in a retrospective, monocentric study. Indications were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (n = 35). Average age of patients at start of LA treatment was 58.1 years for males and 62.5 years for females. Medium interval between the first cardiovascular event and LA treatment was 6.4 5.6 years and the average LA treatment period was 6.8 4.9 years. On average treatments were performed once a week, via peripheral venous access in 79.3% of non-hemodialysis patients. In patients with hypercholesterolemia initial pre-LA LDL-C was lowered from 176.4 67.0 mg/dL by 66.7 10.8% per session, achieving a long-term interval mean value of 119.8 34.7 mg/dL, i.e. reduction by 32.1 19.6% (p < 0.0001). In patients with isolated elevated Lp(a) initial pre-LA Lp(a) was lowered from 127.2 67.3 mg/dL by 66.8 5.8% per session, achieving a long-term interval mean value of 60.0 19.5 mg/dL, i.e. reduction by 52.8 23.0% (p < 0.0001). After start of LA the average annual rate of major adverse coronary events (MACE) of all patients declined by 79.7% (p < 0.0001). Subgroup analysis showed decline by 73.7% (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4% (p < 0.0001) in patients with isolated elevated Lp(a). Adverse events (AE) occurred in 1.1% of treatments. LA treatment of patients with high risk for CVD due to LDL and/or Lp(a) hyperlipoproteinemia was effective, safe, and well tolerated. The number of cardiovascular events, at least during a six-year period, declined by 80%. PMID:25936320

  14. Demonstrating the Safety of Long-Term Dry Storage - 13468

    SciTech Connect

    McCullum, Rod; Brookmire, Tom; Kessler, John; Leblang, Suzanne; Levin, Adam; Martin, Zita; Nesbit, Steve; Nichol, Marc; Pickens, Terry

    2013-07-01

    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)

  15. Safety, Tolerability, and Compliance with Long-Term Antimalarial Chemoprophylaxis in American Soldiers in Afghanistan.

    PubMed

    Saunders, David L; Garges, Eric; Manning, Jessica E; Bennett, Kent; Schaffer, Sarah; Kosmowski, Andrew J; Magill, Alan J

    2015-09-01

    Long-term antimalarial chemoprophylaxis is currently used by deployed U.S. military personnel. Previous small, short-term efficacy studies have shown variable rates of side effects among patients taking various forms of chemoprophylaxis, though reliable safety and tolerability data on long-term use are limited. We conducted a survey of troops returning to Fort Drum, NY following a 12-month deployment to Operation Enduring Freedom, Afghanistan from 2006 to 2007. Of the 2,351 respondents, 95% reported taking at least one form of prophylaxis during their deployment, and 90% were deployed for > 10 months. Compliance with daily doxycycline was poor (60%) compared with 80% with weekly mefloquine (MQ). Adverse events (AEs) were reported by approximately 30% with both MQ and doxycycline, with 10% discontinuing doxycycline compared with 4% of MQ users. Only 6% and 31% of soldiers reported use of bed nets and skin repellents, respectively. Compliance with long-term malaria prophylaxis was poor, and there were substantial tolerability issues based on these anonymous survey results, though fewer with MQ than doxycycline. Given few long-term antimalarial chemoprophylaxis options, there is an unmet medical need for new antimalarials safe for long-term use. PMID:26123954

  16. Long-term efficacy and safety of oxycodone–naloxone prolonged release in geriatric patients with moderate-to-severe chronic noncancer pain: a 52-week open-label extension phase study

    PubMed Central

    Guerriero, Fabio; Roberto, Anna; Greco, Maria Teresa; Sgarlata, Carmelo; Rollone, Marco; Corli, Oscar

    2016-01-01

    Background Two-thirds of older people suffer from chronic pain and finding valid treatment options is essential. In this 1-yearlong investigation, we evaluated the efficacy and safety of prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 (mean 81.7) years. Methods In this open-label prospective study, patients with moderate-to-severe noncancer chronic pain were prescribed OXN-PR for 1 year. The primary endpoint was the proportion of patients who achieved ≥30% reduction in pain intensity after 52 weeks of treatment, without worsening bowel function. The scheduled visits were at baseline (T0), after 4 weeks (T4), and after 52 weeks (T52). Results Fifty patients completed the study. The primary endpoint was achieved in 78% of patients at T4 and 96% at T52 (P<0.0001). Pain intensity, measured on a 0–10 numerical rating scale, decreased from 6.0 at T0 to 2.8 at T4 and to 1.7 at T52 (P<0.0001). Mean daily dose of oxycodone increased from 10 to 14.4 mg (T4) and finally to 17.4 mg (T52). Bowel Function Index from 35.1 to 28.7 at T52. No changes were observed in cognitive functions (Mini-Mental State Examination evaluation), while daily functioning improved (Barthel Index from 53.1 to 61.0, P<0.0001). The Screener and Opioid Assessment for Patients with Pain-Revised score at 52 weeks was 2.6 (standard deviation 1.6), indicating a low risk of aberrant medication-related behavior. In general, OXN-PR was well tolerated. Conclusion This study of the long-term treatment of chronic pain in a geriatric population with OXN-PR shows satisfying analgesic effects achieved with a stable low daily dose, coupled with a good safety profile and, in particular, with a reduction of constipation, often present during opioid therapy. Our findings support the indications of the American Geriatrics Society, suggesting the use of opioids to treat pain in older people not responsive to acetaminophen or nonsteroidal anti-inflammatory drugs. PMID:27143857

  17. Assessment of Countermeasure Efficacy for Long-Term Space Missions

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

    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.

  18. Efficacy and safety of betahistine treatment in patients with Meniere’s disease: primary results of a long term, multicentre, double blind, randomised, placebo controlled, dose defining trial (BEMED trial)

    PubMed Central

    Adrion, Christine; Fischer, Carolin Simone; Wagner, Judith; Gürkov, Robert; Mansmann, Ulrich

    2016-01-01

    Study question What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere’s disease, compared with placebo? Methods The BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). Adults aged 21-80 years (mean age 56 years) with definite unilateral or bilateral Meniere’s disease were recruited from March 2008 to November 2012. Participants received placebo (n=74), low dose betahistine (2×24 mg daily, (n=73)), or high dose betahistine (3×48 mg daily, (n=74)) over nine months. The primary outcome was the number of attacks per 30 days, based on patients’ diaries during a three month assessment period at months seven to nine. An internet based randomisation schedule performed a concealed 1:1:1 allocation, stratified by study site. Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function. Study answer and limitations Incidence of attacks related to Meniere’s disease did not differ between the three treatment groups (P=0.759). Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. The overall monthly attack rate fell significantly by the factor 0.758 (0.705 to 0.816; P<0.001). The population based, mean monthly incidence averaged over the assessment period was 2.722 (1.304 to 6.309), 3.204 (1.345 to 7.929), and 3.258 (1.685 to 7.266) for the placebo, low dose betahistine, and high dose betahistine groups, respectively. Results were consistent for all secondary outcomes. Treatment was well tolerated with no unexpected safety findings. Without a control group of patients who did not receive any intervention to follow the natural course of the disease, the placebo effect could not be accurately assessed and differentiated from spontaneous remission and fluctuation of symptoms. What this study adds Current evidence is limited as to whether betahistine prevents vertigo attacks caused by Meniere’s disease, compared with placebo. The trial provides information on symptom relief on placebo intervention which is relevant for the design of future studies on potential disease modifying treatments in patients with Meniere’s disease. Funding, competing interests, data sharing Support from the German Federal Ministry of Education and Research (BMBF support code 01KG0708). Potential competing interests have been reported in full at the end of the paper on thebmj.com. Data are available from the corresponding author (Michael.Strupp@med.uni-muenchen.de) or biostatistician (mansmann@ibe.med.uni-muenchen.de). Study registration EudraCT no 2005-000752-32; ISRCTN no ISRCTN44359668. PMID:26797774

  19. Long-Term Efficacy of Adalimumab in Patients With Intestinal Behcet's Disease: Eight Consecutive Cases.

    PubMed

    Tanida, Satoshi; Mizoshita, Tsutomu; Nishie, Hirotada; Ozeki, Keiji; Katano, Takahito; Shimura, Takaya; Kubota, Eiji; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

    2016-04-01

    The long-term efficacy and safety of adalimumab (ADA) for the treatment of intestinal Behcet's disease (BD) in the clinical setting have not been evaluated previously. This retrospective study evaluated the 52-week efficacy of ADA in BD patients. A total of eight patients who were refractory to conventional therapy were given ADA (160/80/40 mg every other week). Marked improvement (MI) was achieved by 10 weeks in five patients (62.5%), and by 52 weeks in six patients (75%). In addition, complete remission was obtained in two patients (25%) at both 10 and 52 weeks. Improvement of global gastrointestinal (GI) symptoms to score 0 was observed in three patients (37.5%) at 10 weeks and four patients (50%) at 52 weeks. Moreover, improvement of endoscopic assessment to score 0 was also seen in four patients (50%) at both 10 and 52 weeks. No adverse events were observed in any patients during the 52 weeks. In conclusion, ADA offers an effective, well-tolerated treatment for intestinal BD in patients who are refractory to conventional therapy. PMID:26985255

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

    PubMed Central

    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

    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. PMID:23040887

  1. Acute And Long-Term Bioeffects And Lamp Safety

    NASA Astrophysics Data System (ADS)

    Andersen, F. Alan

    1980-10-01

    Knowledge of both acute and chronic biological effects is currently used to evaluate lamp safety. In some cases, a quantitative basis for avoiding exposures greater than a certain value can be stated. In other cases, however, only a qualitative estimate of the hazard is available. In a discussion that uses mercury vapor lamps, tanning booths, and sodium vapor lamps as examples, the interplay between the two types of data leading to an evaluation of lamp safety is described.

  2. Long-term safety and effectiveness of tanezumab as treatment for chronic low back pain.

    PubMed

    Gimbel, Joseph S; Kivitz, Alan J; Bramson, Candace; Nemeth, Mary Anne; Keller, David S; Brown, Mark T; West, Christine R; Verburg, Kenneth M

    2014-09-01

    A noncontrolled, randomized, multicenter study (NCT00924664) evaluated long-term safety and effectiveness of tanezumab in patients with chronic low back pain following a randomized placebo- and active-controlled parent study that evaluated analgesic efficacy. Patients were randomized to tanezumab 10mg (n=321) or 20mg (n=527) administered at 8-week intervals via 3 intravenous injections followed by 4 subcutaneous injections. Effectiveness analyses included change from parent study baseline in Brief Pain Inventory Short Form, Roland Morris Disability Questionnaire, and Patient's Global Assessment of low back pain. Safety assessments included adverse event documentation, physical/neurological examinations, and laboratory tests. Mean treatment duration during the extension study was 194 and 202 days with tanezumab 10 and 20mg, respectively. Both tanezumab doses provided similar and sustained improvements in all effectiveness outcomes. The most frequently reported adverse events were arthralgia, paresthesia, and hypoesthesia. Adverse events initially described as osteonecrosis were reported in 6 patients (tanezumab 10mg, n=2; tanezumab 20mg, n=4); 9 additional patients (tanezumab 10mg, n=7; tanezumab 20mg, n=2) underwent total joint replacement (TJR). A blinded, independent adjudication committee reviewed all 6 patients with reported osteonecrosis and 4 of the 9 patients undergoing TJR. Adjudication outcomes were osteonecrosis (n=0), worsening osteoarthritis (n=5; 1 rapidly progressive), and another diagnosis or indeterminate (n=5). Tanezumab 10mg had better tolerability than tanezumab 20mg, and may represent an effective long-term treatment for chronic low back pain. PMID:24937440

  3. Long-term safety of pegloticase in chronic gout refractory to conventional treatment

    PubMed Central

    Becker, Michael A; Baraf, Herbert S B; Yood, Robert A; Dillon, Aileen; Vázquez-Mellado, Janitzia; Ottery, Faith D; Khanna, Dinesh; Sundy, John S

    2013-01-01

    Objective To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout. Methods This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks (monthly). Safety was evaluated as the primary outcome, with special interest in gout flares and infusion-related reactions (IRs). Secondary outcomes included urate-lowering and clinical efficacy. Results Patients (n=149) received a mean±SD of 28±18 pegloticase infusions and were followed for a mean of 25±11 months. Gout flares and IRs were the most frequently reported adverse events; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment. In 10 of the 11 patients with a serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum uric acid levels remained <6 mg/dl in most randomised controlled trial (RCT)-defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence. Conclusions The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment; no new safety signals were identified. Improvements in clinical status, in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment. PMID:23144450

  4. Short-term cognitive-behavioral therapy for binge eating disorder: long-term efficacy and predictors of long-term treatment success.

    PubMed

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

    2014-07-01

    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

  5. Improving patient safety in a UK dental hospital: long-term use of clinical audit.

    PubMed

    Ashley, M P; Pemberton, M N; Saksena, A; Shaw, A; Dickson, S

    2014-10-01

    The improvement of patient safety has been a long-term aim of healthcare organisations and following recent negative events within the UK, the focus on safety has rightly increased. For over twenty years, clinical audit has been the tool most frequently used to measure safety-related aspects of healthcare and when done so correctly, can lead to sustained improvements. This paper explains how clinical audit is used as a safety improvement tool in an English dental hospital and gives several examples of projects that have resulted in long-term improvements in secondary dental care. PMID:25303590

  6. Long-term efficacy and safety of incobotulinumtoxinA and conventional treatment of poststroke arm spasticity: a prospective, non-interventional, open-label, parallel-group study

    PubMed Central

    Dressler, Dirk; Rychlik, Reinhard; Kreimendahl, Fabian; Schnur, Nicole; Lambert-Baumann, Judith

    2015-01-01

    Objective To compare the efficacy and safety of incobotulinumtoxinA with conventional antispastic therapy for poststroke arm spasticity in routine clinical practice over a 1-year period. Design Prospective, non-interventional, open-label, parallel-group study. Setting 47 centres in Germany. Participants Patients with poststroke arm spasticity; 108 receiving incobotulinumtoxinA, 110 conventional therapy. Intervention Conventional antispastic treatment including oral antispastic medications, physiotherapy and occupational therapy or 3-monthly incobotulinumtoxinA injections plus conventional therapy if required. Main outcome measures The main outcome measure was changes in muscle tone (Ashworth Scale) over the 1-year treatment period. Changes in functional disability (Disability Assessment Scale) and quality of life (Short-Form-12 Health Survey) were additionally assessed. Ratings for therapy outcome (Goal Attainment Scale), and efficacy and tolerability of treatment (Global Clinical Impression Scale) were also obtained. Results Muscle tone improved for all spasticity patterns with the Ashworth Scale responder rates between 63% and 86% (incobotulinumtoxinA) and 16–27% (conventional therapy). Median improvement in functional disability was –1.0 (incobotulinumtoxinA) and 0.0 (conventional measures) for all domains. Treatment goals were attained by 93% of incobotulinumtoxinA patients and 30% of patients under conventional therapy. Most physicians (93%) and patients (90%) rated efficacy as good or very good under incobotulinumtoxinA; the proportions were much lower under conventional therapy (36% and 37%). Tolerability under incobotulinumtoxinA was considered good or very good by 99% of physicians and patients (76% and 66%, respectively, under conventional therapy). Quality of life under incobotulinumtoxinA improved by 8.0 (physical score) and 10.8 (mental score) and by 0.8 and 5.7, respectively, under conventional therapy. Conclusions IncobotulinumtoxinA combined with rehabilitation and oral medication produces a much more robust improvement in all aspects of arm spasticity than conventional antispastic treatment. Effects are stable over a period of 1 year, whereas adverse effects are negligible. IncobotulinumtoxinA should be considered the treatment of choice for poststroke arm spasticity. PMID:26719317

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

    PubMed Central

    2013-01-01

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

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

    SciTech Connect

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

    2007-12-01

    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.

  9. Long-term (60-month) results for the implantable miniature telescope: efficacy and safety outcomes stratified by age in patients with end-stage age-related macular degeneration

    PubMed Central

    Boyer, David; Freund, K Bailey; Regillo, Carl; Levy, Marc H; Garg, Sumit

    2015-01-01

    Background The purpose of this study was to evaluate the long-term results of an implantable miniature telescope (IMT) in patients with bilateral, end-stage, age-related macular degeneration (AMD). Methods A prospective, open-label, multicenter clinical trial with fellow eye controls enrolled 217 patients (mean age 76 years) with AMD and moderate-to-profound bilateral central visual acuity loss (20/80–20/800) resulting from untreatable geographic atrophy, disciform scars, or both. A subgroup analysis was performed with stratification for age (patient age 65 to <75 years [group 1; n=70] and patient age ≥75 years [group 2; n=127]), with a comparative evaluation of change in best-corrected distance visual acuity (BCDVA), quality of life, ocular complications from surgery, adverse events, and endothelial cell density (ECD). Follow-up in an extension study was 60 months. Results Data were available for 22, 38, and 31 patients in group 1 and 42, 46, and 32 patients in group 2 at 36, 48, and 60 months, respectively. Mean BCDVA improvement from baseline to 60 months was 2.41±2.69 lines in all patients (n=76), with 2.64±2.55 lines in group 1 and 2.09±2.88 lines in group 2. Quality of life scores were significantly higher in group 1. The most common significant surgery-related ocular complications in group 1 were iritis >30 days after surgery (7/70; 10%) and persistent corneal edema (3/70; 4.3%); and in group 2 were a decrease in BCDVA in the implanted eye or IMT removal (10/127 each; 7.9%), corneal edema >30 days after surgery (9/127; 7.1%), and persistent corneal edema (6/127; 4.7%). Significant adverse events included four corneal transplants, comprising two (2.9%) in group 1 and two (1.6%) in group 2. At 60 months, one patient in group 1 (3.2%) and three patients in group 2 (9.4%) had lost ≥2 lines of vision. The IMT was removed in one (1.4%) and ten (7.9%) patients in group 1 and group 2, respectively. Mean ECD loss was 20% at 3 months. Chronic loss was 3% per year. ECD loss was less in group 1 than in group 2 (35% versus 40%, respectively) at 60 months. Conclusion Long-term results show substantial retention of improvement in BDCVA. Chronic ECD loss was consistent with that reported for conventional intraocular lenses. The IMT performed as well in group 1 (the younger group) as it did in group 2 through month 60. Younger patients retained more vision than their older counterparts and had fewer adverse events. Although not a specified outcome for this study, patients younger than 65 years also fared better than those in group 2 and retained more vision with fewer adverse events through month 60. PMID:26124633

  10. 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

    2012-01-01

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

  11. Influence of advancing age on clinical presentation, treatment efficacy and safety, and long-term outcome of pre-excitation syndromes: a retrospective cohort study of 961 patients included over a 25-year period

    PubMed Central

    Brembilla-Perrot, Béatrice; Olivier, Arnaud; Sellal, Jean-Marc; Manenti, Vladimir; Brembilla, Alice; Villemin, Thibaut; Admant, Philippe; Beurrier, Daniel; Bozec, Erwan; Girerd, Nicolas

    2016-01-01

    Objectives There are very little data on pre-excitation syndrome (PS) in the elderly. We investigated the influence of advancing age on clinical presentation, treatment and long-term outcome of PS. Setting Single-centre retrospective study of patient files. Participants In all, 961 patients (72 patients ≥60 years (mean 68.5±6), 889 patients <60 years (mean 30.5±14)) referred for overt pre-excitation and indication for electrophysiological study (EPS) were followed for 5.3±5 years. Usual care included 24 h Holter monitoring, echocardiography and EPS. Patients underwent accessory pathway (AP) ablation if necessary. Primary and secondary outcome measures Occurrence of atrial fibrillation (AF) or procedure-induced adverse event. Results Electrophysiological data and recourse to AP ablation (43% vs 48.5%, p=0.375) did not significantly differ between the groups. Older patients more often had symptomatic forms (81% vs 63%, p=0.003), history of spontaneous AF (8% vs 3%, p=0.01) or adverse presentation (poorly tolerated arrhythmias: 18% vs 7%, p=0.0009). In multivariable analysis, patients ≥60 years had a significantly higher risk of history of AF (OR=4.2, 2.1 to 8.3, p=0.001) and poorly tolerated arrhythmias (OR=3.8, 1.8 to 8.1, p=0.001). Age ≥60 years was associated with an increased major AP ablation complication risk (10% vs 1.9%, p=0.006). During follow-up, occurrence of AF (13.9% vs 3.6%, p<0.001) and incidence of poorly tolerated tachycardia (4.2% vs 0.6%, p=0.001) were more frequent in patients ≥60 years, although frequency of ablation failure or recurrence was similar (20% vs 15.5%, p=0.52). In multivariable analysis, patients ≥60 years had a significantly higher risk of AF (OR=2.9, 1.2 to 6.8, p≤0.01). Conclusions In this retrospective monocentre study, patients ≥60 years referred for PS work up appeared at higher risk of AF and adverse presentation, both prior and after the work up. These results suggest that, in elderly patients, the decision for EPS and AP ablation should be discussed in light of their suspected higher risk of events and ablation complications. However, these findings should be further validated in future prospective multicentre studies. PMID:27188807

  12. Resilience Engineering in Critical Long Term Aerospace Software Systems: A New Approach to Spacecraft Software Safety

    NASA Astrophysics Data System (ADS)

    Dulo, D. A.

    Safety critical software systems permeate spacecraft, and in a long term venture like a starship would be pervasive in every system of the spacecraft. Yet software failure today continues to plague both the systems and the organizations that develop them resulting in the loss of life, time, money, and valuable system platforms. A starship cannot afford this type of software failure in long journeys away from home. A single software failure could have catastrophic results for the spaceship and the crew onboard. This paper will offer a new approach to developing safe reliable software systems through focusing not on the traditional safety/reliability engineering paradigms but rather by focusing on a new paradigm: Resilience and Failure Obviation Engineering. The foremost objective of this approach is the obviation of failure, coupled with the ability of a software system to prevent or adapt to complex changing conditions in real time as a safety valve should failure occur to ensure safe system continuity. Through this approach, safety is ensured through foresight to anticipate failure and to adapt to risk in real time before failure occurs. In a starship, this type of software engineering is vital. Through software developed in a resilient manner, a starship would have reduced or eliminated software failure, and would have the ability to rapidly adapt should a software system become unstable or unsafe. As a result, long term software safety, reliability, and resilience would be present for a successful long term starship mission.

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

    PubMed Central

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

    1995-01-01

    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 of a multicentre, randomised, double blind, placebo controlled trial that assessed the effect of oral anticoagulant treatment on mortality as well as cerebrovascular and cardiovascular morbidity in 3404 hospital survivors of acute myocardial infarction. MAIN OUTCOME MEASURES--The effect of anticoagulant treatment on recurrent myocardial infarction, cerebrovascular events, and vascular events (the composite endpoint of reinfarction, cerebrovascular event, and vascular death). RESULTS--Long term anticoagulant treatment was associated with a reduction in mortality of 10% (95% confidence interval -11% to 27%), recurrent myocardial infarction of 53% (41% to 62%), cerebrovascular events of 40% (10% to 60%) and vascular events of 35% (24% to 45%). Treatment effect with respect to recurrent myocardial infarction was comparable among all subgroups of patients. Although treatment effect appeared to be somewhat smaller in females than in males (-11% v -45%), and in patients with diabetes compared to those without (-14% v -42%) with respect to vascular events, none of these differences reached statistical significance. In multivariate analysis, more advanced age, previous myocardial infarction, diabetes mellitus, and heart failure during admission were independently associated with increased incidence of cardiovascular complications. CONCLUSIONS--The relative benefit of long term anticoagulant therapy in survivors of myocardial infarction is not modified by known prognostic factors for cardiovascular disease. PMID:7546987

  14. A long-term efficacy study of gene replacement therapy for RPGR-associated retinal degeneration.

    PubMed

    Wu, Zhijian; Hiriyanna, Suja; Qian, Haohua; Mookherjee, Suddhasil; Campos, Maria M; Gao, Chun; Fariss, Robert; Sieving, Paul A; Li, Tiansen; Colosi, Peter; Swaroop, Anand

    2015-07-15

    Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene account for >70% of X-linked retinitis pigmentosa (XLRP) and 15-20% of all inherited retinal degeneration. Gene replacement therapy for RPGR-XLRP was hampered by the relatively slow disease progression in mouse models and by difficulties in cloning the full-length RPGR-ORF15 cDNA that includes a purine-rich 3'-coding region; however, its effectiveness has recently been demonstrated in four dogs with RPGR mutations. To advance the therapy to clinical stage, we generated new stable vectors in AAV8 or AAV9 carrying mouse and human full-length RPGR-ORF15-coding sequence and conducted a comprehensive long-term dose-efficacy study in Rpgr-knockout mice. After validating their ability to produce full-length proteins that localize to photoreceptor connecting cilia, we evaluated various vector doses in mice during a 2-year study. We demonstrate that eyes treated with a single injection of mouse or human RPGR-ORF15 vector at an optimal dose maintained the expression of RPGR-ORF15 throughout the study duration and exhibited higher electroretinogram amplitude, thicker photoreceptor layer and better targeting of opsins to outer segments compared with sham-treated eyes. Furthermore, mice that received treatment at an advanced age also showed remarkable preservation of retinal structure and function. Retinal toxicity was observed at high vector doses, highlighting the importance of careful dose optimization in future clinical experiments. Our long-term dose-efficacy study should facilitate the design of human trials with human RPGR-ORF15 vector as a clinical candidate. PMID:25877300

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

    ERIC Educational Resources Information Center

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

    2009-01-01

    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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

    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…

  17. Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: a French multicenter study.

    PubMed

    Néel, Antoine; Henry, Benoit; Barbarot, Sebastien; Masseau, Agathe; Perrin, François; Bernier, Claire; Kyndt, Xavier; Puechal, Xavier; Weiller, Pierre-Jean; Decaux, Olivier; Ninet, Jacques; Hot, Arnaud; Aouba, Achille; Astudillo, Leonardo; Berthelot, Jean-Marie; Bonnet, Fabrice; Brisseau, Jean-Marie; Cador, Bérangère; Closs-Prophette, Fabienne; Dejoie, Thomas; de Korwin, Jean-Dominique; Dhote, Robin; Fior, Renato; Grosbois, Bernard; Hachulla, Eric; Hatron, Pierre-Yves; Jardel, Henry; Launay, David; Lorleac'h, Adrien; Pottier, Pierre; Moulis, Guillaume; Serratrice, Jacques; Smail, Amar; Hamidou, Mohamed

    2014-10-01

    The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown. PMID:25220180

  18. Long-term efficacy of microbiology-driven periodontal laser-assisted therapy.

    PubMed

    Martelli, F S; Fanti, E; Rosati, C; Martelli, M; Bacci, G; Martelli, M L; Medico, E

    2016-03-01

    Periodontitis represents a highly prevalent health problem, causing severe functional impairment, reduced quality of life and increased risk of systemic disorders, including respiratory, cardiovascular and osteoarticular diseases, diabetes and fertility problems. It is a typical example of a multifactorial disease, where a polymicrobial infection inducing chronic inflammation of periodontal tissues is favoured by environmental factors, life style and genetic background. Since periodontal pathogens can colonise poorly vascularised niches, antiseptics and antibiotics are typically associated with local treatments to manage the defects, with unstable outcomes especially in early-onset cases. Here, the results of a retrospective study are reported, evaluating the efficacy of a protocol (Periodontal Biological Laser-Assisted Therapy, Perioblast™) by which microbial profiling of periodontal pockets is used to determine the extent and duration of local neodymium-doped yttrium aluminium garnet (Nd:YAG) laser irradiation plus conventional treatment. The protocol was applied multicentrically on 2683 patients, and found to produce a significant and enduring improvement of all clinical and bacteriological parameters, even in aggressive cases. Microbiome sequencing of selected pockets revealed major population shifts after treatment, as well as strains potentially associated with periodontitis in the absence of known pathogens. This study, conducted for the first time on such a large series, clearly demonstrates long-term efficacy of microbiology-driven non-invasive treatment of periodontal disease. PMID:26740323

  19. Short- and long-term efficacy of endoscopic balloon dilation in Crohn’s disease strictures

    PubMed Central

    de’Angelis, Nicola; Carra, Maria Clotilde; Borrelli, Osvaldo; Bizzarri, Barbara; Vincenzi, Francesca; Fornaroli, Fabiola; De Caro, Giuseppina; de’Angelis, Gian Luigi

    2013-01-01

    AIM: To evaluate short- and long-term efficacy of endoscopic balloon dilation in a cohort of consecutive patients with symptomatic Crohn’s disease (CD)-related strictures. METHODS: Twenty-six CD patients (11 men; median age 36.8 year, range 11-65 years) with 27 symptomatic strictures underwent endoscopic balloon dilation (EBD). Both naive and post-operative strictures, of any length and diameter, with or without associated fistula were included. After a clinical and radiological assessment, EBD was performed with a Microvasive Rigiflex through the scope balloon system. The procedure was considered successful if no symptom reoccurred in the following 6 mo. The long-term clinical outcome was to avoid surgery. RESULTS: The mean follow-up time was 40.7 ± 5.7 mo (range 10-94 mo). In this period, forty-six EBD were performed with a technical success of 100%. No procedure-related complication was reported. Surgery was avoided in 92.6% of the patients during the entire follow-up. Two patients, both presenting ileocecal strictures associated with fistula, failed to respond to the treatment and underwent surgical strictures resection. Of the 24 patients who did not undergo surgery, 11 patients received 1 EBD, and 13 required further dilations over time for the treatment of relapsing strictures (7 patients underwent 2 dilations, 5 patients 3 dilations, and 1 patient 4 dilations). Overall, the EBD success rate after the first dilation was 81.5%. No difference was observed between the EBD success rate for naive (n = 12) and post-operative (n = 15) CD related strictures (P > 0.05). CONCLUSION: EBD appears to be a safe and effective procedure in the therapeutic management of CD-related strictures of any origin and dimension in order to prevent surgery. PMID:23674873

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

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

    SciTech Connect

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

    2012-07-01

    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.

  2. The long term storage of radioactive waste and spent fuel: safety and policy considerations

    SciTech Connect

    Rowat, J.; Metcalf, P.

    2007-07-01

    Storage is a necessary step in the overall management of radioactive waste. In recent years, due to the unavailability of disposal facilities, storage facilities intended originally as temporary, have had their lifetimes extended and consideration has been given, in some countries, to the use of long term storage (LTS) as a management option. In 2003, the IAEA published a position paper titled 'The Long Term Storage of Radioactive Waste: Safety and Sustainability'. The position paper, which written for a non-specialist audience, focused on seven key factors for safety and sustainability of LTS, namely: safety, maintenance/institutional control, retrieval, security, costs, community attitudes and retention of information. The Agency is preparing a follow-up report to the position paper that elaborates in a more technical manner upon the issues raised in the position paper and issues important for implementation of LTS. It also provides some discussion of the reasons for implementing a LTS option and contrasts LTS with aspects of other management options. The present paper provides an overview of the draft follow-up report. (authors)

  3. Efficacy of long-term coral tissue storage in ethanol for genotyping studies

    NASA Astrophysics Data System (ADS)

    Berkelmans, R.; Doyle, J.; van Oppen, M. J. H.; Asbridge, E. F.; Brown, A. R.

    2014-03-01

    With climate change threatening the future of coral reefs, there is an urgent need for effective coral tissue preservation and repositories from which DNA can be extracted. Most collections use 95 % ethanol as the storage medium, but its efficacy for long-term storage for short-fragment DNA use remains poorly documented. We conducted an accelerated DNA aging trial on three species of coral to ascertain whether ethanol-stored tissue and skeleton samples could yield fit-for-purpose DNA at time scales of 100+ yrs. We conclude that even using a crude DNA extraction technique, samples kept at 40 °C for 20 months yielded DNA of sufficient quality for Symbiodinium and coral host genotyping. If stored at -20 °C, these samples are likely to still yield useable DNA after 100 yrs. Ethanol-stored samples compared favorably in terms of DNA quality, quantity and sample integrity with those stored in an analogue of the commercial storage buffer RNA later ®.

  4. Long-Term Efficacy of Adalimumab in Patients With Intestinal Behcet’s Disease: Eight Consecutive Cases

    PubMed Central

    Tanida, Satoshi; Mizoshita, Tsutomu; Nishie, Hirotada; Ozeki, Keiji; Katano, Takahito; Shimura, Takaya; Kubota, Eiji; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

    2016-01-01

    The long-term efficacy and safety of adalimumab (ADA) for the treatment of intestinal Behcet’s disease (BD) in the clinical setting have not been evaluated previously. This retrospective study evaluated the 52-week efficacy of ADA in BD patients. A total of eight patients who were refractory to conventional therapy were given ADA (160/80/40 mg every other week). Marked improvement (MI) was achieved by 10 weeks in five patients (62.5%), and by 52 weeks in six patients (75%). In addition, complete remission was obtained in two patients (25%) at both 10 and 52 weeks. Improvement of global gastrointestinal (GI) symptoms to score 0 was observed in three patients (37.5%) at 10 weeks and four patients (50%) at 52 weeks. Moreover, improvement of endoscopic assessment to score 0 was also seen in four patients (50%) at both 10 and 52 weeks. No adverse events were observed in any patients during the 52 weeks. In conclusion, ADA offers an effective, well-tolerated treatment for intestinal BD in patients who are refractory to conventional therapy. PMID:26985255

  5. Growth Hormone and Treatment Controversy; Long Term Safety of rGH

    PubMed Central

    DiVall, Sara A.; Radovick, Sally

    2013-01-01

    The availability of recombinant human growth hormone (rGH) for treatment of growth disorders has provided an unlimited supply for replacement in patients with growth hormone insufficiency but also for short stature due to Turner syndrome, renal failure, Prader-Willi syndrome, small for gestational age and idiopathic short stature. Considering the potential for side effects in the use of a growth promoting agent, the community of physicians and pharmaceutical manufacturers developed systematic methods to survey for short and long term effects. Recently published data from the National Cooperative Growth Study (NCGS), managed by Genentech, concluded that GH has a ‘favorable profile’. In 2012, results from the European Union’s Safety and Appropriateness of GH treatment in Europe (EU SAGhE) study about the long term mortality in GH treated patients were published in two separate manuscripts. This review will examine the issue of safety of rGH in order that practitioners are informed as they consider initiation of therapy with patients. PMID:23772352

  6. Long-term efficacy of surgical ablation of atrial fibrillation in a low-volume centre

    PubMed Central

    Zyśko, Dorota; Bielicki, Grzegorz; Obremska, Marta; Goździk, Anna; Kustrzycki, Wojciech

    2015-01-01

    Surgical ablation is a recommended procedure for patients with atrial fibrillation (AF) undergoing a cardiac surgery operation. However, the procedure is associated with significant risk of late recurrence of AF. The aim of the study was to assess the long-term efficacy of the procedure with respect to the comorbidities. The study group consisted of 22 patients: 9 women and 13 men, who underwent surgical AF ablation in the 2008-2013 period. The patients were interviewed by telephone and were asked to send their recently performed 12-lead electrocardiography (ECG). The semi-structured interview consisted of 25 items regarding the history of AF, concomitant comorbidities, lifelong syncopal history, smoking, family history of premature cardiovascular diseases, and current medical treatment. Furthermore, the Epworth test was performed to measure the daytime sleepiness, which in turn is related to the presence of obstructive sleep apnoea. On the basis of the obtained data, the CHADS2, and Epworth scale scores were calculated for each patient. As a result of the study six patients (27%) had sinus rhythm or paced dual chamber rhythm, and 16 patients had atrial fibrillation. The multivariate analysis revealed that Epworth scale scoring > 9, CHADS2 score > 0, and persistent type of AF were related to poor outcome of surgical ablation procedure. In conclusion, patients with AF treated with surgical ablation have similar prognosis of sinus rhythm maintenance to those treated with radiofrequency ablation. Moreover, the same predisposing factors play a significant role in AF recurrence both in surgical patients and in patients treated with radiofrequency ablation. PMID:26855645

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    SciTech Connect

    Kalva, Sanjeeva P.; Marentis, Theodore C.; Yeddula, Kalpana; Somarouthu, Bhanusupriya; Wicky, Stephan; Stecker, Michael S.

    2011-04-15

    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.

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

    SciTech Connect

    DeHart, M.D.

    1999-08-01

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

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

    SciTech Connect

    Villagran, J.E.

    2012-07-01

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

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

    PubMed

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

    2015-03-01

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

  13. [Drug supply and patient safety in long-term care facilities for the elderly].

    PubMed

    Uhrhan, T; Schaefer, M

    2010-05-01

    Nursing home residents are a continuously growing population with a need for intense pharmacotherapy due to numerous comorbid conditions. Polypharmacy and the frequent use of psychotropic medication increase the risk of adverse drug events, which may result in risk of increased morbidity and mortality in frail, elderly patients. The requirement to solve individual therapeutic problems has to be supported by not only an adequate and need-based pharmaceutical supply but also by suitable organizational and logistic solutions. In the nursing home environment, ineffective communication between the various professional groups involved in medical treatment may lead to inappropriate or unintentional medication use. In the present survey, data and research results that are relevant to assess the medical treatment situation in long-term care facilities particularly with regard to the safety of pharmacotherapy are presented. The two problem areas of patient-customized therapy and the handling of pharmaceuticals in the context of institutional care are addressed separately. PMID:20376418

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

    PubMed

    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

    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

  15. Long-term safety of oral transmucosal fentanyl citrate for breakthrough cancer pain.

    PubMed

    Payne, R; Coluzzi, P; Hart, L; Simmonds, M; Lyss, A; Rauck, R; Berris, R; Busch, M A; Nordbrook, E; Loseth, D B; Portenoy, R K

    2001-07-01

    This open-label study evaluated the long-term safety and tolerability of oral transmucosal fentanyl citrate (OTFC) in ambulatory cancer patients with breakthrough pain undergoing cancer care at 32 university- or community-based practices. Patients had participated in a previous short-term titration trial of OTFC, were experiencing at least one episode per day of breakthrough pain, and had achieved relief of their breakthrough pain with an opioid. Patients received OTFC units at a starting dosage strength determined in the short-term trial (200-1600 microg). Outcome measures included number of successfully treated breakthrough pains, global satisfaction rating (0 = poor through 4 = excellent), and side effects. In total, 41,766 units of OTFC were used to treat 38,595 episodes of breakthrough pain in 155 patients. Number of treatment days ranged from 1 to 423 (mean, 91 days). Patients averaged 2.9 breakthrough pain episodes per day. About 92% of episodes were successfully treated with OTFC and there was no trend toward decreased effectiveness over time. Most patients (61%) did not require dose escalation during treatment. Global satisfaction ratings were consistently above 3, indicating very good to excellent relief. Common adverse events associated with OTFC were somnolence (9%), constipation (8%), nausea (8%), dizziness (8%), and vomiting (5%). Six patients (4%) discontinued therapy due to an OTFC-related adverse event. There were no reports of abuse and no concerns about the safety of the drug raised by patients or families. OTFC was used safely and effectively during long-term treatment of breakthrough pain in cancer patients at home. PMID:11516599

  16. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab

    PubMed Central

    Topalian, Suzanne L.; Sznol, Mario; McDermott, David F.; Kluger, Harriet M.; Carvajal, Richard D.; Sharfman, William H.; Brahmer, Julie R.; Lawrence, Donald P.; Atkins, Michael B.; Powderly, John D.; Leming, Philip D.; Lipson, Evan J.; Puzanov, Igor; Smith, David C.; Taube, Janis M.; Wigginton, Jon M.; Kollia, Georgia D.; Gupta, Ashok; Pardoll, Drew M.; Sosman, Jeffrey A.; Hodi, F. Stephen

    2016-01-01

    Purpose Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients and Methods Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Results Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31 %), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71 %) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Conclusion Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma. PMID:24590637

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

    PubMed

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

    2015-05-01

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

  18. The Efficacy of Short- and Long-Term Therapy in the Treatment of Childhood Sexual Abuse: A Review of the Literature.

    ERIC Educational Resources Information Center

    Aoto-Sullivan, Stacey Y.

    This paper presents a review of the short- and long-term treatments for children who have been sexually abused. Short-term group therapy, long-term group therapy, short-term individual, and long-term individual therapy were each evaluated in terms of efficacy in alleviating symptoms associated with sexual abuse. The paper also evaluates the…

  19. [On the efficacy of long-term psychodynamic psychotherapy for complex psychological disorders].

    PubMed

    Leichsenring, F; Rabung, S

    2009-11-01

    Rief and Hofmann (Nervenarzt 80:593-597) criticize in a very detailed comment our meta-analysis of long-term psychodynamic psychotherapy (JAMA 300:1551-1565). Although our article clearly included information that our meta-analysis addressed long-term psychodynamic psychotherapy of at least 50 sessions or at least 1 year duration, Rief and Hofmann allege that we studied "psychoanalysis" or "long-term psychoanalysis". Then they "show" for some of the studies we included that these studies did not address "psychoanalysis" or "long-term psychoanalysis" - which they did indeed not, but had never been claimed by us. For all other points of criticism put forward by the authors we show that they are not tenable as well. In addition, we show that Rief and Hofmann use omissions and allegations that give the impression that we deliberately violated principles of good scientific practice. This is reputation-damaging behaviour that clearly goes beyond a scientific discussion among researchers and constitutes a special act which itself violates the principles of good scientific practice. PMID:19851742

  20. Quantitative Assessment of Countermeasure Efficacy for Long-Term Space Missions

    NASA Technical Reports Server (NTRS)

    Feiveson, Alan H.

    2000-01-01

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

  1. Long-Term Efficacy and Toxicity of Cholinesterase Inhibitors in the Treatment of Alzheimer Disease

    PubMed Central

    Hogan, David B

    2014-01-01

    Though the symptoms of Alzheimer disease go on for years, the phase 3 trials of the cholinesterase inhibitors (ChEIs), the current mainstay of symptomatic pharmacotherapy for this condition, were typically of only 3- to 6-months’ duration. We have limited data on long-term (that is, a year or more) therapy with these agents. In this review, we explore the available information on the biological and clinical effects of long-term ChEI therapy, what happens when these agents are discontinued, and examine what others have recommended. An individualized approach to deciding on whether to carry on with a ChEI should be taken. If continued, treatment goals should be clarified and patients monitored over time, for both drug-related benefits and adverse effects. PMID:25702360

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

    PubMed Central

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

    2014-01-01

    Background Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. Objective To assess effectiveness and safety of BT in asthma patients 5 years post therapy. Methods BT-treated subjects from the Asthma Intervention Research 2 (AIR2) Trial (ClinicalTrials.gov NCT01350414) were evaluated annually for 5 years to assess long-term safety of BT and durability of treatment effect. Outcomes assessed post-BT included severe exacerbations, adverse events, healthcare utilization, spirometry data, and high resolution computed tomography (HRCT) scans. Results 162/190 BT-treated subjects (85.3%) from the AIR2 Trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and Emergency Room visits, and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months prior to BT treatment (average 5 year reduction in proportions: 44% for exacerbations and 78% for ER visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in Years 2 through 5 as compared to the first year after BT. Pre-BD FEV1 values remained stable between years 1 and 5 after BT, despite a 17% reduction in average daily inhaled corticosteroid dose. HRCT scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. Conclusions These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ER visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking ICS (inhaled corticosteroids) and LABA (long-acting-β2-agonists). PMID:23998657

  3. Safety of long-term use of lisinopril for congestive heart failure.

    PubMed

    Moyses, C; Higgins, T J

    1992-10-01

    Early clinical experience with lisinopril suggested that it was well tolerated in congestive heart failure (CHF). An analysis of data from greater than 1,000 patients treated with lisinopril has been performed to examine the long-term safety of lisinopril in CHF. Of these, 620 have been studied for up to nearly 4 years, and a further 440 have been studied in comparative trials for 3 months. When patients who received lisinopril or placebo for the same period were compared, the proportion of lisinopril patients reporting an adverse event was 44.1% compared with 39.4% on placebo. Over a 4-year period, 205 patients (33.1%) discontinued treatment. About 33% of these died, 33% withdrew due to clinical adverse events, 21 (3.4%) were withdrawn because of adverse laboratory findings, and 56 (9.0%) withdrew for reasons unrelated to treatment. Sixteen patients (2.6%) withdrew because lisinopril was deemed ineffective. The most frequently reported drug-related adverse laboratory findings were increases in blood urea nitrogen, blood urea, serum creatinine, and plasma potassium. There appeared to be no differences in the pattern of adverse events with respect to the race of the patient. Elderly patients and those with the most severe forms of heart failure appeared to be at greater risk for an adverse event. Evaluation of the safety of lisinopril compared with enalapril, captopril, and digoxin in controlled clinical trials shows all the angiotensin-converting enzyme inhibitors to be equally well tolerated with a closely similar range of adverse events, suggesting that the satisfactory safety profile of lisinopril is shared by other drugs of this class.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1329480

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

    PubMed

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

    2007-01-01

    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

  5. Long-Term Marine Traffic Monitoring for Environmental Safety in the Aegean Sea

    NASA Astrophysics Data System (ADS)

    Giannakopoulos, T.; Gyftakis, S.; Charou, E.; Perantonis, S.; Nivolianitou, Z.; Koromila, I.; Makrygiorgos, A.

    2015-04-01

    The Aegean Sea is characterized by an extremely high marine safety risk, mainly due to the significant increase of the traffic of tankers from and to the Black Sea that pass through narrow straits formed by the 1600 Greek islands. Reducing the risk of a ship accident is therefore vital to all socio-economic and environmental sectors. This paper presents an online long-term marine traffic monitoring work-flow that focuses on extracting aggregated vessel risks using spatiotemporal analysis of multilayer information: vessel trajectories, vessel data, meteorological data, bathymetric / hydrographic data as well as information regarding environmentally important areas (e.g. protected high-risk areas, etc.). A web interface that enables user-friendly spatiotemporal queries is implemented at the frontend, while a series of data mining functionalities extracts aggregated statistics regarding: (a) marine risks and accident probabilities for particular areas (b) trajectories clustering information (c) general marine statistics (cargo types, etc.) and (d) correlation between spatial environmental importance and marine traffic risk. Towards this end, a set of data clustering and probabilistic graphical modelling techniques has been adopted.

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

    SciTech Connect

    Michael D. Kinney and William D. Barrick

    2008-09-01

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

  7. Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients with symptoms.

    PubMed Central

    Zehender, M; Hohnloser, S; Geibel, A; Furtwängler, A; Olschewski, M; Meinertz, T; Just, H

    1992-01-01

    OBJECTIVE--To assess the clinical criteria predicting the short and long-term efficacy of propafenone, an agent with class IC antiarrhythmic activity and a broad pharmacological profile. DESIGNS--Prospective study of propafenone at doses of 450 to 900 mg/day during a six week dose titration period (including a placebo phase with two separate 24 Holter recordings). Responders to treatment were followed for one year. PATIENTS--One hundred patients with frequent ventricular arrhythmias (greater than 30 extrasystoles/h) of Lown class III and IVA/B and without evidence of myocardial infarction within the past six months. ANALYSIS--Multivariate regression analysis of spontaneous arrhythmia variability and of different clinical variables to determine the short and long-term efficacy and safety of propafenone. MEASUREMENTS AND MAIN RESULTS--Propafenone 450 mg/day was effective in 30/100 patients (30%), and at 600 mg/day another 14 responded. The efficacy of propafenone correlated with a low spontaneous arrhythmia variability and, as shown by multivariate analysis, with a lower patient age (p less than 0.05). When the dose was increased to 900 mg/day a further six (12%) patients responded. However, with increasing doses of propafenone, the one year probability of effective treatment decreased from 86% (450 mg/day) to 67% (600 mg/day) and to 44% (900 mg/day). After restudying the patients at three, six, and 12 months and after dose adjustment in 11/44 patients (25%), 31 patients (70%) remained responders. Loss of permanent antiarrhythmic efficacy was best predicted by the initial dose that achieved a response. No patient died suddenly or had arrhythmogenic effects during Holter monitoring. Side effects occurred in 36% of patients but these rarely limited long-term treatment. CONCLUSIONS--A younger age, low spontaneous arrhythmia variability, and particularly a low titration dose were the best predictors of the short and long term efficacy of propafenone. All other responders should have repeated Holter recordings during the first year of treatment. PMID:1622701

  8. Self-efficacy beliefs predict sustained long-term sick absenteeism in individuals with chronic musculoskeletal pain.

    PubMed

    Busch, H; Göransson, S; Melin, B

    2007-09-01

    Recovery beliefs are assumed to predict rehabilitation outcomes and return-to-work in various clinical conditions but are less frequently assessed in musculoskeletal disorders. We tested the hypothesis that recovery beliefs constitute a risk factor for sustained long-term sick absenteeism in men and women suffering from nonspecific chronic musculoskeletal disorders. A total of 233 subjects with a recent or ongoing experience of long-term sick leave were included in a prospective design. Subjects answered a postal baseline questionnaire and were followed up via register data for 1 year. Multivariate logistic regression analyses indicated that subjects with negative recovery beliefs (OR: 2.41; CI: 1.22-4.77), low sense of mastery (OR: 2.08; CI: 1.27-3.40), perceived high mental demands at work (OR: 1.77; CI: 1.05-2.99), and prior experiences of long-term sick absenteeism (OR: 1.86; CI: 1.02-3.37) had an increased probability of receiving sickness benefits at follow-up. We conclude that prolonged sickness absence contributes strongly to increase patients' sense of helplessness, lower self-efficacy, and hinder future work return. To improve work return, patients' maladaptive beliefs should be clarified and challenged early in the rehabilitation process. PMID:17714102

  9. Safety of the long-term use of proton pump inhibitors.

    PubMed

    Thomson, Alan B R; Sauve, Michel D; Kassam, Narmin; Kamitakahara, Holly

    2010-05-21

    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. PMID:20480516

  10. Long-term Efficacy of Intravenous Immunoglobulin Therapy for Moderate to Severe Childhood Atopic Dermatitis

    PubMed Central

    Jee, Sue-Jung; Kim, Joo-Hwa; Baek, Hey-Sung; Lee, Ha-Baik

    2011-01-01

    Purpose The present study investigates the long-term effects of intravenous immunoglobulin (IVIg) therapy for the treatment of moderate to severe childhood atopic dermatitis (AD). Previous research indicates that IVIg can treat severe AD; however, the effectiveness of IVIg has not been confirmed in prospective, blinded clinical trials. Methods Forty eligible children with moderate to severe AD, as defined by the criteria of Hanifin and Rajka, were enrolled in a randomized, placebo-controlled study. After the completion of an initial screening visit (V0), the patients were randomly allocated into therapy (n=30) and control (n=10) groups (V1). Thirty children were each treated with three injections of 2.0 g/kg IVIg at 1-month intervals over a 12-week period. Ten children were treated with placebo. Assessments were conducted after each injection (V2, V3, and V4) and at 3 (V5) and 6 months (V6) after completed treatment. Results The disease severity index was significantly decreased at V5 compared with the value at V1 (P<0.05). There were no significant changes in the total IgE level or total eosinophil count in peripheral blood at the last injection (V4) compared with the value at V1. The interleukin (IL)-5/interferon (IFN)-γ ratio was assessed in T-helper 1 (Th1) and Th2 cells. The ratio significantly decreased between V1 and V5, after which it increased, such that the ratio at V6 was not significantly different from that at V1. Compared with the level at V1, the intercellular cell adhesion molecule-1 level at V4 did not differ significantly, but the level at V5 was lower. Conclusions This study suggests that IVIg therapy may clinically improve AD in patients after 3 months of therapy, but the improvement may decline by 6 months after therapy. PMID:21461247

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Potent and long-term antiangiogenic efficacy mediated by FP3-expressing oncolytic adenovirus.

    PubMed

    Choi, Il-Kyu; Shin, Hyewon; Oh, Eonju; Yoo, Ji Young; Hwang, June Kyu; Shin, Kyungsub; Yu, De-Chao; Yun, Chae-Ok

    2015-11-01

    Various ways to inhibit vascular endothelial growth factor (VEGF), a key facilitator in tumor angiogenesis, are being developed to treat cancer. The soluble VEGF decoy receptor (FP3), due to its high affinity to VEGF, is a highly effective and promising strategy to disrupt VEGF signaling pathway. Despite potential advantage and potent therapeutic efficacy, its employment has been limited by very poor in vivo pharmacokinetic properties. To address this challenge, we designed a novel oncolytic adenovirus (Ad) expressing FP3 (RdB/FP3). To demonstrate the VEGF-specific nature of RdB/FP3, replication-incompetent Ad expressing FP3 (dE1/FP3) was also generated. dE1/FP3 was highly effective in reducing VEGF expression and functionally elicited an antiangiogeneic effect. Furthermore, RdB/FP3 exhibited a potent antitumor effect compared with RdB or recombinant FP3. Consistent with these data, RdB/FP3 was shown to greatly decrease VEGF expression level and vessel density and increase apoptosis in both tumor endothelial and tumor cells, verifying potent suppressive effects of RdB/FP3 on VEGF-mediated tumor angiogenesis in vivo. Importantly, the therapeutic mechanism of antitumor effect mediated by RdB/FP3 is associated with prolonged VEGF silencing efficacy and enhanced oncolysis via cancer cell-specific replication of oncolytic Ad. Taken together, RdB/FP3 provides a new promising therapeutic approach in the treatment of cancer and angiogenesis-related diseases. PMID:25944623

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

    SciTech Connect

    Vicini, Frank A. . E-mail: fvicini@beaumont.edu; Antonucci, J. Vito; Wallace, Michelle R.N.; Gilbert, Samuel; Goldstein, Neal S.; Kestin, Larry; Chen, Peter; Kunzman, Jonathan; Boike, Thomas; Benitez, Pamela; Martinez, Alvaro

    2007-06-01

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

  15. Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects

    PubMed Central

    Misof, Barbara M; Fratzl-Zelman, Nadja; Paschalis, Eleftherios P; Roschger, Paul; Klaushofer, Klaus

    2015-01-01

    It is well established that long-term antiresorptive use is effective in the reduction of fracture risk in high bone turnover osteoporosis. Nevertheless, during recent years, concerns emerged that longer bone turnover reduction might favor the occurrence of fatigue fractures. However, the underlying mechanisms for both beneficial and suspected adverse effects are not fully understood yet. There is some evidence that their effects on the bone material characteristics have an important role. In principle, the composition and nanostructure of bone material, for example, collagen cross-links and mineral content and crystallinity, is highly dependent on tissue age. Bone turnover determines the age distribution of the bone structural units (BSUs) present in bone, which in turn is decisive for its intrinsic material properties. It is noteworthy that the effects of bone turnover reduction on bone material were observed to be dependent on the duration of the antiresorptive therapy. During the first 23 years, significant decreases in the heterogeneity of material properties such as mineralization of the BSUs have been observed. In the long term (510 years), the mineralization pattern reverts towards normal heterogeneity and degree of mineralization, with no signs of hypermineralization in the bone matrix. Nevertheless, it has been hypothesized that the occurrence of fatigue fractures (such as atypical femoral fractures) might be linked to a reduced ability of microdamage repair under antiresorptive therapy. The present article examines results from clinical studies after antiresorptive, in particular long-term, therapy with the aforementioned potentially positive or negative effects on bone material. PMID:25709811

  16. In Vivo Transplantation of Enteric Neural Crest Cells into Mouse Gut; Engraftment, Functional Integration and Long-Term Safety

    PubMed Central

    Cooper, Julie E.; McCann, Conor J.; Natarajan, Dipa; Choudhury, Shanas; Boesmans, Werend; Delalande, Jean-Marie; Vanden Berghe, Pieter; Burns, Alan J.; Thapar, Nikhil

    2016-01-01

    Objectives Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs) into ganglionic and aganglionic mouse gut in vivo and analysing functional integration and long-term safety. Design Neurospheres generated from yellow fluorescent protein (YFP) expressing ENCCs selected from postnatal Wnt1-cre;R26R-YFP/YFP murine gut were transplanted into ganglionic hindgut of wild-type littermates or aganglionic hindgut of Ednrbtm1Ywa mice (lacking functional endothelin receptor type-B). Intestines were then assessed for ENCC integration and differentiation using immunohistochemistry, cell function using calcium imaging, and long-term safety using PCR to detect off-target YFP expression. Results YFP+ ENCCs engrafted, proliferated and differentiated into enteric neurons and glia within recipient ganglionic gut. Transplanted cells and their projections spread along the endogenous myenteric plexus to form branching networks. Electrical point stimulation of endogenous nerve fibres resulted in calcium transients (F/F0 = 1.16±0.01;43 cells, n = 6) in YFP+ transplanted ENCCs (abolished with TTX). Long-term follow-up (24 months) showed transplanted ENCCs did not give rise to tumours or spread to other organs (PCR negative in extraintestinal sites). In aganglionic gut ENCCs similarly spread and differentiated to form neuronal and glial networks with projections closely associated with endogenous neural networks of the transition zone. Conclusions Transplanted ENCCs successfully engrafted into recipient ganglionic and aganglionic gut showing appropriate spread, localisation and, importantly, functional integration without any long-term safety issues. This study provides key support for the development and use of enteric neural stem cell therapies. PMID:26824433

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

    ERIC Educational Resources Information Center

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

    2005-01-01

    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…

  18. The impact of systematic occupational health and safety management for occupational disorders and long-term work attendance.

    PubMed

    Dellve, Lotta; Skagert, Katrin; Eklöf, Mats

    2008-09-01

    Despite several years of conducting formalized systematic occupational health and safety management (SOHSM), as required by law in Sweden and most other industrialized countries, there is still little evidence on how SOHSM should be approached to have an impact on employees' health. The aim of this study was to investigate the importance of SOHSM, considering structured routines and participation processes, for the incidence of occupational disorders and the prevalence of long-term work attendance among home care workers (HCWs). Municipal human service organizations were compared concerning (a) their structured routines and participation processes for SOHSM and (b) employee health, i.e. the municipal five-year incidence of occupational disorders and prevalence of work attendance among HCWs. National register-based data from the whole population of HCWs (n=154 773) were linked to register-data of occupational disorders and prevalence of long-term work attendance. The top managers and safety representatives in selected high- and low-incidence organizations (n=60) answered a questionnaire about structure and participation process of SOHSM. The results showed that prevalence of long-term work attendance was higher where structure and routines for SOHSM (policy, goals and plans for action) were well organized. Highly structured SOHSM and human resource management were also related to high organizational incidence of reported occupational disorders. Allocated budget and routines related to HCWs' influence in decisions concerning performance of care were also related to long-term work attendance. The participation processes had a weak effect on occupational disorders and work attendance among HCWs. Reporting occupational disorders may be a functional tool to stimulate the development of effective SOHSM, to improve the work environment and sustainable work ability. PMID:18599173

  19. Initial development of patient-reported instrument assessing harm, efficacy, and misuse of long-term opioid therapy.

    PubMed

    Becker, William C; Fiellin, David A; Black, Anne C; Kostovich, Carol T; Kerns, Robert D; Fraenkel, Liana

    2016-01-01

    Guidelines on long-term opioid therapy recommend frequent reassessment of harm, efficacy, and misuse of these potentially harmful and sometimes ineffective medications. In primary care, there is a need for a brief, patient-reported instrument. This report details the initial steps in the development of such an instrument. An interdisciplinary team of clinician-scientists performed four discrete steps in this study: (1) conceptualization of the purpose and function of the instrument, (2) assembly of an item pool, (3) expert rating on which items were most important to include in the instrument, and (4) modification of expert-selected items based on a reading level check and cognitive interviews with patients. A diverse panel of 47 subject matter experts was presented with 69 items to rate on a 1-9 scale in terms of importance for inclusion in the instrument. The panel highly rated 37 items: 8 related to harm, 4 related to efficacy, and 25 related to misuse. These 37 items were then tested for patient comprehension and modified as needed. Next steps in development will include further item reduction, testing against a gold standard, and assessment of the instrument's effect on clinical outcomes. PMID:27006339

  20. Service improvement system to enhance the safety of patients admitted on long-term warfarin.

    PubMed

    Warcel, Dana; Johnson, Daniel; Shah, Neeraj; Shreeve, Norman

    2014-01-01

    It is common for hospital inpatients on warfarin to suffer from fluctuations in their INR (international normalised ratio). Raised INRs are potentially very dangerous and may result in acute life-threatening haemorrhages. Conversely, low INRs may increase the risk for the development of venous thromboembolism. Having observed many deranged INRs among hospital inpatients, we decided to focus our project on identifying the contributing factors to deranged INRs and ways to address this problem. We analysed the warfarin prescriptions on all drug charts and surveyed the junior doctor staff. Our results revealed poor knowledge and confidence levels on warfarin prescribing among junior doctor staff. This is likely to be reflected in the poor completion rate of warfarin prescriptions. We instituted practical changes to resolve the issue: most importantly, a change to the warfarin administration time from 6 pm to 2 pm, supported by a poster campaign to increase awareness of the problem. The objective of these changes was to reduce prescribing errors by reducing warfarin prescriptions out-of-hours, by the on-call doctors. We repeated the audit cycle twice. Although our interventions were successfully introduced as shown in our second audit cycle, the changes that were implemented were not sustained as shown in the third audit cycle. We identified a need for annual intervention to educate new junior doctor staff to ensure that the positive outcomes achieved are maintained in the long term. PMID:26734259

  1. Effects of an active accelerator pedal on driver behaviour and traffic safety after long-term use in urban areas.

    PubMed

    Várhelyi, András; Hjälmdahl, Magnus; Hydén, Christer; Draskóczy, Magda

    2004-09-01

    The long-term effects of the active accelerator pedal (AAP) were evaluated in the city of Lund in 2000 and 2001. The system, installed in 284 vehicles, produced a counterforce in the accelerator pedal at the speed limit. It could, however be overridden by pressing the accelerator pedal harder. The results showed that test drivers' compliance with the speed limits improved considerably. Reduction in average speeds and less speed variation by the test vehicles indicate a great traffic-safety potential. Travel times were unaffected, while emission volumes decreased significantly. PMID:15203350

  2. Long-Term PEG-J Tube Safety in Patients With Advanced Parkinson's Disease

    PubMed Central

    Epstein, Michael; Johnson, David A; Hawes, Robert; Schmulewitz, Nathan; Vanagunas, Arvydas D; Gossen, E Roderich; Robieson, Weining Z; Eaton, Susan; Dubow, Jordan; Chatamra, Krai; Benesh, Janet

    2016-01-01

    OBJECTIVES: The objectives of this study were to present procedure- and device-associated adverse events (AEs) identified with long-term drug delivery via percutaneous endoscopic gastrojejunostomy (PEG-J). Levodopa-carbidopa intestinal gel (LCIG, also known in US as carbidopa-levodopa enteral suspension, CLES) is continuously infused directly to the proximal small intestine via PEG-J in patients with advanced Parkinson's disease (PD) to overcome slow and erratic gastric emptying and treat motor fluctuations that are not adequately controlled by oral or other pharmacological therapy. METHODS: An independent adjudication committee of three experienced (>25 years each) gastroenterologists reviewed gastrointestinal procedure- and device-associated AEs reported for PD patients (total n=395) enrolled in phase 3 LCIG studies. The rate, clinical significance, and causality of the procedure/device events were determined. RESULTS: The patient median exposure to PEG-J at the data cutoff was 480 days. Procedure- and device-associated serious AEs (SAEs) occurred in 67 (17%) patients. A total of 42% of SAEs occurred during the first 4 weeks following PEG-J placement. SAEs of major clinical significance with the highest procedural incidence were peritonitis (1.5%), pneumonia (1.5%), and abdominal pain (1.3%). The most common non-serious procedure- and device-associated AEs were abdominal pain (31%), post-operative wound infection (20%), and procedural pain (23%). In all, 17 (4.3%) patients discontinued treatment owing to an AE. CONCLUSIONS: In conclusion, incidences of PEG-J AEs with the LCIG delivery system and PEG-J longevity were compared favorably with ranges described in the PEG/PEG-J literature. A low discontinuation rate in this study suggests acceptable procedural outcomes and AE rates in PD patients treated with this PEG-J drug delivery system. PMID:27030949

  3. Long-term efficacy of recombinant human growth hormone therapy in short-statured patients with Noonan syndrome

    PubMed Central

    Jeong, Insook; Kang, Eungu; Cho, Ja Hyang; Kim, Gu-Hwan; Lee, Beom Hee; Choi, Jin-Ho

    2016-01-01

    Purpose Noonan syndrome (NS) is characterized by short stature, heart anomalies, developmental delays, dysmorphic features, cryptorchidism, and coagulation defects. Several studies reported the short-term effects of recombinant human growth hormone (rhGH) treatment on the improvement of height. This study was performed to evaluate the long-term efficacy of rhGH in children with NS in Korea. Methods This study included 15 prepubertal NS children who received rhGH subcutaneously at a dose of 50–75 µg/kg/day for 6 days a week for at least >3 years. Preand posttreatment data, such as height, weight, bone age, insulin-like growth factor 1 (IGF-1), and IGF binding protein 3 (IGFBP-3) levels, were collected every 6 months. Results Chronologic age and bone age at the start of treatment were 7.97±1.81 and 5.09±2.12 years, respectively. Height standard deviation score (SDS) was increased from –2.64±0.64 to –1.54±1.24 years after 3 years (P<0.001). Serum IGF-1 SDS levels were elevated from –1.28±1.03 to –0.10±0.94 (P<0.001). Height SDS was more increased in subjects without PTPN11 mutations compared to those with mutations after 3 years (P=0.012). However, the other parameters, including bone age, IGF-1 SDS, and IGFBP-3 SDS, were not significantly different between patients with and without PTPN11 mutations. Conclusion Although this study included a relatively small number of patients, long-term rhGH therapy in NS patients was safe and effective at improving height, growth velocity, and serum IGF-1 levels, in accordance with previous studies. However, the meticulous monitoring of potential adverse events is still needed because of high dose of rhGH and preexisting hyperactivity of RAS-MAPK pathway. Patients with PTPN11 mutations demonstrated a decreased response to rhGH therapy compared to those without mutations. PMID:27104176

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

    SciTech Connect

    Van Luik, Abe

    2009-07-17

    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.

  5. Climate considerations in long-term safety assessments for nuclear waste repositories.

    PubMed

    Näslund, Jens-Ove; Brandefelt, Jenny; Liljedahl, Lillemor Claesson

    2013-05-01

    For a deep geological repository for spent nuclear fuel planned in Sweden, the safety assessment covers up to 1 million years. Climate scenarios range from high-end global warming for the coming 100 000 years, through deep permafrost, to large ice sheets during glacial conditions. In contrast, in an existing repository for short-lived waste the activity decays to low levels within a few tens of thousands of years. The shorter assessment period, 100 000 years, requires more focus on climate development over the coming tens of thousands of years, including the earliest possibility for permafrost growth and freezing of the engineered system. The handling of climate and climate change in safety assessments must be tailor-made for each repository concept and waste type. However, due to the uncertain future climate development on these vast time scales, all safety assessments for nuclear waste repositories require a range of possible climate scenarios. PMID:23619797

  6. Computerised clinical decision support systems to improve medication safety in long-term care homes: a systematic review

    PubMed Central

    Marasinghe, Keshini Madara

    2015-01-01

    Objectives Computerised clinical decision support systems (CCDSS) are used to improve the quality of care in various healthcare settings. This systematic review evaluated the impact of CCDSS on improving medication safety in long-term care homes (LTC). Medication safety in older populations is an important health concern as inappropriate medication use can elevate the risk of potentially severe outcomes (ie, adverse drug reactions, ADR). With an increasing ageing population, greater use of LTC by the growing ageing population and increasing number of medication-related health issues in LTC, strategies to improve medication safety are essential. Methods Databases searched included MEDLINE, EMBASE, Scopus and Cochrane Library. Three groups of keywords were combined: those relating to LTC, medication safety and CCDSS. One reviewer undertook screening and quality assessment. Results Overall findings suggest that CCDSS in LTC improved the quality of prescribing decisions (ie, appropriate medication orders), detected ADR, triggered warning messages (ie, related to central nervous system side effects, drug-associated constipation, renal insufficiency) and reduced injury risk among older adults. Conclusions CCDSS have received little attention in LTC, as attested by the limited published literature. With an increasing ageing population, greater use of LTC by the ageing population and increased workload for health professionals, merely relying on physicians’ judgement on medication safety would not be sufficient. CCDSS to improve medication safety and enhance the quality of prescribing decisions are essential. Analysis of review findings indicates that CCDSS are beneficial, effective and have potential to improve medication safety in LTC; however, the use of CCDSS in LTC is scarce. Careful assessment on the impact of CCDSS on medication safety and further modifications to existing CCDSS are recommended for wider acceptance. Due to scant evidence in the current literature, further research on implementation and effectiveness of CCDSS is required. PMID:25967986

  7. Long-Term Efficacy of Various Natural or “Green” Insecticides against Bed Bugs: A Double-Blind Study

    PubMed Central

    Goddard, Jerome

    2014-01-01

    Bed bugs are resurging throughout the world, and, thus, effective pest control strategies are constantly needed. A few studies have evaluated 25(b) and other natural, or so-called “green” products, as well as over-the-counter insecticides for bed bugs, but additional studies are needed to determine efficacy of bed bug control products. This double-blinded research project was initiated to examine long-term effectiveness of six commercially available natural or “green” insecticides against bed bugs and to compare them with three known traditional residual products. Water was used as a control. Products were evaluated against both susceptible and resistant strains of bed bugs (1200 bugs each), and two different substrates were used. Temprid® (Bayer Corporation, Monheim, Germany), Transport® (FMC Corp., Philadelphia, PA, USA), Invader® (FMC Corporation, Philadelphia, PA USA), Cimexa® (Rockwell Laboratories, Kansas City, MO, USA), and BBT-2000® (Swepe-Tite LLC, Tupelo, MS, USA) were the only products which showed any substantial (>40%) bed bug control upon exposure to treated substrates after the six-month waiting period, although results with the resistant bed bug strain were much reduced. Alpine dust® (BASF Corporation, Florham Park, NJ, USA) killed 27% of bed bugs or less, depending on strain and substrate. EcoRaider® (North Bergen, NJ, USA) and Mother Earth D® (Whitmire Microgen, Florham Park, NJ, USA) (diatomaceous earth) produced 11% control or less. Cimi-Shield Protect® (Pest Barrier, Carson, CA, USA) showed no activity against bed bugs in this study. Analysis using SAS software showed a three-way interaction between treatment, substrate, and bed bug strain (Numerator DF 9; Denominator DF 80; F = 4.90; p < 0.0001). PMID:26462950

  8. Long-Term Efficacy of Various Natural or "Green" Insecticides against Bed Bugs: A Double-Blind Study.

    PubMed

    Goddard, Jerome

    2014-01-01

    Bed bugs are resurging throughout the world, and, thus, effective pest control strategies are constantly needed. A few studies have evaluated 25(b) and other natural, or so-called "green" products, as well as over-the-counter insecticides for bed bugs, but additional studies are needed to determine efficacy of bed bug control products. This double-blinded research project was initiated to examine long-term effectiveness of six commercially available natural or "green" insecticides against bed bugs and to compare them with three known traditional residual products. Water was used as a control. Products were evaluated against both susceptible and resistant strains of bed bugs (1200 bugs each), and two different substrates were used. Temprid(®) (Bayer Corporation, Monheim, Germany), Transport(®) (FMC Corp., Philadelphia, PA, USA), Invader(®) (FMC Corporation, Philadelphia, PA USA), Cimexa(®) (Rockwell Laboratories, Kansas City, MO, USA), and BBT-2000(®) (Swepe-Tite LLC, Tupelo, MS, USA) were the only products which showed any substantial (>40%) bed bug control upon exposure to treated substrates after the six-month waiting period, although results with the resistant bed bug strain were much reduced. Alpine dust(®) (BASF Corporation, Florham Park, NJ, USA) killed 27% of bed bugs or less, depending on strain and substrate. EcoRaider(®) (North Bergen, NJ, USA) and Mother Earth D(®) (Whitmire Microgen, Florham Park, NJ, USA) (diatomaceous earth) produced 11% control or less. Cimi-Shield Protect(®) (Pest Barrier, Carson, CA, USA) showed no activity against bed bugs in this study. Analysis using SAS software showed a three-way interaction between treatment, substrate, and bed bug strain (Numerator DF 9; Denominator DF 80; F = 4.90; p < 0.0001). PMID:26462950

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

    NASA Technical Reports Server (NTRS)

    Jeevarajan, Judith

    2012-01-01

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

  10. Long-term treatment of venous thromboembolism.

    PubMed

    Becattini, Cecilia; Manina, Giorgia

    2014-05-01

    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

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

    PubMed

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

    2013-10-01

    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

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

    PubMed

    Loman, L Anthony; Siegel, Gary L

    2015-01-01

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

  13. Long-term safety of polypropylene knots under scleral flaps for transsclerally sutured posterior chamber lenses.

    PubMed Central

    Van Meter, W S

    1997-01-01

    PURPOSE: To evaluate the safety of polypropylene knots used in TS-SPCL combined with PK and AV over time. METHOD: A retrospective review of 26 consecutive cases of TS-SPCL by one surgeon (WSVM) with at least 12 months follow-up (mean 26, range 12-62). All patients had a double strand polypropylene knot buried under partial thickness scleral flaps at 2 and 8 o'clock. Knots were rotated into the globe (R) in 10 cases, and could not be buried (N) in 13 cases, and in 3 cases 1 knot was buried. RESULTS: No cases of suture erosion occurred in R or N. One or more polypropylene sutures were visible in 17 patients (8 R, 9 T) at last exam. Twenty-three of 52 knots were rotated into the globe, and 70% of rotated knots were not even visible at the slit lamp at final visit. There was no evidence of conjunctival erosion in any patient. There was no lens dislocation and no endophthalmitis. CONCLUSION: The combination of partial thickness scleral flaps with double strand polypropylene knots reduces the incidence of suture erosion through the conjunctive if knots cannot be rotated into the globe. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:9440177

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

    SciTech Connect

    Pruess, Karsten; Birkholzer, Jens; Zhou, Quanlin

    2009-02-01

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

  15. Long-term safety and stability of angiogenesis induced by balanced single-vector co-expression of PDGF-BB and VEGF164 in skeletal muscle

    PubMed Central

    Gianni-Barrera, Roberto; Burger, Maximilian; Wolff, Thomas; Heberer, Michael; Schaefer, Dirk J.; Gürke, Lorenz; Mujagic, Edin; Banfi, Andrea

    2016-01-01

    Therapeutic angiogenesis by growth factor delivery is an attractive treatment strategy for ischemic diseases, yet clinical efficacy has been elusive. The angiogenic master regulator VEGF-A can induce aberrant angiogenesis if expressed above a threshold level. Since VEGF remains localized in the matrix around expressing cells, homogeneous dose distribution in target tissues is required, which is challenging. We found that co-expression of the pericyte-recruiting factor PDGF-BB at a fixed ratio with VEGF from a single bicistronic vector ensured normal angiogenesis despite heterogeneous high VEGF levels. Taking advantage of a highly controlled gene delivery platform, based on monoclonal populations of transduced myoblasts, in which every cell stably produces the same amount of each factor, here we rigorously investigated a) the dose-dependent effects, and b) the long-term safety and stability of VEGF and PDGF-BB co-expression in skeletal muscle. PDGF-BB co-expression did not affect the normal angiogenesis by low and medium VEGF doses, but specifically prevented vascular tumors by high VEGF, yielding instead normal and mature capillary networks, accompanied by robust arteriole formation. Induced angiogenesis persisted unchanged up to 4 months, while no tumors appeared. Therefore, PDGF-BB co-expression is an attractive strategy to improve safety and efficacy of therapeutic angiogenesis by VEGF gene delivery. PMID:26882992

  16. 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

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

    2012-01-01

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

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

    PubMed

    Frazzoli, Chiara; Petrini, Carlo; Mantovani, Alberto

    2009-01-01

    Development is defined sustainable when it meets the needs of the present without compromising 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 generations to come. Under this respect, the assessment of long-term, transgenerational risks is still hampered by serious scientific uncertainties. Critical issues to the development of a sustainable food safety framework may include: endocrine disrupters as emerging contaminants that specifically target developing organisms; toxicological risks assessment in Countries at the turning point of development; translating knowledge into toxicity indexes to support risk management approaches, such as hazard analysis and critical control points (HACCP); the interplay between chemical hazards and social determinants. Efforts towards the comprehensive knowledge and management of key factors of sustainable food safety appear critical to the effectiveness of the overall sustainability policies. PMID:19567981

  18. Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

    PubMed Central

    Downs, Matthew E.; Buch, Amanda; Sierra, Carlos; Karakatsani, Maria Eleni; Chen, Shangshang; Konofagou, Elisa E.; Ferrera, Vincent P.

    2015-01-01

    Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4–20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of’ visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4–5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used. PMID:25945493

  19. Factors influencing long-term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib.

    PubMed

    Brümmendorf, Tim H; Cortes, Jorge E; Khoury, Hanna J; Kantarjian, Hagop M; Kim, Dong-Wook; Schafhausen, Philippe; Conlan, Maureen G; Shapiro, Mark; Turnbull, Kathleen; Leip, Eric; Gambacorti-Passerini, Carlo; Lipton, Jeff H

    2016-01-01

    The dual SRC/ABL1 tyrosine kinase inhibitor bosutinib is indicated for adults with Ph+ chronic myeloid leukaemia (CML) resistant/intolerant to prior therapy. This analysis of an ongoing phase 1/2 study (NCT00261846) assessed effects of baseline patient characteristics on long-term efficacy and safety of bosutinib 500 mg/day in adults with imatinib (IM)-resistant (IM-R; n = 196)/IM-intolerant (IM-I; n = 90) chronic phase (CP) CML. Median treatment duration was 24·8 months (median follow-up, 43·6 months). Cumulative major cytogenetic response (MCyR) rate [95% confidence interval (CI)], was 59% (53-65%); Kaplan-Meier (KM) probability of maintaining MCyR at 4 years was 75% (66-81%). Cumulative incidence of on-treatment progression/death at 4 years was 19% (95% CI, 15-24%); KM 2-year overall survival was 91% (87-94%). Significant baseline predictors of both MCyR and complete cytogenetic response (newly attained/maintained from baseline) at 3 and 6 months included prior IM cytogenetic response, baseline MCyR, prior interferon therapy and <6 months duration from diagnosis to IM treatment initiation and no interferon treatment before IM. The most common adverse event (AE) was diarrhoea (86%). Baseline bosutinib-sensitive BCR-ABL1 mutation was the only significant predictor of grade 3/4 diarrhoea; no significant predictors were identified for liver-related AEs. Bosutinib demonstrates durable efficacy and manageable toxicity in IM-R/IM-I CP-CML patients. PMID:26537529

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  1. School-based prevention program associated with increased short- and long-term retention of safety knowledge.

    PubMed

    Klas, Karla S; Vlahos, Peter G; McCully, Michael J; Piche, David R; Wang, Stewart C

    2015-01-01

    Validation of program effectiveness is essential in justifying school-based injury prevention education. Although Risk Watch (RW) targets burn, fire, and life safety, its effectiveness has not been previously evaluated in the medical literature. Between 2007 and 2012, a trained fire service public educator (FSPE) taught RW to all second grade students in one public school district. The curriculum was delivered in 30-minute segments for 9 consecutive weeks via presentations, a safety smoke house trailer, a model-sized hazard house, a student workbook, and parent letters. A written pre-test (PT) was given before RW started, a post-test (PT#1) was given immediately after RW, and a second post-test (PT#2) was administered to the same students the following school year (ranging from 12 to 13 months after PT). Students who did not complete the PT or at least one post-test were excluded. Comparisons were made by paired t-test, analysis of variance, and regression analysis. After 183 (8.7%) were excluded for missing tests, 1,926 remaining students scored significantly higher (P = .0001) on PT#1 (mean 14.8) and PT#2 (mean 14.7) than the PT (mean 12.1). There was 1 FSPE and 36 school teachers with class size ranging from 10 to 27 (mean 21.4). Class size was not predictive of test score improvement (R = 0%), while analysis of variance showed that individual teachers trended toward some influence. This 6-year prospective study demonstrated that the RW program delivered by an FSPE effectively increased short-term knowledge and long-term retention of fire/life safety in early elementary students. Collaborative partnerships are critical to preserving community injury prevention education programs. PMID:25159554

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  4. Safety and immunologic benefits of conversion to sirolimus in kidney transplant recipients with long-term exposure to calcineurin inhibitors

    PubMed Central

    Yu, Ji Hyun; Kim, Kyoung Woon; Kim, Bo-Mi; Chung, Byung Ha; Cho, Mi-La; Choi, Bum Soon; Park, Cheol Whee; Kim, Yong-Soo; Yang, Chul Woo

    2016-01-01

    Background/Aims: Sirolimus (SRL) is a promising immunosuppressant replacingcalcineurin inhibitors (CNIs). This study was performed to evaluate the safetyand immunologic benefits of conversion to SRL in stable kidney transplant (KT)recipients exposed to CNIs for long periods. Methods: Fourteen CNI-treated KT recipients with stable renal function for morethan 10 years were included. Either 2 or 3 mg per day of SRL was administeredwhile CNIs were reduced by half starting on day 1, and then stopped 2 weeks afterSRL introduction. The safety of SRL conversion was assessed considering thegraft function, acute rejection, and graft loss. Immunologic alterations were measuredvia serial changes of T cell and B cell subsets after SRL conversion. Adverseeffects of SRL conversion were also evaluated. Results: Conversion to SRL was successful in nine patients (64.2%). Conversionto SRL preserved graft function as compared to the baseline value (p = 0.115). Noacute rejection or allograft loss was observed during the follow-up period. Immunemonitoring of T and B cells revealed a regulatory T cells increase after SRL conversion (p = 0.028). Most adverse events developed within 6 weeks after SRLconversion, and oral mucositis was the main cause of SRL withdrawal. Conclusions: Conversion to SRL can be safe and has immunologic benefits in KTrecipients with long-term CNI exposure. Close monitoring of mucocutaneous adverseevents is, however, required in the early period after SRL conversion. PMID:26968190

  5. Long-term (52 weeks) safety and tolerability of umeclidinium in Japanese patients with chronic obstructive pulmonary disease.

    PubMed

    Yamagata, Eiji; Soutome, Toru; Hashimoto, Kenichi; Mihara, Kazuko; Tohda, Yuji

    2016-05-01

    Objective Umeclidinium bromide (UMEC) 62.5 μg is a long-acting muscarinic antagonist (LAMA) that is administered once daily via inhalation for chronic obstructive pulmonary disease (COPD) treatment. The objective of this study was to evaluate the safety and tolerability of long-term treatment with UMEC 125 μg in Japanese patients with COPD. Methods This was a 52 week, multicenter, open-label study to evaluate the safety and tolerability of UMEC 125 μg once daily delivered via a novel dry powder inhaler (nDPI) in Japanese patients with COPD. The primary endpoint was the incidence and severity of all adverse events (AEs) throughout the 52 week treatment period. Clinical trial registration number ClinicalTrials.gov identifier is NCT01702363. Results A total of 153 patients were enrolled in the study. Of these, 131 patients started treatment with UMEC 125 μg, and 111 patients (85%) completed the study. AEs did not differ greatly in incidence over the various time periods (Weeks 0 to 12, 13 to 24, 25 to 36, and 37 to 52 of treatment) and did not increase with continued treatment. The incidence of drug-related AEs associated with the pharmacological effects of LAMAs (including constipation, blurred vision, and thirst) was low. Serious adverse events (SAEs) during the treatment period were reported in 17 patients (13%). SAEs reported in more than one patient were COPD exacerbation and pneumonia (3 patients each, 2%). One SAE of angina pectoris was considered to be drug related. No fatalities were reported during this study. Conclusions No new AEs were identified beyond those attributable to the pharmacological effects of LAMAs. UMEC 125 μg was well tolerated over 52 weeks of treatment in Japanese patients with COPD. PMID:26782971

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

    PubMed Central

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

    2009-01-01

    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. PMID:19927047

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

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Rimal, Rajiv N.

    2001-01-01

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

  9. Long term studies comparing the efficacy of cell-free versus cell-associated HVT vaccines against Marek's disease.

    PubMed

    Eidson, C S; Page, R K; Giambrone, J J; Kleven, S H

    1976-09-01

    In long-term field trials lasting approximately 12 months attempts were made to determine whether the cell-free HVT vaccine was as effective in reducing MD losses as the cell-associated HVT vaccine. Four trials were conducted in which flocks were vaccinated with either the cell-free or the cell-associated HVT vaccine. The cell-free HVT vaccine was as safe and effective in preventing MD as the cell-associated HVT vaccine. Although there were some losses due to MD in all flocks, there were also losses due to lymphoid leukosis, multiple hemangioma, liposarcoma or coccidiosis. Egg production was essentially the same in flocks vaccinated with the cell-free HVT vaccine as in those vaccinated with the cell-associated HVT vaccine. PMID:995809

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

    PubMed Central

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

    2014-01-01

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

  11. Long-term Angiogenesis Efficacy Using a Heparin-Conjugated Fibrin (HCF) Delivery System with HBM-MSCs

    PubMed Central

    Kim, Ae-Kyeong; Kim, Min-Hee; Kim, Byung-Soo; Kim, Dong-Ik

    2012-01-01

    Background and Objectives: Heparin-conjugated fibrin (HCF) is suitable for the release and localization of bFGF. We analyzed the effects of a bFGF delivery system using HCF with human bone marrow-derived mesenchymal stem cells (HBM- MSCs) in a dog ischemic limb model. Methods and Results: Animals were divided into HBM-MSCs, HBM-MSCs+HCF, bFGF-HCF, and HBM-MSCs+ bFGF-HCF groups. A total of 1×107 HBM-MSCs were injected per animal, and the amount of bFGF was 1 mg per dog. Ischemic muscles were harvested at eight weeks and six months after injection of cells. The HBM-MSCs+ bFGF-HCF group exhibited decreased proportions of capillaries and arterioles six months after transplantation. However, there were more cells positive for the angiogenic factors, VEGF and PDGF, in the eight-week specimens compared with those harvested six months after transplantation. Conclusions: Our results demonstrated that a single injection of HBM-MSCs did not have significant long-term angiogenic effects; however, a bFGF delivery system using HCF exerted prolonged angiogenic effects when combined with HBM-MSCs. PMID:24298352

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

    SciTech Connect

    Toma Cajthaml; Vaclav Sasek

    2005-11-01

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

  13. Dose-response efficacy and long-term effect of the hypocholesterolemic effect of octadecylpectinamide in rats.

    PubMed

    Marounek, Milan; Volek, Zdeněk; Dušková, Dagmar; Tůma, Jan; Taubner, Tomáš

    2013-09-12

    The dose-response efficiency and long-term effect of the hypocholesterolemic effect of octadecylpectinamide was examined in female rats fed diets containing cholesterol at 10 g/kg. In our first experiment, amidated pectin supplied at 20 g/kg, 40 g/kg and 60 g/kg significantly decreased serum cholesterol from 3.32 μmol/ml (control) to 1.23 μmol/ml in a dose-dependent manner. In a second experiment, the hypocholesterolemic effect of amidated pectin supplied at 20 g/kg persisted after 3 months of feeding. In both experiments, the amidated pectin significantly decreased the concentrations of cholesterol in hepatic tissue and triacylglycerols in serum. The serum concentration of aspartate aminotransferase significantly increased in rats fed amidated pectin at 60 g/kg for 4 weeks, and at 20 g/kg for 3 months. In conclusion, amidated pectin at a low dose and used for a period shorter than 3 months might be considered as an effective hypocholesterolemic and lipid-lowering agent that may substitute typical antilipidemic drugs. PMID:23911514

  14. Short- and long-term efficacy of forest thinning to mitigate drought impacts in mountain forests in the European Alps.

    PubMed

    Elkin, Ché; Giuggiola, Arnaud; Rigling, Andreas; Bugmann, Harald

    2015-06-01

    In many regions of the world, drought is projected to increase under climate change, with potential negative consequences for forests and their ecosystem services (ES). Forest thinning has been proposed as a method for at least temporarily mitigating drought impacts, but its general applicability and longer-term impacts are unclear. We use a process-based forest model to upscale experimental data for evaluating the impacts of forest thinning in a drought-susceptible valley in the interior of the European Alps, with the specific aim of assessing (1) when and where thinning may be most effective and (2) the longer-term implications for forest dynamics. Simulations indicate that forests will be impacted by climate-induced increases in drought across a broad elevation range. At lower elevations, where drought is currently prevalent, thinning is projected to temporarily reduce tree mortality, but to have minor impacts on forest dynamics in the longer term. Thinning may be particularly useful at intermediate and higher elevations as a means of temporarily reducing mortality in drought-sensitive species such as Norway spruce and larch, which currently dominate these elevations. However, in the longer term, even intense thinning will likely not be sufficient to prevent a climate change induced dieback of these species, which is projected to occur under even moderate climate change. Thinning is also projected to have the largest impact on long-term forest dynamics at intermediate elevations, with the magnitude of the impact depending on the timing and intensity of thinning. More intense thinning that is done later is projected to more strongly promote a transition to more drought-tolerant species. We conclude that thinning is a viable option for temporarily reducing the negative drought impacts on forests, but that efficient implementation of thinning should be contingent on a site-specific evaluation of the near term risk of significant drought, and how thinning will impact the rate and direction of climate driven forest conversion. PMID:26465044

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

    PubMed Central

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

    2015-01-01

    Cystic fibrosis (CF) is a fatal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene whose mortality is conditioned by a progressive decline in lung function. Bacterial infections play a key role in this decline. Chronic bacterial infection in CF patients varies over time and the presence of Pseudomonas aeruginosa in sputum is a marker of poor prognosis. P. aeruginosa is eradicated from the airways using inhaled antibiotics administered in various formulations and devices. Antipseudomonal antibiotics have extended the survival of CF patients to 40 years. Tobramycin is a bactericidal aminoglycoside antibiotic with demonstrated activity against gram-negative microorganisms. Initially, the drug was administered as an inhaled parenteral solution. Subsequently, a specific tobramycin inhalation solution was developed. PulmoSphere™ technology enables dry tobramycin powder to be formulated for inhalation (tobramycin inhalation powder) using a small and portable capsule-based breath-activated device (T-326). Chronic colonization by P. aeruginosa is the main indication for aerosol antibiotic therapy. The American Cystic Fibrosis Foundation, European guidelines, and Spanish consensus guidelines provide different recommendations for eradication. PMID:25792839

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

    PubMed

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

    2000-08-01

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

  17. Efficacy of Soil-Applied Neonicotinoid Insecticides for Long-term Protection Against Emerald Ash Borer (Coleoptera: Buprestidae).

    PubMed

    Smitley, David R; Herms, Daniel A; Davis, Terrance W

    2015-10-01

    Protection of green ash trees (Fraxinus pennsylvanica Marshall) from the emerald ash borer (EAB), Agrilus planipennis Fairmaire, by soil applications of neonicotinoids (imidacloprid, clothianidin, and dinotefuran) was tested at five locations between 2005 and 2013. Application rate and spring versus fall application dates were evaluated in tests with neighborhood street trees and in one plantation of 65 ash trees. Insecticide treatments of ash trees at all five sites were initiated as the leading edge of the EAB invasion began to kill the first ash trees at each location. Trees were treated and evaluated at each site for 4 to 7 yr. Spring applications of imidacloprid were more efficacious than fall applications. Application rates of 0.8 g a.i./cm dbh or greater per year gave a higher level of protection and were more consistent than rates of 0.56 g a.i./cm dbh per year or less. The number of years between the first observation of canopy loss due to EAB and death of most of the control trees varied from three to seven years among test sites, depending on how many non-treated ash trees were nearby. PMID:26453723

  18. Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long-term results.

    PubMed

    Cervantes, Francisco; Isola, Ignacio M; Alvarez-Larrn, Alberto; Hernndez-Boluda, Juan-Carlos; Correa, Juan-Gonzalo; Pereira, Arturo

    2015-11-01

    The efficacy of danazol was assessed in 50 patients with myelofibrosis and anemia using the recently revised criteria of the International Working Group for Myelofibrosis Research and Treatment. According to them, anemia response (clinical improvement) is defined as transfusion cessation in transfusion-dependent patients or an Hb increase >2g/dl in patients without transfusion requirements, both maintained for at least 12weeks. Median follow-up from danazol start was 36months (interquartile range [IQR] 19.2-58.8). Anemia response was achieved in 15 patients (30%), including 5 of the 27 with transfusion dependency (18.5%) and 10 of the 23 without transfusion requirements (43.5%). Median time to response was 5months (IQR 4-7) and median duration of the response 14months (IQR 10-21). Among responder patients, 5 discontinued therapy due to toxicity or personal decision and 1 died from spleen rupture while being in response. A trend for worse response was seen in transfusion-dependent patients (p?=?0.055). A platelet increase >50??10(9)/l was observed in 3 of 13 thrombocytopenic patients, all of whom had moderate thrombocytopenia. Toxicity was usually moderate, leading to treatment withdrawal in only 4 patients. Danazol is effective in 30% of patients with anemia-associated myelofibrosis. The responses are less frequent in patients with transfusion dependency. PMID:26122869

  19. Efficacy and safety of ginseng.

    PubMed

    Kitts, D; Hu, C

    2000-12-01

    Ginseng (Panax ginseng, C.A. Meyer) has been a popular herbal remedy used in eastern Asian cultures for thousands of years. In North America, the ginseng species indigenous to both Canada and the United States (Panax quinquefolium) represents an important industry for both domestic and export markets. There are numerous theories and claims describing the efficacy of ginseng, which can combat stress, enhance both the central and immune systems and contribute towards maintaining optimal oxidative status against certain chronic disease states and aging. Risk issues concerning the safety of ginseng at recommended dosages are less prominent and scientifically based. While some epidemiological or clinical studies have reported indications of efficacy for specific health benefits or potential toxicity, there are an equal number of studies that provide contradictory evidence. This situation has led to questionable conclusions concerning specific health benefits or risks associated with ginseng. Recent advances in the development of standardized extracts for both Panax ginseng (G-115) and Panax quinquefolius (CNT-2000) have and will continue to assist in the assessment of efficacy and safety standards for ginseng products. This paper reviews the scientific literature and evidence for ginseng efficacy and safety derived mostly from in vitro and animal studies and places emphasis on the need for more randomized, double-blinded, placebo clinical studies that can provide unequivocal conclusions. An example of the efficacy and safety of ginseng is provided with the description of biological activity of a North American ginseng extract (NAGE), which includes illustrating mechanisms for antioxidant activity without prooxidant properties. PMID:11276295

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

    PubMed Central

    Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

    2014-01-01

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

  1. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... 8 sec Click to watch this video Most Care Provided at Home Click for more information Long- ...

  2. The long-term efficacy and tolerability of oral deferasirox for patients with transfusion-dependent β-thalassemia in Taiwan.

    PubMed

    Chang, Hsiu-Hao; Lu, Meng-Yao; Peng, Steven Shinn-Forng; Yang, Yung-Li; Lin, Dong-Tsamn; Jou, Shiann-Tarng; Lin, Kai-Hsin

    2015-12-01

    Deferasirox is a novel once-daily, oral iron chelator. The aim of this study was to evaluate the long-term efficacy and tolerability of deferasirox in Taiwanese patients with transfusion-dependent β-thalassemia who have been treated with deferasirox for 7 years. Taiwanese patients aged ≥2 years with transfusion-dependent β-thalassemia whose serum ferritin levels were ≥1000 ng/mL and had started deferasirox treatment since December 2005 at the National Taiwan University Hospital were enrolled. Sixty patients were recruited for analysis, and 11 (18.3 %) patients discontinued deferasirox during the study. In the 42 patients included in the efficacy analysis, the mean serum ferritin levels decreased significantly by 2566 ng/mL after 7 years of treatment (P < 0.001). Forty-one of these patients received a cardiac T2* evaluation after 3 years of deferasirox treatment, and the mean cardiac T2* value increased significantly from 30.6 ± 16.6 to 45.9 ± 22.6 ms after 7 years of deferasirox treatment (P < 0.001). Deferasirox-related adverse events assessed by investigators were reported in 46 (76.7 %) patients. The most common adverse events related to deferasirox were skin rashes (n = 29, 48.3 %), followed by abdominal pain (n = 23, 38.3 %) and diarrhea (n = 16, 26.7 %). Most adverse events were manageable. This study demonstrated that long-term treatment with deferasirox was effective in improving iron overload, including cardiac iron overload, in patients with transfusion-dependent β-thalassemia. Deferasirox was well tolerated; however, the incidences of common adverse events related to deferasirox appeared higher in our Taiwanese patients than other studies. PMID:26404899

  3. Long-term neuropsychological safety of subgenual cingulate gyrus deep brain stimulation for treatment-resistant depression.

    PubMed

    Bogod, Nicholas M; Sinden, Marci; Woo, Cindy; Defreitas, Vanessa G; Torres, Ivan J; Howard, Andrew K; Ilcewicz-Klimek, Magdalena I; Honey, Christopher R; Yatham, Lakshmi N; Lam, Raymond W

    2014-04-01

    Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) is a promising investigational intervention for treatment-resistant depression (TRD), but long-term outcome data are limited. Serial neuropsychological evaluations, using a comprehensive battery, were conducted on four subjects with TRD prior to surgery, and up to 42 months post-operatively. Reliable change methodology suggested general stability and/or select statistically reliable improvement in cognitive abilities over time. This is the first known set of multi-year neuropsychological follow-up data for SCG DBS for TRD. Observed improvements are likely attributable to reduced depressive symptomatology, recovery of functional capacities, and/or specific practice effects of repeated assessment. PMID:24763760

  4. Long-term, open-label, safety study of once-daily ropinirole extended/prolonged release in early and advanced Parkinson's disease.

    PubMed

    Makumi, Clare W; Asgharian, Afsaneh; Ellis, Jeffrey; Shaikh, Soraya; Jimenez, Teri; VanMeter, Susan

    2016-01-01

    Long-term safety of once-daily ropinirole extended/prolonged release (ropinirole XL/PR) was evaluated in subjects with early and advanced Parkinson's disease (PD) in this study, 101468/248. Subjects (n = 419) who completed one of three prior studies evaluating ropinirole XL/PR for the treatment of PD were enrolled in this open-label, multicenter, extension study, and were to be followed for up to 73 months. Ropinirole XL/PR was titrated/continued, and adjusted as appropriate during the maintenance phase (maximum 24 mg/d). Levodopa (L-dopa) and other nondopamine agonist PD medications were permitted. Safety outcomes that were investigated included frequency of adverse events (AEs). Subjects' preference regarding once daily versus three times daily study medication regimens was also investigated in a subset of the study population. The median duration of ropinirole XL/PR exposure was 1275 d. Most subjects (87%) reported at least one AE, with the most common (≥ 10%) AEs being, back pain (14%), hallucinations (13%), somnolence (11%) and peripheral edema (11%). Twenty-five percent of subjects discontinued the study prematurely due to an AE during the treatment period. Long-term treatment with ropinirole XL/PR was not associated with any new or unexpected safety concerns in patients with early and advanced PD, and a majority of subjects preferred the once-daily dosing regimen. PMID:25495896

  5. Transplantation of a horseshoe kidney from a living donor: Case report, long term outcome and donor safety

    PubMed Central

    Justo-Janeiro, Jaime Manuel; Orozco, Eduardo Prado; Reyes, Francisco J.Roberto Enríquez; de la Rosa Paredes, René; de Lara Cisneros, Luis G.Vázquez; Espinosa, Alfonso Lozano; Naylor, Jesús Mier

    2015-01-01

    Introduction The use of a horseshoe kidney in renal transplant remains controversial, when it is found in the evaluation of a living donor, anatomical, surgical and ethical issues are involved. Presentation of Case An uncomplicated horseshoe kidney was detected in a 51-year-old woman who was the only suitable donor for her 30-year-old son. Kidneys were fused in the inferior pole and no vascular or urinary abnormalities were detected during imaging evaluation. The surgical procedure was approved by the hospital transplant committee. A laparotomy was performed by means of a medial upper incision. The isthmus of the kidney was divided using a harmonic scalpel and the left segment was used; it had 2 arteries too distant to create a common one, thus anastomosed separately. The renal vein was side-to-side anastomosed to the right external iliac vein and a Lich-Gregoir ureteral implant was made. There were no intraoperative or postoperative complications in the donor who currently remains asymptomatic. Recipient developed a delayed graft function (DGF), and was discharged on the 12th day after surgery. After 24 months of surgery, renal function has remained stable with a serum creatinine of 128 μmol/L (1.45 mg/dL). Discussion There are 7 reports of a horseshoe kidney from living donors in 8 patients without morbidity and a good long term outcome of all recipients. Conclusion If we anticipate a low operative risk and there is a suitable anatomy, we may consider the use of horseshoe kidneys from living donors a viable alternative. PMID:26299249

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    2003-02-24

    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.

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

    PubMed Central

    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.

    2014-01-01

    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

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

    PubMed

    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

    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

  11. Tackling Communication Barriers Between Long-Term Care Facility and Emergency Department Transfers to Improve Medication Safety in Older Adults.

    PubMed

    Callinan, Stephanie M; Brandt, Nicole J

    2015-07-01

    In 2013, the American College of Emergency Physicians, American Geriatrics Society, Emergency Nurses Association, and Society for Academic Emergency Medicine created geriatric emergency department guidelines, making recommendations for staffing/administration, follow up and transitions of care, education, quality improvement, equipment/supplies, and other policies, procedures, and protocols to be implemented. Awareness of these guidelines, as well as communication barriers, can help improve the delivery of care for older adults during transitions in care, particularly regarding medication safety. PMID:26126025

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2012-04-01

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

  14. Long-Term Once-Daily Tiotropium Respimat® Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised, Placebo-Controlled Study

    PubMed Central

    Ohta, Ken; Ichinose, Masakazu; Tohda, Yuji; Engel, Michael; Moroni-Zentgraf, Petra; Kunimitsu, Satoko; Sakamoto, Wataru; Adachi, Mitsuru

    2015-01-01

    Background This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β2-agonist (LABA). Methods 285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209). Primary objective: to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV1) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score. Results At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV1 and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24. Conclusions The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose. Trial Registration ClinicalTrials.gov NCT01340209 PMID:25894430

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

    NASA Astrophysics Data System (ADS)

    Munier, R.

    2011-12-01

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

  16. Long-Term Efficacy and Toxicity of Low-Dose-Rate {sup 125}I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer

    SciTech Connect

    Kittel, Jeffrey A.; Reddy, Chandana A.; Smith, Kristin L.; Stephans, Kevin L.; Tendulkar, Rahul D.; Ulchaker, James; Angermeier, Kenneth; Campbell, Steven; Stephenson, Andrew; Klein, Eric A.; Wilkinson, D. Allan; Ciezki, Jay P.

    2015-07-15

    Purpose/Objectives: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. Methods and Materials: From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with {sup 125}I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer–specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. Results: The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Conclusions: Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.

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

    NASA Astrophysics Data System (ADS)

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

    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.

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

    TOXLINE Toxicology Bibliographic Information

    Stein Gold L; Kircik L; Fowler J; Jackson JM; Tan J; Draelos Z; Fleischer A; Appell M; Steinhoff M; Lynde C; Sugarman J; Liu H; Jacovella J; Ivermectin Phase 3 Study Group

    2014-11-01

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

  19. Long Term Prognosis

    MedlinePlus

    ... TERM PROGNOSIS The long-term outlook of pediatric cardiomyopathy continues to be unpredictable because it occurs with ... a child also depends on the type of cardiomyopathy and the stage the disease is first diagnosed. ...

  20. Mark I containment long-term program safety evaluation report, resolution of generic technical activity A-7. Report for February 1977-December 1979

    SciTech Connect

    Not Available

    1980-07-01

    During testing for an advanced Boiling Water Reactor (BWR) containment system design (Mark III), suppression pool hydrodynamic loads were identified which had not been considered in the original design of the Mark I containment system. To address this issue, a Mark I Owners Group was formed and the assessment was divided into a short-term and long-term program. The results of the NRC staff's review of the Mark I Containment Short Term Program are described in NUREG-0408. This report describes the results of the NRC staff's review of the generic Mark I Containment Long Term Program (LTP). The LTP was conducted to provide a generic basis to define suppression pool hydrodynamic loads and the related structural acceptance criteria, such that a comprehensive reassessment of each Mark I containment system would be performed. A series of experimental and analytical programs were conducted by the Mark I Owners Group to provide the necessary bases for the generic load definition and structural assessment techniques. The generic methods proposed by the Mark I Owners Group, as modified by the NRC staff's requirements, will be used to perform plant-unique analyses, which will identify the plant modifications, if any, that will be needed to restore the originally intended margin of safety in the Mark I containment designs.

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

    PubMed Central

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

    1987-01-01

    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

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

    PubMed Central

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

    2013-01-01

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

  3. Long-term Efficacy of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A 5-year Follow-up Study in China

    PubMed Central

    Jiang, Lu-Lu; Liu, Jin-Long; Fu, Xiao-Li; Xian, Wen-Biao; Gu, Jing; Liu, Yan-Mei; Ye, Jing; Chen, Jie; Qian, Hao; Xu, Shao-Hua; Pei, Zhong; Chen, Ling

    2015-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN DBS) is effective against advanced Parkinson's disease (PD), allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. Methods: Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson's Disease Rating Scale Part III (UPDRS III), Parkinson's Disease Questionnatire-39, Parkinson's Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. Results: In the “off” state (off medication), DBS improved UPDRS III scores by 35.87% in 5 years, compared with preoperative baseline (P < 0.001). In the “on” state (on medication), motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% (P < 0.001) from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years (by 52.96%, P < 0.001). The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 μs, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively. Conclusions: STN DBS is an effective intervention for PD, although associated with a slightly diminished efficacy after 5 years. Compared with other studies, patients in our study required lower voltage and medication for satisfactory symptom control. PMID:26365958

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

    PubMed Central

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

    2014-01-01

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

  5. Premarket Safety and Efficacy Studies for ADHD Medications in Children

    PubMed Central

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

    2014-01-01

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

  6. How to treat climate evolution in the assessment of the long-term safety of disposal facilities for radioactive waste: examples from Belgium

    NASA Astrophysics Data System (ADS)

    van Geet, M.; de Craen, M.; Mallants, D.; Wemaere, I.; Wouters, L.; Cool, W.

    2009-02-01

    In order to protect man and the environment, long-lasting, passive solutions are needed for the different categories of radioactive waste. In Belgium, three main categories of conditioned radioactive waste (termed A, B and C) are defined by radiological and thermal power criteria. It is expected that Category A waste - low and intermediate level short-lived waste - will be disposed in a near-surface facility, whereas Category B and C wastes - high-level and other long-lived radioactive waste - will be disposed in a deep geological repository. In both cases, the long-term safety of a given disposal facility is evaluated. Different scenarios and assessment cases are developed illustrating the range of possibilities for the evolution and performance of a disposal system without trying to predict its precise behaviour. Within these scenarios, the evolution of the climate will play a major role as the time scales of the evaluation and long term climate evolution overlap. In case of a near-surface facility (Category A waste), ONDRAF/NIRAS is considering the conclusions of the IPCC, demonstrating that a global warming is nearly unavoidable. The consequences of such a global warming and the longer term evolutions on the evolution of the near-surface facility are considered. In case of a geological repository, in which much longer time frames are considered, even larger uncertainties exist in the various climate models. Therefore, the robustness of the geological disposal system towards the possible results of a spectrum of potential climate changes and their time of occurrence will be evaluated. The results of climate modelling and knowledge of past climate changes will merely be used as guidance of the extremes of climate changes to be considered and their consequences.

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

    PubMed Central

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

    2013-01-01

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

  8. Long-term treatment of chronic migraine with OnabotulinumtoxinA: efficacy, quality of life and tolerability in a real-life setting.

    PubMed

    Kollewe, Katja; Escher, Claus M; Wulff, Dirk U; Fathi, Davood; Paracka, Lejla; Mohammadi, Bahram; Karst, Matthias; Dressler, Dirk

    2016-05-01

    Botulinum toxin was shown to be effective in treatment of chronic migraine. We wanted to explore its efficacy and tolerability in chronic application under real-life conditions. For this, 27 consecutive patients (age 45.6 ± 10.8 years, 25 females, 2 males) received altogether 176 injection series (IS) with 189.7 ± 45.8MU onabotulinumtoxinA (Botox(®)) according to the PREEMPT scheme. During the study period altogether 6.5 ± 2.9 (min 4, max 13) IS were applied per patient (total treatment time of 73.1 ± 36.9 weeks). 96 % of the patients reported benefit. Monthly headache days were reduced from 18.9 ± 3.9 to 8.7 ± 4.5 (p < 0.001, -53.7 %), migraine days from 16.8 ± 4.9 to 7.4 ± 4.6 (p < 0.001, -55.1 %), autonomic days from 8.6 ± 7.5 to 2.7 ± 4.2 (p < 0.001, -71.9 %) and medication days from 14.2 ± 4.6 to 8.3 ± 4.2 (p < 0.001, -71.1 %). Health-related quality of life improved by 0.6-1.5 standard deviations (SD) (Short Form Health Survey), migraine-related quality of life by 1.4-2.0 SD (Migraine-Specific Quality of Life Questionnaire) and by 1.9 SD (Headache Impact Test), depression by 1.1 SD (Beck Depression Inventory). Subjective global clinical improvement was 2.6 ± 0.6 (Global Clinical Improvement Scale). All improvements were stable throughout the entire study period. Adverse effects were infrequent, mild and transient. Botulinum toxin provides highly effective and safe long-term treatment of chronic migraine. PMID:27032774

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

    PubMed Central

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

    2015-01-01

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

  10. Short-, middle- and long-term safety of superparamagnetic iron oxide-labeled allogeneic bone marrow stromal cell transplantation in rat model of lacunar infarction.

    PubMed

    Tan, Chengbo; Shichinohe, Hideo; Abumiya, Takeo; Nakayama, Naoki; Kazumata, Ken; Hokari, Masaaki; Hamauchi, Shuji; Houkin, Kiyohiro

    2015-06-01

    Recently, both basic and clinical studies demonstrated that bone marrow stromal cell (BMSC) transplantation therapy can promote functional recovery of patients with CNS disorders. A non-invasive method for cell tracking using MRI and superparamagnetic iron oxide (SPIO)-based labeling agents has been applied to elucidate the behavior of transplanted cells. However, the long-term safety of SPIO-labeled BMSCs still remains unclear. The aim of this study was to investigate the short-, middle- and long-term safety of the SPIO-labeled allogeneic BMSC transplantation. For this purpose, BMSCs were isolated from transgenic rats expressing green fluorescent protein (GFP) and were labeled with SPIO. The Na/K ATPase pump inhibitor ouabain or vehicle was stereotactically injected into the right striatum of wild-type rats to induce a lacunar lesion (n = 22). Seven days after the insult, either BMSCs or SPIO solution were stereotactically injected into the left striatum. A 7.0-Tesla MRI was performed to serially monitor the behavior of BMSCs in the host brain. The animals were sacrificed after 7 days (n = 7), 6 weeks (n = 6) or 10 months (n = 9) after the transplantation. MRI demonstrated that BMSCs migrated to the damage area through the corpus callosum. Histological analysis showed that activated microglia were present around the bolus of donor cells 7 days after the allogeneic cell transplantation, although an immunosuppressive drug was administered. The SPIO-labeled BMSCs resided and started to proliferate around the route of the cell transplantation. Within 6 weeks, large numbers of SPIO-labeled BMSCs reached the lacunar infarction area from the transplantation region through the corpus callosum. Some SPIO nanoparticles were phagocytized by microglia. After 10 months, the number of SPIO-positive cells was lower compared with the 7-day and 6-week groups. There was no tumorigenesis or severe injury observed in any of the animals. These findings suggest that BMSCs are safe after cell transplantation for the treatment of stroke. PMID:25376270

  11. Long-Term Effects of a Brief, Video-Based Parenting Education Program on Parenting Knowledge, Attitudes, and Self-Efficacy in College Students

    ERIC Educational Resources Information Center

    Sigel, Benjamin A.

    2010-01-01

    Scope and Method of Study: The focus of this project was to evaluate the effectiveness of a brief parent education program, as a teaching and preventative tool for nonexpectant individuals. The study was designed to test whether or not this parent education program would be effective long-term in positively impacting parenting knowledge, approval…

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2000-04-01

    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

  14. Improved safety of biologic therapy for rheumatoid arthritis over the 8-year period since implementation in Japan: long-term results from a multicenter observational cohort study.

    PubMed

    Kojima, Toshihisa; Takahashi, Nobunori; Funahashi, Koji; Asai, Shuji; Terabe, Kenya; Kaneko, Atsushi; Hirano, Yuji; Hayashi, Masatoshi; Miyake, Hiroyuki; Oguchi, Takeshi; Takagi, Hideki; Kanayama, Yasuhide; Yabe, Yuichiro; Watanabe, Tsuyoshi; Fujibayashi, Takayoshi; Shioura, Tomone; Ito, Takayasu; Yoshioka, Yutaka; Ishikawa, Hisato; Asai, Nobuyuki; Takemoto, Toki; Kojima, Masayo; Ishiguro, Naoki

    2016-04-01

    This study aimed to compare the long-term safety of biologics by initiation year of treatment in patients with rheumatoid arthritis (RA) in Japan. RA patients who started their first biologics including infliximab, etanercept, adalimumab, and tocilizumab between 2003 and 2008 were identified in the Tsurumai Biologics Communication Registry (TBCR), multicenter observational cohort, and followed for 2 years or until discontinuation of the drugs. We identified baseline predictors for adverse events (AEs) resulting in discontinuation of the first TNFI using Cox proportional hazards regression analysis. A total of 874 cases (1,340 person-years) were observed. During the observation period, 96 AEs (4.7 events/100 person-years) occurred. From 2003 to 2008, there were significant changes in disease duration, Steinbrocker stage, and disease activity in those aged ≤64 years with no increase of incidence of AEs, whereas those aged >64 years had no significant changes in these variables. In the later initiation year of treatment with biologics, the fewer AEs were observed (log-rank, p = 0.017, 2008 vs. 2003-2005). Multivariate analysis showed that the initiation year significantly impacted the incidence of AEs 6 months into the observation period [initiation at 2008 (vs. 2003-2005): OR: 0.30, 95 % CI: (0.14-0.68)] after adjusting for variables at baseline. The decrease of AEs in the later initiation year was evident in those aged >64 years. The safety of biologic therapy improved over the course of the 8 years from its implementation in Japan. PMID:26846135

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

    PubMed Central

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

    2008-01-01

    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. PMID:19158974

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

    PubMed Central

    2013-01-01

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

  17. Long-term Efficacy of Micro-focused Ultrasound with Visualization for Lifting and Tightening Lax Facial and Neck Skin Using a Customized Vectoring Treatment Method

    PubMed Central

    Werschler, Pam Schell

    2016-01-01

    Background: Micro-focused ultrasound with visualization has been cleared by the United States Food and Drug Administration to noninvasively lift the eyebrow, lift submental and neck tissue, and improve lines and wrinkles of the décolleté. Objective: The objective of this prospective, open-label pilot study was to evaluate the efficacy and safety of patient-specific, customized micro-focused ultrasound with visualization treatment with vertical vectoring to lift and tighten facial and neck tissue. Methods and materials: Subjects 25 to 60 years of age (N=20) with areas of skin laxity on the face and neck were enrolled and treated. A dual depth treatment was administered using a vectored pattern. Subjects were evaluated after 90 days, 180 days, and one year. Results: Overall improvements in Subject Global Aesthetic Improvement Scale and Physician Global Aesthetic Improvement Scale scores were reported by 90 and 100 percent of subjects at 90 and 180 days, respectively, and 95 percent for both measures at one year. Six of 14 evaluable subjects were rated as improved by blinded assessment at one year. Self-reported improvements maintained for up to one year included less sagging (79%), fewer lines and wrinkles (58%), and smoother skin texture (47%). Conclusion: Based on these results, treatment with micro-focused ultrasound with visualization with vertical vectoring demonstrated appreciable lifting and tightening of facial and neck tissue resulting in improved Global Aesthetic Improvement Scale scores and a high degree of patient satisfaction for up to one year. ClinicalTrials.gov Identifier: NCT01708512. PMID:27047630

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

    SciTech Connect

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

    1985-05-17

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

  19. Safety, tolerability, and efficacy of oral therapies for relapsing-remitting multiple sclerosis.

    PubMed

    Oh, Jiwon; O'Connor, Paul W

    2013-08-01

    Treatment options for relapsing-remitting multiple sclerosis (RRMS) have been continuously expanding in recent years, and the emergence of a number of oral disease-modifying agents (DMAs) has significantly changed the landscape of therapeutic options for MS patients. Many of these oral DMAs have demonstrated satisfactory safety and tolerability profiles in clinical trial settings, but the long-term safety of these agents is an important concern. This review discusses salient points on the safety and clinical efficacy of the approved and emerging novel oral therapies in RRMS, including fingolimod, teriflunomide, dimethyl fumarate, laquinimod, and cladribine. PMID:23801528

  20. Fingolimod Real World Experience: Efficacy and Safety in Clinical Practice

    PubMed Central

    Fonseca, Joaquim

    2015-01-01

    Fingolimod is a multiple sclerosis treatment licensed in Europe since 2011. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. As usual, in these trials the inclusion and exclusion criteria were designed to obtain a homogeneous population, with interchangeable characteristics in the different treatment arms. Although this is the best strategy to achieve a robust answer to the investigation question, it does not guaranty the treatment efficacy in the clinical practice, since in the real world there are concomitant treatments, comorbidities, adherence, and persistence challenges. But, to make informed treatment decision for a real life patient, we need to have evidence of the treatment efficacy, what has been called treatment effectiveness. This work aims to review fingolimod effectiveness, using, as source of information, abstracts, posters, and manuscripts. This unorthodox strategy was developed because more than half of the published experience with fingolimod is still on abstracts and posters. Only a small part of the studies reviewed are already published in peer reviewed journals. Fingolimod seems to be, at least, as effective and safe as it was on clinical trials, and with its long-term experience no new safety signals were observed. PMID:26693475

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

    PubMed

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

    2008-12-01

    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

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

    PubMed

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

    2014-12-01

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

  3. Efficacy and HIV drug resistance profile of second-line ART among patients having received long-term first-line regimens in rural China

    PubMed Central

    Wang, Jing; Wang, Zhe; Liu, Jia; Yue, Yanchao; Yang, Shimei; Huang, Huimin; He, Cui; Liao, Lingjie; Xing, Hui; Ruan, Yuhua; Shao, Yiming

    2015-01-01

    Antiretroviral therapy has significantly expanded and an increased proportion of patients have switched to second-line regimens in China. We describe the outcomes of second-line therapy among patients having received long-term first-line ART. A prospective follow-up study was conducted in rural areas in China. We compared the virological, immunological outcomes and genotypic drug resistance (DR) profiles before and after regimen switches. A total of 303 patients were enrolled, 283 (93.4%) were retained at 12 months. Of 90 participants with HIV-RNA ≥ 1000 copies/ml before switch, the proportion of viral load (VL) ≥ 1000 copies/ml at 6 and 12 months was 49.4% and 43.9%, respectively. Of 213 patients with HIV-RNA < 1000 copies/ml before switch, the proportion of VL ≥ 1000 copies/ml at 6 and 12 months was 4.8% and 6.5%, respectively. The rates of drug resistance to NNRTIs, NRTIs, PIs decreased from 65.5%, 53.3%, and 1.1% before regimen switch to 26.8%, 18.3%, and 0% at 12 months, respectively. DDI-based initial ART regimens and missing doses in past month were associated with HIV RNA ≥ 1000 copies/ml at 12 months. The results showed that patients having received long-term first-line ART and experiencing virological failure had good virological outcomes after switching to second-line treatment in China. PMID:26445885

  4. Long-term efficacy of a short period of taping followed by an exercise program in a cohort of patients with patellofemoral pain syndrome.

    PubMed

    Paoloni, Marco; Fratocchi, Giancarlo; Mangone, Massimiliano; Murgia, Massimiliano; Santilli, Valter; Cacchio, Angelo

    2012-03-01

    Patellofemoral pain syndrome (PFPS) is a common source of anterior knee pain. While treatment for PFPS may be successful in the short term, long-term results are less promising. The purpose of this study was to record long-term pain and functionality outcomes following rehabilitation in patients affected by PFPS. A prospective cohort study of 44 patients with a diagnosis of PFPS and an activation imbalance between the vastus medialis obliquus (VMO) and vastus lateralis (VL) muscles were enrolled. Patients underwent patellar taping (2 weeks) followed by a rehabilitation program lasting until the end of the third month. Primary outcome measures were pain and the functional level of the patellofemoral joint. Secondary outcome measures were surface electromyographic (sEMG) onset timing of the VMO/VL during seated knee extension and squat and isometric knee extensor muscle strength. Significant differences in all the outcome measures were observed between the affected and unaffected sides before treatment. The pain score significantly decreased both posttreatment (Δ = -4.7; 95% CI = -5.4 to -3.9) and at the 12-month follow-up (Δ = -5.5; 95% CI = -6.1 to -4.8), while the functional level significantly increased both posttreatment (Δ = 24; 95% CI = 18.3 to 30.2) and at the 12-month follow-up (Δ = 26; 95% CI = 21.4 to 30.6). Posttreatment, 35/44 patients (79.5%) and 31/44 patients (70.5%) achieved normal sEMG onset timing of the VMO and VL in the seated knee extension exercise and in the squat exercise, respectively. A short period of patellar taping followed by an exercise program results in long-lasting pain control in PFPS associated with muscular dysfunction. PMID:22048741

  5. PleurX drain use in the management of malignant ascites: safety, complications, long-term patency and factors predictive of success

    PubMed Central

    Tapping, C R; Ling, L; Razack, A

    2012-01-01

    Objectives The aim of this article was to assess the success, safety, complication profile and factors associated with long-term patency of tunnelled peritoneal drains (PleurX) in the treatment of refractory malignant ascites. Methods Over a 4-year period, 28 consecutive patients (32 drain insertions) with refractory malignant ascites were treated with a PleurX drain. The study group comprised 7 males and 21 females (mean age, 61 years). A combination of fluoroscopic and ultrasound guidance was used to insert 4 drains; the remaining 28 drains were inserted under ultrasound guidance alone. Patient history, biochemical profiles, pathological and procedural records and clinical follow-up until death were reviewed. Statistical analysis included multivariate logistic regression analysis and KaplanMeier curves (p<0.05 was considered significant). Results There was a 100% technical success rate for the insertion of the drain; there were no procedure-related deaths and no major complications. Only minor complications were reported: three (10%) immediate; three (10%) early; and two (7%) late. Factors significantly associated with these complications included current chemotherapy, low haemoglobin levels, low albumin levels, high white cell count and high c-reactive protein levels. The length of time the drains remained in situ, and therefore patent, ranged from 5 to 365 days (mean, 113 days). Out of the original 28 tunnelled drains, 24 (86%) remained in situ and functioning until the patients death. Four (14%) drains dislodged and a subsequent PleurX drain was inserted on the opposite side of the abdominal wall. These new drains remained patent until the patients death. The annual event rate was 0.45 events per year. A comorbid diagnosis of renal disease or chemotherapy was significantly related to a decreased length of patency. Conclusion The use of tunnelled peritoneal drains is safe and effective and we would advocate their use as a first-line approach in patients with refractory malignant ascites. Care and regular follow-up is indicated following insertion of the drain in all patients, especially those on chemotherapy and those with a pre-procedure diagnosis of renal disease. PMID:21427184

  6. Long-term testing

    SciTech Connect

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

    1994-12-31

    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.

  7. Long-Term Residual Efficacy of Spinetoram on Concrete and Steel Surfaces for the Management of Three Stored Product Beetle Species.

    PubMed

    Vassilakos, Thomas N; Athanassiou, Christos G

    2015-08-01

    In this study, the residual efficacy of spinetoram on concrete and galvanized steel surfaces was evaluated under fixed laboratory conditions against the rice weevil, Sitophilus oryzae (L.), the confused flour beetle, Tribolium confusum Jacquelin du Val, and the sawtoothed grain beetle, Oryzaephilus surinamensis (L.). Spinetoram was applied at the dose rates of 0.025 and 0.1 mg (active ingredient)/cm(2), on steel surfaces that were stored in continuous darkness and on concrete surfaces that were stored either in continuous darkness or in 12:12 (L:D) photoperiod. The experimental period for the residual effect of spinetoram was 6 mo. Bioassays were conducted for all types of surfaces and storage conditions at monthly intervals starting from the initial application period (seven bioassays in total). For each bioassay, mortality of the exposed adult beetles was measured after 3 and 7 d of exposure. Among the tested species, T. confusum was the least susceptible, regardless of the surface type, storage conditions, and dose rate. Regarding the bioassays conducted in the surfaces stored in darkness, spinetoram proved very persistent and no reduction in the efficacy was noted throughout the experimental period. Moreover, there were no differences in spinetoram efficacy between the two types of surfaces. Conversely, in light [12:12 (L:D)] conditions spinetoram efficacy was notably reduced after the first month, but remained stable for the rest of the period. The results of this study indicate that spinetoram was persistent with long residual efficacy against major stored grain beetle species on the most common types of surfaces in continuous darkness, while the presence of light reduced its efficacy. PMID:26470356

  8. Safety and Efficacy of Neonatal Vaccination

    PubMed Central

    Demirjian, Alicia; Levy, Ofer

    2009-01-01

    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. PMID:19089811

  9. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer.

    PubMed

    Saad, Fred; Gleason, Donald M; Murray, Robin; Tchekmedyian, Simon; Venner, Peter; Lacombe, Louis; Chin, Joseph L; Vinholes, Jeferson J; Goas, J Allen; Zheng, Ming

    2004-06-01

    In a placebo-controlled randomized clinical trial, zoledronic acid (4 mg via a 15-minute infusion every 3 weeks for 15 months) reduced the incidence of skeletal-related events (SREs) in men with hormone-refractory metastatic prostate cancer. Among 122 patients who completed a total of 24 months on study, fewer patients in the 4-mg zoledronic acid group than in the placebo group had at least one SRE (38% versus 49%, difference = -11.0%, 95% confidence interval [CI] = -20.2% to -1.3%; P =.028), and the annual incidence of SREs was 0.77 for the 4-mg zoledronic acid group versus 1.47 for the placebo group (P=.005). The median time to the first SRE was 488 days for the 4-mg zoledronic acid group versus 321 days for the placebo group (P =.009). Compared with placebo, 4 mg of zoledronic acid reduced the ongoing risk of SREs by 36% (risk ratio = 0.64, 95% CI = 0.485 to 0.845; P =.002). Patients in the 4-mg zoledronic acid group had a lower incidence of SREs than did patients in the placebo group, regardless of whether they had an SRE prior to entry in the study. Long-term treatment with 4 mg of zoledronic acid is safe and provides sustained clinical benefits for men with metastatic hormone-refractory prostate cancer. PMID:15173273

  10. 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

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

    2013-08-01

    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

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

    SciTech Connect

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

    2009-11-15

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

  12. Long-Term Efficacy of Modified-Release Recombinant Human Thyrotropin Augmented Radioiodine Therapy for Benign Multinodular Goiter: Results from a Multicenter, International, Randomized, Placebo-Controlled, Dose-Selection Study

    PubMed Central

    Hegedüs, Laszlo; Pacini, Furio; Pinchera, Aldo; Leung, Angela M.; Vaisman, Mario; Reiners, Christoph; Wemeau, Jean-Louis; Huysmans, Dyde A.; Harper, William; Rachinsky, Irina; de Souza, Hevelyn Noemberg; Castagna, Maria G.; Antonangeli, Lucia; Braverman, Lewis E.; Corbo, Rossana; Düren, Christian; Proust-Lemoine, Emmanuelle; Marriott, Christopher; Driedger, Albert; Grupe, Peter; Watt, Torquil; Magner, James; Purvis, Annie; Graf, Hans

    2014-01-01

    Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine (131I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with 131I therapy. Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2±9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9–242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated 131I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. Results: At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44±12.7% (SD) in the placebo group, 41±21.0% in the 0.01 mg MRrhTSH group, and 53±18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal 131I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4±23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. Conclusions: When used as adjuvant to 131I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤0.03 mg, indicating that the lower threshold for efficacy is around this level. PMID:24341527

  13. Long-Term Safety and Longevity of a Mixture of Polymethyl Methacrylate and Cross-Linked Dextran (Lipen-10®) after Penile Augmentation: Extension Study from Six to 18 Months of Follow-Up

    PubMed Central

    Kim, Ma Tae; Ko, Kyungtae; Lee, Won Ki; Kim, Sae Chul

    2015-01-01

    Purpose The goal of this study was to investigate the long-term efficacy and safety of a mixture of polymethyl methacrylate (PMMA) and cross-linked dextran Lipen-10® used for penile augmentation under the physical impact generated during sexual intercourse. Materials and Methods From March 2010 to October 2011, a total of 20 patients with a mean age of 44 years (interquartile range, 20~70 years) who requested penile augmentation participated in this study. Lipen-10® filler is a mixture of 75% cross-linked dextran, 15% PMMA, and 10% hypromellose solution. With the patient in the supine position, Lipen-10® was injected into the subcutaneous tissue between the dartos fascia and Buck's fascia of the penis using a fanning technique. Penile length and circumference were measured before the procedure and six, 12, and 18 months after the procedure. Values were compared using the Student's t-test and the paired t-test. Results A total of 15 patients completed this study. The increases in circumference and length observed six months after the procedure were found to have been maintained without change at 12 and 18 months of follow-up. At 12 and 18 months of follow-up, no abnormal findings were observed. Pelvic magnetic resonance imaging conducted at 18 months of follow-up showed no trace of the injected filler having migrated to other sites, and the volume was well maintained. Conclusions Lipen-10®, a mixture of PMMA and cross-linked dextran, showed good durability and tolerability over 18 months of follow-up during which the participants were sexually active. PMID:26770941

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

    PubMed Central

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

    2012-01-01

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

  15. 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

    2014-01-01

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

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

    PubMed

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

    2013-06-01

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

  17. Prior infection with influenza virus but not vaccination leaves a long-term immunological imprint that intensifies the protective efficacy of antigenically drifted vaccine strains.

    PubMed

    Kim, Jin Hyang; Liepkalns, Justine; Reber, Adrian J; Lu, Xiuhua; Music, Nedzad; Jacob, Joshy; Sambhara, Suryaprakash

    2016-01-20

    The role of pre-existing immunity for influenza vaccine responses is of great importance for public health, and thus has been studied in various contexts, yet the impact of differential priming on vaccine responses in the midst of antigenic drift remains to be elucidated. To address this with antigenically related viruses, mice were first primed by either infection or immunization with A/Puerto Rico/8/34 (PR8) virus, then immunized with whole-inactivated A/Fort Monmouth/1/47 (FM1) virus. The ensuing vaccine responses and the protective efficacy of FM1 were superior in PR8 infection-primed mice compared to PR8 immunization-primed or unprimed mice. Increased FM1-specific Ab responses of PR8 infection-primed mice also broadened cross-reactivity against contemporary as well as antigenically more drifted strains. Further, prior infection heightened the protective efficacy of antigenically distant strains, such as A/Brisbane/59/2006 infection followed by immunization with split pandemic H1N1 vaccine (A/California/07/2009). Therefore, influenza infection is a significant priming event that intensifies future vaccine responses against drift strains. PMID:26706277

  18. A Long-term Co-perfused Disseminated Tuberculosis-3D Liver Hollow Fiber Model for Both Drug Efficacy and Hepatotoxicity in Babies

    PubMed Central

    Srivastava, Shashikant; Pasipanodya, Jotam G.; Ramachandran, Geetha; Deshpande, Devyani; Shuford, Stephen; Crosswell, Howland E.; Cirrincione, Kayle N.; Sherman, Carleton M.; Swaminathan, Soumya; Gumbo, Tawanda

    2016-01-01

    Treatment of disseminated tuberculosis in children ≤ 6 years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose–response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100 mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children ≤ 6 years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity. PMID:27211555

  19. A Long-term Co-perfused Disseminated Tuberculosis-3D Liver Hollow Fiber Model for Both Drug Efficacy and Hepatotoxicity in Babies.

    PubMed

    Srivastava, Shashikant; Pasipanodya, Jotam G; Ramachandran, Geetha; Deshpande, Devyani; Shuford, Stephen; Crosswell, Howland E; Cirrincione, Kayle N; Sherman, Carleton M; Swaminathan, Soumya; Gumbo, Tawanda

    2016-04-01

    Treatment of disseminated tuberculosis in children≤6years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose-response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children≤6years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity. PMID:27211555

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

    NASA Astrophysics Data System (ADS)

    Nottingham, Mary E.

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

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

    PubMed

    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

    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

  2. The long-term analgesic efficacy of a single-shot fascia iliaca compartment block in burn patients undergoing skin-grafting procedures.

    PubMed

    Cuignet, O; Mbuyamba, J; Pirson, J

    2005-01-01

    In a previous study, we assessed the efficacy of a continuous fascia iliaca compartment block (FICB) in reducing the pain at thigh autograft skin donor sites. However, a continuous local anesthetic infusion may cause toxicity or infection. In this prospective, randomized double-blind study, we compared the analgesic efficacy of FICB when given as a single shot vs continuous infusion during the 72-hour postoperative period up to the first dressing change (1dc). After ethical committee approval and informed consent, 81 adults (with 1% to 20% total burn surface area) who were scheduled for split-skin graft harvest procedures of the thigh underwent the FICB procedure before general or spinal anesthesia. Via FICB, patients received a bolus of 40 ml followed by 10 ml/hr consisting of either ropivacaine 0.2% for bolus and infusion (continuous, n = 27), or ropivacaine 0.2% for bolus and saline for infusion (single-shot, n = 27), or saline for both bolus and infusion (control, n = 27) until 1dc. Postoperative analgesia consisted of morphine via a patient-controlled analgesia device. We compared cumulative morphine consumption, static and dynamic pain scores, and side effects related to morphine or ropivacaine during the 72 hours up to 1dc. A single block had the same morphine sparing-effect as the continuous technique. Both techniques were equally effective in diminishing dynamic pain and reducing the side effects normally associated with morphine. However, patients receiving a single block experienced less residual paresia and were more satisfied with their pain-relief treatment than those who received a continuous infusion. A single-shot FICB is an easy, inexpensive, and efficient method for diminishing pain at thigh donor sites during a 72-hour postoperative period and has limited side effects and no residual paresia. PMID:16151286

  3. Long-term consequences of foodborne infections.

    PubMed

    Batz, Michael B; Henke, Evan; Kowalcyk, Barbara

    2013-09-01

    Foodborne infections with Campylobacter, E. coli O157:H7, Listeria monocytogenes, Salmonella, Shigella, Toxoplasma gondii, and other pathogens can result in long-term sequelae to numerous organ systems. These include irritable bowel syndrome, inflammatory bowel disease, reactive arthritis, hemolytic uremic syndrome, chronic kidney disease, Guillain-Barré Syndrome, neurological disorders from acquired and congenital listeriosis and toxoplasmosis, and cognitive and developmental deficits due to diarrheal malnutrition or severe acute illness. A full understanding of the long-term sequelae of foodborne infection is important both for individual patient management by clinicians, as well as to inform food safety and public health decision making. PMID:24011832

  4. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

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

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

    PubMed Central

    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

    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. PMID:22185325

  6. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

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

  7. Long-term efficacy of risperidone long-acting injectable in bipolar disorder with psychotic features: a prospective study of 3-year outcomes.

    PubMed

    Malempati, Rao Narasimha; Bond, David J; Kunz, Mauricio; Malemati, Chaitanya; Cheng, Amy; Yatham, Lakshmi N

    2011-05-01

    Bipolar disorder (BD) with psychotic features is a difficult-to-treat form of the illness that is associated with a poor prognosis. We hypothesized that treatment with adjunctive risperidone long-acting injectable (RLAI) is well-tolerated and efficacious in treating patients with psychotic BD. Ten patients with BDI or BDII with psychotic features who were refractory to earlier treatments were prescribed adjunctive open-label RLAI 25-62.5 mg q twice weekly. The patients were followed prospectively for 3 years. The severity of mood and psychotic symptoms was measured using clinical rating scales, and information regarding relapses, hospitalizations, extra-pyramidal symptom, weight gain, and other side effects was also gathered. Young Mania Rating Scale scores, Montgomery Asberg Depression Rating Scale scores, psychosis rating scale scores, and the numbers of mood episodes and hospitalizations were reduced during 3 years of RLAI therapy compared with an equivalent pretreatment period. Only three patients experienced relapses with psychotic symptoms. Functional outcomes were also improved, with substantial numbers of previously disabled patients able to return to gainful employment and independent living. RLAI was associated with minimal extra-pyramidal symptom, modest weight gain, and few other side effects. Adjunctive RLAI can be considered as a treatment option in patients with psychotic BD. PMID:21372721

  8. Poor Long-Term Efficacy of Prevnar-13 in Sickle Cell Disease Mice Is Associated with an Inability to Sustain Pneumococcal-Specific Antibody Titers

    PubMed Central

    Rogers, Kara; Cotte, Christina; Adami, Alexander J.; Bracken, Sonali J.; Salmon, Sharon; Secor, Eric R.; Thrall, Roger S.; Andemariam, Biree; Metzger, Dennis W.

    2016-01-01

    Background One of the most common causes of morbidity and mortality in children with sickle cell disease (SCD) is infection with the pneumococcal bacterium (Streptococcus pneumoniae). Unfortunately, the polysaccharide-conjugate vaccine appears to be less effective in individuals with SCD when compared to the general population. We sought to better understand the relative efficacy of pneumococcal vaccination in a SCD mouse challenge model. Methods Transgenic control and SCD mice were monitored for mortality after intranasal pneumococcal infection or pneumococcal vaccination with Prevnar-13 and type-matched challenge. Anti-pneumococcal antibody titers were measured by ELISA and opsonophagocytosis was measured in vitro. Results Mortality after pneumococcal infection was similar between control and SCD mice. However, after three intramuscular polysaccharide-conjugate vaccinations, all control mice were protected following high-dose intranasal infection, whereas 60% of SCD mice died. Anti-pneumococcal antibody titers showed initial IgG and IgM responses in both groups, but waning titers were observed in the SCD group, even after boosting. When functionally assayed in vitro, serum from SCD mice 13 weeks after a second booster shot maintained little to no ability to opsonize pneumococci, while serum from control mice sustained a significantly higher capacity opsonization. Thus, it appears that SCD mice do not maintain antibody responses to pneumococcal polysaccharides after Prevnar-13 vaccination, thereby leaving them susceptible to mortality after type-matched infection. Conclusion Our results emphasize the need to better understand the correlates of immune protection in SCD so that pneumococcal vaccines can be improved and mortality reduced in this susceptible population. PMID:26910228

  9. Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: a nationwide survey in Japan.

    PubMed

    Tanaka, Akemi; Okuyama, Torayuki; Suzuki, Yasuyuki; Sakai, Norio; Takakura, Hiromitsu; Sawada, Tomo; Tanaka, Toju; Otomo, Takanobu; Ohashi, Toya; Ishige-Wada, Mika; Yabe, Hiromasa; Ohura, Toshihiro; Suzuki, Nobuhiro; Kato, Koji; Adachi, Souichi; Kobayashi, Ryoji; Mugishima, Hideo; Kato, Shunichi

    2012-11-01

    Hematopoietic stem cell transplantation (HSCT) has not been indicated for patients with mucopolysaccharidosis II (MPS II, Hunter syndrome), while it is indicated for mucopolysaccharidosis I (MPS I) patients <2 years of age and an intelligence quotient (IQ) of ≥ 70. Even after the approval of enzyme replacement therapy for both of MPS I and II, HSCT is still indicated for patients with MPS I severe form (Hurler syndrome). To evaluate the efficacy and benefit of HSCT in MPS II patients, we carried out a nationwide retrospective study in Japan. Activities of daily living (ADL), IQ, brain magnetic resonance image (MRI) lesions, cardiac valvular regurgitation, and urinary glycosaminoglycan (GAG) were analyzed at baseline and at the most recent visit. We also performed a questionnaire analysis about ADL for an HSCT-treated cohort and an untreated cohort (natural history). Records of 21 patients were collected from eight hospitals. The follow-up period in the retrospective study was 9.6 ± 3.5 years. ADL was maintained around baseline levels. Cribriform changes and ventricular dilatation on brain MRI were improved in 9/17 and 4/17 patients, respectively. Stabilization of brain atrophy was shown in 11/17 patients. Cardiac valvular regurgitation was diminished in 20/63 valves. Urinary GAG concentration was remarkably lower in HSCT-treated patients than age-matched untreated patients. In the questionnaire analysis, speech deterioration was observed in 12/19 patients in the untreated cohort and 1/7 patient in HSCT-treated cohort. HSCT showed effectiveness towards brain or heart involvement, when performed before signs of brain atrophy or valvular regurgitation appear. We consider HSCT is worthwhile in early stages of the disease for patients with MPS II. PMID:23022072

  10. 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

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

    2010-01-01

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

  11. Long term follow-up study to evaluate immunogenicity and safety of a single dose of live attenuated hepatitis a vaccine in children

    PubMed Central

    Mitra, Monjori; Shah, Nitin; Faridi, MMA; Ghosh, Apurba; Sankaranarayanan, VS; Aggarwal, Anju; Chatterjee, Suparna; Bhattacharyya, Nisha; Kadhe, Ganesh; Vishnoi, Gaurav; Mane, Amey

    2015-01-01

    Worldwide, viral hepatitis continues to be a cause of considerable morbidity and mortality. Mass immunization with a single dose of live attenuated HAV has been shown to significantly reduce disease burden in the community. This was a phase IV, 5-year follow up study carried out at 4 centers (Kolkata, Delhi, Mumbai and Chennai) across India. The subjects with antibody titer <20 mIU/mL at baseline were evaluated for long term immunogenicity. Of the 503 subjects enrolled, 349 subjects were baseline seronegative with an anti-HAV antibody titer <20 mIU/mL. Overall, 343 subjects could be followed up at some point of time during this 5 y post vaccination period. In the last year (60 months) of follow-up, 108 subjects (97.3%) of 111 subjects (who came for follow-up at the end of 5 y) had a protective antibody titer (anti-HAV antibody titer >20 mIU/mL). The seroconversion rates considering seroprotection levels of anti-HAV antibody titer >20 mIU/mL, following vaccination starting from 6 weeks, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months were 95.1%, 97.9%, 98.3%, 96.2%, 97.8%, 92.6% and 97.3%, respectively. The geometric mean concentration (GMC) over the years increased from 64.9 mIU/mL at 6 weeks to 38.1 mIU/mL and 135.2 mIU/mL at 6 months and 12 months, respectively and was maintained at 127.1 mIU/mL at 60 months. In conclusion, the result of this 5-year follow up study showed that the single dose of live attenuated vaccine is well tolerated and provides long-term immunogenicity in healthy Indian children. PMID:26018443

  12. 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

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

    2014-03-01

    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

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

    PubMed Central

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

    2014-01-01

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

  14. Long-term Local and Systemic Safety of Poly(L-lactide-co-epsilon-caprolactone) after Subcutaneous and Intra-articular Implantation in Rats.

    PubMed

    Ramot, Yuval; Nyska, Abraham; Markovitz, Elana; Dekel, Assaf; Klaiman, Guy; Zada, Moran Haim; Domb, Abraham J; Maronpot, Robert R

    2015-12-01

    The use of biodegradable materials is gaining popularity in medicine, especially in orthopedic applications. However, preclinical evaluation of biodegradable materials can be challenging, since they are located in close contact with host tissues and might be implanted for a long period of time. Evaluation of these compounds requires biodegradability and biocompatibility studies and meticulous pathology examination. We describe 2 preclinical studies performed on Sprague-Dawley rats for 52 weeks, to evaluate clinical pathology, biocompatibility, biodegradability, and systemic toxicity after implantation of 2-layered films or saline-inflated balloon-shaped implants of downsized InSpace™ devices (termed "test device"). The test devices are made from a copolymer of poly-L-lactide-co-∊-caprolactone in a 70:30 ratio, identical to the device used in humans, intended for the treatment of rotator cuff tears. Intra-articular film implantation and subcutaneous implantation of the downsized device showed favorable local and systemic tolerability. Although the implanted materials have no inherent toxic or tumorigenic properties, one animal developed a fibrosarcoma at the implantation site, an event that is associated with a rodent-predilection response where solid materials cause mesenchymal neoplasms. This effect is discussed in the context of biodegradable materials along with a detailed description of expected pathology for biodegradable materials in long-term rodent studies. PMID:26296630

  15. Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients

    PubMed Central

    Bank, J. R.; Rabelink, T. J.; de Fijter, J. W.; Reinders, M. E. J.

    2015-01-01

    Despite excellent short-term graft survival after renal transplantation, the long-term graft outcome remains compromised. It has become evident that a combination of sustained alloreactivity and calcineurin-inhibitor- (CNI-) related nephrotoxicity results in fibrosis and consequently dysfunction of the graft. New immunosuppressive regimens that can minimize or eliminate side effects, while maintaining efficacy, are required to improve long-term graft survival. In this perspective mesenchymal stromal cells (MSCs) are an interesting candidate, since MSCs have immunosuppressive and regenerative properties. The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results. Recently, the first phase II studies have been started. One of the most difficult and challenging aspects in those early phase trials is to define accurate endpoints that can measure safety and efficacy of MSC treatment. Since both graft losses and acute rejection rates declined, alternative surrogate markers such as renal function, histological findings, and immunological markers are used to measure efficacy and to provide mechanistic insight. In this review, we will discuss the current status of MSCs in renal transplantation with a focus on the endpoints used in the different experimental and clinical studies. PMID:26258149

  16. Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients.

    PubMed

    Bank, J R; Rabelink, T J; de Fijter, J W; Reinders, M E J

    2015-01-01

    Despite excellent short-term graft survival after renal transplantation, the long-term graft outcome remains compromised. It has become evident that a combination of sustained alloreactivity and calcineurin-inhibitor- (CNI-) related nephrotoxicity results in fibrosis and consequently dysfunction of the graft. New immunosuppressive regimens that can minimize or eliminate side effects, while maintaining efficacy, are required to improve long-term graft survival. In this perspective mesenchymal stromal cells (MSCs) are an interesting candidate, since MSCs have immunosuppressive and regenerative properties. The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results. Recently, the first phase II studies have been started. One of the most difficult and challenging aspects in those early phase trials is to define accurate endpoints that can measure safety and efficacy of MSC treatment. Since both graft losses and acute rejection rates declined, alternative surrogate markers such as renal function, histological findings, and immunological markers are used to measure efficacy and to provide mechanistic insight. In this review, we will discuss the current status of MSCs in renal transplantation with a focus on the endpoints used in the different experimental and clinical studies. PMID:26258149

  17. [Human papillomavirus vaccine. Efficacy and safety].

    PubMed

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. PMID:25937455

  18. Assuring the safety and efficacy of therapies.

    PubMed

    Stolley, P D

    1974-01-01

    The randomized, controlled clinical trial now makes it possible to test the hypothesis that 1 form of treatment is preferable to another and to express the results in the form of the probability of the differences found being because of chance or not. The means exist to evaluate much of medical and surgical therapy, and the problems of evaluating surgical procedures, increasing drug use and adverse reactions to therapy are discussed. The purpose is to raise key issues and critical questions. The example of a minor epidemic of drug induced cancer is described to illustrate the use of the epidemiologic method in detecting adverse effects and for its implications for the development of of a more resonsible public policy to prevent such occurrences. The example of the use of DES in pregnancy and the resulting minor "epidemic" of adenocarcinoma of the vagina among the adolescent daughters of these women was chosen because this example of an adverse drug reaction reveals 1) the complexities of detection; 2) the role of the epidemiologist; 3) the possible results of uncritical acceptance of therapeutic reports; and 4) the need for a new policy of drug regulation. Advances in the epidemiologic detection of adverse effects, along with the development and application of the controlled clinical trial have provided the needed evidence for the development of new governmental regulations which ensure safety and efficacy. Such evidence suggests that regulation should be expanded to require that manufacturers of new drugs introduced into the market demonstrate, in addition to safety and efficacy, the relative efficacy of their products over existing formulations. Surgical procedures also need to be subjected to scrutiny. More attention needs to be paid to the ecologic consequences of drugs and food additives. PMID:4597990

  19. Replacement therapy for hereditary alpha1-antitrypsin deficiency. A program for long-term administration.

    PubMed

    Barker, A F; Siemsen, F; Pasley, D; D'Silva, R; Buist, A S

    1994-05-01

    This retrospective chart review describes the efficacy and safety of long-term administration of intravenous alpha1-antitrypsin (AAT) in 14 patients with hereditary AAT deficiency and COPD. During the 12- to 48-month observation period, 12 to 14 patients had stabilization of functional status; 4 patients had reductions in hospitalizations. Thirteen of 14 patients had no decline in pulmonary function. Three patients had self-limited adverse reactions to the AAT with one patient requiring a brief hospitalization. PMID:8181327

  20. OSLER and ODYSSEY LONG TERM: PCSK9 inhibitors on the right track of reducing cardiovascular events

    PubMed Central

    Hassan, Mohamed

    2015-01-01

    Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors have emerged as a novel treatment option in patients with hypercholesterolemia. Evolocumab and alirocumab have achieved consistent and significant (around 60%) reduction in low-density lipoprotein cholesterol (LDL-C) levels when added to statin therapy in short term studies. The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER), and The Long-term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM) studies are two phase 3, multicentre, randomized, placebo controlled studies that were conducted to evaluate the long term efficacy and safety of evolocumab and alirocumab respectively in reducing lipids and cardiovascular (CV) events. Both studies demonstrated additional 48–53% reduction of CV events when added to statin therapy. Most adverse events occurred with similar frequency in the two groups; however the rate of neurocognitive adverse events was higher with evolocumab and alirocumab than with placebo. These data provide strong support for the notion that lower LDL-C goal is better, and may confirm the role of PCSK9 inhibitors as a new frontier in lipid management. The results of larger long-term outcome studies are still awaited. PMID:26566525

  1. Integrated analysis of long-term safety in patients with chronic immune thrombocytopaenia (ITP) treated with the thrombopoietin (TPO) receptor agonist romiplostim.

    PubMed

    Cines, Douglas B; Gernsheimer, Terry; Wasser, Jeffrey; Godeau, Bertrand; Provan, Drew; Lyons, Roger; Altomare, Ivy; Wang, Xuena; Lopez, Angela

    2015-09-01

    A safety analysis of pooled data from clinical studies of romiplostim, a thrombopoietin (TPO) receptor agonist, in which patients with immune thrombocytopaenia (ITP) received romiplostim, placebo, or medical standard of care (SOC) Rodeghiero et al. (Eur J Haematol 91:423-436, 2013), has been updated. Included are data from 14 trials spanning 2002-2011; placebo- and SOC-arm data are pooled. Most patients (n = 1059) were female (61 %) and Caucasian (85 %); 38 % had undergone splenectomy; 23 were children. Mean (SD) baseline platelet count was 20.6 (16.5) × 10(9)/L. Mean (SD) weekly dose of romiplostim was 4.2 (2.8) µg/kg; total exposure was 1520 patient-years. Overall, 921 patients received romiplostim only, 65 received placebo/SOC only, and 73 received placebo/SOC followed by romiplostim. Rates of haemorrhage (romiplostim, 205/100 patient-years; placebo/SOC, 263/100), thrombosis (both, 5.5/100 patient-years), haematological malignancy/myelodysplastic syndrome (romiplostim, 0.5/100 patient-years; placebo/SOC, 2.7/100), and non-haematological tumours (romiplostim, 2.2/100 patient-years; placebo/SOC, 3.6/100) were comparable among groups. Bone marrow reticulin was reported in 17 patients and collagen in one patient receiving romiplostim; one patient receiving placebo/SOC had reticulin reported. Three patients developed neutralizing antibodies to romiplostim, but not to endogenous TPO. This integrated analysis of the safety profile of romiplostim in patients with ITP is consistent with previously reported studies; no new safety concerns emerged. PMID:26201709

  2. Long Term Illness and Wages

    ERIC Educational Resources Information Center

    Sandy, Robert; Elliott, Robert R.

    2005-01-01

    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…

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

    PubMed Central

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

    2014-01-01

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

  4. International Progress in Developing Cases for Long-term Safety of Repositories for Transuranic and Long-Lived Intermediate Level Wastes. Summary of the Third International Workshop

    SciTech Connect

    Mathieson, J.; Hooper, A.; Alexander, W. R.; Shiotsuki, M.; Kamei, G.

    2006-07-01

    In January 2005 an international workshop was held in Oxford, UK to discuss research progress in the disposability of transuranic (TRU) waste (also known as long-lived intermediate level waste). This was the third such workshop, with two previous ones being held in Switzerland in 1996 and Japan in 1999. Whilst TRU/ILW represents more complex waste-forms than high-level waste (HLW) or spent fuel (SF), it is recognised that it has not received the same amount of attention. This paper summarises the themes discussed at the workshop and the conclusions derived. Moreover, it provides a status report and future direction of work in relation to TRU and ILW wastes. The overall conclusion of the workshop was recognition of the uncertainties surrounding the subject and outstanding issues where further work was required. However, there were no insurmountable obstacles to making safety cases for the disposal of TRU/ILW waste - safety assessment strategies were judged to be at a mature stage. (authors)

  5. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

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

  6. [S3 guidelines on long-term opioid treatment in non-cancer pain : Recommendations for opioid use in clinical rheumatology].

    PubMed

    Krasselt, M; Häuser, W; Petzke, F; Baerwald, C

    2016-03-01

    The long-term use of opioids for chronic pain can be problematic in many respects. Besides potentially harmful and considerable undesired side effects and possible drug abuse, the indications for prescription, efficacy and safety in the long run have to be considered. The recently updated S3 guidelines on long-term opioid treatment in non-cancer pain (LONTS) provide recommendations with the highest currently available evidence. This article summarizes the most relevant contents for the clinical rheumatologist. PMID:26558623

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

    PubMed

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

    2013-01-01

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

  8. 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)

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

    2014-05-01

    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.

  9. Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials

    PubMed Central

    West, Jonathan; Ogston, Simon; Foerster, John

    2016-01-01

    Background Methotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse. Objective In order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods). Results In terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1–60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5–5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1–14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time. Limitations Meta-analyses for efficacy and safety, respectively, employed non-identical selection criteria. Conclusions These meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes. PMID:27168193

  10. Prucalopride: safety, efficacy and potential applications.

    PubMed

    Quigley, Eamonn M M

    2012-01-01

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

  11. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

    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.

  12. Management of atopic dermatitis: safety and efficacy of phototherapy

    PubMed Central

    Patrizi, Annalisa; Raone, Beatrice; Ravaioli, Giulia Maria

    2015-01-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disease that can affect all age groups. It is characterized by a relapsing course and a dramatic impact on quality of life for patients. Environmental interventions together with topical devices represent the mainstay of treatment for AD, in particular emollients, corticosteroids, and calcineurin inhibitors. Systemic treatments are reserved for severe cases. Phototherapy represents a valid second-line intervention in those cases where non-pharmacological and topical measures have failed. Different forms of light therapy are available, and have showed varying degrees of beneficial effect against AD: natural sunlight, narrowband (NB)-UVB, broadband (BB)-UVB, UVA, UVA1, cold-light UVA1, UVA and UVB (UVAB), full-spectrum light (including UVA, infrared and visible light), saltwater bath plus UVB (balneophototherapy), Goeckerman therapy (coal tar plus UVB radiation), psoralen plus UVA (PUVA), and other forms of phototherapy. In particular, UVA1 and NB-UVB have gained importance in recent years. This review illustrates the main trials comparing the efficacy and safety of the different forms of phototherapy. No sufficiently large randomized controlled studies have been performed as yet, and no light modality has been defined as superior to all. Parameters and dosing protocols may vary, although clinicians mainly refer to the indications included in the American Academy of Dermatology psoriasis guidelines devised by Menter et al in 2010. The efficacy of phototherapy (considering all forms) in AD has been established in adults and children, as well as for acute (UVA1) and chronic (NB-UVB) cases. Its use is suggested with strength of recommendation B and level of evidence II. Home phototherapy can also be performed; this technique is recommended with strength C and level of evidence III. Phototherapy is generally considered to be safe and well tolerated, with a low but established percentage of short-term and long-term adverse effects, with the most common being photodamage, xerosis, erythema, actinic keratosis, sunburn, and tenderness. A carcinogenic risk related to UV radiation has not been excluded. Phototherapy also has some limitations related to costs, availability, and patient compliance. In conclusion, phototherapy is an optimal second-line treatment for AD. It can be used as monotherapy or in combination with systemic drugs, in particular corticosteroids. It must be performed conscientiously, especially in children, and must take into account the patient’s features and overall condition. PMID:26491366

  13. Management of atopic dermatitis: safety and efficacy of phototherapy.

    PubMed

    Patrizi, Annalisa; Raone, Beatrice; Ravaioli, Giulia Maria

    2015-01-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disease that can affect all age groups. It is characterized by a relapsing course and a dramatic impact on quality of life for patients. Environmental interventions together with topical devices represent the mainstay of treatment for AD, in particular emollients, corticosteroids, and calcineurin inhibitors. Systemic treatments are reserved for severe cases. Phototherapy represents a valid second-line intervention in those cases where non-pharmacological and topical measures have failed. Different forms of light therapy are available, and have showed varying degrees of beneficial effect against AD: natural sunlight, narrowband (NB)-UVB, broadband (BB)-UVB, UVA, UVA1, cold-light UVA1, UVA and UVB (UVAB), full-spectrum light (including UVA, infrared and visible light), saltwater bath plus UVB (balneophototherapy), Goeckerman therapy (coal tar plus UVB radiation), psoralen plus UVA (PUVA), and other forms of phototherapy. In particular, UVA1 and NB-UVB have gained importance in recent years. This review illustrates the main trials comparing the efficacy and safety of the different forms of phototherapy. No sufficiently large randomized controlled studies have been performed as yet, and no light modality has been defined as superior to all. Parameters and dosing protocols may vary, although clinicians mainly refer to the indications included in the American Academy of Dermatology psoriasis guidelines devised by Menter et al in 2010. The efficacy of phototherapy (considering all forms) in AD has been established in adults and children, as well as for acute (UVA1) and chronic (NB-UVB) cases. Its use is suggested with strength of recommendation B and level of evidence II. Home phototherapy can also be performed; this technique is recommended with strength C and level of evidence III. Phototherapy is generally considered to be safe and well tolerated, with a low but established percentage of short-term and long-term adverse effects, with the most common being photodamage, xerosis, erythema, actinic keratosis, sunburn, and tenderness. A carcinogenic risk related to UV radiation has not been excluded. Phototherapy also has some limitations related to costs, availability, and patient compliance. In conclusion, phototherapy is an optimal second-line treatment for AD. It can be used as monotherapy or in combination with systemic drugs, in particular corticosteroids. It must be performed conscientiously, especially in children, and must take into account the patient's features and overall condition. PMID:26491366

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

    PubMed Central

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

    2011-01-01

    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. PMID:21779718

  15. Entecavir: a potent antiviral with minimal long-term resistance in nucleoside-naive chronic hepatitis B patients.

    PubMed

    Cheng, Pin-Nan; Chang, Ting-Tsung

    2008-10-01

    Entecavir has demonstrated safety and efficacy in the treatment of chronic hepatitis B infection. It is the prototype for the cyclopentane class of nucleoside/nucleotide chronic hepatitis B antiviral agents. It has a high potency and, due to its structural formula and mechanism of action, entecavir is associated with emergence of minimal resistance in the long-term treatment of nucleoside-naive patients. Research suggests that long-term treatment may be required for chronic hepatitis B patients, especially those who acquire HBV early in life, to achieve maximum viral suppression and improve outcomes. Several recent studies have evaluated the long-term safety, efficacy and development of resistance in nucleoside-naive patients treated with entecavir. Results indicate that the long-term use of entecavir is well tolerated and associated with continuous clinical improvement -- with an increasing number of patients achieving undetectable levels of HBV DNA, HBeAg seroconversion and minimal resistance. These data underscore the position of entecavir for first-line therapy and highlight its role in the long-term treatment of chronic hepatits B. PMID:18847396

  16. The safety and efficacy issues of progestin-only oral contraceptives--an epidemiologic perspective.

    TOXLINE Toxicology Bibliographic Information

    Chi I

    1993-01-01

    Progestogen-only oral contraceptives (POCs) are generally considered a good contraceptive choice for brestfeeding women and for women who want to use an oral form of contraception, but are not suited for, or cannot tolerate the side effects of, estrogen-containing preparations. However, a number of POCs' safety, efficacy and other related issues remain to be addressed. This paper reviews recent literature and evaluates these issues from an epidemiologic perspective. The small number of users imposes severe limitations in designing epidemiologic studies to address POCs' long-term safety issues, but available information suggests POCs are at least as safe as, if not safer than, COCs. Compared to COCs, POCs are more likely to cause menstrual disturbances which, in turn, could affect their acceptability and lead to poor compliance and hence higher pregnancy rates. POCs' efficacy has been estimated to be between 1.4 and 4.3 pregnancies per 100 woman-years of use. Lower pregnancy rates approaching those of COCs have been reported in centers with good counseling. POCs' benefits outweigh their risks. However, more studies are needed to further address POCs' safety and efficacy issues.

  17. The safety and efficacy issues of progestin-only oral contraceptives--an epidemiologic perspective.

    PubMed

    Chi, I

    1993-01-01

    Progestogen-only oral contraceptives (POCs) are generally considered a good contraceptive choice for brestfeeding women and for women who want to use an oral form of contraception, but are not suited for, or cannot tolerate the side effects of, estrogen-containing preparations. However, a number of POCs' safety, efficacy and other related issues remain to be addressed. This paper reviews recent literature and evaluates these issues from an epidemiologic perspective. The small number of users imposes severe limitations in designing epidemiologic studies to address POCs' long-term safety issues, but available information suggests POCs are at least as safe as, if not safer than, COCs. Compared to COCs, POCs are more likely to cause menstrual disturbances which, in turn, could affect their acceptability and lead to poor compliance and hence higher pregnancy rates. POCs' efficacy has been estimated to be between 1.4 and 4.3 pregnancies per 100 woman-years of use. Lower pregnancy rates approaching those of COCs have been reported in centers with good counseling. POCs' benefits outweigh their risks. However, more studies are needed to further address POCs' safety and efficacy issues. PMID:8435997

  18. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia.

    PubMed

    Bhusal, Santosh; Diomampo, Sherilyn; Magrey, Marina N

    2016-01-01

    Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness. PMID:26937205

  19. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia

    PubMed Central

    Bhusal, Santosh; Diomampo, Sherilyn; Magrey, Marina N

    2016-01-01

    Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness. PMID:26937205

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

    PubMed Central

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

    2015-01-01

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

  1. Long-term effects of fingolimod in multiple sclerosis

    PubMed Central

    O'Connor, Paul; Radue, Ernst-Wilhelm; Polman, Chris; Hohlfeld, Reinhard; Selmaj, Krzysztof; Ritter, Shannon; Schlosshauer, Rolf; von Rosenstiel, Philipp; Zhang-Auberson, Lixin; Francis, Gordon

    2015-01-01

    Objective: To assess long-term safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Patients completing FTY720 Research Evaluating Effects of Daily Oral Therapy in MS (FREEDOMS) were eligible for this dose-blinded, parallel-group extension study, continuing fingolimod 0.5 mg/day or 1.25 mg/day, or switching from placebo to either dose, randomized 1:1. Efficacy variables included annualized relapse rate (ARR), brain volume loss (BVL), and confirmed disability progression (CDP). Between-group analyses were conducted in the intent-to-treat (ITT) population from FREEDOMS baseline to end of study. Within-group analyses compared years 0–2 (FREEDOMS) and years 2–4 (extension) in the extension ITT population. Results: Of 1,272 patients (FREEDOMS ITT population), 1,033 were eligible, and 920 enrolled in the extension study (continuous-fingolimod: 0.5 mg [n = 331], 1.25 mg [n = 289]; placebo–fingolimod: 0.5 mg [n = 155], 1.25 mg [n = 145]); 916 formed the extension ITT population (n = 330; n = 287; n = 154; n = 145) and 773 (84%) completed. In the continuous-fingolimod groups, ARR was lower (p < 0.0001), BVL was reduced (p < 0.05), and proportionately more patients were free from 3-month CDP (p < 0.05) than in a group comprising all placebo–fingolimod patients. Within each placebo–fingolimod group, ARR was lower (p < 0.001, both) and BVL was reduced after switching (p < 0.01, placebo–fingolimod 0.5 mg). Rates and types of adverse events were similar across groups; no new safety issues were reported. Conclusion: Efficacy benefits of fingolimod during FREEDOMS were sustained during the extension; ARR and BVL were reduced after switching. Classification of evidence: This study provides Class IV evidence that long-term fingolimod treatment is well-tolerated and reduces relapse rates, disability progression, and MRI effects in patients with RRMS. PMID:25795646

  2. Safety and Efficacy of Solitaire Stent Thrombectomy

    PubMed Central

    Campbell, Bruce C.V.; Hill, Michael D.; Rubiera, Marta; Menon, Bijoy K.; Demchuk, Andrew; Donnan, Geoffrey A.; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I.; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M.; Stouch, Bruce C.; Mitchell, Peter J.; Jovin, Tudor G.; Saver, Jeffrey L.

    2016-01-01

    Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29–5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. Conclusions— Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups. PMID:26888532

  3. Timber beams subjected to long - term loading

    NASA Astrophysics Data System (ADS)

    Sógel, K.

    2010-09-01

    Wood is a significant structural material, which is often used for timber bearing structures. Elements of timber structures must especially satisfy safety requirements, which are expressed by the ultimate limit states in the established standards. The structure must also satisfy the serviceability limit states. Local and global deformations make it impossible for the structure to serve the purpose it was designed for. It is important to take the deflections and their possible increase into account in the design to provide a structure which can be used during the whole period of service. Based on earlier examinations, it is known that a timber element over the course of long-term loading shows creep behavior. The structure of wood is able to adapt to the conditions of the surrounding environment. The properties of wood are especially affected by the relative humidity of the air and then by the type, intensity and duration of the loading. The most important factors affecting the serviceability of timber structures are volume changes caused by humidity and additional deflections caused by the effects of long-term loading. These phenomena emphasize the importance of serviceability limit states for timber structures. The paper deals with a long-term experimental investigation of timber girders that are currently often used. The aim was to obtain the deflection curves and mark the time dependence and the final deflections. The paper will also define the approximations for simulating the time-dependent deflections and obtain the creep coefficients for calculating the final deflections of the girders investigated.

  4. A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease

    PubMed Central

    van Rhee, Frits; Casper, Corey; Voorhees, Peter M.; Fayad, Luis E.; van de Velde, Helgi; Vermeulen, Jessica; Qin, Xiang; Qi, Ming; Tromp, Brenda; Kurzrock, Razelle

    2015-01-01

    Background Multicentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD. Methods This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented. Results Median treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. Conclusions All MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab. PMID:26327301

  5. Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients.

    PubMed

    Stirnemann, Jérôme; Kaddouri, Najett; Khellaf, Medhi; Morin, Anne-Sophie; Prendki, Virginie; Michel, Marc; Mekinian, Arsène; Bierling, Philippe; Fenaux, Pierre; Godeau, Bertrand; Fain, Olivier

    2016-03-01

    Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 10(9) platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6-13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan-Meier curve). Predictive factors (univariate analysis) of an initial and long-term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost. PMID:25976731

  6. A systematic review of safety and efficacy of hepatopancreatoduodenectomy for biliary and gallbladder cancers

    PubMed Central

    Zhou, Yanming; Zhang, Zuobing; Wu, Lupeng; Li, Bin

    2015-01-01

    Objectives To review the evidence on the safety and efficacy of hepatopancreatoduodenectomy for biliary and gallbladder cancers. Methods Medline and EMBASE were systematically searched for papers of hepatopancreatoduodenectomy in patients with biliary and gallbladder cancers. Results Eighteen studies involving 397 patients were reviewed. Major hepatectomy was undertaken in 81.3% of the 397 patients and the R0 resection rate was 71.3%. The morbidity and mortality rates were 78.9% and 10.3%, respectively. The 5-year overall survival rate ranged from 3% to 50% (median = 31%). The 5-year survival rate in patients who underwent curative resection was 18–68.8% (median = 51.3%), and 0% in patients who received non-curative resection. Conclusions Hepatopancreatoduodenectomy is a challenging procedure with high morbidity and mortality rates. However, this procedure can provide a chance of long-term survival in patients in whom curative resection is feasible. PMID:26776844

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

    PubMed

    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

    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

  8. Consumer Direction in Long-Term Care.

    ERIC Educational Resources Information Center

    Generations, 2000

    2000-01-01

    Issue includes 17 theme articles on long-term care, covering legal issues, federal role, state programs, demonstration programs, family caregivers, home health care, home care workers, culturally appropriate long-term care, financial support, and cognitive impairments. (SK)

  9. Long-Term Care Ombudsman Program

    MedlinePlus

    ... Contact Us Administration on Aging (AoA) 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 2013 indicate that ...

  10. Long-term equilibrium tides

    NASA Astrophysics Data System (ADS)

    Shaffer, John A.; Cerveny, Randall S.

    1998-08-01

    Extreme equilibrium tides, or ``hypertides,'' are computed in a new equilibrium tidal model combining algorithms of a version of the Chapront ELP-2000/82 Lunar Theory with the BER78 Milankovitch astronomical expansions. For the recent past, a high correspondence exists between computed semidiurnal tide levels and a record of coastal flooding demonstrating that astronomical alignment is a potential influence on such flooding. For the Holocene and near future, maximum tides demonstrate cyclic variations with peaks at near 5000 B.P. and 4000 A.P. On the late Quaternary timescale, variations in maximum equilibrium tide level display oscillations with periods of approximately 10,000, 100,000 and 400,000 years, because of precessional shifts in tidal maxima between vernal and autumnal equinoxes. While flooding occurs under the combined effects of tides and storms via ``storm surges,'' the most extensive flooding will occur with the coincidence of storms and the rarer hypertides and is thus primarily influenced by hypertides. Therefore we suggest that astronomical alignment's relationship to coastal flooding is probabilistic rather than deterministic. Data derived from this model are applicable to (1) archaeological and paleoclimatic coastal reconstructions, (2) long-term planning, for example, radioactive waste site selection, (3) sealevel change and paleoestuarine studies or (4) ocean-meteorological interactions.

  11. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    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.

  12. Long-term use of everolimus in lung transplant patients.

    PubMed

    Parada, M T; Alba, A; Sepúlveda, C; Melo, J

    2011-01-01

    Everolimus has been successfully used in solid organ transplantation, especially of the heart and kidney, but much less often in lung transplantation. The aim of this study was to evaluate the efficacy and safety of long-term use of everolimus in lung transplantation in Chile. We retrospectively analyzed patients receiving everolimus between 2005 and 2010 in terms of indication, lung and kidney function, rejection episodes, infections, malignancy appearance, and adverse events. Ten of 60 lung transplant recipients were converted to everolimus (16%) at some point after transplantation: four due to calcineurin inhibitor nephropathy (RD); four bronchiolitis obliterans syndrome (BOS); one lymphoma; and one, graft pulmonary fibrosis. Among patients with RD, at a mean follow-up of 25 months (range = 3-60), renal function remained stable with baseline of 42.7 mL/min and final creatinine clearance of 45.7 mL/min; lung function did not deteriorate. BOS patients, with an average of 30 months' follow-up (range = 12-48), showed baseline forced expiratory volume in the first second of 49% (r: 41-57) without variation in three patients, but with a decrease in another one after 12 months. One patient discontinued everolimus due to intolerance after 1 year. Two patients developed neoplasias: skin cancer and multiple myeloma. There were 14 infection episodes in seven patients, including 10 involving the respiratory tract infections. Only one patient developed dyslipidemia after everolimus initiation. Two patients died: one due to multiple myeloma and another to BOS. There was no rejection episode. Everolimus was effective and safe when used in combination with low doses of calcineurin inhibitor over long-term follow-up of lung transplant patients. PMID:21839261

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

    PubMed Central

    2014-01-01

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

  14. Efficacy and safety of metformin or oral contraceptives, or both in polycystic ovary syndrome

    PubMed Central

    Yang, Young-Mo; Choi, Eun Joo

    2015-01-01

    Background Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects approximately 10% of reproductive-aged women throughout their lives. Women with PCOS present with heterogeneous symptoms including ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Therefore, lifelong individualized management should be considered. Pharmacological agents commonly used to manage the symptoms are metformin and oral contraceptive pills. Although these medications have been beneficial in treating PCOS symptoms, their efficacy and safety are still not entirely elucidated. This study aimed to report the efficacy and safety of metformin, oral contraceptives, or their combination in the treatment of PCOS and to define their specific individual roles. Methods A literature search of original studies published in PubMed and Scopus was conducted to identify studies comparing metformin with oral contraceptives or evaluating the combination of both in PCOS. Results Eight clinical trials involving 313 patients were examined in the review. The intervention dosage of metformin ranged from 1,000 to 2,000 mg/d and that of oral contraceptives was ethinylestradiol 35 µg and cyproterone acetate 2 mg. Lower body mass index was observed with regimens including metformin, but increased body mass index was observed in monotherapy with oral contraceptives. Administration of metformin or oral contraceptives, especially as monotherapy, had a negative effect on lipid profiles. In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels. In the included studies, significant side effects due to metformin or oral contraceptives were not reported. Conclusion The clinical trials suggest that metformin or oral contraceptives are at least patient convenient, efficacious, and safe for the treatment of PCOS. However, well-designed, prospective, long-term, large-scale, randomized clinical trials are necessary to elucidate the efficacy and safety of metformin, oral contraceptives, or both in the treatment of PCOS, and to elucidate their individual roles in the treatment of this condition. PMID:26366087

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

    PubMed Central

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

    2015-01-01

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

  16. Long-Term Effects of Peace Workshops in Protracted Conflicts

    ERIC Educational Resources Information Center

    Malhotra, Deepak; Liyanage, Sumanasiri

    2005-01-01

    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…

  17. Multimethod Behavioral Treatment of Long-Term Selective Mutism.

    ERIC Educational Resources Information Center

    Watson, T. Steuart; Kramer, Jack J.

    1992-01-01

    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…

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

    PubMed

    Kim, Eun Young

    2015-01-01

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

  19. [Long-term use of benzodiazepines].

    PubMed

    Gorgels, W J; Oude Voshaar, R C; Mol, A J; Breteler, M H; van de Lisdonk, E H; Zitman, F G

    2001-07-14

    Benzodiazepines are the most prescribed drugs in the Netherlands. There is scarcely an indication for long-term benzodiazepine use. Long-term use may lead to dependency and is associated with an increased risk of accidents/falls and cognitive function impairment. Therefore national and international guidelines advocate a conservative prescription policy, especially with respect to long-term prescription. It appears that these guidelines are not followed in practice. A standard sized general practice in the Netherlands contains, on average, 75 long-term benzodiazepine users. There appear to be both patient and GP related factors which influence the maintenance of this long-term use of benzodiazepines. PMID:11484430

  20. Efficacy and safety of miconazole for oral candidiasis: a systematic review and meta-analysis.

    PubMed

    Zhang, L-W; Fu, J-Y; Hua, H; Yan, Z-M

    2016-04-01

    The objective of this study is to assess the efficacy and safety of miconazole for treating oral candidiasis. Twelve electronic databases were searched for randomized controlled trials evaluating treatments for oral candidiasis and complemented by hand searching. The clinical and mycological outcomes, as well as adverse effects, were set as the primary outcome criteria. Seventeen trials were included in this review. Most studies were considered to have a high or moderate level of bias. Miconazole was more effective than nystatin for thrush. For HIV-infected patients, there was no significant difference in the efficacy between miconazole and other antifungals. For denture wearers, microwave therapy was significantly better than miconazole. No significant difference was found in the safety evaluation between miconazole and other treatments. The relapse rate of miconazole oral gel may be lower than that of other formulations. This systematic review and meta-analysis indicated that miconazole may be an optional choice for thrush. Microwave therapy could be an effective adjunct treatment for denture stomatitis. Miconazole oral gel may be more effective than other formulations with regard to long-term results. However, future studies that are adequately powered, large-scale, and well-designed are needed to provide higher-quality evidence for the management of oral candidiasis. PMID:26456226

  1. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients.

    PubMed

    Bringhen, Sara; Larocca, Alessandra; Rossi, Davide; Cavalli, Maide; Genuardi, Mariella; Ria, Roberto; Gentili, Silvia; Patriarca, Francesca; Nozzoli, Chiara; Levi, Anna; Guglielmelli, Tommasina; Benevolo, Giulia; Callea, Vincenzo; Rizzo, Vincenzo; Cangialosi, Clotilde; Musto, Pellegrino; De Rosa, Luca; Liberati, Anna Marina; Grasso, Mariella; Falcone, Antonietta P; Evangelista, Andrea; Cavo, Michele; Gaidano, Gianluca; Boccadoro, Mario; Palumbo, Antonio

    2010-12-01

    In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179. PMID:20807892

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

    SciTech Connect

    Vaidya, Jayant S.; Baum, Michael; Tobias, Jeffrey S.; Wenz, Frederik; Massarut, Samuele; Keshtgar, Mohammed; Hilaris, Basil; Saunders, Christobel; Williams, Norman R.; Brew-Graves, Chris; Corica, Tammy; Roncadin, Mario; Kraus-Tiefenbacher, Uta; Suetterlin, Marc; Bulsara, Max; Joseph, David

    2011-11-15

    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.

  3. Transuranic waste: long-term planning

    SciTech Connect

    Young, K.C.

    1985-07-01

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

  4. Long-term plutonium storage: Design concepts

    SciTech Connect

    Wilkey, D.D.; Wood, W.T.; Guenther, C.D.

    1994-08-01

    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.

  5. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    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.

  6. Viability of long-term gene therapy in the cochlea.

    PubMed

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

    2014-01-01

    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

  7. Viability of Long-Term Gene Therapy in the Cochlea

    PubMed Central

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

    2014-01-01

    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

  8. Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients.

    PubMed

    Belcaro, Gianni; Cesarone, Maria Rosaria; Dugall, Mark; Pellegrini, Luciano; Ledda, Andrea; Grossi, Maria Giovanna; Togni, Stefano; Appendino, Giovanni

    2010-12-01

    In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis. PMID:21194249

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

    PubMed Central

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

    2015-01-01

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

  10. Antipsychotic agents: efficacy and safety in schizophrenia

    PubMed Central

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

    2012-01-01

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

  11. Long-Term Antiplatelet Mono- and Dual Therapies After Ischemic Stroke or Transient Ischemic Attack: Network Meta-Analysis

    PubMed Central

    Xie, Wuxiang; Zheng, Fanfan; Zhong, Baoliang; Song, Xiaoyu

    2015-01-01

    Background The latest guidelines do not make clear recommendations on the selection of antiplatelet therapies for long-term secondary prevention of stroke. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy and safety of long-term antiplatelet therapies after ischemic stroke or transient ischemic attack. Methods and Results We performed a network meta-analysis of randomized controlled trials to compare 11 antiplatelet therapies in patients with ischemic stroke or transient ischemic attack. In December 2014, we searched Medline, Embase, and the Cochrane Library database for trials. The search identified 24 randomized controlled trials including a total of 85 667 patients with antiplatelet treatments for at least 1 year. Cilostazol significantly reduced stroke recurrence in comparison with aspirin (odds ratio 0.66, 95% credible interval 0.44 to 0.92) and dipyridamole (odds ratio 0.57, 95% credible interval 0.34 to 0.95), respectively. Cilostazol also significantly reduced intracranial hemorrhage compared with aspirin, clopidogrel, terutroban, ticlopidine, aspirin plus clopidogrel, and aspirin plus dipyridamole. Aspirin plus clopidogrel could not significantly reduce stroke recurrence compared with monotherapies but caused significantly more major bleeding than all monotherapies except terutroban. The pooled estimates did not change materially in the sensitivity analyses of the primary efficacy outcome. Conclusions Long-term monotherapy was a better choice than long-term dual therapy, and cilostazol had the best risk–benefit profile for long-term secondary prevention after stroke or transient ischemic attack. More randomized controlled trials in non–East Asian patients are needed to determine whether long-term use of cilostazol is the best option for the prevention of recurrent stroke. PMID:26304937

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

    PubMed Central

    Fong, Angie HC; Lai, Timothy YY

    2013-01-01

    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. PMID:23766636

  13. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Español Text Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions ... In inhaled form, they are used exclusively for long-term control; they are not very effective for acute ...

  14. Long Term Preservation of Digital Information.

    ERIC Educational Resources Information Center

    Lorie, Raymond A.

    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…

  15. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

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

  16. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

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

  17. Long-term preservation of Anammox bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ClinicalTrials.gov

    2015-11-17

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

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

    ClinicalTrials.gov

    2012-09-27

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

  1. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  2. TNFα blockade in human diseases: An overview of efficacy and safety

    PubMed Central

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

    2008-01-01

    Tumor necrosis factor-alpha (TNFα) 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-TNFα 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 TNFα 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 TNFα 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 TNFα 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 TNFα antagonism. PMID:17916445

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

    PubMed Central

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

    2012-01-01

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

  4. Sofosbuvir-based therapy for patients with chronic hepatitis C: Early experience of its efficacy and safety in Korea

    PubMed Central

    Cho, Yuri; Cho, Eun Ju; Lee, Jeong-Hoon; Yu, Su Jong; Yoon, Jung-Hwan

    2015-01-01

    Background/Aims The previous standard treatment for chronic hepatitis C (CHC) patients, comprising a combination of pegylated interferon (IFN) and ribavirin, was associated with suboptimal efficacy and severe adverse reactions. A new era of direct-acting antivirals is now dawning in Korea. Early experience of applying sofosbuvir-based therapy to CHC patients in Korea is reported herein. Methods Data on efficacy and safety were collected for CHC patients treated with a combination of sofosbuvir plus ribavirin or sofosbuvir/ledipasvir with or without ribavirin. Results This retrospective study included 25 consecutive patients who received sofosbuvir-based therapy (19 with genotype 1b and 6 with genotype 2) at Seoul National University Hospital from May 2014 to April 2015. A virologic response was achieved at week 4 by 85.7% and 80% of the patients with genotypes 1b and 2, respectively. The HCV-RNA level decreased more slowly in IFN-experienced than in treatment-naïve patients with genotype 1b. However, the sustained virologic response at week 12 (SVR12) rate did not differ among these patients, and was as high as 100%. The presence of cirrhosis significantly increased the risk of a virologic response failure at week 4 (OR, 11.0; P=0.011) among patients with HCV genotype 1b. Only five patients (20%) experienced minor adverse events, including grade 1 fatigue and headache. The hemoglobin level decreased slightly after sofosbuvir-based therapy, but there was no case of premature discontinuation of this therapy. Conclusions In a real clinical practice, sofosbuvir-based therapy for CHC patients in Korea achieved optimal antiviral efficacy with insignificant adverse events. Long-term follow-up data are warranted to ensure the sustained antiviral efficacy and long-term safety of sofosbuvir-based IFN-free therapy. PMID:26770924

  5. Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

    PubMed Central

    Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

    2015-01-01

    Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine. PMID:26193319

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

    PubMed Central

    Argoff, Charles E; Gloth, F Michael

    2011-01-01

    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

  7. Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis

    PubMed Central

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

    2014-01-01

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

  8. Mental Health in Long Term Care Settings.

    ERIC Educational Resources Information Center

    Shore, Herbert

    1978-01-01

    There are many ways in which long-term care facilities attempt to cope with the mental health problems of the elderly. The author reviews five factors crucial to effective care for the aged in these facilities. (Author/RK)

  9. Long-term care in international perspective

    PubMed Central

    Doty, Pamela

    1988-01-01

    The findings of a study of long-term care policies in 18 countries are reported in this article. Initial data were collected by a questionnaire survey under the auspices of the International Social Security Association. These data were supplemented by published documents and government statistics obtained while researching long-term care for the International Social Security Association and, subsequently, for the Organization for Economic Cooperation and Development. The principal focus is a cross-national comparison of institutionalization rates for the elderly. Differences in use rates for medically oriented facilities are less than those for nonmedical residential long-term care facilities. Only a small amount of variation is related to demographic differences, such as older or more female elderly populations in those countries with higher institutionalization rates. Included also is a description of the modes of financing long-term care. PMID:10312969

  10. Long Term Effects of Food Poisoning

    MedlinePlus

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

  11. Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome

    PubMed Central

    Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

    2016-01-01

    Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a novel avenue to modulate and protect the vaginal microbiota. Trial Registration U.S. National Institutes of Health ClinicalTrials.gov NCT02314429 PMID:27093291

  12. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  13. Long-term theranostic hydrogel system for solid tumors.

    PubMed

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

    2012-03-01

    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

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

    PubMed Central

    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

    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. PMID:22157987

  15. Safety and efficacy of the Pipeline Embolization Device in 100 small intracranial aneurysms.

    PubMed

    Chalouhi, Nohra; Zanaty, Mario; Whiting, Alex; Yang, Steven; Tjoumakaris, Stavropoula; Hasan, David; Starke, Robert M; Hann, Shannon; Hammer, Christine; Kung, David; Rosenwasser, Robert; Jabbour, Pascal

    2015-06-01

    OBJECT Flow diverters are increasingly used for treatment of intracranial aneurysms. In most series, the Pipeline Embolization Device (PED) was used for the treatment of large, giant, complex, and fusiform aneurysms. Little is known about the use of the PED in small aneurysms. The purpose of this study was to assess the safety and efficacy of the PED in small aneurysms (≤ 7 mm). METHODS A total of 100 consecutive patients were treated with the PED at the authors' institution between May 2011 and September 2013. Data on procedural safety and efficacy were retrospectively collected. RESULTS The mean aneurysm size was 5.2 ± 1.5 mm. Seven patients (7%) had sustained a subarachnoid hemorrhage. All except 5 aneurysms (95%) arose from the anterior circulation. The number of PEDs used was 1.2 per aneurysm. Symptomatic procedure-related complications occurred in 3 patients (3%): 1 distal parenchymal hemorrhage that was managed conservatively and 2 ischemic events. At the latest follow-up (mean 6.3 months), 54 (72%) aneurysms were completely occluded (100%), 10 (13%) were nearly completely occluded (≥ 90%), and 11 (15%) were incompletely occluded (< 90%). Six aneurysms (8%) required further treatment. Increasing aneurysm size (OR 3.8, 95% CI 0.99-14; p = 0.05) predicted retreatment. All patients achieved a favorable outcome (modified Rankin Scale Score 0-2) at follow-up. CONCLUSIONS In this study, treatment of small aneurysms with the PED was associated with low complication rates and high aneurysm occlusion rates. These findings suggest that the PED is a safe and effective alternative to conventional endovascular techniques for small aneurysms. Randomized trials with long-term follow-up are necessary to determine the optimal treatment that leads to the highest rate of obliteration and the best clinical outcomes. PMID:25635478

  16. Long-term efficacy and downstream mechanism of anti-annexinA2 monoclonal antibody (anti-ANX A2 mAb) in a pre-clinical model of aggressive human breast cancer.

    PubMed

    Sharma, Mahesh C; Tuszynski, George P; Blackman, Marc R; Sharma, Meena

    2016-04-01

    There is considerable direct evidence that calcium binding protein ANX A2 is a potential target for treating aggressive breast cancer. The most compelling data are based on the finding of ANX A2 overexpression in aggressive triple negative human breast cancer (TNBC) cell lines and in human breast cancer tissues. Previously, we and others reported a unique role of ANX A2 in cancer invasion, including breast cancer. Moreover, we demonstrated that anti-ANX A2 mAb-mediated immunoneutralization of ANX A2 inhibited invasive human breast cancer growth in a xenograft model. We further evaluated the long-term effects of multiple treatments with anti-ANX A2 mAb and its mechanism of inhibition on human breast tumor growth. We now demonstrate that three treatments with anti-ANX A2 mAb led to significant inhibition of breast tumor growth in immunodeficient mice, and that the anti-tumor response was demonstrable from day 94. After treatment, we followed tumor growth for 172 days and demonstrated 67% inhibition of tumor growth without detectable adverse effects. Biochemical analysis demonstrated that anti-ANX A2 mAb treatment caused significant inhibition of conversion of tissue plasminogen activator (tPA) in the tumor microenvironment. This led to disruption of plasmin generation that consequently inhibited activation of MMP-9 and MMP-2. These results suggest that ANX A2 plays an important role in aggressive breast tumor growth by regulating proteolytic pathways in the tumor microenvironment. ANX A2 may represent a new target for the development of therapeutics for treatment of aggressive breast cancer. PMID:26797420

  17. Use of omeprazole in Zollinger-Ellison syndrome: a prospective nine-year study of efficacy and safety.

    PubMed

    Metz, D C; Strader, D B; Orbuch, M; Koviack, P D; Feigenbaum, K M; Jensen, R T

    1993-12-01

    H+, K(+)-ATPase inhibitors such as omeprazole are the antisecretory agents of choice for the management of gastric acid hypersecretory states, including the Zollinger-Ellison syndrome. However, long-term follow-up data on the overall efficacy and safety of these agents in large numbers of patients are lacking. In the current study we examined the long-term efficacy and safety of omeprazole in 116 patients with Zollinger-Ellison syndrome treated with oral omeprazole at a single centre for up to 114 months (mean +/- S.E.M. = 38 +/- 3 months). The initial omeprazole maintenance dose was established according to the acute upward dose titration method in 89/116 patients (77%). Gastric acid output was effectively controlled using 60 mg of omeprazole once daily in 41/89 patients (46%) and 22/89 patients (25%) required twice daily omeprazole therapy. The mean ranitidine equivalent dose for patients who required 60 mg omeprazole once daily (2.5 +/- 0.2 g/day) was significantly lower than the mean ranitidine equivalent dose for patients who required more than 60 mg omeprazole once daily (4.3 +/- 0.3 g/day). Long-term omeprazole maintenance therapy was discontinued in 36/116 patients (31%) but in no cases was discontinuation due either to drug-induced side-effects or uncontrolled gastric acid output. Fasting serum gastrin levels were significantly elevated above pre-treatment levels at only one time point during follow-up and were likely due to tumour growth rather than a drug effect. The final long-term omeprazole maintenance doses were lower than the initial doses but correlated closely with the pre-omeprazole basal acid output (r = 0.41, P < 0.001) and ranitidine equivalent dose requirements (r = 0.49, P < 0.001). We conclude that omeprazole effectively and safely controls gastric acid hypersecretion in all patients with Zollinger-Ellison syndrome for up to nine years without evidence by tachyphylaxis. PMID:8161665

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

    PubMed Central

    Barnes, Joanne

    2003-01-01

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

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

    SciTech Connect

    Berczi, V. Bottomley, J. R.; Thomas, S. M.; Taneja, S.; Gaines, P. A.; Cleveland, T. J.

    2007-09-15

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

  20. Review of efficacy and safety of laxatives use in geriatrics

    PubMed Central

    Izzy, Manhal; Malieckal, Anju; Little, Erin; Anand, Sury

    2016-01-01

    AIM: To study the efficacy and safety of pharmacological treatment of constipation in geriatrics. METHODS: PubMed, MEDLINE, google scholar, and Ovid were searched to identify human studies performed on the use of laxatives in elderly with constipation, which were conducted between January 1990 and January 2013 using the specified keywords. Controlled studies that enrolled geriatric patients with a diagnosis of constipation and addressed the efficacy and/or the safety of pharmacological treatments were included. Studies were excluded from this review if they were non-controlled trials, case series, or case reports. RESULTS: Out of twenty three studies we initially retrieved in our search, only nine studies met the eligibility criteria of being controlled trials within geriatrics. The laxatives examined in the nine studies were senna, lactulose, sorbital, polyethylene glycol (PEG), lubiprostone, linaclotide, and prucalopride. In those studies, senna combinations had a higher efficacy than sorbitol or lactulose as well as, a very good adverse effect profile. PEG was also shown to be safe and effective in geriatric population. Furthermore, it has been shown that PEG is as safe in geriatrics as in general population. New agents like lubiprostone and prucalopride show promising results but the data about these agents in geriatrics are still limited which warrants further investigation. CONCLUSION: Senna combinations and PEG appear to have a more favorable profile over the other traditionally used laxatives in elderly patients with constipation. PMID:27158549

  1. Efficacy and Safety of Fingolimod in an Unselected Patient Population

    PubMed Central

    Andelova, Michaela; Naegelin, Yvonne; Stippich, Christoph; Kappos, Ludwig; Lindberg, Raija L. P.; Sprenger, Till; Derfuss, Tobias

    2016-01-01

    Background Fingolimod is a first in class oral compound approved for the treatment of relapsing-remitting multiple sclerosis (RR-MS). The aim of this study was to evaluate clinical and neuroradiological responses to fingolimod as well as the safety and tolerability in RR-MS patients in clinical practice. In addition, a panel of pro-inflammatory serum cytokines was explored as potential biomarker for treatment response. Methods We conducted a retrospective, non-randomized, open-label, observational study in 105 patients with RR-MS and measured cytokines in longitudinal serum samples. Results Compared to the year before fingolimod start the annualized relapse rate was reduced by 44%. Also, the percentage of patients with a worsening of the EDSS decreased. Accordingly, the fraction of patients with no evidence of disease activity (no relapse, stable EDSS, no new active lesions in MRI) increased from 11% to 38%. The efficacy and safety were comparable between highly active patients or patients with relevant comorbidities and our general patient population. Conclusions The efficacy in reducing relapses was comparable to that observed in the phase III trials. In our cohort fingolimod was safe and efficacious irrespective of comorbidities and previous treatment. PMID:26734938

  2. Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

    SciTech Connect

    Calin-Jageman, Robert J

    2009-09-12

    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.

  3. The opioid epidemic and the long-term opioid therapy for chronic noncancer pain revisited: a transatlantic perspective.

    PubMed

    Häuser, Winfried; Petzke, Frank; Radbruch, Lukas; Tölle, Thomas R

    2016-05-01

    The rise of opioid prescriptions and associated deaths ('opioid epidemic') in North America has evoked worldwide discussions on the long-term efficacy and safety of long-term opioid therapy (LtOT) for chronic noncancer pain (CNCP). We discuss if the opioid epidemic is a real worldwide or a more North American phenomenon. We consider reasons of the opioid epidemic. We highlight differences in the appraisal of the evidence of recent systematic reviews on LtOT for CNCP of US and European authors. We discuss similarities and differences of recent North American and European guidelines on LtOT for chronic CNCP. We point out potential indications and contraindications of LtOT in CNCP syndromes. PMID:26988312

  4. Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization

    PubMed Central

    Jung, Sung-Cherl; Eun, Su-Yong

    2014-01-01

    At central synapses, activity-dependent synaptic plasticity has a crucial role in information processing, storage, learning, and memory under both physiological and pathological conditions. One widely accepted model of learning mechanism and information processing in the brain is Hebbian Plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are respectively activity-dependent enhancement and reduction in the efficacy of the synapses, which are rapid and synapse-specific processes. A number of recent studies have a strong focal point on the critical importance of another distinct form of synaptic plasticity, non-Hebbian plasticity. Non-Hebbian plasticity dynamically adjusts synaptic strength to maintain stability. This process may be very slow and occur cell-widely. By putting them all together, this mini review defines an important conceptual difference between Hebbian and non-Hebbian plasticity. PMID:25598658

  5. Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis

    PubMed Central

    Du, Xiao-Long; Kong, Ling-Shang; Meng, Qing-You; Qian, Aimin; Li, Wen-Dong; Chen, Hong; Li, Xiao-Qiang; Li, Cheng-Long

    2015-01-01

    Background: Catheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT. Methods: A retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively. Results: The mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50–99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study. Conclusions: Treatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications. PMID:26112721

  6. Androgens and male aging: current evidence of safety and efficacy

    PubMed Central

    Gooren, Louis J.

    2010-01-01

    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. PMID:20154699

  7. Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study.

    TOXLINE Toxicology Bibliographic Information

    Marini H; Bitto A; Altavilla D; Burnett BP; Polito F; Di Stefano V; Minutoli L; Atteritano M; Levy RM; D'Anna R; Frisina N; Mazzaferro S; Cancellieri F; Cannata ML; Corrado F; Frisina A; Adamo V; Lubrano C; Sansotta C; Marini R; Adamo EB; Squadrito F

    2008-12-01

    CONTEXT: Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain.OBJECTIVE: We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy.DESIGN: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year.PATIENTS AND INTERVENTIONS: Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses.MAIN OUTCOMES: Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers.RESULTS: After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups.CONCLUSIONS: After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women.

  8. Efficacy and safety of sertindole in schizophrenia: a clinical review.

    PubMed

    Zoccali, Rocco A; Bruno, Antonio; Muscatello, Maria Rosaria Anna

    2015-06-01

    Sertindole is an atypical antipsychotic reintroduced into the European market in 2005 after a reevaluation of its risks and benefits, under the agreement that close electrocardiographic screening would be conducted. It has a high affinity for dopamine D2, serotonin 5-HT2A and 5-HT2C, and ?1 adrenergic receptors. Moreover, sertindole shows modest affinity for H1-histaminergic and muscarinic receptors. The pharmacological properties, clinical efficacy, safety, and tolerability of sertindole are covered in this article based on a literature review from 1990 to 2014. Given current available findings, sertindole is at least effective as haloperidol, risperidone, and olanzapine on schizophrenia symptoms. Regarding its efficacy on cognitive symptoms, sertindole effect is supported by both preclinical and clinical studies versus haloperidol and olanzapine; however, its role on cognition needs further clarification. Concerning safety and tolerability issues, sertindole is characterized by a low potential to cause sedation and extrapyramidal symptoms, and by an acceptable metabolic profile; nevertheless, cardiac safety remains a major concern, and the electrocardiographic monitoring should be carried out during treatment to substantially reduce cardiovascular risk. In conclusion, although it has an equivalent profile compared to other antipsychotic drugs, sertindole actually remains a second-line choice for schizophrenic patients intolerant to at least one other antipsychotic agent. PMID:25830594

  9. Efficacy and safety of endobronchial valves for advanced emphysema: a meta analysis

    PubMed Central

    Liu, Hua; Xu, Meng; Xie, Yiqun; Gao, Jie

    2015-01-01

    Objective A meta-analysis was undertaken to evaluate the efficacy and safety of bronchoscopic lung volume reduction with endobronchial valves (EBV) for advanced emphysema. Methods A systematic search was performed from PubMed, EMBASE, CNKI, Cochrane Library database. Randomized control clinical trials on treatment of emphysema for 3-12 months with the EBV compared with standard medications and sham EBV were reviewed. Inclusion criteria were applied to select patients with advanced emphysema treated with EBV. The primary outcome was the percentage of the forced expiratory volume in the first second (FEV1%). Secondary outcomes included St George’s Respiratory Questionnaire (SGRQ) score, the distance of the 6-minute walk (6MWD) test, the Modified Medical Research Council (MMRC) dyspnoea score, cycle ergometry workload, and the rate of the six major complications at 3 or 12 months. Fixed- or random-effects models were used and weighted mean differences (WMD), relative risks (RR) and 95% confidence intervals (CI) were calculated. Results Three trials (565 patients) were considered in the meta-analysis. EBV patients yielded greater increases in FEV1% than standard medications (WMD =6.71; 95% CI, 3.31 to 10.10; P=0.0001), EBV patients also demonstrated a significant change for SGRQ score (WMD =−3.64; 95% CI, −5.93 to −1.34; P=0.002), MMRC dyspnoea score (WMD =−0.26; 95% CI, −0.44 to -0.08; P=0.004), and cycle ergometry workload (WMD =4.18; 95% CI, 2.14 to 6.22; P<0.0001). A similar level was evident for 6MWD (WMD =11.66; 95% CI, −3.31 to 26.64; P=0.13). EBV may increase the rate of hemoptysis (RR =5.15; 95% CI, 1.16 to 22.86; P=0.03), but didn’t increase the adverse events including mortality, respiratory failure, empyema, pneumonia, pneumothrax. The overall rates for complications compared EBV with standard medications and sham EBV was not significant (RR =2.03; 95% CI, 0.98 to 4.21; P=0.06). Conclusions EBV lung volume reduction for advanced emphysema showed superior efficacy and a good safety and tolerability compared with standard medications and sham EBV, further more randomized controlled trial (RCT) studies are needed to pay more attention to the long-term efficacy and safety of bronchoscopic lung volume reduction with EBV in advanced emphysema. PMID:25922709

  10. The efficacy and safety of urethral injection therapy for urinary incontinence in women: a systematic review

    PubMed Central

    Matsuoka, Priscila Katsumi; Locali, Rafael Fagionato; Pacetta, Aparecida Maria; Baracat, Edmund Chada; Haddad, Jorge Milhem

    2016-01-01

    To evaluate the efficacy and safety of different bulking agents for treating urinary incontinence in women, a systematic review including only randomized controlled trials was performed. The subjects were women with urinary incontinence. The primary outcomes were clinical and urodynamic parameters. The results were presented as a weighted mean difference for non-continuous variables and as relative risk for continuous variables, both with 95% confidence intervals. Initially, 942 studies were identified. However, only fourteen eligible trials fulfilled the prerequisites. Altogether, the review included 1814 patients in trials of eight different types of bulking agents, and all studies were described and analyzed. The measured outcomes were evaluated using a large variety of instruments. The most common complications of the bulking agents were urinary retention and urinary tract infection. Additionally, there were certain major complications, such as one case of death after use of autologous fat. However, the lack of adequate studies, the heterogeneous populations studied, the wide variety of materials used and the lack of long-term follow-up limit guidance of practice. To determine which substance is the most suitable, there is a need for more randomized clinical trials that compare existing bulking agents based on standardized clinical outcomes. PMID:26934239

  11. The efficacy and safety of urethral injection therapy for urinary incontinence in women: a systematic review.

    PubMed

    Matsuoka, Priscila Katsumi; Locali, Rafael Fagionato; Pacetta, Aparecida Maria; Baracat, Edmund Chada; Haddad, Jorge Milhem

    2016-02-01

    To evaluate the efficacy and safety of different bulking agents for treating urinary incontinence in women, a systematic review including only randomized controlled trials was performed. The subjects were women with urinary incontinence. The primary outcomes were clinical and urodynamic parameters. The results were presented as a weighted mean difference for non-continuous variables and as relative risk for continuous variables, both with 95% confidence intervals. Initially, 942 studies were identified. However, only fourteen eligible trials fulfilled the prerequisites. Altogether, the review included 1814 patients in trials of eight different types of bulking agents, and all studies were described and analyzed. The measured outcomes were evaluated using a large variety of instruments. The most common complications of the bulking agents were urinary retention and urinary tract infection. Additionally, there were certain major complications, such as one case of death after use of autologous fat. However, the lack of adequate studies, the heterogeneous populations studied, the wide variety of materials used and the lack of long-term follow-up limit guidance of practice. To determine which substance is the most suitable, there is a need for more randomized clinical trials that compare existing bulking agents based on standardized clinical outcomes. PMID:26934239

  12. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction

    PubMed Central

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost–benefit ratio. PMID:27143910

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

    PubMed

    McClung, E C; Blumenthal, P D

    2012-04-01

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

  14. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction.

    PubMed

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost-benefit ratio. PMID:27143910

  15. EX-PRESS Glaucoma Filtration Device: efficacy, safety, and predictability

    PubMed Central

    Chan, Jessica E; Netland, Peter A

    2015-01-01

    Trabeculectomy has been the traditional primary surgical therapy for open-angle glaucoma. While trabeculectomy is effective in lowering intraocular pressure, complications associated with the procedure have motivated the development of alternative techniques and devices, including the EX-PRESS Glaucoma Filtration Device. This review describes the efficacy, safety, complication rates, and potential advantages and disadvantages of the EX-PRESS Glaucoma Filtration Device. EX-PRESS implantation is technically simpler compared with that of trabeculectomy, with fewer surgical steps. Vision recovery has been more rapid after EX-PRESS implantation compared with trabeculectomy. Intraocular pressure variation is lower during the early postoperative period, indicating a more predictable procedure. While efficacy of the EX-PRESS implant has been comparable to trabeculectomy, postoperative complications appear less common after EX-PRESS implantation compared with trabeculectomy. The EX-PRESS Glaucoma Filtration Device appears to be safe and effective in the surgical management of open-angle glaucoma. PMID:26366105

  16. Safety and efficacy of pediculicides for head lice.

    PubMed

    Burkhart, Craig G; Burkhart, Craig N

    2006-01-01

    Head lice infestation is a common and growing problem, primarily affecting school-aged children. There are growing numbers of treatment failures due to the emergence of treatment-resistant lice to the popular over-the-counter products that have been used for the past several decades. Resistance has also decreased the efficacy of lindane, a prescription pediculicide that has been commonly used for several generations. Malathion, recently reintroduced in the US as a prescription pediculicide, has been associated with some treatment resistance depending upon its formulation. Other insecticidal treatments, such as ivermectin, will have to be developed further, given the limited options presently available for the treatment of head lice. Given the number of anecdotal and market-driven reported studies on head lice, assessment of topical lice therapies requires standardised in vitro testing. Based on concerns about safety and decreasing efficacy due to resistance, a reassessment of the general topic of pediculicides for head lice is warranted. PMID:16370965

  17. 24 CFR 232.11 - Establishment and maintenance of long-term debt service reserve account.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... long-term debt service reserve account. 232.11 Section 232.11 Housing and Urban Development Regulations... Establishment and maintenance of long-term debt service reserve account. (a) To be eligible for insurance under... Safety Equipment (subpart C of this part), if HUD determines the mortgage presents an atypical...

  18. 24 CFR 232.11 - Establishment and maintenance of long-term debt service reserve account.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... long-term debt service reserve account. 232.11 Section 232.11 Housing and Urban Development Regulations... Establishment and maintenance of long-term debt service reserve account. (a) To be eligible for insurance under... Safety Equipment (subpart C of this part), if HUD determines the mortgage presents an atypical...

  19. Long-term Outcomes after Severe Shock

    PubMed Central

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

    2014-01-01

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

  20. Scenarios for long-term analysis

    SciTech Connect

    Wolbers, Stephen; /Fermilab

    2009-01-01

    Data Preservation and Long-Term Analysis of High Energy Physics (HEP) Experiments data is described and summarized in this talk. The summary covers information presented at the First Workshop on Data Preservation and Long-Term Analysis. Experiments representing e{sup +}e{sup -} collisions (LEP, B Factories and CLEO), ep collisions (H1 and ZEUS), p{bar p} collisions (CDF and D0) and others presented interesting information related to utilizing the large datasets collected over many years at these HEP facilities. Many questions and issues remain to be explored.

  1. Efficacy and safety performance of the Innovo insulin doser.

    PubMed

    Valk, Niek K; Cerny, Gerhard; Sieber, Jochen; Lytzen, Lene; Berg, Birgitte

    2004-02-01

    Innovo (Novo Nordisk A/S, Hillerød, Denmark) is a new insulin injection system that offers built-in memory and a large, clear display to provide patients with more control during insulin injections. The aim of this trial was to compare the efficacy and safety of Innovo and NovoPen 3 (Novo Nordisk A/S) in patients experienced in using insulin injection devices. Participants included 217 adults who had used NovoPen 3 or other durable pen systems for at least 6 months. This multinational, multicenter, open, randomized crossover trial comprised two treatment periods of equal duration (6 or 12 weeks). Efficacy was determined using hemoglobin A1c (HbA1c) and blood glucose concentrations, and safety parameters were the frequency and severity of hypoglycemic events. Daily insulin dose was also recorded. The effect of device type on change in HbA1c was not significant. The adjusted treatment differences between Innovo and NovoPen 3 were 0.088% [confidence interval (CI), -0.031 to 0.208%] and 0.005% (CI, -0.086 to 0.096%) for the German and Dutch/Austrian sites, respectively. Blood glucose profiles were not affected significantly by device type. Treatment differences were 0.04 mmol/L (CI, -0.57 to 0.48 mmol/L) and 0.21 mmol/L (CI, -0.13 to 0.55 mmol/L) for the German and Dutch/Austrian sites, respectively. Innovo and NovoPen 3 did not differ with regard to safety: There were no differences in numbers of various types of adverse events, or in percentage of patients experiencing one or more hypoglycemic event. This study demonstrates that the Innovo insulin doser is as safe and efficacious as NovoPen 3. PMID:15000770

  2. Long-term surveillance plan for the Mexican Hat disposal site Mexican Hat, Utah

    SciTech Connect

    1997-06-01

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

  3. Interim long-term surveillance plan for the Cheney disposal site near, Grand Junction, Colorado

    SciTech Connect

    1997-08-01

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

  4. Safety and efficacy of targeted agents monotherapy in advanced NSCLC.

    PubMed

    Zhang, Qi; Wu, Yi-Long

    2016-01-01

    The emergence of targetted therapy has revolutionised the treatment of advanced NSCLC. Increasing numbers of driver genes and related targetted agents have supplied more powerful weapons for conquering NSCLC. Depending on whether there are clear targets and therapeutic effects, we can now rank targetted agents into three categories: agents with explicit targets and pure effects, agents with theoretical targets but with no effective biomarkers, agents with vague targets and lower effects. The latest clinical data on the safety and efficacy of monotherapy with three kinds of agents will be reviewed respectively in this article. PMID:26558941

  5. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    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…

  6. Long-Term Impacts of Educational Interventions

    ERIC Educational Resources Information Center

    Deming, David James

    2010-01-01

    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

  7. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  8. Long-Term Stability of Social Participation

    ERIC Educational Resources Information Center

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    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…

  9. Long-Term Stability of Tutor Performance.

    ERIC Educational Resources Information Center

    Dolmans, Diana H. J. M.; And Others

    1996-01-01

    Examined the extent to which tutor ratings remained stable in the long term by evaluating 291 ratings of 140 tutors at Maastricht University in the Netherlands between 1992 and 1995. The results indicated that, if the aggregated score and overall judgement are used to interpret the precision of individual scores, four and two occasions,…

  10. NATIONAL LONG TERM CARE SURVEY (NLTCS)

    EPA Science Inventory

    National Long Term Care Surveys (NLTCS) are surveys of the entire aged population with a particular emphasis on the functionally impaired. Longitudinal study of the health and well-being of elderly Americans. Information about the population of chronically disabled elderly person...

  11. Long-Term Care Research and Policy

    ERIC Educational Resources Information Center

    Kemper, Peter

    2003-01-01

    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…

  12. 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...

  13. Long Term Care Aide. Course Outline.

    ERIC Educational Resources Information Center

    Wilbee, Judy

    This course outline is intended to assist the instructor in the development of a curriculum for a long-term care aide program by specifying one component of the curriculum--the objectives. These objectives, or competencies expected as outcomes for student performance on completion of the program, describe the capabilities an individual must…

  14. Long-term lysimeter data on evapotranspiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long term crop evapotranspiration (ET) data measured using large weighing lysimeters have only been gathered in a few places in the world, yet are of great importance for ground truthing of many models of plant water use, mesoscale climate, remote sensing estimation of ET, climate change and climate...

  15. Long-term cropping systems study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This long-term study has been conducted on the Agronomy Farm at ARDC since the early 1970’s. In the beginning, the objectives were mainly related to crop production as affected by different cropping systems. The cropping systems included in the study are Continuous Corn, Soybean, and Sorghum; 2-year...

  16. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  17. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

    This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship between plan…

  18. Advanced Diabetic Nephropathy with Nephrotic Range Proteinuria: A Pilot Study of the Long-Term Efficacy of Subcutaneous ACTH Gel on Proteinuria, Progression of CKD, and Urinary Levels of VEGF and MCP-1

    PubMed Central

    Tumlin, J. A.; Galphin, C. M.; Rovin, B. H.

    2013-01-01

    Background and Objective. Adrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open-label pilot trial of ACTH gel in patients with advanced diabetic nephropathy. Study Design. Twenty-three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months. Outcome. The primary endpoint was the percentage of patients achieving a complete remission (<300 mg/24 hours) within 6 months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, and urinary cytokine markers. Results. After 6 months of ACTH gel therapy, 8 of 14 (57%) patients achieved a complete (n = 1) or partial (n = 7) remission. In the low-dose ACTH gel group (16 units), urinary protein fell from 6709 + 953 to 2224 + 489 mg/24 hrs (P < 0.001). In contrast, 2 of 6 patients in the 32-unit group achieved partial remission, but aggregate proteinuria (5324 + 751 to 5154 + 853 mg/24 hours) did not change. Urinary VEGF increased from 388 to 1346 pg/mg urinary creatinine (P < 0.02) in the low-dose group but remained unchanged in the high-dose group. Conclusion. ACTH gel stabilizes renal function and reduces urinary protein for up to 6 months after treatment. The ClinTrials.gov identifier is NCT01028287. PMID:24159603

  19. Safety and efficacy of the modified peroral endoscopic myotomy with shorter myotomy for achalasia patients: a prospective study.

    PubMed

    Wang, J; Tan, N; Xiao, Y; Chen, J; Chen, B; Ma, Z; Zhang, D; Chen, M; Cui, Y

    2015-01-01

    Peroral endoscopic myotomy (POEM) has been developed as a minimally invasive endoscopic treatment for achalasia for years. However, the optimal length of submucosal tunnel and myotomy of muscle bundles during procedure of POEM has not yet been determined, so we aim to assess safety and efficacy of modified POEM with shorter myotomy of muscle bundles in achalasia patients. Consecutive achalasia patients had been performed modified POEM with shorter myotomy, and assessed by symptoms, high-resolution manometry, and barium swallow examinations before and 3 months after POEM for safety and efficacy evaluation. Modified POEM with shorter submucosal tunnel (mean length 6.8 cm) and endoscopic myotomy of muscle bundles (total mean length 5.4 cm) were completed in 46 consecutive achalasia patients. During the 3-month follow up in all cases, significant improvement of symptoms (a significant drop in the Eckardt score 8.4 ± 3.2 vs. 2.7 ± 1.9; P < 0.001), decreased lower esophageal sphincter pressure (39.4 ± 10.1 vs. 24.4 ± 9.1 mmHg; P < 0.001) and integrated relaxation pressure (38.6 ± 10.4 vs. 25.7 ± 9.6 mmHg; P < 0.01), and a drop in height of esophagus barium-contrast column (5.4 ± 3.1 vs. 2.6 ± 1.8 cm; P < 0.001) were observed. The frequencies of adverse events were lower in those under endotracheal anesthesia and CO2 insufflations compared with intravenous anesthesia and air insufflations. Only three patients were found to have gastroesophageal reflux disease on follow up. Modified POEM with shorter myotomy under endotracheal anesthesia and CO2 insufflations shows its good safety and excellent short-term efficacy in the treatment of achalasia. But further studies are warranted to assess the long-term efficacy. PMID:25214469

  20. Long Term Proton Pump Inhibitor Use and Gastrointestinal Cancer

    PubMed Central

    Graham, David Y.; Genta, Robert M.

    2010-01-01

    Proton pump inhibitors profoundly affect the stomach and have been associated with carcinoid tumors in female rats. There is now sufficient experience with this class of drugs to allow reasonable estimation of their safety in terms of cancer development. Long term proton pump inhibitor use is associated with an increase in gastric inflammation and development of atrophy among those with active Helicobacter pylori infections. The actual risk is unknown but is clearly low. However, it can be markedly reduced or eliminated by H. pylori eradication leading to the recommendation that patients considered for long term proton pump inhibitor therapy be tested for H. pylori infection and if present, it should be eradicated. Oxyntic cell hyperplasia, glandular dilatations, and fundic gland polyps may develop in H. pylori-uninfected patients, but these changes are believed to be reversible and without significant cancer risk. PMID:19006608

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

    PubMed

    Guedes, Erika Paniago; Hohl, Alexandre; de Melo, Thais Gomes; Lauand, Felipe

    2013-01-01

    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. PMID:23697612

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

    PubMed Central

    2013-01-01

    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. PMID:23697612

  3. Long-term efficacy of a rural community-based integrated intervention for prevention and management of chronic obstructive pulmonary disease: a cluster randomized controlled trial in China's rural areas

    PubMed Central

    Yuan, X.; Tao, Y.; Zhao, J.P.; Liu, X.S.; Xiong, W.N.; Xie, J.G.; Ni, W.; Xu, Y.J.; Liu, H.G.

    2015-01-01

    This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD. PMID:26352697

  4. Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa

    PubMed Central

    Sacchetti, Marta; Mantelli, Flavio; Merlo, Daniela; Lambiase, Alessandro

    2015-01-01

    Aims. Several treatments have been proposed to slow down progression of Retinitis pigmentosa (RP), a hereditary retinal degenerative condition leading to severe visual impairment. The aim of this study is to systematically review data from randomized clinical trials (RCTs) evaluating safety and efficacy of medical interventions for the treatment of RP. Methods. Randomized clinical trials on medical treatments for syndromic and nonsyndromic RP published up to December 2014 were included in the review. Visual acuity, visual field, electroretinogram, and adverse events were used as outcome measures. Results. The 19 RCTs included in this systematic review included trials on hyperbaric oxygen delivery, topical brimonidine tartrate, vitamins, docosahexaenoic acid, gangliosides, lutein, oral nilvadipine, ciliary neurotrophic factor, and valproic acid. All treatments proved safe but did not show significant benefit on visual function. Long term supplementation with vitamin A showed a significantly slower decline rate in electroretinogram amplitude. Conclusions. Although all medical treatments for RP appear safe, evidence emerging from RCTs is limited since they do not present comparable results suitable for quantitative statistical analysis. The limited number of RCTs, the poor clinical results, and the heterogeneity among studies negatively influence the strength of recommendations for the long term management of RP patients. PMID:26339504

  5. Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

    PubMed

    Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

    2016-03-01

    The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment. PMID:26852913

  6. [Dermatology - the key to ensure a good long term clinical response].

    PubMed

    Sahil, Maral; Boehncke, Wolf-Henning

    2016-01-13

    After efficacy and safety have been used for many years to evaluate therapies and treatment success in medicine, patient reported outcomes are now increasingly being incorported in this process. This trend acknowledges that patient adherence is a prerequisit for the good long-term outcome of a treatment. In the field of dermatology, namely for psoriasis, current guidelines already recommend to base clinical decision-making on a combination of objective as well as patient-reported outcomes. These parameters provide the basis for the concept of happy drug survival, building on the belief that a good quality of life reflects meaningful treatment success from the patient's point of view, motivating him to carry on with the therapy. PMID:26946698

  7. Long-term motor cortex stimulation for phantom limb pain.

    PubMed

    Pereira, Erlick A C; Moore, Tom; Moir, Liz; Aziz, Tipu Z

    2015-04-01

    We present the long-term course of motor cortex stimulation to relieve a case of severe burning phantom arm pain after brachial plexus injury and amputation. During 16-year follow-up the device continued to provide efficacious analgesia. However, several adjustments of stimulation parameters were required, as were multiple pulse generator changes, antibiotics for infection and one electrode revision due to lead migration. Steady increases in stimulation parameters over time were required. One of the longest follow-ups of motor cortex stimulation is described; the case illustrates challenges and pitfalls in neuromodulation for chronic pain, demonstrating strategies for maintaining analgesia and overcoming tolerance. PMID:25340991

  8. Efficacy and Safety of Drug-Eluting Stents in the Real World: 8-Year Follow-Up

    PubMed Central

    Pellegrini, Denise Oliveira; Gomes, Vitor Osório; Lasevitch, Ricardo; Smidt, Luis; Azeredo, Marco Aurélio; Ledur, Priscila; Bodanese, Rodrigo; Sinnott, Leonardo; Moriguchi, Emílio; Caramori, Paulo

    2014-01-01

    Background: Drug-eluting stents have been used in daily practice since 2002, with the clear advantages of reducing the risk of target vessel revascularization and an impressive reduction in restenosis rate by 50%-70%. However, the occurrence of a late thrombosis can compromise long-term results, particularly if the risks of this event were sustained. In this context, a registry of clinical cases gains special value. Objective: To evaluate the efficacy and safety of drug-eluting stents in the real world. Methods: We report on the clinical findings and 8-year follow-up parameters of all patients that underwent percutaneous coronary intervention with a drug-eluting stent from January 2002 to April 2007. Drug-eluting stents were used in accordance with the clinical and interventional cardiologist decision and availability of the stent. Results: A total of 611 patients were included, and clinical follow-up of up to 8 years was obtained for 96.2% of the patients. Total mortality was 8.7% and nonfatal infarctions occurred in 4.3% of the cases. Target vessel revascularization occurred in 12.4% of the cases, and target lesion revascularization occurred in 8% of the cases. The rate of stent thrombosis was 2.1%. There were no new episodes of stent thrombosis after the fifth year of follow-up. Comparative subanalysis showed no outcome differences between the different types of stents used, including Cypher®, Taxus®, and Endeavor®. Conclusion: These findings indicate that drug-eluting stents remain safe and effective at very long-term follow-up. Patients in the "real world" may benefit from drug-eluting stenting with excellent, long-term results. PMID:25098375

  9. Age specific differences in efficacy and safety for the CYD-tetravalent dengue vaccine.

    PubMed

    Wilder-Smith, Annelies; Massad, Eduardo

    2016-04-01

    CYD-TDV is the first dengue vaccine to have completed Phase 3 efficacy trials. Efficacy was consistently higher in those aged 9 and above for all variables studied: efficacy against virologically confirmed dengue of any severity and serotype, serotype specific efficacy, efficacy dependent on baseline seropositivity, efficacy against hospitalizations and efficacy against severe disease. Because of the higher efficacy and the absence of a safety signal, the age group with the best benefit of the use of CYD-TDV is individuals aged 9 and above - the age group for which licensure is now being sought. PMID:26775653

  10. Enteral feeding pumps: efficacy, safety, and patient acceptability

    PubMed Central

    White, Helen; King, Linsey

    2014-01-01

    Enteral feeding is a long established practice across pediatric and adult populations, to enhance nutritional intake and prevent malnutrition. Despite recognition of the importance of nutrition within the modern health agenda, evaluation of the efficacy of how such feeds are delivered is more limited. The accuracy, safety, and consistency with which enteral feed pump systems dispense nutritional formulae are important determinants of their use and acceptability. Enteral feed pump safety has received increased interest in recent years as enteral pumps are used across hospital and home settings. Four areas of enteral feed pump safety have emerged: the consistent and accurate delivery of formula; the minimization of errors associated with tube misconnection; the impact of continuous feed delivery itself (via an enteral feed pump); and the chemical composition of the casing used in enteral feed pump manufacture. The daily use of pumps in delivery of enteral feeds in a home setting predominantly falls to the hands of parents and caregivers. Their understanding of the use and function of their pump is necessary to ensure appropriate, safe, and accurate delivery of enteral nutrition; their experience with this is important in informing clinicians and manufacturers of the emerging needs and requirements of this diverse patient population. The review highlights current practice and areas of concern and establishes our current knowledge in this field. PMID:25170284

  11. A prospective, multicenter, observational study of long-term decitabine treatment in patients with myelodysplastic syndrome

    PubMed Central

    Jeong, Seong Hyun; Kim, Yoo-Jin; Lee, Je-Hwan; Kim, Yeo-Kyeoung; Kim, Soo Jeong; Park, Sung Kyu; Do, Young Rok; Kim, Inho; Mun, Yeung-Chul; Kim, Hoon Gu; Lee, Won Sik; Yi, Hyeon Gyu; Joo, Young-Don; Choi, Chul Won; Kim, Suk Ran; Na, Sang Min; Jang, Jun Ho

    2015-01-01

    This prospective observational study evaluated the efficacy and safety of long-term decitabine treatment in patients with myelodysplastic syndrome (MDS). Decitabine 20 mg/m2/day was administered intravenously for 5 consecutive days every 4 weeks to MDS patients in intermediate-1 or higher International Prognostic Scoring System (IPSS) risk categories. Active antimicrobial prophylaxis was given to prevent infectious complications. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to response were evaluated, as were adverse events. The final analysis included 132 patients. IPSS risk was intermediate-2/high in 34.9% patients. The patients received a median of 5 cycles, with responders receiving a median of 8 cycles (range, 2-30). ORR was 62.9% (complete response [CR], 36; partial response [PR], 3; marrow complete response [mCR], 19; and hematologic improvement, 25). Among responders, 39% showed first response at cycle 3 or later. OS at 2 years was 60.9%, with 17% progressing to acute myeloid leukemia. PFS at 2 years was 51.0%. Patients achieving mCR showed comparable survival outcomes to those with CR/PR. With active antibiotic prophylaxis, febrile neutropenia events occurred in 61 of 1,033 (6%) cycles. Long-term decitabine treatment with antibiotic prophylaxis showed favorable outcomes in MDS patients, and mCR predicted favorable survival outcomes. PMID:26517692

  12. Long term mortality in burned children

    PubMed Central

    Stamboulian, Daniel; Lede, Roberto

    2015-01-01

    Studies about risk factors for mortality in burn children are scarce and are even less in the follow up of this population across time. Usually, after complete event attendance, children are not follow-up as risk patients, burn injury affects all facets of life. Integration of professionals from different disciplines has enabled burn centers to develop collaborative methods of assessing the quality of care delivered to patients with burns. In this editorial we comment the paper of Duke et al. The authors highlight the importance of maintaining a long-term monitoring of children who suffered burns. The importance of this original study is to promote the reconsideration of clinical guides of long-term follow-up of burn patients. PMID:26835375

  13. [Bariatric surgery - significance, risks, long term consequences].

    PubMed

    Schubert, T; Jahn, U; Eben, E; Deuber, H J

    2013-03-21

    In recent years the number of bariatric surgery has markedly increased in industrial nations. Surgery provides a more rapid decrease of body weight than conservative approach. However a long term conservative follow up therapy is mandatory to stabilize reduced weight. Due to increasing knowledge from long term follow up of surgically treated obese patients there is a growing body of evidence that frequently there is necessity of reoperations and of substitution both of trace elementsand of minerals or vitamins due to their hampered enteral resorption. Additionally therapy of surgery induced endocrine alterations not seldom is necessary.These insights are of outstanding importance because meanwhile an enlargement of the indications for bariatric surgery as a therapeutic option for metabolic disorders is being discussed. This review refers to the recent internationally published papers concerning consequences of bariatric surgery. PMID:23678666

  14. Long-term variability of climate

    SciTech Connect

    Pielke, R.A.; Zeng, X. )

    1994-01-01

    In this research note, the authors address the following general question: In a nonlinear dynamical system (such as the climate system), can a known short-periodic variation lead to significant long-term variability It is known for chaos studies (e.g., Lorenz 1991) that any perturbations in chaotic dynamic systems can lead to a red-noise spectrum; however, whether a significant long-term variability can be induced is unknown. To perform this study, an idealized nonlinear model developed by Lorenz (1984, 1990) is used. The model and the results are presented in sections 2 and 3, respectively. Finally, the implications of this research to the understanding of the natural variability of the climate system due to internal dynamics will be discussed in section 4. 14 refs., 6 figs., 1 tab.

  15. Long-term results of viscocanalostomy and phacoviscocanalostomy: a twelve-year follow-up study

    PubMed Central

    Gunenc, Uzeyir; Ozturk, Taylan; Arikan, Gul; Kocak, Nilufer

    2015-01-01

    AIM To evaluate the long-term efficacy and safety results of viscocanalostomy and phacoviscocanalostomy. METHODS The charts of 49 glaucoma patients who underwent viscocanalostomy or phacoviscocanalostomy surgery between February 1999 and August 2004 were reviewed retrospectively. Thirty-one eyes of 21 glaucoma patients who underwent filtering procedure with a postoperative follow-up of at least 5y were included in the study. Results of complete ophthalmologic examinations were recorded and statistically analyzed. Long-term surgical outcome was defined as an overall success when intraocular pressure (IOP) was found as ≤20 mm Hg with or without antiglaucomatous medication at the last follow-up visit, while it was defined as a complete success when IOP was measured ≤20 mm Hg without antiglaucomatous medication. RESULTS Mean age was 68.1±9.6y (range: 32-81y). Mean follow-up time was 101.5±27.3mo (range: 60-144mo). Viscocanalostomy was performed in 8 eyes (25.8%) and phacoviscocanalostomy was performed in 23 eyes (74.2%). The mean preoperative IOP was 23.1±7.6 mm Hg with 2.1±1.0 medications, while mean IOP was 16.8±3.8 mm Hg with 0.9±1.1 medication at the last follow-up visit. Both the IOP decrease and the reduction in the antiglaucomatous medication were statistically significant (P<0.001 and P<0.001). No case required further glaucoma surgery. Overall success and complete success were found as 87.1% and 51.6%, respectively. Complete success rate was statistically higher in phacoviscocanalostomy group compared with the viscocanalostomy group (P=0.031), however there was no significant difference in overall success rate between two groups (P=0.072). CONCLUSION Both viscocanalostomy and phacoviscocanalostomy provide good IOP reduction in the long-term period. PMID:26682166

  16. Long-term Results of Endovascular Stent Graft Placement of Ureteroarterial Fistula

    SciTech Connect

    Okada, Takuya Yamaguchi, Masato; Muradi, Akhmadu Nomura, Yoshikatsu; Uotani, Kensuke; Idoguchi, Koji; Miyamoto, Naokazu Kawasaki, Ryota; Taniguchi, Takanori; Okita, Yutaka; Sugimoto, Koji

    2013-08-01

    PurposeTo evaluate the safety, efficacy, and long-term results of endovascular stent graft placement for ureteroarterial fistula (UAF).MethodsWe retrospectively analyzed stent graft placement for UAF performed at our institution from 2004 to 2012. Fistula location was assessed by contrast-enhanced computed tomography (CT) and angiography, and freedom from hematuria recurrence and mortality rates were estimated.ResultsStent graft placement for 11 UAFs was performed (4 men, mean age 72.8 {+-} 11.6 years). Some risk factors were present, including long-term ureteral stenting in 10 (91 %), pelvic surgery in 8 (73 %), and pelvic radiation in 5 (45 %). Contrast-enhanced CT and/or angiography revealed fistula or encasement of the artery in 6 cases (55 %). In the remaining 5 (45 %), angiography revealed no abnormality, and the suspected fistula site was at the crossing area between urinary tract and artery. All procedures were successful. However, one patient died of urosepsis 37 days after the procedure. At a mean follow-up of 548 (range 35-1,386) days, 4 patients (36 %) had recurrent hematuria, and two of them underwent additional treatment with secondary stent graft placement and surgical reconstruction. The hematuria recurrence-free rates at 1 and 2 years were 76.2 and 40.6 %, respectively. The freedom from UAF-related and overall mortality rates at 2 years were 85.7 and 54.9 %, respectively.ConclusionEndovascular stent graft placement for UAF is a safe and effective method to manage acute events. However, the hematuria recurrence rate remains high. A further study of long-term results in larger number of patients is necessary.

  17. Long-term course of opioid addiction.

    PubMed

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed. PMID:25747921

  18. Long-term sequelae of electrical injury

    PubMed Central

    Wesner, Marni L.; Hickie, John

    2013-01-01

    Abstract Objective To summarize the current evidence-based knowledge about the long-term sequelae of injuries from electrical current. Quality of evidence MEDLINE was searched for English-language articles published in the past 20 years using the following search terms: electrical, injuries, wound, trauma, accident, sequelae, long-term, follow-up, and aftereffects. For obvious reasons, it is unethical to randomly study electrical injury in controlled clinical trials. By necessity, this topic is addressed in less-rigorous observational and retrospective work and case studies. Therefore, the strength of the literature pertaining to the long-term sequelae of electrical injury is impaired by the necessity of retrospective methods and case studies that typically describe small cohorts. Main message There are 2 possible consequences of electrical injury: the person either survives or dies. For those who survive electrical injury, the immediate consequences are usually obvious and often require extensive medical intervention. The long-term sequelae of the electrical injury might be more subtle, pervasive, and less well defined, but can include neurologic, psychological, and physical symptoms. In the field of compensation medicine, determining causation and attributing outcome to an injury that might not result in objective clinical findings becomes a considerable challenge. Conclusion The appearance of these consequences of electrical injury might be substantially delayed, with onset 1 to 5 or more years after the electrical injury. This poses a problem for patients and health care workers, making it hard to ascribe symptoms to a remote injury when they might not arise until well after the incident event. PMID:24029506

  19. Long-term consequences of anorexia nervosa.

    PubMed

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof

    2013-07-01

    Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. PMID:23706279

  20. In vitro and in vivo efficacy and safety evaluation of metapristone and mifepristone as cancer metastatic chemopreventive agents.

    PubMed

    Wang, Jichuang; Chen, Jianzhong; Zhu, Yewei; Zheng, Ning; Liu, Jian; Xiao, Yingying; Lu, Yusheng; Dong, Haiyan; Xie, Jingjing; Yu, Suhong; Shao, Jingwei; Jia, Lee

    2016-03-01

    Malignant melanoma, the most deadly form of skin cancer, has a high propensity for metastatic spread and is notoriously chemotherapy-resistant. Metapristone is the primary metabolite of mifepristone (RU486) and shows biological activities similar to RU486. In the present study, we comprehensively investigated the efficacy of metapristone as a metastatic chemopreventive against melanoma B16F10 cells in vitro and in vivo, and evaluated the safety profile of both drugs in mice. Metapristone showed less cytostatic effect in vitro and in vivo in comparison with mifepristone. However, metapristone interfered the adhesion of B16F10 cells to fibronectin by down-regulating cellular expression of integrin α4. Chemopreventive pretreatment followed by oral administration of metapristone and mifepristone (2.5, 10, 50mg/kg/day for 35 days) to melanoma C57BL/6 mouse model showed significant attenuation of pulmonary metastatic development. Oral administration of high doses of metapristone and mifepristone to normal mice for 35 days (25, 100, 250mg/kg/day) resulted in a dose-dependent increase in mouse liver weight that was more severe with mifepristone than metapristone. The long-term toxicity study revealed more changes by mifepristone in counts of erythrocytes, leukocytes and platelets than by metapristone. In conclusion, metapristone may fit into a new class of cancer metastatic chemopreventive agents. It showed a safety and efficacy profile better than mifepristone. PMID:26898454

  1. Safety and efficacy of the Yukon Choice Flex sirolimus-eluting coronary stent in an all-comers population cohort

    PubMed Central

    Xhepa, E.; Tada, T.; Cassese, S.; King, L.; Ott, I.; Fusaro, M.; Kastrati, A.; Byrne, R.A.

    2014-01-01

    Aims The use of biodegradable-polymer drug-eluting stents has been shown to provide favorable results when compared with durable polymer drug-eluting stents and long-term follow up data have recently shown significant reductions in terms of very late stent thrombosis. Aim of the present study was to assess the safety and efficacy profile of a novel biodegradable polymer DES, the Yukon Choice Flex sirolimus-eluting stent. Methods We report here the one-year clinical outcomes associated with the use of the Yukon Choice Flex sirolimus-eluting stent in an all-comers patient population. The present stent represents a further refinement of the stent platform tested in the ISAR TEST 3 and 4 randomized clinical trials. A total of 778 consecutive patients undergoing implantation of this stent were enrolled in the present observational study and prospectively followed for one year. Results The use of the Yukon Choice Flex stent in a patient population with complex coronary lesion morphology was associated with optimal immediate angiographic results. At one year follow up the rates of death, myocardial infarction, definite stent thrombosis and ischemia-driven target lesion revascularization were respectively 2.4%, 1.9%, 0.3% and 11.3%. Conclusions The use of the sirolimus-eluting biodegradable polymer Yukon Choice Flex stent in an all-comers population of patients with complex coronary artery disease is associated with a favorable safety and efficacy profile up to one year follow up. PMID:24973842

  2. Long-term use of sildenafil.

    PubMed

    Carson, Culley C

    2003-03-01

    The treatment of erectile dysfunction (ED) has been revolutionised by new agents to inhibit the enzyme PDE5. The scientific basis of this treatment of ED includes relaxation of the corpus cavernosum smooth muscle tissue by inhibition of PDE5 that breaks down cGMP, the key pathway for the production of erectile function in humans. Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of sildenafil (Viagra, Pfizer) - the first approved selective PDE inhibitor for the treatment of ED. Sildenafil is inhibitory of PDE5 at a rate tenfold higher than for the next PDE (PDE6), which produces visual changes through the retinal rods. Its clinical effectiveness has been well documented in the majority of men with ED irrespective of aetiology. The aetiology of ED, also, does not appear to effect the function of sildenafil in relaxing corpus cavernosum smooth muscle tissue. Adverse events are usually associated with the vascular changes from PDE5 inhibition. These include headache and flushing. Each of these adverse events, however, declines with medication use. With the use of sildenafil, it has been clearly, clinically demonstrated that the selective inhibition of PDE5 is an appropriate, effective, safe method for the treatment of ED of all aetiologies and severities. PMID:12614192

  3. High throughput prediction of the long-term stability of pharmaceutical macromolecules from short-term multi-instrument spectroscopic data.

    PubMed

    Maddux, Nathaniel R; Iyer, Vidyashankara; Cheng, Weiqiang; Youssef, Ahmed M K; Joshi, Sangeeta B; Volkin, David B; Ralston, John P; Winter, Gerhard; Middaugh, C Russell

    2014-03-01

    Changes in the measurements of a macromolecular biopharmaceutical's physical form are often used to predict changes in the drug's long-term stability. These can in turn be used as important markers of changes to a drug's efficacy and safety. Such stability estimates traditionally require human judgment and are frequently tentative. We introduce methods for developing mathematical models that predict a drug's long-term storage stability profile from measurements of short-term physical form and behavior. We measured the long-term (2 year) chemical and colloidal stability of Granulocyte Colony Stimulating Factor (GCSF) in 16 different liquid formulations. Shortly after formulations were placed on stability, we also employed various spectroscopic techniques to characterize the short-term thermal unfolding response of GCSF in the 16 formulations. The short-term data were processed using several data reduction methods, including reduction to spectra at low temperature, to melt curves, and to transition temperatures. Least squares fitting was used to predict the long-term stability measurements from the reduced short-term spectroscopic measurements. On the basis of the cross-validation and a permutation test, many of the long-term stability predictions have less than 1% probability of occurring by chance. PMID:24421157

  4. Treating patients with venous thromboembolism: initial strategies and long-term secondary prevention.

    PubMed

    Huisman, Menno V; Bounameaux, Henri

    2005-08-01

    Therapy for venous thromboembolism (VTE) currently involves a minimum of 3 months of anticoagulation. After cessation of therapy, however, recurrent venous thrombosis occurs at rates of 6 to 9% per year. Clinical trials have demonstrated the benefits of extending anticoagulation beyond 3 months for the prevention of recurrent VTE events. Despite this, many eligible patients do not receive the required thromboprophylaxis and the incidence of recurrent VTE remains too high for a preventable condition. A reason for failure to use prophylaxis is the fear of bleeding complications with current oral anticoagulants such as warfarin. Warfarin has an unpredictable pharmacokinetic profile and a variable dose-response relationship that requires frequent coagulation monitoring and dose adjustments to maintain a target intensity that is both safe and effective. Alternative strategies for long-term prophylaxis, which may potentially provide more consistent anticoagulant responses and reduce coagulation monitoring requirements, include the use of low-molecular-weight heparin (LMWH), treatment with warfarin at a lower intensity, and the introduction of novel anticoagulants. The long-term use of LMWH has been found to be a particularly favorable treatment option for cancer patients in whom it is difficult to control the intensity of anticoagulation. In clinical trials, LMWH significantly reduced the risk of recurrent VTE without increasing bleeding risk. The parenteral administration of the LMWHs, however, is a drawback for long-term use in the outpatient setting. A clinical trial assessing the efficacy and safety of long-term low-intensity warfarin treatment found this therapy to be better than placebo, but another study showed that conventional intensity warfarin was significantly more efficacious than low-intensity warfarin. New therapies in development that may offer improved safety-efficacy profiles are the synthetic pentasaccharides fondaparinux and idraparinux and the oral direct thrombin inhibitor ximelagatran. Parenterally administered fondaparinux has been shown to be as effective as LMWH for the acute treatment (5 to 7 days) of symptomatic deep vein thrombosis. Idraparinux, with once-weekly parenteral dosing, is currently being assessed in phase III clinical trials for the long-term secondary prevention of VTE. Ximelagatran is the first oral agent in the new class direct thrombin inhibitors. With a fast onset of action and oral administration, ximelagatran is a candidate for both acute and chronic therapy. The Thrombin Inhibitor in Venous Thromboembolism (THRIVE) clinical trial program has demonstrated that this agent has a favorable benefit-risk profile compared with standard therapy for the initial treatment (6 months) and secondary prevention (up to 18 months) of VTE. However, in a substantial proportion (6 to 13%) of patients given extended ximelagatran therapy, elevated serum transaminase enzymes developed, typically in the first 2 to 4 months of treatment. Even though these elevations usually abated without clinical sequelae whether or not treatment was continued, their clinical relevance remains unclear. In addition, locally reported coronary events occurred more frequently in ximelagatran-treated patients during the initial 6 months of treatment, the reason for which is yet unclear. The consistent anticoagulant response and fixed oral dosing without coagulation monitoring allows ximelagatran to overcome many of the limitations inherent to current treatment options for VTE treatment and secondary prevention, provided the problem of liver enzyme elevation and coronary events is resolved. PMID:16123915

  5. Long Term Hydrologic Observatories: Issues and Priorities

    NASA Astrophysics Data System (ADS)

    Band, L. E.

    2002-05-01

    Long Term Hydrologic Observatories (LTHO) are one of the center pieces of the CUAHSI initiative and require careful consideration of a set of scientific and logistical issues. They are conceived as major research facilities to address critical hydrologic science and management questions identified by the research community, and which require large scale, long term observations. Recent NSF and NRC white papers on the future of hydrology outline a set of science initiatives and questions focussing on variability and predictability in the hydrologic cycle at multiple scales, the coupling of hydrologic processes with atmospheric and ecosystem processes, and interactions of hydrologic systems with human societal activities. The LTHO will serve to provide the research community with a network of sites for long term, multiple scale data collection, experimental design and implementation, and hypothesis testing to address these issues. In order to maximize their scientific return, we need to identify a balance between the number of sites in the network to gain representation in different environmental conditions, and the amount of resources available for each site to assure comprehensive sampling and experimentation. Some of the topical aspects of the LTHO mission have been implemented in the form of a subset of the more hydrologically oriented LTER sites, the ARS and WEB experimental watersheds, and through the long term monitoring program of the USGS. However, these efforts have either not been at the scales envisioned for the LTHO (e.g. 104-105 km2), have not emphasized long term measurement, or have not addressed the development of a comprehensive, multidisciplinary information base necessary to respond to the driving scientific and management questions. The LTHO can be designed to build on and integrate these ongoing efforts by identifying larger basins that contain longer term LTER, ARS or WEB sites, or implement more comprehensive, multidisciplinary data collection schemes in monitored basins. Critical issues to address will be identification of core data that all LTHO sites will collect, the degree of standardization in sampling and analysis methods that can be achieved, and how the resulting information will be made available to the research community. A significant difference between these sites and previous experimental watersheds will be that, in general, the LTHO will be too large to restrict scientific activity within the watersheds to LTHO or CUAHSI sanctioned projects. Therefore, the LTHO will require significant outreach and collaboration with local community, municipal, county and state governments who may have a much greater presence and range of environmental monitoring than the LTHO will provide.

  6. Efficacy and safety of monotherapy by pegvisomant, a growth hormone receptor antagonist, in Japanese patients with acromegaly.

    PubMed

    Shimatsu, Akira; Nagashima, Masahito; Hashigaki, Satoshi; Ohki, Nobuhiko; Chihara, Kazuo

    2016-04-25

    Pegvisomant is a GH receptor antagonist and strong inhibitor of insulin-like growth factor I (IGF-I) production. The treatment goal for acromegaly is to normalize serum IGF-I levels and attenuate associated symptoms. The efficacy and safety of pegvisomant as treatment for acromegaly have been reported in Caucasians, but not in Japanese. Here we report the clinical experience of using pegvisomant in Japanese patients with acromegaly. The efficacy and safety data for pegvisomant from two open-labeled clinical studies in Japan, conducted from 2004 to 2007, were re-analyzed using the new Japanese age- and sex-matched normative ranges for IGF-I. Eighteen patients with active acromegaly were enrolled in an initial pivotal study, and 16 of them were moved to a long-term (max 168 weeks) extension study. The dose of pegvisomant in the extension study was adjusted to 10-30 mg per day according to IGF-I levels. IGF-I normalization was observed in 81.3% (13/16 patients) during the extension study. The mean percentage decrease from baseline in serum IGF-I level was 64.7% at the time of last observation. The clinical symptoms and overall health status were improved, and the ring size was reduced over time until Week 12 and maintained. For safety, no clinically significant changes were observed both in the pituitary tumor size and the anti-GH antibody level. Three subjects were withdrawn from the studies due to an abnormal elevation of liver enzymes which resolved after discontinuation. Pegvisomant demonstrated excellent clinical efficacy and was well tolerated in Japanese patients with acromegaly. PMID:26796763

  7. The efficacy and safety of perioperative antiplatelet therapy.

    PubMed

    Merritt, J Christopher; Bhatt, Deepak L

    2004-02-01

    Widespread adoption of the antiplatelet agents into everyday clinical practice has revolutionized contemporary care of the cardiovascular patient. Major adverse cardiovascular events including death, myocardial infarction, stroke, and recurrent angina have all been shown to be significantly decreased when these agents are employed in the treatment of coronary atherosclerosis, acute coronary syndromes, myocardial infarction, and in the setting of percutaneous coronary intervention. As a growing number of patients on antiplatelet therapy are undergoing various surgical procedures, the potential risks and benefits these drugs pose perioperatively will become increasingly important. Available data indicate that, when used appropriately, these drugs can be used safely prior to surgery. Efficacy in improving surgical outcomes and in preventing adverse cardiovascular events postoperatively has also been demonstrated. The purpose of this review is to examine the perioperative safety and efficacy of the most widely used antiplatelet agents: aspirin; the thienopyridine clopidogrel; and the glycoprotein (GP) IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban. This information, coupled with emerging platelet monitoring techniques, may help provide additional assistance to the clinician to manage therapy and guide appropriate timing of both cardiac and noncardiac surgery. PMID:15277784

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

    PubMed Central

    Harrow, Martin

    2013-01-01

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

  9. Long-term use of adalimumab in the treatment of moderate to severe plaque psoriasis: a review of the literature

    PubMed Central

    Moore, Angela Y; Richardson, Blakely S

    2010-01-01

    Psoriasis is a chronic T-cell-mediated inflammatory disease that primarily affects the skin and joints. Patients with moderate to severe psoriasis constitute about 30% of the psoriasis population. Treatment of this group is challenging due to the long-term side effects, toxicities and inconvenience of conventional treatments such as phototherapy, methotrexate and cyclosporine. However, recent advances in our understanding of the pathogenesis of psoriasis have led to the popular use of biologics, which offer a safer, more convenient and effective targeted therapy. Adalimumab was originally approved for treating rheumatoid arthritis. Currently, adalimumab is also approved for treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy or when other systemic therapies are medically less appropriate. Since the onset of the use of biologics, there have been concerns over safety and efficacy when used as long-term therapy. This paper reviews all publications, posters and abstracts reporting original data on the efficacy and/or safety of adalimumab in patients treated for chronic plaque psoriasis for more than 1 year. PMID:21437059

  10. Rationale for long-term treatment of bipolar disorder and evidence for long-term lithium treatment.

    PubMed

    Goodwin, Frederick K

    2002-01-01

    Because of the great morbidity and mortality associated with bipolar disorder, long-term treatment is necessary to prevent recurrence and reduce the loss of productivity and increased medical costs associated with this illness. The agent with the most evidence of efficacy and the only U.S. Food and Drug Administration-approved medication for maintenance treatment of bipolar disorder is lithium. Lithium may cause a prophylactic response in more than two thirds of patients with bipolar disorder and reduce suicide risk by more than 8-fold. However, lithium may be more effective for patients with classical features such as fully remitting courses and typical manic symptoms than for patients with nonclassical bipolar features such as mixed states and rapid cycling. Because lithium may be toxic at only twice the therapeutic dose, physicians should consider patients' ages and medical history when prescribing this drug. Monitoring requirements; possible side effects; changes in the illness including more treatment-resistant forms; and the introduction of newer agents, which are supported by more marketing and continuing medical education programs than the essentially generic drug lithium, have contributed to the decline in lithium prescription rates in the last 15 years in the United States. However, long-term treatment with lithium continues to be effective in many patients, especially if the dose is periodically evaluated as patients experience changes in their physical health and lithium tolerance. Until newer agents have comparable evidence of efficacy, lithium will be considered a first-line long-term treatment for bipolar disorder, either as monotherapy or in combination therapy. PMID:12392347

  11. Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients

    PubMed Central

    Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Ulanski, Lawrence J.; Miller, Luke; Podella, Carla

    2014-01-01

    Background: Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities. PMID:25329968

  12. Safety and efficacy of Bixa orellana (achiote, annatto) leaf extracts.

    PubMed

    Stohs, Sidney J

    2014-07-01

    Bixa orellana leaf preparations have been used for many years by indigenous people for a variety of medicinal applications. Published research studies in animals indicate that various extracts of Bixa leaves exhibit antioxidant, broad antimicrobial (antibacterial and antifungal), anti-inflammatory, analgesic, hypoglycemic, and antidiarrheal activities. No studies have specifically assessed the ability of leaf extracts to inhibit urogenital infections although Bixa products have been used in folkloric medicine to treat gonorrhea and other infections. Few human studies have been conducted and published using Bixa leaf preparations. Many more studies have been conducted and published involving Bixa seed (annatto) extracts than with leaf extracts. No subchronic safety (toxicity) studies have been conducted in animals. A 6 month study in humans given 750 mg of leaf powder per day demonstrated no significant or serious adverse effects. Bixa leaf extracts appear to be safe when given under current conditions of use. However, additional human and animal controlled safety and efficacy studies are needed. In addition, detailed chemical analyses are required to establish structure-function relationships. PMID:24357022

  13. Safety and efficacy of phage therapy via the intravenous route.

    PubMed

    Speck, Peter; Smithyman, Anthony

    2016-02-01

    Increasing development of antimicrobial resistance is driving a resurgence in interest in phage therapy: the use of bacteriophages to treat bacterial infections. As the lytic action of bacteriophages is unaffected by the antibiotic resistance status of their bacterial target, it is thought that phage therapy may have considerable potential in the treatment of a wide range of topical and localized infections. As yet this interest has not extended to intravenous (IV) use, which is surprising given that the historical record shows that phages are likely to be safe and effective when delivered by this route. Starting almost 100 years ago, phages were administered intravenously in treatment of systemic infections including typhoid, and Staphylococcal bacteremia. There was extensive IV use of phages in the 1940s to treat typhoid, reportedly with outstanding efficacy and safety. The safety of IV phage administration is also underpinned by the detailed work of Ochs and colleagues in Seattle who have over four decades' experience with IV injection into human subjects of large doses of highly purified coliphage PhiX174. Though these subjects included a large number of immune-deficient children, no serious side effects were observed over this extended time period. The large and continuing global health problems of typhoid and Staphylococcus aureus are exacerbated by the increasing antibiotic resistance of these pathogens. We contend that these infections are excellent candidates for use of IV phage therapy. PMID:26691737

  14. Efficacy and food safety considerations of poultry competitive exclusion products.

    PubMed

    Wagner, Robert Doug

    2006-11-01

    Competitive exclusion (CE) products are anaerobic cultures of bacteria that are applied to poultry hatchlings to establish a protective enteric microbiota that excludes intestinal colonization by human food-borne pathogens. For safety of the poultry flock and human consumers, the identities of bacteria in CE products need to be known. A CE product is a culture of intestinal contents from adult chickens. It may be microbiologically defined by analysis of bacteria isolated from the culture, but many bacteria are hard to reliably isolate, identify, and characterize with conventional techniques. Sequence analysis of 16S ribosomal RNA (rRNA) genes may be more reliable than conventional techniques to identify CE bacteria. Bacteria in CE products may contain antimicrobial drug resistance and virulence mechanisms that could be transferred to the enteric bacteria of the food animal and to the human consumer. Detection methods for specific antimicrobial drug resistance and virulence genes and the integrase genes of conjugative transposons, mostly utilizing PCR technology, are being developed that can be applied to assess these risks in CE bacteria. With improvements in efficacy, bacterial identification, and detection and control of the possible risks of gene transfer, CE product technology can be made a more effective food safety tool. PMID:17039457

  15. Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders.

    PubMed

    Parellada, Eduard; Kouniakis, Filippos; Siurkute, Aldona; Schreiner, Andreas; Don, Liana

    2010-05-01

    This postauthorization safety study evaluated the long-term safety, tolerability, and efficacy of risperidone long-acting injectable (RLAI) in routine clinical practice. In this 6-month, multicenter, European, naturalistic study, patients were included if, during routine clinical practice, long-term antipsychotic therapy with RLAI was deemed necessary by the treating physician. Efficacy measures included Clinical Global Impression-Severity and Global Assessment of Functioning. Safety was evaluated by recording treatment-emergent adverse events (AE). RLAI was initiated in 5134 patients (aged 14-94 years); predominantly male (58.6%) with paranoid schizophrenia (69.8%). RLAI initial doses were 25 mg every 2 weeks (37.0% patients), 37.5 mg (18.0%), and 50 mg (44.4%). Treatment was completed by 4314 patients (84.0%). RLAI was discontinued on account of loss to follow-up (n=346; 6.7%), insufficient response (n=116; 2.3%), and AEs (n=106; 2.1%). Clinical Global Impression-Severity significantly improved from baseline to endpoint (P<0.001). Patient functioning on the Global Assessment of Functioning scale also significantly improved from baseline to endpoint (45.4 + or - 16.0 vs. 62.4 + or - 17.7, respectively, P<0.001). Treatment-emergent AEs were recorded by 1018 (20%) of patients. AEs occurring in > or = 5% of patients were akathisia, extrapyramidal disorders, depression, psychotic disorder, anxiety, and weight gain. Serious AEs were reported by 384 (8%) patients. This study confirms good safety, tolerability, and efficacy with RLAI in routine clinical practice. PMID:20305567

  16. Lessons from the past: Long-term safety and survival outcomes of a prematurely terminated randomized controlled trial on prophylactic vs. hemoglobin-based administration of erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia

    PubMed Central

    MOUNTZIOS, GIANNIS; ARAVANTINOS, GERASIMOS; ALEXOPOULOU, ZOI; TIMOTHEADOU, ELENI; MATSIAKOU, FOTINI; CHRISTODOULOU, CHRISTOS; LASCHOS, KONSTANTINOS; GALANI, ELENI; KOUTRAS, ANGELOS; BAFALOUKOS, DIMITRIOS; LINARDOU, HELENA; PECTASIDES, DIMITRIOS; VARTHALITIS, IOANNIS; PAPAKOSTAS, PAVLOS; KALOFONOS, HARALAMBOS P.; FOUNTZILAS, GEORGE

    2016-01-01

    Prophylactic erythropoiesis-stimulating agent (ESA) administration for chemotherapy-induced anemia (CIA) is not supported by current guidelines. Long-term follow-up of patients WHO had been treated with ESA for CIA in the past may provide useful information. In 2002, we undertook a prospective, randomized phase III trial of prophylactic vs. hemoglobin (Hb)-based (threshold: 11 mg/dl) ESA administration in patients with solid tumors and CIA. ESA administration FOR CIA was permanently suspended in 2007 in view of published data at that time, while patient surveillance continued. Among 630 evaluable patients, 38.6% were male, 50.9% had advanced cancer at diagnosis, 40.6% had Hb levels <12 mg/dl at baseline and 47.9% received ESA prophylactically (1:1 randomization). The major tumor types included colorectal (36.0%), breast (20.6%), non-prostate genitourinary (11.0%) and lung CANCER (8.4%). After a median follow-up of 85.4 months, 358 patients had relapsed and 380 had succumbed to the disease. Patients in the prophylactic ESA group (GROUP A; experimental arm), as compared with those in the Hb-based group (GROUP B; iron supplementation alone), exhibited A significantly more prominent increase in median Hb levels, particularly in the subset of patients with non-metastatic disease (two-sided P<0.01) among patients receiving chemotherapy for advanced cancer, those who received ESAs prophylactically exhibited a lower incidence of CIA (all grades: P=0.014, grades 3–4: P=0.034) and fatigue (all grades: P<0.001, grades 3–4: P=0.055), but a higher rate of a composite outcome encompassing all thrombosis-related events (all grades: P=0.043, grades 3–4: P=0.099). These differences were less prominent in the group of patients who received adjuvant treatment. There were no significant differences in overall mortality and relapse/progression rates between the two groups. therefore, prophylactic, compared with Hb-based, administration of ESAs for CIA in patients with solid tumors, was found to be associated with a significantly lower incidence of anemia and fatigue, but with a marginally higher rate of thrombosis-related adverse events, particularly in patients receiving first-line chemotherapy for advanced cancer. PMID:26893865

  17. A long-term, observational cohort study on the safety of low-dose glucocorticoids in ankylosing spondylitis: adverse events and effects on bone mineral density, blood lipid and glucose levels and body mass index

    PubMed Central

    Zhang, Yu-Ping; Gong, Yao; Zeng, Qing Yu; Hou, Zhi-Duo; Xiao, Zheng-Yu

    2015-01-01

    Objectives This study aimed to investigate the risk of adverse events and effects on bone mineral density (BMD), blood lipid and glucose levels and body mass index (BMI) of low-dose glucocorticoid (GC) treatment in ankylosing spondylitis. Design We performed a retrospective, observational cohort study. Adverse effects were compared between GC users and non-GC users, and we analysed differences in the duration of GC exposure (no GC exposure, <6 months, 6 months to 2 years and >2 years). Setting Outpatient clinic in a tertiary general hospital in China, rheumatology follow-up visits over the past 30 years. Participants We included 830 patients with ankylosing spondylitis who were followed up for at least 6 months without a previous history or current complications of active gastrointestinal problems, hypertension, psychiatric or mental problems, diabetes mellitus, tuberculosis and hepatitis. The median follow-up time was 1.6 years (range 0.5–15 years, a total of 1801 patient-years). Results A total of 555 (66.9%) patients were treated with low-dose GCs, and the median cumulative duration of GC therapy was 1.3 years (range 0.1–8.5 years). Dermatological incidents, including acne, bruisability and cutaneous infections, were the most common adverse events, with a cumulative incidence rate of 5.4% (22.2 events per 1000 patient-years), followed by a puffy and rounded face (1.6%), symptoms of weight gain (1.1%) and serious infections (1.0%). The rates of all other types of adverse events were less than 1%. The GC groups (GC users and non-GC users) and the duration of GC therapy were not associated with the frequency of low BMD, dyslipidaemia, hyperglycaemia or obesity (p<0.05). Conclusions Adverse events during long-term treatment of low-dose GCs are limited. Low-dose GCs do not have an adverse effect on BMD, blood lipid and glucose levels and BMI. PMID:26041488

  18. Long-Term Recency in Anterograde Amnesia.

    PubMed

    Talmi, Deborah; Caplan, Jeremy B; Richards, Brian; Moscovitch, Morris

    2015-01-01

    Amnesia is usually described as an impairment of a long-term memory (LTM) despite an intact short-term memory (STM). The intact recency effect in amnesia had supported this view. Although dual-store models of memory have been challenged by single-store models based on interference theory, this had relatively little influence on our understanding and treatment of amnesia, perhaps because the debate has centred on experiments in the neurologically intact population. Here we tested a key prediction of single-store models for free recall in amnesia: that people with amnesia will exhibit a memory advantage for the most recent items even when all items are stored in and retrieved from LTM, an effect called long-term recency. People with amnesia and matched controls studied, and then free-recalled, word lists with a distractor task following each word, including the last (continual distractor task, CDFR). This condition was compared to an Immediate Free Recall (IFR, no distractors) and a Delayed Free Recall (DFR, end-of-list distractor only) condition. People with amnesia demonstrated the full long-term recency pattern: the recency effect was attenuated in DFR and returned in CDFR. The advantage of recency over midlist items in CDFR was comparable to that of controls, confirming a key prediction of single-store models. Memory deficits appeared only after the first word recalled in each list, suggesting the impairment in amnesia may emerge only as the participant's recall sequence develops, perhaps due to increased susceptibility to output interference. Our findings suggest that interference mechanisms are preserved in amnesia despite the overall impairment to LTM, and challenge strict dual-store models of memory and their dominance in explaining amnesia. We discuss the implication of our findings for rehabilitation. PMID:26046770

  19. Long-term EARLINET dust observations

    NASA Astrophysics Data System (ADS)

    Mona, Lucia; Amiridis, Vassilis; Amodeo, Aldo; Binietoglou, Ioannis; D'Amico, Giuseppe; Schwarz, Anja; Papagiannopoulos, Nikolaos; Papayannis, Alexandros; Sicard, Michael; Comeron, Adolfo; Pappalardo, Gelsomina

    2015-04-01

    Systematic observations of Saharan dust events over Europe are performed from May 2000 by EARLINET, the European Aerosol Research LIdar NETwork. EARLINET is a coordinated network of stations that make use of advanced lidar methods for the vertical profiling of aerosols. The backbone of EARLINET network is a common schedule for performing the measurements and the quality assurance of instruments/data. Particular attention is paid to monitoring the Saharan dust intrusions over the European continent. The geographical distribution of the EARLINET stations is particularly appealing for the dust observation, with stations located all around the Mediterranean and in the center of the Mediterranean (Italian stations) where dust intrusions are frequent, and with several stations in the central Europe where dust penetrates occasionally. All aerosol backscatter and extinction profiles related to observations collected during these alerts are grouped in the devoted "Saharan dust" category of the EARLINET database. This category consists of about 4700 files (as of December 2013). Case studies involving several stations around Europe selected from this long-term database have been provided the opportunity to investigate dust modification processes during transport over the continent. More important, the long term EARLINET dust monitoring allows the investigation of the horizontal and vertical extent of dust outbreaks over Europe and the climatological analysis of dust optical intensive and extensive properties at continental scale. This long-term database is also a unique tool for a systematic comparison with dust model outputs and satellite-derived dust products. Because of the relevance for both dust modeling and satellite retrievals improvement, results about desert dust layers extensive properties as a function of season and source regions are investigated and will be presented at the conference. First comparisons with models outputs and CALIPSO dust products will be presented. ACKNOWLEDGMENTs The financial support by the European Community through the ACTRIS Research Infrastructure Action under the 7th Framework Programme under ACTRIS Grant Agreement n° 262254 is gratefully acknowledged.

  20. Long-Term Recency in Anterograde Amnesia

    PubMed Central

    Talmi, Deborah; Caplan, Jeremy B.; Richards, Brian; Moscovitch, Morris

    2015-01-01

    Amnesia is usually described as an impairment of a long-term memory (LTM) despite an intact short-term memory (STM). The intact recency effect in amnesia had supported this view. Although dual-store models of memory have been challenged by single-store models based on interference theory, this had relatively little influence on our understanding and treatment of amnesia, perhaps because the debate has centred on experiments in the neurologically intact population. Here we tested a key prediction of single-store models for free recall in amnesia: that people with amnesia will exhibit a memory advantage for the most recent items even when all items are stored in and retrieved from LTM, an effect called long-term recency. People with amnesia and matched controls studied, and then free-recalled, word lists with a distractor task following each word, including the last (continual distractor task, CDFR). This condition was compared to an Immediate Free Recall (IFR, no distractors) and a Delayed Free Recall (DFR, end-of-list distractor only) condition. People with amnesia demonstrated the full long-term recency pattern: the recency effect was attenuated in DFR and returned in CDFR. The advantage of recency over midlist items in CDFR was comparable to that of controls, confirming a key prediction of single-store models. Memory deficits appeared only after the first word recalled in each list, suggesting the impairment in amnesia may emerge only as the participant’s recall sequence develops, perhaps due to increased susceptibility to output interference. Our findings suggest that interference mechanisms are preserved in amnesia despite the overall impairment to LTM, and challenge strict dual-store models of memory and their dominance in explaining amnesia. We discuss the implication of our findings for rehabilitation. PMID:26046770

  1. Long term efficacy of DOTS regimens for tuberculosis: systematic review

    PubMed Central

    2008-01-01

    Objective To identify published studies assessing tuberculosis recurrence after successful treatment with standard short course regimens for six months to determine the strength and sufficiency of evidence to support current guidelines. Design Systematic review. Data sources Medline, Embase, Cochrane clinical trials register, specialist tuberculosis journals, and reference lists. Only English language publications were eligible. Review methods Studies were included irrespective of methodology or quality. Abstracted information included inclusion and exclusion criteria for participants, duration of follow-up, and definitions of treatment success and disease recurrence. The primary outcome was the proportion of successfully treated patients recorded with recurrent tuberculosis during the follow-up period. Results 17 study arms from 16 studies met the inclusion criteria; 10 were controlled clinical trials and six were either studies done under programmatic conditions or observational studies from functioning tuberculosis programmes. Although several clinical trials supported the use of daily treatment regimens, studies reporting tuberculosis recurrence after intermittent regimens were limited. Few studies carried out under routine programmatic conditions reported disease recurrence. Overall there was wide variation in recurrence after successful treatment, ranging from 0% to 14%. Considerable heterogeneity across studies precluded the systematic assessment of factors contributing to tuberculosis recurrence. Conclusions Despite DOTS (directly observed treatment, short course) being implemented for more than 10 years and millions of patients treated for tuberculosis, few studies have assessed the ability of standard DOTS regimens to result in lasting cure for patients treated under routine programmatic conditions. PMID:18250104

  2. Long-Term Efficacy of Postpartum Intravenous Iron Therapy

    PubMed Central

    Zimmermann, Roland

    2014-01-01

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

  3. Safety and Efficacy of Sodium Hyaluronate Gel and Chitosan in Preventing Postoperative Peristomal Adhesions After Defunctioning Enterostomy

    PubMed Central

    Hu, Jiancong; Fan, Dejun; Lin, Xutao; Wu, Xianrui; He, Xiaosheng; He, Xiaowen; Wu, Xiaojian; Lan, Ping

    2015-01-01

    Abstract Peristomal adhesions complicate closure of defunctioning enterostomy. The efficacy and safety of sodium hyaluronate gel and chitosan in preventing postoperative adhesion have not been extensively studied. This study aims to evaluate the safety and efficacy of sodium hyaluronate gel and chitosan in the prevention of postoperative peristomal adhesions. This was a prospective randomized controlled study. One hundred and fourteen patients undergoing defunctioning enterostomy were enrolled. Patients were randomly assigned to receive sodium hyaluronate gel (SHG group) or chitosan (CH group) or no antiadhesion treatment (CON group) during defunctioning enterostomy. The safety outcomes included toxicities, stoma-related complications, and short-term and long-term postoperative complications. Eighty-seven (76.3%) of the 114 patients received closure of enterostomy, during which occurrence and severity of intra-abdominal adhesions were visually assessed by a blinded assessor. Incidence of adhesion appears to be lower in patients received sodium hyaluronate gel or chitosan but differences did not reach a significant level (SHG group vs CH group vs CON group: 62.1% vs 62.1% vs 82.8%, P = 0.15). Compared with the CON group, severity of postoperative adhesion was significantly decreased in the SHG and CH group (SHG group vs CH group vs CON group: 31.0% vs 27.6% vs 62.1%; P = 0.01). There was no significant difference in the occurrence of postoperative complications and other safety outcomes among the 3 groups. Sodium hyaluronate gel or chitosan smeared around the limbs of a defunctioning enterostomy was safe and effective in the prevention of postoperative peristomal adhesions. PMID:26705233

  4. Long Term Archiving and CCSDS Standards

    NASA Astrophysics Data System (ADS)

    Boucon, Danièle

    This article presents some conceptual and implementation CCSDS -Consultative Committee for Space Data Systemsstandards for long term archiving. It focuses on the most recent one, the Producer Archive Interface Specification (PAIS) standard. This standard, currently available as a draft on the CCSDS web site, will be published by the beginning of 2014. It will enable the Producer to share with the Archive a sufficiently precise and unambiguous formal definition of the Digital Objects to be produced and transferred, by means of a model. It will also enable a precise definition of the packaging of these objects in the form of Submission Information Packages (SIPs), including the order in which they should be transferred.

  5. Long-Term Wind Power Variability

    SciTech Connect

    Wan, Y. H.

    2012-01-01

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

  6. Human Behaviour in Long-Term Missions

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  7. Long-term effects of sibling incest.

    PubMed

    Daie, N; Witztum, E; Eleff, M

    1989-11-01

    Although sexual abuse of children is recognized as a serious problem, sibling incest has received relatively little attention. A distinction has been made between power-oriented sibling incest and nurturance-oriented incest. The authors review the relevant literature and present four clinical examples. The cases illustrate the broad range of sibling incest and demonstrate its effects, including the long-term consequences for the perpetrator. Lasting difficulties in establishing and maintaining close relationships, especially sexual ones, are prominent features of each case. Without denying the occurrences of benign sex-play between siblings, the authors emphasize exploitation and abuse as pathogenic aspects of sibling incest. PMID:2808310

  8. Technique for long-term feline tracheostomy.

    PubMed

    Hanson, D G

    1983-06-01

    When long-term feline tracheostomy is desired for experimental purposes, a permanent stoma may be established by a modification of the technique described by Miles. Crusting, injury, and obstruction of the stoma are bypassed during healing by an intratracheal tube stent. With the bypass tube in place, the animal breathes humidified air through its nose, and tracheal crusting is minimized. A stout neck dressing prevents scratching and injury to the stoma until it is healed. The technique provides a well-healed, well-tolerated permanent stoma with minimal special animal care. PMID:6342586

  9. Preclinical Evaluation of Efficacy and Safety of an Improved Lentiviral Vector for the Treatment of β-Thalassemia and Sickle Cell Disease

    PubMed Central

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

    2015-01-01

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

  10. The NordiNet® International Outcome Study and NovoNet® ANSWER Program®: rationale, design, and methodology of two international pharmacoepidemiological registry-based studies monitoring long-term clinical and safety outcomes of growth hormone therapy (Norditropin®)

    PubMed Central

    Höybye, Charlotte; Sävendahl, Lars; Christesen, Henrik Thybo; Lee, Peter; Pedersen, Birgitte Tønnes; Schlumpf, Michael; Germak, John; Ross, Judith

    2013-01-01

    Objective Randomized controlled trials have shown that growth hormone (GH) therapy has effects on growth, metabolism, and body composition. GH therapy is prescribed for children with growth failure and adults with GH deficiency. Carefully conducted observational study of GH treatment affords the opportunity to assess long-term treatment outcomes and the clinical factors and variables affecting those outcomes, in patients receiving GH therapy in routine clinical practice. Design The NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web Enabled Research (ANSWER Program®) are two complementary, non-interventional, observational studies that adhere to current guidelines for pharmacoepidemiological data. Patients The studies include pediatric and adult patients receiving Norditropin®, as prescribed by their physicians. Measurements The studies gather long-term data on the safety and effectiveness of reallife treatment with the recombinant human GH, Norditropin®. We describe the origins, aims, objectives, and design methodology of the studies, as well as their governance and validity, strengths, and limitations. Conclusion The NordiNet® IOS and ANSWER Program® studies will provide valid insights into the effectiveness and safety of GH treatment across a diverse and large patient population treated in accordance with real-world clinical practice and following the Good Pharmacoepidemiological Practice and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. PMID:23658497

  11. 17 CFR 256.224 - Other long-term debt.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Other long-term debt. 256.224... COMPANY ACT OF 1935 6. Long-Term Debt § 256.224 Other long-term debt. This account shall include all long-term debt to nonassociates and not subject to current settlement. Note: Subaccounts shall be...

  12. Safety and Efficacy of Bimatoprost for Eyelash Growth in Postchemotherapy Subjects

    PubMed Central

    Baumann, Leslie; Bruce, Suzanne; Ahluwalia, Gurpreet; Weng, Emily; Daniels, Selena

    2015-01-01

    Objective: To evaluate long-term efficacy and safety of bimatoprost for treatment of chemotherapy-induced eyelash hypotrichosis. Design: One-year, multicenter, double-masked, parallel-group study. Setting: Twenty-one centers in the United States and one center in the United Kingdom. Participants: This study randomized (3:1) 130 subjects to bimatoprost 0.03% or vehicle applied topically to upper eyelid margins for six months. All subjects used bimatoprost for a second six months. Measurements: Responders for the primary composite end point achieved ≥1-grade improvement in Global Eyelash Assessment score and ≥3-point improvement in Confidence, Attractiveness, and Professionalism domain score of the Eyelash Satisfaction Questionnaire at Month 4. Secondary assessments included eyelash length, thickness, and darkness, using digital image analysis. Results: The responder rate was significantly higher with bimatoprost versus vehicle at Month 4 (37.5% vs. 18.2%; p=0.041) and Month 6 (46.9% vs. 18.2%; p=0.004). Significant improvements favoring bimatoprost occurred in eyelash length (p=0.008), thickness (p<0.001), or darkness (p=0.029) at Month 4, with similar results at Month 6 (p<0.001, length; p<0.001, thickness; p=0.002, darkness). Responder rates reached 61.5 percent at Month 12 for subjects continuing bimatoprost and 67.6 percent for those switched from vehicle to bimatoprost. Conjunctival hyperemia (16.7%) and punctate keratitis (9.4%) were the most common adverse events. Conclusion: Bimatoprost provides rapid eyelash recovery, whether started shortly after chemotherapy (4 to 12 weeks) or delayed for six months, with minimal adverse events. Clinical trial registry: NCT00907426 PMID:26060513

  13. Cross-sectional Survey and Retrospective Analysis of a Large Cohort of Adults With Type 1 Diabetes With Long-Term Continuous Subcutaneous Insulin Infusion Treatment

    PubMed Central

    Morera, Julia; Vicente, Angel; Rod, Anne; Parienti, Jean-Jacques; Reznik, Yves

    2014-01-01

    Background. Continuous subcutaneous insulin infusion (CSII) is an established modality for intensive insulin treatment of type 1 diabetes (T1D), but long-term data concerning satisfaction, CSII function use, safety, and efficacy in real-life conditions are scarce. Methods. We analyzed a cohort of adult patients with T1D treated with CSII for more than 1 year in a single diabetes center. We performed a cross-sectional survey in 2010 (tolerance/satisfaction and behavior forms) and a retrospective analysis of medical records (including HbA1c level, hospitalization, and catheter infections). The primary objective was to assess long-term tolerance/satisfaction, and secondary objectives were safety and efficacy. Results. There were 295 patients analyzed. After a median duration of CSII use of 5 years, overall satisfaction was high for about 90% of patients. Mean CSII-related discomfort scores were low for work, recreation, and sleep and moderate for sport and sexual activity (2.5 ± 1.9, 2.6 ± 1.8, 2.6 ± 2.1, 3.4 ± 2.3, and 4.0 ± 2.9 of 10, respectively). Despite a high level of diabetes education, only one third of patients were using advanced CSII functions. During long-term follow-up, the safety of CSII treatment was good; the hospitalization rate was 0.18 patients/year, and catheter infections were scarce. The HbA1c level dropped about −0.5% independently from CSII duration (P < .05). Conclusions. In this adult cohort, satisfaction and tolerance, together with safety, of CSII were maintained at long-term follow up. The sole basic functions of CSII were currently used by patients. A 0.5% decrease in the HbA1c level was maintained during the study period. PMID:24876454

  14. Preclinical Rodent Toxicity Studies for Long Term Use of Ceftriaxone

    PubMed Central

    Ratti, Elena; Berry, James D.; Greenblatt, David J.; Loci, Lorena; Ellrodt, Amy Swartz; Shefner, Jeremy M.; Cudkowicz, Merit E.

    2015-01-01

    A 6-month rodent toxicology and pharmacokinetic (PK) study was performed to provide supportive safety data for long-term use of intravenous ceftriaxone in a clinical trial in patients with amyotrophic lateral sclerosis (ALS). Ceftriaxone was administered by subcutaneous injection at up to 2 g/kg/day to Sprague-Dawley Crl:CD (SD) rats. Ceftriaxone was found to be safe and well tolerated. Specifically, no significant differences in body weight and food consumption were observed between the treatment and control groups. With the exception of in red cell parameters decrease, there were no ceftriaxone-related changes in hematology, coagulation, clinical chemistry and urinalysis parameters. Injection site trauma and associated reversible anemia, likely due to chronic blood loss at the injection site, were all attributable to subcutaneous route of administration. Cecum dilatation and some skin changes were reversible after recovery period, while bile duct dilatation, observed only in a few animals, persisted. Changes in the non-glandular stomach do not have a human correlate. The no-observed-adverse-effect dose level (NOAEL) was 0.5 g/kg/day ceftriaxone in both sexes. Ceftriaxone showed rapid absorption with half-life values ranging between 1 and 1.5 hours. Additionally, there was no evidence of accumulation and a virtually complete elimination by 16 hours after the last dose. Overall there were no toxicologically meaningful drug-related animal findings associated with the long-term administration (6 months) of ceftriaxone. These results support safety of long-term use of ceftriaxone in human clinical trials. PMID:26705515

  15. Peptide-Based Anti-PCSK9 Vaccines - An Approach for Long-Term LDLc Management

    PubMed Central

    Galabova, Gergana; Brunner, Sylvia; Winsauer, Gabriele; Juno, Claudia; Wanko, Bettina; Mairhofer, Andreas; Lührs, Petra; Schneeberger, Achim; von Bonin, Arne; Mattner, Frank; Schmidt, Walter; Staffler, Guenther

    2014-01-01

    Background Low Density Lipoprotein (LDL) hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9) to modulate circulating LDL cholesterol (LDLc) concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb) therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models. Methods and Finding PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt) mice, Ldlr+/− mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC) concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested. Conclusions Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans. PMID:25474576

  16. Efficacy of a Food Safety Comic Book on Knowledge and Self-Reported Behavior for Persons Living with AIDS

    PubMed Central

    Dworkin, Mark S.; Peterson, Caryn E.; Gao, Weihua; Mayor, Angel; Hunter, Robert; Negron, Edna; Fleury, Alison; Besch, C. Lynn

    2013-01-01

    Introduction Persons living with AIDS are highly vulnerable to foodborne enteric infections with the potential for substantial morbidity and mortality. Educational materials about foodborne enteric infections intended for this immunocompromised population have not been assessed for their efficacy in improving knowledge or encouraging behavior change. Methods/Results AIDS patients in four healthcare facilities in Chicago, New Orleans, and Puerto Rico were recruited using fliers and word of mouth to healthcare providers. Those who contacted research staff were interviewed to determine food safety knowledge gaps and risky behaviors. A food safety educational comic book that targeted knowledge gaps was created, piloted, and provided to these patients who were instructed to read it and return at least 2 weeks later for a follow-up interview. The overall food safety score was determined by the number of the 26 knowledge/belief/behavior questions from the survey answered correctly. Among 150 patients who participated in both the baseline and follow-up questionnaire, the intervention resulted in a substantial increase in the food safety score (baseline 59%, post-intervention 81%, p<0.001). The intervention produced a significant increase in all the food safety knowledge, belief, and behavior items that comprised the food safety score. Many of these increases were from baseline knowledge below 80 percent to well above 90%. Most (85%) of the patients stated they made a change to their behavior since receiving the educational booklet. Conclusion This comic book format intervention to educate persons living with AIDS was highly effective. Future studies should examine to what extent long-term behavioral changes result. PMID:24124447

  17. Long-term reductions in tinnitus severity

    PubMed Central

    Folmer, Robert L

    2002-01-01

    Background This study was undertaken to assess long-term changes in tinnitus severity exhibited by patients who completed a comprehensive tinnitus management program; to identify factors that contributed to changes in tinnitus severity within this population; to contribute to the development and refinement of effective assessment and management procedures for tinnitus. Methods Detailed questionnaires were mailed to 300 consecutive patients prior to their initial appointment at the Oregon Health & Science University Tinnitus Clinic. All patients were then evaluated and treated within a comprehensive tinnitus management program. Follow-up questionnaires were mailed to the same 300 patients 6 to 36 months after their initial tinnitus clinic appointment. Results One hundred ninety patients (133 males, 57 females; mean age 57 years) returned follow-up questionnaires 6 to 36 months (mean = 22 months) after their initial tinnitus clinic appointment. This group of patients exhibited significant long-term reductions in self-rated tinnitus loudness, Tinnitus Severity Index scores, tinnitus-related anxiety and prevalence of current depression. Patients who improved their sleep patterns or Beck Depression Inventory scores exhibited greater reductions of tinnitus severity scores than patients who continued to experience insomnia and depression at follow-up. Conclusions Individualized tinnitus management programs that were designed for each patient contributed to overall reductions in tinnitus severity exhibited on follow-up questionnaires. Identification and treatment of patients experiencing anxiety, insomnia or depression are vital components of an effective tinnitus management program. Utilization of acoustic therapy also contributed to improvements exhibited by these patients. PMID:12234379

  18. Craniopharyngioma in Children: Long-term Outcomes

    PubMed Central

    STEINBOK, Paul

    2015-01-01

    The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

  19. Sleep facilitates long-term face adaptation

    PubMed Central

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as ‘storage’. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation—which are usually not considered to play a relevant role in mnemonic processes—with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  20. Long term changes in the polar vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  1. Sleep facilitates long-term face adaptation.

    PubMed

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  2. Long-Term Care Policy: Singapore's Experience.

    PubMed

    Chin, Chee Wei Winston; Phua, Kai-Hong

    2016-01-01

    Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co-payment and targeting of state support to the low-income population through means-tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers. PMID:26808468

  3. [Long-term results after liver transplantation].

    PubMed

    Schrem, H; Till, N; Becker, T; Bektas, H; Manns, M P; Strassburg, C P; Klempnauer, J

    2008-02-01

    Liver transplantation has been reported to reach excellent results for selected indications. We analysed the results of liver transplantation in our centre over a period of 23 years, with a total of 2,114 consecutive liver transplants in 1,773 patients (eras I-III 5.5 years each, era IV 6.5 years). Overall 20-year survival after liver transplantation was 29.8%. The most frequent leading causes of death were infections of various origins (30%), tumour recurrence (14.2%), and pneumonia (8.4%). The most frequent leading causes for graft loss were infection of various origins (19.6%), initial nonfunction of the graft (14.6%), and tumour recurrence (9.6%). Both long-term patient and graft survival were significantly better after primary liver transplantation than after first retransplantation (P<0.001). Patient and graft long-term survival improved significantly across all four consecutive eras (P<0.001). In era IV, the most recent, 5-year patient survival reached 96% for PBC, 89.4% for PSC, 78.5% for biliary atresia, 70% for acute liver failure, 69.1% for HBV-related cirrhosis, 61.3% for hepatocellular carcinoma, and 56% for HCV-related cirrhosis. PMID:18209988

  4. Long-term anticoagulation. Indications and management.

    PubMed Central

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

    1989-01-01

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

  5. Long-term preservation of anammox bacteria.

    PubMed

    Rothrock, Michael J; Vanotti, Matias B; Szögi, Ariel A; Gonzalez, Maria Cruz Garcia; Fujii, Takao

    2011-10-01

    Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass was frozen or lyophilized at two different freezing temperatures (-60°C and in liquid nitrogen (-200°C)) in skim milk media (with and without glycerol), and the reactivation of anammox activity was monitored after a 4-month storage period. Of the different preservation treatments tested, only anammox biomass preserved via freezing in liquid nitrogen followed by lyophilization in skim milk media without glycerol achieved stoichiometric ratios for the anammox reaction similar to the biomass in both the parent bioreactor and in the freshly harvested control treatment. A freezing temperature of -60°C alone, or in conjunction with lyophilization, resulted in the partial recovery of the anammox bacteria, with an equal mixture of anammox and nitrifying bacteria in the reactivated biomass. To our knowledge, this is the first report of the successful reactivation of anammox biomass preserved via sub-zero freezing and/or lyophilization. The simple preservation protocol developed from this study could be beneficial to accelerate the integration of anammox-based processes into current treatment systems through a highly efficient starting anammox biomass. PMID:21590289

  6. Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals

    PubMed Central

    Zhang, Ming-Duo; Li, Xin-He; Nie, Mao-Xiao; Feng, Ting-Ting; Zhao, Xin; Wang, Lu-Ya; Zhao, Quan-Ming

    2016-01-01

    Objective In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs). Methods PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted. Results Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61–0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57–0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33–0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents. Conclusion Our results indirectly suggest that BP-stainless DESs may offer more benefits than BP-alloy DESs in the era of BP-DESs. Further well-designed RCTs comparing BP-stainless with BP-alloy DESs are needed to confirm which platform is better. PMID:27032086

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

    PubMed Central

    2010-01-01

    Background Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment. Methods Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to