Science.gov

Sample records for long-term safety evaluation

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

    SciTech Connect

    Richard, R.F.

    1995-05-11

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

  2. 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.

  3. Long-term safety evaluation of a novel oxygen-coordinated niacin-bound chromium (III) complex.

    PubMed

    Shara, Michael; Kincaid, Anthony E; Limpach, Aimee L; Sandstrom, Robert; Barrett, Laura; Norton, Neil; Bramble, J D; Yasmin, Taharat; Tran, Janet; Chatterjee, Archana; Bagchi, Manashi; Bagchi, Debasis

    2007-07-01

    Chromium (III) is an essential micronutrient required for normal protein, fat and carbohydrate metabolism, as well as helps insulin metabolize fat, turn protein into muscle and convert sugar into energy. A broad spectrum of research investigations including in vitro, in vivo and clinical studies demonstrated the beneficial effects of novel oxygen- coordinated niacin-bound chromium (III) complex (NBC) in promoting glucose-insulin sensitivity, lipid profile, cardioprotective ability and lean body mass. This study examined the long-term safety of NBC by orally administering either 0 or 25 ppm or the human equivalency dose of 1000 microg elemental chromium (III) as NBC per day for 52 consecutive weeks to male and female Sprague-Dawley rats. Animals of each group and each gender were sacrificed on 26, 39, or 52 weeks of treatment. Body weight, physical and ocular health, feed and water intake, selected organ weights as such and as a percentage of liver and brain weight, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluations were conducted. At 26, 39, or 52 weeks of treatment, body weight gain was significantly reduced by 7.7%, 8.1% and 14.9% in male rats, and 5.5%, 11.4% and 9.6% in female rats, respectively, in the NBC treatment groups. No significant changes were observed in hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluation between control and NBC groups at these time points. These findings, thus far, are in agreement with the subchronic studies in terms of the safety of NBC. PMID:17555823

  4. Long-term safety of retinoid therapy.

    PubMed

    Vahlquist, A

    1992-12-01

    The concern about long-term toxicity of oral synthetic retinoids has developed because many patients, especially those with genodermatoses, require lifelong therapy. Several organ systems are at risk, especially the hepatic, skeletal, and cardiovascular systems. Although acute hepatotoxicity is a rare side effect of etretinate and acitretin therapy, prospective studies have not demonstrated chronic liver toxicity. The frequency of bone changes induced by retinoids is difficult to estimate, because this adverse effect is usually asymptomatic and requires x-ray or scintigraphic examination for detection. Atherosclerosis develops in many patients who receive long-term retinoid therapy, but the extent to which the process is aggravated by drug-induced hyperlipidemia is not known. Many patients have now been treated with either etretinate or isotretinoin continuously for as many as 15 years and have not developed any signs of severe chronic toxicity. However, continued intense surveillance is recommended for patients expected to require lifelong therapy. PMID:1460122

  5. 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.

  6. Long-term safety evaluation of bimatoprost ophthalmic solution 0.03%: a pooled analysis of six double-masked, randomized, active-controlled clinical trials

    PubMed Central

    Wirta, David; VanDenburgh, Amanda M; Weng, Emily; Whitcup, Scott M; Kurstjens, Sef; Beddingfield, Frederick C

    2011-01-01

    Background: Bimatoprost ophthalmic solution 0.03% was approved in the US for reducing intraoccular pressure (IOP) based on two double-masked, active-controlled clinical trials. Four additional long-term studies (≥12 months) were conducted; however, the aggregate safety profile of the six studies has not been reported. Methods: Adverse events (AEs) were pooled from six double-masked, active-controlled, long-term clinical trials in which subjects received bimatoprost 0.03% once daily (QD) or twice daily (BID) as an eyedrop. AE terms were converted to MedDRA (V.11.0) Preferred Terms and analyzed. Results: In total, 1409 patients received more than one dose of bimatoprost 0.03% QD or BID. Most AEs were mild in severity and reported by 86.7% (QD) and 94.8% (BID) of subjects (≤12 months of treatment). AEs reported through month 12 (aggregate incidence of ≥5%) were conjunctival hyperemia, increased eyelash growth, eye pruritus, periocular skin hyperpigmentation, eye irritation, dry eye, and hypertrichosis. AE onset was generally reported within four months of treatment. The cumulative incidence of common AEs in the QD treatment group at 24–48 months was similar to that measured at 12 months of treatment. Conclusion: Bimatoprost 0.03% has a favorable safety and tolerability profile as characterized by six long-term studies. Common AEs were due to the known pharmacological activity of bimatoprost and reversible with treatment cessation. PMID:21691584

  7. 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

  8. 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

  9. 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

  10. 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.

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

    PubMed Central

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

    2014-01-01

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

  12. The long-term safety and tolerability of ispaghula husk.

    PubMed

    Oliver, S D

    2000-06-01

    The safety and tolerability of ispaghula husk, which can now be used as an adjunct to diet for the treatment of mild-to-moderate hypercholesterolaemia, was assessed in 93 healthy subjects over a 52-week period. The study looked at the nutritional, biochemical, and haematological effects of ispaghula. Over the study period there were small but statistically significant changes in some measurements of minerals and vitamin levels, and in some haematological and biochemical parameters. However, none of these were of clinical significance, with the possible exception of changes in vitamin B12 levels. A daily dose of 10.5 g ispaghula was well tolerated and the majority of adverse events recorded were minor, of short duration and either unrelated or possibly related to the study treatment. The results suggest that ispaghula husk can be used with confidence for the long-term treatment of mild-to-moderate hypercholesterolaemia. PMID:10944885

  13. 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

  14. 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

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

    PubMed

    Mitra, Monjori; Shah, Nitin; Faridi, Mma; Ghosh, Apurba; Sankaranarayanan, V S; 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

  16. 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)

  17. Evaluation of Nonacog Beta Pegol Long-term Safety in the Immune-deficient Rowett Nude Rat (Crl:NIH-Foxn1rnu).

    PubMed

    Rasmussen, Caroline E; Nowak, Jette; Larsen, Julie M; Bottomley, Anna; Rowles, Alison; Offenberg, Hanne

    2016-07-01

    Nonacog beta pegol is a 40-kDa polyethylene glycosylated (PEGylated) human recombinant coagulation factor IX, intended for the treatment of hemophilia B. Human coagulation factors are immunogenic in animals; therefore, to evaluate the long-term toxicity of nonacog beta pegol, an immune-deficient, athymic rat (Rowett nude; Crl:NIH-Foxn1(rnu)) was used. Rats (n = 216) were given intravenous nonacog beta pegol 0, 40, 150, 600, or 1,200 IU/kg every 5th day for 26 weeks. To avoid infections, the animals were housed in a full-barrier environment with sterilized food and bedding. Standard toxicity end points were unaffected by treatment. All treated animals were exposed to nonacog beta pegol throughout the study, and no animals developed antidrug antibodies. Immunohistochemical staining revealed PEG in choroid plexus epithelial cells in a dose-dependent manner. Transmission electron microscopy showed that PEG was distributed in cytoplasmic vesicles of these cells, with no apparent effect on cellular organelle structures. Fourteen (6.5%) animals were euthanized or died prematurely due to nontreatment-related infections in the urogenital system and skin. In conclusion, the athymic rat is a suitable model for testing chronic toxicity of human proteins that are immunogenic in animals. Nonacog beta pegol was generally well tolerated, with no adverse effect of PEG on choroid plexus epithelial cells. PMID:26940713

  18. PLUME-SCALER-EVALUATING LONG-TERM MONITORING WELL NETWORKS

    EPA Science Inventory

    EPA's Subsurface Protection and Remediation Division is developing a new computer application called PLUME-SCALER to evaluate long term monitoring well networks using typically available historical site water level data. PLUME-SCALER can be used to determine if there are enough ...

  19. [Drug-eluting stents: long-term safety].

    PubMed

    Karpov, Iu A; Samko, A N; Buza, V V

    2009-01-01

    The review concerns the problem of late thromboses of drug-eluting stents and their influence on late prognosis of the patients; presents long-term results of the trial of sirolimus-eluting stents implanted to patients with coronary heart disease; analyses mechanisms of development of late stent thrombosis, data from different meta-analyses and registers comparing long-term outcomes in patients with implanted sirolimus-eluting stents and metallic stents; suggests risk factors of late thromboses of drug-eluting stents; presents original evidence on 3.5-year follow-up of patients with implanted sirolimus-eluting stents and metallic stents. PMID:19537584

  20. Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children

    PubMed Central

    Watanaveeradej, Veerachai; Simasathien, Sriluck; Mammen, Mammen P.; Nisalak, Ananda; Tournay, Elodie; Kerdpanich, Phirangkul; Samakoses, Rudiwilai; Putnak, Robert J.; Gibbons, Robert V.; Yoon, In-Kyu; Jarman, Richard G.; De La Barrera, Rafael; Moris, Philippe; Eckels, Kenneth H.; Thomas, Stephen J.; Innis, Bruce L.

    2016-01-01

    We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1–4 waned during the 1–3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response. PMID:27022153

  1. Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children.

    PubMed

    Watanaveeradej, Veerachai; Simasathien, Sriluck; Mammen, Mammen P; Nisalak, Ananda; Tournay, Elodie; Kerdpanich, Phirangkul; Samakoses, Rudiwilai; Putnak, Robert J; Gibbons, Robert V; Yoon, In-Kyu; Jarman, Richard G; De La Barrera, Rafael; Moris, Philippe; Eckels, Kenneth H; Thomas, Stephen J; Innis, Bruce L

    2016-06-01

    We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1-4 waned during the 1-3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response. PMID:27022153

  2. 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…

  3. Economic evaluation in long-term clinical trials.

    PubMed

    Hlatky, Mark A; Boothroyd, Derek B; Johnstone, Iain M

    2002-10-15

    Economic endpoints have been increasingly included in long-term clinical trials, but they pose several methodologic challenges, including how best to collect, describe, analyse and interpret medical cost data. Cost of care can be measured by converting billed charges, performing detailed micro-costing studies, or by measuring use of key resources and assigning cost weights to each resource. The latter method is most commonly used, with cost weights based either on empirical regression models or administratively determined reimbursement rates. In long-term studies, monetary units should be adjusted to reflect cost inflation and discounting. The temporal pattern of accumulating costs can be described using a modification of the Kaplan-Meier curve. Regression analyses to evaluate factors associated with cost are best performed on the log of costs due to their typically skewed distribution.Cost-effectiveness analysis attempts to measure the value of a new therapy by calculating the difference in cost between the new therapy and the standard therapy, divided by the difference in benefit between the new therapy and the standard therapy. The cost-effectiveness ratio based on the results of a randomized trial may change substantially with longer follow-up intervals, particularly for therapies that are initially expensive but eventually improve survival. A model that projects long-term patterns of cost and survival expected beyond the end of completed follow-up can provide an important perspective in the setting of limited trial duration. PMID:12325104

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

    PubMed Central

    Kim, Young Hyo; Jang, Tae Young

    2014-01-01

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

  5. 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

  6. 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

  7. SULFURIC ACID REMOVAL PROCESS EVALUATION: LONG-TERM RESULTS

    SciTech Connect

    Gary M. Blythe; Richard McMillan

    2002-07-03

    longer-term (approximately 25-day) full-scale tests on two different units. The longer-term tests were conducted to confirm the effectiveness of the sorbents tested over extended operation on two different boilers, and to determine balance-of-plant impacts. The first long-term test was conducted on FirstEnergy's BMP, Unit 3, and the second test was conducted on AEP's Gavin Plant, Unit 1. The Gavin Plant testing provided an opportunity to evaluate the effects of sorbent injected into the furnace on SO{sub 3} formed across an operating SCR reactor. This report presents the results from those long-term tests. The tests determined the effectiveness of injecting commercially available magnesium hydroxide slurry (Gavin Plant) and byproduct magnesium hydroxide slurry (both Gavin Plant and BMP) for sulfuric acid control. The results show that injecting either slurry could achieve up to 70 to 75% overall sulfuric acid removal. At BMP, this overall removal was limited by the need to maintain acceptable electrostatic precipitator (ESP) particulate control performance. At Gavin Plant, the overall sulfuric acid removal was limited because the furnace injected sorbent was less effective at removing SO{sub 3} formed across the SCR system installed on the unit for NOX control than at removing SO{sub 3} formed in the furnace. The long-term tests also determined balance-of-plant impacts from slurry injection during the two tests. These include impacts on boiler back-end temperatures and pressure drops, SCR catalyst properties, ESP performance, removal of other flue gas species, and flue gas opacity. For the most part the balance-of-plant impacts were neutral to positive, although adverse effects on ESP performance became an issue during the BMP test.

  8. Long-term evaluation of corneal endothelial cell transplantation.

    PubMed Central

    Mohay, J; Wood, T O; McLaughlin, B J

    1997-01-01

    PURPOSE: This report describes the clinical course, refractive changes, confocal microscopic and histological evaluation of corneal endothelial cell transplantation in rabbits with long-term follow-up. METHODS: Transplantation of corneal endothelial cells using a cell/carrier device was performed in 19 rabbits. Clinical evaluation between 1-25 months included slit-lamp examination, keratometry, retinoscopy and surface topography. Two grafts in rabbits with 12 and 24 month survivals were evaluated in vivo by 3D tandem scanning confocal microscopy. The same grafts were then processed for transmission electron microscopy. BrdU labeling of the grafted cells in one transplant was performed in order to distinguish between host and grafted endothelial cells. RESULTS: All grafts cleared and remained clear for an average of one year without signs of rejection or inflammation. Postoperative refraction data and topography of the transplants showed progressive development of myopia and steep corneas compared to the unoperated eyes in each case. Confocal microscopy in vivo demonstrated a regular hexagonal pattern of the transplanted endothelial cells and a thickened Descemet's membrane, which correlated with the light and electron microscopic findings. BrdU labeling of the grafted endothelial cells showed a homogenous labeling of cell nuclei 6 months after the transplantation. CONCLUSIONS: This study demonstrates that corneal endothelial cells grown on a biomaterial can be replaced and remain functional for a long period of time. Images FIGURE 1 FIGURE 2A FIGURE 2B FIGURE 2C FIGURE 3A FIGURE 3B FIGURE 4 FIGURE 5 FIGURE 6A FIGURE 6B FIGURE 7 FIGURE 8A FIGURE 8B FIGURE 8C FIGURE 8D FIGURE 8E FIGURE 8F FIGURE 9 PMID:9440167

  9. 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

  10. 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

  11. 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

  12. Long-term efficacy and safety of a generic atorvastatin in usual clinical care setting.

    PubMed

    Ong, L M; Punithavathi, N; Lena, Y L L; Mahanim, O; Leekha, S

    2011-08-01

    A multicentre study was conducted to assess the long term efficacy and safety of a generic atorvastatin in the treatment of primary hypercholesterolaemia. Eighty five patients who received 10mg or 20 mg of atorvastatin for 8 weeks depending on target cholesterol goal were followed up by their own physicians and had final evaluation at 52 weeks. Reduction in mean low density Lipoprotein (LDL-C) was 36.5%, 37.9% and 32.2% at weeks 4, 8 and 52 respectively. LDL-C target was maintained in 81% and 69% of patients at week 8 and 52 respectively without drug related serious adverse events. Generic atorvastatin is safe and effective in usual clinical care setting. PMID:22111443

  13. Right ventricular septal pacing: Safety and efficacy in a long term follow up

    PubMed Central

    Occhetta, Eraldo; Quirino, Gianluca; Baduena, Lara; Nappo, Rosaria; Cavallino, Chiara; Facchini, Emanuela; Pistelli, Paolo; Magnani, Andrea; Bortnik, Miriam; Francalacci, Gabriella; Dell’Era, Gabriele; Plebani, Laura; Marino, Paolo

    2015-01-01

    AIM: To evaluate the safety and efficacy of the permanent high interventricular septal pacing in a long term follow up, as alternative to right ventricular apical pacing. METHODS: We retrospectively evaluated: (1) 244 patients (74 ± 8 years; 169 men, 75 women) implanted with a single (132 pts) or dual chamber (112 pts) pacemaker (PM) with ventricular screw-in lead placed at the right ventricular high septal parahisian site (SEPTAL pacing); (2) 22 patients with permanent pacemaker and low percentage of pacing (< 20%) (NO pacing); (3) 33 patients with high percentage (> 80%) right ventricular apical pacing (RVA). All patients had a narrow spontaneous QRS (101 ± 14 ms). We evaluated New York Heart Association (NYHA) class, quality of life (QoL), 6 min walking test (6MWT) and left ventricular function (end-diastolic volume, LV-EDV; end-systolic volume, LV-ESV; ejection fraction, LV-EF) with 2D-echocardiography. RESULTS: Pacing parameters were stable during follow up (21 mo/patient). In SEPTAL pacing group we observed an improvement in NYHA class, QoL score and 6MWT. While LV-EDV didn’t significantly increase (104 ± 40 mL vs 100 ± 37 mL; P = 0.35), LV-ESV slightly increased (55 ± 31 mL vs 49 ± 27 mL; P = 0.05) and LV-EF slightly decreased (49% ± 11% vs 53% ± 11%; P = 0.001) but never falling < 45%. In the RVA pacing control group we observed a worsening of NYHA class and an important reduction of LV-EF (from 56% ± 6% to 43% ± 9%, P < 0.0001). CONCLUSION: Right ventricular permanent high septal pacing is safe and effective in a long term follow up evaluation; it could be a good alternative to the conventional RVA pacing in order to avoid its deleterious effects. PMID:26322189

  14. 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

  15. Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia

    PubMed Central

    Vishnu, Prakash; Aboulafia, David M

    2016-01-01

    Inhibition of platelet production and mediated by antiplatelet antibodies is a well-known mechanism causing low platelet counts in immune thrombocytopenia (ITP). Use of thrombopoietin receptor agonists increases platelet counts and decreases the risk of bleeding in patients with ITP. Two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are approved by the US Food and Drug Administration to treat thrombocytopenia in adults, and most recently, children with persistent or chronic ITP. This review focuses on the efficacy data and safety analysis of the pooled data from the clinical trials evaluating romiplostim for treatment of adults with ITP. The rates of hemorrhage, thrombosis, hematologic and nonhematologic cancers, and myelodysplastic syndrome were not overrepresented among the groups who received romiplostim versus placebo or other standard-of-care treatments. Yet, as after-market experience with thrombopoietin receptor agonists increases, there are emerging reports of increased incidence of thrombosis and bone marrow reticulin among patients who are treated with long-term use of these agents. Ongoing clinical research will continue to evaluate romiplostim’s efficacy and safety in other primary and secondary thrombocytopenic states. PMID:27307776

  16. Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes

    PubMed Central

    Löfqvist, Malin; Leinonen, Mika; Goldbach-Mansky, Raphaela; Olivecrona, Hans

    2016-01-01

    Objective. Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. Methods. A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. Results. In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. Conclusion. In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. Trial registration: ClincialTrials.gov, clinicaltrials.gov, NCT00069329 PMID:27143789

  17. 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

  18. 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.

  19. Overview of short- and long-term tolerability and safety of brexpiprazole in patients with schizophrenia.

    PubMed

    Kane, John M; Skuban, Aleksandar; Hobart, Mary; Ouyang, John; Weiller, Emmanuelle; Weiss, Catherine; U Correll, Christoph

    2016-07-01

    Second-generation antipsychotics have demonstrated efficacy for patients with schizophrenia but are associated with wide-ranging side effects. Brexpiprazole, a serotonin-dopamine activity modulator, has demonstrated efficacy in adult patients with schizophrenia. This paper provides an overview of the safety and tolerability of brexpiprazole in patients with schizophrenia through examination of pooled safety data from one Phase 2 and two Phase 3 6-week, short-term studies, and two open-label, 52-week, long-term studies. In the short-term studies, there were no reports of treatment-emergent adverse events (TEAEs) with an incidence≥5% and twice that of placebo in patients treated with brexpiprazole 2-4mg. In the long-term studies, TEAEs reported by ≥5% of patients were schizophrenia (10.7%), insomnia (8.0%), weight increase (7.7%), headache (6.0%), and agitation (5.2%). Akathisia rates were low in the short- (5.8%, pooled brexpiprazole group) and long-term studies (4.6%). Sedation rates were low in the short- (2.3%, pooled brexpiprazole group) and long-term studies (0.9%). Mean body weight increase was 1.1kg in both short- and long-term studies. For all studies, changes from baseline to last visit in laboratory parameters, electrocardiogram values, and vital signs were small and not clinically relevant. Changes in lipid profiles or other metabolic parameters were also small. Collectively, these studies suggest that brexpiprazole was well tolerated, with a favorable safety profile that does not exhibit significant rates of important adverse events that can be seen with existing antipsychotics (akathisia, sedation, weight gain, or QTc prolongation), and therefore may provide a useful treatment option for patients with schizophrenia. ClinicalTrials.gov: NCT00905307; NCT01396421; NCT01393613; NCT01649557; NCT01397786. PMID:27188270

  20. 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

  1. 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

  2. Evaluation of hand function in patients undergoing long term haemodialysis

    PubMed Central

    Limaye, V; Frankham, A; Disney, A; Pile, K

    2001-01-01

    OBJECTIVE—Haemodialysis is associated with the deposition of β2 microglobulin in musculoskeletal structures, leading to the syndrome of dialysis related amyloidosis and impairment of hand function. This study aimed at assessing hand function using the Sollerman test in a cross section of patients undergoing haemodialysis.
METHODS—Recipients of haemodialysis underwent the Sollerman test of hand grip function, which assesses 20 activities of daily living using eight grip types, and the JAMAR grip strength test, visual analogue scales (VAS) for pain (VAS-P) and function (VAS-F), and Health Assessment Questionnaire (HAQ) were determined. Results—Thirty five subjects (26 male), with mean age 53.2 years, participated. The average duration of haemodialysis was 6.2 years (range one month to 25 years). The median Sollerman score was 77, with 19/35 (54%) patients receiving haemodialysis having a score below the lower normal value of 78-80. The log Sollerman score correlated poorly with age (rs=0.16, p=0.35), and significantly with the HAQ score (rs=−0.66, p<0.00005), duration of haemodialysis (rs=−0.39, p<0.05), VAS-F (rs=−0.41, p<0.05), VAS-P (rs=−0.34, p<0.05), and JAMAR score (rs=0.57, p<0.05). Sollerman scores were highly correlated between dominant and non-dominant hands (rs=0.69, p<000005).
CONCLUSIONS—Hand dysfunction is a common finding among patients undergoing long term haemodialysis. The Sollerman test accurately reflects patient function as measured by HAQ, VAS-F, and grip strength, but less so pain. Its use for the early detection of dialysis related amyloidosis and in the serial monitoring of the effects of hand treatment programmes is encouraged.

 PMID:11171692

  3. Long-term Efficacy and Safety of Sitagliptin in Elderly Patients with Type 2 Diabetes Mellitus.

    PubMed

    Tada, Yuko; Kanazawa, Ippei; Notsu, Masakazu; Tanaka, Ken-Ichiro; Kiyohara, Nobuaki; Sasaki, Motofumi; Sugimoto, Toshitsugu

    2016-01-01

    Objective We herein conducted a retrospective study to evaluate the long-term efficacy and safety of sitagliptin treatment in elderly patients with type 2 diabetes mellitus. Methods We analyzed the changes in glycemic control in 112 Japanese type 2 diabetes patients over 65 years of age treated with 50 mg/day sitagliptin. Hemoglobin A1c (HbA1c) levels, liver and kidney functions, and usage of hypoglycemic agents were recorded for 24 months. Results HbA1c levels were significantly decreased, and the significance of HbA1c reduction was maintained during the observation period [from 7.7±1.1% to 7.2±0.7% (p<0.001) at the end of observational period]. The %change in HbA1c levels was significantly and negatively correlated with the baseline HbA1c levels (r=-0.51, p<0.001), but not with age, duration of diabetes, or the estimated glomerular filtration rate (eGFR). No patient experienced severe hypoglycemia episodes, and aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and the eGFR remained unchanged. The dose of sulfonylurea was finally decreased in 72% of patients treated with sulfonylurea. Conclusion Sitagliptin treatment continually decreases the HbA1c level for 24 months and is useful to reduce the dose of sulfonylurea in elderly patients with type 2 diabetes. PMID:27181532

  4. 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

  5. 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.

  6. Long-term safety assessment of live attenuated tetravalent dengue vaccines: deliberations from a WHO technical consultation.

    PubMed

    Bentsi-Enchill, Adwoa D; Schmitz, Julia; Edelman, Robert; Durbin, Anna; Roehrig, John T; Smith, Peter G; Hombach, Joachim; Farrar, Jeremy

    2013-05-28

    Dengue is a rapidly growing public health threat with approximately 2.5 billion people estimated to be at risk. Several vaccine candidates are at various stages of pre-clinical and clinical development. Thus far, live dengue vaccine candidates have been administered to several thousands of volunteers and were well-tolerated, with minimal short-term safety effects reported in Phase I and Phase II clinical trials. Based on the natural history of dengue, a theoretical possibility of an increased risk of severe dengue as a consequence of vaccination has been hypothesized but not yet observed. In October 2011, the World Health Organization (WHO) convened a consultation of experts in dengue, vaccine regulation and vaccine safety to review the current scientific evidence regarding safety concerns associated with live attenuated dengue vaccines and, in particular, to consider methodological approaches for their long-term evaluation. In this paper we summarize the scientific background and methodological considerations relevant to the safety assessment of these vaccines. Careful planning and a coordinated approach to safety assessment are recommended to ensure adequate long-term evaluation of dengue vaccines that will support their introduction and continued use. PMID:23570986

  7. Evidence for Long-term Efficacy and Safety of Gene Therapy for Wiskott–Aldrich Syndrome in Preclinical Models

    PubMed Central

    Marangoni, Francesco; Bosticardo, Marita; Charrier, Sabine; Draghici, Elena; Locci, Michela; Scaramuzza, Samantha; Panaroni, Cristina; Ponzoni, Maurilio; Sanvito, Francesca; Doglioni, Claudio; Liabeuf, Marie; Gjata, Bernard; Montus, Marie; Siminovitch, Katherine; Aiuti, Alessandro; Naldini, Luigi; Dupré, Loïc; Roncarolo, Maria Grazia; Galy, Anne; Villa, Anna

    2009-01-01

    Wiskott–Aldrich Syndrome (WAS) is a life-threatening X-linked disease characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancies. Gene therapy could represent a therapeutic option for patients lacking a suitable bone marrow (BM) donor. In this study, we analyzed the long-term outcome of WAS gene therapy mediated by a clinically compatible lentiviral vector (LV) in a large cohort of wasnull mice. We demonstrated stable and full donor engraftment and Wiskott–Aldrich Syndrome protein (WASP) expression in various hematopoietic lineages, up to 12 months after gene therapy. Importantly, we observed a selective advantage for T and B lymphocytes expressing transgenic WASP. T-cell receptor (TCR)-driven T-cell activation, as well as B-cell's ability to migrate in response to CXCL13, was fully restored. Safety was evaluated throughout the long-term follow-up of primary and secondary recipients of WAS gene therapy. WAS gene therapy did not affect the lifespan of treated animals. Both hematopoietic and nonhematopoietic tumors arose, but we excluded the association with gene therapy in all cases. Demonstration of long-term efficacy and safety of WAS gene therapy mediated by a clinically applicable LV is a key step toward the implementation of a gene therapy clinical trial for WAS. PMID:19259069

  8. 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)

  9. Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy

    PubMed Central

    Ford, Ian; Murray, Heather; Packard, Chris J.

    2016-01-01

    Background— Extended follow-up of statin-based low-density lipoprotein cholesterol lowering trials improves the understanding of statin safety and efficacy. Examining cumulative cardiovascular events (total burden of disease) gives a better appreciation of the clinical value of statins. This article evaluates the long-term impact of therapy on mortality and cumulative morbidity in a high-risk cohort of men. Methods and Results— The West of Scotland Coronary Prevention Study was a primary prevention trial in 45- to 64-year-old men with high low-density lipoprotein cholesterol. A total of 6595 men were randomized to receive pravastatin 40 mg once daily or placebo for an average of 4.9 years. Subsequent linkage to electronic health records permitted analysis of major incident events over 20 years. Post trial statin use was recorded for 5 years after the trial but not for the last 10 years. Men allocated to pravastatin had reduced all-cause mortality (hazard ratio, 0.87; 95% confidence interval, 0.80–0.94; P=0.0007), attributable mainly to a 21% decrease in cardiovascular death (hazard ratio, 0.79; 95% confidence interval, 0.69–0.90; P=0.0004). There was no difference in noncardiovascular or cancer death rates between groups. Cumulative hospitalization event rates were lower in the statin-treated arm: by 18% for any coronary event (P=0.002), by 24% for myocardial infarction (P=0.01), and by 35% for heart failure (P=0.002). There were no significant differences between groups in hospitalization for noncardiovascular causes. Conclusion— Statin treatment for 5 years was associated with a legacy benefit, with improved survival and a substantial reduction in cardiovascular disease outcomes over a 20-year period, supporting the wider adoption of primary prevention strategies. PMID:26864092

  10. 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

  11. Evaluation of long-term infusion of dexmedetomidine in critically ill patients: A retrospective analysis

    PubMed Central

    Abuhasna, Said; Al Jundi, Amer; Abdelatty, Wael; urRahman, Masood

    2012-01-01

    Background: Dexmedetomidine is an α2-receptor agonist used for sedation in the intensive care unit (ICU). It is currently FDA indicated for short-term use (i.e., less than 24 h). Objectives: To compare the safety and efficacy of dexmedetomidine if given long- term (>24 h) to short-term infusion (up to 24 h) for mechanically ventilated critically ill patients. Materials and Methods: The medical records of 73 patients were evaluated. Primary outcomes were significant changes in blood pressure or heart rate. Secondary outcomes included hospital and intensive care unit (ICU) length of stay (LOS), ventilator time, rate of reintubation, and rate of death. Statistical Analysis: Pair wise comparisons were based on independent student t-test for continuous data and Chi-square test for categorical data. Statistical difference was defined as P value < 0.05. Results: Of the patients evaluated, 50 received dexmedetomidine for more than 24 h and 23 patients received this agent for 24 h. Patients were similar at baseline except for age. Patients who received dexmedetomidine for more than 24 h were similar to the short-infusion arm in terms of the rate of bradycardia (8.6% vs10%; P = 0.22), hypotension episodes (30.4% vs 28%; P= 0.2), requirement of treatment for those episodes (37% vs 42%; P= 0.43), hospital LOS (30 days vs 38 days; P = 0.45), ICU LOS (14 days vs 19 days; P = 0.44), ventilation days (8 days vs 14 days; P =0.58), rate of reintubation (4% vs 10%; P = 0.79) and mortality (P = 0.2). Conclusion: Long-term dexmedetomidine infusion (> 24 h) had similar safety and clinical outcomes in patients receiving this agent for short-term. Due to the retrospective nature of our investigation, more well-designed studies are needed to confirm these findings. PMID:22837894

  12. Safety of long-term use of linezolid: results of an open-label study

    PubMed Central

    Vazquez, Jose A; Arnold, Anthony C; Swanson, Robert N; Biswas, Pinaki; Bassetti, Matteo

    2016-01-01

    Objective The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days). In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs) included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk, and central scotomas in each eye. Conclusion In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy. PMID:27621644

  13. 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.

  14. [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

  15. 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.

  16. 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

  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. Self-contained self-rescuer long term field evaluation: combined eighth and ninth phase results

    SciTech Connect

    2006-10-15

    The National Institute for Occupational Safety and Health (NIOSH) National Personal Protective Technology Laboratory (NPPTL) and the Mine Safety and Health Administration (MSHA) conduct a Long Term Field Evaluation (LTFE) program to evaluate deployed self-contained self rescuers (SCSRs). The objective of the program is to evaluate how well SCSRs endure the underground coal mining environment with regard to both physical damage and aging when they are deployed in accordance with Federal regulations (30 CFR 75.1714). This report presents findings of the combined eighth and ninth phases of the LTFE. For these phases, over four hundred SCSRs were evaluated. The units tested include the CSE SR-100, Draeger Oxy K-Plus, MSA Life-saver 60, and the OCENCO EBA 6.5. The OCENCO 20 was evaluated only in Phase 9. Testing was performed between December 2000 and April 2004. Results of the evaluation indicate that all SCSRs experience some performance degradation due to the mining environment. Observed degradation varies from elevated levels of carbon dioxide, high breathing resistance, and reduced capacity. Mechanical degradation to the SCSR components included breathing hoses, chemical beds, outer cases and seals. The LTFE tests discussed in this report are different from tests performed for SCSR certification to the requirements of 42 Code of Federal Regulations, Part 84 (42 CFR, Part 84). LTFE tests reported here are conducted to an end point, oxygen depletion, to enable comparison of the duration of new and deployed SCSRs. The method for obtaining deployed SCSRs for this evaluation was not a random selection from the deployed population of SCSRs. Although the results of these tests are useful for observing performance of the tested SCSRs, they are not representative of all deployed SCSRs. 9 refs., 10 figs., 9 tabs., 3 apps.

  19. Microcomputer programs for the evaluation of predictable long-term exposure.

    PubMed

    Re, M

    1985-07-01

    Some methods proposed for evaluation of predictable long-term exposure by statistical treatment of workshift exposure values are considered. Predictable long-term exposure is a useful parameter for risk assessment procedures, as it allows the evaluation of workplace hazards by taking into account interday variability of exposure to air contaminants. Statistical calculations required for evaluating predictable long-term exposure may be performed easily by hand-held programmable calculators. The programs reported here are for use with a Texas Instruments TI-59 hand-held programmable calculator equipped with a PC-100 C thermal printer. They are designed for users inexperienced in programming, since an interactive approach has been adopted that helps communication between user and computer. PMID:3880190

  20. Improving Service Quality in Long-term Care Hospitals: National Evaluation on Long-term Care Hospitals and Employees Perception of Quality Dimensions

    PubMed Central

    Kim, Jinkyung; Han, Woosok

    2012-01-01

    Objectives To investigate predictors for specific dimensions of service quality perceived by hospital employees in long-term care hospitals. Methods Data collected from a survey of 298 hospital employees in 18 long-term care hospitals were analysed. Multivariate ordinary least squares regression analysis with hospital fixed effects was used to determine the predictors of service quality using respondents’ and organizational characteristics. Results The most significant predictors of employee-perceived service quality were job satisfaction and degree of consent on national evaluation criteria. National evaluation results on long-term care hospitals and work environment also had positive effects on service quality. Conclusion The findings of the study show that organizational characteristics are significant determinants of service quality in long-term care hospitals. Assessment of the extent to which hospitals address factors related to employeeperceived quality of services could be the first step in quality improvement activities. Results have implications for efforts to improve service quality in longterm care hospitals and designing more comprehensive national evaluation criteria. PMID:24159497

  1. Evaluating the Long-Term Impacts of AmeriCorps Service on Participants. PRGS Dissertation

    ERIC Educational Resources Information Center

    Epstein, Diana

    2009-01-01

    Since 1993, over 500,000 people have served in AmeriCorps national service programs. This dissertation evaluates the long-term impacts of AmeriCorps service on participants, particularly in the areas of civic engagement, future volunteerism, appreciation of diversity, and a number of other job and life skills. It fills a gap by using both…

  2. Evaluating long-term trends in littoral benthic macroinvertebrate communities of lakes recovering from acid deposition.

    PubMed

    Lento, Jennifer; Dillon, Peter J; Somers, Keith M

    2012-12-01

    The Mann-Kendall test has been proposed as a nonparametric method to evaluate trends in long-term water quality datasets with missing values, serial correlation, and non-normality. However, this test has rarely been used to evaluate long-term trends in biological data. In this study, we used the Mann-Kendall test to evaluate trends in 15 years of data on benthic macroinvertebrate communities from 17 Precambrian Shield lakes. We also used the van Belle and Hughes test of trend homogeneity to assess whether common among-lake temporal trends existed. We assumed that evidence of a common regional trend among lakes would support the hypothesis of long-term biological recovery from past acidification. We found decreasing proportions of Chironomidae and increasing proportions of Ephemeroptera, Plecoptera, and Trichoptera (EPT) in both single-lake and multi-lake trend analysis. Moreover, six of the nine lakes with significant trends in more than one benthos metric displayed a significant decrease in Chironomidae and increase in EPT concurrently, indicating a shift towards more acid-sensitive taxa. Weak trends in several of the biological metrics indicated that recovery in these lakes has been impeded. Results of this study indicate that the Mann-Kendall and van Belle and Hughes trend tests are useful statistical tools to evaluate long-term patterns in biological data. PMID:22193633

  3. 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

  4. Computer simulation of microgravity long-term effects and risk evaluation

    NASA Astrophysics Data System (ADS)

    Perez-Poch, Antoni

    The objective of this work is to analyse and simulate possible long-term effects of microgravity on the human pulmonary function. It is also studied the efficacy of long-term regular exercise on relevant cardiovascular parameters when the human body is also exposed to microgravity. Little is known today about what long-term effects microgravity may cause on pulmonary function. It does not exist a complete explanation of the possible risks involved, although some experiments are under way on the ISS in order to evaluate them. Computer simulations are an important tool which may be used to predict and analyse these possible effects, and compare them with in-flight experiments. We based our study on a previous computer model (NELME: Numerical Evaluation of Long-term Microgravity Effects) which was developed in our laboratory and validated with the available data, focusing on the cardiovascular parameters affected by changes in gravity exposure. In this previous work we simulated part of the cardiovascular systems and we applied it to evaluate risks of blood-forming organs malfunction. NELME is based on an electrical-like control system model of the physiological changes, that may occur when gravity changes are applied. The computer implementation has a modular architecture. Hence, different output parameters, potential effects, organs and countermeasures can be easily implemented and evaluated. In this work we added a module to the system to analyse the pulmonary function with a gravity input parameter, as well as exposure time. We then conducted a battery of simulations when different values of g are applied for long-term exposures. We found no significant evidence of changes and no risks were foreseen. We also carried out an EVA simulation as a perturbation in the system (intense exercise, changes in breathed air) and studied the acute response. This is of great importance as current mission requirements do not allow data collection immediately following real EVAs

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

    PubMed Central

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

    2013-01-01

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

  7. 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

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

    PubMed Central

    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

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

    PubMed

    Monsivais, Jose Jesus; Monsivais, Diane Burn

    2014-07-01

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

  10. 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.

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

    PubMed Central

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

    2014-01-01

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

  12. Female long term survivors after allo-HSCT: evaluation and management

    PubMed Central

    Shanis, Dana; Merideth, Melissa; Pulanic, Tajana Klepac; Savani, Bipin N; Battiwalla, Minoo; Stratton, Pamela

    2011-01-01

    Female long term survivors of allogeneic hematopoietic stem cell transplantation incur a significant burden of late effects. Genital GVHD, HPV reactivation, ovarian failure and infertility, sexual dysfunction and osteoporosis are concerns that can significantly impact quality of life. This review examines the risk, pathogenesis, clinical presentation and implications of these common complications. Recommendations are provided for evaluation and management of these late effects, and other obstetric and gynecologic issues that may arise in this patient population. PMID:22221788

  13. 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

  14. Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease.

    PubMed

    Fanaroff, Alexander C; Roe, Matthew T

    2016-08-01

    Aspirin has been the cornerstone of therapy for the secondary prevention treatment of patients with cardiovascular disease since landmark trials were completed in the late 1970s and early 1980s that demonstrated the efficacy of aspirin for reducing the risk of ischemic events. Notwithstanding the consistent benefits demonstrated with aspirin for both acute and chronic cardiovascular disease, there are a number of toxicities associated with aspirin that have been showcased by recent long-term clinical trials that have included an aspirin monotherapy arm. As an inhibitor of cyclooxygenase (COX), aspirin impairs gastric mucosal protective mechanisms. Previous trials have shown that up to 15-20 % of patients developed gastrointestinal symptoms with aspirin monotherapy, and approximately 1 % of patients per year had a clinically significant bleeding event, including 1 in 1000 patients who suffered an intracranial or fatal bleed. These risks have been shown to be compounded for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI) who are also treated with other antithrombotic agents during the acute care/procedural period, as well as for an extended time period afterwards. Given observations of substantial increases in bleeding rates from many prior long-term clinical trials that have evaluated aspirin together with other oral platelet inhibitors or oral anticoagulants, the focus of contemporary research has pivoted towards tailored antithrombotic regimens that attempt to either shorten the duration of exposure to aspirin or replace aspirin with an alternative antithrombotic agent. While these shifts are occurring, the safety profile of aspirin when used for the secondary prevention treatment of patients with established cardiovascular disease deserves further consideration. PMID:27028617

  15. Model-based prediction of the acute and long-term safety profile of naproxen in rats

    PubMed Central

    Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert; Della Pasqua, Oscar

    2015-01-01

    Background and Purpose Despite the increasing importance of biomarkers as predictors of drug effects, toxicology protocols continue to rely on the experimental evidence of adverse events (AEs) as a basis for establishing the link between indicators of safety and drug exposure. Furthermore, biomarkers may facilitate the translation of findings from animals to humans. Combined with a model-based approach, biomarker data have the potential to predict long-term effects arising from prolonged drug exposure. Here, we used naproxen as a paradigm to explore the feasibility of a biomarker-guided approach for the prediction of long-term AEs in humans. Experimental Approach An experimental toxicology protocol was set up for evaluating the effects of naproxen in rats, in which four active doses were tested (7.5, 15, 40 and 80 mg·kg−1). In addition to AE monitoring and histology, a few blood samples were also collected for the assessment of drug exposure, TXB2 and PGE2 levels. Non-linear mixed effects modelling was used to analyse the data and identify covariate factors on the incidence and severity of AEs. Key Results Modelling results showed that besides drug exposure, maximum PGE2 inhibition and treatment duration were also predictors of gastrointestinal ulceration. Although PGE2 levels were clearly linked to the incidence rates, it appeared that ulceration severity is better predicted by measures of drug exposure. Conclusions and Implications These results show that the use of a model-based approach provides the opportunity to integrate pharmacokinetics, pharmacodynamics and toxicity data, enabling optimization of the design, analysis and interpretation of toxicology experiments. PMID:25884765

  16. Evaluation of Long-Term Migration Testing from Can Coatings into Food Simulants: Polyester Coatings.

    PubMed

    Paseiro-Cerrato, Rafael; Noonan, Gregory O; Begley, Timothy H

    2016-03-23

    FDA guidance for food contact substances recommends that for food packaging intended for use at sterilized, high temperature processed, or retorted conditions, a migration test with a retort step at 121 °C for 2 h followed by a 10 day migration test at 40 °C should be performed. These conditions are in intended to simulate processing and long-term storage. However, can coatings may be in contact with food for years, and there are very few data evaluating if this short-term testing accurately simulates migration over extended time periods. A long-term migration test at 40 °C with retorted and non-retorted polyester cans using several food simulants (water, 3% acetic acid, 10% ethanol, 50% ethanol, and isooctane) was conducted to verify whether traditional migration testing protocols accurately predict migration from food contact materials used for extended time periods. Time points were from 1 day to 515 days. HPLC-MS/MS was used to analyze polyester monomers, and oligomer migration was monitored using HPLC-DAD/CAD and HPLC-MS. Concentrations of monomers and oligomers increased during the migration experiments, especially in ethanol food simulants. The data suggest that current FDA migration protocols may need to be modified to address changes in migrants as a result of long-term storage conditions. PMID:26917426

  17. Review of Meniscal Allograft Transplantation Focusing on Long-term Results and Evaluation Methods.

    PubMed

    Lee, Bum-Sik; Kim, Jong-Min; Sohn, Dong-Wook; Bin, Seong-Il

    2013-03-01

    With recognition of the biomechanical role of the meniscus, such as load distribution and joint stability in the knee joint, there has been a shift in the treatment of meniscal tears from open total meniscectomy to preservation of the meniscal functions as much as possible with symptomatic relief. Recently, technical development of meniscal surgery, with advanced arthroscopic equipment and instruments, enables biological reconstruction of load bearing functions in the meniscus deficient knee through allograft tissue transplantation as well as repair of torn menisci. Meniscal allograft transplantation (MAT) has been considered as one of the few viable treatment options for the young meniscectomized knees based on various animal experiments and clinical studies. Still, there is insufficient evidence for the long-term chondroprotective effect of human MAT. Some long-term follow-up studies showed that the technique resulted in graft degeneration, deformation, and tear, and structural changes in the remodeling process in early MAT cases, disrupting functional restoration of the original meniscus. Nevertheless, advanced outcomes are documented in some recent studies. The purpose of this article is to review the mid- and long-term follow-up results of MAT and to improve understanding of MAT with evaluation methods of meniscal transplants using magnetic resonance imaging or second-look arthroscopy. PMID:23508067

  18. 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

  19. Long term effect and safety of Wharton's jelly-derived mesenchymal stem cells on type 2 diabetes

    PubMed Central

    Hu, Jianxia; Wang, Yangang; Gong, Huimin; Yu, Chundong; Guo, Caihong; Wang, Fang; Yan, Shengli; Xu, Hongmei

    2016-01-01

    Cellular therapies offer novel opportunities for the treatment of type 2 diabetes mellitus (T2DM). The present study evaluated the long-term efficacy and safety of infusion of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) on T2DM. A total of 61 patients with T2DM were randomly divided into two groups on the basis of basal therapy; patients in group I were administered WJ-MSC intravenous infusion twice, with a four-week interval, and patients in group II were treated with normal saline as control. During the 36-month follow-up period, the occurrence of any adverse effects and the results of clinical and laboratory examinations were recorded and evaluated. The lack of acute or chronic adverse effects in group I was consistent with group II.. Blood glucose, glycosylated hemoglobin, C-peptide, homeostasis model assessment of pancreatic islet β-cell function and incidence of diabetic complications in group I were significantly improved, as compared with group II during the 36-month follow-up. The results of the present study demonstrated that infusion of WJ-MSC improved the function of islet β-cells and reduced the incidence of diabetic complications, although the precise mechanisms are yet to be elucidated. The infusion of WJ-MSC may be an effective option for the treatment of patients with type 2 diabetes. PMID:27588104

  20. [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

  1. Advanced Evaluation of the Long-Term Stability of Oxygen Evolution Electrocatalysts.

    PubMed

    Maljusch, Artjom; Conradi, Oliver; Hoch, Sascha; Blug, Matthias; Schuhmann, Wolfgang

    2016-08-01

    Evaluation of the long-term stability of electrocatalysts is typically performed using galvanostatic polarization at a predefined current density. A stable or insignificant increase in the applied potential is usually interpreted as high long-term stability of the tested catalyst. However, effects such as (i) electrochemical degradation of a catalyst due to its oxidation, (ii) blocking of the catalyst surface by evolved gas bubbles, and (iii) detachment of the catalyst from the electrode surface may lead to a decrease of the catalyst's active surface area being exposed to the electrolyte. In order to separate these effects and to evaluate the true electrochemical degradation of electrocatalysts, an advanced evaluation protocol based on subsequently performed electrochemical impedance, double layer capacitance, cyclic voltammetry, and galvanostatic polarization measurements was developed and used to evaluate the degradation of IrO2 particles drop-coated on glassy carbon rotating disk electrode using Nafion as a binder. A flow-through electrochemical cell was developed enabling circulation of the electrolyte leading to an efficient removal of evolved oxygen bubbles even at high current densities of up to 250 mA/cm(2). The degradation rate of IrO2 was evaluated over 225 test cycles (0.733 ± 0.022 mV/h) with a total duration of galvanostatic polarization measurements of over 55 h. PMID:27398712

  2. 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

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

    PubMed Central

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

    2008-01-01

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

  4. Polysomnographic and long-term video electroencephalographic evaluation of cases presenting with parasomnias.

    PubMed

    Yiş, Uluç; Kurul, Semra Hiz; Öztura, Ibrahim; Ecevit, Mustafa Cenk; Dirik, Eray

    2013-09-01

    The aim of this study is to evaluate the clinical, electroencephalographic and polysomnographic features of patients presenting with parasomnias. Cases who were admitted for differentiating parasomnias from epilepsy were included in the study. Clinical features of cases were recorded and routine sleep electroencephalography was obtained from all cases. Cases whose symptoms strongly suggested nocturnal seizure underwent all night video electroencephalography monitoring. Polysomnography was obtained to evaluate the quality of breathing from patients whose symptoms suggested obstructive sleep apnea. Twenty-three patients with no neurological disorder were included in the study. The mean age of the patients was 11.7 ± 2.8 [7-17] years. Twelve patients (52 %) presented with sleep terrors and 11 patients (48 %) presented with sleep walking. All of the patients underwent a routine sleep electroencephalographic study and 15 patients (65 %) whose symptoms strongly suggested nocturnal epilepsy underwent long-term video electroencephalographic evaluation. Ten patients (43 %) underwent polysomnographic study. Three patients (20 %) who underwent long-term video electroencephalographic evaluation were diagnosed to have nocturnal frontal lobe epilepsy and two patients (20 %) who underwent polysomnography had pathological sleep apnea. Eleven patients (48 %) had a psychiatric disorder like major depression, anxiety disorder, hyperactivity disorder and obsessive-compulsive disorder. Childhood cases presenting with parasomnias should be searched for nocturnal epileptic disorders, sleep disordered breathing and psychiatric disorders. PMID:23135782

  5. Evaluation of different validation strategies and long term effects in NIR calibration models.

    PubMed

    Sileoni, Valeria; Marconi, Ombretta; Perretti, Giuseppe; Fantozzi, Paolo

    2013-12-01

    Stable and reliable NIR calibration models for the barley malt quality assessment were developed and exhaustively evaluated. The measured parameters are: fine extract, fermentability, pH, soluble nitrogen, viscosity, friability and free-amino nitrogen. The reliability of the developed calibration models was evaluated comparing the classic leave-one-out internal validation with a more challenging one exploiting re-sampling scheme. The long-term effects, intended as possible alterations of the NIR method predictive power, due to the variation between samples collected in different years, were evaluated through an external validation which demonstrated the stability of the developed calibration models. Finally, the accuracy and the precision of the developed calibration models were evaluated in comparison with the reference methods. This exhaustive evaluation offers a realistic idea of the developed NIR methods predictive power for future unknown samples and their application in the beer industry. PMID:23871006

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

    PubMed Central

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

    2014-01-01

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

  7. 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

  8. Long-term evaluation of a liquid crystal polymer (LCP)-based retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Jeong, Joonsoo; Bae, So Hyun; Seo, Jong-Mo; Chung, Hum; Kim, Sung June

    2016-04-01

    Objective. The aim of this study is to evaluate the long-term reliability of a recently presented liquid crystal polymer (LCP) -based retinal prosthesis in vitro as well as in vivo. Because an all-polymer implant introduces another intrinsic leak type due to gas permeation, for which the traditional helium leak test for metallic packages was not designed to quantify, a new method to investigate its durability is required. Approach. We designed and carried out a series of reliability tests specifically for all-polymer implants by quantitatively investigating moisture ingress through various pathways of the polymer surface, and the polymer-polymer and polymer-metal adhesions. Moisture permeation through the bulk material was estimated by analytic calculation, while water ingress through the adhesively sealed LCP-LCP and LCP-metal interfaces was investigated using the separate parts of an electrode array and a package in an accelerated aging condition. In vivo tests were done in rabbits to examine the long-term biocompatibility and implantation stability by fundus observation and optical coherence tomography (OCT) imaging. Main results. The analytic calculation estimated good barrier properties of the LCP. Samples of the LCP-based electrode array failed after 114 days in 87 °C saline as a result of water penetration through the LCP-metal interface. An eye-conformable LCP package survived for 87 days in an accelerated condition at 87 °C. The in vivo results confirmed that no adverse effects were observed around the retina 2.5 years after the implantation of the device. Significance. These long-term evaluation results show the potential for the chronic use of LCP-based biomedical implants to provide an alternative to traditional metallic packages.

  9. Long Term Stability Evaluation of Prostacyclin Released from Biomedical Device Through Turbiscan Lab Expert

    PubMed Central

    Celia, Christian; Locatelli, Marcello; Cilurzo, Felisa; Cosco, Donato; Gentile, Emanuela; Scalise, Daniela; Carafa, Maria; Ventura, Cinzia Anna; Fleury, Mathias; Tisserand, Christelle; Barbacane, Renato C.; Fresta, Massimo; Marzio, Luisa Di; Paolino, Donatella

    2015-01-01

    Therapeutic guidelines indicate prostacyclin as the first line of treatment in inflammation and vascular diseases. Prostacyclins prevent formation of the platelet plug involved in primary hemostasis by inhibiting platelet activation and, combined with thromboxane, are effective vasodilators in vascular damage. Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease II guidelines indicates prostacyclins; in particular, Iloprost, as the first therapeutic option for treating peripheral arterial disease. However, therapeutic efficacy of Iloprost has witnessed several drawbacks that have occurred in patients receiving repeated weekly administration of the drug by intravenous infusions. Adverse reactions arose under perfusion with Iloprost for 6 h and patient compliance was drastically decreased. Biomedical devices could provide a suitable alternative to overcome these drawbacks. In particular, elastomeric pumps, filled with Iloprost isotonic solution, could slowly release the drug, thus decreasing its side effects, representing a valid alternative to hospitalization of patients affected by peripheral arterial disease. However, the home therapy treatment of patients requires long-term stability of Iloprost in solution-loaded elastomeric pumps. The aim of this work was to investigate the long-term stability of Iloprost isotonic solution in biomedical devices using Turbiscan technology. Turbiscan Lab Expert (L’Union, France) predicts the long-term stability of suspensions, emulsions and colloidal formulations by measuring backscattering and transmission of particulates dispersed in solution. The formulations were evaluated by measuring the variation of physical-chemical properties of colloids and suspensions as a function of backscattering and transmission modifications. In addition, the release profile of Iloprost isotonic solution from the biomedical device was evaluated. PMID:25381994

  10. Detecting long-term growth trends using tree rings: a critical evaluation of methods.

    PubMed

    Peters, Richard L; Groenendijk, Peter; Vlam, Mart; Zuidema, Pieter A

    2015-05-01

    Tree-ring analysis is often used to assess long-term trends in tree growth. A variety of growth-trend detection methods (GDMs) exist to disentangle age/size trends in growth from long-term growth changes. However, these detrending methods strongly differ in approach, with possible implications for their output. Here, we critically evaluate the consistency, sensitivity, reliability and accuracy of four most widely used GDMs: conservative detrending (CD) applies mathematical functions to correct for decreasing ring widths with age; basal area correction (BAC) transforms diameter into basal area growth; regional curve standardization (RCS) detrends individual tree-ring series using average age/size trends; and size class isolation (SCI) calculates growth trends within separate size classes. First, we evaluated whether these GDMs produce consistent results applied to an empirical tree-ring data set of Melia azedarach, a tropical tree species from Thailand. Three GDMs yielded similar results - a growth decline over time - but the widely used CD method did not detect any change. Second, we assessed the sensitivity (probability of correct growth-trend detection), reliability (100% minus probability of detecting false trends) and accuracy (whether the strength of imposed trends is correctly detected) of these GDMs, by applying them to simulated growth trajectories with different imposed trends: no trend, strong trends (-6% and +6% change per decade) and weak trends (-2%, +2%). All methods except CD, showed high sensitivity, reliability and accuracy to detect strong imposed trends. However, these were considerably lower in the weak or no-trend scenarios. BAC showed good sensitivity and accuracy, but low reliability, indicating uncertainty of trend detection using this method. Our study reveals that the choice of GDM influences results of growth-trend studies. We recommend applying multiple methods when analysing trends and encourage performing sensitivity and reliability

  11. 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 2–3 years, significant decreases in the heterogeneity of material properties such as mineralization of the BSUs have been observed. In the long term (5–10 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

  12. 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

  13. Predictions of long-term performance of granular iron permeable reactive barriers: field-scale evaluation.

    PubMed

    Jeen, Sung-Wook; Gillham, Robert W; Przepiora, Andrzej

    2011-04-01

    Long-term performance is a key consideration for the granular iron permeable reactive barrier (PRB) technology because the economic benefit relies on sustainable operation for substantial periods of time. However, predictions on the long-term performance have been limited mainly because of the lack of reliable modeling tools. This study evaluated the predictive capability of a recently-developed reactive transport model at two field-scale PRBs, both having relatively high concentrations of dissolved carbonate in the native groundwater. The first site, with 8 years of available monitoring data, was a funnel-and-gate installation, with a low groundwater velocity through the gate (about 0.12 m d(-1)). The loss in iron reactivity caused by secondary mineral precipitation was small, maintaining relatively high removal rates for chlorinated organics. The simulated concentrations for most constituents in the groundwater were within the range of the monitoring data. The second site, with monitoring data available for 5 years, was a continuous wall PRB, designed for a groundwater velocity of 0.9 m d(-1). A comparison of measured and simulated aqueous concentrations suggested that the average groundwater velocity through the PRB could be lower than the design value by a factor of two or more. The distribution and amounts of carbonate minerals measured in core samples supported the decreased groundwater velocity used in the simulation. The generally good agreement between the simulated and measured aqueous and solid-phase data suggest that the model could be an effective tool for predicting long-term performance of granular iron PRBs, particularly in groundwater with high concentrations of carbonate. PMID:21237528

  14. Hydrodynamic evaluation of long term impacts of climate change and coastal effluents in the Arabian Gulf.

    PubMed

    Elhakeem, Abubaker; Elshorbagy, Walid

    2015-12-30

    A comprehensive basin wide hydrodynamic evaluation has been carried out to assess the long term impacts of climate change and coastal effluents on the salinity and seawater temperature of the Arabian Gulf (AG) using Delft3D-Flow model. The long term impacts of climate change scenarios A2 and B1 of the IPCC-AR4 on the AG hydrodynamics were evaluated. Using the current capacity and production rates of coastal desalination, power, and refinery plants, two projection scenarios until the year 2080 with 30 year intervals were developed namely the realistic and the optimistic discharge scenarios. Simulations of the individual climate change scenarios ascertained overall increase of the AG salinity and temperature and decrease of precipitation. The changes varied spatially with different scenarios as per the depth, proximity to exchange with ocean water, flushing, vertical mixing, and flow restriction. The individual tested scenarios of coastal projected discharges showed significant effects but within 10-20 km from the outfalls. PMID:26522165

  15. Automated analysis of phantom images for the evaluation of long-term reproducibility in digital mammography

    NASA Astrophysics Data System (ADS)

    Gennaro, G.; Ferro, F.; Contento, G.; Fornasin, F.; di Maggio, C.

    2007-03-01

    The performance of an automatic software package was evaluated with phantom images acquired by a full-field digital mammography unit. After the validation, the software was used, together with a Leeds TORMAS test object, to model the image acquisition process. Process modelling results were used to evaluate the sensitivity of the method in detecting changes of exposure parameters from routine image quality measurements in digital mammography, which is the ultimate purpose of long-term reproducibility tests. Image quality indices measured by the software included the mean pixel value and standard deviation of circular details and surrounding background, contrast-to-noise ratio and relative contrast; detail counts were also collected. The validation procedure demonstrated that the software localizes the phantom details correctly and the difference between automatic and manual measurements was within few grey levels. Quantitative analysis showed sufficient sensitivity to relate fluctuations in exposure parameters (kVp or mAs) to variations in image quality indices. In comparison, detail counts were found less sensitive in detecting image quality changes, even when limitations due to observer subjectivity were overcome by automatic analysis. In conclusion, long-term reproducibility tests provided by the Leeds TORMAS phantom with quantitative analysis of multiple IQ indices have been demonstrated to be effective in predicting causes of deviation from standard operating conditions and can be used to monitor stability in full-field digital mammography.

  16. Long-term cardiovascular evaluation of patients with Hodgkin's disease treated by thoracic mantle radiation therapy

    SciTech Connect

    Applefeld, M.M.; Slawson, R.G.; Spicer, K.M.; Singleton, R.T.; Wesley, M.N.; Wiernik, P.H.

    1982-04-01

    The long-term cardiac effects of anterior-weighted thoracic mantle field radiotherapy were assessed in 25 patients treated for Hodgkin's disease. These patients underwent an evaluation that included a careful history and physical examination, ECG, M-mode echocardiogram, exercise ECG-gated radionuclide ventriculography, and cardiac catheterization. In these 25 patients evaluated 37-144 months (median, 96) after completion of thoracic mantle radiotherapy, eight had constrictive pericarditis; eight had occult constrictive pericarditis; three had an abnormal response to fluid challenge; three had suspected or proven occlusive coronary artery disease; and one each had a cardiomyopathy and diminished functional capacity on exercise testing. Only one patient appears to be normal after evaluation. The clinical spectrum of delayed-appearing radiation-induced cardiac disease in patients treated by anterior-weighted thoracic mantle fields and our suggestions for its treatment are discussed.

  17. Short-term and long-term safety and tolerability of interferon β-1b in multiple sclerosis.

    PubMed

    Reder, Anthony T; Oger, Joel F; Kappos, Ludwig; O'Connor, Paul; Rametta, Mark

    2014-05-01

    Clinical trials have generated a wealth of data on the safety profile of interferon β-1b for patients with multiple sclerosis (MS). In general, interferon β-1b has not been associated with serious or life-threatening side effects during long-term treatment. Flu-like symptoms, injection site reactions, depression, and elevated liver transaminases were the most common adverse events in clinical trials. This review will discuss the rates of these and other common adverse events observed in 3 clinical trials of interferon β-1b: BENEFIT, BEYOND, and the 16-year Long-Term Follow-up (LTF) of the pivotal interferon β-1b trial in MS, as well as how these adverse events may influence patient and physician decision making when selecting a disease-modifying therapy. In addition, we will discuss the effects of interferon β-1b on mortality in the 16-year and 21-year LTF studies. PMID:25876467

  18. 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…

  19. 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

  20. 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

  1. Evaluation of the long-term sound reduction performance of resilient materials in floating floor systems

    NASA Astrophysics Data System (ADS)

    Lee, Jung-Yoon; Kim, Jong-Mun; Kim, Jinyoung; Kim, Jeongho

    2016-03-01

    Building multi-dwelling units is one of the practical engineering solutions to housing shortage in urban areas with high population density. However, noise from upstairs is a major issue. The use of resilient materials in floating floor structures is recognized as an effective method to reduce such noise. In general, soft materials are considered as better resilient materials due to their superior performance in impact sound reduction. However, it is often overlooked that the sound reduction performance of soft resilient materials is susceptible to being degraded over time when subjected to a long-term load. In this study, the long-term performance of eight resilient materials is evaluated by monitoring their dynamic stiffness for 270 days under the two sustained load conditions: 250 N and 500 N. According to the experimental study, the dynamic stiffness increases consistently with loading time for all resilient materials. This leads to a decrease in the sound reduction performance. More rapid reduction in the dynamic stiffness and hence in the sound reduction performance is observed when a larger sustained load is applied. A greater decrease in the sound reduction performance is found in soft resilient materials.

  2. The development and evaluation of mutual support groups in long-term care homes.

    PubMed

    Theurer, Kristine; Wister, Andrew; Sixsmith, Andrew; Chaudhury, Habib; Lovegreen, Loren

    2014-06-01

    This article describes the development of a new mutual support group intervention for long-term care homes (LTCH); evaluates the processes, structure, and content of the intervention; and addresses replication and sustainability. Tom Kitwood's model of personhood is used as the basis for developing a weekly discussion group using themes chosen by participants and theme-associated music, readings, and photographs. A mixed-methods qualitative process evaluation design encompasses focus groups, systematic observation of six resident groups, individual resident interviews (N = 65), and staff interviews (N = 7) in three LTCH in British Columbia, Canada. Resident reports and observations indicate positive benefits including a decrease in loneliness, the development of friendships, and increased coping skills, understanding, and support. Participating staff reported numerous benefits and described how the unique group structure fosters active participation of residents with moderate-severe cognitive impairment. This preliminary study suggests that mutual support groups have potential to offset loneliness, helplessness, and depression within LTCH. PMID:24781963

  3. Impact of medical students' descriptive evaluations on long-term course development

    PubMed Central

    Wahlqvist, Mats; Skott, Annika; Björkelund, Cecilia; Dahlgren, Gösta; Lonka, Kirsti; Mattsson, Bengt

    2006-01-01

    Background In medical education, feedback from students is helpful in course evaluation. However, the impact of medical students' feedback on long-term course development is seldom reported. In this project we studied the correspondence between medical students' descriptive evaluations and key features of course development over five years. Methods Qualitative content analysis was used. The context was consultation skills courses in the middle of the Göteborg undergraduate curriculum during five years. An analysis of 158 students' descriptive evaluations was brought together with an analysis of key features of course development; learning objectives, course records, protocols from teachers' evaluations and field notes. Credibility of data was tested by two colleagues and by presenting themes at seminars and conferences. Authors' experiences of evaluating the course over many years were also used. Results A corresponding pattern was found in students' descriptive evaluations and key features of course development, indicating the impact of students' open-ended feed-back. Support to facilitators and a curriculum reform also contributed. Students' descriptive feedback was both initiating and validating longitudinal course implementation. During five years, students' descriptive evaluations and teachers' course records were crucial sources in a learner-centred knowledge-building process of course development. Conclusion Students' descriptive evaluations and course records can be seen as important instruments in developing both courses and students' learning. Continuity and endurance in the evaluation process must be emphasized for achieving relevant and useful results. PMID:16638146

  4. 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

  5. Congenital adrenal hyperplasia: long-term evaluation of feminizing genitoplasty and psychosocial aspects.

    PubMed

    Gupta, D K; Shilpa, Sharma; Amini, A C; Gupta, M; Aggarwal, Gautam; Deepika, Gupta; Kamlesh, Khatri

    2006-11-01

    Analyzing the long-term outcome in females with congenital adrenal hyperplasia (CAH) is crucial to evaluate effectiveness of treatment strategies. The aim of the study was to evaluate the long-term results in patients with CAH after feminizing surgery from the pediatric intersex clinic. Of 163 patients of CAH being followed (1980-2005), 50 responded for review. The patients had undergone feminizing genitoplasty and hormonal therapy. Evaluation included filling a detailed questionnaire along with physical examination and a structured interview in privacy. Assessment was performed for cosmetic results (50), psychosocial adjustment (42) above 5-year age, and functional outcome in 19 cases above 14-year age. Mean age at clitoroplasty was 3.6 years (1-16 years) and at time of the study was 14.6 years (4-23 years), with a mean post-op follow up of 6 years after the final surgery (6 months-17 years). The cosmetic outcome of clitoroplasty was excellent in 37, satisfactory in 10, and poor in 3. Gender identity was female, male, and mixed in 45, 4, and 1, respectively. The attitude to self and life was positive in 36 and negative in 6. The functional outcome of vaginoplasty was satisfactory, unsatisfactory, and undetermined in 11, 4, and 4, respectively. Endocrine control was satisfactory in 36/50. A novel assessment system has been adopted for analyzing the results of clitoroplasty and vaginoplasty. Endocrine control and surgical treatment are complimentary to each other to achieve satisfactory results in majority of CAH patients. PMID:16947028

  6. Criteria for the evaluation and certification of long-term digital archives in the earth sciences

    NASA Astrophysics Data System (ADS)

    Klump, Jens

    2010-05-01

    Digital information has become an indispensable part of our cultural and scientific heritage. Scientific findings, historical documents and cultural achievements are to a rapidly increasing extent being presented in electronic form - in many cases exclusively so. However, besides the invaluable advantages offered by this form, it also carries a serious disadvantage: users need to invest a great deal of technical effort in accessing the information. Also, the underlying technology is still undergoing further development at an exceptionally fast pace. The rapid obsolescence of the technology required to read the information combined with the frequently imperceptible physical decay of the media themselves represents a serious threat to preservation of the information content. Many data sets in earth science research are from observations that cannot be repeated. This makes these digital assets particularly valuable. Therefore, these data should be kept and made available for re-use long after the end of the project from which they originated. Since research projects only run for a relatively short period of time, it is advisable to shift the burden of responsibility for long-term data curation from the individual researcher to a trusted data repository or archive. But what makes a trusted data repository? Each trusted digital repository has its own targets and specifications. The trustworthiness of digital repositories can be tested and assessed on the basis of a criteria catalogue. This is the main focus of the work of the nestor working group "Trusted repositories - Certification". It identifies criteria which permit the trustworthiness of a digital repository to be evaluated, both at the organisational and technical levels. The criteria are defined in close collaboration with a wide range of different memory organisations, producers of information, experts and other interested parties. This open approach ensures a high degree of universal validity, suitability for

  7. Gasbuggy, New Mexico Long-Term Hydrologic Monitoring Program Evaluation Report

    SciTech Connect

    2009-06-01

    This report summarizes an evaluation of the Long-Term Hydrologic Monitoring Program (LTHMP) that has been conducted since 1972 at the Gasbuggy, New Mexico underground nuclear detonation site. The nuclear testing was conducted by the U.S. Atomic Energy Commission under the Plowshare program, which is discussed in greater detail in Appendix A. The detonation at Gasbuggy took place in 1967, 4,240 feet below ground surface, and was designed to fracture the host rock of a low-permeability natural gas-bearing formation in an effort to improve gas production. The site has historically been managed under the Nevada Offsites Project. These underground nuclear detonation sites are within the United States but outside of the Nevada Test Site where most of the experimental nuclear detonations conducted by the U.S. Government took place. Gasbuggy is managed by the U.S. Department of Energy (DOE) Office of Legacy Management (LM ).

  8. Apples and oranges? A review of evaluations of community-based long-term care.

    PubMed Central

    Hughes, S L

    1985-01-01

    This article synthesizes the contradictory findings of the community-based long-term care evaluation literature by grouping 13 studies into three models of care tested. All studies are reviewed according to tenets of internal and external/construct validity to ascertain what is "known" and "not known" about the effectiveness of this new type of care, and to specify areas needing further research. Findings suggest that increased preoperational specification of underlying theory, increased sophistication in targeting services to high-risk groups, use of multivariate analysis, and the development of more relevant outcome measures will improve the quality of future study findings, thereby contributing to theory and model building in this field. PMID:3932261

  9. 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

  10. Evaluation of long-term maintenance of a large medical knowledge base.

    PubMed Central

    Giuse, D A; Giuse, N B; Miller, R A

    1995-01-01

    OBJECTIVE: Evaluate the effects of long-term maintenance activities on existing portions of a large internal medicine knowledge base. DESIGN: Five physicians who were not among the original developers of the knowledge base independently updated a total of 15 QMR disease profiles; each updated submission was modified by a review of group serving as the "gold standard, " and the pre- and post-study versions of each updated disease profile were compared. MEASUREMENTS: Numbers and types of changes, defined as any difference between the original version and the final version of a disease profile; reason for each change; and bibliographic references cited by the physicians as supporting evidence. RESULTS: A total of 16% of all entries were modified by the updating process; up to 95% of the entries in a disease profile were affected. The two most common modifications were changes to the frequency of an entry, and creation of a new entry. Laboratory findings were affected much more often than were history, symptom, or physical exam findings. The dominant reason for changes was appearance of new evidence in the medical literature. The literature cited ranged from 1944 to the present. CONCLUSIONS: This study provides an evaluation of the rate of change within the QMR medical knowledge base due to long-term maintenance. The results show that this is a demanding activity that may profoundly affect certain portions of a knowledge base, and that different types of knowledge (e.g., simple laboratory vs expensive or invasive laboratory findings) are affected by the process in different ways. PMID:7496879

  11. Efficacy and safety of hydrostatic balloon dilation of ileocolonic Crohn's strictures. A prospective long-term analysis.

    PubMed

    Gevers, A M; Couckuyt, H; Coremans, G; Hiele, M; Rutgeerts, P

    1994-01-01

    Gastro-intestinal stricture frequently is a complication in Crohn's disease and often recurs after surgical resection. Stenosis with acute inflammation can be treated by anti-inflammatory medication. A conservative approach of sclerotic strictures has been possible since the introduction of Gruentzig balloon catheters for dilating stenosis in different parts of the gastro-intestinal tract. We present a prospective follow-up study in 55 patients, on the long-term results and safety of hydrostatic balloon dilations of ileo-colonic Crohn's strictures. PMID:7709702

  12. 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

  13. Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Wise, Andrew K.; Fallon, James B.; Shepherd, Robert K.

    2015-06-01

    Objective. Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. Approach. We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. Main results. In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as ‘partial-FMP’ stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). Significance. The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode

  14. 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

  15. Evaluation of the long-term performance of six alternative disposal methods for LLRW

    SciTech Connect

    Kossik, R.; Sharp, G.; Chau, T.

    1995-12-31

    The State of New York has carried out a comparison of six alternative disposal methods for low-level radioactive waste (LLRW). An important part of these evaluations involved quantitatively analyzing the long-term (10,000 yr) performance of the methods with respect to dose to humans, radionuclide concentrations in the environment, and cumulative release from the facility. Four near-surface methods (covered above-grade vault, uncovered above-grade vault, below-grade vault, augered holes) and two mine methods (vertical shaft mine and drift mine) were evaluated. Each method was analyzed for several generic site conditions applicable for the state. The evaluations were carried out using RIP (Repository Integration Program), an integrated, total system performance assessment computer code which has been applied to radioactive waste disposal facilities both in the U.S. (Yucca Mountain, WIPP) and worldwide. The evaluations indicate that mines in intact low-permeability rock and near-surface facilities with engineered covers generally have a high potential to perform well (within regulatory limits). Uncovered above-grade vaults and mines in highly fractured crystalline rock, however, have a high potential to perform poorly, exceeding regulatory limits.

  16. Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration.

    PubMed

    Lu, Bin; Malcuit, Christopher; Wang, Shaomei; Girman, Sergej; Francis, Peter; Lemieux, Linda; Lanza, Robert; Lund, Raymond

    2009-09-01

    Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively. Good Manufacturing Practice-compliant hESC-RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photoreceptor integrity in a dose-dependent fashion without teratoma formation or untoward pathological reactions. Near-normal functional measurements were recorded at >60 days survival in RCS rats. To further address safety concerns, a Good Laboratory Practice-compliant study was carried out in the NIH III immune-deficient mouse model. Long-term data (spanning the life of the animals) showed no gross or microscopic evidence of teratoma/tumor formation after subretinal hESC-RPE transplantation. These results suggest that hESCs could serve as a potentially safe and inexhaustible source of RPE for the efficacious treatment of a range of retinal degenerative diseases. PMID:19521979

  17. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia.

    PubMed

    Tsunemi, Yuichiro; Irisawa, Ryokichi; Yoshiie, Hiromu; Brotherton, Betsy; Ito, Hisahiro; Tsuboi, Ryoji; Kawashima, Makoto; Manyak, Michael

    2016-09-01

    Androgenetic alopecia is an androgen-induced pattern of progressive hair loss, which occurs in genetically predisposed people. This study aimed to determine long-term safety, tolerability and efficacy of dutasteride 0.5 mg, an inhibitor of 5-α-reductase, in Japanese male patients with androgenetic alopecia. This was a multicenter, open-label, prospective outpatient study (clinicaltrials.gov NCT01831791, GSK identifier ARI114264) in which patients took dutasteride 0.5 mg p.o. once daily for 52 weeks. Primary end-points included adverse event assessment, incidence of drug-related adverse event and premature discontinuations. Secondary end-points included hair growth, hair restoration and global improvement in hair. A total of 120 patients were enrolled, of whom 110 completed 52 weeks of treatment. Nasopharyngitis, erectile dysfunction and decreased libido were the most frequently reported adverse events and most adverse events were mild. Drug-related adverse events were reported with an incidence of 17%, none of which led to study withdrawal. Hair growth (mean target area hair count at week 52), hair restoration (mean target area hair width at week 52) and global appearance of hair (mean of the median score at week 52) improved from baseline during the study. As a potential future treatment option for male androgenetic alopecia, dutasteride 0.5 mg exhibited long-term safety, tolerability and efficacy within this study population. PMID:26893187

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

    PubMed

    Gilad, Gad M; Gilad, Varda H

    2014-11-01

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

  19. 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

  20. EVALUATION OF RADIONUCLIDE ACCUMULATION IN SOIL DUE TO LONG-TERM IRRIGATION

    SciTech Connect

    De Wesley Wu

    2006-04-16

    Radionuclide accumulation in soil due to long-term irrigation is an important part of the model for predicting radiation dose in a long period of time. The model usually assumes an equilibrium condition in soil with a constant irrigation rate, so that radionuclide concentration in soil does not change with time and can be analytically solved. This method is currently being used for the dose assessment in the Yucca Mountain project, which requires evaluating radiation dose for a period of 10,000 years. There are several issues associated with the method: (1) time required for the equilibrium condition, (2) validity of constant irrigation rate, (3) agricultural land use for a long period of time, and (4) variation of a radionuclide concentration in water. These issues are evaluated using a numerical method with a simple model built in the GoldSim software. Some key radionuclides, Tc-99, Np-237, Pu-239, and Am-241 are selected as representative radionuclides. The results indicate that the equilibrium model is acceptable except for a radionuclide that requires long time to accumulate in soil and that its concentration in water changes dramatically with time (i.e. a sharp peak). Then the calculated dose for that radionuclide could be overestimated using the current equilibrium method.

  1. Long-term leaching test of incinerator bottom ash: Evaluation of Cu partition

    SciTech Connect

    Lin, Cheng-Fang Wu, Chung-Hsin; Liu, Yen-Chiun

    2007-07-01

    Two types of leaching tests were performed on the bottom ash from municipal solid waste incinerators. A short-term batch test specified by the America Nuclear Society (ANS) and long-term column tests with acetic acid (pH 5.2) as leaching solution were used to evaluate copper leachability. The Cu leaching after the 5-d ANS test is about 1% of the original Cu content of 5300 mg/kg. Upon addition of a stabilizing agent, the Cu leaching quantity is reduced; the extent of reduction depends on the type of chemical used (phosphate, carbonate and sulfide). The 1.6% Na{sub 2}S addition showed negligible Cu leaching, and Na{sub 2}S was, therefore, used in subsequent column tests. The 30-d column test indicates a steady increase of Cu leaching amount with time and reaches about 1.5% of the original Cu content after 30 d. A 180-d column test further increased the Cu leaching to about 5.1% of the original Cu content, whereas no appreciable Cu leaching was found with the addition of 1.6% Na{sub 2}S. A sequential extraction was conducted on the raw ash, ash with the addition of Na{sub 2}S and the residue ash after 30 d of operation to characterize Cu affinity for different solid fractions. The data were used to evaluate the fate of Cu through these interactions.

  2. Evaluating Clouds in Long-Term Cloud-Resolving Model Simulations with Observational Data

    NASA Technical Reports Server (NTRS)

    Zeng, Xiping; Tao, Wei-Kuo; Zhang, Minghua; Peters-Lidard, Christa; Lang, Stephen; Simpson, Joanne; Kumar, Sujay; Xie, Shaocheng; Eastman, Joseph L.; Shie, Chung-Lin; Geiger, James V.

    2006-01-01

    Two 20-day, continental midlatitude cases are simulated with a three-dimensional (3D) cloud-resolving model (CRM) and compared to Atmospheric Radiation Measurement (ARM) data. This evaluation of long-term cloud-resolving model simulations focuses on the evaluation of clouds and surface fluxes. All numerical experiments, as compared to observations, simulate surface precipitation well but over-predict clouds, especially in the upper troposphere. The sensitivity of cloud properties to dimensionality and other factors is studied to isolate the origins of the over prediction of clouds. Due to the difference in buoyancy damping between 2D and 3D models, surface precipitation fluctuates rapidly with time, and spurious dehumidification occurs near the tropopause in the 2D CRM. Surface fluxes from a land data assimilation system are compared with ARM observations. They are used in place of the ARM surface fluxes to test the sensitivity of simulated clouds to surface fluxes. Summertime simulations show that surface fluxes from the assimilation system bring about a better simulation of diurnal cloud variation in the lower troposphere.

  3. Long-term clinical evaluation of fixed dentures--two to fifteen years after insertion.

    PubMed

    Hubálková, H; Charvát, J; Dostálová, T; Linetskiy, I

    2005-01-01

    Fixed denture durability is characterized as a period of time for which a dental appliance satisfies functional and esthetic requirements. First of all, its durability is based on the properties of materials it is made of, and depends, at the same time, on the characteristics of biological environment, in which the denture is placed. The purpose of this study was a long-term monitoring of changes taking place in the fixed dental constructions during their application in the oral cavity. These changes were to be evaluated for different types of materials used for fixed dentures manufacturing, namely metal alloys, ceramics, and plastics. A set of 454 full crowns from 134 patients divided in 6 clinical studies was examined and both qualitative and quantitative changes evaluated after 2 and 8 to 15 years after cementation. Clinical assessment adopted the United States Public Health Service System criteria. Alloys of precious metals veneered with ceramics are considered the optimal method of choice for both high precision of execution and consideration of future changes brought on by the use of the dentures. PMID:16007909

  4. Long-term performance evaluation of wood fibre fills. Final report

    SciTech Connect

    Kilian, A.P.; Ferry, C.D.

    1992-08-01

    The paper presents the results of a research project to determine the long-term performance of wood fiber embankments, that were constructed by the Washington State Department of Transportation (WSDOT) beginning in 1972. At the time of their construction, concern existed that wood fiber fills would only provide a 15 to 20 year service life. Performance of existing wood fiber fills was evaluated based on the quality of the wood fiber material, quality of the effluent, and condition of the pavement. A visual classification system rating the wood fiber from fresh to completely decomposed was developed and used in order to establish a criteria from which all wood fiber material could be rated. Visual examination in conjunction with laboratory tests were used as determining aspects for the effluent quality. The WSDOT Pavement Management System was used to evaluate relative pavement performance. Site descriptions are presented giving specific characteristics and properties of the fills inventoried. An analysis of this information was done to determine the effectiveness of the fills. Over half the wood fiber samples were found to be nearly fresh or fresh and none were found to be completely decomposed. In all but one case, the pavement quality over the wood fiber fills surpassed the comparative highway segment rating indicating the wood fill's performance exceeded that of the surrounding area.

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

    PubMed

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

    2013-10-01

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

  6. Interlaboratory evaluation of Hyalella azteca and Chironomus tentans short-term and long-term sediment toxicity tests

    USGS Publications Warehouse

    Norberg-King, T. J.; Sibley, P.K.; Burton, G.A.; Ingersoll, C.G.; Kemble, N.E.; Ireland, S.; Mount, D.R.; Rowland, C.D.

    2006-01-01

    Methods for assessing the long-term toxicity of sediments to Hyalella azteca and Chironomus tentans can significantly enhance the capacity to assess sublethal effects of contaminated sediments through multiple endpoints. Sublethal tests allow us to begin to understand the relationship between short-term and long-term effects for toxic sediments. We present an interlaboratory evaluation with long-term and 10-d tests using control and contaminated sediments in which we assess whether proposed and existing performance criteria (test acceptability criteria [TAC]) could be achieved. Laboratories became familiar with newly developed, long-term protocols by testing two control sediments in phase 1. In phase 2, the 10-d and long-term tests were examined with several sediments. Laboratories met the TACs, but results varied depending on the test organism, test duration, and endpoints. For the long-term tests in phase 1, 66 to 100% of the laboratories consistently met the TACs for survival, growth, or reproduction using H. azteca, and 70 to 100% of the laboratories met the TACs for survival and growth, emergence, reproduction, and hatchability using C. tentans. In phase 2, fewer laboratories participated in long-term tests: 71 to 88% of the laboratories met the TAC for H. azteca, whereas 50 to 67% met the TAC for C. tentans. In the 10-d tests with H. azteca and C. tentans, 82 and 88% of the laboratories met the TAC for survival, respectively, and 80% met the TAC for C. tentans growth. For the 10-d and long-term tests, laboratories predicted similar toxicity. Overall, the interlaboratory evaluation showed good precision of the methods, appropriate endpoints were incorporated into the test protocols, and tests effectively predicted the toxicity of sediments. ?? 2006 SETAC.

  7. Evaluating the Clinical and Physiological Effects of Long Term Ultraviolet B Radiation on Guinea Pigs (Cavia porcellus)

    PubMed Central

    Watson, Megan K.; Stern, Adam W.; Labelle, Amber L.; Joslyn, Stephen; Fan, Timothy M.; Leister, Katie; Kohles, Micah; Marshall, Kemba; Mitchell, Mark A.

    2014-01-01

    Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended. PMID:25517408

  8. Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis.

    PubMed

    Boster, Aaron L; Ford, Corey C; Neudorfer, Orit; Gilgun-Sherki, Yossi

    2015-06-01

    Glatiramer acetate (GA) is approved for relapsing-remitting multiple sclerosis in 57 countries worldwide, with more than 2 million patient-years of exposure and over 20 years of continuous clinical use without new safety concerns. GA has an overall favorable risk-benefit profile: 30% reduced annual relapse rate and decreased brain lesion activity. In clinically definite MS or clinically isolated syndrome, GA slows brain atrophy, which may be related to its unique anti-inflammatory and neuroprotective mechanisms of action. Early treatment with GA delays the onset of clinically definite MS more effectively than late treatment in clinically isolated syndrome. GA is not associated with immunosuppression, autoimmune disease, infections or development of neutralizing antibodies. A new three-times-weekly formulation of GA is available to potentially reduce the incidence of injection-related side effects. Other safety advantages of GA include its pregnancy rating (Category B) and limited uncontrolled data suggesting that tolerability is similar in children with MS. PMID:25924547

  9. 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

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

    PubMed

    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

  11. Long-term urodynamic evaluation of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer.

    PubMed

    Wang, Dong; Li, Li-Jun; Liu, Jing; Qiu, Ming-Xing

    2014-09-01

    The long-term urodynamics of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer remain unclear in the clinical setting. The present prospective observational study was conducted between January 2010 and December 2012 to evaluate the 6-month and 12-month follow-up data of urodynamic changes of bladder cancer patients who were initially treated by laparoscopic radical cystectomy with orthotopic ileal neobladder. A total of 53 eligible patients were included, and all patients were followed up for at least 12 months, with a median time of 18 months. During the follow-up period, no patients reported difficulty urinating, and the daily frequency of urination and the urine output were gradually improved with time. Dynamic urodynamic examinations showed that the maximum flow rate (11.4±1.1 vs. 7.3±1.4 ml/sec; P<0.001), residual urine content (22.8±10.5 vs. 40.7±12.7 ml; P<0.001), maximum bladder capacity (373.8±62.2 vs. 229.7±56.3 ml; P<0.001) and maximum bladder pressure during filling (35.8±6.7 vs. 26.4±7.0 cm H2O; P<0.001) at 12 months were all improved significantly compared with that at 6 months after the initial surgical treatment. However, there were no significant differences in maximum bladder pressure during voiding (75.7±24.7 vs. 73.1±24.7 cm H2O; P=0.618) and bladder compliance (26.9±13 vs. 27.4±13.1 cm H2O; P=0.848) at 12 and 6 months after initial surgical treatment. In conclusion, the urodynamics of this orthotopic ileal neobladder gradually improve, and its long-term urine storage and voiding functions are acceptable. PMID:25120652

  12. Long-term evaluation of home-based pulmonary rehabilitation in patients with COPD

    PubMed Central

    Grosbois, Jean Marie; Gicquello, Alice; Langlois, Carole; Le Rouzic, Olivier; Bart, Frédéric; Wallaert, Benoit; Chenivesse, Cécile

    2015-01-01

    Introduction Personalized, global pulmonary rehabilitation (PR) management of patients with COPD is effective, regardless of the place in which this rehabilitation is provided. The objective of this retrospective observational study was to study the long-term outcome of exercise capacity and quality of life during management of patients with COPD treated by home-based PR. Methods Home-based PR was administered to 211 patients with COPD (mean age, 62.3±11.1 years; mean forced expiratory volume in 1 second, 41.5%±17.7%). Home-based PR was chosen because of the distance of the patient’s home from the PR center and the patient’s preference. Each patient was individually managed by a team member once a week for 8 weeks with unsupervised continuation of physical exercises on the other days of the week according to an individual action plan. Exercise conditioning, therapeutic patient education, and self-management were included in the PR program. The home assessment comprised evaluation of the patient’s exercise capacity by a 6-minute stepper test, Timed Up and Go test, ten times sit-to-stand test, Hospital Anxiety and Depression score, and quality of life (Visual Simplified Respiratory Questionnaire, VQ11, Maugeri Respiratory Failure 28). Results No incidents or accidents were observed during the course of home-based PR. The 6-minute stepper test was significantly improved after completion of the program, at 6 months and 12 months, whereas the Timed Up and Go and ten times sit-to-stand test were improved after PR and at 6 months but not at 12 months. Hospital Anxiety and Depression and quality of life scores improved after PR, and this improvement persisted at 6 months and 12 months. Conclusion Home-based PR for unselected patients with COPD is effective in the short term, and this effectiveness is maintained in the medium term (6 months) and long term (12 months). Home-based PR is an alternative to outpatient management provided all activities, such as exercise

  13. Long-term evaluation of myoblast seeded patches implanted on infarcted rat hearts.

    PubMed

    Giraud, Marie-Noëlle; Flueckiger, Remy; Cook, Stéphane; Ayuni, Erick; Siepe, Matthias; Carrel, Thierry; Tevaearai, Hendrik

    2010-06-01

    Cell transplantation presents great potential for treatment of patients with severe heart failure. However, its clinical application was revealed to be more challenging than initially expected in experimental studies. Further investigations need to be undertaken to define the optimal treatment conditions. We previously reported on the epicardial implantation of a bio-engineered construct of skeletal myoblast-seeded polyurethane and its preventive effect on progression toward heart failure. In the present study, we present a long-term evaluation of this functional outcome. Left anterior descending coronary ligation was performed in female Lewis rats. Two weeks later, animals were treated with either epicardial implantation of biograft, acellular scaffold, sham operation, or direct intramyocardial skeletal myoblast injection. Functional assessments were performed with serial echocardiographies every 3 months and end point left ventricle pressure was assessed. Hearts were then harvested for histological examinations. Myocardial infarction induced a slow and progressive reduction in fractional shortening after 3 months. Progression toward heart failure was significantly prevented for up to 6 months after injection of myoblasts and for up to 9 months following biograft implantation. Nevertheless, this effect vanished after 12 months, with immunohistological examinations revealing an absence of the transplanted myoblasts within the scaffold. We demonstrated that tissue therapy is superior to cell therapy for stabilization of heart function. However, beneficial effects are transient. PMID:20482708

  14. 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

  15. 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

  16. Long-term safety and effectiveness of sildenafil citrate in men with erectile dysfunction

    PubMed Central

    McMurray, James G; Feldman, Robert A; Auerbach, Stephen M; DeRiesthal, Herb; Wilson, Neal

    2007-01-01

    Because sildenafil citrate is a treatment, not a cure, for erectile dysfunction (ED), many men may choose to use it for an extended period. Men with ED who had previously completed 1 of 4 double-blind trials with short-term open-label extension (combined duration, 0.9–1.2 years) were eligible for this 4-year, open-label, extension study, which assessed the safety and effectiveness of flexible doses (25, 50, and 100 mg sildenafil) used as needed. Adverse events that were serious or led to dosing changes or discontinuation (temporary or permanent) were recorded. Many of the 979 participants (mean age, 58 [range, 27–82] years; mean ED duration, 4.5 years) had concomitant hypertension (28%), diabetes (22%), or hyperlipidemia (14%). Overall, 37 (3.8%) had treatment-related adverse events (none serious) requiring dosage change or discontinuation and 62 (6.3%) discontinued because of insufficient response. At each yearly assessment, more than 94% of participants responded affirmatively to the questions: “Are you satisfied with the effect of treatment on your erections?” and “If yes, has treatment improved your ability to engage in sexual activity?” These results argue against the loss of tolerability or the development of tachyphylaxis over a prolonged period of as needed, flexible-dose sildenafil treatment of men with ED. PMID:18516312

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

    PubMed Central

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

    2010-01-01

    Objective: The combination of inhaled corticosteroid (ICS) and long-acting β2-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS. Methods: This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged >12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC0–24h) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored. Results: The incidence of >1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 μg, 77.3% [n = 109]; FP/S 250/50 μg, 82.4% [n = 56]; MF/F 400/10 μg, 79.2% [n = 103]; FP/S 500/50 μg, 76.9% [n = 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 μg, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC0–24 h observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2–6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10

  18. 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

  19. Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience.

    PubMed

    Martino, M; Console, G; Dattola, A; Callea, I; Messina, G; Moscato, T; Massara, E; Irrera, G; Fedele, R; Gervasi, A; Bresolin, G; Iacopino, P

    2009-08-01

    Healthy donors (HDs) who were mobilized using lenograstim (LENO) and who were undergoing peripheral haematopoietic progenitor cell collection with apheresis (HPC-A) were enrolled in a surveillance protocol. In all, 184 HDs have been assessed with a median follow-up of 62 months (range 2-155). HDs received LENO at a median dose of 10 microg/kg (range 5-15). Bone pain was reported as the most frequent short-term adverse event (71.2%). Other commonly observed short-term symptoms included fatigue (19.0%), fever (5.4%), headache (27.7%), nausea (12.0%) and insomnia (22.3%). Spleen size increased in 4.3% of the donors. No vascular disorders or cardiac disease occurred. Long-term follow-up included monitoring of adverse events, neoplastic disease or other pathologies. Transit ischaemic attack occurred in one donor (39 months post-donation). One autoimmune event was reported at 28 months post-recombinant human granulocyte (rhG)-CSF (ankylosing spondylitis); one donor with a history of chronic obstructive pulmonary disease developed secondary polyglobulia (50 months post-rhG-CSF). One donor was diagnosed with lung cancer at 19 months post-donation. No haematological disease was observed. In conclusion, the short-term safety appears to be verified, whereas, although the study identified no increased risks of malignancy among HDs who received rhG-CSF, long-term safety requires more complete data sets, especially a longer follow-up and a larger number of HDs. PMID:19182833

  20. Evaluating and ranking threats to the long-term persistence of polar bears

    USGS Publications Warehouse

    Atwood, Todd C.; Marcot, Bruce G.; Douglas, David C.; Amstrup, Steven C.; Rode, Karyn D.; Durner, George M.; Bromaghin, Jeffrey F.

    2015-01-01

    The polar bear (Ursus maritimus) was listed as a globally threatened species under the U.S. Endangered Species Act (ESA) in 2008, mostly due to the significant threat to their future population viability from rapidly declining Arctic sea ice. A core mandate of the ESA is the development of a recovery plan that identifies steps to maintain viable populations of a listed species. A substantive evaluation of the relative influence of putative threats to population persistence is helpful to recovery planning. Because management actions must often be taken in the face of substantial information gaps, a formalized evaluation hypothesizing potential stressors and their relationships with population persistence can improve identification of relevant conservation actions. To this end, we updated a Bayesian network model previously used to forecast the future status of polar bears worldwide. We used new information on actual and predicted sea ice loss and polar bear responses to evaluate the relative influence of plausible threats and their mitigation through management actions on the persistence of polar bears in four ecoregions. We found that polar bear outcomes worsened over time through the end of the century under both stabilized and unabated greenhouse gas (GHG) emission pathways. Under the unabated pathway (i.e., RCP 8.5), the time it took for polar bear populations in two of four ecoregions to reach a dominant probability of greatly decreased was hastened by about 25 years. Under the stabilized GHG emission pathway (i.e., RCP 4.5), where GHG emissions peak around the year 2040, the polar bear population in the Archipelago Ecoregion of High Arctic Canada never reached a dominant probability of greatly decreased, reinforcing earlier suggestions of this ecoregion’s potential to serve as a long-term refugium. The most influential drivers of adverse polar bear outcomes were declines to overall sea ice conditions and to the marine prey base. Improved sea ice conditions

  1. Long Term Follow-up Report of Four BAWP Programs. Evaluation of the Bay Area Writing Project. Technical Report.

    ERIC Educational Resources Information Center

    Stahlecker, James

    Prepared as part of the evaluation of the Bay Area Writing Project (BAWP), this report provides results of surveys evaluating four types of BAWP programs (elementary and secondary school-year inservice programs, university extension special courses, and summer invitational programs), showing that BAWP programs have long-term effects on student and…

  2. Long-term geochemical evaluation of the coastal Chicot aquifer system, Louisiana, USA

    NASA Astrophysics Data System (ADS)

    Borrok, David M.; Broussard, Whitney P.

    2016-02-01

    Groundwater is increasingly being overdrafted in the Gulf and Atlantic Coastal regions of the United States. Geochemical data associated with groundwater in these aquifers can provide important information on changes in salinity, recharge, and reaction pathways that can be used to improve water management strategies. Here we evaluated long-term geochemical changes associated with the 23,000 km2 Chicot aquifer system in Louisiana, USA. The Chicot aquifer is currently being overdrafted by about 1,320,000 m3 per day. We compiled selected bulk geochemical data from samples collected from 20 wells in the Chicot aquifer from 1993 to 2015. Oxygen and hydrogen isotope measurements were additionally completed for the 2014 samples. We identified three zones of groundwater with distinctive geochemical character; (1) A groundwater recharge zone in the northern part of the study area with low pH, low salinity, and low temperature relative to other groundwater samples, (2) a groundwater recharge zone in the southeastern part of the study area with low temperature, high alkalinity, and higher Ca and Mg concentrations compared to the other groundwater samples, and (3) groundwater in the southwestern part of the aquifer system with high salinity, high temperature, and a ∼1:1 Na/Cl ratio. The geochemistry of these regions has been relatively stable over the last ∼20 years. However, in the drought year of 2011, the estimated extent of zones with elevated salinity increased substantially. Geochemical evidence suggests that there was increased infiltration of deeper, more salt-rich waters into the shallower Chicot aquifer.

  3. 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

  4. 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.

  5. 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

  6. Evaluation of Long-Term Impacts of Tillage and Cropping Systems in Alabama, USA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development of sustainable agriculture production systems depends on the use of reliable crop rotations and tillage systems. Understanding the interaction between different cropping and tillage systems as they affect crop yields over the long-term is essential for determining the best alternatives ...

  7. An Evaluation of Persistence of Treatment Effects during Long-Term Treatment of Destructive Behavior

    ERIC Educational Resources Information Center

    Wacker, David P.; Harding, Jay W.; Berg, Wendy K.; Lee, John F.; Schieltz, Kelly M.; Padilla, Yaniz C.; Nevin, John A.; Shahan, Timothy A.

    2011-01-01

    Eight young children who displayed destructive behavior maintained, at least in part, by negative reinforcement received long-term functional communication training (FCT). During FCT, the children completed a portion of a task and then touched a communication card attached to a microswitch to obtain brief breaks. Prior to and intermittently…

  8. DEVELOMENT AND EVALUATION OF A MODEL FOR ESTIMATING LONG-TERM AVERAGE OZONE EXPOSURES TO CHILDREN

    EPA Science Inventory

    Long-term average exposures of school-age children can be modelled using longitudinal measurements collected during the Harvard Southern California Chronic Ozone Exposure Study over a 12-month period: June, 1995-May, 1996. The data base contains over 200 young children with perso...

  9. EVALUATION OF LONG-TERM NOX REDUCTION ON PULVERIZED-COAL-FIRED STEAM GENERATORS

    EPA Science Inventory

    The report gives results of analyzing long-term nitrogen oxide (NOx) emission data from eight pulverized-coal-fired steam generators, for the purpose of quantifying the effectiveness of various combustion modifications. All boilers, but one, were modified to reduce NOx emissions....

  10. Evaluation of long-term bedload virtual velocity in gravel-bed rivers (Ardenne, Belgium)

    NASA Astrophysics Data System (ADS)

    Houbrechts, Geoffrey; Levecq, Yannick; Peeters, Alexandre; Hallot, Eric; Van Campenhout, Jean; Denis, Anne-Cécile; Petit, François

    2015-12-01

    In many gravel-bed rivers, bed material transfer has been interrupted or perturbed by anthropogenic activities. Currently, restoration projects are being conducted in many countries in order to re-establish bedload continuity. However, until now, few studies have provided indications of the velocity of bed material over the long-term (at least decade to century time-scale). In the context of river restoration projects (e.g. weir removal, addition of spawning gravel), these data are nevertheless crucial to predict the downstream propagation of the geomorphological and biological benefits (e.g. supply-transport equilibrium, morphological and substratum diversity). In our study, PIT-tag tracers were used in eight medium-sized gravel-bed rivers (Ardenne Region, Belgium) to propose a flow competence relationship based on specific stream power, on the one hand, and to determine the long-term virtual velocity of the bed material corresponding to the median diameter (D50) of the surface layer of riffles, on the other hand. After each flow event that exceeded the threshold for sediment entrainment, tagged particles were sought and located, even when they were buried in the subsurface layer. Afterwards, all of the data were used to estimate the virtual velocity of the bed material over the long-term using three approaches. Finally, the results were compared with long-term transport estimations based on iron slag dispersed by the rivers since the end of the middle ages.

  11. An Evaluation of the Long-Term Effectiveness of a Women's Leadership Development Program

    ERIC Educational Resources Information Center

    Ericksen, Kirsten S.

    2009-01-01

    The purpose of this study was to investigate the Women's Institute for Leadership Development (W.I.L.D.) program to determine the immediate and long-term impact as defined by the alumni program participants from three cohorts (2008, 2005, 2003). A secondary focus of the career transition decision-making of recent W.I.L.D. participants was also…

  12. Evaluation of Long Term Effect of RV Apical Pacing on Global LV Function by Echocardiography

    PubMed Central

    Tilkar, Mahendra; Jain, Siddhant; Mondal, Subrata; Sarkar, Piyabi; Modi, Nitin

    2016-01-01

    Introduction We very often face pacemaker implanted patients during follow-up with shortness of breath and effort intolerance inspite of normal clinical parameters. Aim The aim of our study is to evaluate the cause of effort intolerance and probable cause of sub-clinical Congestive Cardiac Failure (CCF) in a case of long term Right Ventricular (RV) apical pacing on global Left Ventricular (LV) function non- invasively by echocardiography. Materials and Methods We studied 54 patients (Male 42, Female 12) of complete heart block (CHB) with RV apical pacing (40 VVI and 14 DCP). Mean duration of pacing was 58+4 months. All patients underwent 24 hours Holter monitoring to determine the percentage of ventricular pacing beats. 2-D Echocardiography was done to assess the regional wall motion of abnormality and global LV ejection fraction by modified Simpson’s rule. These methods were coupled with the Doppler derived Myocardial Performance Index (MPI), tissue Doppler imaging, and mechanical regional dyssynchrony with 3-D Echocardiography. Data were analysed from 54 RV- apical paced patients and compared with age and body surface area of 60 controlled subjects (Male 46, Female 14). Results Evaluation of LV function in 54 patients demonstrated regional wall motion abnormality and Doppler study revealed both LV systolic and diastolic dysfunction compare with control subjects (regional wall motion abnormality 80±6% vs 30±3% with p-value<0.0001) which is proportional to the percentage of ventricular pacing beats (mean paced beat 78%). Global LVEF 50±4% vs 60±2% (p-valve <0.0001) and MPI 0.46 ±0.12 v/s 0.36±0.09 (p-value <0.0001). Conclusion RV–apical pacing induces iatrogenic electrical dyssynchrony which leads to remodeling of LV and produces mechanical dyssynchrony which is responsible for LV dysfunction. Alternate site of RV pacing and/or biventricular pacing should be done to maintain biventricular electrical synchrony which will preserve the LV function. PMID

  13. Evaluation of three long term mass balance records in Jotunheimen, southern Norway

    NASA Astrophysics Data System (ADS)

    Andreassen, Liss M.

    2013-04-01

    The accuracy of glacier surface mass-balance measurements depends on both the accuracy of the point observations and inter- and extrapolation of point values to spatially distributed values. Long series of measurements will seldom be perfectly homogeneous because of changes in personnel and procedure, and as there will be changes in glacier area (and elevation) when averaging the data. The Jotunheimen massif is the highest area in mainland Norway. Direct surface mass balance has been measured at Storbreen since 1949 and Hellstugubreen and Gråsubreen since 1962. These three mountain glaciers are reference glaciers of the World Glacier Monitoring Service. Four more glaciers in Jotunheimen were measured for shorter periods in the 1960/1970s. Moreover, measurements started on a small ice patch in 2010. The reference glaciers have been mapped repeatedly since measurements began, latest by laser scanning in 2009. The geodetic method has been used to calculate the cumulative surface mass balance. In this study the direct and geodetic mass balance results are presented and evaluated. Measurements reveal a remarked mass balance gradient in this region with smaller mass turnover towards east. All three long term glaciers have had a cumulative mass deficit since measurements began; over 1962-2010 the mean surface mass balance was -0.34 m w.e./a. The mass deficit has accelerated over the past decade, and the mean mass balance over 2001-2010 was -0.84 m w.e./a. Storbreen has lost about 1/5 of its volume since measurements began in 1949. Results reveal that the geodetic and direct measurements compare well for the glaciers, also for the latest mapping period 1997-2009, although discrepancies occur in some periods. Calibration and correction of the direct records with the geodetic results may be appropriate for some periods. The glacier changes of the three reference glaciers are finally compared with results from other glaciers in southern Norway for evaluation of the local and

  14. Evaluation of Late Adverse Events in Long-Term Wilms' Tumor Survivors

    SciTech Connect

    Dijk, Irma van; Oldenburger, Foppe; Cardous-Ubbink, Mathilde C.; Geenen, Maud M.

    2010-10-01

    Purpose: To evaluate the prevalence and severity of adverse events (AEs) and treatment-related risk factors in long-term Wilms' tumor (WT) survivors, with special attention to radiotherapy. Methods and Materials: The single-center study cohort consisted of 185 WT survivors treated between 1966 and 1996, who survived at least 5 years after diagnosis. All survivors were invited to a late-effects clinic for medical assessment of AEs. AEs were graded for severity in a standardized manner. Detailed radiotherapy data enabled us to calculate the equivalent dose in 2 Gy fractions (EQD{sub 2}) to compare radiation doses in a uniform way. Risk factors were evaluated with multivariate logistic regression analysis. Results: Medical follow-up was complete for 98% of survivors (median follow-up, 18.9 years; median attained age, 22.9 years); 123 survivors had 462 AEs, of which 392 had Grade 1 or 2 events. Radiotherapy to flank/abdomen increased the risk of any AE (OR, 1.08 Gy{sup -1} [CI, 1.04-1.13]). Furthermore, radiotherapy to flank/abdomen was associated with orthopedic events (OR, 1.09 Gy{sup -1} [CI, 1.05-1.13]) and second tumors (OR, 1.11 Gy{sup -1} [CI, 1.03-1.19]). Chest irradiation increased the risk of pulmonary events (OR, 1.14 Gy{sup -1} [CI, 1.06-1.21]). Both flank/abdominal and chest irradiation were associated with cardiovascular events (OR, 1.05 Gy{sup -1} [CI, 1.00-1.10], OR, 1.06 Gy{sup -1} [CI, 1.01-1.12]) and tissue hypoplasia (OR, 1.17 Gy{sup -1} [CI, 1.10-1.24], OR 1.10 Gy{sup -1} [CI, 1.03-1.18]). Conclusion: The majority of AEs, overall as well as in irradiated survivors, were mild to moderate. Nevertheless, the large amount of AEs emphasizes the importance of follow-up programs for WT survivors.

  15. Evaluating Indicator-Based Methods of "Measuring Long-Term Impacts of a Science Center on Its Community"

    ERIC Educational Resources Information Center

    Jensen, Eric Allen

    2016-01-01

    This article addresses some of the challenges faced when attempting to evaluate the long-term impact of informal science learning interventions. To contribute to the methodological development of informal science learning research, we critically examine (Falk and Needham (2011) "Journal of Research in Science Teaching," 48: 1-12.) study…

  16. Long-Term Effects of Outpatient Geriatric Evaluation and Management on Health Care Utilization, Cost, and Survival

    ERIC Educational Resources Information Center

    Engelhardt, Joseph B.; Toseland, Ronald W.; Gao, Jian; Banks, Steven

    2006-01-01

    Purpose: The long-term effectiveness and efficiency of an outpatient geriatric evaluation and management (GEM) program was compared to usual primary care (UPC). Design and Method: A randomized controlled group design was used. Health care utilization, cost of care, and survival were assessed during a 48-month period among a sample of 160 male…

  17. Grazing Management Contributions to Net Global Warming Potential: A Long-Term Evaluation in the Northern Great Plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of grassland ecosystems as net sinks or sources of greenhouse gases (GHG) is limited by a paucity of information regarding management impacts on the flux of methane (CH4) and nitrous oxide (N2O). Furthermore, no long-term evaluation of net global warming potential (GWP) for grassland ecosy...

  18. Comprehensive evaluation of long-term hydrological data sets: Constraints of the Budyko framework

    NASA Astrophysics Data System (ADS)

    Greve, Peter; Orlowsky, Boris; Seneviratne, Sonia I.

    2013-04-01

    An accurate estimate of the climatological land water balance is essential for a wide range of socio-economical issues. Despite the simplicity of the underlying water balance equation, its individual variables are of complex nature. Global estimates, either derived from observations or from models, of precipitation (P ) and especially evapotranspiration (ET) are characterized by high uncertainties. This leads to inconsistent results in determining conditions related to the land water balance and its components. In this study, we consider the Budyko framework as a constraint to evaluate long-term hydrological data sets within the period from 1984 to 2005. The Budyko framework is a well established empirically based relationsship between ET-P and Ep-P , with Ep being the potential evaporation. We use estimates of ET associated with the LandFlux-EVAL initiative (Mueller et. al., 2012), either derived from observations, CMIP5 models or land-surface models (LSMs) driven with observation-based forcing or atmospheric reanalyses. Data sets of P comprise all commonly used global observation-based estimates. Ep is determined by methods of differing complexity with recent global temperature and radiation data sets. Based on this comprehensive synthesis of data sets and methods to determine Ep, more than 2000 possible combinations for ET-P in conjunction with Ep-P are created. All combinations are validated against the Budyko curve and against physical limits within the Budyko phase space. For this purpose we develop an error measure based on the root mean square error which combines both constraints. We find that uncertainties are mainly induced by the ET data sets. In particular, reanalysis and CMIP5 data sets are characterized by low realism. The realism of LSMs is further not primarily controlled by the forcing, as different LSMs driven with the same forcing show significantly different error measures. Our comprehensive approach is thus suitable to detect uncertainties

  19. Evaluating long-term gully dynamics by data fusion from field measurements, photogrammetry and modelling

    NASA Astrophysics Data System (ADS)

    Vanwalleghem, Tom; Hayas, Antonio; Román, Andrea; Hervas, César; Laguna, Ana; Peña, Adolfo; Giráldez, Juan Vicente

    2014-05-01

    shows the power of combining data from different sources in order to elucidate complex geomorphic processes, such as long-term gully erosion dynamics, where information from individual sources limits our understanding.

  20. DEVELOPMENT OF A LONG-TERM MONITORING SYSTEM TO EVALUATE COVER SYSTEM PERFORMANCE

    SciTech Connect

    Kumthekar, U.; Chiou, J. D.; Prochaska, M.; Benson, C. H.

    2002-02-25

    Environmental remediation at the Fernald Environmental Management Project is nearing completion, but long-term technology needs continue to emerge at the site. Remote, real-time, autonomous monitoring technologies are needed to ensure the integrity of the site and its remedy systems once cleanup is complete. The Fernald Post Closure Stewardship Technology Project (PCSTP), through the work of the Integrating Stewardship Technology Team (ISTT), has selected technologies to address initial site needs. This paper will explore the monitoring requirements of the Fernald On-Site Disposal Facility (OSDF), the parameters selected as critical for comprehensive long-term monitoring of the facility, and the process by which technologies were chosen to monitor those parameters.

  1. Evaluating the Long-Term Performance of Geosynethic Clay Liners Exposed to Freeze-Thaw

    SciTech Connect

    Robert K. Podgorney; Jesse E. Bennett

    2006-02-01

    Geosynethic clay liners have become an increasingly common component in landfill liner and cover systems since their introduction in the early 1980’s. An important consideration for landfills and covers constructed in the frost zone of cold climates is the possible deterioration in performance due to freeze-thaw cycling over the design life of the liner or cover system, which can be up to 1,000 years. The literature contains several examples showing that geosynethic clay liners can withstand a limited number of freeze-thaw events, but data on long-term performance are lacking The objective of this study was to examine the long-term performance of geosynethic clay liners exposed to repeated freeze-thaw cycles, encompassing their application as a final cover as well as a bottom liner. Laboratory analysis of hydraulic conductivity was performed after as many as 150 freeze-thaw cycles, with no appreciable changes observed. Based upon an analytical heat transfer analysis, this equates to [at least] 150 years of field service for placement depths greater then approximately 30 cm below the surface of the liner. The long-term insusceptibility of GCLs to increased hydraulic conductivity as a response to repeated freeze-thaw cycling is largely due to the self-healing characteristics of the sodium bentonite used in their construction. GCLs perform well and maintain efficiency as a barrier to flow after 150 freeze-thaw cycles. Other factors, such as permeant chemistry, physical disturbance, desiccation, etc., may be much more important factors to consider when planning for the long-term performance of GCLs.

  2. Bleaching teeth treated endodontically: long-term evaluation of a case series.

    PubMed

    Amato, Massimo; Scaravilli, Maria Serena; Farella, Mauro; Riccitiello, Francesco

    2006-04-01

    The chromatic stability of nonvital discolored teeth, subjected to the combined intracoronal bleaching technique and to endodontic treatment, was evaluated at a distance of 16 yr (1989-2005). The series comprised 50 patients (age range 7-30 yr) selected from among those attending the Dental Clinic at "Federico II" University, Naples, between 1987 and 1989. After 16 yr, only 35 cases could be evaluated: in 22 of these cases (62.9%) the color had remained stable and was similar to that of adjacent teeth, indicating a successful outcome of the combined bleaching technique. There were 13 cases (37.1%) classified as failures because of marked color relapse. Radiology showed none of the cases re-examined to have undergone internal or external root resorption. These results confirm the validity of the combined intracoronal bleaching technique in terms of efficacy, rapid esthetic result, and safety. PMID:16554217

  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. Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib.

    PubMed

    Cortes, Jorge E; Jean Khoury, H; Kantarjian, Hagop; Brümmendorf, Tim H; Mauro, Michael J; Matczak, Ewa; Pavlov, Dmitri; Aguiar, Jean M; Fly, Kolette D; Dimitrov, Svetoslav; Leip, Eric; Shapiro, Mark; Lipton, Jeff H; Durand, Jean-Bernard; Gambacorti-Passerini, Carlo

    2016-06-01

    Vascular and cardiac safety during tyrosine kinase inhibitor (TKI) therapy is an emerging issue. We evaluated vascular/cardiac toxicities associated with long-term bosutinib treatment for Philadelphia chromosome-positive (Ph+) leukemia based on treatment-emergent adverse events (TEAEs) and changes in QTc intervals and ejection fraction in two studies: a phase 1/2 study of second-/third-/fourth-line bosutinib for Ph+ leukemia resistant/intolerant to prior TKIs (N = 570) and a phase 3 study of first-line bosutinib (n = 248) versus imatinib (n = 251) in chronic phase chronic myeloid leukemia. Follow-up time was ≥48 months (both studies). Incidences of vascular/cardiac TEAEs in bosutinib-treated patients were 7%/10% overall with similar incidences observed with first-line bosutinib (5%/8%) and imatinib (4%/6%). Few patients had grade ≥3 vascular/cardiac events (4%/4%) and no individual TEAE occurred in >2% of bosutinib patients. Exposure-adjusted vascular/cardiac TEAE rates (patients with events/patient-year) were low for second-line or later bosutinib (0.037/0.050) and not significantly different between first-line bosutinib (0.015/0.024) and imatinib (0.011/0.017; P ≥ 0.267). Vascular/cardiac events were managed mainly with concomitant medications (39%/44%), bosutinib treatment interruptions (18%/21%), or dose reductions (4%/8%); discontinuations due to these events were rare (0.7%/1.0%). Based on logistic regression modelling, performance status >0 and history of vascular or cardiac disorders were prognostic of vascular/cardiac events in relapsed/refractory patients; hyperlipidemia/hypercholesterolemia and older age were prognostic of cardiac events. In newly diagnosed patients, older age was prognostic of vascular/cardiac events; history of diabetes was prognostic of vascular events. Incidences of vascular and cardiac events were low with bosutinib in the first-line and relapsed/refractory settings following long-term treatment in patients

  5. Evaluation of long-term gas hydrate production testing locations on the Alaska north slope

    USGS Publications Warehouse

    Collett, T.S.; Boswell, R.; Lee, M.W.; Anderson, B.J.; Rose, K.; Lewis, K.A.

    2011-01-01

    The results of short duration formation tests in northern Alaska and Canada have further documented the energy resource potential of gas hydrates and justified the need for long-term gas hydrate production testing. Additional data acquisition and long-term production testing could improve the understanding of the response of naturally-occurring gas hydrate to depressurization-induced or thermal-, chemical-, and/or mechanical-stimulated dissociation of gas hydrate into producible gas. The Eileen gas hydrate accumulation located in the Greater Prudhoe Bay area in northern Alaska has become a focal point for gas hydrate geologic and production studies. BP Exploration (Alaska) Incorporated and ConocoPhillips have each established research partnerships with U.S. Department of Energy to assess the production potential of gas hydrates in northern Alaska. A critical goal of these efforts is to identify the most suitable site for production testing. A total of seven potential locations in the Prudhoe Bay, Kuparuk, and Milne Point production units were identified and assessed relative to their suitability as a long-term gas hydrate production test site. The test site assessment criteria included the analysis of the geologic risk associated with encountering reservoirs for gas hydrate testing. The site selection process also dealt with the assessment of the operational/logistical risk associated with each of the potential test sites. From this review, a site in the Prudhoe Bay production unit was determined to be the best location for extended gas hydrate production testing. The work presented in this report identifies the key features of the potential test site in the Greater Prudhoe Bay area, and provides new information on the nature of gas hydrate occurrence and potential impact of production testing on existing infrastructure at the most favorable sites. These data were obtained from well log analysis, geological correlation and mapping, and numerical simulation

  6. Evaluation of long-term gas hydrate production testing locations on the Alaska North Slope

    USGS Publications Warehouse

    Collett, Timothy; Boswell, Ray; Lee, Myung W.; Anderson, Brian J.; Rose, Kelly K.; Lewis, Kristen A.

    2011-01-01

    The results of short duration formation tests in northern Alaska and Canada have further documented the energy resource potential of gas hydrates and justified the need for long-term gas hydrate production testing. Additional data acquisition and long-term production testing could improve the understanding of the response of naturally-occurring gas hydrate to depressurization-induced or thermal-, chemical-, and/or mechanical-stimulated dissociation of gas hydrate into producible gas. The Eileen gas hydrate accumulation located in the Greater Prudhoe Bay area in northern Alaska has become a focal point for gas hydrate geologic and production studies. BP Exploration (Alaska) Incorporated and ConocoPhillips have each established research partnerships with U.S. Department of Energy to assess the production potential of gas hydrates in northern Alaska. A critical goal of these efforts is to identify the most suitable site for production testing. A total of seven potential locations in the Prudhoe Bay, Kuparuk, and Milne Point production units were identified and assessed relative to their suitability as a long-term gas hydrate production test site. The test site assessment criteria included the analysis of the geologic risk associated with encountering reservoirs for gas hydrate testing. The site selection process also dealt with the assessment of the operational/logistical risk associated with each of the potential test sites. From this review, a site in the Prudhoe Bay production unit was determined to be the best location for extended gas hydrate production testing. The work presented in this report identifies the key features of the potential test site in the Greater Prudhoe Bay area, and provides new information on the nature of gas hydrate occurrence and potential impact of production testing on existing infrastructure at the most favorable sites. These data were obtained from well log analysis, geological correlation and mapping, and numerical simulation.

  7. Evaluation of long-term gas hydrate production testing locations on the Alaska North Slope

    USGS Publications Warehouse

    Collett, Timothy S.; Boswell, Ray; Lee, Myung W.; Anderson, Brian J.; Rose, Kelly K.; Lewis, Kristen A.

    2012-01-01

    The results of short-duration formation tests in northern Alaska and Canada have further documented the energy-resource potential of gas hydrates and have justified the need for long-term gas-hydrate-production testing. Additional data acquisition and long-term production testing could improve the understanding of the response of naturally occurring gas hydrate to depressurization-induced or thermal-, chemical-, or mechanical-stimulated dissociation of gas hydrate into producible gas. The Eileen gashydrate accumulation located in the Greater Prudhoe Bay area in northern Alaska has become a focal point for gas-hydrate geologic and production studies. BP Exploration (Alaska) Incorporated and ConocoPhillips have each established research partnerships with the US Department of Energy to assess the production potential of gas hydrates in northern Alaska. A critical goal of these efforts is to identify the most suitable site for production testing. A total of seven potential locations in the Prudhoe Bay, Kuparuk River, and Milne Point production units were identified and assessed relative to their suitability as a long-term gas-hydrate-production test sites. The test-site-assessment criteria included the analysis of the geologic risk associated with encountering reservoirs for gas-hydrate testing. The site-selection process also dealt with the assessment of the operational/logistical risk associated with each of the potential test sites. From this review, a site in the Prudhoe Bay production unit was determined to be the best location for extended gas-hydrate-production testing. The work presented in this report identifies the key features of the potential test site in the Greater Prudhoe Bay area and provides new information on the nature of gas-hydrate occurrence and the potential impact of production testing on existing infrastructure at the most favorable sites. These data were obtained from well-log analysis, geological correlation and mapping, and numerical

  8. Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study

    PubMed Central

    Nishimoto, N; Miyasaka, N; Yamamoto, K; Kawai, S; Takeuchi, T; Azuma, J

    2009-01-01

    Objectives: To evaluate the safety and efficacy of 5-year, long-term tocilizumab monotherapy for patients with rheumatoid arthritis. Methods: In an open-label, long-term extension trial following an initial 3-month randomised phase II trial, 143 of the 163 patients who participated in the initial blinded study received tocilizumab monotherapy (8 mg/kg) every 4 weeks. Concomitant therapy with non-steroidal anti-inflammatory drugs and/or oral prednisolone (10 mg daily maximum) was permitted. All patients were evaluated with American College of Rheumatology (ACR) improvement criteria, disease activity score (DAS) in 28 joints, and the European League Against Rheumatism response, as well as for safety issues. Results: 143 patients were enrolled in the open-label, long-term extension trial and 94 (66%) patients had completed 5 years as of March 2007. 32 patients (22%) withdrew from the study due to adverse events and one patient (0.7%) due to unsatisfactory response. 14 patients withdrew because of the patient’s request or other reasons. The serious adverse event rate was 27.5 events per 100 patient-years, with 5.7 serious infections per 100 patient-years, based on a total tocilizumab exposure of 612 patient-years. Of the 88 patients receiving corticosteroids at baseline, 78 (88.6%) were able to decrease their corticosteroid dose and 28 (31.8%) discontinued corticosteroids. At 5 years, 79/94 (84.0%), 65/94 (69.1%) and 41/94 (43.6%) of the patients achieved ACR20, ACR50, and ACR70 improvement criteria, respectively. Remission defined as DAS28 less than 2.6 was achieved in 52/94 (55.3%) of the patients. Conclusion: In this 5-year extension study, tocilizumab demonstrated sustained long-term efficacy and a generally good safety profile. PMID:19019888

  9. 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

  10. Combined liposuction and excision of lipomas: long-term evaluation of a large sample of patients.

    PubMed

    Copeland-Halperin, Libby R; Pimpinella, Vincenza; Copeland, Michelle

    2015-01-01

    Background. Lipomas are benign tumors of mature fat cells. They can be removed by liposuction, yet this technique is seldom employed because of concerns that removal may be incomplete and recurrence may be more frequent than after conventional excision. Objectives. We assessed the short- and long-term clinical outcomes and recurrence of combined liposuction and limited surgical excision of subcutaneous lipomas. Methods. From 2003 to 2012, 25 patients with 48 lipomas were treated with liposuction followed by direct excision through the same incision to remove residual lipomatous tissue. Initial postoperative follow-up ranged from 1 week to 3 months, and long-term outcomes, complications, and recurrence were surveyed 1 to 10 years postoperatively. Results. Lipomas on the head, neck, trunk, and extremities ranged from 1 to 15 cm in diameter. Early postoperative hematoma and seromas were managed by aspiration. Among 23 survey respondents (92%), patients were uniformly pleased with the cosmetic results; none reported recurrent lipoma. Conclusions. The combination of liposuction and excision is a safe alternative for lipoma removal; malignancy and recurrence are uncommon. Liposuction performed through a small incision provides satisfactory aesthetic results in most cases. Once reduced in size, residual lipomatous and capsular tissue can be removed without expanding the incision. These favorable outcomes support wider application of this technique in appropriate cases. PMID:25694827

  11. Combined Liposuction and Excision of Lipomas: Long-Term Evaluation of a Large Sample of Patients

    PubMed Central

    Copeland-Halperin, Libby R.; Pimpinella, Vincenza

    2015-01-01

    Background. Lipomas are benign tumors of mature fat cells. They can be removed by liposuction, yet this technique is seldom employed because of concerns that removal may be incomplete and recurrence may be more frequent than after conventional excision. Objectives. We assessed the short- and long-term clinical outcomes and recurrence of combined liposuction and limited surgical excision of subcutaneous lipomas. Methods. From 2003 to 2012, 25 patients with 48 lipomas were treated with liposuction followed by direct excision through the same incision to remove residual lipomatous tissue. Initial postoperative follow-up ranged from 1 week to 3 months, and long-term outcomes, complications, and recurrence were surveyed 1 to 10 years postoperatively. Results. Lipomas on the head, neck, trunk, and extremities ranged from 1 to 15 cm in diameter. Early postoperative hematoma and seromas were managed by aspiration. Among 23 survey respondents (92%), patients were uniformly pleased with the cosmetic results; none reported recurrent lipoma. Conclusions. The combination of liposuction and excision is a safe alternative for lipoma removal; malignancy and recurrence are uncommon. Liposuction performed through a small incision provides satisfactory aesthetic results in most cases. Once reduced in size, residual lipomatous and capsular tissue can be removed without expanding the incision. These favorable outcomes support wider application of this technique in appropriate cases. PMID:25694827

  12. An evaluation of controlled permeability formwork for long-term durability of structural concrete elements

    SciTech Connect

    Suryavanshi, A.K.; Swamy, R.N.

    1997-07-01

    The long-term performance of a concrete slab (CPF slab) exposed to chloride ingress and atmospheric carbonation from the surface generated by controlled permeability formwork (CPF) is investigated. The results are compared with a similar slab exposed to long-term chloride ingress and atmospheric carbonation from the cast face (Control slab). Techniques such as X-ray diffraction (XRD) and differential thermal analyses (DTA) were employed to determine the resistance against carbonation while, mercury porosimetry was used for investigating the pore size distribution at the surface of the slabs. Amount of acid soluble chlorides was determined by using Volhard`s method. The CPF employed at the bottom of the mould was not fully effective in its intended purpose of generating a permanent and dense impermeable concrete layer adjacent to it when the design water-cement (w/c) ration of the concrete mix was 0.60. This resulted in an almost similar extent of carbonation at the surface for both CPF and control slabs as shown by XRD and DTA studies. Similarly, there were no significant differences in the amount of chlorides and their depths of penetration for both CPF and control slabs, although the former was marginally superior in chloride penetration resistance at the surface.

  13. Long-term evaluation of the degradation behavior of three apatite-forming calcium phosphate cements.

    PubMed

    An, Jie; Liao, Hongbing; Kucko, Nathan W; Herber, Ralf-Peter; Wolke, Joop G C; van den Beucken, Jeroen J J P; Jansen, John A; Leeuwenburgh, Sander C G

    2016-05-01

    Calcium phosphate cements (CPCs) are injectable bone substitutes with a long clinical history because of their biocompatibility and osteoconductivity. Nevertheless, their cohesion upon injection into perfused bone defects as well as their long-term degradation behavior remain major clinical challenges. Therefore, the long-term degradation behavior of two types of α-tricalcium phosphate-based, apatite-forming CPCs was compared to a commercially available apatite-forming cement, that is HydroSet(TM) . Carboxyl methylcellulose (CMC) was used as cohesion promotor to improve handling properties of the two experimental cements, whereas poly (d, l-lactic-co-glycolic) acid (PLGA) microparticles were added to introduce macroporosity and stimulate CPC degradation. All three CPCs were injected into defects drilled into rabbit femoral condyles and explanted after 4, 12, or 26 weeks, after which the bone response was assessed both qualitatively and quantitatively. CPCs without PLGA microparticles degraded only at the periphery of the implants, while the residual CPC volume was close to 90%. On the contrary, bone ingrowth was observed not only at the periphery of the CPC, but also throughout the center of the implants after 26 weeks of implantation for the PLGA-containing CPCs with a residual CPC volume of approximately 55%. In conclusion, it was shown that CPC containing CMC and PLGA was able to induce partial degradation of apatite-forming CPCs and concomitant replacement by bone tissue. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1072-1081, 2016. PMID:26743230

  14. Long-term food consumption and body weight changes in neotame safety studies are consistent with the allometric relationship observed for other sweeteners and during dietary restrictions.

    PubMed

    Flamm, W Gary; Blackburn, George L; Comer, C Phil; Mayhew, Dale A; Stargel, W Wayne

    2003-10-01

    In long-term safety studies with neotame, a new high-intensity sweetener 7000-13,000 times sweeter than sucrose, the percent changes (%Delta) in body weight gain (BWG) in Sprague-Dawley rats were several-fold greater than the %Delta in overall food consumption (FC). This study investigates the question of whether the changes in BWG were adverse or secondary to small, long-term decrements in FC. The hypothesis tested in Sprague-Dawley rats was that the relationship between long-term %Delta in FC and %Delta in BWG is linear and in a ratio of 1:1. The %Delta in FC were compared to %Delta in BWG after 52 weeks on study in one saccharin (825 rats), two sucralose (480 rats), two neotame (630 rats), and five dietary restriction (>1000 rats) studies. Non-transformed plotting of data points demonstrated an absence of linearity between %Delta in FC and %Delta in BWG; however, log-log evaluation demonstrated a robust (R2=0.97) linear relationship between %Delta in FC and %Delta in BWG. This relationship followed the well-known allometric equation, y=bxa where x is %DeltaFC, y is %DeltaBWG, b is %DeltaBWG when DeltaFC=1, and a is the log-log slope. Thus, in Sprague-Dawley rats at week 52, the long-term relationship between %Delta in FC and %Delta in BWG was determined to be: %DeltaBWG=3.45(%DeltaFC0.74) for males and %DeltaBWG=5.28(%DeltaFC0.68) for females. Sexes were statistically different but study types, i.e., the high-intensity sweeteners saccharin and sucralose versus dietary restriction, were not. The %Delta in BWG are allometrically consistent with the observed %Delta in FC for these high-intensity sweeteners, including neotame. BW parameters are not appropriate endpoints for setting no-observed-effect levels (NOELs) when materials with intense taste are admixed into food. An approach using objective criteria is proposed to delineate BW changes due to toxicity from those secondary to reduced FC. PMID:14550756

  15. Long-term health-related and economic consequences of short-term outcomes in evaluation of perinatal interventions

    PubMed Central

    2010-01-01

    Background Many perinatal interventions are performed to improve long-term neonatal outcome. To evaluate the long-term effect of a perinatal intervention follow-up of the child after discharge from the hospital is necessary because serious sequelae from perinatal complications frequently manifest themselves only after several years. However, long-term follow-up is time-consuming, is not in the awareness of obstetricians, is expensive and falls outside the funding-period of most obstetric studies. Consequently, short-term outcomes are often reported instead of the primary long-term end-point. With this project, we will assess the current state of affairs concerning follow-up after obstetric RCTs and we will develop multivariable prediction models for different long-term health outcomes. Furthermore, we would like to encourage other researchers participating in follow-up studies after large obstetric trials (> 350 women) to inform us about their studies so that we can include their follow-up study in our systematic review. We would invite these researchers also to join our effort and to collaborate with us on the external validation of our prediction models. Methods/Design A systematic review of neonatal follow-up after obstetric studies will be performed. All reviews of the Cochrane Pregnancy and Childbirth group will be assessed for reviews on interventions that aimed to improve neonatal outcome. Reviews on interventions primary looking at other aspects than neonatal outcome such as labour progress will also be included when these interventions can change the outcome of the neonate on the short or long-term. Our review will be limited to RCTs with more than 350 women. Information that will be extracted from these RCTs will address whether, how and for how long follow-up has been performed. However, in many cases long-term follow-up of the infants will not be feasible. An alternative solution to limited follow-up could be to develop prediction models to estimate

  16. Long-term environmental effects and flight service evaluation of composite materials

    NASA Technical Reports Server (NTRS)

    Dexter, H. Benson

    1987-01-01

    Results of a NASA-Langley sponsored research program to establish the long term effects of realistic flight environments and ground based exposure on advanced composite materials are presented. The effects of moisture, ultraviolet radiation, aircraft fuels and fluids, sustained stress, and fatigue loading are reported. Residual strength and stiffness as a function of exposure time and exposure location are reported for seven different material systems after 10 years of worldwide outdoor exposure. Flight service results of over 300 composite components installed on rotorcraft and transport aircraft are included. Over 4 million total component flight hours were accumulated on various aircraft since initiation of flight service in 1973. Service performance, maintenance characteristics, and residual strength of numerous composite components installed on commercial and military aircraft are reported as a function of flight hours and years in service. Residual strength test results of graphite/epoxy spoilers with 10 years of worldwide service and over 28,000 flight hours are reported.

  17. [Long-term evaluation of a psychological training for obese children and their parents (TAKE)].

    PubMed

    Roth, Binia; Munsch, Simone; Meyer, Andrea H

    2011-01-01

    Cognitive-behavioral parent-child-programmes have shown the best effects in treating childhood obesity so far. With TAKE (Training adipöser Kinder und ihrer Eltern) we introduce a psychologically-informed training, that includes physical activity, nutrition and eating behavior but also addresses psychological issues like self-confidence, body image, social and anti-bullying skills. Long-term data from up to 64 month-follow-up showed moderate effects on body-mass index standard deviation scores (BMI-SDS), and positive effects on children's psychological wellbeing. Maternal psychopathology predicted the course of BMI-SDS in children. Results underline the importance of psychological treatment for obese children to facilitate weight change and to reduce their psychological vulnerability which in turn may prevent the further development of behavior problems, eating disorders and affective disorders. PMID:21614842

  18. Long-Term Follow-Up of a Revascularized Immature Necrotic Tooth Evaluated by CBCT

    PubMed Central

    She, C. M. L.; Cheung, G. S. P.; Zhang, C. F.

    2016-01-01

    This case study reports the successful treatment of an immature upper premolar with periapical pathosis and sinus tract using revascularization technique. Clinical and radiographic examination demonstrated the recovery of vitality, continued root development, and periapical healing at the 7-month follow-up. In addition, severe calcification of the canal was noted at the 36-month follow-up. At the 66-month follow-up, cone-beam computed tomography (CBCT) revealed complete periapical healing, apical closure, increase in root length and thickness of dentin, and severe calcification of the root canal. Even though the nature of tissue within the root canal is unknown, revascularization appears to give good clinical and radiographic success. This case report highlights that severe calcification of the canal is one of the long-term outcomes of revascularized root canals. PMID:26949550

  19. Evaluating long-term performance of in situ vitrified waste forms: Methodology and results

    SciTech Connect

    McGrail, B.P.; Olson, K.M.

    1992-11-01

    In situ vitrification (ISV) is an emerging technology for the remediation of hazardous and radioactive waste sites. The concept relies on the principle of Joule heating to raise the temperature of a soil between an array of electrodes above the melting temperature. After cooling, the melt solidifies into a massive glass and crystalline block similar to naturally occurring obsidian. Determining the long-term performance of ISV products in a changing regulatory environment requires a fundamental understanding of the mechanisms controlling the dissolution behavior of the material. A series of experiments was performed to determine the dissolution behavior of samples produced from the ISV processing of typical soils from the Idaho National Engineering Laboratory subsurface disposal area. Dissolution rate constant measurements were completed at 90{degrees}C over the pH range 2 to 11 for one sample obtained from a field test of the ISV process.

  20. Evaluating long-term performance of in situ vitrified waste forms: Methodology and results

    SciTech Connect

    McGrail, B.P.; Olson, K.M.

    1992-11-01

    In situ vitrification (ISV) is an emerging technology for the remediation of hazardous and radioactive waste sites. The concept relies on the principle of Joule heating to raise the temperature of a soil between an array of electrodes above the melting temperature. After cooling, the melt solidifies into a massive glass and crystalline block similar to naturally occurring obsidian. Determining the long-term performance of ISV products in a changing regulatory environment requires a fundamental understanding of the mechanisms controlling the dissolution behavior of the material. A series of experiments was performed to determine the dissolution behavior of samples produced from the ISV processing of typical soils from the Idaho National Engineering Laboratory subsurface disposal area. Dissolution rate constant measurements were completed at 90[degrees]C over the pH range 2 to 11 for one sample obtained from a field test of the ISV process.

  1. Long term storage of dilute acid pretreated corn stover feedstock and ethanol fermentability evaluation.

    PubMed

    Zhang, Jian; Shao, Shuai; Bao, Jie

    2016-02-01

    This study reported a new solution of lignocellulose feedstock storage based on the distributed pretreatment concept. The dry dilute sulfuric acid pretreatment (DDAP) was conducted on corn stover feedstock, instead of ammonia fiber explosion pretreatment. Then the dry dilute acid pretreated corn stover was stored for three months during summer season with high temperature and humidity. No negative aspects were found on the physical property, composition, hydrolysis yield and ethanol fermentability of the long term stored pretreated corn stover, plus the additional merits including no chemicals recovery operation, anti-microbial contaminant environment from stronger acid and inhibitor contents, as well as the mild and slow hydrolysis in the storage. The new pretreatment method expanded the distributed pretreatment concept of feedstock storage with potential for practical application. PMID:26639616

  2. Evaluating causes of trends in long-term dissolved reactive phosphorus loads to Lake Erie.

    PubMed

    Daloğlu, Irem; Cho, Kyung Hwa; Scavia, Donald

    2012-10-01

    Renewed harmful algal blooms and hypoxia in Lake Erie have drawn significant attention to phosphorus loads, particularly increased dissolved reactive phosphorus (DRP) from highly agricultural watersheds. We use the Soil and Water Assessment Tool (SWAT) to model DRP in the agriculture-dominated Sandusky watershed for 1970-2010 to explore potential reasons for the recent increased DRP load from Lake Erie watersheds. We demonstrate that recent increased storm events, interacting with changes in fertilizer application timing and rate, as well as management practices that increase soil stratification and phosphorus accumulation at the soil surface, appear to drive the increasing DRP trend after the mid-1990s. This study is the first long-term, detailed analysis of DRP load estimation using SWAT. PMID:22962949

  3. Experimental evaluation of stable long term operation of semiconductor magnetic sensors at ITER relevant environment

    NASA Astrophysics Data System (ADS)

    Bolshakova, I.; Belyaev, S.; Bulavin, M.; Brudnyi, V.; Chekanov, V.; Coccorese, V.; Duran, I.; Gerasimov, S.; Holyaka, R.; Kargin, N.; Konopleva, R.; Kost, Ya.; Kuech, T.; Kulikov, S.; Makido, O.; Moreau, Ph; Murari, A.; Quercia, A.; Shurygin, F.; Strikhanov, M.; Timoshyn, S.; Vasil'evskii, I.; Vinichenko, A.

    2015-08-01

    The paper deals with radiation resistant sensors and their associated measuring instrumentation developed in the course of R and D activities carried out in the framework of an international collaboration. The first trial tests of three-dimensional (3D) probes with Hall sensors have been performed in European tokamaks TORE SUPRA (2004) and JET (2005). Later in 2009 six sets of 3D probes were installed in JET and now continue to operate. The statistical analysis performed in 2014 on the basis of the JET database have demonstrated stable long term operation of all 18 sensors of 3D probes. The results of measurements conducted at the neutron fluxes of nuclear reactors have demonstrated the operability of the sensors up to high neutron fluences of F  >  1018n • cm-2 that exceeds the maximum one for the locations of steady state sensors in ITER over its total lifetime.

  4. Evaluation of low-dosage environmental mutagens with a long-term, cultured epithelial cell line

    SciTech Connect

    Li, C.S.; Lin, R.H.

    1996-12-31

    Polycyclic or polynuclear aromatic hydrocarbons (PAHs) are a group of compounds consisting of at least two fused aromatic rings and are common environmental contaminants in soil, water, and air. Additionally, some PAHs are considered to be mutagenic, carcinogenic, and cytotoxic compounds. BaA (Benz(a)anthracene) and BaP (Benzo(a)pyrene) are the two major unsubstituted PAHs identified by the USEPA as priority pollutants. BaA is suspected to be a human carcinogen by the US Department of Health and Human Services, whereas BaP is regarded as an animal carcinogen. It is estimated that the emission concentrations of BaA and BaP from mainstream cigarette smoke are 20-70 ng per g cigarette and 20-40 ng per g cigarette, respectively, with an average sidestream to mainstream weight ratio of 3. In addition, BaA and BaP are also the main emissions from diesel particulate extracts with mean concentrations of 500 ppm and 40 ppm, respectively. From a recent report concerning PAHs in urban areas all over the world, the airborne concentration of BaP was typically found to be in the range of 1-20 ng/m{sup 3} in Europe and 1 ng/m{sup 3} in the U.S.A. For BaA, the concentrations commonly ranged from I to 50 ng/m{sup 3} in Europe and from 0.1 to 1 ng/m{sup 3} in the U.S.A. Therefore, the long term exposure to these two compounds may cause health effects. This study examines long-term cultured epithelial cell lines exposed to BaP or BaA, in vitro, and the frequency of HGPRT mutants. 19 refs., 3 figs.

  5. Robustness-based evaluation of long-term river basin planning under climate change

    NASA Astrophysics Data System (ADS)

    Taner, M. U.; Ray, P. A.; Brown, C. M.

    2015-12-01

    This work develops a bottom-up, multi-stage planning framework for the sustainable development of river basin systems under deep climate uncertainty. The research focuses on whether and when it is desirable to invest for costly water infrastructure projects, and how to select among a set of project alternatives in order achieve the desired economic benefits with a relatively low level of risk. The proposed framework begins with identifying a set of climate conditions to represent the future vulnerability domain of the system using simulation analysis. The conditions identified in the simulation analysis are then used to develop a scenario-tree, to represent the manner in which the uncertainties may evolve over the course of the planning period. Next, optimal decisions are repeatedly explored through a multi-stage optimization model, by varying the probability weights employed in the scenario-tree. The resulting vector of optimal decisions are post-processed to identify robust choices that are least sensitive to the scenario probabilities. The proposed planning framework is illustrated for the Niger Basin, over a 45-year planning period from 2015 to 2060. The Niger Basin is a transboundary system facing a series of challenges including endemic poverty, inadequate infrastructure and weak adaptive capacity to climate variability and change. The case study assesses long-term economic benefits from four new dam projects, and from a range of expansions across the eleven irrigation zones. The climate scenarios are obtained by first generating new climate variability realizations from a stochastic weather generator, and then placing climate change factors on the generated climate realizations. Basin runoff response to climate scenarios are simulated by a series of monthly, two-compartment water balance models. Long-term economic benefits are estimated from the sectors of irrigated agriculture, hydropower, navigation, fishing, and environmental protection, using a mixed

  6. Life Outcomes of Anterior Temporal Lobectomy: Serial Long-term Follow-up Evaluations

    PubMed Central

    Jones, Jana E.; Blocher, Jacquelyn B.; Jackson, Daren C.

    2014-01-01

    Background At three time points, this study examined long-term psychosocial life outcomes of individuals who underwent anterior temporal lobectomy (ATL) compared to individuals with temporal lobe epilepsy that were medically managed. Objective Participants were on average 17 years post-surgery. Seizure frequency, employment, driving, independent living, financial independence, mental health, and quality of life were examined at each follow-up assessment, and predictors of outcomes were examined. Methods All participants were diagnosed with medically intractable complex partial seizures of temporal lobe origin with or without secondary generalization. A structured clinical interview was utilized at all three time points. Information was obtained regarding seizure frequency, anti-epilepsy medications, employment, driving status, financial assistance, and independent living. Additionally, questions regarding quality of life, satisfaction with surgery, and presence of depression or anxiety were included. Results Surgery resulted in significantly improved and sustained seizure outcomes. At the first, second, and third follow-ups 67%, 72%, and 67% of participants in the surgery group remained seizure free in the year prior to follow-up interview. At each follow-up, 97%, 84%, and 84% reported that they would undergo surgery again. Seizure freedom predicted driving outcomes at all three time points, but was not a significant predictor for employment, independent living or financial independence. Psychosocial life outcomes in the surgical group were improved and maintained over time when compared to the medically managed group. Conclusion This systematic long-term investigation provides strong support for the positive impact of ATL on psychosocial life outcomes including driving, employment, independent living, and financial independence. PMID:24056319

  7. Safety and long-term effect of the probiotic FK-23 in patients with hepatitis C virus infection.

    PubMed

    Oo, Khin May; Lwin, Aye Aye; Kyaw, Yi Yi; Tun, Win Maw; Fukada, Kazutake; Goshima, Akiko; Shimada, Takashi; Okada, Shigeru

    2016-01-01

    A clinical trial was conducted on 39 adult HCV-positive subjects to determine the safety and long-term effect of the probiotic FK-23 (heat-treated Enterococcus faecalis strain FK-23). Asymptomatic anti-HCV positive adults who fulfilled the selection criteria and gave voluntary consent were recruited from attendees of the Hepatitis Carrier Clinic, Department of Medical Research (Lower Myanmar). Each subject was given 2,700 mg of FK-23 per day by oral route. Blood samples were taken at enrollment and every 3 months and tested for alanine aminotransferase (ALT) and aspartate transaminase (AST). Viral load, urea, total protein, hemoglobin and platelet count were determined every 6 months. Among the subjects, 23 completed 36 months, 31 completed 24 months, 35 completed 12 months and 37 completed 6 months of probiotic therapy. Significant decreases in mean ALT levels were observed at 3 months (34. 9 ± 15.1 IU/l) as compared with the initial level (64.8 ± 17.5 IU/l) and persisted up to 36 months (43.7 ± 25.2 IU/l). Decrease of AST was detected after 9 months (46.2 ± 21.7 IU/l) of probiotic therapy as compared with the initial level (64.3 ± 28.7 IU/l). FK-23 was safe based on the stable levels of biochemical and hematological parameters and the absence of untoward side effects. The FK-23 preparation was well tolerated and accepted by the subjects. PMID:27508113

  8. Safety and long-term effect of the probiotic FK-23 in patients with hepatitis C virus infection

    PubMed Central

    OO, Khin May; LWIN, Aye Aye; KYAW, Yi Yi; TUN, Win Maw; FUKADA, Kazutake; GOSHIMA, Akiko; SHIMADA, Takashi; OKADA, Shigeru

    2016-01-01

    A clinical trial was conducted on 39 adult HCV-positive subjects to determine the safety and long-term effect of the probiotic FK-23 (heat-treated Enterococcus faecalis strain FK-23). Asymptomatic anti-HCV positive adults who fulfilled the selection criteria and gave voluntary consent were recruited from attendees of the Hepatitis Carrier Clinic, Department of Medical Research (Lower Myanmar). Each subject was given 2,700 mg of FK-23 per day by oral route. Blood samples were taken at enrollment and every 3 months and tested for alanine aminotransferase (ALT) and aspartate transaminase (AST). Viral load, urea, total protein, hemoglobin and platelet count were determined every 6 months. Among the subjects, 23 completed 36 months, 31 completed 24 months, 35 completed 12 months and 37 completed 6 months of probiotic therapy. Significant decreases in mean ALT levels were observed at 3 months (34. 9 ± 15.1 IU/l) as compared with the initial level (64.8 ± 17.5 IU/l) and persisted up to 36 months (43.7 ± 25.2 IU/l). Decrease of AST was detected after 9 months (46.2 ± 21.7 IU/l) of probiotic therapy as compared with the initial level (64.3 ± 28.7 IU/l). FK-23 was safe based on the stable levels of biochemical and hematological parameters and the absence of untoward side effects. The FK-23 preparation was well tolerated and accepted by the subjects.

  9. Accelerated forgetting? An evaluation on the use of long-term forgetting rates in patients with memory problems

    PubMed Central

    Geurts, Sofie; van der Werf, Sieberen P.; Kessels, Roy P. C.

    2015-01-01

    The main focus of this review was to evaluate whether long-term forgetting rates (delayed tests, days, to weeks, after initial learning) are more sensitive measures than standard delayed recall measures to detect memory problems in various patient groups. It has been suggested that accelerated forgetting might be characteristic for epilepsy patients, but little research has been performed in other populations. Here, we identified eleven studies in a wide range of brain injured patient groups, whose long-term forgetting patterns were compared to those of healthy controls. Signs of accelerated forgetting were found in three studies. The results of eight studies showed normal forgetting over time for the patient groups. However, most of the studies used only a recognition procedure, after optimizing initial learning. Based on these results, we recommend the use of a combined recall and recognition procedure to examine accelerated forgetting and we discuss the relevance of standard and optimized learning procedures in clinical practice. PMID:26106343

  10. Accelerated forgetting? An evaluation on the use of long-term forgetting rates in patients with memory problems.

    PubMed

    Geurts, Sofie; van der Werf, Sieberen P; Kessels, Roy P C

    2015-01-01

    The main focus of this review was to evaluate whether long-term forgetting rates (delayed tests, days, to weeks, after initial learning) are more sensitive measures than standard delayed recall measures to detect memory problems in various patient groups. It has been suggested that accelerated forgetting might be characteristic for epilepsy patients, but little research has been performed in other populations. Here, we identified eleven studies in a wide range of brain injured patient groups, whose long-term forgetting patterns were compared to those of healthy controls. Signs of accelerated forgetting were found in three studies. The results of eight studies showed normal forgetting over time for the patient groups. However, most of the studies used only a recognition procedure, after optimizing initial learning. Based on these results, we recommend the use of a combined recall and recognition procedure to examine accelerated forgetting and we discuss the relevance of standard and optimized learning procedures in clinical practice. PMID:26106343

  11. Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care

    PubMed Central

    Urowitz, M; van Vollenhoven, R; Aranow, C; Fettiplace, J; Oldham, M; Wilson, B; Molta, C; Roth, D; Gordon, D

    2016-01-01

    Objective To examine long-term organ damage and safety following treatment with belimumab plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). Methods Pooled data were examined from two ongoing open-label studies that enrolled patients who completed BLISS-52 or BLISS-76. Patients received belimumab every four weeks plus SoC. SLICC Damage Index (SDI) values were assessed every 48 weeks (study years) following belimumab initiation (baseline). The primary endpoint was change in SDI from baseline at study years 5–6. Incidences of adverse events (AEs) were reported for the entire study period. Results The modified intent-to-treat (MITT) population comprised 998 patients. At baseline, 940 (94.2%) were female, mean (SD) age was 38.7 (11.49) years, and disease duration was 6.7 (6.24) years. The mean (SD) SELENA-SLEDAI and SDI scores were 8.2 (4.18) and 0.7 (1.19), respectively; 411 (41.2%) patients had organ damage (SDI = 1: 235 (23.5%); SDI ≥ 2: 176 (17.6%)) prior to belimumab. A total of 427 (42.8%) patients withdrew overall; the most common reasons were patient request (16.8%) and AEs (8.5%). The mean (SD) change in SDI was +0.2 (0.48) at study years 5–6 (n = 403); 343 (85.1%) patients had no change from baseline in SDI score (SDI +1: 46 (11.4%), SDI +2: 13 (3.2%), SDI +3: 1 (0.2%)). Of patients without organ damage at baseline, 211/241 (87.6%) had no change in SDI and the mean change (SD) in SDI was +0.2 (0.44). Of patients with organ damage at baseline, 132/162 (81.5%) had no change in SDI and the mean (SD) change in SDI was +0.2 (0.53). The probability of not having a worsening in SDI score was 0.88 (95% CI: 0.85, 0.91) and 0.75 (0.67, 0.81) in those without and with baseline damage, respectively (post hoc analysis). Drug-related AEs were reported for 433 (43.4%) patients; infections/infestations (282, 28.3%) and gastrointestinal disorders (139, 13.9%) were the most common. Conclusion Patients with SLE treated with long-term

  12. 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

  13. Evaluation of a long-term hindcast simulation for the Columbia River estuary

    NASA Astrophysics Data System (ADS)

    Kärnä, Tuomas; Baptista, António M.

    2016-03-01

    In order to simulate the biogeochemical function of estuaries across the land-ocean continuum, circulation models must represent a cascade of complex physical processes spanning several spatial and temporal scales. Furthermore, governing physical processes tend to vary under different flow regimes, in response to external forcings. Model validation must therefore cover all relevant flow regimes and span sufficiently long time to represent transient and slowly-varying phenomena. We focus in a multi-year hindcast simulation of the Columbia River estuary - a mesotidal, river-dominated estuary that is also influenced by coastal upwelling in an Eastern Boundary Current system. Model skill is assessed against long-term observational time series, covering the lower estuary (for salinity) as well as most of the tidal river (for water temperature and elevation). In addition, high-resolution profiles of velocity and salinity are used to study salt transport mechanisms at a single station. Results indicate that the model captures the estuarine dynamics of the system, but the skill depends on the flow regime: In general the model performs far better during spring tides (i.e., under partially mixed or time-dependent salt wedge regimes) than under neap tides (i.e., salt wedge and strongly stratified regimes). While the model accurately represents tidal salt transport mechanisms, it tends to underestimate gravitational transport which becomes more important under neap tide conditions. Furthermore, the skill decreases during high river discharge periods, because the model has difficulty capturing the extremely strong stratification characteristic to those periods.

  14. Evaluating the feasibility of biological waste processing for long term space missions

    NASA Technical Reports Server (NTRS)

    Garland, J. L.; Alazraki, M. P.; Atkinson, C. F.; Finger, B. W.; Sager, J. C. (Principal Investigator)

    1998-01-01

    Recycling waste products during orbital (e.g., International Space Station) and planetary missions (e.g., lunar base, Mars transit mission, Martian base) will reduce storage and resupply costs. Wastes streams on the space station will include human hygiene water, urine, faeces, and trash. Longer term missions will contain human waste and inedible plant material from plant growth systems used for atmospheric regeneration, food production, and water recycling. The feasibility of biological and physical-chemical waste recycling is being investigated as part of National Aeronautics and Space Administration's (NASA) Advanced Life Support (ALS) Program. In-vessel composting has lower manpower requirements, lower water and volume requirements, and greater potential for sanitization of human waste compared to alternative bioreactor designs such as continuously stirred tank reactors (CSTR). Residual solids from the process (i.e. compost) could be used a biological air filter, a plant nutrient source, and a carbon sink. Potential in-vessel composting designs for both near- and long-term space missions are presented and discussed with respect to the unique aspects of space-based systems.

  15. Evaluating the feasibility of biological waste processing for long term space missions.

    PubMed

    Garland, J L; Alazraki, M P; Atkinson, C F; Finger, B W

    1998-01-01

    Recycling waste products during orbital (e.g., International Space Station) and planetary missions (e.g., lunar base, Mars transit mission, Martian base) will reduce storage and resupply costs. Wastes streams on the space station will include human hygiene water, urine, faeces, and trash. Longer term missions will contain human waste and inedible plant material from plant growth systems used for atmospheric regeneration, food production, and water recycling. The feasibility of biological and physical-chemical waste recycling is being investigated as part of National Aeronautics and Space Administration's (NASA) Advanced Life Support (ALS) Program. In-vessel composting has lower manpower requirements, lower water and volume requirements, and greater potential for sanitization of human waste compared to alternative bioreactor designs such as continuously stirred tank reactors (CSTR). Residual solids from the process (i.e. compost) could be used a biological air filter, a plant nutrient source, and a carbon sink. Potential in-vessel composting designs for both near- and long-term space missions are presented and discussed with respect to the unique aspects of space-based systems. PMID:11541774

  16. Long term evaluation of etiological treatment of chagas disease with benznidazole.

    PubMed

    Cancado, J Romeu

    2002-01-01

    The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of the treatment of

  17. 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

  18. Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection.

    PubMed

    Shen, Cheng-Huang; Wang, Shou-Chieh; Wang, Shou-Tsung; Lin, Shu-Mei; Wu, Jiann-Der; Lin, Chang-Te; Liu, Yi-Wen

    2016-09-01

    Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction remains unclear. The present study aimed to investigate the physiological, histological and molecular changes on ketamine‑associated cystitis (KC) in a mouse model. Both male and female Balb/c mice were separately distributed into the control group (normal saline) and ketamine group, which received ketamine hydrochloride (100 mg/kg/day) daily by intraperitoneal injection for a total period of 20 weeks. In each group, the urine was analyzed by gas chromatography‑mass spectrometry to measure the concentration of ketamine and its metabolites. Urinary frequency and urine volume were examined to investigate the urinary voiding functions. Mice bladders were excised for cDNA microarray and hematoxylin and eosin (HE) staining. The ketamine and metabolites were detected only in ketamine‑treated mice urine. The voiding interval was reduced in the male mice group after 20 week ketamine administration. Additionally, the result of cDNA array analysis revealed a number of gene expression levels involved in chronic wound healing response and collagen accumulation, which were closely associated with fibrosis progression in the connective tissue. In HE staining of the bladder tissue, the ketamine-injected mice exhibited prominently denser blood vessel distribution in the submucosal layer. Based on the evidence in the present study, a mechanism that delineates fibrosis formation of urinary bladder induced by the pathogenesis of ketamine abuse can be constructed. PMID:27431428

  19. Long-term Evaluation of Radiation-Induced Optic Neuropathy After Single-Fraction Stereotactic Radiosurgery

    SciTech Connect

    Leavitt, Jacqueline A.; Stafford, Scott L.; Link, Michael J.; Pollock, Bruce E.

    2013-11-01

    Purpose: To determine the long-term risk of radiation-induced optic neuropathy (RION) in patients having single-fraction stereotactic radiosurgery (SRS) for benign skull base tumors. Methods and Materials: Retrospective review of 222 patients having Gamma Knife radiosurgery for benign tumors adjacent to the anterior visual pathway (AVP) between 1991 and 1999. Excluded were patients with prior or concurrent external beam radiation therapy or SRS. One hundred twenty-nine patients (58%) had undergone previous surgery. Tumor types included confirmed World Health Organization grade 1 or presumed cavernous sinus meningioma (n=143), pituitary adenoma (n=72), and craniopharyngioma (n=7). The maximum dose to the AVP was ≤8.0 Gy (n=126), 8.1-10.0 Gy (n=39), 10.1-12.0 Gy (n=47), and >12 Gy (n=10). Results: The mean clinical and imaging follow-up periods were 83 and 123 months, respectively. One patient (0.5%) who received a maximum radiation dose of 12.8 Gy to the AVP developed unilateral blindness 18 months after SRS. The chance of RION according to the maximum radiation dose received by the AVP was 0 (95% confidence interval [CI] 0-3.6%), 0 (95% CI 0-10.7%), 0 (95% CI 0-9.0%), and 10% (95% CI 0-43.0%) for patients receiving ≤8 Gy, 8.1-10.0 Gy, 10.1-12.0 Gy, and >12 Gy, respectively. The overall risk of RION in patients receiving >8 Gy to the AVP was 1.0% (95% CI 0-6.2%). Conclusions: The risk of RION after single-fraction SRS in patients with benign skull base tumors who have no prior radiation exposure is very low if the maximum dose to the AVP is ≤12 Gy. Physicians performing single-fraction SRS should remain cautious when treating lesions adjacent to the AVP, especially when the maximum dose exceeds 10 Gy.

  20. Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection

    PubMed Central

    Shen, Cheng-Huang; Wang, Shou-Chieh; Wang, Shou-Tsung; Lin, Shu-Mei; Wu, Jiann-Der; Lin, Chang-Te; Liu, Yi-Wen

    2016-01-01

    Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction remains unclear. The present study aimed to investigate the physiological, histological and molecular changes on ketamine-associated cystitis (KC) in a mouse model. Both male and female Balb/c mice were separately distributed into the control group (normal saline) and ketamine group, which received ketamine hydrochloride (100 mg/kg/day) daily by intraperitoneal injection for a total period of 20 weeks. In each group, the urine was analyzed by gas chromatography-mass spectrometry to measure the concentration of ketamine and its metabolites. Urinary frequency and urine volume were examined to investigate the urinary voiding functions. Mice bladders were excised for cDNA microarray and hematoxylin and eosin (HE) staining. The ketamine and metabolites were detected only in ketamine-treated mice urine. The voiding interval was reduced in the male mice group after 20 week ketamine administration. Additionally, the result of cDNA array analysis revealed a number of gene expression levels involved in chronic wound healing response and collagen accumulation, which were closely associated with fibrosis progression in the connective tissue. In HE staining of the bladder tissue, the ketamine-injected mice exhibited prominently denser blood vessel distribution in the submucosal layer. Based on the evidence in the present study, a mechanism that delineates fibrosis formation of urinary bladder induced by the pathogenesis of ketamine abuse can be constructed. PMID:27431428

  1. Long-term testing and evaluation of cathode components in a commercial aluminum cell

    SciTech Connect

    Gee, J.T.; Tucker, K.W; Joo, L.A.; Stewart, D.V.; Alcorn, T.; Tabereaux, A.

    1989-08-01

    Since 1886, essentially all primary aluminum has been produced in Hall-Heroult electrolytic cells which electrochemically reduce alumina to the metal in an energy/capital intensive process. Nearly five per cent of the electrical energy generated in the United States is consumed in this Hall-Heroult process, at the rate of 6--8 kwh/lb of aluminum produced. It has been in the aluminum industry's interest for the past several decades to utilize titanium diboride in some capacity as the cell cathode, either with conventional consumable carbon anodes or ultimately with nonconsumable, inert anodes. Eventual achievement of either or both of these goals will represent a technological breakthrough and make possible a significant reduction in the energy requirement to produce aluminum. The overall objective and achievement of this program was to better define the technical and economic viability of graphite-containing titanium diboride materials in low-cost shapes for use as cathodes in aluminum electrolytic cells as a precursor to subsequent demonstration and commercial application. Included are mathematical models for the prediction of cost-reducing cathode shapes, optimizing ratios of electrode areas, voltage reduction, and the effect on current efficiency from reduced anode-cathode distance. As part of the program, cathode shapes were produced using proprietary material processing technologies. Long-term commercial and medium-term pilot cell operations for data acquisition and cathode longevity determinations were completed, as were analyses of as-fabricated and as-tested cathodes, development of possible failure mechanisms, development of cathode holder/anode stops and an assessment of energy savings and technical/economic viability.

  2. Re-Evaluation of Development of the TMDL Using Long-Term Monitoring Data and Modeling

    NASA Astrophysics Data System (ADS)

    Squires, A.; Rittenburg, R.; Boll, J.; Brooks, E. S.

    2012-12-01

    Since 1996, 47,979 Total Maximum Daily Loads (TMDLs) have been approved throughout the United States for impaired water bodies. TMDLs are set through the determination of natural background loads for a given water body which then estimate contributions from point and nonpoint sources to create load allocations and determine acceptable pollutant levels to meet water quality standards. Monitoring data and hydrologic models may be used in this process. However, data sets used are often limited in duration and frequency, and model simulations are not always accurate. The objective of this study is to retrospectively look at the development and accuracy of the TMDL for a stream in an agricultural area using long-term monitoring data and a robust modeling process. The study area is the Paradise Creek Watershed in northern Idaho. A sediment TMDL was determined for the Idaho section of Paradise Creek in 1997. Sediment TMDL levels were determined using a short-term data set and the Water Erosion Prediction Project (WEPP) model. Background loads used for the TMDL in 1997 were from pre-agricultural levels, based on WEPP model results. We modified the WEPP model for simulation of saturation excess overland flow, the dominant runoff generation mechanism, and analyzed more than 10 years of high resolution monitoring data from 2001 - 2012, including discharge and total suspended solids. Results will compare background loading and current loading based on present-day land use documented during the monitoring period and compare previous WEPP model results with the modified WEPP model results. This research presents a reevaluation of the TMDL process with recommendations for a more scientifically sound methodology to attain realistic water quality goals.

  3. Evaluating the adequacy of climate change information to support long-term water resource planning

    NASA Astrophysics Data System (ADS)

    Brekke, L. D.; Clark, M. P.; Gutmann, E. D.; Pruitt, T.; Mizukami, N.; Mendoza, P. A.; Rasmussen, R.; Arnold, J.; Raff, D. A.; Rajagopalan, B.

    2013-12-01

    The National Center for Atmospheric Research (NCAR), the Department of Interior's Bureau of Reclamation (Reclamation) and the U.S. Army Corps of Engineers (USACE) are partnering to understand appropriate applications of downscaling methods and hydrologic analysis used to produce projections of hydroclimate impacts used in long-term water resources planning and management. The overall objectives of this project are to determine the extent to which the portrayal of hydroclimate impacts depends on methodological choices, understand why different methods produce different results, and provide guidance on the suitability of different methods to provide state-of-the-art intelligence for water resources planning and management. Research questions include: (1) How does the portrayal of hydrologic impacts under climate change depend on the chosen downscaling method and resolution (i.e. dynamical downscaling using regional climate models versus non-dynamical downscaling using statistical or empirical methods)? (2) How does the portrayal of hydrologic impacts under climate change depend on the choice/configuration of hydrologic model(s) used for impact assessment and the parameter estimation strategy? This presentation provides a synthesis of methods and key findings. Main results are (i) high-resolution dynamic downscaling using a model such as the Weather Research and Forecasting model (WRF) is required to properly capture precipitation processes over complex terrain in the Colorado Headwaters region, and climate change scenarios from the 4-km WRF simulations are very different from current guidance being provided to water managers; (ii) WRF simulations at 12-km and 36-km have poor correspondence to observations, and very different change signals to the 4-km WRF simulations; (iii) the statistical downscaling methods examined struggle to adequately capture daily precipitation characteristics that are important to hydrologic impacts, such as wet-day frequency and spatial

  4. Results of the Recent Immigrant Pregnancy and Perinatal Long-term Evaluation Study (RIPPLES)

    PubMed Central

    Ray, Joel G.; Vermeulen, Marian J.; Schull, Michael J.; Singh, Gita; Shah, Rajiv; Redelmeier, Donald A.

    2007-01-01

    Background People who immigrate to Western nations may experience fewer chronic health problems than original residents of those countries, which raises concerns about long-term environmental or lifestyle factors in those countries. We tested whether the “healthy immigrant effect” extends to the risk of placental dysfunction during the short interval of pregnancy. Methods We conducted a population-based retrospective cohort study of data for 796 105 women who had a first documented obstetric delivery in Ontario between 1995 and 2005. Recency of immigration was determined for each woman as the time from her enrolment in universal health insurance to her date of delivery, classified as less than 3 months, 3–5 months, 6–11 months, 12–23 months, 24–35 months, 36–47 months, 48–59 months and 5 years or more (the referent). The primary composite outcome was maternal placental syndrome (defined as a diagnosis of pre-eclampsia or eclampsia, placental abruption or placental infarction). Results The mean age of the women was 28.8 years. Maternal placental syndrome occurred in 45 216 women (5.7%). The risk of this outcome was lowest among the women who had immigrated less than 3 months before delivery (3.8%) and highest among those living in Ontario at least 5 years (6.0%), for a crude odds ratio (OR) of 0.62 (95% confidence interval [CI] 0.54–0.71). After adjustment for maternal age, income status, pre-existing hypertension, diabetes mellitus, multiple gestation and receipt of prenatal ultrasonography, the risk of maternal placental syndrome was correlated with the number of months since immigration in a gradient manner (OR, 95% CI): less than 3 months (0.53, 0.47–0.61), 3–5 months (0.68, 0.61–0.76), 6–11 months (0.67, 0.63–0.71), 12–23 months (0.69, 0.66–0.73), 24–35 months (0.75, 0.70–0.79), 36–47 months (0.75, 0.70–0.80) and 48–59 months (0.82, 0.77–0.87). Interpretation There was a progressively lower risk of maternal placental

  5. 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

  6. 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

  7. 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 ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  8. Evaluating, Migrating, and Consolidating Databases and Applications for Long-Term Surveillance and Maintenance Activities at the Rocky Flats Site

    SciTech Connect

    Surovchak, S.; Marutzky, S.; Thompson, B.; Miller, K.; Labonte, E.

    2006-07-01

    The U.S. Department of Energy (DOE) Office of Legacy Management (LM) is assuming responsibilities for long-term surveillance and maintenance (LTS and M) activities at the Rocky Flats Environmental Technology Site (RFETS) during fiscal year 2006. During the transition, LM is consolidating databases and applications that support these various functions into a few applications which will streamline future management and retrieval of data. This paper discussed the process of evaluating, migrating, and consolidating these databases and applications for LTS and M activities and provides lessons learned that will benefit future transitions. (authors)

  9. Evaluation of the long-term energy analysis program used for the 1978 EIA Administrator's Report to Congress

    SciTech Connect

    Peelle, R. W.; Weisbin, C. R.; Alsmiller, Jr., R. G.

    1981-10-01

    An evaluation of the Long-Term Energy Analysis Program (LEAP), a computer model of the energy portion of the US economy that was used for the 1995-2020 projections in its 1978 Annual Report to Congress, is presented. An overview of the 1978 version, LEAP Model 22C, is followed by an analysis of the important results needed by its users. The model is then evaluated on the basis of: (1) the adequacy of its documentation; (2) the local experience in operating the model; (3) the adequacy of the numerical techniques used; (4) the soundness of the economic and technical foundations of the model equations; and (5) the degree to which the computer program has been verified. To show which parameters strongly influence the results and to approach the question of whether the model can project important results with sufficient accuracy to support qualitative conclusions, the numerical sensitivities of some important results to model input parameters are described. The input data are categorized and discussed, and uncertainties are given for some parameters as examples. From this background and from the relation of LEAP to other available approaches for long-term energy modeling, an overall evaluation is given of the model's suitability for use by the EIA.

  10. 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

  11. 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

  12. Evaluating Long-Term Outcomes of Treatments for Drug and Alcohol Addiction.

    ERIC Educational Resources Information Center

    Horton, Arthur M. Ed.; McKay, James R. Ed.

    2001-01-01

    Articles in this special issue are reviews that focus on issues related to the evaluation of addiction treatment outcomes over longer term followup periods (2 years or more). The primary conclusion that can be drawn is that research evaluations of substance abuse treatment should reflect, to a greater degree, the chronic nature of addiction. (SLD)

  13. Evaluation and prediction of long-term environmental effects of nonmetallic materials, second phase

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Changes in the functional properties of a number of nonmetallic materials were evaluated experimentally as a function of simulated space environments and to use such data to develop models for accelerated test methods useful for predicting such behavioral changes. The effects of changed particle irradiations on candidate space materials are evaluated.

  14. Dynamic Evaluation of Long-Term Air Quality Model Simulations Over the Northeastern U.S.

    EPA Science Inventory

    Dynamic model evaluation assesses a modeling system's ability to reproduce changes in air quality induced by changes in meteorology and/or emissions. In this paper, we illustrate various approaches to dynamic mode evaluation utilizing 18 years of air quality simulations perform...

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

    PubMed Central

    Böhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

    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

  16. Introduction: Evaluating long-term impacts of harvesting crop residues on soil quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilizing crop residues as biofuel feedstocks will involve trade-offs between bioenergy production and agroecosystem services. Consequently, agricultural production managers and policymakers need to critically evaluate current functions of crop residues in light of increasing demands for agricultura...

  17. NightCool: Nocturnal Radiation Cooling Concept Long Term Performance Evaluation

    SciTech Connect

    Parker, Danny S.; Sherwin, John R.; Hermelink, Andreas; Moyer, Neil

    2009-12-01

    This report is about an experimental evaluation that has been conducted on a building-integrated night sky cooling system designed to substantialy reduce space cooling needs in homes in North American climates.

  18. Impact of a Student Response System on Short- and Long-Term Learning in a Drug Literature Evaluation Course

    PubMed Central

    Liu, Flora C.; Gettig, Jacob P.

    2010-01-01

    Objective To evaluate the effectiveness of a student response system on short- and long-term learning in a required second-year pharmacy course. Method Student volunteers enrolled in the course Drug Literature Evaluation were blinded and randomized to 1 of 2 groups. Group 1 attended a lecture in which the instructor used a student response system. Group 2 attended the same lecture by the same instructor an hour later, but no student response system was used. A 16-point unannounced quiz on the lecture material was administered to both groups at the end of class. Approximately 1 month later, both groups were given another unannounced quiz on the same material to test long-term student learning. Results One hundred seventy-nine (92.3%) students participated in both quizzes. Students who attended the class in which the student response system was used scored an average 1 point higher on quiz 1 than students who were assigned to the control group (10.7 vs. 9.7; p = 0.02). No significant difference was seen between the quiz 2 scores of the 2 groups (9.5 vs. 9.5; p = 0.99). Conclusions The use of a student response system can positively impact students' short-term learning; however, that positive effect did not appear to last over time. Faculty members may want to consider the use of student response systems to enhance student learning in large lecture classes. PMID:20221357

  19. PERFORMANCE EVALUATION AT A LONG-TERM FOOD PROCESSING LAND TREATMENT SITE

    EPA Science Inventory

    The objective of this project was to determine the performance of a full scale, operating overland flow land (GEL) treatment system treating nonhazardous waste. Performance was evaluated in terms of treatment of the applied waste and the environmental impact of the system, partic...

  20. Evaluating Long-Term Effects of the Golden Lion Tamarin Environmental Education Program in Brazil

    ERIC Educational Resources Information Center

    Engels, Christine Archer; Jacobson, Susan K.

    2007-01-01

    The authors evaluated the environmental education program of the Golden Lion Tamarin Association in Brazil by comparing results of a 2001 survey with baseline data from 1986. Responses of 666 residents and results from 4 focus groups revealed an increase in public support for the tamarin and its habitat and an increase in general environmental…

  1. Evaluating measures to assess soil health in long-term agroecosystem trials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Monitoring and assessing soil health is an important component of any land management system with a vision of sustaining soil resources. Soil organic matter(SOM)characteristics are key to soil health and responsive to tillage regime and crop management. As metrics of soil health, we evaluated surfac...

  2. Evaluating Long-Term Complex Professional Development: Using a Variation of the Cohort Control Design

    ERIC Educational Resources Information Center

    Sample Mcmeeking, Laura B.; Cobb, R. Brian; Basile, Carole

    2010-01-01

    This paper introduces a variation on the post-test only cohort control design and addresses questions concerning both the methodological credibility and the practical utility of employing this design variation in evaluations of large-scale complex professional development programmes in mathematics education. The original design and design…

  3. [An evaluation of the long-term results of palatopharyngeal closure function after velopharyngeal ring ligation].

    PubMed

    Zhang, S; Wei, F; Zhang, P

    1997-08-01

    16 cases were selected randomly from a group of 36 postoperative patients who underwent velopharyngeal ring ligation 16 years ago for evaluation of pronunciation, pharyngeal radiography, and electric endostroboskop to evaluate the patients' velopharygeal closure function. It was found that the pronunciation function of 93% patients were in good status. The results showed that centripetal force of velopharyngeal ring ligation made the velopharyngeal cavity reduced from the right to left and from anterior to posterior sides. It was good for sphincter of velopharyngeal moving, which could reduce the space of pharyngeal cavity and add the length of soft palate. The velopharyngeal closure was improved, which produced a good condition for the recovery of pronunciation function, at the same time, the change of pharyngeal cavity adapts to the patient's growth without limiting the growth and development of nasovelopharyngeal. PMID:11480008

  4. Long-term prospective evaluation of intestinal anastomosis using stainless steel staples in 14 dogs.

    PubMed

    Benlloch-Gonzalez, Manuel; Gomes, Eymeric; Bouvy, Bernard; Poncet, Cyrill

    2015-07-01

    This prospective clinical study evaluated the use, complications, and clinical and ultrasonographic follow-ups of end-to-end intestinal anastomoses with skin staples in naturally occurring diseases in canine small and large intestines. Intestinal anastomoses were performed in 14 dogs and pre-, peri-, and postoperative data were recorded. Postoperative clinical and ultrasound evaluations were performed at regular intervals for 1 year. The mean time taken to construct the anastomosis was 5 min. There were no intraoperative complications. Hemorrhage and colonic stricture were the main postoperative complications. Staple loss occurred in 2 cases. Absence of wall layering and focal wall thickening were observed in all cases at each ultrasonographic follow-up. Hyperechoic fat was observed in all but 1 of the cases at month 1. Nine dogs were alive with normal digestive function at the end of the study. The skin stapler technique enabled rapid construction of consistent anastomoses with inexpensive stapling material. PMID:26130833

  5. Long-term evaluation of porous PEGT/PBT implants for soft tissue augmentation.

    PubMed

    Lamme, Evert N; Druecke, Daniel; Pieper, Jeroen; May, Paul S; Kaim, Peter; Jacobsen, Frank; Steinau, Hans-Ulrich; Steinstraesser, Lars

    2008-01-01

    Porous PEGT/PBT implants with different physico-chemical characteristics were evaluated to identify its potential as biodegradable and biofunctional soft tissue filler. Implants (50 x 10 x 5 mm3) were implanted subcutaneously in mini-pigs and tissue response, tissue volume generated and its consistency were assessed quantitatively with a 52 weeks follow-up. The absence of wound edema, skin irritation, and chronic inflammation demonstrated biocompatibility of all implants evaluated. The hydrophobic implants induced the mildest foreign body response, generated highest amount of connective tissue and demonstrated a decrease in copolymer MW of 34-37% compared to 90% decrease of the hydrophilic implants. The rate and extent of copolymer fragmentation seems to be the determining factor of success of soft tissue augmentation using porous PEGT/PBT copolymer implants. PMID:18089674

  6. Long-term prospective evaluation of intestinal anastomosis using stainless steel staples in 14 dogs

    PubMed Central

    Benlloch-Gonzalez, Manuel; Gomes, Eymeric; Bouvy, Bernard; Poncet, Cyrill

    2015-01-01

    This prospective clinical study evaluated the use, complications, and clinical and ultrasonographic follow-ups of end-to-end intestinal anastomoses with skin staples in naturally occurring diseases in canine small and large intestines. Intestinal anastomoses were performed in 14 dogs and pre-, peri-, and postoperative data were recorded. Postoperative clinical and ultrasound evaluations were performed at regular intervals for 1 year. The mean time taken to construct the anastomosis was 5 min. There were no intraoperative complications. Hemorrhage and colonic stricture were the main postoperative complications. Staple loss occurred in 2 cases. Absence of wall layering and focal wall thickening were observed in all cases at each ultrasonographic follow-up. Hyperechoic fat was observed in all but 1 of the cases at month 1. Nine dogs were alive with normal digestive function at the end of the study. The skin stapler technique enabled rapid construction of consistent anastomoses with inexpensive stapling material. PMID:26130833

  7. Clinical evaluation of direct composite restoration done for midline diastema closure – long-term study

    PubMed Central

    Prabhu, R.; Bhaskaran, S.; Geetha Prabhu, K. R.; Eswaran, M. A.; Phanikrishna, G.; Deepthi, B.

    2015-01-01

    Purpose of the Study: The aim of this study was to evaluate clinically the performance of composite resin used to restore midline diastema between the maxillary and mandibular central incisors. Methodology: Direct composite restorations were done for 45 patients with midline diastema between the maxillary and mandibular central incisors. Standard protocols were followed for the placement of composite resin for the diastema closure, and recall visits were made for every 6 months for a period of 60 months for evaluation of the success of these restorations made. Qualified dental personnel examined the restorations made. Results: Clinical evaluations were done after the restorations had been in place for an average of 6 months. Results indicate that none of the restorations were totally lost, and resulting in a 91% overall retention rate for the period of 60 months. About 62% of the restorations made had no noticeable color difference with that of the adjacent tooth, and gingival health indicated 73% of the sample was without any signs of inflammation. Conclusions: Composites restored for diastemas exhibit satisfactory survival rates placed with recommended placement protocols and without occlusal loading. PMID:26538917

  8. Experiences in long-term evaluation of mercury emission monitoring systems

    SciTech Connect

    Chin-Min Cheng; Hung-Ta Lin; Qiang Wang; Chien-Wei Chen; Chia-Wei Wang; Ming-Chung Liu; Chi-Kuan Chen; Wei-Ping Pan

    2008-09-15

    Six mercury continuous emission monitoring (CEM) systems provided by two leading mercury (Hg) CEM system manufacturers were tested at five coal combustion utilities. The linearity, response time, day-to-day stability, efficiency of the Hg speciation modules, and ease of use were evaluated by following procedures specified in the Code of Federal Regulation Title 40 Part 75 (40 CFR Part 75). Mercury monitoring results from Hg CEM systems were compared to an EPA-recognized reference method. A sorbent trap sampling system was also evaluated in this study to compare the relative accuracy to the reference method as well as to Hg CEM systems. A conceptual protocol proposed by U.S. EPA (Method 30A) for using an Hg CEM system as the reference method for the Hg relative accuracy (RA) test was also followed to evaluate the workability of the protocol. This paper discusses the operational experience obtained from these field studies and the remaining challenges to overcome while using Hg CEM systems and the sorbent trap method for continuous Hg emission monitoring. 3 refs., 5 figs., 11 tabs.

  9. Long-term quantitative evaluation of liver transplantation in familial amyloid polyneuropathy (Portuguese V30M).

    PubMed

    de Carvalho, Mamede; Conceição, Isabel; Bentes, Carla; Luís, M L Sales

    2002-06-01

    Familial amyloid polyneuropathy (FAP) is associated with massive endoneurial and extracellular deposition of amyloid, which isformed from a mutated transthyretin (TTR) protein. Ninety percent of TTR protein is produced in liver. Liver transplantation (LT) is the only treatment that can halt FAP clinical progression. We studied 35 LT patients. The mean age of the first symptoms was 36.6 years (ranging from 27 to 56), 19 were males, and 16 females, they underwent LT after a mean time of 5 years of symptomatic disease. Fifteen patients followed for more than 24 months after LT had periodic evaluations with clinical and neurophysiological scores (CS and NS). Ten were first evaluated before LT (mean follow-up time of 44 months after LT), and 5 were evaluated only after LT (or a mean time of 41 months). Five patients were followed periodically before LT (mean time of 44 months) to study the natural course of this condition. The mortality rate was of 14% in the first 6 months and was related to known complications of the surgery. No deaths occurred in the period 6 months to 1 year after LT. Five patients (14%) died 1-2 years after LT, 4 of whom were transplanted in advance stages. In the survival group, CS tended to stabilize shortly after LT and to remain invariable later on. The NSprogressed in the first year following LT, and subsequently it did not increase significantly. LT changed the natural course of FAP-I. PMID:12440485

  10. 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

  11. 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

  12. Evaluation and prediction of long-term environmental effects of nonmetallic materials

    NASA Technical Reports Server (NTRS)

    Papazian, H.

    1985-01-01

    The properties of a number of nonmetallic materials were evaluated experimentally in simulated space environments in order to develop models for accelerated test methods useful for predicting such behavioral changes. Graphite-epoxy composites were exposed to thermal cycling. Adhesive foam tapes were subjected to a vacuum environment. Metal-matrix composites were tested for baseline data. Predictive modeling designed to include strength and aging effects on composites, polymeric films, and metals under such space conditions (including the atomic oxygen environment) is discussed. The Korel 8031-00 high strength adhesive foam tape was shown to be superior to the other two tested.

  13. Long-term evaluation of granulocyte-colony stimulating factor on hypoxic-ischemic brain damage in infant rats

    PubMed Central

    Fathali, Nancy; Lekic, Tim; Zhang, John H.

    2011-01-01

    Purpose Hypoxia-ischemia (HI), as a major cause of fetal brain damage, has long-lasting neurological implications. Therefore, therapeutic interventions that attenuate the neuropathological outcome of HI while also improving the neuro-functional outcome are of paramount clinical importance. The aim of this study was to investigate the long-term functional and protective actions of granulocyte-colony stimulating factor (G-CSF) treatment in an experimental model of cerebral HI. Methods Postnatal day-7 Sprague-Dawley rats were subjected to HI surgery, which entailed ligation of the right common carotid artery followed by 2 h of hypoxia (8% O2). Treatment consisted of subcutaneous injection of G-CSF at 1 h after hypoxia followed by an additional one injection per day for 5 days (6 total injections) or for 10 days (11 total injections). Animals were euthanized 5 weeks post-insult for extensive evaluation of neurological deficits and assessment of brain, spleen, heart, and liver damage. Results G-CSF treatment promoted somatic growth and prevented brain atrophy and under-development of the heart. Moreover, reflexes, limb placing, muscle strength, motor coordination, short-term memory, and exploratory behavior were all significantly improved by both G-CSF dosing regimens. Conclusions Long-term neuroprotection afforded by G-CSF in both morphological and functional parameters after a hypoxic-ischemic event in the neonate provides a rationale for exploring clinical translation. PMID:20461500

  14. ASIM: a system for monitoring and evaluating the long-term care of the elderly and disabled.

    PubMed Central

    Lagergren, M

    1993-01-01

    OBJECTIVE. A system for monitoring and evaluating the long-term care of the elderly and disabled is presented, and its problems of completeness, reliability, and validity are discussed. DATA SOURCES/STUDY SETTING. Half-yearly (before 1987) and yearly (after 1987) surveys were taken from 1984 to 1990 of all persons living in the city of Solna, Sweden, who at May 1 and November 1, or November 1, were receiving long-term care services from the municipality or county council, or both. STUDY DESIGN. Completeness of observations was studied by linking survey and admission/discharge observations and checking for breaks in the chain of care. Reliability was estimated by comparing involuntary double registrations. Validity of the chosen measures of need was tested by comparing them with the actual provision of care services. DATA COLLECTION. Registrations concerning actually provided services, assessed need, social environment, and disability were collected on a regular basis by the staff responsible for the care services. PRINCIPAL FINDINGS. Completeness was estimated to be more than 99 percent after a special procedure was carried out for filling in gaps in the "care chain." Reliability testing of the disability measures showed between .69 and .76 Kappa coefficient of agreement. Disability variables were shown to explain 56 percent of variance in the need measure "appropriate level of care." CONCLUSIONS. Tests of completeness, reliability, and validity showed satisfactory results with regard to the purpose of the monitoring system and the limitations inherent in a system intended for routine application. PMID:8463108

  15. Long-term three-dimensional cell culture and anticancer drug activity evaluation in a microfluidic chip.

    PubMed

    Ziółkowska, Karina; Stelmachowska, Agnieszka; Kwapiszewski, Radosław; Chudy, Michał; Dybko, Artur; Brzózka, Zbigniew

    2013-02-15

    In this work, we present a microfluidic array of microwells for long-term tumor spheroid cultivation and anticancer drug activity evaluation. The three-dimensional microfluidic system was obtained by double casting of poly(dimethylsiloxane). Spheroids of HT-29 human carcinoma cells were cultured in the microsystem for four weeks. After two weeks of the culture growth slowdown and stop were observed and high cell viability was determined within next two weeks. The characteristics of a homeostasis-like state were achieved. A cytostatic drug (5-fluorouracil) was introduced into the microsystem with different frequency (every day or every second day) and different concentrations. The geometry and construction of the microsystem enables flushing away of unaggregated (including dead) cells while viable spheroids remain inside microwells and decreasing spheroid diameter can be observed and measured as an indicator of decreasing cell viability. The results have shown differences in response of spheroids to different concentrations of 5-fluorouracil. It was also observed, that higher frequency of drug dosing resulted in more rapid spheroid diameter decrease. The presented microfluidic system is a solution for cell-based studies in an in vivo-like microfluidic environment. Moreover, observation of decreasing spheroid dimensions is a low-cost, label-free and easy-to-conduct mean of a quantitative determination of a 3D cellular model response to a applied drug. It is suitable for long-term observation of spheroid response, in a contrary to other viability assays requiring termination of a culture. PMID:22770829

  16. Long-term evaluation of the performance of four point-of-use water filters.

    PubMed

    Pérez-Vidal, Andrea; Diaz-Gómez, Jaime; Castellanos-Rozo, Jose; Usaquen-Perilla, Olga Lucía

    2016-07-01

    Despite technological advances water supply quality and poor access to safe water remain a major problem in developing countries, especially in rural areas. Point-of-use (POU) water treatment has been shown to be a viable option to produce safe drinking water quality. The aim of this study was to evaluate, under laboratory conditions over 14 months, the performance of four household filtration systems: membrane filter (MF), one-candle ceramic filter (1CCF), two-candle ceramic filter (2CCF) and pot ceramic filter (PCF). The evaluation was made using spiked water having the required concentrations of turbidity, Escherichia coli and Total Dissolved Solids (TDS). The results show that all systems have high removal efficiencies for turbidity (98-99%), and E. coli 4-5 Log Reduction Value (LRV). The poorest efficiency was for TDS (9-18%). The MF and the CCF displayed no significant difference in efficiencies for these parameters. The PCF had less significant differences for turbidity removal than the other systems. The average filtration rate for all systems decreased during the operation time. The CPF showed the major potential to be used in rural communities mainly for its low operational level and maintenance requirements as well as its local craftsmanship. It was observed that the efficiency of the systems is highly sensitive to cleaning and maintenance activities and therefore, the system sustainability will depend considerably on the training and education of the potential users. PMID:27105031

  17. Using probabilities of enterococci exceedance and logistic regression to evaluate long term weekly beach monitoring data.

    PubMed

    Aranda, Diana; Lopez, Jose V; Solo-Gabriele, Helena M; Fleisher, Jay M

    2016-02-01

    Recreational water quality surveillance involves comparing bacterial levels to set threshold values to determine beach closure. Bacterial levels can be predicted through models which are traditionally based upon multiple linear regression. The objective of this study was to evaluate exceedance probabilities, as opposed to bacterial levels, as an alternate method to express beach risk. Data were incorporated into a logistic regression for the purpose of identifying environmental parameters most closely correlated with exceedance probabilities. The analysis was based on 7,422 historical sample data points from the years 2000-2010 for 15 South Florida beach sample sites. Probability analyses showed which beaches in the dataset were most susceptible to exceedances. No yearly trends were observed nor were any relationships apparent with monthly rainfall or hurricanes. Results from logistic regression analyses found that among the environmental parameters evaluated, tide was most closely associated with exceedances, with exceedances 2.475 times more likely to occur at high tide compared to low tide. The logistic regression methodology proved useful for predicting future exceedances at a beach location in terms of probability and modeling water quality environmental parameters with dependence on a binary response. This methodology can be used by beach managers for allocating resources when sampling more than one beach. PMID:26837832

  18. An evaluation of long-term preservation methods for brown bear (Ursus arctos) faecal DNA samples

    USGS Publications Warehouse

    Murphy, M.A.; Waits, L.P.; Kendall, K.C.; Wasser, S.K.; Higbee, J.A.; Bogden, R.

    2002-01-01

    Relatively few large-scale faecal DNA studies have been initiated due to difficulties in amplifying low quality and quantity DNA template. To improve brown bear faecal DNA PCR amplification success rates and to determine post collection sample longevity, five preservation methods were evaluated: 90% ethanol, DETs buffer, silica-dried, oven-dried stored at room temperature, and oven-dried stored at -20??C. Preservation effectiveness was evaluated for 50 faecal samples by PCR amplification of a mitochondrial DNA (mtDNA) locus (???146 bp) and a nuclear DNA (nDNA) locus (???200 bp) at time points of one week, one month, three months and six months. Preservation method and storage time significantly impacted mtDNA and nDNA amplification success rates. For mtDNA, all preservation methods had ??? 75% success at one week, but storage time had a significant impact on the effectiveness of the silica preservation method. Ethanol preserved samples had the highest success rates for both mtDNA (86.5%) and nDNA (84%). Nuclear DNA amplification success rates ranged from 26-88%, and storage time had a significant impact on all methods but ethanol. Preservation method and storage time should be important considerations for researchers planning projects utilizing faecal DNA. We recommend preservation of faecal samples in 90% ethanol when feasible, although when collecting in remote field conditions or for both DNA and hormone assays a dry collection method may be advantageous.

  19. Early work load tests for evaluation of long-term prognosis of acute myocardial infarction.

    PubMed Central

    Granath, A; Södermark, T; Winge, T; Volpe, U; Zetterquist, S

    1977-01-01

    Exercise tests performed 3 and 9 weeks after acute myocardial infarction in 205 patients were found to give prognostic information on the survival during a follow-up period of 2 to 5 years. The appearance of tachycardia, major ventricular arrhythmias, or anginal complaints during these early exercise tests was thus accompanied by a significantly increased mortality during the observation period. Ventricular arrhythmias disclosed by exercise proved to be of higher prognostic significance than those recorded at rest on the same occasions. The usefulness of early exercise tests in the evaluation of the response to antiarrhythmic treatment after acute myocardial infarction as well as of the prognostic importance of the effects was documented in a smaller series of patients. PMID:884025

  20. Long term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

    PubMed Central

    Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-hoon; Dodam, John R; Cohn, Leah A; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R

    2014-01-01

    Background Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodeling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, airway hyperresponsiveness (AHR), and remodeling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Methods Cats with chronic, experimentally-induced asthma received six intravenous infusions of MSCs (0.36–2.5X10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for one year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia; pulmonary mechanics and clinical scoring to assess AHR; and thoracic computed tomographic (CT) scans to assess structural changes (airway remodeling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA p=0.0311; BWT p=0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodeling by month 8, though

  1. Evaluation of Long-Term Calibrations of the AVHRR Visible Radiances

    NASA Technical Reports Server (NTRS)

    Rossow, William B.; Ferrier, Joseph

    2015-01-01

    Two systematic calibrations have been compiled for the visible radiances measured by the series of AVHRR instruments flown on the NOAA operational polar weather satellites: one by the International Satellite Cloud Climatology Project (ISCCP), anchored on NASA ER-2 underflights in the 1980s and early 1990s and covering the period 1981-2009, and one by the PATMOS-x project, anchored on comparisons to the MODIS instruments on the Aqua and Terra satellites in the 2000s and covering the period 1979-2010 (this result also includes calibration for the near-IR channels). Both methods have had to extend their anchor calibrations over a long series of instruments using different vicarious approaches, so a comparison provides an opportunity to evaluate how well this extension works by cross-checking the results at the anchor points. The basic result of this comparison is that for the ''afternoon'' series of AVHRRs, the calibrations agree to within their mutual uncertainties. However, this retrospective evaluation also shows that the representation of the time variations can be simplified. The ISCCP procedure had much more difficulty extending the calibration to the ''morning'' series of AVHRRs with the calibrations for NOAA-15 and NOAA-17 exceeding the estimated uncertainties. Given the general agreement, a new calibration for all AVHRR visible radiances (except TIROS-N, NOAA-6, NOAA-19, and MetOp-A) is proposed that is based on the average of the best linear fits to the two time records. The estimated uncertainty of these calibrations is 63% absolute (scaled radiance units).

  2. Long-term testing and evaluation of cathode components in a commercial aluminum cell

    SciTech Connect

    Church, K.D.; Morris, E.G.; Joo, L.A. ); Stewart, D.V.; Morgan, W.R.; Tabereaux, A. )

    1990-04-01

    Since 1886, essentially all primary aluminum has been produced in Hall-Heroult electrolytic cells which electrochemically reduce alumina to the metal in an energy/capital intensive process. Nearly five per cent of the electrical energy generated in the United States in consumed in this Hall-Heroult process, at the rate of 6--8 kwh/lb. of aluminum produced. It has been in the aluminum industry's interest for the past several decades to utilize titanium diboride in some capacity as the cell cathode, either with conventional consumable carbon anodes or ultimately with nonconsumable, inert anodes. Eventual achievement of either or both of these goals will represent a technological breakthrough and make possible a significant reduction in the energy requirement to produce aluminum. The overall objective and achievement of this program was to better define the technical and economic viability of graphite-containing titanium diboride materials in low-cost shapes for use as cathodes in aluminum electrolytic cells as a precursor to subsequent demonstration and commercial application. This report covers the development of possible failure mechanisms, evaluations of the thermal shock resistance of non-cylindrical shapes, and an assessment of energy savings and technical/economic viability. In this program, titanium diboride-graphite (TiB{sub 2}-G) materials was demonstrated to be superior to dense TiB{sub 2} materials which had been previously evaluated in studies by others in terms of longevity, thermal shock properties, and the ability to manufacture large, complex components. 129 figs., 5 tabs.

  3. Evaluation of spinal toxicity and long-term spinal reflex function following intrathecal levobupivacaine in the neonatal rat

    PubMed Central

    Hamurtekin, Emre; Fitzsimmons, Bethany L.; Shubayev, Veronica I.; Grafe, Marjorie R.; Deumens, Ronald; Yaksh, Tony L.; Walker, Suellen M.

    2013-01-01

    Background Neuraxial anesthesia is utilized in children of all ages. Local anesthetics produce dose-dependent toxicity in certain adult models, but the developing spinal cord may also be susceptible to drug-induced apoptosis. In postnatal rodents, we examined effects of intrathecal levobupivacaine on neuropathology and long-term sensorimotor outcomes. Methods Postnatal day 3 (P3) or P7 rat pups received intrathecal levobupivacaine 2.5mg/kg (0.5%) or saline. Mechanical withdrawal thresholds and motor block were assessed. Spinal cord tissue analysis included: apoptosis counts (activated-caspase-3, Fluoro-Jade C) at 24 h; glial reactivity at 7 days; and histopathology in cord and cauda equina at 24 h and 7 days. Long-term spinal function in young adults (P35) was assessed by hindlimb withdrawal thresholds, electromyography responses to suprathreshold stimuli, and gait analysis. Results Intrathecal levobupivacaine produced spinal anesthesia at P3 and P7. No increase in apoptosis or histopathological change was seen in the cord or cauda equina. In the P3 saline group, activated-caspase-3 (mean±SEM per lumbar cord section 6.1±0.3) and Fluoro-Jade C (12.1±1.2) counts were higher than at P7, but were not altered by levobupivacaine (P=0.62 and P=0.11, two-tailed Mann-Whitney test). At P35, mechanical withdrawal thresholds, thermal withdrawal latency and electromyographic reflex responses did not differ across P3 or P7 levobupivacaine or saline groups (one way ANOVA with Bonferroni comparisons). Intrathecal bupivacaine at P3 did not alter gait. Conclusion Single dose intrathecal levobupivacaine 0.5% did not increase apoptosis or produce spinal toxicity in neonatal rat pups. This study provides preclinical safety data relevant to neonatal use of neuraxial local anesthesia. PMID:23514721

  4. Technique for liposuction fat reimplantation and long-term volume evaluation by magnetic resonance imaging.

    PubMed

    Hörl, H W; Feller, A M; Biemer, E

    1991-03-01

    Injection with one's own fat tissue remains controversial due to a lack of objective data pertaining to postoperative volume control. Facial defects in a total of 53 patients were repaired using autogenous fat tissue. The fatty tissue was obtained from the lower abdomen, buttocks, or inner portion of the upper thigh and then suspended before injection in a solution of 250 ml Ringer's solution, 50 ml distilled water, and 0.7 ml hyaluronidase. The fatty tissue was collected by a filter integrated within the suction system and subsequently prepared, as follows: (1) Cell detritus, blood constituents, and local anesthetic were flushed away by using a physiological Ringer's solution. (2) The defects were filled by using a finely calibrated, locked injection, whereby the desired amount of fatty tissue could be accurately instilled. (3) Injection was carefully performed directly under the cutis through a large lumen cannula and under close observation to avoid the injection of any fatty tissue intracutaneously. Before the procedure, the augmented areas had been evaluated by using magnetic resonance imaging (in T1-weighted images). Postoperatively, the sites were once again documented for volume at control intervals of 6 days, and 3, 6, 9, and 12 months. The volumes were computer-calculated integrally from the sum of the area of all the layers according to the following formula:v = (d + g).E(ai). Despite the use of hyaluronidase as well as an atraumatic liposuction technique, microscopic examination revealed 40% of the aspirated cells to have defective cell membranes. Without hyaluronidase, this figure rose to 50%. One-year follow-up in 10 patients showed that through the break-down of these damaged cells, a particularly high volume loss of 49% was documentable at 3 months after the procedure. Further follow-up at 6 months showed that average volume decline had risen to a total of 55%, whereas, at 9 months as well as 12 months, no further loss could be detected. Autogenous

  5. 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

  6. Bacterial decomposition of coral mucus as evaluated by long-term and quantitative observation

    NASA Astrophysics Data System (ADS)

    Tanaka, Y.; Ogawa, H.; Miyajima, T.

    2011-06-01

    Coral mucus released from Acropora formosa and Montipora digitata was incubated with bacteria under dark conditions for 1 year to evaluate the quantitative degradability. All the mucus samples showed a similar decomposition pattern: about 80% of total organic carbon (TOC) in the mucus was mineralized within 1 month, while some mucus was slowly decomposed over the 1 year. Regression analysis using an exponential curve considering three degradability pools (labile, semilabile, and refractory) fitted the changes of the TOC concentrations very well ( r 2 > 0.99). Compiling the data on the two coral species, the labile organic C in the coral mucus had mineralization rates of 10-18% d-1 and accounted for 79-87% of the initial TOC in the mucus. Semilabile organic C had mineralization rates of 0.3-1.6% d-1 and accounted for 11-18% of the initial TOC. Refractory organic C accounted for 6% at most. These results suggest that not all coral mucus is rapidly decomposed by bacteria but some mucus remains as semilabile and refractory organic matter for several months.

  7. Discriminative evaluative conditioning in the long-term after severe accidental injury.

    PubMed

    Oe, Misari; Schumacher, Sonja; Schnyder, Ulrich; Mueller-Pfeiffer, Christoph; Wilhelm, Frank H; Kuelen, Eveline; Martin-Soelch, Chantal

    2016-06-30

    Impairments in classical fear conditioning and deficits in discriminative learning are observed in posttraumatic stress disorder (PTSD). However, it is unknown whether similar impairments can be found with types of discriminative learning other than classical conditioning, such as evaluative conditioning (EC), in which the valence of a stimulus can be transferred to other stimuli. In this study, we investigated whether EC is also influenced by traumatic experiences independently of presence of PTSD. We tested 14 accident survivors with remitted PTSD, 14 survivors without PTSD, and 16 non-trauma controls. We used behavioral measures, psychophysiological indicators, and subjective ratings for tasks. General effects of learning were observed across groups and conditioning/extinction. Trauma controls had slower reaction times (RTs) to the aversive conditioned stimulus compared to appetitive conditioned and neutral stimuli, as well as slower RTs and increased accuracy during conditioning than during extinction. Remitted PTSD participants showed opposite results, demonstrating decreased accuracy and slower RTs during conditioning as compared to during extinction. No discriminative effect was found in the non-trauma controls and the remitted PTSD participants. These results suggest that a traumatic experience influences EC, and that this influence differs between individuals who have and have not developed PTSD after traumatic exposure. PMID:27107667

  8. Long-term evaluation of extracorporeal shock wave lithotripsy in the treatment of salivary stones.

    PubMed

    Schmitz, S; Zengel, P; Alvir, I; Andratschke, M; Berghaus, A; Lang, S

    2008-01-01

    Extracorporeal shock wave lithotripsy is a rather new therapeutical method in the treatment of sialolithiasis. The objective was to evaluate retrospectively the results of the extracorporeal shock wave lithotripsy therapy performed with a Minilith SL 1 lithotripter on 167 out-patients with symptomatic stones (average size 5.94 mm) of the salivary glands over an observation period of seven years. A successful treatment with total stone disintegration was achieved in 51 (31 per cent) patients. In 92 (55 per cent) patients treatment was partially successful, with disappearance of the symptoms but a sonographically still identifiable stone. Treatment failure occurred in 24 (14 per cent) patients who then underwent surgery. The mean follow-up period was 35.6 months (minimum three, maximum 83), after which 83.2 per cent of the initially successfully treated patients were still free of symptoms.Therefore, extracorporeal shock wave lithotripsy, as a non-invasive treatment alternative with few side effects, is an efficient technique for the therapy of sialolithiasis in selected patients. PMID:17466089

  9. 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

  10. A long-term cephalometric evaluation of treated Class II division 2 malocclusions.

    PubMed

    Binda, S K; Kuijpers-Jagtman, A M; Maertens, J K; van 't Hof, M A

    1994-08-01

    A retrospective study was conducted in order to evaluate post-retention changes of skeletal, dental, and soft-tissue variables in Class II division 2 malocclusions. Data were obtained from lateral cephalograms of children with Class II division 2 malocclusions which were taken before orthodontic treatment (T00; n = 81), post-retention (T0; n = 81), 2 years post-retention (T2; n = 65) and 5 years post-retention (T5; n = 44). A two-way ANOVA with sex and age as predictors was applied. Significant sex and age influences for the increments were mostly found during treatment (T00-T0), but especially for skeletal variables also during T0-T5. The changes over time were more pronounced for males than for females. The changes over time were less pronounced in older age groups. Sagittal and vertical facial dimensions were increased by growth and therapy. The skeletal Class II pattern was reduced significantly during T00-T0. Several skeletal variables indicated an anterior rotational growth pattern of the mandible post-retention. The interincisal angle and the overbite were reduced, and the upper incisors were torqued during treatment. The inclination of upper and especially lower incisors showed some relapse post-retention. The overbite and the interincisal angle increased significantly post-retention. The lip line was lowered during treatment. The soft-tissues showed horizontal and vertical growth during treatment while there were no remarkable changes afterwards. Due to growth the nose and the chin became more pronounced in the face.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7957655