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Sample records for long-term safety efficacy

  1. 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

  2. Long-term botulinum toxin efficacy, safety, and immunogenicity.

    PubMed

    Mejia, Nicte I; Vuong, Kevin Dat; Jankovic, Joseph

    2005-05-01

    To determine the long-term efficacy of botulinum toxin (BTX) treatments, we analyzed longitudinal follow-up data on 45 patients (32 women; mean age, 68.8 years) currently followed in the Baylor College of Medicine Movement Disorders Clinic, who have received BTX treatments continuously for at least 12 years (mean 15.8 +/- 1.5 years). Their mean response rating after the last injection, based one a previously described scale 0-to-4 scale (0 = no effect; 4 = marked improvement) was 3.7 +/- 0.6 and the mean total duration of response was 15.4 +/- 3.4 weeks. Although the latency and total duration of the response to treatment have not changed over time, the peak duration of response (P < 0.005) and dose per visit (P < 0.0001) have increased since the initial visit. Furthermore, global rating (P < 0.02) and peak effect (P < 0.05) have improved. In total, 20 adverse events occurred in 16 of 45 (35.6%) patients after their initial visit and 11 adverse events in 10 of 45 (22.2%) patients at their most recent injection visit. Antibody (Ab) testing was carried out in 22 patients due to nonresponsiveness; blocking Abs were confirmed by the mouse protection assay in 4 of 22 (18%) patients. Of the Ab-negative patients, 16 resumed responsiveness after dose adjustments and 2 persisted as nonrespondents. Except for 1 patient, the 4 Ab-positive and the 2 clinical nonresponders are being treated with BTX-B. This longest reported follow-up of BTX injections confirms the long-term efficacy and safety of this treatment.

  3. Long-term safety and efficacy of continuous intrathecal baclofen.

    PubMed

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

    2002-10-01

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

  4. 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

  5. [Further enhance the long-term myopia control efficacy and safety of orthokeratology].

    PubMed

    Xie, Peiying

    2014-01-01

    Strategies and methods of myopia prevention and control has been more and more. In recent years optical correction method is focusing on promoting the retinal mid-peripheral myopic defocus, improving the visual quality and promoting the accommodative function. Among the all, orthokeratology is the most notable optometry technology. This article will combine research progress both local and international achievements, the present situation of the domestic popularized the technique, and the existing problems. From the realistic approach, keep improving, the pursuit of stability, the pursuit of harmony and eliminate the false five aspects, to discuss how to promote orthokeratology for the myopia control with long-term stably efficacy and safety. How to promote the harmony and cooperation between doctors, patients and manufactures. And how to correctly guide the orthokeratology Having both specification and continued development. PMID:24709125

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

    PubMed

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

    2015-01-01

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

  7. 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

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

    PubMed Central

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

    2016-01-01

    Objectives To evaluate the long-term efficacy and safety of tocilizumab (TCZ) in clinical patients with rheumatoid arthritis (RA) refractory to synthetic disease-modifying antirheumatic drugs, anti-tumor necrosis factor agents, and B-cell depletion therapy with rituximab (RTX). Methods We conducted a single-center retrospective study of 22 patients with RA treated with TCZ. We collected data including demographics and medication histories. We recorded clinical parameters including tender joint counts and swollen joint counts, and laboratory parameters including inflammatory makers and lipid profiles over regular intervals of TCZ treatment. Results In all, 22 patients with RA were included, 20 of whom were female. The median age at the first dose of TCZ was 62 years (range: 35–75 years). The mean duration of the disease from diagnosis with RA to May 2015 was 15.7 years (range: 6–30 years). A total of 15 out of 22 patients remained on TCZ at the end of the study, and in all, there was an improvement in markers of disease activity following initiating TCZ. The effect was sustained for a mean of 35 months (SD±15.5 months, range: 9–72 months). Of the 17 patients who failed to respond to RTX previously, 12 patients remained on TCZ. In all, eight out of 22 patients developed adverse events, five of whom discontinued TCZ. In contrast to previously documented short-term data, TCZ did not result in a statistically significant (P<0.05) long-term deterioration in lipid profile for any of the lipid parameters measured in our cohort (mean ± SD at initiation of TCZ to most recent follow-up: total cholesterol 5.25±1.05 to 5.28±0.77 mmol/L, high-density lipoprotein 1.72±0.54 to 1.67±0.43 mmol/L, low-density lipoprotein 3.05±0.98 to 2.98±0.81 mmol/L, and cholesterol to high-density lipoprotein ratio 3.41±1.23 to 3.40±1.22). Conclusion The efficacy of TCZ in patients with RA refractory to disease-modifying drugs, including anti-tumor necrosis factor blockade and RTX

  9. The safety and long-term efficacy of zonisamide as adjunctive therapy for focal epilepsy.

    PubMed

    Schulze-Bonhage, Andreas

    2015-01-01

    Epilepsy is a chronic disease which affects 1% of the population worldwide. As treatment is required for many years or decades, the long-term efficacy and tolerability of antiepileptic drugs are particularly important. Zonisamide (ZNS) is a second-generation antiepileptic drug with a unique structure and multiple mechanisms of action. Here, recently published long-term outcomes of patient cohorts with focal epilepsy undergoing ZNS treatment are discussed. Whereas ZNS monotherapy maintains similar seizure control efficacy to carbamazepine after 2 years of treatment, seizure-free rates are low in pharmacoresistant patients undergoing late adjunctive therapy. In preselected patient populations derived from double-blind studies, long-term seizure reduction and responder rates support sustained ZNS efficacy, good adherence and long-term retention. Adverse effects include somnolence and weight decrease, but data suggest that long-term treatment with ZNS is safe with only rare newly occurring adverse effects, and good long-term tolerability also regarding mood, behavior, cognition and bone maturation.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  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 safety and efficacy of telmisartan/amlodipine single pill combination in the treatment of hypertension

    PubMed Central

    Billecke, Scott S; Marcovitz, Pamela A

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2009-10-01

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

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

    PubMed Central

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

    2011-01-01

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

  4. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Böhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

    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.

  7. 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

  8. 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

  9. 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.

  10. [Requirements for long-term follow-up on efficacy and safety of advanced therapy medicinal products. Risk management and traceability].

    PubMed

    Klug, B; Reinhardt, J; Schröder, C

    2010-01-01

    Advanced therapy medicinal products (ATMPs) are an innovative treatment option. To promote timely access of the innovative medicinal product and to safeguard public health, new elements have been introduced into legislation. A key element of the ATMP regulation is the requirement for long-term follow-up on safety and efficacy of patients enrolled in clinical trials with ATMPs, which is beyond the routine requirements on pharmacovigilance. For gene therapy medicinal products, a guideline on long-term follow-up, which lays down the technical requirements, is available. A further key element of the ATMP regulation is the traceability of the starting materials used to manufacture the ATMP. A common European coding system is imperative to ensure the traceability of starting materials, especially across the borders of European Member States.

  11. 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

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

    PubMed

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

    2009-03-01

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

  13. Efficacy of ibandronate: a long term confirmation

    PubMed Central

    Di Munno, Ombretta; Delle Sedie, Andrea

    2010-01-01

    Data deriving from randomized clinical trials, observational studies and meta-analyses, including treatment regimens unlicensed for use in clinical practice, clearly support that 150 mg once-monthly oral and 3 mg quarterly i.v. doses of ibandronate are associated with efficacy, safety and tolerability; notably both these marketed regimens, which largely correspond to ACE ≥10.8 mg, may in addition provide a significant efficacy on non-vertebral and clinical fracture (Fx) efficacy. The MOBILE and the DIVA LTE studies confirmed a sustained efficacy of monthly oral and quarterly i.v. regimens respectively, over 5 years. Furthermore, improved adherence rates with monthly ibandronate, deriving from studies evaluating large prescription databases, promise to enhance fracture protection and decrease the social and economic burden of postmenopausal osteoporosis. PMID:22461287

  14. Efficacy of ibandronate: a long term confirmation.

    PubMed

    Di Munno, Ombretta; Delle Sedie, Andrea

    2010-01-01

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

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

    PubMed

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

    2014-08-01

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

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

    PubMed Central

    Lee, Cheng-Ling; Kuo, Hann-Chorng

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Safety and efficacy of long-term combination therapy with bezafibrate and ezetimibe in patients with dyslipidemia in the prospective, observational J-COMPATIBLE study

    PubMed Central

    2013-01-01

    Background There are numerous reports describing the efficacy of fenofibrate in combination with ezetimibe for treating dyslipidemia. In contrast, a study combining bezafibrate and ezetimibe has not yet been conducted. In this study, we examined the safety, including the risk of gallstone formation, and the efficacy of long-term combination therapy with bezafibrate and ezetimibe for treating dyslipidemia. Methods Dyslipidemic patients treated with 400 mg/day bezafibrate in combination with 10 mg/day ezetimibe for the first time were eligible. We selected 157 institutions in Japan and conducted a 12-month prospective observational study, with patients enrolled on the day they started combination therapy. Safety of the combination was examined in terms of the type, onset, and severity of adverse drug reactions (ADRs). Efficacy was evaluated in terms of the changes in low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), and non-HDL cholesterol (non-HDL-C) levels from the start of combination therapy (baseline) to the last observation carried forward (LOCF). Lipid levels were assessed at 1, 3, 6, and 12 months after starting combination therapy. Results We enrolled 665 patients in this observational study. Safety was evaluated in 659, and ADRs occurred in 42 patients (6.4%). The most frequent ADRs were blood creatine phosphokinase increase (1.5%) and myalgia (0.8%). Asymptomatic gallstones were observed in four patients (0.6%). Effectiveness was evaluated in 622 patients. LDL-C, HDL-C, TG, and non-HDL-C levels improved significantly from baseline to LOCF by −17.4%, 8.8%, –40.5%, and −21.6%, respectively (all, p < 0.001). Lipid levels also improved from baseline to each evaluation time-point. Conclusions Bezafibrate in combination with ezetimibe is safe and effective, and is potentially useful for comprehensive management of dyslipidemia. PMID:24195788

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

    PubMed Central

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

    2015-01-01

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

  20. 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

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

    PubMed

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

    2015-09-01

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

  2. Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study

    PubMed Central

    Goemans, Nathalie M.; Tulinius, Már; van den Hauwe, Marleen; Kroksmark, Anna-Karin; Buyse, Gunnar; Wilson, Rosamund J.; van Deutekom, Judith C.; de Kimpe, Sjef J.; Lourbakos, Afrodite; Campion, Giles

    2016-01-01

    Background Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD) patients with amenable mutations. Methods This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968), 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks. All subjects had a planned treatment interruption (weeks 73–80), followed by intermittent dosing (weeks 81–188). Results Subjects received a median (range) total dose of 5.93 (5.10 to 6.02) mg/kg drisapersen. After 177 weeks (last efficacy assessment), median (mean [SD]) six-minute walk distance (6MWD) improved by 8 (-24.5 [161]) meters for the 10 subjects able to complete the 6MWD at baseline (mean age [SD]: 9.5 [1.9] years). These statistics include 2 subjects unable to complete the test at later visits and who scored “zero”. When only the 8 ambulant subjects at week 177 were taken into account, a median (mean [SD]) increase of 64 (33 [121]) meters in 6MWD was observed. Of 7 subjects walking ≥330 m at extension baseline, 5 walked farther at week 177. Of 3 subjects walking <330 m, 2 lost ambulation, while 1 declined overall but walked farther at some visits. Over the 188 weeks, the most common adverse events were injection-site reactions, raised urinary α1-microglobulin and proteinuria. Dystrophin expression was detected in all muscle biopsies obtained at week 68 or 72. Conclusion Drisapersen was generally well tolerated over 188 weeks. Possible renal effects, thrombocytopenia and injection-site reactions warrant continued monitoring. Improvements in the 6MWD at 12 weeks were sustained after 3.4 years of dosing for most patients. For a small, uncontrolled study, the outcomes are encouraging, as natural history studies would anticipate a decline of over 100 meters over a 3-year period in a comparable

  3. Safety of long-term PPI therapy.

    PubMed

    Reimer, Christina

    2013-06-01

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

  4. Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse

    PubMed Central

    Donega, Vanessa; Nijboer, Cora H.; van Velthoven, Cindy T. J.; Youssef, Sameh A.; de Bruin, Alain; van Bel, Frank; Kavelaars, Annemieke; Heijnen, Cobi J.

    2015-01-01

    Background: For clinical translation, we assessed whether intranasal mesenchymal stem cell (MSC) treatment after hypoxia–ischemia (HI) induces neoplasia in the brain or periphery at 14 mo. Furthermore, the long-term effects of MSCs on behavior and lesion size were determined. Method: HI was induced in 9-d-old mice. Pups received an intranasal administration of 0.5 × 106 MSCs or vehicle at 10 d post-HI. Full macroscopical and microscopical pathological analysis of 39 organs per mouse was performed. Sensorimotor behavior was assessed in the cylinder-rearing test at 10 d, 28 d, 6 mo, and 9 mo. Cognition was measured with the novel object recognition test at 3 and 14 mo post-HI. Lesion size was determined by analyzing mouse-anti-microtubule-associated protein 2 (MAP2) and mouse-anti-myelin basic protein (MBP) staining at 5 wk and 14 mo. Results: At 14 mo post-HI, we did not observe any neoplasia in the nasal turbinates, brain, or other organs of HI mice treated with MSCs. Furthermore, our results show that MSC-induced improvement of sensorimotor and cognitive function is long lasting. In contrast, HI-vehicle mice showed severe behavioral impairment. Recovery of MAP2- and MBP-positive area lasted up to 14 mo following MSC treatment. Conclusion: Our results provide strong evidence of the long-term safety and positive effects of MSC treatment following neonatal HI in mice. PMID:26270577

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  8. Efficacy and Safety of a Hyaluronic Acid Filler to Correct Aesthetically Detracting or Deficient Features of the Asian Nose: A Prospective, Open-Label, Long-Term Study

    PubMed Central

    Liew, Steven; Scamp, Terrence; de Maio, Mauricio; Halstead, Michael; Johnston, Nicole; Silberberg, Michael; Rogers, John D.

    2016-01-01

    Background There is increasing interest among patients and plastic surgeons for alternatives to rhinoplasty, a common surgical procedure performed in Asia. Objectives To evaluate the safety, efficacy, and longevity of a hyaluronic acid filler in the correction of aesthetically detracting or deficient features of the Asian nose. Methods Twenty-nine carefully screened Asian patients had their noses corrected with the study filler (Juvéderm VOLUMA [Allergan plc, Dublin, Ireland] with lidocaine injectable gel), reflecting individualized treatment goals and utilizing a standardized injection procedure, and were followed for over 12 months. Results A clinically meaningful correction (≥1 grade improvement on the Assessment of Aesthetic Improvement Scale) was achieved in 27 (93.1%) patients at the first follow-up visit. This was maintained in 28 (96.6%) patients at the final visit, based on the independent assessments of a central non-injecting physician and the patients. At this final visit, 23 (79.3%) patients were satisfied or very satisfied with the study filler and 25 (86.2%) would recommend it to others. In this small series of patients, there were no serious adverse events (AEs), with all treatment-related AEs being mild to moderate, transient injection site reactions, unrelated to the study filler. Conclusions Using specific eligibility criteria, individualized treatment goals, and a standardized injection procedure, the study filler corrected aesthetically detracting or deficient features of the Asian nose, with the therapeutic effects lasting for over 12 months, consistent with a high degree of patient satisfaction. This study supports the safety and efficacy of this HA filler for specific nose augmentation procedures in selected Asian patients. Level of Evidence: 3 Therapeutic PMID:27301371

  9. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.

    PubMed

    Moore, Angela; Kempers, Steven; Murakawa, George; Weiss, Jonathan; Tauscher, Amanda; Swinyer, Leonard; Liu, Hong; Leoni, Matthew

    2014-01-01

    Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be related to the study drug was higher at the beginning and decreased over the course of the study. Similar safety profiles were observed between the subjects who had received or not received concomitant therapies for the inflammatory lesions of rosacea. Effect of topical BT gel 0.5% on erythema severity was observed after the first application and the durability of the effect was maintained until the end of the study at month 12, with no tachyphylaxis observed. In conclusion, once-daily topical BT gel 0.5% is safe and consistently effective for the long-term treatment of moderate to severe erythema of rosacea, even in the presence of concomitant therapies for the inflammatory lesions of rosacea.

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. Long-term efficacy, safety, and tolerability of rilpivirine (RPV, TMC278) in HIV type 1-infected antiretroviral-naive patients: week 192 results from a phase IIb randomized trial.

    PubMed

    Wilkin, Aimee; Pozniak, Anton L; Morales-Ramirez, Javier; Lupo, Sergio H; Santoscoy, Mario; Grinsztejn, Beatriz; Ruxrungtham, Kiat; Rimsky, Laurence T; Vanveggel, Simon; Boven, Katia

    2012-05-01

    TMC278-C204 (NCT00110305), a 96-week trial of the nonnucleoside reverse transcription inhibitor (NNRTI) rilpivirine (RPV, TMC278) in 368 HIV-1-infected, treatment-naive patients, was extended to investigate long-term safety and efficacy. Week 192 analysis results are presented. This was a long-term follow-up of a Phase IIb, randomized trial. No significant RPV dose-response relationships with respect to the primary endpoint (composite ITT-TLOVR algorithm) were observed at week 48 or 96. All RPV-treated patients were switched to open-label 75 mg qd at week 96 and then to 25 mg qd, the Phase III dose, at approximately week 144 as it gave the best benefit-risk balance. All control patients continued receiving open-label efavirenz (EFV) 600 mg qd. At week 192, 59% of RPV- and 61% of EFV-treated patients maintained confirmed viral load <50 copies/ml (ITT-TLOVR algorithm). The mean changes from baseline in CD4 cell count were similar in both groups (RPV: 210 cells/mm(3) vs. EFV: 225 cells/mm(3)). No new safety concerns were noted between week 48 and 192. In the week 192 analysis, RPV compared with EFV was associated with a lower overall incidence of grade 2-4 adverse events (AEs) at least possibly related to treatment, including rash (p<0.001) and neurologic AEs (p<0.05 Fisher's exact test, post hoc analyses) Incidences of serious AEs, grade 3 or 4 AEs, and discontinuations due to AEs were similar across groups. Increases in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were significantly lower with RPV than with EFV. RPV continued to show sustained efficacy similar to EFV at week 192 with a generally more favorable safety profile. PMID:21902621

  13. Long-term safety concerns with proton pump inhibitors.

    PubMed

    Ali, Tauseef; Roberts, David Neil; Tierney, William M

    2009-10-01

    Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide. Their use has resulted in dramatic improvements in treatment of peptic ulcer disease and gastroesophageal reflux disease. Despite an acceptable safety profile, mounting data demonstrate concerns about the long-term use of PPIs. To provide a comprehensive review regarding the concerns of long-term PPI use, a literature search was performed to identify pertinent original and review articles. Despite study shortcomings, the collective body of information overwhelmingly suggests an increased risk of infectious complications and nutritional deficiencies. Data regarding any increased risk in gastric or colon malignancy are less convincing. PPIs have revolutionized the management and complications of acid-related disorders with a high margin of safety; however, with the data available, efforts to reduce the dosing of or discontinue the use of PPIs must be reassessed frequently.

  14. Safety of long-term large doses of aspartame.

    PubMed

    Leon, A S; Hunninghake, D B; Bell, C; Rassin, D K; Tephly, T R

    1989-10-01

    Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a randomized, double-blind, placebo-controlled, parallel-group design in 108 male and female volunteers aged 18 to 62 years. Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks. No persistent changes over time were noted in either group in vital signs; body weight; results of standard laboratory tests; fasting blood levels of aspartame's constituent amino acids (aspartic acid and phenylalanine), other amino acids, and methanol; or blood formate levels and 24-hour urinary excretion of formate. There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject. These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day.

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

    PubMed

    Chantelau, E; Spraul, M; Mühlhauser, I; Gause, R; Berger, M

    1989-07-01

    A follow-up study of 116 Type 1 (insulin-dependent) diabetic patients on long-term continuous subcutaneous insulin infusion was conducted after 4.5 +/- 0.2 years. The average HbA1c-value of these patients decreased by 1% to 6.7 +/- 0.1% during this observation period. Typical side effects of continuous subcutaneous insulin infusion such as skin inflammation at the catheter insertion site occurred with similar frequency as has been reported previously by other authors. Diabetic ketoacidosis (0.14 per patient year) and disabling hypoglycaemia (0.1 per patient year, including 0.05 hypoglycaemic coma per patient-year) occurred at substantially lower rates than in other comparable studies with Type 1 diabetic patients at a similar degree of metabolic control. Subgroup evaluation suggested that a normal (less than 5.6%) HbA1c-value at follow-up was associated with increased incidence of disabling hypoglycaemia, whereas poor metabolic control (HbA1c greater than 7.5%) was associated with increased rates of skin complications and hospital treatment for ketoacidosis. Thus, under the policies of this diabetes centre, continuous subcutaneous insulin infusion has proved to be beneficial to a large proportion of experienced adult Type 1 diabetic patients, who voluntarily had opted for, and continued with, this particular mode of insulin treatment.

  16. The long-term safety of antiepileptic drugs.

    PubMed

    Gaitatzis, Athanasios; Sander, Josemir W

    2013-06-01

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

  17. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  20. Long term follow-up concerning safety and efficacy of novel adhesion prophylactic agent for laparoscopic myomectomy in the prospective randomized ADBEE study.

    PubMed

    Cezar, Cristina; Tchartchian, Garri; Korell, Matthias; Ziegler, Nicole; Senshu, Kazuhisa; De Wilde, Maya Sophie; Herrmann, Anja; Larbig, Angelika; De Wilde, Rudy Leon

    2016-08-01

    We conducted a prospective randomized single blind - subject study in the University Clinic of Gynecology of Pius-Hospital Oldenburg. The primary objective of the ADBEE study was to assess the safety and manageability of ADBLOCK when used as an adjunct to laparoscopic surgery for the primary of myomas in women wishing to improve pregnancy outcomes. The study population included 32 women aged between 18-45 years, in good general health condition, who have not completed their family planning and who are undergoing primary ('virgin') laparoscopic myomectomy with an aim to improve pregnancy outcomes. The patients were randomized in 2 groups, ADBLOCK arm with 21 patients and surgery only arm with 11 patients. The study was single blind - subject and the investigators were blinded to treatment group assignment until completion of uterine suturing and prior to removal of the endoscope. A vigorous follow-up of subjects was organized, focusing on its two critical characteristics: completeness and duration. Completeness represented the percentage of subjects who returned to every planed follow - up appointments. The patients were evaluated in a specific period of time, which defined the duration of follow-up. Safety of the ADBLOCK was estimated after analyzing and documentation of any adverse events occurred, clinical and physical examination of patients as well as evaluation of laboratory measures. There were 25 adverse events reported in ADBLOCK treatment group and 12 events in NO-ADBLOCK group over the 24-months treatment. All adverse events in both treatment arms were not anticipated, with all events in the ADBLOCK group being resolved. At 28 days, there was no significant difference in proportion of events between the two treatments (p = 0.440). Overall, the number of events reported was low and the severity of events was generally mild with an unlikely or no relationship to treatment. There were no unanticipated device related adverse events seen in both treatment

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

    PubMed Central

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

    2014-01-01

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

  2. Session 6: Infant nutrition: future research developments in Europe EARNEST, the early nutrition programming project: EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research.

    PubMed

    Fewtrell, M S

    2007-08-01

    Increasing evidence from lifetime experimental studies in animals and observational and experimental studies in human subjects suggests that pre- and postnatal nutrition programme long-term health. However, key unanswered questions remain on the extent of early-life programming in contemporary European populations, relevant nutritional exposures, critical time periods, mechanisms and the effectiveness of interventions to prevent or reverse programming effects. The EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST) consortium brings together a multi-disciplinary team of scientists from European research institutions in an integrated programme of work that includes experimental studies in human subjects, modern prospective observational studies and mechanistic animal work including physiological studies, cell-culture models and molecular techniques. Theme 1 tests early nutritional programming of disease in human subjects, measuring disease markers in childhood and early adulthood in nineteen randomised controlled trials of nutritional interventions in pregnancy and infancy. Theme 2 examines associations between early nutrition and later outcomes in large modern European population-based prospective studies, with detailed measures of diet in pregnancy and early life. Theme 3 uses animal, cellular and molecular techniques to study lifetime effects of early nutrition. Biomedical studies are complemented by studies of the social and economic importance of programming (themes 4 and 5), and themes encouraging integration, communication, training and wealth creation. The project aims to: help formulate policies on the composition and testing of infant foods; improve the nutritional value of infant formulas; identify interventions to prevent and reverse adverse early nutritional programming. In addition, it has the potential to develop new products through industrial

  3. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination.

    PubMed

    Naud, Paulo S; Roteli-Martins, Cecilia M; De Carvalho, Newton S; Teixeira, Julio C; de Borba, Paola C; Sanchez, Nervo; Zahaf, Toufik; Catteau, Gregory; Geeraerts, Brecht; Descamps, Dominique

    2014-01-01

    HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15-25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). Cervical samples were tested for HPV DNA every 6 months, and cyto-pathological examinations were performed annually. During HPV-023, no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group. Vaccine efficacy (VE) against HPV-16/18 incident infection was 100% (95%CI: 66.1, 100). Over the 113 months (9.4 years), VE was 95.6% (86.2, 99.1; 3/50 cases in vaccine and placebo groups, respectively) against incident infection, 100% (84·1, 100; 0/21) against 6-month persistent infection (PI); 100% (61·4, 100; 0/10) against 12-month PI; 97·1% (82.5, 99.9; 1/30) against ≥ ASC-US; 95·0% (68.0, 99.9; 1/18) against ≥ LSIL; 100% (45.2, 100; 0/8) against CIN1+; and 100% (-128.1, 100; 0/3) against CIN2+ associated with HPV-16/18. All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine. PMID:25424918

  4. 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)

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

    PubMed

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

    2013-06-01

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

  6. 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

  7. 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.

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

    PubMed Central

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

    2016-01-01

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

  9. Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study

    PubMed Central

    Teófilo, Eugénio; Rocha-Pereira, Nuno; Kuhlmann, Birger; Antela, Antonio; Knechten, Heribert; Santos, Jesús; Jiménez-Expósito, Maria Jesús

    2016-01-01

    Background: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. Objective: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. Methods: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. Results: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. Conclusions: In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function. PMID:26899539

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

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

    PubMed Central

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

    2016-01-01

    Study question What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere’s disease, compared with placebo? Methods The BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). Adults aged 21-80 years (mean age 56 years) with definite unilateral or bilateral Meniere’s disease were recruited from March 2008 to November 2012. Participants received placebo (n=74), low dose betahistine (2×24 mg daily, (n=73)), or high dose betahistine (3×48 mg daily, (n=74)) over nine months. The primary outcome was the number of attacks per 30 days, based on patients’ diaries during a three month assessment period at months seven to nine. An internet based randomisation schedule performed a concealed 1:1:1 allocation, stratified by study site. Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function. Study answer and limitations Incidence of attacks related to Meniere’s disease did not differ between the three treatment groups (P=0.759). Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. The overall monthly attack rate fell significantly by the factor 0.758 (0.705 to 0.816; P<0.001). The population based, mean monthly incidence averaged over the assessment period was 2.722 (1.304 to 6.309), 3.204 (1.345 to 7.929), and 3.258 (1.685 to 7.266) for the placebo, low dose betahistine, and high dose betahistine groups, respectively. Results were consistent for all secondary outcomes. Treatment was well tolerated with no unexpected safety findings. Without a control group of

  12. Acute And Long-Term Bioeffects And Lamp Safety

    NASA Astrophysics Data System (ADS)

    Andersen, F. Alan

    1980-10-01

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

  13. 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.

  14. 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

  15. Teacher Self-Efficacy as a Long-Term Predictor of Instructional Quality in the Classroom

    ERIC Educational Resources Information Center

    Künsting, Josef; Neuber, Victoria; Lipowsky, Frank

    2016-01-01

    In this longitudinal study, we examined teachers' self-efficacy as a long-term predictor of their mastery goal orientation and three dimensions of instructional quality: supportive classroom climate, effective classroom management, and cognitive activation. Mastery goal orientation was also analyzed as a predictor of instructional quality.…

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety.

    PubMed

    Westhoff, Carolyn

    2003-08-01

    Depot-medroxyprogesterone acetate (Depo-Provera(R)) is a highly effective, nondaily hormonal contraceptive option that has been available in the United States for a decade, and worldwide for 40 years. Benefits and risks of hormonal therapy are often under scrutiny; however, long-term clinical experience has established the safety of this long-acting contraceptive. This article reviews the contraceptive efficacy, potential noncontraceptive health benefits and long-term safety of with regard to risk of cardiovascular events, breast and gynecologic malignancy and osteopenia. Comparisons with other hormonal contraceptives are made as clinically appropriate. Common patient management issues, including effects on menstrual cycle, body weight and mood, are also addressed. Finally, this review provides recommendations for appropriate patient selection.

  19. 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.

  20. Predictors of self-efficacy in women on long-term sick leave.

    PubMed

    Andersén, Åsa; Larsson, Kjerstin; Lytsy, Per; Kristiansson, Per; Anderzén, Ingrid

    2015-12-01

    Self-efficacy has been shown to be related to sick leave and to be a predictor of return to work after sickness absence. The aim of this study was to investigate whether factors related to sick leave predict self-efficacy in women on long-term sick leave because of pain and/or mental illness. This cross-sectional study uses baseline data from 337 Swedish women with pain and/or mental illness. All included women took part in vocational rehabilitation. Data were collected through a sick leave register and a baseline questionnaire. General self-efficacy, sociodemographics, self-rated health, anxiety, depression, view of the future, and social support were measured and analyzed by univariate and multivariate linear regression analyses. The full multivariate linear regression model, which included mental health factors together with all measured factors, showed that anxiety and depression were the only predictive factors of lower self-efficacy (adjusted R2=0.46, P<0.001) and explained 46% of the variance in self-efficacy. The mean scores of general self-efficacy were low, especially in women born abroad, those with low motivation, those with uncertainties about returning to work, and women reporting distrust. Anxiety and depression are important factors to consider when targeting self-efficacy in vocational rehabilitation.

  1. 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.

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

    PubMed Central

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

    2015-01-01

    Background The purpose of this study was to evaluate the long-term results of an implantable miniature telescope (IMT) in patients with bilateral, end-stage, age-related macular degeneration (AMD). Methods A prospective, open-label, multicenter clinical trial with fellow eye controls enrolled 217 patients (mean age 76 years) with AMD and moderate-to-profound bilateral central visual acuity loss (20/80–20/800) resulting from untreatable geographic atrophy, disciform scars, or both. A subgroup analysis was performed with stratification for age (patient age 65 to <75 years [group 1; n=70] and patient age ≥75 years [group 2; n=127]), with a comparative evaluation of change in best-corrected distance visual acuity (BCDVA), quality of life, ocular complications from surgery, adverse events, and endothelial cell density (ECD). Follow-up in an extension study was 60 months. Results Data were available for 22, 38, and 31 patients in group 1 and 42, 46, and 32 patients in group 2 at 36, 48, and 60 months, respectively. Mean BCDVA improvement from baseline to 60 months was 2.41±2.69 lines in all patients (n=76), with 2.64±2.55 lines in group 1 and 2.09±2.88 lines in group 2. Quality of life scores were significantly higher in group 1. The most common significant surgery-related ocular complications in group 1 were iritis >30 days after surgery (7/70; 10%) and persistent corneal edema (3/70; 4.3%); and in group 2 were a decrease in BCDVA in the implanted eye or IMT removal (10/127 each; 7.9%), corneal edema >30 days after surgery (9/127; 7.1%), and persistent corneal edema (6/127; 4.7%). Significant adverse events included four corneal transplants, comprising two (2.9%) in group 1 and two (1.6%) in group 2. At 60 months, one patient in group 1 (3.2%) and three patients in group 2 (9.4%) had lost ≥2 lines of vision. The IMT was removed in one (1.4%) and ten (7.9%) patients in group 1 and group 2, respectively. Mean ECD loss was 20% at 3 months. Chronic loss was 3% per

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

    PubMed Central

    2012-01-01

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

  4. Treatment of hypertension after renal transplantation: long-term efficacy of verapamil, enalapril, and doxazosin.

    PubMed

    Martínez-Castelao, A; Hueso, M; Sanz, V; Rejas, J; Alsina, J; Grinyó, J M

    1998-12-01

    Normal blood pressure is a good marker of graft survival after renal transplantation, and effective antihypertensive treatment reduces the progression of graft damage. We conducted a long-term follow-up study of 88 hypertensive renal transplant recipients, all of whom were taking sustained cyclosporine A (CsA) immunosuppression. The patients were treated for at least three years, and initially received 240 mg/day of verapamil (N = 24, group I), 5 mg/day of enalapril (N = 24, group II) or 1 mg/day of doxazosin (N = 40, group III). Baseline creatinine did not differ in the three groups, but proteinuria was higher in the enalapril group (7 patients had proteinuria > 1.5 g/day). Treatment was withdrawn in 5 patients in the verapamil group, 5 in the enalapril group and 2 in the doxazosin group due to drug-related side effects. Blood pressure (BP) control at three years was equivalent in the three groups (systolic BP, group I 157 +/- 12; group II 149 +/- 19; group III 154 +/- 21; diastolic BP, group I 90 +/- 8.7, group II 84 +/- 9.8, group III 90.5 +/- 16; mean BP, group I 113 +/- 7, group II 106 +/- 10, group III 106 +/- 29). Two patients in group I, 3 in group II and 15 in group III required additional antihypertensive drugs. CsA levels increased in the verapamil-treated patients, allowing for an early decrease in CsA doses (1 year doses, 3.3 +/- 1 mg/kg body wt/day in group I, 4.3 +/- 1.6 in group II, 3.7 +/- 1.6 in group III). Six cardiovascular events occurred, 3 in group I, 1 in group II, and 2 in group III patients. One patient died in the enalapril group and another in the doxazosin group. Eight verapamil-treated patients, 8 enalapril-treated patients and 4 doxazosin-treated patients lost their grafts due to biopsy-proven chronic transplant nephropathy. In conclusion, the three antihypertensive agents are effective in reducing blood pressure, with no clear advantage of one above any other. Verapamil allows the CsA dose to be reduced, thus decreasing the cost of

  5. Clobetasol propionate shampoo 0.05% is efficacious and safe for long-term control of moderate scalp psoriasis.

    PubMed

    Poulin, Yves; Papp, Kim; Bissonnette, Robert; Barber, Kirk; Kerrouche, Nabil; Villemagne, Hervé

    2010-05-01

    We evaluated in this study the efficacy and safety of an alternate regimen using clobetasol propionate 0.05% shampoo (CP shampoo) for long-term control of scalp psoriasis. Patients with moderate scalp psoriasis (Global Severity Score [GSS] of 3 on a 0-5 scale) first received CP shampoo once daily for 4 weeks. Patients with a GSS 2) occurred, patients received the 4-week daily CP shampoo treatment. Patients who had a GSS efficacious and safe for long-term management of moderate scalp psoriasis.

  6. 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…

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

    PubMed

    Ricroch, Agnès E

    2013-05-25

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

  8. Sanguinaria toothpaste and oral rinse regimen clinical efficacy in short- and long-term trials.

    PubMed

    Kuftinec, M M; Mueller-Joseph, L J; Kopczyk, R A

    1990-01-01

    Short- and long-term testing of sanguinaria toothpaste and oral rinse used individually have yielded both positive and negative results. This review evaluates the results of a number of clinical trials testing the regimen use of sanguinaria products for periods ranging from 14 days to six months. Review of these trials establishes the clinical efficacy of the two products in combination. The regimen approach produces consistently positive reductions in plaque, gingival inflammation and bleeding parameters for up to six months with no adverse hard tissue effects and only one reversible adverse soft tissue effect observed among the 260 subjects tested. In addition, no adverse microbiological shifts in the normal oral flora were observed.

  9. 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

  10. Long-term efficacy of prism adaptation on spatial neglect: preliminary results on different spatial components.

    PubMed

    Rusconi, Maria Luisa; Carelli, Laura

    2012-01-01

    This study describes the long-term effectiveness on spatial neglect recovery of a 2-week treatment based on prism adaptation (PA). Seven right-brain-damaged patients affected by chronic neglect were evaluated before, after two weeks of the PA treatment and at a follow-up (variable between 8 and 30 months after the end of PA). Neglect evaluation was performed by means of BIT (conventional and behavioral), Fluff Test, and Comb and Razor Test. The results highlight an improvement, after the PA training, in both tasks performed using the hand trained in PA treatment and in behavioral tasks not requiring a manual motor response. Such effects extend, even if not significantly, to all BIT subtests. These results support previous findings, showing that PA improves neglect also on imagery tasks with no manual component, and provide further evidence for long-lasting efficacy of PA training. Dissociations have been found with regard to PA efficacy on peripersonal, personal, and representational neglect, visuospatial agraphia and neglect dyslexia. In particular, we found no significant differences between the pre-training and post-training PA session in personal neglect measures, and a poor recovery of neglect dyslexia after PA treatment. The recruitment of a larger sample could help to confirm the effectiveness of the prismatic lenses with regard to the different clinical manifestations of spatial neglect.

  11. Long-term results of the mucosal ablation of Barrett's esophagus: efficacy and recurrence

    PubMed Central

    Saligram, Shreyas; Tofteland, Nathan; Wani, Sachin; Gupta, Neil; Mathur, Sharath; Vennalaganti, Prashanth; Kanakadandi, Vijay; Giacchino, Maria; Higbee, April; Lim, Diego; Rastogi, Amit; Bansal, Ajay; Sharma, Prateek

    2015-01-01

    Background and study aims: It has been postulated that the endoscopic ablation of Barrett’s esophagus can lead to complete eradication of the disease. This study was undertaken to evaluate the efficacy of endoscopic eradication therapy for Barrett’s esophagus and the rates of recurrence of intestinal metaplasia. Patients and methods: As part of an initial randomized controlled trial, patients with nondysplastic or low grade dysplastic Barrett’s esophagus underwent mucosal ablation. Following ablation, the patients had annual surveillance endoscopies. Recurrence was defined as the presence of intestinal metaplasia after initial complete eradication had been achieved. Results: A total of 28 patients with Barrett’s esophagus were followed for a mean of 6.4 years after ablation therapy. At baseline, the majority of the patients had nondysplastic Barrett’s esophagus (79 %). Initial complete eradication of intestinal metaplasia was achieved at a mean of 4.1 months. During long-term follow-up, initial recurrence of intestinal metaplasia was seen in 14 of the 28 of patients (50 %) at a mean of 40 months, and further maintenance ablation therapy was applied. At the final follow-up, 36 % of the patients had complete eradication of intestinal metaplasia, 18 % of the patients had intestinal metaplasia, and 21 % had died of unrelated causes; invasive esophageal adenocarcinoma had developed in 1 patient. Conclusions: The long-term results of this study demonstrate a recurrence rate of 50 % after complete eradication of Barrett’s esophagus with endoscopic eradication therapy. In addition, re-recurrence (in 36 %), even after further maintenance endoscopic eradication therapy, and deaths unrelated to the disease (21 %) occurred. Complete remission of Barrett’s esophagus appears to be a difficult goal to achieve. These results call into question the role of ablation in patients with low risk Barrett’s esophagus. PMID:26171429

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

  13. 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

  14. 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.

  15. Long-term persistence and efficacy of spinosad against Rhyzopertha dominica (Coleoptera: Bostrychidae) in wheat.

    PubMed

    Daglish, Gregory J; Nayak, Manoj K

    2006-02-01

    A laboratory study was undertaken to determine the persistence and efficacy of spinosad against Rhyzopertha dominica (F.) in wheat stored for 9 months at 30 degrees C and 55 and 70% relative humidity. The aim was to investigate the potential of spinosad for protecting wheat from R. dominica during long-term storage in warm climates. Wheat was treated with spinosad at 0.1, 0.5 and 1 mg kg(-1) grain and sampled after 0, 1.5, 3, 4.5, 6, 7.5 and 9 months of storage for bioassays and residue analyses. Residues were estimated to have declined by 30% during 9 months of storage at 30 degrees C and there was no effect of relative humidity. Spinosad applied at 0.5 or 1 mg kg(-1) was completely effective for 9 months, with 100% adult mortality after 14 days of exposure and no live F1 adults produced. Adult mortality was <100% in some samples of wheat treated with 0.1 mg kg(-1) of spinosad, and live progeny were produced in all samples treated at this level. The results show that spinosad is likely to be an effective grain protectant against R. dominica in wheat stored in warm climates.

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  18. 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.

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

    PubMed Central

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

    2016-01-01

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

  20. 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.

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    2013-10-01

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

  4. Long-term Efficacy of Trabeculectomy on Chinese Patients with Pigmentary Glaucoma: A Prospective Case Series Observational Study

    PubMed Central

    Qing, Guo-Ping; Wang, Ning-Li; Wang, Tao; Chen, Hong; Mou, Da-Peng

    2016-01-01

    Background: Though trabeculectomy is often performed on patients with medically refractive pigmentary glaucoma (PG), the clinical outcomes of surgical treatment on PG remain unknown. The aim of this study was to summarize the long-term efficacy and safety of trabeculectomy on PG. Methods: This was a prospective case series observational study. Eighteen consecutive PG patients were followed up for 8 years after trabeculectomy from May 2006 to April 2007. Visual acuity (VA), best-corrected visual acuity (BCVA), slit lamp biomicroscopy, intraocular pressure (IOP) measurement, Humphrey visual field analysis (VFA), and stereoscopic funduscopy were performed on admission and every 6 months after the surgery. Postoperative IOP, VA, BCVA, VFA, adjunctive anti-glaucoma medication, treatment-related side-effects, changes in blebs, and main clinical findings in the anterior segment of PG were recorded and compared with the baseline. Results: Eighteen PG eyes from 18 patients, with average preoperative IOP of 34.5 ± 4.7 mmHg (range: 21–47 mmHg, 1 mmHg=0.133 kPa) were enrolled in this study. All enrolled patients completed the follow-up visits and required examinations. Eight years after trabeculectomy, all surgical eyes (18/18) had satisfactory IOP control with an average of 13.7 ± 2.5 mmHg (range: 9–19 mmHg), which was significantly lower than baseline (P = 0.001). Majority (15/18) of the PG eyes had stable VA, BCVA, VFA, and optic disc cupping parameters. Functional blebs still existed in 12/18 of the PG eyes at the last follow-up visit. Unanimously, pigmentation in the anterior segment attenuated with time after surgical treatment. No severe side-effects were recorded in any of the surgical eyes. Conclusions: All surgical PG eyes in this study had satisfactory IOP control 8 years after the surgery with well-preserved visual function. The long-term efficacy and safety of trabeculectomy are promising in PG patients. PMID:27231161

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Aoto-Sullivan, Stacey Y.

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

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

    NASA Technical Reports Server (NTRS)

    Feiveson, Alan H.

    2000-01-01

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

  9. 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.

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

    PubMed

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

    2011-07-01

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

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

    PubMed Central

    Hogan, David B

    2014-01-01

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

  12. 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.

  13. Double-blind study comparing the long-term efficacy of the COX-2 inhibitor nimesulide and naproxen in patients with osteoarthritis.

    PubMed

    Kriegel, W; Korff, K J; Ehrlich, J C; Lehnhardt, K; Macciocchi, A; Moresino, C; Pawlowski, C

    2001-10-01

    This double-blind one-year study compares the long-term efficacy and safety of nimesulide with naproxen in patients with osteoarthritis (OA) of the knee or hip. Patients were randomised to nimesulide 100 mg twice daily (n = 183) or naproxen 250 mg morning, 500 mg evening (n = 187). The primary efficacy variable was change in pain intensity (WOMAC A scale) at 6 months. Nimesulide tablets showed at least equivalent efficacy to naproxen tablets in reducing pain intensity at 6 and 12 months (nimesulide -22.5% at 6 and 12 months; naproxen -22.4% at 6 months, -19.9% at 12 months; non-inferiority proven). At 6 months the investigator assessed efficacy as 'good' or 'excellent' in 59.3% of nimesulide and 56.4% of naproxen-treated patients, with corresponding values for patient assessment of 57% and 52.7%. Both treatments were well tolerated, with fewer related gastrointestinal adverse events reported with nimesulide (77 cases, 47.5%) than with naproxen (96 cases, 54.5%). This study shows nimesulide to be as effective as naproxen in the long-term treatment of OA and to be associated with fewer gastrointestinal side-effects.

  14. 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

  15. Acute, short- and long-term efficacy of oral bevantolol in patients with coronary artery disease: a placebo-controlled, randomized, double-blind study.

    PubMed

    Gimeno, J V; Ferrer, J; Olague, J; Bordes, P; Serra, J; Estruch, G; Mainer, V; Algarra, F J

    1986-09-01

    The efficacy and safety of bevantolol (new cardioselective beta-blocking agent without intrinsic sympathetic activity) were evaluated in chronic stable angina pectoris. Acute effects on heart rate (HR) and pulmonary function (forced expiratory volume in the first second, FEV1, and vital capacity, VC) (double-blind placebo, propranolol, 80 mg, and bevantolol, 150 mg) and the antianginal efficacy during early (double-blind placebo period) and chronic bevantolol therapy (long-term follow-up for 52 weeks) were studied. Bevantolol reduces HR in the same way as propranolol (both p less than 0.01). Pulmonary function is modified significantly only by propranolol (decreasing FEV1, p less than 0.05). Bevantolol reduces antianginal attacks and nitroglycerin consumption (p less than 0.01) and improves exercise tolerance (p less than 0.01) during early and chronic therapy.

  16. Acute, short- and long-term efficacy of oral bevantolol in patients with coronary artery disease: a placebo-controlled, randomized, double-blind study.

    PubMed

    Gimeno, J V; Ferrer, J; Olague, J; Bordes, P; Serra, J; Estruch, G; Mainer, V; Algarra, F J

    1986-09-01

    The efficacy and safety of bevantolol (new cardioselective beta-blocking agent without intrinsic sympathetic activity) were evaluated in chronic stable angina pectoris. Acute effects on heart rate (HR) and pulmonary function (forced expiratory volume in the first second, FEV1, and vital capacity, VC) (double-blind placebo, propranolol, 80 mg, and bevantolol, 150 mg) and the antianginal efficacy during early (double-blind placebo period) and chronic bevantolol therapy (long-term follow-up for 52 weeks) were studied. Bevantolol reduces HR in the same way as propranolol (both p less than 0.01). Pulmonary function is modified significantly only by propranolol (decreasing FEV1, p less than 0.05). Bevantolol reduces antianginal attacks and nitroglycerin consumption (p less than 0.01) and improves exercise tolerance (p less than 0.01) during early and chronic therapy. PMID:3530572

  17. Testing the Immediate and Long-Term Efficacy of a Tier 2 Kindergarten Mathematics Intervention

    ERIC Educational Resources Information Center

    Clarke, Ben; Doabler, Christian; Smolkowski, Keith; Kurtz Nelson, Evangeline; Fien, Hank; Baker, Scott K.; Kosty, Derek

    2016-01-01

    This study examined the efficacy of a kindergarten mathematics intervention program, ROOTS, focused on developing whole-number understanding in the areas of counting and cardinality and operations and algebraic thinking for students at risk in mathematics. The study utilized a randomized block design with students within classrooms randomly…

  18. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome.

    PubMed

    Hendriksz, Christian J; Parini, Rossella; AlSayed, Moeenaldeen D; Raiman, Julian; Giugliani, Roberto; Solano Villarreal, Martha L; Mitchell, John J; Burton, Barbara K; Guelbert, Norberto; Stewart, Fiona; Hughes, Derralynn A; Berger, Kenneth I; Slasor, Peter; Matousek, Robert; Jurecki, Elaina; Shaywitz, Adam J; Harmatz, Paul R

    2016-09-01

    Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and

  19. Association between long-term efficacy of cinacalcet and parathyroid gland volume in haemodialysis patients with secondary hyperparathyroidism.

    PubMed

    Tanaka, Motoko; Nakanishi, Shohei; Komaba, Hirotaka; Itoh, Kazuko; Matsushita, Kazutaka; Fukagawa, Masafumi

    2008-08-01

    Purpose. Secondary hyperparathyroidism with nodular hyperplasia is resistant to medical therapies. Cinacalcet is an effective treatment for severe secondary hyperparathyroidism. This multicentre retrospective study was designed to determine the long-term efficacy of cinacalcet in patients with nodular hyperplasia, the advanced type of parathyroid hyperplasia. Subjects and methods. The study subjects were 20 haemodialysis patients with secondary hyperparathyroidism. Patients with ultrasonographically confirmed large parathyroid glands (volume >0.5 cm(3)) were considered to have nodular hyperplasia (n = 8). Cinacalcet was started at the dose of 25 mg/day and titrated up to 100 mg/day to achieve the target intact-parathyroid hormone (iPTH) level of <250 pg/ml. Serum iPTH, corrected calcium, serum phosphorus, calcium × phosphorus product were measured and compared over the 48-week period of treatment with cinacalcet in all 20 patients and over 120 weeks in 6 of the patients (2 with nodular hyperplasia and 4 with non-nodular hyperplasia). We also examined the achievement rate of K/DOQI guideline treatment targets. The dosages of vitamin D preparation, sevelamer hydrochloride and calcium- containing phosphate binder were adjusted for the above target values. Results. iPTH levels were significantly lower at 48 weeks in both groups. However, corrected calcium levels, serum phosphorus levels and calcium phosphorus products were within the target values in the non-nodular hyperplasia group (n = 12), while the target value could not be achieved in the nodular hyperplasia group. In the long-term follow-up group, the levels of iPTH, corrected calcium, serum phosphorus and calcium × phosphorus products were significantly higher in nodular hyperplasia than in non-nodular hyperplasia. Conclusion. Our study suggests that cinacalcet lacks long-term efficacy in nodular hyperplasia, especially for controlling serum calcium and phosphorus levels.

  20. The antimicrobial efficacy of a new central venous catheter with long-term broad-spectrum activity.

    PubMed

    Schierholz, J M; Fleck, C; Beuth, J; Pulverer, G

    2000-07-01

    Indwelling vascular catheters are a major cause of nosocomial sepsis. Prevention of colonization of polymeric surfaces by continuous release of bactericidal, highly biocompatible antimicrobials incorporated into polymers has been investigated as a promising new approach. An antimicrobial polyurethane catheter was investigated by HPLC and various antimicrobial assays. Controlled drug delivery governed by the physico-chemical mass transfer from the polyurethane bulk provided long-term release of the antimicrobial substances from the material to the outer surface and catheter lumen. The in vitro activity of catheters coated with miconazole and rifampicin against 158 clinical isolates of catheter-associated infections was evaluated. Incubated in physiological NaCl at 37 degrees C, the half-life of inhibitory activity of catheters coated with miconazole or rifampicin exceeded 3 weeks. In static and dynamic adhesion assays, coated catheters were able to prevent colonization with Staphylococcus aureus, Staphylococcus epidermidis and enterococci. To produce catheters resistant to infection, a potent antimicrobial efficacy combined with an excellent biocompatibility over time is needed. The long lasting efficacy of the antimicrobial polyurethane alloy as well as the increased antifungal activity of miconazole combined with rifampicin may be regarded as a promising improvement for long-term central venous access.

  1. The antimicrobial efficacy of a new central venous catheter with long-term broad-spectrum activity.

    PubMed

    Schierholz, J M; Fleck, C; Beuth, J; Pulverer, G

    2000-07-01

    Indwelling vascular catheters are a major cause of nosocomial sepsis. Prevention of colonization of polymeric surfaces by continuous release of bactericidal, highly biocompatible antimicrobials incorporated into polymers has been investigated as a promising new approach. An antimicrobial polyurethane catheter was investigated by HPLC and various antimicrobial assays. Controlled drug delivery governed by the physico-chemical mass transfer from the polyurethane bulk provided long-term release of the antimicrobial substances from the material to the outer surface and catheter lumen. The in vitro activity of catheters coated with miconazole and rifampicin against 158 clinical isolates of catheter-associated infections was evaluated. Incubated in physiological NaCl at 37 degrees C, the half-life of inhibitory activity of catheters coated with miconazole or rifampicin exceeded 3 weeks. In static and dynamic adhesion assays, coated catheters were able to prevent colonization with Staphylococcus aureus, Staphylococcus epidermidis and enterococci. To produce catheters resistant to infection, a potent antimicrobial efficacy combined with an excellent biocompatibility over time is needed. The long lasting efficacy of the antimicrobial polyurethane alloy as well as the increased antifungal activity of miconazole combined with rifampicin may be regarded as a promising improvement for long-term central venous access. PMID:10882687

  2. 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

  3. 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

  4. 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…

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

    SciTech Connect

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

    2007-06-01

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

  6. 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

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

    PubMed

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

    2013-02-01

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

  8. Long-term efficacy of a psychological intervention program for patients with refractory bipolar disorder: a pilot study.

    PubMed

    González-Isasi, Ana; Echeburúa, Enrique; Mosquera, Fernando; Ibáñez, Berta; Aizpuru, Felipe; González-Pinto, Ana

    2010-04-30

    The aim of this research was to test the long-term efficacy of combined standard treatment (pharmacotherapy and adjunctive psychosocial treatment based on a cognitive-behavioral model) compared with standard drug treatment for patients with recurrent bipolar disorder. Twenty patients selected according to DSM-IV-TR criteria were randomized to 1) combined treatment or 2) control treatment. A multigroup experimental design with repeated assessment measures (pre-treatment, post-treatment, 6-month follow-up, and 12-month follow-up) was used. Results of the repeated measurement analysis showed a significant increment in scores of Global Activity Functioning within the combined treatment group during the follow-up, which was not observed in the control treatment group. Therefore, the effectiveness of psychotherapy tends to increase with time, and this improvement is not significant until 12 months of follow-up.

  9. Clobetasol propionate shampoo 0.05% is efficacious and safe for long-term control of scalp psoriasis.

    PubMed

    Poulin, Yves; Papp, Kim; Bissonnette, Robert; Guenther, Lyn; Tan, Jerry; Lynde, Charles; Kerrouche, Nabil; Villemagne, Hervé

    2010-01-01

    Clobetasol propionate (CP) shampoo 0.05% is an efficacious and safe treatment for scalp psoriasis. The aim of this double-blind, randomized, placebo-controlled study was to determine if CP shampoo is suitable for long-term disease control. Participants with moderate to severe scalp psoriasis (global severity score [GSS] of 3 or 4 on a scale of 0 [clear] to 5 [very severe]) first received once daily CP shampoo treatment for up to 4 weeks. Responders were subsequently randomized to receive the CP shampoo or vehicle twice weekly maintenance regimen for up to 6 months. When relapse occurred (defined as GSS > 2), participants resumed once daily CP shampoo treatment; when symptoms diminished (GSS < or = 2), they readopted the twice weekly maintenance regimen. At all visits significantly more participants treated with CP shampoo did not relapse compared with participants treated with vehicle (P < .001). Only approximately one-third of participants treated with vehicle remained relapse free at 1 month, while this rate was observed approximately 3.5 months later (4.5 months after baseline of maintenance phase) in the CP shampoo group. After 6 months 31.1% (33/106) of participants in the CP shampoo group were still relapse free versus 8.1% (9/111) of participants in the vehicle group. There was no greater incidence of skin atrophy, telangiectasia, or hypothalamic-pituitary-adrenal (HPA) axis suppression in the CP shampoo group compared with the vehicle group. Clobetasol propionate shampoo is efficacious and safe for acute management and long-term maintenance of moderate to severe scalp psoriasis.

  10. Blockade of NMDA receptors unmasks a long-term depression in synaptic efficacy in rat prefrontal neurons in vitro.

    PubMed

    Hirsch, J C; Crepel, F

    1991-01-01

    All the experiments were carried out in slices of rat prefrontal cortex maintained in vitro. The effect of 2-amino-5-phosphonovalerate (APV) was tested on the postsynaptic potential (PSP) recorded in layer V pyramidal cells, in response to single or high frequency stimulation of the superficial layers I-II. Wash-out of Mg2+ increased the amplitude and duration of the PSPs. This effect resulted from activation of N-methyl-D-aspartate (NMDA) receptors since it was suppressed by bath application of APV. Furthermore, in every cell tested in Mg2+ containing medium (N = 16), exposure to APV reversibly reduced both mono- and polysynaptic components of the PSPs, indicating that, even in the control solution, activation of NMDA-coupled channels contributed to these synaptic events. Finally, the anomalous voltage-dependence of the EPSP in the presence of Mg2+ and its sensitivity to APV suggests that at least a fraction of the NMDA receptors are postsynaptically located. Tetanization was applied to the afferents of cells bathed in control- or APV-medium. Long-term potentiation (LTP) or long-term depression (LTD) is defined as an increase or a decrease respectively, of the PSPs peak amplitude or initial slope, lasting 20 min. In the control medium, LTP in synaptic efficacy was observed in 34% of the cells and LTD in 48% (N = 23). When exposed to APV, none of the cells tested (N = 16) showed LTP of the response. In contrast, the tetanus induced a LTD of the PSP amplitude or slope in 14 out of these 16 cells. The percentage of cells showing LTD in synaptic efficacy (87%) when the NMDA receptors activation was blocked was significantly higher than that in control-medium.

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

    PubMed

    Frazzoli, Chiara; Petrini, Carlo; Mantovani, Alberto

    2009-01-01

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

  12. 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.

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

    PubMed

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

    2016-01-01

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

  14. Mid- and Long-Term Efficacy of Non-Invasive Ventilation in Obesity Hypoventilation Syndrome: The Pickwick's Study.

    PubMed

    López-Jiménez, María José; Masa, Juan F; Corral, Jaime; Terán, Joaquín; Ordaz, Estrella; Troncoso, Maria F; González-Mangado, Nicolás; González, Mónica; Lopez-Martínez, Soledad; De Lucas, Pilar; Marín, José M; Martí, Sergi; Díaz-Cambriles, Trinidad; Díaz-de-Atauri, Josefa; Chiner, Eusebi; Aizpuru, Felipe; Egea, Carlos; Romero, Auxiliadora; Benítez, José M; Sánchez-Gómez, Jesús; Golpe, Rafael; Santiago-Recuerda, Ana; Gómez, Silvia; Barbe, Ferrán; Bengoa, Mónica

    2016-03-01

    The Pickwick project was a prospective, randomized and controlled study, which addressed the issue of obesity hypoventilation syndrome (OHS), a growing problem in developed countries. OHS patients were divided according to apnea-hypopnea index (AHI) ≥30 and <30 determined by polysomnography. The group with AHI≥30 was randomized to intervention with lifestyle changes, noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP); the group with AHI<30 received NIV or lifestyle changes. The aim of the study was to evaluate the efficacy of NIV treatment, CPAP and lifestyle changes (control) in the medium and long-term management of patients with OHS. The primary variables were PaCO2 and days of hospitalization, and operating variables were the percentage of dropouts for medical reasons and mortality. Secondary medium-term objectives were: (i)to evaluate clinical-functional effectiveness on quality of life, echocardiographic and polysomnographic variables; (ii)to investigate the importance of apneic events and leptin in the pathogenesis of daytime alveolar hypoventilation and change according to the different treatments; (ii)to investigate whether metabolic, biochemical and vascular endothelial dysfunction disorders depend on the presence of apneas and hypopneasm and (iv)changes in inflammatory markers and endothelial damage according to treatment. Secondary long-term objectives were to evaluate: (i)clinical and functional effectiveness and quality of life with NIV and CPAP; (ii)changes in leptin, inflammatory markers and endothelial damage according to treatment; (iii)changes in pulmonary hypertension and other echocardiographic variables, as well as blood pressure and incidence of cardiovascular events, and (iv)dropout rate and mortality.

  15. Mid- and Long-Term Efficacy of Non-Invasive Ventilation in Obesity Hypoventilation Syndrome: The Pickwick's Study.

    PubMed

    López-Jiménez, María José; Masa, Juan F; Corral, Jaime; Terán, Joaquín; Ordaz, Estrella; Troncoso, Maria F; González-Mangado, Nicolás; González, Mónica; Lopez-Martínez, Soledad; De Lucas, Pilar; Marín, José M; Martí, Sergi; Díaz-Cambriles, Trinidad; Díaz-de-Atauri, Josefa; Chiner, Eusebi; Aizpuru, Felipe; Egea, Carlos; Romero, Auxiliadora; Benítez, José M; Sánchez-Gómez, Jesús; Golpe, Rafael; Santiago-Recuerda, Ana; Gómez, Silvia; Barbe, Ferrán; Bengoa, Mónica

    2016-03-01

    The Pickwick project was a prospective, randomized and controlled study, which addressed the issue of obesity hypoventilation syndrome (OHS), a growing problem in developed countries. OHS patients were divided according to apnea-hypopnea index (AHI) ≥30 and <30 determined by polysomnography. The group with AHI≥30 was randomized to intervention with lifestyle changes, noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP); the group with AHI<30 received NIV or lifestyle changes. The aim of the study was to evaluate the efficacy of NIV treatment, CPAP and lifestyle changes (control) in the medium and long-term management of patients with OHS. The primary variables were PaCO2 and days of hospitalization, and operating variables were the percentage of dropouts for medical reasons and mortality. Secondary medium-term objectives were: (i)to evaluate clinical-functional effectiveness on quality of life, echocardiographic and polysomnographic variables; (ii)to investigate the importance of apneic events and leptin in the pathogenesis of daytime alveolar hypoventilation and change according to the different treatments; (ii)to investigate whether metabolic, biochemical and vascular endothelial dysfunction disorders depend on the presence of apneas and hypopneasm and (iv)changes in inflammatory markers and endothelial damage according to treatment. Secondary long-term objectives were to evaluate: (i)clinical and functional effectiveness and quality of life with NIV and CPAP; (ii)changes in leptin, inflammatory markers and endothelial damage according to treatment; (iii)changes in pulmonary hypertension and other echocardiographic variables, as well as blood pressure and incidence of cardiovascular events, and (iv)dropout rate and mortality. PMID:26656679

  16. 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.

  17. 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.

  18. Long-term efficacy and toxicity of abacavir/lamivudine/nevirapine compared to the most prescribed ARV regimens before 2013 in a French Nationwide Cohort Study.

    PubMed

    de Boissieu, Paul; Dramé, Moustapha; Raffi, François; Cabie, André; Poizot-Martin, Isabelle; Cotte, Laurent; Garraffo, Rodolphe; Delobel, Pierre; Huleux, Thomas; Rey, David; Bani-Sadr, Firouzé

    2016-09-01

    Data on the long-term efficacy and safety of abacavir/lamivudine (ABC/3TC) and nevirapine (NVP) are scarce. This combination has the advantage of simplifying treatment and improving long-term tolerance. The aim of this study was to compare the rate of any discontinuation of antiretroviral (ARV) regimen because of virologic failure (VF), and/or adverse drug reaction (ADR) among patients receiving stable ARV regimens for at least 6 months.ABC/3TC/NVP was compared to ABC/3TC with either ritonavir-boosted darunavir (DRV/r) or ritonavir-boosted atazanavir (ATV/r), unboosted ATV, or tenofovir/emtricitabine (TDF/FTC) with either one of the following: ATV/r, unboosted ATV, DRV/r, efavirenz (EFV), or NVP, in the French prospective multicenter Dat'AIDS cohort.The study enrolled 16,511 patients treated with following ARV regimens: ABC/3TC/NVP (n = 1089), TDF/FTC/NVP (n = 1542), ABC/3TC/DRV/r (n = 1065), ABC/3TC/ATV/r (n = 1847), ABC/3TC/ATV (n = 563), TDF/FTC/ATV/r (n = 3519), TDF/FTC/DRV/r (n = 2767), TDF/FTC/ATV (n = 419), and TDF/FTC/EFV (n = 3700). Mean follow-up was 36 ± 24 months. Patients treated with ABC/3TC/NVP received this regimen as a switch regimen in 97% of cases. By multivariable analysis, the risk of treatment discontinuation due to VF was similar between ABC/3TC/NVP and other ARV regimens, except for TDF/FTC/ATV and ABC/3TC/ATV, which were associated with a higher risk of treatment interruption due to VF (hazard ratio [HR] 1.99; 95% confidence interval [CI] 1.29-3.06 and HR 2.19; 95% CI 1.51-3.18, respectively). Treatment discontinuation due to ADR was lowest with the ABC/3TC/NVP regimen. Other ARV regimens were associated with a 1.80- to 3.19-fold increase in the risk of treatment discontinuation due to ADR (P < 0.0001 for all comparisons).ABC/3TC/NVP as a simplification regimen is a long-term effective regimen with lower discontinuation due to long-term toxicity compared with other standard ARV regimens. PMID

  19. Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis

    PubMed Central

    Pazianas, Michael; Cooper, Cyrus; Ebetino, F Hal; Russell, R Graham G

    2010-01-01

    Bisphosphonates are the leading drugs for the treatment of osteoporosis. In randomized controlled trials (RCTs), alendronate, risedronate, and zoledronate have shown to reduce the risk of vertebral, nonvertebral, and hip fractures, whereas RCTs with ibandronate show antifracture efficacy at vertebral sites. Bisphosphonates are generally well tolerated and safe. Nevertheless, adverse events have been noted, and it is important to consider the strength of the evidence for causal relationships. Effects on the gastrointestinal tract and kidney function are well recognized, as are transient acute-phase reactions. Atrial fibrillation was first identified as a potential adverse event in a zoledronate trial, but subsequent trials and analyses failed to substantiate an association with bisphosphonates. Case reports have suggested a relationship between oral bisphosphonates and esophageal cancer, but this has not been demonstrated in epidemiologic studies. A possible association between bisphosphonate use and osteonecrosis of the jaw (ONJ) has also been suggested. However, the risk of ONJ in patients with osteoporosis appears to be very low, with no evidence from prospective RCTs of a causal association. There are reports of occasional occurrence of subtrochanteric or diaphyseal fractures in osteoporotic patients, but an association with bisphosphonate therapy is not substantiated by epidemiologic studies or prospective RCTs. PMID:20668715

  20. 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

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

    PubMed Central

    Van Meter, W S

    1997-01-01

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

  2. 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

  3. 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

  4. 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

  5. Acute and long-term safety and tolerability of risperidone in children with autism.

    PubMed

    Aman, Michael G; Arnold, L Eugene; McDougle, Christopher J; Vitiello, Benedetto; Scahill, Lawrence; Davies, Mark; McCracken, James T; Tierney, Elaine; Nash, Patricia L; Posey, David J; Chuang, Shirley; Martin, Andres; Shah, Bhavik; Gonzalez, Nilda M; Swiezy, Naomi B; Ritz, Louise; Koenig, Kathleen; McGough, James; Ghuman, Jaswinder K; Lindsay, Ronald L

    2005-12-01

    Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as

  6. Long-term efficacy of liraglutide in Indian patients with Type 2 diabetes in a real-world setting

    PubMed Central

    Kaur, Parjeet; Mahendru, Shama; Mithal, Ambrish

    2016-01-01

    Background: Long-term efficacy of liraglutide, a glucagon-like peptide-1 analog, on body weight and glycemic control has not been studied in Indian Type 2 diabetes mellitus (T2DM) subjects. Aim: To evaluate the effect of liraglutide on glycemic control and body weight for 1 year in Indian T2DM patients. Methods: Liraglutide was prescribed to 96 obese patients with T2DM and followed up for 1 year. Clinical parameters were measured at baseline and 3, 6, 9, and 12 months. Dosage of liraglutide and other medications was adjusted according to clinical judgment. Results: 1 year data were available for 74 patients. Mean age was 50.9 ± 9.6 years. Mean duration of diabetes was 11.6 ± 6.3 years. Glycosylated hemoglobin (HbA1c) significantly decreased from 8.9 ± 1.3% at baseline to 7.4 ± 1.2% at 1 year. Body weight significantly declined from 98.9 ± 16.0 kg at baseline to 93.8 ± 15.0 kg at 1 year. After an initial decline, subset of patients had an increase in mean HbA1c (n = 30/74) and mean body weight (n = 33/74) after 6 months of liraglutide initiation. Baseline HbA1c and baseline body weight were positively associated with a reduction of HbA1c and body weight at 1 year, respectively. No major side effects occurred. Conclusion: Liraglutide treatment resulted in a significant and sustained reduction in HbA1c and body weight over 1 year in Indian T2DM patients. Magnitude of reduction of HbA1c and body weight at 1 year was positively associated with baseline HbA1c and baseline weight, respectively. PMID:27730066

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

    PubMed Central

    Goddard, Jerome

    2014-01-01

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

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

    PubMed

    Goddard, Jerome

    2014-11-28

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

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

    PubMed

    Goddard, Jerome

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  13. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2004-01-01

    Data on adjuvant chemotherapy in early-stage uterine sarcomas are conflicting and most often based on small patient groups with relatively short duration of follow-up. Approximately 60% of patients present with stage I disease with an overall 5-year survival of 30-50% when treated with surgery alone. This study examines the efficacy and results of long-term follow-up of a multiagent chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) as adjuvant treatment for patients with stage I uterine sarcoma. Between 1982 and 1999, 24 evaluable patients with completely staged uterine sarcomas received adjuvant multiagent chemotherapy with vincristine sulfate (1mg /m(2)) on days 1 and 4, doxorubicin (40 mg /m(2)) and cyclophosphamide (400 mg /m(2)) on day 2, and dacarbazine (200 mg /m(2)) on days 1 through 4 for a total of nine monthly cycles or until recurrence of disease was documented. Survival distributions were calculated by the Kaplan-Meier method, and statistical significance was determined with the log-rank test. Factors significant on univariate analysis were analyzed in a multivariate fashion using Cox proportional hazards model. The histologic distribution of patients was 46% leiomyosarcoma, 33% mixed mullerian tumors, 13% stromal sarcomas, 4% adenosarcomas, and 4% hemangiosarcoma. The patients received 206 of a planned 216 cycles of chemotherapy. The median follow-up of the patient population was 93 months (range 11-213 months). Eight patients (33%) developed recurrent disease. The median time to recurrence was 19 months (range 7-184 months). The estimated survival for the entire group was 88, 75, and 69% at 2, 5, and 15 years, respectively. Factors that did not affect survival included age, histology, and tumor grade. Four patients required dose reductions secondary to grade 2-3 toxicities (hematologic). Grade 1 neurotoxicity was observed in six patients (25%) and grade 2 neurotoxicity in one patient (4%). Adjuvant CYVADIC

  16. Long-term efficacy of endovascular vs open surgical repair for complicated type-B aortic dissection: a single-center retrospective study and meta-analysis

    PubMed Central

    Zhu, Y.; Wang, B.; Meng, Q.; Liu, J.; Zhai, S.; He, J.

    2016-01-01

    This study aimed to evaluate the long-term survival and risk factors of traditional open surgical repair (OSR) vs thoracic endovascular aneurysm repair (TEVAR) for complicated type-B aortic dissection (TBAD). A total of 118 inpatients (45 OSR vs 73 TEVAR) with TBAD were enrolled from January 2004 to January 2015. Kaplan-Meier curves and Cox proportional hazards analysis were performed to identify the long-term survival rate and independent predictors of survival, respectively. Meta-analysis was used to further explore the long-term efficacy of OSR and TEVAR in the eight included studies using Review Manager 5.2 software. An overall 10-year survival rate of 41.9% was found, and it was similar in the two groups (56.7% OSR vs 26.1% TEVAR; log-rank P=0.953). The risk factors of long-term survival were refractory hypertension (OR=11.1; 95%CI=1.428-86.372; P=0.021] and preoperative aortic diameter >55 mm (OR=4.5; 95%CI=1.842-11.346; P=0.001). Long-term survival rate did not differ significantly between OSR and TEVAR (hazard ratio=0.87; 95%CI=0.52-1.47; P=0.61). Compared with OSR, TEVAR did not show long-term advantages for patients with TBAD. Refractory hypertension and total aortic diameter >55 mm can be used to predict the long-term survival of TBAD in the Chinese Han population. PMID:27254661

  17. 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…

  18. Long-term engraftment of single genetically modified human epidermal holoclones enables safety pre-assessment of cutaneous gene therapy.

    PubMed

    Larcher, Fernando; Dellambra, Elena; Rico, Laura; Bondanza, Sergio; Murillas, Rodolfo; Cattoglio, Claudia; Mavilio, Fulvio; Jorcano, José L; Zambruno, Giovanna; Del Rio, Marcela

    2007-09-01

    Predicting the risks of permanent gene therapy approaches involving the use of integrative gene-targeting vectors has become a critical issue after the unfortunate episode of a clinical trial in children with X-linked severe combined immunodeficiency (X-SCID). Safety pre-assessment of single isolated gene-targeted stem cells or their derivative clones able to regenerate their tissue of origin would be a major asset in addressing untoward gene therapy effects in advance. Human epidermal stem cells, which have extensive proliferative potential in vitro, theoretically offer such a possibility as a method of assessment. By means of optimized organotypic culture and grafting methods, we demonstrate the long-term in vivo regenerative capacity of single gene-targeted human epidermal stem cell clones (holoclones). Both histopathological analysis of holoclone-derived grafts in immunodeficient mice and retroviral insertion site mapping performed in the holoclone in vitro and after grafting provide proof of the feasibility of pre-assessing genotoxicity risks in isolated stem cells before transplantation into patients. Our results provide an experimental basis for previously untested assumptions about the in vivo behavior of epidermal stem cells prospectively isolated in vitro and pave the way for a safer approach to cutaneous gene therapy.

  19. 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

  20. 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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  2. 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. PMID:27508113

  3. 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

  4. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Daecke, W; Kusnierczak, D; Loew, M

    2002-07-01

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

  7. Long-Term Efficacy of Oxybutynin for Palmar and Plantar Hyperhidrosis in Children Younger than 14 Years.

    PubMed

    Wolosker, Nelson; Teivelis, Marcelo P; Krutman, Mariana; de Paula, Rafael P; Schvartsman, Claudio; Kauffman, Paulo; de Campos, José R M; Puech-Leão, Pedro

    2015-01-01

    Oxybutynin for treating hyperhidrosis in children has been evaluated only in short-term studies. We aimed to investigate the long-term effects of oxybutynin in treating children with palmar and plantar hyperhidrosis who had not undergone surgery and who were monitored for at least 6 months (median 19.6 mos). A cohort of 97 patients was evaluated retrospectively, with particular attention to 59 children (ages 4-14 yrs) who were treated for longer than 6 months. Their quality of life (QOL) was evaluated using a validated clinical questionnaire before and after 6 weeks of pharmacologic therapy. A self-assessment of hyperhidrosis was performed after 6 weeks and after the last consultation. By their final office visit, more than 91% of the children with hyperhidrosis treated with oxybutynin experienced moderate or great improvement in their level of sweating and 94.9% experienced improvement in QOL. More than 90% of children reported improvement of hyperhidrosis at other sites. Dry mouth was the most common side effect. Oxybutynin appears to be an effective treatment option for children with hyperhidrosis, and positive results are maintained over the long term (median 19.6 mos).

  8. Long-term safety of tiotropium delivered by Respimat® SoftMist™ Inhaler: patient selection and special considerations

    PubMed Central

    Tan, Ching Kuo; Say, Gui Quan; Geake, James B

    2016-01-01

    Tiotropium bromide is a long-acting inhaled muscarinic antagonist used in patients with chronic respiratory disease. It has been available since 2002 as a single-dose dry powder formulation via the HandiHaler® dry powder inhaler (DPI) device, and since 2007 as the Respimat® SoftMist™ Inhaler (SMI). The latter is a novel method of medication delivery that utilizes a multidose aqueous solution to deliver the drug as a fine mist. Potential benefits include more efficient drug deposition throughout the respiratory tract, reduced systemic exposure, and greater ease of use and patient satisfaction compared with the use of HandiHaler DPI. Although tiotropium bromide delivered via the HandiHaler DPI has been clearly shown to improve lung function, dyspnea, and quality of life and to reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), there is accumulating evidence regarding the use of tiotropium HandiHaler in other respiratory diseases characterized by airflow limitation, such as asthma and cystic fibrosis. Developed more recently, tiotropium delivered via the Respimat SMI appears to have a similar efficacy and safety profile to the HandiHaler DPI, and early data raising the possibility of safety concerns with its use in COPD have been refuted by more recent evidence. The benefits over the HandiHaler DPI, however, remain unclear. This paper will review the evidence for tiotropium delivered via the Respimat SMI inhaler, in particular as an alternative to the HandiHaler DPI, and will focus on the safety profile for each of the chronic lung diseases in which it has been trialed, as well as an approach to appropriate patient selection. PMID:27703365

  9. 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 ...

  10. Pairing of pre- and postsynaptic activities in cerebellar Purkinje cells induces long-term changes in synaptic efficacy in vitro.

    PubMed

    Crepel, F; Jaillard, D

    1991-01-01

    1. An in vitro slice preparation of rat cerebellar cortex was used to analyse long-lasting modifications of synaptic transmission at parallel fibre (PF)-Purkinje cell (PC) synapses. These use-dependent changes were induced by pairing PF-mediated EPSPs evoked at low frequency (1 Hz) with different levels of membrane polarization (or bioelectrical activities) of PCs for 15 min. 2. Experiments were performed on forty-eight PCs recorded intracellularly in a conventional perfused chamber, and in fifty other cells maintained in a static chamber either in the presence (n = 21) or in the absence (n = 29) of 400 nM-phorbol 12,13-dibutyrate (PDBu). 3. In these three experimental conditions, PF-mediated EPSPs were always measured on PCs maintained at a holding potential of -75 mV, and further hyperpolarized by constant hyperpolarizing pulses. This allowed us both to test the input resistance of PCs and to avoid their firing during PF-mediated EPSPs. 4. In all cells retained for the present study, latencies of PF-mediated EPSPs evoked at 0.2 Hz were stable during the pre-pairing period, and the same was true for their amplitude and time course. 5. In the perfused chamber, pairing of PF-mediated EPSPs with the same hyperpolarization of PCs as that used for measurements of synaptic responses had no effect on these EPSPs in 30% of PCs. It induced long-term depression (LTD) and long-term potentiation (LTP) in 23 and 47% of the tested cells respectively (n = 17). 6. In the perfused chamber, pairing of PF-mediated EPSPs with moderate depolarization of PCs (n = 19) giving rise to a sustained firing of sodium spikes significantly favoured the appearance of LTP as compared to the previous pairing protocol. However, there were still 27 and 15% of cells which showed no modification and LTD respectively. 7. In contrast, pairing of PF-mediated EPSPs with calcium (Ca2+) spikes evoked by strong depolarization of PCs (n = 12) led to LTD of synaptic transmission in nearly half of the tested

  11. The long-term efficacy of a behavioral parent training intervention for families with 2-year-olds.

    PubMed

    Tucker, S; Gross, D; Fogg, L; Delaney, K; Lapporte, R

    1998-06-01

    The effectiveness of a behavioral parent training (BPT) intervention for improving maternal self-efficacy, maternal stress, and the quality of mother-toddler interactions has been demonstrated (Gross, Fogg, & Tucker, 1995). The 1-year follow-up of the 46 parents of toddlers (assigned to an intervention or comparison group) who participated in that study is reported. It was hypothesized that (a) BPT would lead to enduring positive changes in parenting self-efficacy, parenting stress, and parent-toddler interactions; and (b) the amount of parent participation in the intervention would be correlated with greater gains in parent-child outcomes at 1 year. All the families were retained and significant gains in maternal self-efficacy, maternal stress, and mother-child interactions were maintained. Minimal BPT effects were found for fathers. BPT dosage was related to reductions in mother critical statements and negative physical behaviors at 1-year postintervention. The findings are consistent with self-efficacy theory and support parenting self-efficacy as a target for BPT in families of young children.

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

    SciTech Connect

    Toma Cajthaml; Vaclav Sasek

    2005-11-01

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

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

    PubMed

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

    2013-09-12

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

  14. Dapagliflozin efficacy and safety: a perspective review

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Efficacy of phosphorus-32 brachytherapy without external-beam radiation for long-term tumor control in patients with craniopharyngioma.

    PubMed

    Ansari, Shaheryar F; Moore, Reilin J; Boaz, Joel C; Fulkerson, Daniel H

    2016-04-01

    OBJECT Radioactive phosphorus-32 (P32) has been used as brachytherapy for craniopharyngiomas with the hope of providing local control of enlarging tumor cysts. Brachytherapy has commonly been used as an adjunct to the standard treatment of surgery and external-beam radiation (EBR). Historically, multimodal treatment, including EBR, has shown tumor control rates as high as 70% at 10 years after treatment. However, EBR is associated with significant long-term risks, including visual deficits, endocrine dysfunction, and cognitive decline. Theoretically, brachytherapy may provide focused local radiation that controls or shrinks a symptomatic cyst without exposing the patient to the risks of EBR. For this study, the authors reviewed their experiences with craniopharyngioma patients treated with P32 brachytherapy as the primary treatment without EBR. The authors reviewed these patients' records to evaluate whether this strategy effectively controls tumor growth, thus avoiding the need for further surgery or EBR. METHODS The authors performed a retrospective review of pediatric patients treated for craniopharyngioma between 1997 and 2004. This was the time period during which the authors' institution had a relatively high use of P32 for treatment of cystic craniopharyngioma. All patients who had surgery and injection of P32 without EBR were identified. The patient records were analyzed for complications, cyst control, need for further surgery, and need for future EBR. RESULTS Thirty-eight patients were treated for craniopharyngioma during the study period. Nine patients (23.7%) were identified who had surgery (resection or biopsy) with P32 brachytherapy but without initial EBR. These 9 patients represented the study group. For 1 patient (11.1%), there was a complication with the brachytherapy procedure. Five patients (55.5%) required subsequent surgery. Seven patients (77.7%) required subsequent EBR for tumor growth. The mean time between the injection of P32 and

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

    PubMed

    Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

    2014-03-01

    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

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

    PubMed Central

    Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

    2014-01-01

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

  1. Long-term 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

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

    PubMed

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

    2010-12-01

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

  3. Efficacy of short term versus long term tube thoracostomy drainage before tetracycline pleurodesis in the treatment of malignant pleural effusions.

    PubMed Central

    Villanueva, A. G.; Gray, A. W.; Shahian, D. M.; Williamson, W. A.; Beamis, J. F.

    1994-01-01

    BACKGROUND--A study was undertaken to compare the efficacy of short term tube thoracostomy drainage with standard tube thoracostomy drainage before instillation of tetracycline for sclerotherapy of malignant pleural effusions. METHODS--The study consisted of a randomised clinical trial in a sequential sample of 25 patients with malignant pleural effusions documented cytopathologically. Fifteen patients were randomly assigned to group 1 (standard protocol) and 10 to group 2 (short term protocol). Patients in group 1 had tube thoracostomy suction drainage until radiological evidence of lung re-expansion was obtained and the amount of fluid drained was < 150 ml/day, before tetracycline (1.5 g) was instilled. The chest tube was removed when the amount of fluid drained after instillation was < 150 ml/day. Patients in group 2 also had suction drainage, but the tetracycline (1.5 g) was instilled when the chest radiograph showed the lung to be re-expanded and the effusion drained, which was usually within 24 hours. The chest tube was removed the next day. RESULTS--The response to tetracycline sclerotherapy in the two groups was the same (80%) but the duration of chest tube drainage was significantly shorter for patients in group 2 (median two days) than for those in group 1 (median seven days). CONCLUSIONS--The duration of chest tube drainage before sclerotherapy for malignant pleural effusions need not be influenced by the amount of fluid drained daily but by radiographic evidence of fluid evacuation and lung re-expansion. Shorter duration of drainage will reduce the length of hospital stay without sacrificing the efficacy of pleurodesis. PMID:7512285

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

    PubMed

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

    2015-02-28

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

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

    PubMed

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

    2015-02-28

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-10-01

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

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

    NASA Astrophysics Data System (ADS)

    Tinnin, Richard Kinna

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

  10. 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

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

    SciTech Connect

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

    2003-02-24

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

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

    NASA Astrophysics Data System (ADS)

    Munier, R.

    2011-12-01

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

  13. Efficacy of Desvenlafaxine 50 mg/d Versus Placebo in the Long-Term Treatment of Major Depressive Disorder: A Randomized, Double-Blind Trial

    PubMed Central

    Vialet, Cécile; Hwang, Eunhee; Tourian, Karen A.

    2015-01-01

    Objective: To examine long-term (11-month) antidepressant efficacy of desvenlafaxine 50 mg/d across a broad range of clinical and functional outcomes in patients with major depressive disorder. Method: Adult outpatients (≥ 18 years) with major depressive disorder (DSM-IV criteria) and a 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 20 at screening and baseline who responded to 8 weeks of open-label desvenlafaxine 50 mg/d and had a continuing stable response through week 20 were randomly assigned to receive placebo or desvenlafaxine 50 mg/d in a 6-month, double-blind, randomized withdrawal period. Depressive symptoms were evaluated using the HDRS-17, 6-item HDRS, and Clinical Global Impressions–Severity of Ilness and –Improvement (CGI-S, CGI-I). Health outcomes included the Work Productivity and Activity Impairment (WPAI) questionnaire and the World Health Organization 5-Item Well-Being Index (WHO-5). The trial was conducted from June 2009 to March 2011 at 87 study sites in 14 countries worldwide. Results: Of 874 patients enrolled in open-label treatment, 548 patients were randomly assigned to receive double-blind placebo (n = 276) or desvenlafaxine 50 mg/d (n = 272). At the end of the 6-month double-blind treatment, improvements in depressive symptoms were better maintained among the desvenlafaxine- than placebo-treated patients on all efficacy endpoints (all P ≤ .001); in the desvenlafaxine group, 21.8% (vs 42.9% in the placebo group) had CGI-I ratings of 5, 6, and 7 (minimally worse/much worse/very much worse), and 74.4% met criteria for remission (placebo: 54.2%). WPAI and WHO-5 scores indicated significantly better productivity and well-being with continued desvenlafaxine (vs placebo, P ≤ .001). Conclusions: Long-term treatment with desvenlafaxine 50 mg/d maintained improvements in major depressive disorder among adult outpatients who exhibited a stable therapeutic response. Trial Registration: ClinicalTrials.gov identifier: NCT

  14. Comparative long-term preclinical safety evaluation of two glatiramoid compounds (glatiramer Acetate, Copaxone(R), and TV-5010, protiramer) in rats and monkeys.

    PubMed

    Ramot, Yuval; Rosenstock, Moti; Klinger, Ety; Bursztyn, Dizza; Nyska, Abraham; Shinar, Doron M

    2012-01-01

    Glatiramer acetate (GA), the active ingredient in Copaxone®, is a complex mixture of polypeptides used for the treatment of relapsing remitting multiple sclerosis. Glatiramoids are related mixtures that may differ in some characteristics of the prototype molecule. Our aim is to describe the long-term toxicity studies with protiramer (TV-5010), a new glatiramoid, in comparison with similar studies conducted with GA. The toxicity of twice-weekly subcutaneous injections of protiramer to Sprague-Dawley rats (twenty-six weeks) and cynomolgus monkeys (fifty-two weeks) was compared with similar studies done with daily subcutaneous injections of GA. Daily treatment with GA was safe and well tolerated, without systemic effects or death. Protiramer administration was not as well tolerated as GA and led to dose- and time-related mortalities, probably mediated through severe injection-site lesions both in rats and in monkeys. Bridging fibrosis in the liver and severe progressive nephropathy were seen in rats. A dose-related increase in eosinophils was observed in monkeys. The protiramer toxicity studies show that minor variations in the manufacturing of glatiramoids may lead to significant toxic effects. It is therefore essential that the safety of any new glatiramoid be studied in long-term preclinical studies before exposing humans. PMID:22083585

  15. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  18. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance

    PubMed Central

    Arciero, Paul J.; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J.; Astrup, Arne

    2016-01-01

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0–12); and (2) mP-CR compared to a HH diet during WM (weeks 13–64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p < 0.01) in weight (10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%–12%), insulin (40%), leptin (>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet. PMID:27483317

  19. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

    PubMed

    Arciero, Paul J; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J; Astrup, Arne

    2016-01-01

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p < 0.01) in weight (10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%-12%), insulin (40%), leptin (>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet. PMID:27483317

  20. Diffuse large B-cell lymphoma associated with the use of biologic and other investigational agents: the importance of long-term post-marketing safety surveillance.

    PubMed

    Goddard, Allison; Borovicka, Judy H; West, Dennis P; Evens, Andrew M; Laumann, Anne

    2011-01-01

    This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thrice-weekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related to the use of any newly available product. In particular, surveillance should focus on the immunomodulating biologic agents in order to identify possible dangerous sequelae.

  1. Clobazam is equally safe and efficacious for seizures associated with Lennox-Gastaut syndrome across different age groups: Post hoc analyses of short- and long-term clinical trial results.

    PubMed

    Ng, Yu-Tze; Conry, Joan; Mitchell, Wendy G; Buchhalter, Jeffrey; Isojarvi, Jouko; Lee, Deborah; Drummond, Rebecca; Chung, Steve

    2015-05-01

    The peak age at onset of Lennox-Gastaut syndrome (LGS) is between 3 and 5years. Patients with LGS frequently experience multiple types of treatment-refractory seizures and require lifelong therapy with several antiepileptic drugs. Here, post hoc analyses of clinical trials (phase III trial OV-1012 and open-label extension trial OV-1004) provide short- and long-term efficacy and safety data of adjunctive clobazam in patients with LGS stratified by age at baseline (≥2 to <12years, ≥12 to <17years, and ≥17years). In OV-1012, 301 patients were screened, 238 were randomized, 217 comprised the modified intention-to-treat population, and 177 completed the study. A total of 267/306 patients (61 of 68 from phase II trial OV-1002 and 206 of 238 from phase III trial OV-1012) entered the open-label extension trial. Demographics and clinical characteristics were similar between different age groups in OV-1012 and OV-1004. No differences in efficacy or adverse events were observed across age groups in OV-1012 and OV-1004. The results of these post hoc analyses show that adjunctive clobazam over the short and longterm was similarly effective and well-tolerated in both pediatric and adult patients with LGS.

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    2015-07-15

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

  4. Long-term safety and tolerability of saxagliptin add-on therapy in older patients (aged ≥65 years) with type 2 diabetes

    PubMed Central

    Iqbal, Nayyar; Allen, Elsie; Öhman, Peter

    2014-01-01

    Background Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ≥65 years and <65 years. Methods Pooled adverse event data from three placebo-controlled trials of 76–206 weeks’ duration in older (≥65 years) and younger (<65 years) patients receiving saxagliptin 5 mg or matching placebo added to metformin, glyburide, or a thiazolidinedione were analyzed. Measurements were calculated from day of first dose to specified event or last dose and included time at risk for adverse events, treatment-related adverse events, serious adverse events, adverse events leading to discontinuation, and events of special interest. Weighted incidence rates (number of events/total time) and incidence rate ratios (saxagliptin/placebo) with 95% confidence intervals were calculated (Mantel-Haenszel test). Results A total of 205 older (mean age 69 years; saxagliptin, n=99; placebo, n=106) and 1,055 younger (mean age 52 years; saxagliptin, n=531; placebo, n=524) patients were assessed. Regardless of age category, the adverse event incidence rates were generally similar between treatments, with confidence intervals for incidence rate ratios bridging 1. Treatment-related adverse events occurred in 36 older patients receiving saxagliptin versus 32 receiving placebo (incidence rate 34.1 versus 27.1 per 100 person-years) and in 150 younger patients in both treatment groups (incidence rate 24.0 versus 27.8 per 100 person-years). With saxagliptin versus placebo, serious adverse events occurred in eight versus 14 older (incidence rate 5.7 versus 9.9 per 100 person-years) and 49 versus 44 younger patients (incidence rate 6.5 versus 6.6 per 100 person-years). There were two deaths (one patient ≥65 years) with saxagliptin and six (none aged ≥65 years

  5. Long-Term, Open-Label, Safety Study of Edivoxetine 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment.

    PubMed

    Ball, Susan G; Atkinson, Sarah; Sparks, JonDavid; Bangs, Mark; Goldberger, Celine; Dubé, Sanjay

    2015-06-01

    Long-term safety, tolerability, and efficacy of adjunctive edivoxetine hydrochloride (hereafter edivoxetine), a highly selective and potent norepinephrine reuptake inhibitor, was assessed in patients with major depressive disorder (MDD) experiencing partial response to selective serotonin reuptake inhibitor treatment. Data are from a multicenter, 54-week, open-label trial of adjunctive edivoxetine 12 to 18 mg once daily in patients with MDD who had experienced partial response by history to 6 or more weeks of current selective serotonin reuptake inhibitor therapy and who had a 17-item GRID Hamilton Rating Scale for Depression total score 16 or higher at study entry. Safety measures included discontinuation rate, treatment-emergent adverse events, serious adverse events, and vital signs. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale. Of 608 patients, 328 (54%) completed the open-label adjunctive treatment. Study discontinuation due to adverse events occurred in 17.0%, and there were 13 serious adverse events (1 death). Treatment-emergent adverse events 5% or higher were nausea, hyperhidrosis, constipation, headache, dry mouth, dizziness, vomiting, insomnia, and upper respiratory tract infection. Mean increases were observed in systolic blood pressure (range, 0.0-2.3 mm Hg), diastolic blood pressure (range, 1.9-3.3 mm Hg), and pulse (range, 5.9-8.4 beats per minute). Mean improvements on the Montgomery-Åsberg Depression Rating Scale (-17.0) were observed from baseline to week 54. The safety profile from this study provides an overview of outcomes associated with edivoxetine and norepinephrine reuptake inhibition as an adjunctive treatment in patients with MDD who were treated up to 1 year. PMID:25815754

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

    PubMed

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

    2013-04-01

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

  7. Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects.

    PubMed

    Hayashi, Noriko; Iida, Tetsuo; Yamada, Takako; Okuma, Kazuhiro; Takehara, Isao; Yamamoto, Takashi; Yamada, Koji; Tokuda, Masaaki

    2010-01-01

    This clinical study was conducted to investigate the safety and effect of D-psicose on postprandial blood glucose levels in adult men and women, including borderline diabetes patients. A randomized double-blind placebo-controlled crossover experiment of single ingestion was conducted on 26 subjects who consumed zero or 5 g of D-psicose in tea with a standard meal. The blood glucose levels at fasting and 30, 60, 90, and 120 min after the meal were compared. The blood glucose level was significantly lower 30 and 60 min after the meal with D-psicose (p<0.01, p<0.05), and a significant decrease was also shown in the area under the curve (p<0.01). The results suggest that D-psicose had an effect to suppress the postprandial blood glucose elevation mainly in borderline diabetes cases. A randomized double-blind placebo-controlled parallel-group experiment of long-term ingestion was conducted on 17 normal subjects who took 5 g of D-psicose or D-glucose with meals three times a day for 12 continuous weeks. Neither any abnormal effects nor clinical problems caused by the continuous ingestion of D-psicose were found.

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2014-11-01

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

  10. The past versus the present, 1980-2004: reduction of mean initial low-dose, long-term glucocorticoid therapy in rheumatoid arthritis from 10.3 to 3.6 mg/day, concomitant with early methotrexate, with long-term effectiveness and safety of less than 5 mg/day.

    PubMed

    Pincus, Theodore; Sokka, Tuulikki; Cutolo, Maurizio

    2015-01-01

    Quantitative observations are presented concerning treatment with glucocorticoids of 308 patients with rheumatoid arthritis (RA) at a weekly academic rheumatology setting over 25 years from 1980 to 2004. A database of all visits included medications and multidimensional health assessment questionnaire scores for physical function, pain and routine assessment of patient index data (RAPID3; and a surrogate RAPID3-EST), completed by each patient at each visit in routine care. Over the 5-year periods of 1980-1984, 1985-1989, 1990-1994, 1995-1999 and 2000-2004, the mean initial prednisone daily dose declined from 10.3 to 6.5, 5.1, 4.1 and 3.6 mg/day, as initial doses were >5 mg/day in 49, 16, 7, 7 and 3% of patients, 5 mg/day in 51, 80, 70, 26 and 10%, and <5 mg/day in 0, 4, 23, 67 and 86%. Reduction of prednisone doses in the respective five-year periods was accompanied by increased and earlier use of methotrexate as the first disease-modifying antirheumatic drug (DMARD) in 10, 26, 57, 71 and 78%, and methotrexate treatment in 10, 26, 74, 82 and 92% of patients within the first year of disease. Higher methotrexate doses in the respective five-year periods were used after 1990, along with lower prednisone doses. Most patients were treated indefinitely with both low-dose prednisone and methotrexate; 80% continued both medications for more than 5 years. The primary adverse events were skin-thinning and bruising. New hypertension, diabetes and cataracts were seen in fewer than 10% of patients. While efficacy and safety cannot be analyzed definitively from observational data, the data suggest that many patients with RA might be treated effectively with weekly low-dose methotrexate along with initial and long-term, low-dose prednisone of <5 mg/day. PMID:25228430

  11. 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

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

    PubMed

    Oh, Jiwon; O'Connor, Paul W

    2013-08-01

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

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

    SciTech Connect

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

    1985-05-17

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

  14. Efficacy and long-term follow-up of IL-1R inhibitor anakinra in adults with Still's disease: a case-series study

    PubMed Central

    2011-01-01

    Introduction To assess the efficacy and safety of the interleukin-1 receptor (IL-1R) inhibitor anakinra in adult patients with refractory Still's disease. Methods Twenty-five patients (13 males and 12 females, median age 32 years, median disease duration seven months) with Still's disease were treated with subcutaneous injections of anakinra (100 mg/day). Treatment was given as adjunct therapy in 16 patients and as standalone in 9 patients for a median time of 15 months (range 1.5-71). The clinical and laboratory parameters during follow-up were recorded. Results In 84% of patients the clinical activity resolved completely within a few days (median time 0.2 months), and response was maintained until the last visit in all but one patient. A complete response of all disease-related symptoms (clinical and laboratory) occurred subsequently within a median time of three months in 80% of patients. A partial clinical and laboratory improvement was shown in 12% and 16% of patients, respectively. The Visualized Analogue Scale and Health Assessment Questionnaire scores significantly decreased during treatment. The proportion of patients achieving the American College of Rheumatology 20 (ACR20) score (20% improvement) was 82% at one month and improved to 100% at one year. The mean oral corticosteroid dose was significantly reduced at each visit. Anakinra was discontinued due to unresponsiveness in one patient and due to relapsing disease in another. Treatment was also withdrawn in three patients with severe skin reactions (urticaria). Seven patients experienced an infection during follow-up. Conclusions The rapid and sustained response in the majority of our patients encourages the use of anakinra in adults with Still's disease. PMID:21682863

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

    PubMed Central

    Werschler, Pam Schell

    2016-01-01

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

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

    PubMed

    Fonseca, Joaquim

    2015-01-01

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

  17. Long term treatment of polymyalgia rheumatica with deflazacort.

    PubMed Central

    Cimmino, M A; Moggiana, G; Montecucco, C; Caporali, R; Accardo, S

    1994-01-01

    OBJECTIVES--To evaluate the long term efficacy and tolerability of deflazacort, a corticosteroid reputed to have only minor side effects, in the treatment of polymyalgia rheumatica (PMR). METHODS--In a prospective open study, deflazacort was administered at an average initial dose of 21.8 mg/day for a mean period of 19 months in 40 patients with PMR. RESULTS--A highly significant improvement of clinical and laboratory parameters occurred one month after therapy onset. This improvement persisted for the whole study period. Laboratory parameters of tolerability did not change during the study. Mild to moderate steroid-related side effects occurred in 57.9% of the patients. CONCLUSIONS--Deflazacort is effective in the treatment of PMR. Its long term safety profile may be superior to that of other corticosteroids. PMID:8017988

  18. Clinical efficacy of macrophage-activating Chinese mixed herbs (MACH) in improvement of embryo qualities in women with long-term infertility of unknown etiology.

    PubMed

    Ushiroyama, Takahisa; Yokoyama, Noriko; Hakukawa, Midori; Sakuma, Kou; Ichikawa, Fumio; Yoshida, Satoshi

    2012-01-01

    Despite the recent technological advances in in vitro fertilization and embryo transfer (IVF-ET), a significant proportion of women still do not become pregnant after long-term infertility, whether it is originally due to older age or other undetermined factors. In the present study, macrophage activating Chinese herbs (MACH) were evaluated for their effects on embryo qualities in women who were undergoing repeated IVF-ET because of long-term infertility. Thirty women, who had significantly low rates of developing good quality cleaved embryos and did not become pregnant after three or more cycles of Assisted Reproductive Technology (ART) procedure, were included in the study. Oral administration of MACH significantly increased the percentage of good quality early stage blastocysts (the number of grade 1 or grade 2 cleaved embryos/the number of retrieved oocytes) from 18.7 ± 16.2% to 36.1 ± 27.1% (1.9-fold increase, p < 0.01). The rate of good quality early stage blastocysts increased in all patients. In 19 patients who desired embryo transfer using late stage blastocysts, MACH significantly increased the percentage of late stage blastocysts from the initial value of 14.8 ± 11.2% to 21.1 ± 23.1% (1.4-fold increase, p < 0.05). The rate of embryonic progress into late stage blastocyst increased in 52.6% (10/19) of the patients. Furthermore, treatment with MACH significantly decreased the plasma follicle stimulating hormone (FSH) concentration on the day of oocyte retrieval from 14.4 ± 3.2 to 10.5 ± 2.4 mIU/ml (p < 0.05). No adverse events were observed with MACH supplementation, and there was no patient dropout. Administration of MACH resulted in improved embryo quality in the difficult cases. The present study demonstrates a new benefit of this herbal blend in women with refractory infertility of unknown etiology. PMID:22298444

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

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

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

    2009-11-15

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

  1. TREATMENT EFFECTS OF WST11 VASCULAR TARGETED PHOTODYNAMIC THERAPY IN UROTHELIAL CELL CARCINOMA AND FEASIBILITY, SAFETY, AND LONG TERM OUTCOMES IN THE UPPER URINARY TRACT OF SWINE

    PubMed Central

    Murray, Katie S; Winter, Ashley G; Corradi, Renato Beluco; LaRosa, Stephen; Jebiwott, Sylvia; Somma, Alexander; Takaki, Haruyuki; Srimathveeravalli, Govindarajan; Lepherd, Michelle; Monette, Sebastien; Kim, Kwanghee; Scherz, Avigdor; Coleman, Jonathan A

    2016-01-01

    Purpose Surgical management of upper tract urothelial carcinoma requires removal of kidney and ureter, compromising renal function. Non-surgical alternatives have potentially prohibitive safety concerns. We examine the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular-targeted photodynamic therapy in a porcine model and report efficacy of WST11 vascular-targeted photodynamic therapy in a murine model. Materials and Methods Following approval, we performed 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4mg/kg) followed by laser illumination (10 minutes) was performed via percutaneous access or retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology was evaluated at several post-ablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy. Results At 24 hours, 50 mW/cm laser fluence produced superficial necrosis of the ureter and deeper necrosis (penetrating the muscularis propria or adventitia) was produced by treatment with 200 mW/cm in the ureter and renal pelvis. At 4 weeks, superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis, or abnormality of lab testing was noted up to 4 weeks. In mice, 80% had no evidence of tumor at 19 days after WST11 vascular-targeted photodynamic therapy. Conclusions Urothelial cell carcinoma appears to be sensitive to WST11 vascular-targeted photodynamic therapy. Depth of WST11 vascular-targeted photodynamic therapy treatment effects can be modulated in a dose-dependent manner by titration of light intensity. Moreover, this treatment modality, applied to the porcine upper urinary tract, is feasible via antegrade and retrograde access. PMID:26860792

  2. Current medical treatment of diabetes type 2 and long term morbidity: how to balance efficacy and safety?

    PubMed

    Carrera Boada, C A; Martínez-Moreno, J M

    2013-03-01

    Current medical treatment of type 2 diabetes mellitus (T2DM) requires special attention to different comorbidities that often are associated with hyperglycemia, such as overweight or obesity, dyslipidemia, hypertension, microvascular or macrovascular complications, etc. .. The control of these factors risk to health is as important as the glucose control in diabetes type 2, it is essential for the antidiabetes drugs consider these risk factors. The consensus statement published by the ADA/EASD and AACE emphasizes that the potential effects of antidiabetes medications on CV risk factors besides hyperglycemia (ie, overweight/obesity, hypertension, and dyslipidemia) should be considered in pharmacotherapy selection. Since T2DM is a progressive disease with worsening HbA1C values over time, monotherapy, even with different agents, will eventually fail to maintain the glycemic target. Because insulin resistance occurs in a variety of organs and tissues, many patients may achieve fasting glycemic control but develop postprandial hyperglycemia. Other issues include the risk for hypoglycaemia or weight gain with traditional glucose-lowering medications. The AACE/ACE algorithm for glycemic control is structured according to categories of HbA1C and suggests an HbA1C goal of =6.5%, although that may not be appropriate for all patients.42 The algorithm recommends monotherapy, dual therapy, or triple therapy based on initial HbA1C level of 6.5% to 7.5%, 7.6% to 9%, and >9% and reserves initiation of insulin therapy until treatment with oral or other injectable agents has failed. GLP-1 receptor agonists and DPP-4 inhibitors are novel options to improve glycemic control and reduce the incidence of weight gain. Combination therapy with newer and traditional agents improves glycemic control with a low incidence of hypoglycemia.

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

    PubMed Central

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

    2015-01-01

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

  4. Colistin: efficacy and safety in different populations.

    PubMed

    Shahbazi, Foroud; Dashti-Khavidaki, Simin

    2015-01-01

    This article reviews mechanisms, incidences, risk factors and preventive modalities of colistin toxicity as well as colistin use in special populations and through special routes. All clinical studies that examined the pharmacokinetic/pharmacodynamic, efficacy and side effects of colistin in the management of multidrug-resistant organisms in different patient population including pediatrics, adults, obese, critically ill, burn or cancer patients with any route of drug administration were considered. Compared with older recommended doses, current dosing approach improves cure rate without significant increase in the rate of colistin-induced nephrotoxicity. Efficacy and safety of high doses of colistin should be considered in the future studies. Also comparing efficacy and safety of different doses of aerosolized colistin and defining the appropriate dose in different populations is another open area of future researches.

  5. Predictors of Pegylated Interferon Alpha and Ribavirin Efficacy and Long-Term Assessment of Relapse in Patients With Chronic Hepatitis C: A One-Center Experience From China

    PubMed Central

    Wu, Qin; Zhan, Feng Yu; Chen, En Qiang; Wang, Cong; Li, Zhen Zhen; Lei, Xue Zhong

    2015-01-01

    Background: Sustained virological response (SVR) and virological relapse maintain pivotal roles in the management of chronic hepatitis C (CHC); however, there is little data regarding the long-term outcomes of patients with CHC in China. Objectives: We aimed to investigate the predictive factors of therapeutic effect and viral relapse in patients who achieved end-of-treatment response (ETR). Patients and Methods: We retrospectively analyzed clinical, biochemical and virological data of 169 adult patients with CHC from China who were not treated with pegylated interferon-alpha (PEG IFN-α) and ribavirin, of which 142 achieved ETR and with a follow-up period ranging from six months to six years. Statistical analysis was performed by SPSS 20.0. Results: Of the 169 patients, 124 (73.4%) achieved SVR and 23 (16.2%) experienced relapses post-therapy in cases of ETR patients. We considered sex, age, alanine aminotransferase, aspartate transaminase, baseline hepatitis C virus RNA level, HCV genotypes, IL28B rs12979860 genotype, rapid virological response (RVR), and early virological response (EVR). For antiviral effect in patients with CHC, HCV genotypes (2, 3) (χ2 = 11.285, P = 0.001), IL28B genotype (rs12979860 CC) (χ2 = 16.552, P < 0.001), RVR (χ2 = 37.339, P < 0.001), and EVR (χ2 = 70.265, P < 0.001) were significantly correlated with achieving SVR. For ETR patients with long-term follow-up, the relapse rate within six months was significantly higher than within other periods during six-year follow-up (χ2 = 7.792, P = 0.005). Relapse was virtually not observed after therapy ceased for 48 weeks. The IL28B genotype (rs12979860 CT/TT) (OR = 0.102; 95% CI, 0.031-0.339; P < 0.001), lower RVR (OR = 0.239; 95% CI, 0.078-0.738; P = 0.013), and EVR (OR = 0.102; 95% CI, 0.016-0.661; P = 0.017) were independent risk factors for relapse. Conclusions: Our study comprehensively explored the predictive factors of therapeutic effect of administered drugs and analyzed viral

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

    PubMed

    Vassilakos, Thomas N; Athanassiou, Christos G

    2015-08-01

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

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

    PubMed

    Vassilakos, Thomas N; Athanassiou, Christos G

    2015-08-01

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

  8. Efficacy and Safety of Human Retinal Progenitor Cells

    PubMed Central

    Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

    2016-01-01

    Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2013-02-15

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

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

    PubMed Central

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

    2014-01-01

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

  12. Pharmacokinetics and efficacy of long-term low-level administration of triclabendazole in urea molasses blocks against induced bovine and bubaline fasciolosis.

    PubMed

    Sanyal, P K; Gupta, S C

    1998-03-31

    The pharmacokinetics and flukicidal efficacy of triclabendazole delivered in low doses on a daily basis through urea molasses blocks were studied in cattle and buffaloes experimentally infected with Fasciola gigantica. The observations were compared with single therapeutic doses at 12.0 and 24.0 mg/kg body weight in cattle and buffaloes, respectively, prior to becoming experimentally infected. After receipt of triclabendazole by cattle and buffaloes at 0.83 and 3.0 mg/kg body weight, respectively, on a daily basis, both the animal species exhibited equilibrium between its absorption and disposition of its metabolites in plasma on day 4 and remained almost unchanged thereafter. The continuous subtherapeutic dosing of triclabendazole through urea molasses block at 0.83 mg/kg body weight in cattle and 3.0 mg/kg body weight in buffalo proved to be efficacious against mature liver flukes. PMID:9653990

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

    PubMed Central

    2013-01-01

    Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was

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

    PubMed

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

    2013-06-01

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

  15. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

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

  16. Long-term effects of the Family Bereavement Program on spousally bereaved parents: Grief, mental health problems, alcohol problems, and coping efficacy.

    PubMed

    Sandler, Irwin; Tein, Jenn-Yun; Cham, Heining; Wolchik, Sharlene; Ayers, Tim

    2016-08-01

    This study reports on the findings from a 6-year follow-up of a randomized trial of the Family Bereavement Program (FBP) on the outcomes for spousally bereaved parents. Spousally bereaved parents (N = 131) participated in the trial in which they were randomly assigned to receive the FBP (N = 72) or literature control (N = 59). Parents were assessed at four time points: pretest, posttest, and 11-month and 6-year follow-up. They reported on mental health problems, grief, and parenting at all four time periods. At the 6-year follow-up, parents reported on additional measures of persistent complex bereavement disorder, alcohol abuse problems, and coping efficacy. Bereaved parents in the FBP as compared to those in the literature control had lower levels of symptoms of depression, general psychiatric distress, prolonged grief, and alcohol problems, and higher coping efficacy (for mothers) at the 6-year follow-up. Multiple characteristics of the parent (e.g., gender, age, and baseline mental health problems) and of the spousal death (e.g., cause of death) were tested as moderators of program effects on each outcome, but only 3 of 45 tests of moderation were significant. Latent growth modeling found that the effects of the FBP on depression, psychiatric distress, and grief occurred immediately following program participation and were maintained over 6 years. Mediation analysis found that improvement in positive parenting partially mediated program effects to reduce depression and psychiatric distress, but had an indirect effect to higher levels of grief at the 6-year follow-up. Mediation analysis also found that improved parenting at the 6-year follow-up was partially mediated by program effects to reduce depression and that program effects to increase coping efficacy at the 6-year follow-up was partially mediated through reduced depression and grief and improved parenting. FBP reduced mental health problems, prolonged grief, and alcohol abuse, and increased coping

  17. Long-term effects of the Family Bereavement Program on spousally bereaved parents: Grief, mental health problems, alcohol problems, and coping efficacy.

    PubMed

    Sandler, Irwin; Tein, Jenn-Yun; Cham, Heining; Wolchik, Sharlene; Ayers, Tim

    2016-08-01

    This study reports on the findings from a 6-year follow-up of a randomized trial of the Family Bereavement Program (FBP) on the outcomes for spousally bereaved parents. Spousally bereaved parents (N = 131) participated in the trial in which they were randomly assigned to receive the FBP (N = 72) or literature control (N = 59). Parents were assessed at four time points: pretest, posttest, and 11-month and 6-year follow-up. They reported on mental health problems, grief, and parenting at all four time periods. At the 6-year follow-up, parents reported on additional measures of persistent complex bereavement disorder, alcohol abuse problems, and coping efficacy. Bereaved parents in the FBP as compared to those in the literature control had lower levels of symptoms of depression, general psychiatric distress, prolonged grief, and alcohol problems, and higher coping efficacy (for mothers) at the 6-year follow-up. Multiple characteristics of the parent (e.g., gender, age, and baseline mental health problems) and of the spousal death (e.g., cause of death) were tested as moderators of program effects on each outcome, but only 3 of 45 tests of moderation were significant. Latent growth modeling found that the effects of the FBP on depression, psychiatric distress, and grief occurred immediately following program participation and were maintained over 6 years. Mediation analysis found that improvement in positive parenting partially mediated program effects to reduce depression and psychiatric distress, but had an indirect effect to higher levels of grief at the 6-year follow-up. Mediation analysis also found that improved parenting at the 6-year follow-up was partially mediated by program effects to reduce depression and that program effects to increase coping efficacy at the 6-year follow-up was partially mediated through reduced depression and grief and improved parenting. FBP reduced mental health problems, prolonged grief, and alcohol abuse, and increased coping

  18. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. 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.

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

    NASA Astrophysics Data System (ADS)

    Nottingham, Mary E.

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

  3. Review of key Belotero Balance safety and efficacy trials.

    PubMed

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

    2013-10-01

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

  4. Postischemic fish oil treatment restores long-term retrograde memory and dendritic density: An analysis of the time window of efficacy.

    PubMed

    Bacarin, Cristiano Correia; Godinho, Jaqueline; de Oliveira, Rúbia Maria Weffort; Matsushita, Makoto; Gohara, Aline Kirie; Cardozo-Filho, Lúcio; Lima, Jéssica de Carvalho; Previdelli, Isolde Santos; Melo, Silvana Regina; Ribeiro, Matheus Henrique Dal Molin; Milani, Humberto

    2016-09-15

    We reported that fish oil (FO) prevented the loss of spatial memory caused by transient, global cerebral ischemia (TGCI), provided the treatment covered the first days prior to and after ischemia. Continuing these studies, trained rats were subjected to TGCI, and FO was administered for 10days, with a time window of efficacy (TWE) of 4, 8 or 12h post-ischemia. Retrograde memory was assessed up to 43days after TGCI. In another experiment, ischemic rats received FO with a 4- or 12-h TWE, and dendritic density was assessed in the hippocampus and cerebral cortex. The brain lipid profile was evaluated in sham-operated and ischemic rats that were treated with FO or vehicle with a 4-h TWE. Ischemia-induced retrograde amnesia was prevented by FO administration that was initiated with either a 4- or 8-h TWE. Fish oil was ineffective after a 12-h TWE. Independent of the TWE, FO did not prevent ischemic neuronal death. In the hippocampus, but not cerebral cortex, TGCI-induced dendritic loss was prevented by FO with a 4-h TWE but not 12-h TWE. The level of docosahexaenoic acid almost doubled in the hippocampus in ischemic, FO-treated rats (4-h TWE). The data indicate that (i) the anti-amnesic effect of FO can be observed with a TWE of up to 8h, (ii) the stimulation of dendritic neuroplasticity may have contributed to this effect, and (iii) DHA in FO may be the main active constituent in FO that mediates the cognitive and neuroplasticity effects on TGCI. PMID:27235715

  5. Postischemic fish oil treatment restores long-term retrograde memory and dendritic density: An analysis of the time window of efficacy.

    PubMed

    Bacarin, Cristiano Correia; Godinho, Jaqueline; de Oliveira, Rúbia Maria Weffort; Matsushita, Makoto; Gohara, Aline Kirie; Cardozo-Filho, Lúcio; Lima, Jéssica de Carvalho; Previdelli, Isolde Santos; Melo, Silvana Regina; Ribeiro, Matheus Henrique Dal Molin; Milani, Humberto

    2016-09-15

    We reported that fish oil (FO) prevented the loss of spatial memory caused by transient, global cerebral ischemia (TGCI), provided the treatment covered the first days prior to and after ischemia. Continuing these studies, trained rats were subjected to TGCI, and FO was administered for 10days, with a time window of efficacy (TWE) of 4, 8 or 12h post-ischemia. Retrograde memory was assessed up to 43days after TGCI. In another experiment, ischemic rats received FO with a 4- or 12-h TWE, and dendritic density was assessed in the hippocampus and cerebral cortex. The brain lipid profile was evaluated in sham-operated and ischemic rats that were treated with FO or vehicle with a 4-h TWE. Ischemia-induced retrograde amnesia was prevented by FO administration that was initiated with either a 4- or 8-h TWE. Fish oil was ineffective after a 12-h TWE. Independent of the TWE, FO did not prevent ischemic neuronal death. In the hippocampus, but not cerebral cortex, TGCI-induced dendritic loss was prevented by FO with a 4-h TWE but not 12-h TWE. The level of docosahexaenoic acid almost doubled in the hippocampus in ischemic, FO-treated rats (4-h TWE). The data indicate that (i) the anti-amnesic effect of FO can be observed with a TWE of up to 8h, (ii) the stimulation of dendritic neuroplasticity may have contributed to this effect, and (iii) DHA in FO may be the main active constituent in FO that mediates the cognitive and neuroplasticity effects on TGCI.

  6. Long term complications of diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000327.htm Long term complications of diabetes To use the sharing ... sores and infections. If it goes on too long, your toes, foot, or leg may need to ...

  7. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  8. Long-term biomass research

    SciTech Connect

    Not Available

    1981-03-01

    Some of DOE's long term R and D programs for biomass are summarized in this article. These include research efforts in the fields of anaerobic digestion, energy farming, short rotation cultivation and aquatic farming. (DMC)

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed

    Hassan, Mohamed

    2015-01-01

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

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

    PubMed Central

    Hassan, Mohamed

    2015-01-01

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

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

    PubMed

    Hassan, Mohamed

    2015-01-01

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

  14. Long-term neurodevelopmental and cardiovascular outcome after intrauterine transfusions for fetal anaemia: a review.

    PubMed

    Lindenburg, Irene T M; van Klink, Jeanine M; Smits-Wintjens, Vivianne E H J; van Kamp, Inge L; Oepkes, Dick; Lopriore, Enrico

    2013-09-01

    Perinatal survival rates after intrauterine transfusions (IUT) for red cell alloimmunisation now exceed 90%, which demonstrates the safety and efficacy of one of the most successful procedures in fetal therapy. However, improved perinatal survival could lead to an increased number of children with long-term disabilities. The importance of long-term follow-up studies in fetal therapy lies in both the necessity of evaluation of antenatal management as well as in evidence-based preconceptional and prenatal counselling. This review describes the possible long-term cardiovascular and neurodevelopmental sequelae after IUT treatment for different indications including red cell alloimmunisation, parvovirus B19 infection, fetomaternal haemorrhage and twin anaemia-polycythaemia sequence.

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. Dopamine favours the emergence of long-term depression versus long-term potentiation in slices of rat prefrontal cortex.

    PubMed

    Law-Tho, D; Desce, J M; Crepel, F

    1995-03-24

    In the present study, we have investigated possible interactions between dopamine and long-term changes in synaptic efficacy induced in layer V pyramidal cells by tetanization of afferents from layer I-II. In the absence of dopamine, we confirmed that high frequency stimulation of excitatory afferents induced long-term potentiation, long-term depression or no change. Inversely, in the presence of dopamine, we have found that the same tetanus led to long-term depression in synaptic transmission in a majority of cells, but no more long-term potentiation. These results suggest that in rat prefrontal cortex, dopamine may determine the direction of activity dependent changes in synaptic efficacy and therefore, plays a functional role in the physiology of this structure.

  18. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  19. A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures.

    PubMed

    Steinhoff, Bernhard J; Eckhardt, Klaus; Doty, Pamela; De Backer, Marc; Brunnert, Marcus; Schulze-Bonhage, Andreas

    2016-05-01

    This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were

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

    PubMed

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

    2013-01-01

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

  1. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

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

  2. Long-term Results of Hemorrhoidal Artery Ligation.

    PubMed

    Yilmaz, İbrahim; Özgür Karakaş, Dursun; Sücüllü, İlker

    2016-03-01

    Aim of this study is to assess the efficacy, safety, and long-term results of doppler-guided hemorrhoidal artery ligation procedure with a 7-year follow-up period for treatment of grade II and III degree hemorrhoidal diseases. The procedure was performed by a specially designed proctoscope to locate and ligate all terminal branches of superior rectal artery. Patients were followed up at postoperative 1st week and 3rd, 12th, and 24th months by physical examination and 7th year by phone questionnaire using Short Form-36. Between November 2006 and May 2007, 50 patients (29 females, mean age = 38.2) underwent this procedure. All patients discharged at operation day and mean return to work was 2.5 days. There were no major complications and mean postoperative Visual Analogous Scale at first week was 1.72. At 24th month, 44 (88%) and 38 (76%) patients at 7th year were symptom free. Doppler-guided hemorrhoidal artery ligation is a safe, effective, and outpatient procedure, which can be the treatment of choice for second- and third-degree hemorrhoidal diseases with satisfactory long-term results.

  3. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study.

    PubMed

    Eastell, Richard; Nagase, Shinichi; Ohyama, Michiyo; Small, Maria; Sawyer, James; Boonen, Steven; Spector, Tim; Kuwayama, Tomohiro; Deacon, Steve

    2011-06-01

    Osteoporosis occurs when there is an imbalance between resorption and formation of bone, with resorption predominating. Inhibitors of cathepsin K may rebalance this condition. This is the first efficacy study of a new cathepsin K inhibitor, ONO-5334. The objective of the study was to investigate the efficacy and safety of ONO-5334 in postmenopausal osteoporosis. This was a 12-month, randomized, double-blind, placebo- and active-controlled parallel-group study conducted in 13 centers in 6 European countries. Subjects included 285 postmenopausal women aged 55 to 75 years with osteoporosis. Subjects were randomized into one of five treatment arms: placebo; 50 mg twice daily, 100 mg once daily, or 300 mg once daily of ONO-5334; or alendronate 70 mg once weekly. Lumbar spine, total hip, and femoral neck BMD values were obtained along with biochemical markers of bone turnover and standard safety assessments. All ONO-5334 doses and alendronate showed a significant increase in BMD for lumbar spine, total hip (except 100 mg once daily), and femoral neck BMD. There was little or no suppression of ONO-5334 on bone-formation markers compared with alendronate, although the suppressive effects on bone-resorption markers were similar. There were no clinically relevant safety concerns. With a significant increase in BMD, ONO-5334 also demonstrated a new mode of action as a potential agent for treating osteoporosis. Further clinical studies are warranted to investigate long-term efficacy as well as safety of ONO-5334.

  4. Anastrozole versus tamoxifen as adjuvant therapy for Japanese postmenopausal patients with hormone-responsive breast cancer: efficacy results of long-term follow-up data from the N-SAS BC 03 trial.

    PubMed

    Aihara, Tomohiko; Yokota, Isao; Hozumi, Yasuo; Aogi, Kenjiro; Iwata, Hiroji; Tamura, Motoshi; Fukuuchi, Atsushi; Makino, Haruhiko; Kim, Ryungsa; Andoh, Masashi; Tsugawa, Koichiro; Ohno, Shinji; Yamaguchi, Takuhiro; Ohashi, Yasuo; Watanabe, Toru; Takatsuka, Yuichi; Mukai, Hirofumi

    2014-11-01

    Aromatase inhibitors are superior to tamoxifen as adjuvant therapy in postmenopausal patients with hormone-responsive breast cancer. We report the follow-up efficacy results from the N-SAS BC 03 trial (UMIN CTRID: C000000056) where anastrozole was compared with tamoxifen as adjuvant therapy in postmenopausal Japanese patients with hormone-responsive early breast cancer. The full analysis set contained 696 patients (anastrozole arm, n = 345; tamoxifen arm, n = 351). The log-rank test was used to compare the two groups in terms of disease-free survival (DFS) and relapse-free survival (RFS); Kaplan-Meier estimates were calculated. The treatment effects were estimated by Cox's proportional hazards model. To examine time-varying effect of hazard ratios, we estimated time-varying hazard ratios at time t [HR(t)] using data from time t up to 12 months. After a median follow-up of 98.5 months, hazard ratios (95% CIs) were 0.90 (0.65-1.24; log-rank p = 0.526) for DFS and 0.83 (0.56-1.23; log-rank p = 0.344) for RFS. Hazard ratios (95% CIs) for DFS and RFS up to 36 months were 0.69 (0.40-1.17) and 0.54 (0.27-1.06) and those after 36 months were 1.06 (0.70-1.59) and 1.05 (0.64-1.73), respectively. Time-varying hazard ratios for both DFS and RFS showed that hazard ratios were initially in favor of anastrozole and approached 1.0 at around 36 months. Superior efficacy of anastrozole to tamoxifen suggested by the initial analysis was not confirmed in the present analysis after a long-term follow-up period. Advantage of anastrozole was the greatest immediately after switching from tamoxifen and then decreased thereafter.

  5. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

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

  6. [Coronary interventions : Current developments for improved long-term results].

    PubMed

    Seidler, T

    2016-09-01

    Based on solid scientific evidence, new generation drug-eluting stents (DES) have become established as the standard of care in interventional cardiology. With at least similar safety and superior efficacy over uncoated bare metal stents (BMS) in various scenarios and including patients with increased bleeding risk, there are probably no remaining indications favoring the use of BMS. Additional developments regarding the platform, drug elution characteristics and polymer design were aimed at optimizing DES with even better outcomes. Although there is no lack of new variations, none has proven to be superior and several non-inferiority trials lacked statistical power, which precludes the label third generation (over second generation or new generation DES). While it is recognized that potential long-term advantages of bioresorbable scaffolds cannot be expected at this stage from the current ABSORB III trial, the safety and efficacy are encouraging. Beyond procedural aspects, such as intracoronary imaging, variations in duration of antiplatelet therapy should help to improve outcomes but still require careful individual weighting of ischemic vs. bleeding risk. PMID:27506215

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

    PubMed Central

    West, Jonathan; Ogston, Simon; Foerster, John

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

    Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke. PMID:21779718

  9. Influenza in long-term care facilities: preventable, detectable, treatable.

    PubMed

    Mossad, Sherif B

    2009-09-01

    Influenza in long-term care facilities is an ever more challenging problem. Vaccination of residents and health care workers is the most important preventive measure. Although vaccine efficacy has been questioned, the preponderance of data favors vaccination. Antiviral resistance complicates postexposure chemoprophylaxis and treatment. Factors that limit the choice of antiviral agents in this patient population include limited vaccine supplies and impaired dexterity and confusion in long-term care residents. PMID:19726556

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

    PubMed Central

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

    2015-01-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disease that can affect all age groups. It is characterized by a relapsing course and a dramatic impact on quality of life for patients. Environmental interventions together with topical devices represent the mainstay of treatment for AD, in particular emollients, corticosteroids, and calcineurin inhibitors. Systemic treatments are reserved for severe cases. Phototherapy represents a valid second-line intervention in those cases where non-pharmacological and topical measures have failed. Different forms of light therapy are available, and have showed varying degrees of beneficial effect against AD: natural sunlight, narrowband (NB)-UVB, broadband (BB)-UVB, UVA, UVA1, cold-light UVA1, UVA and UVB (UVAB), full-spectrum light (including UVA, infrared and visible light), saltwater bath plus UVB (balneophototherapy), Goeckerman therapy (coal tar plus UVB radiation), psoralen plus UVA (PUVA), and other forms of phototherapy. In particular, UVA1 and NB-UVB have gained importance in recent years. This review illustrates the main trials comparing the efficacy and safety of the different forms of phototherapy. No sufficiently large randomized controlled studies have been performed as yet, and no light modality has been defined as superior to all. Parameters and dosing protocols may vary, although clinicians mainly refer to the indications included in the American Academy of Dermatology psoriasis guidelines devised by Menter et al in 2010. The efficacy of phototherapy (considering all forms) in AD has been established in adults and children, as well as for acute (UVA1) and chronic (NB-UVB) cases. Its use is suggested with strength of recommendation B and level of evidence II. Home phototherapy can also be performed; this technique is recommended with strength C and level of evidence III. Phototherapy is generally considered to be safe and well tolerated, with a low but established percentage of short-term and long-term

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

    PubMed

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

    2015-01-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disease that can affect all age groups. It is characterized by a relapsing course and a dramatic impact on quality of life for patients. Environmental interventions together with topical devices represent the mainstay of treatment for AD, in particular emollients, corticosteroids, and calcineurin inhibitors. Systemic treatments are reserved for severe cases. Phototherapy represents a valid second-line intervention in those cases where non-pharmacological and topical measures have failed. Different forms of light therapy are available, and have showed varying degrees of beneficial effect against AD: natural sunlight, narrowband (NB)-UVB, broadband (BB)-UVB, UVA, UVA1, cold-light UVA1, UVA and UVB (UVAB), full-spectrum light (including UVA, infrared and visible light), saltwater bath plus UVB (balneophototherapy), Goeckerman therapy (coal tar plus UVB radiation), psoralen plus UVA (PUVA), and other forms of phototherapy. In particular, UVA1 and NB-UVB have gained importance in recent years. This review illustrates the main trials comparing the efficacy and safety of the different forms of phototherapy. No sufficiently large randomized controlled studies have been performed as yet, and no light modality has been defined as superior to all. Parameters and dosing protocols may vary, although clinicians mainly refer to the indications included in the American Academy of Dermatology psoriasis guidelines devised by Menter et al in 2010. The efficacy of phototherapy (considering all forms) in AD has been established in adults and children, as well as for acute (UVA1) and chronic (NB-UVB) cases. Its use is suggested with strength of recommendation B and level of evidence II. Home phototherapy can also be performed; this technique is recommended with strength C and level of evidence III. Phototherapy is generally considered to be safe and well tolerated, with a low but established percentage of short-term and long-term

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  14. Naturalistic long-term use of methylphenidate in bipolar disorder.

    PubMed

    Lydon, Eric; El-Mallakh, Rif S

    2006-10-01

    Antidepressant use seems to be problematic in bipolar disorder. The dopaminergic agent, bupropion, seems to be equally effective to serotoninergic agents but with greater safety. Methylphenidate is a stimulant medication that is sometimes used as an antidepressant in bipolar adults and is frequently used in children with comorbid bipolar and attention-deficit disorder. There are no data available for the safety of long-term methylphenidate in adults. A retrospective chart review of bipolar patients who received methylphenidate while attending a bipolar clinic was conducted. Data regarding side effects and symptoms were collected. Sixteen charts were reviewed. The mean duration of methylphenidate treatment was 14 months (+/-SD, +/-17.5 months; range, 1-60 months). Five had comorbid attention-deficit disorder, the remainder received the methylphenidate for depression. The mean dose was 16.3 mg/d (+/-SD, +/-8.7 mg/d; range, 5-40 mg/d). Several mild to moderate side effects were reported. Two patients (12.5%) discontinued methylphenidate because of adverse side effects. When available (44% of the sample), general assessment of function increased from (+/-SD) 48.3 +/- 9.9 to 69.3 +/- 10.6 (P = 0.006). Methylphenidate seems to be safe in the naturalistic setting. Controlled studies are needed to confirm its efficacy and safety in bipolar depression.

  15. Long-term Nicotine Replacement Therapy

    PubMed Central

    Schnoll, Robert A.; Goelz, Patricia M.; Veluz-Wilkins, Anna; Blazekovic, Sonja; Powers, Lindsay; Leone, Frank T.; Gariti, Peter; Wileyto, E. Paul; Hitsman, Brian

    2015-01-01

    and extended treatment arms (20.3% vs 23.8%; OR, 1.17 [95% CI, 0.69-1.98]; P = .57). Similarly, we found no difference in week 52 abstinence rates between participants in the extended and standard treatment arms (26.0% vs 21.7%; OR, 1.33 [95% CI, 0.72-2.45]; P = .36). Treatment duration was not associated with any adverse effects or adherence to the counseling regimen, but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the standard and extended treatment arms (mean [SD], 3.94 [2.5], 4.61 [2.0], and 4.7 [2.4] patches/wk, respectively; F2,522 = 6.03; P = .003). CONCLUSIONS AND RELEVANCE The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01047527 PMID:25705872

  16. Safety and Efficacy of Solitaire Stent Thrombectomy

    PubMed Central

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

    2016-01-01

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

  17. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

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

  18. Long-term equilibrium tides

    NASA Astrophysics Data System (ADS)

    Shaffer, John A.; Cerveny, Randall S.

    1998-08-01

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

  19. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

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

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

  20. How does the efficacy and safety of Oralair(®) compare to other products on the market?

    PubMed

    Larenas-Linnemann, Désirée

    2016-01-01

    Due to differences between allergen immunotherapy (AIT) trials in patient populations, trial design (including primary efficacy variables), the definition of a pollen season, data analysis, and comparisons between AIT products with existing data, is not possible nor valid. The efficacy of two grass pollen AIT tablets, Oralair(®) and Grazax(®)/Grastek(®), should not be compared by looking at the percentage of score improvement in their respective trials. However, the evidence available concerning the efficacy and safety in trials can be compared by paying close attention to the scientific quality of the trials, details in the administration schedules, and safety issues. It can be concluded due to the high level of evidence available, that Oralair(®) is effective in a pre (2-months)-coseasonal schedule to reduce symptoms and medication use, and improve a patients' quality of life during the treatment season. For the long-term, where the quality of efficacy evidence is moderate at 2-year posttreatment due to a high dropout rate, the pre (4-months)-coseasonal schedule should be used. No clinical efficacy data exists for starting treatment in-season, but the clinical onset of action of Oralair(®) is detectable after only 1 month of treatment. In the pivotal trials in Europe and the USA, no tablet-related epinephrine was needed, though some rare severe local reactions have been reported. Research for Grazax(®)/Grastek(®) showed that the long-term efficacy needs a continuous 3-year administration (moderate-low quality evidence available), and in two patients, tablet-related epinephrine was given. Further details on the comparative efficacy of both tablets would only be possible if both were evaluated in the same, adequately powered trial. PMID:27313458

  1. How does the efficacy and safety of Oralair® compare to other products on the market?

    PubMed Central

    Larenas-Linnemann, Désirée

    2016-01-01

    Due to differences between allergen immunotherapy (AIT) trials in patient populations, trial design (including primary efficacy variables), the definition of a pollen season, data analysis, and comparisons between AIT products with existing data, is not possible nor valid. The efficacy of two grass pollen AIT tablets, Oralair® and Grazax®/Grastek®, should not be compared by looking at the percentage of score improvement in their respective trials. However, the evidence available concerning the efficacy and safety in trials can be compared by paying close attention to the scientific quality of the trials, details in the administration schedules, and safety issues. It can be concluded due to the high level of evidence available, that Oralair® is effective in a pre (2-months)-coseasonal schedule to reduce symptoms and medication use, and improve a patients’ quality of life during the treatment season. For the long-term, where the quality of efficacy evidence is moderate at 2-year posttreatment due to a high dropout rate, the pre (4-months)-coseasonal schedule should be used. No clinical efficacy data exists for starting treatment in-season, but the clinical onset of action of Oralair® is detectable after only 1 month of treatment. In the pivotal trials in Europe and the USA, no tablet-related epinephrine was needed, though some rare severe local reactions have been reported. Research for Grazax®/Grastek® showed that the long-term efficacy needs a continuous 3-year administration (moderate-low quality evidence available), and in two patients, tablet-related epinephrine was given. Further details on the comparative efficacy of both tablets would only be possible if both were evaluated in the same, adequately powered trial. PMID:27313458

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

    PubMed Central

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

    2015-01-01

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

  3. The interpretation of long-term trials of biologic treatments for psoriasis: trial designs and the choices of statistical analyses affect ability to compare outcomes across trials.

    PubMed

    Langley, R G; Reich, K

    2013-12-01

    Psoriasis is a chronic disease requiring long-term therapy, which makes finding treatments with favourable long-term safety and efficacy profiles crucial. The goal of this review is to provide the background needed to evaluate properly long-term studies of biologic treatments for psoriasis. Firstly, important elements of design and analysis strategies are described. Secondly, data from published trials of biologic therapies for psoriasis are reviewed in light of the design and analysis choices implemented in the studies. Published reports of clinical trials of biologic treatments (adalimumab, alefacept, etanercept, infliximab or ustekinumab) that lasted 33 weeks or longer and included efficacy results and statistical analysis were reviewed. Study designs and statistical analyses were evaluated and summarized, emphasizing patient follow-up methods and handling of missing data. Various trial designs and data handling methods are used in long-term studies of biologic psoriasis treatments. Responder analyses in long-term trials can be conducted in responder enrichment, re-treated nonresponder or intent-to-treat trials. Missing data can be handled in four ways, including, from most to least conservative, nonresponder imputation, last-observation-carried-forward, as-observed analysis and anytime analysis. Long-term clinical trials have shown that adalimumab, alefacept, etanercept, infliximab and ustekinumab are efficacious for psoriasis treatment; however, without common standards for these trials, direct comparisons of these agents are difficult. Understanding differences in trial design and data handling is essential to make informed treatment decisions.

  4. The interpretation of long-term trials of biologic treatments for psoriasis: trial designs and the choices of statistical analyses affect ability to compare outcomes across trials.

    PubMed

    Langley, R G; Reich, K

    2013-12-01

    Psoriasis is a chronic disease requiring long-term therapy, which makes finding treatments with favourable long-term safety and efficacy profiles crucial. The goal of this review is to provide the background needed to evaluate properly long-term studies of biologic treatments for psoriasis. Firstly, important elements of design and analysis strategies are described. Secondly, data from published trials of biologic therapies for psoriasis are reviewed in light of the design and analysis choices implemented in the studies. Published reports of clinical trials of biologic treatments (adalimumab, alefacept, etanercept, infliximab or ustekinumab) that lasted 33 weeks or longer and included efficacy results and statistical analysis were reviewed. Study designs and statistical analyses were evaluated and summarized, emphasizing patient follow-up methods and handling of missing data. Various trial designs and data handling methods are used in long-term studies of biologic psoriasis treatments. Responder analyses in long-term trials can be conducted in responder enrichment, re-treated nonresponder or intent-to-treat trials. Missing data can be handled in four ways, including, from most to least conservative, nonresponder imputation, last-observation-carried-forward, as-observed analysis and anytime analysis. Long-term clinical trials have shown that adalimumab, alefacept, etanercept, infliximab and ustekinumab are efficacious for psoriasis treatment; however, without common standards for these trials, direct comparisons of these agents are difficult. Understanding differences in trial design and data handling is essential to make informed treatment decisions. PMID:23937204

  5. Improving Short-Term Sun Safety Practices among Adolescent Survivors of Childhood Cancer: A Randomized Controlled Efficacy Trial

    PubMed Central

    Mays, Darren; Black, Jessica Donze; Mosher, Revonda B.; Shad, Aziza T.; Tercyak, Kenneth P.

    2012-01-01

    Introduction Skin cancer is one of the most common secondary neoplasms among childhood cancer survivors. However, little evidence exists for effective interventions to promote sun safety behaviors within this population. Methods This small-scale randomized controlled trial examined the efficacy of the Survivor Health and Resilience Education (SHARE) Program intervention, a multiple health behavior change intervention designed to increase sun safety practices among adolescent survivors of childhood cancer. Adolescent survivors of childhood cancer (11-21 years) were randomly allocated to a group-based behavioral intervention (n = 38) or wait-list control (n = 37). Self-reported sun safety behaviors were assessed using a valid, 8-item scale at baseline and 1-month post-intervention. Results Controlling for baseline sun safety, gender, and seasonal influences, intervention participants reported significantly more sun safety practices (e.g., using sunscreen, reapplying sunscreen regularly) at 1-month post-intervention than control participants (B = 2.64, 95% CI = 1.02, 4.27, p = 0.002). Conclusions The results suggest that SHARE was efficacious in producing improvements in short-term self-reported sun safety practices among adolescent survivors of childhood cancer. Future research is needed to build upon this work by incorporating objective measures of sun safety behaviors and examining intervention durability. Implications for Cancer Survivors Behavioral interventions addressing lifestyle factors, including sun safety behaviors, among adolescent survivors of childhood cancer should be integrated into long-term care to reduce the risk for secondary malignancies and diseases. PMID:21359690

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

    PubMed Central

    2014-01-01

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

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

    PubMed Central

    Yang, Young-Mo; Choi, Eun Joo

    2015-01-01

    -designed, prospective, long-term, large-scale, randomized clinical trials are necessary to elucidate the efficacy and safety of metformin, oral contraceptives, or both in the treatment of PCOS, and to elucidate their individual roles in the treatment of this condition. PMID:26366087

  8. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer

    PubMed Central

    Gettinger, Scott N.; Horn, Leora; Gandhi, Leena; Spigel, David R.; Antonia, Scott J.; Rizvi, Naiyer A.; Powderly, John D.; Heist, Rebecca S.; Carvajal, Richard D.; Jackman, David M.; Sequist, Lecia V.; Smith, David C.; Leming, Philip; Carbone, David P.; Pinder-Schenck, Mary C.; Topalian, Suzanne L.; Hodi, F. Stephen; Sosman, Jeffrey A.; Sznol, Mario; McDermott, David F.; Pardoll, Drew M.; Sankar, Vindira; Ahlers, Christoph M.; Salvati, Mark; Wigginton, Jon M.; Hellmann, Matthew D.; Kollia, Georgia D.; Gupta, Ashok K.; Brahmer, Julie R.

    2015-01-01

    Purpose Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non–small-cell lung cancer (NSCLC) receiving nivolumab in this trial. Patients and Methods Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. Results Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. Conclusion Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing. PMID:25897158

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

    PubMed

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

    2016-04-01

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

  10. Transuranic waste: long-term planning

    SciTech Connect

    Young, K.C.

    1985-07-01

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

  11. Long-term plutonium storage: Design concepts

    SciTech Connect

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

    1994-08-01

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

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

    SciTech Connect

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

    2011-11-15

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

  13. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Long-term efficacy of implantable cardiac resynchronization therapy plus defibrillator for primary prevention of sudden cardiac death in patients with mild heart failure: an updated meta-analysis.

    PubMed

    Sun, Wei-Ping; Li, Chun-Lei; Guo, Jin-Cheng; Zhang, Li-Xin; Liu, Ran; Zhang, Hai-Bin; Zhang, Ling

    2016-07-01

    Previous studies of implantable cardiac resynchronization therapy plus defibrillator (CRT-D) therapy used for primary prevention of sudden cardiac death have suggested that CRT-D therapy is less effective in patients with mild heart failure and a wide QRS complex. However, the long-term benefits are variable. We performed a meta-analysis of randomized trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Three studies (3858 patients) with a mean follow-up of 66 months were included. Overall, CRT-D therapy was associated with significantly lower all-cause mortality than was implantable cardioverter defibrillator (ICD) therapy (OR, 0.78; 95 % CI, 0.63-0.96; P = 0.02; I (2) = 19 %). However, the risk of cardiac mortality was comparable between two groups (OR, 0.74; 95 % CI, 0.53-1.01; P = 0.06). CRT-D treatment was associated with a significantly lower risk of hospitalization for heart failure (OR, 0.67; 95 % CI, 0.50-0.89; P = 0.005; I (2) = 55 %). The composite outcome of all-cause mortality and hospitalization for heart failure was also markedly lower with CRT-D therapy than with ICD treatment alone (OR, 0.67; 95 % CI, 0.57-0.77; P < 0.0001; I (2) = 0 %). CRT-D therapy decreased the long-term risk of mortality and heart failure events in patients with mild heart failure with a wide QRS complex. However, long-term risk of cardiac mortality was similar between two groups. More randomized studies are needed to confirm these findings, especially in patients with NYHA class I heart failure or patients without LBBB.

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

    PubMed

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

    2016-01-01

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

  17. Fear of Falling in New Long-Term Care Enrollees

    PubMed Central

    Gillespie, Suzanne M.; Friedman, Susan M.

    2007-01-01

    OBJECTIVES To measure the prevalence of fear of falling in older adults at the time of long- term care (LTC) enrollment and identify potentially treatable risk factors for low fall related self-efficacy. DESIGN Prospective cohort study. SETTING Three LTC programs in Upstate New York. PARTICIPANTS 112 new enrollees in LTC, aged 55 or older, who passed a cognitive screen. MEASUREMENTS Self-reported falls, the falls efficacy scale (FES), medical conditions, the short geriatric depression scale, and physical performance measures (Berg balance scale, hip flexor, knee extensor and grip strength, gait speed and a six-minute walk). RESULTS Of the 54 subjects (48.2%) who reported fear of falling, 41 (75.9%) reported activity modification secondary to fear. Fearful subjects were more likely to be female (P=.003), report low back pain (P=.030) and lower extremity arthritis (P=.048). Fearful subjects were weaker at the hip (P<.001) and knee (P=.001), and had shorter six-minute walk distances. Subjects with better FES scores had better Berg scores (P<.001), had greater hip and knee strength, had faster gait speeds and walked further in six minutes (P<.001, P=.006, P=.001 and P=.001 respectively). Subjects with low FES scores and fearful subjects were more likely to have depressive symptoms (P=.003, P=.044, respectively). CONCLUSION Falls and fear of falling are more common in new LTC enrollees than in previously described community dwelling and SNF cohorts. Attention to associated characteristics like depression, arthritis, low back pain and lower extremity weakness may identify opportunities to reduce fear and improve patient safety during this transitional period. PMID:17570309

  18. Safety and Efficacy of Prehospital Diltiazem

    PubMed Central

    Luk, Jeffrey H.; Walsh, Brian; Yasbin, Paul

    2013-01-01

    Introduction: Very few studies exist on the use of diltiazem in the prehospital setting. Some practitioners believe this medication is prone to causing hypotension in this setting. Our goals were to determine whether the prehospital administration of diltiazem induced hypotension and to evaluate the efficacy of the drug. Methods: Our two-tiered system is located in a suburban region of New Jersey with advanced life support (ALS) care provided by fly-car units. The ALS units do not transport patients, and all of them are hospital based. The ALS providers are employed by the hospital system. In New Jersey, all ALS care requires online medical control, including the administration of diltiazem. We retrospectively reviewed patient care records for those who were believed to be in rapid atrial fibrillation and were given diltiazem in a suburban emergeny medical services system over a 22-month period. We examined the differences between heart rate (HR) and blood pressure (BP) on the initial evaluation and on arrival to the emergency department (ED). A hypotensive response was defined as a final systolic BP (SBP) less than 90 mmHg and a drop in SBP of at least 10 mmHg. Diltiazem was considered effective if the ED HR was <100 beats per minute (bpm) or if it decreased ≥20%. Results: During the study period, 26,979 patients were transported. Of these patients, 2,488 had a documented rhythm of atrial fibrillation or atrial flutter. Of the 320 patients who received diltiazem, 42 patient encounters were excluded for incomplete data, yielding 278 patients for analysis. The average initial SBP was 139 mmHg and the average diastolic BP was 84 mmHg. The average diltiazem dosage was 16.7 mg. Two patients became hypotensive. The average initial HR was 154 bpm. On arrival to the ED, 33% of the patients had an HR < 100 bpm and 69% had a drop in HR ≥ 20%. The overall efficacy of prehospital diltiazem was 73%. Conclusion: In the prehospital setting, diltiazem is associated with a

  19. Financing long-term care in Canada.

    PubMed

    Jacobs, P; Mills, C; Hollander, M

    1997-06-01

    Financial policies relating to long-term care in Canada are changing rapidly in response to demands for health care reform. This chapter focuses on the financial structure of institutional care, primarily nursing homes, in the western provinces of Alberta and British Columbia. Community-based long-term care is discussed briefly.

  20. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

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

  1. Long-term preservation of Anammox bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. Long-term Use of Opioids for Complex Chronic Pain

    PubMed Central

    Von Korff, Michael R.

    2014-01-01

    Increased opioid prescribing for back pain and other chronic musculoskeletal pain conditions has been accompanied by dramatic increases in prescription opioid addiction and fatal overdose. Opioid-related risks appear to increase with dose. While short-term randomized trials of opioids for chronic pain have found modest analgesic benefits (a one-third reduction in pain intensity on average), the long-term safety and effectiveness of opioids for chronic musculoskeletal pain is unknown. Given the lack of large, long-term randomized trials, recent epidemiologic data suggests the need for caution when considering long-term use of opioids to manage chronic musculoskeletal pain, particularly at higher dosage levels. Principles for achieving more selective and cautious use of opioids for chronic musculoskeletal pain are proposed. PMID:24315147

  3. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

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

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

    ClinicalTrials.gov

    2012-09-27

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

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

    PubMed Central

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

    2011-01-01

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

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

    ClinicalTrials.gov

    2016-08-01

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

  7. Platelet concentrates: Balancing between efficacy and safety?

    PubMed

    Lozano, Miguel; Cid, Joan

    2016-01-01

    Platelet transfusions continue to be the mainstay to treat patients with quantitative and qualitative platelet disorders. Each year, about 10 millions of platelet transfusions are administered to patients worldwide with marked differences in usage between regions depending on socioeconomic development of the countries. Unfortunately, its use is associated to immune and non-immune side effects. Among the non-immune, bacterial contamination is still the major infectious risk. When bacterial culture methods are introduced for preventing bacterial septic reactions it has been found that this strategy reduce to one half the septic reactions, but do not eliminate completely that risk. To remove completely the risk, a new bacteria detection test at the time of issuance in the case of platelets stored for four or five days would be needed. Pathogen inactivation (PI) methods already in the market (based in the addition of amotosalen (A-L) or riboflavin (R-L) and the illumination with ultraviolet light) or under development (ultraviolet light C and agitation) have shown to be efficacious in the inactivation of bacteria and no cases of septic reactions associated to a pathogen-reduced product has been identified. However, it has been shown that PI technologies have measurable effects on platelet in vitro parameters and reduce the recovery and survival of treated platelets in vivo. Although these effects do not hamper the hemostatic capacity of treated platelets, an increased usage associated with PI technologies has been reported. This increase in utilization seems to be the toll to be paid if we want to completely eliminate the risk of bacterial sepsis in the recipients of platelet transfusion. PMID:27476010

  8. Pathologies in Living Kidney Donors Diagnosed in the Long-Term Care System.

    PubMed

    Kwapisz, M; Kieszek, R; Jędrzejko, K; Domagała, P; Bieniasz, M; Gozdowska, J; Zygier, D; Drozdowski, J; Zatorski, M; Nowaczyk, M; Palczewski, P; Pączek, L; Durlik, M; Chmura, A; Kwiatkowski, A

    2016-06-01

    Kidney donation should not lead to deterioration of the donor's health condition, both during the perisurgical period and in the long term. Safety of a living kidney donor becomes a prerequisite for his/her qualification. Detailed diagnostic procedures are performed to exclude any abnormalities of his/her health condition. Additionally, a long-term post-donation follow-up system for kidney donors has been set up in Poland besides the restrictive qualification system. Transplantation centers are obligated to provide a diagnostic procedures for living organ donors as a part of the monitoring of their health condition and to ensure them a medical follow-up for 10 years after the donation. A total of 141 cases of unilateral nephroureterectomy performed in 2003-2014 to obtain a kidney for transplantation were considered. Medical files of post-donation diagnostic or therapeutic methods and their outcomes were retrospectively analyzed. The aim of the study was to assess the efficacy of monitoring of donors' health condition within the framework of the long-term follow-up system for kidney donors in the aspect of detection of the donation-independent abnormalities. PMID:27496424

  9. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

    PubMed Central

    2016-01-01

    Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control. PMID:27689098

  10. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

    PubMed Central

    2016-01-01

    Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.

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

    PubMed Central

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

    2015-01-01

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

  12. Meta-analysis of the efficacy and safety of bronchial thermoplasty in patients with moderate-to-severe persistent asthma.

    PubMed

    Wu, Q; Xing, Y; Zhou, X; Wang, D

    2011-01-01

    This meta-analysis assessed the efficacy and safety of a novel intervention for asthma, bronchial thermoplasty (BT), in patients with moderate-to-severe persistent asthma. An electronic literature search identified three randomized controlled trials (RCT) of BT that recruited 421 patients in total. Outcomes of interest were the Asthma Quality of Life Questionnaire (AQLQ) score, morning peak expiratory flow (PEF), tolerability and safety. Compared with standard medications and sham BT treatment, BT significantly improved AQLQ scores and PEF from baseline to the end of the trials. There were more respiratory adverse events and hospitalizations for adverse respiratory events with BT than with medications or sham treatment during the treatment period, but most events resolved, on average, within a week. This effect of BT treatment was not seen during the posttreatment period. Additional long-term RCT are required to confirm whether BT provides benefit to patients with moderate-to-severe persistent asthma.

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

    PubMed Central

    Argoff, Charles E; Gloth, F Michael

    2011-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Lessard, Collette R; Hopkins, Matthew R

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

    Objective: Maraviroc, a chemokine co-receptor type 5 (CCR5) antagonist, has demonstrated comparable efficacy and safety to efavirenz, each in combination with zidovudine/lamivudine, over 96 weeks in the Maraviroc vs. Efavirenz Regimens as Initial Therapy (MERIT) study. Here we report 5-year findings. Design: A randomized, double-blind, multicenter phase IIb/III study with an open-label extension phase. Methods: Treatment-naive patients with CCR5-tropic HIV-1 infection (Trofile) received maraviroc 300 mg twice daily or efavirenz 600 mg once daily, and zidovudine/lamivudine 300 mg/150 mg twice daily. After the last patient's week 96 visit, the study was unblinded and patients could enter a nominal 3-year open-label phase. Endpoints at the 5-year nominal visit (week 240) included proportion of patients (CCR5 tropism re-confirmed by enhanced sensitivity Trofile) with viral load (plasma HIV-1 RNA) below 50 and 400 copies/ml, and change from baseline in CD4+ cell count, as well as safety. Results: The proportion of patients maintaining viral load below 50 copies/ml was similar between treatment arms throughout the study and at week 240 (maraviroc 50.8% vs. efavirenz 45.9%). Maraviroc-treated patients had a greater increase from baseline in mean CD4+ cell count than efavirenz-treated patients at week 240 (293 vs. 271 cells/μl, respectively). Fewer patients on maraviroc vs. efavirenz experienced treatment-related adverse events (68.9 vs. 81.7%) and discontinued as a result of any adverse event (10.6 vs. 21.3%). Conclusion: Maraviroc maintained similar long-term antiviral efficacy to efavirenz over 5 years in treatment-naive patients with CCR5-tropic HIV-1. Maraviroc was generally well tolerated with no unexpected safety findings or evidence of long-term safety concerns. PMID:24983542

  17. Long Term Effects of Food Poisoning

    MedlinePlus

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

  18. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Español Text Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic ... and sprinkle forms are available for young children. Long-Acting Beta2-Agonists Medications in the beta 2 - ...

  19. Efficacy and safety of adalimumab in ankylosing spondylitis

    PubMed Central

    Mounach, Aziza; El Maghraoui, Abdellah

    2014-01-01

    Ankylosing spondylitis (AS) is the most common and most severe subtype of spondyloarthritis. It also may be an outcome of any of the other spondyloarthritis subtypes. AS preferentially affects the sacroiliac joints and the tip of the column, with a tendency to later ankylosis. Peripheral joints, enthesis, and other extra-articular involvement may be observed. Tumor necrosis factor (TNF) inhibitors are now well-established, effective drugs in the treatment of AS symptoms. Adalimumab, which is a fully human monoclonal antibody that binds to and neutralizes TNF, has demonstrated efficacy in treating AS symptoms, including axial involvement, peripheral arthritis, enthesitis, uveitis, gut involvement, and psoriasis. Furthermore, adalimumab has showed an overall acceptable safety profile. In this paper, we review the efficacy and safety profile of adalimumab in the treatment of AS, and discuss its differences from the other anti-TNF drugs reported in the literature.

  20. Efficacy and safety of endoscopic submucosal dissection under general anesthesia

    PubMed Central

    Yamashita, Kanefumi; Shiwaku, Hironari; Ohmiya, Toshihiro; Shimaoka, Hideki; Okada, Hiroki; Nakashima, Ryo; Beppu, Richiko; Kato, Daisuke; Sasaki, Takamitsu; Hoshino, Seiichiro; Nimura, Satoshi; Yamaura, Ken; Yamashita, Yuichi

    2016-01-01

    AIM: To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) under general anesthesia. METHODS: From January 2011 to July 2014, 206 consecutive patients had undergone ESD under general anesthesia for neoplasms of the stomach, esophagus, and colorectum were enrolled in this retrospective study. The efficacy and safety of ESD under general anesthesia were assessed. RESULTS: The en bloc resection rate of esophageal, gastric, and colorectal lesions was 100.0%, 98.3%, and 96.1%, respectively. The complication rate of perforation and bleeding were 0.0% and 0.0% in esophageal ESD, 1.7% and 1.7% in gastric ESD, and 3.9% and 2.0% in colorectal ESD, respectively. No cases of aspiration pneumonia were observed. All complications were managed by conservative treatment, with no surgical intervention required. CONCLUSION: With the cooperation of an anesthesiologist, ESD under general anesthesia appears to be a useful method, decreasing the risk of complications. PMID:27433293

  1. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

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

  2. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine

    PubMed Central

    Naud, Paulo S; Roteli-Martins, Cecilia M; De Carvalho, Newton S; Teixeira, Julio C; de Borba, Paola C; Sanchez, Nervo; Zahaf, Toufik; Catteau, Gregory; Geeraerts, Brecht; Descamps, Dominique

    2014-01-01

    HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15–25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). Cervical samples were tested for HPV DNA every 6 months, and cyto-pathological examinations were performed annually. During HPV-023, no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group. Vaccine efficacy (VE) against HPV-16/18 incident infection was 100% (95%CI: 66.1, 100). Over the 113 months (9.4 years), VE was 95.6% (86.2, 99.1; 3/50 cases in vaccine and placebo groups, respectively) against incident infection, 100% (84·1, 100; 0/21) against 6-month persistent infection (PI); 100% (61·4, 100; 0/10) against 12-month PI; 97·1% (82.5, 99.9; 1/30) against ≥ ASC-US; 95·0% (68.0, 99.9; 1/18) against ≥ LSIL; 100% (45.2, 100; 0/8) against CIN1+; and 100% (–128.1, 100; 0/3) against CIN2+ associated with HPV-16/18. All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine. PMID:25424918

  3. Efficacy and Safety of Roflumilast in Korean Patients with COPD

    PubMed Central

    Lee, Jae Seung; Hong, Yoon Ki; Park, Tae Sun; Lee, Sei Won; Oh, Yeon-Mok

    2016-01-01

    Purpose Roflumilast is the only oral phosphodiesterase 4 inhibitor approved to treat chronic obstructive pulmonary disease (COPD) patients [post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted] with chronic bronchitis and a history of frequent exacerbations. This study evaluated the efficacy and safety of roflumilast in Korean patients with COPD and compared the efficacy based on the severity of airflow limitation. Materials and Methods A post-hoc subgroup analysis was performed in Korean COPD patients participating in JADE, a 12-week, double-blinded, placebo-controlled, parallel-group, phase III trial in Asia. The primary efficacy endpoint was the mean [least-squares mean adjusted for covariates (LSMean)] change in post-bronchodilator FEV1 from baseline to each post-randomization visit. Safety endpoints included adverse events (AEs) and changes in laboratory values, vital signs, and electrocardiograms. Results A total of 260 Korean COPD patients were recruited, of which 207 were randomized to roflumilast (n=102) or placebo (n=105) treatment. After 12 weeks, LSMean post-bronchodilator FEV1 increased by 43 mL for patients receiving roflumilast and decreased by 60 mL for those taking placebo. Adverse events were more common in the roflumilast group than in the placebo group; however, the types and frequency of AEs were comparable to those reported in previous studies. Conclusion Roflumilast significantly improved lung function with a tolerable safety profile in Korean COPD patients irrespective of the severity of airflow limitation. PMID:27189287

  4. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures.

    PubMed

    Mash, D C; Kovera, C A; Pablo, J; Tyndale, R F; Ervin, F D; Williams, I C; Singleton, E G; Mayor, M

    2000-09-01

    Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyibogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.

  5. Long-term home care research.

    PubMed

    Green, J H

    1989-11-01

    The population of seniors is growing and health service reimbursement is shrinking. Long-term home health care services were developed with an assumption that the services would decrease costs. This assumption has not been validated. What has been recognized is that long-term home health care targets a new and growing population of frail seniors who need services but are probably not at risk for institutionalization. The impact of long-term home care services on the health status and quality of life of seniors and caregivers has been limited by outcome measurement problems. There are indications that the services improved life satisfaction and reduced services needs, but further evaluations need to replicate the outcomes. In effect, long-term outcomes have not been sufficiently explored. Further research also needs to assist us in identifying outcomes for certain services with precise target populations. Public policy questions are ahead. Should a program that can increase costs, has demonstrated some but not dramatic impacts on quality of life and health status, and has the possibility of expansion, be funded? The question is obviously debatable. From a nursing perspective of health promotion and prevention, the answer is "yes." Funding should be continued in conjunction with increased research on the program impacts. In Kane's (1988) analysis of the Channeling experiments, she summarized the situation effectively: Knowing these facts, we are now in a position to reformulate public policies to design a system of long-term care that satisfies the preferences of consumers and protects them from catastrophic long-term expenses, while promoting the triple virtues of acceptable, quality, equitable access, and defensible costs. . . Nothing in the Channeling results should prevent us from going ahead and trying to develop both community based and institutionally based long-term services in which this country can take pride.

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

    SciTech Connect

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

    2007-09-15

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

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

    PubMed

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

    2016-04-01

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

  8. Medium- to long-term results of a randomized controlled trial to assess the efficacy of arthoscopic-subacromial decompression versus mini-open repair for the treatment of medium-sized rotator cuff tears

    PubMed Central

    Birch, Ann; Temperley, David; Odak, Saurabh; Walton, Michael J; Haines, John F; Trail, Ian

    2015-01-01

    Background We report on the medium- to long-term results of a randomized controlled trial (RCT) aiming to determine whether rotator cuff repair confers any advantage over arthroscopic sub-acromial decompression (ASAD) alone in the management of medium-sized rotator cuff tears. Methods Ethical approval was sought to follow-up patients previously enrolled in a completed and previously published RCT comparing the outcome of ASAD with mini-open cuff repair for the treatment of rotator cuff tear. Forty-two patients were enrolled in the original study, with a mean of 64 years (range 54 years to 77 years). Results Fifteen of the original 17 patients randomized to ASAD alone and 18 of the original 25 patients randomized to cuff repair were available for follow-up. Each patient underwent American Shoulder and Elbow Surgeons (ASES), Disabilities of the Arm, Shoulder and Hand (DASH) and Constant scoring, and clinical and ultrasound examination. Mean duration of follow-up was 7 years (range 5 years to 11 years). There was no statistically significant difference in terms of ASES, DASH and Constant scores at follow-up between the two groups. Some 33% of patients in the cuff-repair group had a proven re-rupture on ultrasound. This patient subgroup had significantly worse Constant scores compared to patients where the repair remained intact. None of the patients from either group developed cuff-tear arthropathy requiring arthroplasty surgery. Conclusions In this medium- to longer-term study, there is no demonstrable significant benefit of cuff repair over decompression alone for the treatment of medium-sized rotator cuff tears, in terms of ASES, DASH and Constant scores for pain, function and strength modules. The presence of cuff tear does not necessitate surgical repair. This conclusion should drive surgical strategies and shared decision-making between patients and surgeons. PMID:27583006

  9. Safety and efficacy of rosiglitazone in the elderly diabetic patient

    PubMed Central

    Viljoen, Adie; Sinclair, Alan

    2009-01-01

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

  10. The opioid epidemic and the long-term opioid therapy for chronic noncancer pain revisited: a transatlantic perspective.

    PubMed

    Häuser, Winfried; Petzke, Frank; Radbruch, Lukas; Tölle, Thomas R

    2016-01-01

    The rise of opioid prescriptions and associated deaths ('opioid epidemic') in North America has evoked worldwide discussions on the long-term efficacy and safety of long-term opioid therapy (LtOT) for chronic noncancer pain (CNCP). We discuss if the opioid epidemic is a real worldwide or a more North American phenomenon. We consider reasons of the opioid epidemic. We highlight differences in the appraisal of the evidence of recent systematic reviews on LtOT for CNCP of US and European authors. We discuss similarities and differences of recent North American and European guidelines on LtOT for chronic CNCP. We point out potential indications and contraindications of LtOT in CNCP syndromes. PMID:26988312

  11. Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

    SciTech Connect

    Calin-Jageman, Robert J

    2009-09-12

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

  12. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2).

    PubMed

    Rubin, Lewis J; Galiè, Nazzareno; Grimminger, Friedrich; Grünig, Ekkehard; Humbert, Marc; Jing, Zhi-Cheng; Keogh, Anne; Langleben, David; Fritsch, Arno; Menezes, Flavia; Davie, Neil; Ghofrani, Hossein-Ardeschir

    2015-05-01

    Riociguat is a soluble, guanylate cyclase stimulator, approved for pulmonary arterial hypertension. In the 12-week PATENT-1 study, riociguat was well tolerated and improved several clinically relevant end-points in patients with pulmonary arterial hypertension who were treatment naïve or had been pretreated with endothelin-receptor antagonists or prostanoids. The PATENT-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from the PATENT-1 study received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was to assess the safety and tolerability of riociguat; exploratory efficacy assessments included 6-min walking distance and World Health Organization (WHO) functional class. Overall, 396 patients entered the PATENT-2 study and 324 (82%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in PATENT-2 was similar to that observed in PATENT-1, with cases of haemoptysis and pulmonary haemorrhage also being observed in PATENT-2. Improvements in the patients', 6-min walking distance and WHO functional class observed in PATENT-1 persisted for up to 1 year in PATENT-2. In the observed population at the 1-year time point, mean±sd 6-min walking distance had changed by 51±74 m and WHO functional class had improved in 33%, stabilised in 61% and worsened in 6% of the patients versus the PATENT-1 baseline. Long-term riociguat was well tolerated in patients with pulmonary arterial hypertension, and led to sustained improvements in exercise capacity and functional capacity for up to 1 year.

  13. Is early nutrition related to short-term health and long-term outcome?

    PubMed

    Szajewska, Hania; Makrides, Maria

    2011-01-01

    This paper summarizes the literature concerning the effects of administering (1) long-chain polyunsaturated fatty acids (LCPUFA), (2) probiotics and/or (3) prebiotics to preterm infants. Clinically relevant, short- and long-term efficacy outcomes, such as those related to a reduced risk of disease, as well as outcomes related to safety, were sought. MEDLINE and the Cochrane Library literature searches performed in September 2010 were limited to randomized controlled trials, their systematic reviews or meta-analyses. LCPUFA supplementation, particularly docosahexaenoic acid (DHA), of infant formula for preterm infants has consistently demonstrated better visual development of preterm infants compared with unsupplemented formulas. There is increasing evidence to suggest that LCPUFA supplementation for preterm infants is also related to improvements in more global measures of development, without any adverse effects. It is, however, important to note that the DHA doses tested in the infant formula interventions for preterm infants have been rather conservative. Newer studies comparing dietary DHA concentrations that match in utero accumulation rates with dietary DHA concentrations typical in the milk of women consuming little fish or in supplemented infant formulas demonstrate that these higher DHA doses are related to improvements in domains of cognitive development. Although further work is needed to better understand the optimal DHA requirements of preterm infants, it is clear that a dietary source of DHA is important to support neurodevelopment. To date, the most promising application of probiotics in preterm infants is the prevention of necrotizing enterocolitis by the administration of certain probiotics. Many other benefits of administering probiotics and/or prebiotics to preterm infants are, however, largely unproven. Efficacy and safety should be established for each probiotic and/or prebiotic product. Further research should specify strain-specific outcomes

  14. Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization

    PubMed Central

    Jung, Sung-Cherl; Eun, Su-Yong

    2014-01-01

    At central synapses, activity-dependent synaptic plasticity has a crucial role in information processing, storage, learning, and memory under both physiological and pathological conditions. One widely accepted model of learning mechanism and information processing in the brain is Hebbian Plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are respectively activity-dependent enhancement and reduction in the efficacy of the synapses, which are rapid and synapse-specific processes. A number of recent studies have a strong focal point on the critical importance of another distinct form of synaptic plasticity, non-Hebbian plasticity. Non-Hebbian plasticity dynamically adjusts synaptic strength to maintain stability. This process may be very slow and occur cell-widely. By putting them all together, this mini review defines an important conceptual difference between Hebbian and non-Hebbian plasticity. PMID:25598658

  15. The pros and cons of long-term opioid therapy.

    PubMed

    Duarte, Rui; Raphael, Jon

    2014-09-01

    Evidence supporting the efficacy of long-term opioid therapy for chronic noncancer pain is scarce. However, weak evidence suggests that those who are able to continue opioids long-term experience clinically significant pain relief. Fear of opioid abuse or addiction should not impede the prescribing of opioids if the patients are carefully selected and monitored. In patients taking opioids who experience intolerable side effects or unsatisfactory pain relief, alternatives should be sought as soon as possible. This report is adapted from paineurope 2014; Issue 1, Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com, at which European health professionals can register online to receive copies of the quarterly publication.

  16. Long-term outcomes of autoimmune pancreatitis.

    PubMed

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-09-14

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  17. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  18. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed.

  19. Interim long-term surveillance plan for the Cheney disposal site near, Grand Junction, Colorado

    SciTech Connect

    1997-08-01

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

  20. Long-term surveillance plan for the Cheney disposal site near Grand Junction, Colorado

    SciTech Connect

    1997-07-01

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

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

    SciTech Connect

    1997-07-01

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

  2. Long-term surveillance plan for the Mexican Hat disposal site Mexican Hat, Utah

    SciTech Connect

    1997-06-01

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

  3. Long-term surveillance plan for the South Clive disposal site Clive, Utah

    SciTech Connect

    1997-09-01

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

  4. Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy

    PubMed Central

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

    2010-01-01

    OBJECTIVE To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks. PMID:20067958

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

    PubMed Central

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

    2016-01-01

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

  6. The Efficacy and Safety of Antipsychotic Medications in the Treatment of Psychosis in Patients with Parkinson's Disease

    PubMed Central

    Stojanović, Radan; Damjanović, Aleksandar; Prostran, Milica

    2016-01-01

    Psychotic symptoms are present in up to 50% of patients with Parkinson's disease. These symptoms have detrimental effects on patients' and caregivers' quality of life and may predict mortality. The pathogenesis of psychotic symptoms in Parkinson's disease is complex, but the use of dopaminergic medications is one of the risk factors. The treatment of psychotic symptoms in Parkinson's disease is complicated due to the ability of antipsychotic medications to worsen motor symptoms. The efficacy of clozapine in the treatment of psychosis in patients with Parkinson's disease has been confirmed in several clinical trials; however, the adverse effects and the necessity of blood count monitoring are the reasons why the use of this drug is challenging. The studies on safety and efficacy of other antipsychotics conflicting results. The use of antipsychotics in these patients is also associated with increased mortality. Psychotic symptoms in Parkinson's disease per se are also proven predictors of mortality. Thus it is necessary to treat psychotic symptoms but the choice of an antipsychotic should be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic option with more favorable adverse effects profile is now available for this indication, but careful postmarketing monitoring is necessary to establish the true picture of this drug's long-term safety and efficacy. PMID:27504054

  7. Long-Term Use of Benzodiazepines

    PubMed Central

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

    1992-01-01

    Problems associated with physical dependence and abuse of benzodiazepines by a small percentage of patients have reduced their popularity from the most commonly prescribed psychoactive drug in the 1970s to being prescribed for mainly short periods. Patients who benefit from long-term benzodiazepine use are nearly ignored by the medical community as a whole. This article details what patient population can improve from long-term benzodiazepine therapy, the risks and benefits of treatment, and how to select appropriate candidates. PMID:21229127

  8. Long-term outcomes after severe shock.

    PubMed

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

    2015-02-01

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

  9. Scenarios for long-term analysis

    SciTech Connect

    Wolbers, Stephen; /Fermilab

    2009-01-01

    Data Preservation and Long-Term Analysis of High Energy Physics (HEP) Experiments data is described and summarized in this talk. The summary covers information presented at the First Workshop on Data Preservation and Long-Term Analysis. Experiments representing e{sup +}e{sup -} collisions (LEP, B Factories and CLEO), ep collisions (H1 and ZEUS), p{bar p} collisions (CDF and D0) and others presented interesting information related to utilizing the large datasets collected over many years at these HEP facilities. Many questions and issues remain to be explored.

  10. The efficacy and safety of urethral injection therapy for urinary incontinence in women: a systematic review

    PubMed Central

    Matsuoka, Priscila Katsumi; Locali, Rafael Fagionato; Pacetta, Aparecida Maria; Baracat, Edmund Chada; Haddad, Jorge Milhem

    2016-01-01

    To evaluate the efficacy and safety of different bulking agents for treating urinary incontinence in women, a systematic review including only randomized controlled trials was performed. The subjects were women with urinary incontinence. The primary outcomes were clinical and urodynamic parameters. The results were presented as a weighted mean difference for non-continuous variables and as relative risk for continuous variables, both with 95% confidence intervals. Initially, 942 studies were identified. However, only fourteen eligible trials fulfilled the prerequisites. Altogether, the review included 1814 patients in trials of eight different types of bulking agents, and all studies were described and analyzed. The measured outcomes were evaluated using a large variety of instruments. The most common complications of the bulking agents were urinary retention and urinary tract infection. Additionally, there were certain major complications, such as one case of death after use of autologous fat. However, the lack of adequate studies, the heterogeneous populations studied, the wide variety of materials used and the lack of long-term follow-up limit guidance of practice. To determine which substance is the most suitable, there is a need for more randomized clinical trials that compare existing bulking agents based on standardized clinical outcomes. PMID:26934239

  11. The efficacy and safety of urethral injection therapy for urinary incontinence in women: a systematic review.

    PubMed

    Matsuoka, Priscila Katsumi; Locali, Rafael Fagionato; Pacetta, Aparecida Maria; Baracat, Edmund Chada; Haddad, Jorge Milhem

    2016-02-01

    To evaluate the efficacy and safety of different bulking agents for treating urinary incontinence in women, a systematic review including only randomized controlled trials was performed. The subjects were women with urinary incontinence. The primary outcomes were clinical and urodynamic parameters. The results were presented as a weighted mean difference for non-continuous variables and as relative risk for continuous variables, both with 95% confidence intervals. Initially, 942 studies were identified. However, only fourteen eligible trials fulfilled the prerequisites. Altogether, the review included 1814 patients in trials of eight different types of bulking agents, and all studies were described and analyzed. The measured outcomes were evaluated using a large variety of instruments. The most common complications of the bulking agents were urinary retention and urinary tract infection. Additionally, there were certain major complications, such as one case of death after use of autologous fat. However, the lack of adequate studies, the heterogeneous populations studied, the wide variety of materials used and the lack of long-term follow-up limit guidance of practice. To determine which substance is the most suitable, there is a need for more randomized clinical trials that compare existing bulking agents based on standardized clinical outcomes. PMID:26934239

  12. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction.

    PubMed

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost-benefit ratio.

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

    PubMed

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

    2010-08-09

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

  14. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction

    PubMed Central

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost–benefit ratio. PMID:27143910

  15. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction.

    PubMed

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost-benefit ratio. PMID:27143910

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

    PubMed Central

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

    2009-01-01

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

  17. Efficacy and safety of rufinamide in pediatric epilepsy.

    PubMed

    Hsieh, David T; Thiele, Elizabeth A

    2013-05-01

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

  18. Long Term Proton Pump Inhibitor Use and Gastrointestinal Cancer

    PubMed Central

    Graham, David Y.; Genta, Robert M.

    2010-01-01

    Proton pump inhibitors profoundly affect the stomach and have been associated with carcinoid tumors in female rats. There is now sufficient experience with this class of drugs to allow reasonable estimation of their safety in terms of cancer development. Long term proton pump inhibitor use is associated with an increase in gastric inflammation and development of atrophy among those with active Helicobacter pylori infections. The actual risk is unknown but is clearly low. However, it can be markedly reduced or eliminated by H. pylori eradication leading to the recommendation that patients considered for long term proton pump inhibitor therapy be tested for H. pylori infection and if present, it should be eradicated. Oxyntic cell hyperplasia, glandular dilatations, and fundic gland polyps may develop in H. pylori-uninfected patients, but these changes are believed to be reversible and without significant cancer risk. PMID:19006608

  19. Characteristics of Long-Term First Marriages.

    ERIC Educational Resources Information Center

    Fenell, David L.

    1993-01-01

    Investigated characteristics of long-term first marriages (over 20 years). Findings from 147 couples revealed: lifetime commitment to marriage, loyalty to spouse, strong moral values, respect for spouse as best friend, commitment to sexual fidelity, desire to be good parent, faith in God, desire to please and support spouse, good companion to…

  20. Long Term Transfer Effect of Metaphoric Allusion.

    ERIC Educational Resources Information Center

    Hayes, David A.; Mateja, John A.

    A study was conducted to investigate the long term transfer effect of metaphoric allusion used to clarify unfamiliar subject matter. Forty-nine high school students were given unfamiliar prose materials variously augmented by metaphoric allusion. The subjects' immediate performance on a transfer task was compared to their performance on an…

  1. Long-Term Stability of Social Participation

    ERIC Educational Resources Information Center

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  2. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

    This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship between plan…

  3. The long term characteristics of greenschist

    NASA Astrophysics Data System (ADS)

    Jang, Bo-An

    2016-04-01

    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

  4. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

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

  5. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  6. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  7. Long-term lysimeter data on evapotranspiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long term crop evapotranspiration (ET) data measured using large weighing lysimeters have only been gathered in a few places in the world, yet are of great importance for ground truthing of many models of plant water use, mesoscale climate, remote sensing estimation of ET, climate change and climate...

  8. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

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

  9. Plutonium packaging and long-term storage

    NASA Astrophysics Data System (ADS)

    Lloyd, Jane A.; Wedman, Douglas E.

    2000-07-01

    It has been demonstrated that the Advanced Recovery and Integrated Extraction System (ARIES) packaging line at Los Alamos National Laboratory can successfully package plutonium to meet DOE requirements for safe long-term storage. The ARIES system has just completed the disassembly and conversion of its first cores ("pits") for nuclear weapons.

  10. Long-Term Sequelae of Stroke

    PubMed Central

    Teasell, Robert W.

    1992-01-01

    Scant attention has been paid to the long-term consequences and complications resulting from a stroke. Many stroke survivors go on to develop a variety of medical, musculoskeletal, and psychosocial complications, years after the acute stroke. The family physician is regularly called upon to deal with these problems, but is often hampered by a lack of resources. PMID:21221264

  11. Efficacy and safety of influenza vaccination in children with asthma.

    PubMed

    Patria, Maria Francesca; Tenconi, Rossana; Esposito, Susanna

    2012-04-01

    The mean global prevalence of asthma among children is approximately 12%, making it the most common chronic disease in children. Influenza infection has been associated with complications such as exacerbations of wheezing and asthma, increased airway hyper-reactivity and hospitalization. Although influenza vaccination is recommended for asthmatic patients by all health authorities, vaccination coverage remains significantly lower than expected and is lowest of all in children. Compliance is affected by the uncertainty of parents and physicians concerning the clinical risk of influenza in asthmatic subjects, the benefits of influenza vaccination in preventing asthma exacerbations and the safety of immunization. The aim of this review is to analyze the rationale for using influenza vaccine, discuss the relationship between influenza and the severity of asthmatic episodes and document the efficacy and safety of influenza vaccination in the pediatric asthmatic population.

  12. Human safety and efficacy of ultraviolet filters and sunscreen products.

    PubMed

    Nash, J F

    2006-01-01

    Ultraviolet (UV) filters are the active ingredients in sunscreens. The concentration and combination of UV filters determine the efficacy of sunscreens as measured by sun protection factor. The safety of individual UV filters, and, more generally, sunscreen products, is a matter of a few related components: objective toxicologic evaluation, phototoxicologic potential, and human health consequences of using products that may reduce some but not all of the solar UV. Of 16 UV filters approved by the US Food and Drug Administration, 9 are used in different combinations in the most currently marketed sunscreens. Most of these compounds are considered safe and effective alone or in combination with other UV filters based on extensive toxicologic/phototoxicologic evaluations and market history. The benefits from proper use of sunscreens outweigh real or perceived human health concerns, establishing a favorable benefit-to-risk ratio. Future UV filters will require complete human safety evaluations alone and in combination with select benchmark ingredients.

  13. Relationship between short- and long-term memory and short- and long-term extinction.

    PubMed

    Cammarota, Martín; Bevilaqua, Lia R M; Rossato, Janine I; Ramirez, Maria; Medina, Jorge H; Izquierdo, Iván

    2005-07-01

    Both the acquisition and the extinction of memories leave short- and long-term mnemonic traces. Here, we show that in male Wistar rats, the short-term memory for a step-down inhibitory avoidance task (IA) is resistant to extinction, and that its expression does not influence retrieval or extinction of long-term memory. It has been known for some time that short- and long-term inhibitory avoidance memory involve separate and parallel processes. Here we show that, instead, short-term extinction of IA long-term memory is the first step towards its long-term extinction, and that this link requires functional NMDA receptors and protein synthesis in the CA1 region of the dorsal hippocampus at the time of the first CS-no US presentation.

  14. Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

    PubMed

    Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

    2016-01-01

    The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment. PMID:26852913

  15. Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

    PubMed

    Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

    2013-01-01

    The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism. PMID:23337477

  16. Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

    PubMed

    Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

    2013-01-01

    The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

  17. Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa

    PubMed Central

    Sacchetti, Marta; Mantelli, Flavio; Merlo, Daniela; Lambiase, Alessandro

    2015-01-01

    Aims. Several treatments have been proposed to slow down progression of Retinitis pigmentosa (RP), a hereditary retinal degenerative condition leading to severe visual impairment. The aim of this study is to systematically review data from randomized clinical trials (RCTs) evaluating safety and efficacy of medical interventions for the treatment of RP. Methods. Randomized clinical trials on medical treatments for syndromic and nonsyndromic RP published up to December 2014 were included in the review. Visual acuity, visual field, electroretinogram, and adverse events were used as outcome measures. Results. The 19 RCTs included in this systematic review included trials on hyperbaric oxygen delivery, topical brimonidine tartrate, vitamins, docosahexaenoic acid, gangliosides, lutein, oral nilvadipine, ciliary neurotrophic factor, and valproic acid. All treatments proved safe but did not show significant benefit on visual function. Long term supplementation with vitamin A showed a significantly slower decline rate in electroretinogram amplitude. Conclusions. Although all medical treatments for RP appear safe, evidence emerging from RCTs is limited since they do not present comparable results suitable for quantitative statistical analysis. The limited number of RCTs, the poor clinical results, and the heterogeneity among studies negatively influence the strength of recommendations for the long term management of RP patients. PMID:26339504

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

    PubMed

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

    2013-04-01

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

  19. Long term results of no-alcohol laser epithelial keratomileusis and photorefractive keratectomy for myopia

    PubMed Central

    Spadea, Leopoldo; Verboschi, Francesca; De Rosa, Vittoria; Salomone, Mariella; Vingolo, Enzo Maria

    2015-01-01

    AIM To evaluate the long term clinical results of mechanical no-alcohol-assisted laser epithelial keratomileusis (LASEK) versus standard photorefractive keratectomy (PRK) for low-moderate myopia. METHODS Twenty-five eyes treated with LASEK and twenty-five eyes treated with PRK were evaluated with a mean follow-up duration of 60mo. Mechanical separation of the epithelium was performed with blunt spatula and without application of alcohol. Laser ablation was performed with the MEL-70 excimer laser. All patients were examined daily until epithelial closure; at 1, 3, 6, and 12mo, and every year subsequently. Main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, haze, efficacy and safety indexes. RESULTS Twenty-one eyes and 22 eyes completed follow-up of 60mo in LASEK and PRK group respectively. Manifest refraction at 60mo follow-up was -0.01 and 0.26 in LASEK and PRK group respectively. In the LASEK group mean UDVA and mean CDVA after 60mo were 20/22 and 20/20 respectively (P>0.01). In the PRK group mean UDVA and mean CDVA at 60mo follow-up were 20/20 and 20/20 after 60mo (P>0.01). The efficacy indexes were 0.87 and 0.95, and the safety indexes were 1.25 and 1.4 respectively for LASEK group and PRK group. CONCLUSION Both standard PRK and no-alcohol LASEK offer safe and effective correction of low-moderate myopia in the long term without any statistically significant difference between the two groups. PMID:26086011

  20. Efficacy and safety of deferasirox in myelodysplastic syndromes.

    PubMed

    Breccia, Massimo; Alimena, Giuliana

    2013-07-01

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

  1. Efficacy and safety of novel anticoagulants in the elderly

    PubMed Central

    Karamichalakis, Nikolaos; Georgopoulos, Stamatis; Vlachos, Konstantinos; Liatakis, Ioannis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P

    2016-01-01

    Atrial fibrillation and venous thromboembolism (VTE) are common disorders associated with maleficent thrombotic events, particularly in the elderly patients. Polypharmacy, co-morbidities, and altered pharmacokinetics, often present in these patients, render the use of anticoagulants quite challenging. Novel oral anticoagulants (NOACs) have recently emerged as alternatives to Vitamin K Antagonists (VKAs) and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety has been well-established in the general population but the balance between benefit and harm in the elderly is still unclear. Routine use in these patients is uncommon. Accumulating data have shown that the benefit of NOACs is consistent among all age groups, featuring equal or greater efficacy in preventing thrombotic events. Excess bleedings were lower with NOACs in comparison to VKAs, but bleeding patterns were disparate among them and head to head comparison is not available. The present review highlights on the efficacy and safety of novel anticoagulants in the elderly population. PMID:27781063

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

    PubMed Central

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

    2014-01-01

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

  3. Protective efficacy and safety of liver stage attenuated malaria parasites

    PubMed Central

    Kumar, Hirdesh; Sattler, Julia Magdalena; Singer, Mirko; Heiss, Kirsten; Reinig, Miriam; Hammerschmidt-Kamper, Christiane; Heussler, Volker; Mueller, Ann-Kristin; Frischknecht, Friedrich

    2016-01-01

    During the clinically silent liver stage of a Plasmodium infection the parasite replicates from a single sporozoite into thousands of merozoites. Infection of humans and rodents with large numbers of sporozoites that arrest their development within the liver can cause sterile protection from subsequent infections. Disruption of genes essential for liver stage development of rodent malaria parasites has yielded a number of attenuated parasite strains. A key question to this end is how increased attenuation relates to vaccine efficacy. Here, we generated rodent malaria parasite lines that arrest during liver stage development and probed the impact of multiple gene deletions on attenuation and protective efficacy. In contrast to P. berghei strain ANKA LISP2(–) or uis3(–) single knockout parasites, which occasionally caused breakthrough infections, the double mutant lacking both genes was completely attenuated even when high numbers of sporozoites were administered. However, different vaccination protocols showed that LISP2(–) parasites protected better than uis3(–) and double mutants. Hence, deletion of several genes can yield increased safety but might come at the cost of protective efficacy. PMID:27241521

  4. A prospective, multicenter, observational study of long-term decitabine treatment in patients with myelodysplastic syndrome.

    PubMed

    Jeong, Seong Hyun; Kim, Yoo-Jin; Lee, Je-Hwan; Kim, Yeo-Kyeoung; Kim, Soo Jeong; Park, Sung Kyu; Do, Young Rok; Kim, Inho; Mun, Yeung-Chul; Kim, Hoon Gu; Lee, Won Sik; Yi, Hyeon Gyu; Joo, Young-Don; Choi, Chul Won; Kim, Suk Ran; Na, Sang Min; Jang, Jun Ho

    2015-12-29

    This prospective observational study evaluated the efficacy and safety of long-term decitabine treatment in patients with myelodysplastic syndrome (MDS). Decitabine 20 mg/m(2)/day was administered intravenously for 5 consecutive days every 4 weeks to MDS patients in intermediate-1 or higher International Prognostic Scoring System (IPSS) risk categories. Active antimicrobial prophylaxis was given to prevent infectious complications. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to response were evaluated, as were adverse events. The final analysis included 132 patients. IPSS risk was intermediate-2/high in 34.9% patients. The patients received a median of 5 cycles, with responders receiving a median of 8 cycles (range, 2-30). ORR was 62.9% (complete response [CR], 36; partial response [PR], 3; marrow complete response [mCR], 19; and hematologic improvement, 25). Among responders, 39% showed first response at cycle 3 or later. OS at 2 years was 60.9%, with 17% progressing to acute myeloid leukemia. PFS at 2 years was 51.0%. Patients achieving mCR showed comparable survival outcomes to those with CR/PR. With active antibiotic prophylaxis, febrile neutropenia events occurred in 61 of 1,033 (6%) cycles. Long-term decitabine treatment with antibiotic prophylaxis showed favorable outcomes in MDS patients, and mCR predicted favorable survival outcomes.

  5. Long-term intrathecal ziconotide for chronic pain: an open-label study.

    PubMed

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

    2009-03-01

    This open-label multicenter study evaluated the long-term safety and efficacy of intrathecal ziconotide and included 78 patients with chronic pain who had completed one of two previous ziconotide clinical trials. Each patient's initial ziconotide dose was based on his or her dose from the study of origin and was adjusted as necessary on the basis of adverse events and analgesic effect. The median ziconotide dose was 6.48 mcg/day (range, 0.00-120.00 mcg/day) at the Initial Visit and ranged from 5.52 to 7.20 mcg/day across all study visits. The most commonly reported new adverse events that were considered ziconotide related were memory impairment (11.3%); dizziness, nystagmus, and speech disorder (8.5% each); nervousness and somnolence (7.0% each); and abnormal gait (5.6%). There was no evidence of increased adverse event incidence at higher cumulative ziconotide doses. Elevations in creatine kinase were noted, but the proportion of patients with creatine kinase elevations did not change from the Initial Visit to the Termination Visit (4.1% each). Stable mean Visual Analog Scale of Pain Intensity scores during the three years of the study suggested no evidence of increased pain intensity with increased duration of ziconotide exposure. Long-term treatment with ziconotide appeared to be well tolerated and effective in patients whose response to ziconotide and ability to tolerate the drug had been previously demonstrated. PMID:18715748

  6. Long-term changes in Saturn's troposphere

    SciTech Connect

    Trafton, L.

    1985-09-01

    Attention is given to the results of a long term monitoring study of Saturn's H/sub 2/ quadrupole and CH/sub 4/ band absorptions outside the equatorial zone, over an interval of half a Saturn year that covers most of the perihelion half of Saturn's elliptical orbit (which is approximately bounded by the equinoxes). Marked long term changes are noted in the CH/sub 4/ absorption, accompanied by weakly opposite changes in the H/sub 2/ absorption. Seasonal changes are inferred on the basis of temporal variations in absorption. Spatial measurements have also been made in the 6450 A NH/sub 3/ band since the 1980 equinox. 42 references.

  7. Long-term reinforced fixed provisional restorations.

    PubMed

    Galindo, D; Soltys, J L; Graser, G N

    1998-06-01

    Extensive prosthodontic treatment often requires fabrication of long-term provisional restorations. Numerous materials and techniques have been described for prolonged insertion of interim restorations. This article describes a procedure for fabrication of long-term reinforced heat-processed provisional restorations based on a diagnostic wax-up. Reinforced heat-processed provisional restorations reduced flexure, which minimizes progressive loss of cement and diminished the possibility of recurrent decay. Occlusal stability and vertical dimension were maintained because of greater wear resistance. Occlusion, tooth contours, and pontic design developed in the provisional restoration were duplicated in the definitive restoration. The use of a matrix from a diagnostic wax-up facilitated fabrication of the prosthesis, and made the procedure less time-consuming and more predictable.

  8. A randomized, 3-phase, 34-week, double-blind, long-term efficacy study of osmotic-release oral system-methylphenidate in adults with attention-deficit/hyperactivity disorder.

    PubMed

    Biederman, Joseph; Mick, Eric; Surman, Craig; Doyle, Robert; Hammerness, Paul; Kotarski, Meghan; Spencer, Thomas

    2010-10-01

    We conducted a 3-phase, double-blind, placebo-controlled, parallel study design of osmotic-release oral system (OROS)-methylphenidate (MPH) in adults (19-60 years of age) with attention deficit/hyperactivity disorder as classified by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Phase 1 of the study was a 6-week, acute efficacy trial (n = 223), phase 2 was a 24-week, double-blind continuation study of responders (n = 96), and phase 3 was a double-blind, placebo-controlled, 4-week discontinuation study (n = 23). The mean daily dosage at phase 1 endpoint was 78.4 ± 31.7 mg (0.97 ± 0.32 mg/kg) OROS-MPH and 96.6 ± 26.5 mg (1.16 ± 0.19 mg/kg) placebo (P < 0.0001). Clinical response at phase 1 endpoint was significantly greater in the OROS-MPH group (62%, n = 67 vs 37%, n = 41; P < 0.001) and was maintained throughout 24 weeks of double-blind treatment. With double-blind, placebo-controlled discontinuation, however, there was no statistically significant difference in the rate of relapse between OROS-MPH responders randomized to placebo and those randomized to continue active treatment (18%, n = 2 vs 0%, n = 0; P = 0.1). As expected, decreased appetite, insomnia, being tense/jittery, mucosal dryness, and neurological symptoms were statistically significantly associated with OROS-MPH treatment. More work is needed to be conducted with larger samples being followed to study completion to better understand the long-lasting impact of pharmacotherapy for adult attention-deficit/hyperactivity disorder.

  9. [Taiwan long-term care insurance and the evolution of long-term care in Japan].

    PubMed

    Huang, Hui-Wen; Liu, Shu-Hui; Pai, Yu-Chu

    2010-08-01

    The proportion of elderly (65 years of age and older) in Taiwan has exceeded 10% since 2008. With more elderly, the number of patients suffering from dementia and disabilities has also been rapidly increasing. Japan also has been facing increasing demand for long-term care due to an aging society. Prior to 2000, social welfare programs in Japan, working to cope with changing needs, typically provided insufficient services, and geriatric patients were hospitalized unnecessarily, wasting medical resources and causing undue patient hardship. In response, Japan launched its long-term care insurance program in April 2000. Under the program, city, town and village-based organizations should take responsibility for providing care to the elderly in their place of residence. The program significantly improved previous financial shortfalls and long-term care supply and demand has been met by existing social welfare organization resources. In Taiwan, the provision of long-term care by county / city authorities has proven inconsistent, with performance deemed poor after its first decade of long-term care operations. Service was found to be affected by differences in available resources and insufficient long-term care administration. The cultures of Taiwan and Japan are similar. The authors visited the Japan Long-Term Care Insurance Institute in August 2009. Main issues involved in the implementation and evolution of the Japan long-term Care Insurance are reported on in this paper. We hope such may be useful information to those working to develop long-term care programs in Taiwan. PMID:20661859

  10. Long-term Results of Endovascular Stent Graft Placement of Ureteroarterial Fistula

    SciTech Connect

    Okada, Takuya Yamaguchi, Masato; Muradi, Akhmadu Nomura, Yoshikatsu; Uotani, Kensuke; Idoguchi, Koji; Miyamoto, Naokazu Kawasaki, Ryota; Taniguchi, Takanori; Okita, Yutaka; Sugimoto, Koji

    2013-08-01

    PurposeTo evaluate the safety, efficacy, and long-term results of endovascular stent graft placement for ureteroarterial fistula (UAF).MethodsWe retrospectively analyzed stent graft placement for UAF performed at our institution from 2004 to 2012. Fistula location was assessed by contrast-enhanced computed tomography (CT) and angiography, and freedom from hematuria recurrence and mortality rates were estimated.ResultsStent graft placement for 11 UAFs was performed (4 men, mean age 72.8 {+-} 11.6 years). Some risk factors were present, including long-term ureteral stenting in 10 (91 %), pelvic surgery in 8 (73 %), and pelvic radiation in 5 (45 %). Contrast-enhanced CT and/or angiography revealed fistula or encasement of the artery in 6 cases (55 %). In the remaining 5 (45 %), angiography revealed no abnormality, and the suspected fistula site was at the crossing area between urinary tract and artery. All procedures were successful. However, one patient died of urosepsis 37 days after the procedure. At a mean follow-up of 548 (range 35-1,386) days, 4 patients (36 %) had recurrent hematuria, and two of them underwent additional treatment with secondary stent graft placement and surgical reconstruction. The hematuria recurrence-free rates at 1 and 2 years were 76.2 and 40.6 %, respectively. The freedom from UAF-related and overall mortality rates at 2 years were 85.7 and 54.9 %, respectively.ConclusionEndovascular stent graft placement for UAF is a safe and effective method to manage acute events. However, the hematuria recurrence rate remains high. A further study of long-term results in larger number of patients is necessary.

  11. Long-term follow-up for noninvasive body contouring treatment in Asians.

    PubMed

    Chang, Shyue-Luen; Huang, Yau-Li; Lee, Mei-Ching; Chang, Chih-Hsiang; Lin, Ying-Fang; Cheng, Chun Yu; Hu, Sindy

    2016-02-01

    There are versatile modalities to achieve noninvasive fat reduction, and most of them have proven to be effective for circumferential reduction of local fat tissue, without any serious or permanent adverse effects. However, the follow-up time is short, ranging from 1 to 24 weeks. Most of the patients would like to know how long will its effect last and whether there is long-term side effect or not. The aim of this study was to assess the long-term efficacy and safety of combination therapy of focused ultrasound and radio frequency for noninvasive body contouring. Thirty-two Asian subjects received three sequential combination therapies of focused ultrasound and radio-frequency treatments every 2 weeks in the abdominal region and were followed up 1 month and 1 year after the last treatment. After a year, 5 patients were loss follow-up and 2 were pregnant. Finally, 25 healthy Asian subjects (18 females and 7 males) were enrolled in this study. Safety parameters and adverse events were recorded. The mean body weight change remained constant without a significant change 1 year after treatment and was 0.1 ± 1.2 kg (p = 0.513). The mean abdominal circumference change between 1 month and 1 year after the last treatment was 0.4 ± 1.2 cm and was not significant (p = 0.169). The relationships between weight change and circumference change of the 23 patients were tested using Spearman's rho correlation coefficient. There was a correlation between weight change and circumference change (0.73; p = 0.000). The procedure was safe without a recordable long-term adverse event. The combination therapies of nonthermally focused ultrasound and radio-frequency treatments for body contouring in the abdominal region are effective and may show positive results for at least a year if patients can maintain their body weight. The procedure is safe without recordable long-term adverse events in this study.

  12. Cutaneous oxalosis after long-term hemodialysis.

    PubMed

    Abuelo, J G; Schwartz, S T; Reginato, A J

    1992-07-01

    A 27-year-old woman undergoing long-term hemodialysis developed cutaneous calcifications on her fingers. A skin biopsy specimen showed that the deposits were calcium oxalate. To our knowledge, only one previous article has reported pathologic and crystallographic studies on calcifications of the skin resulting from dialysis oxalosis. We speculate that vitamin C supplements, liberal tea consumption, an increased serum ionized calcium concentration, and the long duration of hemodialysis contributed to the production of these deposits.

  13. Long-term course of opioid addiction.

    PubMed

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  14. Consequences of long-term hyperparathyroidism.

    PubMed

    Graal, M B; Wolffenbuttel, B H

    1998-07-01

    We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, severe and long-standing hypocalcaemia ('hungry bone syndrome') developed after parathyroidectomy. We discuss the consequences of hyperparathyroidism, especially the effects on bone, the complications of parathyroidectomy and the possibilities of preoperative treatment with bisphosphonates.

  15. Long-term consequences of anorexia nervosa.

    PubMed

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof

    2013-07-01

    Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. PMID:23706279

  16. Short and long-term cosmesis of cervical thyroidectomy scars.

    PubMed

    Dordea, M; Aspinall, S R

    2016-01-01

    Introduction Multiple surgical approaches to the thyroid gland have been described via cervical or extracervical routes. Improved cosmesis, patient satisfaction, reduced pain (procedure dependent) and early discharge have all been reported for minimally invasive approaches with similar safety profiles and long-term outcomes to conventional surgery. This review summarises the current evidence base for improved cosmesis with minimally invasive cervical approaches to the thyroid gland compared with conventional surgery. Methods A systematic review was undertaken. The MEDLINE(®), Embase™ and Cochrane databases were searched for relevant articles. Results A total of 57 papers thyroid papers were identified. Of those, 20 reported some form of cosmetic outcome assessment. There were 6 randomised controlled trials with 412 patients (evidence level 2B), 7 cohort studies with 3,073 patients (level 3B) and 7 non-comparative case series with 1,575 patients (level 4). There was significant heterogeneity between studies in terms of wound closure technique, timing of scar assessment and scar assessment scales (validated and non-validated). Most studies performed early scar assessments, some using non-validated scar assessment tools. Conclusions Assessment of cosmesis is complex and requires rigorous methodology. Evidence from healing/remodelling studies suggests scar maturation is a long-term process. This calls into question the value of early scar assessment. Current evidence does not support minimally invasive surgical approaches to the thyroid gland if improved long-term cosmesis is the goal. PMID:26688393

  17. Electrodes for long-term esophageal electrocardiography.

    PubMed

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

    2013-09-01

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

  18. [Long-term survival after severe trauma].

    PubMed

    Mutschler, W; Mutschler, M; Graw, M; Lefering, R

    2016-07-01

    Long-term survival after severe trauma is rarely addressed in German trauma journals although knowledge of life expectancy and identification of factors contributing to increased mortality are important for lifetime care management, development of service models, and targeting health promotion and prevention interventions. As reliable data in Germany are lacking, we compiled data mainly from the USA and Australia to describe life expectancy, risk factors, and predictors of outcome in patients experiencing traumatic spinal cord injury, traumatic brain injury, and polytrauma. Two years after trauma, life expectancy in all three categories was significantly lower than that of the general population. It depends strongly on severity of disability, age, and gender and is quantifiable. Whereas improvements in medical care have led to a marked decline in short-term mortality, surprisingly long-term survival in severe trauma has not changed over the past 30 years. Therefore, there is need to intensify long-term trauma patient care and to find new strategies to limit primary damage. PMID:27342106

  19. Titanium for long-term tritium storage

    SciTech Connect

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  20. Long-term EEG in children.

    PubMed

    Montavont, A; Kaminska, A; Soufflet, C; Taussig, D

    2015-03-01

    Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development.

  1. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  2. Management of drug-drug interactions: considerations for special populations--focus on opioid use in the elderly and long term care.

    PubMed

    Lynch, Tom

    2011-09-01

    Elderly patients and residents in long term care facilities requiring pain medication often have multiple pharmacologic and physiologic factors that can impact the choice of analgesic. One particular problem with prescribing opioids to the elderly and long term care residents is that opioid safety and efficacy have not been well studied in these populations, and it may be difficult to predict how these patients will respond to opioid treatment. As people age, numerous physiological changes occur, which may affect opioid pharmacokinetics and the potential for drug-drug interactions (DDIs). Long term care residents include the elderly but also include many younger patients who require assistance for a variety of reasons, such as physical or mental disability. Many elderly and long term care patients have cognitive deficits that impede communication about their pain, thus making detection of opioid DDIs more difficult. Knowledge of the patient's medical history and current prescriptions can help guide the pain management team in the selection of treatment, help minimize the risk of DDIs, and provide these patients with the pain relief they require. There are several practice management recommendations for opioid therapy in the elderly and long term care residents, with the goal of optimizing analgesia while avoiding adverse events and drug interactions.

  3. Enteral feeding pumps: efficacy, safety, and patient acceptability

    PubMed Central

    White, Helen; King, Linsey

    2014-01-01

    Enteral feeding is a long established practice across pediatric and adult populations, to enhance nutritional intake and prevent malnutrition. Despite recognition of the importance of nutrition within the modern health agenda, evaluation of the efficacy of how such feeds are delivered is more limited. The accuracy, safety, and consistency with which enteral feed pump systems dispense nutritional formulae are important determinants of their use and acceptability. Enteral feed pump safety has received increased interest in recent years as enteral pumps are used across hospital and home settings. Four areas of enteral feed pump safety have emerged: the consistent and accurate delivery of formula; the minimization of errors associated with tube misconnection; the impact of continuous feed delivery itself (via an enteral feed pump); and the chemical composition of the casing used in enteral feed pump manufacture. The daily use of pumps in delivery of enteral feeds in a home setting predominantly falls to the hands of parents and caregivers. Their understanding of the use and function of their pump is necessary to ensure appropriate, safe, and accurate delivery of enteral nutrition; their experience with this is important in informing clinicians and manufacturers of the emerging needs and requirements of this diverse patient population. The review highlights current practice and areas of concern and establishes our current knowledge in this field. PMID:25170284

  4. Efficacy and Safety of Oral or Nasal Fentanyl for Treatment of Breakthrough Pain in Cancer Patients: A Systematic Review.

    PubMed

    Rogríguez, Dulce; Urrutia, Gerard; Escobar, Yolanda; Moya, Jordi; Murillo, Maite

    2015-09-01

    Formulations of fentanyl that use buccal, sublingual, or nasal transmucosal routes of administration have been developed for the treatment of BTP in opioid-tolerant patients with cancer. The purposes of this analysis were to identify and review published data describing the efficacy and safety of different oral or nasal transmucosal fentanyl formulations for treatment of cancer-related BTP, based on a critical analysis of scientific literature. Oral transmucosal or intranasal fentanyl is an effective treatment for management of BTP episodes due to a potent analgesic effect, rapid onset of action, and sustained effect. Furthermore, it is a reasonably safe treatment, causing generally mild adverse events not leading to treatment discontinuation. Nevertheless, further progress in standardizing methodology, definitions, and criteria used both in research and in clinical practice is needed in order to generate quality information allowing a better understanding of the comparable efficacy of available formulations of fentanyl. A more rigorous assessment of long-term safety is also needed to establish a balance between benefits and risks of the available options.

  5. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up.

    PubMed

    Steinberg, Martin H; McCarthy, William F; Castro, Oswaldo; Ballas, Samir K; Armstrong, F Danny; Smith, Wally; Ataga, Kenneth; Swerdlow, Paul; Kutlar, Abdullah; DeCastro, Laura; Waclawiw, Myron A

    2010-06-01

    A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. PMID:20513116

  6. Functional interpretation of metabolomics data as a new method for predicting long-term side effects: treatment of atopic dermatitis in infants.

    PubMed

    Lee, Seul Ji; Woo, Sung-il; Ahn, Soo Hyun; Lim, Dong Kyu; Hong, Ji Yeon; Park, Jeong Hill; Lim, Johan; Kim, Mi-kyeong; Kwon, Sung Won

    2014-12-10

    Topical steroids are used for the treatment of primary atopic dermatitis (AD); however, their associated risk of serious complications is great due to the presence of vulnerable lesions in young children with AD. Topical calcineurin inhibitors (TCIs) are steroid-free, anti-inflammatory agents used for topical AD therapy. However, their use is prohibited in infants <2 years of age because of their carcinogenic potential. We conducted a randomized, double-blind trial to evaluate the efficacy of TCIs as a secondary AD treatment for children <2 years of age by comparing 1% pimecrolimus cream with 0.05% desonide cream. We performed urinary metabolomics to predict long-term side effects. The 1% pimecrolimus cream displayed similar efficacy and exceptional safety compared with the 0.05% desonide cream. Metabolomics-based long-term toxicity tests effectively predicted long-term side effects using short-term clinical models. This applicable method for the functional interpretation of metabolomics data sets the foundation for future studies involving the prediction of the toxicity and systemic reactions caused by long-term medication administration.

  7. Short-term and long-term effects of osteoporosis therapies.

    PubMed

    Reid, Ian R

    2015-07-01

    Progress continues to be made in the development of therapeutics for fracture prevention. Bisphosphonates are now available orally and intravenously, often as inexpensive generics, and remain the most widely used interventions for osteoporosis. The major safety concern associated with the use of bisphosphonates is the development of femoral shaft stress fractures and, although rare, this adverse event affords the principal rationale for restricting bisphosphonate therapy to those individuals with femoral T-scores <-2.5, and for providing drug holidays in those individuals requiring therapy for >5 years. Newer antiresorptive therapies, in the form of denosumab and cathepsin K inhibitors, might increase efficacy and possibly circumvent some of the safety concerns associated with bisphosphonate use (for example, gastrointestinal and renal complications). The combination of teriparatide with antiresorptives markedly increases effects on BMD; new anabolic agents are also very promising in this regard. However, whether or not these changes in BMD translate into improved efficacy of fracture prevention remains to be determined. Vitamin D is important for the prevention of osteomalacia, but does not influence BMD or fracture risk in patients not deficient in vitamin D. The balance of risks and benefits of calcium supplementation is contentious, but patients should be encouraged to adhere to a balanced diet aimed at maintaining a healthy body weight. Consideration of a patient's risk of falling, and its mitigation, are also important. In this Review, I summarize the short-term and long-term effects of osteoporosis therapies. PMID:25963272

  8. Chronic Hepatitis B: Integrating Long-Term Treatment Data and Strategies to Improve Outcomes in Clinical Practice

    PubMed Central

    Afdhal, Nezam H.; Bacon, Bruce R.; Brown, Robert S.

    2011-01-01

    A number of agents can reduce viral replication in patients with chronic hepatitis B, but most patients do not undergo a curative response to these drugs and therefore require long-term therapy. Thus, recent studies have investigated the long-term safety, efficacy, and resistance profiles of several antiviral nucleotide/nucleoside agents: lamivudine, telbivudine, adefovir dipivoxil, entecavir, and tenofovir. The most recent data have revealed that lamivudine and telbivudine produce high rates of resistance when treatment is continued for 2–5 years; as a result, these agents are no longer preferred for first-line monotherapy. Entecavir and tenofovir, on the other hand, appear to have favorable safety and efficacy profiles when used as monotherapy, with very low rates of resistance over 5 years. In order to help clinicians incorporate these data into clinical practice, this monograph will review recently published data on hepatitis B antiviral medications, as well as explore when to consider cessation of therapy. The treatment of special patient populations and the need to screen patients for hepatocellular carcinoma will also be discussed. PMID:22557938

  9. Efficacy and Safety of Split Peroneal Tendon Lateral Ankle Stabilization.

    PubMed

    Shibuya, Naohiro; Bazán, D Issac; Evans, Andrew M; Agarwal, Monica R; Jupiter, Daniel C

    2016-01-01

    Chronic lateral ankle instability is a common condition. Split peroneal tendon lateral ankle stabilization, a modification of the Chrisman-Snook procedure, is biomechanically stable and often used for severe and/or recurrent chronic lateral ankle instability. The purpose of the present study was to evaluate the efficacy and safety of this technique. Specifically, the midterm recurrence of instability and postoperative complications, such as stiffness, neurologic pain, and wound healing complications, were evaluated. We evaluated 30 consecutive procedures with a minimal follow-up period of 1 year. The mean follow-up period was 25 ± 13 (median 19, range 13 to 62) months. Five patients (17%) developed recurrent ankle instability, of whom 4 underwent revision surgery. One superficial infection and two wound disruptions developed. Two patients experienced stiffness and eight (27%) surgically induced neurologic complaints, such as sural neuritis. Finally, 2 patients developed complex regional pain syndrome.

  10. [Special recommendations for lipid-lowering treatment: efficacy and safety].

    PubMed

    Martinez, Tania Leme da Rocha; Nascimento, Helena Maria do

    2005-10-01

    Pharmacologic lipid-lowering interventions should be monitored periodically to assess efficacy and safety parameters. Statins are usually well-tolerated drugs and major side effects include increased serum liver and muscle enzymes (AST, ALT, CK). Treatment should be stopped or diminished in case of significant increase of AST or ALT (> 3x ULN), or CK (> 10x ULN). Other lipid lowering agents may also produce hepatotoxicity or myositis, especially in association with statins (fibrates and nicotinic acid) or in presence of metabolic abnormalities (thyroid, liver or renal disorders). Nicotinic acid can also increase glucose and uric acid plasma levels. Laboratory tests might be performed prior to hypolipidemic drug treatment and should be repeated every three months during the first year and then at 6-mo intervals. Shorter intervals should be recommended in individual cases.

  11. Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients

    PubMed Central

    Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Ulanski, Lawrence J.; Miller, Luke; Podella, Carla

    2014-01-01

    Background: Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities. PMID:25329968

  12. Safety and Efficacy of Supervised Strength Training Adopted in Pregnancy

    PubMed Central

    O’Connor, Patrick J.; Poudevigne, Melanie S.; Cress, M. Elaine; Motl, Robert W.; Clapp, James F.

    2014-01-01

    Objective Describe safety and efficacy of a supervised, low-to-moderate intensity strength training program adopted during pregnancy among women at increased risk for back pain. Methods 32 women adopted strength training twice per week for 12 weeks. Data on musculoskeletal injuries, symptoms, blood pressure, and the absolute external load used for 5 of 6 exercises were obtained during each session. A submaximal lumbar extension endurance exercise test was performed at weeks 5, 10, and 13. Results The mean (± SD) exercise session attendance rate was 80.5% (± 11.3%). No musculoskeletal injuries occurred. Potentially adverse symptoms (eg, dizziness) were infrequent (2.1% of sessions). Repeated-measures ANOVA showed large increases in the external load across 12 weeks (all P values < .001) and the percentage increases in external load from weeks 1 to 12 were 36% for leg press, 39% for leg curl, 39% for lat pull down, 41% for lumbar extension and 56% for leg extension. Training was associated with a 14% increase in lumbar endurance. Blood pressure was unchanged following acute exercise sessions and after 12 weeks of exercise training. Conclusion The adoption of a supervised, low-to-moderate intensity strength training program during pregnancy can be safe and efficacious for pregnant women. PMID:21487130

  13. Long-term EARLINET dust observations

    NASA Astrophysics Data System (ADS)

    Mona, Lucia; Amiridis, Vassilis; Amodeo, Aldo; Binietoglou, Ioannis; D'Amico, Giuseppe; Schwarz, Anja; Papagiannopoulos, Nikolaos; Papayannis, Alexandros; Sicard, Michael; Comeron, Adolfo; Pappalardo, Gelsomina

    2015-04-01

    Systematic observations of Saharan dust events over Europe are performed from May 2000 by EARLINET, the European Aerosol Research LIdar NETwork. EARLINET is a coordinated network of stations that make use of advanced lidar methods for the vertical profiling of aerosols. The backbone of EARLINET network is a common schedule for performing the measurements and the quality assurance of instruments/data. Particular attention is paid to monitoring the Saharan dust intrusions over the European continent. The geographical distribution of the EARLINET stations is particularly appealing for the dust observation, with stations located all around the Mediterranean and in the center of the Mediterranean (Italian stations) where dust intrusions are frequent, and with several stations in the central Europe where dust penetrates occasionally. All aerosol backscatter and extinction profiles related to observations collected during these alerts are grouped in the devoted "Saharan dust" category of the EARLINET database. This category consists of about 4700 files (as of December 2013). Case studies involving several stations around Europe selected from this long-term database have been provided the opportunity to investigate dust modification processes during transport over the continent. More important, the long term EARLINET dust monitoring allows the investigation of the horizontal and vertical extent of dust outbreaks over Europe and the climatological analysis of dust optical intensive and extensive properties at continental scale. This long-term database is also a unique tool for a systematic comparison with dust model outputs and satellite-derived dust products. Because of the relevance for both dust modeling and satellite retrievals improvement, results about desert dust layers extensive properties as a function of season and source regions are investigated and will be presented at the conference. First comparisons with models outputs and CALIPSO dust products will be

  14. Human Behaviour in Long-Term Missions

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  15. Long Term Analysis for the BAM device

    NASA Astrophysics Data System (ADS)

    Bonino, D.; Gardiol, D.

    2011-02-01

    Algorithms aimed at the evaluation of critical quantities are based on models with many parameters, which values are estimated from data. The knowledge, with high accuracy, of these values and the control of their temporal evolution are important features. In this work, we focus on the latter subject, and we show a proposed pipeline for the BAM (Basic Angle Monitoring) Long Term Analysis, aimed at the study of the calibration parameters of the BAM device and of the Basic Angle variation, searching for unwanted trends, cyclic features, or other potential unexpected behaviours.

  16. Long-term outcomes in multiple gestations.

    PubMed

    Rand, Larry; Eddleman, Keith A; Stone, Joanne

    2005-06-01

    Children born from a multiple gestation are at increased risk for cerebral palsy, learning disability, and language and neurobehavioral deficits. With the increased incidence of multiple pregnancies and use of assisted reproductive technology (ART), these issues are more commonly affecting parents. Long-term outcomes are a critical part of preconceptual and early pregnancy counseling for parents faced with a multiple gestation or considering ART, and the provider should be well versed on issues surrounding zygosity, gestational age, higher-order multiples, and the effects of options such as multifetal pregnancy reduction. PMID:15922795

  17. Long-Term Wind Power Variability

    SciTech Connect

    Wan, Y. H.

    2012-01-01

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

  18. Long-term effects of sibling incest.

    PubMed

    Daie, N; Witztum, E; Eleff, M

    1989-11-01

    Although sexual abuse of children is recognized as a serious problem, sibling incest has received relatively little attention. A distinction has been made between power-oriented sibling incest and nurturance-oriented incest. The authors review the relevant literature and present four clinical examples. The cases illustrate the broad range of sibling incest and demonstrate its effects, including the long-term consequences for the perpetrator. Lasting difficulties in establishing and maintaining close relationships, especially sexual ones, are prominent features of each case. Without denying the occurrences of benign sex-play between siblings, the authors emphasize exploitation and abuse as pathogenic aspects of sibling incest.

  19. Long-term space flights - personal impressions

    NASA Astrophysics Data System (ADS)

    Polyakov, V. V.

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

  20. 17 CFR 256.224 - Other long-term debt.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Other long-term debt. 256.224... COMPANY ACT OF 1935 6. Long-Term Debt § 256.224 Other long-term debt. This account shall include all long-term debt to nonassociates and not subject to current settlement. Note: Subaccounts shall be...

  1. 17 CFR 256.224 - Other long-term debt.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Other long-term debt. 256.224... COMPANY ACT OF 1935 6. Long-Term Debt § 256.224 Other long-term debt. This account shall include all long-term debt to nonassociates and not subject to current settlement. Note: Subaccounts shall be...

  2. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support....

  3. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support....

  4. Safety and Efficacy of Sodium Hyaluronate Gel and Chitosan in Preventing Postoperative Peristomal Adhesions After Defunctioning Enterostomy

    PubMed Central

    Hu, Jiancong; Fan, Dejun; Lin, Xutao; Wu, Xianrui; He, Xiaosheng; He, Xiaowen; Wu, Xiaojian; Lan, Ping

    2015-01-01

    Abstract Peristomal adhesions complicate closure of defunctioning enterostomy. The efficacy and safety of sodium hyaluronate gel and chitosan in preventing postoperative adhesion have not been extensively studied. This study aims to evaluate the safety and efficacy of sodium hyaluronate gel and chitosan in the prevention of postoperative peristomal adhesions. This was a prospective randomized controlled study. One hundred and fourteen patients undergoing defunctioning enterostomy were enrolled. Patients were randomly assigned to receive sodium hyaluronate gel (SHG group) or chitosan (CH group) or no antiadhesion treatment (CON group) during defunctioning enterostomy. The safety outcomes included toxicities, stoma-related complications, and short-term and long-term postoperative complications. Eighty-seven (76.3%) of the 114 patients received closure of enterostomy, during which occurrence and severity of intra-abdominal adhesions were visually assessed by a blinded assessor. Incidence of adhesion appears to be lower in patients received sodium hyaluronate gel or chitosan but differences did not reach a significant level (SHG group vs CH group vs CON group: 62.1% vs 62.1% vs 82.8%, P = 0.15). Compared with the CON group, severity of postoperative adhesion was significantly decreased in the SHG and CH group (SHG group vs CH group vs CON group: 31.0% vs 27.6% vs 62.1%; P = 0.01). There was no significant difference in the occurrence of postoperative complications and other safety outcomes among the 3 groups. Sodium hyaluronate gel or chitosan smeared around the limbs of a defunctioning enterostomy was safe and effective in the prevention of postoperative peristomal adhesions. PMID:26705233

  5. Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders

    PubMed Central

    Frenk, Nathan Elie; Sebastianes, Fernando; Lerario, Antonio Marcondes; Fragoso, Maria Candida Barisson Villares; Mendonca, Berenice Bilharinho; de Menezes, Marcos Roberto

    2016-01-01

    OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. RESULTS: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. CONCLUSION: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks. PMID:27759849

  6. Safety and efficacy of Bixa orellana (achiote, annatto) leaf extracts.

    PubMed

    Stohs, Sidney J

    2014-07-01

    Bixa orellana leaf preparations have been used for many years by indigenous people for a variety of medicinal applications. Published research studies in animals indicate that various extracts of Bixa leaves exhibit antioxidant, broad antimicrobial (antibacterial and antifungal), anti-inflammatory, analgesic, hypoglycemic, and antidiarrheal activities. No studies have specifically assessed the ability of leaf extracts to inhibit urogenital infections although Bixa products have been used in folkloric medicine to treat gonorrhea and other infections. Few human studies have been conducted and published using Bixa leaf preparations. Many more studies have been conducted and published involving Bixa seed (annatto) extracts than with leaf extracts. No subchronic safety (toxicity) studies have been conducted in animals. A 6 month study in humans given 750 mg of leaf powder per day demonstrated no significant or serious adverse effects. Bixa leaf extracts appear to be safe when given under current conditions of use. However, additional human and animal controlled safety and efficacy studies are needed. In addition, detailed chemical analyses are required to establish structure-function relationships.

  7. Bowel preparation for colonoscopy: efficacy, tolerability and safety.

    PubMed

    Martens, Pieter; Bisschops, Raf

    2014-06-01

    Adequate cleansing of the bowel is important for a reliable and diagnostic colonoscopy. Proper bowel preparation is directly correlated to the diagnostic performance of colonoscopy, procedure time, cost price and the complication rate. The ideal bowel preparation agent should be efficient, safe and well tolerated by the patient. Numerous agents have become commercially available overtime. Current agents can be classified according to their tonicity, as being isotonic or hypertonic. Poly-ethylene glycol based solutions balanced with electrolytes are the prototype of isotonic bowel preparations. Poly-ethylene solutions are safe and efficient in cleaning the bowel. Volume related side-effects are common, leading to innovations such as split dosing, and low volume solution combined with another laxative. Sodium phosphate and magnesium oxide are hypertonic agents. They are efficient and well tolerated, but safety issues regarding sodium phosphate has hampered its success. Because most physician are likely to prescribe bowel preparation agents for colonoscopy, they should be aware of the range of preparations commercially available and their limitations. This review focuses on the efficacy, tolerability and safety of current available bowel preparation agents. PMID:25090824

  8. Efficacy and food safety considerations of poultry competitive exclusion products.

    PubMed

    Wagner, Robert Doug

    2006-11-01

    Competitive exclusion (CE) products are anaerobic cultures of bacteria that are applied to poultry hatchlings to establish a protective enteric microbiota that excludes intestinal colonization by human food-borne pathogens. For safety of the poultry flock and human consumers, the identities of bacteria in CE products need to be known. A CE product is a culture of intestinal contents from adult chickens. It may be microbiologically defined by analysis of bacteria isolated from the culture, but many bacteria are hard to reliably isolate, identify, and characterize with conventional techniques. Sequence analysis of 16S ribosomal RNA (rRNA) genes may be more reliable than conventional techniques to identify CE bacteria. Bacteria in CE products may contain antimicrobial drug resistance and virulence mechanisms that could be transferred to the enteric bacteria of the food animal and to the human consumer. Detection methods for specific antimicrobial drug resistance and virulence genes and the integrase genes of conjugative transposons, mostly utilizing PCR technology, are being developed that can be applied to assess these risks in CE bacteria. With improvements in efficacy, bacterial identification, and detection and control of the possible risks of gene transfer, CE product technology can be made a more effective food safety tool.

  9. Safety and efficacy of Bixa orellana (achiote, annatto) leaf extracts.

    PubMed

    Stohs, Sidney J

    2014-07-01

    Bixa orellana leaf preparations have been used for many years by indigenous people for a variety of medicinal applications. Published research studies in animals indicate that various extracts of Bixa leaves exhibit antioxidant, broad antimicrobial (antibacterial and antifungal), anti-inflammatory, analgesic, hypoglycemic, and antidiarrheal activities. No studies have specifically assessed the ability of leaf extracts to inhibit urogenital infections although Bixa products have been used in folkloric medicine to treat gonorrhea and other infections. Few human studies have been conducted and published using Bixa leaf preparations. Many more studies have been conducted and published involving Bixa seed (annatto) extracts than with leaf extracts. No subchronic safety (toxicity) studies have been conducted in animals. A 6 month study in humans given 750 mg of leaf powder per day demonstrated no significant or serious adverse effects. Bixa leaf extracts appear to be safe when given under current conditions of use. However, additional human and animal controlled safety and efficacy studies are needed. In addition, detailed chemical analyses are required to establish structure-function relationships. PMID:24357022

  10. Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: two-year results including pharmacokinetics and concomitant hydroxyurea.

    PubMed

    Vichinsky, Elliott; Torres, Marcela; Minniti, Caterina P; Barrette, Stephane; Habr, Dany; Zhang, Yiyun; Files, Beatrice

    2013-12-01

    We report a prospective, randomized, Phase II study of deferasirox and deferoxamine (DFO) in sickle cell disease patients with transfusional iron overload, with all patients continuing on deferasirox after 24 weeks, for up to 2 years. The primary objective was to evaluate deferasirox safety compared with DFO; long-term efficacy and safety of deferasirox was also assessed. We also report, for the first time, the safety and pharmacokinetics of deferasirox in patients concomitantly receiving hydroxyurea. Deferasirox (n = 135) and DFO (n = 68) had comparable safety profiles over 24 weeks. Adverse events (AEs) secondary to drug administration were reported in 26.7% of patients in the deferasirox cohort and 28.6% in the DFO cohort. Gastrointestinal disorders were more common with deferasirox, including diarrhea (10.4% versus 3.6%) and nausea (5.2% versus 3.6%). The most common AE in the DFO group was injection-site pain irritation, which occurred in 7% of patients. Acute renal failure occurred in one patient on deferasirox who was continued on medication despite progressive impairment of renal function parameters. Serum ferritin levels were reduced in both treatment groups. Patients continuing on deferasirox for up to 2 years demonstrated an absolute median serum ferritin decrease of -614 ng/mL (n = 96). Increasing deferasirox dose was associated with improved response and a continued manageable safety profile. Concomitant hydroxyurea administration (n = 28) did not appear to influence the efficacy, safety (including liver and kidney function), and pharmacokinetic parameters of deferasirox.

  11. Efficacy of a Food Safety Comic Book on Knowledge and Self-Reported Behavior for Persons Living with AIDS

    PubMed Central

    Dworkin, Mark S.; Peterson, Caryn E.; Gao, Weihua; Mayor, Angel; Hunter, Robert; Negron, Edna; Fleury, Alison; Besch, C. Lynn

    2013-01-01

    Introduction Persons living with AIDS are highly vulnerable to foodborne enteric infections with the potential for substantial morbidity and mortality. Educational materials about foodborne enteric infections intended for this immunocompromised population have not been assessed for their efficacy in improving knowledge or encouraging behavior change. Methods/Results AIDS patients in four healthcare facilities in Chicago, New Orleans, and Puerto Rico were recruited using fliers and word of mouth to healthcare providers. Those who contacted research staff were interviewed to determine food safety knowledge gaps and risky behaviors. A food safety educational comic book that targeted knowledge gaps was created, piloted, and provided to these patients who were instructed to read it and return at least 2 weeks later for a follow-up interview. The overall food safety score was determined by the number of the 26 knowledge/belief/behavior questions from the survey answered correctly. Among 150 patients who participated in both the baseline and follow-up questionnaire, the intervention resulted in a substantial increase in the food safety score (baseline 59%, post-intervention 81%, p<0.001). The intervention produced a significant increase in all the food safety knowledge, belief, and behavior items that comprised the food safety score. Many of these increases were from baseline knowledge below 80 percent to well above 90%. Most (85%) of the patients stated they made a change to their behavior since receiving the educational booklet. Conclusion This comic book format intervention to educate persons living with AIDS was highly effective. Future studies should examine to what extent long-term behavioral changes result. PMID:24124447

  12. Toward a comprehensive long term nicotine policy

    PubMed Central

    Gray, N; Henningfield, J; Benowitz, N; Connolly, G; Dresler, C; Fagerstrom, K; Jarvis, M; Boyle, P

    2005-01-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source. PMID:15923465

  13. Long term changes in the polar vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  14. Long-Term Care Policy: Singapore's Experience.

    PubMed

    Chin, Chee Wei Winston; Phua, Kai-Hong

    2016-01-01

    Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co-payment and targeting of state support to the low-income population through means-tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers. PMID:26808468

  15. Long-term anticoagulation. Indications and management.

    PubMed Central

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

    1989-01-01

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

  16. Long-term outcome in personality disorders.

    PubMed

    Stone, M H

    1993-03-01

    Personality disorders meeting DSM or ICD criteria represent the severe end of the broad spectrum of personality configurations involving maladaptive traits. The literature regarding long-term outcome of personality disorders is sparse. Most attention is devoted to formerly institutionalised patients with borderline, antisocial, or schizotypal disorders. Borderline patients at 10-25-year follow-up have a wide range of outcomes, from clinical recovery (50-60%) to suicide (3-9%). Certain factors (e.g. artistic talent) conduce to higher recovery rates, others (e.g. parental cruelty) to lower rates. Schizoid and schizotypal patients tend to remain isolated, and to lead marginal lives. The long-term outcome in antisocial persons is bleak if psychopathic traits are prominent. Personality traits and their corresponding disorders are egosyntonic, harden into habit, and are both slow to change and hard to modify. There is no one treatment of choice. Psychoanalysis and related methods work best within the anxious/inhibited group; cognitive/behavioural techniques are well suited to the disorders requiring limit setting and the amelioration of maladaptive habits. PMID:8453424

  17. Long term perfusion system supporting adipogenesis.

    PubMed

    Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L

    2015-08-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogenesis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  18. Long Term Changes in the Polar Vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2016-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented. The unusual meteorological conditions of the 2015 south polar vortex and the 2010/11 and 2015/16 north polar vortices will be compared to other recent years.

  19. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  20. Long-term mechanical ventilation and nutrition.

    PubMed

    Ambrosino, Nicolino; Clini, Enrico

    2004-05-01

    Mechanical ventilation (MV) in chronic situations is commonly used, either delivered invasively or by means of non-invasive interfaces, to control hypoventilation in patients with chest wall, neuromuscular or obstructive lung diseases (either in adulthood or childhood). The global prevalence of ventilator-assisted individuals (VAI) in Europe ranges from 2 to 30 per 100000 population according to different countries. Nutrition is a common problem to face with in patients with chronic respiratory diseases: nonetheless, it is a key component in the long-term management of underweight COPD patients whose muscular disfunction may rapidly turn to peripheral muscle waste. Since long-term mechanical ventilation (LTMV) is usually prescribed in end-stage respiratory diseases with poor nutritional status, nutrition and dietary intake related problems need to be carefully assessed and corrected in these patients. This paper aims to review the most recent innovations in the field of nutritional status and food intake-related problems of VAI (both in adulthood and in childhood).

  1. Toward a comprehensive long term nicotine policy.

    PubMed

    Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

    2005-06-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source. PMID:15923465

  2. Long-term Trend of Sunspot Numbers

    NASA Astrophysics Data System (ADS)

    Gao, P. X.

    2016-10-01

    Using the Hilbert–Huang Transform method, we investigate the long-term trend of yearly mean total sunspot numbers in the time interval of 1700–2015, which come from the World Data Center—the sunspot Index and long-term solar observations. The main findings of this study are summarized below. (1) From the adaptive trend, which is extracted from the yearly mean total sunspot numbers, we can find that the value gradually increases during the time period 1700–1975, then decreases gradually from 1975 to 2015. (2) The Centennial Gleissberg Cycle is extracted from the yearly mean total sunspot numbers and confirms that a new grand minimum is in progress; the Dalton Minimum, the Gleissberg Minimum, and low level of solar activity during solar cycle 24 (the part of the new grand minimum) all can be understood as minima of the Centennial Gleissberg Cycle. (3) Based on the adaptive (overall) trend, and the 100-year and longer timescale trend of yearly mean total sunspot numbers, we can infer that the level of solar activity during the new grand minimum may be close to that during the Gleissberg Minimum, slightly higher than that during the Dalton Minimum, and significantly higher than that during the Maunder Minimum. Our results do not support the suggestion that a new grand minimum, somewhat resembling the Maunder Minimum, is in progress.

  3. Long term perfusion system supporting adipogenesis.

    PubMed

    Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L

    2015-08-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogenesis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight.

  4. Efficacy and safety of topical cyclosporine A 0.05% in vernal keratoconjunctivitis

    PubMed Central

    Yücel, Ozlem Eski; Ulus, Nihal Demir

    2016-01-01

    INTRODUCTION While corticosteroids are an effective choice of treatment for severe vernal keratoconjunctivitis (VKC), their long-term use is restricted due to side effects. This study was conducted to evaluate the efficacy and safety of topical cyclosporine A (CsA) 0.05% in the treatment of VKC. METHODS A total of 30 patients with VKC that was resistant to topical corticosteroids, antihistamines and mast cell stabilisers were treated with topical CsA 0.05%. Patients were evaluated at Weeks 4, 8 and 12 after the initiation of therapy. Symptoms and signs observed before and after treatment were recorded and scores were assigned. Scores for symptoms and signs, the need for topical corticosteroids and ocular side effects were evaluated. RESULTS At baseline, the median values of the symptom and sign scores were 10.0 (range 5.0–18.0) and 6.0 (range 2.0–13.0), respectively. At Week 4 of treatment with topical CsA 0.05%, the median values of the symptom and sign scores were 3.0 (range 0–14.0) and 3.0 (range 0–8.0), respectively. The reductions in the symptom and sign scores were statistically significant. The reduction in the need for corticosteroid was statistically significant by Week 12 of therapy. No significant side effects were reported. CONCLUSION Topical CsA 0.05%, which can help to reduce corticosteroid usage, is an effective and safe alternative for the treatment of resistant VKC. Further studies are needed to determine the optimal duration of therapy and possibility of recurrence. PMID:26768065

  5. Safety and Efficacy of Bimatoprost for Eyelash Growth in Postchemotherapy Subjects

    PubMed Central

    Baumann, Leslie; Bruce, Suzanne; Ahluwalia, Gurpreet; Weng, Emily; Daniels, Selena

    2015-01-01

    Objective: To evaluate long-term efficacy and safety of bimatoprost for treatment of chemotherapy-induced eyelash hypotrichosis. Design: One-year, multicenter, double-masked, parallel-group study. Setting: Twenty-one centers in the United States and one center in the United Kingdom. Participants: This study randomized (3:1) 130 subjects to bimatoprost 0.03% or vehicle applied topically to upper eyelid margins for six months. All subjects used bimatoprost for a second six months. Measurements: Responders for the primary composite end point achieved ≥1-grade improvement in Global Eyelash Assessment score and ≥3-point improvement in Confidence, Attractiveness, and Professionalism domain score of the Eyelash Satisfaction Questionnaire at Month 4. Secondary assessments included eyelash length, thickness, and darkness, using digital image analysis. Results: The responder rate was significantly higher with bimatoprost versus vehicle at Month 4 (37.5% vs. 18.2%; p=0.041) and Month 6 (46.9% vs. 18.2%; p=0.004). Significant improvements favoring bimatoprost occurred in eyelash length (p=0.008), thickness (p<0.001), or darkness (p=0.029) at Month 4, with similar results at Month 6 (p<0.001, length; p<0.001, thickness; p=0.002, darkness). Responder rates reached 61.5 percent at Month 12 for subjects continuing bimatoprost and 67.6 percent for those switched from vehicle to bimatoprost. Conjunctival hyperemia (16.7%) and punctate keratitis (9.4%) were the most common adverse events. Conclusion: Bimatoprost provides rapid eyelash recovery, whether started shortly after chemotherapy (4 to 12 weeks) or delayed for six months, with minimal adverse events. Clinical trial registry: NCT00907426 PMID:26060513

  6. Long-term use of adalimumab in the treatment of rheumatic diseases

    PubMed Central

    Papagoras, Charalampos; Voulgari, Paraskevi V; Drosos, Alexandros A

    2009-01-01

    Adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor-alpha (TNFα), has been evaluated in various randomized placebo-controlled trials in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis. In the short time frame of these trials adalimumab has been shown to be effective in reducing disease activity, slowing radiographic disease progression and improving patients’ quality of life, while at the same time demonstrating an acceptable safety profile. Furthermore, release of adalimumab on the market, prospective observational studies, as well as open-label extensions of the original double-blind trials have provided experience and data about the long-term efficacy and safety of the drug. Initial effectiveness, in terms of reducing disease activity, is sustained, while in most cases patients treated with adalimumab experienced a slower radiographic progression and consequently less disability and improved health-related quality-of-life outcomes. Moreover, long-standing treatment of thousands of patients with adalimumab outside the controlled context of clinical trials was not related to new safety signals, with the most common adverse events being respiratory infections. The most common serious adverse events seem to be tuberculosis reactivation, while a putative association with malignant lymphoma development is not yet proven. Besides, both of these adverse reactions pertain to the whole TNFα blocker group. In conclusion, adalimumab is a safe and effective option for the treatment of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis.

  7. Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals

    PubMed Central

    Zhang, Ming-Duo; Li, Xin-He; Nie, Mao-Xiao; Feng, Ting-Ting; Zhao, Xin; Wang, Lu-Ya; Zhao, Quan-Ming

    2016-01-01

    Objective In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs). Methods PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted. Results Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61–0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57–0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33–0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents. Conclusion Our results indirectly suggest that

  8. Long-Term Efficacy of Postpartum Intravenous Iron Therapy

    PubMed Central

    Zimmermann, Roland

    2014-01-01

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

  9. Long-term performance of filtration layer

    NASA Astrophysics Data System (ADS)

    Radfar, A.; Rockaway, T. D.

    2013-12-01

    Permeable pavements are commonly employed to capture and divert stormwater before it enters the stormwater or sewer conveyance systems. During a storm event, runoff water passes through the permeable pavement surface, enters a storage gallery and finally exfiltrates into the surrounding soil. Thus, the ability of the system to store an appropriate volume of runoff water is an important consideration for stormwater control design. Traditionally, crushed stone or other porous material has been used to provide the necessary interstitial void space to store the runoff water. Unfortunately, over time the available void space within the storage gallery is reduced due to settlement, biological growth and sediment accumulation. This gradual reduction in void space reduces the long-term effectiveness of these stormwater controls by limiting its ability to store and pass runoff water. This study examined the long-term performance of the storage gallery layer with respect to its ability to both store and pass runoff water. As the porosity within the storage gallery decreased, it was anticipated that volumetric water content within the gallery would increase and that time necessary to drain the gallery would increase as well. The effects of the gallery porosity were assessed over a one-year study using both laboratory experimentation and monitoring data from naturally occurring rain events. Changes in gallery porosity were first assessed by correlating monitoring piezometer data with surface infiltration testing; building a relation between know volume of poured water being used for the test and the associated pressure head at the base of the gallery. As a known volume of water enters the system, volume change in the gallery directly correlate to increases in pressure head. Second, the time required for water to permeate through pavers and gallery layer to trigger the TDRs in the filtration layer and the time to drain it from the crushed stone were calculated and compared by

  10. Managing soils for long-term productivity

    PubMed Central

    Syers, J. K.

    1997-01-01

    Meeting the goal of long-term agricultural productivity requires that soil degradation be halted and reversed. Soil fertility decline is a key factor in soil degradation and is probably the major cause of declining crop yields. There is evidence that the contribution of declining soil fertility to soil degradation has been underestimated.
    Sensitivity to soil degradation is implicit in the assessment of the sustainability of land management practices, with wide recognition of the fact that soils vary in their ability to resist change and recover subsequent to stress. The concept of resilience in relation to sustainability requires further elaboration and evaluation.
    In the context of soil degradation, a decline in soil fertility is primarily interpreted as the depletion of organic matter and plant nutrients. Despite a higher turnover rate of organic matter in the tropics there is no intrinsic difference between the organic matter content of soils from tropical and temperate regions. The level of organic matter in a soil is closely related to the above and below ground inputs. In the absence of adequate organic material inputs and where cultivation is continuous, soil organic matter declines progressively. Maintaining the quantity and quality of soil organic matter should be a guiding principle in developing management practices.
    Soil microbial biomass serves as an important reservoir of nitrogen (N), phosphorus (P) and sulphur (S), and regulates the cycling of organic matter and nutrients. Because of its high turnover rate, microbial biomass reacts quickly to changes in management and is a sensitive indicator for monitoring and predicting changes in soil organic matter. Modelling techniques have been reasonably successful in predicting changes in soil organic matter with different organic material inputs, but there is little information from the tropics.
    Nutrient depletion through harvested crop components and residue removal, and by leaching and soil

  11. Efficacy and Safety of Tribendimidine Against Clonorchis sinensis

    PubMed Central

    Qian, Men-Bao; Yap, Peiling; Yang, Yi-Chao; Liang, Hai; Jiang, Zhi-Hua; Li, Wei; Tan, Yu-Guang; Zhou, Hui; Utzinger, Jürg; Zhou, Xiao-Nong; Keiser, Jennifer

    2013-01-01

    Background. Clonorchiasis is of considerable public health importance, particularly in the People's Republic of China (PR China), where most of the 15 million individuals infected with Clonorchis sinensis are currently concentrated. Praziquantel is the drug of choice, but tribendimidine might be an alternative. Methods. We performed a randomized open-label trial in Guangxi, PR China, to assess the efficacy and safety of 400 mg tribendimidine once, 400 mg tribendimidine daily for 3 days, and 75 mg/kg praziquantel in 1 day divided in 3 doses against parasitological-confirmed C. sinensis infections. Cure and egg reduction rates were determined 3 weeks posttreatment using available case analysis. Clinical symptoms were documented at baseline, and adverse events were recorded and graded 3 and 24 hours after each dose. Results. A total of 74 patients were included in the final analysis. Single-dose tribendimidine achieved a cure rate of 44%, whereas cure rates of 58% and 56% were obtained for tribendimidine administered for 3 days and praziquantel, respectively. High egg reduction rates (97.6%–98.8%) were observed for all treatment regimens. Single-dose tribendimidine was the best-tolerated treatment scheme. Patients treated with praziquantel experienced significantly more adverse events than did tribendimidine recipients (P < .05). Conclusions. Tribendimidine has an efficacy comparable to praziquantel in the treatment of C. sinensis infection and resulted in fewer adverse events compared to praziquantel. Larger clinical trials are warranted among C. sinensis–infected patients to determine the potential of tribendimidine against clonorchiasis and other helminthiases. Clinical Trials Registration. Controlled-Trials.com, ISRCTN80829842. PMID:23223597

  12. Efficacy and Safety of Bone Marrow Cell Transplantation for Chronic Ischemic Heart Disease: A Meta-Analysis

    PubMed Central

    Xiao, Chun; Zhou, Shijie; Liu, Yueqiang; Hu, Huozhen

    2014-01-01

    Background Although bone marrow-derived cells (BMCs) have shown great therapeutic potential in patients with chronic ischemic heart disease (CIHD), the exact efficacy and safety of BMCs therapy is still not completely defined. Material/Methods We searched PubMed, OVID, EMBASE, the Cochrane Library, and ClinicalTrials.gov and finally identified 20 qualified trials in this meta-analysis. Assessment of efficacy was based on left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) improvement, by weighted mean difference (WMD) with 95% confidence intervals (CIs). Results of all-cause death, ventricular arrhythmia, recurrent myocardial infarction, and cerebrovascular accident were pooled to assess safety. Subgroup analysis was performed by stratifying RCTs into 2 subgroups of those with revascularization and without revascularization. Results BMC transplantation significantly improved LVEF in patients with revascularization (3.35%, 95% CI 0.72% to 5.97%, p=0.01; I2=85%) and without revascularization (3.05%, 95% CI 0.65% to 5.45%, p=0.01; I2=86%). In patients without revascularization, BMC transplantation was associated with significantly decreased LVESV (−11.75 ml, 95% CI −17.81 ml to −5.69 ml, p=0.0001; I2=81%), and LVEDV (−7.80 ml, 95% CI −15.31 ml to −0.29 ml, p=0.04; I2=39%). Subgroup analysis showed that the route of transplantation, baseline LVEF, and type of cells delivered could influence the efficacy of BMC transplantation. Conclusions Autologous transplantation of BMCs was safe and effective for patients who were candidates for revascularization with CABG/PCI and those who were not. However, large clinical trials and long-term follow-up are required to confirm these benefits. PMID:25270584

  13. Emotional behavior in long-term marriage.

    PubMed

    Carstensen, L L; Gottman, J M; Levenson, R W

    1995-03-01

    In exploring the emotional climate of long-term marriages, this study used an observational coding system to identify specific emotional behaviors expressed by middle-aged and older spouses during discussions of a marital problem. One hundred and fifty-six couples differing in age and marital satisfaction were studied. Emotional behaviors expressed by couples differed as a function of age, gender, and marital satisfaction. In older couples, the resolution of conflict was less emotionally negative and more affectionate than in middle-aged marriages. Differences between husbands and wives and between happy and unhappy marriages were also found. Wives were more affectively negative than husbands, whereas husbands were more defensive than wives, and unhappy marriages involved greater exchange of negative affect than happy marriages.

  14. Long-term monitoring for closed sites

    SciTech Connect

    Golchert, N.W.; Sedlet, J.; Veluri, V.R.

    1985-01-01

    A procedure is presented for planning and implementing a long-term environmental monitoring program for closed low-level radioactive waste disposal sites. The initial task in this procedure is to collect the available information on the legal/regulatory requirements, site and area characteristics, source term, pathway analysis, and prior monitoring results. This information is coupled with parameters such as half-life and retardation factors to develop a monitoring program. As examples, programs are presented for a site that has had little or no waste migration, and for sites where waste has been moved by suface water, by ground water, and by air. Sampling techniques and practices are discussed relative to how a current program would be structured and projections are made on techniques and practices expected to be available in the future. 8 refs., 2 figs.

  15. Long term evolution of comet Halleys orbit.

    NASA Astrophysics Data System (ADS)

    Dvorak, R.; Kribbel, J.

    1987-03-01

    The aim of the paper is to study the long term evolution of comet Halleys orbit taking into account small errors in the initial conditions. Recent papers deal with mapping methods to model cometary dynamics; (e.g. Petrosky and Broucke, 1987 and Chirikov and Vecheslavov, 1986). They will be discussed critically and compared with our own results. We then tested the model using numerical integration methods. For the moment we limited our calculation to 2.105 years, but a 106 year integration is still in progress. We show the expected dynamical evolution of Hallyes orbit taking into account also smaller and larger errors of the initial conditions (nongravitational effects are only roughly estimated). Finally we discuss alsothe controversal opinions concerning the role of the planets (especially the earth).

  16. Long-term control of root growth

    DOEpatents

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene

    1992-05-26

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

  17. Energy medicine for long-term disabilities.

    PubMed

    Trieschmann, R B

    1999-01-01

    Energy medicine techniques derive from traditional Chinese medicine and are based upon the concept that health and healing are dependent upon a balance of vital energy, a still mind, and controlled emotions. Physical dysfunctions result from disordered patterns of energy of long standing and reversal of the physical problem requires a return to balanced and ordered energy. Qi Gong (Chi Kung) is a system which teaches an individual to live in a state of energy balance. Shen Qi is a sophisticated form of Qi Gong which relies on no external physical interventions but rather relies on mind control to prevent illness, heal existing physical and emotional problems, and promote health and happiness. This paper will describe the use of these techniques with people who have long-term physical disabilities.

  18. [Enteral nutrition through long-term jejunostomy].

    PubMed

    Fernández, T; Neira, P; Enríquez, C

    2008-01-01

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

  19. Radiation risk during long-term spaceflight

    NASA Astrophysics Data System (ADS)

    Petrov, V. M.

    Cosmonauts` exposure to cosmic rays during long-term spaceflight can cause unfavorable effects in health and risk for the crew members` lives. All unfavorable effects induced by exposure should be taken into consideration for the risk estimation. They should include both the acute deterministic effects and delayed effects called stochastic. On the ground the limitation of unfavorable consequences of acute exposure is achieved by means of establishing dose limits. But in space applications this approach can't be acceptable. Establishing a fixed dose limit is adequate to introducing indefinite reserve coefficient and therefore ineffective usage of spacecraft resource. The method of radiation risk calculation caused by acute and delayed effects of cosmonauts' exposure is discussed and substantiated in the report. Peculiarities of the impact of permanent radiation sources (galactic cosmic rays and trapped radiation) and the variable one (solar cosmic rays) are taken into consideration.

  20. Long-term control of root growth

    SciTech Connect

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

    1992-05-26

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

  1. Reducing long-term reservoir performance uncertainty

    SciTech Connect

    Lippmann, M.J.

    1988-04-01

    Reservoir performance is one of the key issues that have to be addressed before going ahead with the development of a geothermal field. In order to select the type and size of the power plant and design other surface installations, it is necessary to know the characteristics of the production wells and of the produced fluids, and to predict the changes over a 10--30 year period. This is not a straightforward task, as in most cases the calculations have to be made on the basis of data collected before significant fluid volumes have been extracted from the reservoir. The paper describes the methodology used in predicting the long-term performance of hydrothermal systems, as well as DOE/GTD-sponsored research aimed at reducing the uncertainties associated with these predictions. 27 refs., 1 fig.

  2. Radiation risk during long-term spaceflight.

    PubMed

    Petrov, V M

    2002-01-01

    Cosmonauts' exposure to cosmic rays during long-term spaceflight can cause unfavorable effects in health and risk for the crew members' lives. All unfavorable effects induced by exposure should be taken into consideration for the risk estimation. They should include both the acute deterministic effects and delayed effects called stochastic. On the ground the limitation of unfavorable consequences of acute exposure is achieved by means of establishing dose limits. But in space applications this approach can't be acceptable. Establishing a fixed dose limit is adequate to introducing indefinite reserve coefficient and therefore ineffective usage of spacecraft resource. The method of radiation risk calculation caused by acute and delayed effects of cosmonauts' exposure is discussed and substantiated in the report. Peculiarities of the impact of permanent radiation sources (galactic cosmic rays and trapped radiation) and the variable one (solar cosmic rays) are taken into consideration. PMID:12539775

  3. Long term performance of radon mitigation systems

    SciTech Connect

    Prill, R.; Fisk, W.J.

    2002-03-01

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes.

  4. Advanced long term cryogenic storage systems

    NASA Technical Reports Server (NTRS)

    Brown, Norman S.

    1987-01-01

    Long term, cryogenic fluid storage facilities will be required to support future space programs such as the space-based Orbital Transfer Vehicle (OTV), Telescopes, and Laser Systems. An orbital liquid oxygen/liquid hydrogen storage system with an initial capacity of approximately 200,000 lb will be required. The storage facility tank design must have the capability of fluid acquisition in microgravity and limit cryogen boiloff due to environmental heating. Cryogenic boiloff management features, minimizing Earth-to-orbit transportation costs, will include advanced thick multilayer insulation/integrated vapor cooled shield concepts, low conductance support structures, and refrigeration/reliquefaction systems. Contracted study efforts are under way to develop storage system designs, technology plans, test article hardware designs, and develop plans for ground/flight testing.

  5. Brodie's abscess. A long-term review.

    PubMed

    Stephens, M M; MacAuley, P

    1988-09-01

    In 20 patients with 21 Brodie's abscesses, a long-term review revealed that 13 occurred in the second decade of life. All had local symptoms for six weeks or more. The tibia was involved in 11 cases and seven of these were in the proximal metaphysis. The erythrocyte sedimentation rate (ESR) was elevated in only six cases. When the ESR was more than 40 mm per hour, recurrence was more likely. Staphylococcus aureus was cultured from 11 abscesses. Curettage and antibiotics for six weeks were adequate for treatment in most cases. However, lesions larger than 3 cm in diameter should be grafted, and patients with an elevated ESR require more aggressive decompression and prolonged antibiotic therapy. Lesions within the neck of the femur pose particular anatomic problems and should not be approached laterally. All cases were followed to full bone maturity. No significant leg length inequality was clinically or roentgenologically apparent. If an abscess was juxtaphyseal, deformity of the epiphysis could develop.

  6. Managing Records for the Long Term - 12363

    SciTech Connect

    Montgomery, John V.; Gueretta, Jeanie

    2012-07-01

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

  7. Long-term dynamics of Typha populations

    USGS Publications Warehouse

    Grace, J.B.; Wetzel, R.G.

    1998-01-01

    The zonation of Typha populations in an experimental pond in Michigan was re-examined 15 years after the original sampling to gain insight into the long-term dynamics. Current distributions of Typha populations were also examined in additional experimental ponds at the site that have been maintained for 23 years. The zonation between T. latifolia and T. angustifolia in the previously studied pond 15 years after the initial sampling revealed that the density and distribution of shoots had not changed significantly. Thus, it appears that previously reported results (based on 7- year old populations) have remained consistent over time. Additional insight into the interaction between these two taxa was sought by comparing mixed and monoculture stands in five experimental ponds that have remained undisturbed for their 23-year history. The maximum depth of T. latifolia, the shallow- water species, was not significantly reduced when growing in the presence of the more flood tolerant T. angustifolia. In contrast, the minimum depth of T. angustifolia was reduced from 0 to 37 cm when in the presence of T. latifolia. When total populations were compared between monoculture and mixed stands, the average density of T. angustifolia shoots was 59.4 percent lower in mixed stands while the density of T. latifolia was 32 percent lower, with T. angustifolia most affected at shallow depths (reduced by 92 percent) and T. latifolia most affected at the deepest depths (reduced by 60 percent). These long-term observations indicate that competitive displacement between Typha taxa has remained stable over time.

  8. Long-term effects of dynamic aortomyoplasty.

    PubMed

    Chachques, J C; Haab, F; Cron, C; Fischer, E C; Grandjean, P; Bruneval, P; Acar, C; Jebara, V A; Fontaliran, F; Carpentier, A F

    1994-07-01

    Aortomyoplasty consists of wrapping the latissimus dorsi muscle (LDM) around the ascending aorta and electrostimulating it during diastole. The ascending aorta will act as an ectopic neo-ventricle compressed during diastole, thus reproducing the effects of long-term diastolic counterpulsation. In 5 goats, the right LDM was transferred to the thoracic cavity after removal of the second rib. The ascending aorta was enlarged by a pericardial patch and wrapped with the LDM. Postoperative electrostimulation was delivered in a counterpulsating manner. Hemodynamic studies were performed at 12 and 24 months postoperatively. Percent increase in the subendocardial viability index (diastolic pressure-time index/systolic tension-time index) was calculated using unassisted and assisted cardiac cycles with the stimulator off versus the stimulator on at a 1:1 ratio in the basal state and after acute heart failure was induced by the administration of high doses of propranolol hydrochloride. Diastolic counterpulsation of the ascending aorta resulted in significant improvement in the subendocardial viability index long term, both in basal state conditions and after induced cardiac failure. During heart failure, aortomyoplasty increased the cardiac output and decreased systemic vascular resistance. Histopathologic studies up to 24 months showed preservation of the histologic structure of the aortic wall and no evidence of thromboembolism. Tight adhesions developed between the aortic wall (including the pericardial patch) and the LDM. The diameters of the enlarged aortas showed no significant differences compared with diameters immediately postoperatively. In conclusion, aortomyoplasty produces chronic diastolic augmentation with preservation of aortic structure. After induction of heart failure, aortomyoplasty offers efficient circulatory support.

  9. Efficacy and Safety of Minoxidil 5% Foam in Combination With a Botanical Hair Solution in Men With Androgenic Alopecia.

    PubMed

    Keaney, Terrence C; Pham, Hanh; von Grote, Erika; Meckfessel, Matthew H

    2016-04-01

    Androgenic alopecia (AGA) is the most common type of hair loss in men, characterized by hair miniaturization, hairline recession, and vertex balding. It affects approximately 50% of men, negatively affecting self-esteem and sociability. Topical minoxidil formulations are approved up to a 5% concentration for men, but patient adherence to treatment is challenged by gradual results that may be perceived as a lack of initial benefit. Herbal extracts, which are also believed to promote healthier-looking hair, have a long history of use in hair care formulations. The safety and efficacy of a twice-daily regimen of 5% minoxidil foam used in combination with a novel botanical hair solution was evaluated in a 12-week, multicenter, single-arm, open label study in 56 subjects with mild to moderate AGA. Assessments included investigator ratings of improvement and subject self-ratings of satisfaction. Investigator ratings indicated significant improvement in scalp hair coverage and perception of overall treatment benefit in as early as 4 weeks (P<.001). Subject self-ratings were significant for improved hair growth and hair appearance in as few as 4 weeks (P<.05). The regimen was well tolerated, and subjects indicated a high degree of satisfaction. Investigator and subject-assessed efficacy and subject satisfaction with this novel regimen provide clinicians with an effective treatment option for AGA that also provides a high level of patient satisfaction, which may help promote patient adherence to long-term treatment. PMID:27050695

  10. Efficacy and safety of a polyherbal formulation in hemorrhoids

    PubMed Central

    Tripathi, Raakhi K.; Bolegave, Somesh S.; Shetty, Parvan A.; Uchil, Dinesh A.; Rege, Nirmala N.; Chawda, Mukesh B.; Rege, Sameer A.

    2015-01-01

    Background: The medical management of hemorrhoids should include an integrated approach. This integrated approach can be achieved by polyherbal formulations containing anti-inflammatory, styptics, analgesics, and laxative effect which reduce inflammation, pain, and bleeding, and increase gastro-intestinal motility and soften stools. One such polyherbal kit is “Arshkeyt™, a 7 day kit,” which consists of oral tablets and powder along with topical cream. Objective: Efficacy and safety of Arshkeyt™, a 7 day kit, a marketed polyherbal formulation was evaluated in comparison with conventional therapy practiced in surgery outpatient departments. Materials and Methods: Patients (n = 90) with hemorrhoids were randomly allocated to receive either Arshkeyt™ or standard therapy (combination of oral Isabgul powder and 2% lidocaine gel) for 14 days. Assessment on the basis of rectal symptoms and proctoscopic examination was done on day 0, 7, and 14 to derive a “composite score” which ranged from 0 to 25 by a blinded evaluator. The primary endpoint was number of patients achieving composite score 0 at the end of therapy (day 14). Inter-group analysis was done using Chi-square test. Results: On day 14, the composite score of 0 was achieved in 15 patients of Arshkeyt™ group versus 6 patients receiving standard therapy. The symptoms and signs which showed significant improvement in Arshkeyt™ group compared to standard treatment group were the tenesmus (visual analog score) score (P = 0.047), anal sphincter spasm (P = 0.0495) and a decrease in the grade of hemorrhoids (P = 0.0205) on day 14. Arshkeyt™ was also more beneficial in case of bleeding hemorrhoids as compared to nonbleeding hemorrhoids (P < 0.05). The incidence of adverse drug reactions in both groups was comparable and no patient required any treatment for the same. Conclusion: “Arshkeyt™, a 7 day kit,” was effective in the treatment of hemorrhoids and had a good safety profile. PMID:26834421

  11. Ocular hypotensive efficacy and safety of once daily carteolol alginate

    PubMed Central

    Demailly, P.; Allaire, C.; Trinquand, C.

    2001-01-01

    BACKGROUND/AIM—Carteolol is a β adrenoceptor antagonist used topically to re