Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

PubMed

Papp, Kim A; Krueger, James G; Feldman, Steven R; Langley, Richard G; Thaci, Diamant; Torii, Hideshi; Tyring, Stephen; Wolk, Robert; Gardner, Annie; Mebus, Charles; Tan, Huaming; Luo, Yingchun; Gupta, Pankaj; Mallbris, Lotus; Tatulych, Svitlana

2016-05-01

Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. There was no dose comparison beyond week 52. Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

An Open-Label Study of the Long-Term Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (RECAP).

PubMed

Costabel, Ulrich; Albera, Carlo; Lancaster, Lisa H; Lin, Chin-Yu; Hormel, Philip; Hulter, Henry N; Noble, Paul W

2017-01-01

RECAP (NCT00662038) was an open-label extension study in patients with idiopathic pulmonary fibrosis (IPF) who completed either the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) 016 phase 3 trial or the Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY) 004/006 phase 3 trials. To obtain long-term safety data for pirfenidone in patients with IPF in RECAP. Of the 1,334 patients who participated in the phase 3 trials, 1,058 entered RECAP. The final analysis from enrollment (September 2008) to June 2015 is presented. Mean (SD) and median (range) pirfenidone exposures in RECAP were 122 (98) weeks and 88 (>0 to 349) weeks, respectively, with a mean daily dose of 2,091.1 mg. Cumulative total exposure was 2,482 patient exposure years (PEY). The treatment-emergent adverse event (TEAE) rate was 701.9 per 100 PEY. The serious TEAE rate was 53.5 per 100 PEY, with the most common serious TEAE being IPF (11.1 per 100 PEY). Of the 231 deaths (9.3 per 100 PEY), the most common cause was IPF (5.4 per 100 PEY). The treatment discontinuation rate due to a TEAE was 17.9 per 100 PEY; discontinuations were due to IPF (7.2 per 100 PEY), pneumonia, respiratory failure, acute respiratory failure, rash (0.5 per 100 PEY each), and nausea (0.4 per 100 PEY). For patients from CAPACITY 004/006 who entered RECAP, the mean change in percent predicted forced vital capacity from RECAP baseline at 180 weeks was -9.6%. Median on-treatment survival from the first pirfenidone dose in RECAP was 77.2 months. RECAP provides long-term follow-up and safety data for pirfenidone that were consistent with the known profile, with no new safety signals observed. © 2017 The Author(s) Published by S. Karger AG, Basel.

Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients.

PubMed

Liu, Yong; Chen, Shao Jun; Li, Shi Ying; Qu, Ling Hui; Meng, Xiao Hong; Wang, Yi; Xu, Hai Wei; Liang, Zhi Qing; Yin, Zheng Qin

2017-09-29

Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients. In our pre-clinical study, purified human fetal-derived retinal progenitor cells (RPCs) were transplanted into the diseased retina of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. Based on these results, we conducted a phase I clinical trial to establish the safety and tolerability of transplantation of RPCs in eight patients with advanced retinitis pigmentosa. Patients were studied for 24 months. After RPC transplantation in RCS rats, we observed moderate recovery of vision and maintenance of the outer nuclear layer thickness. Most importantly, we did not find tumor formation or immune rejection. In the retinis pigmentosa patients given RPC injections, we also did not observe immunological rejection or tumorigenesis when immunosuppressive agents were not administered. We observed a significant improvement in visual acuity (P < 0.05) in five patients and an increase in retinal sensitivity of pupillary responses in three of the eight patients between 2 and 6 months after the transplant, but this improvement did not appear by 12 months. Our study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa. WHO Trial Registration, ChiCTR-TNRC-08000193 . Retrospectively registered on 5 December 2008.

Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study.

PubMed

Vassilopoulos, Dimitrios; Delicha, Evie M; Settas, Loukas; Andrianakos, Alexandros; Aslanidis, Spyros; Boura, Panagiota; Katsounaros, Marios; Athanassiou, Panagiotis; Tempos, Konstantinos; Skarantavos, Grigorios; Antoniadis, Christodoulos; Papazoglou, Sotirios; Sakkas, Lazaros; Galanopoulou, Vassiliki; Skopouli, Fotini; Boki, Kyriaki; Daoussis, Dimitrios; Vritzali, Eleni; Sfikakis, Petros P

2016-01-01

To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice. This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to ≥1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months. 234 patients (mean age: 59±12.5, 79.5% women, mean DAS28: 5.35±1.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient-years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age ≥65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy. Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation.

Long-term effects of employer-based programs to motivate safety belt use

DOT National Transportation Integrated Search

1987-02-01

This report reviews the procedures and results of 28 different programs that increased employees' use of vehicle safety belts at ten work settings (with 141 to 6,727 employees) ranging from a minimum long-term gain of 12% over baseline to a maximum g...

A double-blind study evaluating the long-term safety of varenicline for smoking cessation.

PubMed

Williams, Kathryn E; Reeves, Karen R; Billing, Clare B; Pennington, Ann M; Gong, Jason

2007-04-01

We assessed the safety of long-term varenicline administration for smoking cessation. In this randomized, double-blind, multicenter trial, eligible adult smokers (18-75 years) who smoked an average of > or =10 cigarettes/day were randomized to either varenicline 1 mg twice daily (BID) or placebo for 52 weeks. Subjects made weekly clinic visits until week 8, and then every 4 weeks until week 52, with a follow-up visit at week 53. The target quit date was the morning of the week 1 clinic visit. Brief counseling was provided at each visit, and vital signs, adverse events (AEs), and smoking status were documented. Other laboratory measures were collected at specified visits. A total of 251 subjects were randomized to varenicline and 126 to placebo. Approximately half of the subjects in each arm completed the study (53.8% varenicline; 46.8% placebo). Treatment-emergent AEs were observed in 96.4% of varenicline- and 82.5% of placebo-treated subjects during the study. Common varenicline-associated AEs were nausea (40.2%), abnormal dreams (22.7%), and insomnia (19.1%). Most AEs were considered mild or moderate in intensity. AEs leading to discontinuation of varenicline treatment included nausea (7.6%), insomnia (3.2%), and abnormal dreams (2.4%). A single varenicline-related serious AE, bilateral subcapsular cataracts, was observed. At week 52, 7-day point prevalence abstinence rates were 36.7% (varenicline) and 7.9% (placebo). Varenicline 1 mg BID can be safely administered for up to 1 year. Varenicline was also a more effective smoking cessation aid than placebo throughout the study, supporting both its short- (12-week) and long-term (52-week) efficacy.

Efficacy and safety of laxatives for chronic constipation in long-term care settings: A systematic review.

PubMed

Alsalimy, N; Madi, L; Awaisu, A

2018-06-09

Constipation is a common disorder among long-term care (LTC) patients due to several factors. However, there are no systematic reviews investigating the use of laxatives for chronic constipation in LTC settings. This study aims to explore the safety and efficacy of laxatives in LTC patients. A systematic review of randomized controlled trials (RCTs) describing the efficacy and safety of laxatives for chronic constipation in LTC patients was conducted using the following databases and search engines: MEDLINE, Cochrane Database of Systematic Reviews, ScienceDirect, ProQuest and Google Scholar. Two of the investigators independently performed the searches, and the data were extracted using a standardized data abstraction tool. Seven RCTs involving 444 patients were included in the review. These studies included senna (with or without fibre, ie Plantago ovata), lactulose, sodium picosulphate, docusate sodium, docusate calcium, isotonic and hypotonic polyethylene glycol and Chinese herbal medicine. Senna and lactulose were the most studied laxatives in LTC patients, and senna was found to be superior to or as effective as other laxatives. Generally, the frequency and severity of adverse drug reactions (ADRs) were similar between the arms of the studies, and no serious ADRs were reported. Considering the short duration of the trials, the lack of trials including newer laxatives and the low quality of some of the included trials, the long-term efficacy and safety of these laxatives are not conclusive. There is a need to conduct more robust RCTs that include newer agents to evaluate long-term outcomes. © 2018 John Wiley & Sons Ltd.

Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

Isaacson, Stuart; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J; Kalu, Uwa; White, William B

2016-10-01

The long-term safety of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Parkinson disease, pure autonomic failure, multiple system atrophy, or nondiabetic autonomic neuropathy was evaluated in a phase 3, multinational, open-label study in patients who previously participated in a double-blind, placebo-controlled clinical trial of droxidopa. A total of 350 patients received droxidopa 100 to 600 mg three times daily. Mean duration of droxidopa exposure was 363 days (range, 2-1133 days). Rates of serious adverse events (AEs), cardiac-related AEs, and supine hypertension were 24%, 5%, and 5%, respectively. Most AEs, including those of a cardiovascular nature, were not attributed by investigators to droxidopa. In this large cohort of patients with neurogenic orthostatic hypotension, droxidopa was well tolerated during long-term use. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Long-term safety and effectiveness of brexpiprazole in Japanese patients with schizophrenia: A 52-week, open-label study.

PubMed

Ishigooka, Jun; Iwashita, Shuichi; Tadori, Yoshihiro

2018-06-01

This study assessed the long-term safety, tolerability, and maintenance of the therapeutic effect of brexpiprazole in Japanese patients with schizophrenia. This 52-week, open-label, flexible-dose (1-4 mg/day) study included patients with schizophrenia who continued treatment from a short-term randomized placebo-controlled fixed-dose (1, 2, or 4 mg/day) trial and de novo patients who switched from other antipsychotics. A total of 282 patients (184 de novo and 98 rolled over from short-term trial) entered the 52-week treatment with brexpiprazole, and 150 (53.2%) patients completed the week-52 assessment. Treatment-emergent adverse events (TEAE) were experienced by 235/281 patients (83.6%), and TEAE reported by ≥10% of all patients were nasopharyngitis (23.1%) and worsening of schizophrenia (22.4%). During the study, most of the TEAE were mild or moderate in severity, and there were no deaths, and no clinically meaningful mean changes in laboratory values, vital signs, or electrocardiogram parameters. Mean scores for the Positive and Negative Syndrome Scale total and Clinical Global Impression-Severity remained stable until week 52. Brexpiprazole was generally safe and well tolerated and maintained therapeutic effects in the long-term treatment of Japanese patients with schizophrenia. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marvy, A.; Lioure, A; Heriard-Dubreuil, G.

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 periodsmore » 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.« less

Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis.

PubMed

Eichenfield, Lawrence F; Call, Robert S; Forsha, Douglass W; Fowler, Joseph; Hebert, Adelaide A; Spellman, Mary; Stein Gold, Linda F; Van Syoc, Merrie; Zane, Lee T; Tschen, Eduardo

2017-10-01

Long-term topical treatment is often required for atopic dermatitis (AD), a chronic inflammatory skin disease. To assess the long-term safety results from a multicenter, open-label, 48-week safety study (AD-303) of patients (N = 517) ≥2 years of age with mild to moderate AD who continued crisaborole treatment, a topical phosphodiesterase-4 inhibitor, after completing a 28-day phase 3 pivotal study (AD-301, AD-302). Global disease severity was assessed in patients every 4 weeks, and if assessed as mild or greater, a 28-day treatment period with crisaborole applied twice daily was initiated. Adverse events (AEs), including treatment-emergent AEs (TEAEs), and serious AEs were analyzed. During the pivotal studies and AD-303, 65% of patients reported ≥1 TEAE, most of which were mild (51.2%) or moderate (44.6%) and considered unrelated to treatment (93.1%). The frequency and severity of TEAEs were consistent. The most frequently reported treatment-related AEs (overall, 10.2%) were dermatitis atopic (3.1%), application-site pain (2.3%), and application-site infection (1.2%). Nine patients (1.7%) discontinued the long-term study because of TEAEs. Long-term efficacy was not analyzed. Crisaborole ointment had a low frequency of treatment-related AEs over 48 weeks of treatment of patients with AD. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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.

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.

Testosterone Replacement Therapy: Long-Term Safety and Efficacy

PubMed Central

Corona, Giovanni; Sforza, Alessandra

2017-01-01

Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented. PMID:28497912

Testosterone Replacement Therapy: Long-Term Safety and Efficacy.

PubMed

Corona, Giovanni; Sforza, Alessandra; Maggi, Mario

2017-08-01

Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired "organic" damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an "ex-juvantibus" criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented. Copyright © 2017 Korean Society for Sexual Medicine and Andrology.

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study.

PubMed

Sekulic, Aleksandar; Migden, Michael R; Basset-Seguin, Nicole; Garbe, Claus; Gesierich, Anja; Lao, Christopher D; Miller, Chris; Mortier, Laurent; Murrell, Dedee F; Hamid, Omid; Quevedo, Jorge F; Hou, Jeannie; McKenna, Edward; Dimier, Natalie; Williams, Sarah; Schadendorf, Dirk; Hauschild, Axel

2017-05-16

In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC. One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety. At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib. This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC. This study was registered prospectively with Clinicaltrials.gov , number NCT00833417 on January 30, 2009.

Long-term 4-year safety of saxagliptin in drug-naive and metformin-treated patients with Type 2 diabetes.

PubMed

Rosenstock, J; Gross, J L; Aguilar-Salinas, C; Hissa, M; Berglind, N; Ravichandran, S; Fleming, D

2013-12-01

To evaluate the safety of saxagliptin ± metformin over 4 years in patients with Type 2 diabetes mellitus. Drug-naive (n = 401; study 11) or metformin-treated (n = 743; study 14) adults with HbA(1c) of 53-86 mmol/mol (7.0-10%) were enrolled in two randomized, placebo-controlled, double-blind trials of saxagliptin 2.5, 5 or 10 mg/day. Patients rescued during or completing 24 weeks of treatment could continue in a 42-month long-term blinded phase, for which the primary goal was assessment of safety and tolerability. Between-group efficacy was not evaluated in the long-term phase of study 11. Time to rescue or discontinuation because of inadequate glycaemic control, change from baseline in HbA(1c) and percentages of patients achieving HbA(1c) < 53 mmol/mol (< 7.0%) were assessed in study 14. No new safety findings were noted during the long-term phase. Most adverse events were mild or moderate, with slightly greater frequency of upper respiratory infections with saxagliptin. Hypoglycaemic event rates were similar with saxagliptin and placebo. In study 14, time to rescue or discontinuation because of inadequate glycaemic control was longer with saxagliptin plus metformin than for placebo plus metformin. From baseline to week 154, HbA(1c) decreased with saxagliptin but increased with placebo. Saxagliptin monotherapy or add-on to metformin is generally safe and well tolerated, with no increased risk of hypoglycaemia, for up to 4 years. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Workplace Violence and Safety Issues in Long-Term Medical Care Facilities: Nurses' Perspectives.

PubMed

Fasanya, Bankole K; Dada, Emmanuel A

2016-06-01

Workplace violence (WPV) is becoming an issue that needs immediate attention in the United States, especially during this period as more states are adopting the "stand your ground laws to promote worker protection." This study was conducted to investigate how WPV has contributed to an unsafe environment for nurses and nursing assistants who work in long-term medical care facilities. A structure questionnaire was used to collect data for the study. Three facilities were sampled and 80 nurses and certified nursing assistants participated in the study. Ninety-two percent (n = 74) were female and 8% (n = 6) were male. Approximately 62% were black or African American, approximately 33% were Caucasians, and only 2% were from other ethnicities. We found that 65% of the participants had experienced WPV while 41% believed that management shows little or no concern for their safety. Approximately 23% of respondents believed that reporting supervisor's WPV act is an unsafe action. In addition, 22% of those who reported that they have experienced WPV believed that the work environment is not safe to perform their duties. This significant difference in perception of workplace safety between those who had experienced WPV and those who had not was significant (t = 3.95, df = 158, p < 0.0001). WPV is an epidemic problem that affects all health-care professionals. The findings of this study could help long-term medical care facilities' management identify the areas to focus on mitigating, controlling, and/or eliminating incidents of WPV.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalva, Sanjeeva P., E-mail: skalva@partners.org; Marentis, Theodore C.; Yeddula, Kalpana

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-evidentmore » 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.« less

Safety analysis of long-term budesonide nasal irrigations in patients with chronic rhinosinusitis post endoscopic sinus surgery.

PubMed

Soudry, Ethan; Wang, Jane; Vaezeafshar, Reza; Katznelson, Laurence; Hwang, Peter H

2016-06-01

Although the safety of topical nasal steroids is well established for nasal spray forms, data regarding the safety of steroid irrigations is limited. We studied the effect of long-term budesonide nasal irrigations (>6 months) on hypothalamic-pituitary-adrenal axis (HPAA) function and intraocular pressure (IOP) in patients post-endoscopic sinus surgery. This was retrospective case series. Adrenal function was assessed by using the high-dose cosyntropin stimulation test. A total of 48 patients were assessed, with a mean duration of budesonide irrigations of 22 months. Stimulated cortisol levels were abnormally low in 11 patients (23%). None reported to have symptoms of adrenal suppression. Three of 4 patients who repeated the study being off budesonide for at least 1 month returned to near normal levels. Logistic regression analysis revealed that concomitant use of both nasal steroid sprays and pulmonary steroid inhalers was significantly associated with HPAA suppression (p = 0.024). Patients with low stimulated cortisol levels were able to continue budesonide irrigations under the supervision of an endocrinologist without frank clinical manifestations of adrenal insufficiency. IOP was within normal limits in all patients. Long-term use of budesonide nasal irrigations is generally safe, but asymptomatic HPAA suppression may occur in selected patients. Concomitant use of both nasal steroid sprays and pulmonary steroid inhalers while using daily budesonide nasal irrigations is associated with an increased risk. Rhinologists should be alerted to the potential risks of long-term use of budesonide nasal irrigations, and monitoring for HPAA suppression may be warranted in patients receiving long-term budesonide irrigation therapy. © 2016 ARS-AAOA, LLC.

Measuring client experiences in long-term care in the Netherlands: a pilot study with the Consumer Quality Index Long-term Care.

PubMed

Triemstra, Mattanja; Winters, Sjenny; Kool, Rudolf B; Wiegers, Therese A

2010-04-12

This study aims to describe the development, testing and optimization of a new standard instrument, the Consumer Quality Index (CQ-index) Long-term Care, for measuring client experiences with long-term care in the Netherlands. Three versions of the CQ-index questionnaires and protocols for study sampling and data collection were developed, designed for interviews with residents of nursing or residential care homes and postal surveys among representatives of psychogeriatric residents and homecare clients. From July to November 2006 a pilot study was conducted among 2,697 clients of 68 nursing or residential care homes, 2,164 representatives of clients in 57 psychogeriatric care institutions, and 1,462 clients of 19 homecare organizations. We performed psychometric analyses and descriptive analyses, and evaluated the pilot study. The pilot study showed the feasibility and usability of the instruments, supported the multidimensionality of the questionnaires and showed first findings on client experiences and possibilities for quality improvement. Nine scales applied to all care settings: shared decision making, attitude and courtesy, information, body care, competence and safety of care, activities, autonomy, mental well-being, and availability of personnel. The pilot resulted in three optimized questionnaires and recommendations for nationwide implementation. The CQ-index Long-term Care provides a good basis to investigate the quality of nursing homes, residential care homes and homecare from the clients' perspective. This standardized instrument enables a nationwide comparison of the quality of long-term care for the purpose of transparency and quality assurance.

Long-Acting β2-Agonists in Asthma: Enantioselective Safety Studies are Needed.

PubMed

Jacobson, Glenn A; Raidal, Sharanne; Hostrup, Morten; Calzetta, Luigino; Wood-Baker, Richard; Farber, Mark O; Page, Clive P; Walters, E Haydn

2018-05-01

Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without ICS. LABAs clearly demonstrate effective bronchodilatation and steroid-sparing activity, but long-term treatment can lead to tolerance of their bronchodilator effects. There are also concerns with regard to the effects of LABAs on bronchial hyperresponsiveness (BHR), where long-term use is associated with increased BHR and loss of bronchoprotection. A complicating factor is that formoterol and salmeterol are both chiral compounds, usually administered as 50:50 racemic (rac-) mixtures of two enantiomers. The chiral nature of these compounds has been largely forgotten in the debate regarding LABA safety and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from the short-acting β2-agonist (SABA) salbutamol. Supportive clinical findings include the fact that patients in emergency departments who demonstrate a blunted response to salbutamol are more likely to benefit from (R)-salbutamol than rac-salbutamol, and resistance to salbutamol appears to be a contributory mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue.

Safety and effectiveness of long-term growth hormone therapy in Japanese patients with adult growth hormone deficiency: a postmarketing, multicenter, observational study.

PubMed

Shimatsu, Akira; Ishii, Hitoshi; Nishinaga, Hiromi; Murai, Osamu; Chihara, Kazuo

2017-07-28

We aimed to evaluate the long-term safety and effectiveness of growth hormone (GH) therapy in Japanese patients with adult growth hormone deficiency (AGHD). In this observational, multicenter study, Norditropin ® (Novo Nordisk A/S, Bagsvaerd, Denmark) was administered as injections of 0.021 mg/kg/week as a starting dose divided into 6-7 doses/week. The dose was increased according to clinical response. Patients' data were obtained from medical records. Measurements (lipids, glucose metabolism, and body composition) taken at baseline; 3, 6, and 12 months; and yearly until the end of the study were collected. Adverse drug reactions (ADRs), serious ADRs, and serious adverse events (SAEs) were evaluated. Of 387 registered patients, 334 were eligible for safety. After GH treatment initiation, a marked decrease in total cholesterol was observed earlier in the child-onset group than in the adult-onset group. LDL-cholesterol also decreased, but no significant differences in changes in LDL-cholesterol between adult-onset and child-onset groups were found. A significant increase in HDL-cholesterol starting 1 year after GH treatment initiation was found in the adult-onset group. There was no effect of GH treatment on glucose metabolism. Because of the small number of dual-energy X-ray absorptiometry data, the overall assessment of changes of body composition was difficult. Fifty-six (16.8%), 12 (3.6%), and 35 (10.5%) patients experienced ADRs, serious ADRs, and SAEs, respectively. This study demonstrated a favorable long-term safety and effectiveness profile of GH therapy in AGHD patients in the real-life Japanese clinical practice setting.

Long-term safety and tolerability of once-daily mesalamine granules in the maintenance of remission of ulcerative colitis.

PubMed

Lichtenstein, Gary R; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2014-08-01

Ulcerative colitis (UC), a chronic, relapsing, and remitting inflammatory bowel disease, requires long-term treatment to maintain remission. In this study, the long-term safety and tolerability of mesalamine granules (MG) therapy was evaluated in the maintenance of UC remission. Previous prospective studies evaluating different oral mesalamine formulations have not exceeded a duration of 14 months. A phase 3, multicenter, 24-month, open-label extension study evaluating MG 1.5 g once daily in patients who achieved previous remission from mild to moderate UC was performed. Eligible patients had successfully participated in 1 of 2 previous 6-month double-blind, placebo-controlled trials or were new patients in remission. Safety assessments included monitoring of adverse events (AEs) and clinical laboratory tests. Risk of UC recurrence was assessed by the occurrence of UC-related AEs. Of the 393 patients enrolled (280 from the double-blind studies; 113 new patients), 388 were included in the safety population. The most common AEs included nasopharyngitis (13.9%), headache (11.6%), and diarrhea (10.8%), and the incidence of these events was generally lower in the MG group versus historical placebo group from the double-blind studies. Pancreatic, renal, and hepatic AEs occurred in 23 patients (5.9%). The risk of UC-related AEs was low and was maintained for 24 months during the open-label study. Once-daily MG has a favorable safety profile for the maintenance of remission for up to 2 years in patients with UC.

Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis

PubMed Central

Iborra, Marisa; Álvarez-Sotomayor, Diego; Nos, Pilar

2014-01-01

Ulcerative colitis (UC) is a chronic, relapsing, and remitting inflammatory disease involving the large intestine (colon). Treatment seeks to break recurrent inflammation episodes by inducing and maintaining remission. Historically, oral systemic corticosteroids played an important role in inducing remission of this chronic disease; however, their long-term use is limited and can lead to adverse events. Budesonide is a synthetic steroid with potent local anti-inflammatory effects and low systemic bioavailability due to high first-pass hepatic metabolism. Several studies have demonstrated oral budesonide’s usefulness in treating active mild to moderate ileocecal Crohn’s disease and microscopic colitis and in an enema formulation for left sided UC. However, there is limited information regarding oral budesonide’s efficacy in UC. A novel oral budesonide formulation using a multimatrix system (budesonide-MMX) to extend drug release throughout the colon has been developed recently and seems to be an effective treatment in active left sided UC patients. This article summarizes budesonide’s long-term safety and efficacy in treating UC. PMID:24523594

Safety of long-term intranasal budesonide delivered via the mucosal atomization device for chronic rhinosinusitis.

PubMed

Manji, Jamil; Singh, Gurkaran; Okpaleke, Christopher; Dadgostar, Anali; Al-Asousi, Fahad; Amanian, Ameen; Macias-Valle, Luis; Finkelstein, Andres; Tacey, Mark; Thamboo, Andrew; Javer, Amin

2017-05-01

Although short-term use (≤2 months) of atomized topical nasal steroids has been shown to be safe and effective, the long-term safety has yet to be demonstrated. The aim of this study was to determine the impact of long-term topical budesonide treatment via the mucosal atomization device (MAD) on the hypothalamic-pituitary-adrenal axis (HPAA) and intraocular pressure (IOP). A cross-sectional study of patients with chronic rhinosinusitis (CRS), with or without nasal polyposis, managed with daily nasal budesonide via MAD was conducted at a tertiary rhinology center. Patients using systemic steroids within 3 months of assessment were excluded. HPAA impact was assessed using the cosyntropin stimulation test for adrenal function and a survey of relevant symptomatology. Patients also underwent tonometry to assess for elevated IOP potentially related to corticosteroid use. A total of 100 CRS patients were recruited with a mean budesonide treatment duration of 23.5 months (range, 6-37 months). Stimulated cortisol response was diminished in 3 patients (3%). No patients with adrenal suppression had relevant symptomatology. IOP was elevated in 6 patients (6%). These findings suggest that there is a risk of adrenal suppression and raised IOP associated with the long-term use of topical nasal budesonide via MAD. Otolaryngologists should consider periodic surveillance for these adverse events in this patient cohort. © 2017 ARS-AAOA, LLC.

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

PubMed Central

Kissin, Igor

2013-01-01

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

Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study

PubMed Central

Nilsson, Anna G; Bergthorsdottir, Ragnhildur; Burman, Pia; Dahlqvist, Per; Ekman, Bertil; Engström, Britt Edén; Ragnarsson, Oskar; Skrtic, Stanko; Wahlberg, Jeanette; Achenbach, Heinrich; Uddin, Sharif; Marelli, Claudio

2017-01-01

Objective To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Design Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Methods Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Results Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). Conclusions In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment. PMID:28292927

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

PubMed

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

Long-term impact of community-based information, education and communication activities on food hygiene and food safety behaviors in Vietnam: a longitudinal study.

PubMed

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

2013-01-01

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. 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 1(st) set of evaluation data in January 2007 (n = 132). To examine the long-term impact of the interventions, we then collected a 2(nd) 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. Childhood diarrhea was significantly reduced from 21.6% at baseline to 7.6% at the 1(st) post-intervention evaluation (P = 0.002), and to 5.9% at the 2(nd) evaluation. Among 17 food hygiene and food safety behaviors measured, a total of 11 behaviors were improved or maintained by the 2(nd) 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 1(st) and at the 2(nd) 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). Flip chart communication administered by community groups is effective for improving multiple food hygiene and food safety behaviors in sustainable ways, and should be included in

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

PubMed

Dellve, Lotta; Skagert, Katrin; Eklöf, Mats

2008-09-01

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

Long-term studies of dopamine agonists.

PubMed

Hubble, Jean P

2002-02-26

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

Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A.

PubMed

Nolan, B; Mahlangu, J; Perry, D; Young, G; Liesner, R; Konkle, B; Rangarajan, S; Brown, S; Hanabusa, H; Pasi, K J; Pabinger, I; Jackson, S; Cristiano, L M; Li, X; Pierce, G F; Allen, G

2016-01-01

The safety, efficacy and prolonged half-life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A-LONG and Kids A-LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739). Eligible subjects could enrol in ASPIRE upon completing A-LONG or Kids A-LONG. There were four treatment groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for subjects in whom optimal treatment could not be achieved with individualized or weekly prophylaxis); and episodic treatment. The primary endpoint was development of inhibitors. A total of 150 A-LONG subjects and 61 Kids A-LONG subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the median time on study was 80.9 (A-LONG) and 23.9 (Kids A-LONG) weeks. The majority of subjects (A-LONG, 92.0%; Kids A-LONG, 57.4%) had ≥100 cumulative rFVIIIFc exposure days. No inhibitors were observed. Adverse events were generally consistent with those expected in the general haemophilia A population. Median annualized bleeding rates (ABRs) were low with individualized [A-LONG: 0.66; Kids A-LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A-LONG: 2.03) and modified (A-LONG: 1.97) prophylaxis. There was no change in prophylactic infusion frequency or total weekly prophylactic dose in the majority of subjects from A-LONG and Kids A-LONG. Interim data from ASPIRE confirm the long-term safety of rFVIIIFc and the maintenance of a low ABR with extended-interval prophylactic dosing in patients with severe haemophilia A. © 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Business Students' Choice of Short-Term or Long-Term Study Abroad Opportunities

ERIC Educational Resources Information Center

Fitzsimmons, Stacey R.; Flanagan, David J.; Wang, Xiaodan

2013-01-01

Recent years have seen a proliferation of short-term study abroad opportunities. Although they are both supplementing and replacing semester-long study abroad programs, research has focused primarily on semester (long-term) programs. We draw on the theory of planned behavior (TPB) to explore factors that predict why students choose long-term and…

Long-term safety and efficacy of perinatal probiotic intervention: Evidence from a follow-up study of four randomized, double-blind, placebo-controlled trials.

PubMed

Lundelin, Krista; Poussa, Tuija; Salminen, Seppo; Isolauri, Erika

2017-03-01

Societies worldwide are faced with a progressive increase in immune-mediated health problems such as allergic, autoimmune, and inflammatory diseases, as well as obesity. Perinatal administration of specific probiotic bacteria is an attractive approach in reducing the risk of these conditions, but long-term efficacy and safety data are lacking. The aim here was to evaluate the clinical benefit and long-term safety of specific probiotics administered during the perinatal period. The probiotic strains used were Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12, Lactobacillus paracasei ST11, and Bifidobacterium longum BL999. The children involved have subsequently undergone prospective long-term follow-up. In addition to physical examination, data were collected by structured questionnaires on non-communicable diseases and continued probiotic use, and growth data from welfare clinics and school nurses. Altogether 303 mother-infant pairs were included in the analysis. Seventy-six of 163 (47%) children receiving perinatal probiotics had developed allergic disease compared with 79 of 140 (56%) receiving placebo (OR 0.67, 95% confidence intervals [CI] 0.43-1.06, p = 0.09). Fifty-nine of 133 (44%) children receiving L. rhamnosus GG perinatally had developed allergic disease, OR 0.62, 95% CI 0.38-0.99, p = 0.047, as compared to placebo. We found no differences in growth or non-communicable disease prevalence between children receiving perinatally probiotics or placebo. Perinatal probiotic administration is safe in long-term follow-up. Children receiving L. rhamnosus GG perinatally tended to have decreased allergy prevalence. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

Gilad, Gad M; Gilad, Varda H

2014-11-01

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

Open-label, long-term safety study of cevimeline in the treatment of postirradiation xerostomia.

PubMed

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

2007-12-01

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. 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). 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). 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.

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

PubMed

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

2015-04-01

The Phenylketonuria (PKU) Demographics, Outcomes and Safety (PKUDOS) registry is designed to provide longitudinal safety and efficacy data on subjects with PKU who are (or have been) treated with sapropterin dihydrochloride. The PKUDOS population consists of 1189 subjects with PKU: N = 504 who were continuously exposed to sapropterin from date of registry enrollment, N = 211 who had intermittent exposure to the drug, and N = 474 with some other duration of exposure. Subjects continuously exposed to sapropterin showed an average 34% decrease in blood phenylalanine (Phe)--from 591 ± 382 μmol/L at baseline to 392 ± 239 μmol/L (p = 0.0009) after 5 years. This drop in blood Phe was associated with an increase in dietary Phe tolerance [from 1000 ± 959 mg/day (pre-sapropterin baseline) to 1539 ± 840 mg/day after 6 years]. Drug-related adverse events (AEs) were reported in 6% of subjects, were mostly considered non-serious, and were identified in the gastrointestinal, respiratory, and nervous systems. Serious drug-related AEs were reported in ≤ 1% of subjects. Similar safety and efficacy data were observed for children<4 years. Long-term data from the PKUDOS registry suggest that sapropterin has a tolerable safety profile and that continuous use is associated with a significant and persistent decrease in blood Phe and improvements in dietary Phe tolerance. Copyright © 2015. Published by Elsevier Inc.

Long-term efficacy and safety of sacral nerve stimulation for fecal incontinence.

PubMed

Mellgren, Anders; Wexner, Steven D; Coller, John A; Devroede, Ghislain; Lerew, Darin R; Madoff, Robert D; Hull, Tracy

2011-09-01

Sacral nerve stimulation is effective in the treatment of urinary incontinence and is currently under Food and Drug Administration review in the United States for fecal incontinence. Previous reports have focused primarily on short-term results of sacral nerve stimulation for fecal incontinence. The present study reports the long-term effectiveness and safety of sacral nerve stimulation for fecal incontinence in a large prospective multicenter study. Patients with fecal incontinent episodes more than twice per week were offered participation in this multicentered prospective trial. Patients showing ≥ 50% improvement during test stimulation were offered chronic implantation of the InterStim Therapy system (Medtronic; Minneapolis, MN). The aims of the current report were to provide 3-year follow-up data on patients from that study who underwent sacral nerve stimulation and were monitored under the rigors of an Food and Drug Administration-approved investigational protocol. One hundred thirty-three patients underwent test stimulation with a 90% success rate, of whom 120 (110 females) with a mean age of 60.5 years and a mean duration of fecal incontinence of 7 years received chronic implantation. Mean length of follow-up was 3.1 (range, 0.2-6.1) years, with 83 patients completing all or part of the 3-year follow-up assessment. At 3 years follow-up, 86% of patients (P < .0001) reported ≥ 50% reduction in the number of incontinent episodes per week compared with baseline and the number of incontinent episodes per week decreased from a mean of 9.4 at baseline to 1.7. Perfect continence was achieved in 40% of subjects. The therapy also improved the fecal incontinence severity index. Sacral nerve stimulation had a positive impact on the quality of life, as evidenced by significant improvements in all 4 scales of the Fecal Incontinence Quality of Life instrument at 12, 24, and 36 months of follow-up. The most common device- or therapy-related adverse events through the

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

PubMed

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

2016-08-01

Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. ClincialTrials.gov, clinicaltrials.gov, NCT00069329. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

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

PubMed Central

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

2016-01-01

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

Planning long-term vegetation studies at landscape scales

USGS Publications Warehouse

Stohlgren, Thomas J.

1995-01-01

Long-term ecological research is receiving more attention now than ever before. Two recent books, Long-term Studies in Ecology: Approaches and Alternatives, edited by Gene Likens (1989), and Long-term Ecological Research: An International Perspective, edited by Paul Risser (1991), prompt the question, “Why are these books so thin?” Except for data from paleoecological, retrospective studies (see below), there are exceptionally few long-term data sets in terrestrial ecology (Strayer et al. 1986; Tilman 1989; this volume). In a sample of 749 papers published in Ecology, Tilman (1989) found that only 1.7% of the studies lasted at least five field seasons. Only one chapter in each of the review books dealt specifically with expanding both the temporal and the spatial scales of ecological research (Berkowitz et al. 1989; Magnuson et al. 1991). Judging by the growing number of landscape-scale long-term studies, however, such as the Long-Term Ecological Research (LTER) Program (Callahan 1991), the U.S. Environmental Protection Agency’s Environmental Monitoring and Assessment Program (EMAP; Palmer et al. 1991), the U.S. Army’s Land Condition-Trend Analysis (LCTA) Program (Diersing et al. 1992), and various agencies’ global change research programs (CEES 1993), there is a growing interest to expand ecological research both temporally and spatially.

The Efficacy and Safety of Long-term Pirfenidone Therapy in Patients with Idiopathic Pulmonary Fibrosis.

PubMed

Ogawa, Kazumasa; Miyamoto, Atsushi; Hanada, Shigeo; Takahashi, Yui; Murase, Kyoko; Mochizuki, Sayaka; Uruga, Hironori; Takaya, Hisashi; Morokawa, Nasa; Kishi, Kazuma

2018-05-18

Objective Pirfenidone (PFD) is often used for years, but the efficacy and safety of long-term PFD therapy in patients with idiopathic pulmonary fibrosis (IPF) are not fully understood. Methods and Patients We retrospectively evaluated 46 patients with IPF who received PFD between February 2009 and August 2014. The efficacy and safety of PFD therapy were compared between 2 groups: long-term therapy patients who received PFD for over 1 year (group L, n=30, 65%) and short-term therapy patients who could not receive PFD for more than 1 year due to worsening of their condition or side effects (group S, n=16, 35%). Results The median age of the 46 patients was 70.5 years, and the median baseline % predicted forced vital capacity (%FVC) was 70.0%. The changes in the FVC in group L were -120 mL and -170 mL at 12 and 24 months after receiving PFD, respectively. The respective median survival times after PFD therapy in groups L and S were 1,612 days and 285 days (p<0.001). The patients in group L experienced a longer time free of acute exacerbation of IPF than those in group S (947 days vs. 145 days, p=0.001). A multivariate analysis revealed that %FVC <60% was a predictor of the inability to receive PFD for over 1 year (odds ratio 0.240, 95% confidence interval 0.060-0.958; p=0.043). With regard to grade 3-5 adverse events, only one patient exhibited grade 3 hyponatremia. Conclusions Long-term PFD therapy is effective, with few severe adverse events.

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

PubMed Central

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

2014-01-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chambers, Mark S.; Jones, Christopher Uwe; Biel, Merrill A.

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 onmore » 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.« less

Long-term efficacy and safety of carotid artery stenting versus endarterectomy: A meta-analysis of randomized controlled trials

PubMed Central

Xu, Biao; Wang, Lian

2017-01-01

Background Many recent trials have investigated the long-term efficacy and safety of endarterectomy versus stenting in treating patients with carotid artery stenosis. We aimed to determine the long-term comparative efficacy and safety of both procedures by pooling this evidence in a meta-analysis. Methods We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published until May 6, 2016. Randomized controlled trials, which reported outcomes of interest with a median follow-up of at least 4-year, were included. Results Eight trials involving 7005 patients and 41824 patient-years of follow-up were included. In terms of the periprocedural outcomes, stenting was associated with a lower risk of myocardial infarction (OR: 0.51; 95% CI: 0.33 to 0.80; P = 0.003) but a higher risk of death or stroke (the composite endpoint, OR: 1.76; 95% CI: 1.38 to 2.25; P < 0.0001), a result that was primarily driven by minor stroke (OR: 2.19; 95% CI: 1.59 to 3.01; P < 0.0001), less so by periprocedural death (OR: 1.68; 95% CI: 0.82 to 3.44; P = 0.16) and major stroke (OR: 1.41; 95% CI: 0.95 to 2.09; P = 0.09). In terms of the long-term outcomes, stenting was associated with a higher risk of stroke (OR 1.45; 95% CI: 1.22 to 1.73; P < 0.0001) and the composite outcome of death or stroke (OR 1.25; 95% CI: 1.05 to 1.48; P = 0.01). No difference was found in long-term all-cause mortality between stenting and endarterectomy (OR: 1.09; 95% CI: 0.95 to 1.26; P = 0.21) and restenosis (OR: 1.48 (95% CI: 0.93 to 2.35; P = 0.10). No evidence of significant heterogeneity was found in any of the analyses. Conclusions Carotid endarterectomy was found to be superior to stenting for short- and long-term outcomes, although endarterectomy was associated with a higher risk of periprocedural myocardial infarction. Carotid endarterectomy should be offered as the first choice for carotid stenosis at present, however, more evidence is needed because rapid progress in

Long-term efficacy and safety of lamotrigine monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures: An open-label extension study.

PubMed

Yasumoto, Sawa; Ohtsuka, Yoko; Sato, Katsuaki; Kurata, Atsuyo; Numachi, Yotaro; Shimizu, Masahiro

2018-05-31

To investigate the efficacy and safety of long-term lamotrigine (LTG) monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures. Six Japanese patients and one South Korean patient were enrolled in the extension phase of the study after completing the 12-week maintenance phase of an open-label clinical study of LTG monotherapy. During the extension phase, patients underwent efficacy and safety evaluation every 12 weeks. Of the seven patients, six patients completed the extension phase. The seizure-free rate confirmed by hyperventilation (HV)-electroencephalography ranged from 71.4% to 100.0% at each visit up to Week 168 of the extension phase. Similar effects were confirmed by HV-clinical signs and seizure diaries. Although no unexpected adverse events were observed, one Japanese patient was withdrawn from the extension phase due to mild drug-related rash developed 842 days after the start of LTG. Although the number of patients is limited, long-term LTG monotherapy appeared to be effective and generally well tolerated in Japanese and South Korean pediatric patients with typical absence seizures. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Long-Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus: A Continuation of a Seventy-Six-Week Phase III Parent Study in the United States.

PubMed

Furie, Richard A; Wallace, Daniel J; Aranow, Cynthia; Fettiplace, James; Wilson, Barbara; Mistry, Prafull; Roth, David A; Gordon, David

2018-06-01

We undertook this US multicenter continuation study (GlaxoSmithKline study BEL112233; ClinicalTrials.gov identifier: NCT00724867) to assess long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) who completed the Study of Belimumab in Subjects with SLE 76-week trial (ClinicalTrials.gov identifier: NCT00410384). Patients continued to receive the same belimumab dose plus standard therapy; patients previously receiving placebo received 10 mg/kg belimumab. The primary outcome measure was long-term safety of belimumab (frequency of adverse events [AEs] and damage assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI], evaluated every 48 weeks [1 study year]). Other assessments included the SLE Responder Index (SRI), flare rates (using the modified SLE Flare Index [SFI]), prednisone use, and B cell levels. Of 268 patients, 140 completed the study and 128 withdrew. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) at baseline was 7.8 ± 3.86. The mean ± SD SDI score increased by 0.4 ± 0.68 from its value at baseline (1.2 ± 1.51). The overall incidence of treatment-related and serious AEs remained stable or declined through study year 7. An SRI response was achieved by 41.9% and 75.6% of patients at the study year 1 and study year 7 midpoints, respectively. At the study year 7 midpoint, relative to baseline, 78.2% had achieved a ≥4-point reduction in the SELENA-SLEDAI score, 98.4% had no new British Isles Lupus Assessment Group (BILAG) A organ domain score and no more than 1 new BILAG B organ domain score, 93.7% had no worsening in the physician's global assessment of disease activity, 20.6% had experienced ≥1 severe SFI flare, the mean decrease in prednisone dose was 31.4%, and the median change in CD20+ B cell numbers was -83.2%. These long-term exposure results

Long-term safety and effectiveness of lopinavir/ritonavir in antiretroviral-experienced HIV-1-infected children.

PubMed

Rudin, Christoph; Wolbers, Marcel; Nadal, David; Rickenbach, Martin; Bucher, Heiner C

2010-06-01

To evaluate the long-term safety and effectiveness of lopinavir/ritonavir (LPV/r) in a population-based cohort of HIV-1-infected children. All children enrolled in the Swiss Mother and Child HIV Cohort Study, treated with LPV/r-based combination antiretroviral treatment (cART) between November 2000 and October 2008, were included. 88 children (25 (28%) protease inhibitor (PI)-naive, 16 (18%) ART-naive) were analysed (251 patient-years on LPV/r). After 48 weeks on LPV/r, 70 children had a median (interquartile range (IQR)) decrease in HIV-1 viral load of 4.25 log (5.45-3.17; PI-naive, n=17) and 2.53 (3.68-1.38; PI-experienced, n=53). Median (IQR) increase in CD4 count was 429 (203-593; PI-naive) and 177 (21-331; PI-experienced) cells/microl. These effects remained stable throughout 192 weeks for 25 children. Treatment was stopped for viral rebound in seven and suspected toxicity in 12 children. Long-term treatment with LPV/r-based cART is safe and effective in HIV-1-infected children.

Long-Term Safety and Efficacy of Enzyme Replacement Therapyfor Fabry Disease

PubMed Central

Wilcox, William R.; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E.; Desnick, Robert J.; Germain, Dominique P.

2004-01-01

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human α-galactosidase A (rh-αGalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-αGalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh-αGalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30–36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh-αGalA IgG antibody titers. Among seroconverted patients, after 30–36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had ⩾4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30–36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile. PMID:15154115

Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice: interim results of the STELLA-LONG TERM post-marketing surveillance study.

PubMed

Nakamura, Ichiro; Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Uno, Satoshi

2018-02-01

Data regarding the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in the real-world setting in Japan are limited. The STELLA-LONG TERM study is an ongoing 3-year post-marketing surveillance study of ipragliflozin in type 2 diabetes (T2D) patients. Here, we report the interim results (including 3-, 12-, and 24-month data). All Japanese patients with T2D who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan were registered in STELLA-LONG TERM. At 3, 12, and 24 months, the safety analysis set comprised 11,053, 5475, and 138 patients, respectively; the efficacy analysis set comprised 8757 patients. Ipragliflozin treatment resulted in statistically significant improvements versus baseline in hemoglobin A1c, fasting plasma glucose concentration, body weight, blood pressure, heart rate, and serum concentrations of low-density lipoprotein cholesterol and triglycerides. The adverse drug reaction incidence rate was 10.71%, the most common reactions being renal and urinary disorders (5.06%), infections and infestations (1.24%), and skin and subcutaneous tissue disorders (1.14%). Ipragliflozin was well tolerated and effective in Japanese patients with T2D; no new safety issues were identified.

Long-term cropping systems study

USDA-ARS?s Scientific Manuscript database

This long-term study has been conducted on the Agronomy Farm at ARDC since the early 1970’s. In the beginning, the objectives were mainly related to crop production as affected by different cropping systems. The cropping systems included in the study are Continuous Corn, Soybean, and Sorghum; 2-year...

Long-term follow-up observation of the safety, immunogenicity, and effectiveness of Gardasil™ in adult women.

PubMed

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

2013-01-01

Previous analyses from a randomized trial in women aged 24-45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN) and external genital lesions (EGL) related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women. Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study [n = 684]) or 29 to 50 years of age (in the original placebo group during the base study [n = 651]). This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years) from both the original base study and the Colombian follow-up. There were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported. Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24-45 year-old women. Clinicaltrials.govNCT00090220.

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

PubMed Central

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

2013-01-01

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

Long-term safety and efficacy of canakinumab in cryopyrin-associated periodic syndrome: results from an open-label, phase III pivotal study in Japanese patients.

PubMed

Yokota, Shumpei; Imagawa, Tomoyuki; Nishikomori, Ryuta; Takada, Hidetoshi; Abrams, Ken; Lheritier, Karine; Heike, Toshio; Hara, Toshiro

2017-01-01

To assess the long-term safety and efficacy of canakinumab in Japanese patients with cryopyrin-associated periodic syndrome (CAPS). In this open-label phase 3 study, Japanese patients aged ≥2 years with CAPS received canakinumab 2-8 mg/kg subcutaneously every 8 weeks. The duration of the core treatment phase was 24 weeks followed by 22 months extension phase. The primary objective was the proportion of patients free of clinical and serologic relapse at week 24. The study enrolled 19 Japanese patients (median age, 14 years; range, 2-48 years) with CAPS [MWS, 7 (36.8%); NOMID, 12 (63.2%)] for a median of 109 weeks. Fifteen patients (79%) achieved a complete response by day 15, 18 (94.7%) by week 24 and all by week 48. At the end of the study, 18 (95%) were free from relapse and 11 (57.9%) were assessed as having no disease activity by the PGA. Thirteen (68%) patients (MWS, 4; NOMID, 9) had their canakinumab dose increased during the trial. All patients experienced at least one adverse event (AE), the most common being infections (100%) and 5 (26.3%) reported serious AEs. No deaths were reported and the only patient who discontinued the study early withdrew consent. Regular canakinumab treatment every 8 weeks at dose levels from 2-8 mg/kg, based on the clinical need, represents a successful strategy to induce rapid and complete response while maintain long-term disease control in Japanese patients with CAPS. The safety profile of canakinumab was consistent with that observed from previous studies.

Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

PubMed

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-08-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.

Long term stability following genioplasty: a cephalometric study.

PubMed

Kumar, B Lakshman; Raju, G Kranthi Praveen; Kumar, N Dilip; Reddy, G Vivek; Naik, B Ravindra; Achary, C Ravindranath

2015-04-01

A receding chin associated with an orthognathic mandible is a common situation and surgical changes in chin position are often required to improve the overall harmony of the face. Genioplasty is one such procedure. Stability of hard and soft tissue changes following genioplasty on a long term basis needs to be assessed. Studies on the stability of hard and soft tissue changes following genioplasty on a short term basis have revealed it as a procedure with good stability. This study is done to assess the stability of hard and soft tissue changes following genioplasty on a long term basis. Pre-surgical, postsurgical and long term post-surgical cephalograms of 15 cases treated by vertical reduction augmentation genioplasty were obtained. Paired t-test was used to compare the changes between pre-surgical, postsurgical and long term postsurgical cephalograms. Findings of this study demonstrated that genioplasty is a stable procedure. After long term follow-up period, there was a relapse of 1.5 mm at the pogonion accounting for 24% of the surgical advancement. This is attributed to the remodeling that occurs at the surgical site, but not the instability due to the surgical procedure. With the present study, it can be concluded that vertical reduction and advancement genioplasty can be considered as an adjunctive procedure that produces predictable results and the bony and soft tissue stability were generally very good.

Dupuytren Contracture Recurrence Following Treatment With Collagenase Clostridium histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]): 5-Year Data.

PubMed

Peimer, Clayton A; Blazar, Philip; Coleman, Stephen; Kaplan, F Thomas D; Smith, Ted; Lindau, Tommy

2015-08-01

Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study was a 5-year noninterventional follow-up study to determine long-term efficacy and safety of collagenase clostridium histolyticum (CCH) treatment for Dupuytren contracture. Patients from previous CCH clinical studies were eligible. Enrolled patients were evaluated annually for contracture and safety at 2, 3, 4, and 5 years after their first injection (0.58 mg) of CCH. In successfully treated joints (≤ 5° contracture following CCH treatment), recurrence was defined as 20° or greater worsening (relative to day 30 after the last injection) with a palpable cord or any medical/surgical intervention to correct new/worsening contracture. A post hoc analysis was also conducted using a less stringent threshold (≥ 30° worsening) for comparison with criteria historically used to assess surgical treatment. Of 950 eligible patients, 644 enrolled (1,081 treated joints). At year 5, 47% (291 of 623) of successfully treated joints had recurrence (≥ 20° worsening)-39% (178 of 451) of metacarpophalangeal and 66% (113 of 172) of proximal interphalangeal joints. At year 5, 32% (198 of 623) of successfully treated joints had 30° or greater worsening (metacarpophalangeal 26% [119 of 451] and proximal interphalangeal 46% [79 of 172] joints). Of 105 secondary interventions performed in the successfully treated joints, 47% (49 of 105) received fasciectomy, 30% (32 of 105) received additional CCH, and 23% (24 of 105) received other interventions. One mild adverse event was attributed to CCH treatment (skin atrophy [decreased ring finger circumference from thinning of Dupuytren tissue]). Antibodies to clostridial type I and/or II collagenase were found in 93% of patients, but over the 5 years of follow-up, this did not correspond to any reported clinical adverse events. Five years after successful CCH treatment, the overall recurrence rate of 47% was comparable with published recurrence rates after

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

PubMed Central

Masumori, Naoya

2013-01-01

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

Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy.

PubMed

Sandborn, W J; Rutgeerts, P; Gasink, C; Jacobstein, D; Zou, B; Johanns, J; Sands, B E; Hanauer, S B; Targan, S; Ghosh, S; de Villiers, W J S; Colombel, J-F; Feagan, B G

2018-05-24

In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported. UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose-adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8-32). All Week 44 completers could enter the long-term extension without further dose adjustment. Placebo patients discontinued following study unblinding. A total of 718 patients (all treated) entered the long-term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient-years) were similar among all placebo and ustekinumab patients (Week 0-96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious

Long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia): survey methods, data management, and long-term population trends.

PubMed

Ojanen, Sami P; Nieminen, Marko; Meyke, Evgeniy; Pöyry, Juha; Hanski, Ilkka

2013-10-01

Long-term observational studies conducted at large (regional) spatial scales contribute to better understanding of landscape effects on population and evolutionary dynamics, including the conditions that affect long-term viability of species, but large-scale studies are expensive and logistically challenging to keep running for a long time. Here, we describe the long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia) that has been conducted since 1991 in a large network of 4000 habitat patches (dry meadows) within a study area of 50 by 70 km in the Åland Islands in Finland. We explain how the landscape structure has been described, including definition, delimitation, and mapping of the habitat patches; methods of field survey, including the logistics, cost, and reliability of the survey; and data management using the EarthCape biodiversity platform. We describe the long-term metapopulation dynamics of the Glanville fritillary based on the survey. There has been no long-term change in the overall size of the metapopulation, but the level of spatial synchrony and hence the amplitude of fluctuations in year-to-year metapopulation dynamics have increased over the years, possibly due to increasing frequency of exceptional weather conditions. We discuss the added value of large-scale and long-term population studies, but also emphasize the need to integrate more targeted experimental studies in the context of long-term observational studies. For instance, in the case of the Glanville fritillary project, the long-term study has produced an opportunity to sample individuals for experiments from local populations with a known demographic history. These studies have demonstrated striking differences in dispersal rate and other life-history traits of individuals from newly established local populations (the offspring of colonizers) versus individuals from old, established local populations. The long-term observational study has stimulated the

Long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia): survey methods, data management, and long-term population trends

PubMed Central

Ojanen, Sami P; Nieminen, Marko; Meyke, Evgeniy; Pöyry, Juha; Hanski, Ilkka

2013-01-01

Long-term observational studies conducted at large (regional) spatial scales contribute to better understanding of landscape effects on population and evolutionary dynamics, including the conditions that affect long-term viability of species, but large-scale studies are expensive and logistically challenging to keep running for a long time. Here, we describe the long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia) that has been conducted since 1991 in a large network of 4000 habitat patches (dry meadows) within a study area of 50 by 70 km in the Åland Islands in Finland. We explain how the landscape structure has been described, including definition, delimitation, and mapping of the habitat patches; methods of field survey, including the logistics, cost, and reliability of the survey; and data management using the EarthCape biodiversity platform. We describe the long-term metapopulation dynamics of the Glanville fritillary based on the survey. There has been no long-term change in the overall size of the metapopulation, but the level of spatial synchrony and hence the amplitude of fluctuations in year-to-year metapopulation dynamics have increased over the years, possibly due to increasing frequency of exceptional weather conditions. We discuss the added value of large-scale and long-term population studies, but also emphasize the need to integrate more targeted experimental studies in the context of long-term observational studies. For instance, in the case of the Glanville fritillary project, the long-term study has produced an opportunity to sample individuals for experiments from local populations with a known demographic history. These studies have demonstrated striking differences in dispersal rate and other life-history traits of individuals from newly established local populations (the offspring of colonizers) versus individuals from old, established local populations. The long-term observational study has stimulated the

Long Term Stability Following Genioplasty: A Cephalometric Study

PubMed Central

Kumar, B Lakshman; Raju, G Kranthi Praveen; Kumar, N Dilip; Reddy, G Vivek; Naik, B Ravindra; Achary, C Ravindranath

2015-01-01

Background: A receding chin associated with an orthognathic mandible is a common situation and surgical changes in chin position are often required to improve the overall harmony of the face. Genioplasty is one such procedure. Stability of hard and soft tissue changes following genioplasty on a long term basis needs to be assessed. Studies on the stability of hard and soft tissue changes following genioplasty on a short term basis have revealed it as a procedure with good stability. This study is done to assess the stability of hard and soft tissue changes following genioplasty on a long term basis. Materials and Methods: Pre-surgical, postsurgical and long term post-surgical cephalograms of 15 cases treated by vertical reduction augmentation genioplasty were obtained. Paired t-test was used to compare the changes between pre-surgical, postsurgical and long term postsurgical cephalograms. Results: Findings of this study demonstrated that genioplasty is a stable procedure. After long term follow-up period, there was a relapse of 1.5 mm at the pogonion accounting for 24% of the surgical advancement. This is attributed to the remodeling that occurs at the surgical site, but not the instability due to the surgical procedure. Conclusion: With the present study, it can be concluded that vertical reduction and advancement genioplasty can be considered as an adjunctive procedure that produces predictable results and the bony and soft tissue stability were generally very good. PMID:25954070

Long term safety of sacral nerve modulation in medicare beneficiaries.

PubMed

Chughtai, Bilal; Sedrakyan, Art; Isaacs, Abby; Lee, Richard; Te, Alexis; Kaplan, Steven

2015-09-01

Sacral nerve stimulation (SNS) is FDA approved as second-line therapy for both urinary and bowel control. However, there is limited evidence regarding long term safety. We determined adverse events associated with SNS among Medicare beneficiaries. We used the 5% national random sample of Medicare claims for 2001-2011 to identify patients. Patients who underwent SNS implantation were identified with Current Procedure Terminology (CPT-4) codes. We determined safety of SNS using analysis of complication occurrences on day of surgery and during 5 years following initial procedure. SAS v9.3 statistical package was used. One thousand four hundred seventy-four patients underwent treatment with SNS in the 5% national sample of Medicare patients within the time period. Representative of real-world patients undergoing SNS surgery, comorbidities included hypertension (69.3%), diabetes (29.4%), chronic pulmonary disease (25.5%), hypothyroidism (25.2%), and depression (22.7%). Few complications occurred on day of surgery. At 90 days, 3.2% of patients had bowel complications, 2.0% urological, 9.4% infectious, and 1.5% stroke. Overall, bowel, neurological health event occurrences were consistent with prior year rates, while infectious events decreased. Of 206 patients who were followed for at least 5 years, 17.3% had devices removed and 11.3% replaced, with 26.1% having at least one of those, leaving 73.9% with original devices. Urological, infectious, and bowel complication occurrences were low after SNS among Medicare beneficiaries with multiple comorbidities. There were infrequent serious complications like hemorrhage and stroke postoperatively. Although SNS appears safe in this high-risk population, a comprehensive registry will ensure continuous safety. © 2014 Wiley Periodicals, Inc.

Open-label, randomized, multicenter, phase III study to evaluate the safety and efficacy of benzoyl peroxide gel in long-term use in patients with acne vulgaris: A secondary publication.

PubMed

Kawashima, Makoto; Nagare, Toshitaka; Katsuramaki, Tsuneo

2017-06-01

An open-label, randomized, multicenter study was conducted to evaluate the safety and efficacy of long-term use of 2.5% and 5% benzoyl peroxide (BPO) gels administrated once daily for 52 weeks to Japanese patients with acne vulgaris. The efficacy of the study drugs was evaluated by counting inflammatory lesions and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. In total, 458 subjects were included in the efficacy and safety analyses. The total lesion count, the efficacy end-point, was similarly changed both in the 2.5% and 5% BPO groups over the course of the study. The median rates of reduction from baseline to week 12 were approximately 65%. Thereafter, the counts were maintained at a reduced level without increasing until week 52. The median rates at week 52 were approximately 80%. Similar trends were observed for inflammatory and non-inflammatory lesion counts. Bacteriological evaluation indicated similar distribution of the minimum inhibitory concentration of each of the antibacterial drugs against Propionibacterium acnes between the values at baseline and at week 52, suggesting that long-term use did not result in changes in the drug sensitivity. The incidence of adverse events was 84.0% in the 2.5% BPO group and 87.2% in the 5% BPO group. Many of the adverse events occurred within the first month and were mild or moderate in severity and transient. The results suggest that both 2.5% and 5% BPO gels are effective and safe for long-term treatment of patients with acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Safety of real-time convection-enhanced delivery of liposomes to primate brain: a long-term retrospective.

PubMed

Krauze, Michal T; Vandenberg, Scott R; Yamashita, Yoji; Saito, Ryuta; Forsayeth, John; Noble, Charles; Park, John; Bankiewicz, Krystof S

2008-04-01

Convection-enhanced delivery (CED) is gaining popularity in direct brain infusions. Our group has pioneered the use of liposomes loaded with the MRI contrast reagent as a means to track and quantitate CED in the primate brain through real-time MRI. When co-infused with therapeutic nanoparticles, these tracking liposomes provide us with unprecedented precision in the management of infusions into discrete brain regions. In order to translate real-time CED into clinical application, several important parameters must be defined. In this study, we have analyzed all our cumulative animal data to answer a number of questions as to whether real-time CED in primates depends on concentration of infusate, is reproducible, allows prediction of distribution in a given anatomic structure, and whether it has long term pathological consequences. Our retrospective analysis indicates that real-time CED is highly predictable; repeated procedures yielded identical results, and no long-term brain pathologies were found. We conclude that introduction of our technique to clinical application would enhance accuracy and patient safety when compared to current non-monitored delivery trials.

Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

PubMed Central

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-01-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis

PubMed Central

Valeyre, Dominique; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; King, Talmadge E; Leff, Jonathan A; Noble, Paul W; Sahn, Steven A; du Bois, Roland M

2014-01-01

Background and objective Pirfenidone is an oral antifibrotic agent that is approved in several countries for the treatment of idiopathic pulmonary fibrosis (IPF). We performed a comprehensive analysis of safety across four clinical trials evaluating pirfenidone in patients with IPF. Methods All patients receiving pirfenidone 2403 mg/day in the Phase 3 CAPACITY studies (Studies 004 and 006) and all patients receiving at least one dose of pirfenidone in one of two ongoing open-label studies in patients with IPF (Studies 002 and 012) were selected for inclusion. Safety outcomes were evaluated from baseline until 28 days after the last dose of study drug. Results A total of 789 patients were included in the analysis. The median duration of exposure to pirfenidone was 2.6 years (range, 1 week–7.7 years), and the cumulative total exposure was 2059 person exposure years (PEY). Gastrointestinal and skin-related events were the most commonly reported adverse events; these were almost always mild to moderate in severity, and rarely led to treatment discontinuation. Elevations (>3× upper limit of normal) in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) occurred in 21/789 (2.7%) patients; the adjusted incidence of AST/ALT elevations was 1.7 per 100 PEY. Conclusions This comprehensive analysis of safety in a large cohort of IPF patients receiving pirfenidone for a total of 2059 PEY demonstrates that long-term treatment with pirfenidone is safe and generally well tolerated. PMID:24836849

Hydrotherapy for the long-term ventilated patient: A case study and implications for practice.

PubMed

Wegner, Sally; Thomas, Peter; James, Christine

2017-11-01

Hydrotherapy of mechanically ventilated patients has been shown to be safe and feasible in both the acute stages of critical illness and in those requiring long term mechanical ventilation. This case study describes the hydrotherapy sessions of a 36 year old female, who after suffering complications of pneumococcal meningitis, became an incomplete quadriplegic and required long term mechanical ventilation. When implementing hydrotherapy with patients on mechanical ventilation a number of factors should be considered. These include staff resources and training, airway and ventilation management, patient preparation and safety procedures. Hydrotherapy can be safely utilised with mechanically ventilated patients, and may facilitate a patient's ability to participate in active exercise and rehabilitation. Copyright © 2017 Australian College of Critical Care Nurses Ltd. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Long-term safety and efficacy of enzyme replacement therapy for Fabry disease.

PubMed

Wilcox, William R; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E; Desnick, Robert J; Germain, Dominique P

2004-07-01

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human alpha -galactosidase A (rh-alpha GalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-alpha GalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh- alpha GalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30-36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh- alpha GalA IgG antibody titers. Among seroconverted patients, after 30-36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had > or =4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile.

Efficacy and Safety of Proton Pump Inhibitors in the Long-Term Aspirin Users: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Dahal, Khagendra; Sharma, Sharan P; Kaur, Jaspreet; Anderson, Billie J; Singh, Gurpinder

Long-term aspirin use in cardiovascular disease prevention may result in gastrointestinal bleeding. Although proton pump inhibitors (PPI) have been shown to reduce the risks of peptic ulcers and dyspeptic symptoms in long-term aspirin users in the randomized controlled trials, there are safety concerns about the long-term use of PPI. What is the safety and efficacy of PPI in patients using aspirin in long term for prevention of cardiovascular diseases and stroke? We searched MEDLINE, EMBASE, CENTRAL, CINAHL, ProQuest, and relevant references from inception through February 2015, and used random-effects model for meta-analysis. A total of 10 publications from 9 studies (n = 6382) were included in the meta-analysis. Compared with control, PPI reduced the risks of peptic ulcers [risk ratio (RR): 0.19; 95% confidence interval: 0.13-0.26; P < 0.00001], gastric ulcers [0.24 (0.16-0.35); P < 0.00001], duodenal ulcers [0.12 (0.05-0.29); P < 0.00001], bleeding ulcers [0.22 (0.10-0.51); P = 0.0004], and erosive esophagitis [0.14 (0.07-0.28); P < 0.00001]. PPI increased the resolution of epigastric pain [1.13 (1.03-1.25); P = 0.01], heartburn [1.24 (1.18-1.31); P < 0.00001], and regurgitation [1.26 (1.13-1.40); P < 0.0001], but did not increase the risks of all-cause mortality [1.72 (0.61-4.87); P = 0.31], cardiovascular mortality [1.80 (0.59-5.44); P = 0.30], nonfatal myocardial infarction/ischemia [0.56 (0.22-1.41); P = 0.22], ischemic stroke/transient ischemic attack [1.09 (0.34-3.53); P = 0.89] and other adverse events. The PPI seems to be effective in preventing peptic ulcers and erosive esophagitis and in resolution of dyspeptic symptoms without increasing adverse events, cardiac risks or mortality in long-term aspirin users.

An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension.

PubMed

Riedl, Marc A; Bernstein, Jonathan A; Craig, Timothy; Banerji, Aleena; Magerl, Markus; Cicardi, Marco; Longhurst, Hilary J; Shennak, Mustafa M; Yang, William H; Schranz, Jennifer; Baptista, Jovanna; Busse, Paula J

2017-01-01

Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study ("rollover patients") and those who did not participate in the double-blind study ("non-rollover patients"), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient's first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab every 2 weeks regardless

Long-Term Safety and Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain: A Phase II Randomized, Double-Blind, Placebo-Controlled Extension Study.

PubMed

Sanga, Panna; Katz, Nathaniel; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Haeussler, Juergen; Thipphawong, John

2017-04-01

To evaluate the long-term safety and efficacy of fulranumab in patients with knee or hip pain caused by moderate-to-severe chronic osteoarthritis (OA). In this phase II double-blind, placebo-controlled extension study, patients who were randomized in equal proportions to receive subcutaneous doses of either placebo or fulranumab (1 mg every 4 weeks, 3 mg every 8 weeks, 3 mg every 4 weeks, 6 mg every 8 weeks, or 10 mg every 8 weeks) in the 12-week double-blind efficacy phase and who completed this double-blind efficacy phase were eligible to continue the dosage throughout a 92-week double-blind extension phase, followed by a 24-week posttreatment follow-up period. Safety assessments included evaluation of treatment-emergent adverse events (TEAEs), pre-identified AEs of interest, and joint replacements. Efficacy assessments included changes from baseline to the end of the double-blind extension phase in scores on the patient's global assessment and the pain and physical function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index. Overall, 401 of the 423 patients who completed the 12-week double-blind efficacy phase entered the extension study. Long-term sustained improvements were observed in all efficacy parameters following fulranumab treatment (1 mg every 4 weeks, 3 mg every 4 weeks, and 10 mg every 8 weeks) as compared with placebo. Similar percentages of patients in both groups experienced TEAEs (88% taking placebo and 91% taking fulranumab; all phases). Across all fulranumab groups, arthralgia (21%) and OA (18%) (e.g., exacerbation of OA pain) were the most common TEAEs. The most common serious TEAEs were the requirement for knee (10%) and hip (7%) arthroplasty, with 80% occurring during the posttreatment follow-up period. Neurologic-related TEAEs (28%; all phases) were generally mild-to-moderate. Overall, 81 joint replacements were performed in 71 patients (8 [11%] receiving placebo and 63 [89%] receiving fulranumab); 15 patients

Long-Term Safety of Topical Bacteriophage Application to the Frontal Sinus Region

PubMed Central

Drilling, Amanda J.; Ooi, Mian L.; Miljkovic, Dijana; James, Craig; Speck, Peter; Vreugde, Sarah; Clark, Jason; Wormald, Peter-John

2017-01-01

Background: Staphylococcus aureus biofilms contribute negatively to a number of chronic conditions, including chronic rhinosinusitis (CRS). With the inherent tolerance of biofilm-bound bacteria to antibiotics and the global problem of bacterial antibiotic resistance, the need to develop novel therapeutics is paramount. Phage therapy has previously shown promise in treating sinonasal S. aureus biofilms. Methods: This study investigates the long term (20 days) safety of topical sinonasal flushes with bacteriophage suspensions. The bacteriophage cocktail NOV012 against S. aureus selected for this work contains two highly characterized and different phages, P68 and K710. Host range was assessed against S. aureus strains isolated from CRS patients using agar spot tests. NOV012 was applied topically to the frontal sinus region of sheep, twice daily for 20 days. General sheep wellbeing, mucosal structural changes and inflammatory load were assessed to determine safety of NOV012 application. Results: NOV012 could lyse 52/61 (85%) of a panel of locally derived CRS clinical isolates. Application of NOV012 to the frontal sinuses of sheep for 20 days was found to be safe, with no observed inflammatory infiltration or tissue damage within the sinus mucosa. Conclusion: NOV012 cocktail appears safe to apply for extended periods to sheep sinuses and it could infect and lyse a wide range of S. aureus CRS clinical isolates. This indicates that phage therapy has strong potential as a treatment for chronic bacterial rhinosinusitis. PMID:28286740

Round window vibroplasty: long-term results.

PubMed

Böheim, Klaus; Mlynski, Robert; Lenarz, Thomas; Schlögel, Max; Hagen, Rudolf

2012-10-01

The round window (RW) approach in the use of the Vibrant Soundbridge(®) (VSB) is a safe and effective treatment of conductive and mixed hearing losses for a period of more than 3 years of device use. To investigate the long-term safety and efficacy as well as user satisfaction of patients with conductive and mixed hearing losses implanted with the VSB using RW vibroplasty. Twelve patients with conductive and mixed hearing losses were evaluated after 40 months of daily VSB use. Safety was assessed by evaluating reports of postoperative medical and surgical complications as well as by changes in bone conduction hearing thresholds. Efficacy outcome measures included aided and unaided hearing thresholds, speech recognition in quiet and in noise and subjective benefit questionnaires. The safety results revealed no significant medical complications. One subject experienced sudden hearing loss after 18-24 months of device use, but still continues to wear the device to her satisfaction. With regard to efficacy, there were no significant changes from short- to long-term results in aided word understanding, functional gain or speech recognition threshold, suggesting that the outcomes are stable over time. Subjective questionnaires revealed either the same or better results compared with the short-term data.

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis.

PubMed

Valeyre, Dominique; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; King, Talmadge E; Leff, Jonathan A; Noble, Paul W; Sahn, Steven A; du Bois, Roland M

2014-07-01

Pirfenidone is an oral antifibrotic agent that is approved in several countries for the treatment of idiopathic pulmonary fibrosis (IPF). We performed a comprehensive analysis of safety across four clinical trials evaluating pirfenidone in patients with IPF. All patients receiving pirfenidone 2403 mg/day in the Phase 3 CAPACITY studies (Studies 004 and 006) and all patients receiving at least one dose of pirfenidone in one of two ongoing open-label studies in patients with IPF (Studies 002 and 012) were selected for inclusion. Safety outcomes were evaluated from baseline until 28 days after the last dose of study drug. A total of 789 patients were included in the analysis. The median duration of exposure to pirfenidone was 2.6 years (range, 1 week-7.7 years), and the cumulative total exposure was 2059 person exposure years (PEY). Gastrointestinal and skin-related events were the most commonly reported adverse events; these were almost always mild to moderate in severity, and rarely led to treatment discontinuation. Elevations (>3× upper limit of normal) in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) occurred in 21/789 (2.7%) patients; the adjusted incidence of AST/ALT elevations was 1.7 per 100 PEY. This comprehensive analysis of safety in a large cohort of IPF patients receiving pirfenidone for a total of 2059 PEY demonstrates that long-term treatment with pirfenidone is safe and generally well tolerated. © 2014 The Authors. Respirology published by Wiley Publishing Asia Pty Ltd on behalf of Asian Pacific Society of Respirology.

Safety improvements at highway-railroad crossing for pedestrians and bicyclists and the assessment of long-term effects of centerline curbing.

DOT National Transportation Integrated Search

2012-06-01

The focus of the research reported herein was on assessing the long-term effectiveness of median barriers at highway-rail : grade crossings (HRGCs), the impacts of barrier maintenance in resurrecting safety, and on exploring and assessing ways : to i...

The PANGAEA study design - a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice.

PubMed

Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

2015-06-18

Fingolimod (Gilenya) is an oral medication for patients with highly active relapsing-remitting Multiple Sclerosis (RRMS). Clinical trials and post-marketing experience on more than 114,000 patients have established a detailed safety profile. Total patient exposure now exceeds 195,000 patient-years as stated in the last financial report (Dec 2014) of the Novartis Pharma AG, Basel, Switzerland. However, less is known about the safety of long-term fingolimod use in daily practice. Here, we describe the study design of PANGAEA (Post-Authorization Non-interventional German sAfety of GilEnyA in RRMS patients), a prospective, multicenter, non-interventional, long-term study to collect safety, efficacy, and pharmacoeconomic data on RRMS patients treated with fingolimod (0.5 mg/daily) under real-world conditions in Germany. PANGAEA is striving to assess a real-world safety and efficacy profile of fingolimod, based on data from 4,000 RRMS patients, obtained during a 60-month observational phase. A pharmacoeconomic sub-study of 800 RRMS patients further collects patient-reported outcome measures of disability, quality of life, compliance, treatment satisfaction, and usage of resources during a 24-month observational phase. Descriptive statistical analyses of the safety set as well as of stratified subgroups such as patients with concomitant diabetes mellitus and pretreated patients (e.g., natalizumab) will be conducted. PANGAEA seeks to confirm the current safety profile of fingolimod obtained in phase I-III clinical trials. The study design presented here will additionally provide guidance on the therapeutic use of fingolimod in clinical practice and possibly assists physicians in making evidence-based decisions.

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

PubMed

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

2016-04-01

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

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

PubMed Central

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

2014-01-01

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

Prevention of fall-related injuries in long-term care: a randomized controlled trial of staff education.

PubMed

Ray, Wayne A; Taylor, Jo A; Brown, Anne K; Gideon, Patricia; Hall, Kathi; Arbogast, Patrick; Meredith, Sarah

2005-10-24

Fall-related injuries, a major public health problem in long-term care, may be reduced by interventions that improve safety practices. Previous studies have shown that safety practice interventions can reduce falls; however, in long-term care these have relied heavily on external funding and staff. The aim of this study was to test whether a training program in safety practices for staff could reduce fall-related injuries in long-term care facilities. A cluster randomization clinical trial with 112 qualifying facilities and 10,558 study residents 65 years or older and not bedridden. The intervention was an intensive 2-day safety training program with 12-month follow-up. The training program targeted living space and personal safety; wheelchairs, canes, and walkers; psychotropic medication use; and transferring and ambulation. The main outcome measure was serious fall-related injuries during the follow-up period. There was no difference in injury occurrence between the intervention and control facilities (adjusted rate ratio, 0.98; 95% confidence interval, 0.83-1.16). For residents with a prior fall in facilities with the best program compliance, there was a nonsignificant trend toward fewer injuries in the intervention group (adjusted rate ratio, 0.79; 95% confidence interval, 0.57-1.10). More intensive interventions are required to prevent fall-related injuries in long-term care facilities.

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

PubMed Central

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

2013-01-01

OBJECTIVE This placebo-controlled study assessed long-term efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes and severe renal impairment (RI). RESEARCH DESIGN AND METHODS In this 1-year, double-blind study, 133 patients with type 2 diabetes (HbA1c 7.0–10.0%) and severe RI (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) at screening were randomized to linagliptin 5 mg (n = 68) or placebo (n = 65) once daily, added to existing background therapy. The primary efficacy end point was HbA1c change from baseline to week 12. Efficacy and safety end points were assessed after 1 year. RESULTS At week 12, adjusted mean HbA1c decreased by −0.76% with linagliptin and −0.15% with placebo (treatment difference, −0.60%; 95% CI −0.89 to −0.31; P < 0.0001). HbA1c improvements were sustained with linagliptin (−0.71%) over placebo (0.01%) at 1 year (treatment difference −0.72%, −1.03 to −0.41; P < 0.0001). Mean insulin doses decreased by −6.2 units with linagliptin and −0.3 units with placebo. Overall adverse event incidence was similar over 1 year (94.1 vs. 92.3%). Incidence of severe hypoglycemia with linagliptin and placebo was comparably low (three patients per group). Linagliptin and placebo had little effect on renal function (median change in eGFR, −0.8 vs. −2.2 mL/min/1.73 m2), and no drug-related renal failure occurred. CONCLUSIONS In patients with type 2 diabetes and severe RI, linagliptin provided clinically meaningful improvements in glycemic control with very low risk of severe hypoglycemia, stable body weight, and no cases of drug-related renal failure. The potential for linagliptin to spare insulin and provide long-term renal safety warrants further investigations. PMID:23033241

Long-term safety and efficacy of adalimumab for intestinal Behçet's disease in the open label study following a phase 3 clinical trial.

PubMed

Inoue, Nagamu; Kobayashi, Kiyonori; Naganuma, Makoto; Hirai, Fumihito; Ozawa, Morio; Arikan, Dilek; Huang, Bidan; Robinson, Anne M; Thakkar, Roopal B; Hibi, Toshifumi

2017-07-01

Intestinal Behçet's disease (BD) is an immune-mediated inflammatory disorder. We followed up the patients and evaluated safety profile and effectiveness of adalimumab for the treatment of intestinal BD through 100 weeks rolled over from the 52 week clinical trial (NCT01243671). Patients initiated adalimumab therapy at 160 mg at week 0, followed by 80 mg at week 2, followed by 40 mg every other week until the end of the study. Long-term safety and all adverse events (AEs) were examined. The efficacy was assessed on the basis of marked improvement (MI) and complete remission (CR) using a composite efficacy index, which combined global gastrointestinal symptoms and endoscopic assessments. Twenty patients were enrolled in this study; 15 patients received adalimumab treatment until study completion. The incidence of AEs through week 100 was 544.4 events/100 person-years, which was comparable to the incidence through week 52 (560.4 events/100 person-years). No unexpected trend was observed and adalimumab was well tolerated. At weeks 52 and 100, 60.0% and 40.0% of patients showed MI, respectively, and 20.0% and 15.0% of patients showed CR, respectively. This report demonstrates 2 years safety and effectiveness of adalimumab in intestinal BD patients. Patients with intestinal BD refractory to conventional treatment receiving up to 2 years of adalimumab treatment demonstrated safety outcomes consistent with the known profile of adalimumab, and the treatment led to sustained reduction of clinical and endoscopic disease activity.

Long-term safety and survival with gefitinib in select patients with advanced non-small cell lung cancer: Results from the US IRESSA Clinical Access Program (ICAP).

PubMed

Hirsch, Fred R; Sequist, Lecia V; Gore, Ira; Mooradian, Meghan; Simon, George; Croft, Elisabeth F; DeVincenzo, Diana; Munley, Jiefen; Stein, Dara; Freivogel, Klaus; Sifakis, Frangiscos; Bunn, Paul A

2018-06-01

This is the first report of long-term (>10 years) safety, tolerability, and survival data on patients with non-small cell lung cancer (NSCLC) who received treatment with gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Patients with advanced NSCLC (N = 191) who entered the IRESSA Clinical Access Program (ICAP) (June 2011 to January 2013) and had previously obtained a clinical benefit from gefitinib therapy (including patients who had received gefitinib since 2001) were analyzed for adverse events (AEs). A subset of patients (n = 79) underwent retrospective chart review to capture demographic, safety, and survival data. Seventy-five of 191 patients (39%) remained on long-term gefitinib therapy as of September 2016. Overall, serious AEs (SAEs) were reported in 64 patients (34%), the majority of which were attributed to underlying disease or comorbidities; only 3 patients (1.6%) had SAEs that were considered as possibly gefitinib-related. In the retrospective chart review cohort, 70% of patients were women; 58% were former smokers, and 30% were never-smokers; 56% were diagnosed with adenocarcinoma, and 13% were diagnosed with squamous carcinoma. Although EGFR mutational status was tested in only 17 patients (22%), it was assumed that most tumors were EGFR-mutation-positive. The median duration of gefitinib therapy was 11.1 years (7.8 years before and 3.5 years during ICAP), with 10-year and 15-year survival rates of 86% and 59%, respectively, from the initiation of therapy. A subset of long-term NSCLC survivors who were receiving gefitinib had an excellent long-term safety profile. Although it is assumed that most of these patients' tumors harbor EGFR mutations, molecular studies of available tumor specimens are planned to uncover the features that predict long-term survival. Cancer 2018;124:2407-14. © 2018 American Cancer Society. © 2018 American Cancer Society.

Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

NASA Astrophysics Data System (ADS)

Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

2017-02-01

Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

PubMed

Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

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

PubMed

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

2015-01-01

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

Nonsurgical Outpatient Therapies for the Management of Female Stress Urinary Incontinence: Long-Term Effectiveness and Durability

PubMed Central

Davila, G. Willy

2011-01-01

Objective. To evaluate long-term effectiveness and safety of conservative and minimally invasive outpatient treatments for female stress urinary incontinence (SUI) through a review of the literature. Methods. PubMed was searched for reports on prospective clinical trials with at least 12-month follow-up of minimally invasive treatments, pelvic floor rehabilitation, or pharmacotherapy in women with SUI. Each report was examined for long-term rates of effectiveness and safety. Results. Thirty-two clinical trial reports were included. Prospective long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months. Poor initial tolerability with duloxetine resulted in substantial discontinuation. Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements, generally good tolerability, and safety. Conclusions. Conservative therapy is an appropriate initial approach for female SUI, but if therapy fails, radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery. PMID:21738529

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

PubMed

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

2014-06-19

Adoptive transfer of donor-derived T lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT) without the risk for uncontrolled graft versus host disease (GvHD). Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. We now report the long-term follow-up of 10 patients infused with such safety switch-modified T cells. We find long-term persistence of iC9-modified (iC9-T) T cells in vivo in the absence of emerging oligoclonality and a robust immunologic benefit, mediated initially by the infused cells themselves and subsequently by an apparently accelerated reconstitution of endogenous naive T lymphocytes. As a consequence, these patients have immediate and sustained protection from major pathogens, including cytomegalovirus, adenovirus, BK virus, and Epstein-Barr virus in the absence of acute or chronic GvHD, supporting the beneficial effects of this approach to immune reconstitution after haplo-HSCT. This study was registered at www.clinicaltrials.gov as #NCT00710892. © 2014 by The American Society of Hematology.

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

PubMed Central

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

2014-01-01

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

Clinical trials with rasagiline: evidence for short-term and long-term effects.

PubMed

Siderowf, Andrew; Stern, Matthew

2006-05-23

Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.

PubMed

Supasyndh, Ouppatham; Sun, Ningling; Kario, Kazuomi; Hafeez, Kudsia; Zhang, Jack

2017-05-01

Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.

Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

PubMed

Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Zhang-Jin; Chan, Wai-Chi; Zhang, Shi-Ping; Ng, Roger Man-Kin; Chan, Connie Lai-Wah; Ho, Lai-Ming; Yu, Yee-Man; Lao, Li-Xing

2017-03-31

Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. ClinicalTrials.gov NCT02475538 .

Perceptions of safety and exposure to violence in public places among working age adults with disabilities or long-term health conditions in the UK: cross sectional study.

PubMed

Emerson, E; Krnjacki, L; Llewellyn, G; Vaughan, C; Kavanagh, A

2016-06-01

To examine perceptions of safety and exposure to violence in public places among working age adults with and without disabilities in the UK and to assess the extent to which any between-group differences may be moderated by gender and socio-economic situation. Cross-sectional study. Secondary analysis of data collected in Wave 3 (2011-13) of Understanding Society. Data were extracted on a subsample of 5069 respondents aged 16 to 64 years (28% of whom had a disability/long-term health condition) who were administered a questionnaire module addressing experiences of harassment. Between-group comparisons were made on four self-reported indicators of safety. Respondents with disabilities/long-term health conditions were significantly more likely to have been attacked (adjusted OR 2.30, 95%CI 1.17-4.50, P < 0.05), insulted (adjusted OR 1.48, 95%CI 1.16-1.90, P < 0.01) and to feel unsafe in public places (adjusted OR 1.32, 95%CI 1.16-1.56, P < 0.01) over the previous 12 months. There were no statistically significant differences between groups with regard to self-reported avoidance of public places. These associations were moderated by both gender and poverty status, with the increased risk of exposure to violence among people with disabilities being greater for both women and people living in poverty. The data add further support to the growing evidence base suggesting that people with a disability/long-term health condition are at significantly increased risk of exposure to interpersonal violence, particularly if they are living in poverty or are women. As such, there is a clear need to develop interventions that are targeted to the particular circumstances and needs of these high risk groups. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2).

PubMed

Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Hoeper, Marius M; Jansa, Pavel; Kim, Nick H; Wang, Chen; Wilkins, Martin R; Fritsch, Arno; Davie, Neil; Colorado, Pablo; Mayer, Eckhard

2015-05-01

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1 baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year. Copyright ©ERS 2015.

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

Long-Term Retention of Basic Science Knowledge: A Review Study

ERIC Educational Resources Information Center

Custers, Eugene J. F. M.

2010-01-01

In this paper, a review of long-term retention of basic science knowledge is presented. First, it is argued that retention of this knowledge has been a long-standing problem in medical education. Next, three types of studies are described that are employed in the literature to investigate long-term retention of knowledge in general. Subsequently,…

Long-Term Topical Diquafosol Tetrasodium Treatment of Dry Eye Disease Caused by Chronic Graft-Versus-Host Disease: A Retrospective Study.

PubMed

Yamane, Mio; Ogawa, Yoko; Fukui, Masaki; Kamoi, Mizuka; Uchino, Miki; Saijo-Ban, Yumiko; Kozuki, Naoyuki; Mukai, Shin; Mori, Takehiko; Okamoto, Shinichiro; Tsubota, Kazuo

2017-12-26

The aim of this study was to assess the safety and efficacy of long-term use of 3% diquafosol ophthalmic solution (DQS), an eye drop for mucin production and water secretion, for treating dry eye disease (DED) caused by chronic graft-versus-host disease (cGVHD). We retrospectively evaluated the safety and efficacy of DQS in 10 patients with mild to moderate cGVHD-induced DED. The efficacy was assessed by (1) degree of symptoms, (2) Schirmer I test value, (3) tear film breakup time (TFBUT), and (4) fluorescein and rose bengal scores. The median duration of DQS treatment was 12.0 months (range 6-17 months). DQS was effective for relieving severe pain caused by cGVHD-related DED. Although the Schirmer I test value was enhanced only marginally, the long-term application of DQS significantly improved the corneal/conjunctival epitheliopathy and tear film stability: the fluorescein score improved from 5.9±0.6 to 1.3±1.1 points (P=1.771×10); rose bengal staining from 4.7±1.6 to 2.0±1.5 points (P=0.008); and TFBUT from 2.6±0.9 to 4.6±1.6 mm (P=0.009). Furthermore, the long-term DQS treatment caused no major adverse events. This study suggested that long-term DQS treatment is a safe and robust approach for alleviating cGVHD-related DED.

A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension.

PubMed

Rakugi, Hiromi; Shimizu, Kohei; Nishiyama, Yuya; Sano, Yuhei; Umeda, Yuusuke

2018-06-01

Patients with essential hypertension who are receiving treatment with an angiotensin II receptor blocker and a calcium channel blocker often develop inadequate blood pressure (BP) control and require the addition of a diuretic. This study aimed to evaluate the long-term safety and efficacy of a triple combination therapy with 20 mg azilsartan (AZL), 5 mg amlodipine (AML) and 12.5 mg hydrochlorothiazide (HCTZ). The phase III, open-label, multicenter study (NCT02277691) comprised a 4-week run-in period and 52-week treatment period. Patients with inadequate BP control despite AZL/AML therapy (n = 341) received 4 weeks' treatment with AZL/AML (combination tablet) + HCTZ (tablet) and 4 weeks' treatment with AZL/AML/HCTZ (combination tablet) in a crossover manner, followed by AZL/AML/HCTZ (combination tablet) from Week 8 of the treatment period up to Week 52. The primary and secondary endpoints were long-term safety and BP (office and home), respectively. Most adverse events (AEs) were mild or moderate in intensity, and no deaths or treatment-related serious AEs were reported. The triple therapy provided consistent BP-lowering effects in both office and home measurements. The triple combination therapy with AZL/AML/HCTZ was well tolerated and effective for 52 weeks in Japanese patients with essential hypertension.

Planning for Long-Term Follow-Up: Strategies Learned from Longitudinal Studies.

PubMed

Hill, Karl G; Woodward, Danielle; Woelfel, Tiffany; Hawkins, J David; Green, Sara

2016-10-01

Preventive interventions are often designed and tested with the immediate program period in mind, and little thought that the intervention sample might be followed up for years or even decades beyond the initial trial. However, depending on the type of intervention and the nature of the outcomes, long-term follow-up may well be appropriate. The advantages of long-term follow-up of preventive interventions are discussed and include the capacity to examine program effects across multiple later life outcomes, the ability to examine the etiological processes involved in the development of the outcomes of interest, and the ability to provide more concrete estimates of the relative benefits and costs of an intervention. In addition, researchers have identified potential methodological risks of long-term follow-up such as inflation of type 1 error through post hoc selection of outcomes, selection bias, and problems stemming from attrition over time. The present paper presents a set of seven recommendations for the design or evaluation of studies for potential long-term follow-up organized under four areas: Intervention Logic Model, Developmental Theory and Measurement Issues; Design for Retention; Dealing with Missing Data; and Unique Considerations for Intervention Studies. These recommendations include conceptual considerations in the design of a study, pragmatic concerns in the design and implementation of the data collection for long-term follow-up, as well as criteria to be considered for the evaluation of an existing intervention for potential for long-term follow-up. Concrete examples from existing intervention studies that have been followed up over the long term are provided.

Planning for Long-Term Follow-up: Strategies Learned from Longitudinal Studies

PubMed Central

Hill, Karl G.; Woodward, Danielle; Woelfel, Tiffany; Hawkins, J. David; Green, Sara

2017-01-01

Preventive interventions are often designed and tested with the immediate program period in mind, and little thought that the intervention sample might be followed up for years, or even decades beyond the initial trial. However, depending on the type of intervention and the nature of the outcomes, long-term follow-up may well be appropriate. The advantages of long-term follow-up of preventive interventions are discussed, and include the capacity to examine program effects across multiple later life outcomes, the ability to examine the etiological processes involved in the development of the outcomes of interest and the ability to provide more concrete estimates of the relative benefits and costs of an intervention. In addition, researchers have identified potential methodological risks of long-term follow-up such as inflation of type 1 error through post-hoc selection of outcomes, selection bias and problems stemming from attrition over time. The present paper presents a set of seven recommendations for the design or evaluation of studies for potential long-term follow-up organized under four areas: Intervention Logic Model, Developmental Theory and Measurement Issues; Design for Retention; Dealing with Missing Data; and Unique Considerations for Intervention Studies. These recommendations include conceptual considerations in the design of a study, pragmatic concerns in the design and implementation of the data collection for long-term follow-up, as well as criteria to be considered for the evaluation of an existing intervention for potential for long-term follow-up. Concrete examples from existing intervention studies that have been followed up over the long-term are provided. PMID:26453453

The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration.

PubMed

Silva, Rufino; Axer-Siegel, Ruth; Eldem, Bora; Guymer, Robyn; Kirchhof, Bernd; Papp, Andras; Seres, Andras; Gekkieva, Margarita; Nieweg, Annette; Pilz, Stefan

2013-01-01

To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). Twenty-four-month, open-label, multicenter, phase IV extension study. Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or

Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study.

PubMed

Long, G V; Flaherty, K T; Stroyakovskiy, D; Gogas, H; Levchenko, E; de Braud, F; Larkin, J; Garbe, C; Jouary, T; Hauschild, A; Chiarion-Sileni, V; Lebbe, C; Mandalà, M; Millward, M; Arance, A; Bondarenko, I; Haanen, J B A G; Hansson, J; Utikal, J; Ferraresi, V; Mohr, P; Probachai, V; Schadendorf, D; Nathan, P; Robert, C; Ribas, A; Davies, M A; Lane, S R; Legos, J J; Mookerjee, B; Grob, J-J

2017-07-01

Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive dabrafenib plus trametinib (n = 211) or dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and <3 organ sites with metastasis) versus only 25% in the unfavourable subgroup (elevated lactate dehydrogenase). The dabrafenib plus trametinib safety profile was consistent with previous clinical trial observations, and no new safety signals were detected with long-term use. These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term

Safety and efficacy of ipragliflozin in elderly versus non-elderly Japanese patients with type 2 diabetes mellitus: a subgroup analysis of the STELLA-LONG TERM study.

PubMed

Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Nakamura, Ichiro; Uno, Satoshi

2018-03-01

This subgroup analysis of STELLA-LONG TERM interim data explored the long-term safety and efficacy of ipragliflozin in non-elderly vs. elderly Japanese type 2 diabetes mellitus (T2DM) patients. STELLA-LONG TERM is an ongoing 3-year prospective surveillance study of Japanese T2DM patients receiving ipragliflozin 50 mg once daily. In this subgroup analysis, patient characteristics, laboratory variables, and adverse drug reactions (ADRs) were compared between non-elderly (<65 years) and elderly (≥65 years) patients. Non-elderly patients had significantly higher body mass index and low-density lipoprotein cholesterol than elderly patients (P < 0.001). The proportion of patients with hemoglobin A1c (HbA1c) <8.0% was significantly higher among elderly patients (P < 0.001). HbA1c, fasting plasma glucose, and body weight significantly decreased from baseline to 3 and 12 months in both groups (all P < 0.05 vs. baseline). The ADR incidence was 10.83% vs. 10.42% in non-elderly and elderly patients. The incidence of skin complications was 0.98% vs. 1.65% and that of renal disorder was 0.47% vs. 0.95% in non-elderly and elderly patients (both P = 0.003). Ipragliflozin was effective in non-elderly and elderly Japanese T2DM patients in a real-world clinical setting. The incidence of renal disorder and skin complications was significantly higher in elderly vs. non-elderly patients.

Disability in long-term care residents explained by prevalent geriatric syndromes, not long-term care home characteristics: a cross-sectional study.

PubMed

Lane, Natasha E; Wodchis, Walter P; Boyd, Cynthia M; Stukel, Thérèse A

2017-02-10

Self-care disability is dependence on others to conduct activities of daily living, such as bathing, eating and dressing. Among long-term care residents, self-care disability lowers quality of life and increases health care costs. Understanding the correlates of self-care disability in this population is critical to guide clinical care and ongoing research in Geriatrics. This study examines which resident geriatric syndromes and chronic conditions are associated with residents' self-care disability and whether these relationships vary across strata of age, sex and cognitive status. It also describes the proportion of variance in residents' self-care disability that is explained by residents' geriatric syndromes versus long-term care home characteristics. We conducted a cross-sectional study using a health administrative cohort of 77,165 long-term care home residents residing in 614 Ontario long-term care homes. Eligible residents had their self-care disability assessed using the RAI-MDS 2.0 activities of daily living long-form score (range: 0-28) within 90 days of April 1st, 2011. Hierarchical multivariable regression models with random effects for long-term care homes were used to estimate the association between self-care disability and resident geriatric syndromes, chronic conditions and long-term care home characteristics. Differences in findings across strata of sex, age and cognitive status (cognitively intact versus cognitively impaired) were examined. Geriatric syndromes were much more strongly associated with self-care disability than chronic conditions in multivariable models. The direction and size of some of these effects were different for cognitively impaired versus cognitively intact residents. Residents' geriatric syndromes explained 50% of the variation in their self-care disability scores, while characteristics of long-term care homes explained an additional 2% of variation. Differences in long-term care residents' self-care disability are

Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST).

PubMed

Vichinsky, Elliott; El-Beshlawy, Amal; Al Zoebie, Azzam; Kamdem, Annie; Koussa, Suzanne; Chotsampancharoen, Thirachit; Bruederle, Andreas; Gilotti, Geralyn; Han, Jackie; Elalfy, Mohsen

2017-09-01

Children with red blood cell disorders may receive regular transfusions from an early age and consequently accumulate iron. Adequate iron chelation therapy can prevent organ damage and delayed growth/development. Deferasirox is indicated for treatment of pediatric patients with chronic iron overload due to transfusional hemosiderosis; however, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years. Deferasirox, a once-daily oral iron chelator, was evaluated in young pediatric patients with transfusional hemosiderosis during the observational 5-year ENTRUST study. Patients aged 2 to less than 6 years at enrollment received deferasirox according to local prescribing information, with the primary objective of evaluating safety, specifically renal and hepatic function. Serum ferritin was observed as a surrogate efficacy parameter. In total, 267 patients (mean age 3.2 years) predominantly with β-thalassemia (n = 176, 65.9%) were enrolled. Mean ± standard deviation deferasirox dose was 25.8 ± 6.5 mg/kg per day over a median of 59.9 months. A total of 145 patients (54.3%) completed 5 years' treatment. The proportion of patients with two or more consecutive postbaseline measurements (≥7 days apart) of serum creatinine higher than age-adjusted upper limit of normal (ULN) and alanine aminotransferase more than five times the ULN was 4.4% (95% confidence interval [CI]: 2.1-7.9) and 4.0% (95% CI: 1.8-7.4), respectively. Median serum ferritin decreased from 1,702 ng/ml at baseline to 1,127 ng/ml at 5 years. There were no new safety signals. Safety and efficacy of deferasirox in young pediatric patients in this long-term, observational study in everyday clinical practice were consistent with the known deferasirox profile. © 2017 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAFV600 mutation-positive metastatic melanoma: 2-year follow-up data and long-term responders' analysis.

PubMed

Blank, Christian U; Larkin, James; Arance, Ana M; Hauschild, Axel; Queirolo, Paola; Del Vecchio, Michele; Ascierto, Paolo A; Krajsova, Ivana; Schachter, Jacob; Neyns, Bart; Garbe, Claus; Chiarion Sileni, Vanna; Mandalà, Mario; Gogas, Helen; Espinosa, Enrique; Hospers, Geke A P; Miller, Wilson H; Robson, Susan; Makrutzki, Martina; Antic, Vladan; Brown, Michael P

2017-07-01

The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAF V600 mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety. This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas ® 4800 BRAF V600 Mutation Test). The primary end-point was safety; efficacy end-points were secondary. An exploratory analysis was performed to assess safety outcomes in patients with long duration of response (DOR) (≥12 or ≥24 months). After a median follow-up of 32.2 months (95% CI, 31.1-33.2 months), 3079/3219 patients (96%) had discontinued treatment. Adverse events (AEs) were largely consistent with previous reports; the most common all-grade treatment-related AEs were arthralgia (37%), alopecia (25%) and hyperkeratosis (23%); the most common grade 3/4 treatment-related AEs were squamous cell carcinoma of the skin (8%) and keratoacanthoma (8%). In the exploratory analysis, patients with DOR ≥12 months (n = 287) or ≥24 months (n = 133) were more likely to experience grade 3/4 AEs than the overall population. No new specific safety signals were observed with longer vemurafenib exposure. After 2 years' follow-up, safety was maintained in this large group of patients with BRAF V600 mutation-positive metastatic melanoma who are more representative of routine clinical practice than typical clinical trial populations. These data suggest that long-term vemurafenib treatment is effective and tolerable without the development of new safety signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Urine metabonomic study on long-term use of total ginsenosides in rats].

PubMed

Xie, Xie; Chen, Shao-Qiu; Lv, Ying-Fang; Wang, Xiao-Yan; Jia, Wei

2014-12-01

Due to its effect of systems regulation and promotion on body, Ginseng is always referred to be long-term used as a dietary supplement. But it was still unclear about its target of the tonic effects and also the side-effects long-term use may bring. Urine metabolomic method is suitable for long-term studies of pharmaco-dynamics, pharmacology and toxicology of traditional Chinese medicine because of its characteristics of non-invasive and monitoring the whole-body metabolism. This study was designed to detect the dynamic variation of rat urine metabolome along with a long-term administration of total ginsenosides using GC-TOF based metabolomic technology. Our result showed that either short-term or chronic administration of ginsenosides did not impact the rat urine metabolome significantly (as the PCA subgroup was not successful). By comparison, the short-term (1-3 w) dose of ginsenosides had the biggest metabolic influence including TCA cycle, catecholamines and neurotransmitter amino acids. Medium-term (6-10 w) dose had a gradually lower effect and long-term (27 w) dose almost had no effect. Our study indicates that both short and long-term administration of ginsenosides showed almost no obvious side-effect on the experimental animals.

Long-term safety of tiotropium/olodaterol Respimat® in patients with moderate-to-very severe COPD and renal impairment in the TONADO® studies.

PubMed

LaForce, Craig; Derom, Eric; Bothner, Ulrich; Kloer, Isabel M; Trampisch, Matthias; Buhl, Roland

2018-01-01

The safety, lung function efficacy, and symptomatic benefits of combined tiotropium and olodaterol in patients with COPD were established in the 1-year TONADO ® studies (NCT01431274; NCT01431287). As tiotropium is predominantly excreted by the kidneys, the long-term safety profile of tiotropium/olodaterol was investigated in patients with renal impairment in a prespecified safety analysis of the TONADO studies. These were 2 replicate, randomized, double-blind, parallel-group, 52-week Phase III studies that assessed tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat ® ) in patients with moderate-to-very severe COPD. In this analysis, renal impairment was defined as mild (creatinine clearance [CLcr] 60-89 mL/min), moderate (CLcr 30-59 mL/min) or severe (CLcr 15-29 mL/min). Adverse events (AEs) were pooled from both studies. Of 3,041 patients included in this analysis, 1,333 (43.8%) had mild, 404 (13.3%) had moderate, and 5 (0.2%) had severe renal impairment; these were distributed equally between treatment groups. Almost one-quarter of all treated patients (23.4%) had a history of cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diabetes. AEs with olodaterol, tiotropium, and tiotropium/olodaterol occurred in 75.1%, 70.8%, and 72.0% of patients with no renal impairment, 75.7%, 74.0%, and 73.3% with mild renal impairment, and 84.3%, 79.5%, and 79.7% with moderate renal impairment, respectively. There was no notable effect of renal impairment on the proportion of patients with an AE, and no differences were observed between tiotropium/olodaterol versus the monocomponents. There was no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects with increasing severity of renal impairment. Over half the patients enrolled in the TONADO studies had renal impairment, and there was a high level of pre-existing cardiovascular

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study

PubMed Central

Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

Aim: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. Methods: The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. Results: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean ± SD changes in LDL cholesterol were −24.2% ± 14.7% with combination therapy, −16.0% ± 16.0% with fenofibrate alone, and −17.4% ± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p < 0.01 for each). The corresponding values for triglycerides were −40.0% ± 29.5%, −40.1% ± 28.7%, and −3.4% ± 32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. Conclusion: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia. PMID:27397061

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study.

PubMed

Oikawa, Shinichi; Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean±SD changes in LDL cholesterol were -24.2%±14.7% with combination therapy, -16.0%±16.0% with fenofibrate alone, and -17.4%± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p＜0.01 for each). The corresponding values for triglycerides were -40.0%±29.5%, -40.1%±28.7%, and -3.4%±32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia.

Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized long-term (ORL) study.

PubMed

Tatsuno, Ichiro; Saito, Yasushi; Kudou, Kentarou; Ootake, Jun

2013-01-01

TAK-085 is an omega-3 preparation that contains eicosapentaenoic acid ethyl-ester (EPA-E) and docosahexaenoic acid-ethyl ester used in the management of hypertriglyceridemia. The aim of the study was to evaluate the long-term safety (adverse events [AEs], laboratory parameters, vital signs, weight, and electrocardiograms) and effects on lipid profiles, especially triglyceride levels, of TAK-085 in Japanese patients with hypertriglyceridemia (triglyceride levels ≥150 mg/dL and <750 mg/dL). In this multicenter, open-label, randomized study, adults with hypertriglyceridemia undergoing lifestyle modification received TAK-085 2 g (2 g once daily; n = 165) or 4 g (2 g twice daily; n = 171), or EPA-E 1.8 g (0.6 g three times daily; n = 167) for 52 weeks. Patients were stratified for co-administration of a statin. TAK-085 was well tolerated throughout the 52-week study. Overall, no substantial differences were found in the tolerability of TAK-085 2 g, TAK-085 4 g, and EPA-E 1.8 g with incidence rates for AEs of 83.6%, 86.0%, and 89.2%, respectively. Most AEs were mild or moderate in severity. Triglyceride levels decreased from baseline in all groups by week 4, and the decreases were maintained throughout the study. At week 52 the reduction in triglycerides with TAK-085 2 g (-13.9%) was similar to that with EPA-E 1.8 g (-12.1%), whereas the reduction seen with TAK-085 4 g (-25.5%) was greater than that with EPA-E 1.8 g, as assessed by point estimates and 95% confidence intervals. TAK-085 was safe and well tolerated for up to 52 weeks of treatment in Japanese patients with hypertriglyceridemia undergoing lifestyle modification. Reductions in triglyceride levels achieved after 4 weeks were maintained at 52 weeks. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Considerations on long-term immuno-intervention in the treatment of multiple sclerosis: an expert opinion.

PubMed

Grigoriadis, Nikolaos; Linnebank, Michael; Alexandri, Nektaria; Muehl, Sarah; Hofbauer, Günther F L

2016-10-01

As management of multiple sclerosis (MS) requires life-long treatment with disease-modifying agents, any risks associated with long-term use should be considered when evaluating therapeutic options. Immune cells of the innate and adaptive immune systems play various roles in the pathogenesis of MS. MS therapies affect the immune system, each with a unique mode of action, and consequently possess different long-term safety profiles. Rare, but serious safety concerns, including an increased risk of infection and cancer, have been associated with immunosuppressant use. The risks associated with newer immunosuppressive agents, which target specific elements of MS disease pathophysiology, are not yet fully established as the duration of clinical trials is relatively short and post-marketing experience is limited. Non-immunosuppressants used to treat MS have well-defined safety profiles established over a large number of patient-years demonstrating them to be well-tolerated long-term treatment options. When considering the long-term use of disease-modifying agents for treating MS, classification as immunosuppressants or non-immunosuppressants can be useful when evaluating potential risks associated with chronic use. A successful therapeutic strategy for any serious, chronic disease such as MS should weigh effectiveness versus long-term safety of available treatments.

Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.

PubMed

Kovalyov, Oleksiy O; Kostyuk, Oleksandr G; Tkachuk, Tetyana V

To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy. Peripheral venous bed status in 41 oncology patients taking long-term chemotherapy treatment is analyzed in the article. Doppler sonography, morphologic and immune histochemical analyses were used in the study. Doppler sonography found qualitative and quantitative changes in forearm veins at different time periods after initiation of chemotherapy in the majority of patients. The major morphologic manifestations of venous wall damage were chemical phlebitis, local or extended hardening of venous wall, venous thrombosis and extravasations with necrosis and subsequent paravasal tissue sclerosis. Alternative vascular access created in 12 patients completely met the adequacy criteria (safety, multiple use, longevity, realization of the designed therapy program). The conclusion was made about inapplicability of forearm veins for long-term administration of cytostatic agents. If it is impossible to use central veins, arteriovenous fistula can become an alternative vascular access.

Long-term safety of PEG 4000 in children with chronic functional constipation: A biochemical perspective

PubMed Central

2010-01-01

Purpose To evaluate the long-term safety of polyethylene glycol (PEG) 4000 in children with constipation, particularly the biochemical aspects of safety. Methods Medical records were evaluated, and 100 children, who had been taking PEG 4000 for more than 6 months, and who had been under clinical and biochemical monitoring, were enrolled. Ages; 6.11±3.12 years, Duration of therapy; 16.93±7.02 months, dose of PEG 4000; 0.72±0.21 g/kg/d. Results None of the children complained of clinical adverse effect. The first biochemical test was performed at 8.05 months after beginning of PEG 4000. Serum phosphate (SP) value was high in 10 children, and leucopenia was noted in one child. The second test was performed in 44 children at 7.57 months after the first test. The SP value was high in four children, including the three children whose initial SP value was high and one new child. Six out of 10 children with high initial SP value became normal and one was lost. Hypernatremia was noted in one child. The third test was done in 15 children at 7.5 months after the second test. The SP value of the new child from the second test was high, but became normal after finishing treatment. Two out of 3 children with high SP value at the second test became normal and one was lost. The fourth test was done in 2 children few months after the third test. All of the results were normal. There were no relation between duration of therapy and hyperphosphatemia, or between dose of PEG 4000 and hyperphosphatemia. Conclusions PEG 4000 is safe for long-term therapy in children with constipation with respect to biochemical parameters. PMID:21189949

Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension.

PubMed

Fein, Henry G; Vaughan, T Brooks; Kushner, Harvey; Cram, David; Nguyen, Dat

2015-10-27

Overweight and obesity are common among patients with Cushing's syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults (N = 50) with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had failed or were not candidates for surgery (SEISMIC, Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome). This analysis examines long-term weight change among patients who received mifepristone in SEISMIC and enrolled in a long-term safety extension (LTE) study. Patients completing the 24-week SEISMIC study and subsequent 6-week off-drug safety evaluation were invited to enroll in the LTE study. Mifepristone doses at the end of SEISMIC were the LTE starting doses. Body weight measures were reviewed at baseline and week 24 of SEISMIC and at LTE month 6, 12, 18, 24, and final visit (last observation collected during the LTE study). Of the 30 patients enrolled in the LTE, evaluable weight data were available for 29 (20/29 female; mean age of 44.7 ± 11.2 years). These patients received mifepristone for a median of 29.2 months (range 8.4-41.9). Mean ± SD weight from SEISMIC baseline to LTE final visit decreased by 10.3 ± 16.3 kg (mean 105.4 ± 34.3 kg to 95.1 ± 32.9 kg), a 9.3 % decrease from baseline weight (P = 0.0008). Of the 29 LTE patients, 18 (62.1 %) lost ≥ 5 % of body weight by the end of the initial 24-week treatment period; this ≥5 % weight loss persisted in 83.3 % (15/18) at LTE final visit. Ten patients (34.5 %) lost ≥ 10 % of initial body weight by week 24 of SEISMIC, which persisted in 80 % at LTE final visit. No new safety signals were detected with long-term mifepristone use. Clinically meaningful weight loss achieved during

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

An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.

PubMed

Johnson, Jeremy R; Lossignol, Dominique; Burnell-Nugent, Mary; Fallon, Marie T

2013-08-01

Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc

Archiving Primary Data: Solutions for Long-Term Studies.

PubMed

Mills, James A; Teplitsky, Céline; Arroyo, Beatriz; Charmantier, Anne; Becker, Peter H; Birkhead, Tim R; Bize, Pierre; Blumstein, Daniel T; Bonenfant, Christophe; Boutin, Stan; Bushuev, Andrey; Cam, Emmanuelle; Cockburn, Andrew; Côté, Steeve D; Coulson, John C; Daunt, Francis; Dingemanse, Niels J; Doligez, Blandine; Drummond, Hugh; Espie, Richard H M; Festa-Bianchet, Marco; Frentiu, Francesca; Fitzpatrick, John W; Furness, Robert W; Garant, Dany; Gauthier, Gilles; Grant, Peter R; Griesser, Michael; Gustafsson, Lars; Hansson, Bengt; Harris, Michael P; Jiguet, Frédéric; Kjellander, Petter; Korpimäki, Erkki; Krebs, Charles J; Lens, Luc; Linnell, John D C; Low, Matthew; McAdam, Andrew; Margalida, Antoni; Merilä, Juha; Møller, Anders P; Nakagawa, Shinichi; Nilsson, Jan-Åke; Nisbet, Ian C T; van Noordwijk, Arie J; Oro, Daniel; Pärt, Tomas; Pelletier, Fanie; Potti, Jaime; Pujol, Benoit; Réale, Denis; Rockwell, Robert F; Ropert-Coudert, Yan; Roulin, Alexandre; Sedinger, James S; Swenson, Jon E; Thébaud, Christophe; Visser, Marcel E; Wanless, Sarah; Westneat, David F; Wilson, Alastair J; Zedrosser, Andreas

2015-10-01

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Short-term and long-term effects of GDP on traffic deaths in 18 OECD countries, 1960-2011.

PubMed

Dadgar, Iman; Norström, Thor

2017-02-01

Research suggests that increases in gross domestic product (GDP) lead to increases in traffic deaths plausibly due to the increased road traffic induced by an expanding economy. However, there also seems to exist a long-term effect of economic growth that is manifested in improved traffic safety and reduced rates of traffic deaths. Previous studies focus on either the short-term, procyclical effect, or the long-term, protective effect. The aim of the present study is to estimate the short-term and long-term effects jointly in order to assess the net impact of GDP on traffic mortality. We extracted traffic death rates for the period 1960-2011 from the WHO Mortality Database for 18 OECD countries. Data on GDP/capita were obtained from the Maddison Project. We performed error correction modelling to estimate the short-term and long-term effects of GDP on the traffic death rates. The estimates from the error correction modelling for the entire study period suggested that a one-unit increase (US$1000) in GDP/capita yields an instantaneous short-term increase in the traffic death rate by 0.58 (p<0.001), and a long-term decrease equal to -1.59 (p<0.001). However, period-specific analyses revealed a structural break implying that the procyclical effect outweighs the protective effect in the period prior to 1976, whereas the reverse is true for the period 1976-2011. An increase in GDP leads to an immediate increase in traffic deaths. However, after the mid-1970s this short-term effect is more than outweighed by a markedly stronger protective long-term effect, whereas the reverse is true for the period before the mid-1970s. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Long-Term Tolerability and Safety of Pharmacological Treatment of Adult Attention-Deficit/Hyperactivity Disorder: A 6-Year Prospective Naturalistic Study.

PubMed

Edvinsson, Dan; Ekselius, Lisa

2018-06-20

Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder typically treated with stimulants and atomoxetine. Data on long-term tolerability and safety of such pharmacological treatment in subjects diagnosed in adulthood are limited. A cohort of adults diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria was followed-up on an average of 6 years after first evaluation. Of 168 adults, 112 (67%) who initiated medication were available for follow-up. Data were obtained from patient record data, self-report forms, and a telephone interview. Of the 112 participants assessed, 57 (51%) were still on treatment with methylphenidate (MPH) at follow-up and 55 (49%) had discontinued. The 3 leading reasons for discontinuing treatment with MPH were lack of effect (29%), elevated mood or hypomania (11%), and losing contact with the prescribing physician (9%). The most common adverse effects in subjects still on treatment with MPH were decreased appetite (28%), dry mouth (24%), anxiousness/restlessness and increased pulse frequency (19% each), decreased sexual desire (17%), and perspiration (15%). Subjects still on treatment reported increased quality of life, a higher level of functioning, and a greater understanding of their way of functioning from those being close compared with nonmedicated subjects. The high attrition rate underscores the need for further research to identify possible modes to increase retention to treatment. Those diagnosed with ADHD and on long-term treatment with stimulants experience mild and tolerable adverse effects.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Ethics and Intimate Sexual Activity in Long-Term Care.

PubMed

Metzger, Eran

2017-07-01

A case is presented in which the staff of a long-term care facility discovers that the husband of a resident with dementia is engaged in sexual activity with her. The case illustrates a dilemma for long-term care facilities that create a home-like environment with a goal of maximizing residents' autonomy while ensuring their safety. An approach to assessing capacity to consent to intimate sexual activity is described, followed by guidelines that nursing homes can implement to support residents who wish to engage in sexual activity. Recommendations are also offered for supporting long-term care staff and family members of residents who are interested in intimate sexual activity. © 2017 American Medical Association. All Rights Reserved.

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.

Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis.

PubMed

Ruperto, Nicolino; Lovell, Daniel J; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhães, Claudia; Chavez-Corrales, J; Huemer, Christian; Kivitz, Alan; Blanco, Francisco J; Foeldvari, Ivan; Hofer, Michael; Horneff, Gerd; Huppertz, Hans-Iko; Job-Deslandre, Chantal; Loy, Anna; Minden, Kirsten; Punaro, Marilynn; Nunez, Alejandro Flores; Sigal, Leonard H; Block, Alan J; Nys, Marleen; Martini, Alberto; Giannini, Edward H

2010-06-01

We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >or=21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008. Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Long-term outcomes of laparoscopic adjustable gastric banding.

PubMed

Khoraki, Jad; Moraes, Marilia G; Neto, Adriana P F; Funk, Luke M; Greenberg, Jacob A; Campos, Guilherme M

2018-01-01

Laparoscopic adjustable gastric banding (LAGB) is an option for the treatment of severe obesity. Few US studies have reported long-term outcomes. We aimed to present long-term outcomes with LAGB. Retrospective study of patients who underwent LAGB at an academic medical center in the US from 1/2005 to 2/2012. Outcomes included weight loss, complications, re-operations, and LAGB failure. 208 patients underwent LAGB. Mean BMI was 45.4 ± 6.4 kg/m 2 . Mean follow-up was 5.6 (0.5-10.7) years. Complete follow-up was available for 90% at one year (186/207), 80% at five years (136/171), and 71% at ten years (10/14). Percentage of excess weight loss at one, five, and ten years was 29.9, 30, and 16.9, respectively. Forty-eight patients (23.1%) required a reoperation. LAGB failure occurred in 118 (57%) and higher baseline BMI was the only independently associated factor (OR 1.1; 95%CI 1.0-1.1; p = 0.016). LAGB was associated with poor short and long-term weight loss outcomes and a high failure rate. With the increased safety profile and greater efficacy of other surgical techniques, LAGB utilization should be discouraged. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs.

PubMed

Jaén, Maria Luisa; Vilà, Laia; Elias, Ivet; Jimenez, Veronica; Rodó, Jordi; Maggioni, Luca; Ruiz-de Gopegui, Rafael; Garcia, Miguel; Muñoz, Sergio; Callejas, David; Ayuso, Eduard; Ferré, Tura; Grifoll, Iris; Andaluz, Anna; Ruberte, Jesus; Haurigot, Virginia; Bosch, Fatima

2017-09-15

Diabetes is a complex metabolic disease that exposes patients to the deleterious effects of hyperglycemia on various organs. Achievement of normoglycemia with exogenous insulin treatment requires the use of high doses of hormone, which increases the risk of life-threatening hypoglycemic episodes. We developed a gene therapy approach to control diabetic hyperglycemia based on co-expression of the insulin and glucokinase genes in skeletal muscle. Previous studies proved the feasibility of gene delivery to large diabetic animals with adeno-associated viral (AAV) vectors. Here, we report the long-term (∼8 years) follow-up after a single administration of therapeutic vectors to diabetic dogs. Successful, multi-year control of glycemia was achieved without the need of supplementation with exogenous insulin. Metabolic correction was demonstrated through normalization of serum levels of fructosamine, triglycerides, and cholesterol and remarkable improvement in the response to an oral glucose challenge. The persistence of vector genomes and therapeutic transgene expression years after vector delivery was documented in multiple samples from treated muscles, which showed normal morphology. Thus, this study demonstrates the long-term efficacy and safety of insulin and glucokinase gene transfer in large animals and especially the ability of the system to respond to the changes in metabolic needs as animals grow older.

Design and methods of a postmarketing pharmacoepidemiology study assessing long-term safety of Prolia® (denosumab) for the treatment of postmenopausal osteoporosis.

PubMed

Xue, Fei; Ma, Haijun; Stehman-Breen, Catherine; Haller, Christine; Katz, Leonid; Wagman, Rachel B; Critchlow, Cathy W

2013-10-01

To describe the rationale and methods for a prospective, open-cohort study assessing the long-term safety of Prolia(®) for treatment of postmenopausal osteoporosis (PMO) in postmarketing settings. Data will be derived from United States Medicare, United Healthcare, and Nordic (Denmark, Sweden, Norway) national registries. Observation will begin on the date of first Prolia(®) regulatory approval (May 26, 2010) and continue for 10 years. Women with PMO will be identified by postmenopausal age, osteoporosis diagnosis, osteoporotic fracture, or osteoporosis treatment. Exposure to Prolia(®) and bisphosphonates will be updated during follow-up; exposure cohorts will be defined based on patient-years during which patients are on- or post-treatment. Nine adverse events (AEs) will be assessed based on diagnosis codes: osteonecrosis of the jaw (ONJ), atypical femoral fracture (AFF), fracture healing complications, hypocalcemia, infection, dermatologic AEs, acute pancreatitis, hypersensitivity, and new primary malignancy. Medical review will confirm selected potential cases of ONJ and AFF. Incidence rates (IRs) of AEs will be described overall and for exposure cohorts; multivariate Cox proportional hazard regression models will compare IRs of AEs across exposure cohorts. Utilization patterns of Prolia(®) for approved, and unapproved indications will be described. This study is based on comprehensive preliminary research and considers methodological challenges specific to the study population. The integrated data systems used in this regulatory committed program can serve as a powerful data resource to assess diverse and rare AEs over time. © 2013 Amgen Inc. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

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.

Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder

PubMed Central

Josiassen, Richard C.; Kane, John M.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

2017-01-01

Background The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD. Methods The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively. Results The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment

Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder.

PubMed

Josiassen, Richard C; Kane, John M; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

2017-08-01

The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD. The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively. The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment (Week 48) indicated that

Long-term Efficacy of Vedolizumab for Crohn's Disease.

PubMed

Vermeire, Severine; Loftus, Edward V; Colombel, Jean-Frédéric; Feagan, Brian G; Sandborn, William J; Sands, Bruce E; Danese, Silvio; D'Haens, Geert R; Kaser, Arthur; Panaccione, Remo; Rubin, David T; Shafran, Ira; McAuliffe, Megan; Kaviya, Arpeat; Sankoh, Serap; Mody, Reema; Abhyankar, Brihad; Smyth, Michael

2017-04-01

Vedolizumab is a gut-selective α4β7 integrin antagonist therapy for ulcerative colitis and Crohn's disease. The GEMINI long-term safety [LTS] trial is an ongoing open-label study investigating the safety of vedolizumab. We present interim exploratory analyses of efficacy in patients with Crohn's disease. Patients from the C13004, GEMINI 2 and GEMINI 3 studies and vedolizumab-naïve patients could enrol in GEMINI LTS and received vedolizumab every 4 weeks. Data were collected from May 22, 2009 to June 27, 2013. Outcomes of clinical response and remission, defined by the Harvey-Bradshaw Index, and health-related quality of life [HRQL] were assessed for up to 152 weeks of treatment in the efficacy population. Among patients with response at week 6 in GEMINI 2 who received vedolizumab continuously, 83% [n=100/120] and 89% [n=62/70] of patients with available data were in remission after 104 and 152 weeks, respectively. Increased dosing frequency from every 8 weeks [GEMINI 2] to every 4 weeks [GEMINI LTS] improved outcomes in patients who had withdrawn early from GEMINI 2, with 47% [n=27/57] experiencing clinical response and 32% [n=18/57] in remission at week 52 of GEMINI LTS [up from 39% and 4% before the dose increase]. Similar improvements were observed regardless of prior tumour necrosis factor [TNF] antagonist exposure. Long-term benefits of HRQL were also observed. The clinical benefits of vedolizumab continued with long-term treatment regardless of prior TNF antagonist exposure. Increased dosing frequency might improve outcomes in patients who lose response to conventional 8-weekly dosing. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment.

PubMed

Horwitz, Mitchell E; Chao, Nelson J; Rizzieri, David A; Long, Gwynn D; Sullivan, Keith M; Gasparetto, Cristina; Chute, John P; Morris, Ashley; McDonald, Carolyn; Waters-Pick, Barbara; Stiff, Patrick; Wease, Steven; Peled, Amnon; Snyder, David; Cohen, Einat Galamidi; Shoham, Hadas; Landau, Efrat; Friend, Etty; Peleg, Iddo; Aschengrau, Dorit; Yackoubov, Dima; Kurtzberg, Joanne; Peled, Tony

2014-07-01

Delayed hematopoietic recovery is a major drawback of umbilical cord blood (UCB) transplantation. Transplantation of ex vivo-expanded UCB shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product consisting of stem cells expanded for 21 days in the presence of nicotinamide and a noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide long-term engraftment. In a phase I trial, 11 adults with hematologic malignancies received myeloablative bone marrow conditioning followed by transplantation with NiCord and a second unmanipulated UCB unit. Safety, hematopoietic recovery, and donor engraftment were assessed and compared with historical controls. No adverse events were attributable to the infusion of NiCord. Complete or partial neutrophil and T cell engraftment derived from NiCord was observed in 8 patients, and NiCord engraftment remained stable in all patients, with a median follow-up of 21 months. Two patients achieved long-term engraftment with the unmanipulated unit. Patients transplanted with NiCord achieved earlier median neutrophil recovery (13 vs. 25 days, P < 0.001) compared with that seen in historical controls. The 1-year overall and progression-free survival rates were 82% and 73%, respectively. UCB-derived hematopoietic stem and progenitor cells expanded in the presence of nicotinamide and transplanted with a T cell-containing fraction contain both short-term and long-term repopulating cells. The results justify further study of NiCord transplantation as a single UCB graft. If long-term safety is confirmed, NiCord has the potential to broaden accessibility and reduce the toxicity of UCB transplantation. Clinicaltrials.gov NCT01221857. Gamida Cell Ltd.

Safety and Durability of Effect with Long-Term, Open-Label Droxidopa Treatment in Patients with Symptomatic Neurogenic Orthostatic Hypotension (NOH303).

PubMed

Isaacson, Stuart; Shill, Holly A; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J

2016-10-19

Neurogenic orthostatic hypotension (nOH) is associated with insufficient norepinephrine release in response to postural change. The objective of this study was to evaluate the long-term safety and durability of efficacy of the norepinephrine precursor droxidopa in patients with symptomatic nOH. This multinational study consisted of 3 sequential phases: a 3-month open-label droxidopa treatment phase followed by a 2-week double-blind, placebo-controlled withdrawal phase, and a 9-month open-label extension phase in which all patients received droxidopa. Patients were adults diagnosed with symptomatic nOH associated with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Efficacy was evaluated using patient- and investigator-reported questionnaire responses and the orthostatic standing test. Safety was assessed through adverse event (AE) reports and vital signs. A total of 102 patients received treatment with droxidopa. Initial improvements from baseline in patient-reported nOH symptom severity and impact on daily activities, evaluated using the Orthostatic Hypotension Questionnaire, exceeded 50% and were maintained throughout the 12-month study. Decreased nOH severity was also reflected in clinician and patient ratings on the Clinical Global Impression questionnaire. Standing systolic and diastolic blood pressures were increased from baseline throughout the study with droxidopa treatment. The most frequently reported AEs were falls, urinary tract infection, and headache. There was a low incidence (≤2%) of cardiac AEs (eg, first-degree atrioventricular block, supraventricular extrasystoles). Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in nOH signs and symptoms.

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…

An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis.

PubMed

Queiroz-Telles, Flavio; Goldani, Luciano Z; Schlamm, Haran T; Goodrich, James M; Espinel-Ingroff, Ana; Shikanai-Yasuda, Maria A

2007-12-01

In previous studies, itraconazole was revealed to be an effective therapy and was considered to be the gold standard treatment for mild-to-moderate acute and chronic clinical forms of paracoccidioidomycosis. A pilot study was conducted to investigate the efficacy, safety, and tolerability of voriconazole for the long-term treatment of acute or chronic paracoccidioidomycosis, with itraconazole as the control treatment. A randomized, open-label study was conducted at 3 Brazilian tertiary care hospitals. Patients were randomized (at a 2 : 1 ratio) to receive oral therapy with voriconazole or itraconazole for 6 months. Patients receiving >or=1 dose of study drug were evaluated for safety; patients with confirmed paracoccidioidomycosis who completed >or=6 months of therapy (treatment-evaluable patients) were evaluated for treatment efficacy. Satisfactory global response was assessed at the end of treatment. Fifty-three patients were evaluated for treatment safety (35 received voriconazole, and 18 received itraconazole). Both drugs were well tolerated. The most common treatment-related adverse events in the voriconazole group included abnormal vision, chromatopsia, rash, and headache; the most common treatment-related adverse events in the itraconazole group included bradycardia, diarrhea, and headache. Liver function test values were slightly higher in patients receiving voriconazole than in those receiving itraconazole; 2 patients in the voriconazole group were withdrawn from treatment because of increased liver function test values. In the intent-to-treat populations, the satisfactory response rate (i.e., complete or partial global response) was 88.6% among the voriconazole group and 94.4% among the itraconazole group. The response rate among treatment-evaluable patients was 100% for both treatment groups; no relapses were observed after 8 weeks of follow-up. This is, to our knowledge, the first study to demonstrate that voriconazole is as well tolerated and effective

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

PubMed

Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

An open-label extension long-term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan.

PubMed

Ichikawa, Hironobu; Hiratani, Michio; Yasuhara, Akihiro; Tsujii, Noa; Oshimo, Takashi; Ono, Hiroaki; Tadori, Yoshihiro

2018-02-01

The purpose of this study was to evaluate the long-term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6-17 years) with autistic disorder (AD) in Japan. In this open-label extension study, patients who had completed a previous randomized, double-blind, placebo-controlled 8-week study were enrolled and were flexibly dosed with aripiprazole (1-15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan. Seventy (81%) out of 86 enrolled patients completed week-48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment-emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was -6.3 in prior placebo patients and -2.6 in prior aripiprazole patients. Aripiprazole was generally safe, well tolerated, and effective in the long-term treatment of irritability associated with AD in Japanese pediatric patients. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-09-01

The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy. © 2014 The authors.

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.

PubMed

de Lind van Wijngaarden, Roderick F A; Siemensma, Elbrich P C; Festen, Dederieke A M; Otten, Barto J; van Mil, Edgar G A H; Rotteveel, Joost; Odink, Roelof J H; Bindels-de Heus, G C B Karen; van Leeuwen, Mariëtte; Haring, Danny A J P; Bocca, Gianni; Houdijk, E C A Mieke; Hoorweg-Nijman, J J Gera; Vreuls, René C F M; Jira, Petr E; van Trotsenburg, A S Paul; Bakker, Boudewijn; Schroor, Eelco J; Pilon, Jan Willem; Wit, Jan M; Drop, Stenvert L S; Hokken-Koelega, Anita C S

2009-11-01

Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. We conducted a multicenter prospective trial. Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)). Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

Long-term safety and efficacy of a novel once-weekly oral trelagliptin as monotherapy or in combination with an existing oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52-week open-label, phase 3 study.

PubMed

Inagaki, Nobuya; Sano, Hiroki; Seki, Yoshifumi; Kuroda, Shingo; Kaku, Kohei

2016-09-01

Trelagliptin is a novel once-weekly oral dipeptidyl peptidase-4 inhibitor for type 2 diabetes mellitus that was first approved in Japan. We evaluated long-term safety and efficacy of trelagliptin in Japanese patients with type 2 diabetes mellitus. This was a phase 3, multicenter, open-label study to evaluate long-term safety and efficacy of trelagliptin. Patients with type 2 diabetes mellitus inadequately controlled despite diet/exercise or treatment with one of the existing oral antidiabetic drugs along with diet/exercise received trelagliptin 100 mg orally once weekly for 52 weeks as monotherapy or combination therapies. The primary end-points were the safety variables, and the secondary end-points were glycosylated hemoglobin and fasting plasma glucose. A total of 680 patients received the following antidiabetic therapies: trelagliptin monotherapy (n = 248), combination with a sulfonylurea (n = 158), a glinide (n = 67), an α-glucosidase inhibitor (n = 65), a biguanide (n = 70), or a thiazolidinedione (n = 72). During the study, 79.8% of the patients experienced at least one adverse event for monotherapy, 87.3% for combination with a sulfonylurea, 77.6% for a glinide, 81.5% for an α-glucosidase inhibitor, 64.3% for a biguanide, and 84.7% for a thiazolidinedione, respectively. Most of the adverse events were mild or moderate. The change in glycosylated hemoglobin from baseline at the end of the treatment period was -0.74 to -0.25% for each therapy. Once-weekly oral trelagliptin provides well-tolerated long-term safety and efficacy in both monotherapy and combination therapies in Japanese patients with type 2 diabetes mellitus. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

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.

Long-Term Chamomile Therapy of Generalized Anxiety Disorder: A Study Protocol for a Randomized, Double-Blind, Placebo- Controlled Trial.

PubMed

Mao, Jun J; Li, Qing S; Soeller, Irene; Rockwell, Kenneth; Xie, Sharon X; Amsterdam, Jay D

2014-11-01

Anxiety symptoms are among the most common reasons for consumers to use Complementary and Alternative Medicine (CAM) therapy. Although many botanicals have been proposed as putative remedies for anxiety symptoms, there has been a paucity of controlled trials of these remedies. A preliminary study of the anxiolytic effect of Chamomile ( Matricaria recutita ) in humans suggests that chamomile may have anxiolytic and antidepressant activity. We now seek to conduct a 5-year randomized, double-blind, placebo-substitution study to examine the short and long-term safety and efficacy of chamomile extract in Generalized Anxiety Disorder (GAD). 180 subjects with moderate to severe GAD will receive initial open-label pharmaceutical-grade chamomile extract 500-1,500 mg daily for 8 weeks. Responders to treatment who remain well for an additional 4 weeks of consolidation therapy, will be randomized to double-blind continuation therapy with either chamomile extract 500-1,500 mg daily or placebo for an additional 26 weeks. The primary outcome will be the time to relapse during study continuation therapy in each treatment condition. Secondary outcomes will include the proportion of subjects in each treatment condition who relapse, as well as the proportion of subjects with treatment-emergent adverse events. Quality of life ratings will also be compared between treatment conditions during short and long-term therapy. Many individuals with mental disorders decline conventional therapy and seek CAM therapies for their symptoms. Thus, the identification of effective CAM therapy is of relevance to reducing the burden of mental illness. This study builds upon our prior findings of significant superiority of chamomile versus placebo in reducing GAD symptoms. We now extend these preliminary findings by conducting a randomized long-term safety and efficacy study of chamomile in GAD.

Long-Term Chamomile Therapy of Generalized Anxiety Disorder: A Study Protocol for a Randomized, Double-Blind, Placebo- Controlled Trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Rockwell, Kenneth; Xie, Sharon X; Amsterdam, Jay D.

2017-01-01

Background Anxiety symptoms are among the most common reasons for consumers to use Complementary and Alternative Medicine (CAM) therapy. Although many botanicals have been proposed as putative remedies for anxiety symptoms, there has been a paucity of controlled trials of these remedies. A preliminary study of the anxiolytic effect of Chamomile (Matricaria recutita) in humans suggests that chamomile may have anxiolytic and antidepressant activity. We now seek to conduct a 5-year randomized, double-blind, placebo-substitution study to examine the short and long-term safety and efficacy of chamomile extract in Generalized Anxiety Disorder (GAD). Methods/Design 180 subjects with moderate to severe GAD will receive initial open-label pharmaceutical-grade chamomile extract 500–1,500 mg daily for 8 weeks. Responders to treatment who remain well for an additional 4 weeks of consolidation therapy, will be randomized to double-blind continuation therapy with either chamomile extract 500–1,500 mg daily or placebo for an additional 26 weeks. The primary outcome will be the time to relapse during study continuation therapy in each treatment condition. Secondary outcomes will include the proportion of subjects in each treatment condition who relapse, as well as the proportion of subjects with treatment-emergent adverse events. Quality of life ratings will also be compared between treatment conditions during short and long-term therapy. Discussion Many individuals with mental disorders decline conventional therapy and seek CAM therapies for their symptoms. Thus, the identification of effective CAM therapy is of relevance to reducing the burden of mental illness. This study builds upon our prior findings of significant superiority of chamomile versus placebo in reducing GAD symptoms. We now extend these preliminary findings by conducting a randomized long-term safety and efficacy study of chamomile in GAD. PMID:29057164

78 FR 66945 - Proposed Collection; 60-Day Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY) Summary: In compliance with the requirement... days of the date of this publication. Proposed Collection: Gulf Long-Term Follow-Up Study (GuLF STUDY... GuLF STUDY is to investigate potential short- and long-term health effects associated with oil spill...

Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors.

PubMed

Scheiman, James M

2002-01-01

Short-term endoscopic studies of the highly selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) rofecoxib and celecoxib have shown that these agents are well tolerated and have efficacy equivalent to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer adverse effects on the upper gastrointestinal (GI) tract. These studies are limited, however, as the detection of endoscopic lesions is not well correlated with symptomatic ulcers and ulcer complications. Outcomes studies of the GI safety are, therefore, essential to understanding how coxibs are likely to perform in a clinical practice setting. Four large outcomes studies (Vioxx Gastrointestinal Outcomes Research, VIGOR; Assessment of Difference Between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness trial, ADVANTAGE; Celecoxib Long-term Arthritis Safety Study, CLASS; and the Successive Celecoxib Efficacy and Safety Studies, SUCCESS) examined the GI safety of rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID (naproxen, ibuprofen, or diclofenac). Reduced risk of upper GI events was seen in patients with multiple risk factors and in patients using low-dose aspirin and corticosteroids concomitantly with a coxib. Results of large outcomes studies provide support for the COX-2 hypothesis and demonstrate the long-term safety and tolerability of coxibs.

Long-term real-time structural health monitoring using wireless smart sensor

NASA Astrophysics Data System (ADS)

Jang, Shinae; Mensah-Bonsu, Priscilla O.; Li, Jingcheng; Dahal, Sushil

2013-04-01

Improving the safety and security of civil infrastructure has become a critical issue for decades since it plays a central role in the economics and politics of a modern society. Structural health monitoring of civil infrastructure using wireless smart sensor network has emerged as a promising solution recently to increase structural reliability, enhance inspection quality, and reduce maintenance costs. Though hardware and software framework are well prepared for wireless smart sensors, the long-term real-time health monitoring strategy are still not available due to the lack of systematic interface. In this paper, the Imote2 smart sensor platform is employed, and a graphical user interface for the long-term real-time structural health monitoring has been developed based on Matlab for the Imote2 platform. This computer-aided engineering platform enables the control, visualization of measured data as well as safety alarm feature based on modal property fluctuation. A new decision making strategy to check the safety is also developed and integrated in this software. Laboratory validation of the computer aided engineering platform for the Imote2 on a truss bridge and a building structure has shown the potential of the interface for long-term real-time structural health monitoring.

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.

PubMed

Surrey, Eric; Taylor, Hugh S; Giudice, Linda; Lessey, Bruce A; Abrao, Mauricio S; Archer, David F; Diamond, Michael P; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Singh, Sukhbir S; Rechberger, Tomasz; Agarwal, Sanjay K; Duan, W Rachel; Schwefel, Brittany; Thomas, James W; Peloso, Paul M; Ng, Juki; Soliman, Ahmed M; Chwalisz, Kristof

2018-06-06

To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate. Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV=50.8%) and 78.1% at 200 mg twice daily (Elaris EM-IV=75.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.8% at 150 mg once daily (Elaris EM-IV=66.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV=67.2%). After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings. Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced

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.

Design of the long-term observational cohort study with recombinant human growth hormone in Korean children: LG Growth Study

PubMed Central

Chung, Sochung; Yoo, Jae-Ho; Choi, Jin Ho; Rhie, Young-Jun; Chae, Hyun-Wook; Kim, Jae Hyun; Hwang, Il Tae; Shin, Choong Ho; Kim, Eun Young

2018-01-01

Purpose Regarding recombinant human growth hormone (rhGH) use in the pediatric population, no long-term follow-up data are available for Korean patients. To fill in the gap of knowledge, a registry study (LG Growth Study) was initiated to assess the safety and effectiveness of four types of rhGH products in real-life settings. Methods A total of 4,000 children will be registered and prospectively followed up at 6-month intervals until 2 years after epiphyseal closure to collect data on treatment and adverse events, with primary interest in malignancies and growth outcomes. Results As of 22 March 2017, approximately 50% (2,024) of the target number of patients have been included in the analysis set: growth hormone deficiency, 1,297 (64.1%); idiopathic short stature, 315 (15.6%); small for gestational age, 206 (10.2%); Turner syndrome, 197 (9.7%); and chronic renal failure, 9 (0.4%). At baseline, median age (years) was 8 (interquartile range [IQR], 5–11); 52% (1,048) were boys; and the majority were at Tanner stage I (83% based on breast/external genitalia, 97% on pubic hair). Median height standard deviation score was -2.26 (IQR, -2.69 to -2.0), and median bone age delay (years) was -1.46 (IQR, -2.26 to -0.78). Conclusions This registry study will provide the opportunity to assess the risk of malignancies as well as the general safety data in Korean pediatric patients receiving rhGH. In addition, the long-term effectiveness of rhGH and comparative data between different disease entities will provide practical insight on the standard rhGH treatment. PMID:29609449

Long-term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years.

PubMed

Lovell, Daniel J; Ruperto, Nicolino; Mouy, Richard; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhaes, Claudia; Chavez-Corrales, J; Huemer, Christian; Kivitz, Alan; Blanco, Francisco J; Foeldvari, Ivan; Hofer, Michael; Huppertz, Hans-Iko; Job Deslandre, Chantal; Minden, Kirsten; Punaro, Marilynn; Block, Alan J; Giannini, Edward H; Martini, Alberto

2015-10-01

The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease-modifying antirheumatic drugs were previously established in a phase III study that included a 4-month open-label lead-in period, a 6-month double-blind withdrawal period, and a long-term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient-reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup. Patients enrolled in the phase III trial could enter the open-label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double-blind period. One hundred fifty-three (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patient-years) of adverse events decreased during the LTE phase (433.61 events during the short-term phase [combined lead-in and double-blind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time. Long-term abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and quality-of-life benefits in patients with JIA. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

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

Long-term treatment of Cushing's disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial.

PubMed

Petersenn, S; Salgado, L R; Schopohl, J; Portocarrero-Ortiz, L; Arnaldi, G; Lacroix, A; Scaroni, C; Ravichandran, S; Kandra, A; Biller, B M K

2017-07-01

Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein. Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was -82.6% (-89.0, -41.9) and -81.8% (-89.8, -67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time. This represents the longest prospective trial of a medical therapy for Cushing's disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing's disease.

Long-term safety and effectiveness of lubiprostone, a chloride channel (ClC-2) activator, in patients with chronic idiopathic constipation.

PubMed

Lembo, Anthony J; Johanson, John F; Parkman, Henry P; Rao, Satish S; Miner, Philip B; Ueno, Ryuji

2011-09-01

Lubiprostone helps relieve constipation in short-term 4-week studies. There are limited data on long-term pharmacological treatment with lubiprostone for chronic idiopathic constipation. To examine the long-term safety and effectiveness of lubiprostone in patients with chronic idiopathic constipation. In this prospective, multicenter, open-labeled trial, 248 patients aged ≥18 years with chronic idiopathic constipation were directed to take lubiprostone 24 mcg BID as needed for 48 weeks. Patients were allowed to decrease the dose in response to the perceived severity of constipation and need for relief. Hematology and chemistry profiles and assessment of constipation symptoms and its severity were performed at all visits. Adverse events (AEs) were recorded. Of the 248 patients who entered the trial, 127 (51%) completed the trial. A dose reduction was observed in 17% of the patients, resulting in an average study medication exposure across the study of approximately 1.7 capsules (or approximately 40.8 mcg) per day. The most common treatment-related AEs were nausea (19.8%), diarrhea (9.7%), abdominal distension (6.9%), headache (6.9%), and abdominal pain (5.2%). No deaths were reported and of the 16 reported serious AEs, one was considered possibly treatment related. Average changes in serum electrolytes were not clinically relevant at any time point during the study. On average, lubiprostone significantly (p < 0.0001) reduced patient-reported constipation severity, abdominal bloating, and abdominal discomfort across 48 weeks when compared to baseline. During this 48-week open-label study, lubiprostone was well tolerated. Bowel symptoms consistently improved over 48 weeks in adult patients with chronic idiopathic constipation.

Safety and efficacy outcomes of long-term treatment up to 4 years with 5% lidocaine medicated plaster in patients with post-herpetic neuralgia.

PubMed

Sabatowski, Rainer; Hans, Guy; Tacken, Ingrid; Kapanadze, Sofia; Buchheister, Bettina; Baron, Ralf

2012-08-01

Prospective evaluation of the long-term efficacy and safety of the 5% lidocaine medicated plaster in patients with post-herpetic neuralgia (PHN). Patients with persisting pain for ≥3 months after acute herpes zoster and a baseline pain intensity of at least 4 on an 11-point numerical rating scale (NRS 0-10) were treated with 5% lidocaine medicated plasters for up to 5 years and monitored in regular intervals. Efficacy parameters are presented for the first 4 years and include patients' recall of pain relief (6-point verbal rating scale (VRS), clinical global impression of change (CGIC), patients' global impression of change PGIC), and the global evaluations of study medication. Safety parameters (clinical examination, skin evaluation, laboratory) and adverse events (AEs) were assessed at regular visits. KF10004/02. A total of 102 patients continuing from a 1 year main study period were included in an extension phase of up to 3 years. Ten patients (9.8%) dropped out due to lack of efficacy and 9 patients (8.8%) due to treatment-related AEs; 56 patients (54.9%) left the study for non-treatment-related reasons. Twenty-seven patients (26.4%) were still under treatment after a total treatment period of 4 years. On average, a pain relief of at least 4.3 (between moderate and a lot) was achieved throughout the study. At all visits the CGIC and the PGIC were much or very much improved in about 80% of patients. At the final visit, study medication was rated at least to be good by 91% of physicians and 89% of patients. Drug-related adverse events (DRAEs) were reported in 19 of 102 patients, mainly mild to moderate localized skin reactions. There were no hints for a reduced analgesic effect or an increase of DRAEs with long-term treatment. This study demonstrates that long-term treatment of ≥12 months with the 5% lidocaine medicated plaster is effective and well tolerated in PHN patients. These findings support the recommendations to use the 5% lidocaine medicated plaster

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.

[Long-term psychiatric hospitalizations].

PubMed

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Near-Term Actions to Address Long-Term Climate Risk

NASA Astrophysics Data System (ADS)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

Long-term weather predictability: Ural case study

NASA Astrophysics Data System (ADS)

Kubyshen, Alexander; Shopin, Sergey

2016-04-01

The accuracy of the state-of-the-art long-term meteorological forecast (at the seasonal level) is still low. Here it is presented approach (RAMES method) realizing different forecasting methodology. It provides prediction horizon of up to 19-22 years under equal probabilities of determination of parameters in every analyzed period [1]. Basic statements of the method are the following. 1. Long-term forecast on the basis of numerical modeling of the global meteorological process is principally impossible. Extension of long-term prediction horizon could be obtained only by the revealing and using a periodicity of meteorological situations at one point of observation. 2. Conventional calendar is unsuitable for generalization of meteorological data and revealing of cyclicity of meteorological processes. RAMES method uses natural time intervals: one day, synodic month and one year. It was developed a set of special calendars using these natural periods and the Metonic cycle. 3. Long-term time series of meteorological data is not a uniform universal set, it is a sequence of 28 universal sets appropriately superseding each other in time. The specifics of the method are: 1. Usage of the original research toolkit consisting of - a set of calendars based on the Metonic cycle; - a set of charts (coordinate systems) for the construction of sequence diagrams (of daily variability of a meteorological parameter during the analyzed year; of daily variability of a meteorological parameter using long-term dynamical time series of periods-analogues; of monthly and yearly variability of accumulated value of meteorological parameter). 2. Identification and usage of new virtual meteorological objects having several degrees of generalization appropriately located in the used coordinate systems. 3. All calculations are integrated into the single technological scheme providing comparison and mutual verification of calculation results. During the prolonged testing in the Ural region, it was

Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study.

PubMed

Konstan, Michael W; McKone, Edward F; Moss, Richard B; Marigowda, Gautham; Tian, Simon; Waltz, David; Huang, Xiaohong; Lubarsky, Barry; Rubin, Jaime; Millar, Stefanie J; Pasta, David J; Mayer-Hamblett, Nicole; Goss, Christopher H; Morgan, Wayne; Sawicki, Gregory S

2017-02-01

The 24-week safety and efficacy of lumacaftor/ivacaftor combination therapy was shown in two randomised controlled trials (RCTs)-TRAFFIC and TRANSPORT-in patients with cystic fibrosis who were aged 12 years or older and homozygous for the F508del-CFTR mutation. We aimed to assess the long-term safety and efficacy of extended lumacaftor/ivacaftor therapy in this group of patients in PROGRESS, the long-term extension of TRAFFIC and TRANSPORT. PROGRESS was a phase 3, parallel-group, multicentre, 96-week study of patients who completed TRAFFIC or TRANSPORT in 191 sites in 15 countries. Patients were eligible if they were at least 12 years old with cystic fibrosis and homozygous for the F508del-CFTR mutation. Exclusion criteria included any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering the study drug to the participant, history of drug intolerance, and history of poor compliance with the study drug. Patients who previously received active treatment in TRANSPORT or TRAFFIC remained on the same dose in PROGRESS. Patients who had received placebo in TRANSPORT or TRAFFIC were randomly assigned (1:1) to receive lumacaftor (400 mg every 12 h)/ivacaftor (250 mg every 12 h) or lumacaftor (600 mg once daily)/ivacaftor (250 mg every 12 h). The primary outcome was to assess the long-term safety of combined therapy. The estimated annual rate of decline in percent predicted FEV 1 (ppFEV 1 ) in treated patients was compared with that of a matched registry cohort. Efficacy analyses were based on modified intention-to-treat, such that data were included for all patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01931839. Between Oct 24, 2013, and April 7, 2016, 1030 patients from the TRANSPORT and TRAFFIC studies enrolled in PROGRESS, and 1029 received at least one dose of study

Long-term prescribing of antidepressants in the older population: a qualitative study

PubMed Central

Dickinson, Rebecca; Knapp, Peter; House, Allan O; Dimri, Vandana; Zermansky, Arnold; Petty, Duncan; Holmes, John; Raynor, David K

2010-01-01

Background High rates of long-term antidepressant prescribing have been identified in the older population. Aims To explore the attitudes of older patients and their GPs to taking long-term antidepressant therapy, and their accounts of the influences on long-term antidepressant use. Design of study Qualitative study using in-depth semi-structured interviews. Setting One primary care trust in North Bradford. Method Thirty-six patients aged ≥75 years and 10 GPs were interviewed. Patients were sampled to ensure diversity in age, sex, antidepressant type, and home circumstances. Results Participants perceived significant benefits and expressed little apprehension about taking long-term antidepressants, despite being aware of the psychological and social factors involved in onset and persistence of depression. Barriers to discontinuation were identified following four themes: pessimism about the course and curability of depression; negative expectations and experiences of ageing; medicine discontinuation perceived by patients as a threat to stability; and passive (therapeutic momentum) and active (therapeutic maintenance) decisions to accept the continuing need for medication. Conclusion There is concern at a public health level about high rates of long-term antidepressant prescribing, but no evidence was found of a drive for change either from the patients or the doctors interviewed. Any apprehension was more than balanced by attitudes and behaviours supporting continuation. These findings will need to be incorporated into the planning of interventions aimed at reducing long-term antidepressant prescribing in older people. PMID:20353660

Long-term results of viscocanalostomy and phacoviscocanalostomy: a twelve-year follow-up study

PubMed Central

Gunenc, Uzeyir; Ozturk, Taylan; Arikan, Gul; Kocak, Nilufer

2015-01-01

AIM To evaluate the long-term efficacy and safety results of viscocanalostomy and phacoviscocanalostomy. METHODS The charts of 49 glaucoma patients who underwent viscocanalostomy or phacoviscocanalostomy surgery between February 1999 and August 2004 were reviewed retrospectively. Thirty-one eyes of 21 glaucoma patients who underwent filtering procedure with a postoperative follow-up of at least 5y were included in the study. Results of complete ophthalmologic examinations were recorded and statistically analyzed. Long-term surgical outcome was defined as an overall success when intraocular pressure (IOP) was found as ≤20 mm Hg with or without antiglaucomatous medication at the last follow-up visit, while it was defined as a complete success when IOP was measured ≤20 mm Hg without antiglaucomatous medication. RESULTS Mean age was 68.1±9.6y (range: 32-81y). Mean follow-up time was 101.5±27.3mo (range: 60-144mo). Viscocanalostomy was performed in 8 eyes (25.8%) and phacoviscocanalostomy was performed in 23 eyes (74.2%). The mean preoperative IOP was 23.1±7.6 mm Hg with 2.1±1.0 medications, while mean IOP was 16.8±3.8 mm Hg with 0.9±1.1 medication at the last follow-up visit. Both the IOP decrease and the reduction in the antiglaucomatous medication were statistically significant (P<0.001 and P<0.001). No case required further glaucoma surgery. Overall success and complete success were found as 87.1% and 51.6%, respectively. Complete success rate was statistically higher in phacoviscocanalostomy group compared with the viscocanalostomy group (P=0.031), however there was no significant difference in overall success rate between two groups (P=0.072). CONCLUSION Both viscocanalostomy and phacoviscocanalostomy provide good IOP reduction in the long-term period. PMID:26682166

Long-term safety and efficacy of autologous platelet lysate drops for treatment of ocular GvHD.

PubMed

Pezzotta, S; Del Fante, C; Scudeller, L; Rossi, G C; Perotti, C; Bianchi, P E; Antoniazzi, E

2017-01-01

Current ocular GvHD (oGvHD) treatments are suboptimal. We investigated the safety and efficacy of long-term continuous treatment with autologous platelet lysate (PL) drops in patients with oGvHD Dry Eye Syndrome (DES) score 2-3 refractory to topical conventional therapy. Ophthalmic evaluation was performed at 6 month intervals. Symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were defined 'responders' when showing a reduction at least one grade on National Institutes of Health Eye Score from baseline at the 6 month visit. Thirty-one patients were included, and 16 (51%) completed 36 months of follow-up (range 6.5-72.7). At 6 months all patients were classified as responders: median GSS symptom score decreased from 70 to 41 (33 at 36 months), median GSS function score reduced from 68 to 46 (33 at 36 months) (all P<0.001). Median Tear Break Up Time improved from 3 to 6 s after 6 months and was maintained over time. All signs improved at 6 and 36 months (clinical and statistical significance). No severe adverse events occurred. Long-term treatment with PL drops is secure and effective for oGvHD and can be an efficient therapy option from initial stages of oGvHD to prevent permanent ocular impairment and improving quality of life.

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

PubMed

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

2015-10-06

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

A Long-term study of three rotating radio transients

NASA Astrophysics Data System (ADS)

Bhattacharyya, B.; Lyne, A. G.; Stappers, B. W.; Weltevrede, P.; Keane, E. F.; McLaughlin, M. A.; Kramer, M.; Jordan, C.; Bassa, C.

2018-04-01

We present the longest-term timing study so far of three Rotating Radio Transients (RRATs) - J1819-1458, J1840-1419 and J1913+1330 - performed using the Lovell, Parkes and Green Bank telescopes over the past decade. We study long-term and short-term variations of the pulse emission rate from these RRATs and report a marginal indication of a long-term increase in pulse detection rate over time for PSR J1819-1458 and J1913+1330. For PSR J1913+1330, we also observe a two orders of magnitude variation in the observed pulse detection rates across individual epochs, which may constrain the models explaining the origin of RRAT pulses. PSR J1913+1330 is also observed to exhibit a weak persistent emission mode. We investigate the post-glitch timing properties of J1819-1458 (the only RRAT for which glitches are observed) and discuss the implications for possible glitch models. Its post-glitch over-recovery of the frequency derivative is magnetar-like and similar behaviour is only observed for two other pulsars, both of which have relatively high magnetic field strengths. Following the over-recovery we also observe that some fraction of the pre-glitch frequency derivative is gradually recovered.

Long-Term Engagement in Formal Volunteering and Well-Being: An Exploratory Indian Study

PubMed Central

Elias, Jereesh K.; Sudhir, Paulomi; Mehrotra, Seema

2016-01-01

Sustained engagement in volunteering and its correlates have been examined in many studies across the globe. However, there is a dearth of research that explores the perspectives of long-term formal volunteers on the nature of changes perceived in oneself as a result of volunteering. Moreover, the linkages between psychological well-being and volunteering have been insufficiently explored. The present study was aimed at addressing these gaps. A heterogeneous sample of 20 long-term formal volunteer engaged in volunteering across different voluntary organisations in a southern metropolitan Indian city formed the primary sample for the study. In addition, a group of 21 short-term volunteers, matched on age, income and gender, was utilised for comparison with long-term volunteers on well-being indices. A semi structured interview schedule was used to explore self-perceived changes attributable to volunteering experience. In addition, a few standardised measures were used to comprehensively assess subjective well-being and psychological well-being. The interview data provided rich descriptions of perceived positive changes in self across cognitive, behavioral and emotional domains. Mirroring these patterns, the quantitative analyses indicated that long-term volunteers experienced higher levels of psychological well-being (sense of mastery and competence, self-acceptance and sense of engagement and growth) than short-term volunteers. The potential mechanisms involved in beneficial outcomes of long-term volunteering and implications for further research are highlighted. PMID:27690114

Long-Term Engagement in Formal Volunteering and Well-Being: An Exploratory Indian Study.

PubMed

Elias, Jereesh K; Sudhir, Paulomi; Mehrotra, Seema

2016-09-27

Sustained engagement in volunteering and its correlates have been examined in many studies across the globe. However, there is a dearth of research that explores the perspectives of long-term formal volunteers on the nature of changes perceived in oneself as a result of volunteering. Moreover, the linkages between psychological well-being and volunteering have been insufficiently explored. The present study was aimed at addressing these gaps. A heterogeneous sample of 20 long-term formal volunteer engaged in volunteering across different voluntary organisations in a southern metropolitan Indian city formed the primary sample for the study. In addition, a group of 21 short-term volunteers, matched on age, income and gender, was utilised for comparison with long-term volunteers on well-being indices. A semi structured interview schedule was used to explore self-perceived changes attributable to volunteering experience. In addition, a few standardised measures were used to comprehensively assess subjective well-being and psychological well-being. The interview data provided rich descriptions of perceived positive changes in self across cognitive, behavioral and emotional domains. Mirroring these patterns, the quantitative analyses indicated that long-term volunteers experienced higher levels of psychological well-being (sense of mastery and competence, self-acceptance and sense of engagement and growth) than short-term volunteers. The potential mechanisms involved in beneficial outcomes of long-term volunteering and implications for further research are highlighted.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Memon, Khairuddin; Lewandowski, Robert J.; Mulcahy, Mary F.

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) guidelinesmore » 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

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

Sugano, Kentaro; Kinoshita, Yoshikazu; Miwa, Hiroto; Takeuchi, Tsutomu

2013-03-26

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. 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. 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. Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in

Science and society: the role of long-term studies in environmental stewardship

Treesearch

Charles T. Driscoll; Kathleen F. Lambert; F. Stuart Chapin; David J. Nowak; Thomas A. Spies; Frederick J. Swanson; David B. Kittredge; Clarisse M. Hart

2012-01-01

Long-term research should play a crucial role in addressing grand challenges in environmental stewardship. We examine the efforts of five Long Term Ecological Research Network sites to enhance policy, management, and conservation decisions for forest ecosystems. In these case studies, we explore the approaches used to inform policy on atmospheric deposition, public...

Are long physician working hours harmful to patient safety?

PubMed

Ehara, Akira

2008-04-01

Pediatricians of Japanese hospitals including not only residents but also attending physicians work long hours, and 8% work for >79 h per week. Most of them work consecutively for >or=32 h when they are on call. The aim of the present study was to evaluate the effect of long work hours on patient safety. The electronic databases MEDLINE and EMBASE to searched identify the English- and Japanese-language literature for studies on work hours, medical errors, patient safety, and malpractice for years 1966-2005. Studies that analyzed the relationship between physician work hours and outcomes directly related to patient safety were selected. Seven studies met the criteria. Four studies suggest that reduction of work hours has a favorable effect on patient safety indicators. In the other three studies no significant changes of the indicators were observed, but no report found that shorter work hours were harmful to patient safety. Decrease of physician work hours is not harmful but favorable to patient safety.

An idealised study for the long term evolution of crescentic bars

NASA Astrophysics Data System (ADS)

Chen, W. L.; Dodd, N.; Tiessen, M. C. H.; Calvete, D.

2018-01-01

An idealised study that identifies the mechanisms in the long term evolution of crescentic bar systems in nature is presented. Growth to finite amplitude (i.e., equilibration, sometimes referred to as saturation) and higher harmonic interaction are hypothesised to be the leading nonlinear effects in long-term evolution of these systems. These nonlinear effects are added to a linear stability model and used to predict crescentic bar development along a beach in Duck, North Carolina (USA) over a 2-month period. The equilibration prolongs the development of bed patterns, thus allowing the long term evolution. Higher harmonic interaction enables the amplitude to be transferred from longer to shorter lengthscales, which leads to the dominance of shorter lengthscales in latter post-storm stages, as observed at Duck. The comparison with observations indicates the importance of higher harmonic interaction in the development of nearshore crescentic bar systems in nature. Additionally, it is concluded that these nonlinear effects should be included in models simulating the development of different bed patterns, and that this points a way forward for long-term morphodynamical modelling in general.

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.

Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis.

PubMed

Lund, Allan M; Borgwardt, Line; Cattaneo, Federica; Ardigò, Diego; Geraci, Silvia; Gil-Campos, Mercedes; De Meirleir, Linda; Laroche, Cécile; Dolhem, Philippe; Cole, Duncan; Tylki-Szymanska, Anna; Lopez-Rodriguez, Monica; Guillén-Navarro, Encarna; Dali, Christine I; Héron, Bénédicte; Fogh, Jens; Muschol, Nicole; Phillips, Dawn; Van den Hout, J M Hannerieke; Jones, Simon A; Amraoui, Yasmina; Harmatz, Paul; Guffon, Nathalie

2018-05-03

Long-term outcome data provide important insights into the clinical utility of enzyme replacement therapies. Such data are presented for velmanase alfa in the treatment of alpha-mannosidosis (AM). Patient data (n = 33; 14 adults, 19 paediatric) from the clinical development programme for velmanase alfa were integrated in this prospectively-designed analysis of long-term efficacy and safety. Patients who participated in the phase I/II or phase III trials and were continuing to receive treatment after completion of the trials were invited to participate in a comprehensive evaluation visit to assess long-term outcomes. Primary endpoints were changes in serum oligosaccharide and the 3-minute stair climb test (3MSCT). Mean (SD) treatment exposure was 29.3 (15.2) months. Serum oligosaccharide levels were significantly reduced in the overall population at 12 months (mean change: -72.7%, P < 0.001) and remained statistically significant at last observation (-62.8%, P < 0.001). A mean improvement of +9.3% in 3MSCT was observed at 12 months (P = 0.013), which also remained statistically significant at last observation (+13.8%, P = 0.004), with a more pronounced improvement detected in the paediatric subgroup. No treatment-emergent adverse events were reported leading to permanent treatment discontinuation. Patients treated with velmanase alfa experienced improvements in biochemical and functional measures that were maintained for up to 4 years. Long term follow-up is important and further supports the use of velmanase alfa as an effective and well-tolerated treatment for AM. Based on the currently available data set, no baseline characteristic can be predictive of treatment outcome. Early treatment during paediatric age showed better outcome in functional endpoints.

Long-Term follow up after intra-Uterine transfusionS; the LOTUS study

PubMed Central

2010-01-01

Background The Leiden University Medical Center (LUMC) is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN) caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT). Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC) antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short- and long-term outcome in surviving children. Methods/Design We set up a large long-term observational follow-up study (LOTUS study), in cooperation with the Sanquin Blood Supply Foundation and the LUMC departments of Obstetrics, Neonatology and ImmunoHematology & Bloodtransfusion. The first part of this study addresses several putative mechanisms associated with blood group alloimmunization in these mothers. The second part of this study determines the incidence of long-term neurodevelopment impairment (NDI) and associated risk factors in children treated with IUT. All women and their life offspring who have been treated with IUT for HDFN in the LUMC from 1987-2008 are invited to participate and after consent, blood or saliva samples are taken. RBC and HLA antigen profile and antibodies are determined by serologic or molecular techniques. Microchimerism populations are tested by real time polymerase chain reaction (RT PCR). All children are tested for their neurological, cognitive and psychosocial development using standardised tests and questionnaires. The primary outcome is neurodevelopmental impairment (NDI), a composite outcome defined as any of the following: cerebral palsy, cognitive or psychomotor development < 2 standard deviation, bilateral blindness and/or bilateral deafness. Discussion The LOTUS study includes the largest cohort of IUT patients ever studied and is the first to investigate post

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.

The Hill plots: A rare long-term vegetation study

Treesearch

Jonathan D. Bakker; Margaret M. Moore; Daniel C. Laughlin

2008-01-01

One legacy of the Fort Valley Experimental Forest is the number and quality of long-term studies associated with it. One such study is the "Hill plots," which began in 1912 and is still being actively studied. Livestock exclosures were built at five sites to examine vegetation recovery when protected from livestock grazing. Sites span a range of soil types...

Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA).

PubMed

Klotsche, Jens; Niewerth, Martina; Haas, Johannes-Peter; Huppertz, Hans-Iko; Zink, Angela; Horneff, Gerd; Minden, Kirsten

2016-05-01

Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation. We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Long-term safety and efficacy of eslicarbazepine acetate in patients with focal seizures: results of the 1-year ESLIBASE retrospective study.

PubMed

Villanueva, V; Serratosa, J M; Guillamón, E; Garcés, M; Giráldez, B G; Toledo, M; Salas-Puig, J; López González, F J; Flores, J; Rodríguez-Uranga, J; Castillo, A; Mauri, J A; Camacho, J L; López-Gomáriz, E; Giner, P; Torres, N; Palau, J; Molins, A

2014-09-01

Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) licensed as adjunctive therapy in adults with partial-onset or focal seizures. To evaluate in a clinical practice setting the long-term efficacy and safety of ESL in patients with focal seizures. ESLIBASE was a retrospective study that included all patients with focal seizures who started ESL between January 2010 and July 2012 at 12 hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1 year. Switching from carbamazepine (CBZ) and oxcarbazepine (OXC) was assessed. Three hundred and twenty-seven patients were included; 78% of patients were taking ≥2 other AEDs at baseline. Most (87%) began ESL because of poor seizure control and 13% because of adverse events (AEs) with CBZ or OXC. After 1 year, 237 patients (72.4%) remained on ESL. At 3, 6 and 12 months, the responder rate was 46.3%, 57.9%, and 52.5%, and 21.0%, 28.0%, and 25.3% of patients were seizure free. The responder rate significantly increased when ESL was combined with a non-sodium channel-targeting drug (non-SC drug) (66.7%) versus an SC drug (47.7%; p<0.001). At 12 months, 40.7% of patients had ≥1 AE; AEs led to treatment discontinuation in 16.2%. Dizziness, nausea, and somnolence were the most common AEs. The tolerability profile improved in >50% of the patients who switched from CBZ or OXC to ESL because of AEs. ESL was well tolerated and effective in a real-world setting over 1 year. Side-effect profile improved when OXC and CBZ recipients were switched to ESL. Copyright © 2014 Elsevier B.V. All rights reserved.

Long-term efficacy of rasagiline in early Parkinson's disease.

PubMed

Lew, Mark F; Hauser, Robert A; Hurtig, Howard I; Ondo, William G; Wojcieszek, Joanne; Goren, Tamar; Fitzer-Attas, Cheryl J

2010-06-01

This study was designed to follow the long-term efficacy, safety, and tolerability of rasagiline for Parkinson's disease (PD) with data collected from all patients who had ever taken rasagiline during the 12-month TEMPO monotherapy trial (N = 398) and subsequent open-label extension. Patients were followed for up to 6.5 years with a mean of 3.5 +/- 2.1 years. After 12 months, additional PD medications were added as required. Of patients remaining in the trial at 2 years, 46% were maintained on rasagiline monotherapy. The majority of patients received a dopamine agonist prior to levodopa as the first additional dopaminergic agent. Analysis using a Kaplan-Meier method indicated that by 5.4 years only 25% of patients progressed to Hoehn & Yahr stage III. Rasagiline was well tolerated, with 11.3% of patients (45/398) withdrawing because of an adverse event. Rasagiline therapy for PD was effective, well tolerated, and safe in this long-term trial.

Safety of long-term high-volume sinonasal budesonide irrigations for chronic rhinosinusitis.

PubMed

Smith, Kristine A; French, Gabrielle; Mechor, Bradford; Rudmik, Luke

2016-03-01

Off-label high-volume sinonasal budesonide irrigations are commonly used during the management of chronic rhinosinusitis (CRS). Although short-term use (4 to 8 weeks) has been demonstrated to be safe, the long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis remain unclear. The objective of this study is to determine whether CRS patients using long-term (minimum greater than 12 months) budesonide sinonasal irrigations have evidence of HPA axis suppression. Patients with CRS being managed with high-volume sinonasal budesonide irrigations were recruited from 2 tertiary level rhinology clinics between March 2014 and July 2015. Inclusion criteria were as follows: (1) adult (age greater than 18 years); (2) guideline-based diagnosis of CRS; (3) previous endoscopic sinus surgery; (4) minimum of twice daily high-volume sinonasal budesonide irrigation (concentration of 1 mg per irrigation; total daily dose of 2 mg); and (5) a minimum of 12-month duration. Exclusion criteria included systemic corticosteroid use within 3 months of HPA axis testing. The primary outcomes were morning (am) serum cortisol levels and, when indicated, cosyntropin stimulation levels. A total of 35 patients fulfilled eligibility criteria and underwent HPA axis testing. Mean duration of budesonide sinonasal irrigation therapy use was 38.2 months (2.9 years). The mean ± standard deviation (SD) am serum cortisol was 431.2 ± 146.9 nmol/L (normal, 200 to 650 nmol/L). Subsequent cosyntropin stimulation tests, in indicated patients (n = 19), demonstrated no evidence of HPA axis suppression. Outcomes from this study suggest that daily high-volume sinonasal budesonide irrigations fail to produce evidence of HPA axis suppression with prolonged courses lasting longer than 2 years. © 2016 ARS-AAOA, LLC.

Long-term actuarial survivorship analysis of an interspinous stabilization system

PubMed Central

Sénégas, Jacques; Pointillart, Vincent; Mangione, Paolo

2007-01-01

In 1986, an interspinous dynamic stabilization system (the prototype of the current Wallis implant) was designed to stiffen unstable operated degenerate lumbar segments with a hard interspinous blocker to limit extension and a tension band around the spinous processes to secure the implant and limit flexion. Restoring physiological mechanical conditions to the treated level(s) while preserving some intervertebral mobility was intended to treat low-back pain related to degenerative instability without increasing stress forces in the adjacent segments. The procedure was easily reversible. If low back pain persisted or recurred, the device was removed and stability was achieved using fusion. The intermediate-term results were promising, but the long-term safety and efficacy of this dynamic interspinous stabilization device has not been previously documented. We retrospectively reviewed the hospital files of all the patients (n = 241) who had this dynamic stabilization system implanted between 1987 and 1995, contacting as many as possible to determine the actuarial survivorship of the system. In this manner, 142 of the 241 patients (58.9%) were contacted by telephone. The endpoints used for the survivorship analysis were ‘any subsequent lumbar operation’ and ‘implant removal’. At 14 years follow-up, values of actuarial survivorship with 95% confidence interval were 75.9 ± 8.3 and 81.3 ± 6.8% for the endpoints ‘any subsequent lumbar operation’ and ‘implant removal’, respectively. There was no difference in survivorship of multiple-level implants with respect to single-level devices. Although the conclusions of the present study must be tempered by the 41% attrition rate, these findings support the long-term safety of this system, and possibly long-term protective action against adjacent-level degeneration by motion preservation. Outcomes at least equivalent to those of fusion were observed without the primary drawbacks of fusion. PMID:17426988

Long-term efficacy and safety of blonanserin in patients with first-episode schizophrenia: a 1-year open-label trial.

PubMed

Ninomiya, Yuriko; Miyamoto, Seiya; Tenjin, Tomomi; Ogino, Shin; Miyake, Nobumi; Kaneda, Yasuhiro; Sumiyoshi, Tomiki; Yamaguchi, Noboru

2014-12-01

The purpose of this study was to evaluate the long-term effectiveness and safety of blonanserin, a second-generation antipsychotic drug developed in Japan, in patients with first-episode schizophrenia. Twenty-three antipsychotic-naïve patients with first-episode schizophrenia were treated within an open-label, 1-year, prospective trial of blonanserin (2-24 mg/day). Clinical evaluations were conducted at baseline and 2, 6, and 12 months after the start of treatment. The main outcome measures were changes in subjective well-being and subjective quality of life, as assessed by the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version and the Schizophrenia Quality of Life Scale-Japanese version, respectively. Secondary outcome measures included the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia-Japanese version, laboratory tests, bodyweight, and extrapyramidal symptoms. Fourteen patients (60.9%) remained on the study at 1 year. In the intention-to-treat analysis, significant improvements were observed in several subscales on the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version, the Schizophrenia Quality of Life Scale-Japanese version, and the Brief Assessment of Cognition in Schizophrenia-Japanese version, and in all factor scores on the Positive and Negative Syndrome Scale. Improvement in depressive symptoms with blonanserin treatment was positively correlated with improvements in subjective well-being and subjective quality of life, as well as verbal memory. No significant changes were noted for any safety measure during the 1-year study period. Blonanserin was well tolerated and effective for the treatment of first-episode schizophrenia in terms of subjective wellness, cognition, and a wide range of pathological symptoms. Further large-scale studies are warranted to confirm our findings. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014

Safety and long-term efficacy of fractional CO2 laser treatment in women suffering from genitourinary syndrome of menopause.

PubMed

Behnia-Willison, Fariba; Sarraf, Sara; Miller, Joseph; Mohamadi, Behrang; Care, Alison S; Lam, Alan; Willison, Nadia; Behnia, Leila; Salvatore, Stefano

2017-06-01

To evaluate the safety and long-term efficacy of fractional CO 2 laser treatment in reducing the severity of symptoms of genitourinary syndrome of menopause (GSM) in menopausal women. 102 women presenting with symptomatic GSM were treated with the fractional CO 2 laser (MonaLisa Touch, DEKA) system across a series of treatments delivered at intervals of six or more weeks. The Australian Pelvic Floor Questionnaire was used to gather data on sexual function and side-effects at three time-points across the study period (prospective panel design study). Wilcoxon signed-rank tests were used to detect statistically and clinically significant changes in sexual function and side-effects occurring from pre- to post-treatment. The primary outcome of this study was an improvement of the symptoms of GSM. The secondary outcome included bladder function and prolapse symptoms. A total of 102 women suffering from moderate to severe GSM were recruited. Eighty-four percent experienced significant improvement in their symptoms after CO 2 laser treatment. Scores on measures of sexual function, dyspareunia, and bothersomeness of sexual issues were improved from pre-treatment to long-term (12-24 month) follow-up. Furthermore, there were improvements on measures of bladder function (P=0.001), prolapse (P=0.001), vaginal sensation (P=0.001), vaginal lubrication (P<0.001) and urge incontinence (P=0.003) from the pre-treatment assessment to the second assessment (i.e. after the third treatment). In this study, fractional microablative CO 2 laser treatment was associated with an improvement in symptoms of GSM and sexual function. Copyright © 2017. Published by Elsevier B.V.

Placenta previa and long-term morbidity of the term offspring.

PubMed

Walfisch, Asnat; Beharier, Ofer; Shoham-Vardi, Ilana; Sergienko, Ruslan; Landau, Daniella; Sheiner, Eyal

2016-08-01

The long-term impact of placenta previa on term infants is unknown. We aimed to investigate whether abnormal placentation increases the risk for long-term morbidity of the term offspring. A population-based cohort study compared the incidence of long-term hospitalizations up to the age of 18 due to cardiovascular, endocrine, neurological, hematological, respiratory and urinary morbidity of children born at term in pregnancies diagnosed with placenta previa and those without. Deliveries occurred between the years 1991-2013 in a tertiary medical center. Multiple pregnancies, and fetal congenital malformations were excluded. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence over time. A multivariable generalized estimating equation (GEE) logistic regression model analysis was used to control for confounders and for maternal clusters. During the study period 233,123 term deliveries met the inclusion criteria; 0.2% (n=502) of the children were born to mothers with placenta previa. During the follow-up period, children born to mothers with placenta previa did not have an increased risk for long-term cardiovascular, endocrine, hematological, neurological, respiratory, and urinary morbidity. Term offsprings of mothers diagnosed with placenta previa do not appear to be at an increased risk for long-term morbidity up to the age of 18. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Very long-term sequelae of craniopharyngioma.

PubMed

Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

2017-06-01

Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review.

PubMed

Cañas, Fernando; Möller, Hans-Jürgen

2010-09-01

Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP). Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency. RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI. Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.

Long-term associative learning predicts verbal short-term memory performance.

PubMed

Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

ORAL TOXICITY OF 1,3-DICHLOROPROPANE: ACUTE, SHORT-TERM, AND LONG-TERM STUDIES IN RATS

EPA Science Inventory

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil...

Early aspirin desensitization in unstable patients with acute coronary syndrome: Short and long-term efficacy and safety.

PubMed

Córdoba-Soriano, Juan Gabriel; Corbí-Pascual, Miguel; López-Neyra, Isabel; Navarro-Cuartero, Javier; Hidalgo-Olivares, Víctor; Barrionuevo-Sánchez, Maria Isabel; Prieto-Mateos, Daniel; Gutiérrez-Díez, Antonio; Gallardo-López, Arsenio; Fuentes-Manso, Raquel; Gómez-Pérez, Alberto; Lafuente-Gormaz, Carlos; Jiménez-Mazuecos, Jesús

2016-11-01

Aspirin hypersensitivity is not a rare condition among patients with acute coronary syndrome. However, despite the publication of several successful desensitization protocols, the procedure is not as widespread as expected. We present a cohort of patients with acute coronary syndrome undergoing aspirin desensitization to evaluate its short- and long-term efficacy and safety and to reinforce data from previous studies. Of 1306 patients admitted to our Coronary Care Unit between February 2011 and February 2013, 24 (1.8%) had a history of aspirin hypersensitivity. All 24 patients underwent an eight-dose aspirin desensitization protocol (0.1, 0.3, 1, 3, 10, 25, 50 and 100 mg of aspirin given by mouth every 15 minutes) after premedication with antihistamines and corticosteroids or antileucotrienes. Previously prescribed β blockers and angiotensin-converting enzyme inhibitors were not discontinued. All patients were desensitized within 72 hours of admission. Those requiring urgent catheterization (five patients with ST segment elevation myocardial infarction) were desensitized within 12 hours of catheterization and the remainder before catheterization. All patients were successfully desensitized and only one presented with an urticarial reaction. The five patients with ST segment elevation myocardial infarction were treated with abciximab until desensitization was complete. All but one patient underwent catheterization and 20 underwent percutaneous coronary intervention, most (66%) with the implantation of a bare metal stent. At follow-up (a minimum of 6-24 months), only two patients had discontinued aspirin, both due to gastrointestinal bleeding, and no hypersensitivy reaction had occurred. Aspirin desensitization is effective and safe in unstable patients with acute coronary syndrome in both the short and long term.

Long-term outcome study of growth factor-treated pressure ulcers.

PubMed

Payne, W G; Ochs, D E; Meltzer, D D; Hill, D P; Mannari, R J; Robson, L E; Robson, M C

2001-01-01

Exogenous application of growth factors have been reported in an attempt to accelerate healing of chronic wounds. Most of the trials were of brief duration with short to no follow-up periods. Long-term outcome studies are sparse for pressure ulcer therapies with success rates around 30% for both operative and nonoperative treatments. Follow-up evaluations were performed serially up to 12 months for patients completing a 35 day blinded, placebo-controlled cytokine clinical trial of pressure ulcers. Fifty-four of 61 patients completed the follow-up period with 68.5% of the patients (37 of 54) being healed after 1 year. Of patients healing > or =85% during the active treatment phase, 84.6% were healed after 1 year compared with 61% of those that healed <85% during treatment (P <0.05). Long-term outcome was better in this growth factor trial than with surgical or standard nonoperative treatment of pressure ulcers. Since only patients receiving exogenously applied cytokines achieved >85% closure during the treatment phase of the trial, the excellent long-term outcome appears attributable to the cytokine therapy.

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

Short-term Action Intentions Overrule Long-Term Semantic Knowledge

ERIC Educational Resources Information Center

van Elk, M.; van Schie, H.T.; Bekkering, H.

2009-01-01

In the present study, we investigated whether the preparation of an unusual action with an object (e.g. bringing a cup towards the eye) could selectively overrule long-term semantic representations. In the first experiment it was found that unusual action intentions activated short-term semantic goal representations, rather than long-term…

Estimating long-term multivariate progression from short-term data.

PubMed

Donohue, Michael C; Jacqmin-Gadda, Hélène; Le Goff, Mélanie; Thomas, Ronald G; Raman, Rema; Gamst, Anthony C; Beckett, Laurel A; Jack, Clifford R; Weiner, Michael W; Dartigues, Jean-François; Aisen, Paul S

2014-10-01

Diseases that progress slowly are often studied by observing cohorts at different stages of disease for short periods of time. The Alzheimer's Disease Neuroimaging Initiative (ADNI) follows elders with various degrees of cognitive impairment, from normal to impaired. The study includes a rich panel of novel cognitive tests, biomarkers, and brain images collected every 6 months for as long as 6 years. The relative timing of the observations with respect to disease pathology is unknown. We propose a general semiparametric model and iterative estimation procedure to estimate simultaneously the pathological timing and long-term growth curves. The resulting estimates of long-term progression are fine-tuned using cognitive trajectories derived from the long-term "Personnes Agées Quid" study. We demonstrate with simulations that the method can recover long-term disease trends from short-term observations. The method also estimates temporal ordering of individuals with respect to disease pathology, providing subject-specific prognostic estimates of the time until onset of symptoms. When the method is applied to ADNI data, the estimated growth curves are in general agreement with prevailing theories of the Alzheimer's disease cascade. Other data sets with common outcome measures can be combined using the proposed algorithm. Software to fit the model and reproduce results with the statistical software R is available as the grace package. ADNI data can be downloaded from the Laboratory of NeuroImaging. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The long-term use of cyproterone acetate in pedophilia: a case study.

PubMed

Cooper, A J; Cernovsky, Z; Magnus, R V

1992-01-01

This investigation reports the long-term use of the antiandrogen cyproterone acetate (CPA) in a pedophile, who was studied continuously over 38 months. Measures of sexual arousal, serum testosterone, and gonadotropin levels were significantly reduced by the drug as compared with placebo and no treatment; prolactin levels were significantly elevated. Some workers have observed that long-term administration of CPA (more than one year, which was then discontinued) produced enduring (in some cases apparently permanent) anti-libidinal effects; however, in the case described, within three weeks of stopping the drug, all measures had returned to pretrial levels. The importance of continuous long-term monitoring in sex offenders receiving an antiandrogen is discussed.

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

Long term and transitional intermittent smokers: a longitudinal study

PubMed Central

Lindstrom, M; Isacsson, S

2002-01-01

Objective: To investigate differences in snuff consumption, sociodemographic and psychosocial characteristics between baseline intermittent smokers that had become daily smokers, stopped smoking or remained intermittent smokers at the one year follow up. Design/setting/participants/measurements: A population of 12 507 individuals interviewed at baseline in 1992-94 and at a one year follow up, aged 45–69 years, was investigated in a longitudinal study. The three groups of baseline intermittent smokers were compared to the reference population (all others) according to sociodemographic, psychosocial, and snuff consumption characteristics. A multivariate logistic regression model was used to assess differences in psychosocial conditions, adjusting for age, sex, country of origin, marital status, education, and snuff consumption. Results: 60% of all baseline intermittent smokers had remained intermittent smokers, 16% had become daily smokers, and 24% had stopped smoking at the one year follow up. The long term intermittent smokers and those who had stopped smoking were young, unmarried, highly educated, and snuff consumers to a higher extent than the reference population. They also had more psychosocial resources than the reference population, while the psychosocial resources of those who had become daily smokers were poorer. Conclusions: The majority of intermittent smokers are long term intermittent smokers. The results suggest that long term intermittent smokers have other psychosocial characteristics than daily smokers. PMID:11891370

Desensitization to Oxcarbazepine: Long-Term Efficacy and Tolerability

PubMed Central

Lee, Jiwon; Park, Eu Gene; Lee, Munhyang

2017-01-01

Background and Purpose Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. Methods This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses. Human leukocyte antigen genotyping was performed to detect the genetic predisposition to Stevens-Johnson syndrome. The desensitization to oxcarbazepine was performed with a starting dosage of 0.1 mg/day. Efficacy was evaluated by comparing the frequency of seizures before and at 1 and 3 years after desensitization. Adverse events occurring during desensitization and the retention rate after desensitization were also investigated. Results Nineteen patients (95%) safely completed the desensitization protocol. One withdrew owing to emotional problems that appeared to be associated with oxcarbazepine. The follow-up period was 4.6±1.2 years (mean±SD), and oxcarbazepine was maintained for more than 3 years after desensitization in 15 patients (83.3%). The response rates were 84.2% and 77.8% at 1 and 3 years after desensitization, respectively. Eight patients remained seizure-free for 3 years, and two discontinued all AEDs. Transient adverse reactions such as mild rash and itching were reported by five patients during desensitization. Conclusions This study has demonstrated the long-term efficacy and safety of desensitization to oxcarbazepine in patients exhibiting cutaneous adverse drug reactions. This favorable outcome should encourage the implementation of desensitization in patients presenting with hypersensitivity to oxcarbazepine as an alternative strategy in clinical practice. PMID:27730770

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

PubMed

Beran, Jiří; Xie, Fang; Zent, Olaf

2014-07-23

Long-term vaccination programs are recommended for individuals living in regions endemic for tick-borne encephalitis (TBE). Current recommendations suggest a first booster vaccine be administered 3 years after a conventional regimen or 12-18 months after a rapid regimen. However, the research supporting subsequent booster intervals is limited. The aim of this study was thus to evaluate the long-term persistence of TBE antibodies in adults and adolescents after a first booster dose with Encepur(®). A total of 323 subjects aged 15 years and over, who had received one of four different primary TBE vaccination series in a parent study, participated in this follow-up Phase IV trial. Immunogenicity and safety were assessed for up to five years after a first booster dose, which was administered three years after completion of the primary series. One subset of subjects was excluded from the booster vaccination since they had already received their booster prior to enrollment. For comparison, immune responses were still recorded for these subjects on Day 0 and on an annual basis until Year 5, but safety information was not collected. Following a booster vaccination, high antibody titers were recorded in all groups throughout the study. Neutralization test (NT) titers of ≥ 10 were noted in at least 94% of subjects at every time point post-booster (on Day 21 and through Years 1-5). These results demonstrated that a first booster vaccination following any primary immunization schedule results in high and long-lasting (>5 years) immune responses. These data lend support to the current belief that subsequent TBE booster intervals could be extended from the current recommendation. NCT00387634. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-term Studies of Marine Halogen Release

NASA Astrophysics Data System (ADS)

Tschritter, J.; Holla, R.; Frieß, U.; Platt, U.

2009-04-01

Institute of Enviromental Physics, Heidelberg, Germany. Long term measurements of atmospheric trace gases using multi-axis DOAS instruments are pursued at the new SOLAS observatory on the island of Sao Vicente, (Cape Verde). This research is part of the SOPRAN (Surface Ocean Processes in the ANthropocene) project (Fördernummer:03F0462F). Reactive halogen species (RHS) such as bromine- and iodine- containing species play major roles in the chemistry of ozone in both the troposphere and lower stratosphere and thus possibly influence the ozone budget on a global scale. In addition iodine-species emitted from the ocean surface have been shown to be responsible for the production of new atmospheric particles in the marine boundary layer. This may have an effect on cloud formation and radiation transfer on local and global scales. Long term measurements of RHS abundances will help to identify their key regions and processes for formation. A new long term Multi-MAX-DOAS instrument has been installed at the SOLAS observatory on the island of Sao Vicente, (Cape Verde). The main focus of these unique measurements is the investigation of reactive halogen chemistry in the subtropical marine boundary layer based on measurements of BrO, IO, and possibly OIO. Because of its wide spectral range also the use for O4-retrievals to gain aerosol profiles is possible. IO has been detected with mixing ratios up to 1.3 ppt. For BrO an upper limit of 2 ppt could be determined.

Work Organization and Health Issues in Long-Term Care Centers

PubMed Central

Zhang, Yuan; Flum, Marian; Nobrega, Suzanne; Blais, Lara; Qamili, Shpend; Punnett, Laura

2018-01-01

This qualitative study explored common and divergent perceptions of caregivers and managers regarding occupational health and safety, work organization, and psychosocial concerns in long-term care centers. Both common and differing issues were identified. Both groups agreed on the importance of ergonomic concerns, the high prevalence of stress, and receptiveness to participatory health promotion programs. However, numerous work organization issues and physical and psychosocial workplace hazards were identified by certified nursing assistants but were not mentioned by managers. The results suggest that different perceptions naturally arise from people's varying positions in the occupational hierarchy and their consequent exposures to health and safety hazards. Improved systems of communication that allow frontline workers to express their concerns would make it possible to create solutions to these problems. PMID:21261239

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load.

PubMed

Galizzi, Nadia; Galli, Laura; Poli, Andrea; Gianotti, Nicola; Carini, Elisabetta; Bigoloni, Alba; Tambussi, Giuseppe; Nozza, Silvia; Lazzarin, Adriano; Castagna, Antonella; Mancusi, Daniela; Termini, Roberta

2018-01-01

A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen. Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015. The primary outcome was durability [no treatment failure (TF)]. Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters. TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason. Patients' follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit. Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters. In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (<100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942). Over a median follow-up of 2.9 years (IQR: 1.9-3.5), 26 subjects discontinued the treatment [10 due to toxicity, 7

Resident smoking in long-term care facilities--policies and ethics.

PubMed Central

Kochersberger, G; Clipp, E C

1996-01-01

Objective: To characterize smoking behavior, facility policies related smoking, and administrators' views of smoking-related problems in Veterans Affairs nursing home care units nationwide. Methods: An anonymous mail survey of long-term care facilities was administered to 106 nursing home supervisors at VA Medical Centers with nursing home care units. The response rate was 82%. Results: Administrators from 106 VA nursing home units reported smoking rates ranging from 5% to 80% of long-term care residents, with an average of 22%. Half of the nursing homes had indoor smoking areas. Frequent complaints from nonsmokers about passive smoke exposure were reported in 23% of the nursing homes. The nursing administrators reported that patient safety was their greatest concern. Seventy- eight percent ranked health effects to the smokers themselves a "major concern," while 70% put health effects to exposed nonsmokers in that category. Smoking in the nursing home was described as a "right" by 59% of respondents and a ¿privilege¿ by 67%. Some individuals reported that smoking was both a right and a privilege. Conclusion: Smoking is relatively common among VA long-term care patients. The promotion of personal autonomy and individual resident rights stressed in the Omnibus Budget Reconciliation Act of 1987 may conflict with administrative concerns about the safety of nursing home smokers and those around them. PMID:8610194

Intelligent power wheelchair use in long-term care: potential users' experiences and perceptions.

PubMed

Rushton, Paula W; Mortenson, Ben W; Viswanathan, Pooja; Wang, Rosalie H; Miller, William C; Hurd Clarke, Laura

2017-10-01

Long-term care (LTC) residents with cognitive impairments frequently experience limited mobility and participation in preferred activities. Although a power wheelchair could mitigate some of these mobility and participation challenges, this technology is often not prescribed for this population due to safety concerns. An intelligent power wheelchair (IPW) system represents a potential intervention that could help to overcome these concerns. The purpose of this study was to explore a) how residents experienced an IPW that used three different modes of control and b) what perceived effect the IPW would have on their daily lives. We interviewed 10 LTC residents with mild or moderate cognitive impairment twice, once before and once after testing the IPW. Interviews were conducted using a semi-structured interview guide, audio recorded and transcribed verbatim for thematic analyses. Our analyses identified three overarching themes: (1) the difference an IPW would make, (2) the potential impact of the IPW on others and (3) IPW-related concerns. Findings from this study confirm the need for and potential benefits of IPW use in LTC. Future studies will involve testing IPW improvements based on feedback and insights from this study. Implications for rehabilitation Intelligent power wheelchairs may enhance participation and improve safety and feelings of well-being for long-term care residents with cognitive impairments. Intelligent power wheelchairs could potentially have an equally positive impact on facility staff, other residents, and family and friends by decreasing workload and increasing safety.

Long-term safety and efficacy of the novel β3 -adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study.

PubMed

Yoshida, Masaki; Kakizaki, Hidehiro; Takahashi, Satoru; Nagai, Shinji; Kurose, Takafumi

2018-05-11

To evaluate the long-term safety and efficacy of vibegron 50 mg and 100 mg, a novel β 3 -adrenoreceptor agonist, in Japanese patients with overactive bladder. This was a 1-year, multicenter, open-label, non-controlled study. After a 1-week observation phase, patients were treated with vibegron for 52 weeks. When the efficacy was insufficient after an 8-week treatment with 50 mg, the dose was increased to 100 mg and maintained for an additional 44 weeks. Among a total of 169 patients receiving one or more doses of vibegron, 118 (69.8%) received vibegron 50 mg for 52 weeks, and the dose was increased to 100 mg in 51 (30.2%) patients. The incidence of drug-related adverse events was 18.1% (21/116) in the vibegron 50 mg group and 11.8% (6/51) in the vibegron 100 mg group. Most frequent drug-related adverse events were dry mouth (3.0%), residual urine volume increased (3.0%), constipation (2.4%) and cystitis (1.8%). Statistically significant changes in overactive bladder symptom variables (daily means of micturitions, urgency episodes, urgency incontinence episodes, incontinence episodes and night-time frequency) from baseline were observed at week 4 and maintained until week 52. The condition of patients who did not respond well to vibegron 50 mg was much improved by increasing the dose to 100 mg. Vibegron improved the quality of life, and the proportion of patients' satisfaction after the treatment with vibegron was high. Long-term (52-week) treatment with vibegron is safe, well-tolerated and effective in patients with overactive bladder. © 2018 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.

Long-Term Impact of Service Learning in Environmental Studies

ERIC Educational Resources Information Center

MacFall, Janet

2012-01-01

Long-term impacts from a senior course in Environmental Studies were evaluated by a survey of program graduates (36 respondents, 50% response rate) who had participated in the course over an 8-year permiod. Each year, the Senior Seminar used a service-learning pedagogy with a different environmentally focused project ranging from web resource…

Long-term monitoring FBG-based cable load sensor

NASA Astrophysics Data System (ADS)

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

2006-03-01

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

Liquid nitrogen spray cryotherapy in Barrett's esophagus with high-grade dysplasia: long-term results.

PubMed

Gosain, Sonia; Mercer, Kim; Twaddell, William S; Uradomo, Lance; Greenwald, Bruce D

2013-08-01

Liquid nitrogen endoscopic spray cryotherapy can safely and effectively eradicate high-grade dysplasia in Barrett's esophagus (BE-HGD). Long-term data on treatment success and safety are lacking. To assess the long-term safety and efficacy of spray cryotherapy in patients with BE-HGD. Single-center, retrospective study. Tertiary-care referral center. A total of 32 patients with BE-HGD of any length. Patients were treated with liquid nitrogen spray cryotherapy every 8 weeks until complete eradication of HGD (CE-HGD) and intestinal metaplasia (CE-IM) was found by endoscopic biopsy. Surveillance endoscopy with biopsies was performed for at least 2 years. CE-HGD, CE-IM, durability of response, disease progression, and adverse events. CE-HGD was 100% (32/32), and CE-IM was 84% (27/32) at 2-year follow-up. At last follow-up (range 24-57 months), CE-HGD was 31/32 (97%), and CE-IM was 26/32 (81%). Recurrent HGD was found in 6 (18%), with CE-HGD in 5 after repeat treatment. One patient progressed to adenocarcinoma, downgraded to HGD after repeat cryotherapy. BE segment length ≥3 cm was associated with a higher recurrence of IM (P = .004; odds ratio 22.6) but not HGD. No serious adverse events occurred. Stricture was seen in 3 patients (9%), all successfully dilated. Retrospective study design, small sample size. In patients with BE-HGD, liquid nitrogen spray cryotherapy has an acceptable safety profile and success rate for eliminating HGD and IM and is associated with a low rate of recurrence or progression to cancer with long-term follow-up. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Factors Related to Healthcare Service Quality in Long-term Care Hospitals in South Korea: A Mixed-methods Study.

PubMed

Sohn, Minsung; Choi, Mankyu

2017-10-01

The environment of long-term care hospitals (LTCHs) is critical to the management of the quality of their services and to patient safety, as highlighted by international studies. However, there is a lack of evidence on this topic in South Korea. This study aimed to examine the factors affecting healthcare quality in LTCHs and to explore the effectiveness of their quality management. This study used a mixed methods approach with quantitative data collected in a national survey and qualitative data from semi-structured interviews with practice-based managers. The samples included 725 nationally representative LTCHs in South Korea for the quantitative analysis and 15 administrators for the in-depth interviews. A higher installation rate of patient-safety and hygiene-related facilities and staff with longer-tenures, especially nurses, were more likely to have better healthcare quality and education for both employees and patients. The need for patient-safety- and hygiene-related facilities in LTCHs that serve older adults reflects their vulnerability to certain adverse events (e.g., infections). Consistent and skillful nursing care to improve the quality of LTCHs can be achieved by developing relevant educational programs for staff and patients, thereby strengthening the relationships between them.

Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy.

PubMed

Mullen, Kevin D; Sanyal, Arun J; Bass, Nathan M; Poordad, Fred F; Sheikh, Muhammad Y; Frederick, R Todd; Bortey, Enoch; Forbes, William P

2014-08-01

Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use. We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, N = 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n = 140). In the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2-1427 d), with 510.5 person-years of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72). Long-term treatment (≥24 mo) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Long term integrity for space station power systems

NASA Technical Reports Server (NTRS)

Leckie, F. A.; Marriott, D. L.

1991-01-01

A study was made of the High Temperature Design Codes ASME N47, British R5, and the French RCC-MR Rules. It is concluded that all these codes provide a good basis of design for space application. The new British R5 is the most complete since it deals with the problem of defects. The ASME N47 was subjected longer to practical application and scrutiny. A draft code is introduced, and a proposed draft for high temperature design in which attempts were made to identify gaps and improvements is suggested. The design is limited by creep characteristics. In these circumstances, life is strongly affected by the selected value of the factor of safety. The factor of safety of primary loads adopted in the codes is 1.5. Maybe a lower value of 1.25 is permissible for use in space. Long term creep rupture data for HAYNES 188 is deficient and it is suggested that extrapolation methods be investigated.

Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

PubMed

Aleman, Jacomien; Moojen, Dirk Jan F; van Ogtrop, Marc L; Poolman, Rudolf W; Franssen, Eric J F

2018-01-01

Objectives : Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections. In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections. Methods : A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l. Results : 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395). Conclusions : In our population of patients with OIRI long-term treatment with conventionally dosed

Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients

PubMed Central

Aleman, Jacomien; Moojen, Dirk Jan F.; van Ogtrop, Marc L.; Poolman, Rudolf W.; Franssen, Eric J.F.

2018-01-01

Objectives: Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections. In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections. Methods: A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l. Results: 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395). Conclusions: In our population of patients with OIRI long-term treatment with conventionally dosed

The value of long-term silvicultural research studies

Treesearch

Wayne D. Shepperd; Carleton B. Edminster

1997-01-01

Reductions in research operating budgets and recent trends in research management philosophy have in many instances forced Forest Service scientists to realign their research programs to compete for short-term grants and other sources of funding. This approach may prove detrimental in silviculture, a discipline where long-term research is critical for: (1) research in...

Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B

PubMed Central

Nathwani, A.C.; Reiss, U.M.; Tuddenham, E.G.D.; Rosales, C.; Chowdary, P.; McIntosh, J.; Della Peruta, M.; Lheriteau, E.; Patel, N.; Raj, D.; Riddell, A.; Pie, J.; Rangarajan, S.; Bevan, D.; Recht, M.; Shen, Y.-M.; Halka, K.G.; Basner-Tschakarjan, E.; Mingozzi, F.; High, K.A.; Allay, J.; Kay, M.A.; Ng, C.Y.C.; Zhou, J.; Cancio, M.; Morton, C.L.; Gray, J.T.; Srivastava, D.; Nienhuis, A.W.; Davidoff, A.M.

2014-01-01

BACKGROUND In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose–response relationship, and the level of persistent or late toxicity. METHODS We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×1012 vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. RESULTS A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. CONCLUSIONS In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; Clinical

Long-term diffusion of U(VI) in bentonite: Dependence on density

DOE PAGES

Joseph, Claudia; Mibus, Jens; Trepte, Paul; ...

2016-10-12

As a contribution to the safety assessment of nuclear waste repositories, U(VI) diffusion through the potential buffer material MX-80 bentonite was investigated at three clay dry densities over six years. Synthetic MX-80 model pore water was used as background electrolyte. Speciation calculations showed that Ca 2UO 2(CO 3) 3(aq) was the main U(VI) species. The in- and out-diffusion of U(VI) was investigated separately. U(VI) diffused about 3 mm, 1.5 mm, and 1 mm into the clay plug at ρ = 1.3, 1.6, and 1.9 g/cm 3, respectively. No through-diffusion of the U(VI) tracer was observed. However, leaching of natural uraniummore » contained in the clay occurred and uranium was detected in all receiving reservoirs. As expected, the effective and apparent diffusion coefficients, D e and D a, decreased with increasing dry density. The D a values for the out-diffusion of natural U(VI) were in good agreement with previously determined values. Surprisingly, D a values for the in-diffusion of U(VI) were about two orders of magnitude lower than values obtained in short-term in-diffusion experiments reported in the literature. Some potential reasons for this behavior that were evaluated are changes of the U(VI) speciation within the clay (precipitation, reduction) or changes of the clay porosity and pore connectivity with time. By applying Archie's law and the extended Archie's law, it was estimated that a significantly smaller effective porosity must be present for the long-term in-diffusion of U(VI). Finally, the results suggest that long-term studies of key transport phenomena may reveal additional processes that can directly impact long-term repository safety assessments.« less

Long-Term Efficacy and Safety of Sensor Augmented Insulin Pump Therapy with Low-Glucose Suspend Feature in Patients with Type 1 Diabetes.

PubMed

Gómez, Ana María; Marín Carrillo, Lisseth Fernanda; Muñoz Velandia, Oscar Mauricio; Rondón Sepúlveda, Martín Alonso; Arévalo Correa, Carol M; Mora Garzón, Edwin; Cuervo Diaz, Maria Camila; Henao Carrillo, Diana Cristina

2017-02-01

Literature supports short-term efficacy and safety of Sensor Augmented Insulin Pump (SAP) therapy in patients with type 1 diabetes (T1D). However, no data are available showing long-term outcomes. Our study describes the long-term outcomes of SAP therapy with low-glucose suspend feature (SAP+LGS) in hypoglycemia in a Colombian population with T1D and hypoglycemia. A cohort study was conducted with T1D patients receiving SAP+LGS therapy who initiated this therapy because of hypoglycemia at San Ignacio University Hospital diabetes center in Bogotá, Colombia. Glycated hemoglobin (A1c) was assessed at least every 6 months, severe hypoglycemia (SH) and hypoglycemia unawareness (HU) incidence yearly. Adherence to therapy was also evaluated. One hundred eleven patients were included in the analysis. Total daily insulin dose was reduced during follow-up (mean difference -0.22 U/kg; 95% confidence interval [CI] -0.18 to -0.26; P < 0.001). A1c levels were reduced from a baseline value of 8.8% ± 1.9% to 7.5% ± 1.0% at 5 months (mean difference -1.3%; 95% CI -1.09 to -1.50; P < 0.001) and 7.1% ± 0.8% (mean difference -1.7%; 95% CI -1.59 to -1.90; P < 0.001) at the end of follow-up (47 months on average). The incidence of SH and HU episodes decreased significantly since the first year, and this effect was maintained over time (P < 0.001). SAP+LGS therapy in T1D patients with hypoglycemia led to a significant and sustained decrease in A1c during long periods of follow-up, as well as a significant reduction in SH and HU. Future randomized clinical trials are desired.

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

PubMed

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

2015-03-01

To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. 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. 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. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

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

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.

Consider long-term care as service alternative.

PubMed

Loria, L S

1987-04-01

The increasing demand for elderly care services, pressures on inpatient average length of stay and payment levels, and potential financial rewards from providing additional services, makes long-term care look attractive to hospitals. Long-term care, however, is not for every hospital. Before deciding to establish long-term care services, management should examine how the service fits within the hospital's strategic plan. The action plan below provides guidance in evaluating a decision to use hospital facilities for long-term care. Examine how long-term care services fit within the hospital's strategic plan. Study area demographics and competitors to assess the need and supply of long-term care services. Survey the medical staff, consumers and payers to determine attitudes, perceptions and interests regarding long-term care services. Develop a facility plan that identifies areas of excess capacity that can be most easily converted into long-term care with minimal effects on hospital operations. Prepare a financial feasibility analysis of the contribution margin and return on investment attributable to long-term care services. Include an impact analysis on hospital operations. Establish a management task force to develop a detailed implementation plan including assigned individual responsibilities and related timetable. Develop an effective marketing plan designed to generate increased patient market share.

Related Studies in Long Term Lithium Battery Stability

NASA Technical Reports Server (NTRS)

Horning, R. J.; Chua, D. L.

1984-01-01

The continuing growth of the use of lithium electrochemical systems in a wide variety of both military and industrial applications is primarily a result of the significant benefits associated with the technology such as high energy density, wide temperature operation and long term stability. The stability or long term storage capability of a battery is a function of several factors, each important to the overall storage life and, therefore, each potentially a problem area if not addressed during the design, development and evaluation phases of the product cycle. Design (e.g., reserve vs active), inherent material thermal stability, material compatibility and self-discharge characteristics are examples of factors key to the storability of a power source.

Long-term effect of urethral dilatation and internal urethrotomy for urethral strictures.

PubMed

Veeratterapillay, Rajan; Pickard, Rob S

2012-11-01

Urethral dilatation and direct visual internal urethrotomy (DVIU) are widely used minimally invasive options to manage men with urethral strictures. Advances in open urethroplasty with better long-term cure rates have fuelled the continuing debate as to which treatment is best for primary and recurrent urethral strictures. We reviewed recent literature to identify contemporary practice of urethral dilatation and DVIU and the long-term outcome of these procedures. Systematic literature search for the period January 2010 to December 2011 showed that urethral dilatation and DVIU remain frequently used treatment options as confirmed by surveys of urologists in the USA and the Netherlands. Multiple reports of laser DVIU confirm the safety of this approach but long-term data were lacking. Stricture free rates from urethra dilatation and DVIU vary from 10 to 90% at 12 months, although adjunctive intermittent self-dilatation can reduce time to recurrence. Although quality-of-life benefit appears good in the short term, repeated procedures may harm sexual function in the long-term. Urethral dilatation and DVIU remain widely used in urethral stricture management but high-level comparative evidence of benefit and harms against urethroplasty in the short and long-term is still lacking.

Musical and Verbal Memory in Alzheimer's Disease: A Study of Long-Term and Short-Term Memory

ERIC Educational Resources Information Center

Menard, Marie-Claude; Belleville, Sylvie

2009-01-01

Musical memory was tested in Alzheimer patients and in healthy older adults using long-term and short-term memory tasks. Long-term memory (LTM) was tested with a recognition procedure using unfamiliar melodies. Short-term memory (STM) was evaluated with same/different judgment tasks on short series of notes. Musical memory was compared to verbal…

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

PubMed

Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

2013-11-11

The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that

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

A Long-Term Outcome Study of Selective Mutism in Childhood

ERIC Educational Resources Information Center

Steinhausen, Hans-Christoph; Wachter, Miriam; Laimbock, Karin; Metzke, Christa Winkler

2006-01-01

Objective: Controlled study of the long-term outcome of selective mutism (SM) in childhood. Method: A sample of 33 young adults with SM in childhood and two age- and gender-matched comparison groups were studied. The latter comprised 26 young adults with anxiety disorders in childhood (ANX) and 30 young adults with no psychiatric disorders during…

Long-term outcomes of acute kidney injury.

PubMed

Coca, Steven G

2010-05-01

The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

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.

Comparison of long-term safety of fixed-dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide.

PubMed

Neutel, Joel M; Cushman, William C; Lloyd, Eric; Barger, Bruce; Handley, Alison

2017-09-01

This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs fixed-dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160-190 mm Hg). Initial AZL-M/CLD 40/12.5 mg/d (n=418) or OLM/HCTZ 20/12.5 mg/d (n=419) could be uptitrated during weeks 4 to 52 (AZL-M/CLD to 80/25 mg; OLM/HCTZ to 40/25 mg [United States] or 20/25 mg [Europe]) to meet blood pressure targets. Treatment-emergent adverse events/serious adverse events occurred in 78.5%/5.7% of patients taking AZL-M/CLD vs 76.4%/6.2% taking OLM/HCTZ. The most frequent adverse events were dizziness (16.3% vs 12.6%), blood creatinine increase (21.5% vs 8.6%), headache (7.4% vs 11.0%), and nasopharyngitis (12.2% vs 11.5%). Hypokalemia was uncommon (1.0% vs 0.7%). Greater blood pressure reductions with AZL-M/CLD by week 2 were maintained throughout the study, despite less uptitration (32.3% vs 48.9% with OLM/HCTZ). Fixed-dose combination AZL-M/CLD showed an encouraging benefit-risk profile when used per standard clinical practice in a titrate-to-target strategy. ©2017 Wiley Periodicals, Inc.

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…

Surgical and conservative treatment of patients with congenital scoliosis: α search for long-term results

PubMed Central

2011-01-01

Background In view of the limited data available on the conservative treatment of patients with congenital scoliosis (CS), early surgery is suggested in mild cases with formation failures. Patients with segmentation failures will not benefit from conservative treatment. The purpose of this review is to identify the mid- or long-term results of spinal fusion surgery in patients with congenital scoliosis. Methods Retrospective and prospective studies were included, reporting on the outcome of surgery in patients with congenital scoliosis. Studies concerning a small numbers of cases treated conservatively were included too. We analyzed mid-term (5 to 7 years) and long-term results (7 years or more), both as regards the maintenance of the correction of scoliosis and the safety of instrumentation, the early and late complications of surgery and their effect on quality of life. Results A small number of studies of surgically treated patients were found, contained follow-up periods of 4-6 years that in the most cases, skeletal maturity was not yet reached, and few with follow-up of 36-44 years. The results of bracing in children with congenital scoliosis, mainly in cases with failure of formation, were also studied. Discussion Spinal surgery in patients with congenital scoliosis is regarded in short as a safe procedure and should be performed. On the other hand, early and late complications are also described, concerning not only intraoperative and immediate postoperative problems, but also the safety and efficacy of the spinal instrumentation and the possibility of developing neurological disorders and the long-term effect these may have on both lung function and the quality of life of children. Conclusions Few cases indicate the long-term results of surgical techniques, in the natural progression of scoliosis. Similarly, few cases have been reported on the influence of conservative treatment. In conclusion, patients with segmentation failures should be treated

Long-term academic stress increases the late component of error processing: an ERP study.

PubMed

Wu, Jianhui; Yuan, Yiran; Duan, Hongxia; Qin, Shaozheng; Buchanan, Tony W; Zhang, Kan; Zhang, Liang

2014-05-01

Exposure to long-term stress has a variety of consequences on the brain and cognition. Few studies have examined the influence of long-term stress on event related potential (ERP) indices of error processing. The current study investigated how long-term academic stress modulates the error related negativity (Ne or ERN) and the error positivity (Pe) components of error processing. Forty-one male participants undergoing preparation for a major academic examination and 20 non-exam participants completed a Go-NoGo task while ERP measures were collected. The exam group reported higher perceived stress levels and showed increased Pe amplitude compared with the non-exam group. Participants' rating of the importance of the exam was positively associated with the amplitude of Pe, but these effects were not found for the Ne/ERN. These results suggest that long-term academic stress leads to greater motivational assessment of and higher emotional response to errors. Copyright © 2014 Elsevier B.V. All rights reserved.

Is modified brief assertiveness training for nurses effective? A single-group study with long-term follow-up.

PubMed

Yoshinaga, Naoki; Nakamura, Yohei; Tanoue, Hiroki; MacLiam, Fionnula; Aoishi, Keiko; Shiraishi, Yuko

2018-01-01

To evaluate the long-term effectiveness of modified brief assertiveness training (with cognitive techniques) for nurses. Most assertiveness training takes a long time to conduct; thus, briefer training is required for universal on-the-job training in the workplace. In this single-group study, nurses received two 90-min training sessions with a 1-month interval between sessions. The degree of assertiveness was assessed by using the Rathus Assertiveness Schedule as the primary outcome, at four time points: pre- and post-training, 3-month follow-up and 6-month follow-up. A total of 33 nurses received the training, and the mean Rathus Assertiveness Schedule score improved from -14.2 (SD = 16.5) pre-training to -10.5 (SD = 18.0) post-training (p < .05). These improvements were maintained until the 6-month follow-up. The pre-post effect size of 0.22 (indicating small effect) was larger than the effect sizes ranging from -0.56 to 0.17 (no effect) reported in previous studies that used brief training. Modified brief assertiveness training seems feasible and may achieve long-term favourable outcomes in improving assertiveness among nurses. The ease of implementation of assertiveness training is important because creating an open environment for communication leads to improved job satisfaction, improved nursing care and increased patient safety. © 2017 The Authors. Journal of Nursing Management Published by John Wiley & Sons Ltd.

Long-term efficacy and safety of self-intracavernous injection of prostaglandin E1 for treatment of erectile dysfunction in China.

PubMed

He, L; Wen, J; Jiang, X; Chen, H; Tang, Y

2011-06-01

The study evaluated the long-term efficacy and safety profiles of self-intracavernous injection of prostaglandin E1 (PGE1) for erectile dysfunction (ED). Four hundred and sixteen ED patients were treated with self-intracavernous injection of PGE1 from January 1998 to December 2007 in our outpatient service. Follow-up was made to investigate the efficacy and side effects of this treatment. It was found that 261 patients (62.7%) felt satisfied and kept using this treatment due to its advantages of satisfactory efficacy and reasonable expense. Twenty-seven of them (6.5%) got rid of PGE1 treatment after five times injections and did not need any other drugs to maintain satisfactory sexual lives. Two hundred and fourteen (51.4%) patients kept using this treatment for over 1 year, 26 (6.2%) over 5 years, 12 (2.9%) over 8 years and 7 (1.7%) over 10 years. The major complications of self-intracavernous injection of PGE1 include fibrosis of corpus cavernosum (three cases), ecchymosis associated with vascular injury due to injection (23 cases) and pain associated with injection (295 cases). There were no patients displaying priapism. It is concluded that self-intracavernous injection of PGE1 is a safe and effective treatment for ED with various aetiologies and a broad range of severity, and no serious complications were observed after long-term application. © 2011 Blackwell Verlag GmbH.

A Comparison of Computer-based and Instructor-led Training for Long-term Care Staff.

ERIC Educational Resources Information Center

Harrington, Susan S.; Walker, Bonnie L.

2002-01-01

Fire safety training was provided to long-term care staff by computer (n=47) or a print-based, instructor-led program (n=47). Compared to 47 controls, both treatment groups significantly increased knowledge. The computer-trained staff were enthusiastic about the learning method and expressed greater interest in additional safety topics. (SK)

Long-Term Learning in a Short-Term Study Abroad Program: "Are We Really Truly Helping the Community?".

PubMed

Caldwell, Penelope; Purtzer, Mary Anne

2015-01-01

To discover long-term learning outcomes in a short-term study abroad program. Students worked directly with community members to identify health issues, implement educational workshops addressing those issues, and evaluate health outcomes. This is a qualitative, descriptive study. Thematic analysis was conducted using a written questionnaire completed one or more years postimmersion. The sample was 41 nursing students who participated in a 10-day immersion experience in remote Honduras. Four themes emerged revealing evidence of long-term learning. Three of these themes, Embracing Other, Gaining Cultural Competencies, and Experiencing an Ethnocentric Shift, are supported in the literature. The fourth theme, Negotiating Ethical Dilemmas, offers a new finding. Although educators have questioned ethical consequences of study abroad programs, there is a paucity of literature indicating that students are the ones doing the questioning. Implications for educators and community members alike include facilitating dialog about collective worldviews related to global health ethics when designing study abroad programs. © 2014 Wiley Periodicals, Inc.

Factors Related to Healthcare Service Quality in Long-term Care Hospitals in South Korea: A Mixed-methods Study

PubMed Central

Sohn, Minsung; Choi, Mankyu

2017-01-01

Objectives The environment of long-term care hospitals (LTCHs) is critical to the management of the quality of their services and to patient safety, as highlighted by international studies. However, there is a lack of evidence on this topic in South Korea. This study aimed to examine the factors affecting healthcare quality in LTCHs and to explore the effectiveness of their quality management. Methods This study used a mixed methods approach with quantitative data collected in a national survey and qualitative data from semi-structured interviews with practice-based managers. The samples included 725 nationally representative LTCHs in South Korea for the quantitative analysis and 15 administrators for the in-depth interviews. Results A higher installation rate of patient-safety and hygiene-related facilities and staff with longer-tenures, especially nurses, were more likely to have better healthcare quality and education for both employees and patients. Conclusion The need for patient-safety- and hygiene-related facilities in LTCHs that serve older adults reflects their vulnerability to certain adverse events (e.g., infections). Consistent and skillful nursing care to improve the quality of LTCHs can be achieved by developing relevant educational programs for staff and patients, thereby strengthening the relationships between them. PMID:29164045

Long-term safety and efficacy of single-tablet combinations of solifenacin and tamsulosin oral controlled absorption system in men with storage and voiding lower urinary tract symptoms: results from the NEPTUNE Study and NEPTUNE II open-label extension.

PubMed

Drake, Marcus J; Chapple, Christopher; Sokol, Roman; Oelke, Matthias; Traudtner, Klaudia; Klaver, Monique; Drogendijk, Ted; Van Kerrebroeck, Philip

2015-02-01

Short-term trials have demonstrated the efficacy and safety of combination therapy using antimuscarinics and α-blockers in men with lower urinary tract symptoms (LUTS). The Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS (oral controlled absorption system) in Males with Lower Urinary Tract Symptoms (NEPTUNE) II is the first long-term study using solifenacin (Soli) and the oral controlled absorption system formulation of tamsulosin (TOCAS). To evaluate long-term (up to 52 wk) safety and efficacy of flexible dosing of two fixed-dose combinations (FDC) of Soli plus TOCAS in men with moderate to severe storage symptoms and voiding symptoms. Patients with both storage and voiding LUTS, maximum urinary flow rate of 4.0-12.0 ml/s, prostate size <75 ml, and postvoid residuals ≤ 150 ml, who completed the 12-wk, double-blind NEPTUNE study could continue in the 40-wk, open-label NEPTUNE II study. FDC of Soli 6 mg plus TOCAS 0.4 mg, or Soli 9 mg plus TOCAS 0.4mg; patients could switch between doses in NEPTUNE II. Safety and efficacy data from NEPTUNE and NEPTUNE II were combined to cover a 52-wk period. Primary efficacy end points were total International Prostate Symptom Score (IPSS) and total urgency and frequency score (TUFS); secondary end points included IPSS storage and voiding subscores, micturition diary variables, and quality of life parameters. In all, 1066 men completed NEPTUNE and received one dose or more of study medication in NEPTUNE II. Treatment-emergent adverse events were reported in 499 (46.8%) patients who participated in NEPTUNE II; most were mild or moderate. Urinary retention occurred in 13 of 1208 (1.1%) patients receiving one or more FDCs in NEPTUNE and/or NEPTUNE II; 8 (0.7%) required catheterisation (acute urinary retention [AUR]). Reductions in total IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment, with mean reductions of 9.0 (standard deviation [SD]: 5.7) and 10.1 (SD: 9.2), respectively, from

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.

Long-term care in international perspective.

PubMed

Doty, P

1988-12-01

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

Long-term verification of functional and structural renal damage after renal sympathetic denervation.

PubMed

Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Wiebe, Jens; Renker, Matthias; Bauer, Timm; Hamm, Christian; Nef, Holger

2016-06-01

Previous studies of renal sympathetic denervation (RSD) excluded patients with impaired renal function to avoid potential RSD-related renal damage. Measurement of the highly sensitive biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) has shown that RSD does not aggravate renal damage during the early post-procedural period. The aim of the present study was to examine the effect of RSD on blood pressure (BP) reduction and renal function after a long-term follow-up. A total of 62 consecutive patients undergoing RSD were included in this study. Serum NGAL and KIM-1 were collected prior to RSD and at 24 hr, 48 hr, and 3 months after RSD. BP measurements, antihypertensive medication use, and safety events were followed over a three-year period. Follow-up data were available over 36.9[±3.4] months in 47 of 62 (75.8%) of the initially included patients. At this time point a significant systolic BP reduction of 23 mm Hg (P > 0.001) was documented, and there were no significant changes in serum creatinine (P = 0.14), blood urea nitrogen (P = 0.33), or estimated glomerular filtration rate (eGFR) (P = 0.2) values. There were also no significant changes documented in patients with impaired renal function (eGFR < 45 mL/min) during the early post- procedural period or the long-term follow-up (P = 0.34). The results of the present study show a sustained effect of RSD on BP reduction after a three-year follow-up, and there was no evidence of renal failure. These results provide verification of the long-term safety and effectiveness of RSD, even in patients with impaired renal function. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Long-term benefits of full-day kindergarten: a longitudinal population-based study

PubMed Central

Brownell, M.D.; Nickel, N.C.; Chateau, D.; Martens, P.J.; Taylor, C.; Crockett, L.; Katz, A.; Sarkar, J.; Burland, E.; Goh, C.Y.

2015-01-01

In the first longitudinal, population-based study of full-day kindergarten (FDK) outcomes beyond primary school in Canada, we used linked administrative data to follow 15 kindergarten cohorts (n ranging from 112 to 736) up to grade 9. Provincial assessments conducted in grades 3, 7, and 8 and course marks and credits earned in grade 9 were compared between FDK and half-day kindergarten (HDK) students in both targeted and universal FDK programmes. Propensity score matched cohort and stepped-wedge designs allowed for stronger causal inferences than previous research on FDK. We found limited long-term benefits of FDK, specific to the type of programme, outcomes examined, and subpopulations. FDK programmes targeted at low-income areas showed long-term improvements in numeracy for lower income girls. Our results suggest that expectations for wide-ranging long-term academic benefits of FDK are unwarranted. PMID:25632172

The Long-Term Consumption of Oats in Celiac Disease Patients Is Safe: A Large Cross-Sectional Study

PubMed Central

Aaltonen, Katri; Laurikka, Pilvi; Huhtala, Heini; Mäki, Markku; Kaukinen, Katri; Kurppa, Kalle

2017-01-01

A strict gluten-free diet (GFD) can be diversified by non-contaminated oats, but there is a shortage of long-term studies concerning its safety. We compared long-term treatment outcomes and factors associated with the introduction of oats between celiac patients on a GFD with or without oats. Eight hundred sixty-nine previously diagnosed celiac patients were interviewed. The validated Gastrointestinal Symptom Rating Scale (GSRS), Psychological General Well-Being (PGWB), and Short-Form 36 Health Survey (SF-36) questionnaires were used to assess symptoms and quality of life, serological tests were performed, and results of histology were confirmed from patient records. We found the median duration of GFD to be 10 years and 82% using oats. Factors predicting the consumption of oats were diagnosis after the year 2000, advice from a dietitian, detection by screening, and mild clinical presentation. Oat consumers and non-consumers did not differ in dietary adherence (96.5% vs. 97.4%, p = 0.746), the prevalence of symptoms (22.9% vs. 22.5%, p = 0.931), positivity for endomysial antibodies (8.8% vs. 6.0%, p = 0.237), histological recovery after one year (63.1% vs. 60.0%, p = 0.773), malignancy (4.8% vs. 3.3%, p = 0.420), osteoporosis/osteopenia (9.2% vs. 11.0%, p = 0.489), or fractures (26.9% vs. 27.9%, p = 0.791). The oat consumers had better SF-36 physical role limitations and general health scores. Based on our results, the long-term consumption of oats in celiac disease patients is safe and may improve quality of life. PMID:28617328

An organizational perspective on the long-term sustainability of a nursing best practice guidelines program: a case study.

PubMed

Fleiszer, Andrea R; Semenic, Sonia E; Ritchie, Judith A; Richer, Marie-Claire; Denis, Jean-Louis

2015-12-03

Many healthcare innovations are not sustained over the long term, wasting costly implementation efforts and often desperately-needed initial improvements. Although there have been advances in knowledge about innovation implementation, there has been considerably less attention focused on understanding what happens following the early stages of change. Research is needed to determine how to improve the 'staying power' of healthcare innovations. As almost no empirical knowledge exists about innovation sustainability in nursing, the purpose of our study was to understand how a nursing best practice guidelines (BPG) program was sustained over a long-term period in an acute healthcare centre. We conducted a qualitative descriptive case study to examine the program's sustainability at the nursing department level of the organization. The organization was a large, urban, multi-site acute care centre in Canada. The patient safety-oriented BPG program, initiated in 2004, consisted of an organization-wide implementation of three BPGs: falls prevention, pressure ulcer prevention, and pain management. Data were collected eight years following program initiation through 14 key informant interviews, document reviews, and observations. We developed a framework for the sustainability of healthcare innovations to guide data collection and content analysis. Program sustainability entailed a combination of three essential characteristics: benefits, institutionalization, and development. A constellation of 11 factors most influenced the long-term sustainability of the program. These factors were innovation-, context-, leadership-, and process-related. Three key interactions between factors influencing program sustainability and characteristics of program sustainability accounted for how the program had been sustained. These interactions were between: leadership commitment and benefits; complementarity of leadership actions and both institutionalization and development; and a

A long-term outcome study of selective mutism in childhood.

PubMed

Steinhausen, Hans-Christoph; Wachter, Miriam; Laimböck, Karin; Metzke, Christa Winkler

2006-07-01

Controlled study of the long-term outcome of selective mutism (SM) in childhood. A sample of 33 young adults with SM in childhood and two age- and gender-matched comparison groups were studied. The latter comprised 26 young adults with anxiety disorders in childhood (ANX) and 30 young adults with no psychiatric disorders during childhood. The three groups were compared with regard to psychiatric disorder in young adulthood by use of the Composite International Diagnostic Interview (CIDI). In addition, the effect of various predictors on outcome of SM was studied. The symptoms of SM improved considerably in the entire SM sample. However, both SM and ANX had significantly higher rates for phobic disorder and any psychiatric disorder than controls at outcome. Taciturnity in the family and, by trend, immigrant status and a severity indicator of SM had an impact on psychopathology and symptomatic outcome in young adulthood. This first controlled long-term outcome study of SM provides evidence of symptomatic improvement of SM in young adulthood. However, a high rate of phobic disorder at outcome points to the fact that SM may be regarded as an anxiety disorder variant.

A 24-Week, Open-Label Extension Study to Investigate the Long-term Safety, Tolerability, and Efficacy of 13.3 mg/24 h Rivastigmine Patch in Patients With Severe Alzheimer Disease.

PubMed

Farlow, Martin R; Grossberg, George T; Sadowsky, Carl H; Meng, Xiangyi; Velting, Drew M

2015-01-01

The long-term safety, tolerability, and efficacy of high-dose 13.3 mg/24 h rivastigmine patch in severe Alzheimer disease was evaluated in a 24-week, open-label extension to the double-blind ACTION study. Safety and tolerability, and efficacy on the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV), Severe Impairment Battery (SIB), and ADCS-Clinical Global Impression of Change (ADCS-CGIC) were assessed. Overall, 197 patients continued on 13.3 mg/24 h patch; 199 uptitrated from 4.6 mg/24 h to 13.3 mg/24 h patch. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar in patients who continued on, and patients who uptitrated to, 13.3 mg/24 h patch (AEs: 57.9% and 59.8%; serious AEs: 16.2% and 16.1%; discontinuations: 11.2% and 12.1%, respectively). Larger mean changes from double-blind baseline were observed in patients uptitrated on the ADCS-ADL-SIV (-4.6; SD=8.7) and SIB (-7.0; SD=16.6), than those who continued on 13.3 mg/24 h patch (-3.9; SD=8.0 and -4.7; SD=16.8, respectively). ADCS-CGIC scores were comparable. There were no clinically relevant between-group differences in safety and tolerability. Greater decline was observed in patients with delayed uptitration to high-dose 13.3 mg/24 h patch than patients who continued on high-dose patch.

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

PubMed Central

Fong, Angie HC; Lai, Timothy YY

2013-01-01

Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed. PMID:23766636

High-power and short-duration ablation for pulmonary vein isolation: Safety, efficacy, and long-term durability.

PubMed

Barkagan, Michael; Contreras-Valdes, Fernando M; Leshem, Eran; Buxton, Alfred E; Nakagawa, Hiroshi; Anter, Elad

2018-05-30

PV reconnection is often the result of catheter instability and tissue edema. High-power short-duration (HP-SD) ablation strategies have been shown to improve atrial linear continuity in acute pre-clinical models. This study compares the safety, efficacy and long-term durability of HP-SD ablation with conventional ablation. In 6 swine, 2 ablation lines were performed anterior and posterior to the crista terminalis, in the smooth and trabeculated right atrium, respectively; and the right superior PV was isolated. In 3 swine, ablation was performed using conventional parameters (THERMOCOOL-SMARTTOUCH ® SF; 30W/30 sec) and in 3 other swine using HP-SD parameters (QDOT-MICRO™, 90W/4 sec). After 30 days, linear integrity was examined by voltage mapping and pacing, and the heart and surrounding tissues were examined by histopathology. Acute line integrity was achieved with both ablation strategies; however, HP-SD ablation required 80% less RF time compared with conventional ablation (P≤0.01 for all lines). Chronic line integrity was higher with HP-SD ablation: all 3 posterior lines were continuous and transmural compared to only 1 line created by conventional ablation. In the trabeculated tissue, HP-SD ablation lesions were wider and of similar depth with 1 of 3 lines being continuous compared to 0 of 3 using conventional ablation. Chronic PVI without stenosis was evident in both groups. There were no steam-pops. Pleural markings were present in both strategies, but parenchymal lung injury was only evident with conventional ablation. HP-SD ablation strategy results in improved linear continuity, shorter ablation time, and a safety profile comparable to conventional ablation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Long-Term Outcomes of Short-Term Statin Use in Healthy Adults: A Retrospective Cohort Study.

PubMed

Mansi, Ishak A; English, Jenny; Zhang, Song; Mortensen, Eric M; Halm, Ethan A

2016-06-01

Data suggest that the beneficial cardiovascular effects of statins are maximized after the first year of statin use; yet, the timeline of statin-associated adverse events is not well delineated. To examine the associations of short-term statin use (≤1 year) with short- and long-term adverse events and beneficial cardiovascular outcomes in a 'healthy' cohort. A cohort study of a healthy Tricare population (fiscal year [FY] 2002 through FY 2011) who have no cardiovascular disease, major comorbidities requiring medications, or functional limitations. Statin users used statins for 90-365 days during FY 2005 as their only prescription medication. Nonusers had medical encounters but did not receive prescription medications during FY 2005, and did not receive any statins throughout the study period from FY 2002 to FY 2011. Outcomes were the occurrence of major acute cardiovascular events, diabetes mellitus and its complications, kidney diseases, musculoskeletal diseases, obesity, cataracts, malignancy, and death. We matched 1525 statin users to 1525 nonusers. During the follow-up period (FY 2006 to FY 2011), statin users had significantly higher odds of developing diabetes and diabetic complications that persisted throughout follow-up (odds ratio [OR] 1.93, 95 % confidence interval [CI] 1.55-2.41 and OR 2.15, 95 % CI 1.20-3.86, respectively). Short-term statin use was not associated with decreased odds of major acute cardiovascular events (OR 1.17, 95 % CI 0.72-1.92). There were no differences in risks of kidney diseases, musculoskeletal diseases, or malignancy. Short-term statin use for primary prevention in this healthy cohort was associated with an increased risk of long-term diabetes and diabetic complications without cardiovascular benefits. Further study using pragmatic studies and prospective observational studies appropriately equipped to eliminate unidentified confounders are urgently needed.

Long-Term Opioid Therapy Reconsidered

PubMed Central

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

2012-01-01

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

Fexapotide triflutate: results of long-term safety and efficacy trials of a novel injectable therapy for symptomatic prostate enlargement.

PubMed

Shore, Neal; Tutrone, Ronald; Efros, Mitchell; Bidair, Mohamed; Wachs, Barton; Kalota, Susan; Freedman, Sheldon; Bailen, James; Levin, Richard; Richardson, Stephen; Kaminetsky, Jed; Snyder, Jeffrey; Shepard, Barry; Goldberg, Kenneth; Hay, Alan; Gange, Steven; Grunberger, Ivan

2018-05-01

These studies were undertaken to determine if fexapotide triflutate 2.5 mg transrectal injectable (FT) has significant long-term (LT) safety and efficacy for the treatment of benign prostatic hyperplasia (BPH). Two placebo controlled double-blind randomized parallel group trials with 995 BPH patients at 72 sites treated 3:2 FT:placebo, with open-label FT crossover (CO) re-injection in 2 trials n = 344 and long-term follow-up (LF) 2-6.75 years (mean 3.58 years, median 3.67 years; FT re-injection CO mean 4.27 years, median 4.42 years) were evaluated. 12 months post-treatment patients elected no further treatment, approved oral medications, FT, or interventional treatment. Primary endpoint variable was change in Symptom Score (IPSS) at 12 months and at LF. CO primary co-endpoints were 3-year incidence of (1) surgery for BPH in FT treated CO patients versus patients crossed over to oral BPH medications and (2) surgery or acute urinary retention in FT-treated CO placebo patients versus placebo patients crossed over to oral BPH medications. 28 CO secondary endpoints assessed surgical and symptomatic outcomes in FT reinjected patients versus conventional BPH medication CO and control subgroups at 2 and 3 years. FT injection had no significant safety differences from placebo. LF IPSS change from baseline was higher in FT treated patients compared to placebo (median FT group improvement - 5.2 versus placebo - 3.0, p < 0.0001). LF incidence of AUR (1.08% p = 0.0058) and prostate cancer (PCa) (1.1% p = 0.0116) were both reduced in FT treated patients. LF incidence of intervention for BPH was reduced in the FT group versus oral BPH medications (8.08% versus 27.85% at 3 years, p < 0.0001). LF incidence of intervention or AUR in placebo CO group with FT versus placebo CO group with oral medications was reduced (6.07% versus 33.3% at 3 years, p < 0.0001). 28/28 secondary efficacy endpoints were reached in LF CO re-injection studies. FT 2.5 mg is a safe

Barriers and Facilitators in Pain Management in Long-Term Care Institutions: A Qualitative Study

ERIC Educational Resources Information Center

Fox, Patricia; Solomon, Patricia; Raina, Parminder; Jadad, Alejandro R.

2004-01-01

The purpose of this study was to identify barriers to the management of pain in long-term care institutions. Formal caregivers practising in four long-term care institutions in Hamilton, Ontario participated in eight focus groups. Participants included 6 physicians, 19 registered nurses, 8 registered practical nurses, 13 health care aides and 8…

[Psychosocial issues of long-term cancer survivors].

PubMed

Weis, J; Faller, H

2012-04-01

Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

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

Fittler, Andras; Bősze, Gergely; Botz, Lajos

2013-09-10

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. 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. 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. The number of active Internet pharmacy websites decreased; 23 of 136 (16.9%) online pharmacies ceased operating within 12 months and only 67 monitored websites (49.3%) were accessible at the end of the four-year observation period. However, not all operated continuously, as about one-fifth (31/136) of all observed online pharmacy websites were inaccessible provisionally. Thus, only 56 (41.2%) Internet-based pharmacies were continuously operational. Thirty-one of the 136 online pharmacies (22.8%) had not provided any contact details, while only 59 (43.4%) displayed all necessary contact information on the website. We found that the declared physical location claims did not correspond to the area of domain registration (according to IP address) for most websites. Although the majority (120/136, 88.2%) of the examined Internet pharmacies distributed various prescription-only medicines, only 9 (6.6%) requested prior

Guidance for implementing the long-term surveillance program for UMTRA Project Title I Disposal Sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-02-01

This guidance document has two purposes: it provides guidance for writing site-specific long-term surveillance plans (LTSP) and it describes site surveillance, monitoring, and long-term care techniques for Title I disposal sites of the Uranium Mill Tailings Radiation Control Act (UMTRCA) (42 USC Section 7901 et seq.). Long-term care includes monitoring, maintenance, and emergency measures needed to protect public health and safety and the environment after remedial action is completed. This document applies to the UMTRCA-designated Title I disposal sites. The requirements for long-term care of the Title I sites and the contents of the LTSPs are provided in U.S. Nuclearmore » Regulatory Commission (NRC) regulations (10 CFR Section 40.27) provided in Attachment 1.« less

Long-Term In-Service Monitoring and Performance Assessment of the Main Cables of Long-Span Suspension Bridges

PubMed Central

Deng, Yang; Liu, Yang; Chen, Suren

2017-01-01

Despite the recent developments in structural health monitoring, there remain great challenges for accurately, conveniently, and economically assessing the in-service performance of the main cables for long-span suspension bridges. A long-term structural health monitoring technique is developed to measure the tension force with a conventional sensing technology and further provide the in-service performance assessment strategy of the main cable. The monitoring system adopts conventional vibrating strings transducers to monitor the tension forces of separate cable strands of the main cable in the anchor span. The performance evaluation of the main cable is conducted based on the collected health monitoring data: (1) the measured strand forces are used to derive the overall tension force of a main cable, which is further translated into load bearing capacity assessment using the concept of safety factor; and (2) the proposed technique can also evaluate the uniformity of tension forces from different cable strands. The assessment of uniformity of strand forces of a main cable offers critical information in terms of potential risks of partial damage and performance deterioration of the main cable. The results suggest the proposed low-cost monitoring system is an option to provide approximate estimation of tension forces of main cables for suspension bridges. With the long-term monitoring data, the proposed monitoring-based evaluation methods can further provide critical information to assess the safety and serviceability performance of main cables. PMID:28621743

Long-Term In-Service Monitoring and Performance Assessment of the Main Cables of Long-Span Suspension Bridges.

PubMed

Deng, Yang; Liu, Yang; Chen, Suren

2017-06-16

Despite the recent developments in structural health monitoring, there remain great challenges for accurately, conveniently, and economically assessing the in-service performance of the main cables for long-span suspension bridges. A long-term structural health monitoring technique is developed to measure the tension force with a conventional sensing technology and further provide the in-service performance assessment strategy of the main cable. The monitoring system adopts conventional vibrating strings transducers to monitor the tension forces of separate cable strands of the main cable in the anchor span. The performance evaluation of the main cable is conducted based on the collected health monitoring data: (1) the measured strand forces are used to derive the overall tension force of a main cable, which is further translated into load bearing capacity assessment using the concept of safety factor; and (2) the proposed technique can also evaluate the uniformity of tension forces from different cable strands. The assessment of uniformity of strand forces of a main cable offers critical information in terms of potential risks of partial damage and performance deterioration of the main cable. The results suggest the proposed low-cost monitoring system is an option to provide approximate estimation of tension forces of main cables for suspension bridges. With the long-term monitoring data, the proposed monitoring-based evaluation methods can further provide critical information to assess the safety and serviceability performance of main cables.

Fondaparinux in the initial and long-term treatment of venous thromboembolism.

PubMed

Pesavento, Raffaele; Amitrano, Maria; Trujillo-Santos, Javier; Di Micco, Pierpaolo; Mangiacapra, Sara; López-Jiménez, Luciano; Falgá, Conxita; García-Bragado, Fernando; Piovella, Chiara; Prandoni, Paolo; Monreal, Manuel

2015-02-01

Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice. We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer. Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05). An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long Periodic Terms in the Solar System

NASA Technical Reports Server (NTRS)

Bretagnon, P.

1982-01-01

The long period variations of the first eight planets in the solar system are studied. First, the Lagrangian solution is calculated and then the long period terms with fourth order eccentricities and inclinations are introduced into the perturbation function. A second approximation was made taking into account the short period terms' contribution, namely the perturbations of first order with respect to the masses. Special attention was paid to the determination of the integration constants. The relative importance of the different contributions is shown. It is useless, for example, to introduce the long period terms of fifth order if no account has been taken of the short period terms. Meanwhile, the terms that have been neglected would not introduce large changes in the integration constants. Even so, the calculation should be repeated with higher order short period terms and fifth order long periods.

Long-term memory, sleep, and the spacing effect.

PubMed

Bell, Matthew C; Kawadri, Nader; Simone, Patricia M; Wiseheart, Melody

2014-01-01

Many studies have shown that memory is enhanced when study sessions are spaced apart rather than massed. This spacing effect has been shown to have a lasting benefit to long-term memory when the study phase session follows the encoding session by 24 hours. Using a spacing paradigm we examined the impact of sleep and spacing gaps on long-term declarative memory for Swahili-English word pairs by including four spacing delay gaps (massed, 12 hours same-day, 12 hours overnight, and 24 hours). Results showed that a 12-hour spacing gap that includes sleep promotes long-term memory retention similar to the 24-hour gap. The findings support the importance of sleep to the long-term benefit of the spacing effect.

Long-term personality data collection in support of spaceflight and analogue research.

PubMed

Musson, David M; Helmreich, Robert L

2005-06-01

This is a review of past and present research into personality and performance at the University of Texas (UT) Human Factors Research Project. Specifically, personality trait data collected from astronauts, pilots, Antarctic personnel, and other groups over a 15-yr period is discussed with particular emphasis on research in space and space analogue environments. The UT Human Factors Research Project conducts studies in personality and group dynamics in aviation, space, and medicine. Current studies include personality determinants of professional cultures, team effectiveness in both medicine and aviation, and personality predictors of long-term astronaut performance. The Project also studies the design and effectiveness of behavioral strategies used to minimize error and maximize team performance in safety-critical work settings. A multi-year personality and performance dataset presents many opportunities for research, including long-term and follow-up studies of human performance, analyses of trends in recruiting and attrition, and the ability to adapt research design to operational changes and methodological advances. Special problems posed by such long-duration projects include issues of confidentiality and security, as well as practical limitations imposed by current peer-review and short-term funding practices. Practical considerations for ongoing dataset management include consistency of assessment instruments over time, variations in data acquisition from one year to the next, and dealing with changes in theory and practice that occur over the life of the project. A fundamental change in how research into human performance is funded would be required to ensure the ongoing development of such long-duration research databases.

Competitive short-term and long-term memory processes in spatial habituation.

PubMed

Sanderson, David J; Bannerman, David M

2011-04-01

Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory.

Long-Term Planning for Nuclear Energy Systems Under Deep Uncertainty

NASA Astrophysics Data System (ADS)

Kim, Lance Kyungwoo

Long-term planning for nuclear energy systems has been an area of interest for policy planners and systems designers to assess and manage the complexity of the system and the long-term, wide-ranging societal impacts of decisions. However, traditional planning tools are often poorly equipped to cope with the deep parametric, structural, and value uncertainties in long-term planning. A more robust, multiobjective decision-making method is applied to a model of the nuclear fuel cycle to address the many sources of complexity, uncertainty, and ambiguity inherent to long-term planning. Unlike prior studies that rely on assessing the outcomes of a limited set of deployment strategies, solutions in this study arise from optimizing behavior against multiple incommensurable objectives, utilizing goal-seeking multiobjective evolutionary algorithms to identify minimax regret solutions across various demand scenarios. By excluding inferior and infeasible solutions, the choice between the Pareto optimal solutions depends on a decision-maker's preferences for the defined outcomes---limiting analyst bias and increasing transparency. Though simplified by the necessity of reducing computational burdens, the nuclear fuel cycle model captures important phenomena governing the behavior of the nuclear energy system relevant to the decision to close the fuel cycle---incorporating reactor population dynamics, material stocks and flows, constraints on material flows, and outcomes of interest to decision-makers. Technology neutral performance criteria are defined consistent with the Generation IV International Forum goals of improved security and proliferation resistance based on structural features of the nuclear fuel cycle, natural resource sustainability, and waste production. A review of safety risks and the economic history of the development of nuclear technology suggests that safety and economic criteria may not be decisive criteria as the safety risks posed by alternative fuel

Medical Underwriting In Long-Term Care Insurance: Market Conditions Limit Options For Higher-risk Consumers

PubMed Central

2016-01-01

A key feature of private long-term care insurance is that medical underwriters screen out would-be buyers who have health conditions that portend near-term physical or cognitive disability. We applied common underwriting criteria based on data from two long-term care insurers to a nationally representative sample of individuals in the target age range for long-term care insurance (50–71 years of age). The screening criteria put upper bounds on the current proportion of Americans who could gain coverage in the individual market without changes to medical underwriting practice. Specifically, our simulations show that, for the target age range, approximately 30% of individuals whose wealth meets minimum industry standards for the suitability of long-term care insurance would have their long-term care insurance application rejected for medical reasons. Among the general population–without considering restrictions on wealth–we estimate that 40% would be disqualified. In evaluating long-term care financing reforms and their potential to increase private insurance rates, as well as to reduce financial pressure on public safety-net programs, policymakers need to consider the role of underwriting in the market for long-term care insurance. PMID:27503976

Career Program Completers. 1989-90 Long-Term Follow-Up Study.

ERIC Educational Resources Information Center

Johnson County Community Coll., Overland Park, KS. Office of Institutional Research.

In summer 1994, a long-term follow-up study was conducted of 1989-90 graduates of career programs at Johnson County Community College (JCCC) in Kansas. A survey was mailed to 536 graduates, certificate holders, and students who left JCCC with marketable skills to assess their satisfaction with JCCC and their jobs. With telephone follow-up, a…

24 CFR 232.11 - Establishment and maintenance of long-term debt service reserve account.

Code of Federal Regulations, 2013 CFR

2013-04-01

... this part, and except with respect to Supplemental Loans to Finance Purchase and Installation of Fire Safety Equipment (subpart C of this part), if HUD determines the mortgage presents an atypical long-term...

24 CFR 232.11 - Establishment and maintenance of long-term debt service reserve account.

Code of Federal Regulations, 2014 CFR

2014-04-01

... this part, and except with respect to Supplemental Loans to Finance Purchase and Installation of Fire Safety Equipment (subpart C of this part), if HUD determines the mortgage presents an atypical long-term...

Long-term Safety and Efficacy of Tapentadol Extended Release Following up to 2 Years of Treatment in Patients With Moderate to Severe, Chronic Pain: Results of an Open-label Extension Trial.

PubMed

Buynak, Robert; Rappaport, Stephen A; Rod, Kevin; Arsenault, Pierre; Heisig, Fabian; Rauschkolb, Christine; Etropolski, Mila

2015-11-01

Tapentadol extended release (ER) has demonstrated efficacy and safety for the management of moderate to severe, chronic pain in adults. This study evaluated the long-term safety and tolerability of tapentadol ER in patients with chronic osteoarthritis or low back pain. Patients were enrolled in this 1-year, open-label extension study after completing one of two 15-week, placebo-controlled studies of tapentadol ER and oxycodone controlled release (CR) for osteoarthritis knee pain (NCT00421928) or low back pain (NCT00449176), a 7-week crossover study between tapentadol immediate release and tapentadol ER for low back pain (NCT00594516), or a 1-year safety study of tapentadol ER and oxycodone CR for osteoarthritis or low back pain (NCT00361504). After titrating the drug to an optimal dose, patients received tapentadol ER (100-250 mg BID) for up to 1 year (after finishing treatment in the preceding studies); patients who were previously treated with tapentadol ER in the 1-year safety study received tapentadol ER continuously for up to 2 years in total. Of the 1,154 patients in the safety population, 82.7% were aged >65 years and 57.9% were female; 50.1% had mild baseline pain intensity. Mean (SD) pain intensity scores (11-point numerical rating scale) were 3.9 (2.38) at baseline (end of preceding study) and 3.7 (2.42) at end point, indicating that pain relief was maintained during the extension study. Improvements in measures of quality of life (eg, EuroQol-5 Dimension and the 36-item Short Form Health Survey [SF-36]) health status questionnaires) achieved during the preceding studies were maintained during the open-label extension study. Tapentadol ER was associated with a safety and tolerability profile comparable to that observed in the preceding studies. The most common treatment-emergent adverse events (incidence ≥10%; n = 1154) were headache (13.1%), nausea (11.8%), and constipation (11.1%). Similar efficacy and tolerability results were shown for patients who

Psychological distress, fatigue and long-term sickness absence: prospective results from the Maastricht Cohort Study.

PubMed

Bültmann, Ute; Huibers, Marcus J H; van Amelsvoort, Ludovic P G M; Kant, Ijmert; Kasl, Stanislav V; Swaen, Gerard M H

2005-09-01

Little is known about psychological distress as a risk factor for the onset of long-term sickness absence and even less about the influence of fatigue in this relationship. We examined the relationship between psychological distress and the onset of long-term sickness absence during 18 months of follow-up while considering fatigue. Analyses were based on 6403 employees participating in the Maastricht Cohort Study. Psychological distress was related to the onset of long-term sickness absence (women relative risk 1.45, 95% confidence interval = 1.23-1.72; men 1.33, 1.21-1.46). Adjustment for fatigue weakened the associations, particularly in women. Caseness analyses revealed different effects of psychological distress and fatigue in the onset of long-term sickness absence in men and women. The findings underline the need for interventions aiming at psychological distress and, depending on the gender, also at fatigue, to reduce the risk of long-term sickness absence.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

PubMed Central

2013-01-01

Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). Results Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study.

PubMed

Elmer, Lawrence W; Surmann, Erwin; Boroojerdi, Babak; Jankovic, Joseph

2012-06-01

This prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson's disease (PD). Patients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson's Disease Rating Scale (UPDRS) II+III total score. Of 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (≈ 5 years, 3 months; range 1-2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II+III total scores remained below double-blind baseline for up to 2 years of open-label treatment. This is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Hill plots: A rare long-term vegetation study (P-53)

Treesearch

Jonathan D. Bakker; Margaret M. Moore; Daniel C. Laughlin

2008-01-01

One legacy of the Fort Valley Experimental Forest is the number and quality of long-term studies associated with it. One such study is the "Hill plots," which began in 1912 and is still being actively studied. Livestock exclosures were built at five sites to examine vegetation recovery when protected from livestock grazing. Sites span a range of soil types...

Long-term follow-up for efficacy and safety of treatment of retinitis pigmentosa with valproic acid.

PubMed

Bhalla, Sheena; Joshi, Deval; Bhullar, Shaminder; Kasuga, Daniel; Park, Yeonhee; Kay, Christine N

2013-07-01

The purpose of this study was to determine the long-term efficacy and safety of valproic acid (VPA) treatment in patients with pigmentary retinal dystrophies. A retrospective chart review was conducted on 31 patients with a diagnosis of pigmentary retinal dystrophy prescribed VPA at a single centre. Visual field (VF), visual acuity (VA), length of treatment, liver enzymes and side effects were analysed. VF areas were defined using Goldmann VF (GVF) tracings recorded before, during and after VPA treatment using the V4e isopter for each eye. Using custom software, planimetric areas of VF were calculated. Five of the patients (10 eyes) had two Goldmann VF tracings, allowing comparison between baseline and follow-up VF. After 9.8 months of VPA, VF decreased by 0.145 cm(2) (26.478%) (p=0.432). For 22 of the patients (41 eyes), VA data was available, and logarithm of the minimum angle of resolution (logMAR) score changed by 0.056 log units (representing a decline in VA) after 14.9 months on VPA (p=0.002). Twelve patients (38.7%) reported negative side effects related to VPA use. VPA plays a complex role in patients with pigmentary retinal dystrophies and may be associated with VA and field decline as well as adverse side effects. Physicians should use caution with using VPA for pigmentary retinal dystrophies.

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

PubMed Central

Fanaroff, Alexander C.; Roe, Matthew T.

2018-01-01

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

Long-term Safety of Living Kidney Donation in an Emerging Economy.

PubMed

Rizvi, S Adibul Hasan; Zafar, Mirza Naqi; Jawad, Fatema; Aziz, Tahir; Hussain, Zafar; Hashmi, Altaf; Hussain, Manzoor; Akhtar, Fazal; Ahmed, Ejaz; Naqvi, Rubina; Naqvi, S A Anwar

2016-06-01

Long-term follow-up and management of donors was undertaken in a specialist kidney transplant unit in Pakistan to identify risk and prevent adverse outcomes in living related kidney donors. In an observation cohort study between 1985 and 2012, 3748 donors were offered free medical follow-up and treatment 6 to 12 months after donation and annually thereafter. Each visit included history, physical examination, blood tests for renal, lipid, glucose profiles, and 24-hour urine for proteinuria and creatinine clearance. Preventive intervention was undertaken for new onset clinical conditions. Donor outcomes were compared with 90 nondonor healthy siblings matched for age, sex, and body mass index. Of the 3748 donors, 2696 (72%) were in regular yearly follow-up for up to 27 years (median, 5.6; interquartile range, 7.9). Eleven (0.4%) died 4 to 22 years after donation with all-cause mortality of 4.0/10 000 person years. Six (0.2%) developed end-stage renal disease 5 to 17 years after donation, (2.7/10 000 person years). Proteinuria greater than 1000 mg/24 hours developed in 28 patients (1%), hypertension in 371 patients (13.7%), and diabetes in 95 patients (3.6%). Therapeutic intervention-controlled protein was less than 1000 mg/24 hours, blood pressure was below 140/90 mm Hg, and glycemic control in 85% up to 15 years after onset. Creatinine clearance fell from 109.8 ± 22.3 mL/min per 1.73 m predonation to 78 ± 17 at 1 year, 84 ± 19 at 5 years, and 70 ± 20 at 25 years. Comparison of 90 nondonor sibling and donor pairs showed significantly higher fasting glucose and hypertension in nondonors. Long-term follow-up of donors has demonstrated end-stage renal disease in 0.6% at 25 years. Regular follow-up identified new onset of disease and allowed interventions that may have prevented adverse outcomes.

Long-term safety of once-daily lixisenatide in Japanese patients with type 2 diabetes mellitus: GetGoal-Mono-Japan.

PubMed

Seino, Yutaka; Yabe, Daisuke; Takami, Akane; Niemoeller, Elisabeth; Takagi, Hiroki

2015-01-01

This 76-week, open-label, parallel-group study assessed the long-term safety of once-daily lixisenatide monotherapy in Japanese patients with type 2 diabetes mellitus. Patients were randomized to receive lixisenatide in a 2-step or a 1-step dose-increase regimen. The primary objective was to assess the safety of lixisenatide at week 24 by a descriptive comparison of the 2- and 1-step groups. As expected with treatment with a glucagon-like peptide-1 agonist, nausea was the most common treatment-emergent adverse event (2-step group: n=12/33 [36.4%] vs 1-step group: n=18/36 [50.0%] up to week 24). In total, 5/33 patients (15.2%; 2-step group) and 2/36 patients (5.6%; 1-step group) prematurely discontinued treatment up to week 24, mainly due to adverse events. Serious treatment-emergent adverse events occurred in 2/33 patients (6.1%; 2-step group) versus 0/36 patients (0%; 1-step group) up to week 24. Symptomatic hypoglycemia occurred in 2/33 patients (6.1%; 2-step group) versus 1/36 patients (2.8%; 1-step group) up to week 24, with no severe events reported. Glycated hemoglobin, fasting plasma glucose, and body weight were reduced from baseline at weeks 24 and 76. In Japanese patients with type 2 diabetes mellitus, once-daily lixisenatide monotherapy was well tolerated, with less nausea with the 2-step regimen. Copyright © 2015. Published by Elsevier Inc.

Zambia : long-term generation expansion study - executive summary.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conzelmann, G.; Koritarov, V.; Buehring, W.

2008-02-28

The objective of this study is to analyze possible long-term development options of the Zambian electric power system in the period up to 2015. The analysis involved the hydro operations studies of the Zambezi river basin and the systems planning studies for the least-cost generation expansion planning. Two well-known and widely accepted computer models were used in the analysis: PC-VALORAGUA model for the hydro operations and optimization studies and the WASP-III Plus model for the optimization of long-term system development. The WASP-III Plus model is a part of the Argonne National Laboratory's Energy and Power Evaluation Model (ENPEP). The analysismore » was conducted in close collaboration with the Zambia Electricity Supply Corporation (ZESCO). On the initiative from The World Bank, the sponsor of the study, ZESCO formed a team of experts that participated in the analysis and were trained in the use of computer models. Both models were transferred to ZESCO free of charge and installed on several computers in the ZESCO corporate offices in Lusaka. In September-October 1995, two members of the ZESCO National Team participated in a 4-week training course at Argonne National Laboratory near Chicago, U.S.A., focusing on the long-term system expansion planning using the WASP and VALORAGUA models. The hydropower operations studies were performed for the whole Zambezi river basin, including the full installation of the Kariba power station, and the Cahora Bassa hydro power station in Mozambique. The analysis also included possible future projects such as Itezhi-Tezhi, Kafue Gorge Lower, and Batoka Gorge power stations. As hydropower operations studies served to determine the operational characteristics of the existing and future hydro power plants, it was necessary to simulate the whole Zambezi river basin in order to take into account all interactions and mutual influences between the hydro power plants. In addition, it allowed for the optimization of reservoir

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…

Estimated long-term outdoor air pollution concentrations in a cohort study

NASA Astrophysics Data System (ADS)

Beelen, Rob; Hoek, Gerard; Fischer, Paul; Brandt, Piet A. van den; Brunekreef, Bert

Several recent studies associated long-term exposure to air pollution with increased mortality. An ongoing cohort study, the Netherlands Cohort Study on Diet and Cancer (NLCS), was used to study the association between long-term exposure to traffic-related air pollution and mortality. Following on a previous exposure assessment study in the NLCS, we improved the exposure assessment methods. Long-term exposure to nitrogen dioxide (NO 2), nitrogen oxide (NO), black smoke (BS), and sulphur dioxide (SO 2) was estimated. Exposure at each home address ( N=21 868) was considered as a function of a regional, an urban and a local component. The regional component was estimated using inverse distance weighed interpolation of measurement data from regional background sites in a national monitoring network. Regression models with urban concentrations as dependent variables, and number of inhabitants in different buffers and land use variables, derived with a Geographic Information System (GIS), as predictor variables were used to estimate the urban component. The local component was assessed using a GIS and a digital road network with linked traffic intensities. Traffic intensity on the nearest road and on the nearest major road, and the sum of traffic intensity in a buffer of 100 m around each home address were assessed. Further, a quantitative estimate of the local component was estimated. The regression models to estimate the urban component explained 67%, 46%, 49% and 35% of the variances of NO 2, NO, BS, and SO 2 concentrations, respectively. Overall regression models which incorporated the regional, urban and local component explained 84%, 44%, 59% and 56% of the variability in concentrations for NO 2, NO, BS and SO 2, respectively. We were able to develop an exposure assessment model using GIS methods and traffic intensities that explained a large part of the variations in outdoor air pollution concentrations.

Long-Term Dynamics of Autonomous Fractional Differential Equations

NASA Astrophysics Data System (ADS)

Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

Quantitative study of long-term solar and climatic changes

NASA Technical Reports Server (NTRS)

Eddy, J. A.

1982-01-01

Long term variations in the diameter and the shape of the Sun were studied. Daily observations of the Sun's diameter made at the Greenwich Observatory between 1836 and 1953 were analysed and interpreted. The data was converted into digital form and then screened and processed. It was found that the horizontal diameter of the Sun measured at Greenwich appears to have decreased systematically between 1880 and 1953 at a rate of 1.2 plus or minus 0.6 minutes of arc per century.

Study Abroad for Global Engagement: The Long-Term Impact of Mobility Experiences

ERIC Educational Resources Information Center

Paige, R. Michael; Fry, Gerald W.; Stallman, Elizabeth M.; Josic, Jasmina; Jon, Jae-Eun

2009-01-01

This paper reports on the preliminary results of a research project "'Beyond immediate impact: Study abroad for global engagement' (SAGE)" which examines the long-term impact of study abroad on various forms of global engagement. The study employs a retrospective tracer study and mixed methods research design. Survey results from 6391 study-abroad…

Long-term characteristics of nuclear emulsion

NASA Astrophysics Data System (ADS)

Naganawa, N.; Kuwabara, K.

2010-02-01

Long-term characteristics of the nuclear emulsion so called ``OPERA film'' used in the neutrino oscillation experiment, OPERA, has been studied for 8 years since its production or refreshing after it. In the results, it turned out to be excellent in sensitivity, amount of random noise, and refreshing characteristics. The retention capacity of latent image of tracks was also studied. The result will open the way to the recycling of 7,000,000 emulsion films which will remain not developed after 5 years of OPERA's run, and other long-term experiments with emulsion.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-06-01

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

Long-term e-cigarette use and smoking cessation: a longitudinal study with US population.

PubMed

Zhuang, Yue-Lin; Cummins, Sharon E; Sun, Jessica Y; Zhu, Shu-Hong

2016-10-01

E-cigarettes have grown popular. The most common pattern is dual use with conventional cigarettes. Dual use has raised concerns that it might delay quitting of cigarette smoking. This study examined the relationship between long-term use of e-cigarettes and smoking cessation in a 2-year period. A nationally representative sample of 2028 US smokers were surveyed in 2012 and 2014. Long-term e-cigarette use was defined as using e-cigarettes at baseline and follow-up. Use of e-cigarettes only at baseline or at follow-up was defined as short-term use. Non-users did not use e-cigarettes at either survey. Quit attempt rates and cessation rates (abstinent for 3 months or longer) were compared across the three groups. At 2-year follow-up, 43.7% of baseline dual users were still using e-cigarettes. Long-term e-cigarette users had a higher quit attempt rate than short-term or non-users (72.6% vs 53.8% and 45.5%, respectively), and a higher cessation rate (42.4% vs 14.2% and 15.6%, respectively). The difference in cessation rate between long-term users and non-users remained significant after adjusting for baseline variables, OR=4.1 (95% CI 1.5 to 11.4) as did the difference between long-term users and short-term users, OR=4.8 (95% CI 1.6 to 13.9). The difference in cessation rate between short-term users and non-users was not significant, OR=0.9 (95% CI 0.5 to 1.4). Among those making a quit attempt, use of e-cigarettes as a cessation aid surpassed that of FDA-approved pharmacotherapy. Short-term e-cigarette use was not associated with a lower rate of smoking cessation. Long-term use of e-cigarettes was associated with a higher rate of quitting smoking. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Impact of recipient body mass index on short-term and long-term survival of pancreatic grafts.

PubMed

Bédat, Benoît; Niclauss, Nadja; Jannot, Anne-Sophie; Andres, Axel; Toso, Christian; Morel, Philippe; Berney, Thierry

2015-01-01

The impact of recipient body mass index on graft and patient survival after pancreas transplantation is not well known. We have analyzed data from all pancreas transplant recipients reported in the Scientific Registry of Transplant Recipients between 1987 and 2011. Recipients were categorized into BMI classes, as defined by the World Health Organization. Short-term (90 days) and long-term (90 days to 5 years) patient and graft survivals were analyzed according to recipient BMI class using Kaplan-Meier estimates. Hazard ratios were estimated using Cox proportional hazard models. A total of 21,075 adult recipients were included in the analysis. Mean follow-up was 5 ± 1.1 years. Subjects were overweight or obese in 39%. Increasing recipient BMI was an independent predictor of pancreatic graft loss and patient death in the short term (P<0.001), especially for obese class II patient survival (hazard ratio, 2.07; P=0.009). In the long term, obesity, but not overweight, was associated with higher risk of graft failure (P=0.01). Underweight was associated with a higher risk of long-term death (P<0.001). These results question the safety of pancreas transplantation in obese patients and suggest that they may be directed to alternate therapies, such as behavioral modifications or bariatric surgery, before pancreas transplantation is considered.

Complex network structure influences processing in long-term and short-term memory.

PubMed

Vitevitch, Michael S; Chan, Kit Ying; Roodenrys, Steven

2012-07-01

Complex networks describe how entities in systems interact; the structure of such networks is argued to influence processing. One measure of network structure, clustering coefficient, C, measures the extent to which neighbors of a node are also neighbors of each other. Previous psycholinguistic experiments found that the C of phonological word-forms influenced retrieval from the mental lexicon (that portion of long-term memory dedicated to language) during the on-line recognition and production of spoken words. In the present study we examined how network structure influences other retrieval processes in long- and short-term memory. In a false-memory task-examining long-term memory-participants falsely recognized more words with low- than high-C. In a recognition memory task-examining veridical memories in long-term memory-participants correctly recognized more words with low- than high-C. However, participants in a serial recall task-examining redintegration in short-term memory-recalled lists comprised of high-C words more accurately than lists comprised of low-C words. These results demonstrate that network structure influences cognitive processes associated with several forms of memory including lexical, long-term, and short-term.

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

Zeitgeists and development trends in long-term care facility design.

PubMed

Wang, Chia-Hui; Kuo, Nai-Wen

2006-06-01

Through literature analysis, in-depth interviews, and the application of the Delphi survey, this study explored long-term care resident priorities with regard to long-term care facility design in terms of both physical and psychological needs. This study further clarified changing trends in long-term care concepts; illustrated the impact that such changes are having on long-term care facility design; and summarized zeitgeists related to the architectural design of long-term care facilities. Results of our Delphi survey indicated the following top five priorities in long-term care facility design: (1) creating a home-like feeling; (2) adhering to Universal Design concepts; (3) providing well-defined private sleeping areas; (4) providing adequate social space; and (5) decentralizing residents' rooms into clusters. The three major zeitgeists related to long-term care facility design include: (1) modern long-term care facilities should abandon their traditional "hospital" image and gradually reposition facilities into homelike settings; (2) institution-based care for the elderly should be de-institutionalized under the concept of aging-in-place; and (3) living clusters, rather than traditional hospital-like wards, should be designed into long-term care facilities.

Developmental Dyslexia and Explicit Long-Term Memory

ERIC Educational Resources Information Center

Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

2010-01-01

The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

Long-term urethral catheterisation.

PubMed

Turner, Bruce; Dickens, Nicola

This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

Standardizing flow cytometric assays in long-term population-based studies

NASA Astrophysics Data System (ADS)

Melzer, Susanne; Bocsi, Jozsef; Tárnok, Attila

2015-03-01

Quantification of leukocyte subpopulations and characterization of antigen-expression pattern on the cellular surface can play an important role in diagnostics. The state of cellular immunology on the single-cell level was analyzed by polychromatic flow cytometry in a recent comparative study within the average Leipzig population (LIFE - Leipzig Research Centre for Civilization Diseases). Data of 1699 subjects were recorded over a long-time period of three years (in a total of 1126 days). To ensure compatibility of such huge data sets, quality-controls on many levels (stability of instrumentation, low intra-laboratory variance and reader independent data analysis) are essential. The LIFE study aims to analyze various cytometric pattern to reveal the relationship between the life-style, the environmental effects and the individual health. We therefore present here a multi-step quality control procedure for long-term comparative studies.

Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy

PubMed Central

Waddington Cruz, Márcia; Amass, Leslie; Keohane, Denis; Schwartz, Jeffrey; Li, Huihua; Gundapaneni, Balarama

2016-01-01

Abstract Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and −7.8 (−44.3, 28.8) kg/m2 × g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis. Trial Registration: ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002. PMID:27494299

Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy.

PubMed

Waddington Cruz, Márcia; Amass, Leslie; Keohane, Denis; Schwartz, Jeffrey; Li, Huihua; Gundapaneni, Balarama

2016-09-01

Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and -7.8 (-44.3, 28.8) kg/m 2 × g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis. ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002.

Prevalence and incidence studies of pressure ulcers in two long-term care facilities in Canada.

PubMed

Davis, C M; Caseby, N G

2001-11-01

A study was initiated to determine the prevalence and incidence of pressure ulcers in two long-term care facilities in Canada, one with 95 residents and the other with 92 residents. The prevalence study was conducted at both facilities on a single day. The incidence study was completed after 41 and 42 days, respectively, at each facility. Data were collected on demographics, medical information, and possible contributing factors. Each resident was assessed for the presence of a pressure ulcer. Each ulcer was staged and anatomical location was noted. The prevalence of pressure ulcers in the two long-term care facilities was 36.8% and 53.2%, respectively. The incidence of pressure ulcers in the two long-term care facilities was 11.7% and 11.6%, respectively. In conclusion, the pressure ulcer prevalence is higher than published figures for the long-term care setting. However, a pressure ulcer incidence of less than 12% in each facility suggests an equal and acceptable level of nursing care in both facilities. The disparity of pressure ulcer prevalence between the two facilities may be explained by a difference of case mix.

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

NASA Astrophysics Data System (ADS)

Gosz, J.

2001-12-01

The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

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

PubMed

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

2015-08-06

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. © 2015 by The American Society of Hematology.

Long-term exposure to air pollution and cardiorespiratory disease in the California teachers study cohort.

PubMed

Lipsett, Michael J; Ostro, Bart D; Reynolds, Peggy; Goldberg, Debbie; Hertz, Andrew; Jerrett, Michael; Smith, Daniel F; Garcia, Cynthia; Chang, Ellen T; Bernstein, Leslie

2011-10-01

Several studies have linked long-term exposure to particulate air pollution with increased cardiopulmonary mortality; only two have also examined incident circulatory disease. To examine associations of individualized long-term exposures to particulate and gaseous air pollution with incident myocardial infarction and stroke, as well as all-cause and cause specific mortality. We estimated long-term residential air pollution exposure for more than 100,000 participants in the California Teachers Study, a prospective cohort of female public school professionals.We linked geocoded residential addresses with inverse distance-weighted monthly pollutant surfaces for two measures of particulate matter and for several gaseous pollutants. We examined associations between exposure to these pollutants and risks of incident myocardial infarction and stroke, and of all-cause and cause-specific mortality, using Cox proportional hazards models. We found elevated hazard ratios linking long-term exposure to particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), scaled to an increment of 10 μg/m3 with mortality from ischemic heart disease (IHD) (1.20; 95% confidence interval [CI], 1.02-1.41) and, particularly among postmenopausal women, incident stroke (1.19; 95% CI, 1.02-1.38). Long-term exposure to particulate matter less than 10 μm in aerodynamic diameter (PM10) was associated with elevated risks for IHD mortality (1.06; 95% CI, 0.99-1.14) and incident stroke (1.06; 95% CI, 1.00-1.13), while exposure to nitrogen oxides was associated with elevated risks for IHD and all cardiovascular mortality. This study provides evidence linking long-term exposure to PM2.5 and PM10 with increased risks of incident stroke as well as IHD mortality; exposure to nitrogen oxides was also related to death from cardiovascular diseases.

Long-term health benefits of physical activity – a systematic review of longitudinal studies

PubMed Central

2013-01-01

Background The treatment of noncommunicable diseases (NCD), like coronary heart disease or type 2 diabetes mellitus, causes rising costs for the health system. Physical activity is supposed to reduce the risk for these diseases. Results of cross-sectional studies showed that physical activity is associated with better health, and that physical activity could prevent the development of these diseases. The purpose of this review is to summarize existing evidence for the long-term (>5 years) relationship between physical activity and weight gain, obesity, coronary heart disease, type 2 diabetes mellitus, Alzheimer’s disease and dementia. Methods Fifteen longitudinal studies with at least 5-year follow up times and a total of 288,724 subjects (>500 participants in each study), aged between 18 and 85 years, were identified using digital databases. Only studies published in English, about healthy adults at baseline, intentional physical activity and the listed NCDs were included. Results The results of these studies show that physical activity appears to have a positive long-term influence on all selected diseases. Conclusions This review revealed a paucity of long-term studies on the relationship between physical activity and the incidence of NCD. PMID:24010994

Long-term care: long-term care insurance--2005. End of Year Issue Brief.

PubMed

Tanner, Rachel; Bercaw, Lawren

2005-12-31

As the "Baby Boom" generation approaches retirement, state and federal lawmakers are struggling to ensure that the nation's long-term care system will provide adequate services for the growing number of senior citizens. A 2003 Administration on Aging report predicted that the elderly population will double by 2030. Accordingly, policymakers must prepare for the impending squeeze on public health and Medicaid resources. Many consumers are exploring private long-term care insurance options as a means of preparing for the cost of eldercare. Yet, a lack of market uniformity has rendered the long-term care insurance industry somewhat difficult for consumers to decipher. In addition, senior care insurance is often costly, particularly for those over age 50.

Long-term medical outcomes among Aboriginal living kidney donors.

PubMed

Storsley, Leroy J; Young, Ann; Rush, David N; Nickerson, Peter W; Ho, Julie; Suon, Vuthana; Karpinski, Martin

2010-08-27

It is unknown whether favorable long-term data on the safety of living kidney donation can be extrapolated to populations at higher risk of chronic kidney disease. Indigenous people (i.e., Aboriginals) have a high prevalence of risk factors for chronic kidney disease and Aboriginal living donor outcomes need to be defined. We performed a retrospective cohort study of all 38 Aboriginal donors donating at our center since 1970 and 76 randomly selected white donor controls to determine the long-term rates of hypertension, diabetes, and renal function postdonation. Follow-up was obtained for 91% of both Aboriginal and white donors (mean follow-up approximately 14 years). Hypertension has been diagnosed more frequently among Aboriginal donors (Ab 42% vs. white 19%, P=0.02). Notably, all 11 Aboriginal donors more than 20 years postdonation have developed hypertension. Diabetes has also been diagnosed more frequently among Aboriginal donors (Ab 19% vs. white 2%, P=0.005), including 5 of 11 (45%) more than 20 years postdonation. Follow-up estimated glomerular filtration rate was higher in Aboriginal donors (Ab 77+/-17 vs. white 67+/-13 mL/min/1.73 m, P=0.002) but not significantly different in adjusted analyses. One Aboriginal donor developed end-stage renal disease 14 years postdonation. Aboriginal living kidney donors at our center have high rates of hypertension and diabetes on long-term follow-up, although renal function is preserved to date. This profile is similar to that of the general unselected Aboriginal population despite detailed medical evaluation before donation. These findings have important implications for donor counseling and may have implications for other high-risk donor populations.

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

PubMed Central

Yanovski, Susan Z.; Yanovski, Jack A.

2014-01-01

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

DETERMINING THE PHARMACOKINETICS AND LONG-TERM BIODISTRIBUTION OF SiO2 NANOPARTICLES IN VIVO USING ACCELERATOR MASS SPECTROMETRY

PubMed Central

Malfatti, Michael A.; Palko, Heather A.; Kuhn, Edward A.; Turteltaub, Kenneth W.

2012-01-01

Biodistribution is an important factor in better understanding silica dioxide nanoparticle (SiNP) safety. Currently, comprehensive studies on biodistribution are lacking, most likely due to the lack of suitable analytical methods. Accelerator mass spectrometry (AMS) was used to investigate the relationship between administered dose, PK, and long-term biodistribution of 14C-SiNPs in vivo. PK analysis showed that SiNPs were rapidly cleared from the central compartment, were distributed to tissues of the reticuloendothelial system, and persisted in the tissue over the 8-week time course, raising questions about the potential for bioaccumulation and associated long-term effects. PMID:23075393

Red blood cell storage duration and long-term mortality in patients undergoing cardiac intervention: a Danish register study.

PubMed

Dencker, D; Pedersen, F; Engstrøm, T; Schroeder, T V; Lönn, L; Johansson, P I; De Backer, O

2017-08-01

To study the effect of red blood cell (RBC) storage duration on long-term mortality in patients undergoing cardiac intervention. RBCs undergo numerous structural and functional changes during storage. Observational studies have assessed the association between RBC storage duration and patient outcomes with conflicting results. Between January 2006 and December 2014, 82 408 patients underwent coronary angiography. Of these, 1856 patients received one to four RBC units within 30 days after this procedure. Patients were allocated according to length of RBC storage duration: short-term (≤11 days), intermediate (IM)-term (12-23 days) and long-term (≥24 days). The study endpoints were 30-day and long-term all-cause mortality. A total of 4168 RBC units were given to 1856 patients. The mean RBC storage duration was 8.5 ± 2.1, 17.7 ± 3.4 and 29.9 ± 3.4 days in the short-term, IM-term and long-term storage groups, respectively. There was no difference in baseline characteristics between the groups. The long-term storage group received significantly more units (2.4 ± 1.0 units) as compared to the short-term (2.0 ± 1.0 units; P < 0.001) and IM-term storage group (2.2 ± 1.0 units; P < 0.01). In the survival analysis, there was no significant difference in all-cause mortality between the groups (log-rank: 0.509 for 30-days mortality; 0.493 for 5-year mortality). Additional stratified analysis demonstrated no association between RBC storage duration and long-term mortality. This study did not find an association between RBC storage duration and 30-days or long-term mortality in patients undergoing cardiac intervention. © 2017 British Blood Transfusion Society.

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

PubMed

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

2016-06-01

To examine long-term organ damage and safety following treatment with belimumab plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). 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. 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. Patients with SLE treated with long-term belimumab plus SoC had a low incidence

Long-Term Monitoring of Global Climate Forcings and Feedbacks

NASA Technical Reports Server (NTRS)

Hansen, J. (Editor); Rossow, W. (Editor); Fung, I. (Editor)

1993-01-01

A workshop on Long-Term Monitoring of Global Climate Forcings and Feedbacks was held February 3-4, 1992, at NASA's Goddard Institute for Space Studies to discuss the measurements required to interpret long-term global temperature changes, to critique the proposed contributions of a series of small satellites (Climsat), and to identify needed complementary monitoring. The workshop concluded that long-term (several decades) of continuous monitoring of the major climate forcings and feedbacks is essential for understanding long-term climate change.

Asthma Medicines: Long-Term Control

MedlinePlus

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

Benefits and Safety of Long-Term Fenofibrate Therapy in People With Type 2 Diabetes and Renal Impairment

PubMed Central

Ting, Ru-Dee; Keech, Anthony C.; Drury, Paul L.; Donoghoe, Mark W.; Hedley, John; Jenkins, Alicia J.; Davis, Timothy M.E.; Lehto, Seppo; Celermajer, David; Simes, R. John; Rajamani, Kushwin; Stanton, Kim

2012-01-01

OBJECTIVE Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2) are at particular cardiovascular risk. Fenofibrate’s safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate’s effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m2 were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m2). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. RESULTS Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m2: 0.68 [0.47–0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m2: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. CONCLUSIONS Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate

Stiripentol efficacy and safety in Dravet syndrome: a 12-year observational study.

PubMed

Myers, Kenneth A; Lightfoot, Paul; Patil, Shekhar G; Cross, J Helen; Scheffer, Ingrid E

2018-06-01

To assess long-term safety and efficacy of stiripentol as an antiepileptic medication for people with Dravet syndrome. A prospective, observational open-label study (2003-2015) of the efficacy and long-term safety of stiripentol in patients with Dravet syndrome and ongoing seizures. Frequency of generalized tonic-clonic seizures, focal seizures, status epilepticus, and adverse events were recorded. Forty-one patients started stiripentol, with median age at enrolment 5 years 7 months (range 11mo-22y) and median duration of treatment 37 months (range 2-141mo). Twenty out of 41 patients had greater than or equal to 50% long-term reduction in frequency of generalized tonic-clonic seizures. Frequency of focal seizures was decreased by greater than or equal to 50% in 11 out of 23 patients over the long-term. Frequency of status epilepticus was decreased by 50% or more in 11 out of 26 patients. The most common adverse events were anorexia, weight loss, sedation, and behavioural changes. One patient had worsening of absence and myoclonic seizures. Another developed recurrent pancreatitis on concurrent valproate. Stiripentol improves long-term seizure frequency in approximately 50% of patients with Dravet syndrome, when used as part of unrestricted polytherapy. Long-term use appears safe. In more than 40% of patients, episodes of status epilepticus markedly decrease after stiripentol initiation. What this paper adds Frequency of status epilepticus is reduced in 40% of patients with Dravet syndrome after stiripentol initiation. Stiripentol is effective for generalized tonic-clonic and focal seizures. Stiripentol can be safely used with a range of antiepileptic drugs. © 2018 Mac Keith Press.

Long-term dizziness handicap in patients with vestibular schwannoma: a multicenter cross-sectional study.

PubMed

Carlson, Matthew L; Tveiten, Øystein Vesterli; Driscoll, Colin L; Neff, Brian A; Shepard, Neil T; Eggers, Scott D; Staab, Jeffrey P; Tombers, Nicole M; Goplen, Frederik K; Lund-Johansen, Morten; Link, Michael J

2014-12-01

(1) To characterize long-term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium-sized vestibular schwannoma (VS) using a validated self-assessment inventory; and (2) to identify clinical variables associated with long-term dizziness handicap. Cross-sectional observational study. Two independent tertiary academic referral centers: one located in the United States and one in Norway. All patients with sporadic VS of less than 3 cm who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via a postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. The overall survey response rate was 79%. A total of 538 respondents (mean age, 64 years; 56% female) were analyzed, and the mean time interval between treatment and survey was 7.7 years. Pretreatment variables associated with greater dizziness handicap included female sex, older age, larger tumor size, preexisting diagnosis of headache or migraine, and symptoms of dizziness predating treatment. Significant posttreatment features strongly associated with poor long-term DHI scores included frequency and severity of ongoing headache. On multivariable analysis, treatment modality did not influence long-term dizziness handicap. At a mean of approximately 8 years following treatment, over half of patients with VS reported ongoing dizziness. The authors have identified several baseline features that may help predict the risk of lasting dizziness. Treatment modality does not appear to influence long-term DHI score. We found a strong association between posttreatment headache and poor dizziness handicap. Future study is needed to further define this relationship. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Integration of devices into long-term condition management: a synthesis of qualitative studies.

PubMed

Gately, Claire; Rogers, Anne; Kirk, Susan; McNally, Rosalind

2008-06-01

Understanding peoples' responses to and ability to incorporate technology for managing long-term conditions into their everyday lives is relevant for informing the development and implementation of new technologies as part of future long-term condition management in domestic environments. Future research and theory building can be facilitated by the synthesis of existing qualitative studies. A systematic search for qualitative studies of health technologies at home was undertaken on OVID CINAHL, OVID Medline and CSA databases for the period 1996-2006. Studies (n = 12) that met the inclusion criteria were synthesized and their analyses subjected to qualitative meta-synthesis. Analyses clustered into five themes: (1) managing multiple uncertainties; (2) the reconstruction of identity; (3) the struggle to remain autonomous while allowing dependence; (4) coming to terms with living a technology-assisted life; and (5) the usability of devices. These translated into a line of argument synthesis in which technology takes on the status of a personified ;other' around which a set of personal and relational attributions are subsequently constructed. These allow the extension of existing illness work to incorporate new technologies. Ambivalence about the value of technologies that are designed to assist with the management of a long-term condition reflects experiences of the disruptive effects of health technologies on personal identities and strategies of managing illness. At the same time, they are highly valued because they provided new opportunities to complete aspects of illness work that were previously impossible.

Initiating Long-Term Soil Productivity Research in Missouri

Treesearch

Felix Ponder

1997-01-01

Management practices necessary for sustaining long-term soil productivity (LTSP) afforest lands are being defined from a network of coordinated, long-term experiments established in vartous ecosystems across the United States and British Columbia according to the same basic study plan. The study was established in the Ozark Region of southeastem Missouri in Shannon...

Efficacy and safety of long-term losartan therapy demonstrated by a prospective observational study in Japanese patients with hypertension: The Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study.

PubMed

Naritomi, Hiroaki; Fujita, Toshiro; Ito, Sadayoshi; Ogihara, Toshio; Shimada, Kazuyuki; Shimamoto, Kazuaki; Tanaka, Heizo; Yoshiike, Nobuo

2008-02-01

The Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study is a nationwide, prospective, multicentered, observational study that was designed to enroll 30,000 hypertensive Japanese patients from more than 3,000 private practitioners. It is the first large-scale observational study to assess the efficacy and safety of losartan, an angiotensin II receptor antagonist, in Japan. Patients were enrolled between June 2000 and May 2002, and followed up to June 2005. The data from 29,850 patients were used for the analysis of safety and efficacy. These patients were treated with losartan mostly at a daily dose of 25-50 mg. The mean follow-up period was 2.9 years. The patients were aged 62.4+/-12.1 years (mean+/-SD) and their mean systolic/diastolic blood pressure was 165.3+/-17.2/94.3+/-11.7 mmHg (mean+/-SD). Mean blood pressure in patients who were evaluated for efficacy decreased from 165.8/94.8 mmHg (n=26,512) at baseline to 145.5/84.4 mmHg after 3 months (n=21,269) and 138.6/80.0 mmHg after 36 months of treatment (n=13,879). Blood pressure was well controlled during the study period by losartan alone or losartan-based combination therapy. In nearly half of the patients, blood pressure was reduced to less than 140/90 mmHg during the study period. In addition to its antihypertensive effect, losartan reduced the uric acid level in patients whose baseline uric acid level was > or =7 mg/dL. Losartan also prevented acceleration of proteinuria. Adverse drug reactions occurred in 1,081 of the 29,850 patients. Long-term losartan therapy was effective and well tolerated in Japanese clinical practice.

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

The interaction of short-term and long-term memory in phonetic category formation

NASA Astrophysics Data System (ADS)

Harnsberger, James D.

2002-05-01

This study examined the role that short-term memory capacity plays in the relationship between novel stimuli (e.g., non-native speech sounds, native nonsense words) and phonetic categories in long-term memory. Thirty native speakers of American English were administered five tests: categorial AXB discrimination using nasal consonants from Malayalam; categorial identification, also using Malayalam nasals, which measured the influence of phonetic categories in long-term memory; digit span; nonword span, a short-term memory measure mediated by phonetic categories in long-term memory; and paired-associate word learning (word-word and word-nonword pairs). The results showed that almost all measures were significantly correlated with one another. The strongest predictor for the discrimination and word-nonword learning results was nonword (r=+0.62) and digit span (r=+0.51), respectively. When the identification test results were partialed out, only nonword span significantly correlated with discrimination. The results show a strong influence of short-term memory capacity on the encoding of phonetic detail within phonetic categories and suggest that long-term memory representations regulate the capacity of short-term memory to preserve information for subsequent encoding. The results of this study will also be discussed with regards to resolving the tension between episodic and abstract models of phonetic category structure.

Factors Affecting Long-Term Abstinence from Substances Use

ERIC Educational Resources Information Center

Elsheikh, Salah Elgaily

2008-01-01

Objective: The purpose of this study is to explore the attitudes of abstainers from drug use that relate to the factors leading to long-term abstinence. Materials and Methods: Cross-sectional study was carried out in Al-Amal Hospital to examine, which attitudes of abstainers related to long-term abstinence. A random survey was conducted on 62…

Retention of gene expression in porcine islets after agarose encapsulation and long-term culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumpala, Pradeep R., E-mail: pdumpala@rixd.org; Holdcraft, Robert W.; Martis, Prithy C.

Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expressionmore » profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. - Highlights: • Effect of agarose encapsulation and 8 week culture on porcine islets was analyzed. • Transcriptome analysis revealed no significant change in a majority (98%) of genes. • Agarose encapsulation allows for long-term culture of porcine islets. • Islet culture allows for functional and microbial testing prior to clinical use.« less

Long-term outcomes of children undergoing video-assisted gastrostomy.

PubMed

Salö, Martin; Santimano, Ana; Helmroth, Sofia; Stenström, Pernilla; Arnbjornsson, Einar Ólafur

2017-01-01

The aims of this study were to assess the short- and long-term complication rates after video-assisted gastrostomy (VAG), the effects of age and gender on long-term complications and the effect of duration of gastrostomy tube retention on the need for gastroraphy when the gastrostomy device was removed. This was a retrospective study of children undergoing VAG at a single institution. Children who died or moved from the area were excluded. The rates of short- and long-term complications developing at 3-6 months or 2 or more years, respectively, were compared. A total of 170 children were studied, out of a cohort of 303 children. The median age at surgery was 2 years. The median duration of postoperative long-term follow-up was 5 years (2-9 years). The complications at the respective short and long-term follow-ups were as follows: granulation tissue, leakage, infection and vomiting. There were no differences in the short- versus long-term complication rates for gender and age. Children needing gastroraphy had used a gastrostomy device significantly longer compared with children with spontaneous closure. Complications after VAG decrease over time. A longer duration of gastrostomy device retention leads to increased need for gastroraphy.

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

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

PubMed

Iqbal, Nayyar; Allen, Elsie; Öhman, Peter

2014-01-01

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. 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). 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) with placebo. Older patients

Long-term bird study records Arctic climate change

NASA Astrophysics Data System (ADS)

Zielinski, Sarah

Alaska's summer of 2005 was the second warmest on record there, with a record retreat of arctic pack ice. As Alaskan temperatures gradually increase, artic birds, such as the black guillemots of Cooper Island, near Barrow, Alaska, are experiencing drastic habitat changes. Though these small black and white birds—the subjects of a long-term study of climate change—fared better this year than they have in the recent past (due to local cool conditions), they are nonetheless struggling to adapt as their artic island summer home becomes subarctic.George Divokyan ornithologist at the Institute of Arctic Biology, University of Alaska Fairbanks, discovered the Cooper Island colony of guillemots in the early 1970s and has spent every summer since 1975 there studying these birds. He presented his latest research during a 3 November talk in Washington, D.C.

VALIDATION OF A METHOD FOR ESTIMATING LONG-TERM EXPOSURES BASED ON SHORT-TERM MEASUREMENTS

EPA Science Inventory

A method for estimating long-term exposures from short-term measurements is validated using data from a recent EPA study of exposure to fine particles. The method was developed a decade ago but long-term exposure data to validate it did not exist until recently. In this paper, ...

Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study.

PubMed

Oertel, Wolfgang; Trenkwalder, Claudia; Beneš, Heike; Ferini-Strambi, Luigi; Högl, Birgit; Poewe, Werner; Stiasny-Kolster, Karin; Fichtner, Andreas; Schollmayer, Erwin; Kohnen, Ralf; García-Borreguero, Diego

2011-08-01

Safety and efficacy of non-ergot dopamine agonists for the treatment of idiopathic restless legs syndrome have been shown in short-term trials. We did a prospective open-label extension of a 6-week, double-blind randomised trial to assess the safety, tolerability, and efficacy of rotigotine transdermal patch for up to 5 years in patients with restless legs syndrome. Patients (aged 18-75 years) with moderate-to-severe idiopathic restless legs syndrome were treated with once-daily rotigotine transdermal patch in 33 centres in Austria, Germany, and Spain between July 31, 2003, and April 15, 2009. The dose was titrated in weekly increments (up to 4 weeks) from 0·5 mg/24 h to a maximum of 4 mg/24 h, and was followed by up to 5 years of maintenance at the optimum dose. Primary safety outcomes included occurrence of adverse events and dropouts. Efficacy assessments were secondary and included the International Restless Legs Syndrome study group severity rating scale (IRLS). Augmentation of symptoms was assessed by means of standard diagnostic criteria and was confirmed by an international expert panel. All patients who received at least one dose of study drug were included in assessments. This study is registered with ClinicalTrials.gov, number NCT00498186. 295 patients entered the open-label study, of whom 126 (43%) completed 5 years of follow-up. 169 (57%) patients discontinued treatment, 89 (30%) because of adverse events and 31 (11%) because of lack of efficacy. 70 patients (24%) discontinued during year 1 of maintenance. The most common adverse events were application site reactions, which occurred in 37% (106/290) of patients in year 1, 17% (38/220) of patients in year 2, 14% (27/191) of patients in year 3, and in less than 6% of patients during year 4 (8/159) and year 5 (8/147). 56 patients (19%) discontinued because of application site reactions. Mean rotigotine dose was 2·43 mg/24 h (SD 1·21) after initial titration and 3·09 mg/24 h (1·07) at the end of

Reforming long-term care financing through insurance

PubMed Central

Meiners, Mark R.

1988-01-01

Until recently, insurance for long-term care was not viewed as feasible. This perception has changed dramatically in the past few years. Several models of long-term care insurance have begun to be tested. Although the application of insurance principles to long-term care is still new, the emergence of private market interest in developing long-term care insurance has been a catalyst to renewed public-policy support for reforming the way we pay for long-term care. States, in particular, have become interested in developing public-private partnerships to support the emergence of long-term care insurance that could help relieve the mounting pressure on Medicaid budgets. PMID:10312962

Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies

PubMed Central

Fleischmann, Roy; Wollenhaupt, Jürgen; Takiya, Liza; Maniccia, Anna; Kwok, Kenneth; Wang, Lisy; van Vollenhoven, Ronald F

2017-01-01

Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who switched from monotherapy to combination therapy (mono→combo) or vice versa (combo→mono) in long-term extension (LTE) studies. Methods Data were pooled from open-label LTE studies (ORAL Sequel (NCT00413699; ongoing; data collected 14 January 2016) and NCT00661661) involving patients who participated in qualifying index studies. Efficacy outcomes included American College of Rheumatology 20/50/70 rates, change from baseline in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index and DAS28-4(ESR) and CDAI low disease activity and remission. Safety was evaluated over 96 months. Results Of the 4967 patients treated, 35.4% initiated tofacitinib monotherapy, 64.6% initiated combination therapy, 2.6% were mono→combo switchers and 7.1% were combo→mono switchers. Patients who switched multiple times were excluded. Of those who initiated monotherapy and combination therapy, 87.8% (1543/1757) and 82.0% (2631/3210), respectively, remained on the same regimen throughout the study; efficacy was maintained. Incidence rates (IRs) for serious adverse events with tofacitinib 5 mg and 10 mg twice daily, respectively, were 9.42 and 8.41 with monotherapy and 8.36 and 10.75 with combination therapy; IRs for discontinuations due to AEs were 7.13 and 6.06 with monotherapy and 7.82 and 8.06 with combination therapy (overlapping CIs). For mono→combo and combo→mono switchers, discontinuations due to AEs were experienced by 0.8% and 0.9%, respectively, within 30 days of switching. Conclusion Tofacitinib efficacy as monotherapy or combination therapy was maintained through month 48 and sustained to month 72, with minimal switching of treatment

Sleep Quality, Short-Term and Long-Term CPAP Adherence

PubMed Central

Somiah, Manya; Taxin, Zachary; Keating, Joseph; Mooney, Anne M.; Norman, Robert G.; Rapoport, David M.; Ayappa, Indu

2012-01-01

Study Objectives: Adherence to CPAP therapy is low in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). The purpose of the present study was to evaluate the utility of measures of sleep architecture and sleep continuity on the CPAP titration study as predictors of both short- and long-term CPAP adherence. Methods: 93 patients with OSAHS (RDI 42.8 ± 34.3/h) underwent in-laboratory diagnostic polysomnography, CPAP titration, and follow-up polysomnography (NPSG) on CPAP. Adherence to CPAP was objectively monitored. Short-term (ST) CPAP adherence was averaged over 14 days immediately following the titration study. Long-term (LT) CPAP adherence was obtained in 56/93 patients after approximately 2 months of CPAP use. Patients were grouped into CPAP adherence groups for ST (< 2 h, 2-4 h, and > 4 h) and LT adherence (< 4 h, > 4 h). Sleep architecture, sleep disordered breathing (SDB) indices, and daytime outcome variables from the diagnostic and titration NPSGs were compared between CPAP adherence groups. Results: There was a significant relationship between ST and LT CPAP adherence (r = 0.81, p < 0.001). Neither ST nor LT adherence were related to demographic variables, baseline severity of untreated SDB, sleep architecture, or measures of daytime impairment. Good CPAP adherence groups had significantly lower %N2 and greater %REM on the titration NPSG. A model combining change in sleep efficiency and change in sleep continuity between the diagnostic and titration NPSGs predicted 17% of the variance in LT adherence (p = 0.006). Conclusions: These findings demonstrate that characteristics of sleep architecture, even on the titration NPSG, may predict some of the variance in CPAP adherence. Better sleep quality on the titration night was related to better CPAP adherence, suggesting that interventions to improve sleep on/prior to the CPAP titration study might be used as a therapeutic intervention to improve CPAP adherence. Citation: Somiah M; Taxin Z; Keating

Long-Term Experience with First-Generation Implantable Neurostimulation Device in Central Sleep Apnea Treatment.

PubMed

Fox, Henrik; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf; Gutleben, Klaus-Jürgen

2017-05-01

Sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) are associated with shorter survival in patients with heart failure. A novel treatment method for this patient group is unilateral phrenic nerve stimulation by the remedē® system (Respicardia Inc., Minnetonka, MN, USA), a transvenously implantable neurostimulation device, which has recently been studied in a large randomized, controlled trial. Previous literature has shown efficacy and safety of the treatment with this first-generation device, but hardly any data are available on long-term clinical parameters, the remedē® device's battery lifetime, device exchangeability, lead position stability, surgical accessibility, and manageability. We performed remedē® device replacements in consecutive patients for battery depletion, and documented clinical parameters, longevity, operation procedure, complications, and difficulties. All patients were on neurostimulation treatment by phrenic nerve neurostimulation when device replacement became necessary. Apnea-hypopnea index (from 45 ± 4/h to 9 ± 4/h), oxygen-desaturation index (from 35 ± 7/h to 7 ± 6/h), and time spent with oxygen saturation of <90% (T < 90% from 5 ± 7% to 0 ± 0%) were improved and improvements remained constant throughout the 4-year follow-up. Mean battery life was 4.2 ± 0.2 years and mean replacement procedure time was 25 ± 5.1 minutes. Apart from conventional X-ray documentation of stable lead positions in a long-term setting, no radiation or contrast dye usage was needed and no major complications occurred. In addition, clinical exercise capacity and sleepiness symptoms improved. Novel remedē® device shows sustained therapy efficacy and safety in terms of stable lead positions over 4 years. Long-term phrenic nerve neurostimulation therapy for central SDB/CSR appears feasible in a clinical routine setting. © 2017 Wiley Periodicals, Inc.

The safety of Lipistart, a medium-chain triglyceride based formula, in the dietary treatment of long-chain fatty acid disorders: a phase I study.

PubMed

MacDonald, Anita; Webster, Rachel; Whitlock, Matthew; Gerrard, Adam; Daly, Anne; Preece, Mary Anne; Evans, Sharon; Ashmore, Catherine; Chakrapani, Anupam; Vijay, Suresh; Santra, Saikat

2018-03-28

Children with long-chain fatty acid β-oxidation disorders (LCFAOD) presenting with clinical symptoms are treated with a specialist infant formula, with medium chain triglyceride (MCT) mainly replacing long chain triglyceride (LCT). It is essential that the safety and efficacy of any new specialist formula designed for LCFAOD be tested in infants and children. In an open-label, 21-day, phase I trial, we studied the safety of a new MCT-based formula (feed 1) in six well-controlled children (three male), aged 7-13 years (median 9 years) with LCFAOD (very long chain acyl CoA dehydrogenase deficiency [VLCADD], n=2; long chain 3-hydroxyacyl CoA dehydrogenase deficiency [LCHADD], n=2; carnitine acyl carnitine translocase deficiency [CACTD], n=2). Feed 1 (Lipistart; Vitaflo) contained 30% energy from MCT, 7.5% LCT and 3% linoleic acid and it was compared with a conventional MCT feed (Monogen; Nutricia) (feed 2) containing 17% energy from MCT, 3% LCT and 1.1% linoleic acid. Subjects consumed feed 2 for 7 days then feed 1 for 7 days and finally resumed feed 2 for 7 days. Vital signs, blood biochemistry, ECG, weight, height, food/feed intake and symptoms were monitored. Five subjects completed the study. Their median daily volume of both feeds was 720 mL (range 500-1900 mL/day). Feed 1 was associated with minimal changes in tolerance, free fatty acids (FFA), acylcarnitines, 3-hydroxybutyrate (3-HB), creatine kinase (CK), blood glucose, liver enzymes and no change in an electrocardiogram (ECG). No child complained of muscle pain or symptoms associated with LCFAOD on either feed. This is the first safety trial reported of an MCT formula specifically designed for infants and children with LCFAOD. In this short-term study, it appeared safe and well tolerated in this challenging group.

The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

ERIC Educational Resources Information Center

Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

2012-01-01

Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

Long-term nitrogen regulation of forest carbon sequestration

NASA Astrophysics Data System (ADS)

Yang, Y.; Luo, Y.

2009-12-01

It is well established that nitrogen (N) limits plant production but unclear how N regulates long-term terrestrial carbon (C) sequestration in response to rising atmospheric C dioxide (CO2)(Luo et al., 2004). Most experimental evidence on C-N interactions is primarily derived from short-term CO2 manipulative studies (e.g. Oren et al., 2001; Reich et al., 2006a), which abruptly increase C inputs into ecosystems and N demand from soil while atmospheric CO2 concentration in the real world is gradually increasing over time (Luo & Reynolds, 1999). It is essential to examine long-term N regulations of C sequestration in natural ecosystems. Here we present results of a synthesis of more than 100 studies on long-term C-N interactions during secondary succession. C significantly accumulates in plant, litter and forest floor in most studies, and in mineral soil in one-third studies during stand development. Substantial increases in C stock are tightly coupled with N accretion. The C: N ratio in plant increases with stand age in most cases, but remains relatively constant in litter, forest floor and mineral soil. Our results suggest that natural ecosystems could have the intrinsic capacity to maintain long-term C sequestration through external N accrual, high N use efficiency, and efficient internal N cycling.

Management training in long-term care.

PubMed

Evashwick, Connie

2002-01-01

The education of health care administrators faces its most dramatic change since the inception of the field. Recent discussions at the national level call for major overhaul of curricula and teaching modalities, including moving education to position students for evidence-based practice. This paper presents recommendations for incorporating training about chronic and long-term care into health care management curricula. It asserts that all health care management students should have a basic knowledge of the fundamental policy, operating, and financing principles of long-term care. The majority of people using the health care delivery system today, and increasingly in the future, suffer from chronic conditions. Long-term care services, although less expansive in structure, far outnumber acute care services and health plans. They will grow in the future to meet the portending demand. To maximize job opportunities and to optimize performance in any job, health care administrators need to know about the long-term care delivery system. This paper delineates critical topics pertaining to long-term care, organized according to 11 fundamental management areas in which the field is developing core competencies. The contents were derived from a year-long process of asking stakeholders in the various facets of long-term care what topics they thought were essential for administrators to know. The topics delineated in this document represent the consensus about essential knowledge that all health care administrators should have about long-term care, whether specializing in long-term care or following a more general management career. The education of health care administrators faces its most dramatic change since the inception ofthe field. Recent discussions at the national level call for major overhaul of curricula and teaching modalities, including moving education to position students to perform according to evidence-based practice. It is thus timely to consider content, as

Surgical Treatment of Nonlesional Neocortical Epilepsy: Long-term Longitudinal Study.

PubMed

Kim, Dong Wook; Lee, Sang Kun; Moon, Hye-Jin; Jung, Ki-Young; Chu, Kon; Chung, Chun-Ki

2017-03-01

The proportion of surgery for nonlesional neocortical epilepsy has recently increased, with a decrease in surgery for mesial temporal lobe epilepsy. However, there are only a few studies regarding the long-term surgical outcome and the potential prognostic factors for patients with nonlesional neocortical epilepsy. To evaluate the long-term surgical outcome and to identify possible prognostic factors in patients with nonlesional neocortical epilepsy. In a surgical cohort from September 1995 to December 2005 at the Seoul National University Hospital, we included 109 consecutive patients without lesions identifiable by magnetic resonance imaging who underwent focal surgical resection for drug-resistant neocortical epilepsy. Follow-up information for at least 10 years was available for all but 1 patient. Univariate and standard multiple logistic regression analyses were performed to identify the predictors of surgical outcomes, and a generalized estimation equation model was used for the longitudinal multiple logistic regression analysis of up to 21 years of follow-up. The patients consisted of 64 men and 45 women with ages at surgery ranging from 7 to 56 years (mean [SD], 27.1 [7.8] years). At 1 year after surgery, 59 of 109 patients (54.1%) achieved seizure freedom, and 64 of 108 patients (59.3%) achieved seizure freedom at the last follow-up. Only 11 of 108 patients (10.2%) experienced definite changes in postoperative seizure status. Localizing patterns in functional neuroimaging (strongest odds ratio [OR], 0.30 [95% CI, 0.14-0.66] for fluorodeoxyglucose-positron emission tomography; 0.37 [95% CI, 0.15-0.87] for ictal single-photon emission computed tomography), concordant results in presurgical diagnostic evaluations (OR, 3.15 [95% CI, 1.42-7.02]), the presence of aura (OR, 3.49 [95% CI, 1.54-7.92]), and complete resection of areas of ictal onset with frequent interictal spikes during the intracranial electroencephalographic study (OR, 0.37 [95% CI, 0

Predicting long-term absenteeism from work in construction industry: a longitudinal study.

PubMed

Hoonakker, Peter; van Duivenbooden, Cor

2012-01-01

In this study we examine whether the Work Ability Index (WAI) has additional value in predicting long-term absenteeism in construction industry. Results of the study show that the WAI has additional value in predicting absenteeism, but that the amount of explained variance is low. This is partly due to the definition of absenteeism in The Netherlands, where this study took place.

Long-term treatment of epilepsy with everolimus in tuberous sclerosis

PubMed Central

Wilfong, Angus A.; Mays, Maxwell; Talley, Christina M.; Agricola, Karen; Tudor, Cindy; Capal, Jamie; Holland-Bouley, Katherine; Franz, David Neal

2016-01-01

Objective: To evaluate the long-term benefit and safety of everolimus for the treatment of medically refractory epilepsy in patients with tuberous sclerosis complex (TSC). Methods: Everolimus was titrated over 4 weeks and continued an additional 8 weeks in a prospective, open-label, phase I/II clinical trial design. Participants demonstrating initial benefit continued treatment until study completion (48 months). The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency compared to baseline. Secondary endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, and quality of life. Results: Of the 20 participants who completed the initial study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants completed the study, all but 1 of whom reported ≥50% reduction in seizure frequency at 48 months. All participants reported at least 1 AE, the vast majority (94%) of which were graded mild or moderate severity. Improvements in behavior and quality of life were also observed, but failed to achieve statistical significance at 48 months. Conclusions: Improved seizure control was maintained for 4 years in the majority of patients with TSC with medically refractory epilepsy treated with everolimus. Long-term treatment with everolimus is safe and well-tolerated in this population. Everolimus may be a therapeutic option for refractory epilepsy in TSC. Classification of evidence: This study provides Class IV evidence that for patients with TSC with medically refractory epilepsy everolimus improves seizure control. PMID:27815402

A role for high frequency hydrochemical sampling in long term ecosystem studies

NASA Astrophysics Data System (ADS)

Sebestyen, S. D.; Shanley, J. B.; Boyer, E. W.; Kendall, C.

2007-12-01

Monitoring of surface waters for major chemical constituents is needed to assess long-term trends and responses to ecological disturbance. However, the typical fixed-interval (weekly, monthly, or quarterly) sampling schemes of most long-term ecosystem studies may not capture the full range of stream chemical variation and do not always provide enough information to discern the landscape processes that control surface water chemistry and solute loadings. To expand upon traditional hydrochemical monitoring, we collected high frequency event-based surface water samples at an upland, forested basin of the Sleepers River Research Watershed (Vermont, USA), one of five intensively studied sites in the Water, Energy, and Biogeochemical Budgets (WEBB) program of the US Geological Survey. We present several examples that highlight the importance of linking long-term weekly data with intensive, high frequency sampling. We used end-member mixing analysis and isotopic approaches to trace sources of stream nutrients (e.g. nitrate, dissolved organic carbon) and quantified how atmospheric pollutants (e.g. nitrogen, sulfate, and mercury) affect stream chemistry. High frequency sampling generates large numbers of samples and is both labor and resource intensive but yields insights into ecosystem functions that are not readily discerned from less-frequent sampling. As the ecological community contemplates the scope and foci of environmental observatories as benchmarks for deciphering the effects of natural and anthropogenic change, incorporating high frequency hydrochemical sampling will further our understanding of ecosystem functions across a range of ecosystem types and disturbance effects.

Xerostomia and medication: a cross-sectional study in long-term geriatric wards.

PubMed

Desoutter, A; Soudain-Pineau, M; Munsch, F; Mauprivez, C; Dufour, T; Coeuriot, J-L

2012-01-01

The purpose of this study was to determine the prevalence of xerostomia in old people living in long-term geriatric wards, and to measure the relationship between xerostomia and etiologic factors such as age and medication (total number of medications, xerogenic medications, anticholinergic medications and medications that induce hypersialorrhea). An observational retrospective, comparative, multicentre epidemiological study. Long-term geriatric wards, in Reims, France. 769 old people living in long-term geriatric wards. Prevalence of xerostomia assessed from age, total number of medications, xerogenic medications, anticholinergic medications and those that induce hypersialorrhea. Multivariable logistic regression was used to calculate Odds Ratios (OR) and their 95% Confidence Intervals (95% CI). Among 769 old people (average age 84.6±8.4 years old), 287 residents suffered from xerostomia (37.3%). Significant predictors of xerostomia were: resident's age OR=1.56, 95% CI (1.30-1.88), p<0.0001 and anticholinergic medications OR=1.35, 95% CI (1.05-1.73), p=0.02. The only protective factor against xerostomia identified was medications that induce hypersialorrhea OR=0.81, 95% CI (0.67-0.98), p=0.03. The total number of medications and xerogenic medications did not play a significant role in xerostomia. Increasing Age and anticholinergic medications induce a dry mouth. Conversely, the total number of medications and xerogenic medications do not influence xerostomia. Medications that induce hypersialorrhea protect against the occurrence of dry mouth.

Vaccination for the expatriate and long-term traveler.

PubMed

Shepherd, Suzanne M; Shoff, William H

2014-06-01

Duration of travel is an important factor in addressing travel health safety due to cumulative risk of exposure to illness and injury. The diverse group of expatriate and long-term business and leisure travelers present a different spectrum of issues for the travel medicine practitioner to address during consultation than does the short-term traveler, due to changes in travel patterns and activities, lifestyle alterations, and increased interaction with local populations. Immunization provides one safe and reliable method of preventing infectious illness in this group. We review travel patterns and available data on illnesses that they may be exposed to, including the increased risk of certain vaccine-preventable illnesses. We review the pre-travel management of these travelers, particularly the increased risk of certain vaccine-preventable illnesses as it applies to routine vaccines, recommended travel vaccines and required travel vaccines.

Verbal Short-Term Memory Reflects the Organization of Long-Term Memory: Further Evidence from Short-Term Memory for Emotional Words

ERIC Educational Resources Information Center

Majerus, Steve; D'Argembeau, Arnaud

2011-01-01

Many studies suggest that long-term lexical-semantic knowledge is an important determinant of verbal short-term memory (STM) performance. This study explored the impact of emotional valence on word immediate serial recall as a further lexico-semantic long-term memory (LTM) effect on STM. This effect is particularly interesting for the study of…

Long-term topical corticosteroid use and risk of skin cancer: a systematic review.

PubMed

Ratib, Sonia; Burden-Teh, Esther; Leonardi-Bee, Jo; Harwood, Catherine; Bath-Hextall, Fiona

2018-06-01

The objective of this systematic review was to synthesize available research evidence to determine the risk of skin cancer in patients with long-term use of topical corticosteroids (TCS). Topical corticosteroids are one of the most commonly prescribed medicines in dermatology and the mainstay of the treatment of atopic dermatitis and other skin conditions such as psoriasis. They are often required for months or years to control the disease and ultimately restore patients' quality of life. In some patients, TCS may have a local immunosuppressive effect and theoretically increase the risk of skin cancer, whilst on the other hand TCS may decrease the risk of skin cancer in patients where TCS are used to treat inflammatory skin disease. To date, no systematic review has been performed to collate evidence on the effect of long-term TCS use on the risk of skin cancer. This review considered studies that included people of all ages, genders and ethnicities, including HIV and transplant participants or participants with genetic diseases (for example, Gorlin-Goltz syndrome) This review considered studies that evaluated long-term use of topical corticosteroids. "Long-term" was defined as using TCS more than once a week for a month or longer. The review included cohort, cross-sectional and case-control observational studies exploring the association between the stated intervention and outcomes. The primary outcome measures of interest were: non-melanoma skin cancer (keratinocyte carcinoma), cutaneous squamous cell carcinoma (cSSC), basal cell carcinoma (BCC) or melanoma skin cancer. Genital and oral skin cancers are considered to be slightly different so we did not include them in this review. We performed a comprehensive search of MEDLINE, Embase and LILACS on November 9, 2017 to identify observational epidemiological studies assessing the association between long-term TCS use and skin cancer. We also searched EThOS at the British Library and three drug safety databases to

Evidence for compliance with long-term medication: a systematic review of randomised controlled trials.

PubMed

King, Michelle A; Pryce, Rebecca L

2014-02-01

Pharmacists play a pivotal role in optimising medication use which often includes actions to maximise compliance with long-term medication. The best evidence to support medication use is derived from randomised controlled trials (RCTs). It is often assumed that 100 % compliance is required to obtain the outcomes identified in the trial. This assumption needs to be examined. To systematically review the reporting of compliance in RCTs of long-term medications. RCTs published in the New England Journal of Medicine, Journal of the American Medical Association, Lancet and BMJ in 2012, were reviewed to identify trials of medications for long-term use in adults. These trials were examined to evaluate the reporting of compliance. The proportion of trials reporting compliance data, the methods used, and the proportion of trials using more than one method to determine compliance. Of the 289 RCTs published in 2012, 25 assessed long-term medications in adults. Compliance was reported in 12 (48 %) studies and only 2 (8 %) studies used more than one method to measure compliance. Pill count was the most commonly reported method for measuring compliance, with patient reports and blood levels also being used. The reporting of compliance in RCTs is poor and the methodology inconsistent. The methods used overestimate compliance. If compliance in a clinical trial is low, the evidence for the effectiveness and most importantly safety of the medication(s) is questionable. Two or more methods, one of which is standardised, should be used to measure compliance in clinical trials. The requirement to report compliance should be included in publication guidelines.

Long-term data archiving

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 recreatemore » 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

Long-term effect of lime-fly ash treated soils.

DOT National Transportation Integrated Search

2003-12-01

In October of 2000 MDOT initiated State Study No. 147, entitled "Long-Term Effect of Lime-Fly Ash Treated Soils." The purpose of this study : was to evaluate the long-term performance of LFA stabilized soil as a base course material. Part of the impe...

[Safety study of long-term video-electroencephalogram monitoring].

PubMed

Ley, M; Vivanco, R; Massot, A; Jiménez, J; Roquer, J; Rocamora, R

2014-01-01

The increased morbidity and mortality and poorer quality of life associated with drug-resistant epilepsy justify admitting patients to epilepsy monitoring units (EMU). These units employ methods that promote the occurrence of seizures, which involves a risk of secondary adverse events. The aim of our study is to characterise and quantify these adverse events in a Spanish EMU. A descriptive, longitudinal and retrospective study of patients admitted consecutively to our EMU. Patients admitted due to status epilepticus, clusters of seizures, or as participants in a clinical trial were excluded. We included 175 patients, of whom 92.1% (161) did not suffer any adverse events. Status epilepticus was present in 3.4% (6); 1.7% (3) had traumatic injury, 1.7% (3) had interictal or postictal psychosis, and 1.1% (2) had cardiorespiratory impairment. There were no risk factors associated with these adverse events. The most frequently-identified adverse events were status epilepticus, traumatic injury, interictal or postictal psychosis, and cardiorespiratory disorders. The frequency of these adverse events was similar to that seen in international literature. The complications detected do not contraindicate VEEGM. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Long-Term Control Medications for Lung Diseases

MedlinePlus

... Asthma Medications Long-Term Control Medications Long-Term Control Medications Make an Appointment Ask a Question Refer Patient Long-term control medications are taken daily to control and prevent ...

Short-term and long-term treatment outcomes with Class III activator

PubMed Central

Ryu, Hyo-kyung; Chong, Hyun-Jeong; An, Ki-Yong

2015-01-01

Objective The purpose of this retrospective study was to investigate short-term and long-term skeletodental outcomes of Class III activator treatment. Methods A Class III activator treatment group (AG) comprised of 22 patients (9 boys, 13 girls) was compared with a Class III control group (CG) comprised of 17 patients (6 boys, 11 girls). The total treatment period was divided into three stages; the initial stage (T1), the post-activator treatment or post-mandibular growth peak stage (T2), and the long-term follow-up stage (T3). Cephalometric changes were evaluated statistically via the Mann-Whitney U-test and the Friedman test. Results The AG exhibited significant increases in the SNA angle, ANB angle, Wits appraisal, A point-N perpendicular, Convexity of A point, and proclination of the maxillary incisors, from T1 to T2. In the long-term follow-up (T1-T3), the AG exhibited significantly greater increases in the ANB angle, Wits appraisal, and Convexity of A point than the CG. Conclusions Favorable skeletal outcomes induced during the Class III activator treatment period were generally maintained until the long-term follow-up period of the post-mandibular growth peak stage. PMID:26445717

Bridge condition assessment based on long-term strain monitoring

NASA Astrophysics Data System (ADS)

Sun, LiMin; Sun, Shouwang

2011-04-01

In consideration of the important role that bridges play as transportation infrastructures, their safety, durability and serviceability have always been deeply concerned. Structural Health Monitoring Systems (SHMS) have been installed to many long-span bridges to provide bridge engineers with the information needed in making rational decisions for maintenance. However, SHMS also confronted bridge engineers with the challenge of efficient use of monitoring data. Thus, methodologies which are robust to random disturbance and sensitive to damage become a subject on which many researches in structural condition assessment concentrate. In this study, an innovative probabilistic approach for condition assessment of bridge structures was proposed on the basis of long-term strain monitoring on steel girder of a cable-stayed bridge. First, the methodology of damage detection in the vicinity of monitoring point using strain-based indices was investigated. Then, the composition of strain response of bridge under operational loads was analyzed. Thirdly, the influence of temperature and wind on strains was eliminated and thus strain fluctuation under vehicle loads is obtained. Finally, damage evolution assessment was carried out based on the statistical characteristics of rain-flow cycles derived from the strain fluctuation under vehicle loads. The research conducted indicates that the methodology proposed is qualified for structural condition assessment so far as the following respects are concerned: (a) capability of revealing structural deterioration; (b) immunity to the influence of environmental variation; (c) adaptability to the random characteristic exhibited by long-term monitoring data. Further examination of the applicability of the proposed methodology in aging bridge may provide a more convincing validation.

Long-term safety assessment of trench-type surface repository at Chernobyl, Ukraine - computer model and comparison with results from simplified models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haverkamp, B.; Krone, J.; Shybetskyi, I.

2013-07-01

The Radioactive Waste Disposal Facility (RWDF) Buryakovka was constructed in 1986 as part of the intervention measures after the accident at Chernobyl NPP (ChNPP). Today, the surface repository for solid low and intermediate level waste (LILW) is still being operated but its maximum capacity is nearly reached. Long-existing plans for increasing the capacity of the facility shall be implemented in the framework of the European Commission INSC Programme (Instrument for Nuclear Safety Co-operation). Within the first phase of this project, DBE Technology GmbH prepared a safety analysis report of the facility in its current state (SAR) and a preliminary safetymore » analysis report (PSAR) for a future extended facility based on the planned enlargement. In addition to a detailed mathematical model, also simplified models have been developed to verify results of the former one and enhance confidence in the results. Comparison of the results show that - depending on the boundary conditions - simplifications like modeling the multi trench repository as one generic trench might have very limited influence on the overall results compared to the general uncertainties associated with respective long-term calculations. In addition to their value in regard to verification of more complex models which is important to increase confidence in the overall results, such simplified models can also offer the possibility to carry out time consuming calculations like probabilistic calculations or detailed sensitivity analysis in an economic manner. (authors)« less

Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

PubMed

Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

2017-08-01

To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

Long-term psychosocial consequences of surgical congenital malformations.

PubMed

Diseth, Trond H; Emblem, Ragnhild

2017-10-01

Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

Reforming Long-Term Care Funding in Alberta.

PubMed

Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

2015-01-01

Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

Embolization of renal angiomyolipomas: short-term and long-term outcomes, complications, and tumor shrinkage.

PubMed

Lee, Shen-Yang; Hsu, Hsiang-Hao; Chen, Yung-Chang; Huang, Chen-Chih; Wong, Yon-Cheong; Wang, Li-Jen; Chuang, Cheng-Keng; Yang, Chih-Wei

2009-11-01

This study retrospectively evaluated outcomes, complications, and tumor shrinkage in renal angiomyolipomas after transcatheter arterial embolization (TAE). All renal angiomyolipoma patients who underwent TAE between August 2000 and December 2008 and had short-term (long-term (>6 months) follow-up images were evaluated. Complications and tumor relapse after TAE were reviewed. The sizes of embolized tumors were measured to calculate size reductions and reduction rates after TAE. Differences in tumor size, size reduction, and reduction rate between different time points (pre-TAE, short-term follow-up, and long-term follow-up) and groups (completely and incompletely embolized) were determined. Eleven renal angiomyolipoma patients who had undergone TAE were included. Seven (63.6%) patients had postembolization syndrome and one had abscess formation following TAE. Two patients had a tumor relapse (18.2%). The mean tumor size was 8.57+/-2.66 cm on pre-TAE images. The mean size reduction was 3.1 cm (33.3%) and 3.8 cm (43.0%) at short-term and long-term follow-up. Tumor sizes differed significantly between pre-TAE and short-term (p=0.004) or long-term images (p=0.022) but not between short-term and long-term images (p=0.059). Results stratified by the completeness of embolization indicate that only the short-term size reduction rate differed significantly (p=0.025), while the long-term reduction rate and short- and long-term follow-up tumor size and size reduction were comparable between the two groups. In conclusion, selective TAE is effective for tumor shrinkage in most renal angiomyolipomas, with acceptable complication and relapse rates. Tumor shrinkage occurring within 6 months after TAE may reflect the long-term effect of TAE.

Economic efficiency of short-term versus long-term water rights buyouts

USDA-ARS?s Scientific Manuscript database

Because of the decline of the Ogallala Aquifer, water districts, regional water managers, and state water officers are becoming increasingly interested in conservation policies. This study evaluates both short-term and long-term water rights buyout policies. This research develops dynamic production...

Reduction of Parenteral Nutrition and Hydration Support and Safety With Long-Term Teduglutide Treatment in Patients With Short Bowel Syndrome-Associated Intestinal Failure: STEPS-3 Study.

PubMed

Seidner, Douglas L; Fujioka, Ken; Boullata, Joseph I; Iyer, Kishore; Lee, Hak-Myung; Ziegler, Thomas R

2018-05-15

Patients with intestinal failure associated with short bowel syndrome (SBS-IF) require parenteral support (PS) to maintain fluid balance or nutrition. Teduglutide (TED) reduced PS requirements in patients with SBS-IF in the randomized, placebo (PBO)-controlled STEPS study (NCT00798967) and its 2-year, open-label extension, STEPS-2 (NCT00930644). STEPS-3 (NCT01560403), a 1-year, open-label extension study in patients with SBS-IF who completed STEPS-2, further monitored the safety and efficacy of TED (0.05 mg/kg/day). Baseline was the start of TED treatment, in either STEPS or STEPS-2. At the end of STEPS-3, patients treated with TED in both STEPS and STEPS-2 (TED-TED) received TED for ≤42 months, and patients treated with TED only in STEPS-2 (no TED treatment [NT]/PBO-TED) received TED for ≤36 months. Fourteen patients enrolled (TED-TED, n = 5; NT/PBO-TED, n = 9) and 13 completed STEPS-3. At the last dosing visit, mean (SD) PS was reduced from baseline by 9.8 (14.4 [50%]) and 3.9 (2.8 [48%]) L/week in TED-TED and NT/PBO-TED, respectively. Mean (SD) PS infusions decreased by 3.0 (4.6) and 2.1 (2.2) days per week from baseline in TED-TED and NT/PBO-TED, respectively. Two patients achieved PS independence; 2 additional patients who achieved independence in STEPS-2 maintained enteral autonomy throughout STEPS-3. All patients reported ≥1 treatment-emergent adverse event (TEAE); 3 patients had TEAEs that were reported as treatment related. No patient had a treatment-related treatment-emergent serious AE. Long-term TED treatment yielded a safety profile consistent with previous studies, sustained efficacy, and a further decline in PS requirements. © 2018 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.

An Instrument for Every Child: A Study on Long-Term Effects of Extended Music Education in German Primary Schools

ERIC Educational Resources Information Center

Krupp-Schleußner, Valerie; Lehmann-Wermser, Andreas

2018-01-01

Does extended music education during primary school foster long-term musical participation? What other factors contribute to long-term musical participation? In our study on "Impacts and Long-Term Effects of Musical Participation," we investigate how the German programme "An Instrument for Every Child (JeKi)," which fosters the…

Adverse event reporting in Czech long-term care facilities.

PubMed

Hěib, Zdenřk; Vychytil, Pavel; Marx, David

2013-04-01

To describe adverse event reporting processes in long-term care facilities in the Czech Republic. Prospective cohort study involving a written questionnaire followed by in-person structured interviews with selected respondents. Long-term care facilities located in the Czech Republic. Staff of 111 long-term care facilities (87% of long-term care facilities in the Czech Republic). None. Sixty-three percent of long-term health-care facilities in the Czech Republic have adverse event-reporting processes already established, but these were frequently very immature programs sometimes consisting only of paper recording of incidents. Compared to questionnaire responses, in-person interview responses only partially tended to confirm the results of the written survey. Twenty-one facilities (33%) had at most 1 unconfirmed response, 31 facilities (49%) had 2 or 3 unconfirmed responses and the remaining 11 facilities (17%) had 4 or more unconfirmed responses. In-person interviews suggest that use of a written questionnaire to assess the adverse event-reporting process may have limited validity. Staff of the facilities we studied expressed an understanding of the importance of adverse event reporting and prevention, but interviews also suggested a lack of knowledge necessary for establishing a good institutional reporting system in long-term care.

Medical Underwriting In Long-Term Care Insurance: Market Conditions Limit Options For Higher-Risk Consumers.

PubMed

Cornell, Portia Y; Grabowski, David C; Cohen, Marc; Shi, Xiaomei; Stevenson, David G

2016-08-01

A key feature of private long-term care insurance is that medical underwriters screen out would-be buyers who have health conditions that portend near-term physical or cognitive disability. We applied common underwriting criteria based on data from two long-term care insurers to a nationally representative sample of individuals in the target age range (50-71 years) for long-term care insurance. The screening criteria put upper bounds on the current proportion of Americans who could gain coverage in the individual market without changes to medical underwriting practice. Specifically, our simulations show that in the target age range, approximately 30 percent of those whose wealth meets minimum industry standards for suitability for long-term care insurance would have their application for such insurance rejected at the underwriting stage. Among the general population-without considering financial suitability-we estimated that 40 percent would have their applications rejected. The predicted rejection rates are substantially higher than the rejection rates of about 20-25 percent of applicants in the actual market. In evaluating reforms for long-term care financing and their potential to increase private insurance rates, as well as to reduce financial pressure on public safety-net programs, policy makers need to consider the role of underwriting in the market for long-term care insurance. Project HOPE—The People-to-People Health Foundation, Inc.

Private long-term care insurance and state tax incentives.

PubMed

Stevenson, David G; Frank, Richard G; Tau, Jocelyn

2009-01-01

To increase the role of private insurance in financing long-term care, tax incentives for long-term care insurance have been implemented at both the federal and state levels. To date, there has been surprisingly little study of these initiatives. Using a panel of national data, we find that market take-up for long-term care insurance increased over the last decade, but state tax incentives were responsible for only a small portion of this growth. Ultimately, the modest ability of state tax incentives to lower premiums implies that they should be viewed as a small piece of the long-term care financing puzzle.

Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease.

PubMed

Hadinegoro, Sri Rezeki; Arredondo-García, Jose Luis; Capeding, Maria Rosario; Deseda, Carmen; Chotpitayasunondh, Tawee; Dietze, Reynaldo; Muhammad Ismail, H I Hj; Reynales, Humberto; Limkittikul, Kriengsak; Rivera-Medina, Doris Maribel; Tran, Huu Ngoc; Bouckenooghe, Alain; Chansinghakul, Danaya; Cortés, Margarita; Fanouillere, Karen; Forrat, Remi; Frago, Carina; Gailhardou, Sophia; Jackson, Nicholas; Noriega, Fernando; Plennevaux, Eric; Wartel, T Anh; Zambrano, Betzana; Saville, Melanie

2015-09-24

A candidate tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries. We report the results of long-term follow-up interim analyses and integrated efficacy analyses. We are assessing the incidence of hospitalization for virologically confirmed dengue as a surrogate safety end point during follow-up in years 3 to 6 of two phase 3 trials, CYD14 and CYD15, and a phase 2b trial, CYD23/57. We estimated vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15. Follow-up data were available for 10,165 of 10,275 participants (99%) in CYD14 and 19,898 of 20,869 participants (95%) in CYD15. Data were available for 3203 of the 4002 participants (80%) in the CYD23 trial included in CYD57. During year 3 in the CYD14, CYD15, and CYD57 trials combined, hospitalization for virologically confirmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group. Pooled relative risks of hospitalization for dengue were 0.84 (95% confidence interval [CI], 0.56 to 1.24) among all participants, 1.58 (95% CI, 0.83 to 3.02) among those under the age of 9 years, and 0.50 (95% CI, 0.29 to 0.86) among those 9 years of age or older. During year 3, hospitalization for severe dengue, as defined by the independent data monitoring committee criteria, occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group. Pooled rates of efficacy for symptomatic dengue during the first 25 months were 60.3% (95% CI, 55.7 to 64.5) for all participants, 65.6% (95% CI, 60.7 to 69.9) for those 9 years of age or older, and 44.6% (95% CI, 31.6 to 55.0) for those younger than 9 years of age. Although the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term

Continuous light absorption photometer for long-term studies

NASA Astrophysics Data System (ADS)

Ogren, John A.; Wendell, Jim; Andrews, Elisabeth; Sheridan, Patrick J.

2017-12-01

A new photometer is described for continuous determination of the aerosol light absorption coefficient, optimized for long-term studies of the climate-forcing properties of aerosols. Measurements of the light attenuation coefficient are made at blue, green, and red wavelengths, with a detection limit of 0.02 Mm-1 and a precision of 4 % for hourly averages. The uncertainty of the light absorption coefficient is primarily determined by the uncertainty of the correction scheme commonly used to convert the measured light attenuation to light absorption coefficient and ranges from about 20 % at sites with high loadings of strongly absorbing aerosols up to 100 % or more at sites with low loadings of weakly absorbing aerosols. Much lower uncertainties (ca. 40 %) for the latter case can be achieved with an advanced correction scheme.

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

PubMed

Vossler, David G; Wechsler, Robert T; Williams, Paulette; Byrnes, William; Therriault, Sheila

2016-10-01

To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of

The associations between workplace bullying, salivary cortisol, and long-term sickness absence: a longitudinal study.

PubMed

Grynderup, Matias Brødsgaard; Nabe-Nielsen, Kirsten; Lange, Theis; Conway, Paul Maurice; Bonde, Jens Peter; Garde, Anne Helene; Gullander, Maria; Kaerlev, Linda; Persson, Roger; Rugulies, Reiner; Vammen, Marianne Agergaard; Høgh, Annie; Hansen, Åse Marie

2017-09-16

Workplace stressors, such as bullying, are strongly related to subsequent long-term sickness absence, but little is known of the possible physiological mechanisms linking workplace stressors and sickness absence. The primary aim of this study was to investigate to what extent cortisol levels were associated with subsequent sickness absence and if cortisol mediated the association between workplace bullying and sickness absence. We additionally investigated possible bidirectional associations between bullying, cortisol, and long-term sickness absence. Participants came from two Danish cohort studies, the "Psychosocial RIsk factors for Stress and MEntal disease" (PRISME) cohort and the "Workplace Bullying and Harassment" (WBH) cohort (n = 5418). Information about exposure to workplace bullying and morning and evening salivary cortisol was collected at three time points with approximately two years in between. After each data collection, all participants were followed for two years in registers, and cases with long-term sickness absence lasting 30 or more consecutive days were identified. The association between cortisol levels and subsequent sickness absence was assessed by logistic regression, while the extent to which the association between bullying and sickness absence was mediated by cortisol was quantified through natural direct and indirect effects. High evening cortisol was associated with a decreased risk of sickness absence (OR = 0.82, 95% CI = 0.68-0.99), but we did not find that high morning cortisol levels (OR = 0.98, 95% CI = 0.81-1.18) or high morning-to-evening slope (OR = 0.99, 95% CI = 0.82-1.18) were associated with subsequent sickness absence. We also tested for reverse causation and found that long-term sickness absence, but not salivary cortisol, was a strong risk factor for subsequent workplace bullying. There was no indication that cortisol mediated the association between workplace bullying and sickness absence. We found no

Long Term Deck Deterioration : final report.

DOT National Transportation Integrated Search

1990-09-01

In May of 1981 the Oregon State Highway Division was asked by the Federal Highway Administration to participate in a long term deck deterioration study. The study, an extension of an earlier study was finalized in 1979, was to run through 1990. Revie...

Measuring forgetting: a critical review of accelerated long-term forgetting studies.

PubMed

Elliott, Gemma; Isaac, Claire L; Muhlert, Nils

2014-05-01

Accelerated long-term forgetting (ALF) refers to abnormal forgetting over hours to weeks despite normal acquisition or initial consolidation. Since standardised assessments of memory typically only test at delays of up to 40-minutes, ALF may go undetected in clinical practice. The memory difficulties associated with ALF can however cause considerable distress to patients. It is important therefore that clinicians are aware that ALF may represent a distinct phenomenon that will require additional and careful assessment to aid patients' understanding of the condition and assist in developing strategies to address its effects. At the same time, ALF may also provide insight into long-term memory processes. Studies of ALF in patients with epilepsy have so far demonstrated mixed results, which may reflect differences in methodology. This review explores the methodological issues that can affect forgetting, such as the effects of age, general cognitive function, test sensitivity and initial learning. It then evaluates the extent to which existing studies have considered these key issues. We outline the points to consider when designing ALF studies that can be used to help improve their validity. These issues can also help to explain some of the mixed findings in studies of ALF and inform the design of standardised tests for assessing ALF in clinical practice. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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

Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity

PubMed Central

Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R.; Baldelli, Pietro; Benfenati, Fabio

2013-01-01

Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows. PMID:23970852

Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity.

PubMed

Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R; Baldelli, Pietro; Benfenati, Fabio

2013-01-01

Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows.

Long-term Efficacy, Safety, and Immunogenicity of Biosimilar Infliximab After One Year in a Prospective Nationwide Cohort.

PubMed

Gonczi, Lorant; Gecse, Krisztina B; Vegh, Zsuzsanna; Kurti, Zsuzsanna; Rutka, Mariann; Farkas, Klaudia; Golovics, Petra A; Lovasz, Barbara D; Banai, Janos; Bene, Laszlo; Gasztonyi, Bea; Kristof, Tunde; Lakatos, Laszlo; Miheller, Pal; Nagy, Ferenc; Palatka, Karoly; Papp, Maria; Patai, Arpad; Salamon, Agnes; Szamosi, Tamas; Szepes, Zoltan; Toth, Gabor T; Vincze, Aron; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

2017-11-01

It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort. A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC). Demographic data were collected and a harmonized monitoring strategy was applied. Clinical remission, response, and biochemical response were evaluated at weeks 14, 30, and 54, respectively. Safety data were registered. Three hundred fifty-three consecutive inflammatory bowel disease (209 CD and 144 UC) patients were included, of which 229 patients reached the week 54 endpoint at final evaluation. Age at disease onset: 24/28 years (median, interquartile range: 19-34/22-39) in patients with CD/UC. Forty-nine, 53, 48% and 86, 81 and 65% of patients with CD reached clinical remission and response by weeks 14, 30, and 54, respectively. Clinical remission and response rates were 56, 41, 43% and 74, 66, 50% in patients with UC. Clinical efficacy was influenced by previous anti-tumor necrosis factor (TNF) exposure in patients with a drug holiday beyond 1 year. The mean C-reactive protein level decreased significantly in both CD and UC by week 14 and was maintained throughout the 1-year follow-up (both UC/CD: P < 0.001). Thirty-one (8.8%) patients had infusion reactions and 32 (9%) patients had infections. Antidrug antibody positivity rates were significantly higher throughout patients with previous anti-TNF exposure; concomitant azathioprine prevented antidrug antibody formation in anti-TNF-naive patients with CD. Results from this prospective nationwide cohort confirm that CT-P13 is effective and safe in inducing and maintaining long-term remission in both CD and UC. Efficacy was influenced by previous anti-TNF exposure; no

The Long-Term Budget Outlook

DTIC Science & Technology

2005-12-01

Revenues Under CBO’s Long-Term Budget Scenarios 56A-8. Real Gross Domestic Product Under CBO’s Long-Term Budget Scenarios 57A-9. Total Surplus or...scenarios suggest that total federal spending for Medicare and Medicaid in 2050 could range anywhere from 7 percent of gross domestic product (GDP)—a...see the Congressional Budget Office’s glossary of budgetary and economic terms, available at www.cbo.gov. 2. The future path of productivity growth

Work and family: associations with long-term sick-listing in Swedish women - a case-control study.

PubMed

Sandmark, Hélène

2007-10-11

The number of Swedish women who are long-term sick-listed is high, and twice as high as for men. Also the periods of sickness absence have on average been longer for women than for men. The objective of this study was to investigate the associations between factors in work- and family life and long-term sick-listing in Swedish women. This case-control study included 283 women on long-term sick-listing > or =90 days, and 250 female referents, randomly chosen, living in five counties in Sweden. Bivariate and multivariate logistic regression analyses with odds ratios were calculated to estimate the associations between long-term sick-listing and factors related to occupational work and family life. Long-term sick-listing in women is associated with self-reported lack of competence for work tasks (OR 2.42 1.23-11.21 log reg), workplace dissatisfaction (OR 1.89 1.14-6.62 log reg), physical workload above capacity (1.78 1.50-5.94), too high mental strain in work tasks (1.61 1.08-5.01 log reg), number of employers during work life (OR 1.39 1.35-4.03 log reg), earlier part-time work (OR 1.39 1.18-4.03 log reg), and lack of influence on working hours (OR 1.35 1.47-3.86 log reg). A younger age at first child, number of children, and main responsibility for own children was also found to be associated with long-term sick-listing. Almost all of the sick-listed women (93%) wanted to return to working life, and 54% reported they could work immediately if adjustments at work or part-time work were possible. Factors in work and in family life could be important to consider to prevent women from being long-term sick-listed and promote their opportunities to remain in working life. Measures ought to be taken to improve their mobility in work life and control over decisions and actions regarding theirs lives.

Long-term safety and efficacy of taliglucerase alfa in pediatric Gaucher disease patients who were treatment-naïve or previously treated with imiglucerase.

PubMed

Zimran, Ari; Gonzalez-Rodriguez, Derlis Emilio; Abrahamov, Aya; Cooper, Peter A; Varughese, Sheeba; Giraldo, Pilar; Petakov, Milan; Tan, Ee Shien; Chertkoff, Raul

2018-02-01

Taliglucerase alfa is an enzyme replacement therapy approved for treatment of Gaucher disease (GD) in children and adults in several countries. This multicenter extension study assessed the efficacy and safety of taliglucerase alfa in pediatric patients with GD who were treatment-naïve (n=10) or switched from imiglucerase (n=5). Patients received taliglucerase alfa 30 or 60U/kg (treatment-naïve) or the same dose as previously treated with imiglucerase every other week. In treatment-naïve patients, taliglucerase alfa 30 and 60U/kg, respectively, reduced mean spleen volume (-18.6 multiples of normal [MN] and -26.0MN), liver volume (-0.8MN and -0.9MN), and chitotriosidase activity (-72.7% and -84.4%), and increased mean Hb concentration (+2.0g/dL and +2.3g/dL) and mean platelet count (+38,200/mm 3 and +138,250/mm 3 ) from baseline through 36 total months of treatment. In patients previously treated with imiglucerase, these disease parameters remained stable through 33 total months of treatment with taliglucerase alfa. Most adverse events were mild/moderate; treatment was well tolerated. These findings extend the taliglucerase alfa safety and efficacy profile and demonstrate long-term clinical improvement in treatment-naïve children receiving taliglucerase alfa and maintenance of disease stability in children switched to taliglucerase alfa. Treatment was well-tolerated, with no new safety signals. This study is registered at www.clinicaltrials.gov as NCT01411228. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

Long-term low-level arsenic exposure is associated with poorer neuropsychological functioning: a Project FRONTIER study.

PubMed

O'Bryant, Sid E; Edwards, Melissa; Menon, Chloe V; Gong, Gordon; Barber, Robert

2011-03-01

Exposure to elements in groundwater (toxic or beneficial) is commonplace yet, outside of lead and mercury, little research has examined the impact of many commonly occurring environmental exposures on mental abilities during the aging process. Inorganic arsenic is a known neurotoxin that has both neurodevelopmental and neurocognitive consequences. The aim of this study was to examine the potential association between current and long-term arsenic exposure and detailed neuropsychological functioning in a sample of rural-dwelling adults and elders. Data were analyzed from 434 participants (133 men and 301 women) of Project FRONTIER, a community-based participatory research study of the epidemiology of health issues of rural-dwelling adults and elders. The results of the study showed that GIS-based groundwater arsenic exposure (current and long-term) was significantly related to poorer scores in language, visuospatial skills, and executive functioning. Additionally, long-term low-level exposure to arsenic was significantly correlated to poorer scores in global cognition, processing speed and immediate memory. The finding of a correlation between arsenic and the domains of executive functioning and memory is of critical importance as these are cognitive domains that reflect the earliest manifestations of Alzheimer's disease. Additional work is warranted given the population health implications associated with long-term low-level arsenic exposure.

Description of the Fork Mountain long-term soil productivity study: site characterization

Treesearch

Mary Beth Adams; James Burger; Lucian Zelazny; John Baumgras

2004-01-01

The effects of air pollution and timber harvesting on soil resources continue to be an important issue in eastern hardwood forests. This publication describes the Fork Mountain Long-term Soil Productivity Study (LTSP), located on the Fernow Experimental Forest, WV, and the pretreatment stand, soil and climatic conditions. Extensive vegetation surveys, biomass...

Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper limb non-unions: long-term assessment.

PubMed

Giannotti, Stefano; Trombi, Luisa; Bottai, Vanna; Ghilardi, Marco; D'Alessandro, Delfo; Danti, Serena; Dell'Osso, Giacomo; Guido, Giulio; Petrini, Mario

2013-01-01

Tissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions. Mesenchymal stromal cells (MSCs) are considered an appealing cell source for clinical intervention. However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized. Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution. We examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb. Our research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components), reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation. Bone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions. Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage. Radiographic healing was evaluated with short- and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively). All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation. Our study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions. This tissue engineering approach resulted in successful clinical and functional outcomes for all patients.

Non-randomized intervention study of naloxone co-prescription for primary care patients on long-term opioid therapy for pain

PubMed Central

Coffin, Phillip O.; Behar, Emily; Rowe, Christopher; Santos, Glenn-Milo; Coffa, Diana; Bald, Matthew; Vittinghoff, Eric

2018-01-01

Background Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States. Objectives To evaluate the feasibility and impact of implementing naloxone prescription to patients prescribed opioids for chronic pain. Design 2-year non-randomized intervention study. Setting 6 safety net primary care clinics in San Francisco. Participants 1985 adults receiving long-term opioids for pain. Intervention Providers and clinic staff were trained and supported in naloxone prescribing. Measurements Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review. Results 38.2% of 1,985 patients on long-term opioids were prescribed naloxone. Patients on higher doses of opioids and with a past 12-month opioid-related emergency department (ED) visit were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month six months after the receipt of the prescription (IRR=0.53, 95%CI=0.34–0.83, P=0.005) and 63% fewer visits after one year (IRR=0.37, 95%CI=0.22–0.64, P<0.001), compared to patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone compared to those who did not (IRR 1.03, 95% CI 0.91–1.27, P = 0.61). Limitations Results are observational and may not be generalizable beyond safety net settings. Conclusion Naloxone can be co-prescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients on opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits such as reducing opioid-related adverse events. Funding Source National Institutes of Health grant R21DA036776 PMID:27366987