Search

Roadworks schemes present a nuisance for road users as they lead in some cases to temporarily reduced road capacity and increased congestion. The introduction of Travel Demand Management (TDM) techniques during roadworks has the potential to reduce the associated negative impacts of temporary reduced capacity, increased journey time and poor customer satisfaction. TDM measures refer in this paper to a wide range of interventions that have the potential to change travel route, time, mode, and/or need. They include measures that promote the use of environmentally sustainable transport modes (e.g. Public Transport, Active Transport, and Shared Mobility) as well as measures that aim to manage traffic within roadworks zones and the surrounding affected areas. This paper presents the processes implemented and outcomes achieved by two ongoing TDM pilots in the UK developed to mitigate the negative impact of roadworks schemes on national and local road networks.

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are two common functional gastrointestinal disorders that impair quality of life and pose a significant economic burden to the health care system. Current therapeutic options include lifestyle modifications, over-the-counter (OTC) agents, antispasmodics, serotonin agonists, and lubiprostone and linaclotide, two prosecretory prescription drugs approved for the treatment of IBS-C and CIC. This review discusses the efficacy and safety of current treatments and emerging therapies for the treatment of IBS-C and CIC, with a focus on the prosecretory agents. A search of the PubMed database (1966-November 2014) was performed to identify relevant articles; clinical trials on emerging agents were also identified by searching the ClinicalTrials.gov registry. OTC laxatives may relieve constipation but do not treat abdominal pain and discomfort. Antispasmodics may provide short-term relief in patients with IBS-C, but their utility is limited by anticholinergic adverse effects. Tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors have shown benefit in providing global symptom relief and in improving abdominal discomfort, but further research is needed. Phase III clinical trials have demonstrated the efficacy of lubiprostone and linaclotide relative to placebo for the short-term treatment of IBS-C and CIC, with improvements reported in stool frequency, perceived constipation severity, and abdominal pain and discomfort. Relatively small response rates, higher costs, and adverse effects associated with lubiprostone and linaclotide will likely render these agents suitable as second-line therapies in the treatment of IBS-C and CIC. Emerging potential treatment options include prucalopride, plecanatide, elobixibat, and tenapanor. Several of these emerging therapies have novel mechanisms of action and may show promise in patients with IBS-C and CIC who have not responded to other therapies.

Purpose The efficacy and safety of the three oral agents approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS) are reviewed. Summary Limitations to parenteral disease-modifying therapies (DMTs) (interferon beta-1a, interferon beta-1b, and glatiramer acetate) for the treatment of RRMS have been addressed by the approval of three oral DMTs: fingolimod, teriflunomide, and dimethyl fumarate. In clinical trials, each of the oral DMTs was superior to placebo in annualized relapse rate, a key indicator of clinical efficacy, and in neuroradiological efficacy. A reduction in disability progression was evident with higher doses of teriflunomide but was not consistently demonstrated with fingolimod or dimethyl fumarate. Each of the oral DMTs demonstrated acceptable safety in clinical trials, with adverse-effect profiles that differ from injectable agents. The safety of both teriflunomide and dimethyl fumarate is supported by long-term use of related agents for other diseases; however, postmarketing surveillance studies are needed to determine the safety of each of the oral DMTs in patients with RRMS. Dimethyl fumarate seems to have the most innocuous safety profile of the three agents. Fingolimod requires first-dose inpatient monitoring due to cardiac safety concerns and multiple laboratory tests prior to initiation of therapy, while teriflunomide has been associated with hepatotoxicity and teratogenicity. Conclusion With the approval of three oral drugs for RRMS—fingolimod, teriflunomide, and dimethyl fumarate—the therapeutic strategy for RRMS has evolved to include options that are efficacious and appear to have administration advantages over established parenteral treatments.

Purpose Preapproval and postapproval availability of published comparative efficacy studies on biological agents approved between 2000 and 2010 was investigated. Methods Approval packages published on the Food and Drug Administration (FDA) website were examined for all biological agents approved between 2000 and 2010 to determine if comparative efficacy studies were available at the time of FDA approval. The availability of comparative efficacy studies published subsequent to approval was determined by searching PubMed for randomized, active-controlled experimental or observational study designs that measured efficacy as the primary endpoint and were relevant to the original FDA-approved indication. Results From 2000 to 2010, 107 biological agents were approved by FDA. Of the biological agents with alternative treatments, 54.6% had comparative efficacy data available at the time of approval. Although standard-reviewed biological agents were more likely to have comparative efficacy trials included in the FDA approval packages than priority-reviewed biological agents, statistically significant differences are unlikely. Subsequent to approval, 58.1% of biological agents had at least one published comparative efficacy trial, representing a 3.5% absolute increase in the availability of comparative efficacy studies since the time of approval. Vaccines and biological agents in the hematologic diseases, oncology, and miscellaneous diseases classes had fewer published postapproval comparative efficacy studies per agent compared with the overall group of biological agents. Conclusion Nearly half of all biological agents approved for marketing between 2000 and 2010 lacked publicly accessible, active-controlled efficacy studies at the time of drug approval; a slightly greater proportion of biological agents had comparative efficacy data published subsequent to their approval.

OBJECTIVE To summarize the efficacy and safety data for use of nebulized lidocaine in intractable cough and asthma. DATA SOURCES A literature search was conducted using PubMed (through November 2012), International Pharmaceutical Abstracts (1970–December 2012), and Cochrane Library (up to 2012) with the search terms nebulization, nebulized or nebulised; administration, inhalation; cough; asthma; and lidocaine. Results were limited to human studies published in the English language. Referenced citations from relevant publications were also reviewed. STUDY SELECTION AND DATA EXTRACTION All articles identified from the data sources were reviewed for inclusion. Clinical trials and descriptive studies that discussed use of nebulized lidocaine for treatment of intractable cough and asthma were included in the review. DATA SYNTHESIS Seventeen studies were identified for review. Seven studies (6 descriptive studies and 1 clinical trial) evaluating the use of nebulized lidocaine in intractable cough reported efficacy in doses ranging from 10 mg to 400 mg. Five clinical trials in asthma showed conflicting results regarding improvement in pulmonary function and glucocorticoid-sparing effects. General improvements in pulmonary function as well as the initial bronchoconstriction induced by nebulized lidocaine in subjects with baseline bronchial hyperreactivity were investigated in 5 studies. Overall, the available evidence does not appear to preclude the use of lidocaine as a treatment option for intractable cough after failure of traditional cough suppressants. Data on its use for short-term glucocorticoid-sparing effects in asthma are conflicting. Study limitations, including design, small sample size, and inconsistencies in method and adjunctive therapies, should be considered. Nebulized lidocaine is well tolerated; however, reports of initial bronchoconstriction have occurred. CONCLUSIONS Although nebulized lidocaine is not first-line therapy in intractable cough and asthma, it may provide an alternative treatment option in patients who cannot tolerate or are unresponsive to other treatments. Appropriate monitoring precautions should be used to ensure patient safety.

This article evaluates the evolution of Americans' sense of solidarity, community, and identity in the age of globalisation through an examination of their involvement with non-governmental organisations (NGOs) and social movements active in the developing world. This analysis draws on Jurgen Habermas' contention that, in this age of an increasingly global and inequitable economy, civil society organisations that extend beyond national borders are more likely than other institutions to engender transnational solidarity. The article focuses primarily on results of an opinion survey conducted by the author, examining to what extent U.S. volunteers for international NGOs exhibit national or transnational senses of belonging. Conclusions include the ideas that this cosmopolitan population may indicate an emerging trend in greater feelings of solidarity with and attachment to developing countries, leading to increased support for more multilateral decision-making. However, this more global consciousness seems unlikely to replace feelings of national attachment and belonging.

Les mouvements progressistes multiculturalistes visent a eradiquer l'inegalite socio-economique par le biais de l'education. Des organismes conservateurs, notamment representant la droite chretienne, se sont opposes de maniere continue au multiculturalisme, en particulier pendant les " guerres culturelles " des annees 1980 et 1990, opposition qui fut renouvelee apres le 11 septembre 2001. Cet article cherche a evaluer les resultats de cette lutte ideologique au travers l'etude de l'image de la societe americaine presentee dans des manuels d'histoire publies avant et apres 2001.

A la lumiere des debats concernant l’identite nationale en France et aux Etats-Unis, cet article cherche a elucider les objectifs nationalistes (au sens developpe dans l’article) de l’enseignement de l’histoire dans les deux pays. Il demontre comment les reecritures de l’histoire scolaire refletent et contribuent a redefinir la nation et, par ce biais, la perpetuent. Il examine la forme que prend le nationalisme dans les deux pays et les valeurs qu’il vehicule, revelant, entre autres, une approche francaise qui applique des methodes inspirees des travaux d’historiens et vise a promouvoir la solidarite, tandis que les manuels americains, sous l’impulsion des mouvements conservateurs des trente dernieres annees, pronent une vision de la memoire nationale fondee sur une unite fantasmee.

Linaclotide (Linzess) for irritable bowel syndrome with constipation and for chronic idiopathic constipation.