The effectiveness, safety and cost-effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: a study protocol for a randomized controlled non-inferiority trial

Smoking cessation medications are effective but often underutilised because of costs and side effects. Cytisine is a plant-based smoking cessation medication with over 50 years of use in Central and Eastern Europe. While cytisine has been found to be well-tolerated and more effective than nicotine replacement therapy, direct comparison with varenicline have not been conducted. This study evaluates the effectiveness, safety and cost-effectiveness of cytisine compared with varenicline.Two arm, parallel group, randomised, non-inferiority trial, with allocation concealment and blinded outcome assessment.Australian population-based study.Adult daily smokers (N=1266) interested in quitting will be recruited through advertisements and Quitline telephone-based cessation support services.Eligible participants will be randomised (1:1 ratio) to receive either cytisine capsules (25-day supply) or varenicline tablets (12-week supply), prescribed in accordance with the manufacturer's recommended dosing regimen. The medication will be mailed to each participant's nominated residential address. All participants will also be offered standard Quitline behavioural support (up to six 10-12 minute sessions).Assessments will be undertaken by telephone at baseline, 4- and 7-months post-randomisation. Participants will also be contacted twice (two and four weeks post-randomisation) to ascertain adverse events, treatment adherence and smoking status. The primary outcome will be self-reported 6-month continuous abstinence from smoking, verified by carbon monoxide at 7-month follow-up. We will also evaluate the relative safety and cost-effectiveness of cytisine compared with varenicline. Secondary outcomes will include self-reported continuous and 7-day point prevalence abstinence and cigarette consumption at each follow-up interview.If cytisine is as effective as varenicline, its lower cost and natural plant-based composition may make it an acceptable and affordable smoking cessation medication that could save millions of lives worldwide

The economic cost of bereavement in Scotland.

Aspects of the socioeconomic costs of bereavement in Scotland were estimated using 3 sets of data. Spousal bereavement was associated with increased mortality and longer hospital stays, with additional annual cost of around {pound}20 million. Cost of bereavement coded consultations in primary care was estimated at around {pound}2.0 million annually. In addition, bereaved people were significantly less likely to be employed in the year of and 2 years after bereavement than non-bereaved matched controls, but there were no significant differences in income between bereaved people and matched controls before and after bereavement

Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial:designing the intervention (ClinicalTrials.gov registration NCT01602705)

Peer reviewedPublisher PD

Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle.

Migration through 3D constrictions can cause nuclear rupture and mislocalization of nuclear proteins, but damage to DNA remains uncertain, as does any effect on cell cycle. Here, myosin II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent block in cell cycle appears unaffected. Co-overexpression of multiple DNA repair factors or antioxidant inhibition of break formation also exert partial effects, independently of rupture. Combined treatments completely rescue cell cycle suppression by DNA damage, revealing a sigmoidal dependence of cell cycle on excess DNA damage. Migration through custom-etched pores yields the same damage threshold, with ∼4-µm pores causing intermediate levels of both damage and cell cycle suppression. High curvature imposed rapidly by pores or probes or else by small micronuclei consistently associates nuclear rupture with dilution of stiff lamin-B filaments, loss of repair factors, and entry from cytoplasm of chromatin-binding cGAS (cyclic GMP-AMP synthase). The cell cycle block caused by constricted migration is nonetheless reversible, with a potential for DNA misrepair and genome variation

Historic 2005 toxic bloom of Alexandrium fundyense in the western Gulf of Maine : 2. Coupled biophysical numerical modeling

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): C07040, doi:10.1029/2007JC004602.A coupled physical/biological modeling system was used to hindcast a massive Alexandrium fundyense bloom that occurred in the western Gulf of Maine in 2005 and to investigate the relative importance of factors governing the bloom's initiation and development. The coupled system consists of a state-of-the-art, free-surface primitive equation Regional Ocean Modeling System (ROMS) tailored for the Gulf of Maine (GOM) using a multinested configuration, and a population dynamics model for A. fundyense. The system was forced by realistic momentum and buoyancy fluxes, tides, river runoff, observed A. fundyense benthic cyst abundance, and climatological nutrient fields. Extensive comparisons were made between simulated (both physical and biological) fields and in situ observations, revealing that the hindcast model is capable of reproducing the temporal evolution and spatial distribution of the 2005 bloom. Sensitivity experiments were then performed to distinguish the roles of three major factors hypothesized to contribute to the bloom: (1) the high abundance of cysts in western GOM sediments; (2) strong ‘northeaster' storms with prevailing downwelling-favorable winds; and (3) a large amount of fresh water input due to abundant rainfall and heavy snowmelt. Model results suggest the following. (1) The high abundance of cysts in western GOM was the primary factor of the 2005 bloom. (2) Wind-forcing was an important regulator, as episodic bursts of northeast winds caused onshore advection of offshore populations. These downwelling favorable winds accelerated the alongshore flow, resulting in transport of high cell concentrations into Massachusetts Bay. A large regional bloom would still have happened, however, even with normal or typical winds for that period. (3) Anomalously high river runoff in 2005 resulted in stronger buoyant plumes/currents, which facilitated the transport of cell population to the western GOM. While affecting nearshore cell abundance in Massachusetts Bay, the buoyant plumes were confined near to the coast, and had limited impact on the gulf-wide bloom distribution.Research support was provided through the Woods Hole Center for Oceans and Human Health, National Science Foundation (NSF) grant OCE-0430723 and National Institute of Environmental Health Science (NIEHS) grant 1-P50-ES012742-01, ECOHAB program through NSF grant OCE-9808173 and NOAA grant NA96OP0099, and GOMTOX program through NOAA grant NA06NOS4780245

Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

<b>Background</b><p></p> It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.<p></p> <b>Methods</b><p></p> Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.<p></p> <b>Results</b><p></p> There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.<p></p> <b>Conclusions</b><p></p> Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

Improving adherence to medication in stroke survivors (IAMSS): a randomised controlled trial: study protocol

Background: Adherence to therapies is a primary determinant of treatment success, yet the World Health Organisation estimate that only 50% of patients who suffer from chronic diseases adhere to treatment recommendations. In a previous project, we found that 30% of stroke patients reported sub-optimal medication adherence, and this was associated with younger age, greater cognitive impairment, lower perceptions of medication benefits and higher specific concerns about medication. We now wish to pilot a brief intervention aimed at (a) helping patients establish a better medication-taking routine, and (b) eliciting and modifying any erroneous beliefs regarding their medication and their stroke. Methods/Design: Thirty patients will be allocated to a brief intervention (2 sessions) and 30 to treatment as usual. The primary outcome will be adherence measured over 3 months using Medication Event Monitoring System (MEMS) pill containers which electronically record openings. Secondary outcomes will include self reported adherence and blood pressure. Discussion: This study shall also assess uptake/attrition, feasibility, ease of understanding and acceptability of this complex intervention. Trial Registration: Current Controlled Trials ISRCTN3827495

An empirical approach to selecting community-based alcohol interventions:combining research evidence, rural community views and professional opinion

<p>Abstract</p> <p>Background</p> <p>Given limited research evidence for community-based alcohol interventions, this study examines the intervention preferences of rural communities and alcohol professionals, and factors that influence their choices.</p> <p>Method</p> <p>Community preferences were identified by a survey of randomly selected individuals across 20 regional Australian communities. The preferences of alcohol professionals were identified by a survey of randomly selected members of the Australasian Professional Society on Alcohol and Other Drugs. To identify preferred interventions and the extent of support for them, a budget allocation exercise was embedded in both surveys, asking respondents to allocate a given budget to different interventions. Tobit regression models were estimated to identify the characteristics that explain differences in intervention preferences.</p> <p>Results</p> <p>Community respondents selected school programs most often (88.0%) and allocated it the largest proportion of funds, followed by promotion of safer drinking (71.3%), community programs (61.4%) and police enforcement of alcohol laws (60.4%). Professionals selected GP training most often (61.0%) and allocated it the largest proportion of funds, followed by school programs (36.6%), community programs (33.8%) and promotion of safer drinking (31.7%). Community views were susceptible to response bias. There were no significant predictors of professionals' preferences.</p> <p>Conclusions</p> <p>In the absence of sufficient research evidence for effective community-based alcohol interventions, rural communities and professionals both strongly support school programs, promotion of safer drinking and community programs. Rural communities also supported police enforcement of alcohol laws and professionals supported GP training. The impact of a combination of these strategies needs to be rigorously evaluated.</p

Model simulations of the Bay of Fundy Gyre : 2. Hindcasts for 2005–2007 reveal interannual variability in retentiveness

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C09005, doi:10.1029/2008JC004948.A persistent gyre at the mouth of the Bay of Fundy results from a combination of tidal rectification and buoyancy forcing. Here we assess recent interannual variability in the strength of the gyre using data assimilative model simulations. Realistic hindcast representations of the gyre are considered during cruises in 2005, 2006, and 2007. Assimilation of shipboard and moored acoustic Doppler current profiler velocities is used to improve the skill of the simulations, as quantified by comparison with nonassimilated drifter trajectories. Our hindcasts suggest a weakening of the gyre system during May 2005. Retention of simulated passive particles in the gyre during that period was highly reduced. A recovery of the dense water pool in the deep part of the basin by June 2006 resulted in a return to particle retention characteristics similar to climatology. Retention estimates reached a maximum during May 2007 (subsurface) and June–July 2007 (near surface). Interannual variability in the strength of the gyre was primarily modulated by the stratification of the dense water pool inside the Grand Manan Basin. These changes in stratification were associated with mixing conditions the preceding fall–winter and/or advectively driven modification of water mass properties.The preparation of this paper was supported by NSF grant OCE-0430724, NIEHS grant 1P50-ES01274201 (Woods Hole Center for Oceans and Human Health), andNOAAgrant NA06NOS4780245 (GOMTOX). Additional support was provided by NSF grant DMS-0417769