BACKGROUND: Tobacco smoking is the cause of many preventable diseases and premature deaths in the UK and around the world. It poses enormous health- and non-health-related costs to the affected individuals, employers, and the society at large. The World Health Organization (WHO) estimates that, globally, smoking causes over US500billionineconomicdamageeachyear.OBJECTIVES:ThispaperexaminesglobalandUKevidenceontheeconomicimpactofsmokingprevalenceandevaluatestheeffectivenessandcosteffectivenessofsmokingcessationmeasures.STUDYSELECTIONSearchmethods:Weusedtwomajorhealthcare/economicresearchdatabases,namelyPubMedandtheNationalInstituteforHealthResearch(NIHR)databasethatcontainstheBritishNationalHealthService(NHS)EconomicEvaluationDatabase;CochraneLibraryofsystematicreviewsinhealthcareandhealthpolicy;andotherhealth−care−relatedbibliographicsources.Wealsoperformedhandsearchingofrelevantarticles,healthreports,andwhitepapersissuedbygovernmentbodies,internationalhealthorganizations,andhealthinterventioncampaignagencies.Selectioncriteria:Thepaperincludescost−effectivenessstudiesfrommedicaljournals,healthreports,andwhitepaperspublishedbetween1992andJuly2014,butincludedonlyeightrelevantstudiesbefore1992.Mostofthepapersreviewedreportedoutcomesonsmokingprevalence,aswellasthedirectandindirectcostsofsmokingandthecostsandbenefitsofsmokingcessationinterventions.Weexcludedpapersthatmerelydescribedtheeffectivenessofaninterventionwithoutincludingeconomicorcostconsiderations.Wealsoexcludedpapersthatcombinesmokingcessationwiththereductionintheriskofotherdiseases.Datacollectionandanalysis:TheincludedstudieswereassessedagainstcriteriaindicatedintheCochraneReviewersHandbookversion5.0.0.Outcomesassessedinthereview:Primaryoutcomesoftheselectedstudiesaresmokingprevalence,directandindirectcostsofsmoking,andthecostsandbenefitsofsmokingcessationinterventions(e.g.,“costperquitter”,“costperlifeyearsaved”,“costperquality−adjustedlifeyeargained,”“presentvalue”or“netbenefits”fromsmokingcessation,and“costsavings”frompersonalhealthcareexpenditure).MAINRESULTS:Themainfindingsofthisstudyareasfollows:1.Thecostsofsmokingcanbeclassifiedintodirect,indirect,andintangiblecosts.About15151 billion. 2. The costs of smoking notwithstanding, it produces some potential economic benefits. The economic activities generated from the production and consumption of tobacco provides economic stimulus. It also produces huge tax revenues for most governments, especially in high-income countries, as well as employment in the tobacco industry. Income from the tobacco industry accounts for up to 7.4% of centrally collected government revenue in China. Smoking also yields cost savings in pension payments from the premature death of smokers. 3. Smoking cessation measures could range from pharmacological treatment interventions to policy-based measures, community-based interventions, telecoms, media, and technology (TMT)-based interventions, school-based interventions, and workplace interventions. 4. The cost per life year saved from the use of pharmacological treatment interventions ranged between US128andUS1,450 and up to US4,400perquality−adjustedlifeyears(QALYs)saved.Theuseofpharmacotherapiessuchasvarenicline,NRT,andBupropion,whencombinedwithGPcounselingorotherbehavioraltreatmentinterventions(suchasproactivetelephonecounselingandWeb−baseddelivery),isbothclinicallyeffectiveandcosteffectivetoprimaryhealthcareproviders.5.Price−basedpolicymeasuressuchasincreaseintobaccotaxesareunarguablythemosteffectivemeansofreducingtheconsumptionoftobacco.A102 to US112perlifeyeargained(LYG)whilereducingsmokingprevalencebyupto30500 and US614perLYG.7.Advertisingmedia,telecommunications,andothertechnology−basedinterventions(suchasTV,radio,print,telephone,theInternet,PC,andotherelectronicmedia)usuallyhavepositivesynergisticeffectsinreducingsmokingprevalenceespeciallywhencombinedtodeliversmokingcessationmessagesandcounselingsupport.However,theoutcomesonthecosteffectivenessofTMT−basedmeasureshavebeeninconsistent,andthismadeitdifficulttoattributeresultstospecificmedia.Thedifferencesinreportedcosteffectivenessmaybepartlyattributedtovaryingmethodologicalapproachesincludingvaryingparametricinputs,differencesinnationalcontexts,differencesinadvertisingcampaignstestedondifferentmedia,anddisparatelevelsofresourcingbetweencampaigns.Duetoitsuniversalreachandlowimplementationcosts,onlinecampaignappearstobesubstantiallymorecosteffectivethanothermedia,thoughitmaynotbeaseffectiveinreducingsmokingprevalence.8.School−basedsmokingprevalenceprogramstendtoreduceshort−termsmokingprevalencebybetween3016,400 to US580,000dependingonthescaleandscopeofintervention.Thecosteffectivenessofschool−basedprogramsshowthatonecouldexpectasavingofapproximatelybetweenUS2,000 and US20,000perQALYsavedduetoavertedsmokingafter2–4yearsoffollow−up.9.Workplace−basedinterventionscouldrepresentasoundeconomicinvestmenttobothemployersandthesocietyatlarge,achievingabenefit−costratioofupto8.75andgenerating12−monthemployercostsavingsofbetween150 and $540 per nonsmoking employee. Implementing smoke-free workplaces would also produce myriads of new quitters and reduce the amount of cigarette consumption, leading to cost savings in direct medical costs to primary health care providers. Workplace interventions are, however, likely to yield far greater economic benefits over the long term, as reduced prevalence will lead to a healthier and more productive workforce. CONCLUSIONS: We conclude that the direct costs and externalities to society of smoking far outweigh any benefits that might be accruable at least when considered from the perspective of socially desirable outcomes (i.e., in terms of a healthy population and a productive workforce). There are enormous differences in the application and economic measurement of smoking cessation measures across various types of interventions, methodologies, countries, economic settings, and health care systems, and these may have affected the comparability of the results of the studies reviewed. However, on the balance of probabilities, most of the cessation measures reviewed have not only proved effective but also cost effective in delivering the much desired cost savings and net gains to individuals and primary health care providers
The P2Y₂ receptor is a uridine/adenosine triphosphate (UTP/ATP)-sensitive G-protein-linked nucleotide receptor that previously has been reported to stimulate the phosphoinositide signaling pathway. Messenger RNA for this receptor has been detected in brain tissue. We have investigated the coupling of the molecularly defined rat P2Y₂ receptor to neuronal N-type Ca²⁺ channels and to M-type K⁺ channels by heterologous expression in rat superior cervical sympathetic (SCG) neurons. After the injection of P2Y₂cRNA, UTP inhibited the currents carried by both types of ion channel. As previously reported [Filippov AK, Webb TE, Barnard EA, Brown DA (1997) Inhibition by heterologously expressed P2Y₂nucleotide receptors of N-type calcium currents in rat sympathetic neurones. Br J Pharmacol 121:849–851], UTP inhibited the Ca²⁺ current (I_{Ca(N)} by up to 64%, with an IC₅₀ of ∼0.5 μm. We now find that UTP also inhibited the K⁺_{M} current (I_{K(M)} by up to 61%, with an IC₅₀ of ∼1.5 μm. UTP had no effect on either current in neurons not injected with P2Y₂ cRNA. Structure–activity relations for the inhibition of I_{Ca(N)} and I_{K(M)} in P2Y₂ cRNA-injected neurons were similar, with UTP ≥ ATP > ITP ≫ GTP,UDP. However, coupling to these two channels involved different G-proteins: pretreatment withPertussis toxin (PTX) did not affect UTP-induced inhibition of I_{K(M)} but reduced inhibition of I_{Ca(N)} by ∼60% and abolished the voltage-dependent component of this inhibition. In unclamped neurons, UTP greatly facilitated depolarization-induced action potential discharges. Thus, the single P2Y₂ receptor can couple to at least two G-proteins to inhibit both Ca²⁺_{N} and K⁺_{M} channels with near-equal facility. This implies that the P2Y₂ receptor may induce a broad range of effector responses in the nervous system
This study examined smokers' awareness of tobacco displays and advertising at point-of-purchase (POP), and whether the association between noticing POP tobacco displays with
prompted purchase of cigarettes and quit intentions varied by socioeconomic status (SES). Logistic regression analyses undertaken with a sample of 2,272 current smokers (aged 18+) from the Netherlands and the UK, who completed the International Tobacco Control Surveys between July 2010 and June 2011. Results showed that overall 76.9% of smokers
were aware of POP tobacco displays comprising 88.3% in the UK and 67.4% in the Netherlands. After adjusting for ovariates, younger smokers in both countries were more
likely to be prompted to purchase cigarettes than older smokers. In the Netherlands, smokers with low SES were more likely to indicate that noticing tobacco displays and
advertising prompted them to purchase cigarettes than those with high SES (OR = 2.34, 95% CI = 1.28 – 4.27), but UK smokers with low SES were less likely to be prompted to
purchase cigarettes (OR = .49, 95% CI = .25 – .95). These findings suggest that retail tobacco displays at POP are
still noticeable, and affect cigarettes purchased and quit
intention, particularly among those in low social groups.
Tobacco legislation should aim at putting cigarettes completely out of sight in retail environments
The relationship between receptor-induced membrane phosphatidylinositol-4'5'-bisphosphate (PIP2) hydrolysis and M-current inhibition was assessed in single-dissociated rat sympathetic neurons by simultaneous or parallel recording of membrane current and membrane-to-cytosol translocation of the fluorescent PIP2/inositol 1,4,5-trisphosphate (IP3)-binding peptide green fluorescent protein-tagged pleckstrin homology domain of phospholipase C (GFP-PLC delta-PH). The muscarinic receptor agonist oxotremorine-M produced parallel time- and concentration-dependent M-current inhibition and GFP-PLC delta-PH translocation; bradykinin also produced parallel time- dependent inhibition and translocation. Phosphatidylinositol-4-phosphate-5-kinase (PI5-K) overexpression reduced both M-current inhibition and GFP-PLC delta-PH translocation by both oxotremorine-M and bradykinin. These effects were partly reversed by wortmannin, which inhibits phosphatidylinositol-4-kinase (PI4-K). PI5-K overexpression also reduced the inhibitory action of oxotremorine-M on PIP2-gated G-protein-gated inward rectifier (Kir3.1/3.2) channels; bradykinin did not inhibit these channels. Overexpression of neuronal calcium sensor-1 protein (NCS-1), which increases PI4-K activity, did not affect responses to oxotremorine-M but reduced both fluorescence translocation and M-current inhibition by bradykinin. Using an intracellular IP3 membrane fluorescence-displacement assay, initial mean concentrations of membrane [PIP2] were estimated at 261 mu M (95% confidence limit; 192-381 mu M), rising to 693 mu M (417-1153 mu M) in neurons overexpressing PI5-K. Changes in membrane [PIP2] during application of oxotremorine-M were calculated from fluorescence data. The results, taken in conjunction with previous data for KCNQ2/3 (Kv7.2/Kv7.3) channel gating by PIP2 (Zhang et al., 2003), accorded with the hypothesis that the inhibitory action of oxotremorine-M on M current resulted from depletion of PIP2. The effects of bradykinin require additional components of action, which might involve IP3-induced Ca2+ release and consequent M-channel inhibition (as proposed previously) and stimulation of PIP2 synthesis by Ca2+-dependent activation of NCS-1
We propose a method by which two radio frequency (RF) communication terminals exchange encryption keys or other data securely. This method draws on the approach developed for quantum key distribution (QKD) for detecting eavesdroppers but our method does not use any quantum properties at all. Instead, by exploiting the effects an eavesdropper has on channel stability, we explore a line-of-sight link radio in which data transfer rates are so high as to approach the Shannon limit. With very steep rises in bit error rate accompanying a small degradation of signal-to-noise limits for certain forward error correction codes, it becomes possible to infer the existence of an eavesdropper before they are able to obtain a complete key. We describe our method and analyse one possible implementation using low density parity check codes with quadrature phase shift keying modulation. The proposed technique is in principle far easier to implement than quantum-based approaches for RF and optical wireless links since the required hardware is readily available and the basic principles are well known and well understood. Finally, we show our method to have a higher key rate and spectral efficiency than those of QKD
In this paper our aim is to show even though access to technology, information or data holds the potential for improved participation, participation is wired into a larger network of actors, artefacts and information practices. We draw on a case study of a weather information system developed and implemented by a non-profit organisation to both describe the configuration of participation, but also critically assess inclusion and exclusion. We present a set of four questions - a basic, practical toolkit - by which we together with the organisation made sense of and evaluated participation in the system
Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir ( 5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log(10) higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo
A fluorescent image analysis procedure to determine the distribution of
species concentration and density in a gas flow is proposed. The fluorescent
emission is due to the excitation of atoms/molecules of a gas that is
intercepted by an electron blade. The intensity of the fluorescent light is
proportional to the local number density of the gas. When the gas flow is a
mixture of different species, this proportionality can be exploited to extract
the contribution associated to the species from the spectral superposition
acquired by a digital camera. This yields a method that simultaneously reveals
species concentrations and mass density of the mixture. The procedure is
applied to two under-expanded sonic jets discharged into a different gas
ambient - Helium into Argon and Argon into Helium - to measure the
concentration and density distribution along the jet axis and across it. A
comparison with experimental and numerical results obtained by other authors
when observing under-expanded jets at different Mach numbers is made with the
density distribution along the axis of the jet. This density distribution
appears to be self-similar.Comment: New figures in portable .eps forma