Do implementation issues influence the effectiveness of medications? The case of nicotine replacement therapy and bupropion in UK Stop Smoking Services

Background: Effective pharmacotherapies are available for smoking cessation but their efficacy is established through randomised controlled trials where the medication is supplied direct to subjects. In health care settings patient access to medicines is often less direct. The process for obtaining supplies of nicotine replacement therapy (NRT) is relatively easy for smokers attending National Health Service (NHS) Stop Smoking Services in the UK, whilst this is not necessarily the case for those wishing to using prescription only medicines (e. g. bupropion and varenicline). This study was a direct comparison of the short-term validated abstinence rates of NRT and bupropion in a clinical setting.Methods: Data were routinely collected from 2626 clients setting a quit date (82% of those registering) with two London NHS Stop Smoking Services that offered behavioural support combined with pharmacotherapy (NRT and bupropion).Results: Contrary to what would be expected from multiple randomised controlled trials, the CO-validated 3-4 week abstinence rate in clients using NRT was higher than for bupropion (42% versus 34%, p = .003). This difference persisted even when controlling for smoking characteristics, demographic variables and treatment variables 1.40 (95% CI = 1.08-1.83).Conclusion: Given that the level of behavioural support received by clients on each medication was identical, the most plausible explanation for the difference in effectiveness between NRT and bupropion perhaps lies with how clients of the Stop Smoking Services obtained their medications. Obtaining NRT was relatively easy for clients throughout the study period whilst this was not the case for bupropion. This study suggests that implementation issues and/or self-selection may influence the effectiveness of medications in health care, as opposed to research, settings

A combinatorial proof of the Degree Theorem in Auter space

We use discrete Morse theory to give a new proof of the Degree Theorem in Auter space A_n. There is a filtration of A_n into subspaces A_{n,k} using the degree of a graph, and the Degree Theorem says that each A_{n,k} is (k-1)-connected. This result is useful, for example to calculate stability bounds for the homology of Aut(F_n). The standard proof of the Degree Theorem is global in nature. Here we give a proof that only uses local considerations, and lends itself more readily to generalization.Comment: Final version, in New York J. Math. (http://nyjm.albany.edu/j/2014/20-13.html). Minor changes from v3. 12 pages, 2 figure

VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research

Accurate variant calling in next generation sequencing (NGS) is critical to understand cancer genomes better. Here we present VarDict, a novel and versatile variant caller for both DNA- and RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood. In addition, VarDict performs amplicon aware variant calling for polymerase chain reaction (PCR)-based targeted sequencing often used in diagnostic settings, and is able to detect PCR artifacts. Finally, VarDict also detects differences in somatic and loss of heterozygosity variants between paired samples. VarDict reprocessing of The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma dataset called known driver mutations in KRAS, EGFR, BRAF, PIK3CA and MET in 16% more patients than previously published variant calls. We believe VarDict will greatly facilitate application of NGS in clinical cancer research

Regional Transportation and Land Use Decision Making in Metropolitan Regions: Findings from Four Case Studies

Throughout the United States, metropolitan regions face increasingly complex issues related to transportation and land use. The diffuse nature of decision making creates a need to better coordinate land use and transportation to address issues such as: congestion, infrastructure costs, and greenhouse gas emissions. Key players in this decision making are regional metropolitan planning organizations (MPOs) with transportation planning authority, regional planning responsibilities, and in some cases regional land use planning authority. The goal of this study was to describe and assess efforts by regional agencies to coordinate land use and transportation. Policies and processes in four key topic areas were examined: 1) Governance: formal and informal decision making approaches; 2) Coordination: strategies used to coordinate land use and transportation; 3) Growth Centers: policies to encourage development in higher density centers; and 4) Transportation Improvement Program (TIP): policies to incorporate smart growth criteria in TIP funding decisions

Quality of life in lung cancer patients: does socioeconomic status matter?

BACKGROUND: As part of a prospective study on quality of life in newly diagnosed lung cancer patients an investigation was carried out to examine whether there were differences among patients' quality of life scores and their socioeconomic status. METHODS: Quality of life was measured at two points in time (baseline and three months after initial treatment) using three standard instruments; the Nottingham Health Profile (NHP), the European Organization for Research and Cancer Treatment Quality of Life Questionnaire (EORTC QLQ-C30) and its lung cancer supplement (QLQ-LC13). Socioeconomic status for each individual patient was derived using Carstairs and Morris Deprivation Category ranging from 1 (least deprived) to 7 (most deprived) on the basis of the postcode sector of their address. RESULTS: In all, 129 lung cancer patients entered into the study. Of these data for 82 patients were complete (at baseline and follow-up). 57% of patients were of lower socioeconomic status and they had more health problems, less functioning, and more symptoms as compared to affluent patients. Of these, physical mobility (P = 0.05), energy (P = 0.01), role functioning (P = 0.04), physical functioning (P = 0.03), and breathlessness (P = 0.02) were significant at baseline. However, at follow-up assessment there was no significant difference between patient groups nor did any consistent pattern emerge. CONCLUSION: At baseline assessment patients of lower socioeconomic status showed lower health related quality of life. Since there was no clear trend at follow-up assessment this suggests that patients from different socioeconomic status responded to treatment similarly. In general, the findings suggest that quality of life is not only the outcome of the disease and its treatment, but is also highly dependent on each patients' socioeconomic characteristics

Don't be so hard on yourself! Changes in self-compassion during the first year of university are associated with changes in well-being

Introduction  Well-being declines during the first year of university. We examined if change in self-compassion was indirectly related to change in well-being through change in psychological need satisfaction during the first year of university.  Methods  First year university students (N=189, 77.2% female) completed self-report questionnaires at the beginning of the first semester and approximately five months later. Path analysis and bootstrapping procedures were used to examine residualized change scores.  Results  Change in self-compassion was positively related to (ps<0.05) change in psychological need satisfaction (β=0.49) and negatively related to change in negative affect (β=−0.24). Change in psychological need satisfaction was positively associated (ps<0.05) with change in vitality (β=0.58) and change in positive affect (β=0.52) and negatively associated with change in negative affect (β=−0.29). Change in self-compassion was indirectly related to change in vitality (b=0.56, 95% bootstrapped bias corrected confidence interval (BcCI)[0.38, 0.77]), positive affect (b=0.41, 95%BcCI [0.27, 0.58]), and negative affect (b=−0.26, 95%BcCI[−0.41, −0.13]) through change in psychological need satisfaction.  Conclusions  During the first year of university, change in self-compassion was associated with change in well-being because self-compassion enhanced psychological need satisfaction. Results highlight the potential of enhancing self-compassion during first year university to help mitigate student declines in well-being

General Practitioners' views on the provision of nicotine replacement therapy and bupropion.

BACKGROUND: Nicotine replacement therapies (NRT) and a new drug, bupropion, are licensed in several countries as aids to smoking cessation. General practitioners (GPs) play a crucial role in recommending or prescribing these medications. In the UK there has been discussion about whether the medications should be reimbursable by the National Health Service (NHS). This study assessed English GPs' attitudes towards reimbursement of NRT and bupropion. METHODS: Postal survey of a randomly selected national sample of GPs; 376 GPs completed the questionnaire after one reminder; effective response rate: 53%. There was no difference between the responses of GPs who responded to the initial request and those who responded only after a reminder suggesting minimal bias due to non-response. RESULTS: Attitudes of GPs were remarkably divided on most issues relating to the medications. Forty-three percent thought that bupropion should not be on NHS prescription while 42% thought that it should be (15% did not know); Fifty percent thought that NRT should not be on NHS prescription while 42% thought it should be (8% did not know). Requiring that smokers attend behavioural support programmes to be eligible to receive the medications on NHS prescription made no appreciable difference to the GPs' views. GPs were similarly divided on whether having the medications reimbursable would add unacceptably to their workload or offer a welcome opportunity to discuss smoking with their patients. A principal components analysis of responses to the individual questions on NRT and bupropion revealed that GPs' attitudes could be understood in terms of a single 'pro-con' dimension accounting for 53% of the total variance which made no distinction between the two medications. CONCLUSIONS: GPs in England appear to be divided in their attitudes to medications to aid smoking cessation and appear not to discriminate in their views between different types of medication or different aspects of their use. This suggests that their attitudes are generated by quite fundamental values. Addressing these values may be important in encouraging GPs to adhere more closely to national and international guidelines

House-level risk factors associated with the colonization of broiler flocks with Campylobacter spp. in Iceland, 2001 – 2004

<p>Abstract</p> <p>Background</p> <p>The concurrent rise in consumption of fresh chicken meat and human campylobacteriosis in the late 1990's in Iceland led to a longitudinal study of the poultry industry to identify the means to decrease the frequency of broiler flock colonization with <it>Campylobacter</it>. Because horizontal transmission from the environment is thought to be the most likely source of <it>Campylobacter </it>to broilers, we aimed to identify broiler house characteristics and management practices associated with flock colonization. Between May 2001 and September 2004, pooled caecal samples were obtained from 1,425 flocks at slaughter and cultured for <it>Campylobacter</it>. Due to the strong seasonal variation in flock prevalence, analyses were restricted to a subset of 792 flocks raised during the four summer seasons. Logistic regression models with a farm random effect were used to analyse the association between flock <it>Campylobacter </it>status and house-level risk factors. A two-stage process was carried out. Variables were initially screened within major subsets: ventilation; roof and floor drainage; building quality, materials and repair; house structure; pest proofing; biosecurity; sanitation; and house size. Variables with p ≤ 0.15 were then offered to a comprehensive model. Multivariable analyses were used in both the screening stage (i.e. within each subset) and in the comprehensive model.</p> <p>Results</p> <p>217 out of 792 flocks (27.4%) tested positive. Four significant risk factors were identified. <it>Campylobacter </it>colonization was predicted to increase when the flock was raised in a house with vertical (OR = 2.7), or vertical and horizontal (OR = 3.2) ventilation shafts, when the producer's boots were cleaned and disinfected prior to entering the broiler house (OR = 2.2), and when the house was cleaned with geothermal water (OR = 3.3).</p> <p>Conclusion</p> <p>The increased risk associated with vertical ventilation shafts might be related to the height of the vents and the potential for vectors such as flies to gain access to the house, or, increased difficulty in accessing the vents for proper cleaning and disinfection. For newly constructed houses, horizontal ventilation systems could be considered. Boot dipping procedures should be examined on farms experiencing a high prevalence of <it>Campylobacter</it>. Although it remains unclear how geothermal water increases risk, further research is warranted to determine if it is a surrogate for environmental pressures or the microclimate of the farm and surrounding region.</p

Metropolitan smart growth centers: An assessment of incentive policies in four regions

JTLU vol. 6, no. 2, pp 21-32 (2013)Across the United States, metropolitan areas face challenges related to transportation and land use. An emerging policy in many regions is to promote development around higher-density, mixed-use (smart-growth) centers that create locally accessible nodes; many of these nodes are also linked to transit stops. Some metropolitan planning organizations (MPOs) have developed regional plans and incentive programs to encourage local governments to develop these centers. Incentives include grants as well as funding criteria in transportation improvement programs (TIP) that favor projects supporting centers. This paper assesses these policies as they have been applied in: (1) Puget Sound, Washington; (2) Portland, Oregon; (3) Denver, Colorado; and (4) San Diego, California. For the four regions we reviewed documents, conducted 40 interviews with key individuals, administered an online survey of 450 experts (response rate = 44 percent), and held a two-day forum involving 40 participants. We found that incentive policies by themselves were having a limited impact because they are new and offer small amounts of funding relative to local government needs and market forces. However, when incentives are combined with plans, policies, and transit investment, they provide a significant foundation for promoting growth around centers. There are a number of ways these policies can be improved, and many policies are transferable to other metropolitan regions