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Introduction Experts recommend integrating smoking-cessation treatments within U.S. mental health settings, but the population health benefits of doing so have not been estimated. This study simulates the impact of widespread cessation treatment for patients with depression under best-case treatment and maximum potential cessation scenarios. Methods Cessation interventions were simulated for U.S. adult smokers seeing a health professional for depression from 2020 to 2100. Interventions included (1) Any Treatment (behavioral counseling, pharmacological, combination) and (2) Pharmacological Treatment (including counseling), combined with increased mental health service utilization each. These were compared with a maximum potential cessation scenario where all patients with major depression quit smoking. Analyses were conducted in 2016–2020. Results Widespread uptake of Any Treatment among patients with depression would avert 32,000 deaths and result in 138,000 life-years gained by 2100; Any Treatment combined with 100% mental health service utilization would result in 53,000 and 231,000, respectively. Pharmacological Treatment would avert 125,000 deaths, with 540,000 life-years gained. Pharmacological Treatment combined with 100% mental health service utilization would result in 203,000 deaths averted and 887,000 life-years gained. Health gains under best-case treatment scenarios represent modest fractions of those projected under maximum potential cessation scenarios at current mental health service utilization levels (835,000 deaths averted, 3.73 million life-years gained) and at 100% utilization (1.11 million deaths averted, 5.07 million life years gained). Conclusions Providing smoking-cessation treatment to patients with depression and increasing mental health service utilization would reduce the toll of tobacco on this population. These gains would be considerably larger if cessation treatments were more effective.

SUMMARYSmoking rates in people with depression and anxiety are twice as high as in the general population, even though people with depression and anxiety are motivated to stop smoking. Most healthcare professionals are aware that stopping smoking is one of the greatest changes that people can make to improve their health. However, smoking cessation can be a difficult topic to raise. Evidence suggests that smoking may cause some mental health problems, and that the tobacco withdrawal cycle partly contributes to worse mental health. By stopping smoking, a person's mental health may improve, and the size of this improvement might be equal to taking antidepressants. In this article we outline ways in which healthcare professionals can compassionately and respectfully raise the topic of smoking to encourage smoking cessation. We draw on evidence-based methods such as cognitive–behavioural therapy (CBT) and outline approaches that healthcare professionals can use to integrate these methods into routine care to help their patients stop smoking.

Background: There is a common perception that smoking generally helps people to manage stress, and may be a form of 'self‐medication' in people with mental health conditions. However, there are biologically plausible reasons why smoking may worsen mental health through neuroadaptations arising from chronic smoking, leading to frequent nicotine withdrawal symptoms (e.g. anxiety, depression, irritability), in which case smoking cessation may help to improve rather than worsen mental health. Objectives: To examine the association between tobacco smoking cessation and change in mental health. Search Methods: We searched the Cochrane Tobacco Addiction Group's Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, and the trial registries clinicaltrials.gov and the International Clinical Trials Registry Platform, from 14 April 2012 to 07 January 2020. These were updated searches of a previously‐conducted non‐Cochrane review where searches were conducted from database inception to 13 April 2012. Selection Criteria: We included controlled before‐after studies, including randomised controlled trials (RCTs) analysed by smoking status at follow‐up, and longitudinal cohort studies. In order to be eligible for inclusion studies had to recruit adults who smoked tobacco, and assess whether they quit or continued smoking during the study. They also had to measure a mental health outcome at baseline and at least six weeks later. Data Collection and Analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcomes were change in depression symptoms, anxiety symptoms or mixed anxiety and depression symptoms between baseline and follow‐up. Secondary outcomes included change in symptoms of stress, psychological quality of life, positive affect, and social impact or social quality of life, as well as new incidence of depression, anxiety, or mixed anxiety and depression disorders. We assessed the risk of bias for the primary outcomes using a modified ROBINS‐I tool. For change in mental health outcomes, we calculated the pooled standardised mean difference (SMD) and 95% confidence interval (95% CI) for the difference in change in mental health from baseline to follow‐up between those who had quit smoking and those who had continued to smoke. For the incidence of psychological disorders, we calculated odds ratios (ORs) and 95% CIs. For all meta‐analyses we used a generic inverse variance random‐effects model and quantified statistical heterogeneity using I2. We conducted subgroup analyses to investigate any differences in associations between sub‐populations, i.e. unselected people with mental illness, people with physical chronic diseases. We assessed the certainty of evidence for our primary outcomes (depression, anxiety, and mixed depression and anxiety) and our secondary social impact outcome using the eight GRADE considerations relevant to non‐randomised studies (risk of bias, inconsistency, imprecision, indirectness, publication bias, magnitude of the effect, the influence of all plausible residual confounding, the presence of a dose‐response gradient). Main Results: We included 102 studies representing over 169,500 participants. Sixty‐two of these were identified in the updated search for this review and 40 were included in the original version of the review. Sixty‐three studies provided data on change in mental health, 10 were included in meta‐analyses of incidence of mental health disorders, and 31 were synthesised narratively. For all primary outcomes, smoking cessation was associated with an improvement in mental health symptoms compared with continuing to smoke: anxiety symptoms (SMD −0.28, 95% CI −0.43 to −0.13; 15 studies, 3141 participants; I2 = 69%; low‐certainty evidence); depression symptoms: (SMD −0.30, 95% CI −0.39 to −0.21; 34 studies, 7156 participants; I2 = 69%' very low‐certainty evidence); mixed anxiety and depression symptoms (SMD −0.31, 95% CI −0.40 to −0.22; 8 studies, 2829 participants; I2 = 0%; moderate certainty evidence). These findings were robust to preplanned sensitivity analyses, and subgroup analysis generally did not produce evidence of differences in the effect size among subpopulations or based on methodological characteristics. All studies were deemed to be at serious risk of bias due to possible time‐varying confounding, and three studies measuring depression symptoms were judged to be at critical risk of bias overall. There was also some evidence of funnel plot asymmetry. For these reasons, we rated our certainty in the estimates for anxiety as low, for depression as very low, and for mixed anxiety and depression as moderate. For the secondary outcomes, smoking cessation was associated with an improvement in symptoms of stress (SMD −0.19, 95% CI −0.34 to −0.04; 4 studies, 1792 participants; I2 = 50%), positive affect (SMD 0.22, 95% CI 0.11 to 0.33; 13 studies, 4880 participants; I2 = 75%), and psychological quality of life (SMD 0.11, 95% CI 0.06 to 0.16; 19 studies, 18,034 participants; I2 = 42%). There was also evidence that smoking cessation was not associated with a reduction in social quality of life, with the confidence interval incorporating the possibility of a small improvement (SMD 0.03, 95% CI 0.00 to 0.06; 9 studies, 14,673 participants; I2 = 0%). The incidence of new mixed anxiety and depression was lower in people who stopped smoking compared with those who continued (OR 0.76, 95% CI 0.66 to 0.86; 3 studies, 8685 participants; I2 = 57%), as was the incidence of anxiety disorder (OR 0.61, 95% CI 0.34 to 1.12; 2 studies, 2293 participants; I2 = 46%). We deemed it inappropriate to present a pooled estimate for the incidence of new cases of clinical depression, as there was high statistical heterogeneity (I2 = 87%). Authors' Conclusions: Taken together, these data provide evidence that mental health does not worsen as a result of quitting smoking, and very low‐ to moderate‐certainty evidence that smoking cessation is associated with small to moderate improvements in mental health. These improvements are seen in both unselected samples and in subpopulations, including people diagnosed with mental health conditions. Additional studies that use more advanced methods to overcome time‐varying confounding would strengthen the evidence in this area.

BackgroundSmoking rates are significantly higher in people with mental health problems, compared to those without. Negative attitudes towards smoking cessation are widespread in inpatient settings towards patients with severe and enduring mental illness. It is not clear if the same attitudes operate in psychological services towards people with common mental illness. We aimed to understand the concerns and views that patients, therapists, and smoking cessation practitioners may have about integrating smoking cessation treatment into psychological treatment for common mental illness and how these concerns may be overcome.MethodsThematic analysis of 23 in-depth interviews. Interviews took place in Improving Access to Psychological Therapies (IAPT) and smoking cessation services in England. Participants were 11 psychological wellbeing practitioners (PWPs), six IAPT patients with common mental illness, and six smoking cessation advisors.OutcomesNone.FindingsIAPT patients reported psychological benefits from smoking, but also described smoking as a form of therapeutic self-harm. PWPs seem positive towards smoking cessation treatment for people with common mental illness. IAPT PWPs and patients accept evidence that smoking tobacco may harm mental health, and quitting might benefit mental health. PWPs report expertise in helping people with common mental illness to make behavioural changes in the face of mood disturbances and poor motivation. IAPT appears to be a natural environment for smoking cessation intervention. PWPs felt confident to offer smoking cessation treatments to IAPT patients, but thought that a reduction in caseload was required to deliver smoking cessation support in an already pressed service.

Tobacco-related health disparities disproportionately affect smokers with major depression (MD). Although tobacco simulation models have been applied to general populations, to date they have not considered populations with a comorbid mental health condition. We developed and calibrated a simulation model of smoking and MD comorbidity for the US adult population using the 2005–2018 National Surveys on Drug Use and Health. We use this model to evaluate trends in smoking prevalence, smoking-attributable mortality and life-years lost among adults with MD, and changes in smoking prevalence by mental health status from 2018 to 2060. The model integrates known interaction effects between smoking initiation and cessation, and MD onset and recurrence. We show that from 2018 to 2060, smoking prevalence will continue declining among those with current MD. In the absence of intervention, people with MD will be increasingly disproportionately affected by smoking compared to the general population; our model shows that the smoking prevalence ratio between those with current MD and those without a history of MD increases from 1.54 to 2.42 for men and from 1.81 to 2.73 for women during this time period. From 2018 to 2060, approximately 484,000 smoking-attributable deaths will occur among adults with current MD, leading to 11.3 million life-years lost. Ambitious tobacco control efforts could alter this trajectory. With aggressive public health efforts, up to 264,000 of those premature deaths could be avoided, translating into 7.5 million life years gained. This model can compare the relative health gains across different intervention strategies for smokers with MD.

BackgroundSmoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).MethodsWe conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.ResultsThere was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.ConclusionsThese findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.

Background:\ud A core outcome set (COS) is a standardised collection of outcomes to be collected and reported in all trials within a research area. A COS can reduce reporting bias and facilitate evidence synthesis. This is currently unavailable for use in community-based bipolar trials. This research aimed to develop such a COS, with input from a full range of stakeholders.\ud \ud Methods:\ud A co-production approach was used throughout. A longlist of outcomes was derived from focus groups with people with a bipolar diagnosis and carers, interviews with healthcare professionals and a rapid review of outcomes listed in bipolar trials on the Cochrane database. An expert panel with personal and/or professional experience of bipolar participated in a modified Delphi process and the COS was finalised at a consensus meeting.\ud \ud Results:\ud Fifty participants rated the importance of each outcome. Sixty-six outcomes were included in Round 1 of the questionnaire; 13 outcomes were added by Round 1 participants and were rated in Round 2. Seventy-six percent of participants (n = 38) returned to Round 2 and 60 outcomes, including 4 outcomes added by participants in Round 1, received a rating of 7–9 by >70% and 1–3 by

Smoking is the leading avoidable cause of illness and premature mortality. The first-line treatments for smoking cessation are nicotine replacement therapy and varenicline. Meta-analyses of experimental studies have shown that participants allocated to the varenicline group were 1.57 times (95% confidence interval 1.29 to 1.91 times) as likely to be abstinent 6 months after treatment as those allocated to the nicotine replacement therapy group. However, there is limited evidence about the effectiveness of varenicline when prescribed in primary care. We investigated the effectiveness and rate of adverse events of these medicines in the general population.To estimate the effect of prescribing varenicline on smoking cessation rates and health outcomes.Clinical Practice Research Datalink.We conducted an observational cohort study using electronic medical records from the Clinical Practice Research Datalink. We extracted data on all patients who were prescribed varenicline or nicotine replacement therapy after 1 September 2006 who were aged ≥ 18 years. We investigated the effects of varenicline on smoking cessation, all-cause mortality and cause-specific mortality and hospitalisation for: (1) chronic lung disease, (2) lung cancer, (3) coronary heart disease, (4) pneumonia, (5) cerebrovascular disease, (6) diabetes, and (7) external causes; primary care diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression, or prescription for anxiety; weight in kg; general practitioner and hospital attendance. Our primary outcome was smoking cessation 2 years after the first prescription. We investigated the baseline differences between patients prescribed varenicline and patients prescribed nicotine replacement therapy. We report results using multivariable-adjusted, propensity score and instrumental variable regression. Finally, we developed methods to assess the relative bias of the different statistical methods we used.People prescribed varenicline were healthier at baseline than those prescribed nicotine replacement therapy in almost all characteristics, which highlighted the potential for residual confounding. Our instrumental variable analysis results found little evidence that patients prescribed varenicline had lower mortality 2 years after their first prescription (risk difference 0.67, 95% confidence interval -0.11 to 1.46) than those prescribed nicotine replacement therapy. They had similar rates of all-cause hospitalisation, incident primary care diagnoses of myocardial infarction and chronic obstructive pulmonary disease. People prescribed varenicline subsequently attended primary care less frequently. Patients prescribed varenicline were more likely (odds ratio 1.46, 95% confidence interval 1.42 to 1.50) to be abstinent 6 months after treatment than those prescribed nicotine replacement therapy when estimated using multivariable-adjusted for baseline covariates. Patients from more deprived areas were less likely to be prescribed varenicline. However, varenicline had similar effectiveness for these groups.Patients prescribed varenicline in primary care were more likely to quit smoking than those prescribed nicotine replacement therapy, but there was little evidence that they had lower rates of mortality or morbidity in the 4 years following the first prescription. There was little evidence of heterogeneity in effectiveness across the population.Future research should investigate the decline in prescribing of smoking cessation products; develop an optimal treatment algorithm for smoking cessation; use methods for using instruments with survival outcomes; and develop methods for comparing multivariable-adjusted and instrumental variable estimates.Not all of our code lists were validated, body mass index and Index of Multiple Deprivation had missing values, our results may suffer from residual confounding, and we had no information on treatment adherence.This trial is registered as NCT02681848.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inSmoking is the number one avoidable cause of ill health and death. Experiments suggest that more smokers will quit after being given the drug varenicline than with any other smoking cessation treatment. However, most of the experiments used to license varenicline had a relatively short follow-up ( 1 year) and did not necessarily recruit participants who were representative of smokers seen in a general practice in the UK, who tend to be older, are sicker and more likely to have neuropsychiatric illnesses. In this study, we investigated the outcomes of 287,079 patients prescribed varenicline or nicotine replacement therapy (e.g. nicotine patches and gum). We followed each patient for up to 4 years after they received their prescriptions and matched their data to information on deaths from the Office for National Statistics and hospital admissions. We investigated how often these patients subsequently attended their general practitioner, and how often they received a diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression or anxiety in primary care. We found that patients who were prescribed varenicline were much more likely to quit smoking up to 4 years after they received treatment and subsequently attended their general practitioner less frequently. These findings were robust across the three different analysis methods we used. We also found that patients prescribed varenicline were much less likely to be ill or to die than those prescribed nicotine replacement therapy. However, these results may be because the patients who were prescribed varenicline were much healthier before they received the prescription. Therefore, these differences in health are unlikely to be caused by taking varenicline or quitting smoking. In conclusion, varenicline helped patients quit smoking, but there was little causal evidence that prescribing patients varenicline causally reduced rates of mortality or morbidity compared with prescribing nicotine replacement therapy.

Aims To investigate whether smokers prescribed varenicline had lower risks of serious ill-health during the 4 years following treatment compared with those prescribed nicotine replacement therapy (NRT). Design Observational cohort study of electronic medical records. Setting A total of 370 UK general practices sampled from the Clinical Practice Research Datalink. Participants A total of 126 718 patients aged 18 and over who were issued smoking cessation prescriptions between 1 September 2006 and 31 March 2014. Measurements Our primary outcome was all-cause mortality within 2 years of first prescription as indicated by linked Office of National Statistics data. Our secondary outcomes were cause-specific mortality, all-cause, cause-specific hospitalization, primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease (COPD), body mass index and attendance rate to primary care within 2 years of first prescription. Risk differences and 95% confidence intervals were estimated by multivariable adjusted regression and propensity score matched regression. We used instrumental variable analysis to overcome residual confounding. Findings People prescribed varenicline were healthier at baseline than those prescribed NRT in almost all characteristics, highlighting the potential for residual confounding. Our instrumental variable analysis results found that people prescribed varenicline had a similar risk of mortality at 2 years [risk difference per 100 patients treated = 0.67, 95% confidence interval (CI) = -0.11 to 1.46)] to those prescribed NRT, and there were similar rates of all-cause hospitalization, incident primary-care diagnoses of myocardial infarction and COPD. People prescribed varenicline subsequently attended primary care less frequently. Conclusions Smokers prescribed varenicline in primary care in the United Kingdom do not appear to be less likely to die, be hospitalized or experience a myocardial infarction or chronic obstructive pulmonary disease during the following 2 years compared with smokers prescribed nicotine replacement therapy, but they gain more weight and attend primary care less frequently.

Aims. To identify production and processing practices that might reduce Campylobacter numbers contaminating chicken broiler carcasses.Methods and Results. Numbers of campylobacters were determined on carcass neck skins after processing or in broiler house litter samples. Supplementary information that described farm layouts, farming conditions for individual flocks, the slaughterhouse layouts and operating conditions inside plants was collected, matched with each Campylobacter test result. Statistical models predicting the numbers of campylobacters on neck skins and in litter were constructed. Carcass microbial contamination was more strongly influenced by on farm production practices compared with slaughterhouse activities. We observed correlations between the chilling, washing and de-feathering stages of processing and numbers of campylobacters on carcasses. There were factors on farm that also correlated with numbers of campylobacters in litter. These included bird gender, the exclusion of dogs from houses, beetle presence in the house litter and the materials used to construct the house frame.Conclusions. Changes to farming practices have greater potential for reducing chicken carcass microbial contamination compared with processing interventions.Significance and impact of the study. Routine commercial practices were identified that were correlated with lowered numbers of campylobacters. Consequently, these practices are likely to be both cost-effective and suitable for adoption into established farms and commercial processing.

Background and aimsVarenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care.DesignCase–cross‐over study.SettingUK‐based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality data sets.ParticipantsAdult smokers observed during periods when exposed and not exposed to either varenicline or NRT.MeasurementsMain outcomes included suicide, self‐harm, myocardial infarction (MI), all‐cause death and cause‐specific death [MI, chronic obstructive pulmonary disease (COPD)]. In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure during the risk period (90 days prior to the event) with the chance of exposure during an earlier single reference period (91–180 days prior to the event) or multiple 90‐day reference periods to increase statistical power.FindingsIn the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, while NRT was associated with MI [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.18–1.67]. Using multiple reference periods, varenicline was associated with an increased risk of self‐harm (OR = 1.32, 95% CI = 1.12–1.56) and suicide (OR = 3.56, 95% CI = 1.32–9.60) but a reduction in all‐cause death (OR = 0.75, 95% CI = 0.61–0.93). NRT was associated with MI (OR = 1.54, 95% CI = 1.36–1.74), self‐harm (OR = 1.30, 95% CI = 1.18–1.44) and deaths from MI (OR = 1.53, 95% CI = 1.11–2.10), COPD (OR = 1.33, 95% CI = 1.14–1.56) and all causes (OR = 1.28, 95% CI = 1.18–1.40) when using multiple reference periods.ConclusionsThere appear to be positive associations between (1) nicotine replacement therapy (NRT) and myocardial infarction, death and risk of self‐harm and (2) varenicline and increased risk of self‐harm and suicide, as well as a negative association between varenicline and all‐cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (nicotine replacement therapy is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self‐harm).

This study aimed to determine the effectiveness and safety of varenicline versus NRT for smoking cessation in people with neurodevelopmental disorders, compared to those without, at up to four years after exposure. We analysed electronic medical records from the Clinical Practice Research Datalink using three different statistical approaches: multivariable logistic regression, propensity score matching (PSM), and instrumental variable analysis. Exposure was prescription of varenicline versus NRT and the primary outcome was smoking cessation at 2-years. We included 235,314 people aged 18 and above with eligible smoking cessation prescriptions in the effectiveness analysis. Smokers with neurodevelopmental disorders were 48% less likely (95% confidence interval: 42%, 54%) to be prescribed varenicline than NRT, compared to smokers without neurodevelopmental disorders. At 2-year follow-up, smokers with neurodevelopmental disorders prescribed varenicline were 38% more likely to quit smoking (95% confidence interval: 6%, 78%). Similar results were obtained using PSM and instrumental variable analyses. There was little evidence showing that varenicline increased the likelihood of mental health related adverse events in people with neurodevelopmental disorders. Varenicline is less likely to be prescribed to people with neurodevelopmental disorders despite results suggesting it is more effective than NRT and little evidence of increased likelihood of mental health related adverse events.

IntroductionSmoking among persons with a mental health disorder is associated with inequitable health, social and economic burden. Randomised controlled trials (RCTs) are considered the gold standard design for the assessment of healthcare intervention efficacy/effectiveness. However, many RCTs of smoking interventions for persons with a mental health disorder lack rigour due to low participant retention. No systematic review has pooled retention rates in randomised trials of smoking interventions for persons with a mental health disorder or explored associated factors. The aims of the systematic review will therefore be to: (1) summarise overall rates of participant retention in smoking cessation and reduction trials involving persons with a mental health disorder (including for experimental and control groups separately) and (2) determine if retention rates vary according to participant, environmental, researcher and study factors.Methods and analysisPsycINFO, EMBASE, MEDLINE, CENTRAL and The Cochrane Tobacco Addiction Review Group Specialised Register will be searched for reports of RCTs of outpatient smoking cessation or reduction interventions for adults with a mental health disorder. The search terms will include MeSH terms and free text words, and there will be no language or date restrictions. All databases will be searched from inception to present. Data will be analysed using the Mantel-Haenszel fixed-effect model, and where substantial heterogeneity (I2>50%) is detected, DerSimonian & Laird inverse-variance random effects model. Pooled estimates and 95% CIs will be calculated for overall participant retention rates and for intervention and control trial arms separately. Associations between participant retention and participant, environmental, researcher and study factors will be assessed via subgroup analyses and, where sufficient data are obtained, meta-regression.Ethics and disseminationThis study does not require ethical approval. The findings of this review will be disseminated via publication in a peer-reviewed open access medical journal and presentations at international scientific meetings.

ObjectivesOur primary objective was to estimate smoking prevalence and prescribing rates of varenicline and nicotine replacement therapy (NRT) in people with and without general practitioner (GP)-recorded dementia. Our secondary objective was to assess and compare quit rates of smokers with versus without GP-recorded dementia who were prescribed varenicline or NRT for smoking cessation.DesignA retrospective cohort study based on the analysis of electronic medical records within the Clinical Practice Research Datalink (2007–2015).Setting683 general practices in England.ParticipantsPeople with and without GP-recorded dementia, aged 18 years and have a code indicating that they are a current smoker.InterventionIndex prescription of varenicline or NRT (from 1 September 2006).Outcome measuresThe primary outcomes were smoking prevalence and prescribing rates of varenicline and NRT (2007–2015). The secondary outcome was smoking cessation at 2 years.ResultsAge and sex-standardised prevalence of smoking was slightly higher in people with GP-recorded dementia than in those without. There were 235 314 people aged 18 years and above prescribed NRT or varenicline. Among smokers with GP-recorded dementia (N=447), 409 were prescribed NRT and 38 varenicline. Smokers with GP-recorded dementia were 74% less likely (95% CI 64% to 82%) to be prescribed varenicline than NRT, compared with smokers without GP-recorded dementia. Compared with people without GP-recorded dementia, people with GP-recorded dementia had consistently lower prescribing rates of varenicline from 2007 to 2015. Two years after prescription, there was no clear evidence for a difference in the likelihood of smoking cessation after prescription of these medications between individuals with and without dementia (OR 1.0, 95% CI 0.8 to 1.2).ConclusionsBetween 2007 and 2015, people with GP-recorded dementia were less likely to be prescribed varenicline than those without dementia. Quit rates following prescription of either NRT or varenicline were similar in those with and without dementia.

Objective We conducted a prospective cohort study of the Clinical Practice Research Database to estimate rates of varenicline and nicotine replacement therapy (NRT) prescribing and the relative effects on smoking cessation, and mental health. Methods We used multivariable logistic regression, propensity score matched regression, and instrumental variable analysis. Exposure was varenicline or NRT prescription. Mental disorders were bipolar, depression, neurotic disorder, schizophrenia, or prescriptions of antidepressants, antipsychotics, hypnotics/anxiolytics, mood stabilizers. Outcomes were smoking cessation, and incidence of neurotic disorder, depression, prescription of antidepressants, or hypnotics/anxiolytics. Follow-ups were 3, 6, and 9 months, and at 1, 2, and 4 years. Results In all patients, NRT and varenicline prescribing declined during the study period. Seventy-eight thousand four hundred fifty-seven smokers with mental disorders aged ≥18 years were prescribed NRT (N = 59 340) or varenicline (N = 19 117) from September 1, 2006 to December 31, 2015. Compared with smokers without mental disorders, smokers with mental disorders had 31% (95% CI: 29% to 33%) lower odds of being prescribed varenicline relative to NRT, but had 19% (95% CI: 15% to 24%) greater odds of quitting at 2 years when prescribed varenicline relative to NRT. Overall, varenicline was associated with decreased or similar odds of worse mental health outcomes than NRT in patients both with and without mental disorders, although there was some variation when analyses were stratified by mental disorder subgroup. Conclusions Smoking cessation medication prescribing may be declining in primary care. Varenicline was more effective than NRT for smoking cessation in patients with mental disorders and there is not clear consistent evidence that varenicline is adversely associated with poorer mental health outcomes. Implications Patients with mental disorders were less likely to be prescribed varenicline than NRT. We triangulated results from three analytical techniques. We found that varenicline was more effective than NRT for smoking cessation in patients with mental disorders. Varenicline was generally associated with similar or decreased odds of poorer mental health outcomes (ie, improvements in mental health) when compared with NRT. We report these findings cautiously as our data are observational and are at risk of confounding.

ObjectiveTo examine the direction and magnitude of the relation between family meal frequency and dietary and family functioning outcomes in children (aged 2–18 years).DesignSystematic literature review with meta-analysis.MethodsIndependent electronic searches, 1 for each outcome of interest, were conducted across 5 databases: PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, and PsycINFO. Studies were included if they were peer-reviewed and published in English in the US through December 2018.Main Outcome MeasuresDiet and family functioning.ResultsDietary outcomes showed some evidence of a positive association between family meal frequency and fruits, vegetables, fruits and vegetables, sugar-sweetened beverages, and the Healthy Eating Index. There was less clear evidence of this relation in snacks, fast food, and desserts. A positive association was found between family meal frequency or dinner family meal frequency and family functioning outcomes. All studies included had cross-sectional and longitudinal study designs.Conclusions and ImplicationsThere is some evidence to show a positive relation between family meal frequency and dietary outcomes. There is stronger evidence for the relation with family functioning outcomes. Most articles included in the systematic reviews were excluded from meta-analysis owing to inadequate data and high methodological diversity across exposure and outcome variables.

A major barrier to clinicians referring service users with psychosis for psychological therapies is the belief that they will not engage. We investigated therapy receipt after discharge, in a sample of service users who had already demonstrated willingness to engage in psychological therapy during an inpatient admission. Only one-third of service users (33%; 16/48) received at least 1 session of evidence-based therapy at 6-month follow-up after discharge. Therapy receipt was more common for service users with (i) lower delusional distress at discharge, (ii) Black and Minority Ethnic (BME) background, and (iii) discharged to an Early Intervention (EI) service.

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Background Evidence shows that the relationship between depression and smoking may be bi-directional, with smoking increasing the risk for subsequent depression, and vice versa—translating into significantly higher smoking rates among those with depression compared to the general population. Computational models can be used to assess trends in smoking but have not been utilized to examine populations with behavioral health comorbidities. We develop the first joint model of smoking and depression, projecting future smoking patterns under a 'status quo' scenario. Methods We use a compartmental model to simulate individuals transitioning across smoking and depressive states from birth to age 99 or death. The model is calibrated to reproduce smoking and depression data from the 2005-2014 U.S. National Survey on Drug Use and Health. Current smokers report smoking within the past year and smoked at least 100 cigarettes in their lifetime while those with depression report a major depressive episode in the past year. Parameters for the effects of smoking and depression on each other were drawn from existing literature. [Smoking and depression model diagram] Results From 2015 to 2050, smoking prevalence among women with depression is projected to decline by 43.5% (27.6% to 15.6%), compared to 46.9% (17.9% to 9.5%) for women who report never having had a depressive episode. Among men with depression, smoking prevalence is expected to decline by 32.0% (34.4% to 23.4%), compared to 39.0% (24.1% to 14.7%) for men who report never being depressed. The likelihood of smoking among those with depression is projected to increase. Conclusions This model can be used to examine trends and identify optimal interventions to address smoking disparities by depressive status. Smoking prevalence among people with depression is expected to decline, though not as rapidly as for those without depression. In the absence of population-level strategies, smoking and tobacco-related diseases will continue to further disproportionately burden people with depression.

Background: There is limited evidence about the effectiveness of varenicline and nicotine replacement therapy (NRT) for long-term smoking cessation in primary care, or whether the treatment effectiveness differs by socioeconomic position (SEP). Therefore, we estimated the long-term effectiveness of varenicline versus NRT ( > 2 years) on smoking cessation, and investigated whether effectiveness differs by SEP. Methods: This is a prospective cohort study of electronic medical records from 654 general practices in England, within the Clinical Practice Research Datalink, using three different analytical methods: multivariable logistic regression, propensity score matching and instrumental variable analyses. Exposure was prescription of varenicline versus NRT, and the primary outcome was smoking cessation at 2 years' follow-up; outcome was also assessed at 3, 6, and 9 months, and at 1 and 4 years after exposure. SEP was defined using the Index of Multiple Deprivation. Results: At 2 years, 28.8% (N=20 362/70 610) of participants prescribed varenicline and 24.3% (N=36 268/149 526) of those prescribed NRT quit; adjusted odds ratio was 1.26 [95% confidence interval (CI): 1.23 to 1.29], P < 0.0001. The association persisted for up to 4 years and was consistent across all analyses. We found little evidence that the effectiveness of varenicline differed greatly by SEP. However, patients from areas of higher deprivation were less likely to be prescribed varenicline; adjusted odds ratio was 0.91 (95% CI: 0.90 to 0.92), P < 0.0001. Conclusions: Patients prescribed varenicline were more likely to be abstinent up to 4 years after first prescription than those prescribed NRT. In combination with other evidence, the results from this study may be used to update clinical guidelines on the use of varenicline for smoking cessation.

IntroductionTobacco is the world’s leading preventable cause of disease and death. People with depression are twice as likely to smoke and are less responsive to standard tobacco treatments as compared with the general population. A Cochrane systematic review of randomised controlled trials of smoking cessation treatment for smokers with current or historical depression found that adding mood management to usual smoking treatment improved quit rates. However, the review did not examine if variation in intervention delivery or intervention functions impacted on treatment effectiveness.With the aim of providing information to develop tailored approaches to treating smoking for people with current depression, we will add-on to the Cochrane review in three ways: (1) use the Template for Intervention Description and Replication checklist to determine if variations in mood management delivery have impact on intervention effectiveness, (2) use the Taxonomy of Behaviour Change techniques for smoking cessation to examine which behaviour change functions are most effective for smoking cessation in people with current depression and (3) examine the difference in change in depression scores between intervention and control arms.Methods and analysisWe will include randomised controlled trials of smokers with current depression as identified by a previous Cochrane review and the in-progress update of this Cochrane review. We will use meta-regression to examine (1) if variations in delivery of mood management impact on smoking cessation intervention effectiveness, (2) determine which behaviour change functions are most effective for smoking cessation and (3) use meta-analysis of the difference in change in depression scores between treatment arms from baseline to follow-up to determine if offering smoking cessation treatment causes psychological harm.Ethics anddisseminationEthical approval is not required for this study. We will disseminate the findings of this work at national and international conferences, and to relevant patient panels.PROSPERO registration numberCRD42017070741.

Design and Shielding of Radiotherapy Treatment Facilities provides readers with a single point of reference for protection advice to the construction and modification of radiotherapy facilities. The book assembles a faculty of national and international experts on all modalities including megavoltage and kilovoltage photons, brachytherapy and high-energy particles, and on conventional and Monte Carlo shielding calculations. This book is a comprehensive reference for qualified experts and radiation-shielding designers in radiation physics and also useful to anyone involved in the design of radiotherapy facilities.

SUMMARY The purpose of this study was to determine whether SEPs would improve the predictive power of VEPs for the prognosis of asphyxiated infants. 57 term infants had SEPs and VEPs recorded during the first three days of life, during the first week and at follow-up visits. All survivors have been followed for 18 to 24 months. 34 had a normal outcome, 12 had severe neurological sequelae and 11 died. The SEPs had both high sensitivity (96 per cent) and negative predictive power (97 per cent); normal SEPs virtually guaranteed normal outcome. The VEPs had both a specificity and positive predictive power of 100 per cent; abnormal VEPs guaranteed abnormal outcome. Both together had a higher predictive power than either alone. The combination of VEPs and SEPs yields a powerful means of prognostication for term asphyxiated infants; the results suggest that both be included in the assessment of this population. RESUME Validite pronostique des PES (potentiels evoques somesthesiques) et PEV (potentiels evoques vistiels) apres anoxie cerebrale neonatale a terme Le but de cette etude etait de determiner si les PES pouvaient ameliorer la valeur predictive des PEV dans le pronostic des enfants anoxiques. 57 nourrissons beneficierent de PES et PEV durant les trois premiers jours de vie, la premiere semaine et lors des suivis ulterieurs. Le devenir fut normal dans 34 cas, il y eu 12 cas de sequelles neurologiques lourdes et 11 deces. Les PES presenternt a la fois une sensibiliteelevee (96 pour cent) et une valeur predictive negative (97 pour cent); un PES normal etait pratiquement la garantie d'un devenir normal. Les PEV avaient a la fois une specificite et une valeur predictive de 100 pour cent; des PEV anormaux etaient totalement relies a un devenir anormal. Les deux examens reunis avaient une valeur predictive meilleure que l'un ou l'autre des examens isoles. La combinaison de PES et PEV est un element puissant de pronostic pour les enfants anoxiques au terme; ces resultats suggerent que les deux examens soient pratiquees dans I'evaluation de la population a risque. ZUSAMMENFASSUNG Prognostische'Zuverlassigkeit von SEPs und VEPs fur reif geborene Kinder mit Asphyxie Es war das Ziel dieser Arbeit festzustellen, ob SEPs die Aussage-Kraft von VEPs fur die Prognose von Kindern mit Asphyxie verbesern konnen. Bei 57 reif geborenen Kindern wurden in den ersten drei Lebenstagen, in der ersten Wochen und bei Kontrolluntersuchungen SEPs und VEPs abgeleitet. Alle Uberlebenden wurden uber 18 bis 24 Monate nachuntersucht. 34 waren gesund, 12 hatten schwere ne'urologische Folgeerscheinungen und 11 starben. Die SEPs hatten eine hohe Sensitivitat (96 Prozent) und eine negative prognostische Aussagekraft (97 Prozent); normale SEPs garantierten sozusagen eine normale Entwicklung. Die VEPs hatten eine Spezifitat und eine positive prognostische Aussagekraft von 100 Prozent; abnorme VEPs garantierten eine abnorme Entwicklung. Beide zusammen hatten eine hohere prognostische Aussagekraft als jedes fur sich allein. Die Kombination von VEPs und SEPs ergibt einen starken prognostichen Parameter fur reif geborene Kinder mit Asphyxie; die Ergebnisse sprechen dafur, das beide zur Beurteilung dieser Kinder herangezogen werden. RESUMEN Fiabilidad pronostica del SEP y del VEP en lactantes a termino con asfixia El proposito de este estudio fue el determinar si el SEP podria mejorar la capacidad predictiva del VEP en el pronostico de lactantes con asfixia. A 57 ninos a termino se les registro el SEP y el VEP durante los tres primeros dias de vida, durante la primera semana y en las visitas siguientes. Todos los supervivientes habian sido seguidos durante 18 a 24 meses. 34 habian seguido un curso normal, 12 tenian secuelas neurologicas graves y 11 murieron. El SEP tenia al mismo tiempo una alta sensibilidad (96 por ciento) y una capacidad predictiva negativa (97 por ciento); un SEP normal virtualmente garantizaba un curso normal. El VEP tenia una especificidad y una capacidad predictiva positiva del 100 por ciento; un VEP anormal garantizaba un curso anormal. Ambos conjuntamente tenian una capacidad predictiva superior a cada uno por separado. La combinacion de VEP y SEP constituye un poderoso medio de pronostico en los lactantes con asfixia; los resultados sugieren que ambos deben ser incluidos en la evalucion de este tipo de poblacion.

Background It is possible that some people who quit smoking experience improved mental health after cessation and therefore remain abstinent, whereas other people who quit may experience worse mental health after cessation and therefore be more likely to relapse to smoking. Thus, in this study we aimed to examine the association between an enduring change in mental health following the cessation period and future risk of relapse. Methods A secondary analysis of prospective data pooled from five placebo-controlled randomised trials for smoking reduction conducted in Europe, USA and Australia. Change in mental health (SF-36, scored 0–100) was measured from baseline to four months for those who were biologically-validated as point-prevalence abstainers at four month follow-up. Thereafter we assessed whether relapse to smoking by 12 months was more likely in those whose mental health had worsened between baseline and four months compared with those who saw no change or an improvement. Results After adjustment for baseline mental health and other major covariates, there was no greater tendency to relapse at 12 months for those whose mental health worsened after cessation compared with those who had no change or an improvement. The odds ratio and 95 % confidence interval was 1.01 (0.97 to 1.05). Conclusions People whose mental health worsens after smoking cessation are at no greater risk of subsequent relapse to smoking than those whose mental health stays the same or improves. Electronic supplementary material The online version of this article (doi:10.1186/s12889-015-2473-z) contains supplementary material, which is available to authorized users.

ObjectivesThe association between smoking reduction and mental health is of particular interest given that many smokers report that smoking offers mental health benefits. We aimed to assess the association between smoking reduction and change in mental health using two different analytical approaches to determine if there was any evidence of an association. There were no prior hypotheses.DesignA secondary analysis of prospective individual level patient data from 5 merged placebo-controlled randomised trials of nicotine replacement therapy for smoking reduction.ParticipantsAll participants were adult smokers, selected because they wanted to reduce but not stop smoking, and had smoked for at least 3 years. Participants were excluded if they were pregnant, breastfeeding, under psychiatric care, deemed to be unfit by a general practitioner, or part of a cessation programme. 2066 participants were enrolled in the trials, 177 participants were biologically validated as prolonged reducers, and 509 as continuing smokers at both 6-week and 18-week follow-ups.Primary outcomeChange in mental health from baseline to an 18-week follow-up was measured using the emotional well-being subscale on the Short Form Health Survey-36.ResultsAfter adjustment for confounding variables, the differences for reducers compared with continuing smokers were: regression modelling −0.6 (95% CI −4.4 to 3.2) and propensity score matching 1.1 (95% CI −2.0 to 4.1).ConclusionsSmoking reduction, sustained for at least 12 weeks, was not associated with change in mental health, suggesting that reducing smoking was no better or worse for mental health than continuing smoking. Clinicians offering smoking reduction as a route to quit can be confident that, on average, smoking reduction is not associated with negative change in mental health.

Ground-penetrating radar is becoming increasingly popular for use as a non-destructive assessment method for investigating reinforced concrete structures. The amount of data collected however can be very large and take a significant level of subjective experience to interpret. This study focuses upon the use of a neural network approach to automate and facilitate the post-processing of ground penetrating radar results. The radar data is reduced to a simplified data set by using an edge detection routine. Signal reflections from reinforcing bars displaying a hyperbolic image format are detected using a multi-layer perceptron (MLP) network with a single hidden layer containing 8 nodes to recognise a simplified hyperbolic shape. Training and testing of the network was carried out making use of an emulsion analogue tank, simulating the properties of concrete, and using real concrete specimens. The results showed that the use of a MLP neural network approach could be quite effective in automating the identification and location of embedded steel reinforcing bars from a radar investigation. Accurate estimation of depth, or cover, requires a reliable knowledge of the dielectric properties of the concrete, and recent work using a specially-developed wideband horn antenna for direct determination of in situ properties is also outlined.

In this paper, we examine ionospheric plasma depletions (or bubbles) and irregularities observed by photometers and a ground-based receiver of the global positioning system (GPS) both located in Brazil, South America. A simultaneous observation reveals that when the ionospheric plasma becomes depleted, the GPS total electron content decreases and the associated phase fluctuations grow. Statistical results show that the plasma bubbles and the significant GPS phase fluctuations generally occur during October-March. The solar activity variation is not obvious in either observation except during the equinoctial months. The GPS phase fluctuations suggest that the most pronounced ionospheric irregularities appear between 20:00 and 01:00 LT, which generally agree with previous ionospheric bubble observations.

There is an increased interest in the use of ground-penetrating radar as a non-destructive assessment method for investigating reinforced concrete structures. The method involves the collection of a large volume of data, which takes a skilled operative significant time to interpret. A neural network approach has been used in this work to automate and facilitate this post-processing procedure. In addition, a novel technique for the estimation of the diameter of reinforcing bars is presented. This method involves the comparison of signals received with the transducer in a fixed location above the bar but with different orientations of the transducer axis. The radar data is first pre-processed by use of an edge detection routine and then the resulting images compared for different orientations. An emulsion analogue tank, simulating the properties of concrete, was used to generate training data and the resulting neural network was then tested on readings from bars in concrete slabs. The results show that data taken with the transducer axis parallel and then orthogonal to the bar can be analysed by means of a MLP neural network to effectively estimate the diameter of embedded steel reinforcing bars.

Smoking is the world’s leading cause of preventable illness and death (1). Accounting for 6 million deaths annually, 600,000 of smoking-related deaths occur in non-smokers exposed to second hand smoke (2). A major risk factor for six of the eight leading causes of death worldwide, smoking affects nearly every organ of the body (3). Smokers usually underestimate their risk of smoking-related diseases (4). Awareness of health concerns are a major motivator to quit (5,6). One in every two smokers will die from their addiction, however quitting substantially reduces this risk (7,8). Making an attempt to quit smoking and then sustaining abstinence are both equally important in ultimately succeeding quitting. Smokers frequently attempt quitting several times unsuccessfully before achieving long-term abstinence (9,10). Smokers who seek support in quitting are much more likely to quit than those who try to quit alone, and the most effective aid for achieving smoking cessation is medication (e.g., nicotine replacement therapy, or varenicline) coupled with tailored behavioral support from specialist stop smoking services, like the National Health Service Stop Smoking Services (NHS SSS) in the UK (11-13).

Juvenile (12-152 g) shortfinned eels Anguilla australis and longfinned eels A. dieffenbachii caught in New Zealand streams were fed squid mantle Nototodarus spp. 4 days per week in laboratory experiments. A linear multiple regression equation showed the amount of food eaten (0-2.7% w day -1 ) explained 77.7% of the variation in specific growth rates ( - 0.60 to +1.07% w day -1 ) among individual eels, while previous growth rates, water temperature (10.0-20.6°C), and eel weight (12-152 g) explained a further 5.6, 1.4 and 0.8%, respectively. Growth in length ranged from -0.3 to +0.9 mm day - 1 . Eels which were starved and then given high rations grew substantially faster than expected. Once growth rates were adjusted for differences in ration and other factors, there were no significant differences in growth rates between species or individual fish. Growth of shortfinned eels fed maximum rations of commercial eel food depended on fish size and water temperatures and ceased below 9.0° C. Growth rates in the wild were substantially less than the maximum possible, after seasonal changes in water temperatures were taken into account, indicating that food supplies and not low water temperatures were controlling growth rates in the wild.

We present an overview of the performance of the High Speed Photometer (HSP), one of the five original instruments on the Hubble Space Telescope (HST). As its name implies, the HSP was designed for precise high time resolution photometry from visual to ultraviolet wavelengths; sample times as short as 10.7 μs were possible. Three image dissectors along with 23 different broad‐ and narrowband filters spanning the spectral range from 1200 to 7500 A were used for photometry of stars and galaxies. A fourth image dissector with associated polarization analyzers allowed the measurement of broadband linear polarization at near‐ultraviolet wavelengths. Simultaneous observations in the blue and red could be made using one of the dissectors and a photomultiplier. Except for an instability in the sensitivity of one of the image dissectors and a reduced throughput in a specialized observational mode, the instrument met or exceeded operational specifications until it was removed from HST in 1993 December. The...

Artificial neural network models are now being widely used in various areas of statistical research. Nevertheless, there is a certain degree of reluctance amongst members of the business profession in applying neural networks to business analysis. One of the major causes of scepticism is the inability of the models to provide explanation on how they reach their decisions. The current experiment is concerned with solving this problem by developing a framework for establishing the impacts of the input variables on the network output. The framework was tested on a feedforward neural network model for turnover forecasting which was developed in co-operation with a British retailer using real world marketing data. The results obtained are compared with those from a sensitivity analysis.

Artificial neural networks are now being extensively used in the area of marketing analysis, as they are well suited to this type of non-linear problem. A retail company planned to improve its performance by using neural networks to predict turnover, and data used in the experiment was provided by the company. The study compares the performance of a combination of neural networks to that of a single neural network. The results show that backpropagation neural networks are effective tools which can give good results in solving a non-linear prediction problem, even when data is poorly represented.

Objective : Recently, transesophageal echocardiography (TEE) has been proposed as the standard for the diagnosis of traumatic disruption of the aorta (TDA), replacing aortography. The purpose of this study was to evaluate the accuracy and practicality of TEE in the diagnosis of TDA. Design : Prospective clinical trial. Materials and Methods : Patients with blunt trauma admitted with a suspected diagnosis of TDA were evaluated with TEE and aortography. Measurements and Main Results : Thirty-four patients were evaluated with TEE and aortography. TEE was unsuccessful in five patients (15%). Of the remaining 29 patients, TEE results were true-positive in four and true-negative in 20. TEE results were false-positive in two patients, and three injuries were missed (two were proximal to the left subclavian artery, and one was a localized aortic disruption). Sensitivity and specificity of TEE were 57% and 91%, respectively, compared with aortography, for which sensitivity was 89% and specificity was 100%. Conclusion : Although the use of TEE in the diagnosis of TDA has several advantages, it is not more accurate than aortography. TEE should not replace aortography as the standard for the diagnosis of TDA.

Background Regulators have issued warnings about the potential adverse effects of the smoking cessation medication varenicline. However, there is little evidence of the long-term effects of varenicline when prescribed in everyday clinical practice. We aimed to investigate the association of varenicline and nicotine replacement therapy (NRT) with adverse outcomes when prescribed in primary care. Methods Using the Clinical Practice Research Datalink (CPRD), we conducted an observational cohort study of electronic medical records and linked mortality and hospital admission data of 126 718 primary care patients in the UK prescribed varenicline (41 742) and NRT (84 976). We used three approaches to overcome potential residual confounding: multivariable adjusted regression, propensity score matching, and instrumental variable regression. The exposure was first prescription of varenicline or nicotine replacement therapy. The primary outcome was all-cause mortality 2 years after first prescription. Secondary outcomes were mortality from cardiovascular and respiratory disease, all-cause hospital admission and for cardiovascular and respiratory disease, incident primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease, and frequency of primary care attendance. Findings In multivariable adjusted analysis, mortality was lower among patients prescribed varenicline than in those prescribed NRT (OR 0·78, 95% CI 0·69 to 0·87; p Interpretation There was little evidence of a substantial increase in risk of adverse outcomes in patients prescribed varenicline as part of their standard clinical care. The regulatory warnings associated with varenicline do not accurately reflect the scientific evidence and should be reconsidered by policy makers and regulators. Funding The research described in this paper was funded by the Medical Research Council (MR/N01006X/1), the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project number 14/49/94). KHT is funded by a clinical lectureship award from the NIHR. RMM is supported by Cancer Research UK (programme grant C18281/A19169) (the Integrative Cancer Epidemiology Programme). TJ is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West, University Hospitals Bristol NHS Foundation Trust. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the abstract for submission.

A simplified version of the specific contact resistance measurement scheme of G. K. Reeves [Solid State Electronics 23, 487 (1980)] has been developed. Its applicability to semiconducting diamond is demonstrated using four sample types: epitaxial films doped to mid 1019 acceptors/cm3 on 〈100〉 and 〈110〉 type IIa substrates; type IIb diamonds 0.25 mm thick, and type IIb diamonds thinned to 0.035–0.05 mm thick. The ohmic contacts were based on a solid‐state annealing process using carbide forming metals. The measured specific contact resistance depends mainly on the doping level in the diamond. Measured values ranged from 8×10−6 Ω cm2 for heavily doped films to 1×10−2 Ω cm2 for lightly doped bulk samples. A simple analysis shows that the contacts to highly doped layers are suitable for device applications.

Background The benefits of hypothermia for preventing ischemic injury are well known, but its application in surgery to protect the whole body during procedures requiring circulatory arrest is currently limited to Methods and Results With the use of extracorporeal cardiac bypass, 14 adult dogs were exsanguinated during cooling; 11 dogs were blood substituted using in combination the “purge” and “maintenance” solutions (group 1), and 3 dogs were perfused throughout with the “purge” solution alone as controls (group 2). After cardiac arrest, the solutions were continuously circulated for 3 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{1}{2}\) \end{document} hours by the extracorporeal pump (flow rate, 40 to 85 mL · kg −1 · min −1 ; mean arterial blood pressure, 25 to 40 mm Hg). The temperature was maintained at P P P =.03), and for CK-BB, the group 1 value was 108±22 versus 617±154 for group 2 ( P =.03). Neurological evaluation using deficit scores (NDS) was based on a modification of the Glasgow Coma Scale score: 0, normal; 1, minimal abnormality; 2, weakness; 3, paralysis; 4, coma; and 5, death. At days 1 and 2 after surgery, NDS (mean±SEM) were 0±0 for the experimental group versus 1.5±0.5 for the control group. At days 3 and 7 after surgery, NDS were 0±0 for group 1 versus 1.0±1.0 for group 2. Conclusions The faster neurological recovery of dogs treated with the “intracellular-type” maintenance solution supports the biochemical data showing the benefits of this type of blood substitute for extending the safe limits of hypothermic cardiac arrest procedures to >3 hours.

This paper discusses the results of a local initiative in the West Midlands (UK) which looked at how businesses in engineering, utilities and foundry trades managed the risks from hand-arm vibration. Inadequacies of health surveillance programmes and the need for enforcement action are outlined.

Objectives: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). Methods: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). Results: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm3(30% vs 47% in remaining subgroups). Conclusions: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes. © 2010 by AAN Enterprises, Inc. All rights reserved.

A compact laser rangefinder has been developed, which incorporates a sealed-off pulsed CO(2) TEA laser and uses direct (i.e., nonheterodyne) detection. This device is essentially eye safe and benefits from the superior atmospheric transmission at 10.6-microm wavelength. Design parameters are presented and illustrated, and system performance is discussed.

Purified peripheral blood polymorphonuclear leucocytes (PMNs) from patients with rheumatoid arthritis (RA) have been found to differ from purified PMNs from normal subjects in ways that are consistent with their prior activation. However, it is currently contentious whether activated PMNs really circulate in patients with RA, or whether they are produced as an in vitro artefact of purification. Recently developed rapid leucocyte fixation and preparation technique showed that the proportion of polarised (activated) PMNs (36.9 (24.7)%, mean (SD); n = 31) was increased relative to that in control subjects (8.1 (5.6)%; n = 12). Serum cytidine deaminase levels, a biochemical marker of PMN lysis, were also increased in patients with RA (11.59 (7.26) U/ml) compared with those in controls (6.82 (3.78) U/ml), but the proportion of polarised PMNs and the levels of cytidine deaminase activity were unrelated to clinical assessments of inflammatory disease activity. Twelve patients who were not receiving drugs or who were receiving only non-steroidal anti-inflammatory drugs (NSAIDs) had more polarised PMNs than 19 patients receiving second line treatment in addition to NSAIDs (patients receiving NSAIDs, 49.6 (25.9)%; patients receiving second line treatment, 27.5 (21.1)%). Fluorescence activated cytometric analysis of CR1 and CR3 expression on PMNs from a randomly selected subgroup of patients with RA showed that the serum level of cytidine deaminase activity was correlated positively with the expression of CR1 (the C3b receptor) on the cell surface and that the proportion of polarised PMNs was positively correlated with the expression of CR3 (or CD11b/CD18), the iC3b receptor that is upregulated on activation. It is suggested that the polarised PMNs which circulate in blood samples from patients with RA represent cells which have been activated but not yet marginated, or activated cells which have marginated but subsequently returned to the circulating pool.

This study explores the behavior of a flat-slab, sensible heat thermal energy storage system, the physical design and operation of which have been optimized to minimize the production of entropy by thermodynamic irreversibilities. The analytical model is developed in Part I of this work. This part includes a description of the numerical model and the presentation and interpretation of the results of a system optimization study. The major results of this study show that: 1) any Second Law model of a thermal energy storage system must include a distributed storage element in order to make realistic estimates the thermodynamic performance of the system; 2) unconstrained optimization of the design of a thermal energy storage system tends to yield a system that is undesirably large, but by constraining the number of transfer units (NTU), it is possible to design systems of a realistic size without seriously degrading the thermodynamic performance; 3) counterflow systems operated without a dwell period are the most efficient type of system; and 4) the use of a dwell period with a counterflow system, or the operation of a system in parallel flow instead of counterflow, degrades the thermodynamic performance of the system and increases the required system size (NTU) in comparison to a counterflow system operated without a dwell period.

Multicolor discrimination is one of the most effective ways of improving the performance of infrared missile warning sensors, particularly for heavy clutter situations. A new tactical airborne multicolor missile warning testbed was developed and fielded as part of a continuing Air Force Research Laboratory (AFRL) initiative focusing on clutter and missile signature measurements for effective missile warning algorithms. The developed sensor test bed is a multi-camera system 1004x1004 FPA coupled with optimized spectral filters integrated with the optics; a reduced form factor microprocessor-based video data recording system operating at 48 Hz; and a real time field programmable gate array processor for algorithm and video data processing capable of 800B Multiply/Accumulates operations per second. A detailed radiometric calibration procedure was developed to overcome severe photon-limited operating conditions due to the sub-nanometer bandwidth of the spectral filters. This configuration allows the collection and real-time processing of temporally correlated, radiometrically calibrated video data in multiple spectral bands. The testbed was utilized to collect false alarm sources spectra and Man-Portable Air Defense System (MANPADS) signatures under a variety of atmospheric and solar illuminating conditions. Signatures of approximately 100 missiles have been recorded.

Effective missile warning and countermeasures remain an unfulfilled goal for the Air Force and others in the DOD community. To make the expectations a reality, newer sensors exhibiting the required sensitivity, field of regard, and spatial resolution are being developed and transitioned. The largest concern is in the first stage of a missile warning system: detection, in which all targets need to be detected with a high confidence and with very few false alarms. Typical fielded sensors are limited in their detection capability by either lack of sensitivity or by the presence of heavy background clutter, sun glints, and inherent sensor noise. Many threat environments include false alarm sources like burning fuels, flares, exploding ordinance, arc welders, and industrial emitters. Multicolor discrimination has been shown as one of the effective ways to improve the performance of missile warning sensors, particularly for heavy clutter situations. Its utility has been demonstrated in multiple demonstration and fielded systems. New exploitations of background and clutter spectral contents, coupled with advanced spatial and temporal filtering techniques, have resulted in a need to have a new baseline algorithm on which future processing advances may be judged against. This paper describes the AFRL Suite IIIc algorithm chain and its performance against long-range dim targets in clutter.

Summary An anaesthetised 48-year-old woman became haemodynamically unstable following biopsy of a thoracic mass suggesting a diagnosis of a thoracic phaeochromocytoma. Surgery was postponed to allow confirmatory investigations and pre-operative adrenoceptor blockade with phenoxybenzamine and labetalol. Nine days later, following resection of her phaeochromocytoma, she suffered an intra-operative asystolic cardiac arrest which was unresponsive to standard resuscitation protocols and required external cardiac pacing. We discuss the issues involved and suggest that the competitive α1 adrenoceptor antagonist doxazosin may be preferable to the covalently bound mixed alpha adrenoceptor antagonist phenoxybenzamine in the pre-operative preparation of patients with phaeochromocytoma.

This paper has reviewed the techniques used for recording evoked potentials in the premature infant and the early developmental changes. The maturational changes in the evoked potentials, including morphological changes, and the very rapid latency changes within the first months of life, provide an invaluable means for assessing and monitoring development within the central nervous system. The maturational changes are such that normative values are requisite, and the norms must take into account both the infant's gestational age at birth as well as the postnatal age. These norms can then be used to aid in the assessment of gestational age, and whether there has or has not been normal maturational development, either in utero or during the postnatal preterm period. Evoked potentials are of increasing value clinically in preterm neonates, primarily because of the difficulty in obtaining reliable neurological evaluation of these infants. Median nerve SEPs may provide reliable information in preterm infants at risk of PVL, and when recorded in the second week of life, predict cerebral palsy. PTN SEPs seem to be even more reliable indicators of outcome, but the difficulty in obtaining them in preterm infants needs to be taken into consideration. Further study is needed in some areas, such as in apnoeic preterm babies clearly to establish the role that evoked potentials (in this case BAEPs) may have in understanding both the aetiology and the clinical course of this dysfunction. In other conditions, such as delayed intrauterine growth, that may lead to neurological sequelae, evoked potentials can provide objective CNS assessment. Evoked potentials may also prove useful in the monitoring of treatment modalities for preterm infants. The evoked potentials are a valuable adjunct in the assessment of preterm neonates and, as their value is recognised, we expect their use to increase.