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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.

ObjectiveTo examine the effectiveness of behavioural weight management interventions for adults with obesity delivered in primary care.DesignSystematic review and meta-analysis of randomised controlled trials.Eligibility criteria for selection of studiesRandomised controlled trials of behavioural weight management interventions for adults with a body mass index ≥25 delivered in primary care compared with no treatment, attention control, or minimal intervention and weight change at ≥12 months follow-up.Data sourcesTrials from a previous systematic review were extracted and the search completed using the Cochrane Central Register of Controlled Trials, Medline, PubMed, and PsychINFO from 1 January 2018 to 19 August 2021.Data extraction and synthesisTwo reviewers independently identified eligible studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tool. Meta-analyses were conducted with random effects models, and a pooled mean difference for both weight (kg) and waist circumference (cm) were calculated.Main outcome measuresPrimary outcome was weight change from baseline to 12 months. Secondary outcome was weight change from baseline to ≥24 months. Change in waist circumference was assessed at 12 months.Results34 trials were included: 14 were additional, from a previous review. 27 trials (n=8000) were included in the primary outcome of weight change at 12 month follow-up. The mean difference between the intervention and comparator groups at 12 months was −2.3 kg (95% confidence interval −3.0 to −1.6 kg, I2=88%, P2=88%, P2=69%, PConclusionsBehavioural weight management interventions for adults with obesity delivered in primary care are effective for weight loss and could be offered to members of the public.Systematic review registrationPROSPERO CRD42021275529.

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.

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.

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.

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.

There is increasing interest in the use of instrumental variable analysis to overcome unmeasured confounding in observational pharmacoepidemiological studies. This is partly because instrumental variable analyses are potentially less biased than conventional regression analyses. However, instrumental variable analyses are less precise, and regulators and clinicians find it difficult to interpret conflicting evidence from instrumental variable compared with conventional regression analyses. In this paper, we describe three techniques to assess which approach (instrumental variable versus conventional regression analyses) is least biased. These techniques are negative control outcomes, negative control populations and tests of covariate balance. We illustrate these methods using an analysis of the effects of smoking cessation therapies (varenicline) prescribed in primary care.

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.

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.

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 critical review of techniques used in the assessment of microleakage in dental restorations is presented. These techniques include the use of air pressure, bacteria, radioisotopes, electrochemistry, chemical tracers and dye penetration. Wide variations in methodologies are revealed.

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.

A number of streptavidin-linked reporter molecules at the endpoint of a five-step detection protocol for viral in situ hybridization using biotinylated probes were examined. DNA-DNA and RNA-RNA model systems were used. Streptavidin linked to either peroxidase or fluorescein was found to be optimal in terms of sensitivity and resolution within individual cells. All other reporter molecules labelled similar numbers of cells with low background reaction. However, streptavidin-5 nm gold followed by silver enhancement gave very high background staining making interpretation of positive signals very difficult.

Optimised immunocytochemical (ICC) and in situ hybridisation (ISH) protocols for long term, formalin fixed, central nervous system tissue infected with measles virus were developed. The effectiveness of 10 proteases for the enzymatic unmasking of formalin fixed antigen and nucleic acid was investigated. Protease VIII gave maximal signal generation with optimal tissue preservation and no background staining for both techniques. The use of a microwave oven as an additional pre-hybridisation step for RNA-RNA in situ hybridisation produced a significant increase in the number of cells labelled for genomic RNA. The ability to show the presence of antigen and nucleic acid in long term, formalin fixed tissue facilitates the use of stored necropsy material available in pathology departments for ICC and ISH investigations.

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.

One of the most important factors affecting the time taken to respond to a visual stimulus is contrast, and studies of reaction time can provide precise, quantitative information about the underlying signal processing. In this study we measured both saccadic and manual reaction times to step increments in target contrast. Our results over a range of initial contrasts are consistent with a simple model consisting of a noisy logarithmic transducer followed by a rise-to-threshold accumulator. A systematic comparison with previous contrast-processing models also shows that the commonly used method of linear regression may not be a particularly sensitive tool in deciding between them. We found similar parameters for the contrast processor in both saccadic and manual reaction times, as might be expected if a common target detection stage precedes each type of reaction.

Categorization is a basic means of organizing the world around us and offers a simple way to process the mass of stimuli one perceives every day. The ability to categorize appears early in infancy, and has important ramifications for the acquisition of other cognitive capacities, but little is known of its development during childhood. We studied 48 children (7-15 years of age) and 14 adults using an animal/nonanimal visual categorization task while event-related potentials (ERPs) were recorded. Three components were measured: P1, N2, and P3. Behaviorally, the children performed the task very similarly to adults, although the children took longer to make categorization responses. Decreases in latencies (N2, P3) and amplitudes (P1, N2, P3) with age indicated that categorization processes continue to develop through childhood. P1 latency did not differ between the age groups. N2 latency, which is associated with stimulus categorization, reached adult levels at 9 years and P3 latency at 11 years of age. Age-related amplitude decreases started after the maturational changes in latencies were finished.

To demonstrate the three-dimensional vascular anatomy of monochorionic placental anastomoses in vivo, both arterioarterial and arteriovenous.Two-dimensional placental mapping techniques were used to locate arterioarterial and arteriovenous anastomoses. A freehand sweep was performed across the anastomotic site, and multiple images were stored to disk, at 17 Hz. These were then segmented to show only color information (vascular flow) using purpose-designed software (CQ analysis) and the files reconstructed into a three-dimensional volume, for multidirectional viewing and movie generation.Both arterioarterial and arteriovenous anastomoses could be visualized in detail. Reconstruction of a dual volume of gray-scale and segmented color images allowed recreation of the vascular anatomy within the placental substance, as well as retention of the original directional flow information.Detailed anastomotic anatomy can be demonstrated three dimensionally in vivo. Given the increasing evidence implicating various anastomotic configurations in pathological intertwin transfusion, this technique may prove useful in the antenatal assessment and treatment of monochorionic twin pregnancies.

This study explored the neurodiagnostic utility of 6 factor scores identified by recent exploratory and confirmatory factor analyses of the WAIS-III and WMS-III: Verbal Comprehension, Perceptual Organization, Processing Speed, Working Memory, Auditory Memory and Visual Memory. Factor scores were corrected for age. education, sex and ethnicity to minimize their influences on diagnostic accuracy. Cut-offs at 1, 1.5 and 2 standard deviations (SDs) below the standardization sample mean were applied to data from the overlapping test normative samples (N = 1073) and 6 clinical samples described in the WAIS-III/WMS-III Technical Manual (N = 126). The analyses suggest that a I SD cut-off yields the most balanced levels of sensitivity and specificity; more strict (1.5 or 2 SD) cut-offs generally result in trading modest gains in specificity for larger losses in sensitivity. Finally, using combinations of WAIS-III/WMS-III factors together as test batteries, we explored the sensitivity and specificity implications of varying diagnostic decision rules (e.g.,1 vs. 2 impaired factors = "impairment"). For most of the disorders considered here, even a small (e.g., 3 factor) WAIS-III/WMS-III battery provides quite good overall diagnostic accuracy.

Sanderson and colleagues wonder whether people try to quit smoking when mood improves and whether this could explain the association between quitting and improved mood in some of our cohorts.1 2 However, in more than half the studies, participants’ mood was assessed initially and then all attempted to quit immediately, so improved mood cannot have caused the decision to quit. Could a third factor explain both the success of quit attempts and improvements in mood? This factor, selectively associated with quitting, would have to …

Lymphatic filarial nematodes are infected with endosymbiotic Wolbachia bacteria. Lipopolysaccharide from these bacteria is the major activator of innate inflammatory responses induced directly by the parasite. Here, we propose a mechanism by which Wolbachia initiates acute inflammatory responses associated with death of parasites, leading to acute filarial lymphangitis and adverse reactions to antifilarial chemotherapy. We also speculate that repeated exposure to acute inflammatory responses and the chronic release of bacteria, results in damage to infected lymphatics and desensitization of the innate immune system. These events will result in an increased susceptibility to opportunistic infections, which cause acute dermatolymphangitis associated with lymphoedema and elephantiasis. The recognition of the contribution of endosymbiotic bacteria to filarial disease could be exploited for clinical intervention by the targeting of bacteria with antibiotics in an attempt to reduce the development of filarial pathology.

Investigations have suggested that frontal lobe abnormalities are a prominent feature of the alcoholic brain, indicated by impaired neuropsychological performance on tests of frontal lobe function and by reduced frontal lobe volume in neuroimaging and neuropathological examinations. White matter compartment volume loss may underlie observed brain shrinkage and cognitive deficits associated with the frontal lobes, although the nature of this change has not been well-characterized.To investigate the susceptibility of frontal lobe white matter to alcohol-associated metabolic change and to understand the nature of alcohol-related white matter injury, 1H magnetic resonance spectroscopy (MRS) was used to measure concentrations of metabolites in frontal white matter (FWM) and parietal white matter (PWM) of recently detoxified alcoholics (RDA) and nonalcoholic controls (CON). Concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were measured in 37 RDA (mean age, 40.4 years; mean length of abstinence, 27.9 days) and 15 CON (mean age, 38.0 years).Analysis of variance (ANOVA) revealed a group by region of interest interaction for concentrations of NAA. Simple effects analysis revealed a significant 14.7% reduction in FWM NAA, while NAA levels in PWM were similar in RDA and CON. In addition, RDA had an 11.8% increase (averaged across both regions of interest) in brain white matter Ins relative to CON. Reductions in FWM NAA were associated with a longer drinking history in the RDA group, but this result was not found when both age and drinking history were used to predict the level of FWM NAA.Alcohol-associated reductions in FWM NAA may be the result of neuronal loss or dysfunction in the metabolism of NAA. While alcohol-induced oxidative stress may cause global brain impairments in the metabolism and subsequent reduction of NAA, the frontal lobes are particularly rich in excitatory amino acid pathways, and axonal damage or destruction secondary to glutamate-mediated excitotoxicity during alcohol withdrawal may cause frontal lobe-specific reductions in NAA. Elevations in brain white matter Ins may reflect astrocyte proliferation as well as an osmotic response to cell shrinkage.

To determine whether it is possible to identify in vivo placental arterio-venous anastomoses (AVAs) by color Doppler flow mapping.Three monochorionic twin pregnancies (one with and two without twin-to-twin transfusion syndrome) underwent placental mapping by color Doppler ultrasound. Placental vessels along the chorionic plate were recorded together with the direction of blood flow and their location in relation to the cord insertions and to superficial arterio-arterial anastomoses. Suggestive AVAs were mapped topographically and results were compared with the findings of formal postnatal placental injection studies.An AVA was identified in each of the three cases. Injection studies showed multiple AVAs. Each antenatally identified AVA was confirmed at placental injection study. Their placental location correlated to other landmarks as predicted by ultrasound.This preliminary report demonstrates that AVAs can be identified using color Doppler ultrasound. This may facilitate planning for highly selective ablation of AVAs, and shorter procedure times. Formal studies are now indicated to determine the accuracy of this technique.

To describe adaptive changes in torsional alignment that follow sustained cyclovergence in healthy humans.Eye movements were recorded binocularly from four healthy subjects using dual-coil scleral annuli. Cyclovergence movements were evoked over periods of 30 to 150 seconds using a stereoscopic display, presenting gratings of lines arranged horizontally, vertically, or at 45 degrees, subtending angles of up to 48 degrees. In- and excyclodisparities of 5 degrees were introduced and removed in a single-step fashion. After stimulation, the time course and magnitude of the decay in cyclovergence was compared with the subject either in darkness or viewing a baseline stimulus of zero cyclodisparity.As reported previously, the cyclovergence response to incyclodisparities was greater than to excyclodisparities. After sustained excyclovergence, however, in all subjects and in response to all orientations of the gratings, the decay in darkness was incomplete, implying an adaptive change in torsional alignment. In response to the horizontal gratings, for incyclovergence there was also an incomplete decay in darkness but to a lesser degree than in response to excyclovergence, and in only three of four subjects. The incyclovergence evoked by the oblique and vertical gratings was of small magnitude, and its decay was unaffected by the presence or absence of a visual stimulus.After sustained cyclovergence, its decay in the absence of a visual stimulus may be incomplete. The residual component may be interpreted, by analogy with horizontal and vertical vergence, as reflecting so-called phoria adaptation for torsional alignment.

Individuals in short-term abstinence from chronic alcohol consumption commonly have neuropsychological impairments with parallel abnormalities in brain structure. Stable, long-term sobriety often results in improvements in both brain structure and function, although the mechanisms underlying these changes are currently not well understood.To investigate further the neurobiological underpinnings of alcohol-associated brain abnormalities in short-term and long-term abstinence from alcohol, proton magnetic resonance spectroscopy (echo time, 35 msec; repetition time, 1.5 sec) was used to assay metabolites in the anterior centrum semiovale, anterior cingulate gyrus, and right thalamus of two groups of non-Korsakoff alcoholic men, at different stages of abstinence, compared with a control group of alcohol-nonabusing men. Absolute concentrations of N-acetylaspartate, choline, myo-inositol, and creatine were measured in four recently detoxified alcoholics (mean age, 48.7 years; median abstinence, 41.5 days), five long-term abstinent alcoholics (mean age, 45.1 years; median abstinence, 1.7 years), and five nonalcoholic controls (mean age, 45.0 years).Although there were no between-group differences in concentrations of N-acetylaspartate, choline, or creatine, recently detoxified alcoholics had significantly higher myo-inositol in the thalamus, compared with controls and long-term abstinent alcoholics, and significantly higher myo-inositol in the anterior cingulate gyrus, compared with the controls.Elevations in myo-inositol in recently detoxified alcoholics are compatible with an acute alcohol cytotoxicity model. myo-Inositol is elevated in hyperosmolar states such as hypernatremia, renal failure, and diabetes; alcohol-induced hyperosmolarity may trigger accumulation of myo-inositol to stabilize the intracellular environment. Increases in myo-inositol may also reflect proliferation or activation of glia. The reduction of myo-inositol to control group levels in long-term abstinent alcoholics may reflect osmolar stability in abstinent alcoholics and/or a reduction in glial cell activation.

Event-related potentials (ERPs) recorded from the human scalp can provide important information about how the human brain normally processes information and about how this processing may go awry in neurological or psychiatric disorders. Scientists using or studying ERPs must strive to overcome the many technical problems that can occur in the recording and analysis of these potentials. The methods and the results of these ERP studies must be published in a way that allows other scientists to understand exactly what was done so that they can, if necessary, replicate the experiments. The data must then be analyzed and presented in a way that allows different studies to be compared readily. This paper presents guidelines for recording ERPs and criteria for publishing the results.

Visual event-related potentials (ERPs) were examined in 16 children (aged 5-14 y) with phenylketonuria (PKU) and 16 age- and sex-matched controls. Lifetime median measures of phenylalanine (Phe) were 230-460 micromol/l. The most recent Phe levels were 56-624 micromol/l. ERPs were recorded whilst the children performed a discrimination task. All stimuli were square wave gratings degree, which appeared for 33 ms. A response to an infrequent grating that differed in orientation or spatial frequency was required. The older children with PKU had a delay in the first peak (P1) of the ERP, and age-related changes in the amplitude of P1. There was attenuation of the second peak across age groups in PKU. There was no evidence of reduced response accuracy or longer reaction times in children with PKU. Latencies of the cognitive P3 were not delayed in PKU. The delayed early peaks are consistent with previous studies that have shown delayed visual evoked potentials in PKU. The lack of differences in reaction time and P3 may be due to relatively good Phe control in children with PKU, or to the simplicity of the task. Suggestions are made for future ERP studies of PKU.

HIV infection often results in neuropsychological (NP) impairment. In order to assess the impact that HIV-related NP deficits may have on automobile driving, we evaluated 68 HIV-seropositive drivers using an NP battery and two PC-based driving simulations. Thirty-two participants were classified as NP impaired; most (72%) evidenced only mild impairment, and none met criteria for HIV-associated dementia. After controlling for degree of immunosuppression and disease stage, NP-impaired participants failed a previously validated driving simulation at a much higher rate than cognitively intact participants [OR = 5.3, 95% CI (1.7, 17.0), p = .006]. Similarly, on a simulation of city driving, NP impaired participants were more likely to fail based upon the number of accidents [OR = 6.1, 95% CI (1.5, 24.6), p = .01]. Simulator performance was predicted by functioning in a number of NP domains, with NP tests accounting for 13-30% of the variance on the simulations. Although it would be premature to extrapolate these findings to impairment in on-the-road driving, they do argue for greater attention to the impact that even mild HIV-related NP deficits may have on driving skills.

The three paradigms presented in this paper demonstrate the value of ERPs in examining the development of early cognitive processes. Although we have presented only three examples, early cognitive processing could be investigated in a wide range of paradigms using ERPs, in normal as well as clinical populations. Clearly, a next step in understanding the age-related changes in these cognitive processes is to employ dipole source localization to examine the involvement of different generators and their maturation. The final conclusion is that developmental studies are important as they can contribute to our understanding of models of processing and of the generators of ERPs, in terms of cognition as well as neuroanatomy. Hence, the models of cognitive processes in adults should include the development of those processes through childhood.

Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan,Price, 1986).

This study examines differential attention deficits in 19 temporal lobe epilepsy (TLE) patients, 15 generalized seizure patients (GSP), and 19 schizophrenic patients, compared to 20 normal controls. All participants were tested on a variable foreperiod reaction time (RT) task and continuous performance test (CPT). Temporal lobe epilepsy patients and schizophrenic patients show crossover deficits on the RT task requiring a conscious, effortful, preparatory motor set; while GSP show impairments on the CPT requiring vigilant, self-directed attention to external stimuli. The results suggest separate cortical and subcortical brain systems in the respective attentional deficits and in the etiologies of TLE, GSP, and schizophrenic disorders.

Suspended animation is defined as the therapeutic induction of a state of tolerance to temporary complete systemic ischemia, i.w., protection-preservation of the whole organism during prolonged circulatory arrest (or = 1 hr), followed by resuscitation to survival without brain damage. The objectives of suspended animation include: a) helping to save victims of temporarily uncontrollable (internal) traumatic (e.g., combat casualties) or nontraumatic (e.g., ruptured aortic aneurysm) exsanguination, without severe brain trauma, by enabling evacuation and resuscitative surgery during circulatory arrest, followed by delayed resuscitation; b) helping to save some nontraumatic cases of sudden death, seemingly unresuscitable before definite repair; and c) enabling selected (elective) surgical procedures to be performed which are only feasible during a state of no blood flow. In the discussion session, investigators with suspended animation-relevant research interests brainstorm on present knowledge, future research potentials, and the advisability of a major research effort concerning this subject. The following topics are addressed: the epidemiologic facts of sudden death in combat casualties, which require a totally new resuscitative approach; the limits and potentials of reanimation research; complete reversibility of circulatory arrest of 1 hr in dogs under profound hypothermia (10 degrees C), induced and reversed by portable cardiopulmonary bypass; the need for a still elusive pharmacologic or chemical induction of suspended animation in the field; asanguinous profound hypothermic low-flow with cardiopulmonary bypass; electric anesthesia; opiate therapy; lessons learned by hypoxia tolerant vertebrate animals, hibernators, and freeze-tolerant animals (cryobiology); myocardial preservation during open-heart surgery; organ preservation for transplantation; and reperfusion-reoxygenation injury in vital organs, including the roles of nitric oxide and free radicals; and how cells (particularly cerebral neurons) die after transient prolonged ischemia and reperfusion. The majority of authors believe that seeking a breakthrough in suspended animation is not utopian, that ongoing communication between relevant research groups is indicated, and that a coordinated multicenter research effort, basic and applied, on suspended animation is justified.

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.

Alternative explanations for depression-related changes in thinking were examined. Forty-one depressed patients and 40 controls completed sentence stems involving social approval or personal achievement such as "If I could always be right then others would __ me." The view that depressive thinking primarily reflects a generalized increase in accessibility of negative constructs predicts patients will give more negative completions (e.g., "dislike"). Alternatively, depression could affect the interrelationships between constructs: Use in depression of schematic mental models implying closer dependence of personal worth--acceptance on success--approval predicts patients may give more positive completions (e.g., "like"). Results supported the latter prediction and suggest that depressive thinking reflects changes in high-level mental models used to interpret experience.

The present study examined neuropsychological (NP) functioning and associated medical, neurological, brain magnetic resonance imaging (MRI), and psychiatric findings in 389 nondemented males infected with Human Immunodeficiency Virus-Type 1 (HIV-1), and in 111 uninfected controls. Using a comprehensive NP test battery, we found increased rates of impairment at each successive stage of HIV infection. HIV-related NP impairment was generally mild, especially in the medically asymptomatic stage of infection, and most often affected attention, speed of information processing, and learning efficiency; this pattern is consistent with earliest involvement of subcortical or frontostriatal brain systems. NP impairment could not be explained on the bases of mood disturbance, recreational drug or alcohol use, or constitutional symptoms; by contrast, impairment in HIV-infected subjects was related to central brain atrophy on MRI, as well as to evidence of cellular immune activation and neurological abnormalities linked to the central nervous system.