Using e-cigarettes for smoking cessation: evaluation of a pilot project in the North West of England.

AIMS: E-cigarettes have been advocated as an effective smoking cessation intervention, with evidence indicating that they are substantially less harmful than conventional cigarettes. As a result, a pilot to encourage people to swap from conventional cigarettes to e-cigarettes was conducted in 2018 in a socially deprived area in the North West of England. This evaluation highlights the key findings from the pilot. METHODS: An analysis of secondary data at 4 weeks (n = 1022) was undertaken to predict those who used solely used e-cigarettes (i.e. had quit tobacco, as confirmed by a carbon monoxide test, CO < 10 ppm) from baseline characteristics, using chi-square tests and logistic regression. Baseline data were demographics, smoking levels and service provider type. RESULTS: Of the 1022 participants who engaged with the pilot 614 were still engaged at 4 weeks, of whom 62% had quit; quitting was more likely in younger participants (aged 18-24) and less likely in those who were sick and disabled. Of those who still smoked tobacco at week 4 (n = 226), smoking had reduced from a baseline of 19.1 cigarettes/day to 8.7. Overall, 37% (381) of those initially enrolled were confirmed to be using an e-cigarette on its own at follow-up. Successful quit was associated with occupation (unemployed, 33% vs intermediate, 47%, p = .023) and residing in the less deprived quintiles of deprivation (50% vs 34% in the most deprived quintile, p = .016). CONCLUSIONS: Making the conservative assumption that all those not in contact at 4 weeks were still smoking tobacco, for every five people entering the scheme, three people stayed on the programme and reduced their cigarette smoking and one person cut out tobacco altogether. E-cigarettes appear to be an effective nicotine replacement therapy; however, further research is required to determine whether e-cigarette users are more likely to reduce their overall nicotine consumption in the longer term.

The impact of public transport on the health of work commuters: a systematic review.

Although the public transport (PT) commute can form a substantial part of the working day, there is a significant gap in our understanding of how it influences health of those who engage in it. The purpose of this systematic review was to therefore generate evidence from 1972 about the extent to which the PT commute (involving train, bus, subway, tram, or metro) impacts on the mental health, physical health and well-being of the working people. We identified 47 studies in English worldwide involving an empirical quantitative focus which met the inclusion criteria. Of these, 23 studies involved over 500 participants. Although initial multi-modal comparisons showed impact on sickness rate, self-rated health complaints, perceived stress level and reduction in sleep, a more homogeneous analysis of rail commuters showed elevation in salivary cortisol, perceived stress, and affective reactions to crowding. Findings also revealed a bias towards use of endogenous self-report measures. On this basis, we argue that it would be of benefit to test theoretical models to account for more objective measures of job and commuting stress. Recommendations were made for flexible working agendas.

Bridging the species gap in translational research for neurodevelopmental disorders.

The prevalence and societal impact of neurodevelopmental disorders (NDDs) continue to increase despite years of research in both patient populations and animal models. There remains an urgent need for translational efforts between clinical and preclinical research to (i) identify and evaluate putative causes of NDD, (ii) determine their underlying neurobiological mechanisms, (iii) develop and test novel therapeutic approaches, and (iv) translate basic research into safe and effective clinical practices. Given the complexity behind potential causes and behaviors affected by NDDs, modeling these uniquely human brain disorders in animals will require that we capitalize on unique advantages of a diverse array of species. While much NDD research has been conducted in more traditional animal models such as the mouse, ultimately, we may benefit from creating animal models with species that have a more sophisticated social behavior repertoire such as the rat (Rattus norvegicus) or species that more closely related to humans, such as the rhesus macaque (Macaca mulatta). Here, we highlight the rat and rhesus macaque models for their role in previous psychological research discoveries, current efforts to understand the neurobiology of NDDs, and focus on the convergence of behavior outcome measures that parallel features of human NDDs.

A window beneath the skin: how computed tomography assessment of body composition can assist in the identification of hidden wasting conditions in oncology that profoundly impact outcomes.

Advancements in image-based technologies and body composition research over the past decade has led to increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation (MA), as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities can be highly prevalent in patients with cancer (ranging between 10 and 90 %), depending on the cohort under investigation and diagnostic criteria used. Importantly, both low muscle mass and low MA have been associated with poorer tolerance to chemotherapy, increased risk of post-operative infectious and non-infectious complications, increased length of hospital stay and poorer survival in patients with cancer. Studies have shown that systemic antineoplastic treatment can exacerbate losses in muscle mass and MA, with reported loss of skeletal muscle between 3 and 5 % per 100 d, which are increased exponentially with progressive disease and proximity to death. At present, no effective medical intervention to improve muscle mass and MA exists. Most research to date has focused on treating muscle depletion as part of the cachexia syndrome using nutritional, exercise and pharmacological interventions; however, these single-agent therapies have not provided promising results. Rehabilitation care to modify body composition, either increasing muscle mass and/or MA should be conducted, and its respective impact on oncology outcomes explored. Although the optimal timing and treatment strategy for preventing or delaying the development of muscle abnormalities are yet to be determined, multimodal interventions initiated early in the disease trajectory appear to hold the most promise.

Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact.

Our understanding of body composition (BC) variability in contemporary populations has significantly increased with the use of imaging techniques. Abnormal BC such as sarcopenia (low muscle mass) and obesity (excess adipose tissue) are predictors of poorer prognosis in a variety of conditions or clinical situations. As a catabolic illness, a defining feature of cancer is muscle loss. Although the conceptual model of wasting in cancer is typically conceived as involuntary weight loss leading to low body weight, recent studies have shown that both sarcopenia and cachexia can be present with obesity. The combination of low muscle and high adipose tissue (sarcopenic obesity) is an emerging abnormal BC phenotype prevalent across the body weight, and hence BMI spectra. Sarcopenia and sarcopenic obesity in cancer are in most instances occult conditions, which have been independently associated with higher incidence of chemotherapy toxicity, shorter time to tumour progression, poorer outcomes of surgery, physical impairment and shorter survival. Although the mechanisms are yet to be fully understood, the associations with poorer clinical outcomes emphasise the value of nutritional assessment as well as the need to develop appropriate interventions to countermeasure abnormal BC. Sarcopenia and sarcopenic obesity create diverse nutritional requirements, highlighting the compelling need for a more comprehensive and differentiated understanding of energy and protein requirements in this heterogeneous population.

Frontiers in nonclinical drug development: biosimilars.

Biopharmaceuticals, produced by recombinant DNA technology, are generally more complicated to produce than small molecule drugs. As patents around the development and manufacturing of these biopharmaceuticals expire, biosimilars are being developed as comparable and more affordable alternatives to improve patient access and market competition. This commentary explains what a biosimilar is; it compares and contrasts biosimilar production with that of small molecule, generic, and other biological drugs; and it describes basic principles of the nonclinical development program for monoclonal antibody biosimilars.

Association of caesarean delivery with child adiposity from age 6 weeks to 15 years.

OBJECTIVES: o assess associations of caesarean section with body mass from birth through adolescence. DESIGN: ongitudinal birth cohort study, following subjects up to 15 years of age. SETTING AND PARTICIPANTS: Children born in 1991-1992 in Avon, UK who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=10 219). PRIMARY OUTCOME: standardized measures of body mass (weight-for length z-scores at 6 weeks, 10 and 20 months; and body mass index (BMI) z-scores at 38 months, 7, 9, 11 and 15 years). Secondary outcome: categorical overweight or obese (BMI: 85th percentile) for age and gender, at 38 months, 7, 9, 11 and 15 years. RESULTS: Of the 10 219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower-birth weights than those born vaginally (-46.1 g, 95% confidence interval(CI): 14.6-77.6 g; P=0.004). In mixed multivariable models adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns, caesarean delivery was consistently associated with increased adiposity, starting at 6 weeks (+0.11 s.d. units, 95% CI: 0.03-0.18; P=0.005), through age 15 (BMI z-score increment+0.10 s.d. units, 95% CI: 0.001-0.198; P=0.042). By age 11 caesarean-delivered children had 1.83 times the odds of overweight or obesity (95% CI: 1.24-2.70; P=0.002). When the sample was stratified by maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In contrast, evidence of an association among children born of normal-weight mothers was weak. CONCLUSION: Cesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to further characterize the association in children of normal weight women. Additional work is also needed to understand the mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.

Metabolic syndrome and leptin are associated with adverse pathological features in male colorectal cancer patients.

AIM: Metabolic syndrome (MetS) describes a clustering of factors including central obesity, hypertension and raised plasma glucose, triglycerides and high-density lipoprotein (HDL) cholesterol. Central obesity is associated with a risk for colorectal cancer, but the impact of MetS on colorectal cancer biology and outcomes is unclear. METHOD: A prospective observational study of colorectal cancer patients was carried out in an Irish population. Patients underwent metabolic and anthropometric assessment before treatment, including measurement of serum hormones and adipokines and CT measurement of visceral fat. MetS was defined according to the International Diabetes Federation definition(3) . RESULTS: One-hundred and thirty consecutive colorectal cancer patients (66 men and 64 women) were recruited. MetS was diagnosed in 38% patients compared with the population norms reported at 21%(21) . Male patients had a significantly greater visceral fat area compared with female patients. MetS was associated with node-positive disease (P = 0.026), percentage nodal involvement (P = 0.033) and extramural vascular invasion (P = 0.049) in male patients but no significant association was observed in female patients. HDL cholesterol was also significantly associated with a more advanced pathological stage (P = 0.014) and node-positive disease (P = 0.028). Leptin was associated with nodal status (P = 0.036), microvascular invasion (P = 0.054), advanced pathological stage (P = 0.046) and more advanced Dukes stage (P = 0.042). CONCLUSION: We report a high prevalence of MetS and visceral obesity in a colorectal cancer population. MetS and plasma leptin are associated with a more aggressive tumour phenotype in male patients only.

Brachial neuritis masquerading as acute coronary syndrome.

BACKGROUND: Brachial neuritis is a frequently misdiagnosed condition which can present to many medical or surgical specialties. OBJECTIVE: To report a case of brachial neuritis with bilateral phrenic nerve involvement and diaphragmatic weakness. CASE DESCRIPTION: A 63-year-old man presented with acute-onset proximal upper extremity pain and weakness. He also developed severe orthopnoea. Examination revealed proximal upper limb wasting and dramatic paradoxical breathing. Cardiac investigations were unremarkable. Electromyographic studies were consistent with a C5 radiculopathy. Phrenic nerve studies were abnormal bilaterally and Sniff test was positive. A diagnosis of brachial neuritis with predominant C5 and bilateral phrenic nerve involvement was made. His symptoms resolved spontaneously over 3 months. CONCLUSIONS: Brachial neuritis can mimic an acute coronary syndrome and is a rare cause of bilateral phrenic neuropathy. Phrenic nerve palsy should be considered in patients presenting with shortness of breath without any underlying respiratory or cardiovascular illness.

Lack of differential pattern in central adiposity and metabolic syndrome in Barrett's esophagus and gastroesophageal reflux disease.

Obesity is an established risk factor for esophageal adenocarcinoma, although the mechanism is unclear. A pathway from reflux to inflammation through metaplasia is the dominant hypothesis, and an added role relating to visceral adiposity and the metabolic syndrome has been mooted in Barrett's esophagus (BE) patients. Whether BE differs from gastroesophageal reflux disease (GERD) in obesity and metabolic syndrome profiles is unclear, and this was the focus of this study. Patients with proven BE or GERD were randomly selected from the unit data registry and invited to attend for metabolic syndrome screening, anthropometry studies including segmental body composition analysis, and laboratory tests including fasting lipids, insulin, and C-reactive protein. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. One hundred and eighteen BE patients and 113 age- and sex-matched GERD controls were studied. The incidence of obesity (body mass index >30 kg/m(2)) was 36% and 38%, respectively, with the pattern of fat deposition predominantly central and an estimated trunk fat mass of 13 and 14 kg, respectively. Using the NCEP criteria, metabolic syndrome was significantly more common in the BE cohort (30% vs 20%, P < 0.05), but there was no significant difference using IDF criteria (42% vs 37%, P= 0.340). Central obesity and the metabolic syndrome are common in both Barrett's and GERD cohorts, but not significantly different, suggesting that central obesity and the metabolic syndrome does not per se impact on the development of BE in a reflux population. In BE, the importance of obesity and the metabolic syndrome in disease progression merits further study.

Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer.

AIMS: Obesity is associated with both an increased risk of postmenopausal breast cancer and increased mortality rates. The mechanism is unclear, and central (visceral) obesity, insulin resistance, altered sex steroids and altered adipokines are mooted as possible factors. These features may cluster in the so-called metabolic syndrome. The relevance of metabolic syndrome to the biology of breast cancer is unknown, and this was the focus of the present study. MATERIALS AND METHODS: All postmenopausal women with newly diagnosed breast cancer (n=105) were recruited. A detailed clinical history was carried out, as well as a body composition analysis, metabolic screen and measurement of adipokines and inflammatory markers. RESULTS: The median age was 68 years (40-94 years) and the mean body mass index was 28.3+/-5.2 kg/m2, with 87% of patients centrally obese. Metabolic syndrome was diagnosed in 39% of patients, and was significantly associated with central obesity (P<0.005) and increased inflammation, with C-reactive protein levels doubling in metabolic syndrome patients compared with non-metabolic syndrome patients (10.3 vs 5.8 mg/l; P=0.084). Patients with a later pathological stage (II-IV) were significantly more likely to be obese (P=0.007), centrally obese (P=0.009), hyperglycaemic (P=0.047) and hyperinsulinaemic (P=0.026); 51% had metabolic syndrome compared with 12% for early stage disease. Patients with node-positive disease were significantly more likely to be hyperinsulaemic (P=0.030) and have metabolic syndrome (P=0.028) than patients with node-negative disease. DISCUSSION: The data suggest that metabolic syndrome and central obesity are common in postmenopausal breast cancer patients, and that metabolic syndrome may be associated with a more aggressive tumour biology.

Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune mediated neuropathy causing demyelination and conduction block thought to occur as the result of an aberrant autoimmune response resulting in peripheral nerve inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5-35% subsequently become dependent to maintain function. Despite a number of small scale trials, the role for alternative long-term immunosuppression remains unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52 antigen present on the surface of lymphocytes and monocytes. A single intravenous infusion results in rapid and profound lymphopoenia lasting >12 months. We report its use and clinical outcome in a small series of patients with severe IVIG-dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to conventional immunosuppression were treated in 5 centres receiving 9 courses of alemtuzumab (dose range 60-150 mg). Following treatment, mean monthly IVIG use fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days. Two patients had prolonged remission, two patients had a partial response and no clear benefit was observed in the remaining three patients (2 Males, 1 Females). Responding patients had a younger age at onset (19.5 years) and shorter disease duration than non-responders. Three patients developed autoimmune disease following treatment. Alemtuzumab may offer an alternative treatment for a subset of early onset IVIG dependent CIDP patients failing conventional immunosuppressive agents, but concerns about toxicity may limit its use.

Vacuolar leucoencephalopathy and pulvinar sign in association with coeliac disease.

Several neurological disorders have been associated with coeliac disease, including epilepsy, ataxia and neuropathy. Here we report a rare case of white matter disease in a 55-year-old man with coeliac disease. He presented with anxiety, headache and left upper limb jerking. He subsequently developed epilepsy and brain MRI revealed diffuse white matter abnormality. He died 6 months after presentation due to status epilepticus and sepsis. Brain biopsy demonstrated vacuolar leucoencephalopathy with no evidence of vCJD. An extensive clinical screen excluded infectious, inflammatory and para-neoplastic causes for this condition. Coeliac disease may be causally associated with vacuolar leucoencephalopathy in this case.

Health-related quality of life assessment at presentation may predict complications and early relapse in patients with localized cancer of the esophagus.

SUMMARY: Health-related quality of life (HR-QOL) assessment in esophageal cancer is increasingly performed. However, the association of baseline HR-QOL in predicting outcome is unclear. This study aimed to assess the impact of HR-QOL scores at diagnosis with major morbidity, mortality, failure to progress to surgery, recurrence within 1 year, and survival in patients with localized esophageal cancer. The European Organization for Research and Treatment of Cancer's quality of life questionnaire was completed at diagnosis. Univariate and multivariate logistic regression were used to investigate the relationship between baseline HR-QOL and outcomes adjusting for confounding variables. A total of 185 patients with localized esophageal cancer were included, 89 undergoing multimodal therapy and 96 surgery alone. Global QOL scores were significantly associated with in-hospital mortality (P = 0.020) but not with major morbidity (P = 0.709) or 1-year survival (P = 0.247). Symptoms of fatigue and dyspnea at baseline were significantly (P < 0.05) associated with major morbidity, in-hospital mortality, and survival in univariate analysis. After adjusting for known confounding variables in multivariate analysis, only worse dyspnea score remained predictive of in-hospital mortality and a worse fatigue score remained predictive of 1-year survival. HR-QOL was of no benefit in predicting survival in multivariate analysis that identified pathological nodal status as the most significant factor. HR-QOL questionnaires may be helpful in preoperative assessment of risk. It is possible that patients with unrecognized micrometastatic disease at the time of surgery may report worse systemic symptoms at diagnosis, in particular fatigue and dyspnea, and these and global QOL scores may also identify poorer reserves that may increase in-hospital morbidity and mortality postoperatively.

The peer group as a context for the development of young adolescent motivation and achievement.

This study investigated the peer group as a context for the socialization of young adolescents' motivation and achievement in school. Social network analysis was used to identify peer groups of adolescents in middle school whose members regularly interacted with each other (N = 331). Actual reports from these peer group members were used to assess peer group characteristics. Multilevel analyses indicated that peer groups did socialize some academic characteristics, controlling for selection factors. Students' peer group context in the fall predicted changes in their liking and enjoyment of school (intrinsic value) and their achievement over the school year. Students' peer group context was unrelated to changes in their beliefs about the importance of school (utility value) or expectancies for success over the school year.