Menopause, reproductive life, hormone replacement therapy and bone phenotype at age 60-64: a British birth cohort

CONTEXT: Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross sectional, or lacking gold standard bone technologies, or information on hormone replacement therapy (HRT) or surgical treatment. OBJECTIVE: To investigate age at menopause, length of reproductive life and HRT use in relation to volumetric and areal bone mineral density (vBMD, aBMD), bone size and strength in women aged 60-64. DESIGN: A birth cohort study followed for 64 years with prospective measures of age at menarche and menopause and monthly HRT histories. SETTING: England, Scotland, Wales Participants: 848 women with known type of menopause and bone measures at 60-64 years Main outcome measures: Peripheral quantitative computed tomography (pQCT) measurements of the distal radius total and trabecular vBMD; diaphyseal radius total and medullary cross sectional area, cortical vBMD and polar strength strain index (SSI); dual energy x-ray absorptiometry (DXA) measurments of aBMD at the lumbar spine and total hip. RESULTS: A ten year increase in age at natural (but not surgical) menopause was associated with 8.2% (95% CI: 1.3,15.1%, p=.02) greater trabecular vBMD and a 6.0% (95% CI 0.51,11.5%, p=.03) greater total vBMD; findings were similar for length of reproductive life. A ten year difference in HRT use was associated with a 6.0% (95% CI 2.6%,9.3%, p<.001) greater polar SSI and a 0.9% (95% CI 0.4%, 1.5%, p=.001) greater cortical vBMD. These estimates changed little on adjustment. Estimates for aBMD were consistent with those for pQCT. CONCLUSIONS: The positive effects on trabecular vBMD of later natural menopause and longer reproductive life persisted into early old age. HRT use was associated with greater radius cortical vBMD and polar SSI, and spine aBMD

The transformation of transport policy in Great Britain? 'New Realism' and New Labour's decade of displacement activity

In a 1999 paper, Goodwin announced ‘the transformation of transport policy in Great Britain’. His central point was that consensus was emerging among policy makers and academics based on earlier work including Transport: The New Realism, which rejected previous orthodoxy that the supply of road space could and should be continually expanded to match demand. Instead a combination of investment in public transport, walking and cycling opportunities and – crucially – demand management should form the basis of transport policy to address rising vehicle use and associated increases in congestion and pollution / carbon emissions. This thinking formed the basis of the 1997 Labour government’s ‘sustainable transport’ policy, but after 13 years in power ministers neither transformed policy nor tackled longstanding transport trends. Our main aim in this paper is to revisit the concept of New Realism and re-examine its potential utility as an agent of change in British transport policy. Notwithstanding the outcome of Labour’s approach to transport policy, we find that the central tenets of the New Realism remain robust and that the main barriers to change are related to broader political and governance issues which suppress radical policy innovation

Recurrent rare copy number variants increase risk for esotropia

Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints. Results: Esotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 × 10-6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95% confidence interval [CI] 5.4-38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95% CI 4.6-25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95% CI 5.4-14.9). Overall, 114 cases (7%) and only 28 controls (0.7%) had one of the three rare duplications. No case nor control had more than one of these three duplications. Conclusions: Rare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia

Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial

Background: The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed. Methods/Design: This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect. Discussion: This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample, and the multicentre design means that knowledge can be shared between recruitment teams. The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of standard smoking cessation service practice. Trial registration: Current Controlled Trials ISRCTN33031001. Registered 27 April 2012

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses

Characteristics Associated with Citation Rate of the Medical Literature

BACKGROUND: The citation rate for articles is viewed as a measure of their importance and impact; however, little is known about what features of articles are associated with higher citation rate. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cohort study of all original articles, regardless of study methodology, published in the Lancet, JAMA, and New England Journal of Medicine, from October 1, 1999 to March 31, 2000. We identified 328 articles. Two blinded, independent reviewers extracted, in duplicate, nine variables from each article, which were analyzed in both univariable and multivariable linear least-squares regression models for their association with the annual rate of citations received by the article since publication. A two-way interaction between industry funding and an industry-favoring result was tested and found to be significant (p = 0.02). In our adjusted analysis, the presence of industry funding and an industry-favoring result was associated with an increase in annual citation rate of 25.7 (95% confidence interval, 8.5 to 42.8) compared to the absence of both industry funding and industry-favoring results. Higher annual rates of citation were also associated with articles dealing with cardiovascular medicine (13.3 more; 95% confidence interval, 3.9 to 22.3) and oncology (12.6 more; 95% confidence interval, 1.2 to 24.0), articles with group authorship (11.1 more; 95% confidence interval, 2.7 to 19.5), larger sample size and journal of publication. CONCLUSIONS/SIGNIFICANCE: Large trials, with group authorship, industry-funded, with industry-favoring results, in oncology or cardiology were associated with greater subsequent citations

Evaluation of a Dutch school-based depression prevention program for youths in highrisk neighborhoods: study protocol of a two-armed randomized controlled trial

Contains fulltext : 102517.pdf (publisher's version ) (Open Access)Background Research has indicated that depression prevention programs attenuate the development of symptoms of depression in adolescents. To implement these programs on a large scale, implementation in a school setting with teachers providing the programs is needed. In the present study, the effectiveness of the Dutch depression prevention program Op Volle Kracht (OVK) provided by school teachers during school hours with adolescents from high risk neighborhoods will be tested. The mediating effects of cognitive distortions and alexithymia will be evaluated as well. We hypothesize that the OVK program will prevent or decrease reported depressive symptoms, and that this association will be mediated by cognitive distortions and alexithymia. Methods/Design Schools with at least 30% of their pupils living in low income areas in the Netherlands are invited to participate in the study. Classes from vocational training up to pre-university level are eligible and 1324 adolescents (11-14 years) will be participating in the study. Randomisation will be done at class level, randomly assigning participants to an intervention group (OVK) and a control group (care as usual), stratifying by school level (high versus low). Trained school teachers will be delivering the program, which covers cognitive-behavioral and social problem-solving skills. Longitudinal data will be collected with self-report measurements administered in the school setting at baseline, post intervention and at two follow ups (at 6 and 12 months). Primary outcome is the level of depressive symptoms, and secondary outcomes include: cognitive errors, response style, attributional style, alexithymia, stressful life events, substance use, happiness, and school grades. Discussion If the OVK program proves to be effective when it is provided by school teachers, a structural implementation of the program in the school curriculum will enhance the quality of the lives of adolescents and their families and will reduce costs in health care. In addition, the results of the study advances current knowledge on the underlying mechanisms of the development of depression and may aid the improvement of depression prevention programs in general.7 p

Post-Mortem diagnosis of dementia by informant interview

Abstract The diagnosis of normal cognition or dementia in the Brazilian Brain Bank of the Aging Brain Study Group (BBBABSG) has relied on postmortem interview with an informant. Objectives: To ascertain the sensitivity and specificity of postmortem diagnosis based on informant interview compared against the diagnosis established at a memory clinic. Methods: A prospective study was conducted at the BBBABSG and at the Reference Center for Cognitive Disorders (RCCD), a specialized memory clinic of the Hospital das Clínicas, University of São Paulo Medical School. Control subjects and cognitively impaired subjects were referred from the Hospital das Clínicas to the RCCD where subjects and their informants were assessed. The same informant was then interviewed at the BBBABSG. Specialists' panel consensus, in each group, determined the final diagnosis of the case, blind to other center's diagnosis. Data was compared for frequency of diagnostic equivalence. For this study, the diagnosis established at the RCCD was accepted as the gold standard. Sensitivity and specificity were computed. Results: Ninety individuals were included, 45 with dementia and 45 without dementia (26 cognitively normal and 19 cognitively impaired but non-demented). The informant interview at the BBBABSG had a sensitivity of 86.6% and specificity of 84.4% for the diagnosis of dementia, and a sensitivity of 65.3% and specificity of 93.7% for the diagnosis of normal cognition. Conclusions: The informant interview used at the BBBABSG has a high specificity and sensitivity for the diagnosis of dementia as well as a high specificity for the diagnosis of normal cognition