Reporting of Human Genome Epidemiology (HuGE) association studies: An empirical assessment

<p>Abstract</p> <p>Background</p> <p>Several thousand human genome epidemiology association studies are published every year investigating the relationship between common genetic variants and diverse phenotypes. Transparent reporting of study methods and results allows readers to better assess the validity of study findings. Here, we document reporting practices of human genome epidemiology studies.</p> <p>Methods</p> <p>Articles were randomly selected from a continuously updated database of human genome epidemiology association studies to be representative of genetic epidemiology literature. The main analysis evaluated 315 articles published in 2001–2003. For a comparative update, we evaluated 28 more recent articles published in 2006, focusing on issues that were poorly reported in 2001–2003.</p> <p>Results</p> <p>During both time periods, most studies comprised relatively small study populations and examined one or more genetic variants within a single gene. Articles were inconsistent in reporting the data needed to assess selection bias and the methods used to minimize misclassification (of the genotype, outcome, and environmental exposure) or to identify population stratification. Statistical power, the use of unrelated study participants, and the use of replicate samples were reported more often in articles published during 2006 when compared with the earlier sample.</p> <p>Conclusion</p> <p>We conclude that many items needed to assess error and bias in human genome epidemiology association studies are not consistently reported. Although some improvements were seen over time, reporting guidelines and online supplemental material may help enhance the transparency of this literature.</p

Distribution pattern of psoriasis, anxiety and depression as possible causes of sexual dysfunction in patients with moderate to severe psoriasis

BACKGROUND: Psoriasis may significantly impair sexual function. Depression and organic factors appear to play a key role in this relation. However, beyond genital psoriasis, the importance of the disease's distribution patterns has not been considered. OBJECTIVES: To research sexual function in psoriasis patients and investigate the roles of anxiety, depression and psoriasis' distribution patterns in sexual dysfunction. METHODS: A comparative study matched for sex and age was performed. Eighty patients with moderate to severe psoriasis and 80 healthy controls were included. The participants completed the Massachusetts General Hospital-Sexual Functioning Questionnaire, the Hospital Anxiety and Depression Scale, and the Self-Administered Psoriasis Area and Severity Index. RESULTS: Psoriasis was associated with sexual dysfunction, odds ratio=5.5 (CI 95% 2.6-11.3; p<0.001). Certain distribution patterns of psoriasis, involving specific body regions, were associated with an increase in sexual dysfunction in the group presenting the disease, odds ratio 7.9 (CI 95% 2.3-33.4; p<0.001). Multivariate logistic regression analysis identified anxiety and depression, and the involvement of these specific areas, as possible independent risk factors for sexual dysfunction in patients with moderate to severe psoriasis. CONCLUSION: This study identifies body areas potentially related to sexual dysfunction, independently of anxiety and depression, in psoriasis patients. The results suggest that the assessment of sexual dysfunction and the involvement of these body areas should be considered as disease severity criteria when choosing the treatment for psoriasis patients

Use of a Cybex NORM dynamometer to assess muscle function in patients with thoracic cancer

<p>Abstract</p> <p>Background</p> <p>The cachexia-anorexia syndrome impacts on patients' physical independence and quality of life. New treatments are required and need to be evaluated using acceptable and reliable outcome measures, e.g. the assessment of muscle function. The aims of this study were to: (i) examine the acceptability and reliability of the Cybex NORM dynamometer to assess muscle function in people with non-small cell lung cancer or mesothelioma; (ii) compare muscle function in this group with healthy volunteers and; (iii) explore changes in muscle function over one month.</p> <p>Methods</p> <p>The test consisted of 25 repetitions of isokinetic knee flexion and extension at maximal effort while seated on a Cybex NORM dynamometer. Strength and endurance for the quadriceps and hamstrings were assessed as peak torque and total work and an endurance ratio respectively. Thirteen patients and 26 volunteers completed the test on three separate visits. Acceptability was assessed by questionnaire, reliability by intraclass correlation coefficients (ICC) and tests of difference compared outcomes between and within groups.</p> <p>Results</p> <p>All subjects found the test acceptable. Peak torque and work done were reliable measures (ICC >0.80), but the endurance ratio was not. Muscle function did not differ significantly between the patient and a matched volunteer group or in either group when repeated after one month.</p> <p>Conclusion</p> <p>For patients with non-small cell lung cancer or mesothelioma, the Cybex NORM dynamometer provides an acceptable and reliable method of assessing muscle strength and work done. Muscle function appears to be relatively well preserved in this group and it appears feasible to explore interventions which aim to maintain or even improve this.</p

HFE gene mutations increase the risk of coronary heart disease in women

The purpose of the present study is to examine HFE gene mutations in relation to newly diagnosed (incident) coronary heart disease (CHD). In a population-based follow-up study of 7,983 individuals aged 55 years and older, we compared the risk of incident CHD between HFE carriers and non-carriers, overall and stratified by sex and smoking status. HFE mutations were significantly associated with an increased risk of incident CHD in women but not in men (hazard ratio [HR] for women = 1.7, 95% confidence interval [CI] 1.2–2.4 versus HR for men = 0.9, 95% CI 0.7–1.2). This increased CHD risk associated with HFE mutations in women was statistically significant in never smokers (HR = 1.8, 95% CI 1.1–2.8) and current smokers (HR = 3.1, 95% CI 1.4–7.1), but not in former smokers (HR = 1.3, 95% CI 0.7–2.4). HFE mutations are associated with increased risk of incident CHD in women

Apical Ischemia Is a Universal Feature of Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) accounts for ≈10% of hypertrophic cardiomyopathy cases and is characterized by apical hypertrophy, apical cavity obliteration, and tall ECG R waves with ischemic-looking deep T-wave inversion. These may be present even with <15 mm apical hypertrophy (relative ApHCM). Microvascular dysfunction is well described in hypertrophic cardiomyopathy. We hypothesized that apical perfusion defects would be common in ApHCM. METHODS: A 2-center study using cardiovascular magnetic resonance short- and long-axis quantitative adenosine vasodilator stress perfusion mapping. One hundred patients with ApHCM (68 overt hypertrophy [≥15 mm] and 32 relative ApHCM) were compared with 50 patients with asymmetrical septal hypertrophy hypertrophic cardiomyopathy and 40 healthy volunteer controls. Perfusion was assessed visually and quantitatively as myocardial blood flow and myocardial perfusion reserve. RESULTS: Apical perfusion defects were present in all overt ApHCM patients (100%), all relative ApHCM patients (100%), 36% of asymmetrical septal hypertrophy hypertrophic cardiomyopathy, and 0% of healthy volunteers (P<0.001). In 10% of patients with ApHCM, perfusion defects were sufficiently apical that conventional short-axis views missed them. In 29%, stress myocardial blood flow fell below rest values. Stress myocardial blood flow was most impaired subendocardially, with greater hypertrophy or scar, and with apical aneurysms. Impaired apical myocardial blood flow was most strongly predicted by thicker apical segments (β-coefficient, -0.031 mL/g per min [CI, -0.06 to -0.01]; P=0.013), higher ejection fraction (-0.025 mL/g per min [CI, -0.04 to -0.01]; P<0.005), and ECG maximum R-wave height (-0.023 mL/g per min [CI, -0.04 to -0.01]; P<0.005). CONCLUSIONS: Apical perfusion defects are universally present in ApHCM at all stages. Its ubiquitous presence along with characteristic ECG suggests ischemia may play a disease-defining role in ApHCM

Preparation of name and address data for record linkage using hidden Markov models

BACKGROUND: Record linkage refers to the process of joining records that relate to the same entity or event in one or more data collections. In the absence of a shared, unique key, record linkage involves the comparison of ensembles of partially-identifying, non-unique data items between pairs of records. Data items with variable formats, such as names and addresses, need to be transformed and normalised in order to validly carry out these comparisons. Traditionally, deterministic rule-based data processing systems have been used to carry out this pre-processing, which is commonly referred to as "standardisation". This paper describes an alternative approach to standardisation, using a combination of lexicon-based tokenisation and probabilistic hidden Markov models (HMMs). METHODS: HMMs were trained to standardise typical Australian name and address data drawn from a range of health data collections. The accuracy of the results was compared to that produced by rule-based systems. RESULTS: Training of HMMs was found to be quick and did not require any specialised skills. For addresses, HMMs produced equal or better standardisation accuracy than a widely-used rule-based system. However, acccuracy was worse when used with simpler name data. Possible reasons for this poorer performance are discussed. CONCLUSION: Lexicon-based tokenisation and HMMs provide a viable and effort-effective alternative to rule-based systems for pre-processing more complex variably formatted data such as addresses. Further work is required to improve the performance of this approach with simpler data such as names. Software which implements the methods described in this paper is freely available under an open source license for other researchers to use and improve

The effectiveness of mindfulness-based interventions in the perinatal period: a systematic review and meta-analysis

Perinatal mental health difficulties are associated with adverse consequences for parents and infants. However, the potential risks associated with the use of psychotropic medication for pregnant and breastfeeding women and the preferences expressed by women for non-pharmacological interventions mean it is important to ensure that effective psychological interventions are available. It has been argued that mindfulness-based interventions may offer a novel approach to treating perinatal mental health difficulties, but relatively little is known about their effectiveness with perinatal populations. This paper therefore presents a systematic review and meta-analysis of the effectiveness of mindfulness-based interventions for reducing depression, anxiety and stress and improving mindfulness skills in the perinatal period. A systematic review identified seventeen studies of mindfulness-based interventions in the perinatal period, including both controlled trials (n = 9) and pre-post uncontrolled studies (n = 8). Eight of these studies also included qualitative data. Hedge’s g was used to assess uncontrolled and controlled effect sizes in separate meta-analyses, and a narrative synthesis of qualitative data was produced. Pre- to post-analyses showed significant reductions in depression, anxiety and stress and significant increases in mindfulness skills post intervention, each with small to medium effect sizes. Completion of the mindfulness-based interventions was reasonable with around three quarters of participants meeting study-defined criteria for engagement or completion where this was recorded. Qualitative data suggested that participants viewed mindfulness interventions positively. However, between-group analyses failed to find any significant post-intervention benefits for depression, anxiety or stress of mindfulness-based interventions in comparison to control conditions: effect sizes were negligible and it was conspicuous that intervention group participants did not appear to improve significantly more than controls in their mindfulness skills. The interventions offered often deviated from traditional mindfulness-based cognitive therapy or mindfulness-based stress reduction programmes, and there was also a tendency for studies to focus on healthy rather than clinical populations, and on antenatal rather than postnatal populations. It is argued that these and other limitations with the included studies and their interventions may have been partly responsible for the lack of significant between-group effects. The implications of the findings and recommendations for future research are discussed

Erratum to: Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: individual patient data (IPD) meta-analysis and health economic evaluation.

Erratum to: Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: individual patient data (IPD) meta-analysis and health economic evaluatio

Design considerations in a sib-pair study of linkage for susceptibility loci in cancer

<p>Abstract</p> <p>Background</p> <p>Modern approaches to identifying new genes associated with disease allow very fine analysis of associaton and can be performed in population based case-control studies. However, the sibpair design is still valuable because it requires few assumptions other than acceptably high penetrance to identify genetic loci.</p> <p>Methods</p> <p>We conducted simulation studies to assess the impact of design factors on relative efficiency for a linkage study of colorectal cancer. We considered two test statistics, one comparing the mean IBD probability in affected pairs to its null value of 0.5, and one comparing the mean IBD probabilities between affected and discordant pairs. We varied numbers of parents available, numbers of affected and unaffected siblings, reconstructing the genotype of an unavailable affected sibling by a spouse and offspring, and elimination of sibships where the proband carries a mutation at another locus.</p> <p>Results</p> <p>Power and efficiency were most affected by the number of affected sibs, the number of sib pairs genotyped, and the risk attributable to linked and unlinked loci. Genotyping unaffected siblings added little power for low penetrance models, but improved validity of tests when there was genetic heterogeneity and for multipoint testing. The efficiency of the concordant-only test was nearly always better than the concordant-discordant test. Replacement of an unavailable affected sibling by a spouse and offspring recovered some linkage information, particularly if several offspring were available. In multipoint analysis, the concordant-only test was showed a small anticonservative bias at 5 cM, while the multipoint concordant-discordant test was generally the most powerful test, and was not biased away from the null at 5 cM.</p> <p>Conclusion</p> <p>Genotyping parents and unaffected siblings is useful for detecting genotyping errors and if allele frequencies are uncertain. If adequate allele frequency data are available, we suggest a single-point affecteds-only analysis for an initial scan, followed by a multipoint analysis of affected and unaffected members of all available sibships with additional markers around initial hits.</p