The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.
In ancestry-stratified models of 5962 European American (EA), ...2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves.
We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5e-08 in the EA and ancestry-combined analysis, respectively Beta(se)=0.025(0.004);Beta(se)=0.021(0.003). No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects.
The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.
Summary
This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23–24 April 2015 (HOME IV). The aim of the meeting was ...to achieve consensus over the preferred outcome instruments for measuring patient‐reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient‐reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient‐reported symptoms were discussed including the Patient‐Oriented SCOring Atopic Dermatitis index, Patient‐Oriented Eczema Measure (POEM), Self‐Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score and, by consensus, POEM was selected as the preferred instrument to measure patient‐reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.
What's already known about this topic?
Previous meetings of the Harmonising Outcome Measures for Eczema (HOME) initiative have achieved international consensus that the domains of clinician‐reported signs, patient‐reported symptoms, quality of life and long‐term control should be measured as the core outcomes for atopic eczema clinical trials.
It has been recommended that clinician‐reported signs should be measured using the Eczema Area and Severity Index.
What does this study add?
During the HOME IV meeting (Spring 2015, Malmö, Sweden), a consensus was achieved that the Patient‐Oriented Eczema Measure should be used to capture patient‐reported symptoms in future atopic eczema trials.
The remaining two core outcome domains of quality of life and long‐term control require further work to determine the preferred core outcome measurement instruments.
The aetiology and pathogenesis of non-genetic forms of frontotemporal dementia (FTD) is unknown and even with the genetic forms of FTD, pathogenesis remains elusive. Given the association between ...systemic inflammation and other neurodegenerative processes, links between autoimmunity and FTD need to be explored.
To describe the prevalence of systemic autoimmune disease in semantic variant primary progressive aphasia (svPPA), a clinical cohort, and in progranulin (PGRN) mutation carriers compared with neurologically healthy normal controls (NC) and Alzheimer's disease (AD) as dementia controls.
Case control.
Academic medical centres.
129 svPPA, 39 PGRN, 186 NC and 158 AD patients underwent chart review for autoimmune conditions. A large subset of svPPA, PGRN and NC cohorts underwent serum analysis for tumour necrosis factor α (TNF-α) levels.
χ(2) Comparison of autoimmune prevalence and follow-up logistic regression.
There was a significantly increased risk of autoimmune disorders clustered around inflammatory arthritides, cutaneous disorders and gastrointestinal conditions in the svPPA and PGRN cohorts. Elevated TNF-α levels were observed in svPPA and PGRN compared with NC.
svPPA and PGRN are associated with increased prevalence of specific and related autoimmune diseases compared with NC and AD. These findings suggest a unique pattern of systemic inflammation in svPPA and PGRN and open new research avenues for understanding and treating disorders associated with underlying transactive response DNA-binding protein 43 aggregation.
Summary
Background
Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating behaviour, and surgery have largely been derived from referral centre populations.
Aim
To ...investigate whether serological markers, susceptibility genes or psychological characteristics are associated with complicated CD or surgery in a population‐based cohort.
Methods
One hundred and eighty‐two members of the Manitoba IBD Cohort with CD phenotyped using the Montreal classification underwent genetic and serological analysis at enrolment and after 5 years. One hundred and twenty‐seven had paired sera at baseline and 5 years later and their data were used to predict outcomes at a median of 9.3 years. Serological analysis consisted of a seven antibody panel, and DNA was tested for CD‐associated NOD2 variants (rs2066845,rs2076756,rs2066847), ATG16L1 (rs3828309, rs2241880) and IL23R (rs11465804). Psychological characteristics were assessed using semi‐structured interviews and validated survey measures.
Results
Sixty‐five per cent had complicated CD and 42% underwent surgery. Multivariate analysis indicated that only ASCA IgG‐positive serology was predictive of stricturing/penetrating behaviour (OR = 3.01; 95% CI: 1.28–7.09; P = 0.01) and ileal CD (OR = 2.2; 95% CI: 1.07–4.54, P = 0.03). Complicated CD behaviour was strongly associated with surgery (OR = 5.6; 95% CI: 2.43–12.91; P < 0.0001), whereas in multivariate analysis, only ASCA IgG was associated (OR = 2.66; 95% CI, 1.40–5.06, P = 0.003). ASCA titre results were similar at baseline and follow‐up. Psychological characteristics were not significantly associated with disease behaviour, serological profile or genotype.
Conclusions
ASCA IgG at baseline was significantly associated with stricturing/penetrating disease at 9–10 years from diagnosis. Stricturing/penetrating disease was significantly associated with surgery. In a model including serology, the genotypes assessed did not significantly associate with complicated disease or surgery.
Background
A gluten‐free diet (GFD) requires tremendous dedication, involving substantive changes to diet and lifestyle that may have a significant impact upon quality of life. The present study ...aimed io assess dietary adherence, knowledge of a GFD, and the emotional and lifestyle impact of a GFD.
Methods
Community dwelling adults following a GFD completed a questionnaire with items related to reasons for avoiding gluten, diagnostic testing, GFD adherence, knowledge and sources of information about a GFD, the Work and Social Adjustment Scale, and the effect of a GFD diet on lifestyle, feelings and behaviours.
Results
Strict GFD adherence among the 222 coeliac disease (CD) patients was 56%. Non‐CD individuals (n = 38) were more likely to intentionally ingest gluten (odds ratio = 3.7; 95% confidence interval = 1.4–9.4). The adverse impact of a GFD was modest but most pronounced in the social domain. Eating shifted from the public to the domestic sphere and there were feelings of social isolation. Affective responses reflected resilience because acceptance and relief were experienced more commonly than anxiety or anger. Non‐CD respondents were less knowledgeable and less likely to consult health professionals. They experienced less anger and depression and greater pleasure in eating than CD respondents.
Conclusions
The findings obtained in the present suggest there is good potential for positive adaptation to the demands of a GFD; nevertheless, there is a measurable degree of social impairment that merits further study. The GFD may be a viable treatment option for conditions other than CD; however, education strategies regarding the need for diagnostic testing to exclude CD are required.
Summary
Background
A gluten‐free diet is the only recommended treatment for coeliac disease.
Aim
To determine the prevalence and characteristics of reactions to gluten among persons with coeliac ...disease on a gluten‐free diet.
Methods
Adults with biopsy proven, newly diagnosed coeliac disease were prospectively enrolled. A survey related to diet adherence and reactions to gluten was completed at study entry and 6 months. The Coeliac Symptom Index, Coeliac Diet Assessment Tool (CDAT) and Gluten‐Free Eating Assessment Tool (GF‐EAT) were used to measure coeliac disease symptoms and gluten‐free diet adherence.
Results
Of the 105 participants, 91% reported gluten exposure <1 per month and median CDAT score was 9 (IQR 8–11), consistent with adequate adherence. A suspected symptomatic reaction to gluten was reported by 66%. Gluten consumption was unsuspected until a reaction occurred (63%) or resulted from problems ordering in a restaurant (29%). The amount of gluten consumed ranged from cross‐contact (30%) to a major ingredient (10%). Median time to symptom onset was 1 h (range 10 min to 48 h), and median symptom duration was 24 h (range 1 h to 8 days). Common symptoms included abdominal pain (80%), diarrhoea (52%), fatigue (33%), headache (30%) and irritability (29%).
Conclusions
Reactions to suspected gluten exposure are common among patients with coeliac disease on a gluten‐free diet. Eating at restaurants and other peoples’ homes remain a risk for unintentional gluten exposure. When following individuals with coeliac disease, clinicians should include questions regarding reactions to gluten as part of their assessment of gluten‐free diet adherence.
The COVID-19 pandemic has had a significant impact on mental health across the globe. People living with a chronic gastrointestinal (GI) disorder might be particularly at risk of mental health ...complications given higher rates of comorbid anxiety and depression compared to the healthy population. As GI disorders affect up to 40% of the population worldwide, this international collaborative study seeks to evaluate the extent of the impact of the COVID-19 pandemic on GI symptoms specifically and more generally on the well-being of those living with chronic GI conditions.
A longitudinal survey with three time points (baseline, 6-month, and 12-month) will be conducted online. Adult participants with GI disorders from multiple countries will be recruited via patient associations, social media advertising, utilizing snowball sampling. Participants will be invited to complete a battery of questionnaires including demographic and health parameters, and measures of gastrointestinal symptoms, fear of COVID-19, perceived impact of COVID-19, illness perceptions, coping, depression, anxiety, stress, catastrophizing, and quality of life, using validated measures where available. Statistical analyses will include univariate descriptive models, multivariate models utilizing regression, mediation, and moderation, and latent growth models.
This project may present novel information to the field of psychogastroenterology and may provide crucial information regarding the areas of impact for individuals with GI disorders during and following the pandemic. Further, this information can guide healthcare providers and patient associations on how to target support related to the pandemic mental health sequelae for these patients.
•COVID-19 has resulted in distress for people with Gastrointestinal (GI) Disorders.•This study will use a longitudinal data collection over a period of 12 months.•Data collection will be conducted in multiple countries.•This will aid the development of health interventions targeting GI populations.
PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, ...predominantly surgically treated cohort.
In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided.
On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors.
PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer.
Abstract Background Depression and anxiety are common in persons with multiple sclerosis (MS), and adversely affect fatigue, medication adherence, and quality of life. Though effective treatments for ...depression and anxiety exist in the general population, their applicability in the MS population has not been definitively established. Objective To determine the overall effect of psychological and pharmacological treatments for depression or anxiety in persons with MS. Methods We searched the Medline, EMBASE, PsycINFO, PsycARTICLES Full Text, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and Scopus databases using systematic review methodology from database inception until March 25, 2015. Two independent reviewers screened abstracts, extracted data, and assessed risk of bias and strength of evidence. We included controlled clinical trials reporting on the effect of pharmacological or psychological interventions for depression or anxiety in a sample of persons with MS. We calculated standardized mean differences (SMD) and pooled using random effects meta-analysis. Results Of 1753 abstracts screened, 21 articles reporting on 13 unique clinical trials met the inclusion criteria. Depression severity improved in nine psychological trials of depression treatment ( N =307; SMD: − 0.45 (95%CI: − 0.74, − 0.16)). The severity of depression also improved in three pharmacological trials of depression treatment (SMD: − 0.63 ( N =165; 95%CI: − 1.07, − 0.20)). For anxiety, only a single trial examined psychological therapy for injection phobia and reported no statistically significant improvement. Conclusion Pharmacological and psychological treatments for depression were effective in reducing depressive symptoms in MS. The data are insufficient to determine the effectiveness of treatments for anxiety.
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