Despite a substantial investment in the development of panels of single nucleotide polymorphism (SNP) markers, the simple sequence repeat (SSR) technology with a limited multiplexing capability remains a standard, even for applications requiring whole-genome information. Diversity arrays technology (DArT) types hundreds to thousands of genomic loci in parallel, as previously demonstrated in a number diploid plant species. Here we show that DArT performs similarly well for the hexaploid genome of bread wheat (Triticum aestivum L.). The methodology previously used to generate DArT fingerprints of barley also generated a large number of high-quality markers in wheat (99.8% allele-calling concordance and approximately 95% call rate). The genetic relationships among bread wheat cultivars revealed by DArT coincided with knowledge generated with other methods, and even closely related cultivars could be distinguished. To verify the Mendelian behaviour of DArT markers, we typed a set of 90 Cranbrook x Halberd doubled haploid lines for which a framework (FW) map comprising a total of 339 SSR, restriction fragment length polymorphism (RFLP) and amplified fragment length polymorphism (AFLP) markers was available. We added an equal number of DArT markers to this data set and also incorporated 71 sequence tagged microsatellite (STM) markers. A comparison of logarithm of the odds (LOD) scores, call rates and the degree of genome coverage indicated that the quality and information content of the DArT data set was comparable to that of the combined SSR/RFLP/AFLP data set of the FW map.
Introduction
The only treatment for celiac disease (CD) is life-long adherence to a gluten-free diet (GFD). Noncompliance is associated with signs and symptoms of celiac disease, yet long-term adherence rates are poor. It is not known how the burden of the GFD compares to other medical treatments, and there are limited data on the socio-economic factors influencing treatment adherence. In this study we compared treatment burden and health state in CD compared with other chronic illnesses and evaluated the relationship between treatment burden and adherence.
Methods
A survey was mailed to participants with: CD, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hypertension (HTN), diabetes mellitus (DM), congestive heart failure (CHF), and end stage renal disease on dialysis (ESRD). Surveys included demographic information and visual analog scales measuring treatment burden, importance of treatment, disease-specific and overall health status.
Results
We collected surveys from 341 celiac and 368 non-celiac participants. Celiac participants reported high treatment burden, greater than participants with GERD or HTN and comparable to ESRD. Conversely, patients with CD reported the highest health state of all groups. Factors associated with high treatment burden in CD included poor adherence, concern regarding food cost, eating outside the home, higher income, lack of college education and time limitations in preparing food. Poor adherence in CD was associated with increased symptoms, income, and low perceived importance of treatment.
Discussion
Participants with CD have high treatment burden but also excellent overall health status in comparison with other chronic medical conditions. The significant burden of dietary therapy for celiac disease argues for the need for safe adjuvant treatment as well as interventions designed to lower the perceived burden of the GFD.
Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.
SUMMARY BackgroundWhile the Crohn's disease activity index (CDAI) is the gold standard for defining clinical endpoints in Crohn's disease (Crohn's) clinical trials, its ability to distinguish symptoms due to inflammation from those that are non-inflammatory has been questioned.
SUMMARY BackgroundGuidelines published by the international gastroenterology societies establish standards of care and seek to improve patient outcomes.
A B S T R A C T Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in patients with hematologic malignancies but carries a significant risk of graft-versus-host disease (GVHD). There are no standard treatments for steroid-refractory (SR) gastrointestinal (GI) acute GVHD (aGVHD). This multicenter, international, retrospective medical record review aimed to evaluate the off-label use of vedolizumab, a gut-selective immunomodulator, for treating SR GI aGVHD. Data were collected from patients' medical records; criteria for extraction included no more than 1 allo-HCT and at least 1 dose of vedolizumab as treatment for SR GI aGVHD (ie, stage 1 to 4 GI aGVHD following 1 previous treatment regimen(s) containing 1 mg/kg methylprednisolone or equivalent). Descriptive analyses of response rate, overall survival (OS), and serious adverse effects (SAEs) were performed. Twenty-nine patients were identified from 7 sites who had received 1 to 10 doses of vedolizumab 300 mg i.v. (median 3 doses) as treatment for SR GI aGVHD. The overall response rate at 6 to 10 weeks after vedolizumab initiation was 64%, and OS at 6 months was 54%. There were 29 SAEs, including 12 infections; 3 SAEs were considered possibly related to vedolizumab, 2 of which were infections. Thirteen SAEs were fatal, 1 of which was possibly vedolizumabrelated. There were 8 nonserious infections and 1 serious infection with confirmed GI origin in 8 patients; there was no apparent pattern in the timing of these infections relative to the initiation of vedolizumab treatment. Further data on the efficacy and safety of vedolizumab in this setting from prospective trials are needed.
Most of the interventional guidelines failed to grade the evidence. When present, most guidelines used lower-quality evidence. Furthermore, most guidelines failed to disclose COIs. When commented on, numerous COIs were present. Future guidelines should clearly state the quality of evidence, use a standard grading system, be transparent regarding potential biases, and provide frequent updates.
Key Points
In adults undergoing allo-HSCT, vedolizumab IV 300 mg was well tolerated and had a low incidence of overall and lower-intestinal aGVHD. These phase 1b data support further evaluation of vedolizumab for the prevention of aGVHD in adults undergoing allo-HSCT.
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