The score statistic of the LD-lod analysis: detecting linkage adaptive to linkage disequilibrium.

PubMed

Huang, J; Jiang, Y

2001-01-01

We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers. Copyright 2001 S. Karger AG, Basel

A Simple Sampling Method for Estimating the Accuracy of Large Scale Record Linkage Projects.

PubMed

Boyd, James H; Guiver, Tenniel; Randall, Sean M; Ferrante, Anna M; Semmens, James B; Anderson, Phil; Dickinson, Teresa

2016-05-17

Record linkage techniques allow different data collections to be brought together to provide a wider picture of the health status of individuals. Ensuring high linkage quality is important to guarantee the quality and integrity of research. Current methods for measuring linkage quality typically focus on precision (the proportion of incorrect links), given the difficulty of measuring the proportion of false negatives. The aim of this work is to introduce and evaluate a sampling based method to estimate both precision and recall following record linkage. In the sampling based method, record-pairs from each threshold (including those below the identified cut-off for acceptance) are sampled and clerically reviewed. These results are then applied to the entire set of record-pairs, providing estimates of false positives and false negatives. This method was evaluated on a synthetically generated dataset, where the true match status (which records belonged to the same person) was known. The sampled estimates of linkage quality were relatively close to actual linkage quality metrics calculated for the whole synthetic dataset. The precision and recall measures for seven reviewers were very consistent with little variation in the clerical assessment results (overall agreement using the Fleiss Kappa statistics was 0.601). This method presents as a possible means of accurately estimating matching quality and refining linkages in population level linkage studies. The sampling approach is especially important for large project linkages where the number of record pairs produced may be very large often running into millions.

Quantification of NSW Ambulance Record Linkages with Multiple External Datasets.

PubMed

Carroll, Therese; Muecke, Sandy; Simpson, Judy; Irvine, Katie; Jenkins, André

2015-01-01

This study has two aims: 1) to describe linkage rates between ambulance data and external datasets for "episodes of care" and "patient only" linkages in New South Wales (NSW), Australia; and 2) to detect and report any systematic issues with linkage that relate to patients, and operational or clinical variables that may introduce bias in subsequent studies if not adequately addressed. During 2010-11, the Centre for Health Record Linkage (CHeReL) in NSW, linked the records for patients attended by NSW Ambulance paramedics for the period July 2006 to June 2009, with four external datasets: Emergency Department Data Collection; Admitted Patient Data Collection; NSW Registry of Births, Deaths and Marriages death registration data; and the Australian Bureau of Statistics mortality data. This study reports linkage rates in terms of those "expected" to link and those who were "not expected" to link with external databases within 24 hours of paramedic attendance. Following thorough data preparation processes, 2,041,728 NSW Ambulance care episodes for 1,116,509 patients fulfilled the inclusion criteria. The overall episode-specific hospital linkage rate was 97.2%. Where a patient was not transported to hospital following paramedic care, 8.6% of these episodes resulted in an emergency department attendance within 24 hours. For all care episodes, 5.2% linked to a death record at some time within the 3-year period, with 2.4% of all death episodes occurring within 7 days of a paramedic encounter. For NSW Ambulance episodes of care that were expected to link to an external dataset but did not, nonlinkage to hospital admission records tended to decrease with age. For all other variables, issues relating to rates of linkage and nonlinkage were more indiscriminate. This quantification of the limitations of this large linked dataset will underpin the interpretation and results of ensuing studies that will inform future clinical and operational policies and practices at NSW Ambulance.

Use of graph theory measures to identify errors in record linkage.

PubMed

Randall, Sean M; Boyd, James H; Ferrante, Anna M; Bauer, Jacqueline K; Semmens, James B

2014-07-01

Ensuring high linkage quality is important in many record linkage applications. Current methods for ensuring quality are manual and resource intensive. This paper seeks to determine the effectiveness of graph theory techniques in identifying record linkage errors. A range of graph theory techniques was applied to two linked datasets, with known truth sets. The ability of graph theory techniques to identify groups containing errors was compared to a widely used threshold setting technique. This methodology shows promise; however, further investigations into graph theory techniques are required. The development of more efficient and effective methods of improving linkage quality will result in higher quality datasets that can be delivered to researchers in shorter timeframes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pregnancy and IBD

MedlinePlus

... Center Home > Resources > Pregnancy and IBD Go Back Pregnancy and IBD Email Print + Share If you have ... on the developing fetus or newborn. EFFECT OF PREGNANCY ON WOMEN WITH IBD Women should be well ...

Ensuring Privacy When Integrating Patient-Based Datasets: New Methods and Developments in Record Linkage.

PubMed

Brown, Adrian P; Ferrante, Anna M; Randall, Sean M; Boyd, James H; Semmens, James B

2017-01-01

In an era where the volume of structured and unstructured digital data has exploded, there has been an enormous growth in the creation of data about individuals that can be used for understanding and treating disease. Joining these records together at an individual level provides a complete picture of a patient's interaction with health services and allows better assessment of patient outcomes and effectiveness of treatment and services. Record linkage techniques provide an efficient and cost-effective method to bring individual records together as patient profiles. These linkage procedures bring their own challenges, especially relating to the protection of privacy. The development and implementation of record linkage systems that do not require the release of personal information can reduce the risks associated with record linkage and overcome legal barriers to data sharing. Current conceptual and experimental privacy-preserving record linkage (PPRL) models show promise in addressing data integration challenges. Enhancing and operationalizing PPRL protocols can help address the dilemma faced by some custodians between using data to improve quality of life and dealing with the ethical, legal, and administrative issues associated with protecting an individual's privacy. These methods can reduce the risk to privacy, as they do not require personally identifying information to be shared. PPRL methods can improve the delivery of record linkage services to the health and broader research community.

Ensuring Privacy When Integrating Patient-Based Datasets: New Methods and Developments in Record Linkage

PubMed Central

Brown, Adrian P.; Ferrante, Anna M.; Randall, Sean M.; Boyd, James H.; Semmens, James B.

2017-01-01

In an era where the volume of structured and unstructured digital data has exploded, there has been an enormous growth in the creation of data about individuals that can be used for understanding and treating disease. Joining these records together at an individual level provides a complete picture of a patient’s interaction with health services and allows better assessment of patient outcomes and effectiveness of treatment and services. Record linkage techniques provide an efficient and cost-effective method to bring individual records together as patient profiles. These linkage procedures bring their own challenges, especially relating to the protection of privacy. The development and implementation of record linkage systems that do not require the release of personal information can reduce the risks associated with record linkage and overcome legal barriers to data sharing. Current conceptual and experimental privacy-preserving record linkage (PPRL) models show promise in addressing data integration challenges. Enhancing and operationalizing PPRL protocols can help address the dilemma faced by some custodians between using data to improve quality of life and dealing with the ethical, legal, and administrative issues associated with protecting an individual’s privacy. These methods can reduce the risk to privacy, as they do not require personally identifying information to be shared. PPRL methods can improve the delivery of record linkage services to the health and broader research community. PMID:28303240

Skin Complications of IBD

MedlinePlus

... Home > Resources > Skin Complications of IBD Go Back Skin Complications of IBD Email Print + Share After arthritis, ... about 5% of people with inflammatory bowel disease. SKIN DISORDERS COMMONLY SEEN IN IBD ERHTHEMA NODOSUM The ...

Phenotypic concordance in familial inflammatory bowel disease (IBD). Results of a nationwide IBD Spanish database.

PubMed

Cabré, Eduard; Mañosa, Míriam; García-Sánchez, Valle; Gutiérrez, Ana; Ricart, Elena; Esteve, Maria; Guardiola, Jordi; Aguas, Mariam; Merino, Olga; Ponferrada, Angel; Gisbert, Javier P; Garcia-Planella, Esther; Ceña, Gloria; Cabriada, José L; Montoro, Miguel; Domènech, Eugeni

2014-07-01

Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (κ index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p<0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (κ=0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Linked Records of Children with Traumatic Brain Injury. Probabilistic Linkage without Use of Protected Health Information.

PubMed

Bennett, T D; Dean, J M; Keenan, H T; McGlincy, M H; Thomas, A M; Cook, L J

2015-01-01

Record linkage may create powerful datasets with which investigators can conduct comparative effectiveness studies evaluating the impact of tests or interventions on health. All linkages of health care data files to date have used protected health information (PHI) in their linkage variables. A technique to link datasets without using PHI would be advantageous both to preserve privacy and to increase the number of potential linkages. We applied probabilistic linkage to records of injured children in the National Trauma Data Bank (NTDB, N = 156,357) and the Pediatric Health Information Systems (PHIS, N = 104,049) databases from 2007 to 2010. 49 match variables without PHI were used, many of them administrative variables and indicators for procedures recorded as International Classification of Diseases, 9th revision, Clinical Modification codes. We validated the accuracy of the linkage using identified data from a single center that submits to both databases. We accurately linked the PHIS and NTDB records for 69% of children with any injury, and 88% of those with severe traumatic brain injury eligible for a study of intervention effectiveness (positive predictive value of 98%, specificity of 99.99%). Accurate linkage was associated with longer lengths of stay, more severe injuries, and multiple injuries. In populations with substantial illness or injury severity, accurate record linkage may be possible in the absence of PHI. This methodology may enable linkages and, in turn, comparative effectiveness studies that would be unlikely or impossible otherwise.

Efficient sequential and parallel algorithms for record linkage.

PubMed

Mamun, Abdullah-Al; Mi, Tian; Aseltine, Robert; Rajasekaran, Sanguthevar

2014-01-01

Integrating data from multiple sources is a crucial and challenging problem. Even though there exist numerous algorithms for record linkage or deduplication, they suffer from either large time needs or restrictions on the number of datasets that they can integrate. In this paper we report efficient sequential and parallel algorithms for record linkage which handle any number of datasets and outperform previous algorithms. Our algorithms employ hierarchical clustering algorithms as the basis. A key idea that we use is radix sorting on certain attributes to eliminate identical records before any further processing. Another novel idea is to form a graph that links similar records and find the connected components. Our sequential and parallel algorithms have been tested on a real dataset of 1,083,878 records and synthetic datasets ranging in size from 50,000 to 9,000,000 records. Our sequential algorithm runs at least two times faster, for any dataset, than the previous best-known algorithm, the two-phase algorithm using faster computation of the edit distance (TPA (FCED)). The speedups obtained by our parallel algorithm are almost linear. For example, we get a speedup of 7.5 with 8 cores (residing in a single node), 14.1 with 16 cores (residing in two nodes), and 26.4 with 32 cores (residing in four nodes). We have compared the performance of our sequential algorithm with TPA (FCED) and found that our algorithm outperforms the previous one. The accuracy is the same as that of this previous best-known algorithm.

Quantifying the Correctness, Computational Complexity, and Security of Privacy-Preserving String Comparators for Record Linkage

PubMed Central

Durham, Elizabeth; Xue, Yuan; Kantarcioglu, Murat; Malin, Bradley

2011-01-01

Record linkage is the task of identifying records from disparate data sources that refer to the same entity. It is an integral component of data processing in distributed settings, where the integration of information from multiple sources can prevent duplication and enrich overall data quality, thus enabling more detailed and correct analysis. Privacy-preserving record linkage (PPRL) is a variant of the task in which data owners wish to perform linkage without revealing identifiers associated with the records. This task is desirable in various domains, including healthcare, where it may not be possible to reveal patient identity due to confidentiality requirements, and in business, where it could be disadvantageous to divulge customers' identities. To perform PPRL, it is necessary to apply string comparators that function in the privacy-preserving space. A number of privacy-preserving string comparators (PPSCs) have been proposed, but little research has compared them in the context of a real record linkage application. This paper performs a principled and comprehensive evaluation of six PPSCs in terms of three key properties: 1) correctness of record linkage predictions, 2) computational complexity, and 3) security. We utilize a real publicly-available dataset, derived from the North Carolina voter registration database, to evaluate the tradeoffs between the aforementioned properties. Among our results, we find that PPSCs that partition, encode, and compare strings yield highly accurate record linkage results. However, as a tradeoff, we observe that such PPSCs are less secure than those that map and compare strings in a reduced dimensional space. PMID:22904698

Quantifying the Correctness, Computational Complexity, and Security of Privacy-Preserving String Comparators for Record Linkage.

PubMed

Durham, Elizabeth; Xue, Yuan; Kantarcioglu, Murat; Malin, Bradley

2012-10-01

Record linkage is the task of identifying records from disparate data sources that refer to the same entity. It is an integral component of data processing in distributed settings, where the integration of information from multiple sources can prevent duplication and enrich overall data quality, thus enabling more detailed and correct analysis. Privacy-preserving record linkage (PPRL) is a variant of the task in which data owners wish to perform linkage without revealing identifiers associated with the records. This task is desirable in various domains, including healthcare, where it may not be possible to reveal patient identity due to confidentiality requirements, and in business, where it could be disadvantageous to divulge customers' identities. To perform PPRL, it is necessary to apply string comparators that function in the privacy-preserving space. A number of privacy-preserving string comparators (PPSCs) have been proposed, but little research has compared them in the context of a real record linkage application. This paper performs a principled and comprehensive evaluation of six PPSCs in terms of three key properties: 1) correctness of record linkage predictions, 2) computational complexity, and 3) security. We utilize a real publicly-available dataset, derived from the North Carolina voter registration database, to evaluate the tradeoffs between the aforementioned properties. Among our results, we find that PPSCs that partition, encode, and compare strings yield highly accurate record linkage results. However, as a tradeoff, we observe that such PPSCs are less secure than those that map and compare strings in a reduced dimensional space.

Impact of specialized inpatient IBD care on outcomes of IBD hospitalizations: A cohort study

PubMed Central

Law, Cindy CY; Sasidharan, Saranya; Rodrigues, Rodrigo; Nguyen, Deanna D; Sauk, Jenny; Garber, John; Giallourakis, Cosmas; Xavier, Ramnik; Khalili, Hamed; Yajnik, Vijay; Ananthakrishnan, Ashwin N

2016-01-01

Background The management of inflammatory bowel diseases (IBD; Crohn’s disease (CD), ulcerative colitis (UC)) is increasingly complex. Specialized care has been associated with improved ambulatory IBD outcomes. Aims To examine if the implementation of specialized inpatient IBD care modified short and long-term clinical outcomes in IBD-related hospitalizations. Methods This retrospective cohort study included IBD patients hospitalized between July 2013 and April 2015 at a single tertiary referral center where a specialized inpatient IBD care model was implemented in July 2014. In-hospital medical and surgical outcomes as well as post-discharge outcomes at 30 and 90 days were analyzed along with measures of quality of in-hospital care. Effect of specialist IBD care was examined on multivariate analysis. Results A total of 408 IBD-related admissions were included. With implementation of specialized IBD inpatient care, we observed increased frequency of use of high-dose biologic therapy for induction (26% vs. 9%, odds ratio (OR) 5.50, 95% CI 1.30 – 23.17) and higher proportion of patients in remission at 90 days after discharge (multivariate OR 1.60, 95% CI 0.99 – 2.69). While there was no difference in surgery by 90 days, among those who underwent surgery, early surgery defined as in-hospital or within 30 days of discharge, was more common in the study period (71%) compared to the control period (46%, multivariate OR 2.73, 95% CI 1.22 – 6.12). There was no difference in length of stay between the two years. Conclusions Implementation of specialized inpatient IBD care beneficially impacted remission and facilitated early surgical treatment. PMID:27482978

Efficient sequential and parallel algorithms for record linkage

PubMed Central

Mamun, Abdullah-Al; Mi, Tian; Aseltine, Robert; Rajasekaran, Sanguthevar

2014-01-01

Background and objective Integrating data from multiple sources is a crucial and challenging problem. Even though there exist numerous algorithms for record linkage or deduplication, they suffer from either large time needs or restrictions on the number of datasets that they can integrate. In this paper we report efficient sequential and parallel algorithms for record linkage which handle any number of datasets and outperform previous algorithms. Methods Our algorithms employ hierarchical clustering algorithms as the basis. A key idea that we use is radix sorting on certain attributes to eliminate identical records before any further processing. Another novel idea is to form a graph that links similar records and find the connected components. Results Our sequential and parallel algorithms have been tested on a real dataset of 1 083 878 records and synthetic datasets ranging in size from 50 000 to 9 000 000 records. Our sequential algorithm runs at least two times faster, for any dataset, than the previous best-known algorithm, the two-phase algorithm using faster computation of the edit distance (TPA (FCED)). The speedups obtained by our parallel algorithm are almost linear. For example, we get a speedup of 7.5 with 8 cores (residing in a single node), 14.1 with 16 cores (residing in two nodes), and 26.4 with 32 cores (residing in four nodes). Conclusions We have compared the performance of our sequential algorithm with TPA (FCED) and found that our algorithm outperforms the previous one. The accuracy is the same as that of this previous best-known algorithm. PMID:24154837

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

PubMed Central

Moltke, Ida; Albrechtsen, Anders; Hansen, Thomas v.O.; Nielsen, Finn C.; Nielsen, Rasmus

2011-01-01

All individuals in a finite population are related if traced back long enough and will, therefore, share regions of their genomes identical by descent (IBD). Detection of such regions has several important applications—from answering questions about human evolution to locating regions in the human genome containing disease-causing variants. However, IBD regions can be difficult to detect, especially in the common case where no pedigree information is available. In particular, all existing non-pedigree based methods can only infer IBD sharing between two individuals. Here, we present a new Markov Chain Monte Carlo method for detection of IBD regions, which does not rely on any pedigree information. It is based on a probabilistic model applicable to unphased SNP data. It can take inbreeding, allele frequencies, genotyping errors, and genomic distances into account. And most importantly, it can simultaneously infer IBD sharing among multiple individuals. Through simulations, we show that the simultaneous modeling of multiple individuals makes the method more powerful and accurate than several other non-pedigree based methods. We illustrate the potential of the method by applying it to data from individuals with breast and/or ovarian cancer, and show that a known disease-causing mutation can be mapped to a 2.2-Mb region using SNP data from only five seemingly unrelated affected individuals. This would not be possible using classical linkage mapping or association mapping. PMID:21493780

Record linkage for pharmacoepidemiological studies in cancer patients.

PubMed

Herk-Sukel, Myrthe P P van; Lemmens, Valery E P P; Poll-Franse, Lonneke V van de; Herings, Ron M C; Coebergh, Jan Willem W

2012-01-01

An increasing need has developed for the post-approval surveillance of (new) anti-cancer drugs by means of pharmacoepidemiology and outcomes research in the area of oncology. To create an overview that makes researchers aware of the available database linkages in Northern America and Europe which facilitate pharmacoepidemiology and outcomes research in cancer patients. In addition to our own database, i.e. the Eindhoven Cancer Registry (ECR) linked to the PHARMO Record Linkage System, we considered database linkages between a population-based cancer registry and an administrative healthcare database that at least contains information on drug use and offers a longitudinal perspective on healthcare utilization. Eligible database linkages were limited to those that had been used in multiple published articles in English language included in Pubmed. The HMO Cancer Research Network (CRN) in the US was excluded from this review, as an overview of the linked databases participating in the CRN is already provided elsewhere. Researchers who had worked with the data resources included in our review were contacted for additional information and verification of the data presented in the overview. The following database linkages were included: the Surveillance, Epidemiology, and End-Results-Medicare; cancer registry data linked to Medicaid; Canadian cancer registries linked to population-based drug databases; the Scottish cancer registry linked to the Tayside drug dispensing data; linked databases in the Nordic Countries of Europe: Norway, Sweden, Finland and Denmark; and the ECR-PHARMO linkage in the Netherlands. Descriptives of the included database linkages comprise population size, generalizability of the population, year of first data availability, contents of the cancer registry, contents of the administrative healthcare database, the possibility to select a cancer-free control cohort, and linkage to other healthcare databases. The linked databases offer a longitudinal

Fungal microbiota dysbiosis in IBD

PubMed Central

Sokol, Harry; Leducq, Valentin; Aschard, Hugues; Pham, Hang-Phuong; Jegou, Sarah; Landman, Cecilia; Cohen, David; Liguori, Giuseppina; Bourrier, Anne; Nion-Larmurier, Isabelle; Cosnes, Jacques; Seksik, Philippe; Langella, Philippe; Skurnik, David; Richard, Mathias L; Beaugerie, Laurent

2017-01-01

Objective The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Design Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. Results We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Conclusions Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis. PMID:26843508

Validity of deterministic record linkage using multiple indirect personal identifiers: linking a large registry to claims data.

PubMed

Setoguchi, Soko; Zhu, Ying; Jalbert, Jessica J; Williams, Lauren A; Chen, Chih-Ying

2014-05-01

Linking patient registries with administrative databases can enhance the utility of the databases for epidemiological and comparative effectiveness research. However, registries often lack direct personal identifiers, and the validity of record linkage using multiple indirect personal identifiers is not well understood. Using a large contemporary national cardiovascular device registry and 100% Medicare inpatient data, we linked hospitalization-level records. The main outcomes were the validity measures of several deterministic linkage rules using multiple indirect personal identifiers compared with rules using both direct and indirect personal identifiers. Linkage rules using 2 or 3 indirect, patient-level identifiers (ie, date of birth, sex, admission date) and hospital ID produced linkages with sensitivity of 95% and specificity of 98% compared with a gold standard linkage rule using a combination of both direct and indirect identifiers. Ours is the first large-scale study to validate the performance of deterministic linkage rules without direct personal identifiers. When linking hospitalization-level records in the absence of direct personal identifiers, provider information is necessary for successful linkage. © 2014 American Heart Association, Inc.

Accuracy of probabilistic and deterministic record linkage: the case of tuberculosis.

PubMed

Oliveira, Gisele Pinto de; Bierrenbach, Ana Luiza de Souza; Camargo, Kenneth Rochel de; Coeli, Cláudia Medina; Pinheiro, Rejane Sobrino

2016-08-22

To analyze the accuracy of deterministic and probabilistic record linkage to identify TB duplicate records, as well as the characteristics of discordant pairs. The study analyzed all TB records from 2009 to 2011 in the state of Rio de Janeiro. A deterministic record linkage algorithm was developed using a set of 70 rules, based on the combination of fragments of the key variables with or without modification (Soundex or substring). Each rule was formed by three or more fragments. The probabilistic approach required a cutoff point for the score, above which the links would be automatically classified as belonging to the same individual. The cutoff point was obtained by linkage of the Notifiable Diseases Information System - Tuberculosis database with itself, subsequent manual review and ROC curves and precision-recall. Sensitivity and specificity for accurate analysis were calculated. Accuracy ranged from 87.2% to 95.2% for sensitivity and 99.8% to 99.9% for specificity for probabilistic and deterministic record linkage, respectively. The occurrence of missing values for the key variables and the low percentage of similarity measure for name and date of birth were mainly responsible for the failure to identify records of the same individual with the techniques used. The two techniques showed a high level of correlation for pair classification. Although deterministic linkage identified more duplicate records than probabilistic linkage, the latter retrieved records not identified by the former. User need and experience should be considered when choosing the best technique to be used. Analisar a acurácia das técnicas determinística e probabilística para identificação de registros duplicados de tuberculose, assim como as características dos pares discordantes. Foram analisados todos os registros de tuberculose no período de 2009 a 2011 do estado do Rio de Janeiro. Foi desenvolvido algoritmo para relacionamento determinístico, usando conjunto de 70 regras, a

Development and validation of a pediatric IBD knowledge inventory device: the IBD-KID.

PubMed

Haaland, Derek; Day, Andrew S; Otley, Anthony

2014-03-01

Questionnaires exist to assess inflammatory bowel disease (IBD)-related knowledge of adults. Owing to wording and content concerns, these were believed to be inappropriate for use in pediatric patients. The aim of this study was to develop a questionnaire to assess disease-related knowledge of pediatric patients with IBD and their parents. Following a formal process of item generation and reduction, the IBD-Knowledge Inventory Device was developed and pilot tested. It was administered to 10- to 17-year-old patients with IBD, and to 1 of each of their parents. To evaluate its discriminatory validity, pediatric residents, nurses, and ward clerks completed the questionnaire. A total of 99 patients (mean 42, Crohn disease 46, age 14(±2) years) and 99 parents completed the IBD-Knowledge Inventory Device. Parent knowledge scores, 15(±4), were higher than those of patients, 11(±4), P < 0.001. Patient and parent knowledge scores were strongly correlated (r = 0.62, P < 0.001). Patient knowledge score was significantly related to disease type (Crohn disease scored higher than ulcerative colitis, P = 0.004) and to perceived knowledge level (P < 0.001) by regression analysis. Similarly, parent knowledge score was significantly related to sex (girls scored higher, P = 0.014), postsecondary education (P < 0.001), and perceived knowledge level (P = 0.002). The questionnaire scores of 23 were 19, 16, and 10, respectively, for residents, nurses, and ward clerks. Both residents and nurses scored significantly higher than ward clerks (P = 0.001 for both). A valid IBD-related knowledge assessment questionnaire was developed for use in older children and adolescents with IBD and their parents.

Statistics on continuous IBD data: Exact distribution evaluation for a pair of full(half)-sibs and a pair of a (great-) grandchild with a (great-) grandparent

PubMed Central

Stefanov, Valeri T

2002-01-01

Background Pairs of related individuals are widely used in linkage analysis. Most of the tests for linkage analysis are based on statistics associated with identity by descent (IBD) data. The current biotechnology provides data on very densely packed loci, and therefore, it may provide almost continuous IBD data for pairs of closely related individuals. Therefore, the distribution theory for statistics on continuous IBD data is of interest. In particular, distributional results which allow the evaluation of p-values for relevant tests are of importance. Results A technology is provided for numerical evaluation, with any given accuracy, of the cumulative probabilities of some statistics on continuous genome data for pairs of closely related individuals. In the case of a pair of full-sibs, the following statistics are considered: (i) the proportion of genome with 2 (at least 1) haplotypes shared identical-by-descent (IBD) on a chromosomal segment, (ii) the number of distinct pieces (subsegments) of a chromosomal segment, on each of which exactly 2 (at least 1) haplotypes are shared IBD. The natural counterparts of these statistics for the other relationships are also considered. Relevant Maple codes are provided for a rapid evaluation of the cumulative probabilities of such statistics. The genomic continuum model, with Haldane's model for the crossover process, is assumed. Conclusions A technology, together with relevant software codes for its automated implementation, are provided for exact evaluation of the distributions of relevant statistics associated with continuous genome data on closely related individuals. PMID:11996673

Crohn’s Disease and Genetic Hitchhiking at IBD5

PubMed Central

Huff, Chad D.; Witherspoon, David J.; Zhang, Yuhua; Gatenbee, Chandler; Denson, Lee A.; Kugathasan, Subra; Hakonarson, Hakon; Whiting, April; Davis, Chadwick T.; Wu, Wilfred; Xing, Jinchuan; Watkins, W. Scott; Bamshad, Michael J.; Bradfield, Jonathan P.; Bulayeva, Kazima; Simonson, Tatum S.; Jorde, Lynn B.; Guthery, Stephen L.

2012-01-01

in expression of OCTN1. Collectively, these data indicate that the 503F variant has increased in frequency due to recent positive selection and that disease-causing variants in linkage disequilibrium with 503F have hitchhiked to relatively high frequency, thus forming the IBD5 risk haplotype. Finally, our association results and expression data support IRF1 as a strong candidate for Crohn’s disease causation. PMID:21816865

Designing an algorithm to preserve privacy for medical record linkage with error-prone data.

PubMed

Pal, Doyel; Chen, Tingting; Zhong, Sheng; Khethavath, Praveen

2014-01-20

Linking medical records across different medical service providers is important to the enhancement of health care quality and public health surveillance. In records linkage, protecting the patients' privacy is a primary requirement. In real-world health care databases, records may well contain errors due to various reasons such as typos. Linking the error-prone data and preserving data privacy at the same time are very difficult. Existing privacy preserving solutions for this problem are only restricted to textual data. To enable different medical service providers to link their error-prone data in a private way, our aim was to provide a holistic solution by designing and developing a medical record linkage system for medical service providers. To initiate a record linkage, one provider selects one of its collaborators in the Connection Management Module, chooses some attributes of the database to be matched, and establishes the connection with the collaborator after the negotiation. In the Data Matching Module, for error-free data, our solution offered two different choices for cryptographic schemes. For error-prone numerical data, we proposed a newly designed privacy preserving linking algorithm named the Error-Tolerant Linking Algorithm, that allows the error-prone data to be correctly matched if the distance between the two records is below a threshold. We designed and developed a comprehensive and user-friendly software system that provides privacy preserving record linkage functions for medical service providers, which meets the regulation of Health Insurance Portability and Accountability Act. It does not require a third party and it is secure in that neither entity can learn the records in the other's database. Moreover, our novel Error-Tolerant Linking Algorithm implemented in this software can work well with error-prone numerical data. We theoretically proved the correctness and security of our Error-Tolerant Linking Algorithm. We have also fully

Designing an Algorithm to Preserve Privacy for Medical Record Linkage With Error-Prone Data

PubMed Central

Pal, Doyel; Chen, Tingting; Khethavath, Praveen

2014-01-01

Background Linking medical records across different medical service providers is important to the enhancement of health care quality and public health surveillance. In records linkage, protecting the patients’ privacy is a primary requirement. In real-world health care databases, records may well contain errors due to various reasons such as typos. Linking the error-prone data and preserving data privacy at the same time are very difficult. Existing privacy preserving solutions for this problem are only restricted to textual data. Objective To enable different medical service providers to link their error-prone data in a private way, our aim was to provide a holistic solution by designing and developing a medical record linkage system for medical service providers. Methods To initiate a record linkage, one provider selects one of its collaborators in the Connection Management Module, chooses some attributes of the database to be matched, and establishes the connection with the collaborator after the negotiation. In the Data Matching Module, for error-free data, our solution offered two different choices for cryptographic schemes. For error-prone numerical data, we proposed a newly designed privacy preserving linking algorithm named the Error-Tolerant Linking Algorithm, that allows the error-prone data to be correctly matched if the distance between the two records is below a threshold. Results We designed and developed a comprehensive and user-friendly software system that provides privacy preserving record linkage functions for medical service providers, which meets the regulation of Health Insurance Portability and Accountability Act. It does not require a third party and it is secure in that neither entity can learn the records in the other’s database. Moreover, our novel Error-Tolerant Linking Algorithm implemented in this software can work well with error-prone numerical data. We theoretically proved the correctness and security of our Error

A novel metadata management model to capture consent for record linkage in longitudinal research studies.

PubMed

McMahon, Christiana; Denaxas, Spiros

2017-11-06

Informed consent is an important feature of longitudinal research studies as it enables the linking of the baseline participant information with administrative data. The lack of standardized models to capture consent elements can lead to substantial challenges. A structured approach to capturing consent-related metadata can address these. a) Explore the state-of-the-art for recording consent; b) Identify key elements of consent required for record linkage; and c) Create and evaluate a novel metadata management model to capture consent-related metadata. The main methodological components of our work were: a) a systematic literature review and qualitative analysis of consent forms; b) the development and evaluation of a novel metadata model. We qualitatively analyzed 61 manuscripts and 30 consent forms. We extracted data elements related to obtaining consent for linkage. We created a novel metadata management model for consent and evaluated it by comparison with the existing standards and by iteratively applying it to case studies. The developed model can facilitate the standardized recording of consent for linkage in longitudinal research studies and enable the linkage of external participant data. Furthermore, it can provide a structured way of recording consent-related metadata and facilitate the harmonization and streamlining of processes.

Evaluating privacy-preserving record linkage using cryptographic long-term keys and multibit trees on large medical datasets.

PubMed

Brown, Adrian P; Borgs, Christian; Randall, Sean M; Schnell, Rainer

2017-06-08

Integrating medical data using databases from different sources by record linkage is a powerful technique increasingly used in medical research. Under many jurisdictions, unique personal identifiers needed for linking the records are unavailable. Since sensitive attributes, such as names, have to be used instead, privacy regulations usually demand encrypting these identifiers. The corresponding set of techniques for privacy-preserving record linkage (PPRL) has received widespread attention. One recent method is based on Bloom filters. Due to superior resilience against cryptographic attacks, composite Bloom filters (cryptographic long-term keys, CLKs) are considered best practice for privacy in PPRL. Real-world performance of these techniques using large-scale data is unknown up to now. Using a large subset of Australian hospital admission data, we tested the performance of an innovative PPRL technique (CLKs using multibit trees) against a gold-standard derived from clear-text probabilistic record linkage. Linkage time and linkage quality (recall, precision and F-measure) were evaluated. Clear text probabilistic linkage resulted in marginally higher precision and recall than CLKs. PPRL required more computing time but 5 million records could still be de-duplicated within one day. However, the PPRL approach required fine tuning of parameters. We argue that increased privacy of PPRL comes with the price of small losses in precision and recall and a large increase in computational burden and setup time. These costs seem to be acceptable in most applied settings, but they have to be considered in the decision to apply PPRL. Further research on the optimal automatic choice of parameters is needed.

New South Wales Child Development Study (NSW-CDS): an Australian multiagency, multigenerational, longitudinal record linkage study

PubMed Central

Carr, Vaughan J; Harris, Felicity; Raudino, Alessandra; Luo, Luming; Kariuki, Maina; Liu, Enwu; Tzoumakis, Stacy; Smith, Maxwell; Holbrook, Allyson; Bore, Miles; Brinkman, Sally; Lenroot, Rhoshel; Dix, Katherine; Dean, Kimberlie; Laurens, Kristin R; Green, Melissa J

2016-01-01

Purpose The initial aim of this multiagency, multigenerational record linkage study is to identify childhood profiles of developmental vulnerability and resilience, and to identify the determinants of these profiles. The eventual aim is to identify risk and protective factors for later childhood-onset and adolescent-onset mental health problems, and other adverse social outcomes, using subsequent waves of record linkage. The research will assist in informing the development of public policy and intervention guidelines to help prevent or mitigate adverse long-term health and social outcomes. Participants The study comprises a population cohort of 87 026 children in the Australian State of New South Wales (NSW). The cohort was defined by entry into the first year of full-time schooling in NSW in 2009, at which time class teachers completed the Australian Early Development Census (AEDC) on each child (with 99.7% coverage in NSW). The AEDC data have been linked to the children's birth, health, school and child protection records for the period from birth to school entry, and to the health and criminal records of their parents, as well as mortality databases. Findings to date Descriptive data summarising sex, geographic and socioeconomic distributions, and linkage rates for the various administrative databases are presented. Child data are summarised, and the mental health and criminal records data of the children's parents are provided. Future plans In 2015, at age 11 years, a self-report mental health survey was administered to the cohort in collaboration with government, independent and Catholic primary school sectors. A second record linkage, spanning birth to age 11 years, will be undertaken to link this survey data with the aforementioned administrative databases. This will enable a further identification of putative risk and protective factors for adverse mental health and other outcomes in adolescence, which can then be tested in subsequent record linkages

Extending the Fellegi-Sunter probabilistic record linkage method for approximate field comparators.

PubMed

DuVall, Scott L; Kerber, Richard A; Thomas, Alun

2010-02-01

Probabilistic record linkage is a method commonly used to determine whether demographic records refer to the same person. The Fellegi-Sunter method is a probabilistic approach that uses field weights based on log likelihood ratios to determine record similarity. This paper introduces an extension of the Fellegi-Sunter method that incorporates approximate field comparators in the calculation of field weights. The data warehouse of a large academic medical center was used as a case study. The approximate comparator extension was compared with the Fellegi-Sunter method in its ability to find duplicate records previously identified in the data warehouse using different demographic fields and matching cutoffs. The approximate comparator extension misclassified 25% fewer pairs and had a larger Welch's T statistic than the Fellegi-Sunter method for all field sets and matching cutoffs. The accuracy gain provided by the approximate comparator extension grew as less information was provided and as the matching cutoff increased. Given the ubiquity of linkage in both clinical and research settings, the incremental improvement of the extension has the potential to make a considerable impact.

Establishing a process for conducting cross-jurisdictional record linkage in Australia.

PubMed

Moore, Hannah C; Guiver, Tenniel; Woollacott, Anthony; de Klerk, Nicholas; Gidding, Heather F

2016-04-01

To describe the realities of conducting a cross-jurisdictional data linkage project involving state and Australian Government-based data collections to inform future national data linkage programs of work. We outline the processes involved in conducting a Proof of Concept data linkage project including the implementation of national data integration principles, data custodian and ethical approval requirements, and establishment of data flows. The approval process involved nine approval and regulatory bodies and took more than two years. Data will be linked across 12 datasets involving three data linkage centres. A framework was established to allow data to flow between these centres while maintaining the separation principle that serves to protect the privacy of the individual. This will be the first project to link child immunisation records from an Australian Government dataset to other administrative health datasets for a population cohort covering 2 million births in two Australian states. Although the project experienced some delays, positive outcomes were realised, primarily the development of strong collaborations across key stakeholder groups including community engagement. We have identified several recommendations and enhancements to this now established framework to further streamline the process for data linkage studies involving Australian Government data. © 2015 Public Health Association of Australia.

Cytokines, IBD and colitis-associated cancer

PubMed Central

Francescone, Ralph; Hou, Vivianty; Grivennikov, Sergei I.

2015-01-01

Inflammatory bowel diseases (IBDs) are debilitating conditions that result in intestinal damage due to chronic inflammation. In addition, the perpetual state of inflammation predisposes individuals to the development of colitis associated cancer (CAC). Because of the immense immune cell infiltration into colon, cytokines produced by immune cells are major players in the initiation and progression of IBD and CAC. In this review, we will explore the functions of many key cytokines and their roles in IBD and CAC, as well as their influences on the immune system and stromal cells. Finally, we will briefly discuss current therapies and current clinical trials targeting cytokines in IBD. PMID:25563695

New South Wales Child Development Study (NSW-CDS): an Australian multiagency, multigenerational, longitudinal record linkage study.

PubMed

Carr, Vaughan J; Harris, Felicity; Raudino, Alessandra; Luo, Luming; Kariuki, Maina; Liu, Enwu; Tzoumakis, Stacy; Smith, Maxwell; Holbrook, Allyson; Bore, Miles; Brinkman, Sally; Lenroot, Rhoshel; Dix, Katherine; Dean, Kimberlie; Laurens, Kristin R; Green, Melissa J

2016-02-11

The initial aim of this multiagency, multigenerational record linkage study is to identify childhood profiles of developmental vulnerability and resilience, and to identify the determinants of these profiles. The eventual aim is to identify risk and protective factors for later childhood-onset and adolescent-onset mental health problems, and other adverse social outcomes, using subsequent waves of record linkage. The research will assist in informing the development of public policy and intervention guidelines to help prevent or mitigate adverse long-term health and social outcomes. The study comprises a population cohort of 87,026 children in the Australian State of New South Wales (NSW). The cohort was defined by entry into the first year of full-time schooling in NSW in 2009, at which time class teachers completed the Australian Early Development Census (AEDC) on each child (with 99.7% coverage in NSW). The AEDC data have been linked to the children's birth, health, school and child protection records for the period from birth to school entry, and to the health and criminal records of their parents, as well as mortality databases. Descriptive data summarising sex, geographic and socioeconomic distributions, and linkage rates for the various administrative databases are presented. Child data are summarised, and the mental health and criminal records data of the children's parents are provided. In 2015, at age 11 years, a self-report mental health survey was administered to the cohort in collaboration with government, independent and Catholic primary school sectors. A second record linkage, spanning birth to age 11 years, will be undertaken to link this survey data with the aforementioned administrative databases. This will enable a further identification of putative risk and protective factors for adverse mental health and other outcomes in adolescence, which can then be tested in subsequent record linkages. Published by the BMJ Publishing Group Limited. For

Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci

PubMed Central

Brorsson, Caroline A.; Pociot, Flemming

2014-01-01

Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs. We explored sequence and structure based attributes of these lncRNAs, and also predicted the structural effects of mapped SNPs within them. We also identified lncRNAs in IBD and T1D that are under recent positive selection. Our analysis identified putative lncRNA secondary structure-disruptive SNPs within and in close proximity (+/−5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable information that could be potentially useful for future structure-function studies on lncRNAs. PMID:25144376

Clonal evolution of colorectal cancer in IBD.

PubMed

Choi, Chang-Ho R; Bakir, Ibrahim Al; Hart, Ailsa L; Graham, Trevor A

2017-04-01

Optimizing the management of colorectal cancer (CRC) risk in IBD requires a fundamental understanding of the evolutionary process underpinning tumorigenesis. In IBD, clonal evolution begins long before the development of overt neoplasia, and is probably accelerated by the repeated cycles of epithelial wounding and repair that are characteristic of the condition. Here, we review the biological drivers of mutant clone selection in IBD with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and CRC. How these data can be leveraged as evolutionary-based biomarkers to predict cancer risk is discussed, as well as how the efficacy of CRC surveillance programmes and the management of dysplasia can be improved. From a research perspective, the longitudinal surveillance of patients with IBD provides an under-exploited opportunity to investigate the biology of the human gastrointestinal tract over space and time.

Evaluating Health Outcomes of Criminal Justice Populations Using Record Linkage: The Importance of Aliases

ERIC Educational Resources Information Center

Larney, Sarah; Burns, Lucy

2011-01-01

Individuals in contact with the criminal justice system are a key population of concern to public health. Record linkage studies can be useful for studying health outcomes for this group, but the use of aliases complicates the process of linking records across databases. This study was undertaken to determine the impact of aliases on sensitivity…

Testing association and linkage using affected-sib-parent study designs.

PubMed

Millstein, Joshua; Siegmund, Kimberly D; Conti, David V; Gauderman, W James

2005-11-01

We have developed a method for jointly testing linkage and association using data from affected sib pairs and their parents. We specify a conditional logistic regression model with two covariates, one that quantifies association (either direct association or indirect association via linkage disequilibrium), and a second that quantifies linkage. The latter covariate is computed based on expected identity-by-descend (ibd) sharing of marker alleles between siblings. In addition to a joint test of linkage and association, our general framework can be used to obtain a linkage test comparable to the mean test (Blackwelder and Elston [1985] Genet. Epidemiol. 2:85-97), and an association test comparable to the Family-Based Association Test (FBAT; Rabinowitz and Laird [2000] Hum. Hered. 50:211-223). We present simulation results demonstrating that our joint test can be more powerful than some standard tests of linkage or association. For example, with a relative risk of 2.7 per variant allele at a disease locus, the estimated power to detect a nearby marker with a modest level of LD was 58.1% by the mean test (linkage only), 69.8% by FBAT, and 82.5% by our joint test of linkage and association. Our model can also be used to obtain tests of linkage conditional on association and association conditional on linkage, which can be helpful in fine mapping. Copyright 2005 Wiley-Liss, Inc.

CMV Infection in Pediatric IBD.

PubMed

Yerushalmy-Feler, Anat; Kern-Isaacs, Sharona; Cohen, Shlomi

2018-03-28

Patients with inflammatory bowel disease (IBD) are predisposed to infections. Cytomegalovirus (CMV) colitis in adult IBD patients, particularly ulcerative colitis (UC), is related to severe or steroid-refractory disease. The aim of this review is to summarize the data on the prevalence and role of CMV colitis in children with IBD. Data on CMV colitis in children continue to be very limited due to its rarity. As in adults, children with coexisting UC and CMV tend to have more severe colitis, are resistant to corticosteroids, and are at high risk for colectomies on short- and long-term follow-up. In children, as in adults, the significance of CMV colitis, in terms of whether CMV is a pathogen that aggravates acute severe colitis or simply reflects disease severity, is still unknown.

Monitoring for Extra-Intestinal Cancers in IBD.

PubMed

Sifuentes, H; Kane, S

2015-11-01

Multiple studies have demonstrated an increased risk for extra-intestinal cancers in inflammatory bowel disease (IBD) patients, mainly from treatment modalities. Prominent cancers that are related to IBD treatment include the following: lymphoproliferative disorders associated with thiopurine use, hepatosplenic T cell lymphoma primarily in younger male patients on thiopurines and anti-tumor necrosis factor (TNF) agents, non-melanoma skin cancers in patients treated with thiopurines and anti-TNF agents, and melanomas in patients who are on monotherapy with anti-TNF agents. In addition, women with IBD may have higher rates of cervical dysplasia and cervical cancer. The focus of this review is to provide a comprehensive overview on extra-intestinal cancers in IBD patients and how to monitor for these malignancies.

Probiotics and antibiotics in IBD.

PubMed

Sokol, Harry

2014-01-01

The involvement of the gut microbiota in the pathogenesis of IBD is supported by many findings and is thus now commonly acknowledged. The imbalance in the composition of the microbiota (dysbiosis) observed in IBD patients is one of the strongest arguments and provides the rationale for a therapeutic manipulation of the gut microbiota. The tools available to achieve this goal include fecal microbiota transplantation, but antibiotics and probiotics have been the most used one until now. Although antibiotics have shown some efficacy in inducing remission in Crohn's disease (CD) and ulcerative colitis (UC), as well as preventing postoperative relapse in CD, they are not currently recommended for the treatment of IBD except for septic complications, notably because of long-term tolerance and ecological issues. Some probiotics have been shown to be as good as 5-aminosalicylic acid to maintain remission in mild-to-moderate UC, but have been disappointing until now in CD in all tested indications. In pouchitis, antibiotics and probiotics have shown efficacy for inducing and maintaining remission, respectively. Targeting the gut microbiota in IBD is an attractive strategy. Current efforts to better understand the host-microbiota interactions in physiological as well as disease settings might lead to the development of rational-based treatments. © 2014 S. Karger AG, Basel.

Validating a Measure of Patient Self-efficacy in Disease Self-management Using a Population-based IBD Cohort: The IBD Self-efficacy Scale.

PubMed

Graff, Lesley A; Sexton, Kathryn A; Walker, John R; Clara, Ian; Targownik, Laura E; Bernstein, Charles N

2016-09-01

Self-efficacy describes a person's confidence in their ability to manage demands, and is predictive of health outcomes in chronic disease such as hospitalization and health status. However, meaningful measurement must be domain (e.g., disease) specific. This study aims to provide validation of the Inflammatory Bowel Disease Self-Efficacy scale (IBD-SE), using a population-based IBD sample. Manitoba IBD Cohort Study participants completed a survey and clinical interview at a mean of 12 years postdiagnosis (n = 121 Crohn's disease; n = 108 ulcerative colitis), which included validated measures of psychological functioning, disability, disease-specific quality of life, perceived health, and current and recent disease activity, in addition to the IBD-SE. The IBD-SE had high internal consistency (Cronbach's α = 0.97), and a 4-factor structure was confirmed. Construct validity was demonstrated as follows: the IBD-SE was strongly correlated with mastery (r = 0.53), highly correlated in the expected directions with measures of psychological well-being (r = 0.70), stress (r = -0.78), distress (r = -0.71), disability (r = -0.48), disease-specific quality of life (r = 0.68), and overall perceived health (r = 0.52) (all P < 0.001). Those with currently inactive disease had higher self-efficacy than the active disease group (Crohn's disease: mean = 232 versus 195, P < 0.001; ulcerative colitis: mean = 233 versus 202, P < 0.01), with similar findings for recent symptomatic disease activity. The IBD-SE is a reliable, valid, and sensitive measure as demonstrated in this population-based sample, supporting its utility in IBD. Because self-efficacy is a modifiable psychological characteristic that can contribute to positive health outcomes, the IBD-SE may prove to be a valuable instrument for research and in targeted intervention with IBD patients.

Helminths and the IBD hygiene hypothesis.

PubMed

Weinstock, Joel V; Elliott, David E

2009-01-01

Helminths are parasitic animals that have evolved over 100,000,000 years to live in the intestinal track or other locations of their hosts. Colonization of humans with these organisms was nearly universal until the early 20th century. More than 1,000,000,000 people in less developed countries carry helminths even today. Helminths must quell their host's immune system to successfully colonize. It is likely that helminths sense hostile changes in the local host environment and take action to control such responses. Inflammatory bowel disease (IBD) probably results from an inappropriately vigorous immune response to contents of the intestinal lumen. Environmental factors strongly affect the risk for IBD. People living in less developed countries are protected from IBD. The "IBD hygiene hypothesis" states that raising children in extremely hygienic environments negatively affects immune development, which predisposes them to immunological diseases like IBD later in life. Modern day absence of exposure to intestinal helminths appears to be an important environmental factor contributing to development of these illnesses. Helminths interact with both host innate and adoptive immunity to stimulate immune regulatory circuitry and to dampen effector pathways that drive aberrant inflammation. The first prototype worm therapies directed against immunological diseases are now under study in the United States and various countries around the world. Additional studies are in the advanced planning stage.

Environmental triggers in IBD: a review of progress and evidence.

PubMed

Ananthakrishnan, Ashwin N; Bernstein, Charles N; Iliopoulos, Dimitrios; Macpherson, Andrew; Neurath, Markus F; Ali, Raja A Raja; Vavricka, Stephan R; Fiocchi, Claudio

2018-01-01

A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.

Current practice in the diagnosis and management of IBD-associated anaemia and iron deficiency in Germany: the German AnaemIBD Study.

PubMed

Blumenstein, Irina; Dignass, Axel; Vollmer, Stephan; Klemm, Wolfgang; Weber-Mangal, Susanne; Stein, Juergen

2014-10-01

Anaemia is a common complication in inflammatory bowel disease (IBD), frequently resulting from iron deficiency. IBD guidelines advocate intravenous iron administration although some patients respond to oral supplementation. This non-interventional study investigates the current status of anaemia management in German IBD patients. Baseline data on pre-study treatment for anaemia were retrospectively analysed in IBD patients with anaemia participating in a prospective trial of the efficacy and safety of ferric carboxymaltose. Data were collected from 55 German gastroenterological centres up to August 2010. Subjects had received care at their centre for at least 12 months prior to baseline. 193 cases of IBD-associated anaemia (115 Crohn's disease, 77 ulcerative colitis) were analysed (mean age: 39 years (18-83), 79 (41%) males). Anaemia and iron status were usually assessed by haemoglobin (100%), serum ferritin (97%), and transferrin saturation (82%). In the previous 6 months, only 84 patients (43.5%) had been treated for anaemia: 47 (56%) with oral iron, 13 (15%) parenteral iron, 16 (19%) oral plus parenteral iron and 8 (10%) transfusions. No patients received erythropoietin stimulating agents. Although intravenous iron supplementation is recommended in IBD patients, current German practice still relies on oral therapy, even in severe anaemia. The high incidence of severe anaemia in this cohort reflects inadequate iron replacement and status monitoring. While the proportion of IBD patients with inadequately treated anaemia/iron deficiency is unknown, greater awareness of existing guidelines for iron deficiency management in IBD patients appears necessary. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Epidemiology of IBD

MedlinePlus

... the United States have examined the relationship between socioeconomic factors and IBD. One study found both ulcerative colitis ... source: National Center for Chronic Disease Prevention and Health Promotion , Centers for Disease Control and Prevention Email ...

[Record linkage of the elderly in the national surveys on the geriatric intermediate care facility].

PubMed

Doi, T; Chen, B

1997-07-01

Geriatric intermediate care facility, GICF, have been established since 1986 in Japan. The term of 'intermediate' denotes a facility midpoint between a hospital and home, with a powerful rehabilitation function. The annual governmental survey on GICF has been applied to all GICFs in Japan since 1989. This survey is a cross-sectional-type survey. For evaluating the role of GICF, we considered a type of cohort study using these surveys for four years by means of a record linkage method. This method is possible, because subjects of a survey for any year become subjects in the survey of the following year, if they have been in a GICF for more than one year. In this paper, for the purpose of preparing for a study of the role of GICF, we report some results about a record linkage for these surveys, and two continuing rates were calculated for these cohorts. Sources were personal records in 1989 to 1992 gathered by The National Survey on GICF in Japan. The record linkage method is as follows. We divided the annual personal records into several files by both the periods of the last admission and the survey year. Three cohorts, i.e. a cohort-89, a cohort-90 and a cohort-91 for persons for whom the first survey was 1989, 1990 and 1991, respectively are thus obtained. Next, we identified individuals from the annual files in each cohort. As personal names were not available, we identified individuals by sex, birth date, date of admission and facility number by the use of a personal computer and a FORTRAN program. Results were as follows. 1. Multiple matched persons were few (0.5% or less), and identification rates were 90% or more, despite the fact that basic linking variables were used. 2. Continuing rates were about 40% and decreased with new cohorts, while those of a fixed cohort were increased as length of stay increased. These reveal that recent admissions who stay continuously at a GICF were decreasing, but the longer the period for which the elderly stays at a GICF, the

Linkage disequilibrium matches forensic genetic records to disjoint genomic marker sets.

PubMed

Edge, Michael D; Algee-Hewitt, Bridget F B; Pemberton, Trevor J; Li, Jun Z; Rosenberg, Noah A

2017-05-30

Combining genotypes across datasets is central in facilitating advances in genetics. Data aggregation efforts often face the challenge of record matching-the identification of dataset entries that represent the same individual. We show that records can be matched across genotype datasets that have no shared markers based on linkage disequilibrium between loci appearing in different datasets. Using two datasets for the same 872 people-one with 642,563 genome-wide SNPs and the other with 13 short tandem repeats (STRs) used in forensic applications-we find that 90-98% of forensic STR records can be connected to corresponding SNP records and vice versa. Accuracy increases to 99-100% when ∼30 STRs are used. Our method expands the potential of data aggregation, but it also suggests privacy risks intrinsic in maintenance of databases containing even small numbers of markers-including databases of forensic significance.

The promise of record linkage for assessing the uptake of health services in resource constrained settings: a pilot study from South Africa.

PubMed

Kabudula, Chodziwadziwa W; Clark, Benjamin D; Gómez-Olivé, Francesc Xavier; Tollman, Stephen; Menken, Jane; Reniers, Georges

2014-05-24

Health and Demographic Surveillance Systems (HDSS) have been instrumental in advancing population and health research in low- and middle- income countries where vital registration systems are often weak. However, the utility of HDSS would be enhanced if their databases could be linked with those of local health facilities. We assess the feasibility of record linkage in rural South Africa using data from the Agincourt HDSS and a local health facility. Using a gold standard dataset of 623 record pairs matched by means of fingerprints, we evaluate twenty record linkage scenarios (involving different identifiers, string comparison techniques and with and without clerical review) based on the Fellegi-Sunter probabilistic record linkage model. Matching rates and quality are measured by their sensitivity and positive predictive value (PPV). Background characteristics of matched and unmatched cases are compared to assess systematic bias in the resulting record-linked dataset. A hybrid approach of deterministic followed by probabilistic record linkage, and scenarios that use an extended set of identifiers including another household member's first name yield the best results. The best fully automated record linkage scenario has a sensitivity of 83.6% and PPV of 95.1%. The sensitivity and PPV increase to 84.3% and 96.9%, respectively, when clerical review is undertaken on 10% of the record pairs. The likelihood of being linked is significantly lower for females, non-South Africans and the elderly. Using records matched by means of fingerprints as the gold standard, we have demonstrated the feasibility of fully automated probabilistic record linkage using identifiers that are routinely collected in health facilities in South Africa. Our study also shows that matching statistics can be improved if other identifiers (e.g., another household member's first name) are added to the set of matching variables, and, to a lesser extent, with clerical review. Matching success is

The promise of record linkage for assessing the uptake of health services in resource constrained settings: a pilot study from South Africa

PubMed Central

2014-01-01

Background Health and Demographic Surveillance Systems (HDSS) have been instrumental in advancing population and health research in low- and middle- income countries where vital registration systems are often weak. However, the utility of HDSS would be enhanced if their databases could be linked with those of local health facilities. We assess the feasibility of record linkage in rural South Africa using data from the Agincourt HDSS and a local health facility. Methods Using a gold standard dataset of 623 record pairs matched by means of fingerprints, we evaluate twenty record linkage scenarios (involving different identifiers, string comparison techniques and with and without clerical review) based on the Fellegi-Sunter probabilistic record linkage model. Matching rates and quality are measured by their sensitivity and positive predictive value (PPV). Background characteristics of matched and unmatched cases are compared to assess systematic bias in the resulting record-linked dataset. Results A hybrid approach of deterministic followed by probabilistic record linkage, and scenarios that use an extended set of identifiers including another household member’s first name yield the best results. The best fully automated record linkage scenario has a sensitivity of 83.6% and PPV of 95.1%. The sensitivity and PPV increase to 84.3% and 96.9%, respectively, when clerical review is undertaken on 10% of the record pairs. The likelihood of being linked is significantly lower for females, non-South Africans and the elderly. Conclusion Using records matched by means of fingerprints as the gold standard, we have demonstrated the feasibility of fully automated probabilistic record linkage using identifiers that are routinely collected in health facilities in South Africa. Our study also shows that matching statistics can be improved if other identifiers (e.g., another household member’s first name) are added to the set of matching variables, and, to a lesser extent, with

Health service utilization in IBD: comparison of self-report and administrative data

PubMed Central

2011-01-01

Background The reliability of self-report regarding health care utilization in inflammatory bowel disease (IBD) is unknown. If proven reliable, it could help justify self-report as a means of determining health care utilization and associated costs. Methods The Manitoba IBD Cohort Study is a population-based longitudinal study of participants diagnosed within 7 years of enrollment. Health care utilization was assessed through standardized interview. Participants (n = 352) reported the total number of nights hospitalized, frequency of physician contacts in the prior 12 months and whether the medical contacts were for IBD-related reasons or not. Reports of recent antibiotic use were also recorded. Actual utilization was drawn from the administrative database of Manitoba Health, the single comprehensive provincial health insurer. Results According to the administrative data, 15% of respondents had an overnight hospitalization, while 10% had an IBD-related hospitalization. Self-report concordance was highly sensitive (92%; 82%) and specific (96%; 97%, respectively). 97% of participants had contact with a physician in the previous year, and 69% had IBD-related visits. Physician visits were significantly under-reported and there was a trend to over-report the number of nights in hospital. Conclusions Self-report data can be helpful in evaluating health service utilization, provided that the researcher is aware of the systematic sources of bias. Outpatient visits are well identified by self-report. The discordance for the type of outpatient visit may be either a weakness of self-report or a flaw in diagnosis coding of the administrative data. If administrative data are not available, self-report information may be a cost-effective alternative, particularly for hospitalizations. PMID:21627808

IBD and Environment: Are There Differences between East and West.

PubMed

Gearry, Richard B

2016-01-01

The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC) occur worldwide with differences in epidemiology, etiology and phenotype between regions. Breakthroughs have occurred in IBD genetics, although the genes that predispose to IBD differ between racial groups. What do we know about the 'envirotype' of those who develop IBD, and are there differences between the East and the West? The strongest IBD risk factor identified to date is a family history of IBD. Whilst likely representing an underlying genetic predisposition, it may also reflect shared environmental factors amongst family members. Cigarette smoking increases the risk of developing CD, whilst smoking is less common in those who develop UC. Having ceased smoking increases the risk of developing UC subsequently. Unlike the West, cigarette smoking appears to play a lesser role in the East. Other environmental risk factors are inconsistent. Studies of migrant populations moving from regions of low to high IBD incidence point to early life as a key time for environmental triggers. In these populations, it is the second generation (those born in the high incidence region) with higher IBD incidence rates than their parents. Early life environmental exposures have been studied exhaustively but, except for having been breastfed, few putative early childhood environmental risk factors have been shown consistently to alter the risk of developing IBD. The identification of IBD environmental risk factors remains elusive in both the East and West. In the West, case-control studies are unlikely to move the field forward without multi-level (phenotype, genotype, diet history, 'envirotype' and microbiome) data, ideally collected prospectively. Cohort studies (such as the Genes, Environment, Microbiome project) may address some of these issues. However, in the East where IBD incidence is still increasing, well-designed comprehensive case-control studies may identify differences that give

Combining Different Privacy-Preserving Record Linkage Methods for Hospital Admission Data.

PubMed

Stausberg, Jürgen; Waldenburger, Andreas; Borgs, Christian; Schnell, Rainer

2017-01-01

Record linkage (RL) is the process of identifying pairs of records that correspond to the same entity, for example the same patient. The basic approach assigns to each pair of records a similarity weight, and then determines a certain threshold, above which the two records are considered to be a match. Three different RL methods were applied under privacy-preserving conditions on hospital admission data: deterministic RL (DRL), probabilistic RL (PRL), and Bloom filters. The patient characteristics like names were one-way encrypted (DRL, PRL) or transformed to a cryptographic longterm key (Bloom filters). Based on one year of hospital admissions, the data set was split randomly in 30 thousand new and 1,5 million known patients. With the combination of the three RL-methods, a positive predictive value of 83 % (95 %-confidence interval 65 %-94 %) was attained. Thus, the application of the presented combination of RL-methods seem to be suited for other applications of population-based research.

IBD-related work disability in the community: Prevalence, severity and predictive factors. A cross-sectional study

PubMed Central

Ramos, Alexis; Sicilia, Beatriz; Vergara, Mercedes; Figuerola, Ariadna; Motos, Jaume; Sastre, Adoración; Villoria, Albert; Gomollón, Fernando

2015-01-01

Background and aims Data on the prevalence of work disability in patients with inflammatory bowel disease (IBD) are heterogeneous. As most studies have been performed in selected, often severe, IBD patients, the true prevalence of disability in the community remains controversial. The aim of this cross-sectional study was to evaluate the prevalence and severity of disability and its predictive factors in a community-based IBD population. Patients and methods Patients recorded in the community-based IBD register at the Hospital Universitario de Burgos were contacted. After informed consent they completed a set of questionnaires including demographic, clinical, disability and quality of life data. The statistical study was performed using SPSS 21. Results A total of 293 patients were included – 151 Crohn's disease (CD), 142 ulcerative colitis (UC), 137 female, mean age: 45 ± 11 years, mean time since diagnosis: 10.6 ± 11 years. Twelve patients (4.1%) had a work-disability pension. In addition, 93 (32%) of all patients had an officially recognized disability degree, which was generally moderate (n = 73, 25%) or severe (N = 16, 5%). Age, time since IBD diagnosis, CD, perianal disease, incontinence, active disease, the need for anti-TNF or psychological treatment, previous surgeries and the number of diagnostic tests and medical visits in the previous year were predictors of disability. Major predictors of qualifying for a disability pension were age, IBD activity, incontinence, need for biological drugs and ostomy. Conclusion Mild to moderate work disability is frequent in IBD. However, only a minority of patients develop severe disability qualifying them for a pension. PMID:26279841

Eye Complications in IBD

MedlinePlus

... Crohn's & Colitis Foundation's IBD Help Center: 888.MY.GUT.PAIN (888.694.8872). The Crohn's & Colitis Foundation ... to a Specialist by phone at (888) MY-GUT-PAIN by email at info@crohnscolitisfoundation.org , or ...

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

PubMed Central

Singh, Siddharth; Dulai, Parambir S.; Zarrinpar, Amir; Ramamoorthy, Sonia; Sandborn, William J.

2017-01-01

Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15–40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research. PMID:27899815

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes.

PubMed

Singh, Siddharth; Dulai, Parambir S; Zarrinpar, Amir; Ramamoorthy, Sonia; Sandborn, William J

2017-02-01

Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15-40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.

History of the Rochester Epidemiology Project: Half a Century of Medical Records Linkage in a US Population

PubMed Central

Rocca, Walter A.; Yawn, Barbara P.; St. Sauver, Jennifer L.; Grossardt, Brandon R.; Melton, L. Joseph

2012-01-01

The Rochester Epidemiology Project (REP) has maintained a comprehensive medical records linkage system for nearly half a century for almost all persons residing in Olmsted County, Minnesota. Herein, we provide a brief history of the REP before and after 1966, the year in which the REP was officially established. The key protagonists before 1966 were Henry Plummer, Mabel Root, and Joseph Berkson, who developed a medical records linkage system at Mayo Clinic. In 1966, Leonard Kurland established collaborative agreements with other local health care providers (hospitals, physician groups, and clinics [primarily Olmsted Medical Center]) to develop a medical records linkage system that covered the entire population of Olmsted County, and he obtained funding from the National Institutes of Health to support the new system. In 1997, L. Joseph Melton III addressed emerging concerns about the confidentiality of medical record information by introducing a broad patient research authorization as per Minnesota state law. We describe how the key protagonists of the REP have responded to challenges posed by evolving medical knowledge, information technology, and public expectation and policy. In addition, we provide a general description of the system; discuss issues of data quality, reliability, and validity; describe the research team structure; provide information about funding; and compare the REP with other medical information systems. The REP can serve as a model for the development of similar research infrastructures in the United States and worldwide. PMID:23199802

The Natural History of IBD: Lessons Learned.

PubMed

Weimers, Petra; Munkholm, Pia

2018-03-01

Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing diseases with unknown etiologies. The purpose of this review is to present the natural disease course evidenced in the latest epidemiology data. The prevalence of IBD is rapidly increasing, affecting five million patients worldwide with the highest incidence observed in Northern Europe and Northern America. It has been shown that both CD and UC patients are at an increased risk for developing cancer of the gastrointestinal tract compared to the general population. Though the disease course of IBD is unpredictable, the rate of surgical treatment has declined potentially as a consequence of the introduction of immunomodulators and new biologic treatment options. Treatments with biological agents and/or immunosuppressive drugs as well as disease monitoring with eHealth devices seem to have a positive impact on the disease course. However, long-term follow-up studies are still lacking and therefore no reliable conclusions can be drawn as of yet. Medical compliance is paramount in the treatment of IBD, and continuous research focusing on approaches that increase compliance is also necessary.

A first study on the incidence and prevalence of IBD in Malaysia--results from the Kinta Valley IBD Epidemiology Study.

PubMed

Hilmi, Ida; Jaya, Fauziah; Chua, Andrew; Heng, Wong Choon; Singh, Harjinder; Goh, Khean-Lee

2015-05-01

Inflammatory bowel disease [IBD] is known to be rare in the Asia Pacific region but epidemiological studies are scarce. Kinta Valley [Ipoh] was chosen as the sample population. Malaysia has a multiethnic population consisting of Malays, Chinese, and Indians. New cases over 2 years were prospectively captured as well as all known existing cases. Total numbers of the population as a whole and of each ethnic group were obtained. Incidence, prevalence, and mean incidence over two decades were then calculated. There were 10 new cases of IBD diagnosed from April 2011 to April 2013. The crude incidence rates of IBD, ulcerative colitis [UC], and Crohn's disease[CD], respectively, were 0.68, 0.46, and 0.20 per 100,000 persons. The highest incidence was among the Indians, 1.91 compared with 0.35 and 0.63 per 100,000 persons among the Malays and the Chinese, respectively. The mean incidence of IBD has increased steadily from 0.07 to 0.69 per 100,000 person-years over the past two decades. The UC:CD ratio was 8:1 from 1990 to 2000 and 3.6:1 from 2000 to 2010. The prevalence rates of IBD, UC, and CD, respectively, were 9.24, 6.67, and 2.17 per 100,000 persons. The highest prevalence also was among the Indians: 24.91 compared with 7.00 and 6.90 per 100,000 persons among the Malay and Chinese races, respectively. The incidence and prevalence rates of IBD are low in Malaysia but the incidence appears to be increasing and marked racial differences exist. As in other Asian countries, the incidence of CD is increasing at a more rapid rate relative to UC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Making a Medical Home for IBD Patients.

PubMed

Kosinski, Lawrence R; Brill, Joel; Regueiro, Miguel

2017-05-01

The transformation from fee for service to fee for value requires structural changes to the way gastroenterologists manage patients with inflammatory bowel disease (IBD). A team-based approach using technology to engage patients is necessary for success. The Patient-Centered Medical Home (PCMH) represents a unique model that brings together these essential features. This paper describes how the PCMH model has been successfully applied to the management of patients with IBD. A review of the literature and three examples of IBD PCMH initiatives are presented in this document: they demonstrate how outcomes can be improved under the PCMH model. Population health and value-based payments will mold and shape how we can position our GI practices. The specialty medical home is an ideal way to begin this transition.

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

PubMed Central

Churches, Tim; Christen, Peter; Lim, Kim; Zhu, Justin Xi

2002-01-01

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. PMID:12482326

Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

PubMed

Paixão, Enny S; Harron, Katie; Andrade, Kleydson; Teixeira, Maria Glória; Fiaccone, Rosemeire L; Costa, Maria da Conceição N; Rodrigues, Laura C

2017-07-17

Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a

History of the Rochester Epidemiology Project: half a century of medical records linkage in a US population.

PubMed

Rocca, Walter A; Yawn, Barbara P; St Sauver, Jennifer L; Grossardt, Brandon R; Melton, L Joseph

2012-12-01

The Rochester Epidemiology Project (REP) has maintained a comprehensive medical records linkage system for nearly half a century for almost all persons residing in Olmsted County, Minnesota. Herein, we provide a brief history of the REP before and after 1966, the year in which the REP was officially established. The key protagonists before 1966 were Henry Plummer, Mabel Root, and Joseph Berkson, who developed a medical records linkage system at Mayo Clinic. In 1966, Leonard Kurland established collaborative agreements with other local health care providers (hospitals, physician groups, and clinics [primarily Olmsted Medical Center]) to develop a medical records linkage system that covered the entire population of Olmsted County, and he obtained funding from the National Institutes of Health to support the new system. In 1997, L. Joseph Melton III addressed emerging concerns about the confidentiality of medical record information by introducing a broad patient research authorization as per Minnesota state law. We describe how the key protagonists of the REP have responded to challenges posed by evolving medical knowledge, information technology, and public expectation and policy. In addition, we provide a general description of the system; discuss issues of data quality, reliability, and validity; describe the research team structure; provide information about funding; and compare the REP with other medical information systems. The REP can serve as a model for the development of similar research infrastructures in the United States and worldwide. Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Design and implementation of a privacy preserving electronic health record linkage tool in Chicago

PubMed Central

Cashy, John P; Jackson, Kathryn L; Pah, Adam R; Goel, Satyender; Boehnke, Jörn; Humphries, John Eric; Kominers, Scott Duke; Hota, Bala N; Sims, Shannon A; Malin, Bradley A; French, Dustin D; Walunas, Theresa L; Meltzer, David O; Kaleba, Erin O; Jones, Roderick C; Galanter, William L

2015-01-01

Objective To design and implement a tool that creates a secure, privacy preserving linkage of electronic health record (EHR) data across multiple sites in a large metropolitan area in the United States (Chicago, IL), for use in clinical research. Methods The authors developed and distributed a software application that performs standardized data cleaning, preprocessing, and hashing of patient identifiers to remove all protected health information. The application creates seeded hash code combinations of patient identifiers using a Health Insurance Portability and Accountability Act compliant SHA-512 algorithm that minimizes re-identification risk. The authors subsequently linked individual records using a central honest broker with an algorithm that assigns weights to hash combinations in order to generate high specificity matches. Results The software application successfully linked and de-duplicated 7 million records across 6 institutions, resulting in a cohort of 5 million unique records. Using a manually reconciled set of 11 292 patients as a gold standard, the software achieved a sensitivity of 96% and a specificity of 100%, with a majority of the missed matches accounted for by patients with both a missing social security number and last name change. Using 3 disease examples, it is demonstrated that the software can reduce duplication of patient records across sites by as much as 28%. Conclusions Software that standardizes the assignment of a unique seeded hash identifier merged through an agreed upon third-party honest broker can enable large-scale secure linkage of EHR data for epidemiologic and public health research. The software algorithm can improve future epidemiologic research by providing more comprehensive data given that patients may make use of multiple healthcare systems. PMID:26104741

Record linkage to correct under‐ascertainment of cancers in HIV cohorts: The Sinikithemba HIV clinic linkage project

PubMed Central

Spoerri, Adrian; Egger, Matthias; Kielkowski, Danuta; Crankshaw, Tamaryn; Cloete, Christie; Giddy, Janet; Bohlius, Julia

2016-01-01

The surveillance of HIV‐related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu‐Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage (PRL) methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non‐Hodgkin's lymphoma and non‐AIDS defining cancers (NADCs) before and after inclusion of linkage‐identified cancers with 95% confidence intervals (CIs). A total of 8,721 records of HIV‐positive patients were linked with 35,536 cancer records. Between 2004 and 2010, we identified 448 cancers, 82% (n = 367) were recorded in the cancer registry only, 10% (n = 43) in the HIV cohort only and 8% (n = 38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91–212) to 877 (95% CI 744–1,041) per 100,000 person‐years after inclusion of linkage‐identified cancers. Incidence rates were highest for KS (432, 95% CI 341–555), followed by cervix (259, 95% CI 179–390) and NADCs (294, 95% CI 223–395) per 100,000 person‐years. Ascertainment of cancer in HIV cohorts is incomplete, PRL is both feasible and essential for cancer ascertainment. PMID:27098265

Review of Saccharomyces boulardii as a treatment option in IBD.

PubMed

Sivananthan, Kavitha; Petersen, Andreas Munk

2018-05-17

Review of the yeast Saccharomyces boulardii as a treatment option for the inflammatory bowel diseases (IBD) ulcerative colitis and Crohn's disease. IBD is caused by an inappropriate immune response to gut microbiota. Treatment options could therefore be prebiotics, probiotics, antibiotics and/or fecal transplant. In this review, we have looked at the evidence for the yeast S. boulardii as a treatment option. Searches in PubMed and the Cochrane Library with the MeSH words 'Saccharomyces boulardii AND IBD', 'Saccharomyces boulardii AND Inflammatory Bowel Disease', 'Saccharomyces boulardii AND ulcerative colitis' and 'Saccharomyces boulardii AND Crohn's disease' gave total a total of 80 articles. After exclusions because of irrelevance, articles in other languages and some articles that were not available, 16 articles were included in this review. Three of the clinical trials showed a positive effect of S. boulardii in IBD patients (two Crohn's disease, one ulcerative colitis), while there was one trial that didn't prove any effect (Crohn's disease). Included Animal trials and cell assays describes different anti-inflammatory mechanisms of S. boulardii supporting a possible effect when treating IBD patients. The number of studies of S. boulardii as treatment for IBD is limited. Furthermore, the existing trials have small populations and short duration. We do not have enough evidence to prove the effect of S. boulardii in IBD. Saccharomyces boulardii is, however, a plausible treatment option in the future, but more placebo-controlled clinical studies on both patients with ulcerative colitis and Crohn's disease are needed.

Liver Disease and IBD

MedlinePlus

... loss, and itching. PSC may not improve with medical treatment for IBD and may ultimately require liver transplantation. The cause is not known and there is no effective medication for PSC. To correct severe narrowing of the bile ducts, a balloon-tipped tube may be inserted into the duct ...

Design and implementation of a privacy preserving electronic health record linkage tool in Chicago.

PubMed

Kho, Abel N; Cashy, John P; Jackson, Kathryn L; Pah, Adam R; Goel, Satyender; Boehnke, Jörn; Humphries, John Eric; Kominers, Scott Duke; Hota, Bala N; Sims, Shannon A; Malin, Bradley A; French, Dustin D; Walunas, Theresa L; Meltzer, David O; Kaleba, Erin O; Jones, Roderick C; Galanter, William L

2015-09-01

To design and implement a tool that creates a secure, privacy preserving linkage of electronic health record (EHR) data across multiple sites in a large metropolitan area in the United States (Chicago, IL), for use in clinical research. The authors developed and distributed a software application that performs standardized data cleaning, preprocessing, and hashing of patient identifiers to remove all protected health information. The application creates seeded hash code combinations of patient identifiers using a Health Insurance Portability and Accountability Act compliant SHA-512 algorithm that minimizes re-identification risk. The authors subsequently linked individual records using a central honest broker with an algorithm that assigns weights to hash combinations in order to generate high specificity matches. The software application successfully linked and de-duplicated 7 million records across 6 institutions, resulting in a cohort of 5 million unique records. Using a manually reconciled set of 11 292 patients as a gold standard, the software achieved a sensitivity of 96% and a specificity of 100%, with a majority of the missed matches accounted for by patients with both a missing social security number and last name change. Using 3 disease examples, it is demonstrated that the software can reduce duplication of patient records across sites by as much as 28%. Software that standardizes the assignment of a unique seeded hash identifier merged through an agreed upon third-party honest broker can enable large-scale secure linkage of EHR data for epidemiologic and public health research. The software algorithm can improve future epidemiologic research by providing more comprehensive data given that patients may make use of multiple healthcare systems. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of a database of health insurance claims: standardization of disease classifications and anonymous record linkage.

PubMed

Kimura, Shinya; Sato, Toshihiko; Ikeda, Shunya; Noda, Mitsuhiko; Nakayama, Takeo

2010-01-01

Health insurance claims (ie, receipts) record patient health care treatments and expenses and, although created for the health care payment system, are potentially useful for research. Combining different types of receipts generated for the same patient would dramatically increase the utility of these receipts. However, technical problems, including standardization of disease names and classifications, and anonymous linkage of individual receipts, must be addressed. In collaboration with health insurance societies, all information from receipts (inpatient, outpatient, and pharmacy) was collected. To standardize disease names and classifications, we developed a computer-aided post-entry standardization method using a disease name dictionary based on International Classification of Diseases (ICD)-10 classifications. We also developed an anonymous linkage system by using an encryption code generated from a combination of hash values and stream ciphers. Using different sets of the original data (data set 1: insurance certificate number, name, and sex; data set 2: insurance certificate number, date of birth, and relationship status), we compared the percentage of successful record matches obtained by using data set 1 to generate key codes with the percentage obtained when both data sets were used. The dictionary's automatic conversion of disease names successfully standardized 98.1% of approximately 2 million new receipts entered into the database. The percentage of anonymous matches was higher for the combined data sets (98.0%) than for data set 1 (88.5%). The use of standardized disease classifications and anonymous record linkage substantially contributed to the construction of a large, chronologically organized database of receipts. This database is expected to aid in epidemiologic and health services research using receipt information.

Qualifying information on deaths and serious injuries caused by road traffic in five Brazilian capitals using record linkage.

PubMed

Mandacaru, Polyana Maria Pimenta; Andrade, Ana Lucia; Rocha, Marli Souza; Aguiar, Fernanda Pinheiro; Nogueira, Maria Sueli M; Girodo, Anne Marielle; Pedrosa, Ana Amélia Galas; Oliveira, Vera Lídia Alves de; Alves, Marta Maria Malheiros; Paixão, Lúcia Maria Miana M; Malta, Deborah Carvalho; Silva, Marta Maria Alves; Morais Neto, Otaliba Libanio de

2017-09-01

Road traffic crashes (RTC) are an important public health problem, accounting for 1.2 million deaths per year worldwide. In Brazil, approximately 40,000 deaths caused by RTC occur every year, with different trends in the Federal Units. However, these figures may be even greater if health databases are linked to police records. In addition, the linkage procedure would make it possible to qualify information from the health and police databases, improving the quality of the data regarding underlying cause of death, cause of injury in hospital records, and injury severity. This study linked different data sources to measure the numbers of deaths and serious injuries and to estimate the percentage of corrections regarding the underlying cause of death, cause of injury, and the severity injury in victims in matched pairs from record linkage in five representative state capitals of the five macro-regions of Brazil. This cross-sectional, population-based study used data from the Hospital Information System (HIS), Mortality Information System (MIS), and Police Road Traffic database of Belo Horizonte, Campo Grande, Curitiba, Palmas, and Teresina, for the year 2013 for Teresina, and 2012 for the other capitals. RecLink III was used to perform probabilistic record linkage by identifying matched pairs to calculate the global correction percentage of the underlying cause of death, the circumstance that caused the road traffic injury, and the injury severity of the victims in the police database. There was a change in the cause of injury in the HIS, with an overall percentage of correction estimated at 24.4% for Belo Horizonte, 96.9% for Campo Grande, 100.0% for Palmas, and 33.2% for Teresina. The overall percentages of correction of the underlying cause of death in the MIS were 29.9%, 11.9%, 4.2%, and 33.5% for Belo Horizonte, Campo Grande, Curitiba, and Teresina, respectively. The correction of the classification of injury severity in police database were 100.0% for Belo

Remote Patient Monitoring in IBD: Current State and Future Directions.

PubMed

Atreja, Ashish; Otobo, Emamuzo; Ramireddy, Karthik; Deorocki, Allyssa

2018-03-07

Mobile apps are now increasingly used in conjunction with telemedicine and wearable devices to support remote patient monitoring (RPM). The goal of this paper is to review the available evidence and assess the scope of RPM integration into standard practices for care and management of chronic disease in general and, more specifically, inflammatory bowel disease (IBD). RPM has been associated with improvements in health outcomes and indicators across a broad range of chronic diseases. However, there is limited data on the effectiveness of RPM in IBD care. From the emerging literature and body of research, we found promising results about the feasibility of integrating RPM in IBD care and RPM's capacity to support IBD improvement in key process and outcome metrics. Concerns regarding privacy and provider acceptability have limited the mass integration of RPM to date. However, with the healthcare industry's move toward value-based population care and the advent of novel payment models for RPM reimbursement, the adoption of RPM into standard IBD care practices will likely increase as the technology continues to improve and become a mainstream tool for healthcare delivery in the near future.

Is pediatric IBD treatment different than in adults?

PubMed

Lev-Tzion, R; Turner, D

2012-06-01

The incidence of pediatric inflammatory bowel disease (IBD) continues to rise in most countries. Approximately 20-25% of IBD patients present before the age of 20, and their management is associated with many unique challenges. These challenges stem both from the inherent differences between children and adults, and from the differences in the nature and course of the disease. Children with IBD are more likely than adults to present with extensive disease ‑ both in Crohn's disease (CD) and ulcerative colitis (UC). Diagnosis requires a high index of suspicion, as children may present with less typical signs such as poor growth and delayed puberty. In the very young patients with inflammatory bowel disease, the pediatric clinician must consider a broader range of immunological and allergic disorders. Optimal management requires recognition of pediatric patterns of presentation, efficacy and adverse-effect profiles, and understanding monitoring aspects unique to pediatrics. These aspects include pediatric disease-related psychological issues, adherence to therapy and transition to adult care. Inadequate attention to growth, puberty or bone health in childhood can result in long-term consequences, such as impaired adult height and increased risk of fractures. Management of pediatric IBD and prevention of adverse long-term consequences relies on a variety of therapies well-known to the adult practitioner, along with therapies that are not widespread in adults, most notably exclusive enteral nutrition (EEN). The latter is as effective as corticosteroids in achieving clinical remission in children, while achieving better results than corticosteroids with regard to mucosal healing and growth. This review discusses the broad variety of issues that form the basis for management of pediatric IBD.

Antibiotics, probiotics and prebiotics in IBD.

PubMed

Bernstein, Charles N

2014-01-01

The dysbiosis theory of inflammatory bowel disease (IBD) posits that there is an alteration in the gut microbiome as an important underpinning of disease etiology. It stands to reason then, that administering agents that could impact on the balance of microbes on the gut could be impactful on the course of IBD. Herein is a review of the controlled trials undertaken to assess the use of antibiotics that would kill or suppress potentially injurious microbes, probiotics that would overpopulate the gut with potentially beneficial microbes or prebiotics that provide a metabolic substrate that enhances the growth of potentially beneficial microbes. With regard to antibiotics, the best data are for the use of nitroimadoles postoperatively in Crohn's disease (CD) to prevent disease recurrence. Otherwise, the data are limited with the regard to any lasting benefit of antibiotics sustaining remission in either CD or ulcerative colitis (UC). A recent meta-analysis concluded that antibiotics are superior to placebo at inducing remission in CD or UC, although the meta-analysis grouped a variety of antibiotics with different spectra of activity. Despite the absence of robust clinical trial data, antibiotics are widely used to treat perineal fistulizing CD and acute and chronic pouchitis. Probiotics have not been shown to have a beneficial role in CD. However, Escherichia coli Nissle 1917 has comparable effects to low doses of mesalamine in maintaining remission in UC. VSL#3, a combination of 8 microbes, has been shown to have an effect in inducing remission in UC and preventing pouchitis. Prebiotics have yet to be shown to have an effect in any form of IBD, but to date controlled trials have been small. The use of antibiotics should be balanced against the risks they pose. Even probiotics may pose some risk and should not be assumed to be innocuous especially when ingested by persons with a compromised epithelial barrier. Prebiotics may not be harmful but may cause

IBD and health-related quality of life -- discovering the true impact.

PubMed

Lönnfors, Sanna; Vermeire, Severine; Greco, Marco; Hommes, Daan; Bell, Chayim; Avedano, Luisa

2014-10-01

Although inflammatory bowel diseases (IBD) significantly impact the patient's quality of life, no European-level data exists on patients' perspectives. The primary objective of this survey was to obtain an international perspective of the impact of IBD on patients' lives. Secondary objectives included obtaining a better understanding of the quality of care, access to care, and differences between countries, age groups, and sub-groups of IBD. The survey questionnaire consisted of 52 questions in six categories. The survey was translated into ten languages, tested on volunteers, and promoted across 25 national IBD associations. Data was collected anonymously online, and participation was optional. 4670 patients completed the survey. Most respondents received a final diagnosis within a year from noticing first symptoms, but 67% had to visit emergency clinic at least once before diagnosis. 85% had been hospitalized in the last five years. 64% felt that gastroenterologists should ask more probing questions and 54% that they did not get to tell something potentially important to their physician. Most respondents experienced symptoms weekly also in remission. Most had been absent from work due to IBD and 24% had received unfair comments about their work performance. 45% felt that IBD had negatively affected their performance in educational settings. The results of this survey can be used in defining strategic priorities and planning projects and awareness raising activities. The unmet needs of IBD patients can be better demonstrated and communicated to the public, health service managers and politicians. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Unmet Communication and Information Needs for Patients with IBD: Implications for Mobile Health Technology.

PubMed

Khan, Sameer; Dasrath, Florence; Farghaly, Sara; Otobo, Emamuzo; Riaz, Muhammad Safwan; Rogers, Jason; Castillo, Anabella; Atreja, Ashish

2016-01-01

In order to develop an application that addresses the most significant challenges facing IBD patients, this qualitative study explored the major hurdles of living with IBD, the information needs of IBD patients, and how application technology may be used to improve quality of life. 15 IBD patients participated in two focus groups of 120 minutes each. Data collection was achieved by combining focus groups with surveys and direct observation of patients looking at a patient-engaged app (HealthPROMISE) screenshots. The survey elicited information on demographics, health literacy and quality of life through the Short IBD Questionnaire (SIBDQ). The needs of IBD patients center around communication as it relates to both patient information needs and navigating the social impacts of IBD on patients' lives: Communication Challenges regarding Information Needs: Patients cited a doctor-patient communication divide where there is a continued lack of goal setting when discussing treatments and a lack of objectivity in disease control. When objectively compared with the SIBDQ, nearly half of the patients in the focus groups wrongly estimated their IBD control.Communication Challenges regarding Social Impacts of IBD: Patients strongly felt that while IBD disrupts routines, adds significant stress, and contributes to a sense of isolation, the impact of these issues would be significantly alleviated through more conversation and better support.Implication for Mobile Health Solutions: Patients want a tool that improves tracking of symptoms, medication adherence and provides education. Physician feedback to patient input on an application is required for long-term sustainability. IBD patients need mobile health technologies that evaluate disease control and the goals of care. Patients feel an objective assessment of their disease control, goal setting and physician feedback will greatly enhance utilization of all mobile health applications.

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1

PubMed Central

Cho, Judy H.; Nicolae, Dan L.; Gold, Leslee H.; Fields, Carter T.; LaBuda, Michele C.; Rohal, Patrick M.; Pickles, Michael R.; Qin, Li; Fu, Yifan; Mann, Jasdeep S.; Kirschner, Barbara S.; Jabs, Ethylin Wang; Weber, James; Hanauer, Stephen B.; Bayless, Theodore M.; Brant, Steven R.

1998-01-01

The idiopathic inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 × 10−4), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 × 10−5), and at chromosome 1p (MLod = 2.65, P = 2.4 × 10−4) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 × 10−4), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 × 10−3), particularly among Ashkenazim (MLod = 1.51, P = 7.8 × 10−3); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC. PMID:9636179

[Occupational mortality in Italy during 1992, assessed through record-linkage between pension records and death certificates].

PubMed

d'Errico, A; Filippi, M; Demaria, M; Picanza, Grazia; Crialesi, Roberta; Costa, G; Campo, G; Passerini, M

2005-01-01

The creation of a surveillance system of occupational mortality in Italy is limited by the low quality of information on occupation in death certificates, since the information is often incomplete or lacking and because only the occupation at the time of death is registered. To evaluate the possible use of INPS (National Institute of Social Security) records for the purpose of surveillance of occupational mortality, in terms of feasibility of setting up a system and of validity of the results obtained. Death records of 218,510 subjects aged 18-74, deceased in the 12 months following the 1991 census, were obtained from ISTAT (Central Statistics Institute). These were combined through record-linkage with the INPS social security archives, which contain the employment records by economic sector going back to 1974, in order to assign these deaths the sector in which they had worked the longest. Mortality by specific causes was evaluated by industry by means of a proportional mortality analysis stratified by sex and occupational status, and adjusted for age, education, marital status, geographical area of birth, drawing a disability pension, employment status at the time of death and work instability. Record-linkage allowed attribution of the longest held job to 70% of the deaths recorded. Results are presented and discussed only on mortality in men due to asbestosis and silicosis, and causes of death with a substantial proportion attributable to occupation: chronic obstructive pulmonary disease (COPD); cancers of the bladder, nasal cavity, larynx, lung and pleura; leukaemia and lymphoma; accidental causes. Among the economic sectors with a significant excess mortality, the following are well documented in the literature: mortality due to COPD in the coal and peat-bog sectors; due to leukaemia among farmers; due to sino-nasal tumours in wood-working and furniture production; due to cancer of the larynx, lung, and pleura in occupations where there was probable exposure

IBD Sharing between Africans, Neandertals, and Denisovans

PubMed Central

Povysil, Gundula

2016-01-01

Interbreeding between ancestors of humans and other hominins outside of Africa has been studied intensively, while their common history within Africa still lacks proper attention. However, shedding light on human evolution in this time period about which little is known, is essential for understanding subsequent events outside of Africa. We investigate the genetic relationships of humans, Neandertals, and Denisovans by identifying very short DNA segments in the 1000 Genomes Phase 3 data that these hominins share identical by descent (IBD). By focusing on low frequency and rare variants, we identify very short IBD segments with high confidence. These segments reveal events from a very distant past because shorter IBD segments are presumably older than longer ones. We extracted two types of very old IBD segments that are not only shared among humans, but also with Neandertals and/or Denisovans. The first type contains longer segments that are found primarily in Asians and Europeans where more segments are found in South Asians than in East Asians for both Neandertal and Denisovan. These longer segments indicate complex admixture events outside of Africa. The second type consists of shorter segments that are shared mainly by Africans and therefore may indicate events involving ancestors of humans and other ancient hominins within Africa. Our results from the autosomes are further supported by an analysis of chromosome X, on which segments that are shared by Africans and match the Neandertal and/or Denisovan genome were even more prominent. Our results indicate that interbreeding with other hominins was a common feature of human evolution starting already long before ancestors of modern humans left Africa. PMID:28158547

Management of Anemia in Patients with Inflammatory Bowel Disease (IBD).

PubMed

Patel, Dhruvan; Trivedi, Chinmay; Khan, Nabeel

2018-03-01

Anemia is the most common complication as well as an extra intestinal manifestation of inflammatory bowel disease (IBD). It is associated with a significant impact on patient's quality of life (QoL); as well it represents a common cause of frequent hospitalization, delay of hospital inpatient discharge and overall increased healthcare burden. In spite of all these, anemia is still often underdiagnosed and undertreated. Our aim in this review is to provide a pathway for physicians to help them achieve early diagnosis as well as timely and appropriate treatment of anemia which in turn would hopefully reduce the prevalence and subsequent complications of this condition among IBD patients. The etiology of anemia among IBD patients is most commonly due to iron deficiency anemia (IDA) followed by anemia of chronic disease. Despite this, more than a third of anemic ulcerative colitis (UC) patients are not tested for IDA and among those tested and diagnosed with IDA, a quarter are not treated with iron replacement therapy. A new algorithm has been validated to predict who will develop moderate to severe anemia at the time of UC diagnosis. While oral iron is effective for the treatment of mild iron deficiency-related anemia, the absorption of iron is influenced by chronic inflammatory states as a consequence of the presence of elevated levels of hepcidin. Also, it is important to recognize that ferritin is elevated in chronic inflammatory states and among patients with active IBD, ferritin levels less than 100 are considered to be diagnostic of iron deficiency. Newer formulations of intra-venous (IV) iron have a good safety profile and can be used for replenishment of iron stores and prevention of iron deficiency in the future. Routine screening for anemia is important among patients with IBD. The cornerstone for the accurate management of anemia in IBD patients lies in accurately diagnosing the type of anemia. All IBD patients with IDA should be considered appropriate for

Safety of TNF-α inhibitors during IBD pregnancy: a systematic review.

PubMed

Nielsen, Ole Haagen; Loftus, Edward V; Jess, Tine

2013-07-31

Tumor necrosis factor (TNF)-α inhibitors are increasingly being used in inflammatory bowel disease (IBD). Because this chronic intestinal disorder often affects women of fertile age, it is essential to assess the effect of biologics on pregnancy outcome. We performed a systematic review of the English-language literature to investigate if treatment with TNF-α blockers during pregnancy in women with IBD increases the risk of spontaneous abortions, preterm delivery, stillbirth, low birth weight, congenital malformations, or risk of infections in the offspring. Of 552 articles and abstracts reviewed, 58 articles or abstracts with unique content were identified and included in this systematic review. However, most presentations were case reports or case series supplied by a limited number of observational studies. No randomized controlled studies were available. TNF-α inhibitors do not seem to affect either outcome of pregnancy in mothers with IBD, or the outcome in the offspring (congenital malformations and immunosuppression). Further, recent data have not identified any increased risk of infections in the first year of life in the offspring of mothers who received biologics, even in combination with immunomodulators (thiopurines). From the present systematic review, no association was found between administration of TNF inhibitors for IBD during pregnancy and adverse pregnancy outcome or congenital abnormalities. Further, no increased relative risk of infections has been reported in the first year of life in offspring of mothers who received biologics. Biologics should be discontinued during pregnancy solely if the IBD is in remission using the same stopping criteria as for patients with IBD in general, as uncontrolled activity of IBD may expose the mother and child to a risk greater than those only potentially coming from the use of TNF-α inhibitors. In such cases, inoculation of the offspring with live vaccines is contraindicated until the biologic agent is no

The IBD interactome: an integrated view of aetiology, pathogenesis and therapy.

PubMed

de Souza, Heitor S P; Fiocchi, Claudio; Iliopoulos, Dimitrios

2017-12-01

Crohn's disease and ulcerative colitis are prototypical complex diseases characterized by chronic and heterogeneous manifestations, induced by interacting environmental, genomic, microbial and immunological factors. These interactions result in an overwhelming complexity that cannot be tackled by studying the totality of each pathological component (an '-ome') in isolation without consideration of the interaction among all relevant -omes that yield an overall 'network effect'. The outcome of this effect is the 'IBD interactome', defined as a disease network in which dysregulation of individual -omes causes intestinal inflammation mediated by dysfunctional molecular modules. To define the IBD interactome, new concepts and tools are needed to implement a systems approach; an unbiased data-driven integration strategy that reveals key players of the system, pinpoints the central drivers of inflammation and enables development of targeted therapies. Powerful bioinformatics tools able to query and integrate multiple -omes are available, enabling the integration of genomic, epigenomic, transcriptomic, proteomic, metabolomic and microbiome information to build a comprehensive molecular map of IBD. This approach will enable identification of IBD molecular subtypes, correlations with clinical phenotypes and elucidation of the central hubs of the IBD interactome that will aid discovery of compounds that can specifically target the hubs that control the disease.

Drug-Herb Interactions in the Elderly Patient with IBD: a Growing Concern.

PubMed

Rahman, Haider; Kim, Marina; Leung, Galen; Green, Jesse A; Katz, Seymour

2017-12-01

Inflammatory bowel disease (IBD), which includes conditions such as Crohn's disease and ulcerative colitis, is becoming more prevalent with the elderly being the fastest growing group. Parallel to this, there is an increasing interest in the use of complementary and alternative medicine (CAM). Nearly half of patients with IBD have used CAM at one time. The elderly patients, however, are burdened by comorbid conditions, polypharmacy, and altered functional status. With increasing use of complementary and alternative medicine in our elderly patients with IBD, it is vital for the provider to provide counsel on drug-herb potential interactions. CAM includes herbal products, diet, dietary supplements, acupuncture, and prayer. In this paper, we will review common CAM, specifically herbs, that are used in patients with IBD including the herb background, suggested use, evidence in IBD, and most importantly, potential interactions with IBD medications used in elderly patients. Most important evidence-based adverse events and drug-herb interactions are summarized. The herbs discussed include Triticum aestivum (wheat grass), Andrographis paniculata (chiretta), Boswellia serrata, tormentil, bilberry, curcumin (turmeric), Plantago ovata (blond psyllium), Oenothera biennis (evening primrose oil), germinated barley foodstuff, an herbal preparation of myrrh, chamomile and coffee extract, chios mastic gum, wormwood (absinthe, thujone), Cannabis sativa (marijuana, THC), tripterygium wilfordii (thunder god vine), Ulmus rubra (slippery elm bark), trigonella foenugraecum (fenugreek), Dioscorea mexicana (wild yam), Harpagophytum procumbens (devil's claw), ginger, cinnamon, licorice, and peppermint.

How to Apply for and Secure EU Funding for Collaborative IBD Research Projects

PubMed Central

Satsangi, Jack; Kitten, Olivier; Chavez, Marcela; Kalla, Rahul; Prel, Nadege; Meuwis, Marie-Alice; Scott, Stephanie; Bonetti, Illaria; Ventham, Nicholas T.

2016-01-01

The European Union offers opportunities for high-level of funding of collaborative European research. Calls are regularly published: after the end of the FP7 funding programme the new round of Horizon 2020 calls started in 2015. Several topics are relevant to inflammatory bowel disease (IBD) challenges, including chronic disease management, biomarker discovery and new treatments developments. The aim of this Viewpoint article is to describe the new Horizon 2020 instrument and the project submission procedures, and to highlight these through the description of tips and tricks, taking advantage of four examples of successful projects in the field of IBD: the SADEL, IBD-BIOM, IBD Character and BIOCYCLE projects. PMID:26744440

Revealing and concealing Ill identity: a performance narrative of IBD disclosure.

PubMed

Defenbaugh, Nicole L

2013-01-01

Revealing a hidden, chronic illness is a risky and vulnerable act. Ill individuals often remain socially stigmatized, and those who live with invisible illness must legitimize their ill identity since they infrequently look sick. For individuals with inflammatory bowel disease (IBD), disclosing one's illness carries unique challenges because of the grotesque and taboo nature of the disease. To this end, the bathroom or "water closet" is more than a functional place-it is a space to hide one's ill identity. For many, the point of departure from safety to vulnerability occurs when there is a desire to disclose. In this descriptive essay, revelation of an invisible illness, IBD, and disclosure to others are explored as embodied and situated communication. Through performance narrative, the author shares stories of her disclosive moments to inform others about IBD, explores how the water closet can be a metaphoric boundary, examines various strategies used in revealing hidden illness, and offers possible implications for IBD disclosure to the self and relationships with others.

Development of the IBD Disk: A Visual Self-administered Tool for Assessing Disability in Inflammatory Bowel Diseases.

PubMed

Ghosh, Subrata; Louis, Edouard; Beaugerie, Laurent; Bossuyt, Peter; Bouguen, Guillaume; Bourreille, Arnaud; Ferrante, Marc; Franchimont, Denis; Frost, Karen; Hebuterne, Xavier; Marshall, John K; OʼShea, Ciara; Rosenfeld, Greg; Williams, Chadwick; Peyrin-Biroulet, Laurent

2017-03-01

The Inflammatory bowel disease (IBD) Disability Index is a validated tool that evaluates functional status; however, it is used mainly in the clinical trial setting. We describe the use of an iterative Delphi consensus process to develop the IBD Disk-a shortened, self-administered adaption of the validated IBD Disability Index-to give immediate visual representation of patient-reported IBD-related disability. In the preparatory phase, the IBD CONNECT group (30 health care professionals) ranked IBD Disability Index items in the perceived order of importance. The Steering Committee then selected 10 items from the IBD Disability Index to take forward for inclusion in the IBD Disk. In the consensus phase, the items were refined and agreed by the IBD Disk Working Group (14 gastroenterologists) using an online iterative Delphi consensus process. Members could also suggest new element(s) or recommend changes to included elements. The final items for the IBD Disk were agreed in February 2016. After 4 rounds of voting, the following 10 items were agreed for inclusion in the IBD Disk: abdominal pain, body image, education and work, emotions, energy, interpersonal interactions, joint pain, regulating defecation, sexual functions, and sleep. All elements, except sexual functions, were included in the validated IBD Disability Index. The IBD Disk has the potential to be a valuable tool for use at a clinical visit. It can facilitate assessment of inflammatory bowel disease-related disability relevant to both patients and physicians, discussion on specific disability-related issues, and tracking changes in disease burden over time.

Inflammatory Bowel Disease (IBD) and Pregnancy

MedlinePlus

... may be at an increased risk for having Vitamin K deficiency. Vitamin K is important in the blood clotting process. Women with IBD should have their nutritional status evaluated by their health care provider prior to and ... supplements may be necessary. What medications ...

Data Linkage: A powerful research tool with potential problems

PubMed Central

2010-01-01

Background Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes. Methods A narrative review, using structured search methods was undertaken. Key words "data linkage" and Mesh term "medical record linkage" were applied to Medline, EMBASE and CINAHL databases between 1991 and 2007. Abstract inclusion criteria were; the article attempted an empirical evaluation of methodological issues relating to data linkage and reported on patient characteristics, the study design included analysis of matched versus unmatched records, and the report was in English. Included articles were grouped thematically according to patient characteristics that were compared between matched and unmatched records. Results The search identified 1810 articles of which 33 (1.8%) met inclusion criteria. There was marked heterogeneity in study methods and factors investigated. Characteristics that were unevenly distributed among matched and unmatched records were; age (72% of studies), sex (50% of studies), race (64% of studies), geographical/hospital site (93% of studies), socio-economic status (82% of studies) and health status (72% of studies). Conclusion A number of relevant patient or population factors may be associated with incomplete data linkage resulting in systematic bias in reported clinical outcomes. Readers should consider these factors in interpreting the reported results of data linkage studies. PMID:21176171

Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients.

PubMed

Santoru, Maria Laura; Piras, Cristina; Murgia, Antonio; Palmas, Vanessa; Camboni, Tania; Liggi, Sonia; Ibba, Ivan; Lai, Maria Antonia; Orrù, Sandro; Blois, Sylvain; Loizedda, Anna Lisa; Griffin, Julian Leether; Usai, Paolo; Caboni, Pierluigi; Atzori, Luigi; Manzin, Aldo

2017-08-25

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract of uncertain origin, which includes ulcerative colitis (UC) and Crohn's disease (CD). The composition of gut microbiota may change in IBD affected individuals, but whether dysbiosis is the cause or the consequence of inflammatory processes in the intestinal tissue is still unclear. Here, the composition of the microbiota and the metabolites in stool of 183 subjects (82 UC, 50 CD, and 51 healthy controls) were determined. The metabolites content and the microbiological profiles were significantly different between IBD and healthy subjects. In the IBD group, Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria were significantly increased, whereas Bacteroidetes and Cyanobacteria were decreased. At genus level Escherichia, Faecalibacterium, Streptococcus, Sutterella and Veillonella were increased, whereas Bacteroides, Flavobacterium, and Oscillospira decreased. Various metabolites including biogenic amines, amino acids, lipids, were significantly increased in IBD, while others, such as two B group vitamins, were decreased in IBD compared to healthy subjects. This study underlines the potential role of an inter-omics approach in understanding the metabolic pathways involved in IBD. The combined evaluation of metabolites and fecal microbiome can be useful to discriminate between healthy subjects and patients with IBD.

Aminosalicylates and colorectal cancer in IBD: a not-so bitter pill to swallow.

PubMed

Ryan, B M; Russel, M G V M; Langholz, E; Stockbrugger, R W

2003-08-01

Inflammatory bowel disease (IBD) is associated with an increased risk of developing intestinal cancer at sites of chronic inflammation. Aminosalicylates, including both sulfasalazine and mesalamine, are the most commonly prescribed anti-inflammatory agents prescribed in IBD. On balance, the body of literature to date suggests that aminosalicylates confer some protection against the development of colonic neoplasia in patients with IBD and in a variety of models, including in the noninflamed gut. This latter observation implies that aminosalicylates may be of chemopreventive value in normal as well as IBD individuals. The current review examines and gives an overview of the evidence from a variety of sources, including epidemiological, in vivo and in vitro studies that have investigated the potential anticancer effects of aminosalicylates.

Prevalence and Impact of Functional Abdominal Pain Disorders in Children With Inflammatory Bowel Diseases (IBD-FAPD).

PubMed

Watson, Kevin L; Kim, Sandra C; Boyle, Brendan M; Saps, Miguel

2017-08-01

We sought to describe the prevalence of the overlap of functional abdominal pain disorders (FAPDs) in children with inflammatory bowel diseases (IBDs), a condition we have designated as IBD-FAPD. We also aimed to describe the psychological profile of this group, and to assess predictors of disease and the impact of IBD-FAPD on quality of life. This cross-sectional prospective study included patients ages 8 to 18 years with a diagnosis of IBD. Disease activity was assessed by physician's global assessment, laboratory studies, and abbreviated Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index scoring. Age-appropriate validated questionnaires were used to diagnose FAPDs according to the Rome III criteria, depression, anxiety symptoms, and quality of life. There were 128 patients recruited. Eighty-one (63%) completed questionnaires (36 girls; 45 boys; mean age 14.4 ± 2.6 years) (62 Crohn disease, 19 ulcerative colitis). The prevalence of IBD-FAPD in clinical remission was 26% (17 Crohn disease, 4 ulcerative colitis; 95% confidence interval: 20.6%-79.4%), with significantly more girls having IBD-FAPD (P = 0.038). Anxiety symptoms were in 14.3% of patients with IBD-FAPD (P = 0.06) and depression in 23.8% (P = 0.006). The average Pediatric Quality of Life Inventory Gastrointestinal Symptoms score for the IBD-FAPD group was significantly lower than those without FAPDs (71 vs 86.5, P = 0.008). In our cohort, the prevalence of IBD-FAPD was 26%. This is the first study to assess all FAPDs using the Rome III criteria and to demonstrate increased anxiety, depression, and worse quality of life in children with IBD-FAPD. The identification of patients predisposed to IBD-FAPD may allow implementing strategies that could improve symptoms and quality of life.

Inflammatory bowel diseases in Faroese-born Danish residents and their offspring: further evidence of the dominant role of environmental factors in IBD development.

PubMed

Hammer, T; Lophaven, S N; Nielsen, K R; von Euler-Chelpin, M; Weihe, P; Munkholm, P; Burisch, J; Lynge, E

2017-04-01

The incidence of inflammatory bowel disease (IBD) is record high in the Faroe Islands, and many Faroese emigrate to Denmark, where the IBD incidence is considerably lower. To study the IBD incidence in first-, second- and third-generation immigrants from the Faroe Islands to Denmark to assess the extent to which the immigrants adopt the lower IBD incidence of their new home country. Data on Faroese-born Danish residents and their children were retrieved from the Danish Central Population Register for 1980-2014. Incident IBD cases were identified from the Danish National Patient Register. Standardised Incidence Ratios (SIRs) were used to compare the IBD risk in immigrants with that of Danes. 95% confidence intervals (CI) were calculated using the square-root transform. First-generation Faroese immigrants had a higher IBD incidence than Danes, SIR 1.25 (95% CI, 0.97-1.59) for men and 1.28 (95% CI, 1.05-1.53) for women. This excess risk derived from ulcerative colitis (UC), SIR 1.44 (95% CI, 1.10-1.87) for men and 1.36 (95% CI, 1.09-1.68) for women. No excess risk was found for Crohn's disease (CD). The UC risk was nearly doubled during the immigrants' first 10 years in Denmark; SIR 2.13 (95% CI, 1.52-2.92) for men and 1.63 (95% CI, 1.19-2.18) for women. Although some impact of genetic dilution cannot be excluded, our findings indicate importance of gene-environment interplay in UC, as the excess UC risk in Faroese immigrants to Denmark disappeared over time and over one generation in men and over two generations in women. © 2017 The Authors. Alimentary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients

PubMed Central

Matijašić, Mario; Meštrović, Tomislav; Perić, Mihaela; Čipčić Paljetak, Hana; Panek, Marina; Vranešić Bender, Darija; Ljubas Kelečić, Dina; Krznarić, Željko; Verbanac, Donatella

2016-01-01

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms. PMID:27104515

Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients.

PubMed

Matijašić, Mario; Meštrović, Tomislav; Perić, Mihaela; Čipčić Paljetak, Hana; Panek, Marina; Vranešić Bender, Darija; Ljubas Kelečić, Dina; Krznarić, Željko; Verbanac, Donatella

2016-04-19

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms.

IBD-INFO Questionnaire: A Multicenter French Up-to-Date Survey of Patient Knowledge in Inflammatory Bowel Disease.

PubMed

Danion, Pauline; Buisson, Anthony; Roblin, Xavier; Mathieu, Nicolas; Charlois, Anne-Laure; Borgerding, Joshua N; Williet, Nicolas; Del Tedesco, Emilie; Flourié, Bernard; Nancey, Stéphane; Boschetti, Gilles

2018-04-23

It has been demonstrated in many chronic conditions, including inflammatory bowel disease (IBD), that better patient knowledge about pathology and treatment improves the course and management of disease. The aim of this study was to develop an updated self-questionnaire to assess patients' level of knowledge of IBD. The IBD-INFO included 3 parts: an original part (Q1) and 2 parts from the translation of the preexisting questionnaires Crohn's and Colitis Knowledge score (CCKNOW) (Q2) and Crohn's and Colitis Pregnancy Knowledge score (CCPKNOW) (Q3). The reliability and discriminatory ability of the questionnaire were validated in 3 groups of non-IBD volunteers with various theoretical knowledge levels. The final questionnaire (64 validated questions) was then tested on 364 in- and out- IBD patients from 4 French university hospitals. The score for each part of the questionnaire was calculated, and factors associated with low scores were identified by univariate and multivariate logistic regression analyses. The scores obtained by the 3 non-IBD volunteer groups differed significantly (P < 0.0001), and the IBD-INFO questionnaire showed excellent internal reliability and consistency (α = 0.98). The median total score obtained by the IBD patients was 27/64 (range, 0-59), and scores for Q1, Q2, and Q3 were, respectively, 10/23 (range, 0-21), 11/24 (range, 0-23), and 4/17 (range, 0-16). In multivariate analysis, lack of a university degree, not being a member of a patient association, not receiving anti-tumor necrosis factor alpha (anti-TNFα) treatment, duration of IBD ≤3 years, male sex, and age >38 years were independent risk factors of a poor IBD-INFO knowledge score. The areas of knowledge least mastered were vaccination, IBD-related cancers, treatments, and pregnancy. Using the IBD-INFO, an updated self-administered questionnaire built to assess IBD patients' knowledge, several risk factors have been highlighted that allow better targeting of patients and areas

Disease severity in familial cases of IBD.

PubMed

Andreu, M; Márquez, L; Domènech, E; Gisbert, J P; García, V; Marín-Jiménez, I; Peñalva, M; Gomollón, F; Calvet, X; Merino, O; Garcia-Planella, E; Vázquez-Romero, N; Esteve, M; Nos, P; Gutiérrez, A; Vera, I; Cabriada, J L; Martín, M D; Cañas-Ventura, A; Panés, J

2014-03-01

Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course. © 2013.

Differential effect of a patient-education transition intervention in adolescents with IBD vs. diabetes.

PubMed

Schmidt, Silke; Markwart, Henriette; Bomba, Franziska; Muehlan, Holger; Findeisen, Annette; Kohl, Martina; Menrath, Ingo; Thyen, Ute

2018-04-01

Patient education programs (PEPs) to improve disease management are part of standard and regular treatment in adolescents with diabetes. In Germany, youth with inflammatory bowel disease (IBD) receive individual counseling but not PEPs in group settings. Generic PEPs have been developed in order to improve transition from child-centered to adolescent health services. The aim of the study was to investigate the effects of a transition-oriented PEP on quality of life (QoL) and self-management in young patients with IBD (PEP naive), compared to patients with diabetes (familiar with PEPs). A 2-day transition workshop was oriented at improving psychosocial skills and addressed both generic as well as specific aspects of the condition. A controlled trial on the outcomes of a generic transition-oriented PEP was conducted in 14- to 20-year-old patients with IBD (n = 99) and diabetes (n = 153). Transition competence and QoL were assessed at baseline and 6-month follow-up. Results show that the intervention lead to a significant increase in QoL only in patients with IBD. The PEP significantly improved transition competence in both groups, however to a higher extent in subjects with IBD. Transition-oriented PEPs can have differential effects in different patient groups. However, this needs further longitudinal investigations. What is Known: • To date, evidence has accumulated concerning the effectiveness of patient education programs (PEPs) in pediatric health care for chronic conditions such as type 1 diabetes, asthma, atopic dermatitis, or obesity but is less documented in inflammatory bowel disease (IBD). In particular, PEPs in the transition period have not been investigated in youth with IBD. • The current study focuses on evaluating a PEP for transition preparation and management designed to be generically used across different chronic conditions since many aspects of managing chronic conditions share commonalities across conditions. The 2-day workshop

Pregnancy associated death in record linkage studies relative to delivery, termination of pregnancy, and natural losses: A systematic review with a narrative synthesis and meta-analysis

PubMed Central

Reardon, David C; Thorp, John M

2017-01-01

Objectives: Measures of pregnancy associated deaths provide important guidance for public health initiatives. Record linkage studies have significantly improved identification of deaths associated with childbirth but relatively few have also examined deaths associated with pregnancy loss even though higher rates of maternal death have been associated with the latter. Following PRISMA guidelines we undertook a systematic review of record linkage studies examining the relative mortality risks associated with pregnancy loss to develop a narrative synthesis, a meta-analysis, and to identify research opportunities. Methods: MEDLINE and SCOPUS were searched in July 2015 using combinations of: mortality, maternal death, record linkage, linked records, pregnancy associated mortality, and pregnancy associated death to identify papers using linkage of death certificates to independent records identifying pregnancy outcomes. Additional studies were identified by examining all citations for relevant studies. Results: Of 989 studies, 11 studies from three countries reported mortality rates associated with termination of pregnancy, miscarriage or failed pregnancy. Within a year of their pregnancy outcomes, women experiencing a pregnancy loss are over twice as likely to die compared to women giving birth. The heightened risk is apparent within 180 days and remains elevated for many years. There is a dose effect, with exposure to each pregnancy loss associated with increasing risk of death. Higher rates of death from suicide, accidents, homicide and some natural causes, such as circulatory diseases, may be from elevated stress and risk taking behaviors. Conclusions: Both miscarriage and termination of pregnancy are markers for reduced life expectancy. This association should inform research and new public health initiatives including screening and interventions for patients exhibiting known risk factors. PMID:29163945

Attachment, childhood abuse, and IBD-related quality of life and disease activity outcomes.

PubMed

Caplan, Rachel A; Maunder, Robert G; Stempak, Joanne M; Silverberg, Mark S; Hart, Tae L

2014-05-01

This study examined attachment style as a moderator of the relationship between childhood abuse and inflammatory bowel disease (IBD)-related outcomes. Study participants were 205 patients with IBD from Mount Sinai Hospital in Toronto. Participants completed self-report questionnaires regarding personal relationships, abuse history, and IBD-related information. Multiple regression models were fit using 3 outcome variables: disease-related quality of life (QOL), disease activity for ulcerative colitis, and disease activity for Crohn's disease. Patients reporting less severe abuse and low levels of avoidant attachment had the highest levels of QOL, whereas patients reporting high levels of avoidant attachment had the lowest levels of QOL, regardless of abuse severity. Patients reporting greater anxious attachment had lower QOL scores. Patients reporting less severe abuse and low levels of avoidant attachment had the lowest levels of disease activity, whereas patients reporting high levels of avoidant attachment had the highest levels of ulcerative colitis-related disease activity, regardless of abuse severity. However, for anxious attachment, there was no significant main effect or significant interaction of abuse by anxious attachment on ulcerative colitis-related disease activity. Childhood abuse and attachment style were not found to be associated with Crohn's disease-related disease activity. Adult attachment style may moderate the relationship between childhood abuse and IBD-related outcomes, by impacting one's QOL and disease activity. Distinct types of insecure attachment styles may impact these relationships differently. Psychological interventions focusing on attachment styles of patients with IBD have the potential to improve IBD-related QOL and disease activity.

Linkage of Maternity Hospital Episode Statistics data to birth registration and notification records for births in England 2005–2014: Quality assurance of linkage of routine data for singleton and multiple births

PubMed Central

2018-01-01

Objectives To quality assure a Trusted Third Party linked data set to prepare it for analysis. Setting Birth registration and notification records from the Office for National Statistics for all births in England 2005–2014 linked to Maternity Hospital Episode Statistics (HES) delivery records by NHS Digital using mothers’ identifiers. Participants All 6 676 912 births that occurred in England from 1 January 2005 to 31 December 2014. Primary and secondary outcome measures Every link between a registered birth and an HES delivery record for the study period was categorised as either the same baby or a different baby to the same mother, or as a wrong link, by comparing common baby data items and valid values in key fields with stepwise deterministic rules. Rates of preserved and discarded links were calculated and which features were more common in each group were assessed. Results Ninety-eight per cent of births originally linked to HES were left with one preserved link. The majority of discarded links were due to duplicate HES delivery records. Of the 4854 discarded links categorised as wrong links, clerical checks found 85% were false-positives links, 13% were quality assurance false negatives and 2% were undeterminable. Births linked using a less reliable stage of the linkage algorithm, births at home and in the London region, and with birth weight or gestational age values missing in HES were more likely to have all links discarded. Conclusions Linkage error, data quality issues, and false negatives in the quality assurance procedure were uncovered. The procedure could be improved by allowing for transposition in date fields, and more discrimination between missing and differing values. The availability of identifiers in the datasets supported clerical checking. Other research using Trusted Third Party linkage should not assume the linked dataset is error-free or optimised for their analysis, and allow sufficient resources for this. PMID:29500200

Role of Th17 Cells in the Pathogenesis of Human IBD

PubMed Central

Gálvez, Julio

2014-01-01

The gastrointestinal tract plays a central role in immune system, being able to mount efficient immune responses against pathogens, keeping the homeostasis of the human gut. However, conditions like Crohn's disease (CD) or ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD), are related to an excessive and uncontrolled immune response against normal microbiota, through the activation of CD4+ T helper (Th) cells. Classically, IBD was thought to be primarily mediated by Th1 cells in CD or Th2 cells in UC, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions. Th17 cells massively infiltrate the inflamed intestine of IBD patients, where they produce interleukin- (IL-) 17A and other cytokines, triggering and amplifying the inflammatory process. However, these cells show functional plasticity, and they can be converted into either IFN-γ producing Th1 cells or regulatory T cells. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut. Deeper insights into their plasticity in inflammatory conditions will contribute to advancing our understanding of the mechanisms that regulate mucosal homeostasis and inflammation in the gut, promoting the design of novel therapeutic approaches for IBD. PMID:25101191

Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children

PubMed Central

Martin, Francois-Pierre; Su, Ming-Ming; Xie, Guo-Xiang; Guiraud, Seu Ping; Kussmann, Martin; Godin, Jean-Philippe; Jia, Wei; Nydegger, Andreas

2017-01-01

AIM To identify metabolic signatures in urine samples from healthy and inflammatory bowel disease (IBD) children. METHODS We applied liquid chromatography and gas chromatography coupled to targeted mass spectrometry (MS)-based metabolite profiling to identify and quantify bile acids and host-gut microbial metabolites in urine samples collected from 21 pediatric IBD patients monitored three times over one year (baseline, 6 and 12 mo), and 27 age- and gender-matched healthy children. RESULTS urinary metabolic profiles of IBD children differ significantly from healthy controls. Such metabolic differences encompass central energy metabolism, amino acids, bile acids and gut microbial metabolites. In particular, levels of pyroglutamic acid, glutamic acid, glycine and cysteine, were significantly higher in IBD children in the course of the study. This suggests that glutathione cannot be optimally synthesized and replenished. Whilst alterations of the enterohepatic circulation of bile acids in pediatric IBD patients is known, we show here that non-invasive urinary bile acid profiling can assess those altered hepatic and intestinal barrier dysfunctions. CONCLUSION The present study shows how non-invasive sampling of urine followed by targeted MS-based metabonomic analysis can elucidate and monitor the metabolic status of children with different GI health/disease status. PMID:28611517

Early childhood measles vaccinations are not associated with paediatric IBD: a population-based analysis.

PubMed

Shaw, Souradet Y; Blanchard, James F; Bernstein, Charles N

2015-04-01

Early childhood vaccinations have been hypothesized to contribute to the emergence of paediatric inflammatory bowel disease [IBD] in developed countries. Using linked population-based administrative databases, we aimed to explore the association between vaccination with measles-containing vaccines and the risk for IBD. This was a case-control study using the University of Manitoba IBD Epidemiology Database [UMIBDED]. The UMIBDED was linked to the Manitoba Immunization Monitoring System [MIMS], a population-based database of immunizations administered in Manitoba. All paediatric IBD cases in Manitoba, born after 1989 and diagnosed before March 31, 2008, were included. Controls were matched to cases on the basis of age, sex, and region of residence at time of diagnosis. Measles-containing vaccinations received in the first 2 years of life were documented, with vaccinations categorized as 'None' or 'Complete', with completeness defined according to Manitoba's vaccination schedule. Conditional logistic regression models were fitted to the data, with models adjusted for physician visits in the first 2 years of life and area-level socioeconomic status at case date. A total of 951 individuals [117 cases and 834 controls] met eligibility criteria, with average age of diagnosis among cases at 11 years. The proportion of IBD cases with completed vaccinations was 97%, compared with 94% of controls. In models adjusted for physician visits and area-level socioeconomic status, no statistically significant association was detected between completed measles vaccinations and the risk of IBD (adjusted odds ratio [AOR]: 1.5; 95% confidence interval [CI]: 0.5-4.4; p = 0.419]. No significant association between completed measles-containing vaccination in the first 2 years of life and paediatric IBD could be demonstrated in this population-based study. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For

Parenting stress in pediatric IBD: relations with child psychopathology, family functioning, and disease severity.

PubMed

Gray, Wendy N; Graef, Danielle M; Schuman, Shana S; Janicke, David M; Hommel, Kevin A

2013-05-01

Parenting stress in pediatric inflammatory bowel disease (IBD) has been under-examined. Data validating use of the Pediatric Inventory for Parents (PIP), a measure of parenting stress associated with caring for a chronically ill child, in chronic diseases with intermittent, unpredictable disease courses, such as IBD, are needed. This study presents validity data in support of the PIP in pediatric IBD and examines relations between parenting stress and important psychosocial and medical outcomes. Adolescents (N = 130) with IBD and their caregivers across 3 sites completed measures of parenting stress, family functioning, and emotional/behavioral functioning. Disease severity was also assessed for each participant. The PIP demonstrates excellent internal consistency. Parenting stress was significantly higher among those with unhealthy general family functioning and those with children with borderline or clinically elevated internalizing symptoms. Caregiving stress was greater among parents of youth with more active Crohn's disease. Results supported the reliability and validity of the PIP for assessing caregiving stress in pediatric IBD. Routine assessment of parenting stress is recommended, particularly among parents reporting unhealthy family functioning and parents of youth with borderline or clinically elevated internalizing symptoms and more active disease.

Biologic agents for IBD: practical insights.

PubMed

Danese, Silvio; Vuitton, Lucine; Peyrin-Biroulet, Laurent

2015-09-01

Six biologic agents are currently approved for the treatment of IBD: four anti-TNF agents (infliximab, adalimumab, golimumab and certolizumab pegol) and two anti-integrin agents (natalizumab and vedolizumab). In Crohn's disease and ulcerative colitis refractory to standard medications, treatment choice among available biologic agents can be challenging. Several parameters should be taken into account to help physicians through the decision-making process, including the comparative effectiveness and long-term safety profile, availability and labelling in the prescriber's country, international guidelines, and cost, as well as patient preferences (such as the route of administration). Herein, we provide practical insights on the use of biologic agents in IBD. The results of head-to-head trials between biologic agents are eagerly awaited to guide decision-making regarding the choice of first-line biologic agents and to determine whether switching within the same drug class or swapping (switching out of the drug class) is preferable after primary or secondary loss of response to the first biologic agent. In the near future, treatment algorithms might evolve with the launch of new drugs (such as ustekinumab, tofacitinib and etrolizumab) and the increased use of biosimilars.

Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease

PubMed Central

Spekhorst, Lieke M; Imhann, Floris; Festen, Eleonora AM; van Bodegraven, Ad A; de Boer, Nanne KH; Bouma, Gerd; Fidder, Herma H; D’Haens, Geert; Hoentjen, Frank; Hommes, Daan W; de Jong, Dirk J; Löwenberg, Mark; Maljaars, PW Jeroen; van der Meulen-de Jong, Andrea E; Oldenburg, Bas; Pierik, Marieke J; Ponsioen, Cyriel Y; Stokkers, Pieter C; Verspaget, Hein W; Visschedijk, Marijn C; van der Woude, C Janneke; Dijkstra, Gerard; Weersma, Rinse K

2017-01-01

Purpose The Dutch IBD Biobank aims to facilitate the discovery of predictors for individual disease course and treatment response in patients with inflammatory bowel disease (IBD). In this paper, we aim to describe the establishment of the Dutch IBD Biobank, including the facilitators and barriers to establishment. Moreover, we aim to provide a complete overview of the content of the Dutch IBD Biobank. Participants Since 2007, every patient with IBD treated in one of the eight Dutch university medical centres is asked to participate in the Dutch IBD Biobank in which 225 standardised IBD-related data items and biomaterials, such as serum, DNA, biopsies and a stool sample, are collected. Findings to date As of June 2014, the Dutch IBD Biobank had enrolled 3388 patients with IBD: 2118 Crohn’s disease (62.5%), 1190 ulcerative colitis (35.1%), 74 IBD-unclassified (2.2%) and 6 IBD-indeterminate (0.2%). The inclusion of patients with IBD is ongoing. The quality of the biomaterials is good and serum, DNA and biopsies have been used in newly published studies. Future plans The genotyping (750 000 genetic variants) of all participants of the Dutch IBD Biobank is currently ongoing, enabling more genetic research. In addition, all participants will start reporting disease activity and outcome measures using an online platform and mobile app. PMID:29122790

Estimating parameters for probabilistic linkage of privacy-preserved datasets.

PubMed

Brown, Adrian P; Randall, Sean M; Ferrante, Anna M; Semmens, James B; Boyd, James H

2017-07-10

Probabilistic record linkage is a process used to bring together person-based records from within the same dataset (de-duplication) or from disparate datasets using pairwise comparisons and matching probabilities. The linkage strategy and associated match probabilities are often estimated through investigations into data quality and manual inspection. However, as privacy-preserved datasets comprise encrypted data, such methods are not possible. In this paper, we present a method for estimating the probabilities and threshold values for probabilistic privacy-preserved record linkage using Bloom filters. Our method was tested through a simulation study using synthetic data, followed by an application using real-world administrative data. Synthetic datasets were generated with error rates from zero to 20% error. Our method was used to estimate parameters (probabilities and thresholds) for de-duplication linkages. Linkage quality was determined by F-measure. Each dataset was privacy-preserved using separate Bloom filters for each field. Match probabilities were estimated using the expectation-maximisation (EM) algorithm on the privacy-preserved data. Threshold cut-off values were determined by an extension to the EM algorithm allowing linkage quality to be estimated for each possible threshold. De-duplication linkages of each privacy-preserved dataset were performed using both estimated and calculated probabilities. Linkage quality using the F-measure at the estimated threshold values was also compared to the highest F-measure. Three large administrative datasets were used to demonstrate the applicability of the probability and threshold estimation technique on real-world data. Linkage of the synthetic datasets using the estimated probabilities produced an F-measure that was comparable to the F-measure using calculated probabilities, even with up to 20% error. Linkage of the administrative datasets using estimated probabilities produced an F-measure that was higher

Pain in IBD Patients: Very Frequent and Frequently Insufficiently Taken into Account

PubMed Central

Ak, Melike; Müller-Mottet, Séverine; Scharl, Sylvie; Biedermann, Luc; Fournier, Nicolas; Frei, Pascal; Pittet, Valerie; Scharl, Michael; Fried, Michael

2016-01-01

Background Pain is a common symptom related to inflammatory bowel disease (IBD). In addition to abdominal pain, pain can also be an extraintestinal manifestation of IBD. Pain treatment is challenging and a substantial part of IBD patients are treated with opioids. Therefore, a better knowledge on pain symptoms is crucial for a better therapeutic approach to this clinical problem. Methods Patients of the Swiss IBD Cohort Study (SIBDCS) (n = 2152) received a questionnaire regarding pain intensity, pain localization and impact of pain on daily life and social activities. Furthermore, the questionnaire investigated the use of pain-specific medication. Results A vast majority of patients (71%) experienced pain during the disease course. For a substantial part of patients (49% in UC and 55% in CD) pain is a longstanding problem (>5 years). Pain in UC was of shorter duration compared to CD (p < 0.01). Abdominal pain (59.5%) and back pain (38.3%) were the main pain localizations. 67% of patients took pain medication; 24% received no pain treatment. The general quality of life was significantly lower in patients suffering of pain compared to those without pain (38 vs. 77; (-100 very bad; 100 very good) p<0.0001). Conclusions Prevalence of pain is high in patients of the SIBDCS. It is a longstanding problem for the majority of the patients affected. Pain was found to be undertreated in the SIBDCS and was significantly associated with health-related quality of life. Thus, an increased awareness is mandatory to address this frequent complication in the course of IBD. PMID:27332879

Seasonal variation in onset and relapse of IBD and a model to predict the frequency of onset, relapse, and severity of IBD based on artificial neural network.

PubMed

Peng, Jiang Chen; Ran, Zhi Hua; Shen, Jun

2015-09-01

Previous research has yielded conflicting data as to whether the natural history of inflammatory bowel disease follows a seasonal pattern. The purpose of this study was (1) to determine whether the frequency of onset and relapse of inflammatory bowel disease follows a seasonal pattern and (2) to establish a model to predict the frequency of onset, relapse, and severity of inflammatory bowel disease (IBD) with meteorological data based on artificial neural network (ANN). Patients with diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) between 2003 and 2011 were investigated according to the occurrence of onset and flares of symptoms. The expected onset or relapse was calculated on a monthly basis over the study period. For artificial neural network (ANN), patients from 2003 to 2010 were assigned as training cohort and patients in 2011 were assigned as validation cohort. Mean square error (MSE) and mean absolute percentage error (MAPE) were used to evaluate the predictive accuracy. We found no seasonal pattern of onset (P = 0.248) and relapse (P = 0.394) among UC patients. But, the onset (P = 0.015) and relapse (P = 0.004) of CD were associated with seasonal pattern, with a peak in July and August. ANN had average accuracy to predict the frequency of onset (MSE = 0.076, MAPE = 37.58%) and severity of IBD (MSE = 0.065, MAPE = 42.15%) but high accuracy in predicting the frequency of relapse of IBD (MSE = 0.009, MAPE = 17.1%). The frequency of onset and relapse in IBD showed seasonality only in CD, with a peak in July and August, but not in UC. ANN may have its value in predicting the frequency of relapse among patients with IBD.

Clinical importance of IL-22 cascade in IBD.

PubMed

Mizoguchi, Atsushi; Yano, Arisa; Himuro, Hidetomo; Ezaki, Yui; Sadanaga, Takayuki; Mizoguchi, Emiko

2018-04-01

IL-22 is a relatively new cytokine that is characterized by several unique biological properties. In the intestines, the effect of IL-22 is restricted mainly to non-lymphoid cells such as epithelial cells. Interestingly, the expression pattern and major cellular source of IL-22 have distinct difference between large and small intestines. IL-22 possesses an ability to constitutively activate STAT3 for promoting epithelial cell regeneration and reinforcing mucosal barrier integrity through stimulating the expression of anti-bacterial peptide and mucins. Of note, IL-22 is characterized as a two-faced cytokine that can play not only protective but also deleterious roles in the intestinal inflammation depending on the cytokine environment such as the expression levels of IL-23, T-bet, and IL-22 binding protein. Most importantly, clinical relevance of IL-22 to inflammatory bowel disease has been well highlighted. Mucosal healing, which represents the current therapeutic goal for IBD, can be induced by IL-22. Indeed, indigo naturalis, which can activate IL-22 pathway through Ahr, has been shown in a clinical trial to exhibit a strong therapeutic effect on ulcerative colitis. Despite the beneficial effect of IL-22, continuous activation of the IL-22 pathway increases the risk of colitis-associated cancer, particularly in patients with an extended history of IBD. This review article discusses how IL-22 regulates colitis, how beneficial versus deleterious effects of IL-22 is determined, and why IL-22 represents a promising target for IBD therapy.

[Record linkage of a large clinical practice patient cohort with the Cancer Registry Schleswig-Holstein].

PubMed

Obi, N; Waldmann, A; Babaev, V; Katalinic, A

2011-07-01

A precondition for the evaluation of outcomes in cohort studies and screening programmes is the availability of follow-up data. In Germany, established cancer registries provide such data for incident primary cancer diseases and mortality. To utilise these cancer registry data a person's identifying code has to be correctly linked to study or programme records, a procedure which, up to date, has been only rarely used in Germany. Exemplarily, the feasibility and validity of record linkage of a cohort of 173 050 patients from the Quality-assured Mamma Diagnostic programme (QuaMaDi) to the cancer registry Schleswig-Holstein was assessed by the accuracy of the classified outcome. Name, date of birth and address of the QuaMaDi cohort members were coded in the confidential administration center of the registry. These codes were passed by the codes of 129 455 female cancer registry records. Datasets were synchronised for each match, so that QuaMaDi participants could be identified in the registry file. In a next step epidemiological registry records were linked to the QuaMaDi study records. The accuracy of classifying outcome was assessed by agreement measures, i. e., Cohen's kappa. In cases of disagreement, a questionnaire has been sent to QuaMaDi patients' gynaecologists to validate the final diagnosis. Synchronisation of both cohorts resulted in 18 689 one to one matches with any kind of malignant tumour, therein 8 449 breast cancers (ICD-10 C50, D05). Absolute agreement between files according to diagnosed or suspected breast cancer was 97.6% with a kappa value of 0.79. When suspicious BIRADS 4 cases from QuaMaDi were excluded, agreement and kappa rose to 99.5% and 0.948, respectively. After correction of the final diagnosis according to the physician's responses, agreement measures slightly improved in both groups of ascertained diagnosis including and excluding the suspected cases. Within QuaMaDi the diagnosed breast cancer cases were predominantly

Fatigue and health-related quality of life in inflammatory bowel disease: results from a population-based study in the Netherlands: the IBD-South Limburg cohort.

PubMed

Romberg-Camps, M J L; Bol, Y; Dagnelie, P C; Hesselink-van de Kruijs, M A M; Kester, A D M; Engels, L G J B; van Deursen, C; Hameeteman, W H A; Pierik, M; Wolters, F; Russel, M G V M; Stockbrügger, R W

2010-12-01

The importance of fatigue in chronic disease has been increasingly recognized; however, little is known about fatigue in inflammatory bowel disease (IBD). The aim of the present study was to investigate the prevalence and severity of fatigue and the impact on health-related quality of life (HRQoL) in patients included in a population-based IBD cohort in the Netherlands. IBD patients, diagnosed between January 1st, 1991, and January 1st, 2003, were followed up for a median of 7.1 years. They completed a questionnaire, which included a disease activity score, the Multidimensional Fatigue Inventory (MFI-20), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the Short Form health survey (SF-36). Hemoglobin levels were recorded. Data were available in 304 Crohn's disease (CD), 368 ulcerative colitis (UC), and 35 indeterminate colitis (IC) patients. During quiescent disease, the prevalence of fatigue was nearly 40%. MFI-20 and HRQoL scores were significantly worse in IBD patients having active disease. In a multivariate analysis, disease activity was positively related with the level of fatigue in both CD and UC. In UC, anemia influenced the general fatigue score independently of disease activity. Disease activity as well as fatigue were independently associated with an impaired IBDQ. In IBD, even in remission, fatigue is an important feature. Both in CD and in UC, fatigue determined HRQoL independently of disease activity or anemia. This implies that in IBD patients physicians need to be aware of fatigue in order to better understand its impact and to improve the HRQoL. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease.

PubMed

Spekhorst, Lieke M; Imhann, Floris; Festen, Eleonora A M; van Bodegraven, Ad A; de Boer, Nanne K H; Bouma, Gerd; Fidder, Herma H; d'Haens, Geert; Hoentjen, Frank; Hommes, Daan W; de Jong, Dirk J; Löwenberg, Mark; Maljaars, P W Jeroen; van der Meulen-de Jong, Andrea E; Oldenburg, Bas; Pierik, Marieke J; Ponsioen, Cyriel Y; Stokkers, Pieter C; Verspaget, Hein W; Visschedijk, Marijn C; van der Woude, C Janneke; Dijkstra, Gerard; Weersma, Rinse K

2017-11-08

The Dutch IBD Biobank aims to facilitate the discovery of predictors for individual disease course and treatment response in patients with inflammatory bowel disease (IBD). In this paper, we aim to describe the establishment of the Dutch IBD Biobank, including the facilitators and barriers to establishment. Moreover, we aim to provide a complete overview of the content of the Dutch IBD Biobank. Since 2007, every patient with IBD treated in one of the eight Dutch university medical centres is asked to participate in the Dutch IBD Biobank in which 225 standardised IBD-related data items and biomaterials, such as serum, DNA, biopsies and a stool sample, are collected. As of June 2014, the Dutch IBD Biobank had enrolled 3388 patients with IBD: 2118 Crohn's disease (62.5%), 1190 ulcerative colitis (35.1%), 74 IBD-unclassified (2.2%) and 6 IBD-indeterminate (0.2%). The inclusion of patients with IBD is ongoing. The quality of the biomaterials is good and serum, DNA and biopsies have been used in newly published studies. The genotyping (750 000 genetic variants) of all participants of the Dutch IBD Biobank is currently ongoing, enabling more genetic research. In addition, all participants will start reporting disease activity and outcome measures using an online platform and mobile app . © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Does conurbation affect the risk of poor mental health? A population based record linkage study.

PubMed

Maguire, A; O'Reilly, D

2015-07-01

To determine if urban residence is associated with an increased risk of anxiety/depression independent of psychosocial stressors, concentrated disadvantage or selective migration between urban and rural areas, this population wide record-linkage study utilised data on receipt of prescription medication linked to area level indicators of conurbation and disadvantage. An urban/rural gradient in anxiolytic and antidepressant use was evident that was independent of variation in population composition. This gradient was most pronounced amongst disadvantaged areas. Migration into increasingly urban areas increased the likelihood of medication. These results suggest increasing conurbation is deleterious to mental health, especially amongst residents of deprived areas. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distribution and phylogenetic analysis of Blastocystis sp. subtypes isolated from IBD patients and healthy individuals in Iran.

PubMed

Mirjalali, H; Abbasi, M R; Naderi, N; Hasani, Z; Mirsamadi, E S; Stensvold, C R; Balaii, H; Asadzadeh Aghdaei, H; Zali, M R

2017-12-01

Blastocystis is a single-celled intestinal parasite commonly found in humans and a broad range of animals all over the world. In humans, its role in health and disease remains unsettled. The aim of our study was to investigate the distribution of Blastocystis and Blastocystis subtypes (ST) in patients with inflammatory bowel disease (IBD) and control subjects. A total of 71 stool samples were collected from IBD patients, 69 and 2 of whom had ulcerative colitis (UC) and Crohn's Disease (CD), respectively. Moreover, 166 stool samples from healthy subjects were included as control samples. All stool samples were cultivated, and 550-bp fragments of the small subunit ribosomal RNA gene was amplified from Blastocystis-positive cultures. All PCR-positive samples were sequenced. Blastocystis was observed in 9 (12.67%) and 35 (21.1%) IBD patients and healthy controls, respectively. There was no statistically significant correlation between IBD and presence of Blastocystis (P = 0.147). There was a statistically significant correlation between age and Blastocystis colonization in the IBD group (P < 0.05), but not among healthy controls. No significant correlation between gender and colonization was observed. ST1 and ST3 were obtained from 1 (12.5%) and 7 (87.5%) IBD patients, respectively, while in the healthy control group, subtypes 1, 2, and 3 were found in 14 (40%), 12 (34.28%), and 9 (25.72%), respectively. Phylogenetic analysis showed no variation in the distribution of subtypes nor intra-subtype genetic diversity between samples acquired from IBD patients and healthy controls. This study showed a trend towards a lower prevalence of Blastocystis in IBD patients than in control subjects. ST3 sequences isolated from IBD patients and control individuals did not appear to differ genetically.

Phenotypic & Genotypic Characteristics of Inflammatory Bowel Disease (IBD) in French-Canadians: comparison with a large North American repository

PubMed Central

Bhat, Mamatha; Nguyen, Geoffrey C.; Pare, Pierre; Lahaie, Raymond; Deslandres, Colette; Bernard, Edmond-Jean; Aumais, Guy; Jobin, Gilles; Wild, Gary; Cohen, Albert; Langelier, Diane; Brant, Steven; Dassopoulos, Themistocles; McGovern, Dermot; Torres, Esther; Duerr, Richard; Regueiro, Miguel; Silverberg, Mark S; Steinhart, Hillary; Griffiths, Anne M.; Elkadri, Abdul; Cho, Judy; Proctor, Deborah; Goyette, Philippe; Rioux, John; Bitton, Alain

2009-01-01

BACKGROUND Phenotype characteristics of inflammatory bowel disease (IBD) may differ significantly among ethnic subpopulations. The aim of this study was to characterize the IBD phenotype in French-Canadians, the most prominent founder population in North America. METHODS Using well-characterized phenotype data in the NIDDK-IBD Genetics Consortium repository on IBD patients, we compared phenotypic characteristics of 202 French-Canadians to those of 1287 other Caucasian patients. These included: diagnosis, anatomical location, disease behaviour, extraintestinal manifestations, surgical history, and family history of IBD. RESULTS French-Canadian CD patients were less likely to have stricturing disease (11 vs 21%, P=0.005; OR 0.45, 95% CI: 0.24– 0.85). Using a stringent definition of ethnicity (3 out of 4 grandparents being French-Canadian, as opposed to self-report, n= 148), French-Canadians had a tendency towards developing fistulizing CD (37% vs 28%, p= 0.07), and there was an increased prevalence of sacroiliitis among French-Canadians with IBD (4% vs 2%, p=0.045). Among French-Canadians, the numbers of current smokers in CD (40 vs 25%, p=0.006) and former smokers in UC (35% vs 20%, p=0.03) were significantly higher. The prevalence of one of the three main variant NOD2 SNPs among French-Canadian CD patients was 43.2%. The 3020insC SNP correlated with small bowel disease in French-Canadians (75% versus 0%, P=0.006). CONCLUSION French-Canadians exhibit an IBD phenotype profile distinct from other Caucasian IBD populations, with an accentuated association between smoking status and IBD. This unique profile may have implications regarding the need for a different approach to management of IBD in this population. PMID:19513023

World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010.

PubMed

Bernstein, Charles N; Fried, Michael; Krabshuis, J H; Cohen, Henry; Eliakim, R; Fedail, Suleiman; Gearry, Richard; Goh, K L; Hamid, Saheed; Khan, Aamir Ghafor; LeMair, A W; Malfertheiner; Ouyang, Qin; Rey, J F; Sood, Ajit; Steinwurz, Flavio; Thomsen, Ole O; Thomson, Alan; Watermeyer, Gillian

2010-01-01

Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohn's disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades. This poses unique issues in diagnosis and management which have been scarcely addressed in the literature or in extant guidelines. Depending on the nature of the complaints, investigations to diagnose either form of IBD or to assess disease activity will vary and will also be influenced by geographic variations in other conditions that might mimic IBD. Similarly, therapy varies depending on the phenotype of the disease being treated and available resources. The World Gastroenterology Organization has, accordingly, developed guidelines for diagnosing and treating IBD using a cascade approach to account for variability in resources in countries around the world.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

PubMed

de Ridder, Lissy; Turner, Dan; Wilson, David C; Koletzko, Sibylle; Martin-de-Carpi, Javier; Fagerberg, Ulrika L; Spray, Christine; Sladek, Malgorzata; Shaoul, Ron; Roma-Giannikou, Eleftheria; Bronsky, Jiri; Serban, Daniela E; Cucchiara, Salvatore; Veres, Gabor; Ruemmele, Frank M; Hojsak, Iva; Kolho, Kaija L; Davies, Ieuan H; Aloi, Marina; Lionetti, Paolo; Veereman-Wauters, Gigi; Braegger, Christian P; Trindade, Eunice; Wewer, Anne V; Hauer, Almuthe; Levine, Arie

2014-02-01

The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

The Scottish school leavers cohort: linkage of education data to routinely collected records for mortality, hospital discharge and offspring birth characteristics

PubMed Central

Stewart, Catherine H; Dundas, Ruth; Leyland, Alastair H

2017-01-01

Purpose The Scottish school leavers cohort provides population-wide prospective follow-up of local authority secondary school leavers in Scotland through linkage of comprehensive education data with hospital and mortality records. It considers educational attainment as a proxy for socioeconomic position in young adulthood and enables the study of associations and causal relationships between educational attainment and health outcomes in young adulthood. Participants Education data for 284 621 individuals who left a local authority secondary school during 2006/2007–2010/2011 were linked with birth, death and hospital records, including general/acute and mental health inpatient and day case records. Individuals were followed up from date of school leaving until September 2012. Age range during follow-up was 15 years to 24 years. Findings to date Education data included all formal school qualifications attained by date of school leaving; sociodemographic information; indicators of student needs, educational or non-educational support received and special school unit attendance; attendance, absence and exclusions over time and school leaver destination. Area-based measures of school and home deprivation were provided. Health data included dates of admission/discharge from hospital; principal/secondary diagnoses; maternal-related, birth-related and baby-related variables and, where relevant, date and cause of death. This paper presents crude rates for all-cause and cause-specific deaths and general/acute and psychiatric hospital admissions as well as birth outcomes for children of female cohort members. Future plans This study is the first in Scotland to link education and health data for the population of local authority secondary school leavers and provides access to a large, representative cohort with the ability to study rare health outcomes. There is the potential to study health outcomes over the life course through linkage with future hospital and death

Strategies that Target Leukocyte Traffic in IBD: Recent Developments

PubMed Central

Rivera-Nieves, Jesús

2015-01-01

Purpose of review We review the most recent developments regarding the targeting of molecules involved in the traffic of leukocytes for the treatment of IBD. Recent Findings We discuss the most important findings of one published phase II trial that targeted the β7 integrin (Etrolizumab), two phase II trials that targeted the α4β7 integrin ligand: Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1, PF-00547659), a phase II targeting the chemokine IP-10 (CXCL10) in Crohn’s and a phase II trial that targeted the sphingosine-1-phosphate receptor-1 (S1P1): ozanimod in patients with ulcerative colitis (UC). Summary Targeting molecules involved in leukocyte traffic has recently become an effective and safe strategy for the treatment of IBD. Novel approaches now not only target the integrins on the lymphocyte surface, but also its endothelial ligand: MAdCAM-1. As with vedolizumab, antibodies against MAdCAM-1 appear most effective in ulcerative colitis rather than in Crohn’s. Targeting chemokines or their receptors does not appear to have the same efficacy as those that target the most stable integrin:immunoglobulin superfamily interactions between the lymphocyte and endothelium. Preliminary results also suggest that the sphingosine-1-phosphate pathway might also be targeted therapeutically in IBD, no longer with parenterally administered antibodies but with orally administered small molecules. PMID:26398681

Perspectives of IBD China: Is Crohn's and Colitis Foundation Model a Solution to Health Care Issues for the Country?

PubMed

Chen, Yan

2018-04-21

The success of the Crohn's and Colitis Foundation of America (CCFA), now Crohn's and Colitis Foundation (CCF) has established a role model for developing countries with an increasing incidence of inflammatory bowel disease (IBD), including China. While there are shared etiopathogenetic pathways and clinical features in IBD between Eastern and Western countries, patients with IBD as well as health care professionals in China are facing distinctive challenges, including the fragmented and inconsistent health insurance, social support system, and three-tiered health care service. Financial burden remains to be a tremendous obstacle to the management of IBD. In addition, poor rapport between patients and clinicians, and the lack of properly trained IBD specialists makes a noticeable gap in the management of IBD between China and Western countries. The China Crohn's &Colitis Foundation (CCCF), closely following the successful model of CCF, was established under the same doctrine, and served as a non-profit, volunteer-driven organization dedicated to improving quality of life of patients in by IBD through education and training.

High Altitude Journeys, Flights and Hypoxia: Any Role for Disease Flares in IBD Patients?

PubMed

Vavricka, Stephan R; Rogler, Gerhard; Biedermann, Luc

2016-01-01

The importance of environmental factors in the pathogenesis including their disease-modifying potential are increasingly recognized in inflammatory bowel disease (IBD) patients, largely driven by the perception that the prevalence and incidence of IBD are on the rise within the last few years, especially in non-western countries. One of those factors is believed to be hypoxia. The role of hypoxia as a modifying or even causative factor in the genesis and maintenance of inflammation has been increasingly elucidated in recent years. Hypoxia is believed to be a main inducing factor of inflammation. This has been studied in different animal experiments as well as in humans exposed to hypoxia. In several studies - mainly in mice - animals exposed to short-term hypoxia accumulated inflammatory cells in multiple organs and showed elevated cytokines in the blood. Comparable studies were performed in humans, mainly in healthy mountaineers. Recently, we reported on the association between IBD flare-up episodes and antecedent journeys to high-altitude region and aircraft travels. According to these findings, we concluded that flights and stays at high altitudes of >2,000 mg are a risk factor for increased disease activity in IBD. To evaluate the potential influence of hypoxia on the course of IBD on a biomolecular level and to test the effects of hypoxia under standardized conditions, we initiated a prospective and controlled investigation in both healthy controls and IBD patients in stable remission. The study participants underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 m above sea level in a hyperbaric pressure chamber and clinical parameters as well as blood and stool samples were collected at several time points. The first results of this study are expected in the near future. © 2016 S. Karger AG, Basel.

Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin.

PubMed

Welch, Martha G; Welch-Horan, Thomas B; Anwar, Muhammad; Anwar, Nargis; Ludwig, Robert J; Ruggiero, David A

2005-01-01

Recent research points to the connection between behavioral and gut disorders. Early adverse events are associated with inflammatory bowel disease (IBD). In animal models, maternal deprivation and social isolation predispose to gastric erosion and brain pathology. This study examined (1) brain effects of chronic gastrointestinal inflammation in a rat model of acquired IBD and (2) whether such changes are resolved by individual secretin (S) or oxytocin (OT) peptide treatment. Neurological manifestations of IBD were mapped by c-fos gene expression in male Sprague-Dawley rats (n = 10) with trinitrobenzene sulfonic acid (TNBS)-induced IBD vs controls (n = 11). IBD was characterized by moderate/severe infiltration of inflammatory cells 10 d after TNBS infusion. Age-matched pairs were processed for immunocytochemical detection of Fos, expressed when neurons are stimulated. S or OT (100 mg/250 mL saline) or equivolume saline was administered iv by Alzet pump for 20 d after disease onset. Degree of resolution of colitis-induced brain activation was assessed by c-fos expression, and mean numbers of Fos-immunoreactive nuclei for each group were compared using Independent Samples T-test. Chronic IBD activated periventricular gray, hypothalamic/visceral thalamic stress axes and cortical domains, and septal/preoptic/amygdala, brain areas abnormal in autism. Single peptide treatment with S or OT did not alter the effects of inflammation on the brain. Brain areas concomitantly activated by visceral inflammation are those often abnormal in autism, suggesting that IBD could be a model for testing treatments of autism. Other single and combined peptide treatments of IBD should be tested. The clinical implications for treating autism, IBD, and concomitant sickness behaviors with peptide therapy, with or without maternal nurturing as a natural equivalent, are presented.

Data pre-processing in record linkage to find the same companies from different databases

NASA Astrophysics Data System (ADS)

Gunawan, D.; Lubis, M. S.; Arisandi, D.; Azzahry, B.

2018-03-01

As public agencies, the Badan Pelayanan Perizinan Terpadu (BPPT) and the Badan Lingkungan Hidup (BLH) of Medan city manage process to obtain a business license from the public. However, each agency might have a different corporate data because of a separate data input process, even though the data may refer to the same company’s data. Therefore, it is required to identify and correlate data that refer to the same company which lie in different data sources. This research focuses on data pre-processing such as data cleaning, text pre-processing, indexing and record comparison. In addition, this research implements data matching using support vector machine algorithm. The result of this algorithm will be used to record linkage of data that can be used to identify and connect the company’s data based on the degree of similarity of each data. Previous data will be standardized in accordance with the format and structure appropriate to the stage of preprocessing data. After analyzing data pre-processing, we found that both database structures are not designed to support data integration. We decide that the data matching can be done with blocking criteria such as company name and the name of the owner (or applicant). In addition to data pre-processing, the result of data classification with a high level of similarity as many as 90 pairs of records.

Disease severity does not affect the interval between IBD diagnosis and the development of CRC: results from two large, Dutch case series.

PubMed

Mooiweer, Erik; Baars, Judith E; Lutgens, Maurice W M D; Vleggaar, Frank; van Oijen, Martijn; Siersema, Peter D; Kuipers, Ernst J; van der Woude, C Janneke; Oldenburg, Bas

2012-05-01

The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (p<0.01)). In patients from referral hospitals, CRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Age Validation in the Long Life Family Study Through a Linkage to Early-Life Census Records

PubMed Central

2013-01-01

Objectives. Studies of health and longevity require accurate age reporting. Age misreporting among older adults in the United States is common. Methods. Participants in the Long Life Family Study (LLFS) were matched to early-life census records. Age recorded in the census was used to evaluate age reporting in the LLFS. The study population was 99% non-Hispanic white. Results. About 88% of the participants were matched to 1910, 1920, or 1930 U.S. censuses. Match success depended on the participant’s education, place of birth, and the number of censuses available to be searched. Age at the time of the interview based on the reported date of birth and early-life census age were consistent for about 89% of the participants, and age consistency within 1 year was found for about 99% of the participants. Discussion. It is possible to match a high fraction of older study participants to their early-life census records when detailed information is available on participants’ family of origin. Such record linkage can provide an important source of information for evaluating age reporting among the oldest old participants. Our results are consistent with recent studies suggesting that age reporting among older whites in the United States appears to be quite good. PMID:23704206

Implementing a self-management strategy in inflammatory bowel disease (IBD): patient perceptions, clinical outcomes and the impact on service.

PubMed

Squires, Seth Ian; Boal, Allan John; Lamont, Selina; Naismith, Graham D

2017-10-01

Patient self-management and its service integration is not a new concept but it may be a key component in the long-term sustainability of inflammatory bowel disease (IBD) service provision, when considering growing disease prevalence and limited resources. The IBD team at the Royal Alexandra and Vale of Leven Hospitals in the Clyde Valley region developed a self-management tool, called the 'flare card'. Patients were asked to complete a questionnaire which reflected their opinion on its viability as a self-management intervention. In addition, its utility in terms of service use over a 10-month period in 2016 was compared with a similar cohort of patients over 10 months in 2015. Patients overall felt that the 'flare card' was a viable self-management tool. Positive feedback identified that the intervention could help them aid control over their IBD, improve medication adherence, reduce symptoms and reflected a feeling of patient-centred IBD care. The comparison between 2015 and 2016 service use revealed a significant reduction in IBD and non-IBD service usage, Steroid prescribing and unscheduled IBD care in the flare card supported cohort. IBD services must continue to adapt to changes within the National Health Service bearing in mind long-term sustainability and continued care provision. The 'flare card' goes further in an attempt to optimise Crohn's disease and ulcerative colitis management by harmonising clinician evaluation and patient's self-initiation of therapy and investigation.

Generational differences in the age at diagnosis with Ibd: genetic anticipation, bias, or temporal effects.

PubMed

Faybush, E M; Blanchard, J F; Rawsthorne, P; Bernstein, C N

2002-03-01

Previous cross-sectional research has demonstrated generational differences in age at diagnosis (AAD) in inflammatory bowel disease (IBD). This observation has at times been ascribed to genetic anticipation, but could also be due to biases related to case ascertainment or follow-up or to temporal changes in IBD epidemiology. We aimed to explore this issue using a population-based database. In 1995 we used the comprehensive administrative databases in the province of Manitoba, Canada to establish a population-based IBD Research Registry that includes clinical and demographic information for persons. We contacted those subjects within our Research Registry who reported having any family members with IBD and their family members for verification of diagnosis and AAD. Differences in AAD between familial pairs were calculated. In addition, to assess whether duration of follow-up accounted for generational differences in AAD, we computed the mean AAD for subjects with and without family histories of IBD based on age at the time of interview (i.e., < 45 and > or = 45 yr of age). Of the 2445 persons with IBD in the Research Registry, 548 reported positive family histories, and 315 of these (58%) were reached by telephone. There were 169 Crohn's disease and 146 ulcerative colitis subjects with positive family histories. The mean AADs for the parents, aunts/uncles, and grandparents were significantly greater than the mean AADs for the children, nieces/nephews, and grandchildren, respectively. There was a doubling of the mean AAD when comparing the grandparent/grandchild cases with the parent/child or aunt/uncle-niece/nephew cases. No statistically significant difference in anticipation was observed, whether or not the older generation was male or female or had Crohn's disease or ulcerative colitis. The AAD was substantially greater for those interviewed at > or = 45 yr of age for subjects with and without family histories. However, there was no substantial difference in mean

The Scottish school leavers cohort: linkage of education data to routinely collected records for mortality, hospital discharge and offspring birth characteristics.

PubMed

Stewart, Catherine H; Dundas, Ruth; Leyland, Alastair H

2017-07-10

The Scottish school leavers cohort provides population-wide prospective follow-up of local authority secondary school leavers in Scotland through linkage of comprehensive education data with hospital and mortality records. It considers educational attainment as a proxy for socioeconomic position in young adulthood and enables the study of associations and causal relationships between educational attainment and health outcomes in young adulthood. Education data for 284 621 individuals who left a local authority secondary school during 2006/2007-2010/2011 were linked with birth, death and hospital records, including general/acute and mental health inpatient and day case records. Individuals were followed up from date of school leaving until September 2012. Age range during follow-up was 15 years to 24 years. Education data included all formal school qualifications attained by date of school leaving; sociodemographic information; indicators of student needs, educational or non-educational support received and special school unit attendance; attendance, absence and exclusions over time and school leaver destination. Area-based measures of school and home deprivation were provided. Health data included dates of admission/discharge from hospital; principal/secondary diagnoses; maternal-related, birth-related and baby-related variables and, where relevant, date and cause of death. This paper presents crude rates for all-cause and cause-specific deaths and general/acute and psychiatric hospital admissions as well as birth outcomes for children of female cohort members. This study is the first in Scotland to link education and health data for the population of local authority secondary school leavers and provides access to a large, representative cohort with the ability to study rare health outcomes. There is the potential to study health outcomes over the life course through linkage with future hospital and death records for cohort members. The cohort may also be

Rifaximin - Chitosan Nanoparticles for Inflammatory Bowel Disease (IBD).

PubMed

Kumar, Jatinder; Newton, Amaldoss M J

2017-01-01

Inflammatory Bowel Disease (IBD) cannot be controlled easily and the recurrence is the most challenging issue for the physicians. There are various controlled and colon targeted drug delivery systems available for the treatment with limited success rate. Nanoparticles prepared by using the colon targeted polymers such as chitosan may improve the IBD due to their smaller size, unique physico chemical properties and targeting potential. The aim of this investigation was designed to formulate and develop a colon targeted polysaccharide nanoparticles of rifaximin (RFX) by using linear polysaccharide chitosan, for the improvement of rifaximin solubility, overall therapeutic efficacy and colon targeting. The research was focused on developing RFX nanoparticles for the treatment of Inflammatory Bowel Disease (IBD) by ionic gelation method. Nanoparticles were subjected to various characterization techniques such as XRD, FTIR and mean particle size (MPS) by Master Sizer and Zeta Sizer. Transmission Electron Microscopy (TEM), drug entrapment efficiency and zeta potential are also determined for the developed formulations. The efficiency of drug release from prepared formulation was studied in vitro by using a dialysis bag diffusion technique in the buffer condition mimicking stomach, intestine and colonic pH conditions. The prepared nanoparticles demonstrated the size in the nano range. The drug release profile was controlled in the upper GI tract and the maximum amount of drug was released in the colonic conditions. The prepared nanoparticles significantly improved the solubility of rifaximin. The zeta potential of the best chitosan preparation was found to be 37.79, which confirms the stability of prepared nanosuspension. Nanoparticles with small particle size found to have high encapsulation efficiency and relatively high loading capacity and predetermined in vitro release profile. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Maternal and perinatal factors associated with hospitalised infectious mononucleosis in children, adolescents and young adults: record linkage study.

PubMed

Mahmud, Imran; Abdel-Mannan, Omar A; Wotton, Clare J; Goldacre, Michael J

2011-02-28

There is current interest in the role of perinatal factors in the aetiology of diseases that occur later in life. Infectious mononucleosis (IM) can follow late primary infection with Epstein-Barr virus (EBV), and has been shown to increase the risk of multiple sclerosis and Hodgkin's disease. Little is known about maternal or perinatal factors associated with IM or its sequelae. We investigated perinatal risk factors for hospitalised IM using a prospective record-linkage study in a population in the south of England. The dataset used, the Oxford record linkage study (ORLS), includes abstracts of birth registrations, maternities and in-patient hospital records, including day case care, for all subjects in a defined geographical area. From these sources, we identified cases of hospitalised IM up to the age of 30 years in people for whom the ORLS had a maternity record; and we compared perinatal factors in their pregnancy with those in the pregnancy of children who had no hospital record of IM. Our data showed a significant association between hospitalised IM and lower social class (p = 0.02), a higher risk of hospitalised IM in children of married rather than single mothers (p < 0.001), and, of marginal statistical significance, an association with singleton birth (p = 0.06). The ratio of observed to expected cases of hospitalised IM in each season was 0.95 in winter, 1.02 in spring, 1.02 in summer and 1.00 in autumn. The chi-square test for seasonality, with a value of 0.8, was not significant.Other factors studied, including low birth weight, short gestational age, maternal smoking, late age at motherhood, did not increase the risk of subsequent hospitalised IM. Because of the increasing tendency of women to postpone childbearing, it is useful to know that older age at motherhood is not associated with an increased risk of hospitalised IM in their children. We have no explanation for the finding that children of married women had a higher risk of IM than those of

Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation.

PubMed

Pedersen, Jannie; LaCasse, Eric C; Seidelin, Jakob B; Coskun, Mehmet; Nielsen, Ole H

2014-11-01

The inhibitor of apoptosis (IAP) family members, notably cIAP1, cIAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

Workplace Accommodation for Persons With IBD: What Is Needed and What Is Accessed.

PubMed

Chhibba, Tarun; Walker, John R; Sexton, Kathryn; Restall, Gayle; Ivekovic, Melony; Shafer, Leigh Ann; Singh, Harminder; Targownik, Laura E; Bernstein, Charles N

2017-10-01

People with inflammatory bowel disease (IBD) often experience periods of illness that interfere with their ability to work. We aimed to understand the need for workplace accommodation during periods of acute illness among persons IBD. Participants were recruited from the population-based University of Manitoba Research Registry and received a survey including questions assessing experiences with workplace accommodations. Data were analyzed using descriptive statistics and multivariate logistic regression modelling. A total of 1143 individuals responded to the survey (46% response rate), of whom 881 had experienced IBD symptoms in the workplace and were included in the analysis. The mean age was 48.3 years (standard deviation, 10.9); 61% were female. Mean IBD duration was 20.6 years (standard deviation, 10.5). Most respondents (73%) described IBD symptoms experienced in the workplace as severe to very severe. The most commonly required accommodations were time to go to medical appointments during working hours (81%), easy access to a toilet (71%), and a chance to take a break when not feeling well (54%). Most accommodations were arranged informally or through a supervisor. The accommodations required were very or somewhat easy to arrange about half the time. Being female, having high symptom severity, and high level of current distress were associated with a need for more accommodations, difficulty implementing accommodations, and not asking for needed accommodations. This study provides important information as to the types of accommodations that are necessary, common practices arranging for these, and level of difficulty arranging accommodations. Furthermore, characteristics associated with greater need for accommodation, reluctance to ask for them, and difficulty in arranging them were identified. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Gut Microbial Flora, Prebiotics, and Probiotics in IBD: Their Current Usage and Utility

PubMed Central

Scaldaferri, Franco; Gerardi, Viviana; Boškoski, Ivo; Bruno, Giovanni; Petito, Valentina; Laterza, Lucrezia; Cammarota, Giovanni; Gaetani, Eleonora; Sgambato, Alessandro; Gasbarrini, Antonio

2013-01-01

Inflammatory bowel diseases are chronic diseases affecting the gastrointestinal tract, whose major forms are represented by Crohn's disease (CD) and ulcerative colitis (UC). Their etiology is still unclear, although several factors have been identified as major determinants for induction or relapses. Among these, the role of the “forgotten organ”, gut microbiota, has become more appreciated in recent years. The delicate symbiotic relationship between the gut microbiota and the host appears to be lost in IBD. In this perspective, several studies have been conducted to assess the role of prebiotics and probiotics in gut microbiota modulation. This is a minireview aimed to address in an easy format (simple questions-simple answers) some common issues about the theme. An update on the role of selected constituents of gut microbiota in the pathogenesis of IBD is presented together with the analysis of the efficacy of gut microbiota modulation by prebiotics and probiotics administration in the management of IBD. PMID:23991417

The effects of body image impairment on the quality of life of non-operated Portuguese female IBD patients.

PubMed

Trindade, Inês A; Ferreira, Cláudia; Pinto-Gouveia, José

2017-02-01

Inflammatory bowel diseases (IBD) and their treatment are known to negatively impact on patients' body image, especially female patients. However, although there are broad evidences of body image impairment in female IBD patients, its negative impact on the quality of life (QoL) of non-operated women is not clearly and specifically studied. The aim of the current study was therefore to analyse, in a sample of non-operated female IBD patients, the factors that contribute to body image impairment and its impact on QoL. Ninety-six non-operated women (39.7 % with CD and 60.3 % with UC), aged between 18 and 40 years old, completed an online survey with validated self-report measures, which included the Body Image Scale and the WHO Brief Quality of Life Assessment Scale. Negative body image was correlated with lower psychological and physical QoL and increased corticosteroids use, associated medical complications, body mass index (BMI), and IBD symptomatology. Regression analyses revealed that BMI and IBD symptomatology significantly predicted body image impairment. Furthermore, results from path analyses indicated that BMI and IBD symptomatology's effect on psychological and physical QoL was mediated through the negative effects of body image impairment. This model explained 31 % of psychological QoL and 41 % of physical QoL. These findings suggest that non-operated female patients are subject to pervasive and harmful effects of body image impairment on psychological and physical functioning. Therefore, psychological interventions aiming to target body dissatisfaction should be implemented in the health care of IBD, independently of patients' operative status.

Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia.

PubMed

Lim, Joon Seo; Lim, Mi Young; Choi, Yongbin; Ko, GwangPyo

2017-04-20

Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD. Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced mouse models of ASD, we found a distinct pattern of microbial dysbiosis that highly recapitulated those reported in clinical cases of ASD and IBD. Moreover, we report that such microbial dysbiosis led to notable perturbations in microbial metabolic pathways that are known to negatively affect the host, especially with regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of serotonin is significantly increased in both poly I:C and VPA mice, and that it correlates with increases of a bacterial genus and a metabolic pathway that are implicated in stimulation of host serotonin production. Our results using animal model identify prenatal environmental risk factors of autism as possible causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a multifaceted role of gut microbiota in the systemic pathogenesis of ASD and hyperserotonemia.

Evaluation of identifier field agreement in linked neonatal records.

PubMed

Hall, E S; Marsolo, K; Greenberg, J M

2017-08-01

To better address barriers arising from missing and unreliable identifiers in neonatal medical records, we evaluated agreement and discordance among traditional and non-traditional linkage fields within a linked neonatal data set. The retrospective, descriptive analysis represents infants born from 2013 to 2015. We linked children's hospital neonatal physician billing records to newborn medical records originating from an academic delivery hospital and evaluated rates of agreement, discordance and missingness for a set of 12 identifier field pairs used in the linkage algorithm. We linked 7293 of 7404 physician billing records (98.5%), all of which were deemed valid upon manual review. Linked records contained a mean of 9.1 matching and 1.6 non-matching identifier pairs. Only 4.8% had complete agreement among all 12 identifier pairs. Our approach to selection of linkage variables and data formatting preparatory to linkage have generalizability, which may inform future neonatal and perinatal record linkage efforts.

Insulin treated diabetes mellitus: causes of death determined from record linkage of population based registers in Leicestershire, UK.

PubMed Central

Raymond, N T; Langley, J D; Goyder, E; Botha, J L; Burden, A C; Hearnshaw, J R

1995-01-01

STUDY OBJECTIVE--Analyses of causes of mortality in people with diabetes using data form death certificates mentioning diabetes provide unreliable estimates of mortality. Under-recording of diabetes as a cause on death certificates has been widely reported, ranging from 15-60%. Using a population based register on people with diabetes and linking data from another source is a viable alternative. Data from the Office of Population Censuses and Surveys (OPCS) are the most acceptable mortality data available for such an exercise, as direct comparison with other published mortality rates is then possible. DESIGN--A locally maintained population-based mortality register and all insulin-treated diabetes mellitus cases notified to the Leicestershire diabetes register (n = 4680) were linked using record linkage software developed in-house (Lynx). This software has been extensively used in a maintenance and update cycle designed to maximise accuracy and minimise duplication and false registration on the diabetes register. Deaths identified were initially coded locally to the International Classification of Diseases, 9th revision (ICD9), and later a linkage was performed to use official OPCS coding. Mortality data identified by the linkage was indirectly standardised using population data for Leicestershire for 1991. Standardised mortality ratios (SMR) were estimated, with 95% confidence intervals. Insulin dependent diabetes (IDDM) was defined as diabetes diagnosed before age 30 years with insulin therapy begun within one year of diagnosis. All other types were considered non-insulin dependent diabetes (NIDDM). Analyses were performed for the whole sample and then for the NIDDM subgroup. Results from these analyses were similar and therefore only whole group analyses are presented. MAIN RESULTS--A total of 370 deaths were identified for the period of 1990-92 inclusive - 56% were in men and 44% in women, median age (range) 71 years (12-94). Approximately 90% of deaths were

Sampling Strategies for Three-Dimensional Spatial Community Structures in IBD Microbiota Research

PubMed Central

Zhang, Shaocun; Cao, Xiaocang; Huang, He

2017-01-01

Identifying intestinal microbiota is arguably an important task that is performed to determine the pathogenesis of inflammatory bowel diseases (IBD); thus, it is crucial to collect and analyze intestinally-associated microbiota. Analyzing a single niche to categorize individuals does not enable researchers to comprehensively study the spatial variations of the microbiota. Therefore, characterizing the spatial community structures of the inflammatory bowel disease microbiome is critical for advancing our understanding of the inflammatory landscape of IBD. However, at present there is no universally accepted consensus regarding the use of specific sampling strategies in different biogeographic locations. In this review, we discuss the spatial distribution when screening sample collections in IBD microbiota research. Here, we propose a novel model, a three-dimensional spatial community structure, which encompasses the x-, y-, and z-axis distributions; it can be used in some sampling sites, such as feces, colonoscopic biopsy, the mucus gel layer, and oral cavity. On the basis of this spatial model, this article also summarizes various sampling and processing strategies prior to and after DNA extraction and recommends guidelines for practical application in future research. PMID:28286741

Practical Considerations and the Intestinal Microbiome in Disease: Antibiotics for IBD Therapy.

PubMed

Fedorak, Richard N; Ismond, Kathleen P

2016-01-01

The inflammatory bowel diseases, Crohn's and ulcerative colitis, have been treated with a range of antibiotics for inducing and maintaining remission, as well as the prevention of post-operative symptoms. To date, many studies have been performed assessing the efficacy of antibiotics when used alone, in combination with other antibiotics, or as an adjunctive therapy to other pharmaceutical treatments. Literature evidence supporting the use of antibiotics in IBD can be ambiguous, especially when considering the potential role of dysbiosis in the gastrointestinal tract. The review considers the systemic effect of antibiotics and the evidence base for their efficacy in the treatment of IBD. © 2016 S. Karger AG, Basel.

Sudden unexpected death in infants in the Oxford Record Linkage Area: The mother

PubMed Central

Fedrick, Jean

1974-01-01

Of the 206 cases of sudden unexpected death in infancy (SUD) 170 were linked with the maternity information and birth certificates on the Oxford Record Linkage files. Statistically highly significant correlations were demonstrated with low maternal age, high parity, and low social class, the last two associations being more marked among the mothers of infants who died after the 12th week. Each case of SUD was then matched with three control livebirths for maternal age, parity, civil state of mother, social class, year and hospital of delivery, and as closely as possible for area of residence. A comparison of mothers of cases with those of the controls revealed a highly significant preponderance of women who were born outside the area, and no significant effect with maternal religion, previous pregnancy loss, or ABO blood group. Other pregnancies occurring to the case and control mothers between 1965 and 1971 were also traced. It was shown that the infant dying an SUD was more likely to have been conceived within six months of the birth of his preceding sib. PMID:4854522

Maternal and perinatal factors associated with hospitalised infectious mononucleosis in children, adolescents and young adults: record linkage study

PubMed Central

2011-01-01

Background There is current interest in the role of perinatal factors in the aetiology of diseases that occur later in life. Infectious mononucleosis (IM) can follow late primary infection with Epstein-Barr virus (EBV), and has been shown to increase the risk of multiple sclerosis and Hodgkin's disease. Little is known about maternal or perinatal factors associated with IM or its sequelae. Methods We investigated perinatal risk factors for hospitalised IM using a prospective record-linkage study in a population in the south of England. The dataset used, the Oxford record linkage study (ORLS), includes abstracts of birth registrations, maternities and in-patient hospital records, including day case care, for all subjects in a defined geographical area. From these sources, we identified cases of hospitalised IM up to the age of 30 years in people for whom the ORLS had a maternity record; and we compared perinatal factors in their pregnancy with those in the pregnancy of children who had no hospital record of IM. Results Our data showed a significant association between hospitalised IM and lower social class (p = 0.02), a higher risk of hospitalised IM in children of married rather than single mothers (p < 0.001), and, of marginal statistical significance, an association with singleton birth (p = 0.06). The ratio of observed to expected cases of hospitalised IM in each season was 0.95 in winter, 1.02 in spring, 1.02 in summer and 1.00 in autumn. The chi-square test for seasonality, with a value of 0.8, was not significant. Other factors studied, including low birth weight, short gestational age, maternal smoking, late age at motherhood, did not increase the risk of subsequent hospitalised IM. Conclusions Because of the increasing tendency of women to postpone childbearing, it is useful to know that older age at motherhood is not associated with an increased risk of hospitalised IM in their children. We have no explanation for the finding that children of married women

Inaccurate Ascertainment of Morbidity and Mortality due to Influenza in Administrative Databases: A Population-Based Record Linkage Study

PubMed Central

Muscatello, David J.; Amin, Janaki; MacIntyre, C. Raina; Newall, Anthony T.; Rawlinson, William D.; Sintchenko, Vitali; Gilmour, Robin; Thackway, Sarah

2014-01-01

Background Historically, counting influenza recorded in administrative health outcome databases has been considered insufficient to estimate influenza attributable morbidity and mortality in populations. We used database record linkage to evaluate whether modern databases have similar limitations. Methods Person-level records were linked across databases of laboratory notified influenza, emergency department (ED) presentations, hospital admissions and death registrations, from the population (∼6.9 million) of New South Wales (NSW), Australia, 2005 to 2008. Results There were 2568 virologically diagnosed influenza infections notified. Among those, 25% of 40 who died, 49% of 1451 with a hospital admission and 7% of 1742 with an ED presentation had influenza recorded on the respective database record. Compared with persons aged ≥65 years and residents of regional and remote areas, respectively, children and residents of major cities were more likely to have influenza coded on their admission record. Compared with older persons and admitted patients, respectively, working age persons and non-admitted persons were more likely to have influenza coded on their ED record. On both ED and admission records, persons with influenza type A infection were more likely than those with type B infection to have influenza coded. Among death registrations, hospital admissions and ED presentations with influenza recorded as a cause of illness, 15%, 28% and 1.4%, respectively, also had laboratory notified influenza. Time trends in counts of influenza recorded on the ED, admission and death databases reflected the trend in counts of virologically diagnosed influenza. Conclusions A minority of the death, hospital admission and ED records for persons with a virologically diagnosed influenza infection identified influenza as a cause of illness. Few database records with influenza recorded as a cause had laboratory confirmation. The databases have limited value for estimating incidence

Transperineal ultrasonography: First level exam in IBD patients with perianal disease.

PubMed

Terracciano, Fulvia; Scalisi, Giuseppe; Bossa, Fabrizio; Scimeca, Daniela; Biscaglia, Giuseppe; Mangiacotti, Michele; Valvano, Maria Rosa; Perri, Francesco; Simeone, Anna; Andriulli, Angelo

2016-08-01

A pelvic magnetic resonance imaging (MRI) represents the front-line method for evaluating perianal disease in patients with inflammatory bowel disease (IBD). Recently, transperineal ultrasonography (TPUS) has been proposed as a simple, safe, time-sparing and useful diagnostic technique to assess different pathological conditions of the pelvic floor. The aim of this prospective single centre study was to evaluate the accuracy of TPUS versus MRI for the detection and classification of perineal disease in IBD patients. From November 2013 to November 2014, 28 IBD patients underwent either TPUS or MRI. Fistulae and abscesses were classified according to Parks' and AGA's classification methods. A concordance was assessed by k statistics. Overall, 33 fistulae and 8 abscesses were recognized by TPUS (30 and 7 by MRI, respectively). The agreement between TPUS and MRI was 75% according to Parks' classification (k=0.67) and 86% according to AGA classification (k=0.83), while it was 36% (k=0.34) for classifying abscesses. TPUS proved to be as accurate as MRI for detecting superficial and small abscesses and for classifying perianal disease. Both examinations may be performed at the initial presentation of the patient, but TPUS is a cheaper, time-sparing procedure. The optimal use of TPUS might be in follow-up patients. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The role of antidepressants in the management of inflammatory bowel disease (IBD): a short report on a clinical case-note audit.

PubMed

Mikocka-Walus, Antonina A; Gordon, Andrea L; Stewart, Benjamin J; Andrews, Jane M

2012-02-01

This study sought to determine the frequency of use and types of antidepressants used in IBD patients and to collect data with respect to any effect of antidepressants on the course of IBD in a usual care setting. A case-note audit was conducted at an IBD Service in a public tertiary hospital. Included patients were those diagnosed with IBD by a gastroenterologist; and have had contact with the IBD Service in the last 6months. Descriptive statistics were used to summarise the data. Overall, 313 patients were eligible and 287 had complete data. Overall, 51 (17.8%) patients were currently taking antidepressants and 71 (24.7%) previously received antidepressants. Eighty-three (28.9%) patients had used an antidepressant at some time. In terms of disease activity while on antidepressants, the majority of patients had inactive disease but presented with what were thought by their clinicians to be functional symptoms. Antidepressants are commonly prescribed in IBD patients. In our cohort, they appear to be mostly used for functional symptoms. The current data do not allow us to judge whether they improve IBD disease activity. Targeted studies are needed to answer this question and to improve practice and patient outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

The inflammatory bowel disease live interinstitutional and interdisciplinary videoconference education (IBD LIVE) series.

PubMed

Regueiro, Miguel D; Greer, Julia B; Binion, David G; Schraut, Wolfgang H; Goyal, Alka; Keljo, David J; Cross, Raymond K; Williams, Emmanuelle D; Herfarth, Hans H; Siegel, Corey A; Oikonomou, Ioannis; Brand, Myron H; Hartman, Douglas J; Tublin, Mitchell E; Davis, Peter L; Baidoo, Leonard; Szigethy, Eva; Watson, Andrew R

2014-10-01

Managing patients with inflammatory bowel disease requires multidisciplinary coordination. Technological advances have enhanced access to care for patients and improved physician interactions. The primary aim of our project was to convene diverse institutions and specialties through a multisite virtual conferencing platform to discuss complex patient management. The case conference is designed to include multiple institutions to exchange ideas, review evidence-based data, and provide input on the management of patients with Crohn's disease and ulcerative colitis. Technology is supplied and coordinated by an information technology specialist and Chorus Call, Inc., an international teleconferencing service provider. The Inflammatory Bowel Disease Live Interinstitutional Interdisciplinary Videoconference Education (IBD LIVE) initiative is accredited by the University of Pittsburgh Medical Center (UPMC) Center for Continuing Education in the Health Sciences for 1 AMA PRA Category 1 Credit per weekly session. IBD LIVE began in 2009 comprising only adult gastroenterology and pediatric gastroenterology from UPMC Presbyterian and Children's Hospitals. Participation steadily increased from 5 sites in 2010 to 11 sites in 2014. Maximum attendance for a single conference was 73 participants with a median of 48. The Continuing Medical Education scores (1 = worst to 5 = best) have a high median overall score (4.6, range 3.2-5.0) with positive responses with regard to the degree to which the conference changed practice. IBD LIVE has been successful and continues to grow. Implementation of the Crohn's and Colitis Foundation of America Virtual Preceptor Program using the IBD LIVE platform will provide expanded national physician access to this professional education activity.

Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy.

PubMed

Gilissen, Lennard P L; Wong, Dennis R; Engels, Leopold G J B; Bierau, Jörgen; Bakker, Jaap A; Paulussen, Aimée D C; Romberg-Camps, Mariëlle J; Stronkhorst, Arnold; Bus, Paul; Bos, Laurens P; Hooymans, Piet M; Stockbrügger, Reinhold W; Neef, Cees; Masclee, Ad A M

2012-07-01

Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is ≥235 pmol/8×10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263 pmol/8×10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235 pmol/8×10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04). Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Relevance of TNBS-Colitis in Rats: A Methodological Study with Endoscopic, Histologic and Transcriptomic Characterization and Correlation to IBD

PubMed Central

Brenna, Øystein; Furnes, Marianne W.; Drozdov, Ignat; van Beelen Granlund, Atle; Flatberg, Arnar; Sandvik, Arne K.; Zwiggelaar, Rosalie T. M.; Mårvik, Ronald; Nordrum, Ivar S.; Kidd, Mark; Gustafsson, Björn I.

2013-01-01

Background Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time points after colitis induction, and 3) compare rat and human IBD mucosal transcriptomic data to evaluate whether TNBS-colitis is an appropriate model of IBD. Methodology/Principal Findings Five female Sprague Daley rats received TNBS diluted in 50% ethanol (18 mg/0.6 ml) rectally. The rats underwent colonoscopy with biopsy at different time points. RNA was extracted from rat biopsies and microarray was performed. PCR and in situ hybridization (ISH) were done for validation of microarray results. Rat microarray profiles were compared to human IBD expression profiles (25 ulcerative colitis Endoscopic score demonstrated mild to moderate colitis after three and seven days, but declined after twelve days. Histologic changes corresponded with the endoscopic appearance. Over-represented Gene Ontology Biological Processes included: Cell Adhesion, Immune Response, Lipid Metabolic Process, and Tissue Regeneration. IL-1α, IL-1β, TLR2, TLR4, PRNP were all significantly up-regulated, while PPARγ was significantly down-regulated. Among genes with highest fold change (FC) were SPINK4, LBP, ADA, RETNLB and IL-1α. The highest concordance in differential expression between TNBS and IBD transcriptomes was three days after colitis induction. ISH and PCR results corresponded with the microarray data. The most concordantly expressed biologically relevant pathways included TNF signaling, Cell junction organization, and Interleukin-1 processing. Conclusions/Significance Endoscopy with biopsies in TNBS-colitis is useful to follow temporal changes of inflammation visually and histologically, and to acquire tissue for gene

Cervical cancer screening in Middle Eastern and Asian migrants to Australia: a record linkage study.

PubMed

Aminisani, Nayyereh; Armstrong, Bruce K; Canfell, Karen

2012-12-01

Australia's organized cervical screening program recommends two-yearly screening for women aged 18-69 years and reminder letters are sent at 27 months. Cervical screening registers hold comprehensive information on screening, but not country of birth. A linkage study was performed in order to assess cervical screening behavior in migrants. To assess screening participation, we linked year 2000 records for 12,541 Middle Eastern/Asian-born women 20-54 years of age, and an age and area matched random sample of 12,143 Australian-born women in the New South Wales (NSW) Midwives Data Collection (MDC), which records country of birth, to screening register records. Screening behavior after 2000 was assessed in women without a recorded prior cervical abnormality. The odds ratios for being screened at least once within a 3 year period, with reference to Australian-born women and adjusted for age, parity, socioeconomic status and smoking, were 0.88 (95% CI: 0.81-0.97) and 0.74 (95% CI: 0.70-0.79) in women born in the Middle East and Asia, respectively. Screening increased with increasing socioeconomic status (SES), absence of smoking and greater parity in Australian-born women but little, if at all, in migrant women. In a sensitivity analysis in which hospital admitted patients were the source of population samples, some patterns were sufficiently different to suggest that selection for illness can affect the strength and direction of associations in linked data. Migrant women from Asian and Middle-eastern countries are less likely than Australian-born women to participate in cervical screening at the recommended interval. Their likelihood of screening is also less related to socioeconomic status, smoking and parity than that in Australian-born women. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sexual Dysfunctions in Men and Women with Inflammatory Bowel Disease: The Influence of IBD-Related Clinical Factors and Depression on Sexual Function.

PubMed

Bel, Linda G J; Vollebregt, Anna M; Van der Meulen-de Jong, Andrea E; Fidder, Herma H; Ten Hove, Willem R; Vliet-Vlieland, Cornelia W; Ter Kuile, Moniek M; de Groot, Helena E; Both, Stephanie

2015-07-01

Inflammatory bowel disease (IBD) is likely to have an impact on sexual function because of its symptoms, like diarrhea, fatigue, and abdominal pain. Depression is commonly reported in IBD and is also related to impaired sexual function. This study aimed to evaluate sexual function and its association with depression among patients with IBD compared with controls. IBD patients registered at two hospitals participated. The control group consisted of a general practitioner practice population. The web-based questionnaire included the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. Other variables evaluated were depression, disease activity, IBD-related quality of life, body image, and fatigue. In total, 168 female and 119 male patients were available for analysis (response rate 24%). Overall, patients with IBD did not significantly differ in prevalence of sexual dysfunctions from controls: female patients 52%, female controls 44%, male patients and male controls both 25%. However, men and women with an active disease scored significantly lower than patients in remission and controls, indicating impaired sexual functioning during disease activity. Significant associations were found between active disease, fatigue, depressive mood, quality of life, and sexual function for both male and female patients. The association between disease activity and sexual function was totally mediated by depression. Male and female IBD patients with an active disease show impaired sexual function relative to patients in remission and controls. Depression is the most important determinant for impaired sexual function in IBD. © 2015 International Society for Sexual Medicine.

Efficacy, Safety, and Interactions of a Live Infectious Bursal Disease Virus Vaccine for Chickens Based on Strain IBD V877.

PubMed

Geerligs, Harm J; Ons, Ellen; Boelm, Gert Jan; Vancraeynest, Dieter

2015-03-01

Infectious bursal disease (IBD) is a highly contagious disease in young chickens which can result in high morbidity and mortality and also in great economic losses. The main target for the virus is the lymphoid tissue with a special predilection for the bursa of Fabricius. Several vaccines are available to control the disease. Intermediate plus vaccines are used in chickens with high maternal antibody titers which face high infection pressure. An example of an intermediate plus vaccine is a live vaccine based on IBD strain V877. The results of an efficacy study in commercial broilers with different levels of maternally derived antibodies (MDA) showed that the V877-based IBD vaccine can break through maternal antibody titers of higher than 1100 as determined by an IBD ELISA. The safety of the vaccine was demonstrated in a study in which specific-pathogen-free (SPF) chickens were vaccinated with a tenfold dose of the vaccine strain and a tenfold dose of the vaccine strain after five back passages in SPF chickens. The vaccine virus caused lesions, as could be expected for an intermediate plus vaccine, but the scores were not much higher than the maximal scores allowed for mild IBD vaccines in the European Pharmacopoeia, and reversion to virulence was absent. In studies in SPF chickens, there were no negative impacts by the IBD V877 vaccine on the efficacy of a live QX-like IB vaccine and a live Newcastle disease La Sota vaccine in vaccination challenge studies, although the IBD vaccine had a negative effect on the antibody response generated by the QX-like IB vaccine. It is concluded that the IBD V877 vaccine has the capacity to break through high levels of MDA, has a satisfactory safety profile, and interactions with other live vaccines are limited. In order to limit bursal lesions after vaccination it is recommended to confirm the presence of MDA before vaccinating with the V877 vaccine.

Health Supervision in the Management of Children and Adolescents With IBD: NASPGHAN Recommendations

PubMed Central

Rufo, Paul A.; Denson, Lee A.; Sylvester, Francisco A.; Szigethy, Eva; Sathya, Pushpa; Lu, Ying; Wahbeh, Ghassan T.; Sena, Laureen M.; Faubion, William A.

2014-01-01

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and

Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations.

PubMed

Rufo, Paul A; Denson, Lee A; Sylvester, Francisco A; Szigethy, Eva; Sathya, Pushpa; Lu, Ying; Wahbeh, Ghassan T; Sena, Laureen M; Faubion, William A

2012-07-01

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and

Securizing data linkage in french public statistics.

PubMed

Guesdon, Maxence; Benzenine, Eric; Gadouche, Kamel; Quantin, Catherine

2016-10-06

Administrative records in France, especially medical and social records, have huge potential for statistical studies. The NIR (a national identifier) is widely used in medico-social administrations, and this would theoretically provide considerable scope for data matching, on condition that the legislation on such matters was respected.The law, however, forbids the processing of non-anonymized medical data, thus making it difficult to carry out studies that require several sources of social and medical data.We would like to benefit from computer techniques introduced since the 70 s to provide safe linkage of anonymized files, to release the current constraints of such procedures.We propose an organization and a data workflow, based on hashing and cyrptographic techniques, to strongly compartmentalize identifying and not-identifying data.The proposed method offers a strong control over who is in possession of which information, using different hashing keys for each linkage. This allows to prevent unauthorized linkage of data, to protect anonymity, by preventing cumulation of not-identifying data which can become identifying data when linked.Our proposal would make it possible to conduct such studies more easily, more regularly and more precisely while preserving a high enough level of anonymity.The main obstacle to setting up such a system, in our opinion, is not technical, but rather organizational in that it is based on the existence of a Key-Management Authority.

Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012-2014.

PubMed

Linde, Ann C; Sweet, Kristin A; Nelson, Kailey; Mamo, Blain; Chute, Sara M

2016-01-01

The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (p<0.001). In the context of a strong screening and surveillance infrastructure, a simple intervention improved the linkage-to-care rate for HBsAg-positive refugees.

Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)

PubMed

Duchmann, R; Kaiser, I; Hermann, E; Mayet, W; Ewe, K; Meyer zum Büschenfelde, K H

1995-12-01

Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen. LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate. PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-gamma), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD.

Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)

PubMed Central

Duchmann, R; Kaiser, I; Hermann, E; Mayet, W; Ewe, K; Meyer zum Büschenfelde, K H

1995-01-01

Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen. LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate. PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-gamma), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD. PMID:8536356

A guide to evaluating linkage quality for the analysis of linked data.

PubMed

Harron, Katie L; Doidge, James C; Knight, Hannah E; Gilbert, Ruth E; Goldstein, Harvey; Cromwell, David A; van der Meulen, Jan H

2017-10-01

Linked datasets are an important resource for epidemiological and clinical studies, but linkage error can lead to biased results. For data security reasons, linkage of personal identifiers is often performed by a third party, making it difficult for researchers to assess the quality of the linked dataset in the context of specific research questions. This is compounded by a lack of guidance on how to determine the potential impact of linkage error. We describe how linkage quality can be evaluated and provide widely applicable guidance for both data providers and researchers. Using an illustrative example of a linked dataset of maternal and baby hospital records, we demonstrate three approaches for evaluating linkage quality: applying the linkage algorithm to a subset of gold standard data to quantify linkage error; comparing characteristics of linked and unlinked data to identify potential sources of bias; and evaluating the sensitivity of results to changes in the linkage procedure. These approaches can inform our understanding of the potential impact of linkage error and provide an opportunity to select the most appropriate linkage procedure for a specific analysis. Evaluating linkage quality in this way will improve the quality and transparency of epidemiological and clinical research using linked data. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

Prevalence, predictors, and clinical consequences of medical adherence in IBD: How to improve it?

PubMed Central

Lakatos, Peter Laszlo

2009-01-01

Inflammatory bowel diseases (IBD) are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment. However, non-adherence has been reported in over 40% of patients, especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism, hospitalization risk, and the health care costs in chronic conditions, is enormous. The causes of medication non-adherence are complex, where the patient-doctor relationship, treatment regimen, and other disease-related factors play key roles. Moreover, subjective assessment might underestimate adherence. Poor adherence may result in more frequent relapses, a disabling disease course, in ulcerative colitis, and an increased risk for colorectal cancer. Improving medication adherence in patients is an important challenge for physicians. Understanding the different patient types, the reasons given by patients for non-adherence, simpler and more convenient dosage regimens, dynamic communication within the health care team, a self-management package incorporating enhanced patient education and physician-patient interaction, and identifying the predictors of non-adherence will help devise suitable plans to optimize patient adherence. This editorial summarizes the available literature on frequency, predictors, clinical consequences, and strategies for improving medical adherence in patients with IBD. PMID:19750566

Prevalence, predictors, and clinical consequences of medical adherence in IBD: how to improve it?

PubMed

Lakatos, Peter Laszlo

2009-09-14

Inflammatory bowel diseases (IBD) are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment. However, non-adherence has been reported in over 40% of patients, especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism, hospitalization risk, and the health care costs in chronic conditions, is enormous. The causes of medication non-adherence are complex, where the patient-doctor relationship, treatment regimen, and other disease-related factors play key roles. Moreover, subjective assessment might underestimate adherence. Poor adherence may result in more frequent relapses, a disabling disease course, in ulcerative colitis, and an increased risk for colorectal cancer. Improving medication adherence in patients is an important challenge for physicians. Understanding the different patient types, the reasons given by patients for non-adherence, simpler and more convenient dosage regimens, dynamic communication within the health care team, a self-management package incorporating enhanced patient education and physician-patient interaction, and identifying the predictors of non-adherence will help devise suitable plans to optimize patient adherence. This editorial summarizes the available literature on frequency, predictors, clinical consequences, and strategies for improving medical adherence in patients with IBD.

Gastroesophageal reflux disease (GERD) and inflammatory bowel disease (IBD): attachment styles and parental bonding.

PubMed

Ercolani, Mauro; Farinelli, Marina; Agostini, Alessandro; Baldoni, Franco; Baracchini, Federica; Ravegnani, Gianni; Bortolotti, Mauro

2010-10-01

The attachment styles and parental bonding by 64 patients (M age = 43.2 yr., SD = 13.3) with Gastroesophageal Reflux Disease (GERD) were compared with those of 64 patients (M age = 42.2 yr., SD = 13.5) with Inflammatory Bowel Disease (IBD) and 126 Healthy participants (M age = 42.2 yr., SD = 12.1). Analysis of scores on the Attachment Style Questionnaire indicated insecure attachment in both the patient and control groups. The Parental Bonding scores indicated perceptions of Affectionless Control by parents in both patient groups. In particular, the mean Father-Protection subscale scores were significantly higher for in the GERD group than in the Healthy and IBD groups.

Month of Conception and Learning Disabilities: A Record-Linkage Study of 801,592 Children.

PubMed

Mackay, Daniel F; Smith, Gordon C S; Cooper, Sally-Ann; Wood, Rachael; King, Albert; Clark, David N; Pell, Jill P

2016-10-01

Learning disabilities have profound, long-lasting health sequelae. Affected children born over the course of 1 year in the United States of America generated an estimated lifetime cost of $51.2 billion. Results from some studies have suggested that autistic spectrum disorder may vary by season of birth, but there have been few studies in which investigators examined whether this is also true of other causes of learning disabilities. We undertook Scotland-wide record linkage of education (annual pupil census) and maternity (Scottish Morbidity Record 02) databases for 801,592 singleton children attending Scottish schools in 2006-2011. We modeled monthly rates using principal sine and cosine transformations of the month number and demonstrated cyclicity in the percentage of children with special educational needs. Rates were highest among children conceived in the first quarter of the year (January-March) and lowest among those conceived in the third (July-September) (8.9% vs 7.6%; P < 0.001). Seasonal variations were specific to autistic spectrum disorder, intellectual disabilities, and learning difficulties (e.g., dyslexia) and were absent for sensory or motor/physical impairments and mental, physical, or communication problems. Seasonality accounted for 11.4% (95% confidence interval: 9.0, 13.7) of all cases. Some biologically plausible causes of this variation, such as infection and maternal vitamin D levels, are potentially amendable to intervention. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

HLA is unlikely to be a major component of risk in familial inflammatory bowl disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathew, C.G.; Naom, I.S.; Hodgson, S.V.

1994-09-01

Inflammatory bowel disease (IBD) is a chronic inflammation of the bowel which is confined to the colon in ulcerative colitis (UC) or may affect any part of the gastrointestinal tract in Crohn`s disease (CD). The cause of IBD is unknown, but a genetic component is suggested by a 10-fold increase in risk to first degree relatives, and a higher concordance of disease in MZ versus DZ twins. Distinct associations of HLA DR2 with UC and DR1/DQw5 with CD have been reported. We are searching for susceptibility genes in IBD by linkage analysis in a panel of 43 families with 3more » or more living affected members, which includes 12 families with CD, 17 with UC and 14 {open_quotes}mixed{close_quotes} families with UC and CD. In view of the reported HLA associations in IBD, we have analyzed 5 microsatellite markers from the major histocompatibility complex for linkage to IBD using both parametric and nonparametric methods. LOD scores were calculated for 4 different genetic models, including both dominant and recessive inheritance, and haplotype sharing was analyzed in affected siblings. LOD scores for the MHC locus were negative in the full data set, and in the 3 classes of family (UC,CD,mixed). Haplotype sharing in affected sibs was very close to that expected if no linkage was present. We conclude that genes from the HLA region are unlikely to be a major component of risk in familial IBD. Linkage analysis of genes which cause chronic colitis when disrupted in transgenic mice is in progress.« less

Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public Health and Epidemiological Studies.

PubMed

Aldridge, Robert W; Shaji, Kunju; Hayward, Andrew C; Abubakar, Ibrahim

2015-01-01

The Enhanced Matching System (EMS) is a probabilistic record linkage program developed by the tuberculosis section at Public Health England to match data for individuals across two datasets. This paper outlines how EMS works and investigates its accuracy for linkage across public health datasets. EMS is a configurable Microsoft SQL Server database program. To examine the accuracy of EMS, two public health databases were matched using National Health Service (NHS) numbers as a gold standard unique identifier. Probabilistic linkage was then performed on the same two datasets without inclusion of NHS number. Sensitivity analyses were carried out to examine the effect of varying matching process parameters. Exact matching using NHS number between two datasets (containing 5931 and 1759 records) identified 1071 matched pairs. EMS probabilistic linkage identified 1068 record pairs. The sensitivity of probabilistic linkage was calculated as 99.5% (95%CI: 98.9, 99.8), specificity 100.0% (95%CI: 99.9, 100.0), positive predictive value 99.8% (95%CI: 99.3, 100.0), and negative predictive value 99.9% (95%CI: 99.8, 100.0). Probabilistic matching was most accurate when including address variables and using the automatically generated threshold for determining links with manual review. With the establishment of national electronic datasets across health and social care, EMS enables previously unanswerable research questions to be tackled with confidence in the accuracy of the linkage process. In scenarios where a small sample is being matched into a very large database (such as national records of hospital attendance) then, compared to results presented in this analysis, the positive predictive value or sensitivity may drop according to the prevalence of matches between databases. Despite this possible limitation, probabilistic linkage has great potential to be used where exact matching using a common identifier is not possible, including in low-income settings, and for vulnerable

IBD in the elderly population: results from a population-based study in Western Hungary, 1977-2008.

PubMed

Lakatos, Peter Laszlo; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos S; Lakatos, Laszlo

2011-02-01

Limited data are available on the incidence and disease course of IBD in the elderly population. Our aim was to analyze the incidence and disease course of IBD according to the age at diagnosis in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. Data of 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 SD 15.9 years; CD: 506, age at diagnosis: 31.5 SD 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. 106 (11.6%) of UC patients and 21 (4.2%) of CD patients were diagnosed with >60 years of age. In UC, the incidence increased from 1.09 to 10.8/10(5) in the elderly, while CD increased to 3.04/10(5) in 2002-2007. In CD, colonic location (elderly: 61.9% vs. pediatric: 24.3%, p=0.001, and adults: 36.8%, p=0.02) and stenosing disease (elderly: 42.9% vs. pediatric: 14.9%, p=0.005, and adults: 19.5%, p=0.01) were more frequent in the elderly. A change in disease behavior was absent in the elderly, while in pediatric and adult CD population it was 20.3% (p=0.037), 19.8% (p=0.036) after 5 years. In UC, extensive disease was more frequent in pediatric patients compared to the elderly (p=0.003, OR: 2.73, 95%CI: 1.38-5.41). In addition, pediatric (57.3%, p<0.001, OR: 6.58; 95%CI: 3.22-12.9) and adult (39.8%, p<0.001, OR: 3.24; 95%CI: 1.91-5.49) patients required more often systemic steroids during follow-up compared to the elderly (17%). Proximal extension at 10 years was 11.6%, but time to extension was not different according to the age at onset. Elderly patients represent an increasing proportion of the IBD population. Stenosing and colon-only disease were characteristic for elderly CD patients, while the disease course in UC was milder. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Inadequate Gestational Weight Gain, the Hidden Link Between Maternal IBD and Adverse Pregnancy Outcomes: Results from the Norwegian Mother and Child Cohort Study.

PubMed

Bengtson, May-Bente; Aamodt, Geir; Mahadevan, Uma; Vatn, Morten H

2017-07-01

Patients with inflammatory bowel disease (IBD) are in general prone to weight loss. We explored the risk of inadequate gestational weight gain (GWG), and the impact of GWG on adverse pregnancy outcomes, among mothers with IBD in the Norwegian Mother and Child Cohort Study (MoBa). The MoBa with 95,200 mothers enrolled from 1999 to 2008, comprised 217 mothers with ulcerative colitis and 166 with Crohn's disease. Demographics were ascertained through a basic questionnaire before the first ultrasound visit and an IBD history and disease activity during pregnancy through a questionnaire mailed out in 2013. Inadequate GWG was based on the US Institute of Medicine recommendations. The associations between IBD and inadequate GWG or adverse pregnancy outcomes were explored, adjusted for diabetes, hypertension, smoking, maternal age, education, and disease activity. Mothers with Crohn's disease (34.3%) and ulcerative colitis (26.7%) were more frequently exposed to inadequate GWG compared with non-IBD mothers (19.4%) (adjusted odds ratio [aOR] = 2.02, 95% confidence interval [CI], 1.42-2.86 and aOR = 1.46, 95% CI, 1.04-2.05, respectively). Mothers with IBD with inadequate GWG (exposed) had a 2-fold risk of small for gestational age infants compared with exposed non-IBD mothers (aOR = 1.93, 95% CI, 1.13-3.29). Exposed mothers with Crohn's disease and ulcerative colitis had a several-fold increased risk of small for gestational age compared with nonexposed IBD mothers (aOR = 4.5, 95% CI, 1.3-16.2, aOR = 5.5, 95% CI, 1.6-18.5). Disease activity was associated with reduced GWG (<13 kg compared with >17.5 kg) (aOR = 3.34, 95% CI, 1.33-8.38). Inadequate GWG should be considered as a risk factor for adverse pregnancy outcomes or as a marker of disease activity.

Using probabilistic record linkage methods to identify Australian Indigenous women on the Queensland Pap Smear Register: the National Indigenous Cervical Screening Project

PubMed Central

Diaz, Abbey; Baade, Peter; Garvey, Gail; Cunningham, Joan; Brotherton, Julia M L; Canfell, Karen; Valery, Patricia C; O'Connell, Dianne L; Taylor, Catherine; Moore, Suzanne P; Condon, John R

2016-01-01

Objective To evaluate the feasibility and reliability of record linkage of existing population-based data sets to determine Indigenous status among women receiving Pap smears. This method may allow for the first ever population measure of Australian Indigenous women's cervical screening participation rates. Setting/participants A linked data set of women aged 20–69 in the Queensland Pap Smear Register (PSR; 1999–2011) and Queensland Cancer Registry (QCR; 1997–2010) formed the Initial Study Cohort. Two extracts (1995–2011) were taken from Queensland public hospitals data (Queensland Hospital Admitted Patient Data Collection, QHAPDC) for women, aged 20–69, who had ever been identified as Indigenous (extract 1) and had a diagnosis or procedure code relating to cervical cancer (extract 2). The Initial Study Cohort was linked to extract 1, and women with cervical cancer in the initial cohort were linked to extract 2. Outcome measures The proportion of women in the Initial Cohort who linked with the extracts (true -pairs) is reported, as well as the proportion of potential pairs that required clerical review. After assigning Indigenous status from QHAPDC to the PSR, the proportion of women identified as Indigenous was calculated using 4 algorithms, and compared. Results There were 28 872 women (2.1%) from the Initial Study Cohort who matched to an ever Indigenous record in extract 1 (n=76 831). Women with cervical cancer in the Initial Study Cohort linked to 1385 (71%) records in extract 2. The proportion of Indigenous women ranged from 2.00% to 2.08% when using different algorithms to define Indigenous status. The Final Study Cohort included 1 372 823 women (PSR n=1 374 401; QCR n=1955), and 5 062 118 records. Conclusions Indigenous status in Queensland cervical screening data was successfully ascertained through record linkage, allowing for the crucial assessment of the current cervical screening programme for Indigenous women. Our study

Using probabilistic record linkage methods to identify Australian Indigenous women on the Queensland Pap Smear Register: the National Indigenous Cervical Screening Project.

PubMed

Whop, Lisa J; Diaz, Abbey; Baade, Peter; Garvey, Gail; Cunningham, Joan; Brotherton, Julia M L; Canfell, Karen; Valery, Patricia C; O'Connell, Dianne L; Taylor, Catherine; Moore, Suzanne P; Condon, John R

2016-02-12

To evaluate the feasibility and reliability of record linkage of existing population-based data sets to determine Indigenous status among women receiving Pap smears. This method may allow for the first ever population measure of Australian Indigenous women's cervical screening participation rates. A linked data set of women aged 20-69 in the Queensland Pap Smear Register (PSR; 1999-2011) and Queensland Cancer Registry (QCR; 1997-2010) formed the Initial Study Cohort. Two extracts (1995-2011) were taken from Queensland public hospitals data (Queensland Hospital Admitted Patient Data Collection, QHAPDC) for women, aged 20-69, who had ever been identified as Indigenous (extract 1) and had a diagnosis or procedure code relating to cervical cancer (extract 2). The Initial Study Cohort was linked to extract 1, and women with cervical cancer in the initial cohort were linked to extract 2. The proportion of women in the Initial Cohort who linked with the extracts (true -pairs) is reported, as well as the proportion of potential pairs that required clerical review. After assigning Indigenous status from QHAPDC to the PSR, the proportion of women identified as Indigenous was calculated using 4 algorithms, and compared. There were 28,872 women (2.1%) from the Initial Study Cohort who matched to an ever Indigenous record in extract 1 (n=76,831). Women with cervical cancer in the Initial Study Cohort linked to 1385 (71%) records in extract 2. The proportion of Indigenous women ranged from 2.00% to 2.08% when using different algorithms to define Indigenous status. The Final Study Cohort included 1,372,823 women (PSR n=1,374,401; QCR n=1955), and 5,062,118 records. Indigenous status in Queensland cervical screening data was successfully ascertained through record linkage, allowing for the crucial assessment of the current cervical screening programme for Indigenous women. Our study highlights the need to include Indigenous status on Pap smear request and report forms in any

Efficacy of vedolizumab as induction therapy in refractory IBD patients: Amulticenter cohort

PubMed Central

Shelton, Edward; Allegretti, Jessica R.; Stevens, Betsy; Lucci, Matthew; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Hamilton, Matthew J; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Ananthakrishnan, Ashwin; Korzenik, Joshua R.; Yajnik, Vijay

2015-01-01

Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials. PMID:26288002

Sustainability of Endovenous Iron Deficiency Anaemia Treatment: Hospital-Based Health Technology Assessment in IBD Patients.

PubMed

Poscia, A; Stojanovic, J; Kheiraoui, F; Proli, E M; Scaldaferri, F; Volpe, M; Di Pietro, M L; Gasbarrini, A; Fabrizio, L; Boccia, S; Favaretti, C

2017-01-01

Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting patients with inflammatory bowel disease (IBD). The Health Technology Assessment approach was applied to evaluate the sustainability of intravenous (IV) iron formulations in the Italian hospital setting, with particular focus on ferric carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition to the efficacy and safety of IV iron formulations currently used in Italy, were retrieved from scientific literature. A hospital-based cost-analysis of the outpatient delivery of IV iron treatments was performed. Organizational and ethical implications were discussed. IDA prevalence in IBD patients varies markedly from 9 to 73%. IV iron preparations were proven to have good efficacy and safety profiles, and ferric carboxymaltose provided a fast correction of haemoglobin and serum ferritin levels in iron-deficient patients. Despite a higher price, ferric carboxymaltose would confer a beneficial effect to the hospital, in terms of reduced cost related to individual patient management and additionally to the patient by reducing the number of infusions and admissions to healthcare facilities. Ethically, the evaluation is appropriate due to its efficacy and compliance. This assessment supports the introduction of ferric carboxymaltose in the Italian outpatient setting.

Poor recall of prior exposure to varicella zoster, rubella, measles, or mumps in patients with IBD.

PubMed

Naganuma, Makoto; Nagahori, Masakazu; Fujii, Toshimitsu; Morio, Junko; Saito, Eiko; Watanabe, Mamoru

2013-02-01

Few studies have measured the levels of antibodies specific for measles, mumps, rubella, and varicella zoster/chickenpox viruses in inflammatory bowel disease (IBD) patients undergoing treatment with immunomodulators/biologics. We prospectively recruited 139 IBD outpatients. Enzyme-linked immunosorbent assays were used as the serological tests for measles, mumps, rubella, and varicella zoster. We defined anti-rubella IgG < 10 IU/mL, anti-measles IgG < 16 IU/mL, and anti-mumps/varicella zoster IgG <4 IU/mL as seronegative for viruses. We also asked participants about past immunizations against or infections with measles, mumps, rubella, and varicella zoster viruses. The proportion of patients with seronegative levels of antibodies specific for varicella zoster, rubella, measles, and mumps viruses was 5%, 30%, 34%, and 37%, respectively. Approximately 40% of the IBD patients did not remember whether they had previously been infected with any of the viruses, and almost one-third of the patients could not remember whether they had previously been vaccinated. Almost 30% of the patients with a past history of rubella or measles did not have seropositive antibody levels. A total of 54% of the patients being treated with immunosuppressant displayed seronegative levels of antibodies specific for at least one of the viruses. Many IBD patients were unaware of whether they had previously been vaccinated against or infected with the viruses causing varicella zoster, rubella, measles, or mumps. Therefore, measuring the current levels of antibodies specific for such viruses is useful for determining whether patients have seropositive antibody levels before immunomodulators/biologics are used for therapy.

Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012–2014

PubMed Central

Sweet, Kristin A.; Nelson, Kailey; Mamo, Blain; Chute, Sara M.

2016-01-01

Objective The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. Methods MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. Results In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (p<0.001). Conclusion In the context of a strong screening and surveillance infrastructure, a simple intervention improved the linkage-to-care rate for HBsAg-positive refugees. PMID:27168670

Genetic Literacy and Patient Perceptions of IBD Testing Utility and Disease Control: A Randomized Vignette Study of Genetic Testing

PubMed Central

Hooker, Gillian W.; Peay, Holly; Erby, Lori; Bayless, Theodore; Biesecker, Barbara B.; Roter, Debra L.

2014-01-01

Background Findings from inflammatory bowel disease (IBD) genome-wide association studies are being translated clinically into prognostic and diagnostic indicators of disease. Yet, patient perception and understanding of these tests and their applicability to providing risk information is unclear. The goal of this study was to determine, using hypothetical scenarios, whether patients with IBD perceive genetic testing to be useful for risk assessment, whether genetic test results impact perceived control, and whether low genetic literacy may be a barrier to patient understanding of these tests. Methods Two hundred fifty seven patients with IBD from the Johns Hopkins gastroenterology clinics were randomized to receive a vignette depicting either a genetic testing scenario or a standard blood testing scenario. Participants were asked questions about the vignette and responses were compared between groups. Results Perceptions of test utility for risk assessment were higher among participants responding to the genetic vignette (P < 0.001). There were no significant differences in perceptions of control over IBD after hypothetical testing between vignettes (P = 0.24). Participant responses were modified by genetic literacy, measured using a scale developed for this study. Participants randomized to the genetic vignette who scored higher on the genetic literacy scale perceived greater utility of testing for risk assessment (P = 0.008) and more control after testing (P = 0.02). Conclusions Patients with IBD perceive utility in genetic testing for providing information relevant to family members, and this appreciation is promoted by genetic literacy. Low genetic literacy among patients poses a potential threat to effective translation of genetic and genomic tests. PMID:24691112

State-Level Immunization Information Systems: Potential for Childhood Immunization Data Linkages.

PubMed

Fuller, Jill E; Walter, Emmanuel B; Dole, Nancy; O'Hara, Richard; Herring, Amy H; Durkin, Maureen S; Specker, Bonny; Wey, Betty

2017-01-01

Objectives Sources of immunization data include state registries or immunization information systems (IIS), medical records, and surveys. Little is known about the quality of these data sources or the feasibility of using IIS data for research. We assessed the feasibility of collecting immunization information for a national children's health study by accessing existing IIS data and comparing the completeness of these data against medical record abstractions (MRA) and parent report. Staff time needed to obtain IIS and MRA data was assessed. Methods We administered a questionnaire to state-level IIS representatives to ascertain availability and completeness of their data for research and gather information about data formats. We evaluated quality of data from IIS, medical records, and reports from parents of 119 National Children's Study participants at three locations. Results IIS data were comparable to MRA data and both were more complete than parental report. Agreement between IIS and MRA data was greater than between parental report and MRA, suggesting IIS and MRA are better sources than parental report. Obtaining IIS data took less staff time than chart review, making IIS data linkage for research a preferred choice. Conclusions IIS survey results indicate data can be obtained by researchers using data linkages. IIS are an accessible and feasible child immunization information source and these registries reduce reliance on parental report or medical record abstraction. Researchers seeking to link IIS data with large multi-site studies should consider acquiring IIS data, but may need strategies to overcome barriers to data completeness and linkage.

The linkage between fluvial meander-belt morphodynamics and the depositional record improves paleoenvironmental interpretations, Western Interior Basin, Alberta, Canada

NASA Astrophysics Data System (ADS)

Durkin, P.; Hubbard, S. M.

2016-12-01

Enhanced stratigraphic interpretations are possible when linkages between morphodynamic processes and the depositional record are resolved. Recent studies of modern and ancient meander-belt deposits have emphasized morphodynamic processes that are commonly understated in the analysis of stratigraphic products, such as intra-point bar erosion and rotation, counter-point-bar (concave bank-bench) development and meander-bend abandonment. On a larger scale, longitudinal changes in meander-belt morphology and processes such as changes in meander-bend migration rate, channel-belt width/depth ratio and sinuosity have been observed as rivers flow through the tidal backwater zone. However, few studies have attempted to recognize the impact of the backwater zone in the stratigraphic record. We consider ancient meander-belt deposits of the Cretaceous McMurray Formation and document linkages between morphodynamic processes and their stratigraphic product to resolve more detailed paleoenvironmental interpretations. The ancient meander belt was characterized by paleochannels that were 600 m wide and up to 50 m deep, resolved in a particularly high quality subsurface dataset consisting of 600 km2 of high-quality 3-D seismic data and over 1000 wellbores. A 3-D geocellular model and reconstructed paleochannel migration patterns reveal the evolutionary history of seventeen individual meander belt elements, including point bars, counter point bars and their associated abandoned channel fills. At the meander-bend scale, intra-point-bar erosion surfaces bound accretion packages characterized by unique accretion directions, internal stratigraphic architecture and lithologic properties. Erosion surfaces and punctuated bar rotation are linked to upstream changes in channel planform geometry (meander cut-offs). We provide evidence for downstream translation and development of counter-point bars that formed in response to valley-edge and intra-meander-belt confinement. At the meander

Commensal-innate immune miscommunication in IBD pathogenesis.

PubMed

Cario, Elke

2012-01-01

Commensal microbiota plays a key role in the health and disease of the host. The innate immune system comprises an essential functional component of the intestinal mucosal barrier, maintaining hyporesponsiveness to omnipresent harmless commensals in the lumen, but rapidly recognizing and combating invading bacteria through diverse antimicrobial mechanisms. Interactions between commensals and innate immune cells are constant, multidimensional and entirely context-dependent. Environment, genetics and host defense differentially modulate commensal-innate immune effects and functions in the intestinal mucosa. In IBD, dysbiosis, mucus layer disruption, impairment in bacterial clearance, intestinal epithelial cell barrier dysfunction and/or immune cell deregulation may lead to commensal-innate immune miscommunication, which critically drives mucosal inflammation and associated cancer. Copyright © 2012 S. Karger AG, Basel.

Describing the linkages of the immigration, refugees and citizenship Canada permanent resident data and vital statistics death registry to Ontario's administrative health database.

PubMed

Chiu, Maria; Lebenbaum, Michael; Lam, Kelvin; Chong, Nelson; Azimaee, Mahmoud; Iron, Karey; Manuel, Doug; Guttmann, Astrid

2016-10-21

Ontario, the most populous province in Canada, has a universal healthcare system that routinely collects health administrative data on its 13 million legal residents that is used for health research. Record linkage has become a vital tool for this research by enriching this data with the Immigration, Refugees and Citizenship Canada Permanent Resident (IRCC-PR) database and the Office of the Registrar General's Vital Statistics-Death (ORG-VSD) registry. Our objectives were to estimate linkage rates and compare characteristics of individuals in the linked versus unlinked files. We used both deterministic and probabilistic linkage methods to link the IRCC-PR database (1985-2012) and ORG-VSD registry (1990-2012) to the Ontario's Registered Persons Database. Linkage rates were estimated and standardized differences were used to assess differences in socio-demographic and other characteristics between the linked and unlinked records. The overall linkage rates for the IRCC-PR database and ORG-VSD registry were 86.4 and 96.2 %, respectively. The majority (68.2 %) of the record linkages in IRCC-PR were achieved after three deterministic passes, 18.2 % were linked probabilistically, and 13.6 % were unlinked. Similarly the majority (79.8 %) of the record linkages in the ORG-VSD were linked using deterministic record linkage, 16.3 % were linked after probabilistic and manual review, and 3.9 % were unlinked. Unlinked and linked files were similar for most characteristics, such as age and marital status for IRCC-PR and sex and most causes of death for ORG-VSD. However, lower linkage rates were observed among people born in East Asia (78 %) in the IRCC-PR database and certain causes of death in the ORG-VSD registry, namely perinatal conditions (61.3 %) and congenital anomalies (81.3 %). The linkages of immigration and vital statistics data to existing population-based healthcare data in Ontario, Canada will enable many novel cross-sectional and longitudinal studies to

Analysis of the contribution of HLA genes to genetic predisposition in inflammatory bowel disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naom, I.; Haris, I.; Hodgson, S.V.

1996-07-01

Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) of unknown etiology. First-degree relatives of IBD patients have a 10-fold increase in risk of developing the same disease, and distinct associations between specific HLA types and both CD and UC have been reported. We have evaluated the contribution of genes at the HLA locus to susceptibility in IBD by linkage analysis of highly informative microsatellite polymorphisms in 43 families with multiple affected cases. No evidence for linkage of HLA to IBD was obtained under any of the four models tested. Analysis of HLA haplotype sharing inmore » affected relatives indicated that the relative risk to a sibling conferred by the HLA locus was 1.11 in UC and 0.75 in CD, with upper (95%) confidence limits of 2.41 and 1.37, respectively. This suggests that other genetic or environmental factors are responsible for most of the familial aggregation in IBD. 31 refs., 1 fig., 2 tabs.« less

Smoking, physical activity, nutrition and lifestyle: environmental factors and their impact on IBD.

PubMed

Cosnes, Jacques

2010-01-01

Current smoking increases the risk of developing Crohn's disease and worsens its course, increasing the need for steroids, immunosuppressants, and re-operations. On the contrary, smoking protects against ulcerative colitis and after disease onset improves its course, decreasing the need for colectomy. Smoking cessation improves Crohn's disease and worsens ulcerative colitis. Achieving smoking cessation in Crohn's disease is thus an important goal of therapy, whereas patients with ulcerative colitis should not be discouraged to quit, because the beneficial effect of smoking for their disease is counterbalanced by the deleterious respiratory and cardiovascular effects of tobacco. Physical activity improves quality of life without detrimental effect on disease activity, and may contribute to increase muscle mass and to prevent osteoporosis. Regarding nutrition, a Western diet may be associated with an increased risk of IBD, and a case-control study revealed an increased consumption of linoleic acid before diagnosis of ulcerative colitis. Liquid diets may improve Crohn's disease flares and decrease the need for steroids; however, there are no defined diets able to improve the disease course, and in Crohn's disease, supplementation with omega-3 fatty acids did not show a significant benefit. Obesity is becoming more prevalent in IBD and may be associated with higher disease activity. In total, adhering to four simple lifestyle factors - never smoking, physical activity, prudent diet and body mass index <25 - may have a strong impact both on the prevention of major chronic diseases and on the course of IBD. Copyright © 2010 S. Karger AG, Basel.

A comparison of accuracy and computational feasibility of two record linkage algorithms in retrieving vital status information from HIV/AIDS patients registered in Brazilian public databases.

PubMed

de Paula, Adelzon Assis; Pires, Denise Franqueira; Filho, Pedro Alves; de Lemos, Kátia Regina Valente; Barçante, Eduardo; Pacheco, Antonio Guilherme

2018-06-01

While cross-referencing information from people living with HIV/AIDS (PLWHA) to the official mortality database is a critical step in monitoring the HIV/AIDS epidemic in Brazil, the accuracy of the linkage routine may compromise the validity of the final database, yielding to biased epidemiological estimates. We compared the accuracy and the total runtime of two linkage algorithms applied to retrieve vital status information from PLWHA in Brazilian public databases. Nominally identified records from PLWHA were obtained from three distinct government databases. Linkage routines included an algorithm in Python language (PLA) and Reclink software (RlS), a probabilistic software largely utilized in Brazil. Records from PLWHA 1 known to be alive were added to those from patients reported as deceased. Data were then searched into the mortality system. Scenarios where 5% and 50% of patients actually dead were simulated, considering both complete cases and 20% missing maternal names. When complete information was available both algorithms had comparable accuracies. In the scenario of 20% missing maternal names, PLA 2 and RlS 3 had sensitivities of 94.5% and 94.6% (p > 0.5), respectively; after manual reviewing, PLA sensitivity increased to 98.4% (96.6-100.0) exceeding that for RlS (p < 0.01). PLA had higher positive predictive value in 5% death proportion. Manual reviewing was intrinsically required by RlS in up to 14% register for people actually dead, whereas the corresponding proportion ranged from 1.5% to 2% for PLA. The lack of manual inspection did not alter PLA sensitivity when complete information was available. When incomplete data was available PLA sensitivity increased from 94.5% to 98.4%, thus exceeding that presented by RlS (94.6%, p < 0.05). RlS spanned considerably less processing time compared to PLA. Both linkage algorithms presented interchangeable accuracies in retrieving vital status data from PLWHA. RlS had a considerably lesser runtime but

Young people's views about consenting to data linkage: findings from the PEARL qualitative study.

PubMed

Audrey, Suzanne; Brown, Lindsey; Campbell, Rona; Boyd, Andy; Macleod, John

2016-03-21

Electronic administrative data exist in several domains which, if linked, are potentially useful for research. However, benefits from data linkage should be considered alongside risks such as the threat to privacy. Avon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study. The Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. Qualitative research was incorporated in the PEARL study to examine participants' views about data linkage and inform approaches to information sharing. This paper focusses on issues of consent. Digitally recorded interviews were conducted with 55 participants aged 17-19 years. Terms and processes relating to consent, anonymization and data linkage were explained to interviewees. Scenarios were used to prompt consideration of linking different sources of data, and whether consent should be requested. Interview recordings were fully transcribed. Thematic analysis was undertaken using the Framework approach. Participant views on data linkage appeared to be most influenced by: considerations around the social sensitivity of the research question, and; the possibility of tangible health benefits in the public interest. Some participants appeared unsure about the effectiveness of anonymization, or did not always view effective anonymization as making consent unnecessary. This was related to notions of ownership of personal information and etiquette around asking permission for secondary use. Despite different consent procedures being explained, participants tended to equate consent with 'opt-in' consent through which participants are 'asked' if their data can be used for a specific study. Participants raising similar concerns came to differing conclusions about whether consent was needed. Views changed when presented with different scenarios, and were sometimes inconsistent. Findings

Ultrasound for assessing disease activity in IBD patients: a systematic review of activity scores.

PubMed

Bots, S; Nylund, K; Löwenberg, M; Gecse, K; Gilja, O H; D'Haens, G

2018-04-19

Ultrasound (US) indices for assessing disease activity in IBD patients have never been critically reviewed. We aimed to systematically review the quality and reliability of available ultrasound (US) indices compared with reference standards for grading disease activity in IBD patients. Pubmed, Embase and Medline were searched from 1990 until June 2017. Relevant publications were identified through full text review after initial screening by 2 investigators. Data on methodology and index characteristics were collected. Study quality was assessed with a modified version of the Quadas-2 tool for risk of bias assessment. Of 20 studies with an US index, 11 studies met the inclusion criteria. Out of these 11 studies, 7 and 4 studied CD and UC activity indices, respectively. Parameters that were used in these indices included bowel wall thickness (BWT), Doppler signal (DS), wall layer stratification (WLS), compressibility, peristalsis, haustrations, fatty wrapping, contrast enhancement (CE) and strain pattern. Study quality was graded high in 5 studies, moderate in 3 studies and low in 3 studies. Ileocolonoscopy was used as the reference standard in 9 studies. In 1 study a combined index of ileocolonoscopy and barium contrast radiography and in 1 study histology was used as the reference standard. Only 5 studies used an established endoscopic index for comparison with US. Several US indices for assessing disease activity in IBD are available; however the methodology for development was suboptimal in most studies. For the development of future indices stringent methodological design is required.

Rheumatic Heart Disease-Attributable Mortality at Ages 5-69 Years in Fiji: A Five-Year, National, Population-Based Record-Linkage Cohort Study.

PubMed

Parks, Tom; Kado, Joseph; Miller, Anne E; Ward, Brenton; Heenan, Rachel; Colquhoun, Samantha M; Bärnighausen, Till W; Mirabel, Mariana; Bloom, David E; Bailey, Robin L; Tukana, Isimeli N; Steer, Andrew C

2015-01-01

Rheumatic heart disease (RHD) is considered a major public health problem in developing countries, although scarce data are available to substantiate this. Here we quantify mortality from RHD in Fiji during 2008-2012 in people aged 5-69 years. Using 1,773,999 records derived from multiple sources of routine clinical and administrative data, we used probabilistic record-linkage to define a cohort of 2,619 persons diagnosed with RHD, observed for all-cause mortality over 11,538 person-years. Using relative survival methods, we estimated there were 378 RHD-attributable deaths, almost half of which occurred before age 40 years. Using census data as the denominator, we calculated there were 9.9 deaths (95% CI 9.8-10.0) and 331 years of life-lost (YLL, 95% CI 330.4-331.5) due to RHD per 100,000 person-years, standardised to the portion of the WHO World Standard Population aged 0-69 years. Valuing life using Fiji's per-capita gross domestic product, we estimated these deaths cost United States Dollar $6,077,431 annually. Compared to vital registration data for 2011-2012, we calculated there were 1.6-times more RHD-attributable deaths than the number reported, and found our estimate of RHD mortality exceeded all but the five leading reported causes of premature death, based on collapsed underlying cause-of-death diagnoses. Rheumatic heart disease is a leading cause of premature death as well as an important economic burden in this setting. Age-standardised death rates are more than twice those reported in current global estimates. Linkage of routine data provides an efficient tool to better define the epidemiology of neglected diseases.

Quantifying sources of bias in longitudinal data linkage studies of child abuse and neglect: measuring impact of outcome specification, linkage error, and partial cohort follow-up.

PubMed

Parrish, Jared W; Shanahan, Meghan E; Schnitzer, Patricia G; Lanier, Paul; Daniels, Julie L; Marshall, Stephen W

2017-12-01

Health informatics projects combining statewide birth populations with child welfare records have emerged as a valuable approach to conducting longitudinal research of child maltreatment. The potential bias resulting from linkage misspecification, partial cohort follow-up, and outcome misclassification in these studies has been largely unexplored. This study integrated epidemiological survey and novel administrative data sources to establish the Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project. Using these data we evaluated and quantified the impact of non-linkage misspecification and single source maltreatment ascertainment use on reported maltreatment risk and effect estimates. The ALCANLink project integrates the 2009-2011 Alaska Pregnancy Risk Assessment Monitoring System (PRAMS) sample with multiple administrative databases through 2014, including one novel administrative source to track out-of-state emigration. For this project we limited our analysis to the 2009 PRAMS sample. We report on the impact of linkage quality, cohort follow-up, and multisource outcome ascertainment on the incidence proportion of reported maltreatment before age 6 and hazard ratios of selected characteristics that are often available in birth cohort linkage studies of maltreatment. Failure to account for out-of-state emigration biased the incidence proportion by 12% (from 28.3% w to 25.2% w ), and the hazard ratio (HR) by as much as 33% for some risk factors. Overly restrictive linkage parameters biased the incidence proportion downwards by 43% and the HR by as much as 27% for some factors. Multi-source linkages, on the other hand, were of little benefit for improving reported maltreatment ascertainment. Using the ALCANLink data which included a novel administrative data source, we were able to observe and quantify bias to both the incidence proportion and HR in a birth cohort linkage study of reported child maltreatment. Failure to account for out

Analysis of ethnic disparities in workers' compensation claims using data linkage.

PubMed

Friedman, Lee S; Ruestow, Peter; Forst, Linda

2012-10-01

The overall goal of this research project was to assess ethnic disparities in monetary compensation among construction workers injured on the job through the linkage of medical records and workers' compensation data. Probabilistic linkage of medical records with workers' compensation claim data. In the final multivariable robust regression model, compensation was $5824 higher (P = 0.030; 95% confidence interval: 551 to 11,097) for white non-Hispanic workers than for other ethnic groups when controlling for injury severity, affected body region, type of injury, average weekly wage, weeks of temporary total disability, percent permanent partial disability, death, or attorney use. The analysis indicates that white non-Hispanic construction workers are awarded higher monetary settlements despite the observation that for specific injuries the mean temporary total disability and permanent partial disability were equivalent to or lower than those in Hispanic and black construction workers.

Vedolizumab in Paediatric Inflammatory Bowel Disease: A Retrospective Multi-Centre Experience From the Paediatric IBD Porto Group of ESPGHAN.

PubMed

Ledder, Oren; Assa, Amit; Levine, Arie; Escher, Johanna C; de Ridder, Lissy; Ruemmele, Frank; Shah, Neil; Shaoul, Ron; Wolters, Victorien M; Rodrigues, Astor; Uhlig, Holm H; Posovsky, Carsten; Kolho, Kaija-Leena; Jakobsen, Christian; Cohen, Shlomi; Shouval, Dror S; de Meij, Tim; Martin-de-Carpi, Javier; Richmond, Lisa; Bronsky, Jiri; Friedman, Mira; Turner, Dan

2017-10-01

Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with inflammatory bowel disease [IBD], but the data in paediatrics are limited. We describe the short-term effectiveness and safety of vedolizumab in a European multi-centre paediatric IBD cohort. Retrospective review of children [aged 2-18 years] treated with vedolizumab from 19 centres affiliated with the Paediatric IBD Porto group of ESPGHAN. Primary outcome was Week 14 corticosteroid-free remission [CFR]. In all, 64 children were included (32 [50%] male, mean age 14.5 ± 2.8 years, with a median follow-up 24 weeks [interquartile range 14-38; range 6-116]); 41 [64%] cases of ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U] and 23 [36%] Crohn's disease [CD]. All were previously treated with anti-tumour necrosis factor [TNF] [28% primary failure, 53% secondary failure]. Week 14 CFR was 37% in UC, and 14% in CD [P = 0.06]. CFR by last follow-up was 39% in UC and 24% in CD [p = 0.24]. Ten [17%] children required surgery, six of whom had colectomy for UC. Concomitant immunomodulatory drugs did not affect remission rate [42% vs 35%; p = 0.35 at Week 22]. There were three minor drug-related adverse events. Only 3 of 16 children who underwent endoscopic evaluation had mucosal healing after treatment (19%). Vedolizumab was safe and effective in this cohort of paediatric refractory IBD. These data support previous findings of slow induction rate of vedolizumab in CD and a trend to be less effective compared with patients with UC. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Syphilis in pregnancy and congenital syphilis in Amazonas State, Brazil: an evaluation using database linkage.

PubMed

Soeiro, Claudia Marques de Oliveira; Miranda, Angélica Espinosa; Saraceni, Valeria; Santos, Marcelo Cordeiro dos; Talhari, Sinesio; Ferreira, Luiz Carlos de Lima

2014-04-01

This study analyzes notification of syphilis in pregnancy and congenital syphilis in Amazo- nas State, Brazil, from 2007 to 2009 and verifies underreporting in databases in the National Information System on Diseases of Notification (SINAN) and the occurrence of perinatal deaths associated with congenital syphilis and not reported in the Mortality Information System (SIM). This was a cross-sectional study with probabilistic record linkage between the SINAN and SIM. There were 666 reports of syphilis in pregnant women, including 224 in 2007 (3.8/1,000), 244(4.5/1,000) in 2008, and 198(4.0/1,000) in 2009. The study found 486 cases of congenital syphilis, of which 153 in 2007 (2.1/1,000), 193 in 2008 (2.6/1,000), and 140 in 2009 (2.0/1,000). After linkage of the SINAN databases, 237 pregnant women (35.6%) had cases of congenital syphilis reported. The SIM recorded 4,905 perinatal deaths, of which 57.8% were stillbirths. Probabilistic record linkage between SIM and SINAN-Congenital Syphilis yielded 13 matched records. The use of SINAN and SIM may not reflect the total magnitude of syphilis, but provide the basis for monitoring and analyzing this health problem, with a view towards planning and management.

Linkages: Effective Keys to Success.

ERIC Educational Resources Information Center

Tindall, Lloyd W.

1986-01-01

Discusses various elements of linkages: informal agreements; formal written agreements; making agreements work; the non-financial agreement; how linkages work at the elementary, secondary, and postsecondary levels in Wisconsin; mandated linkages; and the importance of linkages in the vocational education and training arena. (CT)

Low Mass Blood Peptides Discriminative of Inflammatory Bowel Disease (IBD) Severity: A Quantitative Proteomic Perspective*

PubMed Central

Yau, Yunki; Duo, Xizi; Zeng, Ming; Campbell, Beth; Shin, Sean; Luber, Raphael; Redmond, Diane; Leong, Rupert W. L.

2016-01-01

Breakdown of the protective gut barrier releases effector molecules and degradation products into the blood stream making serum and plasma ideal as a diagnostic medium. The enriched low mass proteome is unexplored as a source of differentiators for diagnosing and monitoring inflammatory bowel disease (IBD) activity, that is less invasive than colonoscopy. Differences in the enriched low mass plasma proteome (<25 kDa) were assessed by label-free quantitative mass-spectrometry. A panel of marker candidates were progressed to validation phase and “Tier-2” FDA-level validated quantitative assay. Proteins important in maintaining gut barrier function and homeostasis at the epithelial interface have been quantitated by multiple reaction monitoring in plasma and serum including both inflammatory; rheumatoid arthritis controls, and non-inflammatory healthy controls; ulcerative colitis (UC), and Crohn's disease (CD) patients. Detection by immunoblot confirmed presence at the protein level in plasma. Correlation analysis and receiver operator characteristics were used to report the sensitivity and specificity. Peptides differentiating controls from IBD originate from secreted phosphoprotein 24 (SPP24, p = 0.000086, 0.009); whereas those in remission and healthy can be differentiated in UC by SPP24 (p = 0.00023, 0.001), α-1-microglobulin (AMBP, p = 0.006) and CD by SPP24 (p = 0.019, 0.05). UC and CD can be differentiated by Guanylin (GUC2A, p = 0.001), and Secretogranin-1 (CHGB p = 0.035). Active and quiescent disease can also be differentiated in UC and CD by CHGB (p ≤ 0.023) SPP24 (p ≤ 0.023) and AMBP (UC p = 0.046). Five peptides discriminating IBD activity and severity had very little-to-no correlation to erythrocyte sedimentation rate, C-reactive protein, white cell or platelet counts. Three of these peptides were found to be binding partners to SPP24 protein alongside other known matrix proteins. These proteins have the potential to improve diagnosis and

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

PubMed

Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q

2015-02-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine.

PubMed

Gerich, Mark E; Quiros, J Antonio; Marcin, James P; Tennyson, Linda; Henthorn, Maria; Prindiville, Thomas P

2010-11-01

6-mercaptopurine (6-MP) is used for the induction and maintenance of remission of inflammatory bowel disease (IBD). 6-MP is converted into 6-methylmercaptopurine (6-MMP) or 6-thioguanine nucleotides (6-TGN) intracellularly. Treatment response in IBD patients correlates with 6-TGN levels. This study prospectively evaluated the effect of allopurinol on 6-MP metabolites in adult and pediatric IBD patients. Additionally, we quantified the prevalence of preferential metabolism towards 6-MMP through a retrospective analysis of IBD patients. Twenty patients (10 adult; 10 pediatric) with evidence of preferential metabolism towards 6-MMP, (6-TGN<250 pmol/8×10⁸ RBCs and 6-MMP>5000 pmol/8×10⁸ RBCs) were prospectively treated with allopurinol 100 mg daily and up to 100 mg of 6-MP. 6-MP dose was adjusted after a 3-week metabolite measurement. The median dose of 6-MP for adults decreased from 100mg daily (range: 37.5-150 mg) to 25mg daily (range: 12.5-50 mg). The median dose of 6-MP for pediatric patients decreased from 50 mg (range: 25-50 mg) to 10.7 mg (range: 10.7 to 21.4 mg). Mean 6-TGN levels in all subjects increased from 197.4 (± 59) to 284.8 (± 107) pmol/8×10⁸ RBCs (p=0.0005). Mean 6-MMP levels in all subjects decreased from a mean of 7719.8 (± 4716) to 404.8 (± 332) pmol/8×10⁸ RBCs (p=0.0004). There were no complications associated with allopurinol therapy. Eighty-eight (30.9%) of 285 IBD patients had evidence of preferential metabolism towards 6-MMP. The proportion of preferential metabolism was equal in adults and pediatric patients. Our results indicate that the addition of allopurinol safely shifts metabolite production in both adult and pediatric IBD patients and that there is a high prevalence of preferential metabolism towards 6-MMP among IBD patients. Published by Elsevier B.V.

Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD

PubMed Central

Lee, Thomas; Clavel, Thomas; Smirnov, Kirill; Schmidt, Annemarie; Lagkouvardos, Ilias; Walker, Alesia; Lucio, Marianna; Michalke, Bernhard; Schmitt-Kopplin, Philippe; Fedorak, Richard; Haller, Dirk

2017-01-01

Objective Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT). Design The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention. Results Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates. Conclusions Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy. Trial registration number clinicaltrial.gov (NCT01067547). PMID:26848182

The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients.

PubMed

Riis, Lene; Vind, Ida; Vermeire, Severine; Wolters, Frank; Katsanos, Kostas; Politi, Patrizia; Freitas, João; Mouzas, Ioannis A; O'Morain, Colm; Ruiz-Ochoa, Victor; Odes, Selwyn; Binder, Vibeke; Munkholm, Pia; Moum, Bjørn; Stockbrügger, Reinhold; Langholz, Ebbe

2007-01-01

The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort. Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files. Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype. The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

Gut Microbiota Dysbiosis as Risk and Premorbid Factors of IBD and IBS Along the Childhood-Adulthood Transition.

PubMed

Putignani, Lorenza; Del Chierico, Federica; Vernocchi, Pamela; Cicala, Michele; Cucchiara, Salvatore; Dallapiccola, Bruno

2016-02-01

Gastrointestinal disorders, although clinically heterogeneous, share pathogenic mechanisms, including genetic susceptibility, impaired gut barrier function, altered microbiota, and environmental triggers (infections, social and behavioral factors, epigenetic control, and diet). Gut microbiota has been studied for inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) in either children or adults, while modifiable gut microbiota features, acting as risk and premorbid factors along the childhood-adulthood transition, have not been thoroughly investigated so far. Indeed, the relationship between variations of the entire host/microbiota/environmental scenario and clinical phenotypes is still not fully understood. In this respect, tracking gut dysbiosis grading may help deciphering host phenotype-genotype associations and microbiota shifts in an integrated top-down omics-based approach within large-scale pediatric and adult case-control cohorts. Large-scale gut microbiota signatures and host inflammation patterns may be integrated with dietary habits, under genetic and epigenetic constraints, providing gut dysbiosis profiles acting as risk predictors of IBD or IBS in preclinical cases. Tracking dysbiosis supports new personalized/stratified IBD and IBS prevention programmes, generating Decision Support System tools. They include (1) high risk or flare-up recurrence -omics-based dysbiosis profiles; (2) microbial and molecular biomarkers of health and disease; (3) -omics-based pipelines for laboratory medicine diagnostics; (4) health apps for self-management of score-based dietary profiles, which can be shared with clinicians for nutritional habit and lifestyle amendment; (5) -omics profiling data warehousing and public repositories for IBD and IBS profile consultation. Dysbiosis-related indexes can represent novel laboratory and clinical medicine tools preventing or postponing the disease, finally interfering with its natural history.

Patient-Perceived Usefulness of Online Electronic Medical Records: Employing Grounded Theory in the Development of Information and Communication Technologies for Use by Patients Living with Chronic Illness

PubMed Central

Winkelman, Warren J.; Leonard, Kevin J.; Rossos, Peter G.

2005-01-01

Objective: Patient use of online electronic medical records (EMR) holds the potential to improve health outcomes. The purpose of this study is to discover how patients living with chronic inflammatory bowel disease (IBD) value Internet-based patient access to electronic patient records. Design: This was a qualitative, exploratory, descriptive study using in-depth interviews and focus groups of a total of 12 patients with IBD of at least one-year duration at University Health Network, a tertiary care center in Toronto, Ontario. Results: Four themes have been elucidated that comprise a theoretical framework of patient-perceived information and communication technology usefulness: promotion of a sense of illness ownership, of patient-driven communication, of personalized support, and of mutual trust. Conclusions: For patients with chronic IBD, simply providing access to electronic medical records has little usefulness on its own. Useful technology for patients with IBD is multifaceted, self-care promoting, and integrated into the patient's already existing health and psychosocial support infrastructure. The four identified themes can serve as focal points for the evaluation of information technology designed for patient use, thus providing a patient-centered framework for developers seeking to adapt existing EMR systems to patient access and use for the purposes of improving health care quality and health outcomes. Further studies in other populations are needed to enhance generalizability of the emergent theory. PMID:15684128

Limited privacy protection and poor sensitivity: Is it time to move on from the statistical linkage key-581?

PubMed

Randall, Sean M; Ferrante, Anna M; Boyd, James H; Brown, Adrian P; Semmens, James B

2016-08-01

The statistical linkage key (SLK-581) is a common tool for record linkage in Australia, due to its ability to provide some privacy protection. However, newer privacy-preserving approaches may provide greater privacy protection, while allowing high-quality linkage. To evaluate the standard SLK-581, encrypted SLK-581 and a newer privacy-preserving approach using Bloom filters, in terms of both privacy and linkage quality. Linkage quality was compared by conducting linkages on Australian health datasets using these three techniques and examining results. Privacy was compared qualitatively in relation to a series of scenarios where privacy breaches may occur. The Bloom filter technique offered greater privacy protection and linkage quality compared to the SLK-based method commonly used in Australia. The adoption of new privacy-preserving methods would allow both greater confidence in research results, while significantly improving privacy protection. © The Author(s) 2016.

A New Method for Assessing How Sensitivity and Specificity of Linkage Studies Affects Estimation

PubMed Central

Moore, Cecilia L.; Amin, Janaki; Gidding, Heather F.; Law, Matthew G.

2014-01-01

Background While the importance of record linkage is widely recognised, few studies have attempted to quantify how linkage errors may have impacted on their own findings and outcomes. Even where authors of linkage studies have attempted to estimate sensitivity and specificity based on subjects with known status, the effects of false negatives and positives on event rates and estimates of effect are not often described. Methods We present quantification of the effect of sensitivity and specificity of the linkage process on event rates and incidence, as well as the resultant effect on relative risks. Formulae to estimate the true number of events and estimated relative risk adjusted for given linkage sensitivity and specificity are then derived and applied to data from a prisoner mortality study. The implications of false positive and false negative matches are also discussed. Discussion Comparisons of the effect of sensitivity and specificity on incidence and relative risks indicate that it is more important for linkages to be highly specific than sensitive, particularly if true incidence rates are low. We would recommend that, where possible, some quantitative estimates of the sensitivity and specificity of the linkage process be performed, allowing the effect of these quantities on observed results to be assessed. PMID:25068293

Linkages between public and non-government sectors in healthcare: A case study from Uttar Pradesh, India.

PubMed

Srivastava, Aradhana; Bhattacharyya, Sanghita; Gautham, Meenakshi; Schellenberg, Joanna; Avan, Bilal I

2016-12-01

Effective utilisation of collaborative non-governmental organisation (NGO)-public health system linkages in pluralistic health systems of developing countries can substantially improve equity and quality of services. This study explores level and types of linkages between public health sector and NGOs in Uttar Pradesh (UP), an underprivileged state of India, using a social science model for the first time. It also identifies gaps and challenges for effective linkage. Two NGOs were selected as case studies. Data collection included semi-structured in-depth interviews with senior staff and review of records and reporting formats. Formal linkages of NGOs with the public health system related to registration, participation in district level meetings, workforce linkages and sharing information on government-supported programmes. Challenges included limited data sharing, participation in planning and limited monitoring of regulatory compliances. Linkage between public health system and NGOs in UP was moderate, marked by frequent interaction and some reciprocity in information and resource flows, but weak participation in policy and planning. The type of linkage could be described as 'complementarity', entailing information and resource sharing but not joint action. Stronger linkage is required for sustained and systematic collaboration, with joint planning, implementation and evaluation.

Assessment of on-time vaccination coverage in population subgroups: A record linkage cohort study.

PubMed

Moore, Hannah C; Fathima, Parveen; Gidding, Heather F; de Klerk, Nicholas; Liu, Bette; Sheppeard, Vicky; Effler, Paul V; Snelling, Thomas L; McIntyre, Peter; Blyth, Christopher C

2018-05-31

Reported infant vaccination coverage at age 12 months in Australia is >90%. On-time coverage of the 2-4-6 month schedule and coverage in specific populations is rarely reported. We conducted a population-based cohort study of 1.9 million Australian births, 1996-2012, combining individual birth and perinatal records with immunisation records through probabilistic linkage. We assessed on-time coverage across 13 demographic and perinatal characteristics of diphtheria-tetanus-pertussis vaccines (DTP) defined as vaccination 14 days prior to the scheduled due date, to 30 days afterwards. On-time DTP vaccination coverage in non-Aboriginal infants was 88.1% for the 2-month dose, 82.0% for 4-month dose, and 76.7% for 6-month dose; 3-dose coverage was 91.3% when assessed at 12 months. On-time DTP coverage for Aboriginal infants was 77.0%, 66.5%, and 61.0% for the 2-4-6 month dose; 3-dose coverage at 12 months was 79.3%. Appreciable differences in on-time coverage were observed across population subgroups. On-time coverage in non-Aboriginal infants born to mothers with ≥3 previous pregnancies was 62.5% for the 6-month dose (47.9% for Aboriginal infants); up to 23.5 percentage points lower than for first-borns. Infants born to mothers who smoked during pregnancy had coverage 8.7-10.3 percentage points lower than infants born to non-smoking mothers for the 4- and 6-month dose. A linear relationship was apparent between increasing socio-economic disadvantage and decreasing on-time coverage. On-time coverage of the 2-4-6 month schedule is only 50-60% across specific population subgroups representing a significant avoidable public health risk. Aboriginal infants, multiparous mothers, and those who are socio-economically disadvantaged are key groups most likely to benefit from targeted programs addressing vaccine timeliness. Copyright © 2018. Published by Elsevier Ltd.

Identifying core NANDA-I nursing diagnoses, NIC interventions, NOC outcomes, and NNN linkages for heart failure.

PubMed

Park, Hyejin

2014-02-01

The purpose of the study was to identify the core nursing diagnoses, interventions, outcomes, and linkages using standardized nursing terminologies for patients with heart failure (HF). For this study a retrospective descriptive design was used. The frequently used NANDA-I, NIC, NOC, and NNN linkages were identified through 272 inpatient records of patients discharged with HF in a midwestern community. The findings indicate that the top 10 NANDA-I, NIC, and NOC accounted for more than 50% of nursing diagnoses, interventions, and outcomes. The most frequently used top 10 NNN linkages were identified for patients with HF. The identified core NANDA-I, NIC, NOC, and NNN linkages for HF from this study provide scope of practice of nurses working in HF clinics. © 2013 NANDA International, Inc.

Data linkage capabilities in Australia: practical issues identified by a Population Health Research Network 'Proof of Concept project'.

PubMed

Mitchell, Rebecca J; Cameron, Cate M; McClure, Rod J; Williamson, Ann M

2015-08-01

To describe the practical issues that need to be overcome to conduct national data linkage projects in Australia and propose recommendations to improve efficiency. Review of the processes, documentation and applications required to conduct national data linkage in Australia. The establishment of state and national data linkage centres in Australia has placed Australia at the forefront of research linking health-related administrative data collections. However, improvements are needed to reduce the clerical burden on researchers, simplify the process of obtaining ethics approval, improve data accessibility, and thus improve the efficiency of data linkage research. While a sound state and national data linkage infrastructure is in place, the current complexity, duplication and lack of cohesion undermines any attempts to conduct research involving national record linkage in a timely manner. Data linkage applications and Human Research Ethics Committee approval processes need to be streamlined and duplication removed, in order to reduce the administrative and financial burden on researchers if national data linkage research is to be viable. © 2015 Public Health Association of Australia.

Rheumatic Heart Disease-Attributable Mortality at Ages 5–69 Years in Fiji: A Five-Year, National, Population-Based Record-Linkage Cohort Study

PubMed Central

Parks, Tom; Kado, Joseph; Miller, Anne E.; Ward, Brenton; Heenan, Rachel; Colquhoun, Samantha M.; Bärnighausen, Till W.; Mirabel, Mariana; Bloom, David E.; Bailey, Robin L.; Tukana, Isimeli N.; Steer, Andrew C.

2015-01-01

Background Rheumatic heart disease (RHD) is considered a major public health problem in developing countries, although scarce data are available to substantiate this. Here we quantify mortality from RHD in Fiji during 2008–2012 in people aged 5–69 years. Methods and Findings Using 1,773,999 records derived from multiple sources of routine clinical and administrative data, we used probabilistic record-linkage to define a cohort of 2,619 persons diagnosed with RHD, observed for all-cause mortality over 11,538 person-years. Using relative survival methods, we estimated there were 378 RHD-attributable deaths, almost half of which occurred before age 40 years. Using census data as the denominator, we calculated there were 9.9 deaths (95% CI 9.8–10.0) and 331 years of life-lost (YLL, 95% CI 330.4–331.5) due to RHD per 100,000 person-years, standardised to the portion of the WHO World Standard Population aged 0–69 years. Valuing life using Fiji’s per-capita gross domestic product, we estimated these deaths cost United States Dollar $6,077,431 annually. Compared to vital registration data for 2011–2012, we calculated there were 1.6-times more RHD-attributable deaths than the number reported, and found our estimate of RHD mortality exceeded all but the five leading reported causes of premature death, based on collapsed underlying cause-of-death diagnoses. Conclusions Rheumatic heart disease is a leading cause of premature death as well as an important economic burden in this setting. Age-standardised death rates are more than twice those reported in current global estimates. Linkage of routine data provides an efficient tool to better define the epidemiology of neglected diseases. PMID:26371755

Genome scan for linkage to asthma using a linkage disequilibrium-lod score test.

PubMed

Jiang, Y; Slager, S L; Huang, J

2001-01-01

We report a genome-wide linkage study of asthma on the German and Collaborative Study on the Genetics of Asthma (CSGA) data. Using a combined linkage and linkage disequilibrium test and the nonparametric linkage score, we identified 13 markers from the German data, 1 marker from the African American (CSGA) data, and 7 markers from the Caucasian (CSGA) data in which the p-values ranged between 0.0001 and 0.0100. From our analysis and taking into account previous published linkage studies of asthma, we suggest that three regions in chromosome 5 (around D5S418, D5S644, and D5S422), one region in chromosome 6 (around three neighboring markers D6S1281, D6S291, and D6S1019), one region in chromosome 11 (around D11S2362), and two regions in chromosome 12 (around D12S351 and D12S324) especially merit further investigation.

Linkages Between Patient-centered Medical Homes and Addiction Treatment Organizations: Results From a National Survey.

PubMed

D'Aunno, Thomas; Pollack, Harold; Chen, Qixuan; Friedmann, Peter D

2017-04-01

To meet their aims of providing comprehensive and coordinated care, patient-centered medical homes (PCMHs) need to coordinate services for individuals with substance use disorders. Yet, the 14,000 addiction treatment (AT) organizations across the United States that provide services for more than 1 million individuals daily are generally ill-prepared to work with PCMHs (eg, AT organizations often lack electronic health records). To examine the extent to which AT organizations have formal linkages through contracts with PCMHs; to identify key dimensions of linkages between PCMHs and AT organizations (eg, shared use of electronic health records); to identify characteristics of AT organizations and their environments associated with these linkages. We draw on data from a 2014 nationally representative survey of directors and clinical supervisors from 695 AT organizations (n=1390 survey respondents). Thirty-eight percent of patients across the nation are receiving treatment in AT organizations linked by contracts to PCMHs. This number increases to 51% in states that expanded Medicaid (vs. only 6.2% of patients in non-Medicaid expansion states). Yet, the great majority of linkages are relatively weak; they do not include the exchange of patient information. Results from multivariable analyses show that larger, nonprofit and publicly owned AT organizations, as well as those located in the northeast and in states that expanded Medicaid coverage, are more likely to have contracts with PCMHs. Without stronger linkages between AT organizations and PCMHs or the development of other models that integrate services, individuals with substance abuse disorders may continue to receive uncoordinated care.

Geographical patterns of the standing and active human gut microbiome in health and IBD.

PubMed

Rehman, Ateequr; Rausch, Philipp; Wang, Jun; Skieceviciene, Jurgita; Kiudelis, Gediminas; Bhagalia, Ketan; Amarapurkar, Deepak; Kupcinskas, Limas; Schreiber, Stefan; Rosenstiel, Philip; Baines, John F; Ott, Stephan

2016-02-01

A global increase of IBD has been reported, especially in countries that previously had low incidence rates. Also, the knowledge of the human gut microbiome is steadily increasing, however, limited information regarding its variation on a global scale is available. In the light of the microbial involvement in IBDs, we aimed to (1) identify shared and distinct IBD-associated mucosal microbiota patterns from different geographical regions including Europe (Germany, Lithuania) and South Asia (India) and (2) determine whether profiling based on 16S rRNA transcripts provides additional resolution, both of which may hold important clinical relevance. In this study, we analyse a set of 89 mucosal biopsies sampled from individuals of German, Lithuanian and Indian origins, using bacterial community profiling of a roughly equal number of healthy controls, patients with Crohn's disease and UC from each location, and analyse 16S rDNA and rRNA as proxies for standing and active microbial community structure, respectively. We find pronounced population-specific as well as general disease patterns in the major phyla and patterns of diversity, which differ between the standing and active communities. The geographical origin of samples dominates the patterns of β diversity with locally restricted disease clusters and more pronounced effects in the active microbial communities. However, two genera belonging to the Clostridium leptum subgroup, Faecalibacteria and Papillibacter, display consistent patterns with respect to disease status and may thus serve as reliable 'microbiomarkers'. These analyses reveal important interactions of patients' geographical origin and disease in the interpretation of disease-associated changes in microbial communities and highlight the added value of analysing communities on both the 16S rRNA gene (DNA) and transcript (RNA) level. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

Irish study of high-density Schizophrenia families: Field methods and power to detect linkage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kendler, K.S.; Straub, R.E.; MacLean, C.J.

Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/ormore » hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one of whom had schizophrenia (S) or poor-outcome schizoaffective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. 75 refs., 6 tabs.« less

Understanding the health and social care needs of people living with IBD: A meta-synthesis of the evidence

PubMed Central

Kemp, Karen; Griffiths, Jane; Lovell, Karina

2012-01-01

AIM: To undertake a metasynthesis of qualitative studies to understand the health and social needs of people living with inflammatory bowel disease (IBD). METHODS: A systematic search strategy identified qualitative studies exploring the phenomenon of living with inflammatory bowel disease. Databases included MEDLINE, PsychInfo, EMBASE, CINAHL and the British Nursing Index via the OVID platform. Qualitative search filters were adapted from Hedges database (http://www.urmc.rochester.edu/hslt/miner/digital_library/tip_sheets/Cinahl_eb_filters.pdf). Qualitative empirical studies exploring the health and social needs of people living with inflammatory bowel disease were selected. Study eligibility and data extraction were independently completed using the Critical Appraisal Skills Programme for qualitative studies. The studies were analysed and synthesised using metasynthesis methodology. The themes from the studies allowed for common translations into a new interpretation of the impact of living with inflammatory bowel disease. RESULTS: Of 1395 studies, six published studies and one unpublished thesis fulfilled the inclusion criteria. First iteration of synthesis identified 16 themes, 2nd iteration synthesised these into three main 2nd order constructs: “detained by the disease”; “living in a world of disease” and “wrestling with life”. “Detained by the disease” is the fear of incontinence, the behaviour the patients display due to the fear, and the impact this has on the individual, such as social isolation and missing out on life events. All of these serve to “pull” the patient back from normal living. “Living in a world of disease” is the long term effects of living with a long term condition and the fear of these effects. “Wrestling with life” is the continued fight to thrive, the “push” to continue normal living. CONCLUSION: The metasynthesis provides a comprehensive representation of living with IBD. The unmistakeable burden of

Menopausal hormone usage and breast cancer in Saskatchewan: a record-linkage cohort study.

PubMed

Risch, H A; Howe, G R

1994-04-01

The association between the occurrence of carcinoma of the breast and previous usage of menopausal estrogens, progestins, and oral contraceptives is examined in a record-linkage study using the Saskatchewan Health Prescription-Drug-Plan Database. Saskatchewan Health is a governmental agency that funds publicly insured health care for essentially all residents of the province. For this study, all women aged 43-49 years in 1976 resident in Saskatchewan were identified from the Saskatchewan Health master registration file. These women were linked by registration beneficiary number to the Drug-Plan Database for the period from January 1976 to June 1987 and to the Provincial Cancer Registry Database for the period from March 1960 to December 1990. The fact and date of death or emigration from the province were obtained through the annual updates of the health plan. Of the 33,003 women initially in the cohort, 213 had a breast cancer diagnosed before 1976 and were omitted from this analysis. Between 1976 and 1990, 742 new primary breast cancer cases occurred. Women taking estrogens unopposed by progestins had an elevated risk of breast cancer, the risk increasing by 7% (relative risk = 1.072, 95% confidence interval 1.02-1.13; p = 0.008) for each 252 tablets used (approximately 1 year of use). Usage of estrogens opposed by progestins showed no association with risk (p = 0.48). Women taking oral contraceptives during this follow-up period also had a higher risk, increasing by 14% (relative risk = 1.144, 95% confidence interval 1.05-1.24; p = 0.002) for every 252 tablets used. These 1-year risk elevations are small but become appreciable at longer durations. For example, at 5 years of unopposed estrogen use, the relative risk is 1.42; for 5 years of oral contraceptive use, it is 1.96.

Frequent emergency department presentations among people who inject drugs: A record linkage study.

PubMed

Nambiar, Dhanya; Stoové, Mark; Dietze, Paul

2017-06-01

People who inject drugs (PWID) have been described as frequent users of health services such as emergency departments (EDs), however few studies have described demographic factors, patterns of substance use and previous health service use associated with frequent use of EDs in this population. Using a combination of self-reported data from a cohort of PWID and administrative ED data obtained through record linkage, we identified longitudinal factors associated with the use of ED services. Bivariate and multivariate analyses were conducted using negative binomial regression to identify exposures associated with both cumulative ED presentations, and logistic regression to identify exposures of frequent ED presentations (defined as three or more annual presentations). Among 612 PWID, over half (58%) presented to EDs at least once and over a third (36%) presented frequently between January 2008 and June 2013. Frequent and cumulative ED presentations were associated with reporting the main drug of choice as cannabis (AOR:1.42, 95%CI:1.07-1.89 and AIRR:2.96, 95%CI:1.44-6.07 respectively) or methamphetamine (AOR:1.62, 95%CI:1.17-2.2 and AIRR:2.42, 95%CI:1.08-5.46 respectively) compared to heroin, and past month use of mental health (AOR:1.42, 95%CI:1.08-1.85 and AIRR:3.32, 95%CI:1.69-6.53 respectively) and outpatient services (AOR:1.47, 95%CI: 1.00-2.16 and AIRR:0.95, 95%CI 1.52-10.28 respectively). PWID who are frequent users of EDs are likely to have complex health and substance use-related needs. EDs should actively refer people who present with cannabis and methamphetamine dependence to harm reduction services. Harm reduction services should ensure people referred from EDs are screened for co-occurring mental health conditions and receive adequate support. Copyright © 2017 Elsevier B.V. All rights reserved.

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice

PubMed Central

Vivio, Emily E.; Kanuri, Navya; Gilbertsen, Joanna J.; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M.

2016-01-01

Background and aims: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn’s disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Methods: Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. Results: One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn’s Disease Activity Index (p = 0.04) and Harvey–Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Conclusions: Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. PMID:26681763

Urinalysis of MMX-mesalazine as a tool to monitor 5-ASA adherence in daily IBD practice.

PubMed

Römkens, Tessa E H; Te Morsche, Rene; Peters, Wilbert; Burger, David M; Hoentjen, Frank; Drenth, Joost P H

2018-03-01

Adherence is pivotal but challenging in ulcerative colitis (UC) treatment. Many methods to assess adherence are subjective or have limitations. (Nac-)5-aminosalicylic acid (5-ASA) urinalysis by high-performance liquid chromatography (HPLC) seems feasible and reproducible in healthy volunteers. We performed a prospective study in adult quiescent UC patients to evaluate the feasibility of spot (Nac-)5-ASA urinalysis by HPLC to assess adherence in daily inflammatory bowel disease (IBD) care. Twenty-nine patients (51.7% male, mean age 52 ± 11 years) were included (median FU 9 months) and weekly spot urine samples were collected. We found large variation in spot (Nac-)5-ASA urinary excretion that was unrelated to brand, dosing schedule or dosage of 5-ASA. In conclusion, spot (Nac-)5-ASA urinalysis is not applicable to assess 5-ASA adherence in daily IBD care. © 2017 The British Pharmacological Society.

Evaluation of IL-17B and IL-17F mRNA expression in peripheral blood mononuclear cells and association with clinical outcome of IBD patients.

PubMed

Safari, Mohammad Taghi; Chaleshi, Vahid; Tarban, Peyman; Nourian, Mahyar; Balaii, Hedieh; Shahrokh, Shabnam; Asadzadeh Aghdaei, Hamid

2017-01-01

In this study, we determined the gene expression analysis of IL-17 gene family for early detection of subclinical inflammation among IBD patients. Cytokines have a vital role in the pathogenesis of inflammatory bowel disease (IBD). Interleukin-17 is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17F is mainly involved in mucosal host defense mechanisms whereas the functions of IL-17B remain largely elusive. In this cross-sectional study, IBD patients divided into two active and inactive groups. Peripheral blood mononuclear cells (PBMCs) from 38 IBD patients which 20 inactive samples and 18 active individuals were collected. Changes of IL-17 F and IL-17B mRNA expression level evaluated by quantitative-real time-PCR. mRNA expression level of IL-17B and IL-17F in CD, UC, active and inactive groups have been assessed and there were no significant differences (P>0.05). Patients were classified into five different categories as follows: i) 5ASA; ii) 5ASA + Pred; iii) 5ASA + AZA; iv) 5ASA + Pred + AZA; v) 5ASA + Pred + AZA + IFX according to medication usage, expression of IL-17F and IL-17B had no differences (p>0.05). Evaluation of IL-17B and IL-17F mRNA expression level illustrate no difference among active and inactive patients. Therefore, IL-17B and IL-17F are not biomarkers in an Iranian IBD patients.

The benefits of data linkage for firefighter injury surveillance

PubMed Central

Widman, Shannon A; LeVasseur, Michael T; Tabb, Loni P

2018-01-01

Background While survey data are available for national estimates of fire events and firefighter fatalities, data on firefighter injury at the national and local levels remain incomplete and unreliable. Data linkage provides a vehicle to maximise case detection and deepen injury description for the US fire service. Methods By linking departmental Human Resources records, despatch data, workers' compensation and first reports of injury, researchers were able to describe reported non-fatal injuries to 3063 uniformed members of the Philadelphia Fire Department (PFD), for the period of 2005 through 2013. Results Among all four databases, the overall linkage rate was 56%. Among three of the four databases, the linkage rate was 88%. Because there was duplication of some variables among the datasets, we were able to deeply describe all the linked injuries in the master database. 45.5% of uniformed PFD members reported at least one injury during the study period. Strains, falls, burns and struck-by injuries were the most common causes. Burns resulted in the highest lost time claim payout, and strains accounted for the highest medical claim cost. More than 70% of injuries occurred in the first 15 years of experience. Discussion Data linkage provided three new benefits: (1) creation of a new variable—years of experience, (2) reduction of misclassification bias when determining cause of injury, leading to more accurate estimates of cost and (3) visualisation of injury rates when controlling for the number of fire department responses, allowing for the generation of hypotheses to investigate injury hot spots. PMID:28196830

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice.

PubMed

Vivio, Emily E; Kanuri, Navya; Gilbertsen, Joanna J; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M; Ciorba, Matthew A

2016-04-01

Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn's disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn's Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD.

PubMed

Ciucci, Thomas; Ibáñez, Lidia; Boucoiran, Agathe; Birgy-Barelli, Eléonore; Pène, Jérôme; Abou-Ezzi, Grazia; Arab, Nadia; Rouleau, Matthieu; Hébuterne, Xavier; Yssel, Hans; Blin-Wakkach, Claudine; Wakkach, Abdelilah

2015-07-01

Under both physiological and pathological conditions, bone volume is determined by the rate of bone formation by osteoblasts and bone resorption by osteoclasts. Excessive bone loss is a common complication of human IBD whose mechanisms are not yet completely understood. Despite the role of activated CD4(+) T cells in inflammatory bone loss, the nature of the T cell subsets involved in this process in vivo remains unknown. The aim of the present study was to identify the CD4(+) T cell subsets involved in the process of osteoclastogenesis in vivo, as well as their mechanism of action. CD4(+) T cells were studied in IL10-/- mice and Rag1-/- mice adoptively transferred with naive CD4(+)CD45RB(high) T cells, representing two well-characterised animal models of IBD and in patients with Crohn's disease. They were phenotypically and functionally characterised by flow cytometric and gene expression analysis, as well as in in vitro cocultures with osteoclast precursors. In mice, we identified bone marrow (BM) CD4(+) T cells producing interleukin (IL)-17 and tumour necrosis factor (TNF)-α as an osteoclastogenic T cell subset referred to as Th17 TNF-α(+) cells. During chronic inflammation, these cells migrate to the BM where they survive in an IL-7-dependent manner and where they promote the recruitment of inflammatory monocytes, the main osteoclast progenitors. A population equivalent to the Th17 TNF-α(+) cells was also detected in patients with Crohn's disease. Our results highlight the osteoclastogenic function of the Th17 TNF-α(+) cells that contribute to bone loss in vivo in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of IL-17B and IL-17F mRNA expression in peripheral blood mononuclear cells and association with clinical outcome of IBD patients

PubMed Central

Safari, Mohammad Taghi; Chaleshi, Vahid; Tarban, Peyman; Nourian, Mahyar; Balaii, Hedieh; Shahrokh, Shabnam; Asadzadeh Aghdaei, Hamid

2017-01-01

Aim: In this study, we determined the gene expression analysis of IL-17 gene family for early detection of subclinical inflammation among IBD patients. Background: Cytokines have a vital role in the pathogenesis of inflammatory bowel disease (IBD). Interleukin-17 is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17F is mainly involved in mucosal host defense mechanisms whereas the functions of IL-17B remain largely elusive. Methods: In this cross-sectional study, IBD patients divided into two active and inactive groups. Peripheral blood mononuclear cells (PBMCs) from 38 IBD patients which 20 inactive samples and 18 active individuals were collected. Changes of IL-17 F and IL-17B mRNA expression level evaluated by quantitative-real time-PCR. Results: mRNA expression level of IL-17B and IL-17F in CD, UC, active and inactive groups have been assessed and there were no significant differences (P>0.05). Patients were classified into five different categories as follows: i) 5ASA; ii) 5ASA + Pred; iii) 5ASA + AZA; iv) 5ASA + Pred + AZA; v) 5ASA + Pred + AZA + IFX according to medication usage, expression of IL-17F and IL-17B had no differences (p>0.05). Conclusion: Evaluation of IL-17B and IL-17F mRNA expression level illustrate no difference among active and inactive patients. Therefore, IL-17B and IL-17F are not biomarkers in an Iranian IBD patients. PMID:29511476

Association between interpregnancy interval and future risk of maternal cardiovascular disease-a population-based record linkage study.

PubMed

Ngo, A D; Roberts, C L; Figtree, G

2016-07-01

To examine the associations between interpregnancy interval and later maternal cardiovascular disease (CVD) risk. Population-based record linkage study. New South Wales, Australia, 1994-2011. 216 467 women having first and second liveborn singleton infants, excluding those with an existing or pregnancy-related CVD risk factor. We linked birth records of mothers to the mothers' subsequent CVD (coronary heart disease, cerebrovascular events, and chronic heart failure) hospitalisation or death. Multivariable Cox proportional hazard regression was used to estimate adjusted hazard ratios (AHR) [95% confidence interval (CI)], accounting for maternal age, parity, socioeconomic status, and smoking during pregnancy. The first occurrence of a CVD hospitalisation or death after the second birth. In comparison with mothers with an interpregnancy interval of 18-23 months (reference category), the AHR among mothers with interpregnancy interval of <12 months was 1.56 (95% CI 1.18-2.07) and of 12-17 months was 1.13 (95% CI 0.84-1.51). The AHRs were 1.40 (95% CI 1.07-1.82), 1.87 (95% CI 1.21-2.89), and 3.41 (95% CI 1.07-10.91), corresponding to interpregnancy intervals of 24-59, 60-119, and ≥120 months, respectively. AHRs of specific CVD categories showed a similar pattern. Interpregnancy interval is associated with the risk of subsequent maternal CVD in a J-shaped fashion. The association is independent of the existing and pregnancy-related CVD risk factors analysed. Both short and long interpregnancy intervals can be used as risk markers to identify women with an elevated CVD risk later in life. Interpregnancy interval is associated with the risk of subsequent maternal cardiovascular disease in a J-shaped fashion. © 2015 Royal College of Obstetricians and Gynaecologists.

Blockade of αEβ7 integrin suppresses accumulation of CD8+ and Th9 lymphocytes from patients with IBD in the inflamed gut in vivo.

PubMed

Zundler, Sebastian; Schillinger, Daniela; Fischer, Anika; Atreya, Raja; López-Posadas, Rocío; Watson, Alastair; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2017-11-01

Therapeutically targeting lymphocyte adhesion is of increasing relevance in IBD. Yet, central aspects of the action of antiadhesion compounds are incompletely understood. We investigated the role of αEβ7 and α4β7 integrins and their blockade by vedolizumab and etrolizumab for trafficking of IBD T lymphocytes in an in vivo model of homing to and retention in the inflamed gut. We explored integrin expression in patients with IBD by flow cytometry and immunohistochemistry, while regulation of integrins was studied in T cell cultures. The functional relevance of integrins was assessed by adhesion assays and a recently established humanised mouse model in dextran sodium sulfate-treated immunodeficient mice. High expression of αEβ7 was noted on CD8 + and CD4 + Th9 cells, while α4β7 was expressed on CD8 + , Th2 and Th17 cells. T cell receptor stimulation and transforming growth factor β were key inducers of αEβ7 on human T cells, while butyric acid suppressed αEβ7. In comparison to α4β7 blockade via vedolizumab, blockade of β7 via etrolizumab surrogate antibody superiorly reduced colonic numbers of CD8 + and Th9 cells in vivo after 3 hours, while no difference was noted after 0.5 hours. AEβ7 expression was higher on CD8 + T cells from patients with IBD under vedolizumab therapy. AEβ7 is of key relevance for gut trafficking of IBD CD8 + T cells and CD4 + Th9 cells in vivo and mainly retention might account for this effect. These findings indicate that blockade of αEβ7 in addition to α4β7 may be particularly effective in intestinal disorders with expansion of CD8 + and Th9 cells such as IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

U.S. Maternally Linked Birth Records May Be Biased for Hispanics and Other Population Groups

PubMed Central

LEISS, JACK K.; GILES, DENISE; SULLIVAN, KRISTIN M.; MATHEWS, RAHEL; SENTELLE, GLENDA; TOMASHEK, KAY M.

2010-01-01

Purpose To advance understanding of linkage error in U.S. maternally linked datasets, and how the error may affect results of studies based on the linked data. Methods North Carolina birth and fetal death records for 1988-1997 were maternally linked (n=1,030,029). The maternal set probability, defined as the probability that all records assigned to the same maternal set do in fact represent events to the same woman, was used to assess differential maternal linkage error across race/ethnic groups. Results Maternal set probabilities were lower for records specifying Asian or Hispanic race/ethnicity, suggesting greater maternal linkage error. The lower probabilities for Hispanics were concentrated in women of Mexican origin who were not born in the United States. Conclusions Differential maternal linkage error may be a source of bias in studies using U.S. maternally linked datasets to make comparisons between Hispanics and other groups or among Hispanic subgroups. Methods to quantify and adjust for this potential bias are needed. PMID:20006273

Patient-Reported Outcomes of Quality of Life, Functioning, and GI/Psychiatric Symptom Severity in Patients with Inflammatory Bowel Disease (IBD).

PubMed

IsHak, Waguih W; Pan, Dana; Steiner, Alexander J; Feldman, Edward; Mann, Amy; Mirocha, James; Danovitch, Itai; Melmed, Gil Y

2017-05-01

Patients with inflammatory bowel disease (IBD) are at risk for psychiatric disorders that impact symptom experience and health-related quality of life (HRQOL). Therefore, comprehensive biopsychosocial assessments should be considered in ambulatory care settings. Patient-Reported Outcomes Measurement Information System (PROMIS) measures created by the National Institutes of Health have shown construct validity in a large IBD internet-based cohort, but their validity in ambulatory settings has not been examined. We sought to validate PROMIS patient-reported measures of HRQOL, functioning, and psychiatric symptom severity at a tertiary IBD clinic. Adult patients (n = 110) completed the PROMIS Global Health scale, PROMIS-29, SF-12, and WHODAS 2.0. Pearson's correlation coefficients (r) determined the relationships between scores to validate the PROMIS Global Health Physical and Mental metrics, compared with the SF-12 and WHODAS 2.0. We compared these measures by disease subtype of Crohn's disease or ulcerative colitis. PROMIS measures were highly correlated (r range = 0.64-0.82) with standard measures of HRQOL and functioning. On the PROMIS Global Health measures, 20.9% had impaired physical health, and 13.7% had impaired mental health. Impairments were reported in pain interference (20% of patients), anxiety (18.2%), satisfaction with social role (15.5%), physical functioning (10.9%), fatigue (10%), depression (7.3%), and sleep disturbance (5.5%). Patients with Crohn's disease had worse scores than those with ulcerative colitis on measures of the global physical health (P = 0.027), physical functioning (P = 0.047), and pain interference (P = 0.0009). PROMIS instruments provide valid assessment of HRQOL and functioning in ambulatory adults with IBD. Of note, patients with Crohn's disease demonstrated significantly worse impairments than those with ulcerative colitis.

[MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

PubMed

Liu, Ren-Hu; Meng, Jin-Ling

2003-05-01

MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor.

Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort.

PubMed

Romberg-Camps, Mariëlle; Kuiper, Edith; Schouten, Leo; Kester, Arnold; Hesselink-van de Kruijs, Martine; Limonard, Charles; Bos, Rens; Goedhard, Jelle; Hameeteman, Wim; Wolters, Frank; Russel, Maurice; Stockbrügger, Reinhold; Dagnelie, Pieter

2010-08-01

The aim was to evaluate overall and disease-specific mortality in a population-based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. At the censoring date, 72 out of 1187 patients had died (21 Crohn's disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7-1.6) for CD, 0.9 (0.7-1.2) for UC and 0.7 (0.2-1.7) for IC. Disease-specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8-16.4) and UC (SMR 3.4, 95% CI: 1.4-7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2-0.9). In this population-based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow-up. Caution in interpreting the finding on mortality risk from cancer is needed as follow-up was probably to short to observe IBD-related cancers.

Variation in hospital rates of induction of labour: a population-based record linkage study.

PubMed

Nippita, Tanya A; Trevena, Judy A; Patterson, Jillian A; Ford, Jane B; Morris, Jonathan M; Roberts, Christine L

2015-09-02

To examine interhospital variation in rates of induction of labour (IOL) to identify potential targets to reduce high rates of practice variation. Population-based record linkage cohort study. New South Wales, Australia, 2010-2011. All women with live births of ≥24 weeks gestation in 72 hospitals. Variation in hospital IOL rates adjusted for differences in case-mix, according to 10 mutually exclusive groups derived from the Robson caesarean section classification; groups were categorised by parity, plurality, fetal presentation, prior caesarean section and gestational age. The overall IOL rate was 26.7% (46,922 of 175,444 maternities were induced), ranging from 9.7% to 41.2% (IQR 21.8-29.8%) between hospitals. Nulliparous and multiparous women at 39-40 weeks gestation with a singleton cephalic birth were the greatest contributors to the overall IOL rate (23.5% and 20.2% of all IOL respectively), and had persisting high unexplained variation after adjustment for case-mix (adjusted hospital IOL rates ranging from 11.8% to 44.9% and 7.1% to 40.5%, respectively). In contrast, there was little variation in interhospital IOL rates among multiparous women with a singleton cephalic birth at ≥41 weeks gestation, women with singleton non-cephalic pregnancies and women with multifetal pregnancies. 7 of the 10 groups showed high or moderate unexplained variation in interhospital IOL rates, most pronounced for women at 39-40 weeks gestation with a singleton cephalic birth. Outcomes associated with divergent practice require determination, which may guide strategies to reduce practice variation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis.

PubMed

Todhunter, Rory J; Casella, George; Bliss, Stuart P; Lust, George; Williams, Alma Jo; Hamilton, Samuel; Dykes, Nathan L; Yeager, Amy E; Gilbert, Robert O; Burton-Wurster, Nancy I; Mellersh, Cathryn C; Acland, Gregory M

2003-04-01

To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

[Integrated management of patients with chronic inflammatory bowel disease in the Rhine-Main Region: results of the first integrated health-care project IBD in Germany].

PubMed

Blumenstein, I; Tacke, W; Filmann, N; Zosel, C; Bock, H; Heuzeroth, V; Zeuzem, S; Schröder, O

2013-07-01

In our previous studies investigating the drug therapy in patients suffering from inflammatory bowel disease (IBD) in the Rhein-Main region, Germany, we detected serious discrepancies between treatment reality and treatment guidelines. Consecutively, patient outcome in this cohort was compromised. Following this pilot project a network between primary deliverers of care for IBD patients and one large health-care insurance company [BKK Taunus (Gesundheit), the second largest insurance company in Hessen, Germany] was established. An analysis of treatment and socioeconomic data from 220 IBD patients (Crohn's disease - CD = 96, ulcerative colitis - UC = 124) entering the integrative health-care programme between 1.1.-30.9.2009 was performed. Remission rates for CD and UC in the integrated health-care programme could be improved from 60 - 73 % (CD) and from 61 - 79 % (UC). Guideline-conform treatment was observed in 81 % of patients with CD and 85 % with UC, respectively. Although medication costs increased, total costs could be cut by 162 304.- €, as secondary costs for hospitalisation and days off work could be reduced. The study shows that networking of deliverers of care for IBD patients with health insurances provides an excellent possibility to optimise medical treatment and can cut down costs significantly. © Georg Thieme Verlag KG Stuttgart · New York.

Knowledge of Fecal Calprotectin and Infliximab Trough Levels Alters Clinical Decision-making for IBD Outpatients on Maintenance Infliximab Therapy.

PubMed

Huang, Vivian W; Prosser, Connie; Kroeker, Karen I; Wang, Haili; Shalapay, Carol; Dhami, Neil; Fedorak, Darryl K; Halloran, Brendan; Dieleman, Levinus A; Goodman, Karen J; Fedorak, Richard N

2015-06-01

Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an objective marker of disease activity or therapeutic drug monitoring affects clinical decisions regarding maintenance infliximab therapy in outpatients with IBD. Consecutive patients with IBD on maintenance infliximab therapy were invited to participate by providing preinfusion stool and blood samples. Fecal calprotectin (FCP) and infliximab trough levels (ITLs) were measured by enzyme linked immunosorbent assay. Three decisions were compared: (1) actual clinical decision, (2) algorithmic FCP or ITL decisions, and (3) expert panel decision based on (a) clinical data, (b) clinical data plus FCP, and (c) clinical data plus FCP plus ITL. In secondary analysis, Receiver-operating curves were used to assess the ability of FCP and ITL in predicting clinical disease activity or remission. A total of 36 sets of blood and stool were available for analysis; median FCP 191.5 μg/g, median ITLs 7.3 μg/mL. The actual clinical decision differed from the hypothetical decision in 47.2% (FCP algorithm); 69.4% (ITL algorithm); 25.0% (expert panel clinical decision); 44.4% (expert panel clinical plus FCP); 58.3% (expert panel clinical plus FCP plus ITL) cases. FCP predicted clinical relapse (area under the curve [AUC] = 0.417; 95% confidence interval [CI], 0.197-0.641) and subtherapeutic ITL (AUC = 0.774; 95% CI, 0.536-1.000). ITL predicted clinical remission (AUC = 0.498; 95% CI, 0.254-0.742) and objective remission (AUC = 0.773; 95% CI, 0.622-0.924). Using FCP and ITLs in addition to clinical data results in an increased number of decisions to optimize management in outpatients with IBD on stable maintenance infliximab therapy.

Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients

PubMed Central

Peng, Xiang; Zhi, Min; Wei, Ming; Li, Ting-Ting; Zhang, Min; Zhang, Yuan-Qi; He, Huan; Su, Mingli; Wang, Wei; Chen, Jun-rong; Tang, Jian; Gao, Xiang; Hu, Pin-Jin; Liang, Xiao-Yan

2017-01-01

Abstract The effectiveness of thalidomide in treating inflammatory bowel disease (IBD) has been widely recognized. Meanwhile, many serious adverse drug reactions have been observed, but no know reports on ovarian reserve function. Female patients, ranging in age between 18 and 40, were referred to our institution to undergo sex hormone detection and ultrasonic scanning for ovarian function assessment, between February 1, 2016 and September 31, 2016. Thirty-three patients treated with thalidomide (group A), 73 patients without thalidomide (group B), and 78 healthy women as control were studied. Menstrual disorder was higher in group A than group B (78.8% vs 57.2%, P < 0.05), and both groups were higher than control group 33.3%, P < 0.05. Anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) in group A were lower than group B, P < 0.05, while estradiol (E2) and follicle-stimulating hormone (FSH) levels were no different between 2 groups. Crohn Disease Endoscopic Index of Severity (CDEIS) and thalidomide were the independent risk factors in diminished ovarian reserve (DOR), and when dose reached 75 mg/day, 5 g total, or when treatment time reached 10 months respectively. These influence may increasing (P < 0.05), but they may recover after stopping (P < 0.05). Thalidomide was an independent risk factor leading to DOR in female IBD patients, the influence may increasing when daily dose and accumulated dose reached 75 mg/day and 5 g total dose, but may be reversed by stopping. PMID:28538364

The benefits of data linkage for firefighter injury surveillance.

PubMed

Widman, Shannon A; LeVasseur, Michael T; Tabb, Loni P; Taylor, Jennifer A

2018-02-01

While survey data are available for national estimates of fire events and firefighter fatalities, data on firefighter injury at the national and local levels remain incomplete and unreliable. Data linkage provides a vehicle to maximise case detection and deepen injury description for the US fire service. By linking departmental Human Resources records, despatch data, workers' compensation and first reports of injury, researchers were able to describe reported non-fatal injuries to 3063 uniformed members of the Philadelphia Fire Department (PFD), for the period of 2005 through 2013. Among all four databases, the overall linkage rate was 56%. Among three of the four databases, the linkage rate was 88%. Because there was duplication of some variables among the datasets, we were able to deeply describe all the linked injuries in the master database. 45.5% of uniformed PFD members reported at least one injury during the study period. Strains, falls, burns and struck-by injuries were the most common causes. Burns resulted in the highest lost time claim payout, and strains accounted for the highest medical claim cost. More than 70% of injuries occurred in the first 15 years of experience. Data linkage provided three new benefits: (1) creation of a new variable-years of experience, (2) reduction of misclassification bias when determining cause of injury, leading to more accurate estimates of cost and (3) visualisation of injury rates when controlling for the number of fire department responses, allowing for the generation of hypotheses to investigate injury hot spots. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hepatotoxicity associated with 6-methyl mercaptopurine formation during azathioprine and 6-mercaptopurine therapy does not occur on the short-term during 6-thioguanine therapy in IBD treatment.

PubMed

van Asseldonk, Dirk P; Seinen, Margien L; de Boer, Nanne K H; van Bodegraven, Ad A; Mulder, Chris J

2012-02-01

High concentrations of methylated thiopurine metabolites, such as 6-methyl mercaptopurine, are associated with hepatotoxicity during administration of the conventional thiopurines azathioprine or 6-mercaptopurine in IBD patients. Metabolization of the non-conventional thiopurine 6-thioguanine does not generate 6-methyl mercaptopurine. Hence, the aim of our study was to evaluate hepatotoxicity during 6-thioguanine in IBD patients who previously failed conventional thiopurines due to 6-methyl mercaptopurine associated hepatotoxicity. A retrospective single center intercept cohort study was performed of IBD patients using 6-thioguanine between January 2006 and July 2010 after failing conventional thiopurine therapy due to 6-methyl mercaptopurine associated hepatotoxicity. The primary outcome was the occurrence of 6-thioguanine induced hepatotoxicity, scaled according to the Common Terminology Criteria for Adverse Events. Nineteen patients were included. Median duration of 6-thioguanine therapy (median daily dosage 21 mg (9-24)) was 23 weeks (6-96). Hepatotoxicity did not reoccur in 15 out of 19, whereas grade 1 toxicity persisted in 4 patients (p<0.001). Median aspartate aminotransferase and alanine aminotransferase concentrations decreased from 34 U/l (20-59) and 64 U/l (15-175) to 23 U/l (18-40; p=0.003) and 20 U/l (14-48; p=0.019), respectively. Hepatotoxicity does not reoccur during 6-thioguanine treatment in most IBD patients who failed conventional thiopurines due to 6-methyl mercaptopurine associated hepatotoxicity. Hence, at least at short-term, 6-thioguanine appears a justifiable alternative thiopurine for these IBD patients. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD.

PubMed

Thorkelson, Gregory; Bielefeldt, Klaus; Szigethy, Eva

2016-06-01

The use of psychotropic medications, particularly antidepressants, is common in patients with inflammatory bowel disease (IBD) in spite of a lack of their robust efficacy in this population. This review provides an overview of the use trends of different classes of antidepressant and anti-anxiety medication and their effects on mood, nervous system function, gastrointestinal physiology and immunity drawing from the literature available in the general population, other medical conditions, and when available, patients with IBD. It also covers the evidence base for the actions, efficacy, and potential complications of antidepressants organized by different classes. We conducted a PubMed search of articles relating the different drug classes probed to the terms above in different populations of interest. All types of articles were accepted including case reports and series, open and randomized trials, reviews, and expert opinion. We also examined the reference lists of the publications found. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are the most commonly prescribed agents for anxiety and depression in patients with IBD, though their efficacy for these conditions in the general population are mild to moderate at best. SSRIs are generally well tolerated, though at higher doses, they, like most antidepressant classes, can be associated with activation, serotonergic syndrome, and increased suicidal ideation. TCAs have many more serious side effects but have some shown efficacy for functional GI symptoms. A newer class, the serotonin noradrenergic reuptake inhibitors (SNRIs), can be effective for refractory depression, anxiety and chronic pain syndromes with a side effect profile similar to both SSRIs and more mild manifestations of TCAs. Mirtazapine has moderate efficacy for depression if sedation and weight gain side effects are tolerated and some small support for use in nausea and vomiting. Bupropion targets dopamine and

Diagnostic outcomes following childhood non-specific abdominal pain: a record-linkage study.

PubMed

Thornton, G C D; Goldacre, M J; Goldacre, R; Howarth, L J

2016-04-01

Non-specific abdominal pain (NSAP) is the most common diagnosis on discharge following admission for abdominal pain in childhood. Our aim was to determine the risk of subsequent hospital diagnosis of organic and functional gastroenterological conditions following a diagnosis of NSAP, and to assess the persistence of this risk. An NSAP cohort of 268,623 children aged 0-16 years was constructed from linked English Hospital Episode Statistics from 1999 to 2011. The control cohort (1,684,923 children, 0-16 years old) comprised children hospitalised with unrelated conditions. Clinically relevant outcomes were selected and standardised rate ratios were calculated. From the NSAP cohort, 15,515 (5.8%) were later hospitalised with bowel pathology and 13,301 (5%) with a specific functional disorder. Notably, there was a 4.84 (95% CI 4.45 to 5.27) times greater risk of Crohn's disease following NSAP and a 4.23 (4.13 to 4.33) greater risk of acute appendicitis than in the control cohort. The risk of irritable bowel syndrome (IBS) was 7.22 (6.65 to 7.85) times greater following NSAP. The risks of inflammatory bowel disease (IBD), IBS and functional disorder (unspecified) were significantly increased in all age groups except <2-year-olds. The risk of underlying bowel pathology remained raised up to 10 years after first diagnosis with NSAP. Only a small proportion of those with NSAP go on to be hospitalised with underlying bowel pathology. However, their risk is increased even at 10 years after the first hospital admission with NSAP. Diagnostic strategies need to be assessed and refined and active surveillance employed for children with NSAP. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Development of an index to define overall disease severity in IBD.

PubMed

Siegel, Corey A; Whitman, Cynthia B; Spiegel, Brennan M R; Feagan, Brian; Sands, Bruce; Loftus, Edward V; Panaccione, Remo; D'Haens, Geert; Bernstein, Charles N; Gearry, Richard; Ng, Siew C; Mantzaris, Gerassimos J; Sartor, Balfour; Silverberg, Mark S; Riddell, Robert; Koutroubakis, Ioannis E; O'Morain, Colm; Lakatos, Peter L; McGovern, Dermot P B; Halfvarson, Jonas; Reinisch, Walter; Rogler, Gerhard; Kruis, Wolfgang; Tysk, Curt; Schreiber, Stefan; Danese, Silvio; Sandborn, William; Griffiths, Anne; Moum, Bjorn; Gasche, Christoph; Pallone, Francesco; Travis, Simon; Panes, Julian; Colombel, Jean-Frederic; Hanauer, Stephen; Peyrin-Biroulet, Laurent

2018-02-01

Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC. Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute. For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities. Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts.

PubMed

Liao, Katherine P; Ananthakrishnan, Ashwin N; Kumar, Vishesh; Xia, Zongqi; Cagan, Andrew; Gainer, Vivian S; Goryachev, Sergey; Chen, Pei; Savova, Guergana K; Agniel, Denis; Churchill, Susanne; Lee, Jaeyoung; Murphy, Shawn N; Plenge, Robert M; Szolovits, Peter; Kohane, Isaac; Shaw, Stanley Y; Karlson, Elizabeth W; Cai, Tianxi

2015-01-01

Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study. We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors. We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that

Impact of a low intensity and broadly inclusive ED care coordination intervention on linkage to primary care and ED utilization.

PubMed

Foster, Sean D; Hart, Kim; Lindsell, Christopher J; Miller, Christopher N; Lyons, Michael S

2018-04-05

We aim to evaluate the effectiveness of a broadly inclusive, comparatively low intensity intervention linking ED patients to a primary care home. This retrospective cohort study evaluated ED patients referred for primary care linkage in a large, urban, academic ED. A care coordination specialist performed a brief interview to gauge access barriers and provide a clinic referral with optional scheduling assistance. Data were abstracted from program records and the electronic medical record. The primary outcome was the proportion of referred individuals who attended at least one primary care appointment. Secondary outcomes included return ED encounters within one year, and factors associated with linkage outcomes. There were 2142 referrals made for 2064 patients; 1688/2142 accepted assistance. Linkage was successful for 1059/1688 (63%, CI95 60% to 65%). Among patients accepting assistance, those without successful linkage were younger (41 vs 45years, difference 3years, CI95 2 to 3), more often male (62% vs 55%,difference 7%, CI95 2% to 12%), and less likely to have a chronic medical condition (37% vs 45%, difference 8%; CI95 3% to 12%) or to have had an appointment scheduled within two weeks (26% vs 33%, difference 7%, CI95 2% to 12%). Insurance status and self-reported barriers to care were not associated with linkage success. Patterns of subsequent ED use were similar, regardless of referral status or linkage outcome. Low intensity, broadly inclusive, ED care coordination linked nearly 50% of patients referred for intervention, and two-thirds of willing participants, with a primary care home. Copyright © 2018 Elsevier Inc. All rights reserved.

Holocene Glacier Fluctuations in the Peruvian Andes Indicate Northern Climate Linkages

NASA Astrophysics Data System (ADS)

Licciardi, Joseph M.; Schaefer, Joerg M.; Taggart, Jean R.; Lund, David C.

2009-09-01

The role of the tropics in triggering, transmitting, and amplifying interhemispheric climate signals remains a key debate in paleoclimatology. Tropical glacier fluctuations provide important insight on regional paleoclimatic trends and forcings, but robust chronologies are scarce. Here, we report precise moraine ages from the Cordillera Vilcabamba (13°20‧S) of southern Peru that indicate prominent glacial events and associated climatic shifts in the outer tropics during the early Holocene and late in the “Little Ice Age” period. Our glacier chronologies differ from the New Zealand record but are broadly correlative with well-dated glacial records in Europe, suggesting climate linkages between the tropics and the North Atlantic region.

Extracts of Feijoa Inhibit Toll-Like Receptor 2 Signaling and Activate Autophagy Implicating a Role in Dietary Control of IBD

PubMed Central

Nasef, Noha Ahmed; Mehta, Sunali; Powell, Penny; Marlow, Gareth; Wileman, Tom; Ferguson, Lynnette R

2015-01-01

Background Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory disease affecting the gut with limited treatment success for its sufferers. This suggests the need for better understanding of the different subtypes of the disease as well as nutritional interventions to compliment current treatments. In this study we assess the ability of a hydrophilic feijoa fraction (F3) to modulate autophagy a process known to regulate inflammation, via TLR2 using IBD cell lines. Method Mouse embryonic fibroblasts (MEF) deleted for ATG5, and two intestinal epithelial cells HCT15 and HCT116, were used to test the anti-inflammatory effect of F3 after stimulating the cells with a TLR2 specific ligand PAM3CSK4. Results F3 was able to reduce TLR2 specific inflammation and stimulate autophagy in MEFs and HCT15 cells but not in HCT116 cells. The anti-inflammatory effect was reduced in the MEF cells deleted for ATG5. In addition, the activation of autophagy by F3 was enhanced by PAM3CSK4. Conclusion F3 of feijoa can interact with cells via a TLR2 specific mechanism and reduce Nuclear factor kappa B (NF-κB) activation in part due to stimulation of autophagy. These results suggest that there is potential benefit in using feijoa extracts as part of dietary interventions to manage IBD in patients. PMID:26110654

Apprenticeship - School Linkage Implementation Manual.

ERIC Educational Resources Information Center

Martin, Sharon T.; And Others

Developed to assist interested sponsors in implementing apprenticeship-school linkage projects, this guide is intended to organize the collective experiences of those who have implemented the demonstration projects to highlight the day-to-day mechanics involved. Section 1 overviews apprenticeship-school linkage. In section 2 factors are described…

Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases.

PubMed

Baujat, Geneviève; Choquet, Rémy; Bouée, Stéphane; Jeanbat, Viviane; Courouve, Laurène; Ruel, Amélie; Michot, Caroline; Le Quan Sang, Kim-Hanh; Lapidus, David; Messiaen, Claude; Landais, Paul; Cormier-Daire, Valérie

2017-06-30

Fibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling, and life-shortening genetic disorder that causes the formation of heterotopic bone within soft connective tissue. Previous studies found that the FOP prevalence was about one in every two million lives. The aim of this study is to estimate the FOP prevalence in France by probabilistic record-linkage of 2 national databases: 1) the PMSI (Programme de médicalisation des systèmes d'information), an administrative database that records all hospitalization activities in France and 2) CEMARA, a registry database developed by the French Centres of Reference for Rare Diseases. Using a capture-recapture methodology to adjust the crude number of patients identified in both data sources, 89 FOP patients were identified, which results in a prevalence of 1.36 per million inhabitants (CI95% = [1.10; 1.68]). FOP patients' mean age was 25 years, only 14.9% were above 40 years, and 53% of them were males. The first symptoms - beside toe malformations- occurred after birth for 97.3% of them. Mean age at identified symptoms was 7 years and above 18 years for only 6.9% of patients. Mean age at diagnosis was 10 years, and above 18 years for 14.9% of the patients. FOP patients were distributed across France. Despite the challenge of ascertaining patients with rare diseases, we report a much higher prevalence of FOP in France than in previous studies elsewhere. We suggest that efforts to identify patients and confirm the diagnosis of FOP should be reinforced and extended at both national and European level.

Sexual selection and sex linkage.

PubMed

Kirkpatrick, Mark; Hall, David W

2004-04-01

Some animal groups, such as birds, seem prone to extreme forms of sexual selection. One contributing factor may be sex linkage of genes affecting male displays and female preferences. Here we show that sex linkage can have substantial effects on the genetic correlation between these traits and consequently for Fisher's runaway and the good-genes mechanisms of sexual selection. Under some kinds of sex linkage (e.g. Z-linked preferences), a runaway is more likely than under autosomal inheritance, while under others (e.g., X-linked preferences and autosomal displays), the good-genes mechanism is particularly powerful. These theoretical results suggest empirical tests based on the comparative method.

Intraepithelial lymphocyte eotaxin-2 expression and perineural mast cell degranulation differentiate allergic/eosinophilic colitis from classic IBD.

PubMed

Torrente, Franco; Barabino, Arrigo; Bellini, Tommaso; Murch, Simon H

2014-09-01

Allergic colitis shows overlap with classic inflammatory bowel disease (IBD). Clinically, allergic colitis is associated with dysmotility and abdominal pain, and mucosal eosinophilia is characteristic. We thus aimed to characterise mucosal changes in children with allergic colitis compared with normal tissue and classic IBD, focusing on potential interaction between eosinophils and mast cells with enteric neurones. A total of 15 children with allergic colitis, 10 with Crohn disease (CD), 10 with ulcerative colitis (UC), and 10 histologically normal controls were studied. Mucosal biopsies were stained for CD3 T cells, Ki-67, eotaxin-1, and eotaxin-2. Eotaxin-2, IgE, and tryptase were localised compared with mucosal nerves, using neuronal markers neurofilament protein, neuron-specific enolase, and nerve growth factor receptor. Overall inflammation was greater in patients with CD and UC than in patients with allergic colitis. CD3 T-cell density was increased in patients with allergic colitis, similar to that in patients with CD but lower than in patients with UC, whereas eosinophil density was higher than in all other groups. Eotaxin-1 and -2 were localised to basolateral crypt epithelium in all specimens, with eotaxin-1+ lamina propria cells found in all of the colitis groups. Eotaxin-2+ intraepithelial lymphocyte (IEL) density was significantly higher in allergic colitis specimens than in all other groups. Mast cell degranulation was strikingly increased in patients with allergic colitis (12/15) compared with that in patients with UC (1/10) and CD (0/1). Tryptase and IgE colocalised on enteric neurons in patients with allergic colitis but rarely in patients with IBD. Eotaxin-2+ IELs may contribute to the periepithelial eosinophil accumulation characteristic of allergic colitis. The colocalisation of IgE and tryptase with mucosal enteric nerves is likely to promote the dysmotility and visceral hyperalgesia classically seen in allergic gastrointestinal inflammation.

Functional impacts of the intestinal microbiome in the pathogenesis of inflammatory bowel disease.

PubMed

Li, Jennifer; Butcher, James; Mack, David; Stintzi, Alain

2015-01-01

: The human intestinal microbiome plays a critical role in human health and disease, including the pathogenesis of inflammatory bowel disease (IBD). Numerous studies have identified altered bacterial diversity and abundance at varying taxonomic levels through biopsies and fecal samples of patients with IBD and diseased model animals. However, inconsistent observations regarding the microbial compositions of such patients have hindered the efforts in assessing the etiological role of specific bacterial species in the pathophysiology of IBD. These observations highlight the importance of minimizing the confounding factors associated with IBD and the need for a standardized methodology to analyze well-defined microbial sampling sources in early IBD diagnosis. Furthermore, establishing the linkage between microbiota compositions with their function within the host system can provide new insights on the pathogenesis of IBD. Such research has been greatly facilitated by technological advances that include functional metagenomics coupled with proteomic and metabolomic profiling. This review provides updates on the composition of the microbiome in IBD and emphasizes microbiota dysbiosis-involved mechanisms. We highlight functional roles of specific bacterial groups in the development and management of IBD. Functional analyses of the microbiome may be the key to understanding the role of microbiota in the development and chronicity of IBD and reveal new strategies for therapeutic intervention.

Cancer incidence among male Swedish veterinarians and other workers of the veterinary industry: a record-linkage study.

PubMed

Travier, Noemie; Gridley, Gloria; Blair, Aaron; Dosemeci, Mustafa; Boffetta, Paolo

2003-08-01

To investigate the risk of cancer among veterinarians in a large record-linkage study from Sweden. We used the nationwide, Swedish Cancer Environment Registry III, which links the Cancer Register data for 1971-1989 to the national population censuses from 1960 and 1970, to compare the incidence of cancer among male veterinarians to that of the remaining part of the active population using multivariable Poisson regression models and standardized incidence ratios. One thousand one hundred and seventy eight men classified as veterinarians or workers in the veterinary industry at either census were identified. Veterinarians in the veterinary industry experienced increased risk of esophageal (relative risk (RR) 3.78, 95% confidence interval (CI) 1.42-10.09), colon (RR: 2.36, 95% CI: 1.42-3.91), pancreatic (RR: 2.10, 95% CI: 0.94-4.68) and brain (RR: 2.51, 95% CI: 1.04-6.03) cancers as well as melanoma of the skin (RR: 2.77, 95% CI: 1.24-6.17). Similar excess risks were observed when veterinarians were compared with individuals of similar socioeconomic status. The increased risks of esophageal, colon, pancreatic and brain cancers as well as melanoma observed among veterinarians did not seem to be explained by the high socio-economic status of this occupational group. Therefore, it is possible that some of these results reflect the carcinogenicity of occupational exposures, including animal viruses, solar or ionizing radiations and anesthetics.

Health services research and data linkages: issues, methods, and directions for the future.

PubMed

Bradley, Cathy J; Penberthy, Lynne; Devers, Kelly J; Holden, Debra J

2010-10-01

Research on pressing health services and policy issues requires access to complete, accurate, and timely patient and organizational data. This paper describes how administrative and health records (including electronic medical records) can be linked for comparative effectiveness and health services research. We categorize the major agents (i.e., who owns and controls data and who carries out the data linkage) into three areas: (1) individual investigators; (2) government sponsored linked data bases; and (3) public-private partnerships that facilitate linkage of data owned by private organizations. We describe challenges that may be encountered in the linkage process, and the benefits of combining secondary databases with primary qualitative and quantitative sources. We use cancer care research to illustrate our points. To fill the gaps in the existing data infrastructure, additional steps are required to foster collaboration among institutions, researchers, and public and private components of the health care sector. Without such effort, independent researchers, governmental agencies, and nonprofit organizations are likely to continue building upon a fragmented and costly system with limited access. Discussion. Without the development and support for emerging information technologies across multiple health care settings, the potential for data collected for clinical and transactional purposes to benefit the research community and, ultimately, the patient population may go unrealized. The current environment is characterized by budget and technical challenges, but investments in data infrastructure are arguably cost-effective given the need to reform our health care system and to monitor the impact of health reform initiatives. © Health Research and Educational Trust.

Accommodating Chromosome Inversions in Linkage Analysis

PubMed Central

Chen, Gary K.; Slaten, Erin; Ophoff, Roel A.; Lange, Kenneth

2006-01-01

This work develops a population-genetics model for polymorphic chromosome inversions. The model precisely describes how an inversion changes the nature of and approach to linkage equilibrium. The work also describes algorithms and software for allele-frequency estimation and linkage analysis in the presence of an inversion. The linkage algorithms implemented in the software package Mendel estimate recombination parameters and calculate the posterior probability that each pedigree member carries the inversion. Application of Mendel to eight Centre d'Étude du Polymorphisme Humain pedigrees in a region containing a common inversion on 8p23 illustrates its potential for providing more-precise estimates of the location of an unmapped marker or trait gene. Our expanded cytogenetic analysis of these families further identifies inversion carriers and increases the evidence of linkage. PMID:16826515

The effects of dutasteride and finasteride on BPH-related hospitalization, surgery and prostate cancer diagnosis: a record-linkage analysis.

PubMed

Cindolo, Luca; Fanizza, Caterina; Romero, Marilena; Pirozzi, Luisella; Autorino, Riccardo; Berardinelli, Francesco; Schips, Luigi

2013-06-01

To investigate differences in the risk of benign prostatic hyperplasia (BPH)-related hospitalization, for surgical and non-surgical reasons, and of new prostate cancer (PCa) diagnosis between patients using finasteride or dutasteride. A retrospective cohort study was conducted using data from record linkage of administrative databases (pharmaceutical prescription data, hospital discharge records, Italian population registry). Men aged ≥ 40 years old who had received a prescription for at least 10 packs/year between January 1, 2004 and December 31, 2004 were included and followed for 5 years. The association of the outcomes was assessed using a multiple Cox proportional hazard model. Propensity score-matched analysis and a 5-1, greedy 1:1 matching algorithm were performed. 8,132 patients were identified. Overall incidence rates of BPH hospitalization and BPH-related surgery were 21.05 (95 % CI 19.52-22.71) and 20.97 (95 % CI 19.45-22.61) per 1,000 person-years, respectively. In the dutasteride group compared with finasteride group, the incidence rate of both events was statistically significant lower: 16.07 versus 21.76 for BPH hospitalization and 15.91 versus 21.69 for BPH-related surgery. The incidence rate of new PCa was also lower for the dutasteride group [8.34 (95 % CI 5.96-11.68) vs. 10.25 (95 % CI 9.15-11.49)]. Dutasteride was associated with a reduction in BPH-related hospitalizations (HR 0.75, 95 % CI 0.58-0.98 and 0.58-0.98 for surgical and non-surgical reasons). The matched analysis confirmed the risk reduction with dutasteride for BPH-related surgery. These findings suggest that the clinical effects of dutasteride and finasteride might be different. Patients treated with dutasteride seem to be less likely to experience BPH-related hospitalization. Comparative studies are needed to confirm these results.

Developing Novel PepT1-Targeted Modulators for Inflammatory Bowel Disease (IBD) Therapy

DTIC Science & Technology

2016-10-01

physiological roles. PepT1 is found in the small intestine where it absorbs dietary degradation products and therapeutic agents such as antibiotics ...results provide a framework for developing more potent ligands in various cellular and animal IBD models, directly addressing Aims 2 and 3 of our... Products …………………………………….………….……………4 7. Participants & Other Collaborating Organizations…….…………….5 8. Special Reporting Requirements…………..………………………5 9

Examination of the Effects of an Intervention Aiming to Link Patients Receiving Addiction Treatment With Health Care: The LINKAGE Clinical Trial.

PubMed

Weisner, Constance M; Chi, Felicia W; Lu, Yun; Ross, Thekla B; Wood, Sabrina B; Hinman, Agatha; Pating, David; Satre, Derek; Sterling, Stacy A

2016-08-01

Research has shown that higher activation and engagement with health care is associated with better self-management. To our knowledge, the linkage intervention (LINKAGE) is the first to engage patients receiving addiction treatment with health care using the electronic health record and a patient activation approach. To examine the effects of an intervention aiming to link patients receiving addiction treatment with health care. A nonrandomized clinical trial evaluating the LINKAGE intervention vs usual care by applying an alternating 3-month off-and-on design over 30 months. Participants were recruited from an outpatient addiction treatment clinic in a large health system between April 7, 2011, and October 2, 2013. Six group-based, manual-guided sessions on patient engagement in health care and the use of health information technology resources in the electronic health record, as well as facilitated communication with physicians, vs usual care. Primary outcomes, measured at 6 months after enrollment, were patient activation (by interview using the Patient Activation Measure), patient engagement in health care (by interview and electronic health record), and alcohol, drug, and depression outcomes (by interview using the Addiction Severity Index for alcohol and drug outcomes and Patient Health Questionnaire (PHQ) for depression). A total of 503 patients were recruited and assigned to the LINKAGE (n = 252) or usual care (n = 251) conditions, with no differences in baseline characteristics between conditions. The mean (SD) age of the patients was 42.5 (11.8) years, 31.0% (n = 156) were female, and 455 (90.5%) completed the 6-month interview. Compared with usual care participants, LINKAGE participants showed an increase in the mean number of log-in days (incidence rate ratio, 1.53; 95% CI, 1.19-1.97; P = .001). Similar results were found across types of patient portal use (communicating by email, viewing laboratory test results and information, and

Academic Performance among Children with Inflammatory Bowel Disease: A Population-Based Study.

PubMed

Singh, Harminder; Nugent, Zoann; Brownell, Marni; Targownik, Laura E; Roos, Leslie L; Bernstein, Charles N

2015-05-01

To determine grade 12 academic performance for children with inflammatory bowel disease (IBD). Children diagnosed with IBD at age<17 years identified from the population-based University of Manitoba IBD Epidemiology Database were matched by age-, sex-, and area of residence to 10 randomly selected controls. Grade 12 educational outcomes (scores on the provincial grade 12 language arts and mathematics standards tests, and enrollment-in-grade-12-by- age-17) were determined by linkage to the province wide Manitoba Education Database. Linear and logistic regression analysis were used to compare the educational outcomes, adjusting for socioeconomic status and comorbidities and evaluate predictors of educational outcomes among children with IBD. Grade 12 educational outcomes among 337 children with IBD were compared with 3093 without IBD. There were no significant differences among the 2 groups in the standardized scores (language arts: P=.31; mathematics: P=.48) or enrollment-in-grade-12-by- age-17 (P=.25). Lower socioeconomic status and diagnosis with mental health problems 6 months prior to and 6 months post-IBD diagnosis were independent predictors of worse educational outcomes. There was no significant effect of age of diagnosis of IBD, type of IBD (ulcerative colitis vs Crohn's disease), use of corticosteroids or immunomodulator agents, hospitalizations, or surgery for IBD. Children with IBD on average achieve similar levels of academic achievement in grade 12 as those without IBD. This study underscores the educational impact of mental health conditions at IBD diagnosis among children. Copyright © 2015 Elsevier Inc. All rights reserved.

EHealth: self-management in inflammatory bowel disease and in irritable bowel syndrome using novel constant-care web applications. EHealth by constant-care in IBD and IBS.

PubMed

Pedersen, Natalia

2015-12-01

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders of unknown aetiology of increasing incidence and changing disease activity or severity. Approximately 60-80% of IBD patients suffer from IBS. Monitoring and treatment goals of IBD are to optimise the disease course by prolonging remission periods and preventing or shortening periods of active disease. Constant-care web-monitoring and treatment approaches with active patient involvement have been proven effective in UC, increasing patients' adherence and improving the disease outcomes.   To assess the feasibility and efficacy of the novel constant-care eHealth applications in: i) CD patients treated with infliximab (IFX), ii) UC patients with active disease on mesalazine, iii) IBS patients and iv) IBD patients with IBS on a low FODMAP diet (LFD).   New constant-care web applications www.cd.constant-care.dk, www.meza.constant-care.dk and www.ibs.constant-care.dk in IBD patients were developed and assessed in this thesis. An integrated inflammatory burden measure of disease activity, consisting of a subjective (clinical indices) and of an objective (faecal calprotectin) part and a treatment guide to drug doses and intervals, was incorporated into the web applications and used by patients. Web-guided IFX treatment in CD demonstrated patients' inter- and intra-individual variability in infusion intervals and provided patients with individualised treatment according to their needs. Web-guided treatment with multimatrix mesalazine was efficacious in a majority of UC patients with mild-to-moderate disease activity. Web-guided IBS-monitoring in IBD and in IBS patients on LFD was shown to be a feasible method that actively involved patients in their disease management and had a positive short-term impact on the disease. Moreover, the new constant-care concepts were demonstrated to be safe and to have a positive impact on quality of life and adherence to treatment and

Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts

PubMed Central

Liao, Katherine P.; Ananthakrishnan, Ashwin N.; Kumar, Vishesh; Xia, Zongqi; Cagan, Andrew; Gainer, Vivian S.; Goryachev, Sergey; Chen, Pei; Savova, Guergana K.; Agniel, Denis; Churchill, Susanne; Lee, Jaeyoung; Murphy, Shawn N.; Plenge, Robert M.; Szolovits, Peter; Kohane, Isaac; Shaw, Stanley Y.; Karlson, Elizabeth W.; Cai, Tianxi

2015-01-01

Background Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study. Methods and Results We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors. Conclusions We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of

The Relevance Aura of Bibliographic Records.

ERIC Educational Resources Information Center

Brooks, Terrence A.

1997-01-01

Analyzes relevance assessments of topical descriptors for bibliographic records for two dimensions: (1) a vertical conceptual hierarchy of broad to narrow descriptors, and (2) a horizontal linkage of related terms. The data were analyzed for a semantic distance and semantic direction effect as postulated by the Semantic Distance Model. (Author/LRW)

IBD Selection for the 288kg Prototype SoLid Module

NASA Astrophysics Data System (ADS)

Saunders, D.; SoLid Collaboration

2017-09-01

The SoLid experiment aims to make a measurement of very short baseline neutrino oscillations using reactor antineutrinos. Key to its sensitivity are the experiment’s high spatial and energy resolution, combined with a very suitable reactor source and excellent background rejection. Placed on the surface at just 5 m from the reactor core, the cosmic flux and reactor output lead to a challenging environment. The fine segmentation of the detector, 5 cm cubes, allows the topology of events to be studied to previously unseen precision. This offers new and unexplored handles for tackling these backgrounds - a key requirement for SoLid physics aims. Using the most recent SoLid prototype (288 kg, 20% scale), we present the first selection to focus on IBD signals. This includes descriptions of SoLid signals and backgrounds, and demonstration that the segmentation can lead to gains in orders of magnitude in background rejection.

The Telehealth Enhancement of Adherence to Medication in Pediatric IBD (TEAM) Trial: Design and Methodology

PubMed Central

Hommel, Kevin A.; Gray, Wendy N.; Hente, Elizabeth; Loreaux, Katherine; Ittenbach, Richard F.; Maddux, Michele; Baldassano, Robert; Sylvester, Francisco; Crandall, Wallace; Doarn, Charles; Heyman, Melvin B.; Keljo, David; Denson, Lee A.

2015-01-01

Medication nonadherence is a significant health care issue requiring regular behavioral treatment. Lack of sufficient health care resources and patient/family time commitment for weekly treatment are primary barriers to receiving appropriate self-management support. We describe the methodology of the Telehealth Enhancement of Adherence to Medication (TEAM) trial for medication nonadherence in pediatric inflammatory bowel disease (IBD). For this trial, participants 11–18 years of age will be recruited from seven pediatric hospitals and will complete an initial 4-week run in to assess adherence to a daily medication. Those who take less than 90% of their prescribed medication will be randomized. A total of 194 patients with IBD will be randomized to either a telehealth behavioral treatment (TBT) arm or education only (EO) arm. All treatment will be delivered via telehealth video conferencing. Patients will be assessed at baseline, post-treatment, 3-, 6-, and 12-months. We anticipate that participants in the TBT arm will demonstrate a statistically significant improvement at post-treatment and 3-, 6-, and 12-month follow-up compared to participants in the EO arm for both medication adherence and secondary outcomes (i.e., disease severity, patient quality of life, and health care utilization). If efficacious, the TEAM intervention could be disseminated broadly and reduce health care access barriers so that patients could receive much needed self-management intervention. PMID:26003436

High-Resolution Detection of Identity by Descent in Unrelated Individuals

PubMed Central

Browning, Sharon R.; Browning, Brian L.

2010-01-01

Detection of recent identity by descent (IBD) in population samples is important for population-based linkage mapping and for highly accurate genotype imputation and haplotype-phase inference. We present a method for detection of recent IBD in population samples. Our method accounts for linkage disequilibrium between SNPs to enable full use of high-density SNP data. We find that our method can detect segments of a length of 2 cM with moderate power and negligible false discovery rate in Illumina 550K data in Northwestern Europeans. We compare our method with GERMLINE and PLINK, and we show that our method has a level of resolution that is significantly better than these existing methods, thus extending the usefulness of recent IBD in analysis of high-density SNP data. We survey four genomic regions in a sample of UK individuals of European descent and find that on average, at a given location, our method detects IBD in 2.7 per 10,000 pairs of individuals in Illumina 550K data. We also present methodology and results for detection of homozygosity by descent (HBD) and survey the whole genome in a sample of 1373 UK individuals of European descent. We detect HBD in 4.7 individuals per 10,000 on average at a given location. Our methodology is implemented in the freely available BEAGLE software package. PMID:20303063

Increased planned delivery contributes to declining rates of pregnancy hypertension in Australia: a population-based record linkage study.

PubMed

Roberts, Christine L; Algert, Charles S; Morris, Jonathan M; Ford, Jane B

2015-10-05

Since the 1990s, pregnancy hypertension rates have declined in some countries, but not all. Increasing rates of early planned delivery (before the due date) have been hypothesised as the reason for the decline. The aim of this study was to explore whether early planned delivery can partly explain the declining pregnancy hypertension rates in Australia. Population-based record linkage study utilising linked birth and hospital records. A cohort of 1,076,122 deliveries in New South Wales, Australia, 2001-2012. Pregnancy hypertension (including gestational hypertension, pre-eclampsia and eclampsia) was the main outcome; pre-eclampsia was a secondary outcome. From 2001 to 2012, pregnancy hypertension rates declined by 22%, from 9.9% to 7.7%, and pre-eclampsia by 27%, from 3.3% to 2.4% (trend p<0.0001). At the same time, planned deliveries increased: prelabour caesarean section by 43% (12.9-18.4%) and labour inductions by 10% (24.8-27.2%). Many maternal risk factors for pregnancy hypertension significantly increased (p<0.01) over the study period including nulliparity, age ≥35 years, diabetes, overweight and obesity, and use of assisted reproductive technologies; some risk factors decreased including multifetal pregnancies, age <20 years, autoimmune diseases and previous pregnancy hypertension. Given these changes in risk factors, the pregnancy hypertension rate was predicted to increase to 10.5%. Examination of annual gestational age distributions showed that pregnancy hypertension rates actually declined from 38 weeks gestation and were steepest from 41 weeks; at least 36% of the decrease could be attributed to planned deliveries. The risk factors for pregnancy hypertension were also risk factors for planned delivery. It appears that an unanticipated consequence of increasing early planned deliveries is a decline in the incidence of pregnancy hypertension. Women with risk factors for hypertension were relatively more likely to be selected for early delivery

Particle swarm optimization with recombination and dynamic linkage discovery.

PubMed

Chen, Ying-Ping; Peng, Wen-Chih; Jian, Ming-Chung

2007-12-01

In this paper, we try to improve the performance of the particle swarm optimizer by incorporating the linkage concept, which is an essential mechanism in genetic algorithms, and design a new linkage identification technique called dynamic linkage discovery to address the linkage problem in real-parameter optimization problems. Dynamic linkage discovery is a costless and effective linkage recognition technique that adapts the linkage configuration by employing only the selection operator without extra judging criteria irrelevant to the objective function. Moreover, a recombination operator that utilizes the discovered linkage configuration to promote the cooperation of particle swarm optimizer and dynamic linkage discovery is accordingly developed. By integrating the particle swarm optimizer, dynamic linkage discovery, and recombination operator, we propose a new hybridization of optimization methodologies called particle swarm optimization with recombination and dynamic linkage discovery (PSO-RDL). In order to study the capability of PSO-RDL, numerical experiments were conducted on a set of benchmark functions as well as on an important real-world application. The benchmark functions used in this paper were proposed in the 2005 Institute of Electrical and Electronics Engineers Congress on Evolutionary Computation. The experimental results on the benchmark functions indicate that PSO-RDL can provide a level of performance comparable to that given by other advanced optimization techniques. In addition to the benchmark, PSO-RDL was also used to solve the economic dispatch (ED) problem for power systems, which is a real-world problem and highly constrained. The results indicate that PSO-RDL can successfully solve the ED problem for the three-unit power system and obtain the currently known best solution for the 40-unit system.

Use of methotrexate in the treatment of inflammatory bowel diseases (IBD)

PubMed Central

Herfarth, Hans H.; Kappelman, Michael D; Long, Millie D; Isaacs, Kim L

2015-01-01

Low-dose methotrexate (MTX) therapy is a well-recognized therapy for many inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis and psoriasis. More than 20 years ago the clinical efficacy of MTX was also established for steroid dependent Crohn’s disease (CD), but it was never broadly adapted as a treatment modality. More recently, MTX has become increasingly used in the pediatric CD population, both as a single agent as well as a concomitant therapy with anti-tumor necrosis factor-alpha (anti-TNF) treatment. This review outlines important pharmacological aspects for the therapeutic application of MTX and the current status of MTX as mono- or combination therapy in both pediatric and adult patients with IBD including new results of MTX monotherapy in steroid dependent ulcerative colitis (UC). PMID:26457382

Model-Based Linkage Analysis of a Quantitative Trait.

PubMed

Song, Yeunjoo E; Song, Sunah; Schnell, Audrey H

2017-01-01

Linkage Analysis is a family-based method of analysis to examine whether any typed genetic markers cosegregate with a given trait, in this case a quantitative trait. If linkage exists, this is taken as evidence in support of a genetic basis for the trait. Historically, linkage analysis was performed using a binary disease trait, but has been extended to include quantitative disease measures. Quantitative traits are desirable as they provide more information than binary traits. Linkage analysis can be performed using single-marker methods (one marker at a time) or multipoint (using multiple markers simultaneously). In model-based linkage analysis the genetic model for the trait of interest is specified. There are many software options for performing linkage analysis. Here, we use the program package Statistical Analysis for Genetic Epidemiology (S.A.G.E.). S.A.G.E. was chosen because it also includes programs to perform data cleaning procedures and to generate and test genetic models for a quantitative trait, in addition to performing linkage analysis. We demonstrate in detail the process of running the program LODLINK to perform single-marker analysis, and MLOD to perform multipoint analysis using output from SEGREG, where SEGREG was used to determine the best fitting statistical model for the trait.

A record-linkage study of the development of hepatocellular carcinoma in persons with hepatitis C infection in Scotland

PubMed Central

McDonald, S A; Hutchinson, S J; Bird, S M; Robertson, C; Mills, P R; Dillon, J F; Goldberg, D J

2008-01-01

We investigated trends in first-time hospital admissions and deaths attributable to hepatocellular carcinoma (HCC) in a large population-based cohort of 22 073 individuals diagnosed with hepatitis C viral (HCV) infection through laboratory testing in Scotland in 1991–2006. We identified new cases of HCC through record-linkage to the national inpatient hospital discharge database and deaths registry. A total of 172 persons diagnosed with HCV were admitted to hospital or died with first-time mention of HCC. Hepatocellular carcinoma incidence increased between 1996 and 2006 (average annual change of 6.1, 95% confidence interval (CI): 0.9–11.6%, P=0.021). The adjusted relative risk of HCC was greater for males (hazard ratio=2.7, 95% CI: 1.7–4.2), for those aged 60 years or older (hazard ratio=2.7, 95% CI: 1.9–4.1) compared with 50–59 years, and for those with a previous alcohol-related hospital admission (hazard ratio=2.5, 95% CI: 1.7–3.7). The risk of individuals diagnosed with HCV developing HCC was greatly increased compared with the general Scottish population (standardised incidence ratio=127, 95% CI: 102–156). Owing to the advancing age of the Scottish HCV-diagnosed population, the annual number of HCC cases is projected to increase, with a consequent increasing burden on the public healthcare system. PMID:18728670

Structural synthesis of linkages for quadruped bio-robot legs

NASA Astrophysics Data System (ADS)

Antonescu, O.; Robu, C.; Antonescu, P.

2016-08-01

The paper presents a few kinematic schemes of planar mechanisms with bars (linkages) used as part of the quadruped robot legs. The Dunshee linkage having only four elements as crank-rocker mechanism is analyzed. Further, the Klann linkage, which is accomplished by amplifying the crank-rocker mechanism with a dyadic kinematic chain, is also presented. More than that, the Jansen linkage, which is obtained by extending and amplifying the crank-rocker mechanism with two dyadic kinematic chains, is also analyzed. At the end of the paper, the authors present a novel linkage application consisting of a quadric kinematic chain.

Long-term Hydroclimate and Pacific Salmon Population Linkages Across a Headwater-to-Coast Continuum in Northern British Columbia, Canada: A Perspective From Multiple Tree-Ring Proxy Records

NASA Astrophysics Data System (ADS)

Welsh, C.; Smith, D. J.; Edwards, T.; Prowse, T.

2016-12-01

Ongoing climate change is expected to have lasting impacts on the runoff behaviour of rivers in northern British Columbia, Canada. Of particular concern is the loss of mountain snowpack and greater rainfall totals altering hydrograph characteristics. Sustained deviations in seasonal streamflow will pose significant challenges for effective watershed management. These ongoing changes highlight the importance of improving our understanding of the long-term biophysical linkages between the storage and release of water and downstream freshwater ecosystems. Such integrated research is particularly relevant to fisheries management as fluctuations in populations of Pacific salmon represent a complex and management-relevant biophysical issue in northern Canada. Unfortunately, hydroclimate and salmon productivity records in this region are sparse and of short duration, constraining our understanding of the impact of climate-induced hydrologic changes and biological responses to the last century. Proxy records derived from tree-rings provide annually or seasonally resolved data and have played a prominent role in attempts to establish how hydroclimate has varied in the past. The objective of my doctoral research is to reconstruct the prehistoric hydroclimate and salmon population trends in the Skeena, Nass and Stikine Watersheds using multiple tree-ring proxies to investigate the long-term biophysical linkages extending across a headwater-to-coast continuum in northern British Columbia, Canada. Ring-width, wood density and stable isotope chronologies using a number of mid-to high-elevation tree species will be constructed across each basin and sub-basin area for the purposes of reconstrucing the predominent temperature and precipiation signature that influence streamflow. Preliminary tree-ring δ18O and δ13C-isotope results indicate a strong negative association with mean monthly relative humidity values, suggesting a physiological control by moisture loss. The results of

Posterior probability of linkage and maximal lod score.

PubMed

Génin, E; Martinez, M; Clerget-Darpoux, F

1995-01-01

To detect linkage between a trait and a marker, Morton (1955) proposed to calculate the lod score z(theta 1) at a given value theta 1 of the recombination fraction. If z(theta 1) reaches +3 then linkage is concluded. However, in practice, lod scores are calculated for different values of the recombination fraction between 0 and 0.5 and the test is based on the maximum value of the lod score Zmax. The impact of this deviation of the test on the probability that in fact linkage does not exist, when linkage was concluded, is documented here. This posterior probability of no linkage can be derived by using Bayes' theorem. It is less than 5% when the lod score at a predetermined theta 1 is used for the test. But, for a Zmax of +3, we showed that it can reach 16.4%. Thus, considering a composite alternative hypothesis instead of a single one decreases the reliability of the test. The reliability decreases rapidly when Zmax is less than +3. Given a Zmax of +2.5, there is a 33% chance that linkage does not exist. Moreover, the posterior probability depends not only on the value of Zmax but also jointly on the family structures and on the genetic model. For a given Zmax, the chance that linkage exists may then vary.

A reference linkage map for Eucalyptus

PubMed Central

2012-01-01

Background Genetic linkage maps are invaluable resources in plant research. They provide a key tool for many genetic applications including: mapping quantitative trait loci (QTL); comparative mapping; identifying unlinked (i.e. independent) DNA markers for fingerprinting, population genetics and phylogenetics; assisting genome sequence assembly; relating physical and recombination distances along the genome and map-based cloning of genes. Eucalypts are the dominant tree species in most Australian ecosystems and of economic importance globally as plantation trees. The genome sequence of E. grandis has recently been released providing unprecedented opportunities for genetic and genomic research in the genus. A robust reference linkage map containing sequence-based molecular markers is needed to capitalise on this resource. Several high density linkage maps have recently been constructed for the main commercial forestry species in the genus (E. grandis, E. urophylla and E. globulus) using sequenced Diversity Arrays Technology (DArT) and microsatellite markers. To provide a single reference linkage map for eucalypts a composite map was produced through the integration of data from seven independent mapping experiments (1950 individuals) using a marker-merging method. Results The composite map totalled 1107 cM and contained 4101 markers; comprising 3880 DArT, 213 microsatellite and eight candidate genes. Eighty-one DArT markers were mapped to two or more linkage groups, resulting in the 4101 markers being mapped to 4191 map positions. Approximately 13% of DArT markers mapped to identical map positions, thus the composite map contained 3634 unique loci at an average interval of 0.31 cM. Conclusion The composite map represents the most saturated linkage map yet produced in Eucalyptus. As the majority of DArT markers contained on the map have been sequenced, the map provides a direct link to the E. grandis genome sequence and will serve as an important reference for

[The effectiveness of compensation system for mesotheliomas due to occupational exposure to asbestos and determinants for requests and awards: an evaluation based on record-linkage between the Veneto Mesothelioma Register and the claims and compensations recorded by the National Insurance Institute (INAIL)].

PubMed

Merler, Enzo; Bressan, Vittoria; Bilato, Anna Maria; Marinaccio, Alessandro

2011-01-01

To determine the rate of requests for compensation and of compensations awarded for mesothelioma cases due to occupational exposure to asbestos; to identify factors that may influence the outcome; to provide an appreciation of the amount of compensation. Record-linkage study at individual level between the new cases of mesothelioma occurred among the residents of the Veneto Region (Northern Italy) between 1999- 2007 and the file of the Insurance Institute, with individual data on all claims and compensations. Adjusted logistic regression models were used to estimated the association between submitting claims and obtaining an award and socio-demographic and other characteristics. 349 on 499 mesotheliomas considered to be due to occupational exposure to asbestos submitted a claim (70% of those of occupational origin) and 72%of claims were accepted. The welfare system covers only 35%of mesothelioma occurred. The probability of submitting and obtaining a claim was associated with gender, cancer site, age at diagnosis, vital status, and residence or local office in charge of the evaluation. A strong discrimination against women is observed. If exposure to asbestos at work was due to a direct manipulation of asbestos, claims were more easily accepted.As a consequence,mesothelioma occurred among construction workers, the occupational activity at the origin of the largest number of occurring mesotheliomas, are more frequently rejected.When submitted by a relative, the lag between a request for compensation and the decision is on average of about two years. This is the first study in Italy using a record-linkage method and was made possible thanks to a population based mesothelioma Register and the availability of memorized information of the Insurance Institute.The welfare system shown clear limitations and there is the need for more appropriate strategies.

A Novel Patient Recruitment Strategy: Patient Selection Directly from the Community through Linkage to Clinical Data.

PubMed

Zimmerman, Lindsay P; Goel, Satyender; Sathar, Shazia; Gladfelter, Charon E; Onate, Alejandra; Kane, Lindsey L; Sital, Shelly; Phua, Jasmin; Davis, Paris; Margellos-Anast, Helen; Meltzer, David O; Polonsky, Tamar S; Shah, Raj C; Trick, William E; Ahmad, Faraz S; Kho, Abel N

2018-01-01

This article presents and describes our methods in developing a novel strategy for recruitment of underrepresented, community-based participants, for pragmatic research studies leveraging routinely collected electronic health record (EHR) data. We designed a new approach for recruiting eligible patients from the community, while also leveraging affiliated health systems to extract clinical data for community participants. The strategy involves methods for data collection, linkage, and tracking. In this workflow, potential participants are identified in the community and surveyed regarding eligibility. These data are then encrypted and deidentified via a hashing algorithm for linkage of the community participant back to a record at a clinical site. The linkage allows for eligibility verification and automated follow-up. Longitudinal data are collected by querying the EHR data and surveying the community participant directly. We discuss this strategy within the context of two national research projects, a clinical trial and an observational cohort study. The community-based recruitment strategy is a novel, low-touch, clinical trial enrollment method to engage a diverse set of participants. Direct outreach to community participants, while utilizing EHR data for clinical information and follow-up, allows for efficient recruitment and follow-up strategies. This new strategy for recruitment links data reported from community participants to clinical data in the EHR and allows for eligibility verification and automated follow-up. The workflow has the potential to improve recruitment efficiency and engage traditionally underrepresented individuals in research. Schattauer GmbH Stuttgart.

A Genetic Linkage Map for Cattle

PubMed Central

Bishop, M. D.; Kappes, S. M.; Keele, J. W.; Stone, R. T.; Sunden, SLF.; Hawkins, G. A.; Toldo, S. S.; Fries, R.; Grosz, M. D.; Yoo, J.; Beattie, C. W.

1994-01-01

We report the most extensive physically anchored linkage map for cattle produced to date. Three-hundred thirteen genetic markers ordered in 30 linkage groups, anchored to 24 autosomal chromosomes (n = 29), the X and Y chromosomes, four unanchored syntenic groups and two unassigned linkage groups spanning 2464 cM of the bovine genome are summarized. The map also assigns 19 type I loci to specific chromosomes and/or syntenic groups and four cosmid clones containing informative microsatellites to chromosomes 13, 25 and 29 anchoring syntenic groups U11, U7 and U8, respectively. This map provides the skeletal framework prerequisite to development of a comprehensive genetic map for cattle and analysis of economic trait loci (ETL). PMID:7908653

Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas.

PubMed

Sun, Xiangqing; Elston, Robert; Falk, Gary W; Grady, William M; Faulx, Ashley; Mittal, Sumeet K; Canto, Marcia I; Shaheen, Nicholas J; Wang, Jean S; Iyer, Prasad G; Abrams, Julian A; Willis, Joseph E; Guda, Kishore; Markowitz, Sanford; Barnholtz-Sloan, Jill S; Chandar, Apoorva; Brock, Wendy; Chak, Amitabh

2016-07-01

Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

The Québec BCG Vaccination Registry (1956-1992): assessing data quality and linkage with administrative health databases.

PubMed

Rousseau, Marie-Claude; Conus, Florence; Li, Jun; Parent, Marie-Élise; El-Zein, Mariam

2014-01-09

Vaccination registries have undoubtedly proven useful for estimating vaccination coverage as well as examining vaccine safety and effectiveness. However, their use for population health research is often limited. The Bacillus Calmette-Guérin (BCG) Vaccination Registry for the Canadian province of Québec comprises some 4 million vaccination records (1926-1992). This registry represents a unique opportunity to study potential associations between BCG vaccination and various health outcomes. So far, such studies have been hampered by the absence of a computerized version of the registry. We determined the completeness and accuracy of the recently computerized BCG Vaccination Registry, as well as examined its linkability with demographic and administrative medical databases. Two systematically selected verification samples, each representing ~0.1% of the registry, were used to ascertain accuracy and completeness of the electronic BCG Vaccination Registry. Agreement between the paper [listings (n = 4,987 records) and vaccination certificates (n = 4,709 records)] and electronic formats was determined along several nominal and BCG-related variables. Linkage feasibility with the Birth Registry (probabilistic approach) and provincial Healthcare Registration File (deterministic approach) was examined using nominal identifiers for a random sample of 3,500 individuals born from 1961 to 1974 and BCG vaccinated between 1970 and 1974. Exact agreement was observed for 99.6% and 81.5% of records upon comparing, respectively, the paper listings and vaccination certificates to their corresponding computerized records. The proportion of successful linkage was 77% with the Birth Registry, 70% with the Healthcare Registration File, 57% with both, and varied by birth year. Computerization of this Registry yielded excellent results. The registry was complete and accurate, and linkage with administrative databases was highly feasible. This study represents the first step towards

Computer-assisted expert case definition in electronic health records.

PubMed

Walker, Alexander M; Zhou, Xiaofeng; Ananthakrishnan, Ashwin N; Weiss, Lisa S; Shen, Rongjun; Sobel, Rachel E; Bate, Andrew; Reynolds, Robert F

2016-02-01

To describe how computer-assisted presentation of case data can lead experts to infer machine-implementable rules for case definition in electronic health records. As an illustration the technique has been applied to obtain a definition of acute liver dysfunction (ALD) in persons with inflammatory bowel disease (IBD). The technique consists of repeatedly sampling new batches of case candidates from an enriched pool of persons meeting presumed minimal inclusion criteria, classifying the candidates by a machine-implementable candidate rule and by a human expert, and then updating the rule so that it captures new distinctions introduced by the expert. Iteration continues until an update results in an acceptably small number of changes to form a final case definition. The technique was applied to structured data and terms derived by natural language processing from text records in 29,336 adults with IBD. Over three rounds the technique led to rules with increasing predictive value, as the experts identified exceptions, and increasing sensitivity, as the experts identified missing inclusion criteria. In the final rule inclusion and exclusion terms were often keyed to an ALD onset date. When compared against clinical review in an independent test round, the derived final case definition had a sensitivity of 92% and a positive predictive value of 79%. An iterative technique of machine-supported expert review can yield a case definition that accommodates available data, incorporates pre-existing medical knowledge, is transparent and is open to continuous improvement. The expert updates to rules may be informative in themselves. In this limited setting, the final case definition for ALD performed better than previous, published attempts using expert definitions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

HIV and cancer registry linkage identifies a substantial burden of cancers in persons with HIV in India

PubMed Central

Godbole, Sheela V.; Nandy, Karabi; Gauniyal, Mansi; Nalawade, Pallavi; Sane, Suvarna; Koyande, Shravani; Toyama, Joy; Hegde, Asha; Virgo, Phil; Bhatia, Kishor; Paranjape, Ramesh S.; Risbud, Arun R.; Mbulaiteye, Sam M.; Mitsuyasu, Ronald T.

2016-01-01

Abstract We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population. Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996–2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4–27 months after HIV registration), late (28–60 months), and overall (4–60 months) incidence periods. Cancers diagnosed prior to or within 3 months of HIV registration were considered prevalent. Of 613 linked cancers to PLHIV, 188 were prevalent, 106 early incident, and 319 late incident. Incident cancers comprised 11.5% AIDS-defining cancers (ADCs), including cervical cancer and non-Hodgkin lymphoma (NHL), but not Kaposi sarcoma (KS), and 88.5% non-AIDS-defining cancers (NADCs). Risk for any incident cancer diagnosis in early, late, and combined periods was significantly elevated among PLHIV (SIRs: 5.6 [95% CI 4.6–6.8], 17.7 [95% CI 15.8–19.8], and 11.5 [95% CI 10–12.6], respectively). Cervical cancer risk was elevated in both incidence periods (SIRs: 9.6 [95% CI 4.8–17.2] and 22.6 [95% CI 14.3–33.9], respectively), while NHL risk was elevated only in the late incidence period (SIR: 18.0 [95% CI 9.8–30.20]). Risks for NADCs were dramatically elevated (SIR > 100) for eye-orbit, substantially (SIR > 20) for all-mouth, esophagus, breast, unspecified-leukemia, colon-rectum-anus, and other/unspecified cancers; moderately elevated (SIR > 10) for salivary gland, penis, nasopharynx, and brain-nervous system, and mildly elevated (SIR > 5) for stomach. Risks for 6 NADCs (small intestine, testis, lymphocytic leukemia, prostate, ovary, and melanoma) were not elevated and 5 cancers, including multiple myeloma not seen. Our study

HIV and cancer registry linkage identifies a substantial burden of cancers in persons with HIV in India.

PubMed

Godbole, Sheela V; Nandy, Karabi; Gauniyal, Mansi; Nalawade, Pallavi; Sane, Suvarna; Koyande, Shravani; Toyama, Joy; Hegde, Asha; Virgo, Phil; Bhatia, Kishor; Paranjape, Ramesh S; Risbud, Arun R; Mbulaiteye, Sam M; Mitsuyasu, Ronald T

2016-09-01

We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population.Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996-2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4-27 months after HIV registration), late (28-60 months), and overall (4-60 months) incidence periods. Cancers diagnosed prior to or within 3 months of HIV registration were considered prevalent.Of 613 linked cancers to PLHIV, 188 were prevalent, 106 early incident, and 319 late incident. Incident cancers comprised 11.5% AIDS-defining cancers (ADCs), including cervical cancer and non-Hodgkin lymphoma (NHL), but not Kaposi sarcoma (KS), and 88.5% non-AIDS-defining cancers (NADCs). Risk for any incident cancer diagnosis in early, late, and combined periods was significantly elevated among PLHIV (SIRs: 5.6 [95% CI 4.6-6.8], 17.7 [95% CI 15.8-19.8], and 11.5 [95% CI 10-12.6], respectively). Cervical cancer risk was elevated in both incidence periods (SIRs: 9.6 [95% CI 4.8-17.2] and 22.6 [95% CI 14.3-33.9], respectively), while NHL risk was elevated only in the late incidence period (SIR: 18.0 [95% CI 9.8-30.20]). Risks for NADCs were dramatically elevated (SIR > 100) for eye-orbit, substantially (SIR > 20) for all-mouth, esophagus, breast, unspecified-leukemia, colon-rectum-anus, and other/unspecified cancers; moderately elevated (SIR > 10) for salivary gland, penis, nasopharynx, and brain-nervous system, and mildly elevated (SIR > 5) for stomach. Risks for 6 NADCs (small intestine, testis, lymphocytic leukemia, prostate, ovary, and melanoma) were not elevated and 5 cancers, including multiple myeloma not seen.Our study demonstrates the feasibility of

DNA linkage studies of degenerative retinal diseases.

PubMed

Daiger, S P; Heckenlively, J R; Lewis, R A; Pelias, M Z

1987-01-01

DNA linkage studies of human genetic diseases have led to rapid characterization of a number of otherwise intractable disease loci. Detection of a linked DNA marker, the first step in "reverse genetics", has permitted cloning of the genes for Duchenne muscular dystrophy, retinoblastoma and chronic granulomatosis disease, among others. Thus, the case for applying these techniques to retinitis pigmentosa and related diseases, and the urgency in capitalizing on molecular developments, is justified and compelling. The first major success regarding RP was in demonstrating linkage of the DNA marker DXS7 (L1.28) to XRP. For autosomal forms of the disease, conventional linkage studies have provided tentative evidence for linkage of ADRP to the Rh blood group on chromosome lp and for linkage of Usher's syndrome to Gc and 4q. These provisional assignments are, at least, an important starting point for DNA analysis. The Support Program for DNA Linkage Studies of Degenerative Retinal Diseases was established to provide access for the scientific community to appropriate families, using the resources of the Human Genetic Mutant Cell Repository to prepare, store and distribute lymphoblast lines. To date, two extensive, well-characterized families are included in the program: the autosomal dominant RP family UCLA-RP01, and the Usher's syndrome families LSU-US01. It is highly likely that rapid progress will be made in mapping and characterizing the inherited retinal dystrophies. We believe the support program will facilitate this progress.

Ignoring Intermarker Linkage Disequilibrium Induces False-Positive Evidence of Linkage for Consanguineous Pedigrees when Genotype Data Is Missing for Any Pedigree Member

PubMed Central

Li, Bingshan; Leal, Suzanne M.

2008-01-01

Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al. [1] that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for autosomal recessive consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. False-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage, and which family members aid in its reduction, is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. For the situation, when parental genotypes are unavailable, false-positive evidence for linkage can be reduced by including genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents in the analysis. PMID:18073490

The Telehealth Enhancement of Adherence to Medication (TEAM) in pediatric IBD trial: Design and methodology.

PubMed

Hommel, Kevin A; Gray, Wendy N; Hente, Elizabeth; Loreaux, Katherine; Ittenbach, Richard F; Maddux, Michele; Baldassano, Robert; Sylvester, Francisco; Crandall, Wallace; Doarn, Charles; Heyman, Melvin B; Keljo, David; Denson, Lee A

2015-07-01

Medication nonadherence is a significant health care issue requiring regular behavioral treatment. Lack of sufficient health care resources and patient/family time commitment for weekly treatment are primary barriers to receiving appropriate self-management support. We describe the methodology of the Telehealth Enhancement of Adherence to Medication (TEAM) trial for medication nonadherence in pediatric inflammatory bowel disease (IBD). For this trial, participants 11-18 years of age will be recruited from seven pediatric hospitals and will complete an initial 4-week run in to assess adherence to a daily medication. Those who take less than 90% of their prescribed medication will be randomized. A total of 194 patients with IBD will be randomized to either a telehealth behavioral treatment (TBT) arm or education only (EO) arm. All treatments will be delivered via telehealth video conferencing. The patients will be assessed at baseline, post-treatment, 3, 6, and 12 months. We anticipate that participants in the TBT arm will demonstrate a statistically significant improvement at post-treatment and 3-, 6-, and 12-month follow-up compared to participants in the EO arm for both medication adherence and secondary outcomes (i.e., disease severity, patient quality of life, and health care utilization). If efficacious, the TEAM intervention could be disseminated broadly and reduce health care access barriers so that the patients could receive much needed self-management intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

Wait times to rheumatology care for patients with rheumatic diseases: a data linkage study of primary care electronic medical records and administrative data.

PubMed

Widdifield, Jessica; Bernatsky, Sasha; Thorne, J Carter; Bombardier, Claire; Jaakkimainen, R Liisa; Wing, Laura; Paterson, J Michael; Ivers, Noah; Butt, Debra; Lyddiatt, Anne; Hofstetter, Catherine; Ahluwalia, Vandana; Tu, Karen

2016-01-01

The Wait Time Alliance recently established wait time benchmarks for rheumatology consultations in Canada. Our aim was to quantify wait times to primary and rheumatology care for patients with rheumatic diseases. We identified patients from primary care practices in the Electronic Medical Record Administrative data Linked Database who had referrals to Ontario rheumatologists over the period 2000-2013. To assess the full care pathway, we identified dates of symptom onset, presentation in primary care and referral from electronic medical records. Dates of rheumatologist consultations were obtained by linking with physician service claims. We determined the duration of each phase of the care pathway (symptom onset to primary care encounter, primary care encounter to referral, and referral to rheumatologist consultation) and compared them with established benchmarks. Among 2430 referrals from 168 family physicians, 2015 patients (82.9%) were seen by 146 rheumatologists within 1 year of referral. Of the 2430 referrals, 2417 (99.5%) occurred between 2005 and 2013. The main reasons for referral were osteoarthritis (32.4%) and systemic inflammatory rheumatic diseases (30.6%). Wait times varied by diagnosis and geographic region. Overall, the median wait time from referral to rheumatologist consultation was 74 (interquartile range 27-101) days; it was 66 (interquartile range 18-84) days for systemic inflammatory rheumatic diseases. Wait time benchmarks were not achieved, even for the most urgent types of referral. For systemic inflammatory rheumatic diseases, most of the delays occurred before referral. Rheumatology wait times exceeded established benchmarks. Targeted efforts are needed to promote more timely access to both primary and rheumatology care. Routine linkage of electronic medical records with administrative data may help fill important gaps in knowledge about waits to primary and specialty care.

CMV Disease in IBD: Comparison of Diagnostic Tests and Correlation with Disease Outcome.

PubMed

Johnson, Jessica; Affolter, Kajsa; Boynton, Kathleen; Chen, Xinjian; Valentine, John; Peterson, Kathryn

2018-04-30

Significance of cytomegalovirus (CMV) in inflammatory bowel disease (IBD) is unclear due to pathobiology, numerous CMV tests, and disparate treatment outcomes. Retrospective chart review was done on patients with positive qualitative CMV tissue polymerase chain reaction (PCR) from 2005-2013 at a tertiary referral hospital. Frequency of PCR+, hematoxylin and eosin staining(HE)+, histopathology and immunohistochemistry (IHC)+ was assessed. IHC was assessed on a sample of PCR- tissues. Surgery rates were correlated with CMV testing and treatment. PCR was done on 310 samples from 180 patients. Thirty-seven samples were PCR+ (51.4% PCR+ only, 35.1% IHC/PCR+, 13.5% HE/IHC/PCR+). The H&E frequently failed to detect CMV identified on extensive IHC. Of 13 PCR- samples tested with IHC, 100% were negative. Twenty-five patients were CMV+ (40% PCR+, 40% IHC/PCR+, 20% HE/IHC/PCR+). Surgery rates increased with number of positive tests: 60% in IHC/PCR+ and 80% in HE/IHC/PCR+, compared to 26.8% in PCR- or PCR+ (P = 0.03, P = 0.02, respectively). There were 20/25 PCR+ patients who received CMV treatment. Surgery occurred in 80% of HE+ patients despite treatment and 100% of IHC+ patients without treatment. Rates of CMV+ testing and surgical risk varied by test modality. PCR+ results were most frequent but alone did not detect clinically significant CMV. HE+ testing was least frequent and associated with highest surgical rate, despite treatment. CMV treatment may benefit IHC+ patients most, supporting immunostaining as optimal diagnostic test for clinically significant CMV in IBD. In PCR+ samples, HE frequently did not detect CMV identified on extensive IHC. In PCR- samples, data suggest IHC is likely negative. Consider using qualitative PCR to guide extensive immunostaining.

A Test of Outreach and Drop-in Linkage Versus Shelter Linkage for Connecting Homeless Youth to Services.

PubMed

Slesnick, Natasha; Feng, Xin; Guo, Xiamei; Brakenhoff, Brittany; Carmona, Jasmin; Murnan, Aaron; Cash, Scottye; McRee, Annie-Laurie

2016-05-01

Outreach and service linkage are key for engaging marginalized populations, such as homeless youth, in services. Research to date has focused primarily on engaging individuals already receiving some services through emergency shelters, clinics, or other programs. Less is known about those who are not connected to services and, thus, likely the most vulnerable and in need of assistance. The current study sought to engage non-service-connected homeless youth (N = 79) into a strengths-based outreach and advocacy intervention. Youth were randomly assigned to receive 6 months of advocacy that focused on linking youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). All youth were assessed at baseline and 3, 6, and 9 months post-baseline. Findings indicated that youth prefer drop-in center services to the shelter. Also, the drop-in center linkage condition was associated with more service linkage overall (B = 0.34, SE = 0.04, p < 0.01) and better alcohol-l [B = -0.39, SE = 0.09, t(75) = -4.48, p < 0.001] and HIV-related outcomes [B = 0.62, SE = 0.10, t(78) = 6.34, p < 0.001] compared to the shelter linkage condition. Findings highlight the importance of outreach and service linkage for reconnecting service-marginalized youth, and drop-in centers as a primary service option for homeless youth.

Linkage studies in primary open angle glaucoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avramopoulos, D.; Grigoriadu, M.; Kitsos, G.

1994-09-01

Glaucoma is a leading cause of blindness worldwide. The majority of glaucoma is associated with an open, normal appearing anterior chamber angle and is termed primary open angle glaucoma (POAG, MIM 137760). It is characterized by elevated intraocular pressure and onset in middle age or later. A subset of POAG with juvenile onset has recently been linked to chromosome 1q in two families with autosomal dominant inheritance. Eleven pedigrees with autosomal dominant POG (non-juvenile-onset) have been identified in Epirus, Greece. In the present study DNA samples have been collected from 50 individuals from one large pedigree, including 12 affected individuals.more » Preliminary results of linkage analysis with chromosome 1 microsatellites using the computer program package LINKAGE Version 5.1 showed no linkage with the markers previously linked to juvenile-onset POAG. Further linkage analysis is being pursued, and the results will be presented.« less

Elevated levels of serum-soluble triggering receptor expressed on myeloid cells-1 in patients with IBD do not correlate with intestinal TREM-1 mRNA expression and endoscopic disease activity.

PubMed

Saurer, Leslie; Rihs, Silvia; Birrer, Michèle; Saxer-Seculic, Nikolina; Radsak, Markus; Mueller, Christoph

2012-10-01

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory responses. We have previously demonstrated a substantial increase in TREM-1-expressing macrophages in the inflamed intestinal mucosa of patients with inflammatory bowel diseases (IBD). TREM-1 is also produced as a soluble receptor (sTREM-1). Here, we aimed to determine whether serum sTREM-1 could be used as a surrogate marker of disease activity in patients with IBD. Intestinal biopsies and concurrently collected sera from patients with Crohn's disease (CD) and Ulcerative colitis (UC) enrolled in the Swiss IBD cohort study were analyzed for intestinal TREM-1 mRNA and serum sTREM-1 expression. TREM-1 mRNA and sTREM-1 were correlated with the endoscopically determined disease activity. Serum sTREM-1 and TREM-1 mRNA expression levels were further determined in sera and colonic tissues collected at various time-points post disease induction in an experimental mouse model of colitis and correlated with disease activity. Expression of TREM-1 mRNA was upregulated in intestinal biopsies from patients with active disease but not in patients with quiescent disease. Serum sTREM-1 was elevated in IBD patients compared to normal controls. No substantial differences in sTREM-1 expression levels were found in patients with active versus quiescent disease. In colitic mice, colonic TREM-1 mRNA and serum sTREM-1 were also upregulated. While colonic TREM-1 mRNA expression levels correlated with disease activity, augmented serum sTREM-1 in fact associated with a milder course of disease. Analysis of sTREM-1 as a surrogate marker of disease activity in patients with IBD warrants caution. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Haplotype Reconstruction in Large Pedigrees with Many Untyped Individuals

NASA Astrophysics Data System (ADS)

Li, Xin; Li, Jing

Haplotypes, as they specify the linkage patterns between dispersed genetic variations, provide important information for understanding the genetics of human traits. However haplotypes are not directly available from current genotyping platforms, and hence there are extensive investigations of computational methods to recover such information. Two major computational challenges arising in current family-based disease studies are large family sizes and many ungenotyped family members. Traditional haplotyping methods can neither handle large families nor families with missing members. In this paper, we propose a method which addresses these issues by integrating multiple novel techniques. The method consists of three major components: pairwise identical-bydescent (IBD) inference, global IBD reconstruction and haplotype restoring. By reconstructing the global IBD of a family from pairwise IBD and then restoring the haplotypes based on the inferred IBD, this method can scale to large pedigrees, and more importantly it can handle families with missing members. Compared with existing methods, this method demonstrates much higher power to recover haplotype information, especially in families with many untyped individuals.

The Québec BCG Vaccination Registry (1956–1992): assessing data quality and linkage with administrative health databases

PubMed Central

2014-01-01

Background Vaccination registries have undoubtedly proven useful for estimating vaccination coverage as well as examining vaccine safety and effectiveness. However, their use for population health research is often limited. The Bacillus Calmette-Guérin (BCG) Vaccination Registry for the Canadian province of Québec comprises some 4 million vaccination records (1926-1992). This registry represents a unique opportunity to study potential associations between BCG vaccination and various health outcomes. So far, such studies have been hampered by the absence of a computerized version of the registry. We determined the completeness and accuracy of the recently computerized BCG Vaccination Registry, as well as examined its linkability with demographic and administrative medical databases. Methods Two systematically selected verification samples, each representing ~0.1% of the registry, were used to ascertain accuracy and completeness of the electronic BCG Vaccination Registry. Agreement between the paper [listings (n = 4,987 records) and vaccination certificates (n = 4,709 records)] and electronic formats was determined along several nominal and BCG-related variables. Linkage feasibility with the Birth Registry (probabilistic approach) and provincial Healthcare Registration File (deterministic approach) was examined using nominal identifiers for a random sample of 3,500 individuals born from 1961 to 1974 and BCG vaccinated between 1970 and 1974. Results Exact agreement was observed for 99.6% and 81.5% of records upon comparing, respectively, the paper listings and vaccination certificates to their corresponding computerized records. The proportion of successful linkage was 77% with the Birth Registry, 70% with the Healthcare Registration File, 57% with both, and varied by birth year. Conclusions Computerization of this Registry yielded excellent results. The registry was complete and accurate, and linkage with administrative databases was highly feasible. This

Linkage Analysis of a Model Quantitative Trait in Humans: Finger Ridge Count Shows Significant Multivariate Linkage to 5q14.1

PubMed Central

Medland, Sarah E; Loesch, Danuta Z; Mdzewski, Bogdan; Zhu, Gu; Montgomery, Grant W; Martin, Nicholas G

2007-01-01

The finger ridge count (a measure of pattern size) is one of the most heritable complex traits studied in humans and has been considered a model human polygenic trait in quantitative genetic analysis. Here, we report the results of the first genome-wide linkage scan for finger ridge count in a sample of 2,114 offspring from 922 nuclear families. Both univariate linkage to the absolute ridge count (a sum of all the ridge counts on all ten fingers), and multivariate linkage analyses of the counts on individual fingers, were conducted. The multivariate analyses yielded significant linkage to 5q14.1 (Logarithm of odds [LOD] = 3.34, pointwise-empirical p-value = 0.00025) that was predominantly driven by linkage to the ring, index, and middle fingers. The strongest univariate linkage was to 1q42.2 (LOD = 2.04, point-wise p-value = 0.002, genome-wide p-value = 0.29). In summary, the combination of univariate and multivariate results was more informative than simple univariate analyses alone. Patterns of quantitative trait loci factor loadings consistent with developmental fields were observed, and the simple pleiotropic model underlying the absolute ridge count was not sufficient to characterize the interrelationships between the ridge counts of individual fingers. PMID:17907812

Linkage to 10q22 for maximum intraocular pressure and 1p32 for maximum cup-to-disc ratio in an extended primary open-angle glaucoma pedigree.

PubMed

Charlesworth, Jac C; Dyer, Thomas D; Stankovich, Jim M; Blangero, John; Mackey, David A; Craig, Jamie E; Green, Catherine M; Foote, Simon J; Baird, Paul N; Sale, Michèle M

2005-10-01

The purpose of this study was to identify genetic contributions to primary open-angle glaucoma (POAG) through investigations of two quantitative components of the POAG phenotype. Genome-wide multipoint variance-components linkage analyses of maximum recorded intraocular pressure (IOP) and maximum vertical cup-to-disc ratio were conducted on data from a single, large Australian POAG pedigree that has been found to segregate the myocilin Q368X mutation in some individuals. Multipoint linkage analysis of maximum recorded IOP produced a peak LOD score of 3.3 (P = 0.00015) near marker D10S537 on 10q22, whereas the maximum cup-to-disc ratio produced a peak LOD score of 2.3 (P = 0.00056) near markers D1S197 to D1S220 on 1p32. Inclusion of the myocilin Q368X mutation as a covariate provided evidence of an interaction between this mutation and the IOP and cup-to-disc ratio loci. Significant linkage has been identified for maximum IOP and suggestive linkage for vertical cup-to-disc ratio. Identification of genes contributing to the variance of these traits will enhance understanding of the pathophysiology of POAG as a whole.

Robustness of linkage strategy that leads to large-scale cooperation.

PubMed

Inaba, Misato; Takahashi, Nobuyuki; Ohtsuki, Hisashi

2016-11-21

One of the most well-known models to characterize cooperation among unrelated individuals is Social dilemma (SD). However there is no consensus about how to solve the SD by itself. Since SDs are often embedded in other social interactions, including indirect reciprocity games (IR), human can coordinate their behaviors across multiple games. Such coordination is called 'linkage'. Recently linkage has been considered as a promising solution to resolve SDs, since excluding SD defectors (i.e. those who defected in SD) from indirectly reciprocal relationships functions as a costless sanction. A previous study performed mathematical modeling and revealed that a linkage strategy, which cooperates in SD and engages in the Standing strategy in IR based on the recipients' behaviors in both SD and IR, was an ESS against a non-linkage strategy which defects in SD and engages in the Standing strategy in IR based on recipients' behaviors only in IR (Panchanathan and Boyd, 2004). In order to investigate the robustness of the linkage strategy, we devised a non-linkage strategy, which cooperates in SD but does not link two games. First, we conducted a mathematical analysis and demonstrated that the linkage strategy was not an ESS against cooperating non-linkage strategy. Second, we conducted a series of agent-based computer simulations to examine how the strategies perform in situations in which various types of errors can occur. Our results showed that the linkage strategy was an ESS only when there are implementation errors in SD. However, the equilibrium of the linkage strategy was unstable when there are perception errors. Since we know that humans are not free from perception errors in their social life, future studies will need to show how perception errors can be overcome in order to provide support for the conclusion that linkage is a plausible solution to SDs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protective Effect of Anthocyanins Extract from Blueberry on TNBS-Induced IBD Model of Mice

PubMed Central

Wu, Lin-Hua; Xu, Zeng-Lai; Dong, Di; He, Shan-An; Yu, Hong

2011-01-01

This study was carried out to evaluate the protective effect of anthocyanins extract of blueberry on trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) model of mice. The study employed female C57BL/6 mice (n = 50), and colitis was induced by intracolonic injection of 0.5 mg of TNBS dissolved in 50% ethanol–phosphate buffered solution. The mice were divided into five groups (n = 10): vehicle, TNBS control and anthocyanins groups that received different doses of anthocyanins extract (10, 20 and 40 mg kg−1) daily for 6 days. Both increase in body weight and diarrhea symptoms were monitored each day. After 6 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay (NO, myeloperoxidase (MPO), interleukin (IL)-12, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ). The results showed that the anthocyanins extract of blueberry rendered strong protection against TNBS-induced colonic damage at a dosage of 40 mg kg−1. When compared with the control, anthocyanins extract significantly prevented loss of body weight and ameliorated the scores of diarrhea, morphology and histology. Treatment with anthocyanins extract restored IL-10 excretion, as well as caused reduction in the levels of NO, MPO, IL-12, TNF-α and IFN-γ. Our research revealed the protective effect of anthocyanins extract from blueberry on TNBS-induced experimental colitis in mice, as well as examined whether high levels of dietary blueberries would lower the risk or have protective effects on human IBD, which may require further investigation. PMID:21785630

Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages

NASA Astrophysics Data System (ADS)

Hahm, Heung Sik; Hurevich, Mattan; Seeberger, Peter H.

2016-09-01

Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans-glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis-glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides.

Progress along developmental tracks for electronic health records implementation in the United States

PubMed Central

Hollar, David W

2009-01-01

The development and implementation of electronic health records (EHR) have occurred slowly in the United States. To date, these approaches have, for the most part, followed four developmental tracks: (a) Enhancement of immunization registries and linkage with other health records to produce Child Health Profiles (CHP), (b) Regional Health Information Organization (RHIO) demonstration projects to link together patient medical records, (c) Insurance company projects linked to ICD-9 codes and patient records for cost-benefit assessments, and (d) Consortia of EHR developers collaborating to model systems requirements and standards for data linkage. Until recently, these separate efforts have been conducted in the very silos that they had intended to eliminate, and there is still considerable debate concerning health professionals access to as well as commitment to using EHR if these systems are provided. This paper will describe these four developmental tracks, patient rights and the legal environment for EHR, international comparisons, and future projections for EHR expansion across health networks in the United States. PMID:19291284

A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations.

PubMed

Kling, Daniel; Tillmar, Andreas; Egeland, Thore; Mostad, Petter

2015-09-01

Several applications necessitate an unbiased determination of relatedness, be it in linkage or association studies or in a forensic setting. An appropriate model to compute the joint probability of some genetic data for a set of persons given some hypothesis about the pedigree structure is then required. The increasing number of markers available through high-density SNP microarray typing and NGS technologies intensifies the demand, where using a large number of markers may lead to biased results due to strong dependencies between closely located loci, both within pedigrees (linkage) and in the population (allelic association or linkage disequilibrium (LD)). We present a new general model, based on a Markov chain for inheritance patterns and another Markov chain for founder allele patterns, the latter allowing us to account for LD. We also demonstrate a specific implementation for X chromosomal markers that allows for computation of likelihoods based on hypotheses of alleged relationships and genetic marker data. The algorithm can simultaneously account for linkage, LD, and mutations. We demonstrate its feasibility using simulated examples. The algorithm is implemented in the software FamLinkX, providing a user-friendly GUI for Windows systems (FamLinkX, as well as further usage instructions, is freely available at www.famlink.se ). Our software provides the necessary means to solve cases where no previous implementation exists. In addition, the software has the possibility to perform simulations in order to further study the impact of linkage and LD on computed likelihoods for an arbitrary set of markers.

Enrollment in HIV Care Two Years after HIV Diagnosis in the Kingdom of Swaziland: An Evaluation of a National Program of New Linkage Procedures.

PubMed

MacKellar, Duncan A; Williams, Daniel; Storer, Nosipho; Okello, Velephi; Azih, Charles; Drummond, Jennifer; Nuwagaba-Biribonwoha, Harriet; Preko, Peter; Morgan, Rebecca L; Dlamini, Makhosazana; Byrd, Johnita; Agolory, Simon; Baughman, Andrew L; McNairy, Margaret L; Sahabo, Ruben; Ehrenkranz, Peter

2016-01-01

To improve early enrollment in HIV care, the Swaziland Ministry of Health implemented new linkage procedures for persons HIV diagnosed during the Soka Uncobe male circumcision campaign (SOKA, 2011-2012) and the Swaziland HIV Incidence Measurement Survey (SHIMS, 2011). Abstraction of clinical records and telephone interviews of a retrospective cohort of HIV-diagnosed SOKA and SHIMS clients were conducted in 2013-2014 to evaluate compliance with new linkage procedures and enrollment in HIV care at 92 facilities throughout Swaziland. Of 1,105 clients evaluated, within 3, 12, and 24 months of diagnosis, an estimated 14.0%, 24.3%, and 37.0% enrolled in HIV care, respectively, after adjusting for lost to follow-up and non-response. Kaplan-Meier functions indicated lower enrollment probability among clients 14-24 (P = 0.0001) and 25-29 (P = 0.001) years of age compared with clients >35 years of age. At 69 facilities to which clients were referred for HIV care, compliance with new linkage procedures was low: referral forms were located for less than half (46.8%) of the clients, and few (9.6%) were recorded in the appointment register or called either before (0.3%) or after (4.9%) their appointment. Of over one thousand clients newly HIV diagnosed in Swaziland in 2011 and 2012, few received linkage services in accordance with national procedures and most had not enrolled in HIV care two years after their diagnosis. Our findings are a call to action to improve linkage services and early enrollment in HIV care in Swaziland.

Tests for linkage and association in nuclear families.

PubMed Central

Martin, E R; Kaplan, N L; Weir, B S

1997-01-01

The transmission/disequilibrium test (TDT) originally was introduced to test for linkage between a genetic marker and a disease-susceptibility locus, in the presence of association. Recently, the TDT has been used to test for association in the presence of linkage. The motivation for this is that linkage analysis typically identifies large candidate regions, and further refinement is necessary before a search for the disease gene is begun, on the molecular level. Evidence of association and linkage may indicate which markers in the region are closest to a disease locus. As a test of linkage, transmissions from heterozygous parents to all of their affected children can be included in the TDT; however, the TDT is a valid chi2 test of association only if transmissions to unrelated affected children are used in the analysis. If the sample contains independent nuclear families with multiple affected children, then one procedure that has been used to test for association is to select randomly a single affected child from each sibship and to apply the TDT to those data. As an alternative, we propose two statistics that use data from all of the affected children. The statistics give valid chi2 tests of the null hypothesis of no association or no linkage and generally are more powerful than the TDT with a single, randomly chosen, affected child from each family. PMID:9311750

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease.

PubMed

Derikx, Lauranne A A P; Smits, Lisa J T; van Vliet, Shannon; Dekker, Evelien; Aalfs, Cora M; van Kouwen, Mariëtte C A; Nagengast, Fokko M; Nagtegaal, Iris D; Hoogerbrugge, Nicoline; Hoentjen, Frank

2017-03-01

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by establishing a Lynch syndrome cohort from the Radboud University Medical Center (Nijmegen, The Netherlands) and the Academic Medical Center (Amsterdam, The Netherlands). Patients with heterozygous germline mutations in MLH1, MSH2 (and EPCAM deletion-mediated MSH2 methylation), MSH6, or PMS2 who were tested and/or treated from 1998 through 2014 were included. Patients who developed IBD were identified by linkage of this cohort to the Dutch nationwide Pathology Registry (PALGA). Subsequently, we compared the risk of CRC between Lynch syndrome patients with IBD and without IBD. Of 1046 patients with Lynch syndrome, 15 developed IBD (1.4%). Patients with Lynch syndrome and IBD were significantly younger (median age, 38.0 y) than patients with Lynch syndrome without IBD (median age, 52.0 y; P = .001). Nevertheless, a similar proportion of patients in each group developed CRC: 4 of the 15 patients (26.7%) with Lynch syndrome and IBD compared with 311 of the 1031 patients (30.2%) with Lynch syndrome without IBD. Patients with Lynch syndrome and IBD developed CRC at a younger age (median age, 36.0 y) than patients with Lynch syndrome without IBD (median age, 46.0 y; P = .045). However, the cumulative incidence of CRC was similar between groups (P = .121). All patients with Lynch syndrome and IBD who developed CRC had ulcerative colitis, producing a higher cumulative incidence of CRC for this IBD subgroup (P < .001). In conclusion, patients with Lynch syndrome and IBD develop CRC risk at a younger age than patients without IBD; patients with ulcerative colitis are at especially high risk. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Incidence of AIDS-Defining and Other Cancers in HIV-Positive Children in South Africa: Record Linkage Study

PubMed Central

Bohlius, Julia; Maxwell, Nicola; Spoerri, Adrian; Wainwright, Rosalind; Sawry, Shobna; Poole, Janet; Eley, Brian; Prozesky, Hans; Rabie, Helena; Garone, Daniela; Technau, Karl-Günter; Maskew, Mhairi; Davies, Mary-Ann; Davidson, Alan; Stefan, D. Cristina; Egger, Matthias

2016-01-01

Background Little is known on the risk of cancer in HIV-positive children in sub-Saharan Africa. We examined incidence and risk factors of AIDS-defining and other cancers in pediatric antiretroviral therapy (ART) programs in South Africa. Methods We linked the records of five ART programs in Johannesburg and Cape Town to those of pediatric oncology units, based on name and surname, date of birth, folder and civil identification numbers. We calculated incidence rates and obtained hazard ratios (HR) with 95% confidence intervals (CI) from Cox regression models including ART, sex, age, and degree of immunodeficiency. Missing CD4 counts and CD4% were multiply imputed. Immunodeficiency was defined according to World Health Organization 2005 criteria. Results Data of 11,707 HIV-positive children were included in the analysis. During 29,348 person-years of follow-up 24 cancers were diagnosed, for an incidence rate of 82 per 100,000 person-years (95% CI 55-122). The most frequent cancers were Kaposi Sarcoma (34 per 100,000 person-years) and Non Hodgkin Lymphoma (31 per 100,000 person-years). The incidence of non AIDS-defining malignancies was 17 per 100,000. The risk of developing cancer was lower on ART (HR 0.29, 95%CI 0.09–0.86), and increased with age at enrolment (>10 versus <3 years: HR 7.3, 95% CI 2.2-24.6) and immunodeficiency at enrolment (advanced/severe versus no/mild: HR 3.5, 95%CI 1.1-12.0). The HR for the effect of ART from complete case analysis was similar but ceased to be statistically significant (p=0.078). Conclusions Early HIV diagnosis and linkage to care, with start of ART before advanced immunodeficiency develops, may substantially reduce the burden of cancer in HIV-positive children in South Africa and elsewhere. PMID:26906162

High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage

PubMed Central

Sieswerda, Elske; Font-Gonzalez, Anna; Reitsma, Johannes B.; Dijkgraaf, Marcel G. W.; Heinen, Richard C.; Jaspers, Monique W.; van der Pal, Helena J.; van Leeuwen, Flora E.; Caron, Huib N.

2016-01-01

Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9–2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5–10 and 20–30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1–16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6–11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources. PMID:27433937

High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage.

PubMed

Sieswerda, Elske; Font-Gonzalez, Anna; Reitsma, Johannes B; Dijkgraaf, Marcel G W; Heinen, Richard C; Jaspers, Monique W; van der Pal, Helena J; van Leeuwen, Flora E; Caron, Huib N; Geskus, Ronald B; Kremer, Leontien C

2016-01-01

Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9-2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5-10 and 20-30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1-16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6-11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources.

The Protective Effects of Exclusive Enteral Nutrition Formulas on Growth Factor Expression and the Proximal Tibial Epiphyseal Growth Plate in a TNBS-Induced IBD Rat Model.

PubMed

Shi, Jieru; Huang, Zhiheng; Wang, Yuhuan; Huang, Ying

2015-07-01

This study aimed to evaluate the effectiveness of different types of nutritional formulas in a rat model of TNBS-induced IBD. IBD was induced with TNBS in 4-week-old rats that were then fed different exclusive enteral nutrition diets for 7 days. The length of the tibia and the number of chondrocytes in the proximal tibias were analyzed at 7 days after supplementation. Immunohistochemical analysis, ELISA and real-time PCR were performed to evaluate the levels of growth hormone receptor (GHR) and insulin-like growth factor-I receptor (IGF-IR), the growth factors IGF-I and insulin-like growth factor-binding protein-3 (IGFBP3) , bone morphogenetic protein (BMP)-2 and BMP-6 respectively. The results demonstrated that the tibia length of the peptide formula group was longer than that of the IBD-Modulen(®) formula and normal diet groups (P < 0.05). Furthermore, the number of chondrocytes of the proximal tibial was more pronounced in the peptide formula group compared to the other groups (P < 0.05). The peptide formula was also more effective in increasing the expression of GHR compared to the other groups (P < 0.05), while the expression of IGF-IR was not significantly different (P > 0.05). In addition, the IGF-I and IGFBP3 levels were more pronounced in the peptide formula supplement group (P < 0.05), and the expression of BMP-2 and BMP-6 mRNA in the proximal tibia growth plate from the peptide formula group was higher than that in the ordinary formula and normal diet groups (P < 0.05). EEN, and particularly a peptide formula, exerted protective effects on the proximal tibial epiphyseal growth plate in a TNBS-induced IBD model.

Usability of a home-based test for the measurement of fecal calprotectin in asymptomatic IBD patients.

PubMed

Bello, Caroline; Roseth, Arne; Guardiola, Jordi; Reenaers, Catherine; Ruiz-Cerulla, Alexandra; Van Kemseke, Catherine; Arajol, Claudia; Reinhard, Christian; Seidel, Laurence; Louis, Edouard

2017-09-01

The aim of our work was to test the usability of fecal calprotectin (FC) home-based test in inflammatory bowel disease (IBD) patients. IBD patients were prospectively recruited. They had to measure FC with a dedicated tool and smartphone application, 5 times at two weeks intervals over an 8 weeks period. They had to fill in a usability questionnaire at the first and the last FC measurement. A System Usability Scale (SUS: 0-100) and the Global Score of Usability (GSU: 0-85) were calculated. FC was also centrally measured by ELISA. Fifty-eight patients were recruited. Forty-two performed at least one FC measurement and 27 performed all the FC requested measurements. The median (IQR) SUS (0-100) at the first and last use were 85 (78-90) and 81 (70-88), respectively; the median (IQR) GSU (0-85) at the first and last use were 74 (69-80) and 77 (68-83), respectively. Adherence to the planned measurements and usability of the tool were higher in females and in less severe disease. The intra-class correlation coefficient between home-based and centrally measured FC was 0.88. The adherence to home-based measurement of FC was fair. Usability scores for the home-based test were high. There was a good correlation with the centrally measured FC by ELISA. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Distribution of lod scores in oligogenic linkage analysis.

PubMed

Williams, J T; North, K E; Martin, L J; Comuzzie, A G; Göring, H H; Blangero, J

2001-01-01

In variance component oligogenic linkage analysis it can happen that the residual additive genetic variance bounds to zero when estimating the effect of the ith quantitative trait locus. Using quantitative trait Q1 from the Genetic Analysis Workshop 12 simulated general population data, we compare the observed lod scores from oligogenic linkage analysis with the empirical lod score distribution under a null model of no linkage. We find that zero residual additive genetic variance in the null model alters the usual distribution of the likelihood-ratio statistic.

Investigator initiated IBD trials in the US: Facts, obstacles and answers

PubMed Central

Herfarth, Hans H; Jackson, Susan; Schliebe, Barbara G.; Martin, Christopher; Ivanova, Anastasia; Anton, Kristen; Sandler, Robert S; Long, Millie D; Isaacs, Kim L; Osterman, Mark T; Sands, Bruce E; Higgins, Peter D; Lewis, James D

2016-01-01

Investigator initiated randomized clinical trials (IITs) are the backbone of academic clinical research. IITs complement the large clinical studies sponsored by industry and address questions, which are usually not the main focus of a commercially directed research but have the purpose to confirm, improve or refute clinically important questions with regard to diagnostic and therapeutic approaches in patient care. The aim of this review is to illustrate the necessary steps to start and complete an IIT in the field of inflammatory bowel diseases (IBD) in the US. The initial milestones for an investigator include structuring a protocol, planning and building of the trial infrastructure, accurately estimating the costs of the trial and gauging the time span for recruitment. Once the trial has begun it is important to keep patient recruitment on target, monitor of the data quality, and document treatment emergent adverse events. This article provides a framework for the different phases of an IIT and outlines potential hurdles, which could hinder a successful execution. PMID:27598744

Sex-specific Linkage Scans in Opioid Dependence

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R.; Palmer, Abraham A.; Gelernter, Joel

2017-01-01

Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6000 single nucleotide polymorphism (SNP) markers were genotyped for 1758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD=3.29; point-wise p=0.00005; empirical autosome-wide p=0.042), which significantly differed from the linkage signal at the same location in EA women (empirical p=0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD=2.18), 104 cM on chromosome 11 (LOD=1.85), and 60.9 cM on chromosome 16 (LOD=1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD=2.32), 152.9 cM on chromosome 6 (LOD=1.86), 16.8 cM on chromosome 7 (LOD=1.95), and 36.1 cM on chromosome 17 (LOD=1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. PMID:27762075

NIR and MR imaging supported hydrogel based delivery system for anti-TNF alpha probiotic therapy of IBD

NASA Astrophysics Data System (ADS)

Janjic, Jelena M.; Berlec, Ales; Bagia, Christina; Liu, Lu S.; Jeric, Irenej; Gach, Michael; Janjic, Bratislav M.; Strukelj, Borut

2016-03-01

Current treatment of inflammatory bowel disease (IBD) is largely symptomatic and consists of anti-inflammatory agents, immune-suppressives or antibiotics, whereby local luminal action is preferred to minimize systemic side-effects. Recently, anti-TNFα therapy has shown considerable success and is now being routinely used. Here we present a novel approach of using perfluorocarbon (PFC) nanoemulsion containing hydrogels (nanoemulgels) as imaging supported delivery systems for anti-TNF alpha probiotic delivery in IBD. To further facilitate image-guided therapy a food-grade lactic acid bacterium Lactococcus lactis capable of TNFα-binding was engineered to incorporate infrared fluorescent protein (IRFP). This modified bacteria was then incorporated into novel PFC nanoemulgels. The nanoemulgels presented here are designed to deliver locally anti-TNFα probiotic in the lower colon and rectum and provide dual imaging signature of gel delivery (MRI) across the rectum and lower colon and bacteria release (NIR). NIR imaging data in vitro demonstrates high IRFP expressing and TNFα-binding bacteria loading in the hydrogel and complete release in 3 hours. Stability tests indicate that gels remain stable for at least 14 days showing no significant change in droplet size, zeta potential and pH. Flow cytometry analyses demonstrate the NIRF expressing bacteria L. lactis binds TNFα in vitro upon release from the gels. Magnetic resonance and near-infrared imaging in vitro demonstrates homogeneity of hydrogels and the imaging capacity of the overall formulation.

A microsatellite genetic linkage map of black rockfish ( Sebastes schlegeli)

NASA Astrophysics Data System (ADS)

Chu, Guannan; Jiang, Liming; He, Yan; Yu, Haiyang; Wang, Zhigang; Jiang, Haibin; Zhang, Quanqi

2014-12-01

Ovoviviparous black rockfish ( Sebastes schlegeli) is an important marine fish species for aquaculture and fisheries in China. Genetic information of this species is scarce because of the lack of microsatellite markers. In this study, a large number of microsatellite markers of black rockfish were isolated by constructing microsatellite-enriched libraries. Female- and male-specific genetic linkage maps were constructed using 435 microsatellite markers genotyped in a full-sib family of the fish species. The female linkage map contained 140 microsatellite markers, in which 23 linkage groups had a total genetic length of 1334.1 cM and average inter-marker space of 13.3 cM. The male linkage map contained 156 microsatellite markers, in which 25 linkage groups had a total genetic length of 1359.6 cM and average inter-marker distance of 12.4 cM. The genome coverage of the female and male linkage maps was 68.6% and 69.3%, respectively. The female-to-male ratio of the recombination rate was approximately 1.07:1 in adjacent microsatellite markers. This paper presents the first genetic linkage map of microsatellites in black rockfish. The collection of polymorphic markers and sex-specific linkage maps of black rockfish could be useful for further investigations on parental assignment, population genetics, quantitative trait loci mapping, and marker-assisted selection in related breeding programs.

Evaluating the Use of Existing Data Sources, Probabilistic Linkage, and Multiple Imputation to Build Population-based Injury Databases Across Phases of Trauma Care

PubMed Central

Newgard, Craig; Malveau, Susan; Staudenmayer, Kristan; Wang, N. Ewen; Hsia, Renee Y.; Mann, N. Clay; Holmes, James F.; Kuppermann, Nathan; Haukoos, Jason S.; Bulger, Eileen M.; Dai, Mengtao; Cook, Lawrence J.

2012-01-01

Objectives The objective was to evaluate the process of using existing data sources, probabilistic linkage, and multiple imputation to create large population-based injury databases matched to outcomes. Methods This was a retrospective cohort study of injured children and adults transported by 94 emergency medical systems (EMS) agencies to 122 hospitals in seven regions of the western United States over a 36-month period (2006 to 2008). All injured patients evaluated by EMS personnel within specific geographic catchment areas were included, regardless of field disposition or outcome. The authors performed probabilistic linkage of EMS records to four hospital and postdischarge data sources (emergency department [ED] data, patient discharge data, trauma registries, and vital statistics files) and then handled missing values using multiple imputation. The authors compare and evaluate matched records, match rates (proportion of matches among eligible patients), and injury outcomes within and across sites. Results There were 381,719 injured patients evaluated by EMS personnel in the seven regions. Among transported patients, match rates ranged from 14.9% to 87.5% and were directly affected by the availability of hospital data sources and proportion of missing values for key linkage variables. For vital statistics records (1-year mortality), estimated match rates ranged from 88.0% to 98.7%. Use of multiple imputation (compared to complete case analysis) reduced bias for injury outcomes, although sample size, percentage missing, type of variable, and combined-site versus single-site imputation models all affected the resulting estimates and variance. Conclusions This project demonstrates the feasibility and describes the process of constructing population-based injury databases across multiple phases of care using existing data sources and commonly available analytic methods. Attention to key linkage variables and decisions for handling missing values can be used to

Bayesian linkage and segregation analysis: factoring the problem.

PubMed

Matthysse, S

2000-01-01

Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian linkage and segregation analysis is one of integration in high-dimensional spaces. In this paper, three available techniques for Bayesian linkage and segregation analysis are discussed: Markov Chain Monte Carlo (MCMC), importance sampling, and exact calculation. The contribution of each to the overall integration will be explicitly discussed.

Mobile assemblies of Bennett linkages from four-crease origami patterns

NASA Astrophysics Data System (ADS)

Zhang, Xiao; Chen, Yan

2018-02-01

This paper deals with constructing mobile assemblies of Bennett linkages inspired by four-crease origami patterns. A transition technique has been proposed by taking the thick-panel form of an origami pattern as an intermediate bridge. A zero-thickness rigid origami pattern and its thick-panel form share the same sector angles and folding behaviours, while the thick-panel origami and the mobile assembly of linkages are kinematically equivalent with differences only in link profiles. Applying this transition technique to typical four-crease origami patterns, we have found that the Miura-ori and graded Miura-ori patterns lead to assemblies of Bennett linkages with identical link lengths. The supplementary-type origami patterns with different mountain-valley crease assignments correspond to different types of Bennett linkage assemblies with negative link lengths. And the identical linkage-type origami pattern generates a new mobile assembly. Hence, the transition technique offers a novel approach to constructing mobile assemblies of spatial linkages from origami patterns.

Mobile assemblies of Bennett linkages from four-crease origami patterns.

PubMed

Zhang, Xiao; Chen, Yan

2018-02-01

This paper deals with constructing mobile assemblies of Bennett linkages inspired by four-crease origami patterns. A transition technique has been proposed by taking the thick-panel form of an origami pattern as an intermediate bridge. A zero-thickness rigid origami pattern and its thick-panel form share the same sector angles and folding behaviours, while the thick-panel origami and the mobile assembly of linkages are kinematically equivalent with differences only in link profiles. Applying this transition technique to typical four-crease origami patterns, we have found that the Miura-ori and graded Miura-ori patterns lead to assemblies of Bennett linkages with identical link lengths. The supplementary-type origami patterns with different mountain-valley crease assignments correspond to different types of Bennett linkage assemblies with negative link lengths. And the identical linkage-type origami pattern generates a new mobile assembly. Hence, the transition technique offers a novel approach to constructing mobile assemblies of spatial linkages from origami patterns.

Dimensional threshold for fracture linkage and hooking

NASA Astrophysics Data System (ADS)

Lamarche, Juliette; Chabani, Arezki; Gauthier, Bertrand D. M.

2018-03-01

Fracture connectivity in rocks depends on spatial properties of the pattern including length, abundance and orientation. When fractures form a single-strike set, they hardly cross-cut each other and the connectivity is limited. Linkage probability increases with increasing fracture abundance and length as small fractures connect to each other to form longer ones. A process for parallel fracture linkage is the "hooking", where two converging fracture tips mutually deviate and then converge to connect due to the interaction of their crack-tip stresses. Quantifying the processes and conditions for fracture linkage in single-strike fracture sets is crucial to better predicting fluid flow in Naturally Fractured Reservoirs. For 1734 fractures in Permian shales of the Lodève Basin, SE France, we measured geometrical parameters in 2D, characterizing three stages of the hooking process: underlapping, overlapping and linkage. We deciphered the threshold values, shape ratios and limiting conditions to switch from one stage to another one. The hook set up depends on the spacing (S) and fracture length (Lh) with the relation S ≈ 0.15 Lh. Once the hooking is initiated, with the fracture deviation length (L) L ≈ 0.4 Lh, the fractures reaches the linkage stage only when the spacing is reduced to S ≈ 0.02 Lh and the convergence (C) is < 0.1 L. These conditions apply to multi-scale fractures with a shape ratio L/S = 10 and for fracture curvature of 10°-20°.

The linkage between childhood bullying behaviour and future offending.

PubMed

Jiang, Depeng; Walsh, Margaret; Augimeri, Leena K

2011-04-01

To examine the linkage between bullying behaviour in early childhood and any subsequent contact with the criminal justice system. A Canadian sample (570 boys and 379 girls) was derived from clients who participated in the evidenced-based programme, SNAP (STOP NOW AND PLAN), between 2001 and 2009. A court order was obtained to access any criminal record data on participants. The Early Assessment Risk Lists (EARL-20B and EARL-21G) and the Child Behavior Checklist (CBCL) were used to identify level of risk and bullying behaviour. Outcome variables included age the child first came in contact with the criminal justice system and frequency. Logistic and Cox regression analyses indicate that the risk of onset of criminal offence for bullies was significantly higher than for non-bullies. The hazard of criminal offence for bullies is 1.9 times (95% CI: 1.1-3.2) than that of non-bullies. This holds true even when adjusted for age, gender and other risk factors. We found a strong linkage between bullying behaviour during childhood and subsequent criminal offending after the age of 12. Criminal convictions for bullies were nearly twice as high for non-bullies up to the child's 18th birthday. EARLs were effective in differentiating risk associated with bullying. Copyright © 2011 John Wiley & Sons, Ltd.

Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.

PubMed Central

Balding, Joanna; Livingstone, Wendy J; Conroy, Judith; Mynett-Johnson, Lesley; Weir, Donald G; Mahmud, Nasir; Smith, Owen P

2004-01-01

The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear. PMID:15223609

Impact of exome sequencing in inflammatory bowel disease

PubMed Central

Cardinale, Christopher J; Kelsen, Judith R; Baldassano, Robert N; Hakonarson, Hakon

2013-01-01

Approaches to understanding the genetic contribution to inflammatory bowel disease (IBD) have continuously evolved from family- and population-based epidemiology, to linkage analysis, and most recently, to genome-wide association studies (GWAS). The next stage in this evolution seems to be the sequencing of the exome, that is, the regions of the human genome which encode proteins. The GWAS approach has been very fruitful in identifying at least 163 loci as being associated with IBD, and now, exome sequencing promises to take our genetic understanding to the next level. In this review we will discuss the possible contributions that can be made by an exome sequencing approach both at the individual patient level to aid with disease diagnosis and future therapies, as well as in advancing knowledge of the pathogenesis of IBD. PMID:24187447

Reporting Errors in Siblings’ Survival Histories and Their Impact on Adult Mortality Estimates: Results From a Record Linkage Study in Senegal

PubMed Central

Helleringer, Stéphane; Pison, Gilles; Kanté, Almamy M.; Duthé, Géraldine; Andro, Armelle

2014-01-01

Estimates of adult mortality in countries with limited vital registration (e.g., sub-Saharan Africa) are often derived from information about the survival of a respondent’s siblings. We evaluated the completeness and accuracy of such data through a record linkage study conducted in Bandafassi, located in southeastern Senegal. We linked at the individual level retrospective siblings’ survival histories (SSH) reported by female respondents (n = 268) to prospective mortality data and genealogies collected through a health and demographic surveillance system (HDSS). Respondents often reported inaccurate lists of siblings. Additions to these lists were uncommon, but omissions were frequent: respondents omitted 3.8 % of their live sisters, 9.1 % of their deceased sisters, and 16.6 % of their sisters who had migrated out of the DSS area. Respondents underestimated the age at death of the siblings they reported during the interview, particularly among siblings who had died at older ages (≥45 years). Restricting SSH data to person-years and events having occurred during a recent reference period reduced list errors but not age and date errors. Overall, SSH data led to a 20 % underestimate of 45q15 relative to HDSS data. Our study suggests new quality improvement strategies for SSH data and demonstrates the potential use of HDSS data for the validation of “unconventional” demographic techniques. PMID:24493063

Reporting errors in siblings' survival histories and their impact on adult mortality estimates: results from a record linkage study in Senegal.

PubMed

Helleringer, Stéphane; Pison, Gilles; Kanté, Almamy M; Duthé, Géraldine; Andro, Armelle

2014-04-01

Estimates of adult mortality in countries with limited vital registration (e.g., sub-Saharan Africa) are often derived from information about the survival of a respondent's siblings. We evaluated the completeness and accuracy of such data through a record linkage study conducted in Bandafassi, located in southeastern Senegal. We linked at the individual level retrospective siblings' survival histories (SSH) reported by female respondents (n = 268) to prospective mortality data and genealogies collected through a health and demographic surveillance system (HDSS). Respondents often reported inaccurate lists of siblings. Additions to these lists were uncommon, but omissions were frequent: respondents omitted 3.8 % of their live sisters, 9.1 % of their deceased sisters, and 16.6 % of their sisters who had migrated out of the DSS area. Respondents underestimated the age at death of the siblings they reported during the interview, particularly among siblings who had died at older ages (≥45 years). Restricting SSH data to person-years and events having occurred during a recent reference period reduced list errors but not age and date errors. Overall, SSH data led to a 20 % underestimate of 45 q 15 relative to HDSS data. Our study suggests new quality improvement strategies for SSH data and demonstrates the potential use of HDSS data for the validation of "unconventional" demographic techniques.

Effects of maltreatment and parental schizophrenia spectrum disorders on early childhood social-emotional functioning: a population record linkage study.

PubMed

Matheson, S L; Kariuki, M; Green, M J; Dean, K; Harris, F; Tzoumakis, S; Tarren-Sweeney, M; Brinkman, S; Chilvers, M; Sprague, T; Carr, V J; Laurens, K R

2017-12-01

Childhood maltreatment and a family history of a schizophrenia spectrum disorder (SSD) are each associated with social-emotional dysfunction in childhood. Both are also strong risk factors for adult SSDs, and social-emotional dysfunction in childhood may be an antecedent of these disorders. We used data from a large Australian population cohort to determine the independent and moderating effects of maltreatment and parental SSDs on early childhood social-emotional functioning. The New South Wales Child Development Study combines intergenerational multi-agency data using record linkage methods. Multiple measures of social-emotional functioning (social competency, prosocial/helping behaviour, anxious/fearful behaviour; aggressive behaviour, and hyperactivity/inattention) on 69 116 kindergarten children (age ~5 years) were linked with government records of child maltreatment and parental presentations to health services for SSD. Multivariable analyses investigated the association between maltreatment and social-emotional functioning, adjusting for demographic variables and parental SSD history, in the population sample and in sub-cohorts exposed and not exposed to parental SSD history. We also examined the association of parental SSD history and social-emotional functioning, adjusting for demographic variables and maltreatment. Medium-sized associations were identified between maltreatment and poor social competency, aggressive behaviour and hyperactivity/inattention; small associations were revealed between maltreatment and poor prosocial/helping and anxious/fearful behaviours. These associations did not differ greatly when adjusted for parental SSD, and were greater in magnitude among children with no history of parental SSD. Small associations between parental SSD and poor social-emotional functioning remained after adjusting for demographic variables and maltreatment. Childhood maltreatment and history of parental SSD are associated independently with poor early

Three Degree of Freedom Parallel Mechanical Linkage

NASA Technical Reports Server (NTRS)

Adelstein, Bernard D. (Inventor)

1998-01-01

A three degree of freedom parallel mechanism or linkage that couples three degree of freedom translational displacements at an endpoint, such as a handle, a hand grip, or a robot tool, to link rotations about three axes that are fixed with respect to a common base or ground link. The mechanism includes a three degree of freedom spherical linkage formed of two closed loops, and a planar linkage connected to the endpoint. The closed loops are rotatably interconnected, and made of eight rigid links connected by a plurality of single degree of freedom revolute joints. Three of these revolute joints are base joints and are connected to a common ground. such that the axis lines passing through the revolute joints intersect at a common fixed center point K forming the center of a spherical work volume in which the endpoint is capable of moving. 'Me three degrees of freedom correspond to the spatial displacement of the endpoint, for instance. The mechanism provides a new overall spatial kinematic linkage composed of a minimal number of rigid links and rotary joints. The mechanism has improved mechanical stiffness, and conveys mechanical power bidirectionally between the human operator and the electromechanical actuators. It does not require gears, belts. cable, screw or other types of transmission elements, and is useful in applications requiring full backdrivability. Thus, this invention can serve as the mechanical linkage for actively powered devices such as compliant robotic manipulators and force-reflecting hand controllers, and passive devices such as manual input devices for computers and other systems.

[Linkage to care among new human immunodeficiency virus diagnoses in Spain].

PubMed

Oliva, Jesús; Malo, Carmen; Fernández, Ana; Izquierdo, Ana; Marcos, Henar; Cevallos, Carlos; Castilla, Jesús; García, Rocio; Díez, Mercedes

2014-03-01

To describe linkage to care among new HIV diagnoses in Spain; and to estimate factors associated to linkage to care within three months after diagnosis. The distribution of the time elapsing between the date of HIV diagnosis and the date of first determination of CD4 (considered to be the date of linkage to care) was calculated among new HIV diagnoses in 2010 in the seven Autonomous Regions participating, where data on date of CD4 count was available. Linkage to care was considered «correct» if done within three months after diagnosis. Factors associated to correct linkage to care were estimated using logistic regression. A total of 1769 new HIV diagnoses were included. Of them, 83.1% had evidence of linkage to care within a year, and 75.7% were linked within three months after diagnosis. Being an injectable drug user (IDU) was the only factor inversely associated with linkage to care within 3 months (OR = 0.3; 95% CI: 0.2-0.6). In Spain linkage to care after HIV diagnosis is good, but there is still room for improvement, especially among IDUs. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Phase-Division-Based Dynamic Optimization of Linkages for Drawing Servo Presses

NASA Astrophysics Data System (ADS)

Zhang, Zhi-Gang; Wang, Li-Ping; Cao, Yan-Ke

2017-11-01

Existing linkage-optimization methods are designed for mechanical presses; few can be directly used for servo presses, so development of the servo press is limited. Based on the complementarity of linkage optimization and motion planning, a phase-division-based linkage-optimization model for a drawing servo press is established. Considering the motion-planning principles of a drawing servo press, and taking account of work rating and efficiency, the constraints of the optimization model are constructed. Linkage is optimized in two modes: use of either constant eccentric speed or constant slide speed in the work segments. The performances of optimized linkages are compared with those of a mature linkage SL4-2000A, which is optimized by a traditional method. The results show that the work rating of a drawing servo press equipped with linkages optimized by this new method improved and the root-mean-square torque of the servo motors is reduced by more than 10%. This research provides a promising method for designing energy-saving drawing servo presses with high work ratings.

Sex-specific linkage scans in opioid dependence.

PubMed

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R; Palmer, Abraham A; Gelernter, Joel

2017-04-01

Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6,000 single nucleotide polymorphism (SNP) markers were genotyped for 1,758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD = 3.29; point-wise P = 0.00005; empirical autosome-wide P = 0.042), which significantly differed from the linkage signal at the same location in EA women (empirical P = 0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD = 2.18), 104 cM on chromosome 11 (LOD = 1.85), and 60.9 cM on chromosome 16 (LOD = 1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD = 2.32), 152.9 cM on chromosome 6 (LOD = 1.86), 16.8 cM on chromosome 7 (LOD = 1.95), and 36.1 cM on chromosome 17 (LOD = 1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Student-Teacher Linkage Verification: Model Process and Recommendations

ERIC Educational Resources Information Center

Watson, Jeffery; Graham, Matthew; Thorn, Christopher A.

2012-01-01

As momentum grows for tracking the role of individual educators in student performance, school districts across the country are implementing projects that involve linking teachers to their students. Programs that link teachers to student outcomes require a verification process for student-teacher linkages. Linkage verification improves accuracy by…

Prospective Industrial Linkage at Aqaba University College, Jordan

ERIC Educational Resources Information Center

Abu-Hamatteh, Zeid; Al-Amyan, Mozfi; Al-Azzam, Farouq

2008-01-01

The present study intends to examine the overall situation and the environment of Aqaba University College (AUC) in relation to industrial-educational interaction, and to discuss existing and possible future industrial linkage strategies. This article presents observations from AUC, as well as suggestions for action on industrial linkage. The…

SNP Discovery and Linkage Map Construction in Cultivated Tomato

PubMed Central

Shirasawa, Kenta; Isobe, Sachiko; Hirakawa, Hideki; Asamizu, Erika; Fukuoka, Hiroyuki; Just, Daniel; Rothan, Christophe; Sasamoto, Shigemi; Fujishiro, Tsunakazu; Kishida, Yoshie; Kohara, Mitsuyo; Tsuruoka, Hisano; Wada, Tsuyuko; Nakamura, Yasukazu; Sato, Shusei; Tabata, Satoshi

2010-01-01

Few intraspecific genetic linkage maps have been reported for cultivated tomato, mainly because genetic diversity within Solanum lycopersicum is much less than that between tomato species. Single nucleotide polymorphisms (SNPs), the most abundant source of genomic variation, are the most promising source of polymorphisms for the construction of linkage maps for closely related intraspecific lines. In this study, we developed SNP markers based on expressed sequence tags for the construction of intraspecific linkage maps in tomato. Out of the 5607 SNP positions detected through in silico analysis, 1536 were selected for high-throughput genotyping of two mapping populations derived from crosses between ‘Micro-Tom’ and either ‘Ailsa Craig’ or ‘M82’. A total of 1137 markers, including 793 out of the 1338 successfully genotyped SNPs, along with 344 simple sequence repeat and intronic polymorphism markers, were mapped onto two linkage maps, which covered 1467.8 and 1422.7 cM, respectively. The SNP markers developed were then screened against cultivated tomato lines in order to estimate the transferability of these SNPs to other breeding materials. The molecular markers and linkage maps represent a milestone in the genomics and genetics, and are the first step toward molecular breeding of cultivated tomato. Information on the DNA markers, linkage maps, and SNP genotypes for these tomato lines is available at http://www.kazusa.or.jp/tomato/. PMID:21044984

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprine or 6-mercaptopurine intolerant IBD patients

PubMed Central

de Boer, Nanne KH; Derijks, Luc JJ; Gilissen, Lennard PL; Hommes, Daniel W; Engels, Leopold GJB; de Boer, Sybrand Y; den Hartog, Gijsbertus; Hooymans, Piet M; Mäkelburg, Anja BU; Westerveld, Barend D; Naber, Anton HJ; Mulder, Chris JJ; de Jong, Dirk J

2005-01-01

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year. METHODS: Database analysis. RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%) and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly. CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials. PMID:16222751

Optimization of Inflammatory Bowel Disease Cohort Studies in Asia.

PubMed

Leung, Wai K

2015-07-01

With the incidence of inflammatory bowel disease (IBD) increasing rapidly in many Asian countries, including Hong Kong, it is important that patient characteristics are better understood. For example, are the phenotypes, behaviors, complications, and even treatment responses found in Asian patients similar to those of their Western counterparts? To formally address these questions, a properly designed local cohort study is needed. Whilst IBD is still relatively uncommon in Asia, the establishment of a local IBD registry will significantly contribute to the answering of these questions. The Hong Kong IBD registry was established to fill the gap in the understanding of IBD patients, and to foster research into IBD in Hong Kong. The Hong Kong IBD registry is a territory-wide registry that includes all public hospitals in Hong Kong. We included all IBD patients who were currently receiving medical care at these hospitals. With the help of the central computer medical record system of the Hospital Authority of Hong Kong, all clinical events, medications usage, endoscopy records, and laboratory results of patients in the registry were captured. Apart from data collection, the registry is also establishing a bio-specimen bank of blood and stool samples of IBD patients for future research. The IBD registry is a very useful platform for population-based studies on IBD in Asia.

Polymorphisms in the TLR4 and TLR5 gene are significantly associated with inflammatory bowel disease in German shepherd dogs.

PubMed

Kathrani, Aarti; House, Arthur; Catchpole, Brian; Murphy, Angela; German, Alex; Werling, Dirk; Allenspach, Karin

2010-12-23

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease.

Intragroup Emotions: Physiological Linkage and Social Presence.

PubMed

Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

2016-01-01

We investigated how technologically mediating two different components of emotion-communicative expression and physiological state-to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

PubMed

Asherson, P; Zhou, K; Anney, R J L; Franke, B; Buitelaar, J; Ebstein, R; Gill, M; Altink, M; Arnold, R; Boer, F; Brookes, K; Buschgens, C; Butler, L; Cambell, D; Chen, W; Christiansen, H; Feldman, L; Fleischman, K; Fliers, E; Howe-Forbes, R; Goldfarb, A; Heise, A; Gabriëls, I; Johansson, L; Lubetzki, I; Marco, R; Medad, S; Minderaa, R; Mulas, F; Müller, U; Mulligan, A; Neale, B; Rijsdijk, F; Rabin, K; Rommelse, N; Sethna, V; Sorohan, J; Uebel, H; Psychogiou, L; Weeks, A; Barrett, R; Xu, X; Banaschewski, T; Sonuga-Barke, E; Eisenberg, J; Manor, I; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Steinhausen, H-C; Taylor, E; Thompson, M; Faraone, S V

2008-05-01

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

An Autosomal Genetic Linkage Map of the Sheep Genome

PubMed Central

Crawford, A. M.; Dodds, K. G.; Ede, A. J.; Pierson, C. A.; Montgomery, G. W.; Garmonsway, H. G.; Beattie, A. E.; Davies, K.; Maddox, J. F.; Kappes, S. W.; Stone, R. T.; Nguyen, T. C.; Penty, J. M.; Lord, E. A.; Broom, J. E.; Buitkamp, J.; Schwaiger, W.; Epplen, J. T.; Matthew, P.; Matthews, M. E.; Hulme, D. J.; Beh, K. J.; McGraw, R. A.; Beattie, C. W.

1995-01-01

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation fullsib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum number of informative meioses within the mapping flock was 222. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes. PMID:7498748

Linkages between ACE Vocational Provision and Mainstream VET.

ERIC Educational Resources Information Center

Saunders, John

A study investigated linkages between adult community education (ACE) and mainstream vocational education and training (VET) in Australia, which enable people to move between the two sectors in their pursuit of vocational learning, and the ways in which linkages might be improved or new ones developed. The data from the study were derived from 69…

Validation of an instrument to measure inter-organisational linkages in general practice.

PubMed

Amoroso, Cheryl; Proudfoot, Judith; Bubner, Tanya; Jayasinghe, Upali W; Holton, Christine; Winstanley, Julie; Beilby, Justin; Harris, Mark F

2007-12-03

Linkages between general medical practices and external services are important for high quality chronic disease care. The purpose of this research is to describe the development, evaluation and use of a brief tool that measures the comprehensiveness and quality of a general practice's linkages with external providers for the management of patients with chronic disease. In this study, clinical linkages are defined as the communication, support, and referral arrangements between services for the care and assistance of patients with chronic disease. An interview to measure surgery-level (rather than individual clinician-level) clinical linkages was developed, piloted, reviewed, and evaluated with 97 Australian general practices. Two validated survey instruments were posted to patients, and a survey of locally available services was developed and posted to participating Divisions of General Practice (support organisations). Hypotheses regarding internal validity, association with local services, and patient satisfaction were tested using factor analysis, logistic regression and multilevel regression models. The resulting General Practice Clinical Linkages Interview (GP-CLI) is a nine-item tool with three underlying factors: referral and advice linkages, shared care and care planning linkages, and community access and awareness linkages. Local availability of chronic disease services has no affect on the comprehensiveness of services with which practices link, however, comprehensiveness of clinical linkages has an association with patient assessment of access, receptionist services, and of continuity of care in their general practice. The GP-CLI may be useful to researchers examining comparable health care systems for measuring the comprehensiveness and quality of linkages at a general practice-level with related services, possessing both internal and external validity. The tool can be used with large samples exploring the impact, outcomes, and facilitators of high

Estimation and test for linkage between markers: a comparison of lod score and χ (2) test in a linkage study of maritime pine (Pinus pinaster Ait.).

PubMed

Gerber, S; Rodolphe, F

1994-06-01

The first step in the construction of a linkage map involves the estimation and test for linkage between all possible pairs of markers. The lod score method is used in many linkage studies for the latter purpose. In contrast with classical statistical tests, this method does not rely on the choice of a first-type error level. We thus provide a comparison between the lod score and a χ (2) test on linkage data from a gymnosperm, the maritime pine. The lod score appears to be a very conservative test with the usual thresholds. Its severity depends on the type of data used.

Linkage mapping in sheep and deer identifies a conserved pecora ruminant linkage group orthologous to two regions of HSA16 and a portion of HSA7Q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broom, J.E.; Tate, M.L.; Dodds, K.G.

1996-05-01

Two orthologous linkage groups have been mapped in sheep and deer. Seven loci have been mapped in deer, and 12 in sheep. The sheep linkage group is assigned of ovine chromosome 24. The linkage groups consist of loci from the short arm of human chromosome 16, spanning the region containing the human Batten disease locus, and from human chromosome 7. One locus from the long arm of human chromosome 16 is also present, demonstrating a previously unknown rearrangement between human and ruminant chromosomes. There is no significant difference in marker order and distances between the two linkage groups, implying thatmore » this linkage pattern was present in the genome of the common ancestor of the pecora ruminants. 35 refs., 1 fig., 2 tabs.« less

Recombination patterns reveal information about centromere location on linkage maps.

PubMed

Limborg, Morten T; McKinney, Garrett J; Seeb, Lisa W; Seeb, James E

2016-05-01

Linkage mapping is often used to identify genes associated with phenotypic traits and for aiding genome assemblies. Still, many emerging maps do not locate centromeres - an essential component of the genomic landscape. Here, we demonstrate that for genomes with strong chiasma interference, approximate centromere placement is possible by phasing the same data used to generate linkage maps. Assuming one obligate crossover per chromosome arm, information about centromere location can be revealed by tracking the accumulated recombination frequency along linkage groups, similar to half-tetrad analyses. We validate the method on a linkage map for sockeye salmon (Oncorhynchus nerka) with known centromeric regions. Further tests suggest that the method will work well in other salmonids and other eukaryotes. However, the method performed weakly when applied to a male linkage map (rainbow trout; O. mykiss) characterized by low and unevenly distributed recombination - a general feature of male meiosis in many species. Further, a high frequency of double crossovers along chromosome arms in barley reduced resolution for locating centromeric regions on most linkage groups. Despite these limitations, our method should work well for high-density maps in species with strong recombination interference and will enrich many existing and future mapping resources. © 2015 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.

Intragroup Emotions: Physiological Linkage and Social Presence

PubMed Central

Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

2016-01-01

We investigated how technologically mediating two different components of emotion—communicative expression and physiological state—to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence. PMID:26903913

Intra-facility linkage of HIV-positive mothers and HIV-exposed babies into HIV chronic care: rural and urban experience in a resource limited setting.

PubMed

Mugasha, Christine; Kigozi, Joanita; Kiragga, Agnes; Muganzi, Alex; Sewankambo, Nelson; Coutinho, Alex; Nakanjako, Damalie

2014-01-01

Linkage of HIV-infected pregnant women to HIV care remains critical for improvement of maternal and child outcomes through prevention of maternal-to-child transmission of HIV (PMTCT) and subsequent chronic HIV care. This study determined proportions and factors associated with intra-facility linkage to HIV care and Early Infant Diagnosis care (EID) to inform strategic scale up of PMTCT programs. A cross-sectional review of records was done at 2 urban and 3 rural public health care facilities supported by the Infectious Diseases Institute (IDI). HIV-infected pregnant mothers, identified through routine antenatal care (ANC) and HIV-exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-delivery. Overall, 1,025 HIV-infected pregnant mothers were identified during ANC between January and June, 2012; 267/1,025 (26%) in rural and 743/1,025 (74%) in urban facilities. Of these 375/1,025 (37%) were linked to HIV clinics [67/267(25%) rural and 308/758(41%) urban]. Of 636 HIV-exposed babies, 193 (30%) were linked to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/636); 8/179 (4.5%)] in rural and 93/457(20.3%) in urban health facilities. Within rural facilities, ANC registration <28 weeks-of-gestation was associated with mothers' linkage to HIV chronic care [AoR, 2.0 95% CI, 1.1-3.7, p = 0.019] and mothers' multi-parity was associated with baby's linkage to EID; AoR 4.4 (1.3-15.1), p = 0.023. Stigma, long distance to health facilities and vertical PMTCT services affected linkage in rural facilities, while peer mothers, infant feeding services, long patient queues and limited privacy hindered linkage to HIV care in urban settings. Post-natal linkage of HIV-infected mothers to chronic HIV care and HIV-exposed babies to EID programs was low. Barriers to linkage to HIV care vary in urban and rural settings. We recommend targeted interventions to rapidly improve linkage to antiretroviral therapy for elimination of MTCT.

Solid-Phase Synthesis of RNA Analogs Containing Phosphorodithioate Linkages.

PubMed

Yang, Xianbin

2017-09-18

The oligoribonucleotide phosphorodithioate (PS2-RNA) modification uses two sulfur atoms to replace two non-bridging oxygen atoms at an internucleotide phosphorodiester backbone linkage. Like a natural phosphodiester RNA backbone linkage, a PS2-modified backbone linkage is achiral at phosphorus. PS2-RNAs are highly stable to nucleases and several in vitro assays have demonstrated their biological activity. For example, PS2-RNAs silenced mRNA in vitro and bound to protein targets in the form of PS2-aptamers (thioaptamers). Thus, the interest in and promise of PS2-RNAs has drawn attention to synthesizing, isolating, and characterizing these compounds. RNA-thiophosphoramidite monomers are commercially available from AM Biotechnologies and this unit describes an effective methodology for solid-phase synthesis, deprotection, and purification of RNAs having PS2 internucleotide linkages. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

An autosomal genetic linkage map of the sheep genome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crawford, A.M.; Ede, A.J.; Pierson, C.A.

1995-06-01

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation full-sib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum numbermore » of informative meioses within the mapping flock was 22. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes. 102 refs., 8 figs., 5 tabs.« less

Recurrence rate of clostridium difficile infection in hospitalized pediatric patients with inflammatory bowel disease.

PubMed

Kelsen, Judith R; Kim, Jason; Latta, Dan; Smathers, Sarah; McGowan, Karin L; Zaoutis, Theodore; Mamula, Petar; Baldassano, Robert N

2011-01-01

The incidence and associated morbidity of Clostridium difficile (CD) infection has been increasing at an alarming rate in North America. Clostridium difficile-associated diarrhea (CDAD) is the leading cause of nosocomial diarrhea in the USA. Patients with CDAD have longer average hospital admissions and additional hospital costs. Evidence has demonstrated that patients with inflammatory bowel disease (IBD) have a higher incidence of CD in comparison to the general population. The aim of this study was to compare the rate of recurrence of CD in hospitalized pediatric patients with IBD compared to hospitalized controls. The secondary aim was to evaluate whether infection with CD resulted in a more severe disease course of IBD. This was a nested case control retrospective study of hospitalized pediatric patients. Diagnosis of CD was confirmed with stool Toxin A and B analysis. The following data were obtained from the medical records: demographic information, classification of IBD including location of disease, IBD therapy, and prior surgeries. In addition, prior hospital admissions within 1 year and antibiotic exposure were recorded. The same information was recorded following CD infection. Cases were patients with IBD and CD; two control populations were also studied: patients with CD but without IBD, and patients with IBD but without CD. For aim 1, a total of 111 eligible patients with IBD and CD infection and 77 eligible control patients with CD infection were included. The rate of recurrence of CD in the IBD population was 34% compared to 7.5% in the control population (P < 0.0001). In evaluating the effect of CD infection on IBD disease severity, we compared the 111 IBD patients with CD to a second control population of 127 IBD patients without CD. 57% of IBD-CD patients were readmitted with an exacerbation of disease within 6 months of infection with CD and 67% required escalation of therapy following CD infection, compared to 30% of IBD patients without CD (P

Data Linkage in VET Research: Opportunities, Challenges and Principles. Discussion Paper

ERIC Educational Resources Information Center

Osborne, Kristen; Fowler, Craig; Circelli, Michelle

2018-01-01

This discussion paper explores the possibilities and risks that data linkage presents for the vocational education and training (VET) sector. Along with a broad overview of the nature of data linkage, it highlights possible applications for data linkage in the VET sector and examines the key challenges associated with its use. A number of case…

Effectiveness of disease-specific cognitive–behavioural therapy on depression, anxiety, quality of life and the clinical course of disease in adolescents with inflammatory bowel disease: study protocol of a multicentre randomised controlled trial (HAPPY-IBD)

PubMed Central

van den Brink, Gertrude; Stapersma, Luuk; El Marroun, Hanan; Henrichs, Jens; Szigethy, Eva M; Utens, Elisabeth MWJ; Escher, Johanna C

2016-01-01

Introduction Adolescents with inflammatory bowel disease (IBD) show a higher prevalence of depression and anxiety, compared to youth with other chronic diseases. The inflammation-depression hypothesis might explain this association, and implies that treating depression can decrease intestinal inflammation and improve disease course. The present multicentre randomised controlled trial aims to test the effectiveness of an IBD-specific cognitive–behavioural therapy (CBT) protocol in reducing symptoms of subclinical depression and anxiety, while improving quality of life and disease course in adolescents with IBD. Methods and analysis Adolescents with IBD (10–20 years) from 7 hospitals undergo screening (online questionnaires) for symptoms of depression and anxiety. Those with elevated scores of depression (Child Depression Inventory (CDI) ≥13 or Beck Depression Inventory (BDI) II ≥14) and/or anxiety (Screen for Child Anxiety Related Disorders: boys ≥26, girls ≥30) receive a psychiatric interview. Patients meeting criteria for depressive/anxiety disorders are referred for psychotherapy outside the trial. Patients with elevated (subclinical) symptoms are randomly assigned to medical care-as-usual (CAU; n=50) or CAU plus IBD-specific CBT (n=50). Main outcomes: (1) reduction in depressive and/or anxiety symptoms after 3 months and (2) sustained remission for 12 months. Secondary outcomes: quality of life, psychosocial functioning, treatment adherence. In addition, we will assess inflammatory cytokines in peripheral blood mononuclear cells and whole blood RNA expression profiles. For analysis, multilevel linear models and generalised estimating equations will be used. Ethics and dissemination The Medical Ethics Committee of the Erasmus MC approved this study. If we prove that this CBT improves emotional well-being as well as disease course, implementation is recommended. Trial registration number NCT02265588. PMID:26966551

Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-γ) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells

PubMed Central

Bisping, G; Lügering, N; Lütke-Brintrup, S; Pauels, H -G; Schürmann, G; Domschke, W; Kucharzik, T

2001-01-01

Intestinal epithelial cells seem to play a key role during IBD. The network of cellular interactions between epithelial cells and lamina propria mononuclear cells is still incompletely understood. In the following co-culture model we investigated the influence of intestinal epithelial cells on cytokine expression of T cytotoxic and T helper cells from patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMC) were purified by a Ficoll–Hypaque gradient followed by co-incubation with epithelial cells in multiwell cell culture insert plates in direct contact as well as separated by transwell filters. We used Caco-2 cells as well as freshly isolated colonic epithelia obtained from surgical specimens. Three-colour immunofluorescence flow cytometry was performed after collection, stimulation and staining of PBMC with anti-CD4, anti-CD8, anti-IFN-γ and anti-IL-4. Patients with IBD (Crohn's disease (CD), n = 12; ulcerative colitis (UC), n = 16) and healthy controls (n = 10) were included in the study. After 24 h of co-incubation with Caco-2 cells we found a significant increase of IFN-γ-producing CD8+ lymphocytes in patients with IBD. In contrast, healthy controls did not respond to the epithelial stimulus. No significant differences could be found between CD and UC or active and inactive disease. A significant increase of IFN-γ+/CD8+ lymphocytes in patients with UC was also seen after direct co-incubation with primary cultures of colonic crypt cells. The observed epithelial–lymphocyte interaction seems to be MHC I-restricted. No significant epithelial cell-mediated effects on cytokine expression were detected in the PBMC CD4+ subsets. Patients with IBD—even in an inactive state of disease—exert an increased capacity for IFN-γ induction in CD8+ lymphocytes mediated by intestinal epithelial cells. This mechanism may be important during chronic intestinal inflammation, as in the case of altered mucosal barrier function epithelial cells may

Appliation of rad-sequencing to linkage mapping in citrus

USDA-ARS?s Scientific Manuscript database

High density linkage maps can be developed for modest cost using high-throughput DNA sequencing to genotype a defined fraction (representation) of the genome. We developed linkage maps in two citrus populations using the RAD (Restriction site Associated DNA) genotyping method which involves restrict...

A Comprehensive Linkage Map of the Dog Genome

PubMed Central

Wong, Aaron K.; Ruhe, Alison L.; Dumont, Beth L.; Robertson, Kathryn R.; Guerrero, Giovanna; Shull, Sheila M.; Ziegle, Janet S.; Millon, Lee V.; Broman, Karl W.; Payseur, Bret A.; Neff, Mark W.

2010-01-01

We have leveraged the reference sequence of a boxer to construct the first complete linkage map for the domestic dog. The new map improves access to the dog's unique biology, from human disease counterparts to fascinating evolutionary adaptations. The map was constructed with ∼3000 microsatellite markers developed from the reference sequence. Familial resources afforded 450 mostly phase-known meioses for map assembly. The genotype data supported a framework map with ∼1500 loci. An additional ∼1500 markers served as map validators, contributing modestly to estimates of recombination rate but supporting the framework content. Data from ∼22,000 SNPs informing on a subset of meioses supported map integrity. The sex-averaged map extended 21 M and revealed marked region- and sex-specific differences in recombination rate. The map will enable empiric coverage estimates and multipoint linkage analysis. Knowledge of the variation in recombination rate will also inform on genomewide patterns of linkage disequilibrium (LD), and thus benefit association, selective sweep, and phylogenetic mapping approaches. The computational and wet-bench strategies can be applied to the reference genome of any nonmodel organism to assemble a de novo linkage map. PMID:19966068

Arctic-midlatitude weather linkages in North America

NASA Astrophysics Data System (ADS)

Overland, James E.; Wang, Muyin

2018-06-01

There is intense public interest in whether major Arctic changes can and will impact midlatitude weather such as cold air outbreaks on the central and east side of continents. Although there is progress in linkage research for eastern Asia, a clear gap is conformation for North America. We show two stationary temperature/geopotential height patterns where warmer Arctic temperatures have reinforced existing tropospheric jet stream wave amplitudes over North America: a Greenland/Baffin Block pattern during December 2010 and an Alaska Ridge pattern during December 2017. Even with continuing Arctic warming over the past decade, other recent eastern US winter months were less susceptible for an Arctic linkage: the jet stream was represented by either zonal flow, progressive weather systems, or unfavorable phasing of the long wave pattern. The present analysis lays the scientific controversy over the validity of linkages to the inherent intermittency of jet stream dynamics, which provides only an occasional bridge between Arctic thermodynamic forcing and extended midlatitude weather events.

High-frequency stock linkage and multi-dimensional stationary processes

NASA Astrophysics Data System (ADS)

Wang, Xi; Bao, Si; Chen, Jingchao

2017-02-01

In recent years, China's stock market has experienced dramatic fluctuations; in particular, in the second half of 2014 and 2015, the market rose sharply and fell quickly. Many classical financial phenomena, such as stock plate linkage, appeared repeatedly during this period. In general, these phenomena have usually been studied using daily-level data or minute-level data. Our paper focuses on the linkage phenomenon in Chinese stock 5-second-level data during this extremely volatile period. The method used to select the linkage points and the arbitrage strategy are both based on multi-dimensional stationary processes. A new program method for testing the multi-dimensional stationary process is proposed in our paper, and the detailed program is presented in the paper's appendix. Because of the existence of the stationary process, the strategy's logarithmic cumulative average return will converge under the condition of the strong ergodic theorem, and this ensures the effectiveness of the stocks' linkage points and the more stable statistical arbitrage strategy.

Linkage of the National Health Interview Survey to air quality data.

PubMed

Parker, Jennifer D; Kravets, Nataliya; Woodruff, Tracey J

2008-02-01

This report describes the linkage between the National Health Interview Survey (NHIS) and air monitoring data from the U.S. Environmental Protection Agency (EPA). There have been few linkages of these data sources, partly because of restrictions on releasing geographic detail from NHIS on public-use files in order to protect participant confidentiality. Pollution exposures for NHIS respondents were calculated by averaging the annual average exposure estimates from EPA air monitors both within 5, 10, 15, and 20 miles of the respondent's block-group location (which is available on restricted NHIS data files) and by county of residence. The 1987-2005 linked data files--referred to as NHIS-EPAAnnualAir--were used to describe the percentage of NHIS respondents linked and the median exposures by linkage method, survey year, and pollutant. Using the 2005 NHIS-EPAAnnualAir data file, the percentage linked and median exposure were described by respondent characteristics, linkage method, and pollutant. Many decisions were made to define pollution exposures for NHIS respondents, including monitor selection, location assignment for NHIS respondents, and geographic linkage criteria. Geographic linkage criteria for assigning area-level exposure estimates affected the percentage and composition of respondents included in the resulting linked sample. Median exposure estimates, however, were similar among geographic linkage methods. NHIS-EPAAnnualAir data files for 1985 through 2005 are currently available to users in the NCHS Research Data Center.

Using Object Oriented Bayesian Networks to Model Linkage, Linkage Disequilibrium and Mutations between STR Markers

PubMed Central

Kling, Daniel; Egeland, Thore; Mostad, Petter

2012-01-01

In a number of applications there is a need to determine the most likely pedigree for a group of persons based on genetic markers. Adequate models are needed to reach this goal. The markers used to perform the statistical calculations can be linked and there may also be linkage disequilibrium (LD) in the population. The purpose of this paper is to present a graphical Bayesian Network framework to deal with such data. Potential LD is normally ignored and it is important to verify that the resulting calculations are not biased. Even if linkage does not influence results for regular paternity cases, it may have substantial impact on likelihood ratios involving other, more extended pedigrees. Models for LD influence likelihoods for all pedigrees to some degree and an initial estimate of the impact of ignoring LD and/or linkage is desirable, going beyond mere rules of thumb based on marker distance. Furthermore, we show how one can readily include a mutation model in the Bayesian Network; extending other programs or formulas to include such models may require considerable amounts of work and will in many case not be practical. As an example, we consider the two STR markers vWa and D12S391. We estimate probabilities for population haplotypes to account for LD using a method based on data from trios, while an estimate for the degree of linkage is taken from the literature. The results show that accounting for haplotype frequencies is unnecessary in most cases for this specific pair of markers. When doing calculations on regular paternity cases, the markers can be considered statistically independent. In more complex cases of disputed relatedness, for instance cases involving siblings or so-called deficient cases, or when small differences in the LR matter, independence should not be assumed. (The networks are freely available at http://arken.umb.no/~dakl/BayesianNetworks.) PMID:22984448

Association of Autism Spectrum Disorders and Inflammatory Bowel Disease

ERIC Educational Resources Information Center

Lee, Maunoo; Krishnamurthy, Jayasree; Susi, Apryl; Sullivan, Carolyn; Gorman, Gregory H.; Hisle-Gorman, Elizabeth; Erdie-Lalena, Christine R.; Nylund, Cade M.

2018-01-01

Autism spectrum disorders (ASD) and inflammatory bowel disease (IBD) both have multifactorial pathogenesis with an increasing number of studies demonstrating gut-brain associations. We aim to examine the association between ASD and IBD using strict classification criteria for IBD. We conducted a retrospective case-cohort study using records from…

The impact of childhood residential mobility on mental health outcomes in adolescence and early adulthood: a record linkage study.

PubMed

Tseliou, Foteini; Maguire, Aideen; Donnelly, Michael; O'Reilly, Dermot

2016-03-01

Understanding the causes of poor mental health in early childhood and adolescence is important as this can be a significant determinant of mental well-being in later years. One potential and relatively unexplored factor is residential mobility in formative years. Previous studies have been relatively small and potentially limited due to methodological issues. The main aim of this study was to investigate the relationship between early residential instability and poor mental health among adolescents and young adults in Northern Ireland. A Census-based record linkage study of 28% of children aged 0-8 years in 2001 in Northern Ireland (n=49,762) was conducted, with six monthly address change assessments from health registration data and self-reported mental health status from the 2011 Census. Logistic regression models were built adjusting for socioeconomic status (SES), household composition and marital dissolution. There was a graded relationship between the number of address changes and mental ill-health (adjusted OR 3.67, 95% CIs 2.11 to 6.39 for 5 or more moves). This relationship was not modified by SES or household composition. Marital dissolution was associated with poor mental health but did not modify the relationship between address change and mental health (p=0.206). There was some indication that movement after the age of five was associated with an increased likelihood of poor mental health. This large study clearly confirms the close relationship between address change in early years and later poor mental health. Residential mobility may be a useful marker for children at risk of poorer mental health in adolescence and early adulthood. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Record Linkage Techniques - 1985. Proceedings of the Workshop on Exact Matching Methodologies

DOT National Transportation Integrated Search

1985-12-01

The Workshop on Exact Matching Methodologies was held on May 9-10, 1985, at the Rosslyn Westpark Hotel in Arlington, Virginia. The conference grew out of the efforts of the Matching Group, Administrative Records Subcommittee, of the Federal Committee...

Linkage of Viral Sequences among HIV-Infected Village Residents in Botswana: Estimation of Linkage Rates in the Presence of Missing Data

PubMed Central

Carnegie, Nicole Bohme; Wang, Rui; Novitsky, Vladimir; De Gruttola, Victor

2014-01-01

Linkage analysis is useful in investigating disease transmission dynamics and the effect of interventions on them, but estimates of probabilities of linkage between infected people from observed data can be biased downward when missingness is informative. We investigate variation in the rates at which subjects' viral genotypes link across groups defined by viral load (low/high) and antiretroviral treatment (ART) status using blood samples from household surveys in the Northeast sector of Mochudi, Botswana. The probability of obtaining a sequence from a sample varies with viral load; samples with low viral load are harder to amplify. Pairwise genetic distances were estimated from aligned nucleotide sequences of HIV-1C env gp120. It is first shown that the probability that randomly selected sequences are linked can be estimated consistently from observed data. This is then used to develop estimates of the probability that a sequence from one group links to at least one sequence from another group under the assumption of independence across pairs. Furthermore, a resampling approach is developed that accounts for the presence of correlation across pairs, with diagnostics for assessing the reliability of the method. Sequences were obtained for 65% of subjects with high viral load (HVL, n = 117), 54% of subjects with low viral load but not on ART (LVL, n = 180), and 45% of subjects on ART (ART, n = 126). The probability of linkage between two individuals is highest if both have HVL, and lowest if one has LVL and the other has LVL or is on ART. Linkage across groups is high for HVL and lower for LVL and ART. Adjustment for missing data increases the group-wise linkage rates by 40–100%, and changes the relative rates between groups. Bias in inferences regarding HIV viral linkage that arise from differential ability to genotype samples can be reduced by appropriate methods for accommodating missing data. PMID:24415932

Linkage of viral sequences among HIV-infected village residents in Botswana: estimation of linkage rates in the presence of missing data.

PubMed

Carnegie, Nicole Bohme; Wang, Rui; Novitsky, Vladimir; De Gruttola, Victor

2014-01-01

Linkage analysis is useful in investigating disease transmission dynamics and the effect of interventions on them, but estimates of probabilities of linkage between infected people from observed data can be biased downward when missingness is informative. We investigate variation in the rates at which subjects' viral genotypes link across groups defined by viral load (low/high) and antiretroviral treatment (ART) status using blood samples from household surveys in the Northeast sector of Mochudi, Botswana. The probability of obtaining a sequence from a sample varies with viral load; samples with low viral load are harder to amplify. Pairwise genetic distances were estimated from aligned nucleotide sequences of HIV-1C env gp120. It is first shown that the probability that randomly selected sequences are linked can be estimated consistently from observed data. This is then used to develop estimates of the probability that a sequence from one group links to at least one sequence from another group under the assumption of independence across pairs. Furthermore, a resampling approach is developed that accounts for the presence of correlation across pairs, with diagnostics for assessing the reliability of the method. Sequences were obtained for 65% of subjects with high viral load (HVL, n = 117), 54% of subjects with low viral load but not on ART (LVL, n = 180), and 45% of subjects on ART (ART, n = 126). The probability of linkage between two individuals is highest if both have HVL, and lowest if one has LVL and the other has LVL or is on ART. Linkage across groups is high for HVL and lower for LVL and ART. Adjustment for missing data increases the group-wise linkage rates by 40-100%, and changes the relative rates between groups. Bias in inferences regarding HIV viral linkage that arise from differential ability to genotype samples can be reduced by appropriate methods for accommodating missing data.

Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer.

PubMed

Beaugerie, Laurent; Carrat, Fabrice; Colombel, Jean-Frédéric; Bouvier, Anne-Marie; Sokol, Harry; Babouri, Abdenour; Carbonnel, Franck; Laharie, David; Faucheron, Jean-Luc; Simon, Tabassome; de Gramont, Aimery; Peyrin-Biroulet, Laurent

2014-09-01

To explore the risk of new or recurrent cancer among patients with IBD and previous cancer, exposed or not to immunosuppressants. Among the 17 047 patients of the CESAME prospective observational cohort who were enrolled from May 2004 to June 2005, and followed-up until December 2007, we identified 405 patients with cancer diagnosed previous to study entry. We calculated the rates of incident cancer in patients with or without previous cancer, and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer. The rate of incident cancer was 21.1/1000 patient-years (PY) and 6.1/1000 PY in patients with and without previous cancer, respectively. The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 (95% CI 1.2 to 3.0, p=0.003). Among patients with previous cancer, the rates of new and recurrent cancers were, respectively, 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry, and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry. There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer. Patients with IBD with a history of cancer are at increased risk of developing any (new or recurrent) cancer, with a predominant incidence of new cancers. Treatment with immunosuppressants has no overall major impact per se on this risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Data linkage between existing healthcare databases to support hospital epidemiology.

PubMed

García Álvarez, L; Aylin, P; Tian, J; King, C; Catchpole, M; Hassall, S; Whittaker-Axon, K; Holmes, A

2011-11-01

Enhancing the use of existing datasets within acute hospitals will greatly facilitate hospital epidemiology, surveillance, the monitoring of a variety of processes, outcomes and risk factors, and the provision of alert systems. Multiple overlapping data systems exist within National Health Service (NHS) hospitals in the UK, and many duplicate data recordings take place because of the lack of linkage and interfaces. This results in hospital-collected data not being used efficiently. The objective was to create an inventory of all existing systems, including administrative, management, human resources, microbiology, patient care and other platforms, to describe the data architecture that could contribute valuable information for a hospital epidemiology unit. These datasets were investigated as to how they could be used to generate surveillance data, key performance indicators and risk information that could be shared at board, clinical programme group, specialty and ward level. An example of an output of this integrated data platform and its application in influenza resilience planning and responsiveness is described. The development of metrics for staff absence and staffing levels may also be used as key indicators for risk-monitoring for infection prevention. This work demonstrates the value of such a data inventory and linkage and the importance of more sophisticated uses of existing NHS data, and innovative collaborative approaches to support clinical care, quality improvement, surveillance, emergency planning and research. Copyright © 2011 The Healthcare Infection Society. All rights reserved.

Tracking linkage to HIV care for former prisoners

PubMed Central

Montague, Brian T.; Rosen, David L.; Solomon, Liza; Nunn, Amy; Green, Traci; Costa, Michael; Baillargeon, Jacques; Wohl, David A.; Paar, David P.; Rich, Josiah D.; Study Group, on behalf of the LINCS

2012-01-01

Improving testing and uptake to care among highly impacted populations is a critical element of Seek, Test, Treat and Retain strategies for reducing HIV incidence in the community. HIV disproportionately impacts prisoners. Though, incarceration provides an opportunity to diagnose and initiate therapy, treatment is frequently disrupted after release. Though model programs exist to support linkage to care on release, there is a lack of scalable metrics with which to assess adequacy of linkage to care after release. The linking data from Ryan White program Client Level Data (CLD) files reported to HRSA with corrections release data offers an attractive means of generating these metrics. Identified only by use of a confidential encrypted Unique Client Identifier (eUCI) these CLD files allow collection of key clinical indicators across the system of Ryan White funded providers. Using eUCIs generated from corrections release data sets as a linkage tool, the time to the first service at community providers along with key clinical indicators of patient status at entry into care can be determined as measures of linkage adequacy. Using this strategy, high and low performing sites can be identified and best practices can be identified to reproduce these successes in other settings. PMID:22561157

Construction of a reference genetic linkage map for carnation (Dianthus caryophyllus L.)

PubMed Central

2013-01-01

Background Genetic linkage maps are important tools for many genetic applications including mapping of quantitative trait loci (QTLs), identifying DNA markers for fingerprinting, and map-based gene cloning. Carnation (Dianthus caryophyllus L.) is an important ornamental flower worldwide. We previously reported a random amplified polymorphic DNA (RAPD)-based genetic linkage map derived from Dianthus capitatus ssp. andrezejowskianus and a simple sequence repeat (SSR)-based genetic linkage map constructed using data from intraspecific F2 populations; however, the number of markers was insufficient, and so the number of linkage groups (LGs) did not coincide with the number of chromosomes (x = 15). Therefore, we aimed to produce a high-density genetic map to improve its usefulness for breeding purposes and genetic research. Results We improved the SSR-based genetic linkage map using SSR markers derived from a genomic library, expression sequence tags, and RNA-seq data. Linkage analysis revealed that 412 SSR loci (including 234 newly developed SSR loci) could be mapped to 17 linkage groups (LGs) covering 969.6 cM. Comparison of five minor LGs covering less than 50 cM with LGs in our previous RAPD-based genetic map suggested that four LGs could be integrated into two LGs by anchoring common SSR loci. Consequently, the number of LGs corresponded to the number of chromosomes (x = 15). We added 192 new SSRs, eight RAPD, and two sequence-tagged site loci to refine the RAPD-based genetic linkage map, which comprised 15 LGs consisting of 348 loci covering 978.3 cM. The two maps had 125 SSR loci in common, and most of the positions of markers were conserved between them. We identified 635 loci in carnation using the two linkage maps. We also mapped QTLs for two traits (bacterial wilt resistance and anthocyanin pigmentation in the flower) and a phenotypic locus for flower-type by analyzing previously reported genotype and phenotype data. Conclusions The improved genetic

Construction of a reference genetic linkage map for carnation (Dianthus caryophyllus L.).

PubMed

Yagi, Masafumi; Yamamoto, Toshiya; Isobe, Sachiko; Hirakawa, Hideki; Tabata, Satoshi; Tanase, Koji; Yamaguchi, Hiroyasu; Onozaki, Takashi

2013-10-26

Genetic linkage maps are important tools for many genetic applications including mapping of quantitative trait loci (QTLs), identifying DNA markers for fingerprinting, and map-based gene cloning. Carnation (Dianthus caryophyllus L.) is an important ornamental flower worldwide. We previously reported a random amplified polymorphic DNA (RAPD)-based genetic linkage map derived from Dianthus capitatus ssp. andrezejowskianus and a simple sequence repeat (SSR)-based genetic linkage map constructed using data from intraspecific F2 populations; however, the number of markers was insufficient, and so the number of linkage groups (LGs) did not coincide with the number of chromosomes (x = 15). Therefore, we aimed to produce a high-density genetic map to improve its usefulness for breeding purposes and genetic research. We improved the SSR-based genetic linkage map using SSR markers derived from a genomic library, expression sequence tags, and RNA-seq data. Linkage analysis revealed that 412 SSR loci (including 234 newly developed SSR loci) could be mapped to 17 linkage groups (LGs) covering 969.6 cM. Comparison of five minor LGs covering less than 50 cM with LGs in our previous RAPD-based genetic map suggested that four LGs could be integrated into two LGs by anchoring common SSR loci. Consequently, the number of LGs corresponded to the number of chromosomes (x = 15). We added 192 new SSRs, eight RAPD, and two sequence-tagged site loci to refine the RAPD-based genetic linkage map, which comprised 15 LGs consisting of 348 loci covering 978.3 cM. The two maps had 125 SSR loci in common, and most of the positions of markers were conserved between them. We identified 635 loci in carnation using the two linkage maps. We also mapped QTLs for two traits (bacterial wilt resistance and anthocyanin pigmentation in the flower) and a phenotypic locus for flower-type by analyzing previously reported genotype and phenotype data. The improved genetic linkage maps and SSR markers developed

Linkage localization of X-linked Charcot-Marie-Tooth disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergoffen, J.; Trofatter, J.; Haines, J.L.

1993-02-01

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived frommore » work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.« less

Identifying risk factors for progression to critical care admission and death among individuals with acute pancreatitis: a record linkage analysis of Scottish healthcare databases

PubMed Central

Mole, Damian J; Gungabissoon, Usha; Johnston, Philip; Cochrane, Lynda; Hopkins, Leanne; Wyper, Grant M A; Skouras, Christos; Dibben, Chris; Sullivan, Frank; Morris, Andrew; Ward, Hester J T; Lawton, Andrew M; Donnan, Peter T

2016-01-01

Objectives Acute pancreatitis (AP) can initiate systemic complications that require support in critical care (CC). Our objective was to use the unified national health record to define the epidemiology of AP in Scotland, with a specific focus on deterministic and prognostic factors for CC admission in AP. Setting Health boards in Scotland (n=4). Participants We included all individuals in a retrospective observational cohort with at least one episode of AP (ICD10 code K85) occurring in Scotland from 1 April 2009 to 31 March 2012. 3340 individuals were coded as AP. Methods Data from 16 sources, spanning general practice, community prescribing, Accident and Emergency attendances, hospital in-patient, CC and mortality registries, were linked by a unique patient identifier in a national safe haven. Logistic regression and gamma models were used to define independent predictive factors for severe AP (sAP) requiring CC admission or leading to death. Results 2053 individuals (61.5% (95% CI 59.8% to 63.2%)) met the definition for true AP (tAP). 368 patients (17.9% of tAP (95% CI 16.2% to 19.6%)) were admitted to CC. Predictors of sAP were pre-existing angina or hypertension, hypocalcaemia and age 30–39 years, if type 2 diabetes mellitus was present. The risk of sAP was lower in patients with multiple previous episodes of AP. In-hospital mortality in tAP was 5.0% (95% CI 4.1% to 5.9%) overall and 21.7% (95% CI 19.9% to 23.5%) in those with tAP necessitating CC admission. Conclusions National record-linkage analysis of routinely collected data constitutes a powerful resource to model CC admission and prognosticate death during AP. Mortality in patients with AP who require CC admission remains high. PMID:27311912

Polymorphisms in the Tlr4 and Tlr5 Gene Are Significantly Associated with Inflammatory Bowel Disease in German Shepherd Dogs

PubMed Central

Kathrani, Aarti; House, Arthur; Catchpole, Brian; Murphy, Angela; German, Alex; Werling, Dirk; Allenspach, Karin

2010-01-01

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease. PMID:21203467

The Hepatitis Testing and Linkage-to-Care Data Review Process: An Approach to Ensuring the Quality of Program Data.

PubMed

Mezzo, Jennifer L; Lamia, Tamara L; Danelski, Lisa L; Schipani, Anne Marie; Stokes, Scott A; Jacobs-Ware, Elizabeth D

2016-01-01

CDC's 2012 Hepatitis Testing and Linkage to Care (HepTLC) initiative was a nationally coordinated effort to conduct hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites. This project provided support for data management and monthly data reviews between awardees and a data manager, which facilitated monitoring of awardee progress and regular program improvement opportunities. CDC provided technical assistance to awardees for testing processes and program improvement, including Internet-based data submission, reporting software and data management to awardees, offering assistance with submitting, and reviewing data in real time. We describe how one awardee, AIDS Resource Center of Wisconsin (ARCW), used the data management process to improve data quality, inform testing processes and implementation, and measure and report missing variables from an online database. From October 2012 through July 2014, ARCW performed 2,255 HCV antibody (anti-HCV) tests and 244 HCV ribonucleic acid (RNA) tests as part of the HepTLC initiative. Participants who tested HCV RNA positive (n=189) were referred to medical care. At the end of the study, no records were missing for the anti-HCV test result or HCV RNA test result variables, and only one record was missing for those who were referred to medical care. Regular data review and monitoring by awardees and CDC-supported data managers provided opportunities for data quality and program improvement. Through regular data review, ARCW reduced the amount of missing data and promoted timely follow-up with participants testing positive for HCV to ensure receipt of results and linkage to care. Other programs can adopt a similar data management model.

Linkage disequilibrium fine mapping of quantitative trait loci: A simulation study

PubMed Central

Abdallah, Jihad M; Goffinet, Bruno; Cierco-Ayrolles, Christine; Pérez-Enciso, Miguel

2003-01-01

Recently, the use of linkage disequilibrium (LD) to locate genes which affect quantitative traits (QTL) has received an increasing interest, but the plausibility of fine mapping using linkage disequilibrium techniques for QTL has not been well studied. The main objectives of this work were to (1) measure the extent and pattern of LD between a putative QTL and nearby markers in finite populations and (2) investigate the usefulness of LD in fine mapping QTL in simulated populations using a dense map of multiallelic or biallelic marker loci. The test of association between a marker and QTL and the power of the test were calculated based on single-marker regression analysis. The results show the presence of substantial linkage disequilibrium with closely linked marker loci after 100 to 200 generations of random mating. Although the power to test the association with a frequent QTL of large effect was satisfactory, the power was low for the QTL with a small effect and/or low frequency. More powerful, multi-locus methods may be required to map low frequent QTL with small genetic effects, as well as combining both linkage and linkage disequilibrium information. The results also showed that multiallelic markers are more useful than biallelic markers to detect linkage disequilibrium and association at an equal distance. PMID:12939203

Clinical and genetic linkage analysis of a large Venezuelan kindred with Usher syndrome.

PubMed

Keogh, Ivan J; Godinho, R N; Wu, T Po; Diaz de Palacios, A M; Palacios, N; Bello de Alford, M; De Almada, M I; MarPalacios, N; Vazquez, A; Mattei, R; Seidman, C; Seidman, J; Eavey, R D

2004-08-01

To undertake a comprehensive investigation into the very high incidence of congenital deafness on the Macano peninsula of Margarita Island, Venezuela. Numerous visits were made to the isolated island community over a 4-year-period. During these visits, it became apparent that a significant number of individuals complained of problems with hearing and vision. Socioeconomic assessments, family pedigrees and clinical histories were recorded on standard questionnaires. All individuals underwent thorough otolaryngologic and ophthalmologic examinations. Twenty milliliters of peripheral venous blood was obtained from each participant. A genome-wide linkage analysis study was performed. Polymorphic microsatellite markers were amplified by polymerase chain reaction and separated on polyacrylamide gels. An ABI 377XL sequencer was used to separate fragments and LOD scores were calculated by using published software. Twenty-four families were identified, comprising 329 individuals, age range 1-80 years, including 184 children. All families were categorized in the lower two (least affluent) socioeconomic categories. A high incidence of consanguinity was detected. Fifteen individuals (11 adults, 4 children) had profound congenital sensorineural hearing loss, vestibular areflexia and retinitis pigmentosa. A maximum LOD score of 6.76 (Linkage >3.0), between markers D11s4186 and D11s911, confirmed linkage to chromosome 11q13.5. The gene myosin VIIA (MYO7A) was confirmed in the interval. Clinical and genetic findings are consistent with a diagnosis of Usher syndrome 1B for those with hearing and vision problems. We report 15 Usher syndrome 1B individuals from a newly detected Latin American socio-demographic origin, with a very high prevalence of 76 per 100,000 population.

Intra-Facility Linkage of HIV-Positive Mothers and HIV-Exposed Babies into HIV Chronic Care: Rural and Urban Experience in a Resource Limited Setting

PubMed Central

Mugasha, Christine; Kigozi, Joanita; Kiragga, Agnes; Muganzi, Alex; Sewankambo, Nelson; Coutinho, Alex; Nakanjako, Damalie

2014-01-01

Introduction Linkage of HIV-infected pregnant women to HIV care remains critical for improvement of maternal and child outcomes through prevention of maternal-to-child transmission of HIV (PMTCT) and subsequent chronic HIV care. This study determined proportions and factors associated with intra-facility linkage to HIV care and Early Infant Diagnosis care (EID) to inform strategic scale up of PMTCT programs. Methods A cross-sectional review of records was done at 2 urban and 3 rural public health care facilities supported by the Infectious Diseases Institute (IDI). HIV-infected pregnant mothers, identified through routine antenatal care (ANC) and HIV-exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-delivery. Results Overall, 1,025 HIV-infected pregnant mothers were identified during ANC between January and June, 2012; 267/1,025 (26%) in rural and 743/1,025 (74%) in urban facilities. Of these 375/1,025 (37%) were linked to HIV clinics [67/267(25%) rural and 308/758(41%) urban]. Of 636 HIV-exposed babies, 193 (30%) were linked to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/636); 8/179 (4.5%)] in rural and 93/457(20.3%) in urban health facilities. Within rural facilities, ANC registration <28 weeks-of-gestation was associated with mothers' linkage to HIV chronic care [AoR, 2.0 95% CI, 1.1–3.7, p = 0.019] and mothers' multi-parity was associated with baby's linkage to EID; AoR 4.4 (1.3–15.1), p = 0.023. Stigma, long distance to health facilities and vertical PMTCT services affected linkage in rural facilities, while peer mothers, infant feeding services, long patient queues and limited privacy hindered linkage to HIV care in urban settings. Conclusion Post-natal linkage of HIV-infected mothers to chronic HIV care and HIV-exposed babies to EID programs was low. Barriers to linkage to HIV care vary in urban and rural settings. We recommend targeted interventions to rapidly improve linkage to

Linkage mechanisms in the vertebrate skull: Structure and function of three-dimensional, parallel transmission systems.

PubMed

Olsen, Aaron M; Westneat, Mark W

2016-12-01

Many musculoskeletal systems, including the skulls of birds, fishes, and some lizards consist of interconnected chains of mobile skeletal elements, analogous to linkage mechanisms used in engineering. Biomechanical studies have applied linkage models to a diversity of musculoskeletal systems, with previous applications primarily focusing on two-dimensional linkage geometries, bilaterally symmetrical pairs of planar linkages, or single four-bar linkages. Here, we present new, three-dimensional (3D), parallel linkage models of the skulls of birds and fishes and use these models (available as free kinematic simulation software), to investigate structure-function relationships in these systems. This new computational framework provides an accessible and integrated workflow for exploring the evolution of structure and function in complex musculoskeletal systems. Linkage simulations show that kinematic transmission, although a suitable functional metric for linkages with single rotating input and output links, can give misleading results when applied to linkages with substantial translational components or multiple output links. To take into account both linear and rotational displacement we define force mechanical advantage for a linkage (analogous to lever mechanical advantage) and apply this metric to measure transmission efficiency in the bird cranial mechanism. For linkages with multiple, expanding output points we propose a new functional metric, expansion advantage, to measure expansion amplification and apply this metric to the buccal expansion mechanism in fishes. Using the bird cranial linkage model, we quantify the inaccuracies that result from simplifying a 3D geometry into two dimensions. We also show that by combining single-chain linkages into parallel linkages, more links can be simulated while decreasing or maintaining the same number of input parameters. This generalized framework for linkage simulation and analysis can accommodate linkages of differing

Use of record linkage to examine alcohol use in pregnancy.

PubMed

Burns, Lucy; Mattick, Richard P; Cooke, Margaret

2006-04-01

To date, no population-level data have been published examining the obstetric and neonatal outcomes for women with an alcohol-related hospital admission during pregnancy compared with the general obstetric population. This information is critical to planning and implementing appropriate services. Antenatal and delivery admissions to New South Wales (NSW) hospitals from the NSW Inpatient Statistics Collection were linked to birth information from the NSW Midwives Data Collection over a 5-year period (1998-2002). Birth admissions were flagged as positive for maternal alcohol use where a birth admission or any pregnancy admission for that birth involved an alcohol-related International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) code. Key demographic, obstetric, and neonatal variables were compared for births to mothers in the alcohol group with births where no alcohol-related ICD10-AM was recorded. A total of 416,834 birth records were analyzed over a 5-year period (1998-2002). In this time, 342 of these were coded as positive for at least 1 alcohol-related ICD-10-AM diagnosis. Mothers in the alcohol group had a higher number of previous pregnancies, smoked more heavily, were not privately insured, and were more often indigenous. They also presented later on in their pregnancy to antenatal services and were more likely to arrive at hospital unbooked for delivery. Deliveries involved less epidural and local and more general anesthesia. Cesarean sections were more common to women in the alcohol group and were performed more often for intrauterine growth retardation. Neonates born to women in the alcohol group were smaller for gestational age, had lower Apgar scores at 5 minutes, and were admitted to special care nursery more often. This study shows that linked population-level administrative data provide a powerful new source of information for examining the maternal and neonatal outcomes

Accuracy of Definitions for Linkage to Care in Persons Living with HIV

PubMed Central

KELLER, Sara C.; YEHIA, Baligh R.; EBERHART, Michael G.; BRADY, Kathleen A.

2013-01-01

Objective To compare the accuracy of linkage to care metrics for patients diagnosed with HIV using retention in care and virologic suppression as the gold standards of effective linkage. Design A retrospective cohort study of patients aged 18 and over with newly-diagnosed HIV infection in the City of Philadelphia, 2007 to 2008. Methods Times from diagnosis to clinic visits or laboratory testing were used as linkage measures. Outcome variables included being retained in care and achieving virologic suppression, 366-730 days after diagnosis. Positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for each linkage measure and retention and virologic suppression outcomes are described. Results Of the 1781 patients in the study, 503 (28.2%) were retained in care in the Ryan White system and 418 (23.5%) achieved virologic suppression 366-730 days after diagnosis. The linkage measure with the highest PPV for retention was having two clinic visits within 365 days of diagnosis, separated by 90 days (74.2%). Having a clinic visit between 21 and 365 days after diagnosis had both the highest NPV for retention (94.5%) and the highest adjusted AUC for retention (0.872). Having two tests within 365 days of diagnosis, separated by 90 days, had the highest adjusted AUC for virologic suppression (0.780). Conclusions Linkage measures associated with clinic visits had higher PPV and NPV for retention, while linkage measures associated with laboratory testing had higher PPV and NPV for retention. Linkage measures should be chosen based on the outcome of interest. PMID:23614992

Weak linkage between the heaviest rainfall and tallest storms.

PubMed

Hamada, Atsushi; Takayabu, Yukari N; Liu, Chuntao; Zipser, Edward J

2015-02-24

Conventionally, the heaviest rainfall has been linked to the tallest, most intense convective storms. However, the global picture of the linkage between extreme rainfall and convection remains unclear. Here we analyse an 11-year record of spaceborne precipitation radar observations and establish that a relatively small fraction of extreme convective events produces extreme rainfall rates in any region of the tropics and subtropics. Robust differences between extreme rainfall and convective events are found in the rainfall characteristics and environmental conditions, irrespective of region; most extreme rainfall events are characterized by less intense convection with intense radar echoes not extending to extremely high altitudes. Rainfall characteristics and environmental conditions both indicate the importance of warm-rain processes in producing extreme rainfall rates. Our results demonstrate that, even in regions where severe convective storms are representative extreme weather events, the heaviest rainfall events are mostly associated with less intense convection.

Failure to find a chromosome 18 pericentric linkage in families with schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Lisi, L.E.; Shields, G.; Lehner, T.

1995-12-18

A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small. 12 refs., 4 tabs.

Tropical-Subpolar Linkages in the North Atlantic during the last Glacial Period

NASA Astrophysics Data System (ADS)

Vautravers, M. J.; Hodell, D. A.

2010-12-01

We studied millennial-scale changes in planktonic foraminifera assemblages from the last glacial period in a high-resolution core (KN166-14-JPC13) recovered from the southern part of the Gardar Drift in the subpolar North Atlantic. Similar to recent findings reported by Jonkers et al. (2010), we also found that the sub-polar North Atlantic Ocean experienced some seasonal warming during each of the Heinrich Events (HEs). In addition, increasing abundances of tropical species are found just prior to the IRD event marking the end of each Bond cycle, suggesting that summer warming may have been involved in triggering Heinrich events. We suggest that tropical-subtropical water transported via the Gulf Stream and North Atlantic Drift may have triggered the collapse of large NH ice-shelves. Sharp decreases in polar species are tied to abrupt warming following Heinrich Events as documented in Greenland Ice cores and other marine records in the North Atlantic. The record bears a strong resemblance to the tropical record of Cariaco basin (Peterson et al., 2000), suggesting strong tropical-subpolar linkages in the glacial North Atlantic. Enhanced spring productivity, possibly related to eddy activity along the Subpolar Front, is recorded by increased shell size, high δ13C in G. bulloides and other biological indices early during the transition from HE stadials to the following interstadial.

An Enhanced Linkage Map of the Sheep Genome Comprising More Than 1000 Loci

PubMed Central

Maddox, Jillian F.; Davies, Kizanne P.; Crawford, Allan M.; Hulme, Dennis J.; Vaiman, Daniel; Cribiu, Edmond P.; Freking, Bradley A.; Beh, Ken J.; Cockett, Noelle E.; Kang, Nina; Riffkin, Christopher D.; Drinkwater, Roger; Moore, Stephen S.; Dodds, Ken G.; Lumsden, Joanne M.; van Stijn, Tracey C.; Phua, Sin H.; Adelson, David L.; Burkin, Heather R.; Broom, Judith E.; Buitkamp, Johannes; Cambridge, Lisa; Cushwa, William T.; Gerard, Emily; Galloway, Susan M.; Harrison, Blair; Hawken, Rachel J.; Hiendleder, Stefan; Henry, Hannah M.; Medrano, Juan F.; Paterson, Korena A.; Schibler, Laurent; Stone, Roger T.; van Hest, Beryl

2001-01-01

A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with the previous sheep linkage map. The new map comprises 1093 markers representing 1062 unique loci (941 anonymous loci, 121 genes) and spans 3500 cM (sex-averaged) for the autosomes and 132 cM (female) on the X chromosome. There is an average spacing of 3.4 cM between autosomal loci and 8.3 cM between highly polymorphic [polymorphic information content (PIC) ≥ 0.7] autosomal loci. The largest gap between markers is 32.5 cM, and the number of gaps of >20 cM between loci, or regions where loci are missing from chromosome ends, has been reduced from 40 in the previous map to 6. Five hundred and seventy-three of the loci can be ordered on a framework map with odds of >1000 : 1. The sheep linkage map contains strong links to both the cattle and goat maps. Five hundred and seventy-two of the loci positioned on the sheep linkage map have also been mapped by linkage analysis in cattle, and 209 of the loci mapped on the sheep linkage map have also been placed on the goat linkage map. Inspection of ruminant linkage maps indicates that the genomic coverage by the current sheep linkage map is comparable to that of the available cattle maps. The sheep map provides a valuable resource to the international sheep, cattle, and goat gene mapping community. PMID:11435411

An AFLP genetic linkage map of pacific abalone ( Haliotis discus hannai)

NASA Astrophysics Data System (ADS)

Qi, Li; Yanhong, Xu; Ruihai, Yu; Akihiro, Kijima

2007-07-01

A genetic linkage map of Pacific abalone ( Haliotis discus hannai) was constructed using AFLP markers based on a two-way pseudo-testeross strategy in a full-sib family. With 33 primer combinations, a total of 455 markers (225 from the female parent and 230 from the male parent) segregated in a 1:1 ratio, corresponding to DNA polymorphism: heterozygous in one parent and null in the other. The female framework map consisted of 174 markers distributed in 18 linkage groups, equivalent to the H. discus hannai haploid chromosome number, and spanning a total length of 2031.4 cM, with an average interval of 13.0 cM between adjacent markers. The male framework map consisted of 195 markers mapped on 19 linkage groups, spanning a total length of 2273.4 cM, with an average spacing of 12.9 cM between adjacent markers. The estimated coverage for the framework linkage maps was 81.2% for the female and 82.1% for the male, on the basis of two estimates of genome length. Fifty-two markers (11.4%) remained unlinked. The level of segregation distortion observed in this cross was 20.4%. These linkage maps will serve as a starting point for linkage studies in the Pacific abalone with potential application for marker-assisted selection in breeding programs.

Genetic linkage analysis in 26 families with Bardet-Biedl syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, A.F.; Bruford, E.A.; Mansfield, D.C.

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by polydactyly, obesity, hypogonadism, retinitis pigmentosa, renal anomalies and mental retardation. Clinical heterogeneity is quite marked both within and between families. Linkage has been reported between Bardet-Biedl syndrome and the D16408 marker in chromosomal region 16q21 in an extended Bedouin kindred and, more recently, in a subset of 17 out of 31 families using the PYGM/D11S913 markers in chromosomal region 11q13. We have analyzed linkage to the 16q21 and 11q13 regions and used markers covering chromosomes 2, 3, 17 and 18 in a set of 26 Bardet-Biedl families, each containing at leastmore » two affected individuals, with a total of 57 affected members. Evidence of linkage to the D11S527 locus has been identified assuming linkage homogeneity with a lod score of 2.72 at a recombination fraction of 0.11 (95% limits 0.03-0.25).« less

A Genetic Linkage Map of the Male Goat Genome

PubMed Central

Vaiman, D.; Schibler, L.; Bourgeois, F.; Oustry, A.; Amigues, Y.; Cribiu, E. P.

1996-01-01

This paper presents a first genetic linkage map of the goat genome. Primers derived from the flanking sequences of 612 bovine, ovine and goat microsatellite markers were gathered and tested for amplification with goat DNA under standardized PCR conditions. This screen made it possible to choose a set of 55 polymorphic markers that can be used in the three species and to define a panel of 223 microsatellites suitable for the goat. Twelve half-sib paternal goat families were then used to build a linkage map of the goat genome. The linkage analysis made it possible to construct a meiotic map covering 2300 cM, i.e., >80% of the total estimated length of the goat genome. Moreover, eight cosmids containing microsatellites were mapped by fluorescence in situ hybridization in goat and sheep. Together with 11 microsatellite-containing cosmids previously mapped in cattle (and supposing conservation of the banding pattern between this species and the goat) and data from the sheep map, these results made the orientation of 15 linkage groups possible. Furthermore, 12 coding sequences were mapped either genetically or physically, providing useful data for comparative mapping. PMID:8878693

Nance-Horan syndrome: linkage analysis in a family from The Netherlands.

PubMed

Bergen, A A; ten Brink, J; Schuurman, E J; Bleeker-Wagemakers, E M

1994-05-01

Linkage analysis was carried out in a Dutch family with Nance-Horan (NH) syndrome. Close linkage without recombination between NH and the Xp loci DXS207, DXS43, and DXS365 (zmax = 3.23) was observed. Multipoint linkage analysis and the analysis of recombinations in multiple informative meioses suggest the genetic order Xcen-DMD (exon 49)-DXS451-(NH, DXS207, DXS365, DXS43)-(STS, DXF30)-Xpter. These data refine the localization of the NH locus on the distal Xp.

Validity of using linked hospital and police traffic crash records to analyse motorcycle injury crash characteristics.

PubMed

Wilson, Suzanne J; Begg, Dorothy J; Samaranayaka, Ari

2012-11-01

Linking hospital discharge and police traffic crash records has been used to provide information on causes and outcomes for hospitalised traffic crash cases. Motorcyclists are particularly vulnerable to injury in a traffic crash, but no published linkage studies have reported in detail on this road user group. The present study examined motorcycle traffic crash injury cases in New Zealand in 2000-2004 by probabilistically linking national hospital discharge records with police traffic crash reports. Injury cases had to have spent at least one night in hospital before being discharged and were defined as serious or moderate based on their International Classification of Disease Injury Severity Scores (ICISS). Despite a robust linkage process, only 46% of cases could be linked to a police record; 60% of the serious injuries and 41% of the moderate. The low linkage was most likely due to under-reporting of crashes to or by the police. While moderate injury cases were expected to be under-reported, the level of under-reporting of cases with serious threat-to-life injuries is concerning. To assess whether the linked dataset could provide valid information on the crash circumstances and injury outcomes of hospitalised motorcycle crash cases, the characteristics of the linked and unlinked hospital discharge cases were compared using chi-square tests and multivariate logistic regression. Serious injury cases were less likely to be linked if only one vehicle was involved, or the injured riders and passengers were younger than 20 years or spent less than one week in hospital. For moderate injury cases, there were also differences in linkage by injured body region and crash month. While these discrepancies need to taken into consideration when interpreting results, the linked hospital-police dataset has the potential to provide insights into motorcycle crash circumstances and outcomes not otherwise obtainable. Copyright © 2011 Elsevier Ltd. All rights reserved.

Autosomal Linkage Scan for Loci Predisposing to Comorbid Dependence on Multiple Substances

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R.; Farrer, Lindsay A.; Elston, Robert C.; Gelernter, Joel

2014-01-01

Multiple substance dependence (MSD) trait comorbidity is common, and MSD patients are often severely affected clinically. While shared genetic risks have been documented, so far there has been no published report using the linkage scan approach to survey risk loci for MSD as a phenotype. A total of 1,758 individuals in 739 families [384 African American (AA) and 355 European American (EA) families] ascertained via affected sib-pairs with cocaine or opioid or alcohol dependence were genotyped using an array-based linkage panel of single-nucleotide polymorphism markers. Fuzzy clustering analysis was conducted on individuals with alcohol, cannabis, cocaine, opioid, and nicotine dependence for AAs and EAs separately, and linkage scans were conducted for the output membership coefficients using Merlin-regression. In EAs, we observed an autosome-wide significant linkage signal on chromosome 4 (peak lod = 3.31 at 68.3 cM; empirical autosome-wide P = 0.038), and a suggestive linkage signal on chromosome 21 (peak lod = 2.37 at 19.4 cM). In AAs, four suggestive linkage peaks were observed: two peaks on chromosome 10 (lod = 2.66 at 96.7 cM and lod = 3.02 at 147.6 cM] and the other two on chromosomes 3 (lod = 2.81 at 145.5 cM) and 9 (lod = 1.93 at 146.8 cM). Three particularly promising candidate genes, GABRA4, GABRB1, and CLOCK, are located within or very close to the autosome-wide significant linkage region for EAs on chromosome 4. This is the first linkage evidence supporting existence of genetic loci influencing risk for several comorbid disorders simultaneously in two major US populations. PMID:22354695

A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy.

PubMed

Iacucci, Marietta; Kaplan, Gilaad G; Panaccione, Remo; Akinola, Oluseyi; Lethebe, Brendan Cord; Lowerison, Mark; Leung, Yvette; Novak, Kerri L; Seow, Cynthia H; Urbanski, Stefan; Minoo, Parham; Gui, Xianyong; Ghosh, Subrata

2018-02-01

Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy. A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification. A total of 270 patients (55% men; age range 20-77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98-22.5 and OR 21.50 (8.65-60.10), respectively). In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.

Immunization history of children with inflammatory bowel disease.

PubMed

Soon, Ing Shian; deBruyn, Jennifer C C; Wrobel, Iwona

2013-04-01

Protection against vaccine-preventable diseases is important in children with inflammatory bowel disease (IBD) due to frequent immunosuppressive therapy use. The chronic relapsing nature and treatment regimen of IBD may necessitate modified timing of immunizations. To evaluate the completeness of immunizations in children with IBD. Immunization records of all children with IBD followed at the Alberta Children's Hospital (Calgary, Alberta) were reviewed. For children with incomplete immunization according to the province of Alberta schedule, the reasons for such were clarified. Demographic data and age at diagnosis were also collected. Immunization records were obtained from 145 (79%) children with IBD. Fifteen children had incomplete routine childhood immunizations, including two with no previous immunizations. The most common incomplete immunizations included hepatitis B (n=9), diphtheria, tetanus, acellular pertussis at 14 to 16 years of age (n=7), and diphtheria, tetanus, acellular pertussis, inactivated polio at four to six years of age (n=6). The reasons for incomplete immunization included use of immunosuppressive therapy at time of scheduled immunization; IBD-related symptoms at time of scheduled immunization; parental refusal; recent move from elsewhere with different immunization schedule; unawareness of routine immunization; and needle phobia. Although the majority of children with IBD had complete childhood immunizations, suboptimal immunizations were present in 10%. With increasing use of immunosuppressive therapy in IBD, physicians caring for children with IBD must periodically evaluate immunization status and ensure the completeness of childhood immunizations.

Genotyping-by-sequencing enables linkage mapping in three octoploid cultivated strawberry families

PubMed Central

Salinas, Natalia; Tennessen, Jacob A.; Zurn, Jason D.; Sargent, Daniel James; Hancock, James; Bassil, Nahla V.

2017-01-01

Genotyping-by-sequencing (GBS) was used to survey genome-wide single-nucleotide polymorphisms (SNPs) in three biparental strawberry (Fragaria × ananassa) populations with the goal of evaluating this technique in a species with a complex octoploid genome. GBS sequence data were aligned to the F. vesca ‘Fvb’ reference genome in order to call SNPs. Numbers of polymorphic SNPs per population ranged from 1,163 to 3,190. Linkage maps consisting of 30–65 linkage groups were produced from the SNP sets derived from each parent. The linkage groups covered 99% of the Fvb reference genome, with three to seven linkage groups from a given parent aligned to any particular chromosome. A phylogenetic analysis performed using the POLiMAPS pipeline revealed linkage groups that were most similar to ancestral species F. vesca for each chromosome. Linkage groups that were most similar to a second ancestral species, F. iinumae, were only resolved for Fvb 4. The quantity of missing data and heterogeneity in genome coverage inherent in GBS complicated the analysis, but POLiMAPS resolved F. × ananassa chromosomal regions derived from diploid ancestor F. vesca. PMID:28875078

Linking temporal medical records using non-protected health information data.

PubMed

Bonomi, Luca; Jiang, Xiaoqian

2017-01-01

Modern medical research relies on multi-institutional collaborations which enhance the knowledge discovery and data reuse. While these collaborations allow researchers to perform analytics otherwise impossible on individual datasets, they often pose significant challenges in the data integration process. Due to the lack of a unique identifier, data integration solutions often have to rely on patient's protected health information (PHI). In many situations, such information cannot leave the institutions or must be strictly protected. Furthermore, the presence of noisy values for these attributes may result in poor overall utility. While much research has been done to address these challenges, most of the current solutions are designed for a static setting without considering the temporal information of the data (e.g. EHR). In this work, we propose a novel approach that uses non-PHI for linking patient longitudinal data. Specifically, our technique captures the diagnosis dependencies using patterns which are shown to provide important indications for linking patient records. Our solution can be used as a standalone technique to perform temporal record linkage using non-protected health information data or it can be combined with Privacy Preserving Record Linkage solutions (PPRL) when protected health information is available. In this case, our approach can solve ambiguities in results. Experimental evaluations on real datasets demonstrate the effectiveness of our technique.

Genome-wide Association Study Identifies African-Specific Susceptibility Loci in African Americans with Inflammatory Bowel Disease

PubMed Central

Brant, Steven R.; Okou, David T.; Simpson, Claire L.; Cutler, David J.; Haritunians, Talin; Bradfield, Jonathan P.; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W.; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J.; Klapproth, Jan-Micheal A.; Quiros, Antonio J.; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S.; Baldassano, Robert N.; Dudley-Brown, Sharon; Cross, Raymond K.; Dassopoulos, Themistocles; Denson, Lee A.; Dhere, Tanvi A.; Dryden, Gerald W.; Hanson, John S.; Hou, Jason K.; Hussain, Sunny Z.; Hyams, Jeffrey S.; Isaacs, Kim L.; Kader, Howard; Kappelman, Michael D.; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S.; Kuemmerle, John F.; Kwon, John H.; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E.; Newberry, Rodney D.; Osuntokun, Bankole O.; Patel, Ashish S.; Saeed, Shehzad A.; Targan, Stephan R.; Valentine, John F.; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Hakonarson, Hakon; Zwick, Michael E.; McGovern, Dermot P.B.; Kugathasan, Subra

2016-01-01

Background & Aims The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. Methods We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified [IBD-U]) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P<5.0×10−8 in meta-analysis with a nominal evidence (P<.05) in each scan were considered to have genome-wide significance. Results We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance associations for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P<1.6×10−6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B, PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. Conclusions We performed a genome-wide association study of African Americans with IBD and identified loci associated with CD and UC in only this population; we also replicated loci identified in European populations. The detection of variants associated with IBD risk in only

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

PubMed

Brant, Steven R; Okou, David T; Simpson, Claire L; Cutler, David J; Haritunians, Talin; Bradfield, Jonathan P; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J; Klapproth, Jan-Micheal A; Quiros, Antonio J; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S; Baldassano, Robert N; Dudley-Brown, Sharon; Cross, Raymond K; Dassopoulos, Themistocles; Denson, Lee A; Dhere, Tanvi A; Dryden, Gerald W; Hanson, John S; Hou, Jason K; Hussain, Sunny Z; Hyams, Jeffrey S; Isaacs, Kim L; Kader, Howard; Kappelman, Michael D; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S; Kuemmerle, John F; Kwon, John H; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E; Newberry, Rodney D; Osuntokun, Bankole O; Patel, Ashish S; Saeed, Shehzad A; Targan, Stephan R; Valentine, John F; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D; Duerr, Richard H; Silverberg, Mark S; Cho, Judy H; Hakonarson, Hakon; Zwick, Michael E; McGovern, Dermot P B; Kugathasan, Subra

2017-01-01

The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10 -8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10 -6 ): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the

Meta-analysis of 32 genome-wide linkage studies of schizophrenia

PubMed Central

Ng, MYM; Levinson, DF; Faraone, SV; Suarez, BK; DeLisi, LE; Arinami, T; Riley, B; Paunio, T; Pulver, AE; Irmansyah; Holmans, PA; Escamilla, M; Wildenauer, DB; Williams, NM; Laurent, C; Mowry, BJ; Brzustowicz, LM; Maziade, M; Sklar, P; Garver, DL; Abecasis, GR; Lerer, B; Fallin, MD; Gurling, HMD; Gejman, PV; Lindholm, E; Moises, HW; Byerley, W; Wijsman, EM; Forabosco, P; Tsuang, MT; Hwu, H-G; Okazaki, Y; Kendler, KS; Wormley, B; Fanous, A; Walsh, D; O’Neill, FA; Peltonen, L; Nestadt, G; Lasseter, VK; Liang, KY; Papadimitriou, GM; Dikeos, DG; Schwab, SG; Owen, MJ; O’Donovan, MC; Norton, N; Hare, E; Raventos, H; Nicolini, H; Albus, M; Maier, W; Nimgaonkar, VL; Terenius, L; Mallet, J; Jay, M; Godard, S; Nertney, D; Alexander, M; Crowe, RR; Silverman, JM; Bassett, AS; Roy, M-A; Mérette, C; Pato, CN; Pato, MT; Roos, J Louw; Kohn, Y; Amann-Zalcenstein, D; Kalsi, G; McQuillin, A; Curtis, D; Brynjolfson, J; Sigmundsson, T; Petursson, H; Sanders, AR; Duan, J; Jazin, E; Myles-Worsley, M; Karayiorgou, M; Lewis, CM

2009-01-01

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (PSR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for ‘aggregate’ genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. PMID:19349958

A record linkage study of outcomes in patients with mild primary hyperparathyroidism: the Parathyroid Epidemiology and Audit Research Study (PEARS).

PubMed

Yu, Ning; Donnan, Peter T; Leese, Graham P

2011-08-01

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, but the majority of cases are perceived to be mild and remain untreated. To determine the risk of mortality and morbidities in patients with mild PHPT. Tayside, Scotland, 1997-2006. A historical, prospective, record-linkage, population-based, matched cohort study. All patients with diagnosed but untreated, mild PHPT. METHOD AND OUTCOME MEASURES: Each patient with PHPT was matched with five population-based comparators, by age, gender and calendar year of PHPT diagnosis, selected from the general population. Primary outcomes were all-cause mortality, fatal and nonfatal cardiovascular disease (CVD). Secondary outcomes were cancer-related deaths and other hospital admitted morbidities, including cerebrovascular disease, fractures, hypertension, psychiatric disease, renal complications, cancer and diabetes. The risk was assessed using the Cox proportional hazards model, adjusting for confounding factors of pre-existing co-morbidities, previous prescription of bisphosphonates, socio-economic deprivation score and the probability of having a calcium check. Compared to the matched cohort, the risk of all cause mortality, fatal and nonfatal CVD was increased in patients with asymptomatic PHPT: adjusted hazard ratios (HR) 1·64 (95% CI: 1·43-1·87), 1·64 (95% CI: 1·32-2·04) and 2·48 (95% CI: 2·13-2·89), respectively. The risk was also increased in all secondary outcomes, with the risk of renal failure and renal stones being the highest, adjusted HRs being 13·83 (95% CI: 10·41-18·37) and 5·15 (95% CI: 2·69-9·83), respectively. Patients with mild PHPT had an increased risk of mortality, fatal and nonfatal CVD, and the risk of developing other co-morbidities was also increased. © 2011 Blackwell Publishing Ltd.

Linkage analysis of the Nail-patella syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campeau, E.; Watkins, D.; Rouleau, G.A.

1995-01-01

Nail-patella syndrome (NPS) is an autosomal dominant disorder characterized by dysplasia of nails and patella, decreased mobility of the elbow, iliac horns, and, in some cases, nephropathy. The disorder has been mapped to the long arm of chromosome 9, but the precise localization and identity of the NPS gene are unknown. Linkage analysis in three NPS families, using highly informative dinucleotide repeat polymorphisms on 9q33-q34, confirmed linkage of NPS to this chromosome. Recombinations were detected, by two-point linkage analysis, between NPS and the centromeric markers D9S60 and the gelsolin gene and the telomeric markers D9S64 and D9S66, in one ofmore » the families. Haplotype analysis suggested an additional recombination between NPS and the argininosuccinate synthetase (ASS) gene. These results localize the NPS gene to an interval on 9q34.1, distal to D9S60 an proximal to ASS, comprising a genetic distance of {approximately}9 cM. This represents a significant refinement in the localization of the NPS gene. 25 refs., 2 figs., 1 tab.« less

NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients

PubMed Central

Meggyesi, Nora; Kiss, Lajos S; Koszarska, Magdalena; Bortlik, Martin; Duricova, Dana; Lakatos, Laszlo; Molnar, Tamas; Leniček, Martin; Vítek, Libor; Altorjay, Istvan; Papp, Maria; Tulassay, Zsolt; Miheller, Pal; Papp, Janos; Tordai, Attila; Andrikovics, Hajnalka; Lukas, Milan; Lakatos, Peter Laszlo

2010-01-01

AIM: To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD). METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCycler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was associated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associated with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathioprine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility loci for IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations. PMID:21049557

Academia-Industry-Government Linkages in Tanzania: Trends, Challenges and Prospects

ERIC Educational Resources Information Center

Mpehongwa, Gasper

2013-01-01

This paper analyzed trends, challenges and prospects of academia-industry-government linkages in Tanzania. Using case study design, and documentary review to gather the required data, the study sought to answer three research questions: (1) what are the trends of academia-industry-government linkages in Tanzania?, (2) what are the challenges…

Robust LOD scores for variance component-based linkage analysis.

PubMed

Blangero, J; Williams, J T; Almasy, L

2000-01-01

The variance component method is now widely used for linkage analysis of quantitative traits. Although this approach offers many advantages, the importance of the underlying assumption of multivariate normality of the trait distribution within pedigrees has not been studied extensively. Simulation studies have shown that traits with leptokurtic distributions yield linkage test statistics that exhibit excessive Type I error when analyzed naively. We derive analytical formulae relating the deviation from the expected asymptotic distribution of the lod score to the kurtosis and total heritability of the quantitative trait. A simple correction constant yields a robust lod score for any deviation from normality and for any pedigree structure, and effectively eliminates the problem of inflated Type I error due to misspecification of the underlying probability model in variance component-based linkage analysis.

Preliminary genetic linkage map of the abalone Haliotis diversicolor Reeve

NASA Astrophysics Data System (ADS)

Shi, Yaohua; Guo, Ximing; Gu, Zhifeng; Wang, Aimin; Wang, Yan

2010-05-01

Haliotis diversicolor Reeve is one of the most important mollusks cultured in South China. Preliminary genetic linkage maps were constructed with amplified fragment length polymorphism (AFLP) markers. A total of 2 596 AFLP markers were obtained from 28 primer combinations in two parents and 78 offsprings. Among them, 412 markers (15.9%) were polymorphic and segregated in the mapping family. Chi-square tests showed that 151 (84.4%) markers segregated according to the expected 1:1 Mendelian ratio ( P<0.05) in the female parent, and 200 (85.8%) in the male parent. For the female map, 179 markers were used for linkage analysis and 90 markers were assigned to 17 linkage groups with an average interval length of 25.7 cm. For the male map, 233 markers were used and 94 were mapped into 18 linkage groups, with an average interval of 25.0 cm. The estimated genome length was 2 773.0 cm for the female and 2 817.1 cm for the male map. The observed length of the linkage map was 1 875.2 cm and 1 896.5 cm for the female and male maps, respectively. When doublets were considered, the map length increased to 2 152.8 cm for the female and 2 032.7 cm for the male map, corresponding to genome coverage of 77.6% and 72.2%, respectively.

[Linkage analysis of a family with familial hypertriglyceridemia].

PubMed

Tang, Xin; Lin, Ying; Liu, Bing; Ma, Shi; Yang, Yang; Yang, Zheng-lin

2009-10-01

To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG). Thirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing. No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes. The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.

Genetic linkage map and comparative genome analysis for the estuarine Atlantic killifish (Fundulus heteroclitus)

EPA Pesticide Factsheets

Genetic linkage maps are valuable tools in evolutionary biology; however, their availability for wild populations is extremely limited. Fundulus heteroclitus (Atlantic killifish) is a non-migratory estuarine fish that exhibits high allelic and phenotypic diversity partitioned among subpopulations that reside in disparate environmental conditions. An ideal candidate model organism for studying gene-environment interactions, the molecular toolbox for F. heteroclitus is limited. We identified hundreds of novel microsatellites which, when combined with existing microsatellites and single nucleotide polymorphisms (SNPs), were used to construct the first genetic linkage map for this species. By integrating independent linkage maps from three genetic crosses, we developed a consensus map containing 24 linkage groups, consistent with the number of chromosomes reported for this species. These linkage groups span 2300 centimorgans (cM) of recombinant genomic space, intermediate in size relative to the current linkage maps for the teleosts, medaka and zebrafish. Comparisons between fish genomes support a high degree of synteny between the consensus F. heteroclitus linkage map and the medaka and (to a lesser extent) zebrafish physical genome assemblies.This dataset is associated with the following publication:Waits , E., J. Martinson , B. Rinner, S. Morris, D. Proestou, D. Champlin , and D. Nacci. Genetic linkage map and comparative genome analysis for the estuarine Atlanti

Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait.

PubMed

Dubé, M P; Mlodzienski, M A; Kibar, Z; Farlow, M R; Ebers, G; Harper, P; Kolodny, E H; Rouleau, G A; Figlewicz, D A

1997-03-01

Hereditary spastic paraplegia (HSP) is a degenerative disorder of the motor system, defined by progressive weakness and spasticity of the lower limbs. HSP may be inherited as an autosomal dominant (AD), autosomal recessive, or an X-linked trait. AD HSP is genetically heterogeneous, and three loci have been identified so far: SPG3 maps to chromosome 14q, SPG4 to 2p, and SPG4a to 15q. We have undertaken linkage analysis with 21 uncomplicated AD families to the three AD HSP loci. We report significant linkage for three of our families to the SPG4 locus and exclude several families by multipoint linkage. We used linkage information from several different research teams to evaluate the statistical probability of linkage to the SPG4 locus for uncomplicated AD HSP families and established the critical LOD-score value necessary for confirmation of linkage to the SPG4 locus from Bayesian statistics. In addition, we calculated the empirical P-values for the LOD scores obtained with all families with computer simulation methods. Power to detect significant linkage, as well as type I error probabilities, were evaluated. This combined analytical approach permitted conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity.

Global linkages between teleconnection patterns and the terrestrial biosphere

NASA Astrophysics Data System (ADS)

Dahlin, Kyla M.; Ault, Toby R.

2018-07-01

Interannual variability in the global carbon cycle is largely due to variations in carbon uptake by terrestrial ecosystems, yet linkages between climate variability and variability in the terrestrial carbon cycle are not well understood at the global scale. Using a 30-year satellite record of semi-monthly leaf area index (LAI), we show that four modes of climate variability - El Niño/Southern Oscillation, the North Atlantic Oscillation, the Atlantic Meridional Mode, and the Indian Ocean Dipole Mode - strongly impact interannual vegetation growth patterns, with 68% of the land surface impacted by at least one of these teleconnection patterns, yet the spatial distribution of these impacts is heterogeneous. Considering the patterns' impacts by biome, none has an exclusively positive or negative relationship with LAI. Our findings imply that future changes in the frequency and/or magnitude of teleconnection patterns will lead to diverse changes to the terrestrial biosphere and the global carbon cycle.

The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.

PubMed

Pujades-Rodriguez, Mar; Assi, Valentina; Gonzalez-Izquierdo, Arturo; Wilkinson, Tim; Schnier, Christian; Sudlow, Cathie; Hemingway, Harry; Whiteley, William N

2018-01-01

Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR. A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer's disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression (cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58). Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.

The acceptability of conducting data linkage research without obtaining consent: lay people's views and justifications.

PubMed

Xafis, Vicki

2015-11-17

A key ethical issue arising in data linkage research relates to consent requirements. Patients' consent preferences in the context of health research have been explored but their consent preferences regarding data linkage specifically have been under-explored. In addition, the views on data linkage are often those of patient groups. As a result, little is known about lay people's views and their preferences about consent requirements in the context of data linkage. This study explores lay people's views and justifications regarding the acceptability of conducting data linkage research without obtaining consent. A qualitative study explored lay people's views regarding consent requirements in data linkage via four hypothetical data linkage scenarios of increasing complexity. Prior to considering the scenarios, participants were provided with information regarding best practice data linkage processes via discussion and a diagrammatic representation of the process. Lay people were able to understand the intricate processes involved in data linkage and the key protections afforded within a short amount of time. They were supportive of data linkage research and, on the whole, believed it should be conducted without consent provided a data linkage organization de-identifies the data used so that researchers do not handle identifiable data. Many thought that de-identified data holds a different status to identifiable data and should be used without specific consent in research that aims to benefit society. In weighing up conflicting values and interests, participants shifted consent preferences before arriving at their final consent preference for each scenario and provided justifications for their choices. They considered the protection of people's information, societal benefits, and the nature and constraints of research and recognized that these need to be balanced. With some exposure to the features of data linkage, lay people have the capacity to understand the

Linkage Disequilibrium Under Recurrent Bottlenecks

PubMed Central

Schaper, E.; Eriksson, A.; Rafajlovic, M.; Sagitov, S.; Mehlig, B.

2012-01-01

To model deviations from selectively neutral genetic variation caused by different forms of selection, it is necessary to first understand patterns of neutral variation. Best understood is neutral genetic variation at a single locus. But, as is well known, additional insights can be gained by investigating multiple loci. The resulting patterns reflect the degree of association (linkage) between loci and provide information about the underlying multilocus gene genealogies. The statistical properties of two-locus gene genealogies have been intensively studied for populations of constant size, as well as for simple demographic histories such as exponential population growth and single bottlenecks. By contrast, the combined effect of recombination and sustained demographic fluctuations is poorly understood. Addressing this issue, we study a two-locus Wright–Fisher model of a population subject to recurrent bottlenecks. We derive coalescent approximations for the covariance of the times to the most recent common ancestor at two loci in samples of two chromosomes. This covariance reflects the degree of association and thus linkage disequilibrium between these loci. We find, first, that an effective population-size approximation describes the numerically observed association between two loci provided that recombination occurs either much faster or much more slowly than the population-size fluctuations. Second, when recombination occurs frequently between but rarely within bottlenecks, we observe that the association of gene histories becomes independent of physical distance over a certain range of distances. Third, we show that in this case, a commonly used measure of linkage disequilibrium, σd2 (closely related to r^2), fails to capture the long-range association between two loci. The reason is that constituent terms, each reflecting the long-range association, cancel. Fourth, we analyze a limiting case in which the long-range association can be described in terms of

Physiological Linkage in Couples and its Implications for Individual and Interpersonal Functioning: A Literature Review

PubMed Central

Timmons, Adela C.; Margolin, Gayla; Saxbe, Darby E.

2015-01-01

Do partners’ levels of physiological arousal become linked in close relationships? The term “physiological linkage” describes covariation between people in their moment-to-moment physiological states. The current review presents a conceptual framework to guide research on linkage in romantic relationships and discusses the potential implications of being “linked.” Evidence of linkage was found across a broad range of physiological indices and in a variety of contexts, including during laboratory-based conflict and in daily life. Four hypotheses regarding how linkage relates to individual and interpersonal functioning are evaluated: (1) co-activation of the sympathetic nervous system or hypothalamic-pituitary adrenal axis is “bad,” (2) moderate physiological linkage is “just right,” (3) physiological linkage is problematic if the individual or couple is overloaded, and (4) the implications of physiological linkage depend on the emotional context. We found partial support for the first hypothesis and determined that more research is needed to evaluate the remaining hypotheses. Linkage in cortisol was negatively associated with relationship satisfaction; but at the same time, linkage in multiple systems was positively associated with indices of relationship connectedness, such as the amount of time spent together and the ability to identify the emotions of one’s partner. These results suggest that linkage may confer benefits but also may put couples at risk if they become entrenched in patterns of conflict or stress. With research in this area burgeoning in recent years, this review indicates that linkage is a promising construct with applications for interventions targeting individual health and couple functioning. PMID:26147932

Identification of Nursing Diagnosis-Outcome-Intervention Linkages for Inpatients in the Obstetrics Department Nursing Unit in South Korea.

PubMed

Yang, Min Ji; Kim, Hye Young; Ko, Eun; Kim, Hyun Kyung

2017-09-08

To identify the NANDA-I-NOC-NIC (NNN) linkages for inpatients of the obstetrics nursing unit using electronic nursing records. In this retrospective, descriptive survey, the electronic nursing records for 220 adult patients aged ≥18 years who were discharged after obstetrics nursing unit were analyzed. The 7 most frequent nursing diagnoses were found to be associated with 9 nursing outcomes and 26 nursing interventions. Herein, the list of nursing diagnoses was observed to comprise the safety/protection domain, the list of nursing outcomes the physiological health domain, and the list of nursing interventions the physiological: complex domain. This result can contribute to improving the nursing quality and will help continuing education and documentation system refinement. © 2017 NANDA International, Inc.

Linkage mapping of beta 2 EEG waves via non-parametric regression.

PubMed

Ghosh, Saurabh; Begleiter, Henri; Porjesz, Bernice; Chorlian, David B; Edenberg, Howard J; Foroud, Tatiana; Goate, Alison; Reich, Theodore

2003-04-01

Parametric linkage methods for analyzing quantitative trait loci are sensitive to violations in trait distributional assumptions. Non-parametric methods are relatively more robust. In this article, we modify the non-parametric regression procedure proposed by Ghosh and Majumder [2000: Am J Hum Genet 66:1046-1061] to map Beta 2 EEG waves using genome-wide data generated in the COGA project. Significant linkage findings are obtained on chromosomes 1, 4, 5, and 15 with findings at multiple regions on chromosomes 4 and 15. We analyze the data both with and without incorporating alcoholism as a covariate. We also test for epistatic interactions between regions of the genome exhibiting significant linkage with the EEG phenotypes and find evidence of epistatic interactions between a region each on chromosome 1 and chromosome 4 with one region on chromosome 15. While regressing out the effect of alcoholism does not affect the linkage findings, the epistatic interactions become statistically insignificant. Copyright 2003 Wiley-Liss, Inc.

Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.

PubMed

Musolf, Anthony M; Simpson, Claire L; Moiz, Bilal A; Long, Kyle A; Portas, Laura; Murgia, Federico; Ciner, Elise B; Stambolian, Dwight; Bailey-Wilson, Joan E

2017-07-01

Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the

Markov chain Monte Carlo linkage analysis: effect of bin width on the probability of linkage.

PubMed

Slager, S L; Juo, S H; Durner, M; Hodge, S E

2001-01-01

We analyzed part of the Genetic Analysis Workshop (GAW) 12 simulated data using Monte Carlo Markov chain (MCMC) methods that are implemented in the computer program Loki. The MCMC method reports the "probability of linkage" (PL) across the chromosomal regions of interest. The point of maximum PL can then be taken as a "location estimate" for the location of the quantitative trait locus (QTL). However, Loki does not provide a formal statistical test of linkage. In this paper, we explore how the bin width used in the calculations affects the max PL and the location estimate. We analyzed age at onset (AO) and quantitative trait number 5, Q5, from 26 replicates of the general simulated data in one region where we knew a major gene, MG5, is located. For each trait, we found the max PL and the corresponding location estimate, using four different bin widths. We found that bin width, as expected, does affect the max PL and the location estimate, and we recommend that users of Loki explore how their results vary with different bin widths.

The quality of Indigenous identification in administrative health data in Australia: insights from studies using data linkage

PubMed Central

2012-01-01

Background Missing or incorrect Indigenous status in health records hinders monitoring of Indigenous health indicators. Linkage of administrative data has been used to improve the ascertainment of Indigenous status. Data linkage was pioneered in Western Australia (WA) and is now being used in other Australian states. This systematic review appraises peer-reviewed Australian studies that used data linkage to elucidate the impact of under-ascertainment of Indigenous status on health indicators. Methods A PubMed search identified eligible studies that used Australian linked data to interrogate Indigenous identification using more than one identifier and interrogated the impact of the different identifiers on estimation of Indigenous health indicators. Results Eight papers were included, five from WA and three from New South Wales (NSW). The WA papers included a self-identified Indigenous community cohort and showed improved identification in hospital separation data after 2000. In CVD hospitalised patients (2000–05), under-identification was greater in urban residents, older people and socially more advantaged Indigenous people, with varying algorithms giving different estimates of under-count. Age-standardised myocardial infarction incidence rates (2000–2004) increased by about 10%-15% with improved identification. Under-ascertainment of Indigenous identification overestimated secular improvements in life expectancy and mortality whereas correcting infectious disease notifications resulted in lower Indigenous/ non-Indigenous rate ratios. NSW has a history of poor Indigenous identification in administrative data systems, but the NSW papers confirmed the usefulness of data linkage for improving Indigenous identification and the potential for very different estimates of Indigenous disease indicators depending upon the algorithm used for identification. Conclusions Under-identification of Indigenous status must be addressed in health analyses concerning Indigenous

Short Communication Mendelian inheritance, linkage, and genotypic disequilibrium in microsatellite loci of Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae-Caesalpinioideae).

PubMed

Moraes, M A; Kubota, T Y K; Silva, E C B; Silva, A M; Cambuim, J; Moraes, M L T; Furlani Junior, E; Sebbenn, A M

2016-07-29

Hymenaea stigonocarpa is a deciduous and monoecious Neotropical tree species pollinated by bats. Due to overexploitation and habitat destruction, the population size has drastically diminished in nature. No previous study has investigated Mendelian inheritance, linkage, and genotypic disequilibrium in the available microsatellite markers in this species. So, our aim was to estimate these parameters using six microsatellite loci in a sample of 470 adults and 219 juveniles from two populations of H. stigonocarpa. In addition, 30 seeds per tree from 35 seed-trees were collected. Each seed was kept record of the seed-trees and fruit origin. Based on the six microsatellite loci, we found that only 10.6% of the cases showed significant deviations from Mendelian segregation and 15.3% showed linkage. We detected no evidence of genotypic disequilibrium between the loci in the adult trees or juveniles. Thus, our results suggest that these loci can be used with great accuracy in future genetic analyses of H. stigonocarpa populations.

ARE COASTAL WETLAND-LAKE LINKAGES IMPORTANT?

EPA Science Inventory

Because coastal werlands typically comprise only a small percentage of the overall surface area in large lakes, an assumption has often been made that functional links between wetlands and the lake proper are of little significance. Recent investigations of functional linkages be...

Conversion from depression to bipolar disorder in a cohort of young people in England, 1999-2011: A national record linkage study.

PubMed

James, Anthony; Wotton, Clare J; Duffy, Anne; Hoang, Uy; Goldacre, Michael

2015-10-01

To estimate the conversion rate from unipolar depression (ICD10 codes F32-F33) to bipolar disorder (BP) (ICD10 codes F31) in an English national cohort. It was hypothesised that early-onset BP (age <18 years) is a more severe form of the disorder, with a more rapid, and higher rate of conversion from depression to BP. This record linkage study used English national Hospital Episode Statistics (HES) covering all NHS inpatient and day case admissions between 1999 and 2011. The overall rate of conversion from depression to BP for all ages was 5.65% (95% CI: 5.48-5.83) over a minimum 4-year follow-up period. The conversion rate from depression to BP increased in a linear manner with age from 10-14 years - 2.21% (95% C: 1.16-4.22) to 30-34 years - 7.06% (95% CI: 6.44-7.55) (F1,23=77.6, p=0.001, R(2)=0.77). The time to conversion was constant across the age range. The rate of conversion was higher in females (6.77%; 95% CI: 6.53-7.02) compared to males, (4.17%; 95% CI: 3.95-4.40) (χ(2)=194, p<0.0001), and in those with psychotic depression 8.12% (95% CI: 7.65-8.62) compared to non-psychotic depression 5.65% (95% CI: 5.48-5.83) (χ(2)=97.0, p<0.0001). The study was limited to hospital discharges and diagnoses were not standardised. Increasing conversion rate from depression to bipolar disorder with age, and constant time for conversion across the age range does not support the notion that early-onset BP is a more severe form of the disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

Two-trait-locus linkage analysis: A powerful strategy for mapping complex genetic traits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schork, N.J.; Boehnke, M.; Terwilliger, J.D.

1993-11-01

Nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, the authors explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. The authors compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. Themore » authors also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one-marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, the authors also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that the authors consider, the authors find that two-trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one-trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, the authors also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. The authors discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models. 37 refs., 1 fig., 4 tabs.« less

The Relevance of Vitamin and Iron Deficiency in Patients with Inflammatory Bowel Diseases in Patients of the Swiss IBD Cohort.

PubMed

Madanchi, Matiar; Fagagnini, Stefania; Fournier, Nicolas; Biedermann, Luc; Zeitz, Jonas; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R; Rogler, Gerhard; Scharl, Michael

2018-04-13

Vitamin and iron deficiencies are common in patients with inflammatory bowel disease (IBD) as a result of chronic intestinal inflammation, increase in demand, or dietary restrictions. Here, we assessed the frequency of complications in relation to deficiency of iron, folate acid, and vitamin B12 in patients enrolled in the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). A total of 2666 patients were included in the study, 1558 with Crohn's disease (CD) and 1108 with ulcerative colitis (UC). Iron deficiency anemia was detected in 19.6% of CD patients and 21.6% of UC patients. In CD patients low BMI and nonsmoker status were positively associated with anemia. In both CD and UC, malabsorption syndrome, defined as failure of the GI tract to absorb 1 or more substances from the diet, was found to be significantly associated with anemia (6.2% and 3.8%, respectively) and current steroid use (40% CD, 52.7% UC). In CD patients with ileal (31.7% vs 20%) and colonic (29.9% vs 25%) disease location folate deficiency was significantly higher than in patients with ileocolonic CD or upper GI involvement. In CD patients, vitamin B12 deficiency was associated with the onset of stenosis and intestinal surgery (42.9% vs 32.8% and 46% vs 33% for patients with versus without B12 deficiency). Our data indicate that due to frequent occurrence of deficiency states, regular monitoring and substitution of vitamins and iron are mandatory and may prevent long-term intestinal and extraintestinal complications in IBD patients.

Linkage Disequilibrium in a Finite Population That Is Partially Selfing

PubMed Central

Golding, G. B.; Strobeck, C.

1980-01-01

The linkage disequilibrium expected in a finite, partially selfing population is analyzed, assuming the infinite allele model. Formulas for the expected sum of squares of the linkage disequilibria and the squared standard linkage disequilibrium are derived from the equilibrium values of sixteen inbreeding coefficients required to describe the behavior of the system. These formulas are identical to those obtained with random mating if the effective population size Ne = (1-½S)N and the effective recombination value re = (1-S)r/(1-½S), where S is the proportion of selfing, are substituted for the population size and the recombination value. Therefore, the effect of partial selfing at equilibrium is to reduce the population size by a factor 1-½S and the recombination value by a factor (1-S)/(1-½S). PMID:17249017

Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis

PubMed Central

Hamshere, Marian L; Segurado, Ricardo; Moskvina, Valentina; Nikolov, Ivan; Glaser, Beate; Holmans, Peter A

2007-01-01

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates. PMID:18466440

Linkage analysis of quantitative refraction and refractive errors in the Beaver Dam Eye Study.

PubMed

Klein, Alison P; Duggal, Priya; Lee, Kristine E; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E; Klein, Barbara E K

2011-07-13

Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10(-3) and 1.48 × 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 × 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10(-3)), a region previously linked to high myopia. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11.

Linkage Analysis of Quantitative Refraction and Refractive Errors in the Beaver Dam Eye Study

PubMed Central

Duggal, Priya; Lee, Kristine E.; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E.; Klein, Barbara E. K.

2011-01-01

Purpose. Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Methods. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Results. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10−4), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10−3 and 1.48 × 10−3, respectively) and to 7p15 of refraction (empiric P = 9.43 × 10−4). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10−3), a region previously linked to high myopia. Conclusions. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11. PMID:21571680

An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report.

PubMed

Olendzki, Barbara C; Silverstein, Taryn D; Persuitte, Gioia M; Ma, Yunsheng; Baldwin, Katherine R; Cave, David

2014-01-16

The Anti-Inflammatory Diet (IBD-AID) is a nutritional regimen for inflammatory bowel disease (IBD) that restricts the intake of certain carbohydrates, includes the ingestion of pre- and probiotic foods, and modifies dietary fatty acids to demonstrate the potential of an adjunct dietary therapy for the treatment of IBD. Forty patients with IBD were consecutively offered the IBD-AID to help treat their disease, and were retrospectively reviewed. Medical records of 11 of those patients underwent further review to determine changes in the Harvey Bradshaw Index (HBI) or Modified Truelove and Witts Severity Index (MTLWSI), before and after the diet. Of the 40 patients with IBD, 13 patients chose not to attempt the diet (33%). Twenty-four patients had either a good or very good response after reaching compliance (60%), and 3 patients' results were mixed (7%). Of those 11 adult patients who underwent further medical record review, 8 with CD, and 3 with UC, the age range was 19-70 years, and they followed the diet for 4 or more weeks. After following the IBD-AID, all (100%) patients were able to discontinue at least one of their prior IBD medications, and all patients had symptom reduction including bowel frequency. The mean baseline HBI was 11 (range 1-20), and the mean follow-up score was 1.5 (range 0-3). The mean baseline MTLWSI was 7 (range 6-8), and the mean follow-up score was 0. The average decrease in the HBI was 9.5 and the average decrease in the MTLWSI was 7. This case series indicates potential for the IBD-AID as an adjunct dietary therapy for the treatment of IBD. A randomized clinical trial is warranted.

Student Apprenticeship Linkage in Vocational Education.

ERIC Educational Resources Information Center

Alabama State Dept. of Education, Montgomery. Div. of Vocational Education Services.

The Student Apprenticeship Linkage Program bridges skill training programs in secondary schools with high technology apprenticeship training programs in industry. The program returns quality to Alabama's Vocational Education System and meets work force needs of business and industry. The program has eight objectives: demonstrate a model for…

The Association between Bankruptcy and Hospital-Presenting Attempted Suicide: A Record Linkage Study

ERIC Educational Resources Information Center

Kidger, Judi; Gunnell, David; Jarvik, Jeffrey G.; Overstreet, Karen A.; Hollingworth, William

2011-01-01

The associations between admissions to an emergency department following attempted suicide and personal bankruptcy in the preceding and subsequent 2 years were evaluated. Records from a level 1 trauma center (June 1993-December 2002) in Seattle, WA, were linked with case files from the local U.S. District Bankruptcy Court (June 1991 onward).…

Modelling of lateral fold growth and fold linkage: Applications to fold-and-thrust belt tectonics

NASA Astrophysics Data System (ADS)

Grasemann, Bernhard; Schmalholz, Stefan

2013-04-01

We use a finite element model to investigate the three-dimensional fold growth and interference of two initially isolated fold segments. The most critical parameter, which controls the fold linkage mode, is the phase difference between the laterally growing fold hinge lines: 1) "Linear-linkage" yields a sub-cylindrical fold with a saddle at the location where the two initial folds linked. 2) "Oblique-linkage" produces a curved fold resembling a Type II refold structure. 3) "Oblique-no-linkage" results in two curved folds with fold axes plunging in opposite directions. 4) "Linear-no-linkage" yields a fold train of two separate sub-cylindrical folds with fold axes plunging in opposite directions. The transition from linkage to no-linkage occurs when the fold separation between the initially isolated folds is slightly larger than one half of the low-amplitude fold wavelength. The model results compare well with previously published plasticine analogue models and can be directly applied to the investigation of fold growth history in fold-and-thust belts. An excellent natural example of lateral fold linkage is described from the Zagros fold-and-thrust belt in the Kurdistan Region of Iraq. The fold growth in this region is not controlled by major thrust faults but the shortening of the Paleozoic to Cenozoic passive margin sediments of the Arabian plate occurred mainly by detachment folding. The sub-cylindrical anticlines with hinge-parallel lengths of more than 50 km have not developed from single sub-cylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification and lateral fold growth. Linkage points are marked by geomorphological saddle points which are structurally the lowermost points of antiforms and points of principal curvatures with opposite sign. Linkage points can significantly influence the migration of mineral-rich fluids and hydrocarbons and are therefore of great economic importance.

Speleothem records of western Mediterranean. Hydrological variability along the Last Interglacial Period and marine linkages

NASA Astrophysics Data System (ADS)

Torner, Judit; Cacho, Isabel; Moreno, Ana; Stoll, Heather; Belmonte, Anchel; Sierro, Francisco J.; Frigola, Jaime; Martrat, Belen; Fornós, Joan; Arnau Fernández, Pedro; Hellstrom, John; Cheng, Hai; Edwards, R. Lawrence

2016-04-01

This study aims to identify and characterize regional hydrological variability in the western Mediterranean region in base to different geochemical parameters (δ18O, δ13C, and Mg/Ca ratios). Speleothems have been recovered from several caves located in southern central Pyrenees one and the others form the Balearic Islands. Their chronologies have been constructed in base on U/Th absolute dating and indicate that the speleothem sequences cover the end of the last interglacial and the glacial inception. One of the most remarkable features of the records is the intense and abrupt shift toward more arid conditions that marks the end of the last interglacial (MIS 5e). Furthermore, our speleothem records also show relatively humid but highly variable hydrological conditions during the interstadial periods from MIS 5c to 5a. These speleothem records have been compared with new generated western Mediterranean marine records from the Balearic Sea (MD99-2343) and Alboran Sea (OPD-977). Marine records include (1) proxies of sea surface temperature and changes in evaporation-precipitation rates based on pair analysis of δ18O and the Mg/Ca ratios in planktonic foraminifera Globigerina bulloides; (2) proxies of deep-water currents associated with the Western Mediterranean Deep Water (WMDW) based on grain size analyses. The results reveal that arid conditions on land were coeval with cold sea surface sub-stages (MIS 5b and 5d), and also with increases in the intensity of the WMDW-related currents. By contrast, humid and hydrological unstable atmosphere conditions were synchronous with sea surface warm sub-stages, and lower WMDW-related currents intensities (MIS 5a, c and e). Consequently, our results highly evidence a strong atmospheric-oceanic coupling, involving parallel changes in both surface but also deep western Mediterranean Sea conditions during the last interglacial period and the glacial inception.

Strike-slip tectonics during rift linkage

NASA Astrophysics Data System (ADS)

Pagli, C.; Yun, S. H.; Ebinger, C.; Keir, D.; Wang, H.

2017-12-01

The kinematics of triple junction linkage and the initiation of transforms in magmatic rifts remain debated. Strain patterns from the Afar triple junction provide tests of current models of how rifts grow to link in area of incipient oceanic spreading. Here we present a combined analysis of seismicity, InSAR and GPS derived strain rate maps to reveal that the plate boundary deformation in Afar is accommodated primarily by extensional tectonics in the Red Sea and Gulf of Aden rifts, and does not require large rotations about vertical axes (bookshelf faulting). Additionally, models of stress changes and seismicity induced by recent dykes in one sector of the Afar triple junction provide poor fit to the observed strike-slip earthquakes. Instead we explain these patterns as rift-perpendicular shearing at the tips of spreading rifts where extensional strains terminate against less stretched lithosphere. Our results demonstrate that rift-perpendicular strike-slip faulting between rift segments achieves plate boundary linkage during incipient seafloor spreading.

How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda.

PubMed

Ware, Norma C; Wyatt, Monique A; Asiimwe, Stephen; Turyamureeba, Bosco; Tumwesigye, Elioda; van Rooyen, Heidi; Barnabas, Ruanne V; Celum, Connie L

2016-01-01

The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC) with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services. We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe, Sheema District, Uganda. The participant sample included both HIV+ men and women (N=47) and HIV-uncircumcised men (N=52). Interview and focus group audio-recordings were translated and transcribed. Each transcript was summarized. The summaries were analyzed inductively to identify emergent themes. Thematic concepts were grouped to develop general constructs and framing propositional statements. Trial participants expressed interest in linking to clinic-based services at testing, but faced obstacles that eroded their initial enthusiasm. Follow-up support by lay counsellors intervened to restore interest and inspire action. Together, home HTC and follow-up support improved morale, created a desire to reciprocate, and provided reassurance that services were trustworthy. In different ways, these functions built links to the health service system. They worked to strengthen individuals' general sense of capability, while making the idea of accessing services more manageable and familiar, thus reducing linkage barriers. Home HTC with follow-up support leads to linkage by building

HIV-1 transmission linkage in an HIV-1 prevention clinical trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leitner, Thomas; Campbell, Mary S; Mullins, James I

2009-01-01

HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determinationmore » in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

Saturation of an intra-gene pool linkage map: toward unified consensus linkage map in common bean

USDA-ARS?s Scientific Manuscript database

Map-based cloning to find genes of interest and marker assisted selection (MAS) requires good genetic maps with high reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers in includin...

Quantifying landscape linkages among giant panda subpopulations in regional scale conservation.

PubMed

Qi, Dunwu; Hu, Yibo; Gu, Xiaodong; Yang, Xuyi; Yang, Guang; Wei, Fuwen

2012-06-01

Understanding habitat requirements and identifying landscape linkages are essential for the survival of isolated populations of endangered species. Currently, some of the giant panda populations are isolated, which threatens their long-term survival, particularly in the Xiaoxiangling mountains. In the present study, we quantified niche requirements and then identified potential linkages of giant panda subpopulations in the most isolated region, using ecological niche factor analysis and a least-cost path model. Giant pandas preferred habitat with conifer forest and gentle slopes (>20 to ≤30°). Based on spatial distribution of suitable habitat, linkages were identified for the Yele subpopulation to 4 other subpopulations (Liziping, Matou, Xinmin and Wanba). Their lengths ranged from 15 to 54 km. The accumulated cost ranged from 693 to 3166 and conifer forest covered over 31%. However, a variety of features (e.g. major roads, human settlements and large unforested areas) might act as barriers along the linkages for giant panda dispersal. Our analysis quantified giant panda subpopulation connectivity to ensure long-term survival. © 2012 ISZS, Blackwell Publishing and IOZ/CAS.

Significant Linkage for Tourette Syndrome in a Large French Canadian Family

PubMed Central

Mérette, Chantal; Brassard, Andrée; Potvin, Anne; Bouvier, Hélène; Rousseau, François; Émond, Claudia; Bissonnette, Luc; Roy, Marc-André; Maziade, Michel; Ott, Jurg; Caron, Chantal

2000-01-01

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS. PMID:10986045

Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis.

PubMed

Mustafa, Z; Chapman, K; Irven, C; Carr, A J; Clipsham, K; Chitnavis, J; Sinsheimer, J S; Bloomfield, V A; McCartney, M; Cox, O; Sykes, B; Loughlin, J

2000-03-01

To examine 11 candidate genes as susceptibility loci for osteoarthritis (OA). A total of 481 families have been ascertained in which at least two siblings have had joint replacement surgery of the hip, or knee, or hip and knee for idiopathic OA. Each candidate gene was targeted using one or more intragenic or closely linked microsatellite marker. The linkage data were analysed unstratified and following stratification by sex and by joint replaced (hip or knee). The analyses revealed suggestive linkage of the type IX collagen gene COL9A1 (6q12-q13) to a subset of 132 families that contained affected females who were concordant for hip OA (female-hip) with a P-value of 0.00053 and logarithm of the odds (LOD) score of 2.33 [corrected P-value of 0. 0016, corrected LOD score of 1.85]. COL9A1 may therefore be a susceptibility locus for female hip OA. In addition, there was weak evidence of linkage to HLA/COL11A2 (6p21.3) in female hip OA with a corrected P-value of 0.016.

On computation of p-values in parametric linkage analysis.

PubMed

Kurbasic, Azra; Hössjer, Ola

2004-01-01

Parametric linkage analysis is usually used to find chromosomal regions linked to a disease (phenotype) that is described with a specific genetic model. This is done by investigating the relations between the disease and genetic markers, that is, well-characterized loci of known position with a clear Mendelian mode of inheritance. Assume we have found an interesting region on a chromosome that we suspect is linked to the disease. Then we want to test the hypothesis of no linkage versus the alternative one of linkage. As a measure we use the maximal lod score Z(max). It is well known that the maximal lod score has asymptotically a (2 ln 10)(-1) x (1/2 chi2(0) + 1/2 chi2(1)) distribution under the null hypothesis of no linkage when only one point (one marker) on the chromosome is studied. In this paper, we show, both by simulations and theoretical arguments, that the null hypothesis distribution of Zmax has no simple form when more than one marker is used (multipoint analysis). In fact, the distribution of Zmax depends on the number of families, their structure, the assumed genetic model, marker denseness, and marker informativity. This means that a constant critical limit of Zmax leads to tests associated with different significance levels. Because of the above-mentioned problems, from the statistical point of view the maximal lod score should be supplemented by a p-value when results are reported. Copyright (c) 2004 S. Karger AG, Basel.