An algorithm to identify rheumatoid arthritis in primary care: a Clinical Practice Research Datalink study

Objective: Rheumatoid arthritis (RA) is a multisystem, inflammatory disorder associated with increased levels of morbidity and mortality. While much research into the condition is conducted in the secondary care setting, routinely collected primary care databases provide an important source of research data. This study aimed to update an algorithm to define RA that was previously developed and validated in the General Practice Research Database (GPRD). Methods: The original algorithm consisted of two criteria. Individuals meeting at least one were considered to have RA. Criterion 1:≥1 RA Read code and a disease modifying antirheumatic drug (DMARD) without an alternative indication. Criterion 2:≥2RA Read codes, with at least one 'strong' code and no alternative diagnoses. Lists of codes for consultations and prescriptions were obtained from the authors of the original algorithm where these were available, or compiled based on the original description and clinical knowledge. 4161 people with a first Read code for RA between 1 January 2010 and 31 December 2012 were selected from the Clinical Practice Research Datalink (CPRD, successor to the GPRD), and the criteria applied. Results: Code lists were updated for the introduction of new Read codes and biological DMARDs. 3577/ 4161 (86%) of people met the updated algorithm for RA, compared to 61% in the original development study. 62.8% of people fulfilled both Criterion 1 and Criterion 2. Conclusions: Those wishing to define RA in the CPRD, should consider using this updated algorithm, rather than a single RA code, if they wish to identify only those who are most likely to have RA

Prevalence of cardiovascular-related comorbidity in ankylosing spondylitis, psoriatic arthritis and psoriasis in primary care: a matched retrospective cohort study

The aim of this study is to compare the prevalence of cardiovascular (CVD)-related comorbidities in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) or psoriasis (Ps) in UK primary care against matched cohorts. Matched retrospective cohort study used a primary care consultation database. Three cohorts were constructed using all patients with a Read code diagnosis of AS, PsA or Ps between 1999 and 2009; each cohort was then compared in a 1:4 ratio to a matched cohort. The prevalence of CVD-related comorbidities (hypertension, ischaemic heart disease, hyperlipidaemia and diabetes mellitus) were identified by the first consultation of a comorbid Read code, in those with an inflammatory condition of interest. The prevalence of CVD-related comorbidities was compared between each inflammatory cohort and their matched cohort using Fisher’s exact test. Ninety-four AS, 106 PsA and 290 Ps patients were identified. Compared with matched cohorts, the most prevalent CVD-related comorbidity in patients with AS was hypertension (35 (37.2 %) vs. 96 matched (25.5 %), p = 0.03); this was also the case for PsA (41 (38.7 %) vs. 114 matched (26.9 %), p = 0.02). No differences were seen in the prevalence of other CVD-related comorbidities in those with AS, PsA or Ps compared to their matched cohorts. Our findings provide UK comparisons of CVD-related comorbidities in patients with AS, PsA and Ps alone; specifically, demonstrating increased prevalence of hypertension in AS and PsA cohorts compared to their matched cohorts. This further supports the argument for more evidence in the need for screening and intervention around CVD comorbidities in inflammatory conditions

A global disorder of imprinting in the human female germ line

Imprinted genes are expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin. Correct imprinting is established by germline-specific modifications; failure of this process underlies several inherited human syndromes. All these imprinting control defects are cis-acting, disrupting establishment or maintenance of allele-specific epigenetic modifications across one contiguous segment of the genome. In contrast, we report here an inherited global imprinting defect. This recessive maternal-effect mutation disrupts the specification of imprints at multiple, non-contiguous loci, with the result that genes normally carrying a maternal methylation imprint assume a paternal epigenetic pattern on the maternal allele. The resulting conception is phenotypically indistinguishable from an androgenetic complete hydatidiform mole, in which abnormal extra-embryonic tissue proliferates while development of the embryo is absent or nearly so. This disorder offers a genetic route to the identification of trans-acting oocyte factors that mediate maternal imprint establishment

Searching for a prodrome for rheumatoid arthritis in the primary care record: a case-control study in the Clinical Practice Research Datalink

Background: Rheumatoid arthritis (RA) has articular and non-articular manifestations. Early, intensive treatment has substantial benefit for both. This requires patients be identified as soon as symptoms develop. Objectives: To determine whether selected signs and symptoms can be identified in the primary care records of patients prior to a formal diagnosis of RA being made and, if so, how early they can be identified. Methods: A case-control study was constructed within the UK Clinical Practice Research Datalink (CPRD). 3577 individuals with 'definite' RA, were matched to 14287 individuals without inflammatory arthritis. An index date was established (i.e. date general practitioner (GP) first appeared to suspect RA). Rates of consultation and consultations for suspected early RA symptoms were compared in cases and controls in the two years prior to the index date using conditional logistic regression, adjusted for number of consultations. Results: The mean (standard deviation) age of participants was 58.8 (14.5) years and 66.8% were female. Rates of any consultation were significantly higher in RA cases than in controls for at least two years prior to the index date. Cases were more likely to have a pre-diagnosis coded consultation for joint, and particularly hand symptoms (aOR 11.44 (9.60, 13.63)), morning stiffness (8.10 (3.54, 18.5)), carpal tunnel syndrome (4.57 (3.54, 5.88)) and other non-articular features. Conclusions: In patients who develop RA, GP consultation rates are higher for at least two years prior to the first recorded suspicion of RA. This study highlights symptoms that should raise a GP’s index of suspicion for RA

Classification of protein domain movements using Dynamic Contact Graphs

A new method for the classification of domain movements in proteins is described and applied to 1822 pairs of structures from the Protein Data Bank that represent a domain movement in two-domain proteins. The method is based on changes in contacts between residues from the two domains in moving from one conformation to the other. We argue that there are five types of elemental contact changes and that these relate to five model domain movements called: ‘‘free’’, ‘‘openclosed’’, ‘‘anchored’’, ‘‘sliding-twist’’, and ‘‘see-saw.’’ A directed graph is introduced called the ‘‘Dynamic Contact Graph’’ which represents the contact changes in a domain movement. In many cases a graph, or part of a graph, provides a clear visual metaphor for the movement it represents and is a motif that can be easily recognised. The Dynamic Contact Graphs are often comprised of disconnected subgraphs indicating independent regions which may play different roles in the domain movement. The Dynamic Contact Graph for each domain movement is decomposed into elemental Dynamic Contact Graphs, those that represent elemental contact changes, allowing us to count the number of instances of each type of elemental contact change in the domain movement. This naturally leads to sixteen classes into which the 1822 domain movements are classified

Knowledge, Attitudes, and Behaviors on Utilizing Mobile Health Technology for TB in Indonesia: A Qualitative Pilot Study

Tuberculosis (TB) infections remain a global health burden with a high incidence rate in South-East Asia, including Indonesia. TB control strategy is founded on early case detection and complete treatment to minimize transmission and prevent the emergence of drug resistance. However, many patients face challenges to comply with daily medication, causing many to adhere inconsistently or stop prematurely. Technological solutions could enhance adherence to treatment and support national screening and follow-up policies. These include telephone video communication, enabling health professionals to watch patients take their medication, address patients' concerns, and provide advice and support. This manuscript describes the outcome of a qualitative pilot study, based on a series of focus group discussions to assess the knowledge, attitudes, and behaviors, on the potential utilization of mobile technology for health purposes with a particular focus on TB treatment follow-up. The findings illustrate that general knowledge of mobile health technologies, of their legal framework of operations, and of their exact potential within the healthcare system is incomplete or poor. The novel findings are as follows: (a) the willingness of participants to learn about these technologies, (b) the open and welcoming attitude toward receiving such information even within frontline community settings, and (c) the willingness to back a government-supported, healthcare-driven set of such initiatives. Potential implementation barriers have also been highlighted. This study is an important first step toward understanding the attitudes and behaviors on utilizing mobile health technology for TB in Indonesia

Profiling quality of care: Is there a role for peer review?

BACKGROUND: We sought to develop a more reliable structured implicit chart review instrument for use in assessing the quality of care for chronic disease and to examine if ratings are more reliable for conditions in which the evidence base for practice is more developed. METHODS: We conducted a reliability study in a cohort with patient records including both outpatient and inpatient care as the objects of measurement. We developed a structured implicit review instrument to assess the quality of care over one year of treatment. 12 reviewers conducted a total of 496 reviews of 70 patient records selected from 26 VA clinical sites in two regions of the country. Each patient had between one and four conditions specified as having a highly developed evidence base (diabetes and hypertension) or a less developed evidence base (chronic obstructive pulmonary disease or a collection of acute conditions). Multilevel analysis that accounts for the nested and cross-classified structure of the data was used to estimate the signal and noise components of the measurement of quality and the reliability of implicit review. RESULTS: For COPD and a collection of acute conditions the reliability of a single physician review was quite low (intra-class correlation = 0.16–0.26) but comparable to most previously published estimates for the use of this method in inpatient settings. However, for diabetes and hypertension the reliability is significantly higher at 0.46. The higher reliability is a result of the reviewers collectively being able to distinguish more differences in the quality of care between patients (p < 0.007) and not due to less random noise or individual reviewer bias in the measurement. For these conditions the level of true quality (i.e. the rating of quality of care that would result from the full population of physician reviewers reviewing a record) varied from poor to good across patients. CONCLUSIONS: For conditions with a well-developed quality of care evidence base, such as hypertension and diabetes, a single structured implicit review to assess the quality of care over a period of time is moderately reliable. This method could be a reasonable complement or alternative to explicit indicator approaches for assessing and comparing quality of care. Structured implicit review, like explicit quality measures, must be used more cautiously for illnesses for which the evidence base is less well developed, such as COPD and acute, short-course illnesses

Factors affecting the prey preferences of jackals (Canidae)

Prey selection by carnivores can be affected by top-down and bottom-up factors. For example, large carnivores may facilitate food resources for mesocarnivores by providing carcasses to scavenge, however mesocarnivores may hunt large prey themselves, and their diets might be affected by prey size and behaviour. We reviewed jackal diet studies and determined how the presence of large carnivores and various bottom-up factors affected jackal prey selection. We found 20 studies of black-backed jackals (Canis mesomelas) from 43 different times or places, and 13 studies of Eurasian golden jackals (Canis aureus) from 23 different times or places reporting on 3900 and 2440 dietary records (i.e. scats or stomach contents), respectively. Black-backed jackals significantly preferred small ( 120 kg) hider species and follower species of any body size. They had a preferred and accessible prey weight range of 14-26 kg, and a predator to ideal prey mass ratio of 1:3.1. Eurasian golden jackal significantly prefer to prey on brown hare (Lepus europaeus; 4 kg), yielding a predator to preferred prey mass ratio of 1:0.6, and a preferred and accessible prey weight range of 0 – 4 kg and 0 – 15 kg, respectively. Prey preferences of jackals differed significantly in the presence of apex predators, but it was not entirely due to carrion availability of larger prey species. Our results show that jackal diets are affected by both top-down and bottom-up factors, because apex predators as well as prey size and birthing behaviour affected prey preferences of jackals. A better understanding of the factors affecting jackal prey preferences, as presented here, could lead to greater acceptance of mesocarnivores and reduced human-wildlife conflict

Motivated proteins: a web application for studying small three-dimensional protein motifs

&lt;b&gt;BACKGROUND:&lt;/b&gt; Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns.We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. &lt;b&gt;DESCRIPTION:&lt;/b&gt; The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. &lt;b&gt;CONCLUSION:&lt;/b&gt; Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schem