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

Trends in prescribing of non-steroidal anti-inflammatory drugs in patients with cardiovascular disease: influence of national guidelines in UK primary care

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, but have potential side effects in patients with cardiovascular disease (CVD). Objectives: To determine trends in NSAIDs prescribing between 2002 and 2010 in patients with CVD, and ascertain whether prescribing patterns changed following publication of major national (the Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Clinical Excellence (NICE)) guidance to GPs. Methods: This was an observational database study of adult patients in 11 practices (Staffordshire, England). NSAIDs were categorised into basic, COX-2 and topical. Study duration was divided on a quarterly basis from 2002-quarter-1 to 2010q4. CVD patients were identified using pre-defined Read Codes recorded in the two years prior to each quarter. Quarterly prevalence was determined. Times of significant changes in prescribing trends were determined using Joinpoint Regression, and compared to dates of the five major guidelines (in 2004q4, 2005q1, 2005q3, 2006q4, 2008q1). Results: In CVD patients, the prescription of basic NSAIDs showed a decreasing trend throughout the study period, from 774 (95% CI, 691-863) per 10000 patients in 2002q1 to 245 (204-291) in 2010q4. COX-2 prescribing increased from 232/10000 (187-286) in 2002q1 to 403/10000 (348-464) in 2004q3. Prescribing then fell sharply to 102/10000 (76-134) in 2005q2 before stabilising around 55/10000. Topical NSAIDs prescribing showed a steady increase, starting at 115/10000 (108-123) in 2002q1 and ending at 270/10000 (258-281) in 2010q4. Similar trends were observed in patients without CVD, particularly a sharp drop in COX-2 prescribing also occurred from 2004q4 when initial MHRA guidance was issued. Conclusion: Despite guidelines and a trend toward decreased prescribing, the use of potentially harmful NSAIDs continued in CVD patients. The MHRA directives potentially might have affected patients without CVD who may have inappropriately restricted their use of COX-2

Conformally rescaled spacetimes and Hawking radiation

We study various derivations of Hawking radiation in conformally rescaled metrics. We focus on two important properties, the location of the horizon under a conformal transformation and its associated temperature. We find that the production of Hawking radiation cannot be associated in all cases to the trapping horizon because its location is not invariant under a conformal transformation. We also find evidence that the temperature of the Hawking radiation should transform simply under a conformal transformation, being invariant for asymptotic observers in the limit that the conformal transformation factor is unity at their location.Comment: 22 pages, version submitted to journa