Approaches to Recording Drug Allergies in Electronic Health Records: Qualitative Study

Background

Drug allergy represent an important subset of adverse drug reactions that is worthy of attention because many of these reactions are potentially preventable with use of computerised decision support systems. This is however dependent on the accurate and comprehensive recording of these reactions in the electronic health record. The objectives of this study were to understand approaches to the recording of drug allergies in electronic health record systems.

Materials and Methods

We undertook a case study comprising of 21 in-depth interviews with a purposefully selected group of primary and secondary care clinicians, academics, and members of the informatics and drug regulatory communities, observations in four General Practices and an expert group discussion with 15 participants from the Allergy and Respiratory Expert Resource Group of the Royal College of General Practitioners.

Results

There was widespread acceptance among healthcare professionals of the need for accurate recording of drug allergies and adverse drug reactions. Most drug reactions were however likely to go unreported to and/or unrecognised by healthcare professionals and, even when recognised and reported, not all reactions were accurately recorded. The process of recording these reactions was not standardised.

Conclusions

There is considerable variation in the way drug allergies are recorded in electronic health records. This limits the potential of computerised decision support systems to help alert clinicians to the risk of further reactions. Inaccurate recording of information may in some instances introduce new problems as patients are denied treatments that they are erroneously believed to be allergic to.     

Changes in direction-specific activity of psoas major and quadratus lumborum in people with recurring back pain differ between muscle regions and patient groups

Psoas major (PM) and quadratus lumborum (QL) muscles have anatomically discrete regions. Redistribution of activity between these regions has been observed in people with low back pain (LBP). We hypothesised that the bias of activity of specific regions of PM and QL towards trunk extension may change depending on whether LBP individuals have more or less erector spinae (ES) activity in an extended/upright lumbar posture. Ten volunteers with recurring episodes of LBP and nine pain-free controls performed isometric trunk efforts in upright sitting. LBP individuals were subgrouped into those with high and low ES electromyographic activity (EMG) when sitting with a lumbar lordosis. Fine-wire electrodes were inserted into fascicles of PM arising from the transverse process (PM-t) and vertebral body (PM-v) and anterior (QL-a) and posterior layers (QL-p) of QL. The LBP group with low ES EMG had greater bias of PM-t, PM-v and QL-p towards trunk extension. The LBP group with high ES activity showed less PM activity towards extension. These findings suggest redistribution of activity within and/or between these muscles with extensor moments. This is likely to be important to consider for effective clinical interventions for individuals with LBP.     

Endoplasmic Reticulum Glycoprotein Quality Control Regulates CD1d Assembly and CD1d-mediated Antigen Presentation

The non-classical major histocompatibility complex (MHC) homologue CD1d presents lipid antigens to innate-like lymphocytes called natural-killer T (NKT) cells. These cells, by virtue of their broad cytokine repertoire, shape innate and adaptive immune responses. Here, we have assessed the role of endoplasmic reticulum glycoprotein quality control in CD1d assembly and function, specifically the role of a key component of the quality control machinery, the enzyme UDP glucose glycoprotein glucosyltransferase (UGT1). We observe that in UGT1-deficient cells, CD1d associates prematurely with β₂-microglobulin (β₂m) and is able to rapidly exit the endoplasmic reticulum. At least some of these CD1d-β₂m heterodimers are shorter-lived and can be rescued by provision of a defined exogenous antigen, α-galactosylceramide. Importantly, we show that in UGT1-deficient cells the CD1d-β₂m heterodimers have altered antigenicity despite the fact that their cell surface levels are unchanged. We propose that UGT1 serves as a quality control checkpoint during CD1d assembly and further suggest that UGT1-mediated quality control can shape the lipid repertoire of newly synthesized CD1d. The quality control process may play a role in ensuring stability of exported CD1d-β₂m complexes, in facilitating presentation of low abundance high affinity antigens, or in preventing deleterious responses to self lipids.     

Herpes simplex virus 1 glycoprotein B and US3 collaborate to inhibit CD1d antigen presentation and NKT cell function

Herpes simplex viruses (HSVs) are prevalent human pathogens that establish latency in human neuronal cells and efficiently evade the immune system. It has been a major medical challenge to eradicate them and, despite intensive efforts, an effective vaccine is not available. We previously showed that upon infection of antigen-presenting cells, HSV type 1 (HSV-1) rapidly and efficiently downregulates the major histocompatibility complex class I-like antigen-presenting molecule, CD1d, and potently inhibits its recognition by CD1d-restricted natural killer T (NKT) cells. It suppresses CD1d expression primarily by inhibiting its recycling to the cell surface after endocytosis. We identify here the viral glycoprotein B (gB) as the predominant CD1d-interacting protein. gB initiates the interaction with CD1d in the endoplasmic reticulum and stably associates with it throughout CD1d trafficking. However, an additional HSV-1 component, the serine-threonine kinase US3, is required for optimal CD1d downregulation. US3 expression in infected cells leads to gB enrichment in the trans-Golgi network (TGN) and enhances the relocalization of both gB and CD1d to this compartment, suggesting that following internalization CD1d is translocated from the endocytic pathway to the TGN by its association with gB. Importantly, both US3 and gB are required for efficient inhibition of CD1d antigen presentation and NKT cell activation. In summary, our results suggest that HSV-1 uses gB and US3 to rapidly inhibit NKT cell function in the initial antiviral response.     

The interferon-inducible gene viperin restricts West Nile virus pathogenesis

Type I interferon (IFN) signaling coordinates an early antiviral program in infected and uninfected cells by inducing IFN-stimulated genes (ISGs) that modulate viral entry, replication, and assembly. However, the specific antiviral functions in vivo of most ISGs remain unknown. Here, we examined the contribution of the ISG viperin to the control of West Nile virus (WNV) in genetically deficient cells and mice. While modest increases in levels of WNV replication were observed for primary viperin(-/-) macrophages and dendritic cells, no appreciable differences were detected in deficient embryonic cortical neurons or fibroblasts. In comparison, viperin(-/-) adult mice infected with WNV via the subcutaneous or intracranial route showed increased lethality and/or enhanced viral replication in central nervous system (CNS) tissues. In the CNS, viperin expression was induced in both WNV-infected and adjacent uninfected cells, including activated leukocytes at the site of infection. Our experiments suggest that viperin restricts the infection of WNV in a tissue- and cell-type-specific manner and may be an important ISG for controlling viral infections that cause CNS disease.     

Vigilance and fitness in grey partridges Perdix perdix: the effects of group size and foraging-vigilance trade-offs on predation mortality

1. Vigilance increases fitness by improving predator detection but at the expense of increasing starvation risk. We related variation in vigilance among 122 radio-tagged overwintering grey partridges Perdix perdix (L.) across 20 independent farmland sites in England to predation risk (sparrowhawk Accipiter nisus L., kill rate), use of alternative antipredation behaviours (grouping and use of cover) and survival. 2. Vigilance was significantly higher when individuals fed in smaller groups and in taller vegetation. In the covey period (in early winter when partridges are in flocks), vigilance and use of taller vegetation was significantly higher at sites with higher sparrowhawk predation risk, but tall vegetation was used less by larger groups. Individuals were constrained in reducing individual vigilance by group size and habitat choice because maximum group size was determined by overall density in the area during the covey period and by the formation of pairs at the end of the winter (pair period), when there was also a significant twofold increase in the use of tall cover. 3. Over the whole winter individual survival was higher in larger groups and was lower in the pair period. However, when controlling for group size, mean survival decreased as vigilance increased in the covey period. This result, along with vigilance being higher at sites with increasing with raptor risk, suggests individual vigilance increases arose to reduce short-term predation risk from raptors but led to long-term fitness decreases probably because high individual vigilance increased starvation risk or indicated longer exposure to predation. The effect of raptors on survival was less when there were large groups in open habitats, where individual partridges can probably both detect predators and feed efficiently. 4. Our study suggests that increasing partridge density and modifying habitat to remove the need for high individual vigilance may decrease partridge mortality. It demonstrates the general principle that antipredation behaviours may reduce fitness long-term via their effects on the starvation-predation risk trade-off, even though they decrease predation risk short-term, and that it may be ecological constraints, such as poor habitat (that lead to an antipredation behaviour compromising foraging), that cause mortality, rather than the proximate effect of an antipredation behaviour such as vigilance.     

Poleward bound: adapting to climate-driven species redistribution

Reviews in Fish Biology and Fisheries - One of the most pronounced effects of climate change on the world’s oceans is the (generally) poleward movement of species and fishery stocks in...     

Oncogenic comparison of human papillomavirus type 58 E7 variants

Human papillomavirus 58 (HPV58) ranks the second or third in East Asian cervical cancers. Current studies on HPV58 are scarce and focus on the prototype. Previously, we identified the three most common circulating HPV58 E7 strains contained amino acid alterations: G41R/G63D (51%), T20I/G63S (22%) and T74A/D76E (14%) respectively. Among them, the T20I/G63S variant (V1) had a stronger epidemiological association with cervical cancer. We therefore suggested that V1 possessed stronger oncogenicity than the other two variants. Here, we performed phenotypic assays to characterize and compare their oncogenicities with HPV58 E7 prototype. Our results showed that overexpression of V1 conferred a higher colony‐forming ability to primary murine epithelial cells than prototype (P < 0.05) and other variants, implicating its higher immortalising potential. Further experiments showed that both V1 and prototype enhanced the anchorage‐independent growth of NIH/3T3 cells (P < 0.001), implicating their stronger transforming power than the two other variants. Moreover, they possessed an increased ability to degrade pRb (P < 0.001), which is a major effector pathway of E7‐driven oncogenesis. Our work represents the first study to compare the oncogenicities of HPV58 E7 prototype and variants. These findings deepened our understanding of HPV58 and might inform clinical screening and follow‐up strategy.