What does a primary care annual review for RA include? A national GP survey

Letter to the edito

Residual erythropoiesis protects against myocardial hemosiderosis in transfusion-dependent thalassemia by lowering labile plasma iron via transient generation of apotransferrin

Cardiosiderosis is a leading cause of mortality in transfusion-dependent thalassemias. Plasma non-transferrin-bound iron and its redox-active component, labile plasma iron, are key sources of iron loading in cardiosiderosis. Risk factors were identified in 73 patients with or without cardiosiderosis. Soluble transferrin receptor-1 levels were significantly lower in patients with cardiosiderosis (odds ratio 21). This risk increased when transfusion-iron loading rates exceeded the erythroid transferrin uptake rate (derived from soluble transferrin receptor-1) by >0.21mg/kg/d (odds ratio 48). Labile plasma iron was >3-fold higher where this uptake rate threshold was exceeded, but non-transferrin-bound iron and transferrin saturation were comparable. Cardiosiderosis risk was also decreased in patients with low liver iron, ferritin and labile plasma iron, or high bilirubin, reticulocyte counts or hepcidin. We hypothesized that high erythroid transferrin uptake rate decreases cardiosiderosis through increased erythroid re-generation of apotransferrin. To test this, iron uptake and intracellular reactive oxygen species were examined in HL-1 cardiomyocytes under conditions modelling transferrin effects on non-transferrin-bound iron speciation with ferric citrate. Intracellular iron and reactive oxygen species increased with ferric citrate concentrations especially where iron-to-citrate ratios exceeded 1:100, i.e. conditions favoring kinetically labile monoferric rather than oligomer species. Excess iron-binding equivalents of apotransferrin inhibited iron uptake, decreased intracellular reactive oxygen species and labile plasma iron, under conditions favoring monoferric species. In conclusion, high transferrin iron utilisation, relative to the transfusion-iron load rate, decreases the cardiosiderotic risk. A putative mechanism is the transient re-generation of apotransferrin by an active erythron, rapidly binding labile plasma iron-detectable ferric monocitrate species

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

“You’re Not the Police. You’re Providing a Library Service”: Reflections on Maintenance and Repair in/of Public Libraries During the COVID-19 Pandemic

This paper explores how services gaps between public libraries, governmental authorities, and other institutions were addressed during the COVID-19 pandemic and how the labor of filling these gaps reveals the repair and maintenance work in and on the public good of the library. The site for this exploration is the project Australian Public Libraries During the COVID-19 Crisis: Implications for Future Policy and Practice, which used mixed-methods questionnaires and interviews to understand the library and information science (LIS) profession’s response to the pandemic. During the pandemic, public institutions labored to maintain services and repair any gaps arising from disrupted services. The extraordinary labor instigated by the pandemic can be used to theorize the ordinary labor of maintaining public institutions such as libraries and how notions of the public good are reaffirmed through individual and institutional acts of care. The maintenance and repair of public libraries as institutions with community service obligations reveals assumptions about essential services, which communities are disadvantaged, and the policing role of libraries. Understanding the repair role of libraries helps researchers and practitioners to theorize and conceptualize their work and service to the community in new ways

Correction to: The association between anxiety and disease activity and quality of life in rheumatoid arthritis: a systematic review and meta-analysis.

The authors of the published original version of the above article wanted to correct the below text in the Abstract section

Incorporation by coordination and release of the iron chelator drug deferiprone from zinc-based metal–organic frameworks

A series of new zinc-based metal–organic framework materials has been prepared in which deferiprone is incorporated as a chelating ligand on infinite or tri-zinc secondary building units following deprotonation. Deferiprone is immediately released from the MOFs on treatments with 1 N hydrochloric acid or buffer, but slow release is observed in ethanoic acid

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe