Assessing the quality of primary care referrals to surgery of patients with diabetes in the East of England: A multi-centre cross-sectional cohort study

Aim: Peri-operative hyperglycaemia is associated with an increased incidence of adverse outcomes. Communication between primary and secondary care is paramount to minimise these harms. National guidance in the UK recommends that the glycated haemoglobin (HbA1c) should be measured within 3 months prior to surgery and that the concentration should be less that 69 mmol/mol (8.5%). In addition, national guidance outlines the minimum dataset that should be included in any letter at the time of referral to the surgeons. Currently, it is unclear how well this process is being carried out. This study investigated the quality of information being handed over during the referral from primary care to surgical outpatients within the East of England. Methods: Primary care referrals to nine different NHS hospital Trusts were gathered over a 1-week period. All age groups were included from 11 different surgical specialties. Referral letters were analysed using a standardised data collection tool based on the national guidelines. Results: A total of 1919 referrals were received, of whom 169 (8.8%) had previously diagnosed diabetes mellitus (DM). However, of these, 38 made no mention of DM in the referral letter but were on glucose-lowering agents. Only 13 (7.7%) referrals for patients with DM contained a recent HbA1c, and 20 (11.8%) contained no documentation of glucose-lowering medication. Conclusion: This study has shown that the quality of referral letters to surgical specialties for patients with DM in the East of England remain inadequate. There is a clear need for improving the quality of clinical data contained within referral letters from primary care. In addition, we have shown that the rate of referral for surgery for people with diabetes is almost 50% higher than the background population with diabetes

Pre-operative cardiopulmonary exercise testing and oesophageal doppler guided fluid therapy in elective colorectal surgery

Recent advances in peri-operative care and surgical technique have influenced the short-term outcomes for patients undergoing elective major colorectal surgery. Intraoperative Goal Directed fluid Therapy (GDT) has been shown to reduce length of stay and decrease morbidity in elective colorectal resections. Pre-operative Cardiopulmonary Exercise testing (CPET) characterises baseline aerobic fitness and may identify 'high-risk' patients more likely to benefit from GDT. COMPETE-C was a randomised, single-centre trial comparing the effect of oesophageal Doppler guided GDT against standard care in patients stratified by CPET as Unfit (AT 8.0-10.9 mI02/kg/min) or Fit (AT >11.0 mI02/kg/min). There was no observed benefit to administration of GDT, and it was associated with prolonged length of stay in patients classified as aerobically fit (8.8 vs. 6.0 days; p=0.06). PicoPEX was a pilot study to evaluate the effect of mechanical bowel preparation and carbohydrate-loading on aerobic fitness as measured by CPET in healthy volunteers. Neither intervention significantly worsened aerobic fitness but their clinical significance on patients undergoing major colorectal surgery was not addressed. A retrospective analysis of patients who underwent elective colorectal surgery during the study period revealed that decreased aerobic fitness was associated with prolonged total postoperative stay, particularly amongst "Very Unfit" patients with AT <8 mI02/kg/min and those undergoing rectal resections. Inability to pe arm a CPET was associated with significantly worse short- and medium- term mortality compared to those who completed the test. Concerns exist regarding the robustness of the evidence from GOT studies due to heterogeneity in the trial design and as the initial clinical benefits observed may have been offset by advances in surgical techniques and peri-operative care, and the type of resection performed. A meta-analysis was conducted to address whether Doppler guided GOT influenced total postoperative stay and complications rates when stratified according to type of resection performed. GOT did not improve outcome in terms of length stay but there was a reduction in complications suffered by those undergoing rectal surgery (p=O.04). Our results highlight the need for a large multi-centre study into the role of GOT with patients stratified according to aerobic fitness, surgical technique and planned resection.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Experimental and Numerical Investigation of Partial Admission of a Radial Turbocharger Turbine for Improved Off-Design Operation

A new partial admission concept for turbocharger turbine operation at off-design is designed and investigated numerically and experimentally in a turbocharger test rig. This new concept is called MEDUSA (Multiple Exhaust Duct with Source Adjustment) and is based on a partial admission turbine system consisting of several separate flow channels that connect the cylinder of the engine and individual nozzle segments of the turbine. The turbine flow is adjusted by the chosen admission rate according to the available exhaust enthalpy. In the present study, a reference turbocharger has been equipped with a four segment partial admission system instead of its conventional Waste-Gate scroll. The numerical results indicate similar loss mechanisms compared to an axial turbine stage, when partial admission is applied. Based on a stator design optimization, a design was chosen for manufacturing and testing on the turbocharger test rig. Despite the fact that the turbocharger efficiency at partial admission for the MEDUSA-system drops, a higher turbine expansion ratio can be achieved to obtain the same compressor operating point. These results indicate an enhanced use of the available exhaust enthalpy at part-load conditions, thus improving the turbocharger performance at low end torque engine speeds.</jats:p

Cysteine Methylation Controls Radical Generation in the Cfr Radical AdoMet rRNA Methyltransferase

The 'radical S-adenosyl-L-methionine (AdoMet)' enzyme Cfr methylates adenosine 2503 of the 23S rRNA in the peptidyltransferase centre (P-site) of the bacterial ribosome. This modification protects host bacteria, notably methicillin-resistant Staphylococcus aureus (MRSA), from numerous antibiotics, including agents (e.g. linezolid, retapamulin) that were developed to treat such organisms. Cfr contains a single [4Fe-4S] cluster that binds two separate molecules of AdoMet during the reaction cycle. These are used sequentially to first methylate a cysteine residue, Cys338; and subsequently generate an oxidative radical intermediate that facilitates methyl transfer to the unreactive C8 (and/or C2) carbon centres of adenosine 2503. How the Cfr active site, with its single [4Fe-4S] cluster, catalyses these two distinct activities that each utilise AdoMet as a substrate remains to be established. Here, we use absorbance and electron paramagnetic resonance (EPR) spectroscopy to investigate the interactions of AdoMet with the [4Fe-4S] clusters of wild-type Cfr and a Cys338 Ala mutant, which is unable to accept a methyl group. Cfr binds AdoMet with high (∼ 10 µM) affinity notwithstanding the absence of the RNA cosubstrate. In wild-type Cfr, where Cys338 is methylated, AdoMet binding leads to rapid oxidation of the [4Fe-4S] cluster and production of 5'-deoxyadenosine (DOA). In contrast, while Cys338 Ala Cfr binds AdoMet with equivalent affinity, oxidation of the [4Fe-4S] cluster is not observed. Our results indicate that the presence of a methyl group on Cfr Cys338 is a key determinant of the activity of the enzyme towards AdoMet, thus enabling a single active site to support two distinct modes of AdoMet cleavage

g-Values for EPR Spectra of Cfr and Ligand Complexes.

<p>g-Values for EPR Spectra of Cfr and Ligand Complexes.</p

EPR Spectra of the Cfr [4Fe-4S] cluster.

<p>Cw-EPR spectra of wild-type Cfr (left hand column) and Cfr Cys338 Ala (right hand column). Experimental spectra are shown as black lines with corresponding simulations beneath (blue lines). A. Wild-type Cfr (105 µM) B. Wild-type Cfr (105 µM) plus AdoMet (300 µM). C. Wild-type Cfr plus AdoHcy (300 µM). D. Cfr Cys338 Ala (105 µM). E. Cfr Cys338 Ala plus AdoMet (300 µM). F. Cfr Cys338 Ala plus AdoHcy (300 µM). Note that all samples were reduced with sodium dithionite (1 mM).</p