Background:
Oral anticoagulation therapy is the treatment of choice to prevent stroke in patients with non valvular atrial fibrillation. Non‐vitamin K antagonist oral anticoagulants (NOACs) are often ...used as alternative to vitamin K antagonists as they do not require INR level monitoring. Before initiating the anticoagulant therapy the risk of stroke should be evaluated using the CHA2DS2‐VASc score and the bleeding risk using the HAS‐BLED score. In our institution the most used NOACs are Apixaban and Rivaroxaban. The recommended dose for Apixaban is 5 mg bd, reduced to 2.5 mg twice bd in patients with age >80, weight < 61 kg or serum creatinine > 133 micromol/litre. The recommended dose for Rivaroxaban is 20 mg od.
Aims:
The aim of this study was to understand the appropriateness of NOACs use in our institution in terms of indication and dose compared to the national guidelines.
Methods:
We performed an audit including all new patients who attended our anticoagulation service in a period of six months and were started on either Apixaban or Rivaroxaban. To do this we evaluated if the indication for anticoagulation was appropriate, if CHA2DS2‐VASc score HAS‐BLED score were documented on the notes. We also evaluated the appropriateness of the dose adjusted for creatinine of Apixaban.
Results:
We included 57 patients, 29 of them were started on Apixaban and 28 on Rivaroxaban. All of the patients had a diagnosis of Non Valvular Atrial Fibrillation. CHA2DS2‐VASc score was documented in 31 patients (54%) and HAS‐BLED score in 32 patients (56%), only 22 patients (38%) had both score properly documented. Out of 31 patients 4 (13%) had a CHA2DS2‐VASc score of 0, and out of 32 patients 2 (6%) had a HAS‐BLED score >3. This mean that in 19% of the patients the anticoagulation therapy was not indicated or contraindicated, but also that in 62% of the patients the appropriateness could not be properly evaluated. Creatinine was documented only in 11 of the patients on Apixaban (38%), in all of them the dose was appropriate for renal function.
Summary/Conclusion:
We included 57 patients, 29 of them were started on Apixaban and 28 on Rivaroxaban. All of the patients had a diagnosis of Non Valvular Atrial Fibrillation. CHA2DS2‐VASc score was documented in 31 patients (54%) and HAS‐BLED score in 32 patients (56%), only 22 patients (38%) had both score properly documented. Out of 31 patients 4 (13%) had a CHA2DS2‐VASc score of 0, and out of 32 patients 2 (6%) had a HAS‐BLED score >3. This mean that in 19% of the patients the anticoagulation therapy was not indicated or contraindicated, but also that in 62% of the patients the appropriateness could not be properly evaluated. Creatinine was documented only in 11 of the patients on Apixaban (38%), in all of them the dose was appropriate for renal function.
Background:
Iron deficiency anaemia is the most common cause of anaemia. Parenteral iron therapy in the UK has to be administered in hospital settings as it comes with risk of allergic reactions and ...anaphylaxis. Clear procedures should be established in each hospital to ensure that parenteral iron therapy is prescribed according to the national guidelines ans audited regularly.
Aims:
The aim of this audit was to estabilish if if the diagnosis of iron deficiency was performed according to the guidelines and if patients were adequately monitored after receiving parenteral iron.
Methods:
Pharmacy provided the list of IV iron prescriptions issued in a period of 12 months. A clinical audit was performed to understand if patients had a documented diagnosis of iron deficiency (low haemoglobin, low ferritin or low transferrin saturation according to the local laboratory ranges); if there was a follow up blood test including the same parameters and if patients who were still iron deficient were prescribed further iron.
Results:
A total of 233 prescription for 227 patients were analysed. Of those 99% had a blood test previous to the iron infusion (99% had full blood count, 94% had ferritin level, 63% had transferrin saturation). Only 80% of patients had confirmed iron deficiency, in 2 % of the patients there was no iron deficiency and in 1 patient there were laboratory signs of iron overload, in the remaining 18% iron status was incomplete as transferrin saturation was not performed.
Follow up was missing in 16% of the cases, in 66% of the patients was done between 2 weeks and three monts, in 20% of the cases after that. All the patients had full blood count, only two thirds had ferritin level done and less than a quarter had transferrin level done. Thirty nine patients (17% o) were found to be still iron deficient but only a fifth of them received further iron therapy. Only 10% had normal iron studies, in the remaining cases iron status was not evaluable.
Summary/Conclusion:
Several issues were identified that will require improvement. First of all we found that some of the prescriptions were unnecessary (2%) or controindicated (0.5%). In a fifth of the cases as iron studies were incomplete, was not possible to establish of the therapy given was appropriate. The main problem was lack of follow up or follow up with incomplete iron studies that made impossible to interpret the iron status in tre quarter of the patients, and missed iron therapy in five out of six patient with documented iron deficiency. Resolving these problem, as they are not isolated to a single department, will be a challenge. Solutions should be found to ensure that there are no inappropriate parenteral iron prescriptions and that patients are monitored adequately and given further therapy when required. Establishing an iron deficiency service to monitor patients could be one of these solutions, but it will require major institution re‐organisation.
Summary Background People with type 2 diabetes are at risk of cognitive impairment and brain atrophy. We aimed to compare the effects on cognitive function and brain volume of intensive versus ...standard glycaemic control. Methods The Memory in Diabetes (MIND) study was done in 52 clinical sites in North America as part of Action to Control Cardiovascular Risk in Diabetes (ACCORD), a double two-by-two factorial parallel group randomised trial. Participants (aged 55–80 years) with type 2 diabetes, high glycated haemoglobin A1c (HbA1c ) concentrations (>7·5%; >58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive glycaemic control targeting HbA1c to less than 6·0% (42 mmol/mol) or a standard strategy targeting HbA1c to 7·0–7·9% (53–63 mmol/mol). Randomisation was via a centralised web-based system and treatment allocation was not masked from clinic staff or participants. We assessed our cognitive primary outcome, the Digit Symbol Substitution Test (DSST) score, at baseline and at 20 and 40 months. We assessed total brain volume (TBV), our primary brain structure outcome, with MRI at baseline and 40 months in a subset of participants. We included all participants with follow-up data in our primary analyses. In February, 2008, raised mortality risk led to the end of the intensive treatment and transition of those participants to standard treatment. We tested our cognitive function hypotheses with a mixed-effects model that incorporated information from both the 20 and 40 month outcome measures. We tested our MRI hypotheses with an ANCOVA model that included intracranial volume and factors used to stratify randomisation. This study is registered with ClinicalTrials.gov , number NCT00182910. Findings We consecutively enrolled 2977 patients (mean age 62·5 years; SD 5·8) who had been randomly assigned to treatment groups in the ACCORD study. Our primary cognitive analysis was of patients with a 20-month or 40-month DSST score: 1378 assigned to receive intensive treatment and 1416 assigned to receive standard treatment. Of the 614 patients with a baseline MRI, we included 230 assigned to receive intensive treatment and 273 assigned to receive standard treatment in our primary MRI analysis at 40 months. There was no significant treatment difference in mean 40-month DSST score (difference in mean 0·32, 95% CI −0·28 to 0·91; p=0·2997). The intensive-treatment group had a greater mean TBV than the standard-treatment group (4·62, 2·0 to 7·3; p=0·0007). Interpretation Although significant differences in TBV favoured the intensive treatment, cognitive outcomes were not different. Combined with the non-significant effects on other ACCORD outcomes, and increased mortality in participants in the intensive treatment group, our findings do not support the use of intensive therapy to reduce the adverse effects of diabetes on the brain in patients with similar characteristics to those of our participants. Funding US National Institute on Aging and US National Heart, Lung, and Blood Institute.
Background:
Errors in administering blood product represent a risk for patient safety. The British Society of Haematology (BSH) published guidelines to promote safe transfusion practice (1). These ...guidelines states that should be recorded: the unique component donation number and the date, start time and the identification of the person administering the component.The guideline also sets the standard for monitoring the patient during the transfusion with pulse, temperature, respiratory rate and blood pressure at the start of the transfusion, after 15 minutes of the start and within one hour from the end.
Transfusion training is mandatory for all health professionals involved in transfusion practice.
Aims:
The aim of this study was to establish if the guidelines established by BSH are applied in clinical practice across different departments.
Methods:
We performed a retrospective audit on transfusion documentation and patient monitoring and in a district general hospital. We included transfusion of red packed cells, platelets and fresh frozen plasma.
Results:
We identified 160 unit transfused (132 RPC, 16 PLTS and 12 FFP). Documentation of donation number and the date, start time and the identification of the person administering the component were complete in 88% of the cases, in 8% of the cases there was no documentation at all (Figure 1A); of the remaining in 80% of the cases was missing the signature of the administering person.
Regarding the monitoring of the patient only 25% of the unit transfusions were monitored according to the guidelines, in 33% of the cases there was no documentation of the patient monitoring. The least monitored parameter was respiratory rate; the most frequent missed monitoring point was the one at the end of the transfusion (Figure 1B).
Summary/Conclusion:
Despite clear guidelines and compulsory training transfusion practice is still poor with more than a tenth of the transfusion being not fully documented in the notes and the number of transfusion episodes lacking adequate patient monitoring information outnumbering the transfusion monitored according to the guidelines (33% vs 25%).
Performing an audit across the entire hospital allowed us to identify the departments where transfusion procedures were not applied systematically with the plan to offer target training and re‐audit to improve transfusion practice.
Substance P has been implicated as a mediator of inflammation. The involvement of this neuropeptide in carrageenan-induced hind paw edema in the rat was assessed. Subcutaneous injection of ...carrageenan into the rat paw caused a significant increase in substance P levels, which preceded the onset of inflammation. While injection of substance P alone caused mild edema, coadministration of submaximal doses of carrageenan and substance P resulted in a synergistic exacerbation in the degree of inflammation. This synergistic response was not detected when the nonamidated precursor of substance P was coinjected with carrageenan. The effects of substance P depletion on inflammation were also evaluated. In animals pretreated with capsaicin followed by injection with carrageenan, no significant increase in either the levels of substance P or the extent of edema was observed when compared to capsaicin-treated controls. These results indicate that substance P may play an important role in the early stages of carrageenan-induced paw edema and that a reduction in the biosynthesis of substance P may lessen the severity of this inflammatory response.
A rapid and sensitive method for the determination of peptidyl alpha-amidation activity has been developed and is based on reverse-phase high-performance liquid chromatographic separation and ...fluorometric detection. A dansylated tripeptide, N-dansyl-Tyr-Val-Gly-OH, is used as the substrate in the assay and the amount of alpha-amidation activity is determined by quantitating the extent of its conversion to product, N-dansyl-Tyr-Val-NH2. Both product and substrate can be detected in a single assay in quantities as low as 5 fmol by isocratic elution using C-18 reverse-phase columns. The method yields highly reproducible results and requires less than 3 min per sample for separation and quantitation. The assay procedure is applicable to the screening of a large number of samples under different pH conditions and is readily adaptable for use in a variety of studies. For example, the procedure is ideal for detecting alpha-amidation activity in various tissues, monitoring activity at the different stages during purification of a particular alpha-amidation enzyme, determining kinetic parameters of the purified enzyme, and identifying both competitive and noncompetitive inhibitors.
Conditioned medium from cultures of rat medullary thyroid carcinoma CA-77 cells was used as a source for purification of the secreted forms of peptidyl alpha-amidating enzyme. The alpha-amidating ...enzyme activity was partially purified using a combination of weak anion exchange and gel filtration chromatography. Subsequent strong anion exchange chromatography at pH 6.0 resolved this partially pure enzyme into four distinct peaks of activity, termed Ia, Ib, II, and III. Peaks Ia and Ib exhibited broad pH optima between pH 6.0-8.5, whereas peaks II and III both exhibited pH optima at approximately pH 5.0. The peak III activity was further purified to electrophoretic homogeneity using hydrophobic interactive chromatography followed by strong anion exchange chromatography at pH 8.0. The enzyme exhibited an apparent molecular mass of 75K, a pH optimum of approximately pH 5.0, and a maximal turnover number of 580 min-1 in the presence of L-ascorbate. Kinetic studies demonstrated that the enzyme probably functions through a ping-pong mechanism with respect to the binding of the glycine-extended peptide substrate and the L-ascorbate cofactor. The peak III enzyme exhibits several distinctive characteristics compared to amidating enzymes isolated and characterized by other laboratories.
A peptidyl alpha-amidating enzyme has been partially purified from conditioned medium derived from cultured medullary thyroid CA-77 cells. The interactions of this enzyme with a series of ...tripeptides, pentapeptides, and mature glycine-extended prohormones has now been studied using a competition assay that features the enzymatic alpha-amidation of N-dansyl-Tyr-Val-Gly. While a peptide C-terminal glycine was obligatory for tight binding to the alpha-amidating enzyme, other peptide structural elements modulated the interaction. Thus, a greater than 1300-fold range in apparent inhibitor constants was observed by substitution at the -1 (penultimate) position in a C-terminal glycine-containing tripeptide with each of the 20 common L-amino acids. Peptide inhibitory potency decreased through the following amino acid groupings: sulfur containing greater than aromatic greater than or equal to histidine greater than nonpolar greater than polar greater than glycine greater than charged. This pattern was qualitatively dissimilar to that observed for a more limited series of substitutions at the -2 position, demonstrating the positional selectivity of these structural requirements. The structure-activity relationships observed with the tripeptides at the -1 position were consistent with the apparent inhibitor constants obtained for a collection of prohormones and their pentapeptide mimics. Finally, selected prohormones and their pentapeptide mimics were equipotent inhibitors, demonstrating that the peptide structural elements important for alpha-amidating enzyme recognition are located entirely within the C-terminal pentapeptide segment.
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