Improving the timeliness of meticillin-resistant Staphylococcus aureus antimicrobial decolonization therapy administration : a descriptive account

SummaryBackgroundIt is important to ensure that the timely administration of appropriate antimicrobial decolonization therapy occurs when patients are identified as meticillin-resistant Staphylococcus aureus (MRSA)-colonized. Computerized Provider Order Entry (CPOE) with embedded Clinical Decision Support (CDS) may help to facilitate this.AimTo investigate changes in the average time from patient admission to administration of MRSA decolonization antimicrobial therapy in the context of various national and local infection control interventions, including the use of CPOE.MethodsData concerning the time of admission and of administration of patients' first MRSA decolonization antimicrobials were extracted from a locally developed CPOE system (Prescribing Investigation and Communications System: PICS) which was introduced at a large university teaching hospital in the UK in 1998. Data were extracted retrospectively from January 2006 to March 2012.FindingsA variety of relevant local and national interventions occurred from 2006 to 2012. Notably, the automatic charting of MRSA decolonization antimicrobial therapy was introduced in December 2007. There was a significant decline of 15.0% per year (95% confidence interval: 11.1–18.7%; P < 0.001) in the time taken from admission to administration of MRSA decolonization antimicrobial therapy during the study period.ConclusionsNumerous factors may have contributed to the observed reductions in the time from admission to administration of MRSA decolonization antimicrobials, including the implementation of specific features within a CPOE system. By rapidly attending to positive MRSA colonizations there is decreased potential for MRSA to spread, which may help to reduce the prevalence of MRSA colonizations within hospitals and improve patient outcomes

Investigating risk factors associated with hyponatremia in hospitalised patients using an electronic prescribing system with health records

Hyponatraemia, defined as a serum sodium concentration of <135mmol/l, is the most commonly encountered electrolyte disturbance in hospital patients. Various studies have shown that hyponatraemia occurs in up to 30% of hospitalised patients. Hyponatraemia has been associated with older age, low body weight, chronic diseases and diuretic therapy to name but a few. This study set out to identify risk factors for hyponatraemia in a large dataset of patients in a UK teaching hospital and to ascertain patient outcomes. Methodology A retrospective case-control study design was used to explore risk factors associated with hyponatraemia. Hospital episode data were extracted from an electronic prescribing system with health records used in an English teaching hospital. We used serum sodium levels measured in adult patients admitted over a one year period (2010-2011) to group patients. A patient was classed as hyponatraemic if their lowest serum sodium result during their in-patient spell was <135mmol/l and classed as non- hyponatraemic if serum sodium was ?135mmol/l (controls). Statistical tests for categorical and non-parametric data were used to examine the null hypothesis that there was no difference in risk factors and outcomes between hyponatraemic and non-hyponatraemic patients. A multivariate logistic regression model of risk factors associated with hyponatraemia was fitted. Results Data from 22,306 patients were analysed and 19% were classified as hyponatraemic during their in-patient spell. The risk of hyponatraemia was greater with increasing age - especially in those aged 60-69 (adjusted OR 2.2; 95% C.I. 1.6-2.9; p<0.001). The risk of hyponatraemia was also found to be greater for patients who were underweight (unadjusted OR 1.4; 1.1-1.7; p<0.001). Patients with Stage 5 renal failure were found to have a three-fold increased risk of hyponatraemia compared to those with less severe renal failure (adjusted OR 2.5; 1.9-3.2; p<0.001). Those patients with a higher Charlson Comorbidity Index (?13) were more likely to have hyponatraemia (adjusted OR 1.3; 1.1-1.6; p<0.05). More hyponatraemic patients were prescribed diuretics compared to non-hyponatraemic patients (thiazides 10.4% vs. 5.1%, loop 6.9% vs. 4.9% and potassium sparing 1.9% vs. 1%, all p<0.001), when entered into the multivariate logistic regression model, thiazide diuretic administration was associated with an increased risk of developing hyponatraemia (adjusted OR 1.7; 95% C.I. 1.3-2.1; p<0.001). Patients who were on NSAIDs and SSRIs were less likely to have hyponatraemia (adjusted OR 0.5; 95% 0.3-0.6 and adjusted OR 0.2; 0.1-0.8; p<0.05 respectively). Increasing severity of hyponatraemia was found to have a higher incidence of all-cause mortality (20% vs. 3%, p<0.001). Conclusions This study demonstrated that approximately 1 in 5 patients experienced hyponatraemia during their admission in this hospital and were more likely to have poorer outcomes than non-hyponatraemics. We concluded that this is a relatively convenient form of data extraction and the results can be used to better understand the risk factors associated with hyponatraemia. Some associations, such as diuretics, have a direct causal relationship and in some cases hyponatraemia may be a marker of increasing comorbidity. The next steps would be to use these results (incorporating them into algorithms) to alert health care professionals and guide them whilst they use electronic prescribing systems, thereby ensuring that patients receive the most appropriate care and management whilst in hospital

Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway

Monoubiquitination and deubiquitination of FANCD2:FANCI heterodimer is central to DNA repair in a pathway that is defective in the cancer predisposition syndrome Fanconi anemia (FA). The \u201cFA core complex\u201d contains the RING-E3 ligase FANCL and seven other essential proteins that are mutated in various FA subtypes. Here, we purified recombinant FA core complex to reveal the function of these other proteins. The complex contains two spatially separate FANCL molecules that are dimerized by FANCB and FAAP100. FANCC and FANCE act as substrate\ua0receptors and restrict monoubiquitination to the FANCD2:FANCI heterodimer in only a DNA-bound form. FANCA and FANCG are dispensable for maximal in\ua0vitro ubiquitination. Finally, we show that the reversal of this reaction by the USP1:UAF1 deubiquitinase only occurs when DNA is disengaged. Our work reveals the mechanistic basis for\ua0temporal and spatial control of FANCD2:FANCI monoubiquitination that is critical for chemotherapy responses and prevention of Fanconi anemia