Excessive polypharmacy and potentially inappropriate prescribing in 147 care homes: a cross-sectional study.

BACKGROUND: Care home residents often have multiple cognitive and physical impairments, and are at high risk of adverse drug events (ADEs). AIM: To describe excessive polypharmacy and potentially inappropriate prescribing predisposing care home residents to ADEs. DESIGN & SETTING: A cross-sectional analysis of all dispensed prescriptions for 147 care home residents in Tayside and Fife, Scotland. METHOD: Prevalence of excessive polypharmacy was examined using multilevel logistic regression, by modelling associations between individual and care home predictors with excessive polypharmacy (≥10 drugs). Prescribing of drugs known to increase the risk of eight clinically important ADE categories was examined. Drugs prescribed within each ADE category, for each resident, were counted. RESULTS: In total, 32.3% (n = 1444/4468) of residents had excessive polypharmacy, which was more common in residents aged 70-74 years (adjusted odds ratio [aOR] 1.86, 95% confidence interval [CI] = 1.04 to 3.34) and 80-84 years (aOR 1.75, 95% CI = 1.01 to 3.02), living in a residential care home (aOR 1.50, 95% CI = 1.19 to 1.88), and located in Fife (aOR 1.37, 95% CI = 1.09 to 1.71). Excessive polypharmacy was less common in residents with dementia (aOR 0.73, 95% CI = 0.64 to 0.84), and 8.9% (95% CI = 5.9% to 11.6%) of the variation was attributable to care home predictors. Potentially inappropriate prescribing of ≥2 drugs was seen across all ADE categories, with highest prevalence seen in drugs predisposing to constipation (35.8%), sedation (27.7%), and renal injury (18.0%). CONCLUSION: Excessive polypharmacy is common in care home residents and is associated with both individual and care home predictors. Potentially inappropriate prescribing of drugs that predisposed residents to all included ADE categories is common. Research is needed to support and evaluate safe care home prescribing practices.

Effects of peri-operative nonsteroidal anti-inflammatory drugs on post-operative kidney function for adults with normal kidney function.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) provide effective analgesia during the post-operative period but can cause acute kidney injury (AKI) when used peri-operatively (at or around the time of surgery). This is an update of a Cochrane review published in 2007. OBJECTIVES: This review looked at the effect of NSAIDs used in the peri-operative period on post-operative kidney function in patients with normal kidney function. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 4 January 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at the use of NSAIDs versus placebo for the treatment of post-operative pain in patients with normal kidney function were included. DATA COLLECTION AND ANALYSIS: Data extraction was carried out independently by two authors as was assessment of risk of bias. Disagreements were resolved by a third author. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI). Meta-analyses were used to assess the outcomes of AKI, change in serum creatinine (SCr), urine output, renal replacement therapy (RRT), death (all causes) and length of hospital stay. MAIN RESULTS: We identified 26 studies (8835 participants). Risk of bias was high in 17, unclear in 6and low in three studies. There was high risk of attrition bias in six studies.Only two studies measured AKI. The use of NSAIDs had uncertain effects on the incidence of AKI compared to placebo (7066 participants: RR 1.79, 95% CI 0.40 to 7.96; I2 = 59%; very low certainty evidence). One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group. Moreover, both of these studies were examining NSAIDs for indications other than analgesia and therefore utilised relatively low doses.Compared to placebo, NSAIDs may slightly increase serum SCr (15 studies, 794 participants: MD 3.23 µmol/L, 95% CI -0.80 to 7.26; I2 = 63%; low certainty evidence). Studies displayed moderate to high heterogeneity and had multiple exclusion criteria including age and so were not representative of patients undergoing surgery. Three of these studies excluded patients if their creatinine rose post-operatively.NSAIDs may make little or no difference to post-operative urine output compared to placebo (6 studies, 149 participants: SMD -0.02, 95% CI -0.31 to 0.27). No reliable conclusions could be drawn from these studies due to the differing units of measurements and measurement time points.It is uncertain whether NSAIDs leads to the need for RRT because the certainty of this evidence is very low (2 studies, 7056 participants: RR 1.57, 95% CI 0.49 to 5.07; I2 = 26%); there were few events and the results were inconsistent.It is uncertain whether NSAIDs lead to more deaths (2 studies, 312 participants: RR 1.44, 95% CI 0.19 to 11.12; I2 = 38%) or increased the length of hospital stay (3 studies, 410 participants: MD 0.12 days, 95% CI -0.48 to 0.72; I2 = 24%). AUTHORS' CONCLUSIONS: Overall NSAIDs had uncertain effects on the risk of post-operative AKI, may slightly increase post-operative SCr, and it is uncertain whether NSAIDs lead to the need for RRT, death or increases the length of hospital stay. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further larger studies using the Kidney Disease Improving Global Outcomes definition for AKI including patients with co-morbidities are required to confirm these findings. .

Impact of antimicrobial stewardship interventions on Clostridium difficile infection and clinical outcomes: segmented regression analyses.

Background: Antimicrobial exposure is associated with increased risk of Clostridium difficile infection (CDI), but the impact of prescribing interventions on CDI and other outcomes is less clear. Objectives: To evaluate the effect of an antimicrobial stewardship intervention targeting high-risk antimicrobials (HRA), implemented in October 2008, and to compare the findings with similar studies from a systematic review. Methods: All patients admitted to Medicine and Surgery in Ninewells Hospital from October 2006 to September 2010 were included. Intervention effects on HRA use (dispensed DDD), CDI cases and mortality rates, per 1000 admissions per month, were analysed separately in Medicine and Surgery using segmented regression of interrupted time series (ITS) data. Data from comparable published studies were reanalysed using the same method. Results: Six months post-intervention, there were relative reductions in HRA use of 33% (95% CI 11-56) in Medicine and 32% (95% CI 19-46) in Surgery. At 12 months, there was an estimated reduction in CDI of 7.0 cases/1000 admissions [relative change -24% (95% CI - 55 to 6)] in Medicine, but no change in Surgery {estimated 0.1 fewer cases/1000 admissions [-2% (95% CI - 116 to 112)]}. Mortality reduced throughout the study period, unaffected by the intervention. In all six comparable studies, HRA use reduced significantly, but reductions in CDI rates were only statistically significant in two and none measured mortality. Pre-intervention CDI rates and trends influenced the intervention effect. Conclusions: Despite large reductions in HRA prescribing and reductions in CDI, demonstrating real-world impact of stewardship interventions remains challenging.

Building a national Infection Intelligence Platform to improve antimicrobial stewardship and drive better patient outcomes: the Scottish experience.

Background: The better use of new and emerging data streams to understand the epidemiology of infectious disease and to inform and evaluate antimicrobial stewardship improvement programmes is paramount in the global fight against antimicrobial resistance. Objectives: To create a national informatics platform that synergizes the wealth of disjointed, infection-related health data, building an intelligence capability that allows rapid enquiry, generation of new knowledge and feedback to clinicians and policy makers. Methods: A multi-stakeholder community, led by the Scottish Antimicrobial Prescribing Group, secured government funding to deliver a national programme of work centred on three key aspects: (i) technical platform development with record linkage capability across multiple datasets; (ii) a proportionate governance approach to enhance responsiveness; and (iii) generation of new evidence to guide clinical practice. Results: The National Health Service Scotland Infection Intelligence Platform (IIP) is now hosted within the national health data repository to assure resilience and sustainability. New technical solutions include simplified 'data views' of complex, linked datasets and embedded statistical programs to enhance capability. These developments have enabled responsiveness, flexibility and robustness in conducting population-based studies including a focus on intended and unintended effects of antimicrobial stewardship interventions and quantification of infection risk factors and clinical outcomes. Conclusions: We have completed the build and test phase of IIP, overcoming the technical and governance challenges, and produced new capability in infection informatics, generating new evidence for improved clinical practice. This provides a foundation for expansion and opportunity for global collaborations.

Reduction in post-operative acute kidney injury following a change in antibiotic prophylaxis policy for orthopaedic surgery: an observational study.

OBJECTIVES: Evidence has shown that a prophylactic antibiotic regimen of flucloxacillin and gentamicin for orthopaedic surgery was associated with increased rates of post-operative acute kidney injury (AKI). This resulted in changes in the national antibiotic policy recommendation for orthopaedic surgical prophylaxis. This study aimed to assess whether this change from flucloxacillin and gentamicin to co-amoxiclav was associated with changes in the rates of AKI and Clostridium difficile infection (CDI). METHODS: An observational study and interrupted time series analyses were used to assess rates of post-operative AKI separately in patients undergoing neck of femur (NOF) repair and other orthopaedic operations that required antibiotic prophylaxis. Incidence rate ratios were used to evaluate changes in CDI rates. RESULTS: Following the change in policy, from flucloxacillin and gentamicin to co-amoxiclav, there was a relative change in rates of post-operative AKI of -63% (95% CI -77% to -49%) at 18 months in the other orthopaedic operations group. In the NOF repair group, there was no change in the rate of post-operative AKI [-10% (95% CI -35%-15%)] at 18 months. The incident rate ratio for CDI in the other orthopaedic operations group was 0.29 (95% CI 0.09-0.96) and in the NOF repair group was 0.76 (95% CI 0.28-2.08). CONCLUSIONS: The use of co-amoxiclav for antibiotic prophylaxis in orthopaedic surgery was associated with a decreased rate of post-operative AKI compared with flucloxacillin and gentamicin and was not associated with increased rates of CDI.

Risk of postoperative acute kidney injury in patients undergoing orthopaedic surgery--development and validation of a risk score and effect of acute kidney injury on survival: observational cohort study.

STUDY QUESTION: What is the predicted risk of acute kidney injury after orthopaedic surgery and does it affect short term and long term survival? METHODS: The cohort comprised adults resident in the National Health Service Tayside region of Scotland who underwent orthopaedic surgery from 1 January 2005 to 31 December 2011. The model was developed in 6220 patients (two hospitals) and externally validated in 4395 patients from a third hospital. Several preoperative variables were selected for candidate predictors, based on literature, clinical expertise, and availability in the orthopaedic surgery setting. The main outcomes were the development of any severity of acute kidney injury (stages 1-3) within the first postoperative week, and 90 day, one year, and longer term survival. STUDY ANSWER AND LIMITATIONS: Using logistic regression analysis, independent predictors of acute kidney injury were older age, male sex, diabetes, number of prescribed drugs, lower estimated glomerular filtration rate, use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and American Society of Anesthesiologists grade. The model's predictive performance for discrimination was good (C statistic 0.74 in development cohort, 0.70 in validation cohort). Calibration was good in the development cohort and after recalibration in the validation cohort. Only the highest risks were over-predicted. Survival was worse in patients with acute kidney injury compared with those without (adjusted hazard ratio 1.53, 95% confidence interval 1.38 to 1.70). This was most noticeable in the short term (adjusted hazard ratio: 90 day 2.36, 1.94 to 2.87) and diminished over time (90 day-one year 1.40, 1.10 to 1.79; >1 year 1.28, 1.10 to 1.48). The model used routinely collected data in the orthopaedic surgery setting therefore some variables that could potentially improve predictive performance were not available. However, the readily available predictors make the model easily applicable. WHAT THIS STUDY ADDS: A preoperative risk prediction model consisting of seven predictors for acute kidney injury was developed, with good predictive performance in patients undergoing orthopaedic surgery. Survival was significantly poorer in patients even with mild (stage 1) postoperative acute kidney injury. FUNDING, COMPETING INTERESTS, DATA SHARING: SB received grants from Tenovus Tayside, Chief Scientist Office, and the Royal College of Physicians and Surgeons of Glasgow; PT receives grants from Novo Nordisk, GlaxoSmithKline, and the New Drugs Committee of the Scottish Medicines Consortium. No additional data are available.

Risk of AKI with gentamicin as surgical prophylaxis.

In 2009, the Scottish government issued a target to reduce Clostridium difficile infection by 30% in 2 years. Consequently, Scottish hospitals changed from cephalosporins to gentamicin for surgical antibiotic prophylaxis. This study examined rates of postoperative AKI before and after this policy change. The study population comprised 12,482 adults undergoing surgery (orthopedic, urology, vascular, gastrointestinal, and gynecology) with antibiotic prophylaxis between October 1, 2006, and September 30, 2010 in the Tayside region of Scotland. Postoperative AKI was defined by the Kidney Disease Improving Global Outcomes criteria. The study design was an interrupted time series with segmented regression analysis. In orthopedic patients, change in policy from cefuroxime to flucloxacillin (two doses of 1 g) and single-dose gentamicin (4 mg/kg) was associated with a 94% increase in AKI (P=0.04; 95% confidence interval, 93.8% to 94.3%). Most patients who developed AKI after prophylactic gentamicin had stage 1 AKI, but some patients developed persistent stage 2 or stage 3 AKI. The antibiotic policy change was not associated with a significant increase in AKI in the other groups. Regardless of antibiotic regimen, however, rates of AKI were high (24%) after vascular surgery, and increased steadily after gastrointestinal surgery. Rates could only be ascertained in 52% of urology patients and 47% of gynecology patients because of a lack of creatinine testing. These results suggest that gentamicin should be avoided in orthopedic patients in the perioperative period. Our findings also raise concerns about the increasing prevalence of postoperative AKI and failures to consistently measure postoperative renal function.