International criteria for acute kidney injury: advantages and remaining challenges

• Acute Kidney Injury (AKI) is defined using widely accepted international criteria that are based on changes in serum creatinine concentration and degree of oliguria. • AKI, when defined in this way, has a strong association with poor patient outcomes, including high mortality rates and longer hospital admissions with increased resource utilisation and subsequent chronic kidney disease. • The detection of AKI using current criteria can assist with AKI diagnosis and stratification of individual patient risk. • The diagnosis of AKI requires clinical judgement to integrate the definition of AKI with the clinical situation, to determine underlying cause of AKI, and to take account of factors that may affect performance of current definitions

Targeting medication non-adherence behavior in selected autoimmune diseases: a systematic approach to digital health program development

Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were discovered. Over one third of articles identified the following risk factors as common contributors to medication non-adherence (percent of studies reporting): patients not understanding treatment (44%), side effects (41%), age (37%), dose regimen (33%), and perceived medication ineffectiveness (33%). An unanticipated finding that emerged was the need for risk stratification tools (81%) with patient-centric approaches (67%). Conclusions This study systematically identifies and categorizes medication non-adherence risk factors in select autoimmune diseases. Findings indicate that patients understanding of their disease and the role of medication are paramount. An unexpected finding was that the majority of research articles called for the creation of tailored, patient-centric interventions that dispel personal misconceptions about disease, pharmacotherapy, and how the body responds to treatment. To our knowledge, these interventions do not yet exist in digital format. Rather than adopting a systems level approach, digital health programs should focus on cohorts with heterogeneous needs, and develop tailored interventions based on individual non-adherence patterns

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Contrast‐enhanced ultrasound assessed renal microvascular perfusion may predict postoperative renal complications following colorectal surgery

Colorectal surgery is associated with an above‐average mortality rate of ~15%. During surgery, maintenance of vital organ perfusion is essential in order to reduce postoperative mortality and morbidity, with renal perfusion of particular importance. Oesophageal Doppler monitors (ODM) are commonly used to try and provide accurate measures of fluid depletion during surgery, however it is unclear to what extent they reflect organ perfusion. In addition, it is not known whether macro‐ and/ or microvascular perfusion indices are associated with renal complications following colorectal surgery. Thirty‐two participants scheduled for colorectal surgery had three measures of macro‐ and microvascular renal blood flow via contrast enhanced ultrasound (CEUS), and simultaneous measures of cardiac output indicies via ODM: i) pre‐operatively; ii) intra‐operatively at the mid‐point of operation, and iii) after the conclusion of surgery. The Postoperative Morbidity Survey (POMS) was used to assess postoperative complications. Intra‐operatively, there was a significant correlation between renal microvascular flow (RT) and renal macrovascular flow (TTI) (rho=0.52; p=0.003). Intra‐operative TTI, but not RT, was associated with cardiac index (rho= ‐0.50; p=0.0003). Intra‐operative RT predicted increases in renal complications (OR 1.46; 95% CI 1.03 to 2.09) with good discrimination (C‐statistic, 0.85). Complications were not predicted by TTI or ODM‐derived indices. There was no relationship between RT and TTI before or after surgery. ODM measures of haemodynamic status do not correlate with renal microvascular blood flow, and as such are likely not suitable to determine vital organ perfusion. Only CEUS‐derived measures of microvascular perfusion were predictive of postoperative renal complications

Variations in clinical decision-making between cardiologists and cardiac surgeons; a case for management by multidisciplinary teams?

OBJECTIVE: To assess variations in decisions to revascularise patients with coronary heart disease between general cardiologists, interventional cardiologists and cardiac surgeons DESIGN: Six cases of coronary heart disease were presented at an open meeting in a standard format including clinical details which might influence the decision to revascularise. Clinicians (n = 53) were then asked to vote using an anonymous electronic system for one of 5 treatment options: medical, surgical (CABG), percutaneous coronary intervention (PCI) or initially medical proceeding to revascularisation if symptoms dictated. Each case was then discussed in an open forum following which clinicians were asked to revote. Differences in treatment preference were compared by chi squared test and agreement between groups and between voting rounds compared using Kappa. RESULTS: Surgeons were more likely to choose surgery as a form of treatment (p = 0.034) while interventional cardiologists were more likely to choose PCI (p = 0.056). There were no significant differences between non-interventional and interventional cardiologists (p = 0.13) in their choice of treatment. There was poor agreement between all clinicians in the first round of voting (Kappa 0.26) but this improved to a moderate level of agreement after open discussion for the second vote (Kappa 0.44). The level of agreement among surgeons (0.15) was less than that for cardiologists (0.34) in Round 1, but was similar in Round 2 (0.45 and 0.45 respectively) CONCLUSION: In this case series, there was poor agreement between cardiac clinical specialists in the choice of treatment offered to patients. Open discussion appeared to improve agreement. These results would support the need for decisions to revascularise to be made by a multidisciplinary panel

Can Broader Diffusion of Value-Based Insurance Design Increase Benefits from US Health Care without Increasing Costs? Evidence from a Computer Simulation Model

Using a computer simulation based on US data, R. Scott Braithwaite and colleagues calculate the benefits of value-based insurance design, in which patients pay less for highly cost-effective services

Computer-assisted and fractal-based morphometric assessment of microvascularity in histological specimens of gliomas

Fractal analysis is widely applied to investigate the vascular system in physiological as well as pathological states. We propose and examine a computer-aided and fractal-based image analysis technique to quantify the microvascularity in histological specimens of WHO grade II and III gliomas. A computer-aided and fractal-based analysis was used to describe the microvessels and to quantify their geometrical complexity in histological specimens collected from 17 patients. The statistical analysis showed that the fractal-based indexes are the most discriminant parameters to describe the microvessels. The computer-aided quantitative analysis also showed that grade III gliomas are generally more vascularized than grade II gliomas. The fractal parameters are reliable quantitative indicators of the neoplastic microvasculature, making them potential surrogate biomarkers. The qualitative evaluation currently performed by the neuropathologist can be combined with the computer-assisted quantitative analysis of the microvascularity to improve the diagnosis and optimize the treatment of patients with brain cancer

Influence of Comorbidities on Therapeutic Progression of Diabetes Treatment in Australian Veterans: A Cohort Study

BACKGROUND: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84–0.91], P<0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. CONCLUSIONS / SIGNIFICANCE: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities.Agnes I. Vitry, Elizabeth E. Roughead, Adrian K. Preiss, Philip Ryan, Emmae N. Ramsay, Andrew L. Gilbert, Gillian E. Caughey, Sepehr Shakib, Adrian Esterman, Ying Zhang and Robyn A. McDermot

Cost-consciousness among Swiss doctors: a cross-sectional survey

BACKGROUND: Knowing what influences physicians attitudes toward health care costs is an important matter, because most health care expenditures are the results of doctors' decisions. Many decisions regarding medical tests and treatments are influenced by factors other than the expected benefit to the patient, including the doctor's demographic characteristics and concerns about cost and income. METHODS: Doctors (n = 1184) in Geneva, Switzerland, answered questions about their cost-consciousness, practice patterns (medical specialty, public.vs. private sector, number of patients per week, time spent with a new patient), work satisfaction, and stress from uncertainty. General linear models were used to identify independent risk factors of higher cost-consciousness. RESULTS: Most doctors agreed that trying to contain costs was their responsibility ("agree" or "totally agree": 90%) and that they should take a more prominent role in limiting the use of unnecessary tests (92%); most disagreed that doctors are too busy to worry about costs (69%) and that the cost of health care is only important if the patient has to pay for it out-of-pocket (88%). In multivariate analyses, cost-consciousness was higher among doctors in the public sector, those who saw fewer patients per week, who were most tolerant of uncertainty, and who were most satisfied with their work. CONCLUSION: Thus even in a setting with very high health care expenditures, doctors' stated cost-consciousness appeared to be generally high, even though it was not uniformly distributed among them