The Future of Rheumatoid Arthritis and Hand Surgery - Combining Evolutionary Pharmacology and Surgical Technique

Rheumatoid arthritis is a systemic autoimmune disease of uncertain aetiology, which is characterized primarily by synovial inflammation with secondary skeletal destructions

External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10–17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03–3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61–1.25), and the pooled c-index was 0.77 (range 0.73–0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV

Recent advances in ankylosing spondylitis: understanding the disease and management

The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease

Improving antibiotic use for complicated urinary tract infections

Guidelines for antimicrobial treatment are important in the process of improving antibiotic use, because they describe appropriate antibiotic use. In this thesis, we demonstrated the value of appropriate antibiotic use (i.e. guideline adherence) in patients with a complicated urinary tract infection (UTI), one of the most prevalent infectious diseases in hospital. Appropriate antibiotic use increases bacterial coverage rates without prescribing unnecessarily broad regimens, which is beneficial for containment of bacterial resistance. Furthermore, appropriate antibiotic use seems to reduce length of hospital stay by more than 2 days and therefore favours patient outcome and health care costs. In current practice, a large variation was shown between departments in the appropriateness of antibiotic use for patients with a complicated UTI. This was to some extent determined by patient characteristics, and only to a limited extent by department or hospital characteristics. No single antibiotic stewardship elements were consistently associated with appropriate antibiotic use. We compared the effectiveness of two different strategies to improve the appropriateness antibiotic use in patients with a complicated UTI. We found that the effectiveness of both strategies was comparable and that better compliance with the strategies was associated with more improvement. Our study emphasize the need for a locally multidisciplinary team of engaged professionals to initiate improvement interventions, as recommended in antimicrobial stewardship programs. Future improvement initiatives should aim to decrease inter-department variation in appropriateness of antibiotic use by focusing on departments with poor baseline performance, as low baseline performance was associated with a larger effect of improvement strategies

A Cluster-Randomized Trial of Two Strategies to Improve Antibiotic Use for Patients with a Complicated Urinary Tract Infection

Contains fulltext : 152505.PDF (publisher's version ) (Open Access)BACKGROUND: Up to 50% of hospital antibiotic use is inappropriate and therefore improvement strategies are urgently needed. We compared the effectiveness of two strategies to improve the quality of antibiotic use in patients with a complicated urinary tract infection (UTI). METHODS: In a multicentre, cluster-randomized trial 19 Dutch hospitals (departments Internal Medicine and Urology) were allocated to either a multi-faceted strategy including feedback, educational sessions, reminders and additional/optional improvement actions, or a competitive feedback strategy, i.e. providing professionals with non-anonymous comparative feedback on the department's appropriateness of antibiotic use. Retrospective baseline- and post-intervention measurements were performed in 2009 and 2012 in 50 patients per department, resulting in 1,964 and 2,027 patients respectively. Principal outcome measures were nine validated guideline-based quality indicators (QIs) that define appropriate antibiotic use in patients with a complicated UTI, and a QI sumscore that summarizes for each patient the appropriateness of antibiotic use. RESULTS: Performance scores on several individual QIs showed improvement from baseline to post-intervention measurements, but no significant differences were found between both strategies. The mean patient's QI sum score improved significantly in both strategy groups (multi-faceted: 61.7% to 65.0%, P = 0.04 and competitive feedback: 62.8% to 66.7%, P = 0.01). Compliance with the strategies was suboptimal, but better compliance was associated with more improvement. CONCLUSION: The effectiveness of both strategies was comparable and better compliance with the strategies was associated with more improvement. To increase effectiveness, improvement activities should be rigorously applied, preferably by a locally initiated multidisciplinary team. TRIAL REGISTRATION: Nederlands Trial Register 1742

Adequacy of an evidence-based treatment guideline for complicated urinary tract infections in the Netherlands and the effectiveness of guideline adherence

Item does not contain fulltextGuideline recommendations on empirical antibiotic treatment are based on the literature, expert opinion, expected pathogens and resistance data, but their adequacy in the real-life setting is often unknown. We investigated the adequacy of the Dutch evidence-based guideline-recommended treatment options for patients with complicated urinary tract infections (UTIs) 2 years after guideline publication and, additionally, the adequacy of actually prescribed empirical therapy for patients treated with guideline-adherent versus non-guideline-adherent therapy. A retrospective, observational multicentre study in the Netherlands included 810 patients with a complicated UTI without special conditions and 174 with a urinary catheter. The susceptibility patterns of cultured uropathogens were compared with guideline-recommended treatment options, which included specific recommendations for patients with a catheter, and with actually prescribed empirical therapy. We considered inadequate coverage rates below 10 % as acceptable. Of the recommended regimens for patients with a UTI without other conditions, only the guideline-recommended combination of amoxicillin-gentamicin was acceptable (inadequate coverage rate 6 %). For patients with a catheter, inadequate coverage rates of recommended regimens ranged from 3 to 24 %. In patients with a UTI without other conditions, actually prescribed guideline-adherent therapy resulted in less broad-spectrum but not in less adequate therapy; in patients with a catheter, actually prescribed guideline-adherent therapy resulted in a higher coverage rate than those prescribed non-guideline-adherent therapy. Due to the continuously changing resistance rates and differences between the epidemiologies of uropathogens assumed in the guideline and those in real life, regular real-life assessments of recommended treatment options are necessary. Guideline adherence seems to be effective for increasing coverage rates without prescribing unnecessarily broad regimens

Using an index-based approach to assess the population-level appropriateness of empirical antibiotic therapy

Objectives: The population-level appropriateness of empirical antibiotic therapy can be conventionally measured by ascertainment of treatment coverage. This method involves a complex resource-intensive case-by-case assessment of the prescribed antibiotic treatment and the resistance of the causative microorganism. We aimed to develop an alternative approach based, instead, on the use of routinely available surveillance data. Methods: We calculated a drug effectiveness index by combining three simple aggregated metrics: relative frequency of aetiological agents, level of resistance and relative frequency of antibiotic use. To evaluate the applicability of our approach, we used this metric to estimate the population-level appropriateness of guideline-compliant and non-guideline-compliant empirical treatment regimens in the context of the Dutch national guidelines for complicated urinary tract infections. Results: The drug effectiveness index agrees within 5% with results obtained with the conventional approach based on a case-by-case ascertainment of treatment coverage. Additionally, we estimated that the appropriateness of 2008 antibiotic prescribing regimens would have declined by up to 4% by year 2011 in the Netherlands due to the emergence and expansion of antibiotic resistance. Conclusions: The index-based framework can be an alternative approach to the estimation of point values and counterfactual trends in population-level empirical treatment appropriateness. In resource-constrained settings, where empirical prescribing is most prevalent and comprehensive studies to directly measure appropriateness may not be a practical proposition, an index-based approach could provide useful information to aid in the development and monitoring of antibiotic prescription guidelines

The additional value of blood cultures in patients with complicated urinary tract infections

Item does not contain fulltextWe evaluated 800 hospitalized patients with a complicated urinary tract infection, from whom both a blood and a urine culture were obtained on the first day of antibiotic treatment. Urine cultures were positive in 70% of patients, and blood cultures were positive in 29%. In 7% of patients, uropathogens caused bacteraemia with a pathogen that was not isolated from urine. Receiving antibiotic therapy at the moment of hospitalization was the only factor independently associated with discordant culture results (OR, 2.06; 95% CI, 1.18-3.61). For those receiving antibiotics at the moment of hospitalization, blood cultures have additional diagnostic value over urine cultures