Retrospective observational study to assess the clinical management and outcomes of hospitalised patients with complicated urinary tract infection in countries with high prevalence of multidrug resistant Gram-negative bacteria (RESCUING)

INTRODUCTION: The emergence of multidrug resistant (MDR) Gram-negative bacteria (GNB), including carbapenemase-producing strains, has become a major therapeutic challenge. These MDR isolates are often involved in complicated urinary tract infection (cUTI), and are associated with poor clinical outcomes. The study has been designed to gain insight into the epidemiology, clinical management, outcome and healthcare cost of patients with cUTI, especially in countries with high prevalence of MDR GNB. METHODS AND ANALYSIS: This multinational and multicentre observational, retrospective study will identify cases from 1 January 2013 to 31 December 2014 in order to collect data on patients with cUTI as a cause of hospital admission, and patients who develop cUTI during their hospital stay. The primary end point will be treatment failure defined as the presence of any of the following criteria: (1) signs or symptoms of cUTI present at diagnosis that have not improved by days 5–7 with appropriate antibiotic therapy, (2) new cUTI-related symptoms that have developed within 30 days of diagnosis, (3) urine culture taken within 30 days of diagnosis, either during or after completion of therapy, that grows ≥104 colony-forming unit/mL of the original pathogen and (4) death irrespective of cause within 30 days of the cUTI diagnosis. SAMPLE SIZE: 1000 patients afford a power of 0.83 (α=0.05) to detect an absolute difference of 10% in the treatment failure rate between MDR bacteria and other pathogens. This should allow for the introduction of about 20 independent risk factors (or their interaction) in a logistic regression model looking at risk factors for failure. ETHICS AND DISSEMINATION: Approval will be sought from all relevant Research Ethics Committees. Publication of this study will be considered as a joint publication by the participating investigator leads, and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE)

Gender Inequalities in Diagnostic Inertia around the Three Most Prevalent Cardiovascular Risk Studies: Protocol for a Population-Based Cohort Study

Evidence shows that objectives for detecting and controlling cardiovascular risk factors are not being effectively met, and moreover, outcomes differ between men and women. This study will assess the gender-related differences in diagnostic inertia around the three most prevalent cardiovascular risk factors: dyslipidemia, arterial hypertension, and diabetes mellitus, and to evaluate the consequences on cardiovascular disease incidence. This is an epidemiological and cohort study. Eligible patients will be adults who presented to public primary health care centers in a Spanish region from 2008 to 2011, with hypertension, dyslipidemia, or/and diabetes and without cardiovascular disease. Participants’ electronic health records will be used to collect the study variables in a window of six months from inclusion. Diagnostic inertia of hypertension, dyslipidemia, and/or diabetes is defined as the registry of abnormal diagnostic parameters—but no diagnosis—on the person’s health record. The cohort will be followed from the date of inclusion until the end of 2019. Outcomes will be cardiovascular events, defined as hospital admission due to ischemic cardiopathy, stroke, and death from any cause. The results of this study could inform actions to rectify the structure, organization and training of health care teams in order to correct the inequality

Cost of hospitalised patients due to complicated urinary tract infections: a retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study

OBJECTIVE: Complicated urinary tract infections (cUTIs) impose a high burden on healthcare systems and are a frequent cause of hospitalisation. The aims of this paper are to estimate the cost per episode of patients hospitalised due to cUTI and to explore the factors associated with cUTI-related healthcare costs in eight countries with high prevalence of multidrug resistance (MDR). DESIGN: This is a multinational observational, retrospective study. The mean cost per episode was computed by multiplying the volume of healthcare use for each patient by the unit cost of each item of care and summing across all components. Costs were measured from the hospital perspective. Patient-level regression analyses were used to identify the factors explaining variation in cUTI-related costs. SETTING: The study was conducted in 20 hospitals in eight countries with high prevalence of multidrug resistant Gram-negative bacteria (Bulgaria, Greece, Hungary, Israel, Italy, Romania, Spain and Turkey). PARTICIPANTS: Data were obtained from 644 episodes of patients hospitalised due to cUTI. RESULTS: The mean cost per case was €5700, with considerable variation between countries (largest value €7740 in Turkey; lowest value €4028 in Israel), mainly due to differences in length of hospital stay. Factors associated with higher costs per patient were: type of admission, infection source, infection severity, the Charlson comorbidity index and presence of MDR. CONCLUSIONS: The mean cost per hospitalised case of cUTI was substantial and varied significantly between countries. A better knowledge of the reasons for variations in length of stays could facilitate a better standardised quality of care for patients with cUTI and allow a more efficient allocation of healthcare resources. Urgent admissions, infections due to an indwelling urinary catheterisation, resulting in septic shock or severe sepsis, in patients with comorbidities and presenting MDR were related to a higher cost

SOBRINA Spanish study-analysing the frequency, cost and adverse events associated with overuse in primary care: protocol for a retrospective cohort study

Introduction Several institutions and quality national agencies have fostered the creation of recommendations on what not to do to reduce overuse in clinical practice. In primary care, their impact has hardly been studied. The frequency of adverse events (AEs) associated with doing what must not be done has not been analysed, either. The aim of this study is to measure the frequency of overuse and AEs associated with doing what must not be done (commission errors) in primary care and their cost. Methods and analysis A coordinated, multicentric, national project. A retrospective cohort study using computerised databases of primary care medical records from national agencies and regional health services will be conducted to analyse the frequency of the overuse due to ignore the do-not-do recommendations, and immediately afterwards, depending on their frequency, a representative random sample of medical records will be reviewed with algorithms (triggers) that determine the frequency of AEs associated with these recommendations. Cost will determine by summation of the direct costs due to the consultation, pharmacy, laboratory and imaging activities according to the cases. Ethics and dissemination The study protocol has been approved by the Ethics Committee of Primary Care Research of the Valencian Community. We aim to disseminate the findings through international peerreviewed journals and on the website (http://www. nohacer. es/). Outcomes will be used to incorporate algorithms into the electronic history to assist in making clinical decisions

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Risk factors for treatment failure and mortality among hospitalized patients with complicated urinary tract infection: A multicenter retrospective cohort study (RESCUING study group)

Background. Complicated urinary tract infections (cUTIs) are responsible for a major share of all antibiotic consumption in hospitals. We aim to describe risk factors for treatment failure and mortality among patients with cUTIs. Methods. A multinational, multicentre retrospective cohort study, conducted in 20 countries in Europe and the Middle East. Data were collected from patients' files on hospitalised patients with a diagnosis of cUTI during 2013-2014. Primary outcome was treatment failure, secondary outcomes included 30 days all-cause mortality,among other outcomes. Multivariable analysis using a logistic model and the hospital as a random variable was performed to identify independent predictors for these outcomes. Results. A total of 981 patients with cUTI were included. Treatment failure was observed in 26.6% (261/981), all cause 30-day mortality rate was 8.7% (85/976), most of these in patients with catheter related UTI (CaUTI). Risk factors for treatment failure in multivariable analysis were ICU admission (OR 5.07, 95% CI 3.18-8.07), septic shock (OR 1.92, 95% CI 0.93-3.98), corticosteroid treatment (OR 1.92, 95% CI 1.12-3.54), bedridden (OR 2.11, 95%CI 1.4-3.18), older age (OR 1.02, 95% CI 1.0071.03-), metastatic cancer (OR 2.89, 95% CI 1.46-5.73) and CaUTI (OR 1.48, 95% CI 1.04-2.11). Management variables, such as inappropriate empirical antibiotic treatment or days to starting antibiotics were not associated with treatment failure or 30-day mortality. More patients with pyelonephritis were given appropriate empirical antibiotic therapy than other CaUTI [110/171; 64.3% vs. 116/270; 43%, p <0.005], nevertheless, this afforded no advantage in treatment failure rates nor mortality in these patients. Conclusions. In patients with cUTI we found no benefit of early appropriate empirical treatment on survival rates or other outcomes. Physicians might consider supportive treatment and watchful waiting in stable patients until the causative pathogen is defined

Adherence to european clinical practice guidelines for secondary prevention of cardiovascular disease : A cohort study

Funding: This study was supported by a grant from the Primary Health Care University Research Institute (IDIAP) Jordi Gol located in Barcelona, Spain (Grant ref: IDIAP 7Z12/006).To provide a better understanding of the actions taken within health systems and their results, this study aims to assess clinicians' adherence to clinical practice guidelines regarding recommended treatments in patients with cardiovascular disease in primary care settings, and to determine the associated factors. We conducted an ambispective cohort study in 21 primary care centres in 8 Spanish regions. Patients diagnosed with coronary heart disease, stroke and/or peripheral arterial disease were included. Patients who received the treatment recommended in the European guidelines on cardiovascular disease prevention (CPG's adherent group) were compared with patients who did not (CPG's non-adherent group). The outcome variables were cardiovascular hospital admissions, all-cause and cardiovascular mortality during follow-up. Of the 438 participants, 38.6% (n = 169) received the drug therapies recommended in the guidelines. The factors that increased the likelihood of good adherence to CPG's were being diagnosed with hypertension (p = 0.001), dyslipidaemia (p < 0.001) or diabetes (p = 0.001), and not having a psychiatric disorder (p = 0.005). We found no statistically significant association between good adherence to CPG's and lower incidence of events (p = 0.853). Clinician adherence to guidelines for secondary prevention of cardiovascular disease was low in the primary care setting

Risk Factors for Colonization with Extended-Spectrum β-Lactamase–producing Bacteria and Intensive Care Unit Admission

Coexisting conditions and previous antimicrobial drug exposure predict colonization

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: the ESCARVAL-RISK study

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all cause mortality and hospitalization due to cardiovascular events in a high-risk population. Methods This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008±2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. Results 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/ HDL-Cholesterol: 8.94, 15.09, 6.92. Conclusions In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers