Background: Ingestion of cranberry (Vaccinium macrocarpon Ait.) has traditionally been utilized for prevention of urinary tract infections. The proanthocyanidins (PACs) in cranberry, in particular the A-type linkages have been implicated as important inhibitors of primarily P-fimbriated E. coli adhesion to uroepithelial cells. Additional experiments were required to investigate the persistence in urine samples over a broader time period, to determine the most effective dose per day and to determine if the urinary anti-adhesion effect following cranberry is detected within volunteers of different origins. Methods: Two separate bioassays (a mannose-resistant hemagglutination assay and an original new human T24 epithelial cell-line assay) have assessed the ex-vivo urinary bacterial anti-adhesion activity on urines samples collected from 32 volunteers from Japan, Hungary, Spain and France in a randomized, double-blind versus placebo study. An in vivo Caenorhabditis elegans model was used to evaluate the influence of cranberry regimen on the virulence of E. coli strain. Results: The results indicated a significant bacterial anti-adhesion activity in urine samples collected from volunteers that consumed cranberry powder compared to placebo (p < 0.001). This inhibition was clearly dose-dependent, prolonged (until 24 h with 72 mg of PAC) and increasing with the amount of PAC equivalents consumed in each cranberry powder regimen. An in vivo Caenorhabditis elegans model showed that cranberry acted against bacterial virulence: E. coli strain presented a reduced ability to kill worms after a growth in urines samples of patients who took cranberry capsules. This effect is particularly important with the regimen of 72 mg of PAC. Conclusions: Administration of PAC-standardized cranberry powder at dosages containing 72 mg of PAC per day may offer some protection against bacterial adhesion and virulence in the urinary tract. This effect may offer a nyctohemeral protection.

Introduction: The aim of the study was to assess whether adults admitted to hospitals with both Intensive Care Units (ICU) and Intermediate Care Units (IMCU) have lower in-hospital mortality than those admitted to ICUs without an IMCU. Methods: An observational multinational cohort study performed on patients admitted to participating ICUs during a four-week period. IMCU was defined as any physically and administratively independent unit open 24 hours a day, seven days a week providing a level of care lower than an ICU but higher than a ward. Characteristics of hospitals, ICUs and patients admitted to study ICUs were recorded. The main outcome was all-cause in-hospital mortality until hospital discharge (censored at 90 days). Results: One hundred and sixty-seven ICUs from 17 European countries enrolled 5,834 patients. Overall, 1,113 (19.1%) patients died in the ICU and 1,397 died in hospital, with a total of 1,397 (23.9%) deaths. The illness severity was higher for patients in ICUs with an IMCU (median Simplified Acute Physiology Score (SAPS) II: 37) than for patients in ICUs without an IMCU (median SAPS II: 29, P <0.001). After adjustment for patient characteristics at admission such as illness severity, and ICU and hospital characteristics, the odds ratio of mortality was 0.63 (95% CI 0.45 to 0.88, P = 0.007) in favour of the presence of IMCU. The protective effect of the IMCU was absent in patients who were admitted for basic observation, for example, after surgery (odds ratio 1.15, 95% CI 0.65 to 2.03, P = 0.630) but was strong in patients admitted to an ICU for other reasons (odds ratio 0.54, 95% CI 0.37 to 0.80, P = 0.002). Conclusions: The presence of an IMCU in the hospital is associated with significantly reduced adjusted hospital mortality for adults admitted to the ICU. This effect is relevant for the patients requiring full intensive treatment. Trial registration: Clinicaltrials.gov NCT01422070. Registered 19 August 2011.

Introduction: Severity assessment and site-of-care decisions for patients with community-acquired pneumonia (CAP) are pivotal for patients' safety and adequate allocation of resources. Late admission to the intensive care unit (ICU) has been associated with increased mortality in CAP. We aimed to review and meta-analyze systematically the performance of clinical prediction rules to identify CAP patients requiring ICU admission or intensive treatment. Methods: We systematically searched Medline, Embase, and the Cochrane Controlled Trials registry for clinical trials evaluating the performance of prognostic rules to predict the need for ICU admission, intensive treatment, or the occurrence of early mortality in patients with CAP. Results: Sufficient data were available to perform a meta-analysis on eight scores: PSI, CURB-65, CRB-65, CURB, ATS 2001, ATS/IDSA 2007, SCAP score, and SMART-COP. The estimated AUC of PSI and CURB-65 scores to predict ICU admission was 0.69. Among scores proposed for prediction of ICU admission, ATS-2001 and ATS/IDSA 2007 scores had better operative characteristics, with a sensitivity of 70% (CI, 61 to 77) and 84% (48 to 97) and a specificity of 90% (CI, 82 to 95) and 78% (46 to 93), but their clinical utility is limited by the use of major criteria. ATS/IDSA 2007 minor criteria have good specificity (91% CI, 84 to 95) and moderate sensitivity (57% CI, 46 to 68). SMART-COP and SCAP score have good sensitivity (79% CI, 69 to 97, and 94% CI, 88 to 97) and moderate specificity (64% CI, 30 to 66, and 46% CI, 27 to 66). Major differences in populations, prognostic factor measurement, and outcome definition limit comparison. Our analysis also highlights a high degree of heterogeneity among the studies. Conclusions: New severity scores for predicting the need for ICU or intensive treatment in patients with CAP, such as ATS/IDSA 2007 minor criteria, SCAP score, and SMART-COP, have better discriminative performances compared with PSI and CURB-65. High negative predictive value is the most consistent finding among the different prediction rules. These rules should be considered an aid to clinical judgment to guide ICU admission in CAP patients.

Care of frail and dependent older adults with multiple chronic conditions is a major challenge for health care systems. The study objective was to test the efficacy of providing integrated care at home to reduce unnecessary hospitalizations, emergency room visits, institutionalization, and mortality in community dwelling frail and dependent older adults. A prospective controlled trial was conducted, in real-life clinical practice settings, in a suburban region in Geneva, Switzerland, served by two home visiting nursing service centers. Three hundred and one community-dwelling frail and dependent people over 60 years old were allocated to previously randomized nursing teams into Control (N = 179) and Intervention (N = 122) groups: Controls received usual care by their primary care physician and home visiting nursing services, the Intervention group received an additional home evaluation by a community geriatrics unit with access to a call service and coordinated follow-up. Recruitment began in July 2009, goals were obtained in July 2012, and outcomes assessed until December 2012. Length of follow-up ranged from 5 to 41 months (mean 16.3). Primary outcome measure was the number of hospitalizations. Secondary outcomes were reasons for hospitalizations, the number and reason of emergency room visits, institutionalization, death, and place of death. The number of hospitalizations did not differ between groups however, the intervention led to lower cumulative incidence for the first hospitalization after the first year of follow-up (69.8%, CI 59.9 to 79.6 versus 87 · 6%, CI 78 · 2 to 97 · 0; p = .01). Secondary outcomes showed that the intervention compared to the control group had less frequent unnecessary hospitalizations (4.1% versus 11.7%, p = .03), lower cumulative incidence for the first emergency room visit, 8.3%, CI 2.6 to 13.9 versus 23.2%, CI 13.1 to 33.3; p = .01), and death occurred more frequently at home (44.4 versus 14.7%; p = .04). No significant differences were found for institutionalization and mortality. Integrated care that included a home visiting multidisciplinary geriatric team significantly reduced unnecessary hospitalizations, emergency room visits and allowed more patients to die at home. It is an effective tool to improve coordination and access to care for frail and dependent older adults. Clinical Trials.gov Identifier: NCT02084108 . Retrospectively registered on March 10th 2014.

Background: Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM). We evaluated the new Graded Prognostic Assessment (GPA) scale in a prospective validation study to compare it with two published prognostic indexes. Methods: A total of 285 newly diagnosed BM (n = 85 with synchronous BM) patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 ± 12.0 years. The median KPS and number of BM was 70 (range, 20-100) and 3 (range, 1-50), respectively. The majority of primary tumours were lung (53%), or breast (17%) cancers. Treatment was administered to 255 (89.5%) patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA) 1, 8.4% and Basic Score for BM (BSBM) 3, 9.1%. Mean follow-up (FU) time was 5.2 ± 4.7 months. Results: During the period of FU, 225 (78.9%) patients died. The 6 months- and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (P < 0.001), BSBM (P < 0.001), Center (P = 0.007), RPA (P = 0.02) and GPA (P = 0.03) were statistically significant for OS. The survival prediction performances' of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell's concordance indexes C were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively. Conclusions: Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability.