Fate of antibacterial spiramycin in river waters.

Spiramycin, a widely used veterinary macrolide antibiotic, was found at traceable levels (nanograms per litre range) in Po River water (N-Italy). The aqueous environmental fate of this antibiotic compound was studied through drug decomposition, the identification of the main and secondary transformation products (TPs), assessment of mineralisation and the investigation of drug TPs toxicity. Initially, laboratory experiments were performed, with the aim of stimulating the antibacterial transformation processes followed in aquatic systems. The TPs were identified through the employment of the liquid chromatography (LC)-mass spectrometry technique. Under illumination, spiramycin degraded rapidly and transformed into numerous organic (intermediate) compounds, of which 11 could be identified, formed through five initial transformation routes. These laboratory simulation experiments were verified in situ to check the mechanism previously supposed. Po River water was sampled and analysed (by LC-high-resolution mass spectrometry) at eight sampling points. Among the previously identified TPs, five of them were also found in the river water. Three of them seem to be formed through a direct photolysis process, while the other two are formed through indirect photolysis processes mediated by natural photo sensitisers. The transformation occurring in the aquatic system involved hydroxylation, demethylation and the detachment of forosamine or mycarose sugars. Toxicity assays using Vibrio fischeri proved that even if spiramycin did not exhibit toxicity, its transformation proceeded through the formation of toxic products.

Effects of clinical pathways in the joint replacement: a meta-analysis.

BACKGROUND: A meta-analysis was performed to evaluate the use of clinical pathways for hip and knee joint replacements when compared with standard medical care. The impact of clinical pathways was evaluated assessing the major outcomes of in-hospital hip and knee joint replacement processes: postoperative complications, number of patients discharged at home, length of in-hospital stay and direct costs. METHODS: Medline, Cinahl, Embase and the Cochrane Central Register of Controlled Trials were searched. The search was performed from 1975 to 2007. Each study was assessed independently by two reviewers. The assessment of methodological quality of the included studies was based on the Jadad methodological approach and on the New Castle Ottawa Scale. Data analysis abided by the guidelines set out by The Cochrane Collaboration regarding statistical methods. Meta-analyses were performed using RevMan software, version 4.2. RESULTS: Twenty-two studies met the study inclusion criteria and were included in the meta-analysis for a total sample of 6,316 patients. The aggregate overall results showed significantly fewer patients suffering postoperative complications in the clinical pathways group when compared with the standard care group. A shorter length of stay in the clinical pathway group was also observed and lower costs during hospital stay were associated with the use of the clinical pathways. No significant differences were found in the rates of discharge to home. CONCLUSION: The results of this meta-analysis show that clinical pathways can significantly improve the quality of care even if it is not possible to conclude that the implementation of clinical pathways is a cost-effective process, because none of the included studies analysed the cost of the development and implementation of the pathways. Based on the results we assume that pathways have impact on the organisation of care if the care process is structured in a standardised way, teams critically analyse the actual organisation of the process and the multidisciplinary team is highly involved in the re-organisation. Further studies should focus on the evaluation of pathways as complex interventions to help to understand which mechanisms within the clinical pathways can really improve the quality of care. With the need for knee and hip joint replacement on the rise, the use of clinical pathways might contribute to better quality of care and cost-effectiveness.

Procollagen I COOH-terminal fragment induces VEGF-A and CXCR4 expression in breast carcinoma cells.

The COOH-terminal fragment of procollagen type I (C3) is produced in tissues with high synthesis of collagen I, such as in breast cancer stroma and in bone. We previously demonstrated that C3 is chemoattractant for breast carcinoma and endothelial cells, and that in tumor cells it induces expression and activation of metalloproteinases (MMP) -2 and -9. Here we demonstrate that C3 induces expression of vascular-endothelial growth factor (VEGF) and of CXCR4, the receptor of the CXCL12/SDF-1 chemokine, in MDA MB 231 breast cancer cells. We show that the changes in gene expression and motility induced by C3 occur in a timely succession and are mediated by multiple and different signaling pathways. C3 induces early phosphorylation of p38/MAPK. Induction of VEGF expression requires continual activity of p38/MAPK and of Protein Kinase C (PKC). Pro-MMP-2 and -9 are induced through a signaling pathway involving G0alpha.i protein, and cell migration requires the activity of a combination of these signaling pathways. Our results suggest that C3 acts as a stromal-derived, cancer-promoting agent active in inducing the migratory phenotype and the survival of cancer cells and determining timely changes in their gene expression that establish conditions promoting tumor angiogenesis and invasion.

[Analysis of the active components of a complex intervention for the care management of stroke patients: impact on in-hospital mortality]. / Analisi delle componenti attive di un intervento complesso di gestione assistenziale del paziente con stroke: impatto sulla mortalità ospedaliera.

We conducted a cohort observational study in 29 Italian hospitals to identify which factors of the acute care management process of ischemic stroke patient can reduce in-hospital mortality. This complex intervention is based on some potential organizational and clinical active components, so data are collected both at organizational unit and individual patient level. We built the variables in relation to presence/absence of clinical-demographic, care-process and organizational characteristics. We compared categorical variables and evaluated the studied independent variables effects on the in-hospital mortality risk at 7 and 30 days from admission. One of the main care success determinants is to be admitted in a stroke unit during the acute-stroke-phase. The most important organizational factor is to be short-time assessed by a stroke team: active role in patients' needs evaluation is provided by the stroke specialists' multidisciplinary team. Antithrombotic therapy is influencing mortality at 7 and 30 days likewise: it is a indispensable factor for the clinical protocols. Our study emphasizes the fact that higher access to different and integrated levels of organized care is associated to better stroke outcomes and that some active and interactive components of the patient's care management have to be identified in the complex intervention.

[The results of the experimental prospective study on the effectiveness and efficiency of the implementation of clinical pathways]. / I risultati dello studio sperimentale prospettico di efficacia ed efficienza dell'implementazione dei percorsi assistenziali.

Our study was undertaken to determine how the use of care pathways in hospital affected the quality of the care of the patients. We performed a cluster-randomized trial. The use of diagnostic procedures and of medical treatments was more appropriate in the care pathways group, as well as the discharge process. As a consequence the outcomes indicators adopted in our study showed better performances in the care pathways group when compared to the usual care group. Our study added evidences on the value of clinical pathways that can be effectively used to improve the quality of hospital care. The use of CP helped to create a constant dialogue within the clinicians, ensured that important areas of treatment were not overlooked and unnecessary delays were prevented by timely interventions. We think that our results are reliable because we adopted a cluster-randomized controlled trial design that is widely accepted as the most reliable method of determining effectiveness of complex interventions in healthcare.

[Evaluation of the work environment in a local healthcare organisation in Italy: practical aspects and public health relevance]. / Studio del clima aziendale di un'Azienda Sanitaria Locale: aspetti pratici e ricadute di Sanità Pubblica.

The aim of this study was to evaluate a model of analysis of the work environment in a healthcare setting in Italy and its potential utility as tool for improving the quality of care and safeguarding the health of users. The experimental model was generated in a publicly funded hospital and in a healthcare district of a local healthcare organisation. A questionnaire was used to evaluate the work environment and its constituents. Sixty-eight percent of those interviewed were aware of the objectives of the organisation, and 74% of the organisational structure. Only 34% however admitted feeling satisfied with the organisation's communication strategies and integration processes. Overall, most workers (84%) reported being highly satisfied with their work even though only half (52%) reported feeling part of the organisation, 34% of being satisfied with the organisation's current career advancement opportunities and 29% of being satisfied with the professional training opportunities offered. Nurses reported the lowest level of satisfaction, especially those working in healthcare districts. The results of this study show that healthcare workers' perception of the work environment are varied in both hospitals and healthcare districts. They also show that the proposed model is useful for evaluating the work environment in a healthcare setting.

[Quality of central venous catheter management protocols in Oncology centres of an Italian region]. / La qualità dei protocolli per la gestione dei cateteri venosi centrali.

The aim of this study was to evaluate the quality of central venous catheter (Port-a-cath, Groshong and Hohn) management protocols in Oncology centres in an Italian region. A retrospective study was performed in 25 hospitals, only 10 of which provided evidence that they utilized a central venous catheter management protocol. The submitted protocols were evaluated in terms of completeness and of adherence to manufacturers' indications and to recommendations of the Centre for Diseases Control. Study results show that overall, there is poor adherence to the basic quality requirements considered and only two of the ten protocols examined were found to be complete. Also, there is wide variability between the protocols with significant differences in the type of instructions provided in the different hospitals.

[Surgical treatment of rectal cancer: prognostic factors for long-term survival]. / Trattamento chirurgico del cancro del retto: fattori prognostici per la sopravvivenza a lungo termine.

The aim of our retrospective study was to verify the results of surgical treatment of rectal cancer in a homogeneous case series, evaluating the various factors that can influence the prognosis and long-term results. The prognostic factors taken into consideration were: Duke's stage; grading; colloid component; location of tumour; type of surgical intervention; age; sex; duration of the symptoms; length of normal rectum below the lower border of the tumour correlated to stage and grading. One hundred and sixty-five patients were operated with a radical approach: 50 abdominoperineal resections (APR) and 115 sphincter-saving resections (SSR) were performed. There were 90 males and 75 females. The mean age was 63 years. Total survival was 61.7% after 5 years and 50% after 10 years. In our study neither the age nor the sex, duration of symptoms or location of the tumours proved to have an influence on survival; while Duke's state turned out to be decisive for survival; also the colloid tumour component proved to have a worse prognosis. The 5-10-year survival rate was respectively 53.6% and 49% in the APR and 65.7% and 50.9% in the SSR (p = n.s.). The data we have collected show that APR and SSR operations have analogous efficiency.

[Epidemiologic study on the performance of a smoking prevention program in an adolescent population]. / Studio epidemiologico per la realizzazione di un programma di prevenzione del tabagismo in una popolazione di adolescenti.

In the last few years, the relative number of adolescent smokers has increased, which indicates the need to boost the adoption of new preventive strategies aimed at this part of the population. In order to be effective, preventive actions should be put in the local setting thoroughly knowing the target population and any specific-predictive factors of the insurgence of smoking addiction. To this purpose, we conducted a study aimed at describing the prevalence of smoking addiction in a population of 2472 adolescents and at identifying any predisposing factors. From the analysis of the results, both predisposing and protective factors emerged, together with many formative requests from the adolescents. On the basis of such results, we were able to create ad hoc preventive interventions. The proposed strategy seems to be potentially valid; however, we will be able to express a more precise judgment only at the end of the implementation phase.

Predicting the need for institutional care shortly after admission to rehabilitation: Rasch analysis and predictive validity of the BRASS Index.

BACKGROUND: Effective discharge planning is increasingly recognised as a critical component of hospital-based Rehabilitation. The BRASS index is a risk screening tool for identification, shortly after hospital admission, of patients who are at risk of post-discharge problems. AIM: To evaluate the internal construct validity and reliability of the Blaylock Risk Assessment Screening Score (BRASS) within the rehabilitation setting. DESIGN: Observational prospective study. SETTING: Rehabilitation ward of an Italian district hospital. POPULATION: One hundred and four consecutively admitted patients. METHODS: Using classical psychometric methods and Rasch analysis (RA), the internal construct validity and reliability of the BRASS were examined. Also, external and predictive validity of the Rasch-modified BRASS (RMB) score were determined. RESULTS: Reliability of the original BRASS was low (Cronbach's alpha=0.595) and factor analyses showed that it was clearly multidimensional. A RA, based on a reduced 7-BRASS item set (RMB), satisfied model's expectations. Reliability was 0.777. The RMB scores strongly correlated with the original BRASS (rho=0.952; P<0.000) and with FIM™ admission scores (rho=-0.853; P<0.000). A RMB score of 12 was associated with an increased risk of nursing home admission (RR=2.1, 95%CI=1.7-2.5), whereas a score of 17 was associated to a higher risk of length of stay >28 days (RR=7.6, 95%CI=1.8-31.9). CONCLUSION: This study demonstrated that the original BRASS was multidimensional and unreliable. However, the RMB holds adequate internal construct validity and is sufficiently reliable as a predictor of discharge problems for group, but not individual use. CLINICAL REHABILITATION IMPACT: The application of tools and methods (such as the BRASS Index) developed under the biomedical paradigm in a Physical and Rehabilitation Medicine setting may have limitations. Further research is needed to develop, within the rehabilitation setting, a valid measuring tool of risk of post-discharge problems at the individual level.

Reduced in-hospital mortality for heart failure with clinical pathways: the results of a cluster randomised controlled trial.

BACKGROUND: Hospital treatment of heart failure (HF) frequently does not follow published guidelines, potentially contributing to HF high morbidity, mortality and economic cost. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was undertaken to determine how clinical pathways (CP) for hospital treatment of HF affected care variability, guidelines adherence, in-hospital mortality and outcomes at discharge. Methods/ DESIGN: Two-arm, cluster-randomised trial. Fourteen community hospitals were randomised either to the experimental arm (CP: appropriate therapeutic guidelines use, new organisation and procedures, patient education) or to the control arm (usual care). The main outcome was in-hospital mortality; secondary outcomes were length and appropriateness of the stay, rate of unscheduled readmissions, customer satisfaction, usage of diagnostic and therapeutic procedures during hospital stay and quality indicators at discharge. All outcomes were measured using validated instruments available in literature. RESULTS: In-hospital mortality was 5.6% in the experimental arm (n = 12); 15.4% in controls (n = 33, p = 0.001). In CP and usual care groups, the mean rates of unscheduled readmissions were 7.9% and 13.9%, respectively. Adjusting for age, smoking, New York Heart Association score, hypertension and source of referral, patients in the CP group, as compared to controls, had a significantly lower risk of in-hospital death (OR 0.18; 95% CI 0.07 to 0.46) and unscheduled readmissions (OR 0.42; 95% CI 0.20 to 0.87). No differences were found between CP and control with respect to the appropriateness of the stay, costs and patient's satisfaction. Except for electrocardiography, all recommended diagnostic procedures were used more in the CP group. Similarly, pharmaceuticals use was significantly greater in CP, with the exception of diuretics and anti-platelets agents. DISCUSSION: The introduction of a specifically tailored CP for the hospital treatment of HF was effective in reducing in-hospital mortality and unscheduled readmissions. This study adds to previous knowledge indicating that CP should be used to improve the quality of hospital treatment of HF. TRIAL REGISTRATION NUMBER: NCT00519038.

FMS*Calciumfluor specifically increases mRNA levels and induces signaling via MAPK 42,44 and not FAK in differentiating rat osteoblasts.

The homeopathic compound of resonance FMS*Calciumfluor (FMS*) reportedly promotes osteogenic differentiation of rat pre-osteoblasts in vitro. Here, we show that the continuous exposure of differentiating rat osteogenic cells (ROB) to FMS* modulates the level of expression of mRNAs for 7 of the 8 osteogenic markers tested. Alkaline phosphatase (AP), osteocalcin (OC), metalloproteinases (MMP-2 and -14), procollagenase C (BMP-1), biglycan (BG) and integrin 1 are expressed at higher levels in FMS*-treated osteoblasts than in control cultures. MMP-2 and -14 mRNA are not down-modulated at mineralization. Also, the pattern of expression induced by FMS* for some of these genes (BMP-1, BG and integrin 1) is changed, but collagen type I (Coll I) mRNA levels are not affected by treatment with FMS*. This suggests that FMS* modulates mRNA levels and that this is not generalized, but gene(s) specific. We also report that exposure to FMS* rapidly and transiently induces activation of mitogen-activated protein kinases (MAPKs) 42,44 in populations of early osteoblasts, but not in pre-osteoblasts, with a cell differentiation stage-dependent and pertussis toxin (PTX)-sensitive response. Subsequent to FMS* MAPK signaling activation, an increase in AP and MMP-14 mRNA is detected, which is also inhibited by PTX, suggesting that FMS* activation of MAPK signaling could be an early event required for the induction of these genes. Exposure to FMS* does not cause changes in the activity of p125 (FAK)-mediated signaling.

Reducing clinical variations with clinical pathways: do pathways work?

OBJECTIVE: To test clinical pathways in a variety of Italian health care organizations in 2000-2002 to measure performance in decreasing process and outcome variations. DESIGN: Creation of indicators, specific for each clinical pathway, to measure variations in the care processes and outcomes. Pre- and post-analysis model to evaluate the possible effect of the clinical pathways on each indicator. SETTING: We tested the clinical pathways in six sites, each with different clinical pathways. RESULTS: Reductions in health care macro-variation phenomena (length of stay, patient pathways, etc.) and in performance micro-variation (variations in diagnostic and therapeutic prescriptions, protocol implementation, etc.) were shown in sites where pathways were implemented successfully. A significant improvement in outcome for patients who were treated according to the clinical pathway for heart failure was also demonstrated. CONCLUSIONS: The overall purpose of clinical pathways is to improve outcome by providing a mechanism to coordinate care and to reduce fragmentation, and ultimately cost. Our results demonstrated that it is possible to achieve this goal. Although controversial elements still exist, we think that clinical pathways can have a positive impact on quality in health care.

In vivo cytogenetic studies of the genotoxic effects of polymethyl methacrylate employed in orthopaedics.

Polymethyl methacrylate (PMMA) is a material employed as a cement in prosthesis that has been found to induce cytogenetic damage in human lymphocytes in vitro. This effect is particularly achieved before the 5th day of the exposition, while after this period no significant variations appeared. In the present study, results of cytogenetic tests in humans are reported. Sister chromatid exchange analysis and micronucleus tests have been performed on lymphocytes of patients who had undergone prosthesization with cemented prosthesis (group A) or with biological anchorage prosthesis, as control (group B). DNA damage was investigated before implantation and 5 d after surgery in both groups. Cytogenetic tests did not show any significant increase in the number of micronuclei and sister chromatid exchanges with respect to control values in patients with PMMA cemented prosthesis.

[Autopsy today: an obsolete practice or an instrument for improving the quality of health care?]. / L'autopsia oggi: una pratica superata o uno strumento per migliorare la qualità delle prestazioni sanitarie?

INTRODUCTION: Autopsies are a fundamental moment of clinical audit that have been progressively decaying. MATERIALS AND METHODS: The autoptic rates of 6 hospitals of Piedmont Region (1639 autopsies, years 1995-97) were calculated. The Positive Predictive Value and Sensitivity (indicators of concordance between clinical and autoptic diagnosis) were calculated for each diagnosis; all discrepancies were classified as type I (adverse impact on patient's survival) and type II (uncertain impact) clinical errors. The diagnostic performance of medical, surgical and emergency staffs were compared with one another. RESULTS: Autopsies are rarely performed on the patients who died in hospital (7.13%). Independently from the diagnosis, the global concordance expresses a Positive Predictive Value of 37.22% and a Sensitivity of 47.71%. 401 type I errors and 307 type II errors were found. The best performance is reached by emergency staff. AIM: To evaluate the use and the meaning of autopsies in today's Italian healthcare organisations.