Diagnostic and infection control strategies for Clostridioides difficile infections in a setting of high antimicrobial resistance prevalence.

Clostridioides difficile (CD) is a major nosocomial pathogen and the leading cause of antibiotic-associated diarrhoea. In light of the strong association between antimicrobial use and CD infections (CDI), it may be hypothesised that areas at higher prevalence of antimicrobial resistance, like the region of Campania in southern Italy, could also have a higher rate of CDI. In this multicentre, region-based, prospective study, we analysed such issues, exploiting CDI incidence data collected from local hospitals. In 2016, the Italian National Centre for Disease Control supported a project involving three Italian regions: Friuli Venezia Giulia, Lazio and Campania. In Campania, a network of 49 hospitals willing to participate in the project was created. The project consisted of two phases: a survey on practice patterns concerning CDI and an epidemiological surveillance study. We identified a stringent need to improve awareness about CDI among the regional health-care community, as a widespread lack of surveillance programmes for CDI control was observed (existing in only 40% of participating facilities). Moreover, almost half of the participating hospitals (n=16, 43%) had no standardised procedures or protocols to control and prevent CDI. In the second phase of the study, we collected data of CDI cases during a six-month surveillance programme. In all, 87 CDI cases were observed, for a total of 903,334 patient bed-days and 122,988 admissions. According to the above data, CDI incidence was 0.96 cases/10000 patient bed-days, much lower than expected based on prior studies conducted elsewhere. The results of our study suggest CDI remains a rather neglected clinical issue in Campania. Despite a high burden of antimicrobial resistance and antimicrobial use in our geographic setting, we observed a very low incidence of CDI. Such a low incidence could be explained by underdiagnosis, but could also be related to actual diet, the lower patient age or the specific genetic background. However, further studies are warranted to either confirm or rebut the above hypotheses.

Antithrombotic and Anti-Inflammatory Effects of Fondaparinux and Enoxaparin in Hospitalized COVID-19 Patients: The FONDENOXAVID Study.

BACKGROUND: Since the outbreak of novel coronavirus SARS-CoV2 around the world, great attention has been paid to the effects of such antithrombotic drugs as heparinoids, because they have antiviral action in vitro and antithrombotic actions in vivo. We conducted a retrospective analysis in inpatients with confirmed COVID-19 on the anti-inflammatory and antithrombotic effects of enoxaparin and fondaparinux at prophylactic doses. METHODS: This retrospective cohort study used patients with confirmed COVID-19 during the first months of the Italian outbreak from February 18 to April 30, 2020. Our aim was to compare clinical characteristics, prophylactic treatment, markers of inflammation, and thrombotic outcomes in inpatients positive for SARS-CoV2 during hospitalization associated with thromboprophylaxis with enoxaparin (40 mg or 60 mg once daily) or fondaparinux (2.5 mg once daily). Statistical analysis was conducted with using MatLab R2016B and ad hoc functions. RESULTS: There were no significatant differences in clinical characteristics between patients that used enoxaparin or fondaparinux as thromboprophylaxis for SARS-CoV2. No differences were found in D-dimer and fibrinogen levels either, which were used as markers of inflammation during the infection at testing on admission and after 3 weeks.Significant differences in CRP, IL6, and LDH were found in patients after 21 days' treatment. DISCUSSION: Increased levels of fibrinogen and D-dimer in patients with confirmed COVID-19 have been reported in several studies. Our results showed that anti-inflammatory effects of fondaparinux and enoxaparin after 3 weeks of prophylactic treatment were similar when levels of fibrinogen and D-dimer were considered. Furthermore, levels of CRP showed a decrease in patients treated with enoxaparin and fondaparinux, although the decrease in the fondaparinux group seems to be more relevant.

Thromboprofilaxys With Fondaparinux vs. Enoxaparin in Hospitalized COVID-19 Patients: A Multicenter Italian Observational Study.

Importance: The use of anticoagulant therapy with heparins decreased mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19). Even if enoxaparin and fondaparinux have the same clinical indication for venous thromboembolism (VTE) prevention; to date, there are no data about the use of fondaparinux in terms of safety, effectiveness, and impact on clinical prognosis among COVID-19 patients. Objective: To evaluate the safety, effectiveness, and clinical impact of VTE prophylaxis with fondaparinux and enoxaparin among COVID-19 patients hospitalized in internal medicine units. Design, Setting, and Participants: This was a retrospective multicenter observation study, including consecutive symptomatic patients with laboratory-proven COVID-19 admitted to internal medicine units of five Italian hospitals from 15th February to 15th March 2020. Main Outcomes and Measures: The primary safety outcome was the composite of major bleeding and clinically relevant non-major bleeding; the primary effectiveness outcome was the composite of all events classified as pulmonary embolism and deep venous thrombosis. The secondary effectiveness outcome included acute respiratory distress syndrome and all-cause death. Results: Among 120 COVID-19 patients enrolled in the study, 74 were taking enoxaparin (4,000 or 6,000 units/day) and 46 fondaparinux (2.5 units/day). No statistically significant difference in demographic and laboratory and clinical characteristics between the two groups has been shown. During a median follow-up of 32 (interquartile range: 14-51) days, the cumulative incidence rates of VTE and bleeding events on pharmacological thromboprophylaxis with heparins were 19% and 8%, respectively. The incidence of both VTE (6.5 vs. 13.5%; P = 0.36) and bleeding events (6.5 vs. 4.1%; P = 0.68) did not show a significant difference between COVID-19 patients on fondaparinux compared with those on enoxaparin therapy. The regression model for the risk of outcome events according to different VTE prophylaxis drugs did not show significant differences. Conclusions and Relevance: Although these results need confirmation by prospective studies including a larger population, our study provides preliminary evidence of a safe and efficacy use of fondaparinux for VTE prophylaxis in hospitalized COVID-19 patients.

Fondaparinux Use in Patients With COVID-19: A Preliminary Multicenter Real-World Experience.

The use of heparin has been shown to decrease the mortality in hospitalized patients with severe COVID-19. The aim of our study was to evaluate the clinical impact of venous thromboembolism prophylaxis with fondaparinux versus enoxaparin among 100 hospitalized COVID-19 patients. The incidence of pulmonary embolism, deep venous thrombosis, major bleeding (MB), clinically relevant non-MB, acute respiratory distress syndrome, and in-hospital mortality was compared between patients on fondaparinux versus enoxaparin therapy. The 2 groups were homogeneous for demographic, laboratory, and clinical characteristics. In a median follow-up of 28 (IQR: 12-45) days, no statistically significant difference in venous thromboembolism (14.5% vs. 5.3%; P = 0.20), MB and clinically relevant non-MB (3.2% vs. 5.3%, P = 0.76), ARDS (17.7% vs. 15.8%; P = 0.83), and in-hospital mortality (9.7% vs. 10.5%; P = 0.97) has been shown between the enoxaparin group versus the fondaparinux group. Our preliminary results support the hypothesis of a safe and effective use of fondaparinux among patients with COVID-19 hospitalized in internal medicine units.

[A critical analysis of the degree of care humanization in the Hospitals of the Provincia Romana San Giovanni di Dio Fatebenefratelli (FBF)]. / Valutazione del grado di Umanizzazione: una indagine critica condotta negli Ospedali della Provincia Romana Fatebenefratelli.

In the Hospitals of the Ordine della Provincia Romana San Giovanni di Dio Fatebenefratelli (FBF) (consisting of four hospitals located in three Italian regions) Patient Centeredness has always been considered a central point. In 2015, the Central Hospitals' Health Direction decided to use a check-list for the evaluation of the degree of Patient Centered Care Facilities, drawn up by the National Agency for Regional Health Services (Age.Na.S) during the 2010 Research Project "Experimentation and transfer of organizational empowerment models for evaluating and improving the quality of health services." The aim of the work was to measure the "Patient Centered Care degree" of the FBF structures by means of the Age.Na.S. check-list in order to identify effective and sustainable improvement measures, and to evaluate the applicability and the critical points of the questionnaire. The check-list was divided into four areas: care systems oriented at citizen's respect and centrality; physical accessibility, liveability and comfort of the places of care; access to information, simplification and transparency; care of the relationship with the patient and the citizen. The four areas were divided into 12 sub-areas, 29 criteria and 144 items with sub-items (248 questions), defined as quantitative or qualitative variables allowing for an evaluation of observed reality. Some items from different areas have been grouped into Focus and Operational Units (UU.OO./Facilities). The results of the Age.Na.S. study were used to compare the results obtained in the Roman Province FBF structures with the national ones. The Medical Directors and the responsible of FBF Quality Systems completed the cheek-list. A working group within the Central Hospitals' Health Direction analysed the data and processed the results, using the same scores provided by Age.Na.S.. The analysis of the results was divided into three levels. Focus and UU.OO./Facilities scores were calculated based on Age.Na.S. INDICATIONS: The distinction into three levels of analysis allowed for a thorough study of results, from the evaluation of the areas to the items. By comparing the results, the overall final value (range 6-6.5) and single area scores are close to the national average for beds number category in all the FBF hospitals. The most critical criteria, recurring in different levels are: 1.1.2 (Activities/projects to promote sociability and continuity with the outside world); 3.2.3 (Content and accessibility of the website); 4.1.2 (Training and support to the staff for the care of the relationship with the patient) and 4.2.3 (Training of the front-office staff), which had a < 4 score in at least three hospitals and generally achieve a value below the national average (level II and III of analysis). The analysis was extremely useful for detecting positive and negative aspects in the structures under examination. It also permitted to plan improvement measures based on set priorities and objective criteria, aimed at enforcing organizational empowerment models for improving the quality of patient-focused health services. However, during the compilation we found difficulties related to the applicability of the questionnaire. Indeed some questions, while having the same impact on the overall score, are less relevant, considering the patient centrality as main aim. It would be desirable that Age.Na.S. considers in a future survey the observations from hospitals joining previous investigations, in order to facilitate the use of the questionnaire and to improve this tool, which proved to be highly effective.

Radical perineal prostatectomy versus radical retropubic prostatectomy after previous prostate surgery: surgical and functional outcomes.

PURPOSE: We performed a retrospective review of our database to evaluate surgical and functional outcomes in men undergoing radical perineal prostatectomy (RPP) versus radical retropubic prostatectomy (RRP) after previous prostate surgery. PATIENTS AND METHODS: A total of 616 men underwent RPP at our institution. A retrospective review of these patients showed that 59 had a history of previous surgical approach for benign prostatic hyperplasia. A second group of 59 match-paired prostate cancer patients with a history of previous prostate surgery, treated by RRP, were recruited in the our database and was used as control group. All patients were followed up at 3, 6 and 12 months and evaluated during an office evaluation with regard to urinary incontinence and erectile dysfunction. RESULTS: Overall complete continence was achieved in 49 (83%), 51 (86.4%) and 55 (93.2%) RPP patients at 3, 6 and 12 months, respectively, versus 39 (66.1%), 42 (71.1%) and 47 (79.6%) RRP patients, respectively (p = 0.03, p = 0.04 and p = 0.03, respectively). No significant difference was reported between the two groups in the overall percentage of preserved normal erectile function. CONCLUSIONS: Radical prostatectomy in patients with previous prostate surgery should be performed with the transperineal rather than the retropubic approach.

Periprostatic nerve block (PNB) alone vs PNB combined with an anaesthetic-myorelaxant agent cream for prostate biopsy: a prospective, randomized double-arm study.

OBJECTIVE: To compare the efficacy of periprostatic nerve block (PNB) alone vs PNB combined with the local administration of a 1.5% lidocaine/0.3% nifedipine cream (Antrolin, Bracco, Milan, Italy). PATIENTS AND METHODS: In a prospective, randomized, double-arm study, 200 patients were randomized to receive PNB alone (group A, 100) or PNB combined with a previous administration of the topical anaesthetic Antrolin (group B, 100). The PNB was applied by infiltrating bilaterally a solution of 5 mL lidocaine 1% and naropine 0.75%. Patients were asked to complete visual analogue scale (VAS) questionnaire (0-10) to score pain and discomfort during probe insertion (VAS1), PNB (VAS2), cores (VAS3), 30 min after biopsy (VAS4), the evening of the procedure (VAS5), and the day after biopsy (VAS6). RESULTS: Pain during probe insertion in group B was significantly less than in group A (VAS1 0.82 vs 2.9; P < 0.001). Pain during periprostatic infiltration was also lower in group B than group A (VAS2 1.4 vs 3.48; P < 0.001). Pain control was similar during biopsy in the two groups (VAS3 1.28 vs 1.2; P = 0.69). The pain scored at VAS4 was significantly less in group B (0.7 vs 1.86, P < 0.001), as was VAS5 (0.68 vs 1.3, P < 0.001). There was no difference in pain perception the day after biopsy (VAS6, 0.32 vs 0.22, P = 0.14). CONCLUSIONS: Antrolin placed with PNB is better than PNB alone in reducing pain and discomfort during transrectal-ultrasonography guided prostate biopsy.

Elevated white blood cell count and outcome in cancer patients with venous thromboembolism. Findings from the RIETE Registry.

A significant association between elevated white blood cell (WBC) count and mortality in patients with cancer has been reported, but the predictive value of elevated WBC on mortality in cancer patients with acute venous thromboembolism (VTE) has not been explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the three-month outcome of cancer patients with acute VTE according to their WBC count at baseline. As of May 2007, 3805 patients with active cancer and acute VTE had been enrolled in RIETE. Of them, 215 (5.7%) had low- (<4,000 cells/microl), 2,403 (63%) normal- (4,000-11,000 cells/microl), 1,187 (31%) elevated (>11,000 cells/microl) WBC count. During the study period 190 patients (5.0%) had recurrent VTE, 156 (4.1%) major bleeding, 889 (23%) died (399 of disseminated cancer, 113 of PE, 46 of bleeding. Patients with elevated WBC count at baseline had an increased incidence of recurrent VTE (odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.2-2.2), major bleeding (OR: 1.5; 95% CI: 1.1-2.1) or death (OR: 2.7; 95% CI: 2.3-3.2). Most of the reported causes of death were significantly more frequent in patients with elevated WBC count. Multivariate analysis confirmed that elevated WBC count was independently associated with an increased incidence of all three complications. In conclusion, cancer patients with acute VTE and elevated WBC count had an increased incidence of VTE recurrences, major bleeding or death. This worse outcome was consistent among all subgroups and persisted after multivariate adjustment.

Etiology of hypercoagulable state in women with recurrent fetal loss without other causes of miscarriage from Southern Italy: new clinical target for antithrombotic therapy.

BACKGROUND: Recurrent fetal loss (RPL) is one of the most common cause of sterility. Several studies identified thrombophilia as the principal cause of recurrent pregnancy loss. However, reported studies often do not evaluate other causes of miscarriages in their inclusion and exclusion criteria. So the aim of our study was to investigate the role of inherited thrombophilia in patients with RPL and without other causes of RPL. PATIENTS AND METHODS: Patients with 2 or more first trimester abortion or with 1 or more late pregnancy loss were considered for this study. In order to evaluate the causes of RPL we looked for chromosomal, endocrine, chronic inflammatory, and infectious alterations. 90 patients affected by unexplained RPL were enrolled and tested for hemostatic alterations. These women were tested for inherited and/or acquired thrombophilia by MTHFR C677T gene polymorphism, factor V Leiden gene polymorphism, PTHRA20210G gene polymorphism, protein S deficiency, protein C deficiency, antithrombin III deficiency, lupus anticoagulant, and anticardiolipin antibodies Ig G and Ig M. RESULTS: Acquired and/or inherited thrombophilia are strongly associated with RPL when other common causes of miscarriage were excluded. 78% of tested women showed hemostatic abnormalities. Several women with combined thrombophilic defects were also identified by our data. CONCLUSION: After a thorough evaluation of other causes of miscarriage women affected by RPL should be tested for thrombophilia. Our data demonstrated 78% of women with one or combined thrombophilic conditions. Differences with previous studies should be related to difference in the inclusion and exclusion criteria and ethnic background. Because these patients often also show a hypercoagulable state, it an antithrombotic treatment before and during pregnancy may improve their clinical outcome (ie, secondary prevention of miscarriage and primary thromboprophylaxis).

Hyperhomocysteinemia in women with unexplained sterility or recurrent early pregnancy loss from Southern Italy: a preliminary report.

BACKGROUND: Hyperhomocysteinemia has been described as a risk factor for unexplained recurrent pregnancy loss. Increased levels of homocysteine may be due to inadequate dietary intake of folate and vitamin B12 and inherited defects within the methionine-homocysteine pathway such as MTHFR C677T gene polymorphism. However, the association between hyperhomocysteinemia and sterility problems have been underlined only for recurrent pregnancy loss while a relationship between hyperhomocysteinemia and female sterility is still matter of discussion. AIM: This study sought to find out a possible relationship between sterility (primary sterility or secondary sterility due to recurrent pregnancy loss) and homocysteine metabolism. PATIENTS AND METHODS: We selected 20 patients with recurrent pregnancy loss, 20 patients with unexplained female sterility and 20 healthy women as control group. Several whole blood samples were collected by venipuncture. Firstly homocysteinemia and other related variables were tested (i.e. folate and vitamin B12 levels); thereafter DNA was extracted by a further whole blood sample collected in EDTA in order to screen MTHFR C677T gene polymorphism. Statistical analysis was performed by chi square test; differences were considered to be significant if p < 0.05. RESULTS: The median fasting total plasma homocysteine concentration was 19.2 +/- 6.14 microM for patients with recurrent pregnancy loss, while was 21.05 +/- 8.78 microM for patients with unexplained sterility, vs 7.85 +/- 3.31 microM of control group (p < 0.05). Fifteen patients with unexplained female sterility showed MTHFR C677T homozigosity vs 17 with recurrent pregnancy loss and 3 in the control group (p < 0.05). On the other hand no significant differences were found in the levels of vitamin B 12 in the three groups, while reduced folate concentrations were found in women with unexplained female sterility and recurrent pregnancy loss (p < 0.05 vs control group. DISCUSSION: MTHFR C677T gene polymorphism is frequent in the studied populations. These data raise questions on the role of the homocysteine metabolism in sterility problems. Even though increased homocysteine (i.e. > 15 microM) and MTHFR C677T homozigosity have already been described as risk factors for recurrent pregnancy loss, few studies evaluated their role in women with unexplained sterility. Further studies on larger series are needed to better understand the role of homocysteine metabolism, including folate metabolism, in this clinical setting.