Sara Balduzzi

Antibiotic Treatment of Severe Exacerbations of Chronic Obstructive Pulmonary Disease with Procalcitonin: A Randomized Noninferiority Trial

Background The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD. Methods and Findings We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], −7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days. Conclusions Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098). Trial Registration ClinicalTrials.gov NCT01125098

The TRIBECA study: (TRI)fecta (B)ioprosthesis (E)valuation versus (C)arpentier Magna-Ease in (A)ortic position

OBJECTIVE To determine whether the Trifecta bioprosthetic aortic valve produces postoperative haemodynamic results comparable with or better than those of the Magna Ease aortic valve bioprosthesis. METHODS We retrospectively reviewed the medical records of patients who had undergone aortic valve replacement with Trifecta or Magna Ease prostheses at eight European institutions between January 2011 and May 2013, and analysed early postoperative haemodynamic performance by means of echocardiography. RESULTS A total of 791 patients underwent aortic valve replacement (469 Magna Ease, 322 Trifecta). Haemodynamic variables were evaluated on discharge and during the follow-up (minimum 6 months, maximum 12 months). The mean gradient and the indexed effective orifice area (IEOA) were as follows: 10 mmHg [interquartile range (IQR): 8-13] and 1.10 cm(2)/m(2) (IQR: 0.95-1.27) for Trifecta; 16 mmHg (IQR: 11-22) and 0.96 cm(2)/m(2) (IQR: 0.77-1.13) for Magna Ease (P < 0.001). These significant differences were maintained across all valve sizes. Similar statistically significant differences were found when patients were matched and/or stratified for preoperative characteristics: body-surface area, ejection fraction, mean gradients and valve size. Severe prosthesis-patient mismatch (IEOA: <0.65 cm(2)/m(2)) was detected in 2 patients (0.6%) with Trifecta and 40 patients (8.5%) with Magna Ease (P < 0.001). CONCLUSIONS The haemodynamic performance of the Trifecta bioprosthesis was superior to that of the Magna Ease valve across all conventional prosthesis sizes, with almost no incidence of severe patient-prosthesis mismatch. The long-term follow-up is needed to determine whether these significant haemodynamic differences will persist, and influence clinical outcomes.

The impact of shift work on the psychological and physical health of nurses in a general hospital: a comparison between rotating night shifts and day shifts

Background Shift work is considered necessary to ensure continuity of care in hospitals and residential facilities. In particular, the night shift is one of the most frequent reasons for the disruption of circadian rhythms, causing significant alterations of sleep and biological functions that can affect physical and psychological well-being and negatively impact work performance. Objectives The aim of this study was to highlight if shift work with nights, as compared with day work only, is associated with risk factors predisposing nurses to poorer health conditions and lower job satisfaction. Methods This cross-sectional study was conducted from June 1, 2015 to July 31, 2015 in 17 wards of a general hospital and a residential facility of a northern Italian city. This study involved 213 nurses working in rotating night shifts and 65 in day shifts. The instrument used for data collection was the “Standard Shift Work Index,” validated in Italian. Data were statistically analyzed. Results The response rate was 86%. The nurses engaged in rotating night shifts were statistically significantly younger, more frequently single, and had Bachelors and Masters degrees in nursing. They reported the lowest mean score in the items of job satisfaction, quality and quantity of sleep, with more frequent chronic fatigue, psychological, and cardiovascular symptoms in comparison with the day shift workers, in a statistically significant way. Conclusion Our results suggest that nurses with rotating night schedule need special attention due to the higher risk for both job dissatisfaction and undesirable health effects.

Echocardiography, Spirometry, and Systemic Acute-Phase Inflammatory Proteins in Smokers with COPD or CHF: An Observational Study

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1β (IL-1 β), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥50 years and with ≥10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

Systematic review of maternal voice interventions demonstrates increased stability in preterm infants

We systematically reviewed how effectively maternal voice interventions supported the clinical outcomes and development of preterm infants. A total of 512 preterm infants were included in 15 studies with different designs, from January 2000 to July 2015. Live and recorded maternal voice interventions were associated with the physiologic and behavioural stabilisation of preterm infants, with fewer cardiorespiratory events, but the evidence was insufficient to evaluate the long‐term effects. Well‐defined determinants and clear setting conditions are needed for such interventions.

Are the Two Human Papillomavirus Vaccines Really Similar? A Systematic Review of Available Evidence: Efficacy of the Two Vaccines against HPV.

Background. When the bivalent and the quadrivalent HPV vaccines were marketed they were presented as having comparable efficacy against cervical cancer. Differences between the vaccines are HPV types included and formulation of the adjuvant. Method. A systematic review was conducted to assess the efficacy of the two vaccines against cervical cancer. Outcomes considered were CIN2+, CIN3+, and AIS. Results. Nine reports (38,419 women) were included. At enrolment mean age of women was 20 years, 90% had negative cytology, and 80% were seronegative and/or DNA negative for HPV 16 or 18 (naïve women). In the TVC-naïve, VE against CIN2+ was 58% (95% CI: 35, 72); heterogeneity was detected, VE being 65% (95% CI: 54, 74) for the bivalent and 43% (95% CI: 23, 57) for the quadrivalent. VE against CIN3+ was 78% (95% CI: <0, 97); heterogeneity was substantial, VE being 93% (95% CI: 77, 98) for the bivalent and 43% (95% CI: 12, 63) for the quadrivalent. VE in the TVC was much lower. No sufficient data were available on AIS. Conclusions. In naïve girls bivalent vaccine shows higher efficacy, even if the number of events detected is low. In women already infected the benefit of the vaccination seems negligible.

Predictors of human epidermal growth factor receptor 2 fluorescence in-situ hybridisation amplification in immunohistochemistry score 2+ infiltrating breast cancer: a single institution analysis

Aims Eligibility for anti-human epidermal growth factor receptor 2 (HER2) treatments in breast cancer requires a correct HER2 status assessment. Testing guidelines recommend fluorescence in-situ hybridisation (FISH) for samples scored as 2+ by immunohistochemistry. This study investigates the correlation between pathological features and FISH amplification in HER2 2+ breast cancer cases. Methods 480 HER2 2+ breast cancer samples were included. The association between tumour grade, hormone receptor status, proliferation index (Ki67) and FISH amplification, using both US Food and Drug Administration (ratio ≥2) and American Society of Clinical Oncologists/College of American Pathologists cut-offs (ratio >2.2) was evaluated. Results 90.2% of the samples were hormone receptor positive. The median Ki67 value was 23.5%; 311 (64.8%) samples showed a Ki67 value of 15% or greater. Tumour grade was evaluable in 421 cases (87.7%), 268 (55.8%) being grade 3. FISH amplification rates were 27.5% (ratio ≥2.0) and 20.8% (ratio >2.2). Grade 3 tumours were more frequently amplified than grades 1–2 tumours: 34% versus 18% (ratio ≥2.0, p<0.001) and 27% versus 9% (ratio >2.2, p<0.001). Samples with Ki67 of 15% or greater showed higher amplification rates than low Ki67 samples: 31% versus 21% (ratio ≥2.0, p=0.022) and 25% versus 12% (ratio >2.2, p=0.003). The OR for FISH amplification was significant in the case of grade 3 and high Ki67 with both cut-offs. Conclusions In this study, high tumour grade and high Ki67 significantly predicted FISH amplification in 480 HER2 2+ breast cancer samples.

The Hemobag: the modern ultrafiltration system for patients undergoing cardiopulmonary by pass

BackgroundThe return of extracorporeal circuit blood at the termination of cardiopulmonary bypass (CPB) is an important feature of blood conservation during cardiac surgery procedures globally. We report our initial clinical evaluation of the Hemobag system a blood-salvaging device designed for whole blood recovery of residual post-CPB volume.MethodsResidual whole blood is hemoconcetrated through the multipass “recovery loop” circuit separate from the CPB and collected in the Hemobag System. This allows the surgeons to continue with surgery, decannulate, and administer protamine simultaneously while the Hemobag is in use and the CPB circuit remains safely primed. We have compared 25 patients receiving the Hemobag to a control group of 25 patients treated with the cell washer that represented our previous standard of care method of circuit blood-salvaging technique.ResultsThe Hemobag system provided significantly higher hemoglobin, hematocrit, fibrinogen, albumin, and total protein levels in the final product reducing the amount of wasted autologous blood cells. There were no device-related complications. There were no significant differences in terms of blood utilization, chest tube drainage and clinical outcomes over the entire postoperative period among groups.ConclusionsThese results suggest that the Hemobag system is a safe and efficient method to multipass hemoconcentrate the residual diluted blood of the CPB circuit. The Hemobag has demonstrated its ability to maximize the composition of the residual CPB volume to achieve the best possible post-CPB hemoglobin, plasma protein and coagulation factors profile for the patient respect to CW.

Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine.

The 4-year end-of-study analysis of the PATRICIA trial published in The Lancet Oncology adds to fi ndings of previous interim analyses. In this trial, Lehtinen and colleagues assessed the effi cacy of a bivalent human papillomavirus (HPV) vaccine, administered to 18 644 healthy women aged 15–25 years, for reduction of high-grade cervical intraepithelial neoplasia (CIN3+). We question the interpretation that the total vaccinated cohort (TVC)-naive population (women who received at least one vaccine dose and completed follow-up, who at baseline had normal cytological fi ndings, were DNA-negative for the 14 oncogenic HPV types investigated, and were seronegative for HPV16/18) is similar to the target population of the immunisation campaign (young adolescent before sexual debut). On the basis of available data, vaccine effi cacy (VE) measured in this subset is signifi cantly better than the one measured in the TVC; the assumption made by Lehtinen and colleagues, that effi cacy in the naive group is the same that will be reached when vaccinating girls aged 12 years, is doubtful. As shown in table 1 of the webappendix (which contains a mistake of inversion in the two categories of women having “less than” and “at least” three sexual partners), naive girls are sexually active: 95% had at least one sexual partner the year before enrolment, 55% used hormonal contraceptive, and 5% used an intrauterine device. Moreover, in a previous report, 35% of this population was also regular condom users. Thus, it is diffi cult to accept the equivalence made: naive girls equal girls not exposed to HPV equal girls before sexual debut. More probably, naive girls, although exposed to HPV, did not become infected with HPV. These girls probably represent a selection of the population engaging in healthier behaviour and possibly have a higher socioeconomic status than the rest of the population: they are not promiscuous (only 5% had three or more sexual partners in the year before enrolment) and are less frequent smokers than the non-naive girls (25% and 36%, respectively, were smokers). In view of the weakness of the assumption made, the effi cacy of HPV vaccine used in real life could be lower than that suggested by Lehtinen and colleagues. Post-marketing eff ectiveness studies will prove useful to clarify these doubts.

“The More the Better” Paradox of Antenatal Ultrasound Examinations in Low-Risk Pregnancy

Objective To investigate whether different antenatal care models could account for differences in operative delivery rates and adverse neonatal outcomes among low-risk pregnant women, and to identify independent variables associated with delivery modes and adverse neonatal outcomes. Study design Retrospective cohort from a single center of singleton, term, live births between January 2012 and June 2014. Rates of cesarean deliveries, operative vaginal deliveries, and neonatal morbidities were analyzed among women followed by private obstetrician-gynecologists versus national health system providers (certified nurse midwifes supervised by obstetrician-gynecologists), and adjusted for potential confounders. Results Among the 2,831 women in our cohort, obstetric and neonatal outcomes were independent of obstetric providers. After we controlled for confounders, private patients having more than four antenatal ultrasound examinations were more likely to undergo cesarean delivery than public patients with four or fewer sonographic assessments (five to eight prenatal scans: relative risk ratio, 3.3; 95% confidence interval [CI] 1.4-8; nine or more prenatal scans: relative risk ratio, 4.1; 95% CI 1.2-14). Conclusions Multiple prenatal ultrasound examinations in low-risk obstetric populations appear to be an independent and potentially modifiable risk factor for cesarean deliveries.