The economic and fiscal impact of incremental use of cell-based quadrivalent influenza vaccine for the prevention of seasonal influenza among healthcare workers in Italy.

BACKGROUND: Seasonal influenza has a significant impact on public health, generating substantial direct healthcare costs, production losses and fiscal effects. Understanding these consequences is crucial to effective decision-making and the development of preventive strategies. This study aimed to evaluate the economic and the fiscal impact of implementing an incremental strategy for seasonal influenza prevention using the cell-based quadrivalent influenza vaccine (QIVc) among healthcare workers (HCWs) in Italy. METHODS: To estimate the economic impact of implementing this strategy, we performed a cost analysis that considered direct healthcare costs, productivity losses and fiscal impact. The analysis considered a 3-year time horizon. A deterministic sensitivity analysis was also conducted. RESULTS: Assuming a vaccination coverage rate of 30% among HCWs, the analysis considered a total of 203 018 vaccinated subjects. On analysing the overall differential impact (including direct costs, indirect costs and fiscal impact), implementing QIVc vaccination as a preventative measure against influenza among HCWs in Italy would yield societal resource savings of €23 638.78 in the first year, €47 277.56 in the second year, and €70 916.35 in the third year, resulting in total resource savings of €141 832.69. CONCLUSIONS: The study demonstrated that implementing the incremental use of QIVc as part of a preventive strategy for seasonal influenza among HCWs in Italy could yield positive economic outcomes, especially in terms of indirect costs and fiscal impact. The resources saved could be utilized to fund further public health interventions. Policy-makers should consider these findings when making decisions regarding influenza prevention strategies targeting HCWs.

Epidemiological Impact of Metabolic Syndrome in Overweight and Obese European Children and Adolescents: A Systematic Literature Review.

The prevalence of overweight and obesity is continuously increasing, both in the adult and pediatric populations, posing a substantial challenge to public health. Understanding the epidemiological burden of metabolic syndrome (MetS) among children, particularly regarding its complications and long-term effects in adulthood, is crucial for identifying effective preventive measures and enhancing the clinical care of obese children. Therefore, by searching two databases, a systematic review was conducted in order to evaluate studies that specifically addressed the epidemiological MetS impact among overweight/obese European children and adolescents. Overall, 15 studies were considered. The epidemiological data concerning the MetS impact were contingent on the diagnostic criteria used and varied across countries, resulting in a prevalence range of 1.44% to 55.8%. Spanish studies were the most numerous (34%), revealing a country prevalence rate ranging from 2.5% to 19.6%. Males (prevalence range: 1.4-55.8%) and subjects with overweight/obesity (prevalence range: 12.9-55.8%) were mainly affected. Obesity emerged as the main risk factor in the MetS development and the consequent onset of cardiovascular complications and diabetes. Knowing the MetS burden and its risk factors could improve their prevention, detection, and treatment, and guide the development of targeted public health interventions to appropriately address the health needs of younger patients.

The Impact of Vaccination on COVID-19 Burden of Disease in the Adult and Elderly Population: A Systematic Review of Italian Evidence.

COVID-19 is a major global health threat, with millions of confirmed cases and deaths worldwide. Containment and mitigation strategies, including vaccination, have been implemented to reduce transmission and protect the population. We conducted two systematic reviews to collect nonrandomized studies investigating the effects of vaccination on COVID-19-related complications and deaths in the Italian population. We considered studies conducted in Italian settings and written in English that contained data on the effects of vaccination on COVID-19-related mortality and complications. We excluded studies that pertained to the pediatric population. In total, we included 10 unique studies in our two systematic reviews. The results showed that fully vaccinated individuals had a lower risk of death, severe symptoms, and hospitalization compared to unvaccinated individuals. The review also looked at the impact of vaccination on post-COVID-19 syndrome, the effectiveness of booster doses in older individuals, and nationwide adverse events. Our work highlights the crucial role that vaccination campaigns have played in reducing the burden of COVID-19 disease in the Italian adult population, positively impacting the pandemic trajectory in Italy.

Cervical cancer elimination in Italy: Current scenario and future endeavors for a value based prevention.

Background: Cervical Cancer (CC) is a vaccine-preventable disease, and it is treatable if diagnosed early and managed properly. However, it is the fourth most common cancer in women worldwide with about 604,127 cases and 341,831 deaths in 2020. In Italy, it represents the fifth most common cancer in women under 50 years of age with about 2,400 new cases in 2020. The CC elimination is today a global public health goal published by the World Health Organization (WHO) in 2020 and a commitment of the European Union that has included it in Europe's Beating Cancer Plan. Therefore, urgent action is needed, at international and national level, to implement value-based interventions regarding vaccination, screening and timely management of the disease. Our study aims to describe the state of the art of Human Papilloma Virus (HPV) prevention in Italy and to get a consensus on indicators for monitoring the progress toward CC elimination at national level. Methods: The study envisaged the following activities: research and synthesis of the evidence on strategies and actions for CC elimination at regional Italian level; identification of indicators to monitor such strategies/actions; organization of a multi-stakeholder consensus to reach the agreement on main indicators to be used in Italy. Results: As for HPV vaccination coverage, the last Italian available data (December 31st, 2020) showed that it was way below the target (95%) with full cycle vaccination coverage ranging from 6 to 61.7% in female adolescents and from 5.4 to 55.4% in male adolescents (2008 birth cohorts). The coverage rate of CC screening is variable with a range of 61.7-89.6%. Furthermore, coverage rates due to organized screening programs (excluding out-of-pocket screening) shows a range from 20.7 to 71.8%. The mapping of the Italian Regions highlighted an important regional heterogeneity in respect to organizational/operational issue of HPV vaccination and CC screening. Indicators for monitoring CC elimination strategies have been drawn from the Australian experience and distinguished by disease outcomes, vaccination coverage, screening participation and treatment uptake. The highest consensus was reached for the following indicators: CC incidence; detection of high-grade cervical disease; CC mortality; full cycle vaccination coverage; screening participation; high-grade cervical disease treatment rates; CC treatment rates. Conclusions: The assessment of the current status of CC elimination as overarching goal beyond the achievement of vaccine, screening and treatment targets represents the first step for the identification of interventions to be implemented to accelerate the path toward CC elimination. Based on this and following the WHO call, a value-based approach is proposed to untangle the full benefit of HPV-related cancers elimination strategies and identify priority and best practices.

The Economic and Fiscal Impact of Influenza Vaccination for Health Care Workers in Italy.

Influenza has a significant impact on the health care system and also on production and economic systems. Vaccinated health care workers (HCWs) are more likely to have improved productivity compared to unvaccinated workers. The study aim was to estimate the economic and fiscal impact of an influenza vaccination program for HCWs in Italy. We performed a cost analysis aimed to estimate the indirect costs (productivity losses due to working days lost) and the increase in tax revenues derived from the increase in vaccination coverage among HCWs. Assuming an incremental increase in vaccination coverage of 10% per year over a period of 5 years, total savings could be obtained in terms of a reduction in productivity losses equal to -€4,475,497.16 and an increase in tax revenues of €327,158.84. This revenue could be used to finance other health interventions. Our results are fundamental in view of the sustainability of health systems and of a value-based allocation of health resources. Therefore, a complete social perspective, including the fiscal impact of flu vaccination, should be adopted to assess the economic value of influenza vaccines. Currently, health policies based on the whole value of flu vaccination are needed.

Economic Aspects in the Management of Diabetic Macular Edema in Italy.

Background: Diabetic Macular Edema (DME) is the most common cause of vision loss in diabetic patients. Currently, the Vascular Endothelial Growth Factor inhibitors (anti-VEGFs) are used as the first line of DME treatment and corticosteroid implants are usually used as a second-line treatment. These implants are a safe and effective therapeutic option that can improve the quality of life of DME patients by reducing the intravitreal injections number. We determined the economic impact related to DME, also from the social perspective, and the consequences of the increased use of the dexamethasone implant. Methods: The analysis compares two scenarios: the first based on the current rate of recourse to the therapeutic alternatives available in the Italian healthcare setting (as is) and the second based on the assumption of an increased recourse to dexamethasone implants (to be). The results are expressed both in terms of the resource absorption associated with the two scenarios and in terms of the cost differential yielded by their comparison. Results: The increased use of the dexamethasone implant allows considerable savings in terms of healthcare professionals' time, follow-up and productivity lost by patients/caregivers. These savings would reduce healthcare costs for the management of DME patients in Italy by €2,058,238 in 5 years. Conclusions: To optimize the healthcare resources allocation, it is necessary to implement treatments that yield not only cost reductions but also a clinical benefit for patients. The dexamethasone implant use is an example of DME management that generates value for patients, health system and society.

Seasonal influenza in children: Costs for the health system and society in Europe.

BACKGROUND: Pediatric influenza causes significant morbidity annually, resulting in an increased economic burden. Therefore, we aimed to summarize existing literature regarding the costs of pediatric influenza in Europe, paying particular attention to the direct and indirect costs considered in the economic evaluations. Knowing health and social costs of childhood influenza is essential to support value-based health decisions to implement effective immunization strategies. METHODS: We searched three databases for articles published to September 3, 2021. Eligible studies were those reporting the economic burden of influenza in the pediatric and youth population in European countries written in English language. RESULTS: Overall, 2225 records were screened, and 9 articles were included. Costs estimates are different across countries and in the age groups considered. Direct costs per episode, whose major expense driver are hospitalizations and pediatric examinations, range from about €74 in Italy to €252 in Germany. Important variations are observed based on age, with the youngest group absorbing in some cases double the resources of the older ones such as (in Italy, in France and in Germany). Regarding indirect costs, workdays lost by parents resulted in higher costs for children <2 years and 2-5 years than those >5 years of age and their economic impact was variable reaching €251 per week in Germany. CONCLUSION: Evidence obtained in our review strengthened the awareness about the economic impact, in terms of direct and indirect costs, of pediatric influenza requiring, as a priority action in Europe, the implementation of influenza vaccination policies in this target population.

Peristomal Skin Complications in Ileostomy and Colostomy Patients: What We Need to Know from a Public Health Perspective.

BACKGROUND: Peristomal skin complications (PSCs) are the most common skin problems seen after ostomy surgery. They have a considerable impact on a patient's quality of life and contribute to a higher cost of care. METHODS: A systematic review was conducted, querying three databases. The analysis was performed on international studies focused on the clinical-epidemiological burden of PSCs in adult patients with ileostomy/colostomy. RESULTS: Overall, 23 studies were considered. The main diseases associated with ostomy surgery were rectal, colon and gynecological cancers, inflammatory bowel diseases, diverticulitis, bowel obstruction and intestinal perforation. Erythema, papules, skin erosions, ulcers and vesicles were the most common PSCs for patients with an ostomy (or stoma). A PSCs incidence ranging from 36.3% to 73.4% was described. Skin complications increased length of stay (LOS) and rates of readmission within 120 days of surgery. CONCLUSIONS: PSCs data are still limited. A knowledge of their burden is essential to support health personnel and decision-makers in identifying the most appropriate responses to patients' needs. Proper management of these complications plays a fundamental role in improving the patient's quality of life. A multidisciplinary approach, as well as increased patient education and their empowerment, are priority measures to be implemented to foster a value-based healthcare.

HPV Vaccination in Women Treated for Cervical Intraepithelial Neoplasia: A Budget Impact Analysis.

Human Papillomavirus (HPV) is the most common sexually transmitted infection. Its progression is related to the development of malignant lesions, particularly cervical intraepithelial neoplasias (CINs). CINs correlate with a higher risk of premature births, and their excisional and ablative treatment further increases this risk in pregnant women. These complications are also correlated with higher healthcare costs for their management. In Italy, more than 26,000 new cases of CINs are estimated to occur yearly and their economic burden is significant. Therefore, the management of these conditions is a public health priority. Since HPV vaccination is associated with a reduced risk of relapse in women surgically treated for HPV-related injuries, we estimated the economic impact of extending HPV vaccination to this target population. This strategy would result in a significant reduction in the general costs of managing these women, resulting in an overall saving for the Italian Health Service of €155,596.38 in 5 years. This lower cost is due not only to the reduced incidence of CINs following vaccination, but also to the lower occurrence of preterm births. Extending HPV vaccination to this target population as part of a care path to be offered to women treated for HPV injuries is therefore desirable.

Control of Probe Density at DNA Biosensor Surfaces Using Poly(l-lysine) with Appended Reactive Groups.

Biosensors and materials for biomedical applications generally require chemical functionalization to bestow their surfaces with desired properties, such as specific molecular recognition and antifouling properties. The use of modified poly(l-lysine) (PLL) polymers with appended oligo(ethylene glycol) (OEG) and thiol-reactive maleimide (Mal) moieties (PLL-OEG-Mal) offers control over the presentation of functional groups. These reactive groups can readily be conjugated to, for example, probes for DNA detection. Here we demonstrate the reliable conjugation of thiol-functionalized peptide nucleic acid (PNA) probes onto predeposited layers of PLL-OEG-Mal and the control over their surface density in the preceding synthetic step of the PLL modification with Mal groups. By monitoring the quartz crystal microbalance (QCM) frequency shifts of the binding of complementary DNA versus the density of Mal moieties grafted to the PLL, a linear relationship between probe density and PLL grafting density was found. Cyclic voltammetry experiments using Methylene Blue-functionalized DNA were performed to establish the absolute probe density values at the biosensor surfaces. These data provided a density of 1.2 × 1012 probes per cm2 per % of grafted Mal, thus confirming the validity of the density control in the synthetic PLL modification step without the need of further surface characterization.

Patients treated with neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy in locally advanced cervical cancer: long-term outcomes, survival and prognostic factors in a single-center 10-year follow-up.

We report the long-term follow-up in patients with locally advanced cervical cancer treated with neoadjuvant chemotherapy (NACT) + radical surgery (RS) + adjuvant chemotherapy (ACT) analyzing prognostic factors which may more influence, in a long time, the survival outcome using univariate and multivariate analysis. In this study, we included all patients with diagnosis of locally advanced cervical cancer (IB2-IIB) treated with NACT + RS + ACT from June 2000 and February 2007 as previously described by Angioli et al. (Gynecol Oncol 127(2):290-6, 2012). The primary end-point of the study was overall survival (OS) in patients with node metastases and in those without positive lymph nodes at the end of 10-year follow-up in order to confirm the prognostic role of nodes involvement for a long period. Moreover, we analyzed the impact of other prognostic factors, such as histotype, tumor size, grading and parametrial invasion. Secondary end-point was evaluated in the subgroup of patients with positive nodes the following prognostic factors: number of positive lymph nodes and site of positive lymph nodes. In the subgroup of patients with positive nodes, the OS was 63 %, and in that with negative nodes, the OS was 75 %. On multivariate analysis, the number of nodal metastases, parametrial involvement, grading and the lesion diameter were noted to be significant factors in determining OS. Neither the histotype nor the lymph nodal site is related to survival. Results suggest that CT alone may be an alternative postoperative therapy for patients with cervical cancer.

Learning curves of a resident surgeon performing transobturator tape procedures for stress urinary incontinence.

OBJECTIVE: To evaluate the number of procedures necessary for an untrained resident surgeon to learn transobturator tension-free vaginal tape (TVT-O) procedures for treatment of stress urinary incontinence (SUI). METHODS: A prospective study was performed among patients aged 18-75 years who underwent TVT-O procedures at a center in Rome, Italy, between March 2, 2009, and November 30, 2012. The TVT-O procedure was performed by a right-handed resident surgeon working under the supervision of an expert surgeon. Total and partial operative times were recorded. RESULTS: Among 18 patients included in analysis, the mean operative time was 22.2minutes (range 7-44). All total operative times fell within the confidence interval after the 10th procedure, with a difference between the mean times recorded in the first nine and the last eight procedures (29.5 vs 13.1minutes; P<0.001). The resident surgeon required nine procedures to learn right tunneling and 13 to learn left tunneling. CONCLUSION: Ten procedures were required for a resident surgeon to learn TVT-O procedures for SUI.

Ten years of HPV vaccines: State of art and controversies.

The human papillomavirus (HPV) represents one of the most common sexually transmitted infections and it has been related to cervical cancer. The HPV vaccines prevent infection with certain species of HPV associated with the development of cervical cancer or genital warts. We carried out a PubMed search up to 2015 evaluating all randomized studies published in literature. This review discusses the current status of HPVs vaccines on the global market, efficacy, safety profiles, controversies and future vaccine developments. Three HPVs vaccines are currently on the global market: bivalent, quadrivalent and ninevalent. Bivalent and quadrivalent vaccines can protect against almost 70% of cervical HPV-related cancerous and precancerous conditions and the ninevalent vaccine, instead, provides a protection against almost 90%. The use of vaccinations raised several controversies in the last years and, currently, is not possible to establish which type of vaccine is most effective, however all of them are safe.

Nanocatalysis in Flow.

Nanocatalysis in flow is catalysis by metallic nanoparticles (NPs; 1-50 nm) performed in microstructured reactors. These catalytic processes make use of the enhanced catalytic activity and selectivity of NPs and fulfill the requirements of green chemistry. Anchoring catalytically active metal NPs within a microfluidic reactor enhances the reagent/catalyst interaction, while avoiding diffusion limitations experienced in classical approaches. Different strategies for supporting NPs are reviewed herein, namely, packed-bed reactors, monolithic flow-through reactors, wall catalysts, and a selection of novel approaches (NPs embedded on nanotubes, nanowires, catalytic membranes, and magnetic NPs). Through a number of catalytic reactions, such as hydrogenations, oxidations, and cross-coupling reactions, the advantages and possible drawbacks of each approach are illustrated.

The role of ovarian fossa evaluation in patients with ovarian endometriosis.

PURPOSE: The aim of this study is to evaluate prospectively the presence of endometriosis in the peritoneum of the ovarian fossa of patients affected by endometriomas and its correlation with the adhesion between this peritoneum and endometrioma. METHODS: Patients presenting ovarian endometriomas and candidate to laparoscopy were considered for inclusion in the study. Patients underwent laparoscopic excision of endometriomas. The presence of adherence of the ovarian fossa to endometrioma was investigated. In all patients, the removal of a peritoneum fragment from the ovarian fossa of the affected ovary was carried out. RESULTS: 68 patients were enrolled in the study. 48 patients presented adhesions to the ovarian fossa. Histopathologic examination of the peritoneum of the ovarian fossa revealed the presence of endometriosis in 87 % of patients presenting adhesions of the endometriomas with ovarian fossa; surprisingly it was present only in 15 % of patients not presenting this condition (p < 0.0001). Pain symptoms were more frequent in patients with endometriomas adhesion to the ovarian fossa. CA125 levels were not statistically significantly different between groups. At 12-month follow-up, four patients presented endometrioma recurrence. All of them presented adhesion of the ovarian fossa to the endometrioma in the first operation. CONCLUSIONS: There is a strong association between adhesion of the endometriomas to the ovarian fossa and the presence of endometriosis on the peritoneal surface of the fossa. This condition significantly correlates with pain symptoms and may predict endometrioma recurrence. The removal of this peritoneum in case of adherent endometrioma may potentially reduce the incidence of recurrence.

A Predictive Score for Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer (SeC-Score): A Single-Centre, Controlled Study for Preoperative Patient Selection.

BACKGROUND: The standard treatments of patients with platinum-sensitive recurrent ovarian cancer (ROC) remains poorly defined. Chemotherapy (CT) and secondary cytoreductive surgery (SCS) represent both valid options, even if several studies demonstrated a greater survival benefit, with survival rates up to 62 months, for platinum-sensitive patients undergoing complete SCS. The purpose of the present study was to develop a predictive model, named SeC-Score (SeC-s), to assess the risk of optimal SCS, including, for the first time in literature, HE4. METHODS: All patients affected by suspicious ROC at radiologic imaging, referred to the Department of Gynecology of Campus Bio-medico of Rome, were prospectively included in the study. The preoperative variables considered in our predictive model were: age, residual tumour (RT) at primary cytoreduction (0 vs. >0 cm), preoperative CA125 and HE4, and ascites at recurrence. After exploratory laparotomy, patients were submitted to secondary SCS (Group A) or addressed to CT (Group B). RESULTS: A total of 135 patients with ROC were considered for the analysis. Preoperative CA125, HE4, ascites, and RT at first surgery were found statistically significant and included into a multivariate logistic regression model to determine the risk to not optimal SCS. In the overall cohort of patients, SeC-s reported sensitivity and specificity of 82 and 83 %, respectively (PPV = 0.79, NPV = 0.81). CONCLUSIONS: Our data support the use of SeC-s to preoperative triage patients suitable of optimal SCS, even if external validation is needed.

Dendrimer-encapsulated Pd nanoparticles as catalysts for C-C cross-couplings in flow microreactors.

The inner walls of glass microreactors were functionalized with dendrimer-encapsulated Pd nanoparticles. The catalysts were efficient for the Heck-Cassar (copper-free Sonogashira) and Suzuki-Miyaura (SMC) cross-coupling reactions. For the Heck-Cassar reaction between iodobenzene and phenylacetylene, the catalytic system exhibited a high turnover frequency (TOF) and on average required milder reaction conditions as compared to other continuous flow cross-couplings. A study of the substituent effect of para-substituted aryl halides revealed a beneficial effect of electron-withdrawing side groups for the SMC. Moreover, a reaction constant (ρ) of 1.5, determined from the Hammett plot, indicated a possible rate-determining step other than the oxidative addition.

Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study.

This study aims to investigate the correlation between preoperative human epididymis protein 4 (HE4) levels, endometrial cancer (EC) staging, and ideal cutoff for stage prediction. All EC patients, treated within January 2009 and February 2014 at the Division of Gynaecologic Oncology of the University Campus Bio-Medico of Rome, were considered for the study. For the first part of the study, we consider an HE4 cutoff of 70 pmol/L. Histotypes (endometrioid versus non-endometrioid), grading (G1, G2, G3), and stage were correlated with HE4 levels. In the second part of the study, the logistic regression was performed in stepwise mood to identify the ideal HE4 cutoff for stage prediction. Two hundred thirty-two patients with surgically staged EC and preoperative HE4 dosage were included in the study. We found that higher HE4 levels correlate with undifferentiated grading (p < 0.05). Moreover, we found that 42, 77, 90, 93 and 100 % of patients classified as International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, II, III, and IV, respectively, presented HE4 levels above the standard cutoff of 70 pmol/L. Based on receiver operating characteristic (ROC) curves, we found the ideal HE4 cutoff as follows: 61.3 pmol/L for FIGO stage IA (sensitivity = 82.3 % and specificity = 96 %), 89.2 pmol/L for FIGO stage IB (sensitivity = 83.3 % and specificity = 96 %), 104.3 pmol/L for FIGO stage II (sensitivity = 80.9 % and specificity = 98.6 %), 152.6 pmol/L for FIGO stage III (sensitivity = 92.5 % and specificity = 98.6 %), and 203.8 pmol/L for FIGO stage IV (sensitivity = 81.8 % and specificity = 99.3 %). Our results suggest a potential role of HE4 in EC stage prediction.