Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial.

BACKGROUND: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP. METHODS: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions. RESULTS: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06-2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk. CONCLUSIONS: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

Non-Thyroidal Illness in Chronic Renal Failure: Triiodothyronine Levels and Modulation of Extra-Cellular Superoxide Dismutase (ec-SOD).

Oxidative stress (OS) is implicated in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyses the dismutation of superoxide anions with a protective role in endothelial cells. In chronic kidney disease (CKD), OS and thyroid dysfunction (low fT3 syndrome) are frequently present, but their relationship has not yet been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into "acute haemodialytic patients" (AH, 1-3 months of treatment) and "chronic haemodialytic patients" (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and its relationships with thyroid hormones. Two basal samples ("basal 1", obtained 3 days after the last dialysis; and "basal 2", obtained 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs. AH in all determinations. Moreover, the same patients had lower TAC values. When the CH patients were divided into two subgroups according to fT3 levels (normal or low), we found significantly lower ec-SOD values in the group with low fT3 in the basal, 5, and 10 min samples. A significant correlation was also observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low fT3 syndrome in patients with CKD, suggest that low fT3 concentrations can influence ec-SOD activity and could therefore potentially contribute to endothelial oxidative damage in these patients.

Protective effect of SARS-CoV-2 preventive measures against ESKAPE and Escherichia coli infections.

BACKGROUND/OBJECTIVES: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID-19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients. SUBJECTS/METHODS: We performed a single-center retrospective study in adult patients admitted to our COVID-19-free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID-19 period (June 1, 2020 - February 28, 2021) and in the corresponding pre-pandemic period (June 1, 2019 - February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders. RESULTS: Overall, 173 patients in the COVID-19 period and 132 in the pre-COVID-19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre-pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28-day hospital mortality were similar in the two groups. In comparison with the pre-pandemic period, no AB was recorded during COVID-19 period, (p = 0.017), while extended-spectrum beta-lactamase-producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug-resistant (p = 0.014). CONCLUSIONS: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID-19 free ICU might also restrain the transmission of ESKAPEEc pathogens.

Let-7a-5p, miR-100-5p, miR-101-3p, and miR-199a-3p Hyperexpression as Potential Predictive Biomarkers in Early Breast Cancer Patients.

BACKGROUND: The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: We retrospectively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system. RESULTS: Event-free survival (EFS) and overall survival (OS) were significantly higher in patients with up-regulation of let-7a-5p (EFS p = 0.006; OS p = 0.0001), mirR-100-5p (EFS s p = 0.01; OS p = 0.03), miR-101-3p (EFS p = 0.05; OS p = 0.01), and miR-199a-3p (EFS p = 0.02; OS p = 0.01) in post-NAC samples, independently from breast cancer subtypes. At multivariate analysis, only let-7a-5p was significantly associated with EFS (p = 0.009) and OS (p = 0.0008). CONCLUSION: Up-regulation of the above miRNAs could represent biomarkers in breast cancer.

Comparison of short- and long-term effectiveness of ixekizumab and secukinumab in real-world practice.

Background: Although secukinumab and ixekizumab both act by inhibiting IL-17A, some scientific evidence suggests that there are differences in efficacy between the two agents. Objective: The aim of this study was to compare the short- and long-term effectiveness of ixekizumab and secukinumab in clinical practice. Methods: A retrospective study was conducted on a cohort of 245 psoriatic patients receiving secukinumab or ixekizumab during the period from September 2016 to December 2019. The proportion of patients achieving PASI75, PASI90, and PASI100 at weeks 12 and 24 was calculated. We recorded the 12- and 24-month drug survival as a measure to assess long-term effectiveness. Results: A higher proportion of patients in the secukinumab group achieved PASI75, 90, and 100 at 12 weeks. The Kaplan-Meier survival curve for any reason of discontinuation showed no differences between the two groups. Instead, the multivariate analysis for ineffectiveness, adjusted for potential confounders, showed a lower drug survival rate in the secukinumab group, with an adjusted HR of 2.57 (95% CI 1.05-6.28, p 0.038). Conclusion: This real-life study demonstrated that ixekizumab and secukinumab are both highly effective in short- and long-term treatment of psoriasis, even though few differences exist concerning speed of action and long-term effectiveness.

Corrigendum to "Anabolic Hormone Deficiencies in Heart Failure with Reduced or Preserved Ejection Fraction and Correlation with Plasma Total Antioxidant Capacity".

[This corrects the article DOI: 10.1155/2020/5798146.].

Evaluation and cost estimation of laboratory test overuse in 43 commonly ordered parameters through a Computerized Clinical Decision Support System (CCDSS) in a large university hospital.

BACKGROUND: Computerized Clinical Decision Support Systems (CCDSS) have become increasingly important in ensuring patient safety and supporting all phases of clinical decision making. The aim of this study is to evaluate, through a CCDSS, the rate of the laboratory tests overuse and to estimate the cost of the inappropriate requests in a large university hospital. METHOD: In this observational study, hospital physicians submitted the examination requests for the inpatients through a Computerized Physician Order Entry. Violations of the rules in tests requests were intercepted and counted by a CCDSS, over a period of 20 months. Descriptive and inferential statistics (Student's t-test and ANOVA) were made. Finally, the monthly comprehensive cost of the laboratory tests was calculated. RESULTS: During the observation period a total of 5,716,370 requests were analyzed and 809,245 violations were counted. The global rate of overuse was 14.2% ± 3.0%. The most inappropriate exams were Alpha Fetoprotein (85.8% ± 30.5%), Chlamydia trachomatis Nucleic Acid Amplification (48.7% ± 8.8%) and Alkaline Phosphatase (20.3% ± 6.5%). The monthly cost of over-utilization was 56,534€ for basic panel, 14,421€ for coagulation, 4,758€ for microbiology, 432€ for immunology exams. All the exams, generated an estimated avoidable cost of 1,719,337€ (85,967€ per month) for the hospital. CONCLUSIONS: The study confirms the wide variability in over-utilization rates of laboratory tests. For these reasons, the real impact of inappropriateness is difficult to assess, but the generated costs for patients, hospitals and health systems are certainly high and not negligible. It would be desirable for international medical communities to produce a complete panel of prescriptive rules for all the most common laboratory exams that is useful not only to reduce costs, but also to ensure standardization and high-quality care.

Surgery-related complications and long-term functional morbidity after segmental colo-rectal resection for deep infiltrating endometriosis (ENDO-RESECT morb).

PURPOSE: Segmental resection has been generally associated with increased peri-operative risk of major complications. While major complications are widely acknowledged, minor complications, such as slight, to moderate infections, peripheral sensory disturbances, bladder voiding dysfunction, postoperative urinary obstruction, and sexual disorders are less reported. The aim of this study is to investigate the surgery-related complications and functional disorders, as well as to evaluate their persistence after long-term follow-up in women undergone segmental resection for deep infiltrating endometriosis. Special attention is given to evaluating impairments of bowel, bladder, and sexual function. METHODS: All clinical data obtained from medical records of women who underwent segmental resection for intestinal endometriosis between October 2005, and November 2017, in Catholic University Institutions. Perioperative morbidity was classified by Extended Clavien-Dindo classification. Postoperative intestinal, voiding, and sexual morbidity was estimated by the compilation of specific questionnaires. RESULTS: Fifty women were included in the study. Forty-three high colorectal resections (86%), 6 low resections (12%), and 1 ultra-low resection (2%) were performed, while in 3 cases (6%) multiple resections were needed. The overall complication rate was 44%. Nineteen women (38%) experienced early complications and 3 women (6%) late complications. Long-term functional postoperative complications were composed of intestinal in 30%, urinary in 50%, and sexual in 64% of the study population. Median follow-up was 55.5 months. CONCLUSIONS: Segmental resection, when indicated, offers a radical and feasible approach for bowel deep infiltrating endometriosis, resulting in an improved general quality of life. The bowel and bladder complications appear to be acceptable and often reversible. Postoperative sexual dysfunctions, such as anorgasmia and insufficient vaginal lubrication, appear to persist over time. Surgeons and women have to be aware of the incidence of this kind of complications.

Allogeneic cord blood transfusions prevent fetal haemoglobin depletion in preterm neonates. Results of the CB-TrIP study.

Repeated red blood cell (RBC) transfusions in preterm neonates are associated with poor outcome and increased risk for prematurity-associated diseases. RBC transfusions cause the progressive replacement of fetal haemoglobin (HbF) by adult haemoglobin (HbA). We monitored HbF levels in 25 preterm neonates until 36 weeks of post-menstrual age (PMA); patients received RBC units from allogeneic cord blood (cord-RBCs) or from adult donors (adult-RBCs), depending on whether cord-RBCs were available. Primary outcome was HbF level at PMA of 32 weeks. Twenty-three neonates survived until this age: 14 received no transfusions, two only cord-RBCs, three only adult-RBCs and four both RBC types. HbF levels in neonates transfused with cord-RBCs were significantly higher than in neonates receiving adult-RBCs (P < 0·0001) or both RBC types (P < 0·0001). Superimposable results were obtained at PMA of 36 weeks. Every adult-RBCs transfusion increased the risk for an HbF in the lowest quartile by about 10-fold, whereas this effect was not evident if combined adult- and cord-RBCs were evaluated. Overall, these data show that transfusing cord-RBCs can limit the HbF depletion caused by conventional RBC transfusions. Transfusing cord blood warrants investigation in randomised trials as a strategy to mitigate the severity of retinopathy of prematurity (NCT03764813).

Anabolic Hormone Deficiencies in Heart Failure with Reduced or Preserved Ejection Fraction and Correlation with Plasma Total Antioxidant Capacity.

BACKGROUND: While anabolic hormone deficit is a common finding in heart failure with reduced ejection fraction (HFrEF), few data are available in heart failure with preserved ejection fraction (HFpEF). METHODS: Blood samples were collected for metabolic (total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glucose) and hormonal (IGF-1, DHEA-S, TSH, fT3, fT4, and T) determination, comparing 30 patients with HFpEF and 20 patients with HFrEF. Total antioxidant capacity was evaluated by using the spectrophotometric method using the latency time in the appearance of the radical species of a chromogen (LAG, sec) as a parameter proportional to antioxidant content of the sample. Echocardiographic parameters were also assessed in the two groups. RESULTS: A high prevalence of testosterone (32% in HFrEF and 72% in HFpEF, p < 0.05) and DHEA-S deficiencies was observed in HFpEF patients. Echocardiographic parameters did not correlate with hormone values. A significant direct correlation between T (r 2 = 0.25, p < 0.05) and DHEA-S (r 2 = 0.19, p < 0.05) with LAG was observed only in HFpEF. CONCLUSION: Anabolic hormone deficiency is clearly shown in HFpEF, as already known in HFrEF. Although longitudinal studies are required to confirm the prognostic value of this observation, our data suggest different mechanisms in modulating antioxidants in the two conditions, with possible therapeutic implications.

Long-term evaluation of quality of life and gastrointestinal well-being after segmental colo-rectal resection for deep infiltrating endometriosis (ENDO-RESECT QoL).

PURPOSES: The primary objective is to assess the long-term quality of life (QoL) and gastrointestinal well-being in patients with endometriosis (DIE) who underwent segmental resection (SR), through specific questionnaires focused on endometriosis and specific gastrointestinal evaluation. The secondary objectives are represented by the evaluation of peri-operative and post-operative outcomes of the procedure. METHODS: This observational cohort study ENDO-RESECT (ClinicalTrials.gov ID: NCT03824054) reports all clinical data about women who underwent SR for DIE between October 2005 and November 2017. In the part of the study dedicated to the QoL assessment, the questionnaires adopted were the Endometriosis Health Profile (EHP30), the Psychological General Well-Being Index and the Hospital Anxiety and Depression Scale, the Gastrointestinal Well-being questionnaire and the Bristol Stool chart. Major post-surgical morbidity and obstetric outcomes were also collected. RESULTS: 50 women (18% stage III and 82% stage IV rAFS) were considered for enrollment. EHP-30 interpretation demonstrated a significant improvement in all continuous variables, except for fertility concerns. The overall gastrointestinal QoL and most of the specific symptoms improved after surgery. Frequent bowel movements appeared in the 13% of the series not resulting in an impairment of general and gastrointestinal QoL. Constipation remained unchanged. Patients with depressive mood managed with laparoscopy, benefited the most from SR; moreover, patients with multinodular bowel localizations experienced a greater reduction in abdominal pain. Median FU after SR was 42.5 months (range 12-157 months). Only three (6%) cases of late major grade III complications were documented. The pregnancy rate was 50%. CONCLUSIONS: Improvement of general QoL and most of gastrointestinal symptoms was documented after SR.

Characterization of Sarcopenia in an IBD Population Attending an Italian Gastroenterology Tertiary Center.

(1) Background: There is growing interest in the assessment of muscular mass in inflammatory bowel disease (IBD) as sarcopenia is associated with important outcomes. The aim of the study was to evaluate the percentage of sarcopenia in IBD patients, characterizing methods for assessment and clinical symptoms associated to it. (2) Methods: Consecutive IBD patients accessing the Fondazione Policlinico Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) were enrolled. Healthy patients, elderly or elderly sarcopenic patients, were enrolled as controls. Skeletal muscle mass was evaluated by Dual Energy X-ray Absorptiometry (DEXA) or Bio-Impedensometric Analysis (BIA). Asthenia degree was assessed by subjective visual analogue scales (VAS). Quality of life was measured by the EQ-5D questionnaire. (3) Results: Patients with IBD showed a significant reduction in skeletal muscle mass than healthy controls with lower DEXA and BIA parameters. Moreover, IBD patients presented a lower perception of muscle strength with a higher incidence of asthenia and reduction in quality of life when compared with healthy controls. A significant association between loss in skeletal muscle mass and high asthenia degree was found, configuring a condition of sarcopenia in about one third of patients with IBD. (4) Conclusions: Sarcopenia is common in IBD patients and it is associated with fatigue perception as well as a reduction in quality of life. Therefore, routine assessment of nutritional status and body composition should be a cornerstone in clinical practice, bringing gastroenterologists and nutritionists closer together for a compact, defined picture.

The benefits of a hospital palliative care team.

AIM: To investigate the association between a hospital palliative care unit assessment and hospital outcome. METHODS: This was a prospective cohort study. Data were assessed from all patients treated and followed by the hospital palliative care team (HPCT) from November 2016 until December 2017. RESULTS: The mean age of the 588 patients was 73.15±13.6 years. All of the patients included in the study were referred to palliative care. A large proportion of patients were affected by cancer, 69.7% (410), while 30.3% (178) were affected by an advanced chronic illness. The three most frequent cancers were: gastrointestinal (n=81, 19.8%), gynaecological (n=66, 16.1%) and lung (n=63, 15.4%); the three most frequent chronic advanced diseases were: advanced dementia (n=45, 25.3%), severe ischaemic/haemorrhagic stroke (n=36, 20.2%) and severe heart failure (n=25, 15.3%). The majority of patients were in clinical wards (n=476, 81.0%) and the average length of stay was 22.9 days. Hospital outcome trends were evaluated in terms of length of stay and number of deaths that occurred in the hospital. In particular, length of stay decreased from 25.8 days to 18.1 days, hospital death from 13 to 0 during the time that the HPCT assessed patients for an appropriate discharge. CONCLUSION: The HPCT is an effective means of managing patients affected by severe illness, reducing the number of deaths that occur within the hospital, long periods of hospitalisation and instances of readmission. However, further studies are required to fully assess the impact of an HPCT on hospital outcomes.

Postoperative respiratory failure in liver transplantation: Risk factors and effect on prognosis.

BACKGROUND: Postoperative respiratory failure (PRF, namely mechanical ventilation >48 hours) significantly affects morbidity and mortality in liver transplantation (LTx). Previous studies analyzed only one or two categories of PRF risk factors (preoperative, intraoperative or postoperative ones). The aims of this study were to identify PRF predictors, to assess the length of stay (LoS) in ICU and the 90-day survival according to the PRF in LTx patients. METHODS: Two classification approaches were used: systematic classification (recipient-related preoperative factors; intraoperative factors; logistic factors; donor factors; postoperative ICU factors; postoperative surgical factors) and patient/organ classification (patient-related general factors; native-liver factors; new-liver factors; kidney factors; heart factors; brain factors; lung factors). Two hundred adult non-acute patients were included. Missing analysis was performed. The competitive role of each factor was assessed. RESULTS: PRF occurred in 36.0% of cases. Among 28 significant PRF predictors at univariate analysis, 6 were excluded because of collinearity, 22 were investigated by ROC curves and by logistic regression analysis. Recipient age (OR = 1.05; p = 0.010), female sex (OR = 2.75; p = 0.018), Model for End-Stage Liver Disease (MELD, OR = 1.09; p<0.001), restrictive lung pattern (OR = 2.49; p = 0.027), intraoperative veno-venous bypass (VVBP, OR = 3.03; p = 0.008), pre-extubation PaCO2 (OR = 1.11; p = 0.003) and Model for Early Allograft Function (MEAF, OR = 1.37; p<0.001) resulted independent PRF risk factors. As compared to patients without PRF, the PRF-group had longer LoS (10 days IQR 7-18 versus 5 days IQR 4-7, respectively; p<0.001) and lower day-90 survival (86.0% versus 97.6% respectively, p<0.001). CONCLUSION: In conclusion, MELD, restrictive lung pattern, surgical complexity as captured by VVBP, pre-extubation PaCO2 and MEAF are the main predictors of PRF in non-acute LTx patients.

Circulating irisin levels in heart failure with preserved or reduced ejection fraction: A pilot study.

Irisin, a recently discovered myokine, has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in patients with heart failure (HF), both with preserved (HFpEF) or reduced (HFrEF) ejection fraction. We have therefore evaluated the circulating irisin levels in HFpEF and HFrEF patients, correlating them with metabolic parameters and total antioxidant capacity (TAC), as index of oxidative stress. Irisin was significantly higher in HFpEF than in HFrEF patients (7.72 ± 0.76 vs 2.77 ± 0.77 ng/ml, respectively). An inverse correlation between irisin and TAC was found in HFpEF, but not in HFrEF. Conversely, no correlation was present with HOMA index. These data support the hypothesis that a different pathophysiological mechanism is involved in the two HF subtypes, and oxidative stress modulates irisin secretion.

How Much do Needlestick Injuries Cost? A Systematic Review of the Economic Evaluations of Needlestick and Sharps Injuries Among Healthcare Personnel.

OBJECTIVE To provide an overview of the economic aspects of needlestick and sharps injury (NSI) management among healthcare personnel (HCP) within a Health Technology Assessment project to evaluate the impact of safety-engineered devices on health care METHODS A systematic review of economic analyses related to NSIs was performed in accordance with the PRISMA statement and by searching PubMed and Scopus databases (January 1997-February 2015). Mean costs were stratified by study approach (modeling or data driven) and type of cost (direct or indirect). Costs were evaluated using the CDC operative definition and converted to 2015 International US dollars (Int$). RESULTS A total of 14 studies were retrieved: 8 data-driven studies and 6 modeling studies. Among them, 11 studies provided direct and indirect costs and 3 studies provided only direct costs. The median of the means for aggregate (direct + indirect) costs was Int$747 (range, Int$199-Int$1,691). The medians of the means for disaggregated costs were Int$425 (range, Int$48-Int$1,516) for direct costs (9 studies) and Int$322 (range, Int$152-Int$413) for indirect costs (6 studies). When compared with data-driven studies, modeling studies had higher disaggregated and aggregated costs, but data-driven studies showed greater variability. Indirect costs were consistent between studies, mostly referring to lost productivity, while direct costs varied widely within and between studies according to source infectivity, HCP susceptibility, and post-exposure diagnostic and prophylactic protocols. Costs of treating infections were not included, and intangible costs could equal those associated with NSI medical evaluations. CONCLUSIONS NSIs generate significant direct, indirect, potential, and intangible costs, possibly increasing over time. Economic efforts directed at preventing occupational exposures and infections, including provision of safety-engineered devices, may be offset by the savings from a lower incidence of NSIs. Infect Control Hosp Epidemiol 2016;37:635-646.

From directive to practice: are pictorial warnings and plain packaging effective to reduce the tobacco addiction?

OBJECTIVES: Tobacco packaging represents an important form of promotion of tobacco products and for this reason plain packaging (PP) can be considered an additional tobacco control measure. In Italy the current tobacco packaging is branded with textual warnings. The study investigated the perception of PP with textual warnings (PPTWs) and pictorial warnings (PPPWs) in Italy. STUDY DESIGN: Cross-sectional. METHODS: The study was conducted on adults who were current, never and former smokers. The participants watched out three types of packages (current packaging, PPTWs and PPPWs) and eight pictorial warnings, and indicated which they considered the most effective ones to motivate smoking cessation or reduction and to prevent the onset. RESULTS: 1065 subjects were recruited. The PPPWs were considered the most effective in motivating to quit, reduce and prevent the smoking habits (ranged 83.4%-96.1%) in all tobacco users and age groups (≤40/>40 years) (P < 0.005). In general PP does not seem to be very effective in quitting for three-quarters of the smokers and 60% declared that they would have still started smoking with PP. The younger group believed less than the older one that PP gives a motivation to quit (29.4% vs 39.1%, P = 0.002). The pictures perceived as most effective in communicating the smoking effects were lung cancer and gangrene (about one-third of the sample). CONCLUSIONS: The textual warnings on tobacco products are a measure of control now outdated. Countries still using them should consider the idea of replace them with pictorial warnings that seem to be more effective. It is also desirable in the near future that these countries introduce the PPPWs.

Oxidative stress and metabolic syndrome: Effects of a natural antioxidants enriched diet on insulin resistance.

BACKGROUND & AIMS: Oxidative stress (OS) could play a role in metabolic syndrome-related manifestations contributing to insulin resistance (IR). The aim of the present study was to gain insight the relationships between OS, IR and other hormones involved in caloric balance, explaining the effects of a natural antioxidant-enriched diet in patients affected by metabolic syndrome. METHODS: We investigated the effects of dietary antioxidants on IR, studying 53 obese (20 males and 33 females, 18-66 years old, BMI 36.3 ± 5.5 kg/m2), with IR evaluated by Homeostasis Model Assessment (HOMA)-index, comparing 4 treatments: hypocaloric diet alone (group A) or plus metformin 1000 mg/daily (group B), natural antioxidants-enriched hypocaloric diet alone (group C) or plus metformin (group D). A personalized program, with calculated antioxidant intake of 800-1000 mg/daily, from fruit and vegetables, was administered to group C and D. The glycemic and insulinemic response to oral glucose load, and concentrations of total-, LDL- and HDL-cholesterol, triglycerides, uric acid, C reactive protein, fT3, fT4, TSH, insulin-like growth factor 1 were evaluated before and after 3-months. Plasma Total antioxidant capacity was determined by H2O2-metmyoglobin system, which interacting with the chromogen ABTS generates a radical with latency time (LAG) proportional to antioxidant content. RESULTS: Despite a similar BMI decrease, we found a significant decrease of HOMA and insulin peak only in group B and D. Insulin response (AUC) showed the greatest decrease in group D (25.60  ±  8.96%) and was significantly lower in group D vs B. No differences were observed in glucose response, lipid metabolism and TAC (expressed as LAG values). TSH values were significantly suppressed in group D vs B. CONCLUSIONS: These data suggest that dietary antioxidants ameliorate insulin-sensitivity in obese subjects with IR by enhancing the effect of insulin-sensitizing drugs albeit with molecular mechanisms which remain yet to be elucidated.

Health technology assessment of belimumab: a new monoclonal antibody for the treatment of systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is treated with anti-inflammatory and immunosuppressive drugs and off-label biologics. Belimumab is the first biologic approved after 50 years as an add-on therapy for active disease. This paper summarizes a health technology assessment performed in Italy. METHODS: SLE epidemiology and burden were assessed using the best published international and national evidences and efficacy and safety of belimumab were synthesized using clinical data. A cost-effectiveness analysis was performed by a lifetime microsimulation model comparing belimumab to standard of care (SoC). Organizational and ethical implications were discussed. RESULTS: Literature review showed that SLE affects 47 per 100,000 people for a total of 28,500 patients in Italy, 50% of whom are affected by active form of the disease despite SoC. These patients, if autoantibodies and anti-dsDNA positive with low complement, are eligible for belimumab. SLE determines work disability and a 2-5-fold increase in mortality. Belimumab with SoC may prevent 4,742 flares in three years being cost-effective with an incremental cost-effectiveness ratio of €32,859 per quality adjusted life year gained. From the organizational perspective, the development of clear and comprehensive clinical pathways is crucial. CONCLUSIONS: The assessment supports the use of belimumab into the SLE treatment paradigm in Italy.