Commentary to Wan et al. (2014): Estimating the standard deviation from the sample size and range or quartiles

This short note proposes two additive corrections to a pair of relations published in Wan et al. in order to extend them to a small sample size condition. In particular we focus the interest on the possibility to provide an estimate to the sample standard deviation when knowing only the sample size, the range and/or the quartiles. Our results allow to explicitely compute standard deviation, for instance with software R or any spreadsheet, for any sample size grater than 2. R codes and data are publicly available.Comment: 8 pages, 3 figure

Biostatistical tools in neurosciences

2010/2011In the present Ph.D. thesis main attention is focused in searching effective methods to improve the coupling of mechanical ventilators to critical care patients breath requirements, exploiting in a statistical framework the neural respiratory drive information. The first Chapter is devoted to offer an outlook, within the neuroscience perspective, on some relevant aspects of mechanical ventilation. Chapter starts recalling the neuroanatomy of human respiration, both in normal lung function and in respiratory disease condition. Consequently, the conventional mechanical ventilation methodology is briefly recalled, presenting also the risks associated to it, posing a particular accent on dyssynchronies which affect the correct interaction between the patient and the ventilator. The current technology of neural control of mechanical ventilation (NAVA) is therefore outlined, together with a review of the technical steps which have characterized its realization. Chapter ends stating the main aim of our Ph.D. research project about the possibility to exploit the random effects modelling in detecting ventilatory dyssynchronies. The second Chapter provides a complete description of the mixed-effects model capabilities in analysing neuroscience experiments, both in neurobiology and in cognitive/psychological sectors. The repeated measures and the longitudinal design experimental schemes are considered; current approaches in literature are discussed as well. The theory of the linear mixed model is illustrated by means of datasets of increasing complexity; the analysis is performed by means of the open source statistical package R. Datasets are mainly drawn from some of our co-authored papers. The third Chapter deals with the frailty models, inherent to random effects within time-to-event experimentations: after a brief recall on survival analysis, both theory and a worked example of frailty model are presented. In the fourth Chapter the limitations in applying mixed model techniques to the digital signal analysis are discussed, focusing also on some limitations still present in the available softwares. The result of our research, i.e. the Analyzer library written by means of Rcode, is presented in details and it is outlined how to import a NAVA Servo Tracker dataset into R, how to plot and how to summarize dataset information. Our Analyzer library represents the core of a machine learning software acting in the state-of-art Neuroscience-informed learning research field. A mixed model technique in analysing the NAVA signals is discussed and compared with an unpublished algorithm able to detect a widespread dyssynchrony known as 'ineffective expiratory effort' with an optimal reliability in terms of sensitivity and specificity. The algorithm is supported also by a mathematical proof, completely discussed in an Appendix of the thesis. The volume ends drawing some conclusions and prompting the path of further researches.XXIII Cicl

Effects of the combined action of a desensitizing gel and toothpaste on dentin hypersensitivity due to dental bleaching

Objectives: The present study is aimed at evaluating the effectiveness of a fluoride- and potassium nitrate-containing gel and toothpaste in reducing dentinal hypersensitivity due to dental bleaching. Materials and methods: Specific inclusion and exclusion criteria were used to recruit patients for the study. They were randomly allocated to a test or a placebo control group. Patients underwent a treatment of home dental bleaching with 10% carbamide peroxide. Dental shades were evaluated in a standardized environment and dentinal hypersensitivity was valuated by means of evaporation stimuli. A nominal scale was used to score the painful reaction. The patients were recalled 8, 15 and 28 days after the baseline for both shade and sensitivity assessment. Statistical analysis was performed using the Student’s T-test. Results: The patients recall rate was 96.9%. The statistical analysis demonstrated a significant reduction of the painful symptoms in the experimental group (p=0.031) while no statistically significant differences were evidenced in the control group at any follow-up recall (p>0.05). Discussion: The tested agents proved to be safe and effective in the short term. Neither pigmentations nor interferences with the bleaching action of peroxides due to the desensitizing agents were observed. The compliance of the patients to the proposed protocol as well as the motivation to maintain good oral hygiene were paramount in the achievement of the reported results. Conclusions: The use of a desensitizing gel and toothpaste containing fluoride and potassium nitrate was effective in reducing dentinal hypersensitivity due to dental bleaching and did not interfere with the bleaching action of peroxides. Clinical significance: Desensitizing gels and toothpastes containing fluoride and potassium nitrate can be considered safe and effective in the control of tooth sensitivity after dental bleaching

LONG-TERM INTRAOCULAR PRESSURE AFTER UNCOMPLICATED PARS PLANA VITRECTOMY FOR IDIOPATHIC EPIRETINAL MEMBRANE

\u2019Purrpose: To investigate long-term intraocular pressure trends after uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane. Methods: Three hundred and sixty-eight eyes of 368 consecutive patients were enrolled. Changes in intraocular pressure 1, 3, 6, and 12 months after surgery and during the fi nal follow-up visit were evaluated in vitrectomized eyes and nonvitrectomized fellow eyes. Results: The median follow-up period was 36 months (range 12 \u2013 92 months). Longitudinal data analysis evidenced a 2.5-mmHg (2.2 mmHg; 2.7 mmHg, 95% con fi dence interval) statis- tically signi fi cant difference in intraocular pressure 30 days after surgery between treated and fellow untreated eyes, gradually recovering to a not signi fi cant 0.2-mmHg ( 2 0.1 mmHg; 0.4 mmHg, 95% con fi dence interval) difference within 26 months. The incidence of late-onset ocular hypertension was 5.7% (21 over 347, 2%; 12%, 95% con fi dence interval) without difference between the treated eyes and the group control. No signi fi cant difference in the incidence of late-onset ocular hypertension and sex, lens status, or gauge of vitrectomy instru- ments was detected. Only patient \u2019 sagewassigni fi cantly higher (mean difference 4.2 years; 0.1 \u2013 8.0 years, Monte Carlo, 95% con fi dence interval) in those who de veloped late-onset ocular hypertension in the vitrectomized eye. Conclusion: Uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane seems not to increase the risk of late-onset ocular hypertension or open-angle glaucoma development.

Early Short-Term Application of High-Frequency Percussive Ventilation Improves Gas Exchange in Hypoxemic Patients

Background: Hypoxemia in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients represents a common finding in the intensive care unit (ICU) and frequently does not respond to standard ventilatory techniques. Objective: To study whether the early short-term application of high-frequency percussive ventilation (HFPV) can improve gas exchange in hypoxemic patients with ALI/ARDS or many other conditions in comparison to conventional ventilation (CV) using the same mean airway pressure (Paw), representing the main determinant of oxygenation and hemodynamics, irrespective of the mode of ventilation. Methods: Thirty-five patients not responding to CV were studied. During the first 12 h after admission to the ICU the patients underwent CV. Thereafter HFPV was applied for 12 h with Paw kept constant. They were then returned to CV. Gas exchange was measured at: 12 h after admission, every 4 h during the HFPV trial, 1 h after the end of HFPV, and 12 h after HFPV. Thirty-five matched patients ventilated with CV served as the control group (CTRL). Results: Pao2/Fio2 and the arterial alveolar ratio (a/A Po2) increased during HFPV treatment and a Pao2/Fio2 steady state was reached during the last 12 h of CV, whereas both did not change in CTRL. Paco2 decreased during the first 4 h of HFPV, but thereafter it remained unaltered; Paco2 did not vary in CTRL. Respiratory system compliance increased after HFPV. Conclusions: HFPV improved gas exchange in patients who did not respond to conventional treatment. This improvement remained unaltered until 12 h after the end of HFPV

N-Glycomic changes in serum proteins in type 2 diabetes mellitus correlate with complications and with metabolic syndrome parameters

Background: Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome. Methods: We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6 +/- 8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5 +/- 12.4 years). N-glycome was evaluated in serum glycoproteins. Results: We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, alpha(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6) A2F. In addition, NG1(6) A2F and NG1(3) A2F, identifying, respectively, monogalactosylated N-glycans with alpha(1,6)- and alpha(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme "unhealthy" phenotype (T2DM+ with MS). Conclusions: Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS

The impact of COVID-19 on myocardial infarctions, strokes and out-of-hospital cardiopulmonary arrests: an observational retrospective study on time-sensitive disorders in the Friuli Venezia Giulia region (Italy)

The COVID-19 global pandemic has changed considerably the way time-sensitive disorders are treated. Home isolation, people's fear of contracting the virus and hospital reorganisation have led to a significant decrease in contacts between citizens and the healthcare system, with an expected decrease in calls to the Emergency Medical Services (EMS) of the Friuli-Venezia Giulia (FVG) region. However, mortality in clinical emergencies like acute ST-elevation myocardial infarction (STEMI), stroke and out-of-hospital cardiopulmonary arrest (OHCA) remained high. An observational retrospective cross-sectional study was carried out in FVG, taking into account the period between March 1, 2020, and May 31, 2020, the first wave of the COVID-19 pandemic, and comparing it with the same period in 2019. The flow of calls to the EMS was analysed and COVID-19 impact on time-sensitive disorders (STEMIs, ischemic strokes and OHCPAs) was measured in terms of hospitalisation, treatment and mortality. Despite a -8.01% decrease (p value ˂0.001) in emergency response, a 10.89% increase in calls to the EMS was observed. A lower number of advanced cardiopulmonary resuscitations (CPR) (75.8 vs 45.2%, p=0.000021 in April) and ROSC (39.1 vs 11.6%, p=0.0001 in April) was remarked, and survival rate dropped from 8.5 to 5%. There were less strokes (-27.5%, p value=0.002) despite a more severe onset of symptoms at hospitalisation with NHISS˃10 in 38.47% of cases. Acute myocardial infarctions decreased as well (-20%, p value=0.05), but statistical significances were not determined in the variables considered and in mortality. Despite a lower number of emergency responses, the number of calls to the EMS was considerably higher. The number of cardiac arrests treated with advanced CPR (ALS) was lower, but mortality was higher. The number of strokes decreased as well, but at the time of hospitalisation the clinical picture of the patient was more severe, thus affecting the outcome when the patient was discharged. Finally, STEMI patients decreased; however, no critical issues were observed in the variables taken into account, neither in terms of response times nor in terms of treatment times

Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO

PURPOSE To verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC).METHODS TRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable RAS and BRAF wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.1. Hypothesizing an ORR of 60% in the control group, 432 cases provided 90% power to a two-sided chi-square test for heterogeneity with a two-sided alpha error of .05 to detect &gt;= 15% differences between arms (ClinicalTrials.gov identifier: NCT03231722).RESULTS From September 2017 to September 2021, 435 patients were enrolled (control group/experimental group: 217/218) in 57 Italian sites. One hundred sixty (73%) patients treated with mFOLFOXIRI plus panitumumab and 165 (76%) patients treated with modified FOLFOX plus panitumumab achieved RECIST response (odds ratio 0.87, 95% CI, 0.56 to 1.34, P= .526). No differences in early tumor shrinkage rate (57%/58%, P = .878) and deepness of response (median: 48%/47%, P = .845) were reported, nor in RO resection rate (25%/29%, P = .317). No significant difference between arms was reported in terms of progression-free survival (median progression-free survival: 12.7 in the experimental group v 12.3 months in the control group, hazard ratio: 0.88, 95% CI, 0.70 to 1.11, P = .277).CONCLUSION The intensification of the upfront chemotherapy backbone in combination with panitumumab does not provide additional benefit in terms of treatment activity at the price of increased gastrointestinal toxicity in patients with RAS and BRAF wt mCRC. (C) 2022 by American Society of Clinical Oncolog

Colorectal neoplastic emergencies in immunocompromised patients: preliminary result from the Web-based International Register of Emergency Surgery and Trauma (WIRES-T trial)

Association of advanced age, neoplastic disease and immunocompromission (IC) may lead to surgical emergencies. Few data exist about this topic. Present study reports the preliminary data from the WIRES-T trial about patients managed for colorectal neoplastic emergencies in immunocompromised patients. The required data were taken from a prospective observational international register. The study was approved by the Ethical Committee with approval n. 17575; ClinicalTrials.gov Identifier: NCT03643718. 839 patients were collected; 753 (80.7%) with mild-moderate IC and 86 (10.3%) with severe. Median age was 71.9 years and 73 years, respectively, in the two groups. The causes of mild-moderate IC were reported such malignancy (753-100%), diabetes (103-13.7%), malnutrition (26-3.5%) and uremia (1-0.1%), while severe IC causes were steroids treatment (14-16.3%); neutropenia (7-8.1%), malignancy on chemotherapy (71-82.6%). Preoperative risk classification were reported as follow: mild-moderate: ASA 1-14 (1.9%); ASA 2-202 (26.8%); ASA 3-341 (45.3%); ASA 4-84 (11.2%); ASA 5-7 (0.9%); severe group: ASA 1-1 patient (1.2%); ASA 2-16 patients (18.6%); ASA 3-41 patients (47.7%); ASA 4-19 patients (22.1%); ASA 5-3 patients (3.5%); lastly, ASA score was unavailable for 105 cases (13.9%) in mild-moderate group and in 6 cases (6.9%) in severe group. All the patients enrolled underwent urgent/emergency surgery Damage control approach with open abdomen was adopted in 18 patients. Mortality was 5.1% and 12.8%, respectively, in mild-moderate and severe groups. Long-term survival data: in mild-moderate disease-free survival (median, IQR) is 28 (10-91) and in severe IC, it is 21 (10-94). Overall survival (median, IQR) is 44 (18-99) and 26 (20-90) in mild-moderate and severe, respectively; the same is for post-progression survival (median, IQR) 29 (16-81) and 28, respectively. Univariate and multivariate analyses showed as the only factor influencing mortality in mild-moderate and severe IC is the ASA score. Colorectal neoplastic emergencies in immunocompromised patients are more frequent in elderly. Sigmoid and right colon are the most involved. Emergency surgery is at higher risk of complication and mortality; however, management in dedicated emergency surgery units is necessary to reduce disease burden and to optimize results by combining oncological and acute care principles. This approach may improve outcomes to obtain clinical advantages for patients like those observed in elective scenario. Lastly, damage control approach seems feasible and safe in selected patients