Radiology-based outcomes, such as progression-free survival (PFS) and objective response rate (ORR), are used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship ...of PFS with overall survival (OS) in clinical trials of systemic therapies targeting advanced hepatocellular carcinoma (HCC) by novel meta-regression methods.
A search of databases (PubMed, American Society of Clinical Oncology (ASCO), and European Society for Medical Oncology (ESMO) Meeting Libraries, Clinicaltrials.gov) for trials of systemic therapies for advanced HCC reporting both OS and PFS was performed. Individual patient data were extracted from PFS and OS Kaplan-Meier curves. Summary median PFS and OS data were obtained from random-effect model. The surrogate relationships of median PFS, first quartile (Q1), third quartile (Q3), and restricted mean survival time (RMST) for OS were evaluated by the coefficient of determination R
. Heterogeneity was explored by meta-regression.
We identified 49 trials, 11 assessing immune-checkpoint inhibitors (ICIs) and 38 multikinase inhibitors (MKIs). Overall, the correlation between median PFS and median OS was weak (R
= 0.20. 95% Confidence Intervals CI-0.02;0.42). Surrogacy robustness varied between treatment classes and PFS endpoints. In ICI trials only, the correlations between Q1-PFS and Q1-OS and between 12-month PFS-RMST and 12-month OS-RMST were high (R
= 0.89, 95%CI 0.78-0.98, and 0.80, 95% CI 0.63-0.96, respectively). Interaction
-values obtained by meta-regression confirmed the robustness of results.
In trials of systemic therapies for advanced HCC, the surrogate relationship of PFS with OS is highly variable depending on treatment class (ICI or MKI) and evaluation time-point. In ICI trials, Q1-PFS and 12-month PFS-RMST are robust surrogate endpoints for OS.
Purpose
To investigate the feasibility of an artificial intelligence (AI)-based semi-automated segmentation for the extraction of ultrasound (US)-derived radiomics features in the characterization of ...focal breast lesions (FBLs).
Material and methods
Two expert radiologists classified according to US BI-RADS criteria 352 FBLs detected in 352 patients (237 at Center A and 115 at Center B). An AI-based semi-automated segmentation was used to build a machine learning (ML) model on the basis of B-mode US of 237 images (center A) and then validated on an external cohort of B-mode US images of 115 patients (Center B).
Results
A total of 202 of 352 (57.4%) FBLs were benign, and 150 of 352 (42.6%) were malignant. The AI-based semi-automated segmentation achieved a success rate of 95.7% for one reviewer and 96% for the other, without significant difference (
p
= 0.839). A total of 15 (4.3%) and 14 (4%) of 352 semi-automated segmentations were not accepted due to posterior acoustic shadowing at B-Mode US and 13 and 10 of them corresponded to malignant lesions, respectively. In the validation cohort, the characterization made by the expert radiologist yielded values of sensitivity, specificity, PPV and NPV of 0.933, 0.9, 0.857, 0.955, respectively. The ML model obtained values of sensitivity, specificity, PPV and NPV of 0.544, 0.6, 0.416, 0.628, respectively. The combined assessment of radiologists and ML model yielded values of sensitivity, specificity, PPV and NPV of 0.756, 0.928, 0.872, 0.855, respectively.
Conclusion
AI-based semi-automated segmentation is feasible, allowing an instantaneous and reproducible extraction of US-derived radiomics features of FBLs. The combination of radiomics and US BI-RADS classification led to a potential decrease of unnecessary biopsy but at the expense of a not negligible increase of potentially missed cancers.
Background: An optimal sequential systemic therapy for advanced hepatocellular carcinoma (HCC) has not been discovered. We developed a decision model based on available clinical trials to identify an ...optimal risk/benefit strategy for sequences of novel systemic agents. Methods: A Markov model was built to simulate overall survival (OS) among patients with advanced HCC. Three first-line (single-agent Sorafenib or Lenvatinib, and combination of Atezolizumab plus Bevacizumab) followed by five second-line treatments (Regorafenib, Cabozantinib, Ramucirumab, Nivolumab, Pembrolizumab) were compared in fifteen sequential strategies. The likelihood of transition between states (initial treatment, cancer progression, death) was derived from clinical trials. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥grade 3) were calculated. The innovative measure, called incremental safety-effectiveness ratio (ISER), of the two best sequential treatments was calculated as the difference in probability of SAEs divided by LYG. Results: Lenvatinib followed by Nivolumab (median OS, 27 months) was the most effective sequence, producing a LYG of 0.75, while Atezolizumab plus Bevacizumab followed by Nivolumab was the safest sequence (SAEs 40%). Accordingly, the net health benefit assessed by ISER favored Lenvatinib followed by Nivolumab, compared to Atezolizumab plus Bevacizumab, followed by Nivolumab in 52% of cases. Conclusion: Further sequential clinical trials or large-scale real-world studies may prove useful to evaluate the net health benefit of the best sequential treatment for advanced HCC.
: Reinfections occur as a response to natural infections wanes and novel strains of SARS-CoV-2 emerge. The present research explored the correlation between sex, age, COVID-19 vaccination, prior ...infection hospitalization, and SARS-CoV-2 reinfection in Sicily, Italy.
: A population-based retrospective cohort study was articulated using the vaccination flux from a regional registry and the Sicilian COVID-19 monitoring system of the Italian Institute of Health. Only adult Sicilians were included in the study, and hazard ratios were calculated using Cox regression.
: Partial vaccination provided some protection (adj-HR: 0.92), when compared to unvaccinated individuals; furthermore, reinfection risk was reduced by full vaccination (adj-HR: 0.43), and the booster dose (adj-HR: 0.41). Males had a lower risk than females of reinfection with SARS-CoV-2 (adj-HR: 0.75). Reinfection with SARS-CoV-2 was diminished by hospitalization during the first infection (adj-HR: 0.78). Reinfection risk was higher among those aged 30-39 and 40-49 compared to those aged 18-29, whereas those aged 60-69, 70-79, and 80+ were statistically protected. Reinfection was significantly more frequent during the wild-type-Alpha, Delta, Delta-Omicron, and Omicron dominance/codominance waves compared to the wild type.
: This study establishes a solid base for comprehending the reinfection phenomenon in Sicily by pinpointing the most urgent policy hurdles and identifying some of the major factors. COVID-19 vaccination, one of the most effective public health tools, protects against reinfection, mostly caused by the Omicron strain. Elderly and hospitalized people's lower risk suggests stricter PPE use.
Background
To assess inter-reader agreement for US BI-RADS descriptors using S-Detect: a computer-guided decision-making software assisting in US morphologic analysis.
Methods
73 solid focal breast ...lesions (FBLs) (mean size: 15.9 mm) in 73 consecutive women (mean age: 51 years) detected at US were randomly and independently assessed according to the BI-RADS US lexicon, without and with S-Detect, by five independent reviewers. US-guided core-biopsy and 24-month follow-up were considered as standard of reference. Kappa statistics were calculated to assess inter-operator agreement, between the baseline and after S-Detect evaluation. Agreement was graded as poor (≤ 0.20), moderate (0.21–0.40), fair (0.41–0.60), good (0.61–0.80), or very good (0.81–1.00).
Results
33/73 (45.2%) FBLs were malignant and 40/73 (54.8%) FBLs were benign. A statistically significant improvement of inter-reader agreement from fair to good with the use of S-Detect was observed for shape (from 0.421 to 0.612) and orientation (from 0.417 to 0.7) (
p
< 0.0001) and from moderate to fair for margin (from 0.204 to 0.482) and posterior features (from 0.286 to 0.522) (
p
< 0.0001). At baseline analysis isoechoic (0.0485) and heterogeneous (0.1978) echo pattern, microlobulated (0.1161) angular (0.1204) and spiculated (0.1692) margins and combined pattern (0.1549) for posterior features showed the worst agreement rate (poor). After S-Detect evaluation, all variables but isoechoic pattern showed an agreement class upgrade with a statistically significant improvement of inter-reader agreement (
p
< 0.0001).
Conclusions
S-Detect significantly improved inter-reader agreement in the assessment of FBLs according to the BI-RADS US lexicon but evaluation of margin and echo pattern needs to be further improved, particularly isoechoic pattern.
Introduction
Clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in old adults from Southern Italy is little known. This study aims to investigate the ...mortality risk related to risk factors, therapy and clinical course and to suggest prognostic indicators based on day-to-day follow-up of clinical and laboratory findings.
Material and methods
It was designed as a retrospective longitudinal cohort study of adult SARS-CoV-2 patients admitted at Partinico COVID Hospital in Palermo, Southern Italy. Patients were recruited between 4 March and 25 April and followed up until 31 May 2020, day-to-day until death or hospital discharge. Clinical data, laboratory tests and treatment data were extracted from medical records and epidemiologic information was obtained by clinical history and the medical interview.
Results
Forty-seven patients (median age = 75 IQR: 59.50–86.00) were followed up during a 87 days observation period, accounting for a total of 1,035 person days. At the end of follow-up, 28 (60%) patients were discharged and 19 (40%) died, so that the estimated incidence density rate was 0.018 deaths per day (18 SARS-CoV-2-related deaths per 1,000 patient days). Diabetes (HR = 8.13, 95% CI: 1.91–34.67), chronic kidney failure (HR = 5.86, 95% CI: 1.36–25.21), dementia (HR = 7.84, 95% CI: 1.80–34.20), and neutrophil/lymphocyte ratio > 7 (HR = 10.37, 95% CI: 2.24–48.14) were found as significant prognostic factors.
Conclusions
The joint evaluation of dementia, diabetes, chronic kidney failure and neutrophil/lymphocyte ratio showed an optimal prognostic value already in the first week of follow-up. The day-to-day follow-up provides essential information for clinical monitoring and treatment of the disease in a hospital setting and improves the disease’s home management, especially for older patients with frailty.
With the ageing population, equitable access to medical care has proven to be paramount for the effective and efficient management of all diseases. Healthcare access can be hindered by cost barriers ...for drugs or exams, long waiting lists or difficult access to the place where the needed healthcare service is provided. The aim of this paper is to investigate whether the probability of facing one of these barriers varies among individuals with different socio-economic status and care needs, controlling for geographical variability.
The sample for this study included 9629 interviews with Italian individuals, aged 15 and over, from the second wave (2015) of the European Health Interview Survey, which was conducted in all EU Member States. To model barriers to healthcare, two-level variance components of logistic regression models with a nested structure given by the four Italian macro-areas were considered.
Of the barriers considered in this study, only two were found to be significantly associated with healthcare utilization. Specifically, they are long waiting lists for specialist service accessibility (adjOR = 1.20, 95% CI (1.07; 1.35)) and very expensive exams for dental visit accessibility (adjOR = 0.84, 95% CI (0.73; 0.96)). Another important result was the evidence of an increasing north-south gradient for all of the considered barriers.
In Italy, healthcare access is generally guaranteed for all of the services, except for specialist and dental visits that face a waiting time and financial barriers. However, barriers to healthcare were differentiated by income and sex. The north-south gradient for healthcare utilization could be explained through the existing differences in organizational characteristics of the several regional healthcare services throughout Italy.
Obstructive sleep apnoea syndrome (OSAS) is the most severe condition on the spectrum of sleep-related breathing disorders (SRBDs). The Paediatric Sleep Questionnaire (PSQ) is one of the most used ...and validated screening tools, but it lacks the comprehensive assessment of some determinants of OSAS, specifically anamnestic assessment and sleep quality. This study aims to assess the accuracy of some specific items added to the original PSQ, particularly related to the patient’s anamnestic history and to the quality of sleep, for the screening of OSAS in a paediatric population living in Sicily (Italy). Fifteen specific items, divided into “anamnestic” and “related to sleep quality” were added to the original PSQ. The whole questionnaire was administered via a digital form to the parents of children at 4 schools (age range: 3–13 years). For each item, sensitivity and specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated. The highest sensitivity (80.0, 95% CI: 28.4; 99.5), in combination with the highest specificity (61.1, 95% CI: 35.7; 82.7), was found for the Item 32 (“assumption of bizarre or abnormal positions during sleep”). This item was found statistically significant for predicting the occurrence of OSAS in children (p-value ≤0.003). The study demonstrates the accuracy of specific items related to sleep quality disturbance for the preliminary assessment of the disease. Although these results should be validated on a larger sample of subjects, they suggest that including the factors discriminating sleep quality could further increase the efficiency and accuracy of PSQ.
Methicillin resistant Staphylococcus aureus (MRSA) is a major etiological agent of infection in neonatal intensive care units (NICUs). Routes of entry of this organism can be different and the ...transmission pathway complex. Colonized neonates are the main endogenous reservoir.
We conducted a prospective three-year study on MRSA colonization recruiting 722 neonates admitted between 2009 and 2012. Nasal swabs were cultured weekly and MRSA isolates were submitted to molecular typing. The annual incidence density of acquisition of MRSA ranged from a maximum of 20.2 cases for 1000 patient-days during the first year to a minimum of 8.8 cases in the second one to raise again up to 13.1 cases during the third year. The mean weekly colonization pressure fluctuated from 19.1% in the first year to 13.4% in the second year and 16.8% in the third year. It significantly correlated with the number of MRSA acquisitions in the following week. Overall, 187 (25.9%) subjects tested positive for MRSA. A non multiresistant, tst positive, ST22-MRSA-IVa spa t223 strain proved to be endemic in the NICU, being identified in 166 (88.8%) out of 187 colonized neonates. Sporadic or epidemic occurrence of other strains was detected.
An MRSA strain belonging to the tst1 positive, UK-EMRSA-15/ "Middle Eastern Variant" appeared to be endemic in the NICU under investigation. During the three-year period, substantial changes occurred in case-mix of patients moving towards a higher susceptibility to MRSA colonization. The infection control procedures were able to decrease the colonization rate from more than 40% to approximately 10%, except for an outbreak due to a CA-MRSA strain, ST1-MRSA-IVa, and a transient increase in the colonization prevalence rate coincident with a period of substantial overcrowding of the ward. Active surveillance and molecular typing contributed to obtain a reliable picture of the MRSA dissemination in NICU.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The newly adopted European directive DE59/2013 mandates adequate patient information in procedures involving ionising radiation. Patient interest in knowing about their radiation dose and ...an effective communication method for dose exposure remain poorly investigated.
Purpose
This study is aimed at investigating both patient interest in radiation dose and an effective method to communicate radiation dose exposure.
Material and methods
The present analysis is based on a multi-centre cross-sectional data collection involving 1,084 patients from four different hospitals ‒ two general and two paediatric hospitals. Anonymous questionnaires were administered, consisting of an initial overview of radiation use in imaging procedures, a patient data section, and an explanatory section providing information in four modalities.
Results
1009 patients were included in the analysis, with 75 refusing participation; 173 participants were relatives of paediatric patients. Initial information provided to patients was considered comprehensible. The information modality with symbols was considered the most readily understandable format by patients, with no appreciable differences in comprehension attributable to social or cultural background. The modality including dose numbers and diagnostic reference levels was preferred by patients with higher socio-economic background. The option ‘None of those’ was selected by one-third of our sample population, composed of four different clusters: female, over 60 years old, unemployed, and from low socio-economic backgrounds.
Conclusions
This study demonstrated a high level of interest amongst patients in knowing about radiation dose exposure. Pictorial representations were well understood by patients from a variety of different ages and education levels. However, a universally comprehensible model of communicating radiation dose information remains to be elucidated.
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