European Network for Health Technology Assessment's Response to COVID-19: Rapid Collaborative Reviews on Diagnostic Tests and Rolling and Rapid Collaborative Reviews on Therapeutics.

OBJECTIVES: In spring 2020, The European network for Health Technology Assessment (EUnetHTA) decided to join forces to produce best evidence to inform health policy in the COVID-19 pandemic. The objective of this paper is to describe the process and output of the coordinated and collaborative activities of EUnetHTA. METHODS: Relevant published and internal documents were retrieved for a descriptive analysis of EUnetHTA processes, methods, and outputs related to EUnetHTA's response to the pandemic. RESULTS: Process: In April 2020, a COVID-19 task force was set up and a survey collected pressing health policy questions across Europe. Two coordinating agencies for diagnostic tests and therapeutics were assigned. A process for prioritization and selection was set up for therapeutics, as well as explicit starting and stopping rules. Methodology: To increase a timely response, it was agreed that the rapid collaborative reviews (rapid CRs) would not require the consultation of manufacturers and the involvement of external experts, but would not differ in the methods and conduct of the systematic search, review, and synthesis of all available evidence, nor in the requirement for reviewing by EUnetHTA partners. Final reports: The joint effort resulted in the production of two rapid CRs on diagnostic tests, nineteen collaborative rolling reviews on therapeutics, three of which later moved to rapid CRs. CONCLUSIONS: During COVID-19 pandemic, the EUnetHTA partners proved capable of prompt collaboration, which allowed speeding up the production and release of high-quality EUnetHTA outputs, while the relationships with the other European institutions facilitated their quick dissemination.

Synthesizing quantitative and qualitative information on multiple comparisons of health interventions to facilitate knowledge transfer: an example from an EUnetHTA multi-HTA.

OBJECTIVE: Presenting an approach to synthesize quantitative and qualitative information from systematic reviews of multiple health interventions. METHODS: Within the context of an EUnetHTA multi-health technology assessment of twenty-three surgical techniques, we developed synthetic single tables, using color gradients and abbreviations, with information on which technologies had been compared, estimates of the size of differences for available comparisons, their clinical relevance, and certainty of the related evidence. RESULTS: The proposed methodology provided, through a single depiction, information normally included in multiple figures/tables such as network plots, league tables, and summary of findings tables. CONCLUSION: Transferring information on benefits, risks, and certainty of the available evidence on health interventions may be challenging, especially when assessing multiple treatments: more pieces of information need to be integrated in order to show an overall picture for each of the chosen outcomes, and usual reporting tools may be targeted to researchers more than to different kinds of decision makers. While more in-depth layers of information can always be added to satisfy needs of different audiences, the proposed tools could favor a quick interpretation of articulated scientific data by both decision makers and researchers.

A COVID-19-Dedicated Facility for the Care of Older Adults During a Health Emergency: An Italian Experience.

Older adults living in long-term care facilities (LTCF) are particularly vulnerable to COVID-19. We describe the clinical characteristics, the course of disease, and the care needs of 38 non-self-sufficient adults with COVID-19 in an LTCF specially set up for those who could not be discharged home or to a standard LTCF. Residents spent an average of 30.5 days in the facility (range 4-77 days). Most of them recovered and were discharged home or to their LTCF of origin. It seems feasible to set up dedicated facilities to treat and provide assistance in the activities of daily living to older adults with COVID-19.

Are Individuals with Substance Use Disorders at Higher Risk of SARS-CoV-2 Infection? Population-Based Registry Study in Northern Italy.

BACKGROUND AND AIM: This study assesses whether individuals with substance use disorder are at greater risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than people in the general population. METHODS: A population-based study was conducted including 3,780 individuals, diagnosed with alcohol or other drug dependence and cared for by the addiction service (AS) in the province of Reggio Emilia. Standardised incidence ratios (SIRs) and relative 95% confidence intervals (CIs) of being tested and of being SARS-CoV-2 positive in the population of interest compared with those in the general population of Reggio Emilia were calculated. RESULTS: Both individuals with alcohol and those with other drug use disorders had a lower risk of being SARS-CoV-2 positive (SIR = 0.69; 95% CI 0.32-1.30, SIR = 0.56; 95% CI 0.24-1.10, respectively), despite higher rates of being tested than the general population (SIR = 1.48; 95% CI 1.14-1.89, SIR = 1.51; 95% CI 1.20-1.86, respectively). Among HIV-negative persons, 12.5% were positive to SARS-CoV-2, while none was positive among HIV-positive persons. HCV-infected AS clients had a higher risk of both being tested for SARS-CoV-2 (SIR = 1.99; 95% CI 1.26-2.98) and of resulting positive (SIR = 1.53; 95% CI 0.50-3.58). CONCLUSIONS: Individuals with alcohol and/or other drug use disorders are at higher risk of being tested for SARS-CoV-2 infection but at lower risk of resulting positive than the general population. Further research is warranted in order to support our findings and to address plausible factors underpinning such associations.

Using text analysis software to identify determinants of inappropriate clinical question reporting and diagnostic procedure referrals in Reggio Emilia, Italy.

BACKGROUND: Inappropriate prescribing of diagnostic procedures leads to overdiagnosis, overtreatment and resource waste in healthcare systems. Effective strategies to measure and to overcome inappropriateness are essential to increasing the value and sustainability of care. We aimed to describe the determinants of inappropriate reporting of the clinical question and of inappropriate imaging and endoscopy referrals through an analysis of general practitioners' (GP) referral forms in the province of Reggio Emilia, Italy. METHODS: A clinical audit was conducted on routinely collected referral forms of all GPs of Reggio Emilia province. All prescriptions for gastroscopy, colonoscopy, neurological and musculoskeletal computerised tomography (CT) and magnetic resonance imaging (MRI) from 2012 to 2017 were included. The appropriateness of referral forms was assessed using Clinika VAP software, which combines semantic analysis of clinical questions and available metadata. Local protocols agreed on by all physicians defined criteria of appropriateness. Two multilevel logistic models were used to identify multiple predictors of inappropriateness of referral forms and to analyse variability among GPs, primary care subdistricts and healthcare districts. RESULTS: Overall, 37% of referral forms were classified as inappropriate, gastroscopy and CT showed higher proportions of inappropriate referrals compared to colonoscopy and MRI. Inappropriateness increased with patient age for CT and MRI; for gastroscopy, it was lower for patients aged 65-84 compared to those younger, and for colonoscopy, it was higher for older patients. Fee exemptions were associated with inappropriateness in MRI referral forms. The effect of GPs' practice organization was consistent across all tests, showing higher inappropriateness for primary care medical networks than in primary care medical groups. Male GPs were associated with inappropriateness in endoscopy, and older GPs were associated with inappropriateness in musculoskeletal CT. While there was moderate variability in the inappropriate prescribing among GPs, there was not among the healthcare districts or primary care subdistricts. CONCLUSIONS: Routinely collected data and IT tools can be useful to identify and monitor diagnostic procedures at high risk of inappropriate prescribing. Assessing determinants of inappropriate referral makes it possible to tailor educational and organizational interventions to those who need them.

Early life weight patterns and risk of obesity at 5 years: A population-based cohort study.

Childhood obesity is a major public health problem in industrialized countries. The aim of this study was to estimate the risk of obesity at age 5 based on BMI categories at age 3 and changes in BMI z-score from birth to 3 years of age. In this population-based study BMI data of 5173 children were collected at ages 3 and 5 and were linked to information relative to birth weight. The prevalence of obesity at age 5 was 3.8%. The risk of obesity for children born large for gestational age was 6.5%, while it was 18.6% for children overweight at age 3 and 62% for children who were obese at 3. An increase in BMI z-score from birth to 3 years increases the risk of obesity at age 5 (OR for increase of one standard deviation 2.8%; 95% CI: 2.46-3.20), but adjusting for BMI z-score at age 3, the effect of trajectory disappears (OR 1.08 95% CI: 0.9-1.29). In other words, if one targeted early preventive interventions to 3-year-olds affected by overweight/obesity (only 9.8% of the study cohort), one could possibly address 71% of children potentially affected by obesity at age 5.

Secondary transmission of COVID-19 in preschool and school settings in northern Italy after their reopening in September 2020: a population-based study.

We report epidemiological investigations of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 41 classes of 36 schools in Reggio Emilia province, northern Italy, from their reopening on 1 September to 15 October 2020. The overall secondary case attack rate was 3.2%, reaching 6.6% in middle and high schools. More timely isolation and testing of classmates could be effective in reducing virus transmission in this setting.

Understanding the association between mother's education level and effectiveness of a child obesity prevention intervention: a secondary analysis of an RCT.

OBJECTIVES: to explain differences in effectiveness of paediatrician-led motivational interviewing (MI) in decreasing body mass index (BMI) between children of mothers with low or high education level. DESIGN: secondary analysis of a randomised control trial. SETTING AND PARTICIPANTS: individually randomized controlled trial previously conducted from 2011 to 2013 in the province of Reggio Emilia (Emilia-Romagna Region, Northern Italy). Eligible participants included in the trial were 372 (187 in the MI group and 185 in the control group) overweight children (BMI percentile >= 85th and < 95th) aged between 4 and 7 years, residing in the province of Reggio Emilia and under the care of paediatrician for >= 12 months. The intervention included 5 MI sessions based on the transtheoretical model of addiction and behavioural change delivered at 1, 4, 7, and 12 months after the baseline visit, when families had to define specific goals in changing physical activity (PA) and diet behaviours. MAIN OUTCOME MEASURES: primary: BMI score variation (ΔBMI) from baseline to 12 months; secondary: percentage of changes in parent-reported PA and dietary behaviours. RESULTS: a significant effect of MI on ΔBMI in children whose mothers had high education level (ΔBMI = -0.62; 95%CI -0.92;-0.32) were observed. Children of women with high education level in MI group had more improvements in set unstructured PA, decreasing screen time and sweet snacks consumption, while children with less educated mothers had improvements in consuming more vegetable soup and less desserts, sweet snacks, and sugary beverages. Highly educated mothers chose for their children to drink fewer sugary beverages and to increase PA. Less educated mothers most frequently chose as goals having breakfast, eating more fruit and vegetables, eating fewer snacks, and having less screen time. Overall achievement was similar in the two strata for diet goals, but higher for PA goals in the high education level stratum. CONCLUSIONS: MI intervention was not effective in reducing BMI in children of mothers with low education level. This does appear to be weakly or not associated with goal choices and achievement within MI, it is rather an effect of unmeasured behaviours which possibly mediate association between MI and BMI reduction.

Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus.

Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naïve SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p < 0.001), BAFF and DNase I concentration (p < 0.01). Contrary, NETolytic activity was lower in SLE patients (p < 0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p < 0.001, p < 0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p < 0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p < 0.01), cfDNA and BAFF levels (p < 0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p < 0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naïve SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression.

High incidence of multiresistant bacterial isolates from bloodstream infections in trauma emergency department and intensive care unit in Serbia.

We investigated the incidence of bloodstream infections (BSIs) in trauma emergency department (ED) and intensive care unit (ICU), to assess ED- and ICU-related predictors of BSI and to describe the most common bacteria causing BSI and their antimicrobial resistance markers. A prospective study was conducted in two trauma ICUs of the ED of Clinical Center of Serbia. Overall, 62 BSIs were diagnosed in 406 patients, of which 13 were catheter-related BSI (3.0/1,000 CVC-days) and 30 BSIs of unknown origin, while 15% were attributed to ED CVC exposure. Lactate ≥2 mmol/L and SOFA score were independent ED-related predictors of BSI, while CVC in place for >7 days and mechanical ventilation >7 days were significant ICU-related predictors. The most common bacteria recovered were Acinetobacter spp., Klebsiella spp., and Pseudomonas aeruginosa. All Staphylococcus aureus and coagulase-negative staphylococci isolates were methicillin-resistant, whereas 66% of Enterococcus spp. were vancomycin-resistant. All isolates of Enterobacteriaceae were resistant to third-generation cephalosporins, whereas 87.5% of P. aeruginosa and 95.8% of Acinetobacter spp. isolates were resistant to carbapenems. ED BSI contributes substantially to overall ICU incidence of BSI. Lactate level and SOFA score can help to identify patients with higher risk of developing BSI. Better overall and CVC-specific control measures in patients with trauma are needed.

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care.

PURPOSE: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. METHODS: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. RESULTS: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. CONCLUSION: Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.

Effects of Human Papillomavirus Awareness and Knowledge on Psychological State of Women Referred to Cervical Cancer Screening.

OBJECTIVE: The aim of the study was to assess the impact of human papillomavirus (HPV) awareness and knowledge on physiological state and quality of life of women referred to colposcopy and/or HPV testing. MATERIALS AND METHODS: A cross-sectional study was carried out at University Hospital, Belgrade, Serbia. The women with abnormal Pap test results obtained at the primary care centers requiring colposcopy and/or HPV testing were included. Before gynecological examination, participants filled the questionnaire on demographic characteristics, gynecological history, questionnaire for the evaluation of HPV awareness and HPV knowledge level, a set of self-report questionnaires assessing the anxiety level, quality of life, and concern about the smear and colposcopy results and perceived risk of developing cervical cancer. RESULTS: Of 324 women, 196 (60.5%) were aware of HPV. They reported higher concern about test results (p < .001), perceived risk of developing cervical cancer (p < .001), and had significantly lower quality of life (p = .004) than women who did not hear anything about this virus. On contrary, better knowledge correlated with younger age (p < .001) and better quality of life (p < .0001) and was associated with lower anxiety, lower concern about smear test results, and lower perceived risk of developing cancer. CONCLUSIONS: Human papillomavirus awareness and knowledge have different impact on psychological state and quality of life. Being aware of HPV is not enough for reducing the stress and anxiety and increasing the coverage of screening. Therefore, it is necessary to increase women's knowledge through more detailed information about HPV in different public health messages and education programs.

Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients.

PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.

Psychological effects of concurrent cytology and colposcopy testing in women referred to cancer counseling outpatient clinic in Belgrade.

PURPOSE: To investigate the psychological effects of PAP smear and colposcopy performed simultaneously and receipt of abnormal tests' results on women's well-being and quality of life (QoL) using different relative questionnaires. METHODS: A prospective cohort study included 324 women with abnormal PAP smear result obtained at the primary care centers, requiring repeat smear test and colposcopy in our hospital. Questionnaires regarding the patient demographic characteristics, 7-point Likert scales which indicate concern about the smear and colposcopy results and risk of developing cervical cancer, Bek Anxiety Inventory (BAI), European QoL questionnaire - Euro QoL (EQ-5D) and visual analogue scale (EQ VAS) were used. Women filled in the questionnaires at the pre-procedural assessment, and again, 7-10 days after testing, just after the reception of results. RESULTS: According to BAI scale, almost one-quarter of women (23.5%) showed mild to severe anxiety; higher level of anxiety had women with abnormal test results (p=0.008). After adjustment for age, the difference reached statistical significance in the follow up period, too (p<0.05). At the pre-procedural assessment, there was no significant difference in the concern about test results (4.09 vs 4.22) and the perceived risk of developing cervical cancer (3.99 vs 4.14) using self-assessment by the Likart scales. However, women with abnormal test results had lower quality of life compared to women with normal PAP smear and colposcopy (mean EQ-VAS score 77.35 ± 15.63 vs 81.14 ± 16.07; p=0.020). CONCLUSIONS: We conclude that referral for evaluation after a first abnormal PAP test leads to anxiety. Close and clear communication about test meaning and its consequences is needed in the organized screening test.

Twenty-Eight-Day Mortality of Blunt Traumatic Brain Injury and Co-Injuries Requiring Mechanical Ventilation.

OBJECTIVE: This paper aims to assess the impact of co-injuries and consequent emergency surgical interventions and nosocomial pneumonia on the 28-day mortality of patients with severe traumatic brain injuries (TBIs). SUBJECTS AND METHODS: One hundred and seventy-seven patients with TBI admitted to the emergency trauma intensive care unit at the Clinical Center of Serbia for more than 48 h were studied over a 1-year period. On admission, the Glasgow Coma Scale (GCS), Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation II score (APACHE II) were calculated. At admission, an isolated TBI was recorded in 45 of the patients, while 44 had three or more co-injuries. RESULTS: Of the 177 patients, 78 (44.1%) died by the end of the 28-day follow-up period. They had a significantly higher ISS score (25 vs. 20; p = 0.024) and more severe head (p = 0.034) and chest (p = 0.013) injuries compared to those who survived. Nonsurvivors had spent more days on mechanical ventilation (9.5 vs. 8; p = 0.041) and had a significantly higher incidence of ventilator-associated pneumonia (VAP) than survivors (67.9 vs. 40.4%; p < 0.001). A high Rotterdam CT score (OR 2.062; p < 0.001) and a high APACHE II score (OR 1.219; p < 0.001) were identified as independent predictors of early TBI-related mortality. CONCLUSION: Patients who had TBI with a high Rotterdam score and a high APACHE II score were at higher risk of 28-day mortality. VAP was a very common complication of TBI and was associated with an early death and higher mortality in the subgroup of patients with a GCS ≤8.

Mitotic crossover promotes leukemogenesis in children born with TEL-AML1 via the generation of loss of heterozygosity at 12p.

TEL-AML1 (ETV6-RUNX1) fusion gene which is formed prenatally in 1% of the newborns, is a common genetic abnormality in childhood Bcell precursor acute lymphoblastic leukemia. But only one child out of a hundred children born with this fusion gene develops leukemia (bottleneck phenomenon) later in its life, if contracts the second mutation. In other words, out of a hundred children born with TEL-AML1 only one child is at risk for leukemia development, which means that TEL-AML1 fusion gene is not sufficient for overt leukemia. There is a stringent requirement for a second genetic abnormality for leukemia development and this is the real or the ultimate cause of the leukemia bottleneck phenomenon. In most cases of TEL-AML1+ leukemia, the translocation t(12;21) is complemented with the loss of the normal TEL gene, not involved in the translocation, on the contralateral 12p. The loss of the normal TEL gene, i.e. loss of heterozygosity at 12p, occurs postnatally during the mitotic proliferation of TEL-AML1+ cell in the mitotic crossing over process. Mitotic crossing over is a very rare event with a frequency rate of 10-6 in a 10 kb region. The exploration and identification of the environmental exposure(s) that cause(s) proliferation of the TELAML1+ cell in which approximately 106 mitoses are generated to cause 12p loss of heterozygosity, i.e. TEL gene deletion, may contribute to the introduction of preventive measures for leukemia.

Effect of an enhanced public health contact tracing intervention on the secondary transmission of SARS-CoV-2 in educational settings: The four-way decomposition analysis.

Background: The aim of our study was to test the hypothesis that the community contact tracing strategy of testing contacts in households immediately instead of at the end of quarantine had an impact on the transmission of SARS-CoV-2 in schools in Reggio Emilia Province. Methods: We analysed surveillance data on notification of COVID-19 cases in schools between 1 September 2020 and 4 April 2021. We have applied a mediation analysis that allows for interaction between the intervention (before/after period) and the mediator. Results: Median tracing delay decreased from 7 to 3.1 days and the percentage of the known infection source increased from 34-54.8% (incident rate ratio-IRR 1.61 1.40-1.86). Implementation of prompt contact tracing was associated with a 10% decrease in the number of secondary cases (excess relative risk -0.1 95% CI -0.35-0.15). Knowing the source of infection of the index case led to a decrease in secondary transmission (IRR 0.75 95% CI 0.63-0.91) while the decrease in tracing delay was associated with decreased risk of secondary cases (1/IRR 0.97 95% CI 0.94-1.01 per one day of delay). The direct effect of the intervention accounted for the 29% decrease in the number of secondary cases (excess relative risk -0.29 95%-0.61 to 0.03). Conclusions: Prompt contact testing in the community reduces the time of contact tracing and increases the ability to identify the source of infection in school outbreaks. Although there are strong reasons for thinking it is a causal link, observed differences can be also due to differences in the force of infection and to other control measures put in place. Funding: This project was carried out with the technical and financial support of the Italian Ministry of Health - CCM 2020 and Ricerca Corrente Annual Program 2023.

Comparing accuracy of tomosynthesis plus digital mammography or synthetic 2D mammography in breast cancer screening: baseline results of the MAITA RCT consortium.

AIM: The analyses here reported aim to compare the screening performance of digital tomosynthesis (DBT) versus mammography (DM). METHODS: MAITA is a consortium of four Italian trials, REtomo, Proteus, Impeto, and MAITA trial. The trials adopted a two-arm randomised design comparing DBT plus DM (REtomo and Proteus) or synthetic-2D (Impeto and MAITA trial) versus DM; multiple vendors were included. Women aged 45 to 69 years were individually randomised to one round of DBT or DM. FINDINGS: From March 2014 to February 2022, 50,856 and 63,295 women were randomised to the DBT and DM arm, respectively. In the DBT arm, 6656 women were screened with DBT plus synthetic-2D. Recall was higher in the DBT arm (5·84% versus 4·96%), with differences between centres. With DBT, 0·8/1000 (95% CI 0·3 to 1·3) more women received surgical treatment for a benign lesion. The detection rate was 51% higher with DBT, ie. 2·6/1000 (95% CI 1·7 to 3·6) more cancers detected, with a similar relative increase for invasive cancers and ductal carcinoma in situ. The results were similar below and over the age of 50, at first and subsequent rounds, and with DBT plus DM and DBT plus synthetic-2D. No learning curve was appreciable. Detection of cancers >= 20 mm, with 2 or more positive lymph nodes, grade III, HER2-positive, or triple-negative was similar in the two arms. INTERPRETATION: Results from MAITA confirm that DBT is superior to DM for the detection of cancers, with a possible increase in recall rate. DBT performance in screening should be assessed locally while waiting for long-term follow-up results on the impact of advanced cancer incidence.

Determinants of survival in patients with chronic heart failure: a population-based study in Reggio Emilia, Italy.

AIMS: We aim to monitor and improve the quality of the heart failure (HF) integrated assistance model defined by national and regional guidelines and implemented in the province of Reggio Emilia, Italy. Specific aims of the audit were to estimate the prevalence of HF, describe the characteristics of patients with HF and the rate of patients enrolled in the integrated care treated in primary care, and identify socioeconomic and geographic determinants of the 4-year survival of these patients. METHODS AND RESULTS: Retrospective analysis of a cohort of prevalent cases of HF, diagnosed before 31 December 2015 in Reggio Emilia, Italy, alive on 1 January 2016, and residing at the time of diagnosis on the provincial territory. Age and sex-adjusted prevalence of HF by area of residence were calculated according to the standard European population 2013. Patients were followed until death or 31 December 2019, whatever came first. The outcome measure of the study was four-year case fatality. Cox proportional hazards models, adjusted for age, sex, and duration of disease were used to determine the association between socio-geographic factors and death. The 4-year case-fatality rate was 36.7%, and it was the highest in the mountains (50.8%) compared with hills (34.6%), lowland (35.4%) and city (37.7%). The prevalence of HF was the lowest in the mountain [149.9, 95% confidence interval (CI) 112.1-187.7] and the highest in the lowland (340.8, 95% CI 308.7-372.9) and city (308, 95% CI 276.0-321.2). Patients living in the mountains had a lower deprivation index, and fewer hospitalizations prior to official diagnosis, although these characteristics were not statistically significant determinants of HF death in multivariate analysis. Behavioural (smoking and obesity) and socio-geographic characteristics (educational level, deprivation index and area of residence) were not significantly associated with mortality in both univariable and multivariable analysis; however, patients who live in mountains (hazard ratio 1.10, 95% CI 0.73-1.66) or hills (hazard ratio 1.11, 95% CI 0.90-1.37) had a slightly higher risk of death than those living in the city. Only 197 (12.1%) of patients in the cohort were enrolled in the integrated care pathway over the course of 4 years. CONCLUSIONS: Although clinical determinants outweigh the geographic and behavioural disparities in the survival of patients with CHF treated in primary care, effective prevention strategies are needed to address environmental and socio-geographic inequalities in access to primary care and to hasten equitable linkage to integrated care.

Recruitment strategies and interventions to increase participation in lung cancer screening programmes: a systematic review protocol.

INTRODUCTION: Despite strong evidence for the efficacy of low-radiation dose CT (LDCT) in reducing lung cancer (LC) mortality, implementing LC screening (LCS) programmes remains a challenge. We aim to systematically review the evidence on the strategies used to recruit the adult population at risk of LC to LDCT within LCS programmes and to estimate the effectiveness of interventions identified, used to reach the potentially eligible population, increase participation and informed choice, and ensure equitable access. METHODS AND ANALYSIS: This sequential systematic literature review will consist of three steps: (1) a scoping review of existing strategies and organisational models for LCS; (2) selecting papers reporting relevant outcomes (test coverage, screening participation and informed choice) and comparing results among different models; (3) a systematic review of interventions implemented to increase participation in LCS programmes. Each step will follow the methodological guidelines provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data sources include electronic databases such as Medline (PubMed version), Embase, CINAHL (Ebsco version), Scopus and Cochrane CENTRAL. The search will be limited to studies published from January 2000 to March 2023 in English, Italian, French, Spanish, Serbian and Croatian language. Findings will be synthesised quantitatively and qualitatively as appropriate. Risk of bias assessment will be only applied to studies selected in the second and third steps. The quality of evidence will be summarised for each outcome using the Grading Recommendation Assessment, Development and Evaluation methodology. ETHICS AND DISSEMINATION: Given that this is a review of existing literature, ethics approval is not required. The results will be published in peer-reviewed scientific journals and presented at relevant conferences. The findings of this review will help guide health authorities in organising LCS programmes and developing recommendations, policies, and actions at national and regional levels. PROSPERO REGISTRATION NUMBER: CRD42023408357.