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New England Journal of Medicine, Volume 392, Issue 18, Page 1847-1856, May 8, 2025.

Message Computer-aided detection (CADe) has increased adenoma detection in randomised trials. However, unlike other detection adjuncts, CADe is lesion specific, that is, it is trained on a specific set of lesions. If the training does not include sufficient examples of precancerous lesion subsets, CADe may not perform adequately for lesions in that subset. In a prospective assessment of a second-generation CADe programme in 165 colonoscopies, we identified 26 flat lesions ≥10 mm in 17 patients. The endoscopist identified 22 of 26 lesions before the CADe programme. In 13 lesions, the CADe either generated no detection signal or only a signal over part of the lesion after colonoscope position or luminal inflation adjustment. Thus, the second-generation CADe algorithm, like the first generation, frequently fails to effectively detect large flat colorectal lesions, which are likely very important lesions that a CADe programme should identify. Details The first CADe…

Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated condition characterised by eosinophilic infiltration of the oesophagus, leading to significant morbidity due to oesophageal dysfunction. The pathogenic course of EoE begins with tissue injury, marked by the intricate interplay of oesophageal barrier dysfunction and T helper 2-mediated inflammation. In response to tissue damage, a subsequent phase of tissue remodelling features a complex interaction between epithelial cells and stromal cells, aimed at tissue repair. The persistence of inflammation drives these mechanisms towards oesophageal fibrostenosis, mainly through the transforming growth factor-dependent, myofibroblast-driven accumulation of the extracellular matrix. Currently, treatment options for EoE are limited, with dietary intervention, proton pump inhibitors and oral steroids serving as first-line therapies. Dupilumab, an antiinterleukin (IL) 4/IL-13 agent, is the only biologic that has been approved by European and American regulatory authorities. However, emerging OMIC technologies significantly advance our understanding of EoE pathogenesis, revealing novel cellular and molecular mechanisms driving the disease. This progress has accelerated the identification of new therapeutic targets and agents, some already under clinical investigation, potentially expanding our therapeutic arsenal and paving the way for more personalised approaches. In this evolving landscape, artificial intelligence (AI) has shown great potential to further elaborate on the complexities of EoE heterogeneity, offering standardised tools for diagnosis, disease phenotyping, and prediction of treatment response. Though still in their early stages, integrating OMICs and AI marks a pivotal step towards precision medicine in EoE.

Introduction
Acute circulatory failure plays a major role in the development of sepsis-related organ dysfunction. Current ‘bundles’ of the Surviving Sepsis Campaign (SSC) include the administration of a fluid loading of 30 mL/kg in the presence of hypotension within the first hour of sepsis identification. The impact of haemodynamic assessment using echocardiography at the early phase of management of septic patients in the Emergency Department (ED) on patient-centred outcomes is unknown.

Methods and analysis
This is a two-parallel arm randomised trial with blinded assessment comparing early haemodynamic assessment using transthoracic echocardiography aimed at guiding therapeutic management to standard of care according to current SSC recommendations in septic patients during initial management in 13 French EDs. Patients with suspected or documented infection and a qualifying quick Sequential Organ Failure Assessment (qSOFA) score (haemodynamic criterion required: systolic blood pressure≤100 mm Hg) will be 1:1 randomised after 500 mL of fluid loading initiation. In the intervention group, echocardiography will allow identifying the haemodynamic profile at the origin of sepsis-induced circulatory failure and monitoring the efficacy and tolerance of fluid resuscitation, or of any other therapeutic intervention according to a predefined therapeutic algorithm. The control group will receive conventional 30 mL/kg fluid resuscitation (unless pulmonary venous congestion) according to SSC recommendations. Primary outcome will be the course of organ dysfunction assessed by the crude change in the modified SOFA score between baseline and 24 hours after randomisation. Secondary outcomes will be the nature of therapeutic interventions resulting from echocardiography (fluid loading, early initiation of vasopressor support or inotrope), the prevalence of the different haemodynamic profiles, the evolution of lactatemia, the safety of the initial therapeutic, the proportion of patients who develop secondarily septic shock, the orientation of patients after ED discharge and both day 7 and in-hospital mortality. We plan to randomise 312 patients.

Ethics and dissemination
Approved by the Ethics Committee CPP Ouest V on 18 January 2021 (ref: 20/075-2-20.10.16.57638). The dissemination plan includes presentations at scientific conferences and publication of results in a peer-reviewed journal.

Trial registration number
NCT04580888.

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Objective
Emergency ambulance services attend a wide array of medical and trauma patients. Infrequently, this includes imminent or out-of-hospital births (OOHBs). This scoping review explores emergency ambulance clinician involvement with OOHBs, and patient and clinician experiences with birthing in the out-of-hospital setting.

Design
Scoping review using the Joanna Briggs Institute framework and ‘participant, concept, context’ criteria.

Data sources
CINAHL, Embase, Medline, Web of Science and Wiley Online were searched until 20 February 2024.

Eligibility criteria for selecting articles
Articles discussing an unplanned OOHB, or a planned home birth with complications where an emergency ambulance was required, were included.

Data extraction and synthesis
Two reviewers independently determined inclusion using Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews guidelines. A data extraction tool summarised findings for descriptive synthesis.

Results
63 articles were included. 36 articles involved retrospective research. 38 articles were published since 2015, with USA (n=17) and Australia (n=13) the highest contributors. Risk factors for OOHBs were varied, with maternal age or being multigravida/multiparous often cited. 99 complications were described, ranging from relatively minor ailments (ie, nausea and vomiting) to life-threatening situations such as maternal or neonatal cardiac arrest. Common management/interventions reported were assisting with birth, maternal intravenous cannulation and medication administration.
Birth parents, partners and clinicians all describe OOHBs as anxiety-provoking but joyous when a healthy neonate is born. The OOHB experience is enhanced for patients when clinicians communicate well, while those who appeared inexperienced increased patient anxiety.
OOHBs experience many challenges to optimal care, categorised as ‘emergency ambulance clinicians desiring additional education and training’, ‘communication and collaboration difficulties’, ‘environmental issues’, ‘technology and aids’ and ‘other’ limitations.

Conclusions
OOHBs are rare events requiring expert assistance to optimise patient outcomes. There remain significant challenges to unplanned OOHBs; ongoing training and skill competency is required to improve patient safety and clinician confidence. Further research investigating patient outcomes and experiences is recommended.

Objectives
To monitor the safety and utilisation of AZD1222 under real-world use in the UK.

Design
A non-interventional post-authorisation active surveillance study.

Setting
Vaccination sites in the UK.

Participants
A total of 17 945 participants were eligible and provided consent to participate in the study between 1 March 2021 and 6 April 2023. Participants were followed up at weeks 1, 4 and 14 and at months 6, 9, 12 and 18 after the first dose of AZD1222 vaccination and prompted to complete electronic data capture forms. A total of 11 219 participants submitted a Follow-Up 1 form and 5189 participants submitted a Follow-Up 7 form (at 18 months).

Primary and secondary outcome measures
The safety of AZD1222, including the identification, assessment and quantification of serious adverse events (SAEs) and adverse events of special interest (AESI), was examined. The utilisation of AZD1222 was described and characterised, including populations with missing information.

Results
The majority of participants were women (n=10 845; 60.4%) and the median age (IQR) was 50 (43, 62) years. Most participants were from white ethnic groups (n=13 112; 73.1%). Headache and fatigue had the highest reported incidence rate (421.28 cases per 1000 person years and 386.00 cases per 1000 person years, respectively). The most frequently reported AESI was anosmia (6.25 cases per 1000 person years). An increased Observed versus Expected (O:E) ratio was seen for anaphylaxis (O:E 7.38 (95% CI 2.80 to 11.95); based on 10 observed cases (expected cases: 1.36)) and anosmia and/or ageusia (O:E 39.23 (95% CI 29.13 to 49.32), based on 58 observed cases (expected cases: 1.48)).

Conclusions
The most frequent vaccinee-reported adverse events (AEs) were headache and fatigue. An increased O:E ratio was seen for the AEs of anaphylaxis and anosmia and/or ageusia. No safety signals were identified throughout the course of this study.

Trial registration number
This study is registered with the HMA-EMA Catalogue of RWD studies (EUPAS44035).

Objective
To evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumour activity of AMG 404, a fully human IgG1 monoclonal antibody targeting programmed cell death-1, in patients with advanced solid tumours.

Design
First-in-human phase I study comprising eight dose expansion cohorts, including cohorts with microsatellite instability-high (MSI-H) tumours and non-small cell lung cancer with high programmed death-ligand 1 expression (NSCLC/PDL1-H, tumour proportion score ≥50%).

Setting
Conducted across 28 global sites.

Participants
This study enrolled adult patients with histologically or cytologically confirmed metastatic or locally advanced solid tumours not amenable to curative treatment with surgery or radiation. The inclusion criteria included a life expectancy of >3 months, ≥1 measurable or evaluable lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) V.1.1, an Eastern Cooperative Oncology Group performance status of ≤2 and adequate haematological, renal and hepatic function. Patients with prior treatment with checkpoint inhibitors, primary brain tumour or untreated or symptomatic brain metastases and leptomeningeal disease and history of other malignancy within the past 2 years were excluded.

Interventions
The planned doses were 240 mg, 480 mg and 1050 mg of AMG 404 administered every 4 weeks (Q4W).

Primary and secondary outcome measures
Primary endpoints were dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, changes in vital signs and clinical laboratory tests. Secondary endpoints included PK parameters, incidence of antidrug (AMG 404) antibodies and antitumour activity assessed per modified RECIST V.1.1 (objective response, duration of response, progression-free survival (PFS), disease control and duration of stable disease).

Results
A total of 171 patients were enrolled; 168 were treated. Median (range) follow-up was 36.3 weeks (1.6–137.1). No DLTs were observed. Grade 3 and serious treatment-related adverse events occurred in 16 (9.5%) and 12 (7.1%) patients, respectively. The 480 mg Q4W dose was selected as the recommended phase II dose. AMG 404 serum exposure increased approximately dose proportionally. The objective response rate (80% CI) was 19.6% (15.7–24.1) for the overall population and 36.6% (26.4–47.8) and 30.8% (14.2–‍52.3) for cohorts with MSI-H tumours (n=41) and NSCLC/PDL1-H (n=13), respectively. The overall disease control rate (80% CI) was 54.8% (49.5–59.9). The median (80% CI) PFS was 3.7 (3.5–4.5) months for the overall population and 14.8 (9.0–not estimable) and 4.4 (2.2–9.7) months for cohorts with MSI-H tumours and NSCLC/PDL1-H, respectively.

Conclusions
AMG 404 monotherapy was tolerable at the tested doses, with encouraging antitumour activity observed across tumour types.

Trial registration number
NCT03853109.

Objectives
The primary aim of this study was to optimise colorectal cancer (CRC) screening strategies and target populations in resource-limited areas through cost-effectiveness analysis, evaluating the best screening methods and appropriate screening ages.

Design
A prospective microsimulation model was used for cost-effectiveness analysis, calibrated with real-world data.

Setting
The study was conducted in Huzhou City, Zhejiang Province, China, focusing on primary and secondary healthcare levels. Data were obtained from the Huzhou Center for Disease Control and Prevention.

Participants
The study included 418 805 local residents who participated in the Huzhou screening programme between 2020 and 2022. Inclusion criteria were individuals aged 45–100 years and residing in the local area.

Interventions
Four initial screening methods were evaluated: single-sample immunochemical faecal occult blood test (iFOBT), double-sample iFOBT, single-sample iFOBT combined with a risk assessment questionnaire and double-sample iFOBT combined with a risk assessment questionnaire. Screening frequencies included annual and biennial intervals.

Primary outcome measures
The primary outcome measure was the cost per incremental quality-adjusted life year (QALY) for different screening strategies. Also, the impact on CRC incidence, related deaths, life years saved (LYS) and QALYs was considered.

Results
The primary data were sourced from the Huzhou screening programme, which included 418 805 individuals from 2020 to 2022. All screening strategies were found to be effective, with the cost per incremental QALY being less than $1036, which is below the minimum standard for middle-income countries. The most effective screening strategy was the annual combined two-sample iFOBT and risk evaluation questionnaires. This approach led to a reduction in CRC incidence and related deaths by 2435 and 1174 cases per 100 000 individuals, respectively, and an increase in LYS by 13 903 years and QALYs by 35 564 years. The recommended ages to begin and end screening were 48 and 72 years, respectively.

Conclusions
All CRC screening strategies demonstrated effectiveness compared with non-screening, with the annual combined two-sample iFOBT and risk evaluation questionnaires emerging as the optimal approach. For additional regions, the best screening strategy can be selected based on the health outcomes and costs we have provided.

Introduction
Pancreatic cancer, an aggressive cancer that presents with few or unspecific symptoms, has a poor prognosis. Thus, diagnosis at an early stage is vital for survival and a chance for curative treatment. Therefore, surveillance programmes for high-risk individuals are of the utmost importance. However, data on the psychological burden among participants in these programmes are limited.

Aims
This study aimed to investigate the psychological burden for participants in a pancreatic cancer surveillance programme and explore whether the psychological burden was related to the individual’s risk level for pancreatic cancer.

Methods
This single-centre cross-sectional study investigated cancer worry, anxiety, coping and perceived physical and mental health using a digital questionnaire, including the following instruments: Cancer Worry Scale (CWS), State–Trait Anxiety Inventory (STAI), 13-Item Sense of Coherence and 12-Item Short-Form Survey. The invited participants (n=413) were healthy individuals with an increased risk of pancreatic cancer enrolled in a pancreatic cancer surveillance programme.

Results
The results indicated high cancer worry among respondents (n=78) with high scores on CWS (mean, 16.45). The majority (69.3%) had scores indicating high cancer worry (≥14). Anxiety was not equally high among respondents (mean STAI-T, 35.13; STAI-S, 35.9). Female sex and younger age were significantly correlated with higher cancer worry and anxiety (p < 0.001). Outcomes in coping and perceived health were similar to those of the normal population. Conclusions Cancer worry is particularly high among participants. No correlation was found between the risk level and psychological burden.

Objectives
Frail older adults need to improve their health through exercise, and effective interventions are necessary to ensure their participation. Exercise with music has been shown to enhance adherence among older adults and improve both physical and mental health outcomes, making it a suitable intervention for frail older adults. This study evaluated the impact of exercise with music on the physical and emotional health of frail, community-dwelling older adults.

Design
A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.

Data sources
MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane Library, PsycINFO, Google Scholar and the Virginia Henderson International Nursing Library were last searched on 14 March 2025.

Eligibility criteria for selecting studies
We included randomised controlled trials (RCTs) and non-RCTs that applied exercise with music to community-dwelling frail older adults.

Data extraction and synthesis
Five independent reviewers used standardised methods to search, screen and code included studies. Study quality was assessed using the revised Cochrane Risk of Bias 2 tool and the Risk of Bias in Non-Randomized Studies of Interventions tool. A meta-analysis and narrative synthesis were conducted, and the findings were summarised using Grading of Recommendation, Assessment, Development, and Evaluation evidence profiles. Publication bias was checked, and sensitivity analyses were used to assess the robustness of the results.

Results
After screening the initial 1425 studies, 17 studies (13 RCTs and 4 non-RCTs) were analysed. The overall risk of bias indicated that two had high risk and three had serious risk among the RCTs, and two had serious risk and two had moderate risk among the non-RCTs included in the meta-analysis. As for physical health outcomes, studies reported on frailty, Timed Up and Go (TUG), handgrip strength, falls, balance, gait speed, endurance and other performance. As for emotional health outcomes, studies reported on depression, social support and activities, quality of life or satisfaction and cognitive function. The pooled analysis suggested that exercise with music may have a positive effect on reducing frailty (standardised mean difference (SMD)=–0.20, 95% CI=–0.34 to –0.07, p=0.003, I2=0%; very low certainty) and decreasing depression levels (SMD=–0.40, 95% CI=–0.65 to –0.15, p=0.002, I2=0%; very low certainty) compared with control group outcomes in non-RCTs. However, there was no effect on the TUG and handgrip strength. A narrative synthesis of evidence suggested potential beneficial effects on frailty and depression.

Conclusions
Exercise with music may help improve frail older adults’ physical and emotional health and potentially reduce the burden of frailty. However, further rigorous investigation is needed, as the evidence has a very low level of certainty. Additionally, results from this review should be interpreted with caution because of concerns associated with the risk of bias. Community-based health professionals should consider using music when providing exercise interventions to frail older adults, while applying tailored approaches that consider their unique needs.

PROSPERO registration number
CRD42022369774.

In this issue of JAMA Internal Medicine, Zhang et al reported that higher consumption of butter is linked to an increased risk of mortality in middle-aged and older adults in the US. Specifically, each 10-g increase per day in butter intake was associated with a 7% increase in total mortality risk. In contrast, a 10-g increase per day in the consumption of plant-based oils, such as canola, soybean, and olive oils, was associated with a 13% lower risk of death from all causes, an 11% lower risk of death from cancer, and a 6% lower risk of death from cardiovascular diseases. This study, involving 3 cohorts including 221 054 men and women whose diets were repeatedly measured and followed over 33 years, highlights significant health benefits from modest dietary changes.

Objective
Potentially inappropriate prescribing is a global health issue with catastrophic consequences in the elderly population. Healthcare providers play a critical role in medication optimisation in elderly patients. The present study aims to explore the perceptions of healthcare professionals (prescribers) regarding the complexities of inappropriate prescribing practices in the elderly population.

Design
A qualitative study using semistructured interviews was conducted. All the data were transcribed verbatim and analysed via Braun and Clarke’s thematic analysis approach.

Setting
Prescribers working in a tertiary care hospital in Karachi, Pakistan.

Participants
Prescribers having more than 5 years of experience in elderly prescribing. Participants were selected using purposive sampling, and recruitment continued until the point of data saturation, meaning no new major themes emerged.

Results
13 prescribers, five females and eight males with an average experience of 15.3 years, were interviewed. The interviews lasted for an average of 15 min. The analysis revealed three primary themes: (1) inappropriate prescribing, characterised by knowledge and awareness of inappropriate prescribing and its assessment tools; (2) complexities in elderly prescribing, highlighting patient factors such as comorbidities, polypharmacy, psychological issues and socioeconomic challenges, as well as prescriber factors; and (3) interventions to improve prescribing, emphasising the role of pharmacists in enhancing medication safety, the importance of effective patient–prescriber relationships through counselling and the need for regulatory measures to monitor prescribing behaviours. Inadequate knowledge of standardised assessment tools such as the Screening Tool to Alert to Right Treatment/Screening Tool of Older Persons’ Prescriptions criteria, time constraints faced by prescribers and fragmented healthcare systems were some of the barriers identified by the respondents in medication optimisation for elderly individuals.

Conclusion
The findings highlight the need for enhanced education on standardised assessment tools and the implementation of targeted interventions. A key recommendation is the integration of clinical pharmacists into care teams to optimise prescribing practices.

Objectives
To document adaptations that were made to the implementation of the two-way texting (2wT) randomised controlled trial (RCT) for voluntary medical male circumcision (VMMC) in South Africa and to provide a nuanced discussion on the differences between adaptations and fidelity in this context.

Design
We conducted a qualitative study using the Framework for Reporting Adaptations and Modifications in Evidence-based Implementation Strategies (FRAME-IS) to examine 2wT adaptations. We reported adaptations to the 2wT intervention using two steps. First, we categorised adaptations in a shared study-specific Google Docs that documented participant engagement with the 2wT system, tracked daily RCT implementation notes, reported software bugs and noted reminder emails about adaptations for the research team. Second, we conducted a qualitative assessment of the influence of adaptations on project outcomes via 10 periodic reflection meetings with VMMC implementers. Reflection documentation included notes from field observations, meeting minutes and informal partner check-ins to complete adaptation documentation. Using the FRAME-IS as a codebook, adaptations were categorised.

Setting
The RCT was conducted in rural and urban VMMC clinics in the North West and Gauteng districts of South Africa.

Participants
Implementation scientists and VMMC implementers who implemented the 2wT pragmatic randomised controlled trial (pRCT) were participants for the adaptation study.

Primary and secondary outcome measures
The primary outcome measure was the adaptations that were made during the implementation of the 2wT pRCT. The secondary outcome measures were fidelity and rigour of implementing adaptations to the 2wT pRCT.

Results
Between June 2021 and February 2022, 13 adaptations were identified in three phases during the implementation of the 2wT pRCT. The first phase of adaptations aimed to augment study recruitment, including conducting weekend VMMC recruitment camps, using mobile outreach services in the rural site, adding two urban sites to increase recruitment, using weekly WhatsApp calls for updates with all implementing teams, using virtual meetings to implement the 2wT strategy remotely during COVID-19 restrictions and allocating one clinician to work outside of normal working hours. The second phase of adaptations further enhanced enrolments, including adding two local language translations in the usability survey for 2wT men and contributing a portion towards the salary of the implementing staff by the research partner. The third phase included the exclusion of two rural clinics as recruitment sites due to inconsistent mobile phone networks, adding another layer of data quality checks to ensure data quality, training non-clinical counsellors to help with enrolling clients, retraining of staff in the rural site with high staff turnover and using both primary and alternative phone numbers for enrolment to reduce loss to follow-up.

Conclusions
This study made adaptations to the 2wT pRCT without compromising the fidelity of the study. The 2wT pRCT balances rigour (fidelity) and relevance (adaptation). Adaptations should not be confined by rigour but should also not go unchallenged or unverified. We conclude that fidelity can be maintained with adaptations that are implemented to close the gap between research in the laboratory and practice.

Trial registration number
The trial from which this study was conducted, ‘Expanding and Scaling Two-way Texting to Reduce Unnecessary Follow-Up and Improve Adverse Event Identification Among Voluntary Medical Male Circumcision (VMMC) Participants in the Republic of South Africa’, was registered at ClinicalTrials.gov (ID: NCT04327271) on 31 March 2020.