Search Results for: Scoperte le cause biologiche della depressione

Introduction
Community-acquired pneumonia is the leading global cause of infection-related death. A subset of patients with pneumonia develops aberrant immune responses, resulting in harmful inflammation, tissue damage and significant mortality. Immunomodulatory therapies aim to blunt this dysregulated immune response and reduce resultant injury. No consensus exists on the use or impacts of immunomodulatory therapies in the management of community-acquired pneumonia. This protocol describes the methods we will use to undertake a systematic review and network meta-analysis of the effects of immunomodulatory therapies on the mortality of patients with community-acquired pneumonia.

Methods
We will undertake a systematic review and network meta-analysis investigating the use of immunomodulatory therapies in community-acquired pneumonia. Our protocol has been developed and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines and prospectively registered with PROSPERO (CRD42024565301). The primary objectives of this work are to compare the impact of immunomodulatory therapies on 28-day and 90-day mortality in adult patients admitted to hospital with a primary diagnosis of community-acquired pneumonia. The secondary objectives of this work are to identify any differences in the effectiveness of these immunomodulatory therapies in managing community-acquired pneumonia of differing aetiology and severity.
We will conduct a literature search of Medline, Embase, Scopus, Web of Science and Global Health for all relevant articles until 30 June 2024. All observational, interventional and epidemiological studies published in English will be included, and each type of study design will be examined separately. All studies will have their titles and abstracts independently screened by two reviewers, followed by a full article eligibility review and data extraction. A third reviewer will adjudicate any disagreements. Data extracted will include, but not be limited to, the study design, country in which it was undertaken, patient characteristics (eg, age, sex, cause of CAP, severity of CAP), details regarding the immunomodulatory therapy and dosing used and the 28-day and 90-day mortality of each study arm.

Analysis
The risk of bias will be assessed using the Risk of Bias in Non-randomised Studies – of Exposure tool for non-randomised studies and the Cochrane Risk of Bias 2 tool for randomised control trials. The quality of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations for network meta-analysis framework. A quantitative synthesis of data is planned for 28-day and 90-day mortality rates.
We will fit a random-effects network meta-analysis model that includes random effects for between-study heterogeneity and for inconsistency. This will be done using the metafor package for R. We will use a contrast-based approach, modelling estimated treatment effects using reference treatments. In the case of the primary objective, this will be the log odds ratio (OR) of mortality in one treatment compared with another.
Each type of study design will be examined separately. Treatments using the same immunotherapy at different doses may be grouped if appropriate.

Ethical approval and dissemination
This will be a systematic review of published literature; therefore, ethical approval is not required. To ensure communication of our findings, we will publish our results in a peer-reviewed journal and present our findings at appropriate local, national and international meetings.

PROSPERO registration number
CRD42024565301.

Background
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality worldwide. Despite the organised CRC screening programme, the uptake rate of the population-based CRC screening was still low. Thus, we will conduct a randomised controlled trial in a community setting to evaluate the effectiveness of a theory-based chatbot in promoting CRC screening uptake.

Methods and analysis
A total of 500 eligible participants will be randomly assigned to a WhatsApp Messenger-initiated chatbot outreach group or a standard text reminder group at a ratio of 1:1. The intervention group will deliver Chinese culturally tailored education texts and videos developed based on the Health Belief Model and the Trans-Theoretical Model. The control group will deliver a standard text reminder of information about the Hong Kong organised CRC screening programme. In addition to the baseline assessment and postintervention assessment, all subjects will be followed up for 3 months and 6 months, respectively. The primary outcome will be the CRC screening uptake rate at the 3 month and 6 month follow-up. The secondary outcomes will be the intention to undergo CRC screening uptake, time interval to participate in and complete screening after recruitment, and reasons for not participating in screening at the 3 month and 6 month follow-up. Quantitative data will be analysed using Student’s t-test, Pearson’s 2 test or Fisher’s exact test. Qualitative data will be analysed by thematic analysis.

Ethics and dissemination
Ethical approval of this trial was granted by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (2022.614). Written informed consent will be obtained from study participants before enrolment. The findings will be disseminated through peer-reviewed journals.

Trial registration number
The study was registered on clinicaltrials.gov (NCT06192862).

Circulation, Ahead of Print. BACKGROUND:Abdominal aortic aneurysms (AAA) present with high morbidity and mortality when they occasionally rupture. No medical therapy has successfully been proven to reduce AAA growth, though both metformin and statins have been identified as potential treatments in multiple meta-analysis. This study aimed to investigate a potential relationship between statin use and AAA growth rates and risk of undergoing repair, rupture, or death.METHODS:The study population included all men with screening-detected AAAs (30–55 mm) from the 2 large, population-based, randomized screening trials; the Viborg Vascular Screening trial (inclusion, 2008–2011) and the Danish Cardiovascular Screening trial (inclusion, 2014–2018). The clinical database was supplemented with data from the nationwide Danish Healthcare Registries, including prescription and outcome data. Statin exposure was quantified by defined daily doses (DDD). The primary outcome was AAA growth rate, whereas secondary outcomes included the need for repair and a composite of repair, rupture, and all-cause death. Growth rates were calculated using linear regression. To evaluate the risk of repair, patients were followed from inclusion until surgery, rupture, death, 5-year follow-up, or December 31, 2021.RESULTS:A total of 998 aneurysmal men (median age, 69.5 [interquartile range (IQR), 67–72] years; median AAA diameter, 35.4 [IQR, 32–41.2] mm) were included. Statin use was significantly associated with reduced AAA growth rate; an increase of 1 DDD statin per day was associated with an adjusted change in growth rate of −0.22 mm/year [95% CI, −0.39 to −0.06];P=0.009). The 5-year adjusted hazard ratio for undergoing repair per doubling of statin dose presented a significantly reduced adjusted hazard ratio (HR) of 0.82 ([95% CI, 0.70–0.97];P=0.023), which was significant after 2.5 years. Statin use was associated with a significantly lower risk of the composite outcome (surgery, rupture, and death) in a dose-dependent manner, with an adjusted HR of 0.83 ([95% CI, 0.73–0.94];P=0.003) per doubling of statin dose. Findings were robust in a variety of sensitivity analyses.CONCLUSIONS:High-dose statin use was associated with decreased AAA growth rates and lowered risk of undergoing repair, rupture, and death. This nonrandomized study suggests that patients with AAA could benefit from high-dose statin use, beyond only targeting associated risk factors.

Introduction
Distal radius fractures account for one-fifth of all fractures in the active elderly population and may cause chronic pain, loss of hand function and reduced work productivity, imposing a significant socioeconomic burden. Most are initially treated with closed reduction and casting, but 30% subsequently require surgery due to insufficient realignment. The current approaches for analgesia for closed reduction are suboptimal. A brachial plexus nerve block provides complete pain relief and muscle relaxation distal to the elbow, potentially creating better conditions for realignment of the fractured bone ends. This may ultimately translate into reduced need for surgery and result in better functional outcomes and fewer complications compared to a haematoma block, which is the current standard care in Denmark.

Methods and analysis
The BLOCK Trial is an investigator-initiated, parallel-group, allocation-concealed, outcome assessor and analyst-blinded, superiority, randomised, controlled, clinical multicentre trial performed at 11 Danish emergency departments. Eligible adult patients with a distal radius fracture who need closed reduction will be included and allocated 1:1 to either an ultrasound-guided brachial plexus nerve block or a haematoma block. The primary outcome is the proportion of patients with distal radius fracture surgery 90 days after closed reduction. We will include 1716 participants to detect or discard a relative risk reduction of surgery of 20%. Secondary outcomes include treatment-related complications, patient-reported wrist function, pain during closed reduction and proportion of patients with unacceptable radiographic fracture position immediately after closed reduction.

Ethics and disseminationf
The trial is approved by the Danish Medicines Agency and the Danish Research Ethics Committees (EU CT number: 2024-512191-35-00). All results will be summarised on www.theblocktrial.com, clinicaltrials.gov and euclinicaltrials.eu after publication. Primary and secondary outcome results from 0 to 90 days will be presented in the main article and submitted to a peer-reviewed journal. Results from outcomes on the 12-month follow-up will be presented separately.

Trial registration number
NCT06678438.

Annals of Internal Medicine, Ahead of Print.

Objectives
To investigate the association between triglyceride-glucose (TyG) index levels at hospital admission and the risk of in-hospital adverse events, including all-cause mortality, in patients with acute myocardial infarction (AMI). The primary hypothesis was that higher TyG index levels are associated with greater risk of adverse in-hospital outcomes.

Design
Retrospective cohort study.

Setting
Tertiary hospital inpatient care in China. The study included consecutively hospitalised patients with AMI between 1 August 2011 and 10 January 2022.

Participants
A total of 3458 patients with AMI were included. The mean age was 60.8 years, and 78.4% were men. Patients were excluded if they had incomplete data for TyG index calculation or outcome ascertainment.

Interventions
No therapeutic intervention was assigned; the study was observational. TyG index was calculated using fasting triglycerides and fasting plasma glucose levels at admission.

Primary and secondary outcome measures
The primary outcome was all-cause in-hospital mortality. Secondary outcomes included cardiogenic shock and fatal rapid arrhythmia. Outcomes were identified through standardised clinical records.

Results
Among 3458 patients, 375 (10.84%) died during hospitalisation, 236 (6.84%) developed cardiogenic shock and 147 (4.25%) experienced fatal rapid arrhythmia. After multivariable adjustment, higher TyG index levels were significantly associated with increased odds of all-cause mortality (OR, 1.27; 95% CI, 1.02 to 1.57; p

The monoclonal antibody nirsevimab demonstrated strong real-world protection against respiratory syncytial virus (RSV)—the leading cause of infant hospitalization in the US—in a meta-analysis published in The Lancet Child & Adolescent Health.

To the Editor The TRAUMOX2 trial compared restrictive and liberal oxygen delivery in adult trauma patients. Hyperoxia-induced reactive oxygen species formation has been shown to cause a myriad of complications, including pulmonary toxicity. Even though the liberal oxygen group had a lower rate of hypoxemic episodes (3.8% vs 6%), they experienced a higher incidence of atelectasis as an adverse event compared with the restrictive oxygen group (34.7% vs 27.6%) (eTable 9 in the article’s Supplement 2). Here, we offer plausible explanations for the findings.

We read with interest the Australian inflammatory bowel disease (IBD) consensus statements for pregnancy by Laube et al, which highlights that patients with IBD in the active stage have reduced fertility with unclear reasons.1 IBD, encompassing ulcerative colitis (UC) and Crohn’s disease (CD), involves gut microbiota and metabolites as key players in its development.2 A recent study revealed ovarian impairment in CD, while polycystic ovary syndrome (PCOS) is a common cause of ovarian dysfunction and infertility in women.3 4 Mounting evidence supported an association between gut microbiota and ovarian function,5 and our recent work revealed that gut microbiota was involved in the pathogenesis of PCOS.6 7 Therefore, we speculated that IBD may induce PCOS by disrupting gut microbiota, leading to alterations in plasma metabolites. Initially, we performed a phenome-wide Mendelian randomisation (MR) analysis based on…

Clinical presentation A 26-year-old man was diagnosed with a 4-month history of ulcerative colitis. At the time of diagnosis, an abdominal CT showed a thickened colorectum (figure 1A) and a normal liver (figure 1B). He was started on mesalazine 4 g/day and received this for approximately 2 months without therapeutic benefit. He clinically deteriorated and was admitted to the hospital with a fever of up to 38.5°C daily, abdominal pain and diarrhoea. Laboratory findings revealed significantly elevated white blood cells (13.86×109/L), C reactive protein (69.5 mg/L) and elevated liver enzymes: aspartate aminotransferase 245 U/L, alanine aminotransferase 368 U/L (normal

Alcohol-associated liver disease (ALD) is a leading cause of chronic liver disease and liver-related mortality worldwide. The progression of ALD can range from simple fatty liver (steatosis) to severe liver damage, including alcohol-associated hepatitis (AH), liver fibrosis or cirrhosis, and hepatocellular carcinoma.1 Research over the past few decades has shown that the mechanisms behind the development of ALD are complex, involving multiple cellular factors and interactions between different organs. At the cellular level, alcohol and its metabolites, such as acetaldehyde, can lead to the production of reactive oxygen species, increase in endoplasmic reticulum stress, mitochondrial damage and megamitochondria formation, impaired autophagy-lysosomal functions, and the accumulation of Mallory-Denk bodies resulting in hepatocyte death and degeneration, as well as increased infiltration of immune cells, particularly neutrophils with high IL-8 expression.1 2 Consequently, these changes also contribute to an increased ductular reaction (DR) and cholestasis, fibrosis,…

Introduction
Severe perinatal asphyxia at term or near term remains a critical public health issue, associated with high risks of neonatal death and hypoxic-ischaemic encephalopathy (HIE). Despite improved clinical guidelines, suboptimal care persists in many cases, and previous audits have demonstrated that up to 50% of asphyxia cases could be associated with suboptimal care. OptiNeoCare is a French study which aims to assess the prevalence and determinants of suboptimal obstetric and neonatal care and evaluate its potential impact on neonatal outcomes.

Materials and methods
This prospective, population-based observational study will include newborns ≥36 weeks’ gestation with severe perinatal asphyxia across 12 French perinatal networks (213 maternity units). Inclusion criteria comprise neonatal death or moderate/severe HIE with confirmed biochemical markers of asphyxia. Data will be collected prospectively from labour wards, transport teams and neonatal intensive care units using an electronic case report form, and the in-situ team will be invited to complete a morbi-mortality review (MMR). Approximately 336 cases will be included over 12 months, with 25% randomly selected for confidential enquiry by two experts. The quality of care will be assessed based on a structured classification of medical errors (diagnostic, therapeutic, preventive and systemic) by a panel of experts including an obstetrician or midwife and a paediatrician. Root cause analysis will identify determinants of suboptimal care. A concordance analysis will compare findings from MMRs and confidential enquiries. Statistical analysis will include multivariable logistic regression to explore associations between care quality and neonatal outcomes.

Ethics and dissemination
Ethical approval was granted by the Ethics Committee for Research in Obstetrics and Gynaecology. Informed non-opposition is required from participants. Results will be shared with participating centres, healthcare professionals and through scientific dissemination.

Trial registration number
ClinicalTrials.gov ID: NCT06322732.

Objectives
To review the available evidence of screening for atherosclerosis in adults in a primary prevention setting with coronary artery calcium scoring (CACS) on the impact on cardiovascular (CV) risk factor control, health behaviour and clinical events.

Design
Systematic review, reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources
We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials through 22 January 2025.

Eligibility criteria
We included randomised controlled trials (RCTs) and prospective cohorts, without language restrictions, comparing adults without cardiovascular diseases undergoing CACS to a control group that either did not undergo CACS or where the participants and physicians were blinded to its result. Outcomes included changes in CV risk factor control, CV therapy, changes in health behaviour at follow-up and clinical events (all-cause and CV mortality and non-fatal CV events).

Data extraction and synthesis
Two independent reviewers extracted data and assessed the risk of bias. Due to substantial heterogeneity among the included studies, a quantitative analysis was not possible.

Results
We identified seven RCTs and one observational study, with participants ranging from 56 to 43 447 with a total of 51 554. Populations were heterogeneous with a mean age range of 42–64 years, % women ranging from 21% to 100% and mean baseline CACS from 1.37 to >100 Agatston units. Interventions following CACS were also heterogeneous, ranging from simply communicating results to participants to initiating statin therapy for detectable CACS. One RCT demonstrated improvement regarding blood pressure (BP) (n=2137; change in systolic BP: CACS: –5 mm Hg; control: –7 mm Hg; p=0.02), several an improvement in blood lipids between groups (five studies, n=3693; eg, low-density lipoprotein (LDL) cholesterol: range –6.0 to –4.9 mg/dL). Results regarding CV medication (seven studies, n=51 104) were more discrepant, with some studies showing a decrease and others an increase in indication for or usage of CV medication. Three trials (n=3338) investigated adherence to CV medication, with only one showing increased adherence to statins (CACS: 63.3%; control: 45.6%; p=0.03). Five trials (n=3692) investigated behavioural changes, with one showing an increased motivation to change lifestyle (CACS: 94%; control: 62.8%; p=0.002) and another a higher adherence in self-reported physical activity (CACS: 96%; control: 59%; p

Objectives
Elevated left ventricular end-diastolic pressure (LVEDP) in ST-segment elevation myocardial infarction (STEMI) has been studied in patients who received thrombolysis or who were treated early in the primary percutaneous coronary intervention (PCI) era; LVEDP was found to be a predictor of adverse outcomes in these retrospective post hoc analyses. The aim of the current analysis is to assess the prognostic value of the elevated LVEDP in STEMI patients undergoing primary PCI in current contemporary practice.

Design
Prospective, single-centre study.

Participants
Our study enrolled STEMI patients with elevated LVEDP undergoing primary PCI at John Hunter Hospital, Newcastle, Australia.

Primary outcome measure
The primary endpoint was the combination of 12-month all-cause mortality and heart failure admissions, comparing different quartiles of LVEDP.

Results
A total of 997 patients underwent primary PCI at our hospital during the 5-year study period (age: 64±13 years, males: 73%; n=728) from 1 January 2015 to 31 December 2019. The median LVEDP for the whole cohort was 27 mm Hg (IQR: 22–31 mm Hg). The median LVEDP was 17 mm Hg (IQR: 13–18 mm Hg) and 33 mm Hg (IQR: 30–36 mm Hg) for 1st and 4th quartiles respectively (p

In un mondo sempre più dominato dagli smartphone e dai tablet, il benessere mentale degli adolescenti potrebbe pagare un prezzo molto alto. Una nuova ricerca dell’Università di Pittsburgh, pubblicata su…

Background
Human papillomavirus (HPV) is the most common cause of cervical cancer in women. However, among adolescent boys, initial exposure to HPV is associated with a higher risk of developing oropharyngeal and oral cancers compared with girls. Notably, the incidence of oropharyngeal cancer has been rising sharply in high-income countries, yet HPV vaccination coverage among adolescent boys remains suboptimal. Therefore, understanding the perceptions of adolescent boys and their parents regarding HPV vaccination in high-income countries is crucial for the development of effective public health strategies.

Objectives
This scoping review aims to explore the perceptions of adolescent boys and their parents regarding HPV vaccination and investigate the facilitating factors and barriers influencing HPV vaccination.

Methods and analysis
The method framework of Arksey and O’Malley, the Joanna Briggs Institute, as well as the recommendations of Levac will be used to conduct the scoping review. This scoping review will be reported in accordance with the PRISMA extension for scoping reviews checklist. A systematic literature search will be performed on Ovid-MEDLINE, CINAHL, Cochrane CENTRAL, Ovid-Embase, PsycINFO and Web of Science. Two reviewers will independently perform the study selection and data extraction. Identified studies will be extracted using a customised extraction template on Covidence and analysed descriptively using narrative synthesis. The review commenced in April 2024 and will be completed in July 2025.

Ethics and dissemination
Formal ethical approval is not required, as primary data will not be collected for this study. The findings will be disseminated through publication in a peer-reviewed journal.

Registration
This protocol has been registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/M5NH2).