Search Results for: Le cause della polmonite nei bambini

Stroke, Ahead of Print. BACKGROUND:Chronic cerebellar lesions of presumed ischemic origin are frequently found in patients with ischemic stroke and as incidental findings. However, the differentiation of embolic lesions from lesions caused by cerebral small vessel disease (SVD) is unclear. We aimed to investigate whether the location of chronic cerebellar ischemic lesions (deep versus cortical) indicates the underlying cause (embolic versus SVD).METHODS:This study was a post hoc data analysis from the multinational ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Patients With Postischemic Stroke With Atrial Fibrillation), which included patients with acute ischemic stroke and atrial fibrillation cohort between 2017 and 2022. For comparison, data from 2 cohorts (DiViNAS [Disease Variability in NOTCH3-Associated SVD] and VASCAMY [Vascular and Amyloid Predictors of Neurodegeneration and Cognitive Decline in Nondemented Subjects]) consisting of participants with hereditary cerebral SVD (ie, Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy) were analyzed (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy cohort). Brain magnetic resonance imaging scans were evaluated for presence and location of chronic cerebellar ischemic lesions. The association between these lesions and the severity of supratentorial SVD was analyzed using univariable and multivariable models, adjusting for key covariables.RESULTS:In the atrial fibrillation cohort (N=790), 278 (35%) patients had chronic cerebellar ischemic lesions (cortical: n=242; deep: n=36). In multivariable analyses, features of cerebral SVD were associated with deep cerebellar ischemic lesions (summary SVD score; odds ratio per point, 2.5 [95% CI, 1.5–3.5];P

Introduction
Membranous nephropathy is an autoimmune kidney disease and the most common cause of nephrotic syndrome in non-diabetic Caucasian adults. Rituximab is now recommended as first-line therapy for membranous nephropathy. However, Kidney Disease Improving Global Outcomes guidelines do not recommend any specific protocol. Rituximab bioavailability is reduced in patients with membranous nephropathy due to urinary drug loss. Underdosing of rituximab is associated with treatment failure. We have previously developed a machine learning algorithm to predict the risk of underdosing. We have retrospectively shown that patients with a high risk of underdosing required higher doses of rituximab to achieve remission. The aim of this prospective study is to evaluate the efficacy of algorithm-driven rituximab treatment in patients with membranous nephropathy compared to standard treatment.

Methods
A multicentre, randomised, controlled, open-label, prospective superiority clinical trial will be conducted in 13 French hospitals. 130 consecutive patients with primary membranous nephropathy and active nephrotic syndrome will be randomised to either the standard protocol control group (two 1 g rituximab infusions on days 0 and 15) or the algorithm-driven rituximab treatment group. In the latter, the rituximab dose will depend on the algorithm-estimated risk of underdosing. Patients with an algorithm-estimated risk of underdosing ≤50% will receive 1 g of rituximab on days 0 and 15. Patients with an algorithm-estimated risk of underdosing between 51% and 75% will receive 1 g of rituximab on days 0, 15 and 30. Finally, patients with an estimated risk of underdosing >75% will receive 1 g of rituximab on days 0, 15, 30 and 45. The primary study outcome is the rate of clinical remission (complete or partial) at month 6 after treatment initiation. The secondary outcomes include clinical remission at month 12, immunological remission, proteinuria, albuminuria, serum creatinine, estimated glomerular filtration rate, phospholipase A2 receptor type 1 antibody titre, anti-rituximab antibody occurrence, lymphocyte count, serum rituximab level and related adverse events.

Ethics and dissemination
The trial received ethics approval from the local ethics boards. The results of this study will confirm whether algorithm-driven rituximab treatment is more effective in inducing remission than the standard regimen and thus may contribute to improving management of patients with membranous nephropathy. The results of our study will be submitted to a peer-review journal.

Trial registration number
NCT06341205 trial number. Registered on 2 April 2024.

Introduction
Breast cancer is a global public health challenge. It is the most commonly diagnosed cancer and the leading cause of cancer-related death in women. Several inequalities remain among women facing this disease, depending on their country of birth and their sociodemographic characteristics. The SENOVIE study (Therapeutic mobility and breast cancer) aims to understand the life trajectories of women born in France and in sub-Saharan Africa treated for breast cancer in four hospitals in the greater Paris area.

Methods and analysis
The SENOVIE study is a mixed methods study, combining a quantitative and a qualitative approach. A quantitative retrospective life-event survey is conducted in four hospital centres in the greater Paris area, France, to (1) understand how breast cancer (diagnosis, treatment and possibly reconstruction) impacts the life trajectories of women in many spheres (migration, family life, professional life, financial situation, etc); (2) study the access to healthcare by women living with breast cancer and their determinants; and (3) examine how gender relations may shape breast cancer experience. Women born in France and women born in sub-Saharan Africa are recruited: 1000 women, including 500 per group. In the standardised, face-to-face questionnaire, each dimension of interest is collected year by year from birth until the time of the survey. Clinical and laboratory information is documented with a short medical questionnaire filled out by the medical teams. The qualitative survey is conducted specifically with women born in sub-Saharan Africa who came to France for treatment to better understand their trajectories and the specific obstacles they faced. To analyse the quantitative data collected, descriptive analyses will be used to visualise trajectories (sequence analysis), along with longitudinal analysis methods (survival models and duration models).

Ethics and dissemination
The study is conducted in accordance with the Declaration of Helsinki. The French Data Protection Authority (Commission Nationale de l’Informatique et des Libertés, declaration number 2231238) and the Committee for Persons’ Protection East I (Comité de Protection des Personnes Est I, national number 2023-A01311-44) approved it. We will disseminate the findings through scientific publications, policy briefs, conferences and workshops.

Trial registration number
The SENOVIE France study is registered on Clinicaltrial.gov (NCT06503393; registration date: 7 September 2024; https://clinicaltrials.gov/study/NCT06503393).

Introduction
Childhood tuberculous meningitis (TBM) is a devastating disease. The long-standing WHO recommendation for treatment is 2 months of intensive phase with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), followed by 10 months of isoniazid and rifampicin. In 2022, WHO released a conditional recommendation that 6 months of intensified antituberculosis therapy (ATT) could be used as an alternative for drug-susceptible TBM. However, this has never been evaluated in a randomised clinical trial. Trials evaluating ATT shortening regimens using high-dose rifampicin and drugs with better central nervous system penetration alongside adjuvant anti-inflammatory therapy are needed to improve outcomes.

Methods and analysis
The Shortened Intensive Therapy for Children with Tuberculous Meningitis (SURE) trial is a phase 3, randomised, partially blinded, factorial trial being conducted in Asia (India and Vietnam) and Africa (Uganda, Zambia and Zimbabwe). It is coordinated by the Medical Research Council Clinical Trial Unit at University College London (MRCCTU at UCL). 400 children (aged 29 days to

Introduction
New-onset supraventricular arrhythmia (NOSVA) is the most common arrhythmia in patients with septic shock and is associated with haemodynamic alterations and increased mortality rates. With no data available from randomised trials, clinical practice for patient management varies widely. In this setting, rate control or rhythm control could be beneficial in limiting the duration of shock and preventing evolution to multiorgan dysfunction.

Methods and analysis
The Control Atrial Fibrillation in Septic shock (CAFS) study is a binational (French and Belgium), multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three management strategies in patients with NOSVA during septic shock. The expected duration of patient enrolment is 42 months, starting from November 2021. Patients will be randomised to receive either risk control (magnesium and control of risk factors for NOSVA), rate control (risk control and low dose of amiodarone) or rhythm control (risk control and cardioversion using high dose of amiodarone with external electrical shock if NOSVA persists) for 7 days. Patients with a history of SVA, NOSVA lasting more than 48 hours, recent cardiac surgery or a contraindication to amiodarone will not be included. We plan to recruit 240 patients. Patients will be randomised on a 1:1:1 basis and stratified by centre. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality and the duration of septic shock defined as time from randomisation to successful weaning of vasopressors. Secondary outcomes include: individual components of the primary endpoint; arterial lactate clearance at day 3; efficacy at controlling cardiac rhythm at day 7; proportion of patients free from organ dysfunction at day 7; ventricular arrhythmia, conduction disorders, thrombotic events, major bleeding events and acute hepatitis related to amiodarone at day 28; intensive care unit and hospital lengths of stay at day 28.

Ethics and dissemination
The study has been approved by the French (Comité Sud-Ouest et Outre-Mer II, France, registration number 2019-A02624-53) and Belgian (Comité éthique de l’hôpital Erasme, Belgium, registration number CCB B4062023000179) ethics committees. Patients will be included after obtaining signed informed consent. The results will be submitted for publication in peer-reviewed journals.

Trial registration number
NCT04844801.

‘Il mondo attraverso i miei occhi’. Foto, disegni e racconti per comprendere

‘Il mondo attraverso i miei occhi’. Foto, disegni e racconti per comprendere

Circulation, Ahead of Print. BACKGROUND:TAP-IT (Thoracentesis to Alleviate Cardiac Pleural Effusion–Interventional Trial) investigated the effect of therapeutic thoracentesis in addition to standard medical therapy in patients with acute heart failure and sizeable pleural effusion.METHODS:This multicenter, unblinded, randomized controlled trial, conducted between August 31, 2021, and March 22, 2024, included patients with acute heart failure, left ventricular ejection fraction ≤45%, and non-negligible pleural effusion. Patients with very large effusions (more than two-thirds of the hemithorax) were excluded. Participants were randomly assigned 1:1 to upfront ultrasound-guided pleural pigtail catheter thoracentesis in addition to standard medical therapy or standard medical therapy alone. The primary outcome was days alive out of the hospital over the following 90 days; key secondary outcomes included length of admission and 90-day all-cause mortality. All outcomes were analyzed according to the intention-to-treat principle.RESULTS:A total of 135 patients (median age, 81 years [25th; 75th percentile, 75; 83]; 33% female; median left ventricular ejection fraction, 25% [25th; 75th percentile, 20%; 35%]) were randomized to either thoracentesis (n=68) or standard medical therapy (n=67). The thoracentesis group had a median of 84 days (77; 86) alive out of the hospital over the following 90 days compared with 82 days (73; 86) in the control group (P=0.42). The mortality rate was 13% in both groups, with no difference in survival probability (P=0.90). There were no differences in the duration of the index admission (control group median, 5 days [3; 8]; thoracentesis group median, 5 days [3; 7;P=0.69]). Major complications occurred in 1% of thoracenteses performed during the study period.CONCLUSIONS:For patients with acute heart failure and pleural effusion, a strategy of upfront routine thoracentesis in addition to standard medical therapy did not increase days alive out of the hospital for 90 days, all-cause mortality, or duration of index admission. The current findings lay the groundwork for future research to confirm the results.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT05017753.

Mapping human behavior to brain circuits has long been a goal for behavioral neurologists and neuropsychologists. Many discoveries were based on detailed psychological and anatomical studies of a single case. A famous example is Henry Gustav Molaison, better known as H.M.

This case-control study analyzes published cases of lesion-induced psychosisTo assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit

Stroke, Ahead of Print. BACKGROUND:Chronic cerebral hypoperfusion-induced white matter lesions are an important cause of vascular cognitive impairment in aging life. TGF-β1 (transforming growth factor β1) is widely recognized as a multifunctional cytokine participating in numerous pathophysiological processes in the central nervous system. In this study, we aimed to evaluate the neuroprotective potentials of TGF-β1 in ischemic white matter lesions.METHODS:A mouse model of bilateral common carotid artery stenosis was established to imitate the ischemic white matter lesions. The agonist of the TGF-β1 pathway was continuously applied via intraperitoneal injection. The Morris water maze test and gait analysis system were used to assess the cognitive and gait disorders in modeling mice. The Luxol fast blue staining, immunofluorescence, and electron microscopy were conducted to determine the severity of demyelinating lesions, microglial activation, and dysfunction of the autophagy-lysosomal pathway in microglia. Furthermore, primary cultured microglia were exposed to extracted myelin debris and TGF-β1 in vitro to explore the underlying mechanisms.RESULTS:As evaluated by behavioral tests, TGF-β1 significantly alleviated the cognitive dysfunction and gait disorder in bilateral common carotid artery stenosis-modeling mice. The demyelinating lesion and remyelination process were also found to be highly improved by activation of the TGF-β1 pathway. The results of immunostaining and electron microscopy showed that TGF-β1 could ameliorate microglial activation and the dysfunction of lipid metabolism in myelin-engulfed microglia. Mechanistically, in primary cultured microglia exposed to myelin debris, administration of TGF-β1 notably mitigated the inflammatory response and accumulation of intracellular lipid droplets via promoting the lipid droplets degradation in the autophagy-lysosomal pathway, as quantified by flow cytometry, immunostaining, Western blot, etc. Yet, the application of autophagy inhibitor (3-methyladenine) significantly reversed the above anti-inflammatory effects of TGF-β1.CONCLUSIONS:TGF-β1 relieved cognitive deficit, demyelinating lesions, and microglia-mediated neuroinflammation in bilateral common carotid artery stenosis modeling by reducing abnormal lipid droplet accumulation and dysfunction of the autophagy-lysosomal pathway in microglia. Clinically, staged activation of the TGF-β1 pathway may become a potential target and promising treatment for ischemic white matter lesions and vascular cognitive impairment.

Circulation, Ahead of Print. Background: One-year outcomes of the TRILUMINATE Pivotal trial found that transcatheter edge-to-edge repair (TEER) for the treatment of severe, symptomatic tricuspid regurgitation (TR) improved quality-of-life compared with medical therapy alone with similar rates of mortality and heart failure hospitalization (HFH). However, additional follow-up is necessary to determine prolonged benefits of tricuspid TEER.Methods: A total of 572 patients with severe, symptomatic TR were randomized to either tricuspid TEER+medical therapy (Device) or medical therapy alone (Control). Two-year prespecified endpoints were (1) recurrent HFH and (2) freedom from all-cause mortality, tricuspid valve surgery and tricuspid valve intervention post treatment visit, assessed in the intention-to-treat population.Results: The annualized rate of recurrent heart failure hospitalizations through 2 years was significantly lower with tricuspid TEER compared with Control (0.19 vs 0.26 events/patient-year, p=0.02; joint frailty model hazard ratio 0.72, one-sided upper confidence limit of 0.93, p=0.02). Freedom from all-cause mortality, tricuspid valve surgery, and tricuspid valve intervention through 2 years was significantly higher with tricuspid TEER compared with Control (77.6% vs 29.3%, p

Objectives
To describe temporal trends in hospitalisation episodes for venous thromboembolic events (VTEs) in England, and compare hospitalisation rates for pulmonary emboli (PEs) and deep vein thrombosis (DVT).

Methods
Retrospective observational study.

Setting
Secondary care in England, UK, between April 1998 and March 2022.

Participants
Individuals with hospitalisations for VTE recorded in the NHS Digital Hospital Episode Statistics dataset.

Primary and secondary outcomes
The primary outcome was temporal trends in hospitalisation episodes for PE, DVT and VTE overall between 1 April 1998 and 31 March 2022. Secondary outcomes included the proportion of all-cause hospital admissions that were due to VTE; the proportion of all VTE hospitalisations that were recorded as primary admission diagnoses; the male/female split in hospitalisation episodes for VTE; and temporal changes in hospitalisation rates by age.

Results
Between 1998 and 2022, hospitalisations for VTE increased by 62.6%, from 109.5 to 178.1 per 100 000 population. This was driven by a 202% increase in hospitalisations for PE (from 40.4 to 122.2 per 100 000 population). In contrast, hospitalisations for DVT decreased by 19.1% over this period (from 69.1 to 55.9 per 100 000 population). Overall, VTE remained stable as a proportion of all-cause hospital admissions between 1998/1999 and 2019/2020 (0.45% and 0.43%, respectively), before increasing after the onset of the COVID-19 pandemic in England (0.59% in 2020/2021 and 0.51% in 2021/2022).

Conclusion
Hospitalisations for VTE increased markedly in England between 1998 and 2022, driven by large increases in hospitalisations for PE. In contrast, hospitalisations for DVT decreased overall, which may reflect the success of primary care DVT management pathways. Our findings suggest that preventative measures are needed to reduce the incidence of hospitalisations for PE.

Objectives
Falls from heights are a leading cause of workplace injuries and fatalities. Ensuring worker fitness is crucial, yet many countries lack formal guidelines for fitness for work (FFW) assessments, posing safety and legal risks. This scoping review sought to identify and map the existing evidence on the assessment of fitness to work at heights.

Design
Scoping review following the Joanna Briggs Institute Scoping Review Methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines.

Data sources
Searches were conducted in March 2024 across ProQuest Central, Google Scholar, PubMed, Scopus, ScienceDirect, Web of Science and PsycINFO. Grey literature was sourced from the websites of organisations including the International Labour Organisation, Safe Work Australia, Canadian Centre for Occupational Health and Safety, Health and Safety Executive (UK), Occupational Safety and Health Administration (USA), WHO, Centre for Construction Research and Training (USA), Institution of Occupational Safety and Health (UK), South African Society of Occupational Medicine, South African Society of Occupational Health Nursing and Institute for Work at Height (South Africa), in addition to general Google searches.

Eligibility criteria for selecting studies
Our inclusion criteria encompassed both peer-reviewed and grey literature that addressed either ‘fitness for work at heights’, ‘fitness for work in high-risk settings requiring work at heights’ or human risk factors associated with working at heights.

Data extraction and synthesis
A data extraction framework and guidance sheet were developed, piloted and refined through team discussions. An iterative review process was followed, with one author extracting and coding data while two authors conducted quality checks. Deductive qualitative content analysis was applied to the extracted data.

Results
68 articles met the inclusion criteria, but only 7 directly addressed fitness to work at heights, with the rest focusing on fitness to work in high-risk settings requiring work at heights or human risk factors associated with work at heights. This highlights a lack of peer-reviewed research specific to the topic. Key challenges included FFW assessments failing to reflect job demands, inconsistent application of FFW evaluations, lack of standardisation and inadequate stakeholder collaboration. Legal tensions between employer safety obligations and worker rights were also noted. Critical human risk factors—such as physical and mental limitations, adverse states, human error and rule violations—significantly affected worker safety, though evidence of their specific impact in this context remained limited. Findings on the economic implications of FFW assessments were also inconclusive.

Conclusion
Assessing FFW at heights is vital for worker safety, yet key challenges persist. This review highlights gaps in evidence on human risk factors and assessment methods. Findings emphasise the need for practice-based research, standardised fitness criteria and interdisciplinary protocols for preplacement assessment and ongoing monitoring.

Objective
Azithromycin has been shown to reduce all-cause child mortality. This subgroup analysis investigates azithromycin’s mortality impact by underweight status using Azithromycine pour la Vie des Enfants au Niger: Implementation et Recherche (AVENIR) trial data.

Design
The AVENIR trial randomised communities into three arms: azithromycin for children aged 1–59 months, azithromycin for infants aged 1–11 months or placebo. Weight-for-age z-score was used to categorise children into subgroups of either moderate to severe underweight or not and severe underweight or not.

Setting
2880 communities with a population of less than 2500 people in the Dosso and Tahoua regions of Niger that participated in the AVENIR trial were included.

Participants
97 572 children aged 1–59 months who had weight captured during at least one census participated.

Results
Underweight subgroups had higher overall mortality compared with non-underweight subgroups. IRDs of deaths in children aged 1–11 months comparing communities receiving azithromycin to children 1–59 months of age to placebo were –6.2 deaths per 1000 person-years (95% CI –9.3 to –2.6) overall, –8.0 (95% CI –15.9 to –0.4) in the moderate to severe subgroup and –11.2 (95% CI –26.0 to –2.1) in the severe subgroup. Similar trends were noted in the azithromycin 1–11 month comparison. Malnutrition was not a statistically significant effect modifier for either comparison.

Conclusions
Although analyses suggest the potential for stronger effects in more severe underweight subgroups, we were unable to demonstrate underweight status as an effect modifier. In fact, azithromycin mass drug administration to children 1–59 months old reduced mortality in all subgroups, and, especially as the number of lives saved would be the highest by treating all subgroups, our results do not support restricting eligibility for this intervention.

Trial registration number
clinicaltrials.gov NCT04224987.

Objective
Azithromycin has been shown to reduce all-cause child mortality. This subgroup analysis investigates azithromycin’s mortality impact by underweight status using Azithromycine pour la Vie des Enfants au Niger: Implementation et Recherche (AVENIR) trial data.

Design
The AVENIR trial randomised communities into three arms: azithromycin for children aged 1–59 months, azithromycin for infants aged 1–11 months or placebo. Weight-for-age z-score was used to categorise children into subgroups of either moderate to severe underweight or not and severe underweight or not.

Setting
2880 communities with a population of less than 2500 people in the Dosso and Tahoua regions of Niger that participated in the AVENIR trial were included.

Participants
97 572 children aged 1–59 months who had weight captured during at least one census participated.

Results
Underweight subgroups had higher overall mortality compared with non-underweight subgroups. IRDs of deaths in children aged 1–11 months comparing communities receiving azithromycin to children 1–59 months of age to placebo were –6.2 deaths per 1000 person-years (95% CI –9.3 to –2.6) overall, –8.0 (95% CI –15.9 to –0.4) in the moderate to severe subgroup and –11.2 (95% CI –26.0 to –2.1) in the severe subgroup. Similar trends were noted in the azithromycin 1–11 month comparison. Malnutrition was not a statistically significant effect modifier for either comparison.

Conclusions
Although analyses suggest the potential for stronger effects in more severe underweight subgroups, we were unable to demonstrate underweight status as an effect modifier. In fact, azithromycin mass drug administration to children 1–59 months old reduced mortality in all subgroups, and, especially as the number of lives saved would be the highest by treating all subgroups, our results do not support restricting eligibility for this intervention.

Trial registration number
clinicaltrials.gov NCT04224987.