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New England Journal of Medicine, Volume 392, Issue 22, Page 2284-2286, June 12, 2025.

Introduction
Polycystic ovary syndrome (PCOS), recognised as the predominant aetiological factor in ovulatory dysfunction-related infertility, accounts for approximately 70% of anovulatory infertility cases. Patients with PCOS have significantly higher anti-Müllerian hormone (AMH) levels than their counterparts undergoing in vitro fertilisation (IVF) for non-PCOS indications (eg, male/tubal factors). Several studies have suggested that a high AMH level is associated with adverse pregnancy outcomes in IVF, particularly preterm delivery. However, most of these studies are retrospective studies, and their results are inconsistent. The majority of AMH measurements are conducted before pregnancy; however, AMH levels fluctuate dynamically during pregnancy. There is a pressing need for a well-structured prospective study to definitively establish whether high AMH levels during pregnancy are associated with IVF/intracytoplasmic sperm injection (ICSI) pregnancy outcomes in PCOS patients.

Methods and analysis
This prospective cohort study will be conducted at four reproductive medicine centres. The plan is to enrol 1,320 PCOS patients and 1320 non-PCOS women who undergo IVF/ICSI and achieve singleton clinical pregnancies. Serum samples will be collected at about 6 weeks of gestation to measure the serum AMH level. Follow-up visits will be conducted at 12, 28 and 37 weeks of gestation, delivery and 6 weeks after delivery to obtain information about pregnancy outcomes and complications. The primary outcome is preterm delivery.

Ethics and dissemination
The study was approved by the Medical Research Ethics Committee of Peking University Third Hospital (M2022618). Informed consent will be obtained from all patients. The results of this clinical study will be presented at scientific conferences and submitted to a peer-reviewed journal.

Trial registration number
ChiCTR2300068554.

Akseer N, Tasic H, Adeyemi O, et al. Concordance and determinants of mothers’ and children’s diets in Nigeria: an in-depth study of the 2018 Demographic and Health Survey. BMJ Open 2023;13:e070876. doi: 10.1136/bmjopen-2022-070876
This article was previously published with an error.
Figure 2 contains an error. Rather than presenting different findings for three age groups, the results were duplicated three times for a single age group. The corrected figure is displayed below for your reference.
Figure 2 (A) Percentage concordance and discordance between maternal and child consumption of specific food groups in past 24 hours. (B) Percentage concordance between maternal and child consumption of specific food groups in past 24 hours (child age 6–11 months). (C) Percentage concordance between maternal and child consumption of food groups (child age 12–23 months).

Una squadra di 50 professionisti al Gaslini

Objectives
Hypertension is one of the silent diseases and is the major cause of many chronic conditions. The treatment services for hypertension and its cardiovascular complications impose high costs on society and the health system. However, in LMCs, there is not enough evidence-based information about the costs of high blood pressure. This study aims to assess the economic burden of hypertension in Iran in 2020.

Design
A prevalence-based cost of illness study.

Setting
Data on hypertension and selected diseases, including their prevalence, incidence, mortality risk and death counts, were sourced from literature reviews, the Global Burden of Disease (GDP) and the Non-Communicable Diseases Research Centre. Cost estimates were derived from health insurance data, surveys, research studies and treatment protocols. Additional data, such as population, employment rates, household activity rates, wage rates and GDP per capita, were obtained from the Statistical Centre of Iran and the World Bank.

Participants and methods
A prevalence-based cost of illness study was used to estimate the economic burden of hypertension. The focus was on the most significant diseases associated with high blood pressure, including coronary heart disease, ischaemic stroke, haemorrhagic stroke and the direct costs of hypertension. Subsequently, the total number of patients was multiplied by the average cost per patient for each disease. To calculate the average cost, inpatient and outpatient, direct non-medical and indirect costs of diseases were estimated and multiplied by a population-attributed fraction of high blood pressure. Direct costs (hospitalisation and outpatient costs and direct non-medical costs) of hypertension were calculated using the bottom-up approach, and the human capital approach was used to calculate indirect costs.

Results
According to the results of the study, the total economic burden of hypertension was $ purchasing power parity (PPP) 12 848.22 million, of which the share of direct medical, non-medical and indirect costs of hypertension were $ PPP 7245.13 million (56.4%), $ PPP 1173.42 million (9.1%) and $ PPP 4429.68 million (34.5%), respectively. The total economic burden of high blood pressure was equal to 23% of the total economic burden of four chronic diseases.

Conclusion
The economic burden of high blood pressure in the country is very high and significant, and it was equivalent to about 1% of the country’s gross domestic product in 2020, which shows the necessity of preventive interventions.

Introduction
Antenatal corticosteroid (ACS) regimens have remained unchanged since the initial trials in 1972, with the optimal regimen still undetermined. The WHO ACTION (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns)-III trial is a three-arm individually randomised double-blind trial evaluating the efficacy and safety of two different ACS dosing regimens (currently used and lower-dose ACS regimens vs placebo) in women with a high probability of having a late preterm birth. This study protocol nested within this trial aims to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) effects of two different ACS dosing regimens in pregnant women in the late preterm period (34–36 weeks) to help inform an optimal dosing regimen.

Methods and analysis
The study will be conducted in two of the five countries participating in the WHO ACTION-III trial—India (Delhi, Belagavi) and Nigeria (Ibadan and Ile-Ife). We will use a population PK approach using sparse sampling to study the PK effects of the two ACS regimens, that is, 6 mg dexamethasone phosphate (DEXp) or 2 mg betamethasone phosphate (BETp), administered intramuscularly every 12 hours for a maximum of four doses or till birth, whichever is earlier, compared with placebo. We will also ascertain the fetal–maternal ratio of DEXp and BETp at birth.
Maternal venous blood samples will be collected at 0, 1–4 hours, 8–12 hours after the first dose, and at 24–36 hours, 48–60 hours, 72–96 hours after the last dose, and immediately after birth, along with cord blood. Concentrations of DEXp and BETp will be measured at set time points using a validated liquid chromatography mass spectroscopy assay. PD parameters measured will include total and differential white blood cell count (by automated analysers using electrical impedance), plasma glucose (hexokinase method) and serum cortisol (using a validated electrochemiluminescence immunoassay), at predefined time points. PK models will be developed for each drug using non-linear mixed effects methods. Optimal dosing will be investigated using Monte Carlo simulations.

Ethics and dissemination
The study has been approved by the WHO Ethics Review Committee and the site-specific ethics committees of the participating leading institutions. Written informed consent will be obtained from all participants. The study results will be published in a peer-reviewed journal and presented at scientific conferences.

Trial registration number
ISRCTN11434567.

Objective
To determine caregiver knowledge of, attitudes towards, and perceptions of feeding practices for infants admitted to a tertiary referral hospital with severe pneumonia, and to identify community feelings about nasogastric tube feeding in Malawi.

Setting
The paediatric ward of a government tertiary referral hospital in Lilongwe, Malawi.

Methods
From March through April 2023, we conducted in-depth interviews with 14 mothers of infants 0–12 months of age hospitalised with severe pneumonia who had been enrolled in an observational study evaluating feeding and swallowing in breastfed infants. In-depth interviews assessed mothers’ attitudes towards hospital feeding practices including nasogastric tube feeding, along with community perceptions of nasogastric tubes. Data were analysed using a thematic analysis approach to assess themes and subthemes of transcripts.

Results
Mothers understood that children with pneumonia are at risk of ‘choking’ during oral feeding; however, they had substantial worries about both withholding breastfeeding and providing nasogastric feeds to their infants through a nasogastric tube. Community perceptions of nasogastric tubes were widely negative and included beliefs that nasogastric tubes cause children to ‘choke’ and die and that medical providers want to harm children. Mothers held strong beliefs about the benefits of breastfeeding.

Conclusion
There are alarming misconceptions in the community around nasogastric tubes and the intentions of medical providers. This leads to maternal concerns about this hospital feeding practice, poor adherence to medical recommendations, and mistrust in the broader healthcare system. To improve hospital outcomes of children with severe pneumonia, caregiver and community education is needed.

Introduction
Breast cancer-related lymphoedema (BCRL) at the arm and/or trunk/breast is a highly feared complication following breast cancer treatment and can be objectified using the state-of-the-art criteria based on volume, extracellular water ratio or skin thickness measurements. Although the incidence of objective BCRL is decreasing due to advances in breast cancer treatment, many patients report a sensation of swelling without the presence of objective BCRL, referred to as subjective BCRL. As little is known about the prevalence and the transitions between different BCRL states (no-subjective-objective) over time, as well as about the underlying mechanisms and contributing factors of subjective BCRL, this will be investigated in the LymphSens study.

Methods and analysis
230 patients with a new diagnosis of unilateral breast cancer will be included in a multicentre longitudinal study. Measurements are performed from presurgery to 12 months postsurgery. The primary objective (aim 1) is to determine the prevalence rate of subjective and objective BCRL at 1, 6 and 12 month(s) postsurgery, as well as transitions between BCRL states (no-subjective-objective BCRL) by a multinomial logistic regression model with generalised estimating equations and transition matrices, respectively. A second objective (aim 2) is to determine factors related to four potential underlying mechanisms (lymphatic, nociceptive, neuropathic and central sensory processing problems) that contribute to the occurrence of subjective BCRL in comparison with no self-reported swelling and objective BCRL. As a third objective (aim 3), within the group of patients with subjective BCRL, we will determine factors related to these four underlying mechanisms that contribute to the severity of subjective BCRL. The analyses for aim 2 and aim 3 will be conducted both at specific time points, that is, 1, 6 and 12 month(s) postsurgery using exploratory analysis and across all time points collectively using multivariable binary logistic regression models or multivariable longitudinal models for repeated measures.

Ethics and dissemination
The LymphSens study protocol received approval from the Ethics Committee of UZ Leuven (S68133) and UZ Antwerp/University of Antwerp (5676-003252). The results of the LymphSens study will be presented at conferences and published in peer-reviewed journals.

Trial registration number
NCT06324721.

Esperti a confronto nella nuova sede dell’Univda

Esperti a confronto nella nuova sede dell’Univda

Esperti a confronto nella nuova sede dell’Univda

Esperti a confronto nella nuova sede dell’Univda

Background
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a 5-year survival rate of 12%. It has two major molecular subtypes: classical and basal, regulated by the master transcription factors (MTFs) GATA6 and Np63, respectively.

Objective
This study sought to uncover the transcriptional regulatory mechanisms controlling PDAC subtype identity.

Design
We integrated primary tumour single-cell RNA-seq, patient-derived xenograft RNA-seq and multispectral imaging to identify MTF-dependent, subtype-specific markers. We created subtype-specific fluorescent reporter systems and conducted drug screenings to find actionable targets. We analysed chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac), MTFs (GATA6, Np63), RNA polymerase II (Pol II), H3K4me3-anchored chromatin topology (HiChIP) and nascent RNA capture sequencing (PRO-seq). Additionally, we used nuclease-dead Cas9 (dCas9) to manipulate transcriptional regulatory mechanisms.

Results
Our approach identified glucocorticoid receptor (GR) agonists as agents that suppress the classical transcriptional programme by interacting with GATA6. GATA6 regulates classical-specific transcription through promoter-proximal pause release. Depletion of GATA6 increased Pol II occupancy at GATA6-bound enhancers and transcriptional start sites, stabilising enhancer–promoter interactions. Artificially inducing pausing at GATA6-bound enhancers with dCas9 abrogated target gene expression and induced pausing at both the enhancer and target gene promoter. Conversely, in basal PDAC Np63 promotes Pol II recruitment and stabilises enhancer–promoter interactions.

Conclusion
This study provides new insights into the transcriptional control and role of GR agonists in controlling PDAC molecular subtype identity.

Objective
To develop models to predict opportunities for improvement in trauma care and compare the performance of these models to the currently used audit filters.

Design
Retrospective registry-based study.

Setting
Single-centre, Scandinavian level one equivalent trauma centre.

Participants
8220 adult trauma patients screened for opportunities for improvement between 2013 and 2022.

Primary and secondary outcome measures
Two machine learning models (logistic regression and XGBoost) and the currently used audit filters were compared. Internal validation by an expanding window approach with annual updates was used for model evaluation. Performance measured by discrimination, calibration, sensitivity and false positive rate of opportunities for improvement prediction.

Results
A total of 8220 patients, with a mean age of 45 years, were analysed; 69% were men with a mean injury severity score of 12. Opportunities for improvement were identified in 496 (6%) patients. Both the logistic regression and XGBoost models were well-calibrated, with intercalibration indices of 0.02 and 0.02, respectively. The models demonstrated higher areas under the receiver operating characteristic curve (AUCs) (logistic regression: 0.71; XGBoost: 0.74). The XGBoost model had a lower false positive rate at a similar sensitivity (false positive rate: 0.63). The audit filters had an AUC of 0.62 and a false positive rate of 0.67.

Conclusions
The logistic regression and XGBoost models outperformed audit filters in predicting opportunities for improvement among adult trauma patients and can potentially be used to improve systems for selecting patients for trauma peer review.

Introduction
Earthen floors are often damp or dusty and difficult to clean, providing an ideal environment for faecal pathogens and parasites. Observational studies have revealed associations between household flooring and health outcomes, but robust experimental evidence is scant. This study will evaluate the impact of an improved household flooring intervention on enteric infections, soil-transmitted helminth (STH) infections and tungiasis through implementation of a cluster-randomised trial in two rural settings in Kwale and Bungoma Counties, Kenya.

Methods and analyses
440 clusters (households) across both sites are allocated to control or intervention group, in which a low-cost, sealed, washable, cement-based floor is installed in eligible buildings of the dwelling, alongside a floor-care guide provided during an induction meeting. Following baseline assessments in both groups, all individuals over 1 year receive albendazole and those infected with tungiasis receive benzyl benzoate. Primary outcomes are as follows: prevalence of enteric infections in children under 5 years assessed via stool surveys and PCR; prevalence of tungiasis infection in children 1–14 years based on clinical exam; and prevalence of STH infection in all household members over 1 year assessed via Kato-Katz. Secondary outcomes include the following: intensity of STH and tungiasis infections; prevalence of caregiver-reported gastrointestinal illness in children under 5; quality of life and well-being measures; and environmental contamination. A process evaluation investigates intervention acceptability, durability, practicality and cost.

Ethics and dissemination
The protocol has been approved by ethics committees of The Kenya Medical Research Institute, The Kenya National Commission for Science Technology and Innovation, and The London School of Hygiene & Tropical Medicine. Following the 12-month implementation period and final assessments, control households are offered improved floors. Results will be disseminated within Kenya, to the Ministries of Health and of Lands, Public Works, Housing and Urban Development, and to subnational leadership and communities. Dissemination will also occur through publications and conference presentations.

Trial registration number
NCT05914363.

Circulation, Ahead of Print. BACKGROUND:Recent studies have highlighted the deleterious role of high phosphate intake in hypertension by means of sympathetic overactivation, yet the underlying mechanisms remain unclear. Dietary phosphate loading triggers physiologic release of FGF23 (fibroblast growth factor–23) from the bone to maintain phosphate homeostasis. Both FGF23 and FGF receptors (FGFRs) are present in the central nervous system, but their role in neural control of blood pressure during phosphate loading is unknown. We investigated central FGF23/FGFR signaling in high-phosphate diet–induced sympathetic dysregulation of blood pressure in rats.METHODS:FGF23 protein levels were measured by immunoprecipitation, immunoblotting, and immunohistochemistry. FGF23 translocation into the brain was determined by injecting infrared-labeled FGF23 intravenously into anesthetized Sprague-Dawley rats. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to hindlimb muscle contraction were measured in decerebrate Sprague-Dawley rats treated with either a normal 0.6% phosphate diet (NP) or a high 1.2% phosphate diet (HP) for 12 weeks before and after intracerebroventricular (ICV) administration of FGFR signaling inhibitors.RESULTS:Excess phosphate intake significantly increased FGF23 protein levels in the brainstem (HP versus NP,P=0.009) and cerebrospinal fluid (HP versus NP,P