Search Results for: Come si esegue la raccolta delle urine delle 24 ore

Introduction
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more spontaneous pregnancy losses from the time of conception until 24 weeks of gestation. Currently, an underlying cause can be identified in only a minority of the losses. Potentially, an impaired maternal immune response targeting the semiallograft pregnancy may lead to miscarriage. While prior studies have explored the use of immune-suppressing corticosteroids to modulate the maternal immune system and hopefully improve pregnancy outcome, the absence of sufficiently powered randomised controlled trials (RCT) underscores the need for further research. The primary aim of this study is to evaluate if prednisolone administration in early pregnancy (20 mg daily for 6 weeks, then tapering doses for 2 weeks) in women with unexplained RPL leads to a higher live birth rate (LBR) in comparison to placebo. Additionally, the study assesses the tolerability, safety and the cost-effectiveness of this intervention. Finally, we will explore the effect of prednisolone in various subgroups (based on maternal age, number of previous pregnancy losses, presence of specific antibodies and pre-pregnancy endometrial immune cell level).

Methods and analysis
This ongoing multicentre, double-blind RCT will randomise 490 women with unexplained RPL and pregnancy

Introduction
The cuff leak test (CLT) is hypothesised to help optimise extubation by assessing for laryngeal oedema which, if unrecognised and untreated, could lead to post-extubation stridor, post-extubation airway obstruction, and reintubation. However, the diagnostic accuracy of the CLT to detect post-extubation stridor (and hence potentially airway obstruction) remains uncertain. Given the equipoise that exists surrounding the CLT, we are conducting a pilot randomised clinical trial (RCT) examining the CLT as part of the pathway to extubation. Herein, we report the protocol for the Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients (COSMIC): a Pilot Feasibility Randomized Clinical trial (RCT).

Methods and analysis
This is a multicentre, international, parallel-group, pragmatic, pilot RCT. We will enrol 100 mechanically ventilated patients in the intensive care unit (ICU) who are deemed ready for extubation and have at least one risk factor for laryngeal oedema. In the intervention arm, respiratory therapists will perform a qualitative CLT before extubation. If a patient passes the CLT (suggesting no laryngeal oedema), extubation will be performed in keeping with standard care. If the patient fails the CLT (suggesting laryngeal oedema), extubation will be delayed allowing for administration of dexamethasone, consideration of diuresis, and the CLT will be repeated in 12–24 hours. In the control arm, patients will be extubated without completing a CLT, without steroid administration, and without delay. Randomization will be by a 1:1 allocation, stratified by centre. The primary feasibility outcomes will include recruitment and protocol adherence. Secondary outcomes will include post-extubation stridor, reintubation within 72 hours, emergency surgical airway within 72 hours, and ICU and hospital mortality within 30 days.

Ethics and dissemination
This trial has been approved by Clinical Trials Ontario, Hamilton Integrated Research Ethics Board, State of Kuwait Ministry of Health, University of Texas Health Committee for the Protection of Human Subjects and Brant Community Health Systems Research Ethics Committee. The trial has received a No Objection Letter from Health Canada. Trial results will be disseminated via publication in peer-reviewed journals.

Trial registration number
NCT05456542.

Introduction
Urinary tract infections (UTIs) are highly prevalent and pose a significant burden among older adults. Accurate diagnosis in this population is challenging due to the high prevalence of pre-existing lower urinary tract symptoms, inability to express symptoms and asymptomatic bacteriuria. Current diagnostic tests are unreliable, often resulting in over- and underdiagnosis. A previous pilot study proposed a higher cut-off for pyuria and identified five promising biomarkers for the diagnosis of UTIs in older adults. The UTI-GOLD study aims to validate these five new biomarkers and the higher leucocyte cut-off as a diagnostic tool for UTIs in older people in a real-world setting.

Methods and analysis
Between August 2024 and December 2027, an observational multicentre diagnostic accuracy study is being conducted across primary, secondary and tertiary healthcare facilities in the Netherlands and the UK. Adults ≥65 years with a suspected UTI will be considered eligible. Patients with pre-existing decision-making incapacity or an indwelling catheter will be excluded. UTI will be defined according to an international consensus-based reference standard. Biomarkers will be measured by liquid chromatography-mass spectrometry (neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase 2 and CXC motif chemokine ligand 9) and enzyme-linked immunosorbent assay (interleukin 6 and azurocidin). Pyuria will be quantified by automated microscopy and/or flow cytometry. Diagnostic accuracy measures will be calculated using the receiver operating characteristic curves, and sensitivity, specificity, likelihood ratios and predictive values will be reported for optimal cut-offs.

Ethics and dissemination
The protocol was reviewed by the local Leiden University Medical Center research committee, who declared on 15 April 2024 that the medical research involving human subject act (Dutch abbreviation: WMO) does not apply to the current study (reference number nWMODIV2_2024025). The study also received approval from the NHS Research Ethics Committee in the UK (reference number 24/LO/0649).
The study findings will be published in a peer-reviewed journal, presented at academic congresses and shared with healthcare providers.

Trial registration number
The study was registered at clinicaltrial.gov on the 24 September 2024 with registration number: NCT06610721.

Introduction
Concurrent with infants’ progression in dietary complexity and gut microbiome diversity, infants gradually change their defecation patterns during the first year of life. However, the links between bowel habits, the gut microbiota and early life nutrition remain unclear. The primary outcome is to characterise the gut microbiome development from birth to 1 year of age. Second, to investigate how bowel habits and nutrition in early life relate to the gut microbiome and metabolome during this period of life, and to explore how the development of the gut microbiome associates with host development.

Methods and analysis
The MOTILITY Mother-Child Cohort (MOTILITY) is a Danish prospective longitudinal cohort study enrolling up to 125 mother–infant dyads. Assessments occur at 36 weeks gestation (visit 1), birth (screening of infant) and 3, 6, 9 and 12 months (±2 weeks) post partum (visits 2–5). At visit 1, maternal anthropometrics, self-collected faecal and urine samples, and questionnaires on bowel habits and lifestyle are obtained. Between visits, infant faecal (biweekly), urine (monthly) and maternal breast milk (monthly until 6 months of age) samples are collected at home, and bowel habits and dietary intake are assessed biweekly by self-reported questionnaires. At visits 2–5, infant blood and saliva samples are collected, and anthropometric measurements are obtained. In addition, dietary intake is recorded thrice throughout the study period for mother and infant, respectively, and infant whole-gut transit time is estimated by sweet corn tests at 9 and 12 months of age. Birth, growth, motor development, sleep patterns, tooth development, overall health and well-being are assessed using questionnaires. Univariate and multivariate statistics will be applied to identify associations between the gut microbiome, early life nutrition and host physiology including bowel habits during the first year of life.

Ethics and dissemination
The MOTILITY study has been approved by the Research Ethics Committee for the Capital Region of Denmark (reference number: H-21063016). Selected results will be made available to the participants in the form of a summary document. Results will be published in peer-review journals and by means of national and international conferences.

Trial registration number
NCT05491161.

Purpose
Breastfeeding is beneficial to the health of both the mother and infant. Despite recommendations to breastfeed by organisations including the WHO and the American Academy of Pediatrics, rates of breastfeeding remain below public health goals. The Mother and Infant Metabolome and Microbiome (MIMM) study is a prospective cohort study of healthy mother-term infant dyads designed to comprehensively assess the perinatal, maternal, neonatal and infant factors that are associated with breastfeeding outcomes and human milk composition.

Participants
MIMM participants were recruited from two medical centres in Boston, Massachusetts, from 2019 to 2023 and are followed for 2 years. Dyads were included if the mother delivered a singleton infant at ≥37 weeks’ gestation, was discharged home

Objective
To co-design a core outcome set with people living with dementia and other stakeholders that can be used to measure the quality of dementia care in home care and residential settings.

Design
Multilevel modified Delphi consensus study. A priori consensus threshold of 70% was used to include or exclude outcomes.

Setting
Routine dementia care provided through home care and residential aged care facilities in Australia.

Participants
A stakeholder panel comprising people living with dementia, formal and family/informal carers of people living with dementia, advocates, policy experts, allied-health professionals, nurses and professionals working in the aged care industry. Round 1 included 10 panellists; subsequent rounds extended the number of participants to 24.

Results
Seven outcome domains (Death, Physiological and clinical, Functional, Life impact, Resources, Adverse events and Education), encompassing 105 individual outcomes were considered by the panel over four rounds.
The 105 outcomes were distilled to 16 outcomes identified as important in home care and 15 in residential aged care. In both settings, nine outcomes (Dignity, Advanced care planning, Meaningful activities, Feeling safe and secure, Emotional wellbeing, Quality of Life, Resource utilisation, Safety incidents and Dementia-specific qualifications for care staff) were considered important.
Additionally, seven outcomes in the home care setting (Behavioural symptoms of dementia, Diagnosis of dementia, Hygiene, Importance of Relationships, Quality of carer and family lives, Dementia care navigation and Opportunities for unpaid carers) and six outcomes in the residential aged care setting (Neuropsychiatric symptoms of dementia, Pain, Hygiene and comfort, Medication safety, Staff carer morale and Adverse effects) were classified as important.

Conclusions
The outcomes identified during this modified Delphi consensus study provide a promising basis for the development of a meaningful, practical and measurable core outcome set that could be used in dementia care settings to improve the quality of routine care provided to people living with dementia.

Introduction
Hypertensive disorders of pregnancy (HDP), including gestational hypertension and pre-eclampsia, affect approximately 10% of pregnancies worldwide and contribute significantly to fetal and maternal morbidity and mortality. Early identification of HDP would facilitate targeted surveillance and personalised care in order to mitigate the severity of complications and improve pregnancy outcomes. Uric acid is a marker of oxidative stress, inflammation and endothelial dysfunction, and has been proposed as a predictor of hypertensive disease. Salurate is a salivary uric acid test that has the potential to identify pregnant women at risk of developing HDP several weeks before clinical manifestation.

Methods and analysis
This is a prospective, multicentre, observational, cohort study with health economics evaluation. Women aged 16 and above, with a viable singleton pregnancy at 1:300 will be eligible for recruitment. Participants will perform weekly remote salivary uric acid testing from enrolment until the conclusion of pregnancy and upload results of colourimetric paper tests via a smartphone application. We will validate a predictive algorithm that analyses colour data from several consecutive samples to detect patterns that predict whether HDP is likely to occur. The primary outcome is test performance for the prediction of HDP. Secondary outcomes include adherence to sampling and test performance for predicting gestational diabetes, stillbirth and fetal growth restriction. Data on pregnancy outcomes will be collected from the medical notes, compared with the predictions made by the algorithm and subjected to statistical analysis.

Ethics and dissemination
Approval has been obtained from Cambridge East Research Ethics Committee (REC reference 24/EE/0123), Medicines and Healthcare products Regulatory Agency (CI/2024/0038/GB) and Health Research Authority (IRAS ID 337290). Results of the study will be published in peer-reviewed journals and presented at national and international conferences.

Trial registration number
ISRCTN17992452.

Protocol version
4, 4 July 2024.

Objectives
To compare the effectiveness of buprenorphine-naloxone (bup/nal) and methadone maintenance therapy (MMT) in the treatment of patients with opioid use disorder (OUD) during the fentanyl era.

Design
Secondary analysis of prospective cohort study data.

Setting
Data for the study were collected from 54 clinical sites across Ontario, Canada, between May 2018 and January 2023.

Participants
To be included in the present study, participants had to be at least 16 years of age, have provided written informed consent and be receiving either MMT or bup/nal therapy for OUD. This study includes data from 2601 participants, of whom 2068 were receiving MMT and 533 were receiving bup/nal for OUD. The mean age of participants was 39.4 years (SD: 10.9), and 45% were female.

Interventions
MMT or bup/nal treatment for OUD.

Outcome measures
We employed a propensity score matched analysis to compare treatment outcomes among patients receiving MMT compared with bup/nal. We used ongoing illicit opioid use as an indicator of treatment outcome. We considered participants with >50% of urine drug screens in the past 12 months positive for non-prescribed opioids to be ‘non-responders’. We conducted subgroup analyses to identify whether treatment type was associated with ongoing non-prescribed opioid use among patients with and without a history of intravenous drug use (IVDU), and whether treatment type was associated with retention in treatment.

Results
Eight per cent of patients on bup/nal were considered non-responders, compared with 11.9% of patients on MMT. We did not find a statistically significant association between treatment type and treatment response. However, we did find that patients on MMT were more likely to stay in treatment for 12 months (OR 1.79, 95% CI 1.45 to 2.22, p

Introduction
Biological disease modifying antirheumatic drugs (bDMARDs) have a central role in the treatment of rheumatoid arthritis (RA). Tumour necrosis factor inhibitors (TNFis) are commonly used as first-line agents, while non-TNFis (tocilizumab, abatacept and rituximab) have shown to be non-inferior to TNFis in head-to-head trials. In case of TNFi inadequate response, using other mechanisms of action provides a better response than using an alternate TNFi. Which non-TNFi bDMARD administered subcutaneously to allow for ambulatory management to choose in case of first line TNFi inadequate response has not been tested in a randomised clinical trial, while observational data support a potential superiority of tocilizumab over abatacept.

Methods and analysis
The SUNSTAR (SUbcutaNeouS Tocilizumab vs Abatacept in TNF Alpha inadequate responders for the treatment of Rheumatoid arthritis) study is a 52-week prospective, randomised, multicentre, open-label, superiority phase IV trial comparing subcutaneous tocilizumab with abatacept in a 1:1 ratio. Patients with active RA (Disease Activity Score-erythrocyte sedimentation rate >3.2 and Clinical Disease Activity Index (CDAI) >10) and with inadequate 3-month response to a first or second TNFi are included in 25 centres in France. The primary outcome is the CDAI improvement at week 24. Intention-to-treat analysis will be applied primarily. The secondary outcome is a composite outcome of the percentage of responders defined as a CDAI

Objective
To quantify the carbon footprint of a sample of clinical trials for neurological disorders.

Design
Cross-sectional study.

Method
Two clinical trial registries were searched on 29 December 2022 for phase 2–4 randomised controlled trials led from and recruiting in the UK, enrolling people with any of the 15 neurological disorders with the highest global burden, that had started recruitment or been registered in the preceding 5 years. Eligible trials were invited to share data to estimate emissions in each of the 10 modules of the Low Carbon Clinical Trials footprinting guidance. The primary outcome measure was kg of carbon dioxide equivalent (CO2e).

Results
318 randomised controlled trials were found, nine were eligible and six shared data (three completed and three ongoing). The module with the highest estimated CO2e for each trial was the Clinical Trial Unit staff emissions (median 24 126 kg CO2e, IQR 10 395–78,867; range 45–79% of overall emissions of each trial); commuting accounted for >50% of CO2e in this module. The second and third highest modules were trial-specific participant assessments (median 11 497 kg CO2e, IQR 825–15,682) and trial supplies and equipment (median 1161 kg CO2e, IQR 226–6632). The total carbon footprint of these six trials involving 2248 participants at 239 sites was 2 63 215 kg CO2e.

Conclusions
Emissions by Clinical Trials Unit staff were the top modifiable carbon hotspot in six randomised controlled trials for people with neurological disorders, which had a total carbon footprint equivalent to 1364 passengers’ return aeroplane journeys between London and Edinburgh.

Objectives
To describe the trends in high remnant cholesterol (HRC) prevalence and identify its risk factors.

Design
A serial cross-sectional study.

Setting
Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2020 were analysed.

Participants
A total of 24 658 adults aged ≥18 years with fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) measured were included.

Outcome measure
Serum TC was measured using an enzymatic method. HDL-C and TG were quantified using photometry. Low-density lipoprotein cholesterol (LDL-C) was estimated by using the Sampson formula. Remnant cholesterol (RC) was defined as TC–HDL-C–LDL-C. HRC was defined as RC≥0.78 mmol/L.

Results
The multivariable-adjusted survey-weighted HRC prevalence decreased from 26.6% (1999–2002) to 13.7% (2015–2020) with a 5.4% reduction per year (plinear-trend

Objectives
This study aimed to investigate the incidence of oral mucous membrane medical device-related pressure injury (MDR-MM PI) and identify its risk factors in critically ill patients undergoing orotracheal intubation, guided by the conceptual framework of pressure injury development. The findings aim to inform effective preventive strategies in intensive care settings.

Design
Prospective cohort study.

Setting
General intensive care unit (ICU) of a tertiary care hospital in China.

Participants
Patients aged ≥18 years who underwent oral endotracheal intubation were included between July 2023 and July 2024. Exclusion criteria were (1) existing oral mucosal injuries before intubation, (2) radiotherapy-induced oral mucositis, (3) patients undergoing oral surgery and (4) intubation duration of less than 24 hours. A total of 420 patients met the criteria and were included in the final analysis.

Outcomes
The outcomes included the incidence of oral MDR-MM PI, the time to oral MDR-MM PI occurrence and the identification of risk factors using multivariate Cox regression analysis.

Results
Among the 420 patients, 43.10% (n=181) developed oral MDR-MM PI, with Stage I accounting for 38.67% and Stage II for 61.33%. The lower lip (38.67%) and upper lip (38.12%) were the most common injury sites. The median time to oral MDR-MM PI occurrence was 8 days (95% CI: 7.134 to 8.866). Significant risk factors identified through multivariate Cox regression included sepsis (HR=2.090, 95% CI: 1.273 to 3.431), lower platelet (PLT) counts (HR=0.997, 95% CI: 0.995 to 0.999) and use of hard bite blocks (HR=1.553, 95% CI: 1.082 to 2.230). Probiotics showed a protective effect (HR=0.632, 95% CI: 0.468 to 0.854, p

Introduction
Undergraduate students report a high level of trait anxiety, which is a risk factor for further psychological decline if unmanaged. Music-based interventions are cost-effective and have been found to improve indices of anxiety. More recently, music with auditory beat stimulation (ABS) has been shown to improve symptoms of anxiety to a greater extent than music alone. While there is limited empirical evidence, music interventions with ABS may also be effective at targeting neurophysiological markers of anxiety. The aim of this study is to evaluate the effectiveness of a novel music with ABS intervention on self-report and neurophysiological indices of anxiety in undergraduate students with trait anxiety. It is hypothesised that relative to a pink noise control, listening to music with ABS will lower self-reported anxiety, reduce salivary cortisol, increase heart rate variability, increase theta and alpha-band electroencephalography (EEG) power and decrease beta and gamma-band EEG power.

Methods and analysis
Fifty Canadian undergraduate students who self-report experiencing anxiety will be recruited for this two-arm randomised controlled trial. Participants will be randomised to a single music session with ABS or pink noise; each intervention ranges from 24 min to 27 min. Outcomes will be assessed at baseline and immediately following the intervention and will be self-reported anxiety and affect (the State-Trait Inventory of Cognitive and Somatic Anxiety and the Self-Assessment Manikin), salivary cortisol, heart rate variability measured by ECG and cortical measures of anxiety (measured by EEG). Repeated measures analyses of covariance will be performed to evaluate the effect of condition assignment on outcome measures.

Ethics and dissemination
This study will be conducted under the Declaration of Helsinki. This study was approved by the Toronto Metropolitan University Research Ethics Board (REB-2020-068) and registered on ClinicalTrials.gov (NCT05442086). The findings of this study will be published in a peer-reviewed journal.

Trial registration number
NCT05442086.

Introduction
Kidney stones constitute a major global healthcare problem and are characterised by high recurrence rates. Thiazide and thiazide-like diuretics (thiazides) have been the standard medical treatment for the prevention of kidney stone recurrence. This clinical routine has recently been challenged by the findings of the large NOSTONE trial that failed to show superiority of hydrochlorothiazide at doses up to 50 mg daily over placebo in preventing a composite of clinical or radiological recurrence in patients at high risk of kidney stone recurrence. If these results also apply to the longer-acting and more potent thiazides indapamide and chlorthalidone remains unknown. No head-to-head comparison of different thiazides for kidney stone recurrence prevention or for the established proxies of recurrence risk, urine relative supersaturation ratios, has ever been conducted.

Methods and analysis
INDAPACHLOR is a single-centre, randomised, double-blind, cross-over trial evaluating the efficacy of indapamide or chlorthalidone compared with hydrochlorothiazide in lowering urine relative supersaturation ratios for calcium oxalate and calcium phosphate in individuals with idiopathic calcium kidney stones. Participants will be allocated to indapamide 2.5 mg once daily, chlorthalidone 25 mg once daily and hydrochlorothiazide 50 mg once daily in a random sequence. The three consecutive active treatment periods of 28 days each will be separated by wash-out periods of 28 days. Inclusion criteria are age ≥18 years and ≥2 stone episodes in the last 10 years with calcium-containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients with secondary causes of calcium kidney stones are excluded. The primary outcomes are the changes in the relative supersaturation ratios of calcium oxalate and calcium phosphate from baseline to day 28 of each treatment period. Secondary outcomes include changes in 24 hours urine and blood parameters from baseline to day 28 of each treatment period. The study targets enrolment of 99 participants to achieve 80% power for detecting a 20% reduction in the relative supersaturation ratios of calcium oxalate and calcium phosphate when treated with indapamide or chlorthalidone and hydrochlorothiazide.

Ethics and dissemination
The study was approved by the Ethics Commission Bern, Switzerland, and the Competent Authority Swissmedic. Results will be disseminated through peer-reviewed publications and conference presentations.

Trial registration numbers
ClinicalTrials.gov (NCT06111885) and Swiss National Clinical Trials Portal (SNCTP000006156).

Protocol version
Version 4.0, 29 November 2024.

Circulation, Volume 151, Issue 24, Page e1073-e1074, June 17, 2025.

Circulation, Volume 151, Issue 24, Page 1752-1754, June 17, 2025.