The paediatric population represents a quarter of the world’s population, and like adult patients, they have also suffered immeasurably from the SARS-CoV-2 pandemic. Immunisation is an effective strategy for reducing the number of COVID-19 cases. With the advancements in vaccination for younger age groups, parents or guardians have raised doubts and questions about adverse effects and the number of doses required. Therefore, systematic reviews focusing on this population are needed to consolidate evidence that can help in decision-making and clinical practice. This protocol aims to assess the safety of COVID-19 vaccines in paediatric patients and evaluate the correlation between the number of vaccine doses and side effects.

We will search the PubMed, ClinicalTrials.gov, Web of Science, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature, Scopus and Cochrane databases for randomised and quasi-randomised clinical trials that list the adverse effects of the COVID-19 vaccine and assess its correlation with the number of doses, without any language restrictions. Two reviewers will select the studies according to the inclusion and exclusion criteria, extract data and asses for risk of bias using the Cochrane risk-of-bias tool. The Review Software Manager (RevMan V.5.4.1) will be used to synthesise the data. We will use the Working Group’s Grading of Recommendations Assessment, Development and Evaluations to grade the strength of the evidence of the results.

Formal ethical approval is not required as no primary data are collected. This systematic review will be disseminated through a peer-reviewed publication.

CRD42023390077.

Social prescribing (SP) is a non-medical intervention in which professionals refer patients to a link worker (LW), who connects them with appropriate support. Children and young people (CYP) with neurodisability often have unmet needs and may bypass community initiatives. We undertook a review of hospital-initiated SP for CYP with neurodisability.

Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance and using Mixed Methods Appraisal Tool.

Medline, PsycINFO, PsycARTICLES, Embase, CINAHL, Scopus, Web of Science and FutureNHS, searched from 1 January 2000 to 19 October 2023, with no language restrictions.

Studies describing SP interventions for CYP (ages 0–25 years) with neurodisability/neurodivergence. Exclusions: interventions outside of secondary care; with no description; or no LW.

Two researchers independently screened references. Data were charted, summarised, quality assessments performed and narratively reviewed.

After removal of duplicates, 518 references were identified. Following screening, eight articles (covering five SP schemes) were included. Rahi et al connected 68 families of CYP newly diagnosed with visual impairment to a community LW. Families needed information about social and educational services, and emotional support. Healthcare professionals had more time for clinical issues. Six papers described three different digital interventions supporting in total 86 CYP with traumatic brain injury and their families. Wade et al (2004, 2005a, 2005b) provided a website with core and individualised sessions, and weekly therapist support. Wade et al (2018) provided a smartphone application, website and weekly meetings with an online coach. These interventions boosted social behaviours. Wade et al (2014, 2015) found that online family problem-solving therapy improved overall child functioning compared with self-guided resources. Toutain et al (2009) provided non-medical support to 11 children with fetal alcohol syndrome and their mothers. No outcome data were provided. Studies reported benefits to health, well-being, healthcare usage, knowledge, skills, satisfaction and service delivery.

Literature describing hospital-initiated SP schemes for CYP with neurodisability, while sparse, suggests potential benefit.

CRD42022384188.

Molar incisor hypomineralisation (MIH) is a qualitative defect of enamel development that occurs in the mineralisation phase. MIH affects one or more permanent molars and, occasionally, permanent incisors. The aim of the proposed study is to evaluate the clinical effect of antimicrobial photodynamic therapy (aPDT) on permanent teeth with MIH through decontamination and sensitivity control.

Patients from 8 to 12 years of age with permanent molars will be randomly allocated to three groups. Group 1: selective chemical–mechanical removal of carious dentinal tissue around the walls of the cavity with Papacárie Duo and a curette followed by the application of aPDT and deproteinisation with Papacárie Duo; group 2: selective removal of carious dentinal tissue around the walls of the cavity with a curette, followed by the application of aPDT and deproteinisation with a 5% sodium hypochlorite solution; group 3: selective removal of carious dentinal tissue using a curette. The selected teeth must have a carious lesion in the dentin and posteruptive enamel breakdown on one or more surfaces with an indication for clinical restorative treatment. The teeth will subsequently be restored using a mixed technique with resin-modified glass ionomer cement and bulk-fill composite resin. The data will be submitted to descriptive statistical analysis. Associations with age and sex will be tested using either the ² test or Fisher’s exact test. Pearson’s correlation coefficients will be calculated to determine the strength of correlations between variables. Comparisons of the microbiological results (colony-forming units) will be performed using analysis of variance and the Kruskal-Wallis test. Kaplan-Meier survival analysis will be performed to assess the performance of the restorations.

This protocol has been approved by the Human Research Ethics Committee of Nove de Julho University (certificate number: 61027522.0.0000.5511/approval date: 23 August 2022). The findings will be published in a peer-reviewed journal.

NCT05443035.

Attention deficit hyperactivity disorder (ADHD) affects 5%–10% of paediatric population and is reportedly more common in children with type 1 diabetes (T1D), exacerbating its clinical course. Proper treatment of ADHD in such patients may thus provide neurological and metabolic benefits. To test this, we designed a non-commercial second phase clinical trial comparing the impact of different pharmacological interventions for ADHD in children with T1D.

This is a multicentre, randomised, open-label, cross-over clinical trial in children and adolescents with ADHD and T1D. The trial will be conducted in four reference paediatric diabetes centres in Poland. Over 36 months, eligible patients with both T1D and ADHD (aged 8–16.5 years, T1D duration >1 year) will be offered participation. Patients’ guardians will undergo online once-weekly training sessions behaviour management for 10 weeks. Afterward, children will be randomised to methylphenidate (long-release capsule, doses 18-36-54 mg) versus lisdexamphetamine (LDX, 30-50-70 mg). Pharmacotherapy will continue for 6 months before switching to alternative medication. Throughout the trial, the participants will be evaluated every 3 months by their diabetologist and online psychological assessments. The primary endpoint (ADHD symptom severity, Conners 3.0 questionnaire) will be assessed by a blinded investigator. Secondary endpoints will include HbA1c, continuous glucose monitoring indices and quality-of-life (PedsQL).

The trial is approved by Bioethical Committee at Medical University of Lodz and Polish regulatory agency (RNN/142/22/KE, UR/DBL/D/263/2022). The results will be communicated to the research and clinical community, and Polish agencies responsible for healthcare policy. Patient organisations focused on paediatric T1D will be notified by a consortium member. We hope to use the trial’s results to promote collaboration between mental health professionals and diabetes teams, evaluate the economic feasibility of using LDX in patients with both diseases and the long run improve ADHD treatment in children with T1D.

EU Clinical Trials Register (EU-CTR, 2022-001906-24) and NCT05957055.

Certain criteria for ventilator-associated events (VAE) definition might influence the type of an event, its detection rate and consequently the resource expenditure in intensive care unit. The Impact of Infections by Antimicrobial-Resistant Microorganisms - Ventilator-Associated Pneumonia (IMPACTO MR-PAV) aims to evaluate the incidence and diagnostic accuracy of ventilator-associated pneumonia (VAP) using the current criteria for VAP surveillance in Brazil versus the VAE criteria defined by the US National Healthcare Safety Network-Center for Diseases Control and Prevention (CDC) criteria.

The study will be conducted in around 15 centres across Brazil from October 2022 to December 2023. Trained healthcare professionals will collect data and compare the incidence of VAP using both the current criteria for VAP surveillance in Brazil and the VAE criteria defined by the CDC. The accuracy of the two criteria for identifying VAP will also be analysed. It will also characterise other events associated with mechanical ventilation (ventilator-associated condition, infection-related ventilator-associated complication) and adjudicate VAP reported to the Brazilian Health Regulatory Agency (ANVISA) using current epidemiological diagnostic criteria.

This study was approved by the Institutional Review Board under the number 52354721.0.1001.0070. The study’s primary outcome measure will be the incidence of VAP using the two different surveillance criteria, and the secondary outcome measures will be the accuracy of the two criteria for identifying VAP and the adjudication of VAP reported to ANVISA. The results will contribute to the improvement of VAP surveillance in Brazil and may have implications for other countries that use similar criteria.

NCT05589727; Clinicaltrials.gov.

Drug–drug interactions (DDIs) are common and can result in patient harm. Electronic health records warn clinicians about DDIs via alerts, but the clinical decision support they provide is inadequate. Little is known about clinicians’ real-world DDI decision-making process to inform more effective alerts.

Apply cognitive task analysis techniques to determine informational cues used by clinicians to manage DDIs and identify opportunities to improve alerts.

Clinicians submitted incident forms involving DDIs, which were eligible for inclusion if there was potential for serious patient harm. For selected incidents, we met with the clinician for a 60 min interview. Each interview transcript was analysed to identify decision requirements and delineate clinicians’ decision-making process. We then performed an inductive, qualitative analysis across incidents.

Inpatient and outpatient care at a major, tertiary Veterans Affairs medical centre.

Physicians, pharmacists and nurse practitioners.

Themes to identify informational cues that clinicians used to manage DDIs.

We conducted qualitative analyses of 20 incidents. Data informed a descriptive model of clinicians’ decision-making process, consisting of four main steps: (1) detect a potential DDI; (2) DDI problem-solving, sensemaking and planning; (3) prescribing decision and (4) resolving actions. Within steps (1) and (2), we identified 19 information cues that clinicians used to manage DDIs for patients. These cues informed their subsequent decisions in steps (3) and (4). Our findings inform DDI alert recommendations to improve clinicians’ decision-making efficiency, confidence and effectiveness.

Our study provides three key contributions. Our study is the first to present an illustrative model of clinicians’ real-world decision making for managing DDIs. Second, our findings add to scientific knowledge by identifying 19 cognitive cues that clinicians rely on for DDI management in clinical practice. Third, our results provide essential, foundational knowledge to inform more robust DDI clinical decision support in the future.

Increasing numbers of young people attending university has raised concerns about the capacity of student mental health services to support them. We conducted a randomised controlled trial (RCT) to explore whether provision of an 8 week mindfulness course adapted for university students (Mindfulness Skills for Students—MSS), compared with university mental health support as usual (SAU), reduced psychological distress during the examination period. Here, we conduct an economic evaluation of MSS+SAU compared with SAU.

Economic evaluation conducted alongside a pragmatic, parallel, single-blinded RCT comparing provision of MSS+SAU to SAU.

616 university students randomised.

The primary economic evaluation assessed the cost per quality-adjusted life year (QALY) gained from the perspective of the university counselling service. Costs relate to staff time required to deliver counselling service offerings. QALYs were derived from the Clinical Outcomes in Routine Evaluation Dimension 6 Dimension (CORE-6D) preference based tool, which uses responses to six items of the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM; primary clinical outcome measure). Primary follow-up duration was 5 and 7 months for the two recruitment cohorts.

It was estimated to cost £1584 (2022 prices) to deliver an MSS course to 30 students, £52.82 per student. Both costs (adjusted mean difference: £48, 95% CI £40–£56) and QALYs (adjusted mean difference: 0.014, 95% CI 0.008 to 0.021) were significantly higher in the MSS arm compared with SAU. The incremental cost-effectiveness ratio (ICER) was £3355, with a very high (99.99%) probability of being cost-effective at a willingness-to-pay threshold of £20 000 per QALY.

MSS leads to significantly improved outcomes at a moderate additional cost. The ICER of £3355 per QALY suggests that MSS is cost-effective when compared with the UK’s National Institute for Health and Care Excellence thresholds of £20 000 per QALY.

Australian and New Zealand Clinical Trials Registry, ACTRN12615001160527.

Determine the prevaccination healthcare impact of COVID-19 in patients with systemic lupus erythematosus (SLE) in England.

Retrospective cohort study of adult patients with SLE from 1 May to 31 October 2020.

Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics (HES) databases from general practitioners across England combining primary care and other health-related data.

Overall, 6145 adults with confirmed SLE diagnosis ≥1 year prior to 1 May 2020 were included. Most patients were women (91.0%), white (67.1%), and diagnosed with SLE at age

Demographics and clinical characteristics were compared. COVID-19 severity was determined by patient care required and procedure/diagnosis codes. COVID-19 cumulative incidence, hospitalisation rates, lengths of stay and mortality rates were determined and stratified by SLE and COVID-19 severity.

Of 6145 patients, 3927 had mild, 1288 moderate and 930 severe SLE at baseline. The majority of patients with moderate to severe SLE were on oral corticosteroids and antimalarial treatments. Overall, 54/6145 (0.88%) patients with SLE acquired and were diagnosed with COVID-19, with 45 classified as mild, 6 moderate and 3 severe COVID-19. Cumulative incidence was higher in patients with severe SLE (1.4%) compared with patients classified as mild (0.8%) or moderate (0.8%). Ten COVID-19-specific hospital admissions occurred (n=6 moderate; n=4 severe). Regardless of COVID-19 status, hospital admission rates and length of stay increased with SLE severity. Of 54 patients with SLE diagnosed with COVID-19, 1 (1.9%) COVID-19-related death was recorded in a patient with both severe SLE and severe COVID-19.

SLE severity did not appear to impact COVID-19 outcomes in this study. The COVID-19 pandemic is evolving and follow-up studies are needed to understand the relationship between COVID-19 and SLE.

Breast cancer survivors (BCSs) experience more severe symptoms of genitourinary syndrome of menopause (GSM) than healthy postmenopausal women. As hormonal therapy with oestrogen should be avoided in BCSs, finding an effective and safe therapy to address vaginal symptoms and sexual dysfunction is urgently needed. Physical methods may be promising alternatives for the specificities of this group of women. This review aims to evaluate the efficacy and safety of physical methods (laser and radiofrequency) for treating GSM in BCSs.

The PubMed, Embase, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases will be searched. A search strategy was developed to retrieve clinical trials that evaluate the efficacy and safety of any physical method (laser or radiofrequency) used for GSM in BCSs. No date or language restrictions will be imposed. Two authors will independently select studies by title, abstract and full text to meet the inclusion criteria. Data will be extracted, and the risk of bias will be evaluated using the Cochrane risk-of-bias tool (RoB 2). Review Manager 5.4.1 will be used for data synthesis. The Grading of Recommendations, Assessment, Development and Evaluation will be used to assess the strength of the evidence.

This study reviews the published data; thus, obtaining ethical approval is unnecessary. The findings of this systematic review will be published in a peer-reviewed journal.

CRD42023387680.

Women with type 2 diabetes (T2DM) are more likely to experience adverse reproductive outcomes, yet preconception care can significantly reduce these risks. For women with T2DM, preconception care includes reproductive planning and patient education on: (1) the importance of achieving glycaemic control before pregnancy, (2) using effective contraception until pregnancy is desired, (3) discontinuing teratogenic medications if pregnancy could occur, (4) taking folic acid, and (5) managing cardiovascular and other risks. Despite its importance, few women with T2DM receive recommended preconception care.

We are conducting a two-arm, clinic-randomised trial at 51 primary care practices in Chicago, Illinois to evaluate a technology-based strategy to ‘hardwire’ preconception care for women of reproductive age with T2DM (the PREPARED (Promoting REproductive Planning And REadiness in Diabetes) strategy) versus usual care. PREPARED leverages electronic health record (EHR) technology before and during primary care visits to: (1) promote medication safety, (2) prompt preconception counselling and reproductive planning, and (3) deliver patient-friendly educational tools to reinforce counselling. Post-visit, text messaging is used to: (4) encourage healthy lifestyle behaviours. English and Spanish-speaking women, aged 18–44 years, with T2DM will be enrolled (N=840; n=420 per arm) and will receive either PREPARED or usual care based on their clinic’s assignment. Data will be collected from patient interviews and the EHR. Outcomes include haemoglobin A1c (primary), reproductive knowledge and self-management behaviours. We will use generalised linear mixed-effects models (GLMMs) to evaluate the impact of PREPARED on these outcomes. GLMMs will include a fixed effect for treatment assignment (PREPARED vs usual care) and random clinic effects.

This study was approved by the Northwestern University Institutional Review Board (STU00214604). Study results will be published in journals with summaries shared online and with participants upon request.

ClinicalTrials.gov Registry (NCT04976881).

In population-based research, disease ascertainment algorithms can be as accurate as, and less costly than, performing supplementary clinical examinations on selected participants to confirm a diagnosis of a neurocognitive disorder (NCD), but they require cohort-specific validation. To optimise the use of the Canadian Longitudinal Study on Aging (CLSA) to understand the epidemiology and burden of NCDs, the CLSA Memory Study will validate an NCD ascertainment algorithm to identify CLSA participants with these disorders using routinely acquired study data.

Up to 600 CLSA participants with equal numbers of those likely to have no NCD, mild NCD or major NCD based on prior self-reported physician diagnosis of a memory problem or dementia, medication consumption (ie, cholinesterase inhibitors, memantine) and/or self-reported function will be recruited during the follow-up 3 CLSA evaluations (started August 2021). Participants will undergo an assessment by a study clinician who will also review an informant interview and make a preliminary determination of the presence or absence of an NCD. The clinical assessment and available CLSA data will be reviewed by a Central Review Panel who will make a final categorisation of participants as having (1) no NCD, (2) mild NCD or, (3) major NCD (according to fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria). These will be used as our gold standard diagnosis to determine if the NCD ascertainment algorithm accurately identifies CLSA participants with an NCD. Weighted Kappa statistics will be the primary measure of agreement. Sensitivity, specificity, the C-statistic and the phi coefficient will also be estimated.

Ethics approval has been received from the institutional research ethics boards for each CLSA Data Collection Site (Université de Sherbrooke, Hamilton Integrated Research Ethics Board, Dalhousie University, Nova Scotia Health Research Ethics Board, University of Manitoba, McGill University, McGill University Health Centre Research Institute, Memorial University of Newfoundland, University of Victoria, Élisabeth Bruyère Research Institute of Ottawa, University of British Columbia, Island Health (Formerly the Vancouver Island Health Authority, Simon Fraser University, Calgary Conjoint Health Research Ethics Board).

The results of this work will be disseminated to public health professionals, researchers, health professionals, administrators and policy-makers through journal publications, conference presentations, publicly available reports and presentations to stakeholder groups.