bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial support interventions for children and adolescents experiencing gender dysphoria or incongruence: a systematic review
Authors: Heathcote Claire , Taylor Jo , Hall Ruth , Jarvis Stuart William , Langton Trilby , Hewitt Catherine Elizabeth , Fraser Lorna
Published: April 2024

Background

National and international guidelines recommend that psychosocial support should be a key component of the care offered to children and adolescents experiencing gender dysphoria/incongruence. However, specific approaches or interventions are not recommended.

Aim

To identify and summarise evidence on the outcomes of psychosocial support interventions for children and adolescents (age 0-18) experiencing gender dysphoria/incongruence.

Methods

Systematic review and narrative synthesis. Database searches (MEDLINE; EMBASE; CINAHL; PsycINFO; Web of Science) were performed in April 2022, with results assessed independently by two reviewers. Peer-reviewed articles reporting the results of studies measuring outcomes of psychosocial support interventions were included. Quality was assessed using the Mixed Methods Appraisal Tool.

Results

Ten studies were included. Half were conducted in the US, with others from Australia, Canada, New Zealand and the UK. Six were pre–post analyses or cohort studies, three were mixed methods, and one was a secondary analysis of intervention data from four trials. Most studies were of low quality. Most analyses of mental health and psychosocial outcomes showed either benefit or no change, with none indicating negative or adverse effects.

Conclusions

The small number of low-quality studies limits conclusions about the effectiveness of psychosocial interventions for children/adolescents experiencing gender dysphoria/incongruence. Clarity on the intervention approach as well as the core outcomes would support the future aggregation of evidence. More robust methodology and reporting is required.

PROSPERO registration number

CRD42021289659.
Gender services for children and adolescents across the EU-15+ countries: an online survey
Authors: Hall Ruth , Taylor Jo , Heathcote Claire , Langton Trilby , Hewitt Catherine Elizabeth , Fraser Lorna
Published: April 2024

Background

Over the last 10-15 years, there has been an increase in the number of children and adolescents referred to gender services, particularly among adolescent birth-registered females. This population shows a higher prevalence of co-occurring mental health difficulties and neurodevelopmental conditions. Some countries have recently restricted access to medical treatments in recognition of the uncertain evidence base.

Aim

To understand the current provision of gender services for children and adolescents across the EU-15+ countries that have comparable high-income healthcare systems, to inform service development in the UK.

Methods

An e-survey of paediatric gender services was conducted between September 2022 and April 2023. It covered service structure, care pathways, interventions and data collection. Data were described and compared to identify similarities and differences among participating services.

Results

15 services in eight countries (Australia, Belgium, Denmark, Norway, Northern Ireland, The Netherlands, Spain and Finland) responded. While a multidisciplinary team was present in all services, its composition and organisation varied. Clinical practice was informed by international guidelines, with four countries following their own national guidelines. Differences were observed in referral criteria, care pathways for prepubertal children and those with co-occurring conditions. Eligibility criteria for medical interventions also varied. Psychosocial support and interventions were limited, and outcome data collection was scarce.

Conclusions

This survey revealed both similarities and key variations in the clinical practice of paediatric gender services across eight different countries. The study emphasises the need for service development that both considers the management of co-occurring conditions and embeds routine data collection in practice.
Interventions to suppress puberty in adolescents experiencing gender dysphoria or incongruence: a systematic review
Authors: Taylor Jo , Mitchell Alex , Hall Ruth , Heathcote Claire , Langton Trilby , Fraser Lorna , Hewitt Catherine Elizabeth
Published: April 2024

Background

Treatment to suppress or lessen effects of puberty are outlined in clinical guidelines for adolescents experiencing gender dysphoria/incongruence. Robust evidence concerning risks and benefits is lacking and there is a need to aggregate evidence as new studies are published.

Aim

To identify and synthesise studies assessing the outcomes of puberty suppression in adolescents experiencing gender dysphoria/incongruence.

Methods

A systematic review and narrative synthesis. Database searches (Medline, Embase, CINAHL, PsycINFO, Web of Science) were performed in April 2022, with results assessed independently by two reviewers. An adapted version of the Newcastle-Ottawa Scale for cohort studies was used to appraise study quality. Only moderate-quality and high-quality studies were synthesised. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were used.

Results

11 cohort, 8 cross-sectional and 31 pre-post studies were included (n=50). One cross-sectional study was high quality, 25 studies were moderate quality (including 5 cohort studies) and 24 were low quality. Synthesis of moderate-quality and high-quality studies showed consistent evidence demonstrating efficacy for suppressing puberty. Height increased in multiple studies, although not in line with expected growth. Multiple studies reported reductions in bone density during treatment. Limited and/or inconsistent evidence was found in relation to gender dysphoria, psychological and psychosocial health, body satisfaction, cardiometabolic risk, cognitive development and fertility.

Conclusions

There is a lack of high-quality research assessing puberty suppression in adolescents experiencing gender dysphoria/incongruence. No conclusions can be drawn about the impact on gender dysphoria, mental and psychosocial health or cognitive development. Bone health and height may be compromised during treatment. More recent studies published since April 2022 until January 2024 also support the conclusions of this review.

PROSPERO registration number

CRD42021289659.
Masculinising and feminising hormone interventions for adolescents experiencing gender dysphoria or incongruence: a systematic review
Authors: Taylor Jo , Mitchell Alex , Hall Ruth , Langton Trilby , Fraser Lorna , Hewitt Catherine Elizabeth
Published: April 2024

Background

Clinical guidelines outline the use of hormones for masculinisation/feminisation in adolescents experiencing gender dysphoria or incongruence. Robust evidence concerning risks and benefits is lacking. There is a need to aggregate evidence as research becomes available.

Aim

Identify and synthesise studies assessing the outcomes of hormones for masculinisation/feminisation in adolescents experiencing gender dysphoria/incongruence.

Methods

Systematic review and narrative synthesis. Database searches (MEDLINE, Embase, CINAHL, PsycINFO, Web of Science) were performed in April 2022, with results assessed independently by two reviewers. An adapted version of the Newcastle-Ottawa Scale for Cohort Studies was used to assess study quality. Moderate- and high-quality studies were synthesised.

Results

12 cohort, 9 cross-sectional and 32 pre–post studies were included (n=53). One cohort study was high-quality. Other studies were moderate (n=33) and low-quality (n=19). Synthesis of high and moderate-quality studies showed consistent evidence demonstrating induction of puberty, although with varying feminising/masculinising effects. There was limited evidence regarding gender dysphoria, body satisfaction, psychosocial and cognitive outcomes, and fertility. Evidence from mainly pre–post studies with 12-month follow-up showed improvements in psychological outcomes. Inconsistent results were observed for height/growth, bone health and cardiometabolic effects. Most studies included adolescents who received puberty suppression, making it difficult to determine the effects of hormones alone.

Conclusions

There is a lack of high-quality research assessing the use of hormones in adolescents experiencing gender dysphoria/incongruence. Moderate-quality evidence suggests mental health may be improved during treatment, but robust study is still required. For other outcomes, no conclusions can be drawn. More recent studies published since April 2022 until January 2024 also support the conclusions of this review.

PROSPERO registration number:CRD42021289659.
Characteristics of children and adolescents referred to specialist gender services: a systematic review
Authors: Taylor Jo , Hall Ruth , Langton Trilby , Fraser Lorna , Hewitt Catherine Elizabeth
Published: April 2024

Background

Increasing numbers of children/adolescents experiencing gender dysphoria/incongruence are being referred to specialist gender services. Services and practice guidelines are responding to these changes.

Aim

This systematic review examines the numbers and characteristics of children/adolescents (under 18) referred to specialist gender or endocrinology services.

Methods

Database searches were performed (April 2022), with results assessed independently by two reviewers. Peer-reviewed articles providing at least birth-registered sex or age at referral were included. Demographic, gender-related, mental health, neurodevelopmental conditions and adverse childhood experience data were extracted. A narrative approach to synthesis was used and where appropriate proportions were combined in a meta-analysis.

Results

143 studies from 131 articles across 17 countries were included. There was a twofold to threefold increase in the number of referrals and a steady increase in birth-registered females being referred. There is inconsistent collection and reporting of key data across many of the studies. Approximately 60% of children/adolescents referred to services had made steps to present themselves in their preferred gender. Just under 50% of studies reported data on depression and/or anxiety and under 20% reported data on other mental health issues and neurodevelopmental conditions. Changes in the characteristics of referrals over time were generally not reported.

Conclusions

Services need to capture, assess and respond to the potentially co-occurring complexities of children/adolescents being referred to specialist gender and endocrine services. Agreement on the core characteristics for collection at referral/assessment would help to ensure services are capturing data as well as developing pathways to meet the needs of these children.

PROSPERO registration numberCRD42021289659.
Care pathways of children and adolescents referred to specialist gender services: a systematic review
Authors: Taylor Jo , Hall Ruth , Langton Trilby , Fraser Lorna , Hewitt Catherine Elizabeth
Published: April 2024

Background

Increasing numbers of children and adolescents experiencing gender dysphoria/incongruence are being referred to specialist gender services. However, little is currently known about the proportions accessing different types of care and treatment following referral.

Aim

This systematic review examines the range of care pathways of children/adolescents (under 18) referred to specialist gender or endocrinology services.

Methods

Database searches were performed (April 2022), with results assessed independently by two reviewers. Peer-reviewed articles providing data for numbers of children and/or adolescents at referral/assessment and their treatment pathways were included. A narrative approach to synthesis was used and where appropriate proportions were combined in a random-effects meta-analysis.

Results

23 studies across nine countries were included, representing 6133 children and/or adolescents with a median age at assessment of 14–16 and overall a higher percentage of birth-registered females. Of those assessed, 36% (95% CI 27% to 45%) received puberty suppression, 51% (95% CI 40% to 62%) received masculinising or feminising hormones, 68% (95% CI 57% to 77%) received puberty suppression and/or hormones and 16% (95% CI 10% to 24%) received surgery. No study systematically reported information about the full pathway or psychological care received by children/adolescents. Follow-up in many studies was insufficient or unclear. Reasons for discontinuation were rarely provided.

Conclusions

Prospective studies with long-term follow-up reporting information about the full range of pathways are needed to understand what happens to children and adolescents referred to specialist gender services. Information about provision of psychological care is needed considering high rates of psychosocial difficulties in this population.

PROSPERO registration numberCRD42021289659.
Weight loss with GLP-1 analogues in preparation for transplantation
Authors: O'Callaghan Marissa , Le Roux Carel , Fabre Aurelie , McCarthy Cormac
Published: April 2024

This case describes a woman in her 20s with a 6-month history of progressive exertional dyspnoea and cough. Examination revealed hypoxia on room air, sinus tachycardia, finger clubbing and bibasal inspiratory crackles. Inflammatory markers were mildly elevated and empirical antimicrobial therapy was commenced. A multidisciplinary discussion consensus diagnosis of acute interstitial pneumonitis was made based on the findings of high-resolution CT of the chest, macrophage predominant bronchoalveolar lavage cell differential and surgical lung biopsy. There was clinical and radiological deterioration despite glucocorticoids and antifibrotic therapy. A body mass index of 37.5 kg/m2precluded her from lung transplant assessment and consideration. Following consultation with the weight management service, she was commenced on glucagon-like peptide 1 (GLP-1) analogue therapy. She had a remarkable response within 6 months, was listed for lung transplantation, and within 18 months of her initial presentation, a double lung transplantation was performed.
Acute primary CMV infection complicated by pneumonitis and ITP in young immunocompetent woman in a regional Queensland Hospital
Authors: Roberts Emma , Ng Wei Yao , Sanjeewa Maduka , De Silva Janath
Published: April 2024

We present the first published case of simultaneous pneumonitis and immune thrombocytopenic purpura secondary to primary cytomegalovirus (CMV) infection in an immunocompetent patient. Treatment with oral valganciclovir for 2 weeks successfully led to complete clinical recovery. CMV is traditionally associated with infection in immunocompromised patients and neonates; however, evidence of severe CMV infections in immunocompetent hosts is emerging. It is important to highlight the broad range of clinical presentations of CMV infections to prevent diagnostic delay and associated morbidity and expense.
Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies
Authors: Lang Justin J , Prince Stephanie A , Merucci Katherine , Cadenas-Sanchez Cristina , Chaput Jean-Philippe , Fraser Brooklyn J , Manyanga Taru , McGrath Ryan , Ortega Francisco B , Singh Ben , Tomkinson Grant R
Published: April 2024

Objective

To examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and health outcomes among adults.

Design

Overview of systematic reviews.

Data source

Five bibliographic databases were searched from January 2002 to March 2024.

Results

From the 9062 papers identified, we included 26 systematic reviews. We found eight meta-analyses that described five unique mortality outcomes among general populations. CRF had the largest risk reduction for all-cause mortality when comparing high versus low CRF (HR=0.47; 95% CI 0.39 to 0.56). A dose–response relationship for every 1-metabolic equivalent of task (MET) higher level of CRF was associated with a 11%–17% reduction in all-cause mortality (HR=0.89; 95% CI 0.86 to 0.92, and HR=0.83; 95% CI 0.78 to 0.88). For incident outcomes, nine meta-analyses described 12 unique outcomes. CRF was associated with the largest risk reduction in incident heart failure when comparing high versus low CRF (HR=0.31; 95% CI 0.19 to 0.49). A dose–response relationship for every 1-MET higher level of CRF was associated with a 18% reduction in heart failure (HR=0.82; 95% CI 0.79 to 0.84). Among those living with chronic conditions, nine meta-analyses described four unique outcomes in nine patient groups. CRF was associated with the largest risk reduction for cardiovascular mortality among those living with cardiovascular disease when comparing high versus low CRF (HR=0.27; 95% CI 0.16 to 0.48). The certainty of the evidence across all studies ranged from very low-to-moderate according to Grading of Recommendations, Assessment, Development and Evaluations.

Conclusion

We found consistent evidence that high CRF is strongly associated with lower risk for a variety of mortality and incident chronic conditions in general and clinical populations.
Unlocking the potential of forage fish to reduce the global burden of disease
Authors: Xia Shujuan , Takakura Jun'ya , Tsuchiya Kazuaki , Park Chaeyeon , Heneghan Ryan F , Takahashi Kiyoshi
Published: April 2024

Red meat consumption is associated with an elevated risk of mortality from non-communicable diseases (NCDs). In contrast, forage fish, as highly nutritious, environmentally friendly, affordable, and the most abundant fish species in the ocean, are receiving increasing interest from a global food system perspective. However, little research has examined the impact of replacing red meat with forage fish in the global diet on diet-related NCDs.

Methods

We based our study on datasets of red meat projections in 2050 for 137 countries and forage fish catches. We replaced the red meat consumption in each country with forage fish (from marine habitats), without exceeding the potential supply of forage fish. We used a comparative risk assessment framework to investigate how such substitutions could reduce the global burden of diet-related NCDs in adults.

Results

The results of our study show that forage fish may replace only a fraction (approximately 8%) of the world’s red meat due to its limited supply, but it may increase global daily per capita fish consumption close to the recommended level. Such a substitution could avoid 0.5–0.75 million deaths and 8–15 million disability-adjusted life years, concentrated in low- and middle-income countries. Forage fish as an alternative to red meat could double (or more) the number of deaths that could be avoided by simply reducing red meat consumption.

Conclusions

Our analysis suggests that forage fish is a promising alternative to red meat. Policies targeting the allocation of forage fish to regions where they are needed, such as the Global South, could be more effective in maximising the potential of forage fish to reduce the global burden of disease.
The reported impact of non-communicable disease investment cases in 13 countries
Authors: Troisi Giuseppe , Small Roy , Chestnov Roman , Andreasyan Diana , Khachatryan Henrik , Phillips Erwin Arthur , Malcolm Taraleen , Kol Hero , Khodjaeva Nargiza , Gebremichael Mussie , Worku Tessema Addisu , Workneh Asmamaw Bezabeh , Davidson Tamu , Harris Michelle , Ibraeva Nurgul , Nurmatova Aigul , Altymysheva Aliina , Go John Juliard , Kontsevaya Anna , Hanbunjerd Krisada , Bunluesin Sushera , Nieveras Olivia , Ekinci Banu , Keskinkiliç Bekir , Erguder Toker , Akiya Oyoo Charles , Kasule Hafisa , Nakanjako Aidah , Shukurov Shukhrat , Kasymova Nazokat , Banda Patrick , Kakoma Ernest , Bakyaita Nathan N , Kulikov Alexey , Tarlton Dudley , Putoud Nadia , Chiossi Scott , Webb Douglas , Banatvala Nicholas
Published: April 2024

Non-communicable diseases (NCDs) are a leading health and development challenge worldwide. Since 2015, WHO and the United Nations Development Programme have provided support to governments to develop national NCD investment cases to describe the socioeconomic dimensions of NCDs. To assess the impact of the investment cases, semistructured interviews and a structured process for gathering written feedback were conducted between July and October 2022 with key informants in 13 countries who had developed a national NCD investment case between 2015 and 2020. Investment cases describe: (1) the social and economic costs of NCDs, including their distribution and projections over time; (2) priority areas for scaled up action; (3) the cost and returns from investing in WHO-recommended measures to prevent and manage NCDs; and (4) the political dimensions of NCD responses. While no country had implemented all the recommendations set out in their investment case reports, actions and policy changes attributable to the investment cases were identified, across (1) governance; (2) financing; and (3) health service access and delivery. The pathways of these changes included: (1) stronger collaboration across government ministries and partners; (2) advocacy for NCD prevention and control; (3) grounding efforts in nationally owned data and evidence; (4) developing mutually embraced ‘language’ across health and finance; and (5) elevating the priority accorded to NCDs, by framing action as an investment rather than a cost. The assessment also identified barriers to progress on the investment case implementation, including the influence of some private sector entities on sectors other than health, the impact of the COVID-19 pandemic, and changes in senior political and technical government officials. The results suggest that national NCD investment cases can significantly contribute to catalysing the prevention and control of NCDs through strengthening governance, financing, and health service access and delivery.
Overnutrition is a risk factor for iron, but not for zinc or vitamin A deficiency in children and young people: a systematic review and meta-analysis
Authors: Tan Xiaomian , Tan Pui Yee , Gong Yun Yun , Moore J Bernadette
Published: April 2024

Introduction

Traditionally associated with undernutrition, increasing evidence suggests micronutrient deficiencies can coexist with overnutrition. Therefore, this work aimed to systematically review the associations between iron, zinc and vitamin A (VA) status and weight status (both underweight and overweight) in children and young people.

Methods

Ovid Medline, Ovid Embase, Scopus and Cochrane databases were systematically searched for observational studies assessing micronutrient status (blood, serum or plasma levels of iron, zinc or VA biomarkers) and weight status (body mass index or other anthropometric measurement) in humans under 25 years of any ethnicity and gender. Risk of bias assessment was conducted using the American Dietetic Association Quality Criteria Checklist. Where possible, random effects restricted maximum likelihood meta-analyses were performed.

Results

After screening, 83 observational studies involving 190 443 participants from 44 countries were identified, with many studies having reported on more than one micronutrient and/or weight status indicator. Iron was the most investigated micronutrient, with 46, 28 and 27 studies reporting data for iron, zinc and VA status, respectively. Synthesising 16 records of OR from seven eligible studies, overnutrition (overweight and obesity) increased odds of iron deficiency (ID) (OR (95% CI): 1.51 (1.20 to 1.82), p<0.0001, I2=40.7%). Odds appeared to be higher for children living with obesity (1.88 (1.33 to 2.43), p<0.0001, I2=20.6%) in comparison to those with overweight (1.31 (0.98 to 1.64), p<0.0001, I2=40.5%), although between group differences were not significant (p=0.08).

Conclusions

Overnutrition is associated with increased risk of ID, but not zinc or VA deficiencies, with an inverted U-shaped relationship observed between iron status and bodyweight. Our results highlight significant heterogeneity in the reporting of micronutrient biomarkers and how deficiencies were defined. Inflammation status was rarely adequately accounted for, and the burden of ID may well be under-recognised, particularly in children and young people living with overnutrition.

PROSPERO registration number

CRD42020221523.
Neonatal hypoglycaemia
Authors: Harding Jane E , Alsweiler Jane M , Edwards Taygen E , McKinlay Chris JD
Published: April 2024

Low blood concentrations of glucose (hypoglycaemia) soon after birth are common because of the delayed metabolic transition from maternal to endogenous neonatal sources of glucose. Because glucose is the main energy source for the brain, severe hypoglycaemia can cause neuroglycopenia (inadequate supply of glucose to the brain) and, if severe, permanent brain injury. Routine screening of infants at risk and treatment when hypoglycaemia is detected are therefore widely recommended. Robust evidence to support most aspects of management is lacking, however, including the appropriate threshold for diagnosis and optimal monitoring. Treatment is usually initially more feeding, with buccal dextrose gel, followed by intravenous dextrose. In infants at risk, developmental outcomes after mild hypoglycaemia seem to be worse than in those who do not develop hypoglycaemia, but the reasons for these observations are uncertain. Here, the current understanding of the pathophysiology of neonatal hypoglycaemia and recent evidence regarding its diagnosis, management, and outcomes are reviewed. Recommendations are made for further research priorities.
Network analysis of stroke systems of care in Korea
Authors: Kang Jihoon , Song Hyunjoo , Kim Seong Eun , Kim Jun Yup , Park Hong-Kyun , Cho Yong-Jin , Lee Kyung Bok , Lee Juneyoung , Lee Ji Sung , Choi Ah Rum , Kang Mi Yeon , Gorelick Philip B , Bae Hee-Joon
Published: April 2024

Background

The landscape of stroke care has shifted from stand-alone hospitals to cooperative networks among hospitals. Despite the importance of these networks, limited information exists on their characteristics and functional attributes.

Methods

We extracted patient-level data on acute stroke care and hospital connectivity by integrating national stroke audit data with reimbursement claims data. We then used this information to transform interhospital transfers into a network framework, where hospitals were designated as nodes and transfers as edges. Using the Louvain algorithm, we grouped densely connected hospitals into distinct stroke care communities. The quality and characteristics in given stroke communities were analysed, and their distinct types were derived using network parameters. The clinical implications of this network model were also explored.

Results

Over 6 months, 19 113 patients with acute ischaemic stroke initially presented to 1009 hospitals, with 3114 (16.3%) transferred to 246 stroke care hospitals. These connected hospitals formed 93 communities, with a median of 9 hospitals treating a median of 201 patients. Derived communities demonstrated a modularity of 0.904, indicating a strong community structure, highly centralised around one or two hubs. Three distinct types of structures were identified: single-hub (n=60), double-hub (n=22) and hubless systems (n=11). The endovascular treatment rate was highest in double-hub systems, followed by single-hub systems, and was almost zero in hubless systems. The hubless communities were characterised by lower patient volumes, fewer hospitals, no hub hospital and no stroke unit.

Conclusions

This network analysis could quantify the national stroke care system and point out areas where the organisation and functionality of acute stroke care could be improved.
Determining the exposure of maternal medicines through breastfeeding: the UmbrelLACT study protocol—a contribution from the ConcePTION project
Authors: Van Neste Martje , Nauwelaerts Nina , Ceulemans Michael , Van Calsteren Kristel , Eerdekens An , Annaert Pieter , Allegaert Karel , Smits Anne
Published: April 2024

Introduction

Breastfeeding is beneficial for the health of the mother and child. However, at least 50% of postpartum women need pharmacotherapy, and this number is rising due to the increasing prevalence of chronic diseases and pregnancies at a later age. Making informed decisions on medicine use while breastfeeding is often challenging, considering the extensive information gap on medicine exposure and safety during lactation. This can result in the unnecessary cessation of breastfeeding, the avoidance of pharmacotherapy or the off-label use of medicines. The UmbrelLACT study aims to collect data on human milk transfer of maternal medicines, child exposure and general health outcomes. Additionally, the predictive performance of lactation and paediatric physiologically based pharmacokinetic (PBPK) models, a promising tool to predict medicine exposure in special populations, will be evaluated.

Methods and analysis

Each year, we expect to recruit 5–15 breastfeeding mothers using pharmacotherapy via the University Hospitals Leuven, the BELpREG project (pregnancy registry in Belgium) or external health facilities. Each request and compound will be evaluated on relevance (ie, added value to available scientific evidence) and feasibility (including access to analytical assays). Participants will be requested to complete at least one questionnaire on maternal and child’s general health and collect human milk samples over 24 hours. Optionally, two maternal and one child’s blood samples can be collected. The maternal medicine concentration in human milk will be determined along with the estimation of the medicine intake (eg, daily infant dose and relative infant dose) and systemic exposure of the breastfed child. The predictive performance of PBPK models will be assessed by comparing the observed concentrations in human milk and plasma to the PBPK predictions.

Ethics and dissemination

This study has been approved by the Ethics Committee Research UZ/KU Leuven (internal study number S67204). Results will be published in peer-reviewed journals and presented at (inter)national scientific meetings.

Trial registration number

NCT06042803.
Is obesity more likely among children sharing a household with an older child with obesity? Cross-sectional study of linked National Child Measurement Programme data and electronic health records
Authors: Firman Nicola , Wilk Marta , Marszalek Milena , Griffiths Lucy , Harper Gill , Dezateux Carol
Published: April 2024

Background/objectives

We identified household members from electronic health records linked to National Child Measurement Programme (NCMP) data to estimate the likelihood of obesity among children living with an older child with obesity.

Methods

We included 126 829 NCMP participants in four London boroughs and assigned households from encrypted Unique Property Reference Numbers for 115 466 (91.0%). We categorised the ethnic-adjusted body mass index of the youngest and oldest household children (underweight/healthy weight <91st, ≥91st overweight <98th, obesity ≥98th centile) and estimated adjusted ORs and 95% CIs of obesity in the youngest child by the oldest child’s weight status, adjusting for number of household children (2, 3 or ≥4), youngest child’s sex, ethnicity and school year of NCMP participation.

Results

We identified 19 702 households shared by two or more NCMP participants (% male; median age, range (years)—youngest children: 51.2%; 5.2, 4.1–11.8; oldest children: 50.6%; 10.6, 4.1–11.8). One-third of youngest children with obesity shared a household with another child with obesity (33.2%; 95% CI: 31.2, 35.2), compared with 9.2% (8.8, 9.7) of youngest children with a healthy weight. Youngest children living with an older child considered overweight (OR: 2.33; 95% CI: 2.06, 2.64) or obese (4.59; 4.10, 5.14) were more likely to be living with obesity.

Conclusions

Identifying children sharing households by linking primary care and school records provides novel insights into the shared weight status of children sharing a household. Qualitative research is needed to understand how food practices vary by household characteristics to increase understanding of how the home environment influences childhood obesity.
PFDN6 contributes to colorectal cancer progression via transcriptional regulation
Authors: Xu Fenghua , Kong LingYang , Sun Xiao , Hui WenXiang , Jiang Lan , Han Wenxin , Xiao ZhiFeng , Li Ning , Chen DongFeng , Zheng Nan , Han Jing , Liu Lei
Published: April 2024

Objective

Colorectal cancer (CRC) is a common cancer worldwide. Although there are several treatments for cancer, the therapeutic effect on CRC remains unsatisfactory, and it is imperative to identify new therapeutic targets.

Design

Prefoldin (PFDN) is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers. However, whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated. In this study, molecular biology, cell culture, transcriptome sequencing and other experimental techniques, combined with bioinformatics, were used to verify the regulatory effects of PFDN6 on CRC.

Results

PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC. Knockdown of PFDN6 reduced the tumour cell number, promoted apoptosis, and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines. Mechanistically, differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.

Conclusion

PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575. These results open new avenues for therapeutic interventions for patients with CRC.
New role of platelets in schizophrenia: predicting drug response
Authors: Zhang Yamin , Zheng Yanghao , Ni Peiyan , Liang Sugai , Li Xiaojing , Yu Hua , Wei Wei , Qi Xueyu , Yu Xueli , Xue Rui , Zhao Liansheng , Deng Wei , Wang Qiang , Guo Wanjun , Li Tao
Published: April 2024

Background

Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.

Aims

We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.

Methods

A total of 2985 patients with schizophrenia were randomised into seven groups. Each group received one of seven antipsychotic treatments and was assessed at 2, 4 and 6 weeks. Clinical symptoms were evaluated using the positive and negative syndrome scale (PANSS). Additionally, we measured blood cell counts and metabolic parameters, such as blood lipids. Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes, while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes.

Results

PLTc significantly increased in patients treated with aripiprazole (F=6.00, p=0.003), ziprasidone (F=7.10, p<0.001) and haloperidol (F=3.59, p=0.029). It exhibited a positive association with white blood cell count and metabolic indicators. Higher baseline PLTc was observed in non-responders, particularly in those defined by the PANSS-negative subscale. In the structural equation model, PLTc, white blood cell count and a latent metabolic variable predicted the rate of change in the PANSS-negative subscale scores. Moreover, higher baseline PLTc was observed in individuals with less metabolic change, although this association was no longer significant after accounting for baseline metabolic values.

Conclusions

Platelet parameters, specifically PLTc, are influenced by antipsychotic treatment and could potentially elevate the risk of venous thromboembolism in patients with schizophrenia. Elevated PLTc levels and associated factors may impede symptom improvement by promoting inflammation. Given PLTc’s easy measurement and clinical relevance, it warrants increased attention from psychiatrists.

Trial registration number

ChiCTR-TRC-10000934.
Risk of developing psoriatic arthritis in psoriasis cohorts with arthralgia: exploring the subclinical psoriatic arthritis stage
Authors: Zabotti Alen , Fagni Filippo , Gossec Laure , Giovannini Ivan , Sticherling Michael , Tullio Annarita , Baraliakos Xenofon , De Marco Gabriele , De Vita Salvatore , Errichetti Enzo , Quartuccio Luca , Silvagni Ettore , Smolen Josef S , Tinazzi Ilaria , Watad Abdulla , Schett Georg , McGonagle Dennis G , Simon David
Published: April 2024

Objective

Subjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis.

Methods

Patients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts. The key outcome was new-onset PsA. Musculoskeletal symptoms including inflammatory and non-inflammatory symptoms before PsA diagnosis were collected. Occurrence of PsA was analysed with survival analysis and cumulative incidence functions (CIFs).

Results

384 patients with PsO were included with a mean follow-up of 33.0 (±20.9) months. 311 of 384 (80.9%) had subclinical PsA with a PsA incidence rate of 7.7 per 100 patient-years. Subclinical PsA displayed a higher risk of PsA development compared with PsO (HR=11.7 (95% CI 1.57 to 86.7), p=0.016). The probability of new-onset PsA estimated by the CIF was 9.4% (95% CI 4.7% to 10.6%) at month 12 and 22.7% (95% CI 17.2% to 28.6%) at month 36. 58.9% of cases reported inflammatory symptoms in the months immediately prior to PsA diagnosis but prior non-inflammatory symptoms were evident in 83.9% prior to PsA diagnosis. Peripheral joint swelling was the predominant PsA presentation pattern (82.1%).

Conclusions

The probability of PsA development among subclinical PsA was relatively high, emphasising the importance of emergent musculoskeletal symptoms when aiming for PsA prevention. Joint swelling was the dominant feature in new-onset PsA, likely reflecting clinical confidence in recognising joint swelling.
Crystalloid resuscitation is associated with decreased treatment delays and improved systolic blood pressures in a blood-constrained setting
Authors: Yost Mark T , Driban Matt , Dissak Delon Fanny Nadia , Mbianyor Mbiarikai A , Kinge Thompson , Njock Richard , Nkusu Daniel , Tsiagadigui Jean-Gustave , Carvalho Melissa , Oke Rasheedat , Chichom-Mefire Alain , Juillard Catherine , Christie S Ariane
Published: April 2024

Objectives

We analyzed resuscitation practices in Cameroonian patients with trauma as a first step toward developing a context-appropriate resuscitation protocol. We hypothesized that more patients would receive crystalloid-based (CB) resuscitation with a faster time to administration than blood product (BL) resuscitation.

Methods

We included patients enrolled between 2017 and 2019 in the Cameroon Trauma Registry (CTR). Patients presenting with hemorrhagic shock (systolic blood pressure (SBP) <100 mm Hg and active bleeding) were categorized as receiving CB, BL, or no resuscitation (NR). We evaluated differences between cohorts with the Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables. We compared time to treatment with the Wilcoxon rank sum test.

Results

Of 9635 patients, 403 (4%) presented with hemorrhagic shock. Of these, 278 (69%) patients received CB, 39 (10%) received BL, and 86 (21%) received NR. BL patients presented with greater injury severity (Highest Estimated Abbreviated Injury Scale (HEAIS) 4 BL vs 3 CB vs 1 NR, p<0.001), and lower median hemoglobin (8.0 g/dL BL, 11.4 g/dL CB, 10.6 g/dL NR, p<0.001). CB showed greater initial improvement in SBP (12 mm Hg CB vs 9 mm Hg BL vs 0 NR mm Hg, p=0.04) compared with BL or no resuscitation, respectively. Median time to treatment was lower for CB than BL (12 vs 131 min, p<0.01). Multivariate logistic regression adjusted for injury severity found no association between resuscitation type and mortality (CB adjusted OR (aOR) 1.28, p=0.82; BL aOR 1.05, p=0.97).

Conclusions

CB was associated with faster treatment, greater SBP elevation, and similar survival compared with BL in Cameroonian patients with trauma with hemorrhagic shock. In blood-constrained settings, treatment delays associated with blood product transfusion may offset the physiologic benefits of an early BL strategy. CB prior to definitive hemorrhage control in this resource-limited setting may be a necessary strategy to optimize perfusion pressure.

Level of evidence and study type

III, retrospective study.
Long-term follow-up of patients with congenital diaphragmatic hernia
Authors: Cimbak Nicole , Buchmiller Terry L
Published: April 2024

Neonates with congenital diaphragmatic hernia encounter a number of surgical and medical morbidities that persist into adulthood. As mortality improves for this population, these survivors warrant specialized follow-up for their unique disease-specific morbidities. Multidisciplinary congenital diaphragmatic hernia clinics are best positioned to address these complex long-term morbidities, provide long-term research outcomes, and help inform standardization of best practices in this cohort of patients. This review outlines long-term morbidities experienced by congenital diaphragmatic hernia survivors that can be addressed in a comprehensive follow-up clinic.
Stable isotope analysis provides novel insights for measuring lake ecosystem recovery following acidification
Authors: Dawson Jade C. , Guzzo Matthew M. , Gunn John M. , Emilson Erik J.S. , McCann Kevin S. , Edwards Brie A.
Published: April 2024

Unstable and simplified freshwater food webs impair the resilience of Canadian fisheries facing environmental stressors. This study utilizes stable isotope analyses to assess trophic recovery to explore food web resiliency in lakes historically impacted by metal mining in Sudbury, Ontario. Carbon (δ13C) and nitrogen (δ15N) stable isotope ratios were quantified in yellow perch ( Perca flavescens), smallmouth bass ( Micropterus dolomieu), and baseline organisms to develop quantitative population metrics and describe dietary niche partitioning. The most severely damaged lake with a barren watershed had the lowest trophic positioning, smallest body size and niche area, and greatest niche overlap among fish species. Semi-barren and forested watershed lakes were more similar to reference lakes in isotopic metrics; however, elevated niche overlap and reduced trophic positioning suggests recovery in these lakes is ongoing. We found that including stable isotope analyses in lake recovery studies provided critical insights not captured by traditional biomonitoring approaches.
UAV avionics safety, certification, accidents, redundancy, integrity, and reliability: a comprehensive review and future trends
Authors: Wanner Devon , Hashim Hashim A. , Srivastava Siddhant , Steinhauer Alex
Published: April 2024

This paper underscores the significance of safety and reliability in the realm of unmanned aerial vehicle (UAV) technologies, and how regulations play a pivotal role in ensuring their responsible use. We have analyzed safety incidents and trends both in Canada and globally, noting a decline in incidents attributed to enhanced regulations. Our comparative analysis of different UAV technologies identified batteries as the most reliable power supply, Global Navigation Satellite System as the most effective navigation system, and light detection and ranging as the optimal optical sensor due to regulatory compliance and system redundancies. We also examined the regulatory framework in Canada, comparing it with the risk-based approach of the European Union Aviation Safety Agency and the efforts of Joint Authorities for Rule-making on Unmanned Systems towards global harmonization. Furthermore, we highlighted emerging trends in automation and flight control technologies, with a focus on European regulations shaping UAV automation trends. In conclusion, by adhering to best practices from other regulatory bodies, embracing emerging trends, and adopting a risk-based approach, Canada can promote the growth of the UAV industry while ensuring safety and reliability in UAV technologies.
Design and dynamic characteristics of automatic vertical drilling tool
Authors: Tian Jialin , He Bo , Guo Linpeng
Published: April 2024

Higher performance is needed in deeper and longer horizontal wellbore drilling. In vertical drilling conditions, wellbore trajectory often be led to deviation due to objective conditions. Based on the engineering issues, this paper presents a new automatic vertical drilling tool, including the innovative design and working mechanism research. This tool working mechanism are carried out, such as the mechanics model of eccentric tube and the relationships between eccentric torque and deflection angle. The eccentric tube torque increases with the wellbore deviation angle. When wellbore deviation angle is constant, the eccentric tube torque reaches maximum value when its deflection angle is 90°. The internal flow parameters are studied by fluid field simulation, such as drilling fluid flow rate, pressure drop, and pressure distribution inside this tool during downhole drilling process. The larger the diameter of switch hole, the higher is the pressure drop around, which leads to the force on push block increasing. The drilling fluid pressure increases with higher input flow rate inside this tool. The comparison of results, the data of simulation and theoretical model calculations, verified the reliability and accuracy of research. This study has provided innovative ideas and reference for drilling tool design and wellbore trajectory control methods.
High-energy QCD dynamics from bottom flavor fragmentation at the Hi-Lumi LHC
Authors: Celiberto Francesco Giovanni
Published: April 2024

We study the inclusive production of hadrons with bottom flavor at the LHC and its luminosity upgrade. We describe the collinear fragmentation of singly b-flavored hadrons, B mesons and $$\Lambda _b$$

Λ
b

baryons, via the determination of fragmentation functions, while for charmed B mesons, $$B_c(^1S_0)$$

B
c

(
1

S
0

)

and $$B_c(^3S_1)$$

B
c

(
3

S
1

)

particles, we employ the novel set, built on the basis of state-of-the-art nonrelativistic QCD inputs. We use the Jethad multimodular working environment to analyze rapidity and transverse-momentum distributions for observables sensitive to the associated emission of two hadrons or a hadron-plus-jet system. Our reference formalism is the $$\mathrm{NLL/NLO^+}$$

NLL
/

NLO
+

hybrid collinear and high-energy factorization, where the standard collinear description is improved by the inclusions of energy logarithms resummed up to the next-to-leading approximation and beyond. We provide corroborating evidence that b-flavor emissions act as fair stabilizers of the high-energy resummation, thus serving as valuable tools for precision studies of high-energy QCD. As a bonus, we highlight that the predicted production-rate hierarchy between noncharmed b-hadrons and charmed $$B_c(^1S_0)$$

B
c

(
1

S
0

)

mesons is in line with recent LHCb estimates. This serves as simultaneous benchmark both for the hybrid factorization and for the single-parton fragmentation mechanism based on initial-scale inputs calculated via the nonrelativistic QCD effective theory.