An overview of autosomal STRs and identity SNPs in a Norwegian population using massively parallel sequencing.

In recent years, probabilistic genotyping software has been adapted for the analysis of massively parallel sequencing (MPS) forensic data. Likelihood ratios (LR) are based on allele frequencies selected from populations of interest. This study provides an outline of sequence-based (SB) allele frequencies for autosomal short tandem repeats (aSTRs) and identity single nucleotide polymorphisms (iSNPs) in 371 individuals from Southern Norway. 27 aSTRs and 94 iSNPs were previously analysed with the ForenSeq™ DNA Signature Prep Kit (Verogen). The number of alleles with frequencies less than 0.05 for sequenced-based alleles was 4.6 times higher than for length-based alleles. Consistent with previous studies, it was observed that sequence-based data (both with and without flanks) exhibited higher allele diversity compared to length-based (LB) data; random match probabilities were lower for SB alleles confirming their advantage to discriminate between individuals. Two alleles in markers D22S1045 and Penta D were observed with SNPs in the 3´ flanking region, which have not been reported before. Also, a novel SNP with a minor allele frequency (MAF) of 0.001, was found in marker TH01. The impact of the sample size on minor allele frequency (MAF) values was studied in 88 iSNPs from Southern Norway (n = 371). The findings were then compared to a larger Norwegian population dataset (n = 15,769). The results showed that the smaller Southern Norway dataset provided similar results, and it was a representative sample. Population structure was analyzed for regions within Southern Norway; FST estimates for aSTR and iSNPs did not indicate any genetic structure. Finally, we investigated the genetic differences between Southern Norway and two other populations: Northern Norway and Denmark. Allele frequencies between these populations were compared, and we found no significant frequency differences (p-values > 0.0001). We also calculated the pairwise FST values per marker and comparisons between Southern and Northern Norway showed small differences. In contrast, the comparisons between Southern Norway and Denmark showed higher FST values for some markers, possibly driven by distinct alleles that were present in only one of the populations. In summary, we propose that allele frequencies from each population considered in this study could be used interchangeably to calculate genotype probabilities.

Prioritization of Randomized Clinical Trial Questions for Children Hospitalized With Common Conditions: A Consensus Statement.

Importance: There is a lack of randomized clinical trial (RCT) data to guide many routine decisions in the care of children hospitalized for common conditions. A first step in addressing the shortage of RCTs for this population is to identify the most pressing RCT questions for children hospitalized with common conditions. Objective: To identify the most important and feasible RCT questions for children hospitalized with common conditions. Design, Setting, and Participants: For this consensus statement, a 3-stage modified Delphi process was used in a virtual conference series spanning January 1 to September 29, 2022. Forty-six individuals from 30 different institutions participated in the process. Stage 1 involved construction of RCT questions for the 10 most common pediatric conditions leading to hospitalization. Participants used condition-specific guidelines and reviews from a structured literature search to inform their development of RCT questions. During stage 2, RCT questions were refined and scored according to importance. Stage 3 incorporated public comment and feasibility with the prioritization of RCT questions. Main Outcomes and Measures: The main outcome was RCT questions framed in a PICO (population, intervention, control, and outcome) format and ranked according to importance and feasibility; score choices ranged from 1 to 9, with higher scores indicating greater importance and feasibility. Results: Forty-six individuals (38 who shared demographic data; 24 women [63%]) from 30 different institutions participated in our modified Delphi process. Participants included children's hospital (n = 14) and community hospital (n = 13) pediatricians, parents of hospitalized children (n = 4), other clinicians (n = 2), biostatisticians (n = 2), and other researchers (n = 11). The process yielded 62 unique RCT questions, most of which are pragmatic, comparing interventions in widespread use for which definitive effectiveness data are lacking. Overall scores for importance and feasibility of the RCT questions ranged from 1 to 9, with a median of 5 (IQR, 4-7). Six of the top 10 selected questions focused on determining optimal antibiotic regimens for 3 common infections (pneumonia, urinary tract infection, and cellulitis). Conclusions and Relevance: This consensus statementhas identified the most important and feasible RCT questions for children hospitalized with common conditions. This list of RCT questions can guide investigators and funders in conducting impactful trials to improve care and outcomes for hospitalized children.

Sociodemographic Factors and Trends in Bronchiolitis-Related Emergency Department Visit and Hospitalization Rates.

Importance: Bronchiolitis is the most common and most cumulatively expensive condition in pediatric hospital care. Few population-based studies have examined health inequalities in bronchiolitis outcomes over time. Objective: To examine trends in bronchiolitis-related emergency department (ED) visit and hospitalization rates by sociodemographic factors in a universally funded health care system. Design, Setting, and Participants: This repeated cross-sectional cohort study was performed from April 1, 2004, to March 31, 2022, using population-based health administrative data from children younger than 2 years in Ontario, Canada. Main Outcome and Measures: Bronchiolitis ED visit and hospitalization rates per 1000 person-years reported for the equity stratifiers of sex, residence location (rural vs urban), and material resources quintile. Trends in annual rates by equity stratifiers were analyzed using joinpoint regression and estimating the average annual percentage change (AAPC) with 95% CI and the absolute difference in AAPC with 95% CI from April 1, 2004, to March 31, 2020. Results: Of 2 921 573 children included in the study, 1 422 088 (48.7%) were female and 2 619 139 (89.6%) lived in an urban location. Emergency department visit and hospitalization rates were highest for boys, those with rural residence, and those with least material resources. There were no significant between-group absolute differences in the AAPC in ED visits per 1000 person-years by sex (female vs male; 0.22; 95% CI, -0.92 to 1.35; P = .71), residence (rural vs urban; -0.31; 95% CI -1.70 to 1.09; P = .67), or material resources (quintile 5 vs 1; -1.17; 95% CI, -2.57 to 0.22; P = .10). Similarly, there were no significant between-group absolute differences in the AAPC in hospitalizations per 1000 person-years by sex (female vs male; 0.53; 95% CI, -1.11 to 2.17; P = .53), residence (rural vs urban; -0.62; 95% CI, -2.63 to 1.40; P = .55), or material resources (quintile 5 vs 1; -0.93; 95% CI -3.80 to 1.93; P = .52). Conclusions and Relevance: In this population-based cohort study of children in a universally funded health care system, inequalities in bronchiolitis ED visit and hospitalization rates did not improve over time.

Clinical prediction models in children that use repeated measurements with time-varying covariates: a scoping review

BACKGROUND: Emerging evidence suggests that clinical prediction models that use repeated (time-varying) measurements within each patient may have higher predictive accuracy than models that use patient information from a single measurement. OBJECTIVE: To determine the breadth of the published literature reporting the development of clinical prediction models in children that use time-varying predictors. DATA SOURCES: MEDLINE, EMBASE and Cochrane databases. ELIGIBILITY CRITERIA: We included studies reporting the development of a multivariable clinical prediction model in children, with or without validation, to predict a repeatedly measured binary or time-to-event outcome and utilizing at least one repeatedly measured predictor. SYNTHESIS METHODS: We categorized included studies by the method used to model time-varying predictors. RESULTS: Of 99 clinical prediction model studies that had a repeated measurements data structure, only 27 (27%) used methods that incorporated the repeated measurements as time-varying predictors in a single model. Among these 27 time-varying prediction model studies, we grouped model types into nine categories: time-dependent Cox regression, generalized estimating equations, random effects model, landmark model, joint model, neural network, K-nearest neighbor, support vector machine and tree-based algorithms. Where there was comparison of time-varying models to single measurement models, using time-varying predictors improved predictive accuracy. CONCLUSIONS: Various methods have been used to develop time-varying prediction models in children, but there is a paucity of pediatric time-varying models in the literature. Incorporating time-varying covariates in pediatric prediction models may improve predictive accuracy. Future research in pediatric prediction model development should further investigate whether incorporation of time-varying covariates improves predictive accuracy.

Consensus reporting guidelines to address gaps in descriptions of ultra-rare genetic conditions.

Genome-wide sequencing and genetic matchmaker services are propelling a new era of genotype-driven ascertainment of novel genetic conditions. The degree to which reported phenotype data in discovery-focused studies address informational priorities for clinicians and families is unclear. We identified reports published from 2017 to 2021 in 10 genetics journals of novel Mendelian disorders. We adjudicated the quality and detail of the phenotype data via 46 questions pertaining to six priority domains: (I) Development, cognition, and mental health; (II) Feeding and growth; (III) Medication use and treatment history; (IV) Pain, sleep, and quality of life; (V) Adulthood; and (VI) Epilepsy. For a subset of articles, all subsequent published follow-up case descriptions were identified and assessed in a similar manner. A modified Delphi approach was used to develop consensus reporting guidelines, with input from content experts across four countries. In total, 200 of 3243 screened publications met inclusion criteria. Relevant phenotypic details across each of the 6 domains were rated superficial or deficient in >87% of papers. For example, less than 10% of publications provided details regarding neuropsychiatric diagnoses and "behavioural issues", or about the type/nature of feeding problems. Follow-up reports (n = 95) rarely contributed this additional phenotype data. In summary, phenotype information relevant to clinical management, genetic counselling, and the stated priorities of patients and families is lacking for many newly described genetic diseases. The PHELIX (PHEnotype LIsting fiX) reporting guideline checklists were developed to improve phenotype reporting in the genomic era.

Association of empiric antibiotic selection and clinical outcomes in hospitalised children with severe orbital infections: a retrospective cohort study.

OBJECTIVE: To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections. DESIGN: Multi-centre observational cohort study using data from 2009 to 2018 clinical records. SETTING: Canadian children's hospitals (7) and community hospitals (3). PATIENTS: Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections. INTERVENTIONS: Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation. MAIN OUTCOME MEASURES: Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates. RESULTS: Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018. CONCLUSIONS: Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes.

GPs' perspectives on diagnostic tests for children: a qualitative interview study.

BACKGROUND: Most healthcare contacts for children in the UK occur in general practice. Diagnostic tests can be beneficial in narrowing differential diagnoses; however, there is substantial variation in the use of tests for children in general practice. Unwarranted variation in testing can lead to variation in quality of care and may exacerbate health inequities. To our knowledge, no previous study has tried to understand why variation in testing exists for children in general practice. AIM: To explore GPs' perspectives on using diagnostic tests for children in primary care and the underlying drivers of variation. DESIGN AND SETTING: Qualitative study in which semi-structured interviews were conducted with GPs and trainee GPs in England. METHOD: Interviews were conducted with 18 GPs and two trainee GPs between April and June 2023. The interviews were transcribed and analysed using reflexive thematic analysis. RESULTS: GPs reflected that their approach to testing in children differed from their approach to testing in adults: their threshold to test was higher, and their threshold to refer to specialists was lower. GPs' perceptions of test utility varied, including objective testing for asthma. Perceived drivers of variation in testing were intrinsic (clinician-specific) factors relating to their risk tolerance and experience; and extrinsic factors, including disease prevalence, parental concern and expectations of health care, workforce changes leading to fragmentation in care, time constraints, and differences in guidelines. CONCLUSION: The findings of this study identify actionable issues for clinicians, researchers, and policymakers to address gaps in education, evidence, and guidance, reduce unwarranted differences in test use, and improve the quality of health care delivered to children in general practice.

Investigative use of human environmental DNA in forensic genetics.

Individuals leave behind traces of their DNA wherever they go. DNA can be transferred to surfaces and items upon touch, can be released into the air, and may be deposited in indoor dust. The mere presence of individuals in a location is sufficient to facilitate either direct or indirect DNA transfer into the surrounding environment. In this study, we analyzed samples recovered from commonly touched surfaces such as light switches and door handles in an office environment. We evaluated two different methods to isolate DNA and co-extract DNA and RNA from the samples. DNA profiles were compared to the references of the inhabitants of the different locations and were analyzed taking into consideration the type of sampled surface, sampling location and information about the activities in a room during the sampling day. Results from DNA samples collected from surfaces were also compared to those from air and dust samples collected in parallel from the same areas. We characterized the amount and composition of DNA found on various surfaces and showed that surface DNA sampling can be used to detect occupants of a location. The results also indicate that combining information from environmental samples collected from different DNA sources can improve our understanding of DNA transfer events in an indoor setting. This study further demonstrates the potential of human environmental DNA as an investigative tool in forensic genetics.

Up in the air: Presence and collection of DNA from air and air conditioner units.

Biological material is routinely collected at crime scenes and from exhibits and is a key type of evidence during criminal investigations. Touch or trace DNA samples from surfaces and objects deemed to have been contacted are frequently collected. However, a person of interest may not leave any traces on contacted surfaces, for example, if wearing gloves. A novel means of sampling human DNA from air offers additional avenues for DNA collection. In the present study, we report on the results of a pilot study into the prevalence and persistence of human DNA in the air. The first aspect of the pilot study investigates air conditioner units that circulate air around a room, by sampling units located in four offices and four houses at different time frames post-cleaning. The second aspect investigates the ability to collect human DNA from the air in rooms, with and without people, for different periods of time and with different types of collection filters. Results of this pilot study show that human DNA can be collected on air conditioner unit surfaces and from the air, with air samples representing the more recent occupation while air conditioner units showing historic use of the room.

Emerging use of air eDNA and its application to forensic investigations - A review.

Biological material is routinely collected at crime scenes and from exhibits and is a key type of evidence during criminal investigations. Improvements in DNA technologies allow collection and profiling of trace samples, comprised of few cells, significantly expanding the types of exhibits targeted for DNA analysis to include touched surfaces. However, success rates from trace and touch DNA samples tend to be poorer compared to other biological materials such as blood. Simultaneously, there have been recent advances in the utility of environmental DNA collection (eDNA) in identification and tracking of different biological organisms and species from bacteria to naked mole rats in different environments, including, soil, ice, snow, air and aquatic. This paper examines the emerging methods and research into eDNA collection, with a special emphasis on the potential forensic applications of human DNA collection from air including challenges and further studies required to progress implementation.

Understanding the use and outcomes of high-flow nasal cannula among infants admitted to Canadian hospitals with bronchiolitis (CanFLO): a protocol for a multicentre, retrospective cohort study.

INTRODUCTION: Bronchiolitis is the most common viral lower respiratory tract infection in children under 2 years of age. Respiratory support with high-flow nasal cannula (HFNC) is increasingly used in this patient population with limited understanding of the patients most likely to benefit and considerable practice variability of use. This study aims to understand the factors associated with failure of HFNC support among patients with bronchiolitis and to describe the current practice variations of HFNC use in patients with bronchiolitis in Canadian hospitals including fluid management and parameters to initiate, escalate and discontinue HFNC support. METHODS AND ANALYSIS: This is a multicentre retrospective cohort study including hospitalised patients aged 0-24 months with bronchiolitis requiring support with HFNC between January 2017 and December 2021. Clinical data will be collected from patient medical records from Canadian hospitals (n=12), including academic and community centres. HFNC failure will be defined as the need for escalation to non-invasive or invasive mechanical ventilation. Factors associated with HFNC failure will be analysed using logistic regression. Descriptive statistics will be used to describe practice variations of HFNC utilisation and management. ETHICS AND DISSEMINATION: Approval from the Research Ethics Boards (REBs) has been obtained for each participating study site prior to onset of data collection including Clinical Trials Ontario for all Ontario hospital sites and REBs from British Columbia Children's Hospital, Stollery Children's Hospital, Montreal Children's Hospital and CHU Sainte-Justine. Study results will be disseminated through presentation at national/international conferences and publication in high-impact, peer-reviewed journals.

Pediatric Esophageal Foreign Bodies: The Role of Socioeconomic Status in Ingestion Patterns.

OBJECTIVE: Pediatric esophageal foreign bodies (EFBs) are common and can result in serious complications. Little is known about the influence of socioeconomic status (SES) on EFB ingestion in children. The goal was to study SES as a risk factor for dangerous foreign body ingestion and in-hospital complications in children. METHODS: This was a retrospective cohort study of children presenting to a tertiary care pediatric hospital with an esophageal foreign body from 2010 to 2021. SES was assessed for each patient by linking their postal code to the Ontario Marginalization Index to determine a quintile score across four dimensions of deprivation: residential instability, material deprivation, dependency, and ethnic concentration. Dangerous EFBs were defined as magnets, batteries, sharp objects, or bones. In-hospital complications included: intensive care unit admission, prolonged length of stay, and postoperative sequelae. RESULTS: A total of 680 patients were included. Dangerous EFB ingestion was higher for children with increased residential instability (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.6) and increased material deprivation (OR, 2.2; CI, 1.9-2.8), which was similarly true for odds of complications. Odds of dangerous EFB ingestion were higher in older children (OR, 1.1; CI, 1.0-1.1) and odds of complications were higher in children with comorbidities (OR, 1.1; CI, 1.0-1.3). CONCLUSION: Higher levels of housing instability and material deprivation are associated with dangerous EFB ingestion and complications related to EFB ingestion. These findings emphasize the role that SES plays on child health outcomes and the need for initiatives to mitigate these disparities. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2945-2953, 2024.

Oxygen Saturation Targets in Infants Hospitalized With Bronchiolitis: A Multicenter Cohort Study.

OBJECTIVES: To examine 2 hospital oxygen saturation target policies and clinical outcomes in infants hospitalized with bronchiolitis. METHODS: This multicenter cohort study used data collected from a randomized clinical trial of infants aged 4 weeks to 24 months, hospitalized with bronchiolitis at children's and community hospitals from 2016 to 2019. We modeled the association between hospital oxygen saturation target policy, either 90% while awake and 88% while asleep (90%/88%) or 90% while awake and asleep (90%/90%), and clinical outcomes. RESULTS: A total of 162 infants were enrolled at 4 hospitals using a 90%/88% oxygen saturation target and 67 infants at 2 hospitals using a 90%/90% target policy. No significant differences between the 90%/88% group and 90%/90% groups were observed for time to discharge (adjusted hazard ratio, 0.83; 95% confidence interval [CI], 0.61-1.14; P = .25), initiation of supplemental oxygen (adjusted odds ratio [aOR], 0.98; 95% CI, 0.47-2.02; P = .95), time to discontinuation of supplemental oxygen (adjusted hazard ratio, 0.75; 95% CI, 0.44-1.27; P = .28), revisits (aOR, 1.38; 95% CI, 0.52-3.71; P = .52), and parent days missed from work (aOR, 2.41; 95% CI, 0.90-6.41; P = .08). Three infants in the 90%/88% group and none in the 90%/90% group were transferred to the ICU. CONCLUSIONS: Among infants hospitalized with bronchiolitis, clinical outcomes were similar between a hospital oxygen saturation target policy of 90% while awake and 88% while asleep compared with 90% while awake and asleep. These findings may inform the design of future trials of oxygen saturation targets in bronchiolitis hospital care.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Hemoglobin Threshold for Blood Transfusion in Young Children Hospitalized with Iron Deficiency Anemia.

Current recommendations advise against blood transfusion in hemodynamically stable children with iron deficiency anemia. In an observational study of 125 children aged 6 through 36 months, hospitalized with iron deficiency anemia, we found that hemoglobin level predicted red blood cell transfusion (area under the curve 0.8862). A hemoglobin of 39 g/L had sensitivity 92% and specificity 72% for transfusion.

How delocalized are the polyacenes?

In an attempt to quantify electron delocalization in polyacenes with up to 50 carbon atoms, we have performed self-consistent field calculations in which the π electrons are constrained to occupy highly localized molecular orbitals (HILOs) centered on a maximum of two, six or ten adjacent carbon atoms. We have also performed similar calculations on simple polyacene analogs consisting only of hydrogen atoms and exhibiting electron delocalization in the σ framework. We find that the energetic cost of localizing the π electrons in the polyacenes is roughly 60, 5 or 0.1 kJ/mol per ring atom for the two-, six- and ten-atom HILOs, respectively, and the use of these localized models overestimates the predicted hydrogenation energies of the acenes by roughly 50%, 4% and 0.1%, respectively. We conclude that the chemistry of polyacenes can be modeled well using highly localized descriptions of the π electrons.

The invisible witness: air and dust as DNA evidence of human occupancy in indoor premises.

Humans constantly shed deoxyribonucleic acid (DNA) into the surrounding environment. This DNA may either remain suspended in the air or it settles onto surfaces as indoor dust. In this study, we explored the potential use of human DNA recovered from air and dust to investigate crimes where there are no visible traces available-for example, from a recently vacated drugs factory where multiple workers had been present. Samples were collected from three indoor locations (offices, meeting rooms and laboratories) characterized by different occupancy types and cleaning regimes. The resultant DNA profiles were compared with the reference profiles of 55 occupants of the premises. Our findings showed that indoor dust samples are rich sources of DNA and provide an historical record of occupants within the specific locality of collection. Detectable levels of DNA were also observed in air and dust samples from ultra-clean forensic laboratories which can potentially contaminate casework samples. We provide a Bayesian statistical model to estimate the minimum number of dust samples needed to detect all inhabitants of a location. The results of this study suggest that air and dust could become novel sources of DNA evidence to identify current and past occupants of a crime scene.

Trends in diagnostic tests ordered for children: a retrospective analysis of 1.7 million laboratory test requests in Oxfordshire, UK from 2005 to 2019.

OBJECTIVE: To better understand testing patterns in children, we measured temporal trends in paediatric testing from 2005 to 2019 in Oxfordshire, UK. DESIGN: Descriptive study of population-based secondary data. SETTING: Oxfordshire University Hospitals National Health Service Trust laboratories. PARTICIPANTS: Children aged 0-15 years in Oxfordshire who received at least one blood test. MAIN OUTCOME MEASURES: We estimated average annual percentage changes (AAPCs) in test use using joinpoint regression models. Temporal changes in age-adjusted rates in test use were calculated overall and stratified by healthcare setting, sex, and age. RESULTS: Between 2005 and 2019, 1 749 425 tests were performed among 113 607 children. Overall test use declined until 2012, when test rates appeared to increase (AAPC 1.5%, 95% CI -0.8% to 3.9%). Most tests were performed in inpatient settings, where testing rates stayed steady (AAPC -0.6%, 95% CI -2.1% to 0.9%). Increases were highest in females, those aged 6-15 years and in the outpatient setting. The greatest increase in testing was for vitamin D (AAPC 26.5%), followed by parathyroid hormone (9.8%), iron studies (9.3%), folate (8.4%), vitamin B12 (8.4%), HbA1c (8.0%), IgA (7.9%) and coeliac (7.7%). CONCLUSIONS: After an initial decline, laboratory test use by children in Oxfordshire demonstrated an apparent increase since 2012. Test use increased in outpatient and general practice settings, however remained steady in inpatient settings. Further research should examine the root causes and implications for test increases, and whether these increases are warranted. We encourage clinicians to consider the individual and systemic implications of performing blood tests in children.

Social connectedness and suicidal ideation: the roles of perceived burdensomeness and thwarted belongingness in the distress to suicidal ideation pathway.

BACKGROUND: Suicide is a serious public health issue. Distress has been identified as a common risk factor, with research also suggesting that a lack of social connectedness is involved. METHODS: This quantitative, cross-sectional study investigated the role of perceived burdensomeness and thwarted belongingness in the psychological distress/suicidal ideation pathway in a community sample of 480 Australian adults. RESULTS: As expected, distress was found to be a strong predictor of suicidal ideation. Perceived burdensomeness and thwarted belongingness both moderated and mediated the relationship between distress and suicidal ideation. Specifically, distress was more strongly linked to suicide ideation when burdensomeness or thwarted belongingness were also high. This moderating effect was stronger for thwarted belongingness than it was for burdensomeness. These variables also mediated the pathway, in that higher distress related to higher burdensomeness and thwarted belonging, which in turn related to higher suicide ideation. This mediating effect was stronger for burdensomeness than for thwarted belonging. CONCLUSIONS: Overall, the findings confirm the importance of our social relatedness in suicide. Increasing belongingness and reducing the perception of being a burden on others may be an important intervention strategy for weakening the link between distress and suicide ideation.