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Article ; Online: Substantially more children receiving antidepressants see a specialist than reported by Jack et al.

Taxiarchi, Vicky P / Chew-Graham, Carolyn A / Pierce, Matthias

2023 Volume 21, Issue 1, Page(s) 345

Abstract: We would like to draw attention to evidence of substantial bias in the article published in this journal by Jack et al. (BMC Med 18:1-12, 2020). They provide an analysis of antidepressant prescribing to children and young people (CYP; ages 5 to 17) in ... ...

Abstract	We would like to draw attention to evidence of substantial bias in the article published in this journal by Jack et al. (BMC Med 18:1-12, 2020). They provide an analysis of antidepressant prescribing to children and young people (CYP; ages 5 to 17) in primary care in England and reported that only 24.7% of CYP prescribed SSRIs for the first time were seen by a child and adolescent psychiatrist-contrary to national guidelines. We believe that their analysis is based on incomplete data that misses a large proportion of specialist mental health contacts. This is because the dataset Jack et al. used to capture specialist mental health contact-The Hospital Episode Statistics (HES) dataset-has poor coverage, as most CYP mental health services do not submit data. We demonstrate the level of underreporting with an analysis of events in a large primary care dataset where there has been a record of definite contact with CYP mental health services. We report that as many as three quarters of specialist CYP contacts with mental health specialists are missed in the HES dataset, indicating that the figure presented by Jack et al. is substantially wrong.
MeSH term(s)	Adolescent ; Humans ; Child ; Secondary Care ; Antidepressive Agents/therapeutic use ; Selective Serotonin Reuptake Inhibitors ; Databases, Factual ; Primary Health Care
Chemical Substances	Antidepressive Agents ; Selective Serotonin Reuptake Inhibitors
Language	English
Publishing date	2023-09-11
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-023-03043-x
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Article ; Online: A comparison of approaches for combining predictive markers for personalised treatment recommendations.

Pierce, Matthias / Emsley, Richard

Trials

2021 Volume 22, Issue 1, Page(s) 20

Abstract: Background: In the presence of heterogeneous treatment effects, it is desirable to divide patients into subgroups based on their expected response to treatment. This is formalised via a personalised treatment recommendation: an algorithm that uses ... ...

Abstract	Background: In the presence of heterogeneous treatment effects, it is desirable to divide patients into subgroups based on their expected response to treatment. This is formalised via a personalised treatment recommendation: an algorithm that uses biomarker measurements to select treatments. It could be that multiple, rather than single, biomarkers better predict these subgroups. However, finding the optimal combination of multiple biomarkers can be a difficult prediction problem. Methods: We described three parametric methods for finding the optimal combination of biomarkers in a personalised treatment recommendation, using randomised trial data: a regression approach that models outcome using treatment by biomarker interactions; an approach proposed by Kraemer that forms a combined measure from individual biomarker weights, calculated on all treated and control pairs; and a novel modification of Kraemer's approach that utilises a prognostic score to sample matched treated and control subjects. Using Monte Carlo simulations under multiple data-generating models, we compare these approaches and draw conclusions based on a measure of improvement under a personalised treatment recommendation compared to a standard treatment. The three methods are applied to data from a randomised trial of home-delivered pragmatic rehabilitation versus treatment as usual for patients with chronic fatigue syndrome (the FINE trial). Prior analysis of this data indicated some treatment effect heterogeneity from multiple, correlated biomarkers. Results: The regression approach outperformed Kraemer's approach across all data-generating scenarios. The modification of Kraemer's approach leads to improved treatment recommendations, except in the case where there was a strong unobserved prognostic biomarker. In the FINE example, the regression method indicated a weak improvement under its personalised treatment recommendation algorithm. Conclusions: The method proposed by Kraemer does not perform better than a regression approach for combining multiple biomarkers. All methods are sensitive to misspecification of the parametric models.
MeSH term(s)	Biomarkers ; Fatigue Syndrome, Chronic ; Humans ; Precision Medicine ; Research Design
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1468-6708
ISSN (online)	1745-6215 ; 1468-6694
ISSN	1468-6708
DOI	10.1186/s13063-020-04901-2
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Article ; Online: A comparison of approaches for combining predictive markers for personalised treatment recommendations

Matthias Pierce / Richard Emsley

Trials, Vol 22, Iss 1, Pp 1-

2021 Volume 8

Abstract: Abstract Background In the presence of heterogeneous treatment effects, it is desirable to divide patients into subgroups based on their expected response to treatment. This is formalised via a personalised treatment recommendation: an algorithm that ... ...

Abstract	Abstract Background In the presence of heterogeneous treatment effects, it is desirable to divide patients into subgroups based on their expected response to treatment. This is formalised via a personalised treatment recommendation: an algorithm that uses biomarker measurements to select treatments. It could be that multiple, rather than single, biomarkers better predict these subgroups. However, finding the optimal combination of multiple biomarkers can be a difficult prediction problem. Methods We described three parametric methods for finding the optimal combination of biomarkers in a personalised treatment recommendation, using randomised trial data: a regression approach that models outcome using treatment by biomarker interactions; an approach proposed by Kraemer that forms a combined measure from individual biomarker weights, calculated on all treated and control pairs; and a novel modification of Kraemer’s approach that utilises a prognostic score to sample matched treated and control subjects. Using Monte Carlo simulations under multiple data-generating models, we compare these approaches and draw conclusions based on a measure of improvement under a personalised treatment recommendation compared to a standard treatment. The three methods are applied to data from a randomised trial of home-delivered pragmatic rehabilitation versus treatment as usual for patients with chronic fatigue syndrome (the FINE trial). Prior analysis of this data indicated some treatment effect heterogeneity from multiple, correlated biomarkers. Results The regression approach outperformed Kraemer’s approach across all data-generating scenarios. The modification of Kraemer’s approach leads to improved treatment recommendations, except in the case where there was a strong unobserved prognostic biomarker. In the FINE example, the regression method indicated a weak improvement under its personalised treatment recommendation algorithm. Conclusions The method proposed by Kraemer does not perform better than a regression approach for ...
Keywords	Personalised medicine ; Stratified medicine ; Precision medicine ; Personalised treatment recommendations ; Predictive biomarkers ; Moderators ; Medicine (General) ; R5-920
Subject code	310
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: Parental Mental Illness and the Likelihood of Child Out-of-Home Care: A Cohort Study.

Nevriana, Alicia / Kosidou, Kyriaki / Hope, Holly / Wicks, Susanne / Dalman, Christina / Pierce, Matthias / Abel, Kathryn M

Pediatrics

2024 Volume 153, Issue 3

Abstract: Objectives: To detail the relationship between parental mental illness and the likelihood of out-of-home care (OHC) among their children, and to identify factors which modify this relationship.: Methods: Using Swedish national registers, children ... ...

Abstract	Objectives: To detail the relationship between parental mental illness and the likelihood of out-of-home care (OHC) among their children, and to identify factors which modify this relationship. Methods: Using Swedish national registers, children born in 2000 to 2011 (n = 1 249 463) were linked to their parents. Time-dependent parental mental illness (nonaffective and affective psychosis, substance misuse, depression, anxiety and stress, eating disorders, personality disorders, attention deficit hyperactivity disorder, autism, and intellectual disability), was identified through International Classification of Diseases codes. Results: After adjustment for socioeconomic factors, children living with mentally ill parents were 4 times as likely to be placed in OHC than children without (95% confidence interval [CI] 4.24-4.61). The highest hazard ratio (HR) was in the youngest children aged 0 to 1 year (5.77, 95% CI 5.42-6.14), exposed to maternal illness (HR 4.56, 95% CI 4.37-4.76), and parental intellectual disability (HR 4.73, 95% CI 4.09-5.46). Children with parental mental illness with multiple risk factors were at particularly high risk. Compared with children without parental mental illness, and those with university-educated parents, children whose parents had mental illness and only had education to age 16 had a 15 times higher risk of OHC (95% CI 13.75-16.54). Conclusions: Children with parental mental illness are considerably more likely to be removed from home into care during childhood, particularly during the first year of life and if they are from socially disadvantaged families. Greater knowledge of these risks should lead to increased support for vulnerable new families.
MeSH term(s)	Child ; Humans ; Young Adult ; Adult ; Cohort Studies ; Intellectual Disability ; Probability ; Parents ; Home Care Services
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	207677-9
ISSN	1098-4275 ; 0031-4005
ISSN (online)	1098-4275
ISSN	0031-4005
DOI	10.1542/peds.2023-061531
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Article ; Online: The causal association between maternal depression, anxiety, and infection in pregnancy and neurodevelopmental disorders among 410 461 children: a population study using quasi-negative control cohorts and sibling analysis.

Hope, Holly / Pierce, Matthias / Gabr, Hend / Radojčić, Maja R / Swift, Eleanor / Taxiarchi, Vicky P / Abel, Kathryn M

Psychological medicine

2024 , Page(s) 1–9

Abstract: Background: To address if the long-standing association between maternal infection, depression/anxiety in pregnancy, and offspring neurodevelopmental disorder (NDD) is causal, we conducted two negative-control studies.: Methods: Four primary care ... ...

Abstract	Background: To address if the long-standing association between maternal infection, depression/anxiety in pregnancy, and offspring neurodevelopmental disorder (NDD) is causal, we conducted two negative-control studies. Methods: Four primary care cohorts of UK children (pregnancy, 1 and 2 years prior to pregnancy, and siblings) born between 1 January 1990 and 31 December 2017 were constructed. NDD included autism/autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy. Maternal exposures included depression/anxiety and/or infection. Maternal (age, smoking status, comorbidities, body mass index, NDD); child (gender, ethnicity, birth year); and area-level (region and level of deprivation) confounders were captured. The NDD incidence rate among (1) children exposed during or outside of pregnancy and (2) siblings discordant for exposure in pregnancy was compared using Cox-regression models, unadjusted and adjusted for confounders. Results: The analysis included 410 461 children of 297 426 mothers and 2 793 018 person-years of follow-up with 8900 NDD cases (incidence rate = 3.2/1000 person years). After adjustments, depression and anxiety consistently associated with NDD (pregnancy-adjusted HR = 1.58, 95% CI 1.46-1.72; 1-year adj. HR = 1.49, 95% CI 1.39-1.60; 2-year adj. HR = 1.62, 95% CI 1.50-1.74); and to a lesser extent, of infection (pregnancy adj. HR = 1.16, 95% CI 1.10-1.22; 1-year adj. HR = 1.20, 95% CI 1.14-1.27; 2-year adj. HR = 1.19, 95% CI 1.12-1.25). NDD risk did not differ among siblings discordant for pregnancy exposure to mental illness HR = 0.97, 95% CI 0.77-1.21 or infection HR = 0.99, 95% CI 0.90-1.08. Conclusions: Maternal risk appears to be unspecific to pregnancy: our study provided no evidence of a specific, and therefore causal, link between in-utero exposure to infection, common mental illness, and later development of NDD.
Language	English
Publishing date	2024-01-11
Publishing country	England
Document type	Journal Article
ZDB-ID	217420-0
ISSN	1469-8978 ; 0033-2917
ISSN (online)	1469-8978
ISSN	0033-2917
DOI	10.1017/S0033291723003604
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Article ; Online: Maternal mental illness and child atopy: a UK population-based, primary care cohort study.

Osam, Cemre Su / Hope, Holly / Ashcroft, Darren M / Abel, Kathryn M / Pierce, Matthias

The British journal of general practice : the journal of the Royal College of General Practitioners

2023 Volume 73, Issue 737, Page(s) e924–e931

Abstract: Background: The number of children exposed to maternal mental illness is rapidly increasing and little is known about the effects of maternal mental illness on childhood atopy.: Aim: To investigate the association between maternal mental illness and ... ...

Abstract	Background: The number of children exposed to maternal mental illness is rapidly increasing and little is known about the effects of maternal mental illness on childhood atopy. Aim: To investigate the association between maternal mental illness and risk of atopy among offspring. Design and setting: Retrospective cohort study using a UK primary care database (674 general practices). Method: In total, 590 778 children (born 1 January 1993 to 30 November 2017) were followed until their 18th birthday, with 359 611 linked to their hospital records. Time-varying exposure was captured for common (depression and anxiety), serious (psychosis), addiction (alcohol and substance misuse), and other (eating and personality disorder) maternal mental illness from 6 months before pregnancy. Using Cox regression models, incidence rates of atopy were calculated and compared for the exposed and unexposed children in primary (asthma, eczema, allergic rhinitis, and food allergies) and secondary (asthma and food allergies) care, adjusted for maternal (age, atopy history, smoking, and antibiotic use), child (sex, ethnicity, and birth year/season), and area covariates (deprivation and region). Results: Children exposed to common maternal mental illness were at highest risk of developing asthma (adjusted hazard ratio [aHR] 1.17, 95% confidence interval [CI] = 1.15 to 1.20) and allergic rhinitis (aHR 1.17, 95% CI = 1.13 to 1.21), as well as a hospital admission for asthma (aHR 1.29, 95% CI = 1.20 to 1.38). Children exposed to addiction disorders were 9% less likely to develop eczema (aHR 0.91, 95% CI = 0.85 to 0.97) and 35% less likely to develop food allergies (aHR 0.65, 95% CI = 0.45 to 0.93). Conclusion: The finding that risk of atopy varies by type of maternal mental illness prompts important aetiological questions. The link between common mental illness and childhood atopy requires GPs and policymakers to act and support vulnerable women to access preventive (for example, smoking cessation) services earlier.
MeSH term(s)	Pregnancy ; Child ; Humans ; Female ; Cohort Studies ; Retrospective Studies ; Mental Disorders/epidemiology ; Eczema ; Asthma/epidemiology ; Mothers ; Rhinitis, Allergic ; Surveys and Questionnaires ; Food Hypersensitivity ; United Kingdom/epidemiology ; Primary Health Care
Language	English
Publishing date	2023-11-30
Publishing country	England
Document type	Journal Article
ZDB-ID	1043148-2
ISSN	1478-5242 ; 0035-8797 ; 0960-1643
ISSN (online)	1478-5242
ISSN	0035-8797 ; 0960-1643
DOI	10.3399/BJGP.2022.0584
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Article ; Online: 5-year mental health outcomes for children and adolescents presenting with psychiatric symptoms to general practitioners in England: a retrospective cohort study.

Senior, Morwenna / Pierce, Matthias / Taxiarchi, Vicky P / Garg, Shruti / Edge, Dawn / Newlove-Delgado, Tamsin / Neufeld, Sharon A S / Abel, Kathryn M

The lancet. Psychiatry

2024 Volume 11, Issue 4, Page(s) 274–284

Abstract: Background: Little information is available on the clinical trajectories of children and adolescents who attend general practice (GP) with psychiatric symptoms. We aimed to examine 5-year service use in English primary care for children and adolescents ... ...

Abstract	Background: Little information is available on the clinical trajectories of children and adolescents who attend general practice (GP) with psychiatric symptoms. We aimed to examine 5-year service use in English primary care for children and adolescents with neurodevelopmental or mental health symptoms or diagnoses. Methods: In this retrospective cohort study, we used anonymised primary care health records from the Clinical Practice Research Datalink Aurum database (CPRD-Aurum). We identified children and adolescents (aged 3-18 years) presenting to primary care in England between Jan 1, 2000, and May 9, 2016, with a symptom or diagnosis of a mental health, behavioural, or neurodevelopmental condition. Participants were excluded if they had less than 1 year of follow-up. We followed up participants from their index date until either death, transfer out of the practice, or the end of data collection on May 5, 2021, and for trajectory analysis we limited follow-up to 5 years. We used group-based multi-trajectory models to identify clusters with similar trajectories over 5 years of follow-up for three primary outcomes: mental health-related GP contacts, psychotropic medication prescriptions, and specialist mental health-care contact. We did survival analysis to examine the associations between trajectory-group membership and hospital admission for self-harm or death by suicide, as indicators of severe psychiatric distress. Findings: We included 369 340 children and adolescents, of whom 180 863 (49·0%) were girls, 188 438 (51·0%) were boys, 39 (<0·1%) were of indeterminate gender, 290 125 (78·6%) were White, 9161 (2·5%) were South Asian, 10 418 (2·8%) were Black, 8115 (2·2%) were of mixed ethnicity, and 8587 (2·3%) were other ethnicities, and the median age at index presentation was 13·6 years (IQR 8·4-16·7). In the best-fitting, seven-group, group-based multi-trajectory model, over a 5-year period, the largest group (low contact; 207 985 [51·2%]) had low rates of additional service contact or psychotropic prescriptions. The other trajectory groups were moderate, non-pharmacological contact (43 836 [13·0%]); declining contact (25 469 [8·7%]); year-4 escalating contact (18 277 [6·9%]); year-5 escalating contact (18 139; 5·2%); prolonged GP contact (32 147 [8·6%]); and prolonged specialist contact (23 487 [6·5%]). Non-White ethnicity and presentation in earlier study years (eg, 2000-2004) were associated with low-contact group membership. The prolonged specialist-contact group had the highest risk of hospital admission for self-harm (hazard ratio vs low-contact group 2·19 [95% CI 2·03-2·36]) and suicide (2·67 [1·72-4·14]). Interpretation: Most children and adolescents presenting to primary care with psychiatric symptoms or diagnoses have low or declining rates of ongoing contact. If these trajectories reflect symptomatic improvement, these findings provide reassurance for children and adolescents and their caregivers. However, these trajectories might reflect an unmet need for some children and adolescents. Funding: National Institute for Health and Care Research and the Wellcome Trust.
MeSH term(s)	Male ; Child ; Female ; Humans ; Adolescent ; Retrospective Studies ; General Practitioners ; Mental Disorders/epidemiology ; Mental Disorders/therapy ; Mental Disorders/psychology ; England/epidemiology ; Psychotropic Drugs ; Outcome Assessment, Health Care
Chemical Substances	Psychotropic Drugs
Language	English
Publishing date	2024-01-27
Publishing country	England
Document type	Journal Article
ISSN	2215-0374
ISSN (online)	2215-0374
DOI	10.1016/S2215-0366(24)00038-5
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Article ; Online: Correspondence for "Parental history of psychiatric disorders and risk of type 1 diabetes in the offspring".

Nevriana, Alicia / Rossides, Marios / Kosidou, Kyriaki / Pierce, Matthias / Dalman, Christina / Wicks, Susanne / Abel, Kathryn M

Diabetes & metabolism

2023 Volume 49, Issue 4, Page(s) 101434

MeSH term(s)	Humans ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/genetics ; Mental Disorders ; Parents/psychology ; Risk Factors
Language	English
Publishing date	2023-02-19
Publishing country	France
Document type	Letter ; Comment
ZDB-ID	1315751-6
ISSN	1878-1780 ; 1262-3636 ; 0338-1684
ISSN (online)	1878-1780
ISSN	1262-3636 ; 0338-1684
DOI	10.1016/j.diabet.2023.101434
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Article ; Online: Hospital inpatient admissions of children of mothers with severe mental illness: A Western Australian cohort study.

Pierce, Matthias / Di Prinzio, Patsy / Dalman, Christina / Abel, Kathryn M / Morgan, Vera A

The Australian and New Zealand journal of psychiatry

2022 Volume 57, Issue 4, Page(s) 528–536

Abstract: Background: Children of parents with mental illness face a number of adversities, potentially contributing to poor health.: Aim: The aim of this study was to quantify the association between maternal severe mental illness and children's hospital ... ...

Abstract	Background: Children of parents with mental illness face a number of adversities, potentially contributing to poor health. Aim: The aim of this study was to quantify the association between maternal severe mental illness and children's hospital admissions. Method: Record linkage cohort study of 467,945 children born in Western Australia between 1 January 1980 and 31 December 2001. Follow-up was from age 28 days until fifth birthday. Linked registers captured information on potential confounders. Rate ratios and adjusted rate ratios measured relative change in the numbers of admissions and total days of stay, while rate differences measured absolute change in outcomes. Cause-specific increases were calculated for ICD-9 chapters and for 'potentially preventable' conditions. Results: After adjusting for potential confounders, children of mothers with severe mental illness had a 46% relative increased rate in hospital admissions (95% confidence interval = [38%, 54%]) and an absolute increase in 0.69 extra days in hospital per child, per year (95% confidence interval = [0.67, 0.70]). The relative increase in admissions was greatest in the child's first year of life (adjusted rate ratio = 1.76, 95% confidence interval = [1.64, 1.88]; rate difference = 0.32, 95% confidence interval = [0.30, 0.34]). Rates of admissions were increased for a range of causes, particularly injuries, infections and respiratory disease, and for conditions classified as 'potentially preventable'. Conclusion: Children of mothers with severe mental illness have a substantial excess in hospital use compared to children of well mothers. This vulnerable group should be targeted with interventions to avert preventable morbidity and premature mortality in later life.
MeSH term(s)	Female ; Child ; Humans ; Infant ; Infant, Newborn ; Mothers ; Cohort Studies ; Australia ; Inpatients ; Mental Disorders/epidemiology ; Hospitals
Language	English
Publishing date	2022-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	221140-3
ISSN	1440-1614 ; 0004-8674
ISSN (online)	1440-1614
ISSN	0004-8674
DOI	10.1177/00048674221100161
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Article ; Online: Self-harm risk in pregnancy: recurrent-event survival analysis using UK primary care data.

Hope, Holly / Pierce, Matthias / Osam, Cemre Su / Morgan, Catharine / John, Ann / Abel, Kathryn M

The British journal of psychiatry : the journal of mental science

2022 Volume 221, Issue 4, Page(s) 621–627

Abstract: Background: Perinatal self-harm is of concern but poorly understood.: Aims: To determine if women's risk of self-harm changes in pregnancy and the first postpartum year, and if risk varies by mental illness, age and birth outcome.: Method: This ... ...

Abstract	Background: Perinatal self-harm is of concern but poorly understood. Aims: To determine if women's risk of self-harm changes in pregnancy and the first postpartum year, and if risk varies by mental illness, age and birth outcome. Method: This was a retrospective cohort study of 2 666 088 women aged 15-45 years from the 1 January 1990 to 31 December 2017 linked to 1 102 040 pregnancies and their outcomes, utilising the Clinical Practice Research Datalink and Pregnancy Register. We identified self-harm events and mental illness (depression/anxiety/addiction/affective/non-affective psychosis/eating/personality disorders) from clinical records and grouped women's age into 5-year bands. They calculated the rate of self-harm during discrete non-perinatal, pregnant and postpartum periods. We used a gap-time, stratified Cox model to manage multiple self-harm events, and calculated the unadjusted and adjusted hazard ratios (adjHR) of self-harm associated with pregnancy and the postpartum compared with non-perinatal periods. Pre-planned interactions tested if risk varied by mental illness, age and birth outcome. Results: The analysis included 57 791 self-harm events and 14 712 319 person-years of follow-up. The risk of self-harm shrank in pregnancy (2.07 Conclusions: Maternity and perinatal mental health services are valuable. Family planning services might have psychological benefit, particularly for young women.
MeSH term(s)	Female ; Humans ; Pregnancy ; Primary Health Care ; Retrospective Studies ; Self-Injurious Behavior/epidemiology ; Self-Injurious Behavior/psychology ; Survival Analysis ; United Kingdom/epidemiology
Language	English
Publishing date	2022-02-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218103-4
ISSN	1472-1465 ; 0007-1250
ISSN (online)	1472-1465
ISSN	0007-1250
DOI	10.1192/bjp.2022.31
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