The relationship between type, timing and duration of exposure to adverse childhood experiences and adolescent self-harm and depression: findings from three UK prospective population-based cohorts.

BACKGROUND: Adverse childhood experiences (ACEs) are well-established risk factors for self-harm and depression. However, despite their high comorbidity, there has been little focus on the impact of developmental timing and the duration of exposure to ACEs on co-occurring self-harm and depression. METHODS: Data were utilised from over 22,000 children and adolescents participating in three UK cohorts, followed up longitudinally for 14-18 years: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Millennium Cohort Study (MCS) and the Environmental Risk (E-Risk) Longitudinal Twin Study. Multinomial logistic regression models estimated associations between each ACE type and a four-category outcome: no self-harm or depression, self-harm alone, depression alone and self-harm with co-occurring depression. A structured life course modelling approach was used to examine whether the accumulation (duration) of exposure to each ACE, or a critical period (timing of ACEs) had the strongest effects on self-harm and depression in adolescence. RESULTS: The majority of ACEs were associated with co-occurring self-harm and depression, with consistent findings across cohorts. The importance of timing and duration of ACEs differed across ACEs and across cohorts. For parental mental health problems, longer duration of exposure was strongly associated with co-occurring self-harm and depression in both ALSPAC (adjusted OR: 1.18, 95% CI: 1.10-1.25) and MCS (1.18, 1.11-1.26) cohorts. For other ACEs in ALSPAC, exposure in middle childhood was most strongly associated with co-occurring self-harm and depression, and ACE occurrence in early childhood and adolescence was more important in the MCS. CONCLUSIONS: Efforts to mitigate the impact of ACEs should start in early life with continued support throughout childhood, to prevent long-term exposure to ACEs contributing to risk of self-harm and depression in adolescence.

Family structure and multisite musculoskeletal pain in adolescence: a Northern Finland Birth Cohort 1986 study.

BACKGROUND: Family structure is suggested to be associated with adolescent pain, but evidence on its association with multisite MS pain is sparse. The purpose of this cross-sectional study was to investigate the potential associations between family structure ('single-parent family', 'reconstructed family', and 'two-parent family') and multisite musculoskeletal (MS) pain in adolescence. METHODS: The dataset was based on the 16-year-old Northern Finland Birth Cohort 1986 adolescents with available data on family structure, multisite MS pain, and a potential confounder (n = 5,878). The associations between family structure and multisite MS pain were analyzed with binomial logistic regression and modelled as unadjusted, as the evaluated potential confounder, mother's educational level, did not meet the criteria for a confounder. RESULTS: Overall, 13% of the adolescents had a 'single-parent family' and 8% a 'reconstructed family'. Adolescents living in a single-parent family had 36% higher odds of multisite MS pain compared to adolescents from two-parent families (the reference) (Odds Ratio [OR]: 1.36, 95% Confidence Interval [CI]: 1.17 to 1.59). Belonging to a 'reconstructed family' was associated with 39% higher odds of multisite MS pain (OR 1.39, 1.14 to 1.69). CONCLUSION: Family structure may have a role in adolescent multisite MS pain. Future research is needed on causality between family structure and multisite MS pain, to establish if there is a need for targeted support.

Associations between diagnostic time intervals and health-related quality of life, clinical anxiety and depression in adolescents and young adults with cancer: cross-sectional analysis of the BRIGHTLIGHT cohort.

BACKGROUND: The association of diagnostic intervals and outcomes is poorly understood in adolescents and young adults with cancer (AYA). We investigated associations between diagnostic intervals and health-related quality of life (HRQoL), anxiety and depression in a large AYA cohort. METHODS: Participants aged 12-24 completed interviews post-diagnosis, providing data on diagnostic experiences and the patient-reported outcomes (PROs) HRQoL, anxiety and depression. Demographic and cancer information were obtained from clinical and national records. Six diagnostic intervals were considered. Relationships between intervals and PROs were examined using regression models. RESULTS: Eight hundred and thirty participants completed interviews. In adjusted models, across 28 of 30 associations, longer intervals were associated with poorer PROs. Patient intervals (symptom onset to first seeing a GP) of ≥1 month were associated with greater depression (adjusted odds ratio (aOR):1.7, 95% Confidence Interval (CI):1.1-2.5) compared to <1 month. ≥3 pre-referral GP consultations were associated with greater anxiety (aOR:1.6, CI:1.1-2.3) compared to 1-2 consultations. Symptom onset to first oncology appointment intervals of ≥2 months was associated with impaired HRQoL (aOR:1.8, CI:1.2-2.5) compared to <2 months. CONCLUSIONS: Prolonged diagnostic intervals in AYA are associated with an increased risk of impaired HRQoL, anxiety and depression. Identifying and delivering interventions for this high-risk group is a priority.

Exploring the causal role of intimate partner violence and abuse on depressive symptoms in young adults: a population-based cohort study.

BACKGROUND: Previous studies have shown an association between experience of intimate partner violence and abuse (IPVA) and depression. Whether this is a causal relationship or explained by prior vulnerability that influences the risk of both IPVA and depression is not known. METHODS: We analysed data from the Avon Longitudinal Study of Parents and Children prospective cohort (N = 1764 women, 1028 men). To assess the causal association between IPVA at 18-21 years old and logged depressive symptom scores at age 23, we used (i) multivariable linear regression, (ii) inverse probability of treatment weighting (IPTW), and (iii) difference-in-difference (DiD) analysis, which compared the mean change in logged depressive symptom scores between ages 16 and 23 between those who experienced IPVA and those who did not. RESULTS: Women who experienced IPVA had on average 26% higher depressive symptom scores after adjustment for measured confounders (ratio of geometric means 1.26, 95% CI 1.13 to 1.40). In men, the difference was 5% (ratio of geometric means 1.05, 95% CI 0.92 to 1.21). Results from IPTW analysis were similar. In the DiD analysis, there was no evidence that being exposed to IPVA affected the change in depressive symptom scores over time compared to being in the non-exposed group for either women (difference-in-differences 1%, -12 to 16%) or men (-1%, -19 to 20%). CONCLUSIONS: Multivariable linear regression and IPTW suggested an association between IPVA and higher depressive symptom score in women but not men, but DiD analysis indicated a null effect in both women and men. This suggests the causal origins of higher depressive symptoms in this young adult population are likely to reflect prior vulnerability that leads to both higher depressive symptoms and increased risk of IPVA exposure.

Associations between Adverse Childhood Experiences and the novel inflammatory marker glycoprotein acetyls in two generations of the Avon Longitudinal Study of Parents and Children birth cohort.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of non-communicable diseases in adulthood, potentially mediated by chronic low-grade inflammation. Glycoprotein acetyls (GlycA) is a marker of chronic and cumulative inflammation. We investigated associations between ACEs and GlycA at different ages, in two generations of the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. METHODS: ALSPAC offspring's total ACE scores were generated for two age periods using prospectively collected data: 0-7y and 0-17y. GlycA was measured using high-resolution proton nuclear magnetic resonance at mean ages 8y, 18y, and 24y. Sample sizes ranged from: n = 5116 (8y) to n = 3085 (24y). ALSPAC mothers (n = 4634) retrospectively reported ACEs experienced before age 18y and GlycA was assessed at mean age 49y. We used multivariable linear regression to estimate associations between ACEs (total ACE score and individual ACEs) and subsequent GlycA in both samples, adjusting for key confounders. RESULTS: Mean GlycA levels were similar in offspring and mothers and over time. In offspring, there was no evidence that ACEs (total score or individual ACE) were associated with GlycA at age 8y or 18y, or 24y after adjustment for maternal age at birth and parity, maternal marital status, household occupational social class, maternal education, maternal smoking, own ethnicity, sex, and age in months. In mothers, there was evidence of a positive association between the total ACE score and GlycA at age 49y (adjusted mean difference 0.007 mmol/L; 95%CI: 0.003, 0.01). Emotional neglect was the only individual ACE associated with higher GlycA after adjusting for confounders and other ACEs. CONCLUSION: Results suggest the association between ACEs and GlycA may emerge in middle age. Future research should explore the extent to which inflammation in adulthood mediates well-documented associations between ACEs and adverse health outcomes in later life.

Socioeconomic position and adverse childhood experiences as risk factors for health-related behaviour change and employment adversity during the COVID-19 pandemic: insights from a prospective cohort study in the UK.

BACKGROUND: Non-pharmaceutical interventions to reduce the spread of COVID-19 may have disproportionately affected already disadvantaged populations. METHODS: We analysed data from 2710 young adult participants of the Avon Longitudinal Study of Parents and Children. We assessed the associations of socioeconomic position (SEP) and Adverse Childhood Experiences (ACEs, e.g. abuse, neglect, measures of family dysfunction) with changes to health-related behaviours (meals, snacks, exercise, sleep, alcohol and smoking/vaping), and to financial and employment status during the first UK lockdown between March-June 2020. RESULTS: Experiencing 4+ ACEs was associated with reporting decreased sleep quantity during lockdown (OR 1.53, 95% CI: 1.07-2.18) and increased smoking and/or vaping (OR 1.85, 95% CI: 0.99-3.43); no other associations were seen between ACEs or SEP and health-related behaviour changes. Adverse financial and employment changes were more likely for people with low SEP and for people who had experienced multiple ACEs; e.g. a history of 4+ ACEs was associated with being furloughed or on other leave during lockdown (OR 1.92, 95% CI: 1.35-2.74). CONCLUSIONS: In this sample of young adults, there was little evidence that lockdown worsened inequalities in health-related behaviours. However, adverse financial and employment consequences of lockdown were more likely to be experienced by people who have already experienced socioeconomic deprivation or childhood adversity, thereby widening social inequalities and demonstrating the need for support into adulthood for those with a history of ACEs.

Being silenced, loneliness and being heard: understanding pathways to intimate partner violence & abuse in young adults. a mixed-methods study.

BACKGROUND: International research shows the significance and impact of intimate partner violence and abuse (IPVA) as a public health issue for young adults. There is a lack of qualitative research exploring pathways to IPVA. METHODS: The current mixed-methods study used qualitative interviews and analysis of longitudinal cohort data, to explore experiences of pathways to IPVA. Semi-structured Interviews alongside Life History Calendars were undertaken to explore 17 young women's (19-25 years) experiences and perceptions of pathways to IPVA in their relationships. Thematic analysis was undertaken. Based on themes identified in the qualitative analysis, quantitative analysis was conducted in data from 2127 female and 1145 male participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort study. We fitted regression models to assess the association of child maltreatment, parental domestic violence, and peer-to-peer victimisation, by age 12, with loneliness during adolescence (ages 13-14), and the association of loneliness during adolescence with IPVA (age 18-21). Mediation analysis estimated the direct effects of maltreatment on IPVA, and indirect effects through loneliness. FINDINGS: All women interviewed experienced at least one type of maltreatment, parental domestic violence, or bullying during childhood. Nearly all experienced IPVA and most had been multi-victimised. Findings indicated a circular pathway: early trauma led to isolation and loneliness, negative labelling and being silenced through negative responses to help seeking, leading to increased experiences of loneliness and intensifying vulnerability to further violence and abuse in young adulthood. The pathway was compounded by intersectionality. Potential ways to break this cycle of loneliness included being heard and supported, especially by teachers. Quantitative analysis confirmed an association between child maltreatment and loneliness in adolescence, and an association between loneliness in adolescence and experience of IPVA in young adult relationships. CONCLUSION: It is likely that negative labelling and loneliness mediate pathways to IPVA, especially among more disadvantaged young women. The impact of early maltreatment on young people's wellbeing and own relationships is compounded by disadvantage, disability and ethnicity. Participants' resilience was enabled by support in the community.

Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: A cohort study.

BACKGROUND: The diagnostic assessment of abdominal symptoms in primary care presents a challenge. Evidence is needed about the positive predictive values (PPVs) of abdominal symptoms for different cancers and inflammatory bowel disease (IBD). METHODS AND FINDINGS: Using data from The Health Improvement Network (THIN) in the United Kingdom (2000-2017), we estimated the PPVs for diagnosis of (i) cancer (overall and for different cancer sites); (ii) IBD; and (iii) either cancer or IBD in the year post-consultation with each of 6 abdominal symptoms: dysphagia (n = 86,193 patients), abdominal bloating/distension (n = 100,856), change in bowel habit (n = 106,715), rectal bleeding (n = 235,094), dyspepsia (n = 517,326), and abdominal pain (n = 890,490). The median age ranged from 54 (abdominal pain) to 63 years (dysphagia and change in bowel habit); the ratio of women/men ranged from 50%:50% (rectal bleeding) to 73%:27% (abdominal bloating/distension). Across all studied symptoms, the risk of diagnosis of cancer and the risk of diagnosis of IBD were of similar magnitude, particularly in women, and younger men. Estimated PPVs were greatest for change in bowel habit in men (4.64% cancer and 2.82% IBD) and for rectal bleeding in women (2.39% cancer and 2.57% IBD) and lowest for dyspepsia (for cancer: 1.41% men and 1.03% women; for IBD: 0.89% men and 1.00% women). Considering PPVs for specific cancers, change in bowel habit and rectal bleeding had the highest PPVs for colon and rectal cancer; dysphagia for esophageal cancer; and abdominal bloating/distension (in women) for ovarian cancer. The highest PPVs of abdominal pain (either sex) and abdominal bloating/distension (men only) were for non-abdominal cancer sites. For the composite outcome of diagnosis of either cancer or IBD, PPVs of rectal bleeding exceeded the National Institute of Health and Care Excellence (NICE)-recommended specialist referral threshold of 3% in all age-sex strata, as did PPVs of abdominal pain, change in bowel habit, and dyspepsia, in those aged 60 years and over. Study limitations include reliance on accuracy and completeness of coding of symptoms and disease outcomes. CONCLUSIONS: Based on evidence from more than 1.9 million patients presenting in primary care, the findings provide estimated PPVs that could be used to guide specialist referral decisions, considering the PPVs of common abdominal symptoms for cancer alongside that for IBD and their composite outcome (cancer or IBD), taking into account the variable PPVs of different abdominal symptoms for different cancers sites. Jointly assessing the risk of cancer or IBD can better support decision-making and prompt diagnosis of both conditions, optimising specialist referrals or investigations, particularly in women.

Causes of death up to 10 years after admissions to hospitals for self-inflicted, drug-related or alcohol-related, or violent injury during adolescence: a retrospective, nationwide, cohort study.

BACKGROUND: Emergency hospital admission with adversity-related injury (ie, self-inflicted, drug-related or alcohol-related, or violent injury) affects 4% of 10-19-year-olds. Their risk of death in the decade after hospital discharge is twice as high as that of adolescents admitted to hospitals for accident-related injury. We established how cause of death varied between these groups. METHODS: We did a retrospective, nationwide, cohort study comparing risks of death in five causal groups (suicide, drug-related or alcohol-related, homicide, accidental, and other causes of death) up to 10 years after hospital discharge following adversity-related (self-inflicted, drug-related or alcohol-related, or violent injury) or accident-related (for which there was no recorded adversity) injury. We included adolescents (aged 10-19 years) who were admitted as an emergency for adversity-related or accident-related injury between April 1, 1997, and March 31, 2012. We excluded adolescents who did not have their sex recorded, died during the index admission, had no valid discharge date, or were admitted with injury related to neither adversity nor accidents. We identified admissions for adversity-related or accident-related injury to the National Health Service in England with the International Classification of Diseases-10 codes in Hospital Episode Statistics data, linked to the Office for National Statistics mortality data for England, to establish cause-specific risks of death between the first day and 10 years after discharge, and to compare risks between adversity-related and accident-related index injury after adjustment for age group, socioeconomic status, and chronic conditions. FINDINGS: We identified 1 080 368 adolescents (388 937 [36·0%] girls, 690 546 [63·9%] boys, and 885 [0·1%] adolescents who did not have their sex recorded). Of these adolescents, we excluded 40 549 (10·4%) girls, 56 107 (8·1%) boys, and all 885 without their sex recorded. Of the 333 009 (30·8%) adolescents admitted with adversity-related injury (181 926 [54·6%] girls and 151 083 [45·4%] boys) and 649 818 (60·2%) admitted with accident-related injury (166 462 [25·6%] girls and 483 356 [74·4%] boys), 4782 (0·5%) died in the 10 years after discharge (1312 [27·4%] girls and 3470 [72·6%] boys). Adolescents discharged after adversity-related injury had higher risks of suicide (adjusted subhazard ratio 4·54 [95% CI 3·25-6·36] for girls, and 3·15 [2·73-3·63] for boys) and of drug-related or alcohol-related death (4·71 [3·28-6·76] for girls, and 3·53 [3·04-4·09] for boys) in the next decade than they did after accident-related injury. Although we included homicides in our estimates of 10-year risks of adversity-related deaths, we did not explicitly present these risks because of small numbers and risks of statistical disclosure. There was insufficient evidence that girls discharged after adversity-related injury had increased risks of accidental deaths compared with those discharged after accident-related injury (adjusted subhazard ratio 1·21 [95% CI 0·90-1·63]), but there was evidence that this risk was increased for boys (1·26 [1·09-1·47]). There was evidence of decreased risks of other causes of death in girls (0·64 [0·53-0·77]), but not in boys (0·99 [0·84-1·17]). Risks of suicide were increased following self-inflicted injury (adjusted subhazard ratio 5·11 [95% CI 3·61-7·23] for girls, and 6·20 [5·27-7·30] for boys), drug-related or alcohol-related injury (4·55 [3·23-6·39] for girls, and 4·51 [3·89-5·24] for boys), and violent injury in boys (1·43 [1·15-1·78]) versus accident-related injury. However, the increased risk of suicide in girls following violent injury versus accident-related injury was not significantly increased (adjusted subhazard ratio 1·48 [95% CI 0·73-2·98]). Following each type of index injury, risks of suicide and risks of drug-related or alcohol-related death were increased by similar magnitudes. INTERPRETATION: Risks of suicide were significantly increased after all types of adversity-related injury except for girls who had violent injury. Risks of drug-related or alcohol-related death increased by a similar magnitude. Current practice to reduce risks of harm after self-inflicted injury should be extended to drug-related or alcohol-related and violent injury in adolescence. Prevention should address the substantial risks of drug-related or alcohol-related death alongside risks of suicide. FUNDING: UK Department of Health.

Time-trends in rates of hospital admission of adolescents for violent, self-inflicted or drug/alcohol-related injury in England and Scotland, 2005-11: population-based analysis.

Background: Incidence of emergency admissions for violent injury in 10- to 18-year olds decreased in England and Scotland between 2005 and 2011, but more steeply in Scotland. To generate hypotheses about causes of these differences, we determined whether trends were consistent across admissions for three common types of adversity-related injury (violent, self-inflicted and drug/alcohol-related). Methods: Emergency admissions to NHS hospitals were captured using Hospital Episode Statistics and Scottish Morbidity Records. Adversity-related injury was defined using ICD-10 codes. Analyses were stratified by sex/age groups (10-12, 13-15 and 16-18 years) and adjusted for background trends in admissions for injury. Results: During 2005-11, rates declined in all sex/age groups in Scotland (reductions adjusted for background trends ranged from -22.0 to -103.7/100 000) and in girls and boys aged <16 years in England (adjusted reductions -12.0 to -49.9/100 000). However, these rates increased in England for both sexes aged 16-18 years (adjusted increases, girls 71.8/100 000; boys 28.0/100 000). However, throughout 2005-11 overall rates remained relatively similar in England and Scotland for both sexes aged <16 years, and remained higher in Scotland for both sexes aged 16-18 years. Conclusions: A greater decline in the rates of emergency admissions for adversity-related injury for adolescents in Scotland compared with England could signal more effective policies in Scotland for reducing violence, self-harm, or drug/alcohol misuse, particularly for 16 to 18-year olds.

10-y Risks of Death and Emergency Re-admission in Adolescents Hospitalised with Violent, Drug- or Alcohol-Related, or Self-Inflicted Injury: A Population-Based Cohort Study.

BACKGROUND: Hospitalisation for adversity-related injury (violent, drug/alcohol-related, or self-inflicted injury) has been described as a "teachable moment", when intervention may reduce risks of further harm. Which adolescents are likely to benefit most from intervention strongly depends on their long-term risks of harm. We compared 10-y risks of mortality and re-admission after adversity-related injury with risks after accident-related injury. METHODS AND FINDINGS: We analysed National Health Service admissions data for England (1 April 1997-31 March 2012) for 10-19 y olds with emergency admissions for adversity-related injury (violent, drug/alcohol-related, or self-inflicted injury; n = 333,009) or for accident-related injury (n = 649,818). We used Kaplan-Meier estimates and Cox regression to estimate and compare 10-y post-discharge risks of death and emergency re-admission. Among adolescents discharged after adversity-related injury, one in 137 girls and one in 64 boys died within 10 y, and 54.2% of girls and 40.5% of boys had an emergency re-admission, with rates being highest for 18-19 y olds. Risks of death were higher than in adolescents discharged after accident-related injury (girls: age-adjusted hazard ratio 1.61, 95% CI 1.43-1.82; boys: 2.13, 95% CI 1.98-2.29), as were risks of re-admission (girls: 1.76, 95% CI 1.74-1.79; boys: 1.41, 95% CI 1.39-1.43). Risks of death and re-admission were increased after all combinations of violent, drug/alcohol-related, and self-inflicted injury, but particularly after any drug/alcohol-related or self-inflicted injury (i.e., with/without violent injury), for which age-adjusted hazard ratios for death in boys ranged from 1.67 to 5.35, compared with 1.25 following violent injury alone (girls: 1.09 to 3.25, compared with 1.27). The main limitation of the study was under-recording of adversity-related injuries and misclassification of these cases as accident-related injuries. This misclassification would attenuate the relative risks of death and re-admission for adversity-related compared with accident-related injury. CONCLUSIONS: Adolescents discharged after an admission for violent, drug/alcohol-related, or self-inflicted injury have increased risks of subsequent harm up to a decade later. Introduction of preventive strategies for reducing subsequent harm after admission should be considered for all types of adversity-related injury, particularly for older adolescents.

Incidence, predictors and clinical characteristics of orolingual angio-oedema complicating thrombolysis with tissue plasminogen activator for ischaemic stroke.

BACKGROUND: Orolingual angio-oedema is a recognised complication of tissue plasminogen activator (tPA) for ischaemic stroke. We investigated its incidence, clinical characteristics and relationship with other factors in patients receiving tPA at a UK centre. METHODS: 530 consecutive patients (median age 70 years) receiving tPA treatment for confirmed ischaemic stroke were included. Cases were defined as those developing angio-oedema within 24 h of initiation of tPA. Angio-oedema was retrospectively classified as mild, moderate or severe using predefined criteria. The primary analysis was the association between prior ACE inhibitor (ACE-I) treatment and angio-oedema. RESULTS: Orolingual angio-oedema was observed in 42 patients (7.9%; 95% CI 5.5% to 10.6%), ranging from 5 to 189 min after initiation of tPA (median 65 min). 12% of the angio-oedema cases were severe (1% of all patients treated with tPA), requiring urgent advanced airway management. 172 patients (33%) were taking ACE-I. In multifactorial analyses, only prior ACE-I treatment remained a significant independent predictor of angio-oedema (odds ratio (OR) 2.3; 95% CI 1.1 to 4.7). CONCLUSIONS: Angio-oedema occurs more frequently than previously reported and is associated with preceding ACE-I treatment. Angio-oedema may be delayed and progress to life-threatening airway compromise, which has implications for the assessment and delivery of thrombolysis.

Establishing reference values for central blood pressure and its amplification in a general healthy population and according to cardiovascular risk factors.

AIMS: Estimated central systolic blood pressure (cSBP) and amplification (Brachial SBP-cSBP) are non-invasive measures potentially prognostic of cardiovascular (CV) disease. No worldwide, multiple-device reference values are available. We aimed to establish reference values for a worldwide general population standardizing between the different available methods of measurement. How these values were significantly altered by cardiovascular risk factors (CVRFs) was then investigated. METHODS AND RESULTS: Existing data from population surveys and clinical trials were combined, whether published or not. Reference values of cSBP and amplification were calculated as percentiles for 'Normal' (no CVRFs) and 'Reference' (any CVRFs) populations. We included 45,436 subjects out of 82,930 that were gathered from 77 studies of 53 centres. Included subjects were apparently healthy, not treated for hypertension or dyslipidaemia, and free from overt CV disease and diabetes. Values of cSBP and amplification were stratified by brachial blood pressure categories and age decade in turn, both being stratified by sex. Amplification decreased with age and more so in males than in females. Sex was the most powerful factor associated with amplification with 6.6 mmHg (5.8-7.4) higher amplification in males than in females. Amplification was marginally but significantly influenced by CVRFs, with smoking and dyslipidaemia decreasing amplification, but increased with increasing levels of blood glucose. CONCLUSION: Typical values of cSBP and amplification in a healthy population and a population free of traditional CVRFs are now available according to age, sex, and brachial BP, providing values included from different devices with a wide geographical representation. Amplification is significantly influenced by CVRFs, but differently in men and women.

Young People and Intimate Partner Violence: Experiences of Institutional Support and Services in England.

Purpose: Young people (YP) are at greater risk of experiencing intimate partner violence and abuse (IPVA), with high prevalence rates at 18-25 years and potentially severe short and long-term health and social impacts. YP often view adult support services as not for them and more research is needed to understand effective responses to IPVA among different groups. Methods: Semi-structured interviews alongside Life History Calendars were undertaken to explore 18 young peoples' (18-25 years) experiences of community and service level responses to their IPVA between 2019-2020. Thematic analysis and case studies were carried out. Results: Participant accounts commonly described what did or did not help within: education; primary care physicians and maternity services; third sector or non-government support organisations; and counselling and support workers. YP wanted clearer information on identifying abuse from a younger age in schools and better access and signposting to specialist services. They benefited the most from equal power dynamics in relationships with professionals where they were supported to make their own decisions. Conclusions: Professionals in all sectors (including schools) need IPVA trauma-informed training that encourages equal power dynamics, with a clear understanding of and access to referral pathways, to be able to respond to the needs of YP experiencing IPVA.

Categories of Intimate Partner Violence and Abuse Among Young Women and Men: Latent Class Analysis of Psychological, Physical, and Sexual Victimization and Perpetration in a UK Birth Cohort.

BACKGROUND: In the UK, around one-third of young people are exposed to Intimate Partner Violence and Abuse (IPVA) by 21 years old. However, types of IPVA victimization in this population (psychological, physical, sexual), and their relationship with impact and perpetration are poorly understood. METHODS: Participants in a UK birth cohort reported IPVA victimization and perpetration by age 21. We carried out a latent class analysis, where we categorized IPVA by types/frequency of victimization, and then assigned individuals to their most probable class. Within these classes, we then estimated rates of reported: 1) types of negative impacts (sad, upset/unhappy, anxious, depressed, affected work/studies, angry/annoyed, drank/took drugs more); 2) types/frequency of perpetration. RESULTS: Among 2130 women and 1149 men, 32% and 24% reported IPVA victimization (of which 89% and 73% reported negative impact); 21% and 16% perpetration. Victimization responses were well represented by five classes, including three apparent in both sexes: No-low victimization (characterized by low probabilities of all types of victimization; average probabilities of women and men belonging to this class were 82% and 70%); Mainly psychological (15% and 12%); Psychological and physical victimization (4% and 7%), and two classes that were specific to women: Psychological and sexual (7%); Multi-victimization (frequent victimization for all three types; 4%). In women, all types of negative impact were most common in the Psychological and sexual and Multi-victimization classes; for men, the Psychological and physical class. In women, all types of perpetration were most common for the Mainly psychological, Psychological and physical and Multi-victimization classes; in men, the Mainly psychological and Psychological and physical classes. DISCUSSION: In this study of young people, we found categories of co-occurrence of types and frequency of IPVA victimization associated with differential rates of negative impact and perpetrating IPVA. This is consistent with emerging evidence of IPVA differentiation and its variable impact in other populations.

Incidence and causes for syringe driver site reactions in palliative care: A prospective hospice-based study.

BACKGROUND: Syringe drivers are routinely used in palliative care for the subcutaneous infusion of drugs for pain and symptom control. Local site reactions occurring at the site of infusion can lead to patient discomfort and the potential for sub-optimal symptom control. AIM: The aim of this study was to investigate whether there was a correlation between drugs administered subcutaneously via a syringe driver and the incidence of syringe driver site reactions, further linking this to time to syringe driver site reaction. DESIGN: Prospective quantitative data collection of syringe driver use for 170 hospice inpatients. SETTING/PARTICIPANTS: Specialist palliative care inpatient facility in the UK. Syringe driver recording forms were retrieved from case notes of consecutive patients who received medication via a syringe driver. RESULTS: An association between the presence of cyclizine and levomepromazine and the incidence of syringe driver site reactions was identified. A marked difference in incidence of syringe driver site reaction was observed between the two study centres (26.5% vs. 7.7%). Although baseline patient characteristics were comparable, a difference in practice between the centres was identified, i.e. use of parenteral cannulae. An association between the time a syringe driver was in situ and the occurrence of a syringe driver site reaction was also demonstrated. CONCLUSIONS: Recommendations can be made for the frequency of syringe driver site changes based on which drugs are in use. Incidental findings from the study have been used to change practice at the hospice study site, with regard to choice of parenteral cannulae.

Stage-specific incidence trends of renal cancers in the East of England, 1999-2016.

OBJECTIVES: To determine stage-specific time-trends in renal cancer incidence. METHODS: We used population-based East Anglia data 1999-2016 (population ∼2 million) on 5,456 primary renal cancer diagnoses, estimating stage-specific annual incidence using Poisson regression, allowing for changing time-trends, and adjusting for sex, age, and socioeconomic deprivation. RESULTS: Renal cancer incidence increased from 9.8-16.4 cases per 100,000 during 1999-2016. Incidence of Stage I, II, and III cases increased over time, most steeply for Stage I, with annual Incidence Rate Ratio [IRR] for Stage I of 1.09 (95 % CI 1.07-1.12) during 1999-2010; and 1.03 (1.00-1.05) during 2011-2016. In contrast, the annual incidence of Stage IV renal cancer decreased during most years, IRR of 0.99 (0.98-1.00) during 2003-2016. CONCLUSION: The findings are consistent with both earlier detection of symptomatic renal cancer and increasing identification of asymptomatic lesions. However, the decreasing incidence of late-stage disease suggests genuine shifts towards earlier diagnosis.

The Spectre of Berkson's Paradox: Collider Bias in Covid-19 Research.

When non-random sampling collides with our understanding of Covid-19 risk, we must be careful not to draw incorrect conclusions about cause and effect. By Annie Herbert, Gareth Griffith, Gibran Hemani and Luisa Zuccolo.

Stage-specific incidence trends of melanoma in an English region, 1996-2015: longitudinal analyses of population-based data.

The aim of this study was to examine temporal trends in overall and stage-specific incidence of melanoma. Using population-based data on patients diagnosed with melanoma in East Anglia, England, 1996-2015, we estimated age-standardized time trends in annual incidence rates for each stage at diagnosis. Negative binomial regression was used to model trends over time adjusted for sex, age group and deprivation, and to subsequently examine variation in stage-specific trends by sex and age group. The age-standardized incidence increased from 14 to 29 cases/100 000 persons (i.e. 4% annually). Increasing incidence was apparent across all stages but was steepest for stage I [adjusted annual increase: 5%, 95% confidence interval (CI): 5-6%, and more gradual for stage II-IV disease (stage II: 3%, 95% CI: 2-4%; stage III/IV: 2%, 95% CI: 1-3%)]. Stage II-IV increase was apparent in men across age groups and in women aged 50 years or older. Increases in incidence were steeper in those aged 70 years or older, and in men. The findings suggest that both a genuine increase in the incidence of consequential illness and a degree of overdiagnosis may be responsible for the observed increasing incidence trends in melanoma in our population during the study period. They also suggest the potentially lower effectiveness of public health awareness campaigns in men and older people.

Risk factors for intimate partner violence and abuse among adolescents and young adults: findings from a UK population-based cohort.

Background: Approximately one-third of young people in the UK have suffered intimate partner violence and abuse (IPVA) on reaching adulthood. We need interventions to prevent IPVA in this population, but there is a lack of evidence on who is at greatest risk. Methods: We analysed questionnaire data from 3,279 participants of the Avon Longitudinal Study of Parents and Children population-based birth cohort. We estimated the prevalence of IPVA victimisation and perpetration by age 21, by sex, demographic, parenting, mental health, externalising behaviour (e.g. smoking), educational, employment, and adverse childhood factors. Results: Overall, 29% of males and 41% of females reported IPVA victimisation, with 20% and 25% reporting perpetration, respectively (16% and 22% both). The most common sub-type was emotional, followed by physical, then sexual. History of self-harm, anti-social behaviour, cannabis or illicit (non-cannabis) drug use among boys and girls was associated with a two-fold increase in likelihood of IPVA (victimisation or perpetration). Males reporting risky sexual behaviour, sexual abuse (not by an intimate partner), or witnessing domestic violence, and females reporting sexual minority status in adolescence were also twice as likely to experience IPVA. Extreme parental monitoring during adolescence was associated with a reduced risk of IPVA in males and females, as was not being in education, employment, or training for young adult men. Conclusions: A range of demographic, mental health, and behavioural factors were associated with increased prevalence of IPVA victimisation or perpetration. Further study of likely complex pathways from these factors to IPVA, to inform primary prevention, is needed.