Self-harm in a primary care cohort of older people: incidence, clinical management, and risk of suicide and other causes of death

BACKGROUND: Self-harm is a major risk factor for suicide, with older adults (older than 65 years) having reportedly greater suicidal intent than any other age group. With the aging population rising and paucity of research focus in this age group, the extent of the problem of self-harm needs to be established. In a primary care cohort of older adults we aimed to investigate the incidence of self-harm, subsequent clinical management, prevalence of mental and physical diagnoses, and unnatural-cause mortality risk, including suicide. METHODS: The UK Clinical Practice Research Datalink contains anonymised patient records from general practice that routinely capture clinical information pertaining to both primary and secondary care services. We identified 4124 adults aged 65 years and older with a self-harm episode ascertained from Read codes recorded during 2001-14. We calculated standardised incidence and in 2854 adults with at least 12 months follow-up examined the frequency of psychiatric referrals and prescription of psychotropic medication after self-harm. We estimated prevalence of mental and physical illness diagnoses before and after self-harm and, using Cox regression in a matched cohort, we examined cause-specific mortality risks. FINDINGS: Overall incidence of self-harm in older adults aged 65 years and older was 4·1 per 10 000 person-years with stable gender-specific rates observed over the 13-year period. After self-harm, 335 (11·7%) of 2854 adults were referred to mental health services, 1692 (59·3%) were prescribed an antidepressant, and 336 (11·8%) were prescribed a tricyclic antidepressant (TCA). Having a diagnosed previous mental illness was twice as prevalent in the self-harm cohort as in the comparison cohort (prevalence ratio 2·10 [95% CI 2·03-2·17]) and with a previous physical health condition prevalence was 20% higher in the self-harm cohort compared to the comparison cohort (1·20 [1·17-1·23]). Adults from the self-harm cohort (n=2454) died from unnatural causes an estimated 20 times more frequently than the comparison cohort (n=48 921) during the first year. A markedly elevated risk of suicide (hazard ratio 145·4 [95% CI 53·9-392·3]) was observed in the self-harm cohort. INTERPRETATION: Within primary care, we have identified a group of older adults at high risk from unnatural death, particularly within the first year of self-harm. We have highlighted a high frequency of prescription of TCAs, known to be potentially fatally toxic in overdose. We emphasise the need for early intervention, careful alternative prescribing, and increased support when older adults consult after an episode of self-harm and with other health conditions. FUNDING: National Institute for Health Research Greater Manchester Patient Safety Translational Research Centre

Changes to healthcare utilisation and symptoms for common mental health problems over the first 21 months of the COVID-19 pandemic: parallel analyses of electronic health records and survey data in England

BACKGROUND: Few studies have investigated the effect of the COVID-19 pandemic on mental health beyond 2020. This study quantifies changes to healthcare utilisation and symptoms for common mental health problems over the pandemic’s first 21 months. METHODS: Parallel cohort studies using primary care database and survey data for adults (≥16 years) in England from January 2015 to December 2021: 16,551,842 from the Clinical Practice Research Datalink (CPRD) and 40,699 from the UK Household Longitudinal Survey (UKHLS). Interrupted time-series models estimated changes in monthly prevalence of presentations and prescribed medications for anxiety and depression (CPRD); and self-reported psychological distress (UKHLS). The pandemic period was divided into five phases: 1st Wave (April–May 2020); post-1st Wave (June–September 2020); 2nd Wave (October 2020–February 2021); post 2nd Wave (March–May 2021); 3rd Wave (June–December 2021). FINDINGS: Primary care presentations for depression or anxiety dropped during the first wave (4.6 fewer monthly appointments per 1000 patients, 4.4–4.8) and remained lower than expected throughout follow-up. Self-reported psychological distress exceeded expected levels during the first (Prevalence Ratio = 1.378, 95% CI 1.289–1.459) and second waves (PR = 1.285, 1.189–1.377), returning towards expected levels during the third wave (PR = 1.038, 0.929–1.154). Increases in psychological distress and declines in presentations were greater for women. The decrease in primary care presentations for depression and anxiety exceeded that for physical health conditions (rheumatoid arthritis, diabetes, urinary tract infections). Anxiety and depression prescriptions returned to pre-pandemic levels during the second wave due to increased repeat prescriptions. INTERPRETATION: Despite periods of distress during the pandemic, we did not find an enduring effect on common mental health problems. The fall in primary care presentations for anxiety or depression suggests changing healthcare utilisation for mental distress and a potential treatment gap. FUNDING: National Institute for Health and Care Research (NIHR)

Risk factors for nonfatal self‐harm and suicide among adolescents: two nested case–control studies conducted in the UK Clinical Practice Research Datalink

Background The characteristics of adolescents who die by suicide have hitherto been examined in uncontrolled study designs, thereby precluding examination of risk factors. The degree to which antecedents of nonfatal self-harm and suicide at young age differ remains unknown. Method We delineated two nested case–control studies of patients aged 10–19 years using the Clinical Practice Research Datalink with interlinked hospital and national mortality records. Cases were adolescents who between 1st January 2003 and 31st December 2018 had died from suicide (N = 324) – study 1; experienced their first self-harm episode (N = 56,008) – study 2. In both studies, cases were matched on sex, age and practice-level deprivation quintile to 25 controls. By fitting conditional logistic regression, we examined how risks varied according to psychiatric diagnoses, prescribed psychotropic medication, patterns of clinical contact and area-level deprivation. Results Suicides occurred more often among boys (66%), but self-harm was more common in girls (68%). Most individuals who self-harmed or died from suicide presented to their GP at least once in the preceding year (85% and 75% respectively). Only a third of cases had one of the examined diagnostic categories recorded. Depression was most strongly associated with elevated risks for both outcomes (self-harm: OR 7.9; 95% CI 7.8–8.2; suicide: OR 7.4; 95% CI 5.5–9.9). Except for autism spectrum disorder, all other diagnostic categories were linked with similar risk elevations for self-harm as for suicide. Whilst self-harm risk rose incrementally with increasing levels of area-level deprivation, suicide risks did not. Conclusions We observed few marked differences in risk factor profiles for nonfatal self-harm versus suicide. As most adolescents who had harmed themselves or died by suicide were known to services in the preceding year, their underlying pathology may not be adequately identified and treated. Our findings highlight the need for a multiagency approach to treatment and prevention

Temporal trends in annual incidence rates for psychiatric disorders and self-harm among children and adolescents in the UK, 2003-2018.

BACKGROUND: There has been growing concern in the UK over recent years that a perceived mental health crisis is affecting children and adolescents, although published epidemiological evidence is limited. METHODS: Two population-based UK primary care cohorts were delineated in the Aurum and GOLD datasets of the Clinical Practice Research Datalink (CPRD). We included data from 9,133,246 individuals aged 1-20 who contributed 117,682,651 person-years of observation time. Sex- and age-stratified annual incidence rates were estimated for attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) (age groups: 1-5, 6-9, 10-12, 13-16, 17-19), depression, anxiety disorders (6-9, 10-12, 13-16, 17-19), eating disorders and self-harm (10-12, 13-16, 17-19) during 2003-2018. We fitted negative binomial regressions to estimate incidence rate ratios (IRRs) to examine change in incidence between the first (2003) and final year (2018) year of observation and to examine sex-specific incidence. RESULTS: The results indicated that the overall incidence has increased substantially in both boys and girls in between 2003 and 2018 for anxiety disorders (IRR 3.51 95% CI 3.18-3.89), depression (2.37; 2.03-2.77), ASD (2.36; 1.72-3.26), ADHD (2.3; 1.73-3.25), and self-harm (2.25; 1.82-2.79). The incidence for eating disorders also increased (IRR 1.3 95% CI 1.06-1.61), but less sharply. The incidence of anxiety disorders, depression, self-harm and eating disorders was in absolute terms higher in girls, whereas the opposite was true for the incidence of ADHD and ASD, which were higher among boys. The largest relative increases in incidence were observed for neurodevelopmental disorders, particularly among girls diagnosed with ADHD or ASD. However, in absolute terms, the incidence was much higher for depression and anxiety disorders. CONCLUSION: The number of young people seeking help for psychological distress appears to have increased in recent years. Changes to diagnostic criteria, reduced stigma, and increased awareness may partly explain our results, but we cannot rule out true increases in incidence occurring in the population. Whatever the explanation, the marked rise in demand for healthcare services means that it may be more challenging for affected young people to promptly access the care and support that they need

On the monotone stability approach to BSDEs with jumps: Extensions, concrete criteria and examples

We show a concise extension of the monotone stability approach to backward stochastic differential equations (BSDEs) that are jointly driven by a Brownian motion and a random measure for jumps, which could be of infinite activity with a non-deterministic and time inhomogeneous compensator. The BSDE generator function can be non convex and needs not to satisfy global Lipschitz conditions in the jump integrand. We contribute concrete criteria, that are easy to verify, for results on existence and uniqueness of bounded solutions to BSDEs with jumps, and on comparison and a-priori $L^{\infty}$-bounds. Several examples and counter examples are discussed to shed light on the scope and applicability of different assumptions, and we provide an overview of major applications in finance and optimal control.Comment: 28 pages. Added DOI https://link.springer.com/chapter/10.1007%2F978-3-030-22285-7_1 for final publication, corrected typo (missing gamma) in example 4.1

Effects of the COVID-19 pandemic on primary care-recorded mental illness and self-harm episodes in the UK: a population-based cohort study

BACKGROUND: The COVID-19 pandemic has adversely affected population mental health. We aimed to assess temporal trends in primary care-recorded common mental illness, episodes of self-harm, psychotropic medication prescribing, and general practitioner (GP) referrals to mental health services during the COVID-19 emergency in the UK. METHODS: We did a population-based cohort study using primary care electronic health records from general practices registered on the UK Clinical Practice Research Datalink (CPRD). We included patient records from Jan 1, 2010, to Sept 10, 2020, to establish long-term trends and patterns of seasonality, but focused primarily on the period January, 2019-September, 2020. We extracted data on clinical codes entered into patient records to estimate the incidence of depression and anxiety disorders, self-harm, prescriptions for antidepressants and benzodiazepines, and GP referrals to mental health services, and assessed event rates of all psychotropic prescriptions and self-harm. We used mean-dispersion negative binomial regression models to predict expected monthly incidence and overall event rates, which were then compared with observed rates to assess the percentage reduction in incidence and event rates after March, 2020. We also stratified analyses by sex, age group, and practice-level Index of Multiple Deprivation quintiles. FINDINGS: We identified 14 210 507 patients from 1697 UK general practices registered in the CPRD databases. In April, 2020, compared with expected rates, the incidence of primary care-recorded depression had reduced by 43·0% (95% CI 38·3-47·4), anxiety disorders by 47·8% (44·3-51·2), and first antidepressant prescribing by 36·4% (33·9-38·8) in English general practices. Reductions in first diagnoses of depression and anxiety disorders were largest for adults of working age (18-44 and 45-64 years) and for patients registered at practices in more deprived areas. The incidence of self-harm was 37·6% (34·8-40·3%) lower than expected in April, 2020, and the reduction was greatest for women and individuals aged younger than 45 years. By September, 2020, rates of incident depression, anxiety disorder, and self-harm were similar to expected levels. In Northern Ireland, Scotland, and Wales, rates of incident depression and anxiety disorder remained around a third lower than expected to September, 2020. In April, 2020, the rate of referral to mental health services was less than a quarter of the expected rate for the time of year (75·3% reduction [74·0-76·4]). INTERPRETATION: Consequences of the considerable reductions in primary care-recorded mental illness and self-harm could include more patients subsequently presenting with greater severity of mental illness and increasing incidence of non-fatal self-harm and suicide. Addressing the effects of future lockdowns and longer-term impacts of economic instability on mental health should be prioritised. FUNDING: National Institute for Health Research and Medical Research Council

The cometary composition of a protoplanetary disk as revealed by complex cyanides

Observations of comets and asteroids show that the Solar Nebula that spawned our planetary system was rich in water and organic molecules. Bombardment brought these organics to the young Earth's surface, seeding its early chemistry. Unlike asteroids, comets preserve a nearly pristine record of the Solar Nebula composition. The presence of cyanides in comets, including 0.01% of methyl cyanide (CH3CN) with respect to water, is of special interest because of the importance of C-N bonds for abiotic amino acid synthesis. Comet-like compositions of simple and complex volatiles are found in protostars, and can be readily explained by a combination of gas-phase chemistry to form e.g. HCN and an active ice-phase chemistry on grain surfaces that advances complexity[3]. Simple volatiles, including water and HCN, have been detected previously in Solar Nebula analogues - protoplanetary disks around young stars - indicating that they survive disk formation or are reformed in situ. It has been hitherto unclear whether the same holds for more complex organic molecules outside of the Solar Nebula, since recent observations show a dramatic change in the chemistry at the boundary between nascent envelopes and young disks due to accretion shocks[8]. Here we report the detection of CH3CN (and HCN and HC3N) in the protoplanetary disk around the young star MWC 480. We find abundance ratios of these N-bearing organics in the gas-phase similar to comets, which suggests an even higher relative abundance of complex cyanides in the disk ice. This implies that complex organics accompany simpler volatiles in protoplanetary disks, and that the rich organic chemistry of the Solar Nebula was not unique.Comment: Definitive version of the manuscript is published in Nature, 520, 7546, 198, 2015. This is the author's versio

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

A new portable vibrator for plaster pouring: effect on the marginal fit at cylinder-abutment

OBJECTIVE: The aim of this study was to test a new portable vibrator for plaster pouring (developed for this purpose), comparing the effect of its use on the accuracy of working cast of implant-supported restorations to the conventional vibrator. MATERIAL AND METHODS: From a master cast with 2 implants, 30 transfer moldings were made randomly and divided into three groups: Group I (GI): pouring performed in an outsourced dental laboratory with conventional plaster vibrator (10 casts), Group II (GII): pouring performed in the laboratory of the Federal University of Santa Catarina (UFSC) with conventional plaster vibrator (10 casts) and Group III (GIII): pouring performed with the portable vibrator fabricated for this study (10 casts). The position of the analogue and marginal adaptation of the infrastructure were verified by testing the single screw on the master model and on the working model. The measurement of misfit was blindly performed with a precision microscope and analyzing unit, Quadra-Check 200. The data were statistically analyzed by analysis of variance (ANOVA) and the Holm-Sidak test (α=0.05). RESULTS: Means±standard deviations were as follows: GI: 19.19±4.73 µm; GII: 21.72±5.41 µm; GIII: 13.5±2.39 µm (P<0.05), with GIII significantly lower as compared to the other groups. CONCLUSION: Within the limitations of this study, it was concluded that a greater accuracy of working cast was achieved when a portable vibrator was used for casting molds