Novel Therapeutic and Program-Based Approaches to Opioid Use Disorders.

Opioid use disorder continues to drive overdose deaths in many countries, including the United States. Illicit fentanyl and its analogues have emerged as key contributors to the complications and mortality associated with opioid use disorder. Medications for opioid use disorder treatment, such as methadone and buprenorphine, are safe and substantially reduce opioid use, infectious complications, and mortality risk, but remain underutilized. Polysubstance use and emerging substances such as xylazine and designer benzodiazepines create additional treatment challenges. Recent clinical and policy innovations in treatment delivery, including telemedicine, bridge clinics, and expanded models for accessing methadone have the potential to increase access to life-saving care for people living with opioid use disorder.

The effectiveness of moderating harmful online content.

In 2022, the European Union introduced the Digital Services Act (DSA), a new legislation to report and moderate harmful content from online social networks. Trusted flaggers are mandated to identify harmful content, which platforms must remove within a set delay (currently 24 h). Here, we analyze the likely effectiveness of EU-mandated mechanisms for regulating highly viral online content with short half-lives. We deploy self-exciting point processes to determine the relationship between the regulated moderation delay and the likely harm reduction achieved. We find that harm reduction is achievable for the most harmful content, even for fast-paced platforms such as Twitter. Our method estimates moderation effectiveness for a given platform and provides a rule of thumb for selecting content for investigation and flagging, managing flaggers' workload.

Iatrogenic harm in functional neurological disorder.

Functional Neurological Disorder (FND) is continuing to gain increasing recognition globally as a valid and potentially treatable disorder. Iatrogenic harm towards patients with FND is significant however, and has been around for centuries. Despite advances in our understanding around the aetiology, pathophysiology, and treatment of FND, many aspects of such harm continue to persist. Avoidance of iatrogenic harm has been highlighted by clinicians as one of the most important therapeutic considerations in FND, however, the sources and range of potential harms, or indeed ways to mitigate them, have not been previously summarised. Using a combination of clinical and research experience and scoping review methodology, this review aims to describe the main sources of iatrogenic harm towards patients with FND, including harm from misdiagnosis, delayed diagnosis and treatment, direct harm from professional interactions, other stigma-related harms, harm related to diagnostic overshadowing and over-diagnosis of FND. We also describe some potential ways to address and prevent such harms, such as ways to reduce misdiagnosis with a focus on rule in signs, optimising teaching and communication, ensuring parity of FND with other medical conditions, and continued integration of patient and professional organisations.

Long-term benefits and harms of early colorectal cancer screening in German individuals with familial cancer risk.

Individuals with a family history of colorectal cancer (CRC) may benefit from early screening with colonoscopy or immunologic fecal occult blood testing (iFOBT). We systematically evaluated the benefit-harm trade-offs of various screening strategies differing by screening test (colonoscopy or iFOBT), interval (iFOBT: annual/biennial; colonoscopy: 10-yearly) and age at start (30, 35, 40, 45, 50 and 55 years) and end of screening (65, 70 and 75 years) offered to individuals identified with familial CRC risk in Germany. A Markov-state-transition model was developed and used to estimate health benefits (CRC-related deaths avoided, life-years gained [LYG]), potential harms (eg, associated with additional colonoscopies) and incremental harm-benefit ratios (IHBR) for each strategy. Both benefits and harms increased with earlier start and shorter intervals of screening. When screening started before age 50, 32-36 CRC-related deaths per 1000 persons were avoided with colonoscopy and 29-34 with iFOBT screening, compared to 29-31 (colonoscopy) and 28-30 (iFOBT) CRC-related deaths per 1000 persons when starting age 50 or older, respectively. For iFOBT screening, the IHBRs expressed as additional colonoscopies per LYG were one (biennial, age 45-65 vs no screening), four (biennial, age 35-65), six (biennial, age 30-70) and 34 (annual, age 30-54; biennial, age 55-75). Corresponding IHBRs for 10-yearly colonoscopy were four (age 55-65), 10 (age 45-65), 15 (age 35-65) and 29 (age 30-70). Offering screening with colonoscopy or iFOBT to individuals with familial CRC risk before age 50 is expected to be beneficial. Depending on the accepted IHBR threshold, 10-yearly colonoscopy or alternatively biennial iFOBT from age 30 to 70 should be recommended for this target group.

Medication non-adherence and self-inflicted violence behaviors among 185,800 patients with schizophrenia in the community: a 12-year cohort study.

BACKGROUND: Despite the importance of medication adherence in treatment effectiveness, little is known about the association between medication non-adherence and self-inflicted violence behaviors. We aimed to assess whether medication non-adherence increased the risk of self-inflicted violence behaviors among schizophrenics in communities (hypothesis 1) and whether the dose-response relationship existed (hypothesis 2). METHODS: This 12-year cohort study in western China recruited 292,667 community-dwelling schizophrenics. The proportion of regular medication (PRM) was calculated by dividing the time of "regular adherence" by the total time of antipsychotic treatment during follow-up period as an indicator of medication adherence. For hypothesis 1, medication adherence was designated as a binary variable with a threshold of 0.8 (PRM); for hypothesis 2, medication adherence was specified as five-category and continuous variables, respectively. Inverse probability weighting and mixed effects Cox proportional hazards models were conducted for confounders control and survival analyses. RESULTS: One hundred eighty-five thousand eight hundred participants were eligible for the final analyses, with a mean age of 47.49 years (SD 14.55 years), of whom 53.6% were female. For hypothesis 1, the medication non-adherence group (PRM < 0.8) had a lower risk of suicide (HR, 0.527, 95% CI, 0.447-0.620), an increased risk of NSSI (HR, 1.229, 95% CI, 1.088-1.388), and non-significant risk of attempted suicide compared with adherence group (PRM ≥ 0.8). For hypothesis 2, the lowest medication adherence (PRM < 0.2) was associated with increased risks of suicide attempt (HR, 1.614, 95% CI, 1.412-1.845), NSSI (HR, 1.873, 95% CI, 1.649-2.126), and a decreased risk of suicide (HR, 0.593, 95% CI, 0.490-0.719). The other non-adherence groups had lower risks for all three self-inflicted violence behaviors. The associations between medication adherence in continuous-variable and three outcomes were consistent with the categorical medication adherence results. CONCLUSIONS: Almost no medication taken as prescribed was associated with an increased risk of suicide attempt and NSSI. However, medication adherence did not appear to prevent completed suicide. Besides, patients with moderate adherence had a lower incidence of suicide attempt and NSSI. These findings highlight the need for a more detailed portrayal of medication adherence and the need to be vigilant for suicide intent in schizophrenics with good medication adherence who may be overlooked previously.

Risk-based lung cancer screening in heavy smokers: a benefit-harm and cost-effectiveness modeling study.

BACKGROUND: Annual screening through low-dose computed tomography (LDCT) is recommended for heavy smokers. However, it is questionable whether all individuals require annual screening given the potential harms of LDCT screening. This study examines the benefit-harm and cost-effectiveness of risk-based screening in heavy smokers and determines the optimal risk threshold for screening and risk-stratified screening intervals. METHODS: We conducted a comparative cost-effectiveness analysis in China, using a cohort-based Markov model which simulated a lung cancer screening cohort of 19,146 heavy smokers aged 50 ~ 74 years old, who had a smoking history of at least 30 pack-years and were either current smokers or had quit for < 15 years. A total of 34 risk-based screening strategies, varying by different risk groups for screening eligibility and screening intervals (1-year, 2-year, 3-year, one-off, non-screening), were evaluated and were compared with annual screening for all heavy smokers (the status quo strategy). The analysis was undertaken from the health service perspective with a 30-year time horizon. The willingness-to-pay (WTP) threshold was adopted as three times the gross domestic product (GDP) of China in 2021 (CNY 242,928) per quality-adjusted life year (QALY) gained. RESULTS: Compared with the status quo strategy, nine risk-based screening strategies were found to be cost-effective, with two of them even resulting in cost-saving. The most cost-effective strategy was the risk-based approach of annual screening for individuals with a 5-year risk threshold of ≥ 1.70%, biennial screening for individuals with a 5-year risk threshold of 1.03 ~ 1.69%, and triennial screening for individuals with a 5-year risk threshold of < 1.03%. This strategy had the highest incremental net monetary benefit (iNMB) of CNY 1032. All risk-based screening strategies were more efficient than the status quo strategy, requiring 129 ~ 656 fewer screenings per lung cancer death avoided, and 0.5 ~ 28 fewer screenings per life-year gained. The cost-effectiveness of risk-based screening was further improved when individual adherence to screening improved and individuals quit smoking after being screened. CONCLUSIONS: Risk-based screening strategies are more efficient in reducing lung cancer deaths and gaining life years compared to the status quo strategy. Risk-stratified screening intervals can potentially balance long-term benefit-harm trade-offs and improve the cost-effectiveness of lung cancer screenings.

Distribution of rapid HCV antibody self-test kits via needle/syringe dispensing machines: Implementation and evaluation of the Vend-C pilot study in Melbourne, Australia.

Recent guidance from the World Health Organization strongly recommended hepatitis C virus (HCV) self-testing. We implemented the Vend-C pilot study to explore the effectiveness and feasibility of distributing rapid HCV antibody self-test kits to people who inject drugs via needle/syringe dispensing machines (SDMs). Over a 51-day study period between August and September 2022, we distributed HCV antibody self-test kits via two SDMs. During the study period, 63 self-test kits were dispensed, averaging 1.2 self-test kits per day. Our access methods for evaluation questionnaires failed to attract participants (n = 4). We implemented the Vend-C pilot study in direct response to recent WHO recommendations. While self-test kits were effectively distributed from the two SDMs, our evaluation methodology failed. Consequently, we cannot determine the success of linkage to care. Even so, with HCV treatment numbers dropping in Australia, innovative engagement solutions are needed, and considering the number of self-test kits provided in our pilot, the model could have an important future place in HCV elimination efforts.

Should a gamete bank verify the non-medical information provided by a donor?

Over the years, cases of fraud have been discovered where donors have been lying about their characteristics. The question raised by such cases is what the responsibility of the gamete bank is for the non-medical information provided by the donor. The problem is that extended donor profiles contain a large amount of information about different aspects of the donor's life and that not all this information can be verified or is worth verifying. Two cases are scrutinized in more detail: education and criminal record. The proposed solution is to split the donor information into a verified and a non-verified part with the non-verified part falling under the responsibility of the donor. The question of what information should be included in the verified part of the donor profile is still open.

Why do errors arise in artificial intelligence diagnostic tools in histopathology and how can we minimize them?

Artificial intelligence (AI)-based diagnostic tools can offer numerous benefits to the field of histopathology, including improved diagnostic accuracy, efficiency and productivity. As a result, such tools are likely to have an increasing role in routine practice. However, all AI tools are prone to errors, and these AI-associated errors have been identified as a major risk in the introduction of AI into healthcare. The errors made by AI tools are different, in terms of both cause and nature, to the errors made by human pathologists. As highlighted by the National Institute for Health and Care Excellence, it is imperative that practising pathologists understand the potential limitations of AI tools, including the errors made. Pathologists are in a unique position to be gatekeepers of AI tool use, maximizing patient benefit while minimizing harm. Furthermore, their pathological knowledge is essential to understanding when, and why, errors have occurred and so to developing safer future algorithms. This paper summarises the literature on errors made by AI diagnostic tools in histopathology. These include erroneous errors, data concerns (data bias, hidden stratification, data imbalances, distributional shift, and lack of generalisability), reinforcement of outdated practices, unsafe failure mode, automation bias, and insensitivity to impact. Methods to reduce errors in both tool design and clinical use are discussed, and the practical roles for pathologists in error minimisation are highlighted. This aims to inform and empower pathologists to move safely through this seismic change in practice and help ensure that novel AI tools are adopted safely.

Multilevel Factors Impacting Substance Use Treatment Access, Engagement, and Racial Equity Among Opioid Overdose Survivors in Boston, MA.

BACKGROUND: There are well-documented racial/ethnic inequities in drug-related overdoses and access to evidence-based opioid use services nationally and in Boston, MA. OBJECTIVE: To qualitatively explore the drivers of racial/ethnic inequities in access to opioid use disorder treatment and services in Boston. DESIGN: Semi-structured qualitative interviews. PARTICIPANTS: Using purposive sampling, researchers recruited 59 opioid overdose survivors in Boston who self-identified as Black, Hispanic or Latino/a/x, and/or White. APPROACH: Interviewers administered a socio-demographic and drug use survey, and used a semi-structured interview guide to explore experiences with and perspectives on substance use treatment and services. KEY RESULTS: Participants' racial/ethnic identities were distributed across three subgroups: non-Hispanic Black (n = 18; 31%), non-Hispanic White (n = 18; 31%), and Latino/a/x (n = 23; 39%). Qualitative analysis identified multiple themes that were organized into four social-ecological levels after analysis. At the individual level, some participants emphasized the importance of personal responsibility and individual motivation in determining access to services. Participants expressed a range of perspectives about using medication for opioid use disorder treatment; Black and Latino/a/x participants were more likely than White participants to have critical perspectives. At the interpersonal level, experiences of bias, stigma, and racism from staff in healthcare and treatment settings were common. At the program/process level, participants described challenges connecting to services following overdose and barriers within specific programs, with Black and Latino/a/x participants experiencing particular gaps. At the systems level, the limited availability of housing, employment, and mental health care negatively impacted treatment access and engagement. CONCLUSION: A racism lens was used during data interpretation to apply the themes at a broader population level. Through this lens, the identified barriers can be understood to have a disproportionate impact on people of color. Findings call for programmatic and policy solutions that address racism, break down stigma, and ensure equitable access to evidence-based services and social supports.

"It's Like A Partnership": Exploring the Primary Care Experiences and Patient-Defined Goals of People Who Use Drugs.

BACKGROUND: Primary care is an important yet underutilized resource in addressing the overdose crisis. Previous studies have identified important aspects of primary care for people who use drugs (PWUD) and have found patient involvement in healthcare decisions and goal-setting to be especially critical. However, there has been limited research describing the primary care goals of PWUD. In harm reduction settings, where it is imperative that PWUD set their own goals, this research gap becomes especially relevant. OBJECTIVE: To explore how PWUD navigate primary care with a focus on understanding their primary care goals. DESIGN: A qualitative study using semi-structured interviews. PARTICIPANTS: PWUD currently engaged in primary care at the Respectful and Equitable Access to Comprehensive Healthcare (REACH) Program, a harm reduction-based primary care program in New York City. APPROACH: Between June 2022 and August 2022, we conducted 17 semi-structured interviews. Informed by phenomenology, transcripts were coded using both inductive and deductive codes and themes were developed using thematic analysis approaches. KEY RESULTS: Phenomenological analysis identified four core components that, together, created an experience that participants described as "a partnership" between patient and provider: (1) patient-provider collaboration around patient-defined healthcare goals; (2) support provided by harm reduction-based approaches to primary care anchored in incrementalism and flexibility; (3) care teams' ability to address healthcare system fragmentation; and (4) the creation of social connections through primary care. This holistic partnership fostered positive primary care experiences and supported participants' self-defined care goals, thereby facilitating meaningful care outcomes. CONCLUSIONS: To best meet the primary care goals of PWUD, these findings underscore the importance of primary care providers and programs facilitating such partnerships through organizational-level support anchored in harm reduction. Future research should explore how these experiences in primary care affect patient health outcomes, ultimately shaping best practices in the provision of high-quality primary care for PWUD.

Efficacy of a short message service brief contact intervention (SMS-SOS) in reducing repetition of hospital-treated self-harm: randomised controlled trial.

BACKGROUND: Hospital-treated self-harm is common and costly, and is associated with repeated self-harm and suicide. AIMS: To investigate the effectiveness of a brief contact intervention delivered via short message service (SMS) text messages in reducing hospital-treated self-harm re-presentations in three hospitals in Sydney (2017-2019), Australia. Trial registration number: ACTRN12617000607370. METHOD: A randomised controlled trial with parallel arms allocated 804 participants presenting with self-harm, stratified by previous self-harm, to a control condition of treatment as usual (TAU) (n = 431) or an intervention condition of nine automated SMS contacts (plus TAU) (n = 373), over 12 months following the index self-harm episode. The primary outcomes were (a) repeat self-harm event rate (number of self-harm events per person per year) at 6-, 12- and 24-month follow-up and (b) the time to first repeat at 24-month follow-up. RESULTS: The event rate for self-harm repetition was lower for the SMS compared with TAU group at 6 months (IRR = 0.79, 95% CI 0.61-1.01), 12 months (IRR = 0.78, 95% CI 0.64-0.95) and 24 months (IRR = 0.78, 95% CI 0.66-0.91). There was no difference between the SMS and TAU groups in the time to first repeat self-harm event over 24 months (HR = 0.96, 95% CI 0.72-1.26). There were four suicides in the TAU group and none in the SMS group. CONCLUSIONS: The 22% reduction in repetition of hospital-treated self-harm was clinically meaningful. SMS text messages are an inexpensive, scalable and universal intervention that can be used in hospital-treated self-harm populations but further work is needed to establish efficacy and cost-effectiveness across settings.

Trends in incidence of self-harm, neurodevelopmental and mental health conditions among university students compared with the general population: nationwide electronic data linkage study in Wales.

BACKGROUND: Concern that self-harm and mental health conditions are increasing in university students may reflect widening access to higher education, existing population trends and/or stressors associated with this setting. AIMS: To compare population-level data on self-harm, neurodevelopmental and mental health conditions between university students and non-students with similar characteristics before and during enrolment. METHOD: This cohort study linked electronic records from the Higher Education Statistics Agency for 2012-2018 to primary and secondary healthcare records. Students were undergraduates aged 18 to 24 years at university entry. Non-students were pseudo-randomly selected based on an equivalent age distribution. Logistic regressions were used to calculate odds ratios. Poisson regressions were used to calculate incidence rate ratios (IRR). RESULTS: The study included 96 760 students and 151 795 non-students. Being male, self-harm and mental health conditions recorded before university entry, and higher deprivation levels, resulted in lower odds of becoming a student and higher odds of drop-out from university. IRRs for self-harm, depression, anxiety, autism spectrum disorder (ASD), drug use and schizophrenia were lower for students. IRRs for self-harm, depression, attention-deficit hyperactivity disorder, ASD, alcohol use and schizophrenia increased more in students than in non-students over time. Older students experienced greater risk of self-harm and mental health conditions, whereas younger students were more at risk of alcohol use than non-student counterparts. CONCLUSIONS: Mental health conditions in students are common and diverse. While at university, students require person-centred stepped care, integrated with local third-sector and healthcare services to address specific conditions.

Attitudes toward and experiences of clinical and non-clinical services among individuals who self-harm or attempt suicide: a systematic review.

The prevalence of self-harm has increased substantially in recent decades. Despite the development of guidelines for better management and prevention of self-harm, service users report that quality of care remains variable. A previous systematic review of research published to June 2006 documented largely negative experiences of clinical services among patients who self-harm. This systematic review summarized the literature published since then to July 2022 to examine contemporary attitudes toward and experience of clinical and non-clinical services among individuals who self-harm and their relatives. We systematically searched for literature using seven databases. Quality of studies was assessed using the Mixed-Methods Appraisal Tool and findings were summarized using a narrative synthesis. We identified 29 studies that met our inclusion criteria, all of which were from high- or middle-income countries and were generally of high methodological quality. Our narrative synthesis identified negative attitudes toward clinical management and organizational barriers across services. Generally, more positive attitudes were found toward non-clinical services providing therapeutic contact, such as voluntary sector organizations and social services, than clinical services, such as emergency departments and inpatient units. Views suggested that negative experiences of service provision may perpetuate a cycle of self-harm. Our review suggests that in recent years there has been little improvement in attitudes toward and experiences of services for patients who self-harm. These findings should be used to reform clinical guidelines and staff training across clinical services to promote patient-centered and compassionate care and deliver more effective, acceptable and accessible services.

Assessing evidence supporting cannabis harm reduction practices for adolescents at clinical high-risk for psychosis: a review and clinical implementation tool.

Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with psychotic disorders in both CHR-P and healthy individuals to bridge the gap between scientific knowledge and practical mental health intervention. There is compelling evidence for cannabis acutely exacerbating psychotic symptoms in CHR-P, but its impact on conversion to psychotic disorder is unclear. Current evidence supports a harm reduction approach in reducing frequency of acute psychotic-like experiences, though whether such interventions decrease CHR-P individuals' risk of conversion to psychotic disorder remains unknown. Specific recommendations include reducing frequency of use, lowering delta-9-tetrahydrocannabinol content in favor of cannabidiol-only products, avoiding products with inconsistent potency like edibles, enhancing patient-provider communication about cannabis use and psychotic-like experiences, and utilizing a collaborative and individualized therapeutic approach. Despite uncertainty surrounding cannabis' causal association with psychotic disorders, cautious attempts to reduce acute psychosis risk may benefit CHR-P individuals uninterested in abstinence. Further research is needed to clarify practices associated with minimization of cannabis-related psychosis risk.

Variation in the clinical management of self-harm by area-level socio-economic deprivation: findings from the multicenter study of self-harm in England.

BACKGROUND: We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England. METHODS: 108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models. RESULTS: Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71-0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74-0.87, p < 0.0001). Referral to substance use services and 'other' services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78-0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79-0.94, p = 0.001). CONCLUSIONS: SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.

Pretreatment cognitive performance is associated with differential self-harm outcomes in 6 v. 12-months of dialectical behavior therapy for borderline personality disorder.

BACKGROUND: Recent findings suggest that brief dialectical behavior therapy (DBT) for borderline personality disorder is effective for reducing self-harm, but it remains unknown which patients are likely to improve in brief v. 12 months of DBT. Research is needed to identify patient characteristics that moderate outcomes. Here, we characterized changes in cognition across brief DBT (DBT-6) v. a standard 12-month course (DBT-12) and examined whether cognition predicted self-harm outcomes in each arm. METHODS: In this secondary analysis of 240 participants in the FASTER study (NCT02387736), cognitive measures were administered at pre-treatment, after 6 months, and at 12 months. Self-harm was assessed from pre-treatment to 2-year follow-up. Multilevel models characterized changes in cognition across treatment. Generalized estimating equations examined whether pre-treatment cognitive performance predicted self-harm outcomes in each arm. RESULTS: Cognitive performance improved in both arms after 6 months of treatment, with no between-arm differences at 12-months. Pre-treatment inhibitory control was associated with different self-harm outcomes in DBT-6 v. DBT-12. For participants with average inhibitory control, self-harm outcomes were significantly better when assigned to DBT-12, relative to DBT-6, at 9-18 months after initiating treatment. In contrast, participants with poor inhibitory control showed better self-harm outcomes when assigned to brief DBT-6 v. DBT-12, at 12-24 months after initiating treatment. CONCLUSIONS: This work represents an initial step toward an improved understanding of patient profiles that are best suited to briefer v. standard 12 months of DBT, but observed effects should be replicated in a waitlist-controlled study to confirm that they were treatment-specific.

Paternal care plasticity: males care more for early- than late-developing embryos in an arboreal breeding treefrog.

BACKGROUND: Parental care benefits offspring but comes with costs. To optimize the trade-off of costs and benefits, parents should adjust care based on intrinsic and/or extrinsic conditions. The harm to offspring hypothesis suggests that parents should invest more in younger offspring than older offspring because younger offspring are more vulnerable. However, this hypothesis has rarely been comprehensively tested, as many studies only reveal an inverse correlation between parental care and offspring age, without directly testing the effects of offspring age on their vulnerability. To test this hypothesis, we studied Kurixalus eiffingeri, an arboreal treefrog with paternal care. We first performed a field survey by monitoring paternal care during embryonic development. Subsequently, we conducted a field experiment to assess the prevalence of egg predators (a semi-slug, Parmarion martensi) and the plasticity of male care. Finally, we conducted a laboratory experiment to assess how embryo age affects predation by P. martensi. RESULTS: Our results showed that (1) male attendance and brooding frequency affected embryo survival, and (2) males attended and brooded eggs more frequently in the early stage than in the late stage. The experimental results showed that (3) males increased attendance frequency when the predators were present, and (4) the embryonic predation by the semi-slug during the early was significantly higher than in the late stage. CONCLUSIONS: Our findings highlight the importance of paternal care to embryo survival, and the care behavior is plastic. Moreover, our results provide evidence consistent with the predictions of the harm to offspring hypothesis, as males tend to care more for younger offspring which are more vulnerable.

Practitioner Review: Treatments for young people who self-harm - challenges and recommendations for research and clinical practice.

BACKGROUND: Self-harm is very common in young people and is associated with suicide. Rates of both self-harm and suicide have increased in young people, particularly in females. There is a clear need to identify new approaches to prevent repeat self-harm. METHOD: We significantly update and build on previous reviews with the aim of identifying issues in research relevant to clinical practice. We identify challenges in developing, implementing and evaluating treatments for self-harm in children and adolescents, suggest a way forward for research, and provide clear and practical guidance for clinicians on how to apply current research evidence in the real world. RESULTS: Currently, there is limited evidence for effective interventions, other than some support for dialectical behaviour therapy for adolescents (DBT-A). To improve research and, by extension, clinical practice, future studies need to address psychosocial factors associated with youth self-harm and suicide, investigate the critical mechanism(s) of action, ensure trials are sufficiently powered and representative, and involve young people more actively in the design, implementation and evaluation of these approaches. Consideration should also be given to alternative research designs, such as pragmatic or adaptive clinical trials, as well as registry-based randomised controlled trials which leverage administrative data collected in routine clinical practice, to help meet these goals. CONCLUSIONS: Recommendations for practice include undertaking comprehensive assessment and formulation, and offering DBT-A where indicated. There should be further development and evaluation (with input from young people) of Cognitive Behavioural-based Therapy adapted for young people. Greater attention to the role of the therapeutic relationship and family involvement (where possible) is also an important considerations, irrespective of the specific therapeutic modality. Finally, more consideration should be given to improving staff training to ensure all clinical staff feel equipped to treat young people who self-harm in a person-centred and compassionate manner.

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.