Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial.

BACKGROUND: Once-daily oral semaglutide is an effective type 2 diabetes treatment. We aimed to investigate a new formulation of oral semaglutide at higher investigational doses versus the approved 14 mg dose in adults with inadequately controlled type 2 diabetes. METHODS: This global, multicentre, randomised, double-blind, phase 3b trial, carried out at 177 sites in 14 countries, enrolled adults with type 2 diabetes, glycated haemoglobin (HbA1c) 8·0-10·5% (64-91 mmol/mol), a BMI of 25·0 kg/m2 or greater, receiving stable daily doses of one to three oral glucose-lowering drugs. Participants were randomly assigned (1:1:1), by means of an interactive web response system, to once-daily oral semaglutide 14 mg, 25 mg, or 50 mg for 68 weeks. Investigators, site personnel, trial participants, and trial sponsor staff were masked to dose assignment throughout the trial. The primary endpoint was change in HbA1c from baseline to week 52, evaluated with a treatment policy estimand in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of trial drug. This trial is registered with ClinicalTrials.gov, NCT04707469, and the European Clinical Trials register, EudraCT 2020-000299-39, and is complete. FINDINGS: Between Jan 15 and Sept 29, 2021, of 2294 people screened, 1606 (n=936 [58·3%] male; n=670 [41·7%] female; mean [SD] age 58·2 [10·8] years) received oral semaglutide 14 mg (n=536), 25 mg (n=535), or 50 mg (n=535). At baseline, mean (SD) HbA1c was 9·0% (0·8; 74·4 mmol/L [SD 8·3]) and mean bodyweight was 96·4 kg (21·6). Mean changes (SE) in HbA1c at week 52 were -1·5 percentage points (SE 0·05) with oral semaglutide 14 mg, -1·8 percentage points (0·06) with 25 mg (estimated treatment difference [ETD] -0·27, 95% CI -0·42 to -0·12; p=0·0006), and -2·0 percentage points (0·06) with 50 mg (ETD -0·53, -0·68 to -0·38; p<0·0001). Adverse events were reported by 404 (76%) participants in the oral semaglutide 14 mg group, 422 (79%) in the 25 mg group, and 428 (80%) in the 50 mg group. Gastrointestinal disorders, which were mostly mild to moderate, occurred more frequently with oral semaglutide 25 mg and 50 mg than with 14 mg. Ten deaths occurred during the trial; none were judged to be treatment related. INTERPRETATION: Oral semaglutide 25 mg and 50 mg were superior to 14 mg in reducing HbA1c and bodyweight in adults with inadequately controlled type 2 diabetes. No new safety concerns were identified. FUNDING: Novo Nordisk.

Impact of COVID-19 restrictions on self-poisoning behaviour with mild analgesics in Danish youth.

BACKGROUND: The COVID-19 pandemic prompted the implementation of precautions to contain the disease, including lockdowns and social isolation. Previous studies have investigated suicide rates among children and adolescents during the pandemic and have found varying results. We speculated how the two lockdowns influenced suicidal behaviour in children and adolescents in Denmark. OBJECTIVE: This study aimed to investigate the effect of lockdowns during the COVID-19 pandemic on suicide attempts, as measured by the incidence rate in all self-poisonings with mild analgesics among children and adolescents. METHODS: This national Danish registry-based study on children and adolescents used Poisson regression and interrupted time series analysis to examine the incidence rates and trends of self-poisonings with mild analgesics from 2019 to mid-2021. RESULTS: For the period of this study, 1655 self-poisonings were registered. During the first lockdown, there was a slight, not statistically significant, decrease in self-poisoning rates (incidence rate ratio [IRR]) 0.98) compared to no lockdown. During the second lockdown, there was a significant increase in self-poisonings for the whole Danish population (IRR 1.85) with girls being slightly higher at risk (IRR 1.87). Being a girl or between the ages of 13-17 years old were risk factors for self-poisoning. CONCLUSION: These findings indicate that the restrictions enforced during the second lockdown greatly impacted youth mental health, especially girls, leading to an 85% increase in self-poisonings. We hope for increased awareness of mental health in children and adolescents during possible future lockdowns.

Risk of repeated suicide attempt after redeeming prescriptions for antidepressants: a register-based study in Denmark.

BACKGROUND: It remains unclear how SSRIs and other antidepressants are associated with the risk of repeated suicide attempts. We aimed to analyse the association between redeemed antidepressant prescriptions and the risk of repeated suicide attempts, hypothesising that antidepressant treatment is associated with increased risk of repeated suicide attempts. METHODS: The study was based on Danish register data and a validated cohort of 1842 suicide attempts. We used three Cox regression models (crude, adjusted and propensity score matched) to analyse the data; these models included both static and dynamic time-dependent factors. RESULTS: 1842 individuals attempted suicide in the study period, with a total of 210 repeated attempts. Individuals redeeming antidepressant prescriptions were more likely to repeat a suicide attempt. All crude models showed all antidepressants to be significant risk factors (HR around 1.39), whereas all adjusted models showed all antidepressants to be insignificant risk factors. CONCLUSION: We found no significant increased risk of repeated suicide attempts in individuals redeeming a prescription for any antidepressant (or only SSRIs) when considering the individuals' baseline risk of repetition. This study is based on validated suicide attempts, register data, and strong epidemiology designs, but it still has some limitations, and the results should be replicated and confirmed in other studies.

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.

AIMS: To evaluate the efficacy and safety of oral semaglutide versus comparators by patient characteristic subgroups in patients with type 2 diabetes. MATERIALS AND METHODS: Change from baseline in glycated haemoglobin (HbA1c) and body weight, and achievement of HbA1c <7.0% with oral semaglutide 7 mg, oral semaglutide 14 mg, flexibly dosed oral semaglutide (flex) and comparators were assessed across baseline subgroups (age, race, ethnicity, diabetes duration, body mass index and HbA1c) from the PIONEER programme. Treatment differences were analysed using a mixed model for repeated measurements for continuous variables and a logistic regression model for the binary endpoint. Pooled safety data were analysed descriptively. RESULTS: Changes from baseline in HbA1c and body weight, and the odds of achieving HbA1c <7.0%, were greater with oral semaglutide 14 mg/flex (n = 1934) and higher or similar with oral semaglutide 7 mg (n = 823) versus comparators (n = 2077) across most subgroups. Changes in HbA1c with oral semaglutide 14 mg/flex were greater for patients with higher baseline HbA1c (HbA1c >9.0%: -1.7% to -2.6%; HbA1c <8.0%: -0.7% to -1.2%). In some trials, Asian patients experienced greater HbA1c reductions with oral semaglutide 14 mg/flex (-1.5% to -1.8%) than other racial groups (-0.6% to -1.6%). The overall incidence of adverse events (AEs) with oral semaglutide was similar to that with comparators and was consistent across subgroups. More gastrointestinal AEs were observed with oral semaglutide, versus comparators, across subgroups. CONCLUSIONS: Oral semaglutide demonstrated consistently greater HbA1c and body weight reductions across a range of patient characteristics, with greater HbA1c reductions seen at higher baseline HbA1c levels.

Recession and risk of suicide in Denmark during the 2009 global financial crisis: an ecological register-based study.

AIM: The aim of this study is to analyse the potential impact from the financial crisis (onset in 2009) on suicide rates in Denmark. The hypothesis is that the global financial crisis raised unemployment which leads to raising the suicide rate in Denmark and that the impact is most prominent in men. METHOD: This study used an ecological study design, including register data from 2001 until 2016 on unemployment, suicide, gender and calendar time which was analysed using Poisson regression models and interrupted time series analysis. RESULTS: The correlation between unemployment and suicide rates was positive in the period and statistically significant for all, but at a moderate level. A dichotomised version of time (calendar year) showed a significant reduction in the suicide rate for women (incidence rate ratio 0.87, P=0.002). Interrupted time series analysis showed a significant decreasing trend for the overall suicide rate and for men in the pre-recession period, which in both cases stagnated after the onset of recession in 2009. The difference between the genders' suicide rate changed significantly at the onset of recession, as the rate for men increased and the rate for women decreased. DISCUSSION: The Danish social welfare model might have prevented social disintegration and suicide among unemployed, and suicide prevention programmes might have prevented deaths among unemployed and mentally ill individuals. CONCLUSIONS: We found some indications for gender-specific differences from the impact of the financial crises on the suicide rate. We recommend that men should be specifically targeted for appropriate prevention programmes during periods of economic downturn.

Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials.

AIMS: To evaluate, through exploratory post hoc subgroup analyses, the efficacy and safety of oral semaglutide versus comparators in Japanese patients enrolled in the global PIONEER 1, 3, 4 and 8 clinical trials. MATERIALS AND METHODS: Patients were randomized to once-daily oral semaglutide 3, 7 or 14 mg or comparator (placebo, sitagliptin 100 mg or liraglutide 1.8 mg). Change from baseline in glycated haemoglobin (HbA1c) and body weight, and proportions of patients attaining HbA1c <7.0% (53 mmol/mol) and body weight loss ≥5%, were analysed at week 26 for all Japanese patients in each trial separately using the treatment policy estimand (regardless of treatment discontinuation or rescue medication use). Adverse events (AEs) were analysed descriptively. RESULTS: Reductions in HbA1c from baseline in Japanese patients were 1.0% to 1.2% (11.3 mmol/mol to 13.3 mmol/mol) and 1.4% to 1.7% (15.7 mmol/mol to 18.3 mmol/mol) for oral semaglutide 7 mg and 14 mg, respectively. HbA1c reductions were similar or greater than with comparators. Body weight reductions were 1.0% to 2.7% and 3.7% to 4.7% for oral semaglutide 7 mg and 14 mg, respectively, and were generally greater with oral semaglutide than comparators. As expected, the main class of AEs was gastrointestinal, and these AEs comprised most commonly mild-to-moderate constipation, nausea and diarrhoea. CONCLUSIONS: Oral semaglutide appears efficacious and well tolerated in Japanese patients across the type 2 diabetes spectrum.

Efficacy and safety of liraglutide in type 1 diabetes by baseline characteristics in the ADJUNCT ONE and ADJUNCT TWO randomized controlled trials.

AIM: To evaluate 26 weeks of liraglutide treatment in type 1 diabetes (T1D) by subgroups in the ADJUNCT ONE and ADJUNCT TWO trials. MATERIALS AND METHODS: ADJUNCT ONE and ADJUNCT TWO were randomized controlled phase 3 trials in 1398 and 835 participants with T1D treated with liraglutide (1.8, 1.2, or 0.6 mg) or placebo (adjuncts to insulin). This post hoc analysis evaluated treatment effects by subgroups: HbA1c (< or ≥8.5%), body mass index (BMI; < or ≥27 kg/m2 ), and insulin regimen (basal bolus or continuous subcutaneous insulin infusion). RESULTS: In both trials at week 26, reductions in HbA1c, body weight, and daily insulin dose did not differ significantly (P > .05) by baseline HbA1c or BMI. Risk of clinically significant hypoglycaemia or hyperglycaemia with ketosis did not differ significantly (P > .05) by baseline HbA1c, BMI, or insulin regimen. At week 26 in ADJUNCT ONE, these risks did not differ (P > .05) between treatment groups. Placebo-adjusted reductions in HbA1c, body weight, and insulin dose (-0.30%-points, -5.0 kg, and -12%, respectively, with liraglutide 1.8 mg), were significant (P < .05), greater than at week 52, and similar to those in ADJUNCT TWO (-0.35%, -4.8 kg, and -10%, respectively, with liraglutide 1.8 mg). CONCLUSIONS: In ADJUNCT ONE and ADJUNCT TWO, the efficacy and glycaemic safety of liraglutide did not depend on subgroups, leaving residual beta-cell function as the only identified variable impacting the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in T1D. These findings support a role for GLP-1 RAs as adjuncts to insulin in T1D, warranting further study.

Parental mental illness, attendance at preventive child healthcare and dental caries in the offspring: a nation-wide population-based cohort study.

PURPOSE: Severe mental illness (SMI) may interfere with parental caregiving practices and offspring development. Adhering to preventive well-child visits and maintaining good oral hygiene during early childhood requires parental involvement. Whether these activities are affected by parental SMI is unclear. The purpose of the present study was to determine whether children exposed to parental SMI are at increased risk of non-attendance to preventive well-child visits and vaccinations at age 0-5 years and of child dental caries experience at age 5 years. Furthermore, interactions between maternal psychiatric and sociodemographic variables in relation to an adverse child outcome were assessed. METHODS: Data were obtained from national Danish health registers. All children born in Denmark between January 1997 and December 2010 were followed from birth until their 6th birthday. RESULTS: 679,339 children were included in the study (51% male). Of these, 49,059 children (7.8%) had at least one parent with a lifetime SMI diagnosis. Children of parents with SMI had elevated odds of missing well-child visits and vaccinations (OR 1.41; 95% CI 1.39-1.44, p < 0.0001), and of child dental caries (OR 1.58; 95% CI 1.55-1.62, p < 0.0001). In the presence of maternal SMI, low socioeconomic classification and single-mother status added more to the elevated risk than specific maternal diagnosis or timing of last psychiatric contact. CONCLUSION: Parents with SMI are less compliant with preventive child healthcare activities than parents without SMI. This indicates a need for practical support to these families in order to prevent inequality in health among their offspring.

Priming of inducible defenses protects Norway spruce against tree-killing bark beetles.

Plants can form an immunological memory known as defense priming, whereby exposure to a priming stimulus enables quicker or stronger response to subsequent attack by pests and pathogens. Such priming of inducible defenses provides increased protection and reduces allocation costs of defense. Defense priming has been widely studied for short-lived model plants such as Arabidopsis, but little is known about this phenomenon in long-lived plants like spruce. We compared the effects of pretreatment with sublethal fungal inoculations or application of the phytohormone methyl jasmonate (MeJA) on the resistance of 48-year-old Norway spruce (Picea abies) trees to mass attack by a tree-killing bark beetle beginning 35 days later. Bark beetles heavily infested and killed untreated trees but largely avoided fungus-inoculated trees and MeJA-treated trees. Quantification of defensive terpenes at the time of bark beetle attack showed fungal inoculation induced 91-fold higher terpene concentrations compared with untreated trees, whereas application of MeJA did not significantly increase terpenes. These results indicate that resistance in fungus-inoculated trees is a result of direct induction of defenses, whereas resistance in MeJA-treated trees is due to defense priming. This work extends our knowledge of defense priming from model plants to an ecologically important tree species.

The effect of daily small text message reminders for medicine compliance amongst young people connected with the outpatient department for child and adolescent psychiatry. A controlled and randomized investigation.

BACKGROUND: Many patients with psychiatric illnesses have difficulty maintaining medication over time. Many take their medicine irregularly and studies show that it is the most vulnerable patients who have the greatest problems adhering to treatment. Often only 50% are still under medical treatment after 6 months. AIM: In this study we investigated whether text message reminders could improve medicine compliance amongst vulnerable young people with psychiatric disorders who were being treated in the outpatient department for child and adolescent psychiatry and who either are under or were to commence medicinal treatment. METHODS: This study was conducted as a randomized controlled trial including all non-acute referrals to an outpatient department for adolescent psychiatry within a group aged 15-20 years starting medical treatment. The patients were followed until the end of their treatment, for a minimum of 3 months. To enhance medicine compliance, text messages were sent daily to one group. No message was sent to the other group. RESULTS: Compliance was not associated with text message intervention in any of the drug interventions. The effect size was calculated to 0.3013, which is low and therefore indicates a weak association between text message and compliance. The power in this study was calculated to 0.3539, which is also low and therefore the likelihood of finding significant association is low. CONCLUSION: This study does not show increased medicine compliance from the text message intervention group. The conclusion of this study is that it is essential that significant resources are spent preparing and testing a text message strategy.

SSRIs and risk of suicide attempts in young people - A Danish observational register-based historical cohort study, using propensity score.

BACKGROUND: SSRIs are widely used in the treatment of mental illness for both children and adults. Studies have found a slightly increased risk of suicidal thoughts and suicide attempts in young people using SSRIs but SSRIs' impact on risk for suicides in youth is not well-established. AIM: Is there indication that SSRIs might raise risk for suicide attempts in young people? METHODS: We used an observational register-based historical cohort design, a large cohort of all Danish individuals born in 1983-1989 (n = 392,458) and a propensity score approach to analyse the impact from SSRIs on risk for suicide attempts. Every suicide attempt and redeemed prescription of SSRIs was analysed by Cox regression. RESULTS: We found a significant overlap between redeeming a prescription on SSRIs and subsequent suicide attempt. The risk for suicide attempt was highest in the first 3 months after redeeming the first prescription. The hazard ratio for suicide attempts after redeeming a prescription was estimated to 5.23, 95% CI 4.82-5.68. CONCLUSION: We conclude that the risk of suicide attempt is higher for young people in the first months after redeeming their first prescription for SSRIs, compared to non-users. For SSRI users with lower propensity score (fewer risk factors for SSRIs) the risk of suicide attempt is estimated to be highest. Although the design may miss some explicit reason for prescription of SSRIs and SSRIs might be a marker for those in high risk rather than a causal risk factor, we would recommend systematic risk assessment in the period after redeeming the first prescription.

Risk factors and study designs used in research of youths' suicide behaviour-an epidemiological discussion with focus on level of evidence.

UNLABELLED: Abstract Introduction: Many different epidemiology study designs have been used to analyse risk factors for suicide behaviour. The purpose of this study was to obtain an insight into the current study design used in research on youths' risk factors for suicide behaviour and to rank the studies according to level of evidence (LoE). METHODS: We searched PubMed and psycINFO in order to identify relevant individual studies. RESULTS: We included 36 studies of children and youth on suicidal behaviour and ideation-many rank low on LoE. For suicide, cohort design was often used, and mental illness (depression, substance abuse and severity of mental illness) was the most common risk factor. Cohort studies are ranked 2b, which is high according to LoE. For suicide attempts, survey was often used, and psychopathology, substance abuse and being exposed to suicidal behaviour were the most common risk factors. For suicidal ideation, survey was the only design used, and substance abuse and psychopathology the most common risk factors. Surveys are ranked 4, which are low according to LoE. Many risk factors were broad and unspecific, and standard definitions of outcome and exposure were rarely used. CONCLUSION: A good study of risk factors for suicidal behaviour would need a high LoE, as a high-powered longitudinal epidemiological study (cohort or case-control) of very specific risk factors. The factors would have high prevention potential, compared with more broad and unspecific risk factors, to which many people are exposed. We would recommend a cohort design (in high-risk populations) or a case-control design to identify risk factors, using clinical and/or register data instead of self-reported information, reporting adjusted estimates and using standard definition of suicidal outcome and risk factors.

Adverse life events as risk factors for behavioural and emotional problems in a 7-year follow-up of a population-based child cohort.

BACKGROUND AND AIM: The aim of the study was to identify risk factors for significant changes in emotional and behavioural problem load in a community-based cohort of Danish children aged 9-16 years, the risk factors being seven parental and two child-related adverse life events. METHODS: Data on emotional and behavioural problems was obtained from parents filling in the Child Behavior Checklist (CBCL) when the child was 8-9 and again when 15 years old. Data on risk factors was drawn from Danish registers. Analysis used was logistic regression for crude and adjusted change. RESULTS: Parental divorce significantly raised the odds ratio of an increase in emotional and behavioural problems; furthermore, the risk of deterioration in problem behaviour rose significantly with increasing number of adverse life events. By dividing the children into four groups based on the pathway in problem load (increasers, decreasers, high persisters and low persisters), we found that children with a consistently high level of behavioural problems also had the highest number of adverse life events compared with any other group. CONCLUSIONS: Family break-up was found to be a significant risk factor. This supports findings in previous studies. The fact that no other risk factor proved to be of significance might be due to lack of power in the study. Children experiencing high levels of adverse life events are at high risk of chronic problem behaviour. Thus these risk factors should be assessed in daily clinical practice.

The joint effect of mental illness and parental suicide attempt on offspring suicide attempt and death: A Danish nationwide, registry-based study using multistate modeling.

AIM: The aim of this study was to analyse the joint impact of moderate-to-severe mental illness and parental suicidal attempts on suicidal attempt and premature death. METHODS: Using the Danish, nationwide health registries, a cohort study was conducted including the birth cohorts 1983-1989. Cox regression and multistate models were used to estimate relative and absolute risks of suicide attempt and premature death. OUTCOME: We included 384,569 individuals and 7,218 individuals experienced their first suicide attempt during follow-up, while 2,762 individuals died of all causes. Joined exposure to parental suicide attempt and own mental illness increased the relative risk of suicide attempt (HR 22.57) and premature death all causes (HR 3.17). The absolute risk of suicide attempt before the age of 35 years was 20 % for offspring exposed to both parental suicide attempts and own mental illness (23 % for women vs. 15 % for men), while the risk of death was 4 % (0.6 % for women vs. 7 % for men). CONCLUSION: Exposure to both parental suicide attempt and own mental illness increases the relative and absolute risks of suicide attempt and premature death with considerable differences across sex. These findings are important in the clinical assessment of individuals with suicidal behavior.

Opening the black box of registration practice for self-harm and suicide attempts in emergency departments: a qualitative study.

BACKGROUND: The World Health Organization has called for improved surveillance of self-harm and suicide attempts worldwide to benefit suicide prevention programs. International comparisons of registrations are lacking, however, and there is a need for systematically collected, high-quality data across countries. The current study investigated healthcare professionals' perceptions of registration practices and their suggestions for ensuring high-quality registration of self-harm and suicide attempts. METHODS: Qualitative interviews (N = 20) were conducted among medical secretaries, medical doctors, nurses, and registration advisers from psychiatric and somatic emergency departments in all regions of Denmark between September 2022 and March 2023. Content analysis was performed using NVivo. RESULTS: Despite great efforts to standardize and assure the quality of registration in Denmark, almost all the healthcare professionals perceived registration practice as inconsistent and unreliable. Codes are often misclassified or unused due to insufficient time, non-standardized training, or insufficient information. The interview informants suggested that coding guidelines should be simplified and made more visible, alongside technical solutions in the electronic health record system. CONCLUSION: The study findings resulted in eight overall recommendations for clinical practice that aim at improving the registration of patients presenting with self-harm or suicide attempts. This would be expected to help improve surveillance and prevention programs.

Incidence and risk factors for suicide attempts in a general population of young people: a Danish register-based study.

OBJECTIVE: To estimate the Danish epidemiological long-term incidence rates for suicide attempts in the general population of children and adolescents, and to analyze the impact from single and multiple risk factors on the risk of suicide attempts. METHOD: We used longitudinal register data from a total cohort of all individuals born between 1983 and 1989 and living in Denmark to calculate incidence rates. From the cohort, we identified all who have attempted suicide, and matched 50 controls to each case. A nested case-control design was used to estimate the impact from risk factors on the risk for index suicide attempts. We established a link to the biological parents and identified risk factors for two generations. Risk factors were analyzed in a conditional logistic regression model. RESULTS: We identified 3718 suicide attempters and 185,900 controls (189,618 individuals, aged 10-21 years). We found increasing incidence rates during the period 1994-2005, and higher incidence rates for girls and the oldest adolescents. Mental illness was the strongest independent risk factor (IRR = 4.77, CI = (4.35-5.23), p < 0.0001), but parental mental illness (psychopharmacological drugs: IRR = 1.27, CI = (1.18-1.37), p < 0.0001) and socio-demographic factors (parents not living together: IRR = 1.38, CI = (1.28-1.48), p < 0.0001) were also significant independent risk factors. Exposure to multiple risk factors increased the risk significantly. CONCLUSIONS: Suicide attempt is a multi-factorial problem, and a problem on the increase in the period studied. Individuals exposed to multiple risk factors are at the highest risk for suicide attempts, and when spotted or in contact with authorities they should be given proper care and treatment to prevent suicide attempts and death.

Greater Combined Reductions of HbA1c ≥ 1.0% and Body Weight Loss ≥ 5.0% or ≥ 10.0% with Orally Administered Semaglutide Versus Comparators.

INTRODUCTION: A post hoc analysis of the PIONEER 1-5 and 8 trials assessed the clinically relevant composite endpoints of HbA1c (glycated haemoglobin) reduction ≥ 1% and body weight loss of ≥ 5% or ≥ 10% with orally administered semaglutide versus comparators. METHODS: In the PIONEER trials, people with type 2 diabetes were randomised to orally administered semaglutide versus placebo (PIONEER 1, 4, 5 and 8), empagliflozin (PIONEER 2), sitagliptin (PIONEER 3) and liraglutide (PIONEER 4) for 26-78 weeks. This analysis assessed the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% at week 26 and at end of treatment, and the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment. RESULTS: Overall, 3506 people in PIONEER 1-5 and 8 were included. At week 26 and at end of treatment, odds of achieving the composite endpoint of an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% were significantly greater with orally administered semaglutide 14 mg than with placebo (PIONEER 1, 4, 5 and 8; all p < 0.0001), empagliflozin 25 mg (PIONEER 2, p < 0.0001), sitagliptin 100 mg (PIONEER 3, p < 0.0001) and liraglutide 1.8 mg (PIONEER 4, p < 0.0001). Odds of achieving the composite endpoint of HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment were also significantly greater with orally administered semaglutide versus comparators. CONCLUSION: In PIONEER 1-5 and 8, odds of achieving clinically relevant reductions in both HbA1c and body weight were significantly greater with orally administered semaglutide versus comparators.

Definitions and incidence rates of self-harm and suicide attempts in Europe: A scoping review.

INTRODUCTION: European countries use various terminologies for self-harm and attempted suicide, which are sometimes used interchangeably. This complicates cross-country comparisons of incidence rates. This scoping review aimed to examine the definitions used and the possibilities to identify and compare incidence rates of self-harm and attempted suicide in Europe. METHODS: A literature search was conducted in Embase, Medline and PsycINFO for studies published from 1990 to 2021, followed by grey literature searches. Data were collected for total populations originating from health care institutions or registries. Results were presented in tabular form supplemented by a qualitative summary by area. RESULTS: A total of 3160 articles were screened, resulting in 43 studies included from databases and further 29 studies from other sources. Most studies used the term 'suicide attempt' rather than 'self-harm' and reported person-based rates with annual incidence rates from age 15+. None of the rates were considered comparable due to different reporting traditions related to classification codes and statistical approaches. CONCLUSION: The present extensive literature on self-harm and attempted suicide cannot be used to compare findings between countries because of the high degree of heterogeneity among studies. International agreement on definitions and registration practices is needed to improve knowledge and understanding of suicidal behaviour.

Suicide trends in Denmark-An ecological study exploring suicide methods from 1995 to 2019.

Suicide is a major public health problem and complex phenomenon, affecting many people around the world. However, the incidence of suicide varies by sex and age, which includes differences in the means used. Therefore, to implement effective preventative interventions, it is important to study these differences to design effective, preventative interventions. This study investigates the trends in suicide rates in Denmark from 1995 to 2019 by analysing changes based on sex, age, and the means used for suicide. Data on all suicide deaths in the study period were extracted from the Danish Register of Causes of Death, and data on the background population were obtained from Statistics Denmark. We used negative binomial regression models to analyse the data, and the obtained estimates as a logarithm of the rate ratios allowed us to compare the results across groups and years. An overall decline in Danish suicide rates was observed during the study period, with the exception of young females aged 15-29 years. The demographic composition did not change significantly, and suicide rates are still highest for males and the elderly aged 60+. Hanging, self-poisoning and firearms remain the most prevalent means of suicide. Suicide prevention initiatives are required, especially interventions targeting males and the elderly. Restricting access to the means of suicide for these groups with high fatality rates may help reduce the overall suicide rate. Moreover, more research is needed to understand the factors that lead to suicide and affect the choice of means, which should also include studying the effects of different suicide prevention strategies on males and females from different age groups.

Young people's risk of suicide attempts after contact with a psychiatric department - a nested case-control design using Danish register data.

BACKGROUND: There seems to be an increased risk of children and adolescents committing or attempting suicide after contact with a psychiatric department. Children and adolescents living in families with low socio-economic status (SES) might have an especially increased suicide attempt risk. METHODS: A complete extraction of Danish register data for every individual born in the period 1983-1989 was made. Of these 403,431 individuals, 3,465 had attempted suicide. In order to control for confounder effects from gender, age and calendar-time, a nested case-control study was designed. A total population of 72,765 individuals was used to analyze the risk of suicide attempts after contact with a psychiatric department. The case-control data were analyzed using conditional logistic regression. RESULTS: This study shows that a child/adolescent's risk of suicide attempt peaks immediately after discharge from last contact with a psychiatric department. The risk of suicide attempt is highest for children and adolescents suffering from personality disorders, depression and substance use disorders. Children and adolescents with previous contact with a psychiatric department and parental income in the lowest third have a significantly higher risk of suicide attempt. Suicide attempters were more likely to have been given several different diagnoses and several different psychopharmacological drugs prior to their attempted suicide. CONCLUSIONS: The findings in this study highlight the need for psychopathology assessment in every case of attempted suicide. This study also shows that well-known risk factors such as contact with a psychiatric department do not affect all individuals in the same way. Individuals from families with low SES had the highest risk. This suggests that the presence of factors influencing both vulnerability and resiliency, e.g., family level of SES, needs to be included in the assessment.