Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.

We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls).

Medication-free participants with MDD (n = 192: 110 female, 81 male, 1 other) and controls (n = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (−1019, −1007, −681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF.

Recent stress correlated positively with blood monocyte methylation at the −681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the −1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD.

These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.

Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.

In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.

This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.

Pain following surgery for cardiac disease is ubiquitous, and optimal management is important. Despite this, there is large practice variation. To address this, the Paediatric Acute Care Cardiology Collaborative undertook the effort to create this clinical practice guideline.

A panel of experts consisting of paediatric cardiologists, advanced practice practitioners, pharmacists, a paediatric cardiothoracic surgeon, and a paediatric cardiac anaesthesiologist was convened. The literature was searched for relevant articles and Collaborative sites submitted centre-specific protocols for postoperative pain management. Using the modified Delphi technique, recommendations were generated and put through iterative Delphi rounds to achieve consensus

60 recommendations achieved consensus and are included in this guideline. They address guideline use, pain assessment, general considerations, preoperative considerations, intraoperative considerations, regional anaesthesia, opioids, opioid-sparing, non-opioid medications, non-pharmaceutical pain management, and discharge considerations.

Postoperative pain among children following cardiac surgery is currently an area of significant practice variability despite a large body of literature and the presence of centre-specific protocols. Central to the recommendations included in this guideline is the concept that ideal pain management begins with preoperative counselling and continues through to patient discharge. Overall, the quality of evidence supporting recommendations is low. There is ongoing need for research in this area, particularly in paediatric populations.

To assess the relationship between food insecurity, sleep quality, and days with mental and physical health issues among college students.

An online survey was administered. Food insecurity was assessed using the ten-item Adult Food Security Survey Module. Sleep was measured using the nineteen-item Pittsburgh Sleep Quality Index (PSQI). Mental health and physical health were measured using three items from the Healthy Days Core Module. Multivariate logistic regression was conducted to assess the relationship between food insecurity, sleep quality, and days with poor mental and physical health.

Twenty-two higher education institutions.

College students (n 17 686) enrolled at one of twenty-two participating universities.

Compared with food-secure students, those classified as food insecure (43·4 %) had higher PSQI scores indicating poorer sleep quality (P < 0·0001) and reported more days with poor mental (P < 0·0001) and physical (P < 0·0001) health as well as days when mental and physical health prevented them from completing daily activities (P < 0·0001). Food-insecure students had higher adjusted odds of having poor sleep quality (adjusted OR (AOR): 1·13; 95 % CI 1·12, 1·14), days with poor physical health (AOR: 1·01; 95 % CI 1·01, 1·02), days with poor mental health (AOR: 1·03; 95 % CI 1·02, 1·03) and days when poor mental or physical health prevented them from completing daily activities (AOR: 1·03; 95 % CI 1·02, 1·04).

College students report high food insecurity which is associated with poor mental and physical health, and sleep quality. Multi-level policy changes and campus wellness programmes are needed to prevent food insecurity and improve student health-related outcomes.

Acute ischemic stroke may affect women and men differently. We aimed to evaluate sex differences in outcomes of endovascular treatment (EVT) for ischemic stroke due to large vessel occlusion in a population-based study in Alberta, Canada.

Over a 3-year period (April 2015–March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. The primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at their premorbid living situation without an increase in the level of care within 90 days of the index stroke event. In adjusted analysis, EVT was associated with an increase of 90-day home-time by an average of 6.08 (95% CI −2.74–14.89, p-value 0.177) days in women compared to an average of 11.20 (95% CI 1.94–20.46, p-value 0.018) days in men. Further analysis revealed that the association between EVT and 90-day home-time in women was confounded by age and onset-to-treatment time.

We found a nonsignificant nominal reduction of 90-day home-time gain for women compared to men in this province-wide population-based study of EVT for large vessel occlusion, which was only partially explained by confounding.

Non-invasive prenatal testing (NIPT) is increasingly being adopted as a screening test in the UK and is currently accessed through certain National Health Service healthcare systems or by private provision. This audit aims to describe reasons for and results of cytogenomic investigations carried out within UK genetic laboratories following an NIPT result indicating increased chance of cytogenomic abnormality (‘high-chance NIPT result’).

A questionnaire was sent out to 24 genetics laboratories in the UK and completed by 18/24 (75%).

Data were returned representing 1831 singleton pregnancies. A total of 1329 (73%) invasive samples were taken following NIPT results showing a high chance of trisomy 21; this was confirmed in 1305 (98%) of these by invasive sampling. Trisomy 21 was confirmed in >99% of patients who also had high-screen risk results or abnormal scan findings. Amongst invasive samples taken due to NIPT results indicating a high chance of trisomy 18, 84% yielded a compatible result, and this number dropped to 49% for trisomy 13 and 51% for sex chromosomes.

In the UK, the majority of patients having invasive sampling for high-chance NIPT results are doing so following an NIPT result indicating an increased chance of common trisomies (92%). In this population, NIPT performs particularly well for trisomy 21, but less well for other indications.

Quetiapine is a novel antipsychotic drug, which is efficacious in the treatment of schizophrenia and also helps reduce craving and consumption of stimulants and alcohol. Due to Quetiapine's promising receptor profile, we set out to examine its efficacy in relapse prevention treatment of alcoholic dependent patients suffering from craving and affective symptoms.

The three center pilot-RCT evaluated 40 alcohol dependent patients after withdrawal (Quetiapine vs. placebo). They were followed up for six months. We used operationalized questionnaires including OCDS-G, Form 90-CR, Form 90 short form-CR, PSQI, MADRS, STAI, BDI and FTND.

We tested the one sided hypothesis that it takes longer for the first severe relapse to occur using Quetiapine compared to a placebo. The primary outcome measure is time to first severe relapse. Further, we tested the two sided hypothesis that Quetiapine will prolong time until first consumption of ethanol, decrease the number of drinking days and increase the number of abstinence days, decrease the cumulative amount of ethanol, decrease craving, improve depression symptoms, improve anxiety symptoms, improve quality of sleep, avoid deterioration of safety variables and decrease nicotine addiction.

Our pilot study is designed to provide evidence for the efficacy of Quetiapine in alcohol relapse prevention. Alcohol dependent patients after withdrawal should display a decrease in persistant craving and should be less afflicted by sleep disorders, excitement or symptoms of depression or anxiety. The poster provides the rational for conducting this study and describes the study protocol including the subject's characteristics.

Research has shown that Quetiapine reduce the craving and consumption for stimulants and alcohol. Due to Quetiapine's particulars and the promising receptor profile concerning addiction medicine, we set out to examine the tolerability and efficacy concerning relapse prevention of withdrawn alcoholics suffering from additional symptoms.

Our case observations attempted to evaluate nine alcoholics after withdrawal suffering from persisting craving, sleep disorder, excitement, depressive symptoms or anxiety symptoms. The patients were treated with quetiapine as relapse prevention and we followed them up in our outpatient clinic.

Eight out of nine patients were abstinent under quetiapine over a period of 2 to 7 months. One of these patients relapsed after he stopped taking the preparation at his own initiative after 10 weeks. The ninths patient stopped taking the preparation immediately because of swollen nasal mucosae. All target symptoms disappeared in the patients after an average of [mean ± SD] 24.5 ± 18.1 days. The overall tolerability was considered to be very good, however initial sleepiness appeared in four patients.

Patients reported to be very satisfied with the medication. Reports about clearly reduced craving seem particularly worthy of attention. Although uncontrolled case observations can only be interpreted with caution quetiapine seems to deserve further investigation. A double-blind placebo-controlled study is in preparation to confirm these preliminary findings. Quetiapine may hold the potential for preventing alcohol relapse in alcoholics suffering from additional above mentioned symptoms, or as an alternative in alcoholics who do neither tolerate acamprosate nor naltrexone.

We have compared oxcarbazepine (OXC) with acamprosate (ACP) in relapse prevention in recently withdrawn alcohol dependent patients. Oxcarbazepine blocks voltage-sensitive sodium channels. Its metabolite reduces high-voltage-activated calcium currents in striatal and cortical neurons, thus reducing glutamatergic transmission at corticostriatal synapses. This reduction is of interest in the treatment of alcohol dependence, since acamprosate modulates NMDA receptors, resulting in an inhibition of glutamatergic transmission. Furthermore, OXC has revealed a mood-stabilizing effect in bipolar affective disorders.

In a randomized open label pilot study 30 detoxified alcohol dependent patients were followed up for six months to assess treatment outcome in pharmacological relapse prevention. 15 alcoholics were treated with OXC and 15 with ACP. We asked for the time until first and heavy relapse and for drinks on drinking days. We assessed craving (OCDS), the severity of depression (ADS) and the degree of state anxiety (STAI).

After withdrawal, time to severe relapse and time to first consumption of any ethanol by OXC patients was not longer than for ACP patients. Abstinent patients in both study groups showed significantly lower OCDS-G than relapsed patients. No undesired effects occurred when OXC patients consumed alcohol.

While the current sample size clearly limits further conclusions from this pilot study, it is noteworthy that OXC is well tolerated. Thus, in medication-based relapse prevention, OXC could have the potential of a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or who suffer from affective lability. OXC certainly merits a larger placebo controlled trial.

Quetiapine is a novel antipsychotic, which is efficacious in the treatment of positive and negative symptoms in schizophrenia. Research has shown that Quetiapine also reduce the craving and consumption for stimulants and alcohol. We set out to examine the tolerability and efficacy concerning relapse prevention of withdrawn alcoholics suffering from additional symptoms.

Our case observations attempted to evaluate nine alcoholics after withdrawal suffering from persisting craving, sleep disorder, excitement, depressive symptoms or anxiety symptoms. We followed the patients up in our outpatient clinic.

Eight out of nine patients were abstinent under quetiapine over a period of 2 to 7 months. One of these patients relapsed after he stopped taking the preparation at his own initiative after 10 weeks. The ninths patient stopped taking the preparation immediately because of swollen nasal mucosae. All target symptoms disappeared in the patients after an average of [mean ± SD] 24.5 ± 18.1 days. The overall tolerability was considered to be very good, however initial sleepiness appeared in four patients.

The tolerability has proven to be very good and patients reported to be very satisfied with the medication. Reports about clearly reduced craving seem particularly worthy of attention. A double-blind placebo-controlled study is in preparation to confirm these preliminary findings. Quetiapine may hold the potential for preventing alcohol relapse in alcoholics suffering from additional above mentioned symptoms, or as an alternative in alcoholics who do neither tolerate acamprosate nor naltrexone.