We aimed to describe the clinical characteristics of female patients presenting with premenstrual disorders to a tertiary service in the UK. We conducted a retrospective case-note review of referrals to the National Female Hormone Clinic from April 2014 to August 2020. Based on clinical assessment, we determined whether the patient met criteria for premenstrual dysphoric disorder or premenstrual exacerbation of an underlying psychiatric disorder.

Of 146 patients seen in clinic for premenstrual disorders, an ICD-10 psychiatric diagnosis was made in 130 (89.0%); a minority 16 (11.0%) did not have a psychiatric diagnosis. Following assessment, 94 patients (64.4%) met criteria for premenstrual dysphoric disorder and 67 (45.6%) had exacerbation of a psychiatric disorder.

Patients presenting to this specialist service had complex psychiatric comorbidity; almost half presented with exacerbation of a psychiatric disorder.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Voices are commonly experienced as communication with a personified ‘other’ with ascribed attitudes, intentionality and personality (their own ‘character’). Phenomenological work exploring voice characterisation informs a new wave of relational therapies. To date, no study has investigated the role of characterisation in behavioural engagement with voices or within psychological therapy for distressing voices.

Baseline characterisation (the degree to which the voice is an identifiable and characterful entity) of the dominant voice was rated (high, medium or low) using a newly developed coding framework, for n = 60 people prior to starting AVATAR therapy. Associations between degree of characterisation and (i) everyday behavioural engagement with voices (The Beliefs about Voices Questionnaire-Revised; n = 60); and (ii) interaction within avatar dialogue [Session 4 Time in Conversation (participant–avatar); n = 45 therapy completers] were explored.

Thirty-three per cent reported high voice characterisation, 42% medium and 25% low. There was a significant association between characterisation and behavioural engagement [H(2) = 7.65, p = 0.022, ɛ2 = 0.130] and duration of participant–avatar conversation [F(2,42) = 6.483, p = 0.004, η2 = 0.236]. High characterisation was associated with increased behavioural engagement compared with medium (p = 0.004, r = 0.34; moderate effect) and low (p = 0.027, r = 0.25; small−moderate effect) with a similar pattern observed for the avatar dialogue [high v. medium: p = 0.008, Hedges’ g = 1.02 (large effect); high v. low: p = 0.023, Hedges' g = 1.03 (large effect)]. No differences were observed between medium and low characterisation.

Complex voice characterisation is associated with how individuals interact with their voice(s) in and out of therapy. Clinical implications and future directions for AVATAR therapy and other relational therapies are discussed.

A growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity.

Using detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder.

CAPsy is population-based first-episode psychosis case–control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments.

We found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence.

Our findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.

Psychosis, and in particular auditory verbal hallucinations (AVHs), are associated with adversity exposure. However, AVHs also occur in populations with no need for care or distress.

This study investigated whether adversity exposure would differentiate clinical and healthy voice-hearers within the context of a ‘three-hit’ model of vulnerability and stress exposure.

Samples of 57 clinical and 45 healthy voice-hearers were compared on the three ‘hits’: familial risk; adversity exposure in childhood and in adolescence/adulthood.

Clinical voice-hearers showed greater familial risk than healthy voice-hearers, with more family members with a history of psychosis, but not with other mental disorders. The two groups did not differ in their exposure to adversity in childhood [sexual and non-sexual, victimisation; discrimination and socio-economic status (SES)]. Contrary to expectations, clinical voice-hearers did not differ from healthy voice-hearers in their exposure to victimisation (sexual/non-sexual) and discrimination in adolescence/adulthood, but reported more cannabis and substance misuse, and lower SES.

The current study found no evidence that clinical and healthy voice-hearers differ in lifetime victimisation exposure, suggesting victimisation may be linked to the emergence of AVHs generally, rather than need-for-care. Familial risk, substance misuse and lower SES may be additional risk factors involved in the emergence of need-for-care and distress.

To assess the utility of an automated, statistically-based outbreak detection system to identify clusters of hospital-acquired microorganisms.

Multicenter retrospective cohort study.

The study included 43 hospitals using a common infection prevention surveillance system.

A space–time permutation scan statistic was applied to hospital microbiology, admission, discharge, and transfer data to identify clustering of microorganisms within hospital locations and services. Infection preventionists were asked to rate the importance of each cluster. A convenience sample of 10 hospitals also provided information about clusters previously identified through their usual surveillance methods.

We identified 230 clusters in 43 hospitals involving Gram-positive and -negative bacteria and fungi. Half of the clusters progressed after initial detection, suggesting that early detection could trigger interventions to curtail further spread. Infection preventionists reported that they would have wanted to be alerted about 81% of these clusters. Factors associated with clusters judged to be moderately or highly concerning included high statistical significance, large size, and clusters involving Clostridioides difficile or multidrug-resistant organisms. Based on comparison data provided by the convenience sample of hospitals, only 9 (18%) of 51 clusters detected by usual surveillance met statistical significance, and of the 70 clusters not previously detected, 58 (83%) involved organisms not routinely targeted by the hospitals’ surveillance programs. All infection prevention programs felt that an automated outbreak detection tool would improve their ability to detect outbreaks and streamline their work.

Automated, statistically-based outbreak detection can increase the consistency, scope, and comprehensiveness of detecting hospital-associated transmission.

A growing body of research suggests that deficient emotional self-regulation (DESR) is common and morbid among attention-deficit/hyperactivity disorder (ADHD) patients. The main aim of the present study was to assess whether high and low levels of DESR in adult ADHD patients can be operationalized and whether they are clinically useful.

A total of 441 newly referred 18- to 55-year-old adults of both sexes with Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition (DSM-5) ADHD completed self-reported rating scales. We operationalized DESR using items from the Barkley Current Behavior Scale. We used receiver operator characteristic (ROC) curves to identify the optimal cut-off on the Barkley Emotional Dysregulation (ED) Scale to categorize patients as having high- versus low-level DESR and compared demographic and clinical characteristics between the groups.

We averaged the optimal Barkley ED Scale cut-points from the ROC curve analyses across all subscales and categorized ADHD patients as having high- (N = 191) or low-level (N = 250) DESR (total Barkley ED Scale score ≥8 or <8, respectively). Those with high-level DESR had significantly more severe symptoms of ADHD, executive dysfunction, autistic traits, levels of psychopathology, and worse quality of life compared with those with low-level DESR. There were no major differences in outcomes among medicated and unmedicated patients.

High levels of DESR are common in adults with ADHD and when present represent a burdensome source of added morbidity and disability worthy of further clinical and scientific attention.

We are developing the novel αIIbβ3 antagonist, RUC-4, for subcutaneously (SC)-administered first-point-of-medical-contact treatment for ST segment elevation myocardial infarction (STEMI).

We studied the (1) pharmacokinetics (PK) of RUC-4 at 1.0, 1.93, and 3.86 mg/kg intravenous (IV), intramuscular (IM), and SC in non-human primates (NHPs); (2) impact of aspirin on RUC-4 IC50 in human platelet-rich plasma (PRP); (3) effect of different anticoagulants on the RUC-4 IC50 in human PRP; and (4) relationship between αIIbβ3 receptor blockade by RUC-4 and inhibition of ADP-induced platelet aggregation.

(1) All doses of RUC-4 were well tolerated, but animals demonstrated variable temporary bruising. IM and SC RUC-4 reached dose-dependent peak levels within 5–15 minutes, with T1/2 s between 0.28 and 0.56 hours. Platelet aggregation studies in NHPs receiving IM RUC-4 demonstrated >80% inhibition of the initial slope of ADP-induced aggregation with all three doses 30 minutes post-dosing, with subsequent dose-dependent loss of inhibition over 4–5 hours. (2) The RUC-4 IC50 for ADP-induced platelet aggregation was unaffected by aspirin treatment (40±9 nM vs 37±5 nM; p = 0.39). (3) The RUC-4 IC50 was significantly higher in PRP prepared from D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK)-anticoagulated blood compared to citrate-anticoagulated blood using either thrombin receptor activating peptide (TRAP) (122±17 vs 66±25 nM; p = 0.05; n = 4) or ADP (102±22 vs 54±13; p<0.001; n = 5). (4) There was a close correspondence between receptor blockade and inhibition of ADP-induced platelet aggregation, with aggregation inhibition beginning with ~40% receptor blockade and becoming nearly complete at >80% receptor blockade.

Based on these results and others, RUC-4 has now progressed to formal preclinical toxicology studies.