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.

Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.

We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.

Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.

Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.

Opioid antagonists may mitigate medication-associated weight gain and/or metabolic dysregulation. ENLIGHTEN-2 evaluated a combination of olanzapine and the opioid antagonist samidorphan (OLZ/SAM) vs olanzapine for effects on weight gain and metabolic parameters over 24 weeks in adults with stable schizophrenia.

This phase 3, double-blind study (ClinicalTrials.gov: NCT02694328) enrolled adults 18–55 yo with stable schizophrenia, randomized 1:1 to once-daily OLZ/SAM or olanzapine. Co-primary endpoints were percent change from baseline in body weight and proportion of patients with ≥10% weight gain at week 24. Waist circumference and fasting metabolic parameters were also measured. Completers could enter a 52-week open-label safety extension.

561 patients were randomized: 550 were dosed, 538 had ≥1 post-baseline weight assessment, and 352 (64%) completed; 10.9% discontinued due to AEs. At week 24, least squares mean (SE) percent weight change from baseline was 4.21 (0.68)% with OLZ/SAM and 6.59 (0.67)% with olanzapine (difference, −2.38 [0.76]%; P=0.003). Fewer patients treated with OLZ/SAM (17.8%) had ≥10% weight gain vs olanzapine (29.8%; odds ratio=0.50; P=0.003). The change from baseline in waist circumference was significantly smaller with OLZ/SAM (P<0.001). Common AEs (≥10%) with OLZ/SAM and olanzapine were weight increased (24.8%, 36.2%), somnolence (21.2%, 18.1%), dry mouth (12.8%, 8.0%), and increased appetite (10.9%, 12.3%), respectively. Metabolic parameter changes were generally small and remained stable with long-term OLZ/SAM treatment.

OLZ/SAM treatment limited weight gain associated with olanzapine. Metabolic parameter changes were generally small, similar between groups over 24 weeks, and remained stable over an additional 52 weeks of open-label OLZ/SAM treatment.

This study was funded by Alkermes, Inc.

The “Stop the Bleed” campaign advocates for non-medical personnel to be trained in basic hemorrhage control. However, it is not clear what type of education or the duration of instruction needed to meet that requirement. The objective of this study was to determine the impact of a brief hemorrhage control educational curriculum on the willingness of laypersons to respond during a traumatic emergency.

This “Stop the Bleed” education initiative was conducted by the University of Texas Health San Antonio Office of the Medical Director (San Antonio, Texas USA) between September 2016 and March 2017. Individuals with formal medical certification were excluded from this analysis. Trainers used a pre-event questionnaire to assess participants knowledge and attitudes about tourniquets and responding to traumatic emergencies. Each training course included an individual evaluation of tourniquet placement, 20 minutes of didactic instruction on hemorrhage control techniques, and hands-on instruction with tourniquet application on both adult and child mannequins. The primary outcome in this study was the willingness to use a tourniquet in response to a traumatic medical emergency.

Of 236 participants, 218 met the eligibility criteria. When initially asked if they would use a tourniquet in real life, 64.2% (140/218) responded “Yes.” Following training, 95.6% (194/203) of participants responded that they would use a tourniquet in real life. When participants were asked about their comfort level with using a tourniquet in real life, there was a statistically significant improvement between their initial response and their response post training (2.5 versus 4.0, based on 5-point Likert scale; P<.001).

In this hemorrhage control education study, it was found that a short educational intervention can improve laypersons’ self-efficacy and reported willingness to use a tourniquet in an emergency. Identified barriers to act should be addressed when designing future hemorrhage control public health education campaigns. Community education should continue to be a priority of the “Stop the Bleed” campaign.

RossEM, RedmanTT, MappJG, BrownDJ, TanakaK, CooleyCW, KharodCU, WamplerDA. Stop the Bleed: The Effect of Hemorrhage Control Education on Laypersons’ Willingness to Respond During a Traumatic Medical Emergency. Prehosp Disaster Med. 2018;33(2):127–132.

To evaluate the effectiveness of a computerized clinical decision support intervention aimed at reducing inappropriate Clostridium difficile testing

Retrospective cohort study

University of Pennsylvania Health System, comprised of 3 large tertiary-care hospitals

All adult patients admitted over a 2-year period

Providers were required to use an order set integrated into a commercial electronic health record to order C. difficile toxin testing. The order set identified patients who had received laxatives within the previous 36 hours and displayed a message asking providers to consider stopping laxatives and reassessing in 24 hours prior to ordering C. difficile testing. Providers had the option to continue or discontinue laxatives and to proceed with or forgo testing. The primary endpoint was the change in inappropriate C. difficile testing, as measured by the number of patients who had C. difficile testing ordered while receiving laxatives.

Compared to the 1-year baseline period, the intervention resulted in a decrease in the proportion of inappropriate C. difficile testing (29.6% vs 27.3%; P=.02). The intervention was associated with an increase in the number of patients who had laxatives discontinued and did not undergo C. difficile testing (5.8% vs 46.4%; P<.01) and who had their laxatives discontinued and underwent testing (5.4% vs 35.2%; P<.01). We observed a nonsignificant increase in the proportion of patients with C. difficile related complications (5.0% vs 8.9%; P=.11).

A C. difficile order set was successful in decreasing inappropriate C. difficile testing and improving the timely discontinuation of laxatives.

Infect Control Hosp Epidemiol 2017;38:1204–1208

Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged.

Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel ‘escape’ rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of ‘secondary gain’.

CD patients had significantly more severe life events and ‘escape’ events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients – significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56–13.70] and healthy controls (OR 5.81, 95% CI 1.86–18.2). In the same time period 53% of CD patients had at least one ‘high escape’ event – again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05–23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events.

Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation.

Cognitive therapy (CT) has considerable utility for psychosomatic medicine (PM) in acute medical settings but, to date, no such cohesive adaptation has been developed. Part I delineated a CT model for acute medical settings focusing on assessment and formulation. In Part II, we review how CT can be applied to common PM clinical challenges. A pragmatic approach is helpful because this review targets PM trainees and educators.

Narrative review is used to discuss the application of CT strategies to common challenges in acute medical settings. Treatment complexities and limitations associated with the PM setting are detailed. Exemplary dialogues are used to model techniques.

We present CT approaches to eight common scenarios: (1) distressed or hopeless patients; (2) patients expressing pivotal distorted cognitions/images; (3) patients who catastrophize; (4) patients who benefit from distraction and activation strategies; (5) panic and anxiety; (6) suicidal patients; (7) patients who are stuck and helpless; (8) inhibited patients. Limitations are discussed.

A CT informed PM assessment, formulation and early intervention with specific techniques offers a novel integrative framework for psychotherapy with the acutely medically ill. Future efforts should focus on dissemination, education of fellows and building research efficacy data.