Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.

The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.

Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED).

We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm.

Emergency department of a university teaching hospital.

Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a ‘high-risk’ area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area.

Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34–92) for FebriDx-negative patients and 203 minutes (IQR, 142–255) for FebriDx-positive patients (difference of −134 minutes; 95% CI, −144 to −122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%–97%).

FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2–positive patients.

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.

Optimal emergent management of traumatic hemorrhagic shock patients requires a better understanding of treatment provided in the prehospital/Emergency Medical Services (EMS) and emergency department (ED) settings.

Described in this research are the initial clinical status, airway management, fluid and blood infusions, and time course of severely-injured hemorrhagic shock patients in the EMS and ED settings from the diaspirin cross-linked hemoglobin (DCLHb) clinical trial.

Data were analyzed from 17 US trauma centers gathered during a randomized, controlled, single-blinded efficacy trial of a hemoglobin solution (DCLHb) as add-on therapy versus standard therapy.

Among the 98 randomized patients, the mean EMS Glasgow Coma Scale (GCS) was 10.6 (SD = 5.0), the mean EMS revised trauma score (RTS) was 6.3 (SD = 1.9), and the mean injury severity score (ISS) was 31 (SD = 17). Upon arrival to the ED, the GCS was 20% lower (7.8 (SD = 5.3) vs 9.7 (SD = 6.3)) and the RTS was 12% lower (5.3 (SD = 2.0) vs 6.0 (SD = 2.1)) than EMS values in blunt trauma patients (P < .001). By ED disposition, 80% of patients (78/98) were intubated. Rapid sequence intubation (RSI) was utilized in 77% (60/78), most often utilizing succinylcholine (65%) and midazolam (50%). The mean crystalloid volume infused was 4.2 L (SD = 3.4 L), 80% of which was infused within the ED. Emergency department blood transfusion occurred in 62% of patients, with an average transfused volume of 1.2 L (SD = 2.0 L). Blunt trauma patients received 2.1 times more total fluids (7.4 L vs 3.5 L, < .001) and 2.4 times more blood (2.4 L vs 1.0 L, P < .001). The mean time of patients taken from injury site to operating room (OR) was 113 minutes (SD = 87 minutes). Twenty-one (30%) of the 70 patients taken to the OR from the ED were sent within 60 minutes of the estimated injury time. Penetrating trauma patients were taken to the OR 52% sooner than blunt trauma patients (72 minutes vs 149 minutes, P < .001).

Both GCS and RTS decreased prior to ED arrival in blunt trauma patients. Intubation was performed using RSI, and crystalloid infusion of three times the estimated blood loss volume (L) and blood transfusion of the estimated blood loss volume (L) were provided in the EMS and ED settings. Surgical intervention for these trauma patients most often occurred more than one hour from the time of injury. Penetrating trauma patients received surgical intervention more rapidly than those with a blunt trauma mechanism.

SloanEP, KoenigsbergM, WeirWB, ClarkJM, O'ConnorR, OlingerM, CydulkaR. Emergency Resuscitation of Patients Enrolled in the US Diaspirin Cross-linked Hemoglobin (DCLHb) Clinical Efficacy Trial. Prehosp Disaster Med. 2015;30(1):1-8.

We report the treatment and follow-up, including MRI, of two patients with idiopathic hypertrophic pachymeningitis and review the English language literature, with emphasis on management and outcome in this rare disorder.

The files of two patients were reviewed, with relevant histopathology and imaging (MRI). The first patient has been followed for sixteen years (the longest MRI-documented postoperative course reported for this condition) and the second for two years. The English language literature was reviewed, including a summary of all reported patients that have been followed with MRI or CT imaging.

Despite extensive investigation, no underlying etiology was determined in either patient. Histopathological studies revealed a chronic inflammatory dural infiltrate in both patients, with granulomas in the first but not the second patient. The first patient underwent surgery twice and has remained stable for sixteen years, despite persistent neurologic deficits. The second patient was managed with dexamethasone after a surgical biopsy, and experienced complete resolution of all neurological deficits and abnormalities seen with MRI.

Although prompt and extensive surgery has been recommended for this condition, the results from our second patient indicate that complete remission can be achieved in some patients with biopsy and steroid therapy. This also supports the view that autoimmune mechanisms underlie idiopathic hypertrophic pachymeningitis. The first patient illustrates that extensive laminectomies may be an effective therapeutic option but chronic discomfort may result. If extensive surgery must be performed, laminoplasty should be done because of the potential for reduced pain and improved long-term spinal stability.