Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

Many Emergency Medical Service (EMS) systems in the United States restrict albuterol therapy by scope of practice to Advanced Life Support (ALS). The State of Delaware has a two-tiered EMS system in which Basic Life Support (BLS) arrives on scene prior to ALS in the majority of respiratory distress calls.

This study sought to evaluate the safety, efficacy, and expedience of albuterol administration by BLS compared to ALS.

This retrospective observational study used data collected from July 2015 through January 2017 throughout a State BLS albuterol pilot program. Pilot BLS agencies participated in a training session on the indications and administration of albuterol, and were then authorized to carry and administer nebulized albuterol. Heart rate (HR), respiratory rate (RR), and pulse oximetry (spO2) were obtained before and after albuterol administration by BLS and ALS. The times from BLS arrival to the administration of albuterol by pilot BLS agencies versus ALS were compared. Study encounters required both BLS and ALS response. Data were analyzed using chi-square and t-test as appropriate.

Three hundred eighty-eight (388) incidents were reviewed. One hundred eighty-five (185) patients received albuterol by BLS pilot agencies and 203 patients received albuterol by ALS. Of note, the population treated by ALS was significantly older than the population treated by BLS (61.9 versus 51.6 years; P <.001). A comparison of BLS arrival time to albuterol administration time showed significantly shorter times in the BLS pilot group compared to the ALS group (3.50 minutes versus 8.00 minutes, respectively; P <.001). After albuterol administration, BLS pilot patients showed improvements in HR (P <.01), RR (P <.01), and spO2 (P <.01). Alternately, ALS treatment patients showed improvement in spO2 (P <.01) but not RR (P = .17) or HR (P = 1.00). Review by ALS or hospital staff showed albuterol was indicated in 179 of 185 BLS patients and administered correctly in 100% of these patients.

Patients both received albuterol significantly sooner and showed superior improvements in vital signs when treated by BLS agencies carrying albuterol rather than by BLS agencies who required ALS arrival for albuterol. Two-tiered EMS systems should consider allowing BLS to carry and administer albuterol for safe, effective, and expedient treatment of respiratory distress patients amenable to albuterol therapy.

Delay in the diagnosis of head and neck cancer can result in significant excess morbidity and mortality. How the pandemic has affected patient presentation in Scotland is unknown.

This retrospective cohort study compared all presentations of head and neck cancer between June and October of 2019 with the same period following the peak of the pandemic in 2020 in West Scotland, a region populated by 2.5 million people.

A total of 528 patients met our inclusion criteria. Compared with 2019, patients in 2020 were more likely to present with a higher American Joint Committee on Cancer stage (odds ratio, 1.67 (95 per cent confidence interval = 1.20 to 2.31); p = 0.002), a longer preceding symptom duration (odds ratio, 2.03 (95 per cent confidence interval = 1.44 to 2.87; p < 0.001) and to have an emergency presentation (odds ratio, 2.53, (95 per cent confidence interval = 1.15 to 5.55; p = 0.017).

Patients are presenting later with more advanced head and neck cancer following the coronavirus disease 2019 pandemic.

YouTube has become the preferred resource for trainees to learn and prepare for surgical cases. This study evaluated the educational quality of YouTube videos detailing thyroidectomy and parathyroidectomy.

YouTube was systematically searched using 11 terms related to thyroidectomy and parathyroidectomy. Four independent clinical reviewers assessed the videos using Laparoscopic Surgery Video Educational Guidelines as well as modified Laparoscopic Surgery Video Educational Guidelines subgroup tools.

Sixty-five videos were identified and evaluated. Overall Laparoscopic Surgery Video Educational Guidelines score was 8.58 ± 3.85 (mean subgroup score, 5.67 ± 2.40). Twenty-eight of 65, 25 of 65 and 12 of 65 videos were deemed medium, low and high quality, respectively. Inter-rater reliability was good for both attending surgeons and residents. Presence of audio or visual commentary had a positive correlation with total Laparoscopic Surgery Video Educational Guidelines scores (R2=0.38). Videos produced by otolaryngologists and US-based physicians scored higher on total scores compared to non-otolaryngology and non-US based physicians.

Some YouTube videos on thyroidectomy and parathyroidectomy exhibit high educational value. Future efforts should increase the number of high-quality YouTube videos containing both audio and visual commentary or create an online repository of videos for medical students and residents to augment their surgical training.

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.

Although behavior therapy reduces tic severity, it is unknown whether it improves co-occurring psychiatric symptoms and functional outcomes for adults with Tourette's disorder (TD). This information is essential for effective treatment planning. This study examined the effects of behavior therapy on psychiatric symptoms and functional outcomes in older adolescents and adults with TD.

A total of 122 individuals with TD or a chronic tic disorder participated in a clinical trial comparing behavior therapy to psychoeducation and supportive therapy. At baseline, posttreatment, and follow-up visits, participants completed assessments of tic severity, co-occurring symptoms (inattention, impulsiveness, hyperactivity, anger, anxiety, depression, obsessions, and compulsions), and psychosocial functioning. We compared changes in tic severity, psychiatric symptoms, and functional outcomes using repeated measure and one-way analysis of variance.

At posttreatment, participants receiving behavior therapy reported greater reductions in obsessions compared to participants in supportive therapy ($\eta _p^2 $ = 0.04, p = 0.04). Across treatments, a positive treatment response on the Clinical Global Impression of Improvement scale was associated with a reduced disruption in family life ($\eta _p^2 $ = 0.05, p = 0.02) and improved functioning in a parental role ($\eta _p^2 $ = 0.37, p = 0.02). Participants who responded positively to eight sessions of behavior therapy had an improvement in tic severity ($\eta _p^2 $ = 0.75, p < 0.001), inattention ($\eta _p^2 $ = 0.48, p < 0.02), and functioning ($\eta _p^2 $ = 0.39–0.42, p < 0.03–0.04) at the 6-month follow-up.

Behavior therapy has a therapeutic benefit for co-occurring obsessive symptoms in the short-term, and reduces tic severity and disability in adults with TD over time. Additional treatments may be necessary to address co-occurring symptoms and improve functional outcomes.

Epistaxis is the most common ENT emergency. This study aimed to assess one-year mortality rates in patients admitted to a large teaching hospital.

This study was a retrospective case note analysis of all patients admitted to the Queen Elizabeth University Hospital in Glasgow with epistaxis over a 12-month period.

The one-year overall mortality for a patient admitted with epistaxis was 9.8 per cent. The patients who died were older (mean age 77.2 vs 68.8 years; p = 0.002), had a higher Cumulative Illness Rating Scale-Geriatric score (9.9 vs 6.7; p < 0.001) and had a higher performance status score (2 or higher vs less than 2; p < 0.001). Other risk factors were a low admission haemoglobin level (less than 128 g/dl vs 128 g/dl or higher; p = 0.025), abnormal coagulation (p = 0.004), low albumin (less than 36 g/l vs more than 36 g/l; p < 0.001) and longer length of stay (p = 0.046).

There are a number of risk factors associated with increased mortality after admission with epistaxis. This information could help with risk stratification of patients at admission and enable the appropriate patient support to be arranged.

Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.

To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.

Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.

Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.

Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.