To determine the prevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) IgG nucleocapsid (N) antibodies among healthcare personnel (HCP) with no prior history of COVID-19 and to identify factors associated with seropositivity.

Prospective cohort study.

An academic, tertiary-care hospital in St. Louis, Missouri.

The study included 400 HCP aged ≥18 years who potentially worked with coronavirus disease 2019 (COVID-19) patients and had no known history of COVID-19; 309 of these HCP also completed a follow-up visit 70–160 days after enrollment. Enrollment visits took place between September and December 2020. Follow-up visits took place between December 2020 and April 2021.

At each study visit, participants underwent SARS-CoV-2 IgG N-antibody testing using the Abbott SARS-CoV-2 IgG assay and completed a survey providing information about demographics, job characteristics, comorbidities, symptoms, and potential SARS-CoV-2 exposures.

Participants were predominately women (64%) and white (79%), with median age of 34.5 years (interquartile range [IQR], 30–45). Among the 400 HCP, 18 (4.5%) were seropositive for IgG N-antibodies at enrollment. Also, 34 (11.0%) of 309 were seropositive at follow-up. HCP who reported having a household contact with COVID-19 had greater likelihood of seropositivity at both enrollment and at follow-up.

In this cohort of HCP during the first wave of the COVID-19 pandemic, ∼1 in 20 had serological evidence of prior, undocumented SARS-CoV-2 infection at enrollment. Having a household contact with COVID-19 was associated with seropositivity.

Obstructive sleep apnea (OSA) is a sleep disorder that is highly comorbid with psychiatric disorders, including depression and anxiety. Excessive daytime sleepiness (EDS) is common in psychiatric disorders and OSA. In participants with OSA, EDS can persist despite use of positive airway pressure (PAP) therapy. This analysis of real-world data aimed to describe EDS and its relationship with PAP use in participants with and without depression.

US residents (≥18 years of age, self-reported physician diagnosis of OSA [from 1/1/2015 to 3/31/2020]) completed a survey in Evidation Health’s Achievement app assessing subjective levels of sleepiness (Epworth Sleepiness Scale [ESS]) and self-reported PAP usage, categorized as nonuse (no PAP use), nonadherent (<4 h/night or <5 d/wk), intermediate (4-6 h/night, ≥5 d/wk), or highly adherent (≥6 h/night, ≥5 d/wk). ESS score >10 defined EDS. A linear model assessed relationships between PAP use and ESS score. P-values are uncontrolled for multiplicity (nominal).

In total, 2289 participants (EDS, n=972; no EDS, n=1317) completed the survey (50.3% female; 82.5% White; mean±standard deviation [SD] age, 44.8 ± 11.1 years). Anxiety and depression were the most common comorbidities and were more common in participants with EDS (49% and 49%, respectively) than those without EDS (41% and 37%, respectively). Overall, EDS was more common among participants with comorbid depression (49%) than those without (38%), even among highly adherent PAP users (46% vs 30%, respectively). In a linear model (PAP users only), an additional 1 h/night of PAP use was associated with lower ESS scores in the subgroup of participants without depression (n=928; estimate [SE], −0.42 [0.09]; P<0.05), but not in the subgroup with depression (n=661; estimate [SE], −0.15 [0.10]; P>0.05). In a sensitivity analysis that excluded participants using medications that cause sleepiness, PAP use was associated with lower ESS scores regardless of depression status; however, EDS remained more common in participants with comorbid depression (46%) than in those without (36%).

In this real-world population of participants with OSA, those with EDS were more likely to have comorbid anxiety or depression. EDS was more common in participants with comorbid depression than those without, even with highly adherent PAP use. PAP use was associated with lower ESS scores in participants without comorbid depression, but not in those with comorbid depression; the use of medications that cause sleepiness may contribute to but does not fully explain this phenomenon.

Axsome Therapeutics and Jazz Pharmaceuticals

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is often associated with numerous medical and psychiatric comorbidities. Patients with OSA experience a variety of symptoms that can be burdensome and affect their quality of life and satisfaction with care. Excessive daytime sleepiness (EDS) is a common symptom of OSA, and can persist despite primary airway therapy (e.g., positive airway pressure [PAP]). This analysis aimed to characterize common comorbidities, as well as symptoms present at OSA diagnosis and their burden in a real-world population of participants with OSA.

US residents (≥18 years of age, self-reported clinician diagnosis of OSA [from 1/1/2015 to 3/31/2020]) completed a survey in Evidation Health’s Achievement app that assessed self-reported sleepiness (Epworth Sleepiness Scale [ESS]), self-reported PAP usage, self-reported physician-diagnosed comorbidities, and information on their symptoms at time of OSA diagnosis. Self-reported PAP use was categorized as nonuse (no PAP use), nonadherent (<4 h/night or <5 d/wk), intermediate (4–6 h/night, ≥5 d/wk), or highly adherent (≥6 h/night, ≥5 d/wk). EDS was defined as ESS score >10. All data were summarized descriptively.

In total, 2289 participants completed the survey (50.3% female; 82.5% White; mean ± standard deviation [SD] age, 44.8 ± 11.1 years; mean ± SD age at OSA diagnosis, 40.7 ± 11.4 years; mean ± SD body mass index, 35.4 ± 8.7 kg/m2); 42.5% had EDS. Among the total population, 30.6% were PAP non-users, 6.7% were nonadherent, 9.8% were intermediate adherent, and 52.9% were highly adherent. Across the study population, the most common self-reported physician-diagnosed comorbidities were anxiety (44%) and depression (42%) followed by hypertension (39%), dyslipidemia (26%), and asthma (21%). Among the symptoms participants reported having had at the time of OSA diagnosis, the most common were EDS (79%), fatigue (79%), snoring (75%), and awakening with a dry mouth or sore throat (63%). Concentration/Memory problems (48%) and mood changes (46%) were also common. In the overall population, the symptoms present at the time of OSA diagnosis that were most likely to be highly burdensome were fatigue (53%), EDS (46%), snoring (35%), difficulty concentrating/memory issues (31%), and mood changes (25%).

These real-world survey data identify anxiety and depression as the most frequently reported comorbidities in a population of participants with OSA, each affecting over 40% of participants. In addition to classic OSA symptoms (e.g., EDS, fatigue, snoring, and awakening with dry mouth/sore throat), concentration/memory problems and mood changes were also common at the time of OSA diagnosis and were among the presenting symptoms most frequently reported as highly burdensome, along with fatigue, EDS, and snoring.

Axsome Therapeutics and Jazz Pharmaceuticals

Dental healthcare personnel (DHCP) are at high risk of exposure to coronavirus disease 2019 (COVID-19). We sought to identify how DHCP changed their use of personal protective equipment (PPE) as a result of the COVID-19 pandemic, and to pilot an educational video designed to improve knowledge of proper PPE use.

The study comprised 2 sets of semistructured qualitative interviews.

The study was conducted in 8 dental clinics in a Midwestern metropolitan area.

In total, 70 DHCP participated in the first set of interviews; 63 DHCP participated in the second set of interviews.

In September–November 2020 and March–October 2021, we conducted 2 sets of semistructured interviews: (1) PPE use in the dental community during COVID-19, and (2) feedback on the utility of an educational donning and doffing video.

Overall, 86% of DHCP reported having prior training. DHCP increased the use of PPE during COVID-19, specifically N95 respirators and face shields. DHCP reported real-world challenges to applying infection control methods, often resulting in PPE modification and reuse. DHCP reported double masking and sterilization methods to extend N95 respirator use. Additional challenges to PPE included shortages, comfort or discomfort, and compatibility with specialty dental equipment. DHCP found the educational video helpful and relevant to clinical practice. Fewer than half of DHCP reported exposure to a similar video.

DHCP experienced significant challenges related to PPE access and routine use in dental clinics during the COVID-19 pandemic. An educational video improved awareness and uptake of appropriate PPE use among DHCP.

Subthreshold/attenuated syndromes are established precursors of full-threshold mood and psychotic disorders. Less is known about the individual symptoms that may precede the development of subthreshold syndromes and associated social/functional outcomes among emerging adults.

We modeled two dynamic Bayesian networks (DBN) to investigate associations among self-rated phenomenology and personal/lifestyle factors (role impairment, low social support, and alcohol and substance use) across the 19Up and 25Up waves of the Brisbane Longitudinal Twin Study. We examined whether symptoms and personal/lifestyle factors at 19Up were associated with (a) themselves or different items at 25Up, and (b) onset of a depression-like, hypo-manic-like, or psychotic-like subthreshold syndrome (STS) at 25Up.

The first DBN identified 11 items that when endorsed at 19Up were more likely to be reendorsed at 25Up (e.g., hypersomnia, impaired concentration, impaired sleep quality) and seven items that when endorsed at 19Up were associated with different items being endorsed at 25Up (e.g., earlier fatigue and later role impairment; earlier anergia and later somatic pain). In the second DBN, no arcs met our a priori threshold for inclusion. In an exploratory model with no threshold, >20 items at 19Up were associated with progression to an STS at 25Up (with lower statistical confidence); the top five arcs were: feeling threatened by others and a later psychotic-like STS; increased activity and a later hypo-manic-like STS; and anergia, impaired sleep quality, and/or hypersomnia and a later depression-like STS.

These probabilistic models identify symptoms and personal/lifestyle factors that might prove useful targets for indicated preventative strategies.

Excited delirium, which has been defined as combativeness, agitation, and altered sensorium, requires immediate treatment in prehospital or emergency department (ED) settings for the safety of both patients and caregivers. Prehospital ketamine use is prevalent, although the evidence on safety and efficacy is limited. Many patients with excited delirium are intoxicated with illicit substances. This investigation explores whether patients treated with prehospital ketamine for excited delirium with concomitant substance intoxication have higher rates of subsequent intubation in the ED compared to those without confirmed substance usage.

Over 28 months at two large community hospitals, all medical records were retrospectively searched for all patients age 18 years or greater with prehospital ketamine intramuscular (IM) administration for excited delirium and identified illicit and prescription substance co-ingestions. Trained abstractors collected demographic characteristics, history of present illness (HPI), urine drug screens (UDS), alcohol levels, and noted additional sedative administrations. Substance intoxication was determined by UDS and alcohol positivity or negativity, as well as physician HPI. Patients without toxicological testing or documentation of substance intoxication, or who may have tested positive due to ED sedation, were excluded from relevant analyses. Subsequent ED intubation was the primary pre-specified outcome. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to compare variables.

Among 86 patients given prehospital ketamine IM for excited delirium, baseline characteristics including age, ketamine dose, and body mass index were similar between those who did or did not undergo intubation. Men had higher intubation rates. Patients testing positive for alcohol, amphetamines, barbiturates, benzodiazepines, ecstasy, marijuana, opiates, and synthetic cathinones, both bath salts and flakka, had similar rates of intubation compared to those negative for these substances. Of 27 patients with excited delirium and concomitant cocaine intoxication, nine (33%) were intubated compared with four of 50 (8%) without cocaine intoxication, yielding a 5.75 OR (95%, CI 1.57 to 21.05; P = .009).

Patients treated with ketamine IM for excited delirium with concomitant cocaine intoxication had a statistically significant 5.75-fold increased rate of subsequent intubation in the ED. Amongst other substances, no other trends with intubation were noted, but further study is warranted.

Prehospital intramuscular (IM) ketamine is increasingly used for chemical restraint of agitated patients. However, few studies have assessed emergency department (ED) follow-up of patients receiving prehospital ketamine for this indication, with previous reports suggesting a high rate of post-administration intubation. This study examines the rate of and reasons for intubation and other airway interventions in agitated patients who received ketamine by Emergency Medical Services (EMS).

This retrospective cohort study included patients who received prehospital ketamine for agitation and were transported to two community hospital EDs. Charts were reviewed for demographics, ketamine dose, and airway intervention by EMS or in the ED. Characteristics of patients who were intubated versus those who did not receive airway intervention were analyzed.

Over 28 months, 86 patients received ketamine for agitation. Fourteen (16.3%) underwent endotracheal intubation. Patients with a higher temperature and a lower Glasgow Coma Score (GCS) were more likely to require intubation. There was no age or dose-dependent association on intubation rate. Intubated patients averaged 39 years old versus 44 for patients not intubated (negative five-year difference; 95% CI, -16 to 6). The mean ketamine dose was 339.3mg in patients intubated versus 350.7mg in patients not (-11.4mg difference; 95% CI, -72.4 to 49.6). The mean weight-based ketamine dose was 4.44mg/kg in patients intubated versus 4.96mg/kg in patients not (-0.53mg/kg difference; 95% CI, -1.49 to 0.43).

The observed rate of intubation in patients receiving prehospital ketamine for agitation was 16.3%. Study data did not reveal an age or dose-dependent rate of intubation. Further research should be conducted to compare the airway intervention rate of agitated patients receiving ketamine versus other sedatives in a controlled fashion.

To characterize the spectrum of BRCA1 and BRCA2 pathogenic germline variants in women from south-west Poland and west Ukraine affected with breast or ovarian cancer. Testing in women at high risk of breast and ovarian cancer in these regions is currently mainly limited to founder mutations.

Unrelated women affected with breast and/or ovarian cancer from Poland (n = 337) and Ukraine (n = 123) were screened by targeted sequencing. Excluded from targeted sequencing were 34 Polish women who had previously been identified as carrying a founder mutation in BRCA1. No prior testing had been conducted among the Ukrainian women. Thus, this study screened BRCA1 and BRCA2 in the germline DNA of 426 women in total.

We identified 31 and 18 women as carriers of pathogenic/likely pathogenic (P/LP) genetic variants in BRCA1 and BRCA2, respectively. We observed five BRCA1 and eight BRCA2 P/LP variants (13/337, 3.9%) in the Polish women. Combined with the 34/337 (10.1%) founder variants identified prior to this study, the overall P/LP variant frequency in the Polish women was thus 14% (47/337). Among the Ukrainian women, 16/123 (13%) women were identified as carrying a founder mutation and 20/123 (16.3%) were found to carry non-founder P/LP variants (10 in BRCA1 and 10 in BRCA2).

These results indicate that genetic testing in women at high risk of breast and ovarian cancer in Poland and Ukraine should not be limited to founder mutations. Extended testing will enhance risk stratification and management for these women and their families.

Poor physical health in severe mental illness (SMI) remains a major issue for clinical practice.

To use electronic health records of routinely collected clinical data to determine levels of screening for cardiometabolic disease and adverse health outcomes in a large sample (n = 7718) of patients with SMI, predominantly schizophrenia and bipolar disorder.

We linked data from the Glasgow Psychosis Clinical Information System (PsyCIS) to morbidity records, routine blood results and prescribing data.

There was no record of routine blood monitoring during the preceding 2 years for 16.9% of the cohort. However, monitoring was poorer for male patients, younger patients aged 16–44, those with schizophrenia, and for tests of cholesterol, triglyceride and glycosylated haemoglobin. We estimated that 8.0% of participants had diabetes and that lipids levels, and use of lipid-lowering medication, was generally high.

Electronic record linkage identified poor health screening and adverse health outcomes in this vulnerable patient group. This approach can inform the design of future interventions and health policy.