Bicuspid aortic valve is considered to have a multifactorial origin. Some research suggests a defect in neural crest cell signalling may increase the risk of developing bicuspid aortic valve, and also impact on the proximal conduction system.

To examine electrocardiographic parameters in unselected newborns from the general population diagnosed with bicuspid aortic valve within 30 days after birth.

This is a substudy of the Copenhagen Baby Heart Study; a multicentre, prospective, population-based cohort study with prenatal inclusion. Cardiac examination, including transthoracic echocardiography and electrocardiography, were obtained within 30 days after birth. Newborns diagnosed with bicuspid aortic valve were matched 1:4 with newborns with structurally normal hearts based on age, sex, gestational age, weight, and length at examination.

A total of 127 newborns with bicuspid aortic valve (84 boys, median age 11 days) and 508 controls (336 boys, median age 11 days) were included. Newborns with bicuspid aortic valve had a significantly longer PR-interval (100 vs 96 ms, p = 0.011) and QRS duration (56 vs 54 ms, p = 0.042), and a significantly lower R-wave amplitude in V6 (759 vs 906 µV, p = 0.047) compared to controls. However, when correcting for multiple testing none of the results were significant.

Newborns from the general population with bicuspid aortic valve demonstrated a slightly longer PR-interval, a longer QRS duration, and a lower maximum R-wave amplitude in V6 than matched controls, although non-significant after correcting for multiple testing. This may represent early signs of conduction abnormalities, but longitudinal follow-up will provide further clarification.

Assessment of response validity is essential to neuropsychological assessment. Although informant report of examinee functioning has previously been associated with examinee-generated performance and cognitive symptom invalidity (PVT; SVT-C), empirically-derived guidelines for interpreting informantreport validity are lacking. This study sought to assess the classification accuracy of a widely used informant-report measure, the Dementia Severity Rating Scale (DSRS), for discriminating examinee-generated PVT and SVT-C.

Data were collected from 145 examinee-informant dyads who completed neuropsychological batteries as part of a routine workup in an epilepsy monitoring unit. PVT status was determined by below-threshold performances on >2 indicators (Test of Memory Malingering, Wechsler Digit Span Age Corrected Scaled Score, Word Memory Test). SVT-C status was determined by above-threshold responses on both the Minnesota Multiphasic Personality Inventory-2-Restructured Form Response Bias Scale (MMPI-2-RF RBS) and Structured Inventory of Malingered Symptomatology Amnestic Disorders subscale (SIMS-AM). After assessing demographic and relational covariance via t-test and chi square analyses, receiver operator characteristic curves were derived to assess the classification accuracy of the DSRS for discriminating examinee PVT and SVT-C status.

DSRS total score demonstrated acceptable accuracy in classifying PVT status (AUC = .77), with cut scores of >21 and >15 yielding .93-.82 specificity and .44-.63 sensitivity. The DSRS also classified SVT-C status with acceptable accuracy (AUC = .71), with the aforementioned cut scores exhibiting .90-.78 specificity and .50-.64 sensitivity. The DSRS also classified SVT-C status using only one indicator (i.e., MMPI-2-RF RBS or SIMS-AM) with acceptable accuracy (AUC = .71-.72), with the aforementioned cut scores exhibiting .92 specificity and .37-.42 sensitivity.

The DSRS can be used to classify examinee-generated PVT and SVT-C on an epilepsy monitoring unit. Results provide empirically-derived psychometric guidelines for interpreting informant-report response validity that are clinically useful and lay the groundwork for future investigations of informant-report response validity.

Power calculations are widely used in the conduct of clinical trials and are often required in funding applications and approvals. There is a recent debate on the role of power calculations in observational studies on existing data with (Hernán J Clin Epidemiol 2022; 144 203-205) and (Moris and Smeden J Clin Epidemiol 2022; 142 261-263) emphasizing the need for planning for all study types without risking discarding imprecise but otherwise relevant studies. In the current study, we construct a graph useful in the planning of a wide range of studies with survival data. We map the minimal detectable effect (MDE) for any possible number of events with a dichotome exposure varying the proportion assigned to the exposure groups.

To provide a visual tool relating the sample size, more precisely the number of events, and the MDE for survival data in unbalanced designs.

The visualization is based on the formulas used by Stata’s power logrank function by (Schoenfeld Biometrics 1983; 39 499-503) and (Freedman Statistics in medicine 1982; 1 121-129), and the MDE is mapped as a function of the number of events. Furthermore, we apply this to an ongoing project on data from the Danish national registers, comparing the risk of developing polycystic ovary syndrome (PCOS) associated with treatment with valproic acid in a population with bipolar disorder or epilepsy.

Preliminary results (Fig. 1) show, as expected, that a larger sample size is required to obtain an MDE close to one. Also, the MDE increases when the assignment among groups is skewed. Moreover, we find a relevant minimal detectable HRR of 1.78 for developing PCOS in a population of 13,839 patients with bipolar disorder or epilepsy, exposed to valproic acid versus those not exposed to valproic acid, with a total of 203 cases of PCOS.

Fig. 1 shows the minimal detectable effect size as a function of the number of events, with α = 0.05 and a power of 1 - β = 0.8, for various assignment ratios φ = PT/PC, where PT and PC are the proportions of patients assigned to the treatment group and the control group, respectively.

Image:

The current visualization and corresponding calculation can be used to guide decisions in the design phase of both observational studies as well as in clinical trials. For observational studies, the sample size, or equivalently, the number of events, could well be fixed, and the MDE may help assess the clinical relevance of conducting the study as in the example with PCOS data. The curves can also provide insight into which efforts might lower the MDE, e.g., whether a small increase in sample size or a different assignment proportion would be most beneficial based on a given sample size.

None Declared

The purpose of this pilot study was to evaluate whether physician assistant (PA) programs in the Midwest integrate both disabilities and emergency preparedness education into 1 curriculum.

A convenience sample was utilized to survey program directors and deans of PA programs. Emails were obtained from the Physician Assistant Education Association. A 26, closed-ended question Qualtrics survey was based on an original study by Tanenhaus et al.1

Out of 43 accredited physician assistant programs surveyed, 9 programs replied (21%), and 1 program did not complete the survey. Six of the 10 programs (66%) responded that their program provided lectures specific to emergency preparedness. All 9 programs responded they do not offer a graduate-level track or concentration in emergency/disaster preparedness, and they do not offer a dual degree or a multidisciplinary program that highlights emergency/disaster preparedness.

This study was conducted to bring awareness to physician assistant students’ education regarding disabilities and emergency preparedness. As public health crises continue to arise, such as coronavirus disease (COVID-19), it is critical to have appropriately trained health care professionals. The study revealed that most programs lack a graduate-level track or concentrations, dual degrees, or extracurricular opportunities related to disabilities and emergency and disaster preparedness.

To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system.

Prospective observational cohort study open to adult employees at the Children’s Hospital of Philadelphia, conducted April 20–December 17, 2020.

Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity.

In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03–3.68), Black race (HR, 2.70; 95% CI, 1.24–5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71–6.88) were associated with statistically significant increased risk for seropositivity.

Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.

Vortioxetine has demonstrated sustained efficacy and favorable safety profile in multiple clinical trials.

This study aims to describe the effectiveness and safety of vortioxetine in real-world clinical practice.

RELIEVE is a prospective, multi-national, observational cohort study of outpatients initiating vortioxetine treatment for MDD at physician’s discretion and followed for 6 months. Data were collected at routine clinical visits. The primary outcome was functioning measured by Sheehan Disability Scale (SDS). Depressive symptoms measured by Patient Health Questionnaire 9-item (PHQ-9), cognitive symptoms measured by PDQ-5 and DSST were key secondary outcomes. Safety outcomes including adverse events were reported. This interim analysis presents results of 527 patients who completed the study and were followed for 6 months. Mixed models of repeated measures were used to assess improvements between baseline and month 6, adjusted for relevant confounders.

A total of 527 patients (mean age, 50.2 years, 65% female) were enrolled from US, Canada, France and Italy, and included in the analysis. Mean SDS total score, PHQ-9, PDQ-5 scores decreased by 8.6, 7.4 and 4.7 respectively from baseline to last visit. Mean DSST score improved by 6.5 from baseline to last visit. Patients’ overall functioning and quality of life significantly improved, sick leave days and underproductive days (both absenteeism and presenteeism) decreased over the entire follow up period. The overall incidence of adverse events(AE) was 25%, with the most common AEs being nausea and headache.

The results confirm the effectiveness and good tolerability of vortioxetine in a broad range of patients in routine clinical practice.

Dr. Mattingly has served as researcher, consultant or speaker for Akili, Alcobra, Alkermes, Allergan, Axsome, Boehringer, Forum, Genentech, Jansen, Lundbeck, Medgenics, Merck, Neos, NLS Pharma, Otsuka, Reckitt Benckiser, Roche, Sage, Shire, Sunovion, Supe

Males have a lower prevalence of depression than females and testosterone may be a contributing factor. A comparison of opposite-sex and same-sex twins can be used indirectly to establish the role of prenatal testosterone exposure and the risk of depression. We therefore aimed to explore differences in depression risk using opposite-sex and same-sex twins.

We included 126 087 opposite-sex and same-sex twins from the Danish Twin Registry followed in nationwide Danish registers. We compared sex-specific incidences of depression diagnosis and prescriptions of antidepressants between opposite-sex and same-sex twins using Cox proportional hazard regression.

During follow-up, 2664 (2.1%) twins were diagnosed with depression and 19 514 (15.5%) twins had purchased at least one prescription of antidepressants. First, in male twins, we found that the opposite-sex male twins had the same risk of depression compared to the same-sex male twins {hazard ratio (HR) = 1.01 [95% confidence interval (CI) 0.88–1.17)]}. Revealing the risk of use of antidepressants, the opposite-sex male twins had a slightly higher risk of 4% (HR = 1.04 (95% CI 1.00–1.11)) compared with the same-sex male twins. Second, in the female opposite-sex twins, we revealed a slightly higher, however, not statistically significant risk of depression (HR = 1.08 (95% CI 0.97–1.29)) or purchase of antidepressants (HR = 1.01 (95% CI 0.96–1.05)) when compared to the same-sex female twins.

We found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life.

High-quality diets, characterised by nutrient-rich foods, are one of the foundations for health and well-being. Indicators of diet quality, antioxidants, are associated with protection against cardiometabolic diseases. The current study explores relationships between plasma antioxidants and cardiometabolic risk among Aboriginal people in Australia.

As part of a community-driven health promotion programme, we conducted a cross-sectional study including a health-behaviour questionnaire, plasma antioxidants and cardiometabolic risk markers (anthropometric, blood pressure measurements, fasting glucose, glycated Hb (HbA1c), lipids, C-reactive protein and albumin-creatinine-ratio) continuous and categorised into population-specific cut-offs. Antioxidants (β-carotene, β-cryptoxanthin, lycopene, lutein-zeaxanthin, retinol and α-tocopherol measured using HPLC) were applied to a principal component analysis, which aggregated these into a single component. Linear regression models were applied to investigate associations between the antioxidant component and cardiometabolic risk markers.

Community in a remote area in Northern Territory, Australia.

A total of 324 Aboriginal people, mean age 35·5 (range 15–75) years.

Antioxidant component levels were higher among individuals with higher self-reported vegetable intake (P < 0·01), higher among individuals with higher self-reported fruit intake (P = 0·05) and lower among current smokers (P = 0·06). Linear regression revealed an inverse association between the antioxidant component and C-reactive protein (β = –0·01, P < 0·01) after adjusting for confounders.

Higher plasma antioxidant levels, indicators of diet quality, were associated with lower levels of high-sensitivity C-reactive protein in this Aboriginal population in remote Australia. This association suggests plasma antioxidants may be protective against inflammation; however, longitudinal studies are needed to examine this potentially protective relationship.

To identify and synthesise the literature on the cost of mental disorders.

Systematic literature searches were conducted in the databases PubMed, EMBASE, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to January 1980–May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses; (2) diagnosis of at least one mental disorder; (3) study population based on the general population; (4) outcome in monetary units. The systematic review was preregistered on PROSPERO (ID: CRD42019127783).

In total, 13 579 potential titles and abstracts were screened and 439 full-text articles were evaluated by two independent reviewers. Of these, 112 articles were included from the systematic searches and 31 additional articles from snowball searching, resulting in 143 included articles. Data were available from 48 countries and categorised according to nine mental disorder groups. The quality of the studies varied widely and there was a lack of studies from low- and middle-income countries and for certain types of mental disorders (e.g. intellectual disabilities and eating disorders). Our study showed that certain groups of mental disorders are more costly than others and that these rankings are relatively stable between countries. An interactive data visualisation site can be found here: https://nbepi.com/econ.

This is the first study to provide a comprehensive overview of the cost of mental disorders worldwide.

South Africa (SA) is a developing country with an ageing population. Adequate nutrition and physical activity (PA) protect against the loss of muscle mass and physical function, both of which are important components of sarcopenia. This study aimed to measure the prevalence of sarcopenia in older black SA women and investigate its associations with PA and protein intake.

Older black SA women (age, 68 (range; 60–85 years) n = 122) completed sociodemographic questionnaires, 24 h urine collection (estimate protein intake), venous blood (hs-C-reactive protein (hs-CRP) and ferritin), functional tests (grip strength, 3 m timed-up-and-go (TUG), 10 m walk test) and PA monitoring (activPAL). Dual-energy x-ray absorptiometry whole-body scans assessed fat and fat-free soft tissue mass (FFSTM).

According to the European Working group on Sarcopenia in Older People (EWGSOP)2, 2.5% (n = 3) had confirmed sarcopenia of a low severity based on normal physical function. Of the total cohort, 9% (n = 11) had low grip strength, 22.1% (n = 27) had a low appendicular skeletal muscle index (ASMI), and no women had low TUG (s) or gait speed (m/s). Higher ASMI was associated with lower hs-CRP (p = 0.05; Rho = -0.209) and higher ferritin (Rho = 0.252; p = 0.019), grip strength (kg, Rho = 0.223; p = 0.015), and gait speed (m/s, Rho = 0.180; p = 0.050). Protein intake suggested intake of 41.8g/day/ or 0.51 g/kg of body mass/day. Higher total protein intake (g/24h), was associated with higher FFSTM (kg) and ASMI (p < 0.001). PA outcomes were not correlated with FFSTM or ASMI (p > 0.05), however, there was a strong positive correlation of TUG (s) and gait speed (m/s) with time spent: 1) stepping per day (min) and; 2) at a high cadence (> 100 steps/min) (all p < 0.01). Daily step count was 7137 ± 3233 (mean ± Standard deviation), with 97.9 ± 38.7 min of total time spent stepping and 12.6 ± 16.8 min spent stepping at a high cadence (> 100 steps/min). Of note, 13.9% (n = 17) of women were completing > 10,000 steps/day.

Based on the EWGSOP2 criteria, there is a low prevalence of sarcopenia in older black SA women, explained by the maintenance of strength and physical function that directly related to PA, especially that performed at higher intensities. In contrast, low muscle mass was relatively prevalent (22.1%) and was associated with low dietary protein and not PA. Notably, it may be important to review the cut-points of EWGSOP2 criteria to be specific to the older SA women from disadvantaged communities.

Osteoporosis was not a public health concern in black South African (SA) women, until recently when it was reported that the prevalence of vertebral fractures was 9.1% in black compared to 5.0% in white SA women. Accordingly, this study aimed to measure bone mineral density (BMD) of older black SA women and to investigate its association with risk factors for osteoporosis, including strength, muscle and fat mass, dietary intake and objectively measured physical activity (PA).

Older black SA women (age, 68 (range; 60–85 years) n = 122) completed sociodemographic and quantitative food frequency questionnaires (QFFQ), fasting venous blood samples (25-hydroxycholecalciferol: Vitamin D-25), 24 h urine collection (estimate protein intake), grip strength and PA monitoring (activPAL). Dual-energy x-ray absorptiometry (DXA) scans of the hip (femoral neck and total) and lumbar spine determined BMD and whole-body scans for fat and fat-free soft tissue mass (FFSTM). WHO classifications were used to determine osteopenia (t-score -2.5 to -1), and osteoporosis (t-score < -2.5).

At the lumbar spine 34.4% of the women (n = 42) had osteopenia and 19.7% (n = 24) had osteoporosis. Osteopenia at the left femoral neck was 32% (n = 40) and osteoporosis was 13.1% (n = 16) of participants. The total left hip BMD indicated osteopenia in 27.9% (n = 34) and osteoporosis in 13.1% (n = 16) of participants. Multinomial regression revealed no differences in age (y) or frequency of falls in the past year between all groups (p = 0.727). Compared to those with normal BMD, participants with osteoporosis at the hip neck and lumbar spine were shorter, weighed less and had a lower body mass index (BMI) (all p < 0.05). When adjusted for height, the osteoporotic group (hip neck and lumbar spine) had lower trunk fat (% whole body), FFSTM (kg) and grip strength (kg), compared to those with normal BMD (p < 0.05). Only protein intake (g; 24 h urine analyses) was lower in women with osteoporosis (all sites) compared to those with normal BMD. Fat, carbohydrate and micronutrient intakes (relative to total daily energy intake), and vitamin D concentrations were not associated with BMD (all sites). Number of daily step count and stepping time (min) were inversely associated with BMI (p < 0.05), but not with BMD (all sites; p > 0.05).

A high prevalence of osteopenia and osteoporosis was evident at the lumbar spine and hip in older black SA women. This study highlights the importance of strength, body composition, and protein intake in maintaining BMD and preventing the development of osteoporosis in older women.

Cognitive dysfunction in unipolar depression (UD) and bipolar disorder (BD) may persist into periods of remission and affect psychosocial function. Attention and memory deficits may be more pronounced during remission in BD compared with UD. However, patients’ subjective experience of cognitive difficulties is poorly understood, and it is unclear whether this differs between BD and UD.

To examine self-reported cognitive function in remitted patients with BD and UD.

Patients with BD (n = 54) and UD (n = 45) were referred to the outpatient clinic at Department of Psychiatry, Copenhagen University Hospital, following hospital discharge.

Affective symptoms and patients’ experience of cognitive symptoms were assessed at their initial consultation at the clinic.

Patients in remission experienced mild to moderate impairment of cognitive function with greatest difficulties in motivation, energy, attention and memory. Subjective experience of cognitive function were similar for BD and UD and were predicted by affective symptoms rather than by diagnosis, age, gender or comorbid alcohol misuse.

The absence of differences between UD and BD in the subjective experience of cognitive difficulties contrasts with evidence of greater objective cognitive dysfunction in BD. This highlights a potential discord between subjective and objective measures of cognitive function. The impact of affective symptoms on the subjectively experienced cognitive difficulties suggests that they reflect mood symptoms rather than objective cognitive deficits. Further investigation of the relation between objective and subjective measures of cognitive function and the influence of affective symptoms is warranted.

To investigate the potential use of smartphone apps to support self-management in young adults with bipolar disorder.

We recruited 89 young adults (18–30 years) with bipolar disorder to complete a cross-sectional online survey. The survey contained quantitative and qualitative questions regarding technology use, current use of disorder-management apps, types of apps desired for disorder management, and app features that users would consider important when selecting apps. Results were analysed using descriptive statistics and thematic analysis.

Almost all participants used a smartphone daily and 40% currently used apps for disorder management. Of those not currently using apps, 79% indicated they would like to try them. On average, participants rated 61% of the self-management strategies listed as desirable for app support, with sleep-management, understanding early warning signs and triggers, and stay-well plans the most frequently endorsed. App features considered important during app selection were ease-of-use, scientific quality, flexibility/customisation, and data privacy.

The results indicate that young adults with bipolar disorder are interested in a wide range of apps for self-management. Participants were interested in apps to support self-management strategies considered clinically important for disorder management. Many of these app needs are currently unmet. Results suggest diversifying and prioritising app capabilities to ensure evidence-based resources for a broader range of app functions are available to consumers.