Obstructive sleep apnea (OSA) has been associated with cognitive deficits as evidenced by neuropsychological testing in the domains of attention/working memory, verbal memory, processing speed, and executive function. OSA is often comorbid with hypertension and has been considered a risk factor for hypertension (Kareem et al., 2018; Tietjens et al., 2019). Both hypertension and OSA have been shown to be independent predictors of memory (Kinoshita et al., 2012). OSA and posttraumatic stress disorder (PTSD) are also frequently co-occurring, especially among veterans. In a group of veterans with a history of PTSD, we seek to explore the effects of sleep apnea and hypertension on cognitive functioning, particularly auditory learning/memory.

One hundred and three male and female participants with comorbid OSA and PTSD symptomology were screened as part of a larger VA Palo Alto Health Care System study. Participants (age: x=56.3, a=13.8, 24-81 years; education: x=14.6, a=2.3, 8-20 years; 9.6% female, 89.6% male) completed a neuropsychological battery, including the CVLT-II and WMS-IV Logical Memory. Presence or absence of hypertension was dichotomously coded and AHI severity was categorically coded. An auditory learning/memory composite variable was created using the z-score transformation method (Dodge et al., 2020). Variables and covariates were entered into a hierarchical regression.

The initial regression model revealed hypertension and OSA severity to be independent predictors of performance on auditory learning/memory (hypertension: ß= -0.71, p<0.01; OSA: ß= -0.42, p<0.01), where presence of hypertension or increased severity of OSA resulted in worse performance on the auditory learning/memory composite.

Results suggest that hypertension and OSA may independently and negatively affect performance on measures of auditory learning/memory in veterans with PTSD symptomology and OSA. Such findings underscore the importance of assessing and treating both hypertension and OSA among veterans with PTSD to improve not only physical health, but also cognitive health. Further research demonstrating similar findings is recommended along with studies investigating whether or not the treatment of hypertension and OSA can improve auditory learning/memory.

Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.

This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.

Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).

Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of robust infection prevention and control (IPAC) practices to maintain patient and staff safety. However, healthcare workers (HCWs) face many barriers that affect their ability to follow these practices. We identified barriers affecting HCW adherence to IPAC practices during the pandemic in British Columbia, Canada.

Cross-sectional web-based survey.

Acute care, long-term care or assisted living, outpatient, mental health, prehospital care, and home care.

Eligible respondents included direct-care providers and IPAC professionals working in these settings in all health authorities across British Columbia.

We conducted a web-based survey from August to September 2021 to assess respondent knowledge and attitudes toward IPAC within the context of the COVID-19 pandemic. Respondents were asked to rate the extent to which various barriers affected their ability to follow IPAC practices throughout the pandemic and to make suggestions for improvement.

The final analysis included 2,488 responses; 36% of respondents worked in acute care. Overall, perceptions of IPAC practice among non-IPAC professionals were positive. The main self-perceived barriers to adherence included inadequate staffing to cover absences (58%), limited space in staff rooms (57%), multibed rooms (51%), and confusing messages about IPAC practices (51%). Common suggestions for improvement included receiving more support from IPAC leadership and clearer communication about required IPAC practices.

Our findings highlight frontline HCW perspectives regarding priority areas of improvement for IPAC practices. They will inform policy and guideline development to prevent transmission of COVID-19 and future emerging infections.

Patients with major depressive disorder (MDD) often do not respond to antidepressant (ADT) monotherapy alone and may require adjunctive treatment to provide adequate symptom relief. Cariprazine (CAR) is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder. Post hoc analysis of data from a randomized controlled trial evaluated clinically relevant improvements in depressive symptom severity with adjunctive cariprazine in patients with MDD and inadequate response to ADT monotherapy.

Post hoc analysis evaluated data from a randomized, double-blind, placebo-controlled MDD trial (NCT03738215) in patients treated with CAR (1.5 mg/d or 3 mg/d) + ADT or placebo + ADT; the primary outcome was change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Post hoc analysis evaluated category shifts from baseline to week 6 in MADRS severity (normal <6, mild 7–19, moderate 20–34, severe ≥35). MADRS severity shifts were reported as the percentage of patients with no change or worsened severity, 1 category improvement, ≥1 category improvement, and ≥2 category improvement. Examples of categorical shifts in depressive symptoms at week 6 include change from severe at baseline to moderate (1 category improvement) and change from severe at baseline to mild (2 category improvement).

Of the 751 patients in the intent-to-treat (ITT) population (CAR: 1.5 mg/d=250, 3.0 mg/d=252; placebo=249), baseline MADRS severity was mild in 1.5%, moderate in 64%, and severe in 35%. Fewer CAR + ADT patients compared to placebo + ADT had no change or worsened MADRS severity at week 6 (CAR: 1.5 mg/d=32%, 3.0 mg/d=33%; placebo=42%). Approximately 68% of patients treated with CAR + ADT demonstrated a MADRS severity improvement of 1 category or greater by week 6 (CAR: 1.5 mg/d=68%, 3.0 mg/d=67%; placebo=58%). A greater percentage of patients in the CAR 1.5 mg/d group also had a 2 or greater category improvement versus CAR 3.0 mg/d or placebo 6 (CAR: 1.5 mg/d=28%, 3.0 mg/d=17%; placebo=19%).

In this post hoc analysis, CAR + ADT was associated with a greater proportion of patients with improvements in depressive symptom severity categories compared with placebo + ADT. These results may suggest that CAR + ADT is associated with clinically meaningful depressive symptom improvement in MDD patients.

AbbVie

Deficits in visuospatial attention, known as neglect, are common following brain injury, but underdiagnosed and poorly treated, resulting in long-term cognitive disability. In clinical settings, neglect is often assessed using simple pen-and-paper tests. While convenient, these cannot characterise the full spectrum of neglect. This protocol reports a research programme that compares traditional neglect assessments with a novel virtual reality attention assessment platform: The Attention Atlas (AA).

The AA was codesigned by researchers and clinicians to meet the clinical need for improved neglect assessment. The AA uses a visual search paradigm to map the attended space in three dimensions and seeks to identify the optimal parameters that best distinguish neglect from non-neglect, and the spectrum of neglect, by providing near-time feedback to clinicians on system-level behavioural performance. A series of experiments will address procedural, scientific, patient, and clinical feasibility domains.

Analyses focuses on descriptive measures of reaction time, accuracy data for target localisation, and histogram-based raycast attentional mapping analysis; which measures the individual’s orientation in space, and inter- and intra-individual variation of visuospatial attention. We will compare neglect and control data using parametric between-subjects analyses. We present example individual-level results produced in near-time during visual search.

The development and validation of the AA is part of a new generation of translational neuroscience that exploits the latest advances in technology and brain science, including technology repurposed from the consumer gaming market. This approach to rehabilitation has the potential for highly accurate, highly engaging, personalised care.

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.

Although rare, coronary artery anomalies can have significant clinical implications. Total anomalous origin of the coronary arteries from the pulmonary artery (TCAPA) represents a rare subtype of coronary artery anomaly for which little is known. The aim of this review was to characterise the presentation, utilised diagnostic modalities, associated cardiac lesions, and treatment strategies in patients with TCAPA.

A systematic review was performed for cases of TCAPA using PubMed, Embase, and Web of Science. Keywords searched included “total anomalous origin of the coronary arteries from the pulmonary artery,” “single ostium anomalous coronary artery from the pulmonary artery,” and “anomalous origin of both coronary arteries from the pulmonary artery.”

Fifty-seven cases of TCAPA were identified in 50 manuscripts. Fifty-eight per cent of patients were male and the median age at presentation was 10 days (mean 1.71 ± 6.6 years, range 0 days–39 years). Most patients were symptomatic at the time of presentation; cyanosis (n = 22) and respiratory distress (n = 14) were the most common symptoms. Cases were most commonly diagnosed at autopsy (n = 26, 45.6%), but operative intervention was pursued in 22 cases (45.6%); aortic re-implantation (n = 14) and a Takeuchi-type repair (n = 7) were the most common routes of repair.

The clinical presentation of patients with TCAPA was found to be variable, likely related to the presence of associated cardiac lesions. TCAPA should be considered in patients with suspected anomalous origin of the left coronary artery from the pulmonary artery for the serious consequences that can occur if not promptly corrected.

Vaginal cancer is a rare malignancy that poses a challenge to treat and cure, as surgical excision requires life-changing procedures because of the proximity and involvement of rectum, bladder and anus. We report in this case study the successful delivery of stereotactic ablative radiotherapy (SABR) for a patient with vaginal cancer after previous radiotherapy.

A 71-year-old white female who presented with dyspareunia and irritative urinary symptoms proven by biopsy was our candidate patient. Subsequent PET/CT revealed a hypermetabolic 3 cm lesion at the 12–1 o’clock position in the distal vagina involving the clitoris. The patient was initially treated with volumetric-modulated arc therapy (VMAT) with simultaneous integrated boost technique to the involved nodes, and later upon recurrence treated with SABR using 30 Gy in six fractions.

To our knowledge, this is the first report of a vaginal cylinder used to physically distance organs at risk from the treatment target and also as a localising device with image guidance for the delivery of SABR using an external beam.

Personal protective equipment (PPE) is worn by prehospital providers (PHPs) for protection from hazardous exposures. Evidence regarding the ability of PHPs to perform resuscitation procedures has been described in adult but not pediatric models. This study examined the effects of PPE on the ability of PHPs to perform resuscitation procedures on pediatric patients.

This prospective study was conducted at a US simulation center. Paramedics wore normal attire at the baseline session and donned full Level B PPE for the second session. During each session, they performed timed sets of psychomotor tasks simulating clinical care of a critically ill pediatric patient. The difference in time to completion between baseline and PPE sessions per task was examined using Wilcoxon signed-rank tests.

A total of 50 paramedics completed both sessions. Median times for task completion at the PPE sessions increased significantly from baseline for several procedures: tracheal intubation (+4.5 s; P = 0.01), automated external defibrillator (AED) placement (+9.5 s; P = 0.01), intraosseous line insertion (+7 s; P < 0.0001), tourniquet (+8.5 s; P < 0.0001), intramuscular injection (+21-23 s, P < 0.0001), and pulse oximetry (+4 s; P < 0.0001). There was no significant increase in completion time for bag-mask ventilation or autoinjector use.

PPE did not have a significant impact on PHPs performing critical tasks while caring for a pediatric patient with a highly infectious or chemical exposure. This information may guide PHPs faced with the situation of resuscitating children while wearing Level B PPE.