The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.

64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.

Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.

LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.

To investigate the occurrence of traumatic stress symptoms (TSS) among healthcare workers active during the COVID-19 pandemic and to obtain insight as to which pandemic-related stressful experiences are associated with onset and persistence of traumatic stress.

This is a multicenter prospective cohort study. Spanish healthcare workers (N = 4,809) participated at an initial assessment (i.e., just after the first wave of the Spain COVID-19 pandemic) and at a 4-month follow-up assessment using web-based surveys. Logistic regression investigated associations of 19 pandemic-related stressful experiences across four domains (infection-related, work-related, health-related and financial) with TSS prevalence, incidence and persistence, including simulations of population attributable risk proportions (PARP).

Thirty-day TSS prevalence at T1 was 22.1%. Four-month incidence and persistence were 11.6% and 54.2%, respectively. Auxiliary nurses had highest rates of TSS prevalence (35.1%) and incidence (16.1%). All 19 pandemic-related stressful experiences under study were associated with TSS prevalence or incidence, especially experiences from the domains of health-related (PARP range 88.4–95.6%) and work-related stressful experiences (PARP range 76.8–86.5%). Nine stressful experiences were also associated with TSS persistence, of which having patient(s) in care who died from COVID-19 had the strongest association. This association remained significant after adjusting for co-occurring depression and anxiety.

TSSs among Spanish healthcare workers active during the COVID-19 pandemic are common and associated with various pandemic-related stressful experiences. Future research should investigate if these stressful experiences represent truly traumatic experiences and carry risk for the development of post-traumatic stress disorder.

To determine whether the gender of clinicians making antimicrobial stewardship recommendations has an impact on intervention acceptance rate.

A retrospective, multivariable analysis of antimicrobial stewardship prospective audit and feedback outcomes.

A multisite healthcare system including Mayo Clinic Rochester (MN), Mayo Clinic Arizona, Mayo Clinic Florida and 17 health-system hospital sites, where prospective audit and feedback is performed and documented within an electronic tool embedded in the medical record.

The study included 143 Mayo Clinic clinicians (84 cisfemales and 59 cismales).

Outcomes were analyzed from July 1, 2017, to June 30, 2022, for intervention rates, communication methods, and intervention acceptance by clinician gender, profession, patient age, and intensive care unit (ICU) status of patient.

Of 81,927 rules, 71,729 rules met study inclusion. There were 18,175 (25%) rules associated with an intervention. Most of the rules were reviewed by pharmacists (86.2%) and stewardship staff (85.5%). Of 10,363 interventions with an outcome documented, 8,829 (85.2%) were accepted and 1,534 (14.8%) were rejected. Female clinicians had 6,782 (86.5%) of 7,843 interventions accepted, and male clinicians had 2,047 (81.2%) of 2,520 interventions accepted (P = .19). Female patients had more interventions than male patients (female vs male: 25.9% vs 24.9%; OR, 1.04; 95% CI, 1.02–1.08; P = .001). Patients in the ICU had a significantly lower intervention acceptance rate (ICU vs non-ICU: 78.2% vs 86.7%; OR, 0.56; 95% CI, 0.45–0.7; P < .001).

Female and male clinicians were equally effective at prospective audit and feedback in a multisite antimicrobial stewardship program. Patients in the ICU were less likely to have stewardship interventions accepted.

To define outpatient parenteral antimicrobial therapy (OPAT) clinical pharmacy practice across the United States, specifically pharmacist functions, design of pharmacist involvement, and to compare pharmacist training of those who practice in OPAT to infectious diseases pharmacists who do not.

A survey of a possible 32 questions was emailed to the American College of Clinical Pharmacists (ACCP) Infectious Diseases Practice and Research Network (PRN) e-mail list. Results were focused on US-based respondents.

In total, 87 pharmacists responded; 27 of these pharmacists (31%) practiced in OPAT.

Training background did not differ between groups. Programs with an OPAT pharmacist were more likely to have a formal OPAT team compared to those without an OPAT pharmacist (P < .001). OPAT pharmacists were early in their careers with 66.7% practicing <5 years in OPAT. Most OPAT pharmacists (66.7%) practiced at an academic medical center with a median full-time equivalent (FTE) of 0.6. Moreover, 63% utilized a collaborative practice agreement and 81.5% shared job functions with other pharmacist roles, most commonly antimicrobial stewardship. Few OPAT programs involved a dispensing component (28%). The median daily census was 43 patients followed by an OPAT pharmacist. Pharmacists performed a variety of tasks in OPAT.

Pharmacist nondispensing involvement in OPAT is an emerging trend in the United States with wide variability in program structure and pharmacist tasks. A ratio of 1 OPAT pharmacist for every 45–70 OPAT patients is proposed to facilitate expansion of pharmacist clinical practice in OPAT.

A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.

This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.

ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.

Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.

We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.

The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).

The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.

Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.

JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.

These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.

First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.

We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.

In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.

The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

To assess the extent of error present in self-reported weight data in the Women’s Health Initiative, variables that may be associated with error, and to develop methods to reduce any identified error.

Prospective cohort study.

Forty clinical centres in the USA.

Women (n 75 336) participating in the Women’s Health Initiative Observational Study (WHI-OS) and women (n 6236) participating in the WHI Long Life Study (LLS) with self-reported and measured weight collected about 20 years later (2013–2014).

The correlation between self-reported and measured weights was 0·97. On average, women under-reported their weight by about 2 lb (0·91 kg). The discrepancies varied by age, race/ethnicity, education and BMI. Compared with normal-weight women, underweight women over-reported their weight by 3·86 lb (1·75 kg) and obese women under-reported their weight by 4·18 lb (1·90 kg) on average. The higher the degree of excess weight, the greater the under-reporting of weight. Adjusting self-reported weight for an individual’s age, race/ethnicity and education yielded an identical average weight to that measured.

Correlations between self-reported and measured weights in the WHI are high. Discrepancies varied by different sociodemographic characteristics, especially an individual’s BMI. Correction of self-reported weight for individual characteristics could improve the accuracy of assessment of obesity status in postmenopausal women.