Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW veterans’ illness (GWVI). GWVI is a poorly understood chronic medical condition, characterized by symptoms indicative of brain function deficits in multiple domains. Among the symptoms of brain impairment GWVI-related chronic headaches and body muscle and joint pain conditions (GWVI-HAP) are the most debilitating, affecting around 64% of the GWVI veterans. Further, depression carries a very high co-morbid rate (>50%) in patients with chronic pain, including GWVI-HAP. In this preliminary study, we examined the integrity of brain function networks in a group of GWI-HAP veterans, with resting state fMRI (rsfMRI).

Data from the first twenty-two GWVI-HAP veterans from two ongoing parallel clinical trials was examined. Of these 14 subjects (GWVI-HAP-DM) had mild depression (Hamilton Rating Scale for Depression (HSRD < 13); and 8 subjects (GWVI-HAP-DS) had moderate to severe depression (HSRD > 14). Written informed consent was obtained from all participants in the protocol approved by the local Institutional Review Board. RsfMRI data was acquired on a Siemens 3T Prisma-Fit MRI scanner using a 10-minute whole-brain high resolution simultaneous multi-slice (SMS) gradient echo echo-planar imaging (EPI) sequence: TR/TE/FA = 2.2 sec/ 27 msec/80°, and analyzed with well-established image processing pipelines. Functional connectivity (FC) to different regions implicated in depression and chronic pain was assessed with seed-based correlation analysis. Between group differences in FC were obtained with 2-sample t-tests.

GWVI-HAP-DS group exhibited significantly (p < 0.05) reduced FC compared to GWVI-HAP-DM between frontal lobe (medial (mPFC), and dorsolateral (dlPFC) prefrontal cortex) and the striatum. This indicates that malfunction of fronto-striatal circuits could be a source of the increased chronic pain and depression seen in veterans with GWVI- HAP-DS. Dysregulation of fronto-striatal networks has been implicated in major depressive disorder as well as many chronic pain conditions. In addition, FC between mPFC, and salience network (SN; anterior insula and dorsal anterior cingulate) and limbic (subgenual and ventral anterior cingulate) regions were also reduced in GWVI-HAP-DS. Similarly, mPFC and SN also exhibited reduced FC to pain processing regions (posterior insula, centromedian thalamus and cerebellum). These FC impairments could reflect greater deficits in regulation of and salience attribution to emotions and nociception in the GWVI-HAP-DS group. Finally, GWVI-HAP-DS also exhibited reduced FC between nodes of the default mode network. DMN impairments also have been observed in many depressive and chronic pain conditions.

The results of this preliminary analysis implicate impairments in cognitive control of emotion and nociception as a mechanism underlying the enhanced chronic pain and depression observed in GWVI-HAP veterans, especially those with moderate to severe depression. A fuller picture of deficits in FC in brain function networks is expected to emerge as more GWI-HAP subjects of both groups along with age matched healthy controls are examined in this ongoing project. Better understanding of impairments in these networks in GWI-HAP will benefit the rehabilitation of veterans with GWI-HAP.

Aging is associated with changes in cortical excitability which may affect motor learning and cognitive function via selective modulation of gamma aminobutyric acid (GABA). Previous studies using magnetic resonance spectroscopy (MRS) to measure GABA in older adults found that increased baseline GABA levels in the sensorimotor cortex (M1S1) were associated with better motor performance. GABA levels in M1S1 have tended to decrease during the execution of a repeated motor sequence. The dynamic change in GABA density in M1S1 in older adults is currently unknown and represents a critical gap in our understanding of how it could impact motor learning and cognitive performance. As such, the purpose of the current study is to quantify changes in cortical GABA during motor learning in the aging brain and examine those changes in relation to motor and cognitive performance. We hypothesize that older adults with greater dynamic range in M1S1 GABA levels will display more efficient motor learning and increased cognitive scores.

We report on a total of 18 healthy older adults aged 64 to 80 years (M = 70.44, SD = 4.99, 12 females). Using MRS at 3T, we measured changes in GABA concentration in M1S1 at rest, during an eight or 12 finger-movement motor entrainment task, and during a recall task. Gannett was used for GABA quantification relative to water. Change in GABA was calculated by subtracting Rest1 GABA from Recall1 GABA. In a separate session, participants completed a battery of cognitive assessments. We computed linear regressions to examine the relationship between dynamic GABA change, recall accuracy of the motor task and cognitive performance.

In relation to motor performance, we found that both greater baseline (Rest1) GABA levels and greater dynamic change in GABA significantly predicted better recall accuracy on the motor task. For cognitive performance, we found that greater dynamic change in GABA significantly predicted better performance on Word Reading in the Stroop Color and Word Test and Delayed Recall in the Hopkins Verbal Learning Test (HVLT). No additional significant relationships were found for the remaining cognitive assessments.

Older adults who were able to accurately perform the task had a greater dynamic change in GABA and increased baseline GABA levels. These adults with greater dynamic change also had better cognitive performance on HVLT Delay and Stroop Word Reading. This modulation of GABA associated with better performance could be related to changes in neuroplasticity. Although these results are in the preliminary stages, they point to a greater understanding of aging related changes in motor and cognitive performance. We’ll continue to explore the relationship between sensory motor performance and changes in GABA concentration as a potential predictor for cognitive performance and future rehabilitation.

Dentists prescribe 10% of all outpatient antibiotics in the United States and are the top specialty prescriber. Data on current antibiotic prescribing trends are scarce. Therefore, we evaluated trends in antibiotic prescribing rates by dentists, and we further assessed whether these trends differed by agent, specialty, and by patient characteristics.

Retrospective study of dental antibiotic prescribing included data from the IQVIA Longitudinal Prescription Data set from January 1, 2012 to December 31, 2019.

The change in the dentist prescribing rate and mean days’ supply were evaluated using linear regression models.

Dentists wrote >216 million antibiotic prescriptions between 2012 and 2019. The annual dental antibiotic prescribing rate remained steady over time (P = .5915). However, the dental prescribing rate (antibiotic prescriptions per 1,000 dentists) increased in the Northeast (by 1,313 antibiotics per 1,000 dentists per year), among oral and maxillofacial surgeons (n = 13,054), prosthodontists (n = 2,381), endodontists (n = 2,255), periodontists (n = 1,961), and for amoxicillin (n = 2,562; P < .04 for all). The mean days’ supply significantly decreased over the study period by 0.023 days per 1,000 dentists per year (P < .001).

From 2012 to 2019, dental prescribing rates for antibiotics remained unchanged, despite decreases in antibiotic prescribing nationally and changes in guidelines during the study period. However, mean days’ supply decreased over time. Dental specialties, such as oral and maxillofacial surgeons, had the highest prescribing rate with increases over time. Antibiotic stewardship efforts to improve unnecessary prescribing by dentists and targeting dental specialists may decrease overall antibiotic prescribing rates by dentists.

The true incidence and risk factors for secondary bacterial infections in coronavirus disease 2019 (COVID-19) remains poorly understood. Knowledge of risk factors for secondary infections in hospitalized patients with COVID-19 is necessary to optimally guide selective use of empiric antimicrobial therapy.

Single-center retrospective cohort study of symptomatic inpatients admitted for COVID-19 from April 15, 2020, through June 30, 2021.

Academic quaternary-care referral center in Portland, Oregon.

The study included patients who were 18 years or older with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR test up to 10 days prior to admission.

Secondary infections were identified based on clinical, radiographic, and microbiologic data. Logistic regression was used to identify risk factors for secondary infection. We also assessed mortality, length of stay, and empiric antibiotics among those with and without secondary infections.

We identified 118 patients for inclusion; 31 (26.3%) had either culture-proven or possible secondary infections among hospitalized patients with COVID-19. Mortality was higher among patients with secondary infections (35.5%) compared to those without secondary infection (4.6%). Empiric antibiotic use on admission was high in both the secondary and no secondary infection groups at 71.0% and 48.3%, respectively.

The incidence of secondary bacterial infection was moderate among hospitalized patients with COVID-19. However, a higher proportion of patients received empiric antibiotics regardless of an identifiable secondary infection. Transfer from an outside hospital, baseline immunosuppressant use, and corticosteroid treatment were independent risk factors for secondary infection. Additional studies are needed to validate risk factors and best guide antimicrobial stewardship efforts.

Anxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction.

In total, 1937 twins aged 22–25 years, including 538 complete pairs from the Twins Early Development Study took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase, participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase, the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase.

Twin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15, 30 and 15%, respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations 0.4–0.5).

Fear acquisition and extinction are heritable, and share some, but not all of the same genetic influences.

Nutritional rehabilitation in anorexia nervosa (AN) is impeded by fear of food, eating and change leading to treatment resistance. Oxytocin exerts prosocial effects on anxiolysis, fear modulation, trust and brain plasticity.

A placebo-controlled RCT examined the effects of self-administered intranasal oxytocin (IN-OT) in AN patients.

To ascertain whether single and repeated doses of IN-OT enhance treatment in AN.

Female AN patients self-administered twice daily 18IU IN-OT (n = 21) or placebo (n = 21) for 4–6 weeks during hospital treatment. Weight and BMI were measured at baseline and after treatment. The Eating Disorders Examination (EDE) was the primary outcome measure. Cognitive rigidity was compared between groups after four weeks repeated dosing. The effects of the first and last doses of IN-OT versus placebo, on salivary cortisol before a high-energy afternoon snack, were compared.

Weight gain was similar in IN-OT and placebo groups. Only the EDE eating concern subscale score was significantly lower after 4–6 weeks (mean 35 days) of IN-OT (p = 0.006). Anticipatory levels of salivary cortisol fell from baseline after the initial dose in contrast to the placebo group where levels increased. After four weeks IN-OT, salivary cortisol was significantly lower (p = 0.023) overall with little anticipatory increase compared to placebo. There were no differences in anxiety scores. Cognitive rigidity was significantly lower in the IN-OT group (p= 0.043)

Self-administered IN-OT might enhance nutritional rehabilitation in AN by reducing eating concern and cognitive rigidity. Lower salivary cortisol before a high-energy snack, suggests reduction of fear rather than anxiety.

The authors have not supplied their declaration of competing interest.

To explore cross-sectional adherence to cancer prevention recommendations by adults enrolled in a prospective cohort in Alberta, Canada.

Questionnaire data were used to construct a composite cancer prevention adherence score for each participant, based on selected personal recommendations published by the World Cancer Research Fund/American Institute for Cancer Research (2007). Data were self-reported on health and lifestyle, past-year physical activity and past-year FFQ. The scores accounted for physical activity, dietary supplement use, body size, and intakes of alcohol, fruit, vegetables and red meat. Tobacco exposure was also included. Scores ranged from 0 (least adherent) to 7 (most adherent).

Alberta’s Tomorrow Project; a research platform based on a prospective cohort.

Adult men and women (n 24 988) aged 35–69 years recruited by random digit dialling and enrolled in Alberta’s Tomorrow Project between 2001 and 2009.

Of the cohort, 14 % achieved adherence scores ≥5 and 60 % had scores ≤3. Overall adherence scores were higher in women (mean (sd): 3·4 (1·1)) than in men (3·0 (1·2)). The extent of overall adherence was also associated with level of education, employment status, annual household income, personal history of chronic disease, family history of chronic disease and age.

Reported adherence to selected personal recommendations for cancer prevention was low in this cohort of adults. In the short to medium term, these results suggest that more work is required to identify behaviours to target with cancer prevention strategies at a population level. Future work will explore the associations between adherence scores and cancer risk in this cohort.

Concerns relating to increased use of psychotropic medication contrast with those of under-treatment and under-recognition of common mental disorders in children and young people (CYP) across developed countries. Little is known about the indications recorded for antidepressant prescribing in primary care in CYP.

This was an electronic cohort study of routinely collected primary-care data from a population of 1.9 million, Wales, UK. Poisson regression was undertaken to model adjusted counts of recorded depression symptoms, diagnoses and antidepressant prescriptions. Associated indications were explored.

3 58 383 registered patients aged 6–18 years between 1 January 2003 and 31 December 2013 provided a total of 19 20 338 person-years of follow-up. The adjusted incidence of antidepressant prescribing increased significantly [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The majority of new antidepressant prescriptions were for citalopram. Recorded depression diagnoses showed a steady decline (IRR = 0.72) while depression symptoms (IRR = 2.41) increased. Just over half of new antidepressant prescriptions were associated with depression (diagnosis or symptoms). Other antidepressant prescribing, largely unlicensed, was associated with diagnoses such as anxiety and pain.

Antidepressant prescribing is increasing in CYP while recorded depression diagnoses decline. Unlicensed citalopram prescribing occurs outside current guidelines, despite its known toxicity in overdose. Unlicensed antidepressant prescribing is associated with a wide range of diagnoses, and while accepted practice, is often not supported by safety and efficacy studies. New strategies to implement current guidance for the management of depression in CYP are required.