Evaluate the association between provider-ordered viral testing and antibiotic treatment practices among children discharged from an ED or hospitalized with an acute respiratory infection (ARI).

Active, prospective ARI surveillance study from November 2017 to February 2020.

Pediatric hospital and emergency department in Nashville, Tennessee.

Children 30 days to 17 years old seeking medical care for fever and/or respiratory symptoms.

Antibiotics prescribed during the child’s ED visit or administered during hospitalization were categorized into (1) None administered; (2) Narrow-spectrum; and (3) Broad-spectrum. Setting-specific models were built using unconditional polytomous logistic regression with robust sandwich estimators to estimate the adjusted odds ratios and 95% confidence intervals between provider-ordered viral testing (ie, tested versus not tested) and viral test result (ie, positive test versus not tested and negative test versus not tested) and three-level antibiotic administration.

4,107 children were enrolled and tested, of which 2,616 (64%) were seen in the ED and 1,491 (36%) were hospitalized. In the ED, children who received a provider-ordered viral test had 25% decreased odds (aOR: 0.75; 95% CI: 0.54, 0.98) of receiving a narrow-spectrum antibiotic during their visit than those without testing. In the inpatient setting, children with a negative provider-ordered viral test had 57% increased odds (aOR: 1.57; 95% CI: 1.01, 2.44) of being administered a broad-spectrum antibiotic compared to children without testing.

In our study, the impact of provider-ordered viral testing on antibiotic practices differed by setting. Additional studies evaluating the influence of viral testing on antibiotic stewardship and antibiotic prescribing practices are needed.

Social connection is associated with better health, including reduced risk of dementia. Personality traits are also linked to cognitive outcomes; neuroticism is associated with increased risk of dementia. Personality traits and social connection are also associated with each other. Taken together, evidence suggests the potential impacts of neuroticism and social connection on cognitive outcomes may be linked. However, very few studies have simultaneously examined the relationships between personality, social connection and health.

We tested the association between neuroticism and cognitive measures while exploring the potential mediating roles of aspects of social connection (loneliness and social isolation).

We conducted a cross-sectional study with a secondary analysis of the Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort, a sample of Canadians aged 45 to 85 years at baseline. We used only self-reported data collected at the first follow-up, between 2015 and 2018 (n= 27,765). We used structural equation modelling to assess the association between neuroticism (exposure) and six cognitive measures (Rey Auditory Verbal Learning Test immediate recall and delayed recall, Animal Fluency Test, Mental Alternation Test, Controlled Oral Word Association Test and Stroop Test interference ratio), with direct and indirect effects (through social isolation and loneliness). We included age, education and hearing in the models and stratified all analyses by sex, females (n= 14,133) and males (n=13,632).

We found positive, statistically significant associations between neuroticism and social isolation (p<0.05) and loneliness (p<0.05), for both males and females. We also found inverse, statistically significant associations between neuroticism and all cognitive measures (p<0.05), except the Stroop Test interference ratio. In these models, there was consistent evidence of indirect effects (through social isolation and loneliness) and, in some cases, evidence of direct effects. We found sex differences in the model results.

Our findings suggest that the association between neuroticism and cognitive outcomes may be mediated by aspects of social connection and differ by sex. Understanding if and how modifiable risk factors mediate the association between personality and cognitive outcomes would help develop and target intervention strategies that improve social connection and brain health.

To compare the agreement and cost of two recall methods for estimating children’s minimum dietary diversity (MDD).

We assessed child’s dietary intake on two consecutive days: an observation on day one, followed by two recall methods (list-based recall and multiple-pass recall) administered in random order by different enumerators at two different times on day two. We compared the estimated MDD prevalence using survey-weighted linear probability models following a two one-sided test equivalence testing approach. We also estimated the cost-effectiveness of the two methods.

Cambodia (Kampong Thom, Siem Reap, Battambang, and Pursat provinces) and Zambia (Chipata, Katete, Lundazi, Nyimba, and Petauke districts).

Children aged 6–23 months: 636 in Cambodia and 608 in Zambia.

MDD estimations from both recall methods were equivalent to the observation in Cambodia but not in Zambia. Both methods were equivalent to the observation in capturing most food groups. Both methods were highly sensitive although the multiple-pass method accurately classified a higher proportion of children meeting MDD than the list-based method in both countries. Both methods were highly specific in Cambodia but moderately so in Zambia. Cost-effectiveness was better for the list-based recall method in both countries.

The two recall methods estimated MDD and most other infant and young child feeding indicators equivalently in Cambodia but not in Zambia, compared to the observation. The list-based method produced slightly more accurate estimates of MDD at the population level, took less time to administer and was less costly to implement.

Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring.

To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK.

We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment.

We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally.

Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.

Primary surgical resection remains the mainstay of management in locally advanced differentiated thyroid cancer. Tyrosine kinase inhibitors have recently shown promising results in patients with recurrent locally advanced differentiated thyroid cancer. This study discussed four patients with locally advanced differentiated thyroid cancer managed with tyrosine kinase inhibitors used prior to surgery in the ‘neoadjuvant’ setting.

Prospective data collection through a local thyroid database from February 2016 identified four patients with locally advanced differentiated thyroid cancer unsuitable for primary surgical resection commenced on neoadjuvant tyrosine kinase inhibitor therapy.

All cases had T4a disease at presentation. Three cases tolerated tyrosine kinase inhibitor therapy for more than 14 months while the last case failed to tolerate treatment at 1 month. All patients subsequently underwent total thyroidectomy to facilitate adjuvant radioactive iodine treatment. Disease-specific survival remains at 100 per cent currently (range, 29–75 months).

Neoadjuvant tyrosine kinase inhibitors in locally advanced differentiated thyroid cancer can be effective in reducing primary tumour extent to potentially facilitate a more limited surgical resection for local disease control.

Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an exciting opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks.

To describe the amount of data collected during a multimodal longitudinal RMT study, in an MDD population.

RADAR-MDD is a multi-centre, prospective observational cohort study. People with a history of MDD were provided with a wrist-worn wearable, and several apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks and cognitive assessments and followed-up for a maximum of 2 years.

A total of 623 individuals with a history of MDD were enrolled in the study with 80% completion rates for primary outcome assessments across all timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. Data availability across all RMT data types varied depending on the source of data and the participant-burden for each data type. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. 110 participants had > 50% data available across all data types, and thus able to contribute to multiparametric analyses.

RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible.

No significant relationships.

To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.

In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.

Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.

343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.

Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.

Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.

Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.

In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.

Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).

343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.

These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.

Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA

Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel