Distinguishing viral versus bacterial lower respiratory tract infection (LRTI) is challenging. We previously developed a rapid, host response-based test (Biomeme HR-B/V assay) using peripheral blood samples to identify viral versus bacterial infection. We assessed the performance of this assay when using nasopharyngeal (NP) samples.

Patients with LRTI were enrolled, and a NP swab sample was run using the HR-B/V assay (assessing 24 gene targets) on the FranklinTM platform. The performance of the prior classifier at identifying viral versus bacterial infection was assessed. A novel predictive model was generated for NP samples using the same 24 targets. Results were validated using external datasets with nasal/NP RNA sequence data.

Nineteen patients (median age 62 years, 52.1% male) were included. When using the prior HR-B/V classifier on NP samples of 19 patients with LRTI (12 viral, 7 bacterial), the area under the receiver operator curve (AUC) for viral versus bacterial infection was 0.786 (0.524–1), with accuracy 0.79 (95% CI 0.57–0.91), positive percent agreement (PPA) 0.43 (95% CI 0.16–0.75), and negative percent agreement (NPA) 1.00 (95% CI 0.76–1). The novel model had AUC 0.881 (95% CI 0.726–1), accuracy 0.84 (95% CI 0.62–0.94), PPA 0.86 (95% CI 0.49–0.97), and NPA 0.83 (95% CI 0.55–0.95) for bacterial infection. Validation in two external datasets showed AUC of 0.932 (95% CI 0.90–0.96) and 0.915 (95% CI 0.88–0.95).

We show that host response in the nasopharynx can distinguish viral versus bacterial LRTI. These findings need to be replicated in larger cohorts with diverse LRTI etiologies.

Everyday functional capacity in older adults is influenced by several factors, with prior studies finding that cognition mediates the relationship between depression and everyday functioning. However, these studies utilized samples with low depression severity and used only one type of functional assessment. We aimed to examine whether cognition mediates the relationship between depression and functioning in older adults with a history of treatment-resistant depression.

Data from 383 participants enrolled in the OPTIMUM Neuro study were analyzed. Participants completed a neuropsychological assessment battery, depression severity interview, self-/informant-rated functioning measures and a performance-based functioning measure. Linear regression was used to determine whether depression scores predicted cognitive domain and everyday functioning scores. Cognitive domain scores predicted by depression were then tested as mediators between depression and functioning.

Higher depression symptoms predicted poorer performance on all measures of functioning as well as the cognitive domains of attention, executive functioning, and immediate memory. Immediate memory partially mediated the relationship between depression and a performance-based measure of functioning, while attention and executive functioning partially mediated the relationship between a self-report measure of functioning and depression.

The relationship between depression severity and poorer functional performance was partially mediated by attention, executive functioning, and immediate memory, with results differing based on the measure of functioning used. Our findings suggest that there may be additional non-cognitive factors influencing this relationship and highlight the importance of using multiple methods to assess functional performance.

This study aimed to evaluate the role of oral antibiotic stepdown therapy in patients with uncomplicated streptococcal bacteremia. Streptococcus species are known pathogens in bloodstream infections (BSIs). Traditionally, BSIs were managed with intravenous (IV) antibiotics; however, growing literature supports oral antibiotics in invasive infections including BSIs.

This was a retrospective cohort study evaluating patients with streptococcal bacteremia between September 2019 and September 2021 at an academic safety-net hospital. Clinical outcomes were compared between patients completing treatment with IV antibiotics versus an oral stepdown regimen. The primary outcome, clinical failure, was a composite of BSI recurrence and infection-related readmission.

Adult patients with at least one positive blood culture for any Streptococcus species were included. Patients with polymicrobial BSIs or complicated bacteremia were excluded.

155 patients were included, 77 (49.7%) received a course of IV antibiotics and 78 (50.3%) received an oral antibiotic stepdown regimen. Clinical failure was not different between the IV and oral groups (15.6% vs. 15.4%, respectively; OR .99 [95% CI, .41 to 2.35]). No differences were observed in 30-day all-cause mortality. Patients that received oral antibiotics had a significantly shorter hospital length of stay by 6 days (6 vs 12 d, p < .01).

Our results suggest that an oral stepdown regimen for uncomplicated streptococcal BSIs is associated with similar outcomes compared to IV antibiotics. Furthermore, oral antibiotics may offer reduced length of stay and avoidance of outpatient central line placement in patients with uncomplicated streptococcal BSIs.

Species of the Burkholderia (B.) cepacia complex (Bcc) have been implicated in multiple nosocomial outbreaks linked to contaminated water-based products, including liquid soaps, mouthwash, and other non-alcoholic aqueous solutions.

We describe two substantial healthcare-associated outbreaks of Bcc (B. cepacia and B. contaminans) in the United Kingdom and Ireland associated with contaminated products. We highlight the challenges during investigation and mitigation, and provide recommendations.

A multidisciplinary, multi-stakeholder investigation across both outbreaks was adopted, involving interviews, trawling questionnaires, and targeted product sampling.

There were 153 and 66 confirmed cases in the B. cepacia and B. contaminans outbreaks, respectively. Cases predominantly comprised hospitalized individuals, and 70% of isolates were recovered from an invasive site. The outbreak strain of B. cepacia was isolated from non-sterile ultrasound gel. An analytical study suggested the B. contaminans cluster was also linked to ultrasound gel; however, a disinfectant wipe product was subsequently identified as the source (0–3 single nucleotide polymorphism differences between case and wipe isolates).

The affected disinfectant wipes were withdrawn. The ultrasound gel was not recalled but health system procurement was suspended, rapid clinical guidance was produced and a National Patient Safety Alert was issued. Inter-organizational partnership was required to mitigate risks.

Identifying the source of outbreaks associated with contaminated products can be challenging, requiring complex multi-stakeholder interventions. We recommend a low threshold for investigation of Bcc clusters, adopting a multidisciplinary approach to investigation and mitigation, implementing interventions focusing on practice, and prompt product removal to protect patients.

Older adults with treatment-resistant depression (TRD) can be treated with augmentation or switched to a different drug.

We aimed to identify factors that moderate the effectiveness of these strategies on treatment outcomes to guide the selection of the optimal strategy for each patient.

We analyzed data from 742 older adults with TRD in the Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) clinical trial. All participants were randomized to one of two treatment strategies, which were augmentation with aripiprazole, bupropion, or lithium; or switching to bupropion or nortriptyline. Treatment outcomes were change in MADRS scores and remission after 10 weeks. Age, burden of comorbid physical illness, number of adequate previous antidepressant trials, presence of executive cognitive impairment, and clinically relevant comorbid anxiety were examined as potential moderators of the effect of the two treatment strategies (augmentation vs. switching) on treatment outcomes.

Overall, augmentation produced more improvement in MADRS scores and produced a higher rate of remission than switching. For change in MADRS scores after 10 weeks of treatment, the number of adequate previous antidepressant trials was the only significant moderator of the superiority of augmentation over switching (b = -1.6, t = -2.1, p = 0.033, 95%CI [-3.0,-0.1]). There were no significant moderators for remission.

Older patients with TRD with less than three previous antidepressant trials benefit more from augmentation than from switching. Future studies validating this finding with different drugs in more diverse samples can facilitate their application in real world settings.

H. Kim Grant / Research support from: Dr. Kim reports grant support from the PSI foundation (R23-21). She is supported by the Canadian Institutes of Health Research (CIHR) and the Temerty Faculty of Medicine (Chisholm Memorial Fellowship)., J. Karp: None Declared, H. Lavretsky Grant / Research support from: Dr. Lavretsky received support from grants (K24 AT009198, R01 AT008383, and R01 MH114981) from the NIH., D. Blumberger Grant / Research support from: Dr. Blumberger reports grants from Canadian Institutes of Health Research (CIHR) and the Temerty family through the Centre for Addiction and Mental Health (CAMH) Foundation during the conduct of the study; nonfinancial support from Magventure (in-kind equipment support for investigator-initiated research); grants from Brainsway (principal investigator of an investigator-initiated study and site principal investigator for sponsored clinical trials), National Institutes of Health (NIH), Brain Canada Foundation, Campbell Family Research Institute, and Patient-Centered Outcomes Research Institute outside the submitted work; received medication supplies for an investigator-initiated trial from Indivior; and has participated in advisory boards for Janssen and Welcony., P. Brown Grant / Research support from: Dr. Brown received additional support from the National Institute of Mental Health OPTIMUM NEURO grant (5R01MH114980)., A. Flint Grant / Research support from: Dr. Flint has received grant support from the US National Institutes of Health, the Patient-Centered Outcomes Research Institute, the Canadian Institutes of Health Research, Brain Canada, the Ontario Brain Institute, and Alzheimer’s Association., E. Lenard: None Declared, P. Miller: None Declared, C. Reynolds Shareolder of: Dr. Reynolds receives payment from the American Association of Geriatric Psychiatry as Editor-in-Chief of the American Journal of Geriatric Psychiatry and royalty income for intellectual property as co-inventor of the Pittsburgh Sleep Quality Index., S. Roose: None Declared, E. Lenze Grant / Research support from: Dr. Lenze received additional support from the Taylor Family Institute for Innovative Psychiatric Research at Washington University School of Medicine, as well as the Washington University Institute of Clinical and Translational Sciences grant (UL1TR002345) from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH)., B. Mulsant Grant / Research support from: Dr. Mulsant received additional support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives or has received during the past three years research support from Brain Canada, the CAMH Foundation, the Canadian Institutes of Health Research, and the US National Institutes of Health (NIH); Capital Solution Design LLC (software used in a study funded by CAMH Foundation), and HAPPYneuron (software used in a study funded by Brain Canada).

Immediate physical assessment and management of patients on psychiatric wards who have been ligaturing is not standardised across the UK. There is little published research or literature on what is needed in terms of medical input and these incidents are usually initially assessed/managed by non-medical staff who are on site at the time of any such incidents. Within CWP NHS Foundation Trust, we have local guidelines (SOP 13 ‘The Management of ligatures in Mental Health and Learning Disability Services’) advising that any inpatient on the adult/older adult psychiatry wards who has ligatured should be seen by a doctor for a medical review,

To review a sample of recorded inpatient ligature incidents to see if Trust guidelines were being adhered to. We hope to use the findings from this audit to review the current guidelines and assess whether or not the additional medical reviews add to or change clinical management already instigated by ward staff. This may be more of an issue when medical staff cover is limited e.g. out of hours.

We accessed recorded ligaturing incidents on adult and older adult inpatient psychiatry wards across our Trust (accessing the ‘Datix’ reporting system) from the period starting 1st January 2022 to 31st May 2024. In total, there were 1127 and we took a sample of 112 picked using a random number generator. We reviewed the documentation from the incident to confirm how many had had a medical review after the incident, how long after the incident they were seen and whether or not the medical review had changed management following the incident.

Approximately 50% of patients had had a medical review post ligature incident. Approximately 4% of patient ligaturing (5/112) or 9% of those who received a medical review (5/55) had new management instigated as a result of the medic review. On review of these cases, there was limited medical input needed including application of steristrips for wound care and asking for ambulance transfer to acute hospital for CT head following seizure after ligaturing. There were no serious harm outcomes from the patients we reviewed in our sample.

Whether or not the we can review guidlines can be reviewed in light of the data is to be discussed following presentation of our results to the Trust. It appears that the initial managment plan, instigated by ward staff, has usually been appropriate and when additional input has been given by the medic on site at review, this has not been felt to have been critical in optimising patient safety. It would still be possible for a medic to review patients when felt by ward staff to be necessary even if guidelines were changed to suggest it was not mandatory for patients to be seen by a medic.

None Declared

Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

To understand the scenarios where health care worker (HCW) masking is most impactful for preventing nosocomial transmission.

A mathematical agent-based model of nosocomial spread with masking interventions. Masking adherence, community prevalence, disease transmissibility, masking effectiveness, and proportion of breakroom (unmasked) interactions were varied. The main outcome measure is the total number of nosocomial infections in patients and HCW populations over a simulated three-month period.

HCW masking around patients and universal HCW masking reduces median patient nosocomial infections by 15% and 18%, respectively. HCW-HCW interactions are the dominant source of HCW infections and universal HCW masking reduces HCW nosocomial infections by 55%. Increasing adherence shows a roughly linear reduction in infections. Even in scenarios where a high proportion of interactions are unmasked “breakroom” interactions, masking is still an effective tool assuming adherence is high outside of these areas. The optimal scenarios where masking is most impactful are those where community prevalence is at a medium level (around 2%) and transmissibility is high.

Masking by HCWs is an effective way to reduce nosocomial transmission at all levels of mask effectiveness and adherence. Increases in adherence to a masking policy can provide a small but important impact. Universal HCW masking policies are most impactful should policymakers wish to target HCW infections. The more transmissible a variant in circulation is, the more impactful HCW masking is for reducing infections. Policymakers should consider implementing masking at the point when community prevalence is optimum for maximum impact.

To assess whether antibiotic duration (AD) and one-year antibiotic-free days (AFD) are associated with key in-hospital and post-discharge outcomes among critically ill adults.

Prospective observational study.

611-bed, quaternary care academic medical center in the United States.

126 critically ill adults (mean age 68.1 ± 15.6 yr, 51.6% male, median APACHE II score 20.5 [IQR 15–25]); 71.4% met sepsis criteria.

Secondary infection was defined as ≥3 consecutive antibiotic days within a year after the index sepsis admission. Multivariate analyses adjusted for age, APACHE II score, BMI, and glucocorticosteroid dose. Time-to-event analysis employed Cox proportional hazards modeling; cumulative infection burden was assessed via nonparametric tests using normalized antibiotic exposure (AD as a proportion of days alive).

Within 30 days, longer AD correlated with increased hospital stay; each additional antibiotic day added ∼0.93 hospital days (P < 0.001) in adjusted linear regression. AD did not predict one-year mortality (OR 1.01, P = 0.739) or readmission (OR 1.01, P = 0.771). Normalized antibiotic exposure significantly differed by cumulative secondary infection episodes (P = 0.0033), with higher exposure among patients experiencing two or more secondary infections (P = 0.026 and P = 0.036, respectively). Cox regression showed a significant association between AD and time to first secondary infection (HR 1.10, 95% CI: 1.04–1.15, P = 0.001), indicating that longer AD predisposed to secondary infection or recurrent antibiotic use.

Extended AD, in critically ill patients, prolongs hospitalization without reducing mortality or readmission rates. These findings highlight the importance of robust antibiotic stewardship practices, where shorter, targeted regimens may minimize unintended complications.