To evaluate the potential sources and current screening strategies for the multidrug-resistant fungal pathogen Candida auris in the US Military Health System (MHS).

Utilizing the Multidrug-Resistant Organism Repository and Surveillance Network (MRSN), 6 instances of C. auris colonization or infection were identified within the MHS in 2024. Relevant medical and social history, drug susceptibilities, and next-generation genetic sequencing were obtained from MRSN and the electronic medical record. Hospital screening protocols for C. auris were reviewed in the affected facilities.

One case of C. auris infection and 5 cases of C. auris colonization in 2024 were identified in the MHS. Only 1 case of colonization was likely related to international travel; 5 patients had no recent travel history before infection or colonization. One patient was an active duty service member. Prior hospitalizations and infections were the most common risk factors present in each case. Two isolates had antimicrobial susceptibilities analyzed, both of which suggested resistance to fluconazole. Two of the 3 facilities had C. auris screening protocols in place to screen select individuals with risk factors; however, only 1 of the 6 cases presented was identified through these screening protocols. No cases of nosocomial transmission were found.

C. auris remains a formidable threat to the MHS, with 6 cases identified in 3 treatment facilities, with 2 isolates demonstrating resistance to azoles. Screening protocols should reflect the domestic and international threats of this pathogen.

The development of guidelines is time-consuming and cost-intensive. The heterogeneity of clinical practice, evidence, and patients’ needs is an issue across Europe. An European core guidance for a specific psychiatric disorder may help to overcome this issue. Here, we present a progress report on the European Psychiatric Association (EPA) proof-of-concept approach to develop a European consensus guidance on the pharmacological treatment of schizophrenia.

All national psychiatric associations in Europe were contacted to provide their schizophrenia guidelines. Six guidelines were rated by three experts, experienced in the development of national and international guidelines, from three different countries (Italy, Hungary, and Germany), and the German schizophrenia guideline published in 2019 was found to have the highest quality. For this proof-of-concept approach, 45 recommendations on the pharmacological treatment of schizophrenia from the German guideline were evaluated in a two-step Delphi process to determine their acceptability throughout the European continent.

44 experts participated in the first round and 40 experts in the second round of the Delphi process. Agreement among the involved experts was reached for 75% of the presented recommendations from the German schizophrenia guidelines. 11 out of 45 recommendations (24.4%) did not reach this level of agreement.

This progress report highlights the possibility of developing a pan-European core guidance on the pharmacological treatment of schizophrenia by adapting national guidelines and reconciling their recommendations. However, several barriers in this adaptation process, such as non-agreement in recommendations with strong scientific evidence in the reconciling process, were identified and must be considered when developing the final guidance.

In RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.

Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).

334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.

TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.

Teva Branded Pharmaceutical Products R&D Inc.

Study Registration Number: NCT03893825

Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.

A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.

Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.

The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).

Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.

pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).

Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.

To determine the association between in-vivo spectroscopy metabolite data, the local connectome, and markers of initial injury severity (I.e., history of loss of consciousness; LoC) in traumatic brain injury (TBI), in a heterogenous sample of Veterans and non-Veterans with a history of remote mild-to-moderate TBI (I.e., >6 months).

Participants with complete PRESS magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) data (N = 41) were sampled from a larger multisite study of chronic mild-to-moderate TBI (Nmiid = 38; Nmoderate = 3; 54% with LoC; 46% with multiple TBI). The sample was predominantly male (76%) with ages ranging from 23-59 (M = 36.9, SD = 10.1), with 98% holding at least a high school degree (M = 14.5 years of education, SD = 2.4). Fully tissue-and-relaxation-corrected metabolite concentration estimates in the dorsal anterior cingulate (30x30x30mm voxel) were modeled using Osprey 2.4.0. Total creatine (tCr), total choline (tCho), total N-acetylaspartate (tNAA), glutamate/glutamine (Glx), and myo-inositol (mI) were analyzed. Logistic regression was used to measure the association between metabolites and history of TBI with LoC. Correlational connectometry using the normalized spin distribution function was performed for metabolites associated with LoC, to characterize the local connectome associated with metabolites of interest, controlling for age and sex, and correcting for multiple comparisons (FDR < .050 with 4000 permutations). A profile approach was used to interpret diffusion metrics, contrasting quantitative anisotropy (QA) with fractional anisotropy (FA). Local connectome tracks were then clustered to identify the larger white matter tract.

Glx (p = .008) and tCr (p = .032) were significantly associated with history of TBI with LoC. Increased Glx was associated with increased QA in 11,001 tracks, accounting for 1.4% of the total white matter tracks in the brain. 90% of tracks were identified in bilateral cingulum (33%), bilateral thalamic (13%), bilateral corticospinal (13%), corpus callosum (12%), left arcuate fasciculus (9%), left frontoparietal aslant tracts (6%), and bilateral inferior fronto-occipital fasciculus (4%) tracts. In contrast, FA was not associated with Glx. The same pattern emerged for tCr, with 10,542 tracks identified predominantly in bilateral cingulum (29%), corpus callosum (21%), bilateral corticospinal (15%), bilateral corticostriatal (7%), bilateral medial lemniscus (7%), left cortico-pontine (3%), left thalamic (2%), and bilateral superior longitudinal fasciculus (2%) tracts. Post-hoc exploratory analyses of mean QA across regions of cingulum found that increased QA was associated with self-report measures of headache intensity, fatigue, and perceived change in executive functioning.

Results provided evidence that multimodal imaging can identify subtle markers of initial TBI severity years after injury. Neurometabolite concentrations were associated with diffuse changes in the local connectome; the pattern of discrepancy between FA and QA was suggestive of reduced potential for neuroplasticity. Exploratory analyses further indicated that variability in white matter density in the cingulum, an important connection for limbic regions, was associated with a range of problems commonly reported in clinical settings, which may be informative for diagnosis and treatment planning.

Determine associations between cognitive outcomes in remote TBI (i.e., at least 6 months post injury), a blood marker of neural degeneration (i.e., Tau), and diffusion kurtosis imaging (DKI) measures (e.g., mean or radial kurtosis). Because DKI imaging is sensitive to the environmental complexity of the imaged area, we sought to investigate regions known to be associated with the cognitive and emotional sequalae of TBI, such as the anterior thalamic radiations, uncinate fasciculus, and the corpus callosum.

41 individuals with mild-to-moderate TBI and a mean age(SD) of 36.1(10.4) years underwent DKI, a blood draw, and neuropsychological assessments. 23 healthy controls (HC) with a mean age(SD) of 35.2(15.2) years underwent the blood draw and assessments, but no imaging. Higher diffusion kurtosis indicates more restricted diffusion, possibly due to greater complexity within the imaged region. Thus, in the context of TBI, DKI can be used as a proxy measurement for biological processes that alter the complexity of imaged environments, such as reactive gliosis. Some people show cognitive deficits long after TBI and this could be associated with increased inflammation and membrane protein aggregates in damaged brain regions. We used bivariate correlations and general linear models to investigate the association of mean kurtosis (MK) in long white matter tracts and Tau (total or phosphorylated) to color-word Stroop scores; a measure of fronto-subcortical function.

In patients with TBI, MK was significantly associated with serum total Tau (TTau) in the right (r=-0.396) and left (r=-0.555) uncinate fasciculus (UF), right (r=-0.402) and left (r=-0.504) anterior thalamic radiations (ATR), and the genu (r=-0.526) and body (r=-0.404) of the corpus callosum (CC). TTau had a significant association with word Stroop scores, F(1,63)=-2.546, p=0.013. However, there was no significant effect of group (i.e., TBI or HC), F(2,63)=-0.426, p=0.672, on cognitive performance. When models were implemented that included both TTau and MK in either the UF or ATR as explanatory variables to predict word Stroop scores, TTau levels and MK in the right UF explained a significant amount of the variance in Stroop performance, F(1,29)=2.215, p=0.025. Further, there was also a significant association between radial kurtosis in the right UF and Stroop word scores (r= 0.366).

Our results show that an indicator of biological complexity (DKI) in cognitively important brain regions is associated with cognitive performance and Tau in patients with remote mild-to-moderate TBI. The UF is a critical fronto-temporal/subcortical pathway that has previously been implicated in the manifestation of executive dysfunction and mood dysregulation in TBI. Tau is an important marker of neurodegeneration implicated in Alzheimer’s disease, Parkinson’s disease, and chronic traumatic encephalopathy (CTE), and DKI is potentially sensitive to markers of neurodegeneration. The association of Tau and DKI measures is novel and shows concordance between blood and brain imaging markers and cognitive performance in patients with mild to moderate TBI.

To measure the impact of an automated hand hygiene monitoring system (AHHMS) and an intervention program of complementary strategies on hand hygiene (HH) performance in both acute-care and long-term care (LTC) units.

Prospective, nonrandomized, before-and-after intervention study.

Single Veterans Affairs Medical Center (VAMC), with 2 acute-care units and 6 LTC units.

An AHHMS that provides group HH performance rates was implemented on 8 units at a VAMC from March 2021 through April 2022. After a 4-week baseline period and 2.5-week washout period, the 52-week intervention period included multiple evidence-based components designed to improve HH compliance. Unit HH performance rates were expressed as the number of dispenses (events) divided by the number of patient room entries and exits (opportunities) × 100. Statistical analysis was performed with a Poisson general additive mixed model.

During the 4-week baseline period, the median HH performance rate was 18.6 (95% CI, 16.5–21.0) for all 8 units. During the intervention period, the median HH rate increased to 21.6 (95% CI, 19.1–24.4; P < .0001), and during the last 4 weeks of the intervention period (exactly 1 year after baseline), the 8 units exhibited a median HH rate of 25.1 (95% CI, 22.2–28.4; P < .0001). The median HH rate increased from 17.5 to 20.0 (P < .0001) in LTC units and from 22.9 to 27.2 (P < .0001) in acute-care units.

The intervention was associated with increased HH performance rates for all units. The performance of acute-care units was consistently higher than LTC units, which have more visitors and more mobile veterans.

To determine how engagement of the hospital and/or vendor with performance improvement strategies combined with an automated hand hygiene monitoring system (AHHMS) influence hand hygiene (HH) performance rates.

Prospective, before-and-after, controlled observational study.

The study was conducted in 58 adult and pediatric inpatient units located in 10 hospitals.

HH performance rates were estimated using an AHHMS. Rates were expressed as the number of soap and alcohol-based hand rub portions dispensed divided by the number of room entries and exits. Each hospital self-assigned to one of the following intervention groups: AHHMS alone (control group), AHHMS plus clinician-based vendor support (vendor-only group), AHHMS plus hospital-led unit-based initiatives (hospital-only group), or AHHMS plus clinician-based vendor support and hospital-led unit-based initiatives (vendor-plus-hospital group). Each hospital unit produced 1–2 months of baseline HH performance data immediately after AHHMS installation before implementing initiatives.

Hospital units in the vendor-plus-hospital group had a statistically significant increase of at least 46% in HH performance compared with units in the other 3 groups (P ≤ .006). Units in the hospital only group achieved a 1.3% increase in HH performance compared with units that had AHHMS alone (P = .950). Units with AHHMS plus other initiatives each had a larger change in HH performance rates over their baseline than those in the AHHMS-alone group (P < 0.001).

AHHMS combined with clinician-based vendor support and hospital-led unit-based initiatives resulted in the greatest improvements in HH performance. These results illustrate the value of a collaborative partnership between the hospital and the AHHMS vendor.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.

The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.

MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.

Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.

MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.

Determine the impact of an automated hand hygiene monitoring system (AHHMS) plus complementary strategies on hand hygiene performance rates and healthcare-associated infections (HAIs).

Retrospective, nonrandomized, observational, quasi-experimental study.

Single, 93-bed nonprofit hospital.

Hand hygiene compliance rates were estimated using direct observations. An AHHMS, installed on 4 nursing units in a sequential manner, determined hand hygiene performance rates, expressed as the number of hand hygiene events performed upon entering and exiting patient rooms divided by the number of room entries and exits. Additional strategies implemented to improve hand hygiene included goal setting, hospital leadership support, feeding AHHMS data back to healthcare personnel, and use of Toyota Kata performance improvement methods. HAIs were defined using National Healthcare Safety Network criteria.

Hand hygiene compliance rates generated by direct observation were substantially higher than performance rates generated by the AHHMS. Installation of the AHHMS without supplementary activities did not yield sustained improvement in hand hygiene performance rates. Implementing several supplementary strategies resulted in a statistically significant 85% increase in hand hygiene performance rates (P < .0001). The incidence density of non–Clostridioies difficile HAIs decreased by 56% (P = .0841), while C. difficile infections increased by 60% (P = .0533) driven by 2 of the 4 study units.

Implementation of an AHHMS, when combined with several supplementary strategies as part of a multimodal program, resulted in significantly improved hand hygiene performance rates. Reductions in non–C. difficile HAIs occurred but were not statistically significant.