To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin.

Retrospective cohort study.

Community health system.

Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10–14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen.

Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI.

The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07–0.56, p < 0.002).

Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.

Medications with anticholinergic properties are associated with a range of adverse effects that tend to be worse in older people.

To investigate medication regimens with high anticholinergic burden, prescribed for older adults under the care of mental health services.

Clinical audit of prescribing practice, using a standardised data collection tool.

Fifty-seven trusts/healthcare organisations submitted data on medicines prescribed for 7915 patients: two-thirds (66%) were prescribed medication with anticholinergic properties, while just under a quarter (23%) had a medication regimen with high anticholinergic burden (total score ≥3 on the anticholinergic effect on cognition (AEC) scale). Some 16% of patients with a diagnosis of dementia or mild cognitive impairment were prescribed medication regimens with a high anticholinergic burden, compared with 35% of those without such diagnoses. A high anticholinergic burden was mostly because of combinations of commonly prescribed psychotropic medications, principally antidepressant and antipsychotic medications with individual AEC scores of 1 or 2.

Adults under the care of older people's mental health services are commonly prescribed multiple medications for psychiatric and physical disorders; these medication regimens can have a high anticholinergic burden, often an inadvertent consequence of the co-prescription of medications with modest anticholinergic activity. Prescribers for older adults should assess the anticholinergic burden of medication regimens, assiduously check for adverse anticholinergic effects and consider alternative medications with less anticholinergic effect where indicated. The use of a scale, such as the AEC, which identifies the level of central anticholinergic activity of relevant medications, can be a helpful clinical guide.

Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood.

Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications.

There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose–response relationship was observed between levels of CA and severity of outcome domains.

Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.

First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP).

We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach.

A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval −16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery.

Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.

Mild traumatic brain injury (mTBI) is common in children. Long-term cognitive and behavioral outcomes as well as underlying structural brain alterations following pediatric mTBI have yet to be determined. In addition, the effect of age-at-injury on long-term outcomes is largely unknown.

Children with a history of mTBI (n = 406; Mage = 10 years, SDage = 0.63 years) who participated in the Adolescent Brain Cognitive Development (ABCD) study were matched (1:2 ratio) with typically developing children (TDC; n = 812) and orthopedic injury (OI) controls (n = 812). Task-based executive functioning, parent-rated executive functioning and emotion-regulation, and self-reported impulsivity were assessed cross-sectionally. Regression models were used to examine the effect of mTBI on these domains. The effect of age-at-injury was assessed by comparing children with their first mTBI at either 0-3, 4-7, or 8-10 years to the respective matched TDC controls. Fractional anisotropy (FA) and mean diffusivity (MD), both MRI-based measures of white matter microstructure, were compared between children with mTBI and controls.

Children with a history of mTBI displayed higher parent-rated executive dysfunction, higher impulsivity, and poorer self-regulation compared to both control groups. At closer investigation, these differences to TDC were only present in one respective age-at-injury group. No alterations were found in task-based executive functioning or white matter microstructure.

Findings suggest that everyday executive function, impulsivity, and emotion-regulation are affected years after pediatric mTBI. Outcomes were specific to the age at which the injury occurred, suggesting that functioning is differently affected by pediatric mTBI during vulnerable periods. Groups did not differ in white matter microstructure.

The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.

The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions.

About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15–20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome.

The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

Attention is the backbone of cognitive systems and is requisite for many cognitive processes vital to everyday functioning, including memory, problem solving, and the cognitive control of behavior. Attention is commonly impaired following traumatic brain injury and is a critical focus of rehabilitation efforts. The development of reliable methods to assess rehabilitation-related changes are paramount. The Attention Network Test (ANT) has been used previously to identify 3 independent, yet interactive attention networks—alerting, orienting, and executive control (EC). We examined the behavioral and neurophysiological robustness and temporal stability of these networks across multiple sessions to assess the ANT’s potential utility as an effective measure of change during attention rehabilitative interventions.

15 healthy young adults completed 4 sessions of the ANT (1 session/7-day period). ANT networks were assessed within the task by contrasting opposing stimulus conditions: cued vs. non-cued trials probed alerting, valid vs. invalid spatial cues probed orienting, and congruent vs. incongruent targets probed EC. Differences in median correct-trial reaction times (RTs) and error rates (ERs) between the condition pairs were assessed to determine attention network scores; robustness of networks effects, as determined by one-sample t-tests at each session, against a mean of 0, determining the presence of significant network effects at each session. Sixty-four-channel electroencephalography (EEG) data were acquired concurrently and processed using Matlab to create condition-related event-related potentials (ERPs)—particularly the cue- and probe-related P1, N1, and P3 deflection amplitudes, measured by using signed-area calculation in regions of interest (ROIs) determined by observation of spherical-spline voltages. This enabled us to examine the robustness of cue- and probe-attention-network ERPs.

All three attention networks showed robust effects. However, only the EC RT and ER network scores remained significantly robust [t(14)s>13.9,ps<.001] across all sessions, indicating that EC is robust in the face of repeated exposure. Session 1 showed the greatest EC-RT robustness effect which became smaller during the subsequent sessions per ANOVAs on Session x Congruency [F(3,42)=10.21,p<.0001], reflecting persistence despite practice effects. RT robustness of the other networks varied across sessions. Alerting and EC ERs were similarly robust across all 4 sessions, but were more variable for the orienting network. ERP results: The cue-locked P1-orienting (valid vs. invalid) was generally larger to valid- than invalid-cues, but the robustness across sessions was variable (significant in only sessions 1 and 4 [t(14)s>2.13,ps<.04], as reflected in a significant main effect of session [p=.0042]. Next, target-locked EC P3s were generally smaller to congruent than incongruent targets [F(1,14)=9.40,p=.0084], showing robust effects only in sessions 3 and 4 [ps<.005].

The EC network RT and ER scores were consistently robust across all sessions, suggesting that this network may be less vulnerable to practice effects across session than the other networks and may be the most reliable probe of attentional rehabilitation. ERP measures were more variable across attention networks with respect to robustness. Behavioral measures of EC-network may be most reliable for assessing progress related to attentional-rehabilitation efforts.

Repetition priming is a form of implicit memory in which prior exposure to a stimulus facilitates the subsequent processing of that stimulus. While explicit memory has consistently been shown to decline with age, the effect of age on implicit memory remains unresolved. Most studies examining age-related effects on priming have utilized words or pictures of real objects with pre-existing representations that may differentially involve implicit and explicit memory processes across age groups. Repetition priming may also be influenced by attentional processes during encoding that are differentially affected by age. In a previous study using word-stem completion, we found that individual differences in cortical arousal, but not spatial attention, influenced the magnitude and temporal dynamics of conceptual priming in healthy older adults. The objective of this study is to investigate whether cortical arousal and spatial attention play differential roles in the magnitude and temporal dynamics of repetition priming in young and older adults using novel shapes that do not have pre-existing representations within memory.

Healthy young (n=25, M age=19.4) and older adults (n=54, M age=70.0) completed a perceptual repetition priming task that was followed by a recognition memory test and an alerting/spatial orienting task from which behavioral measures of cortical arousal and spatial attention were derived. Older adults also completed a battery of neuropsychological tests. In the perceptual priming task, participants made a speeded judgment on whether novel nonverbal shapes had “closed” or “open” perimeters. Each shape was presented twice: half following the first presentation (immediate repetition) and half after three intervening items (delayed repetition). Participants were then shown closed and open versions of each shape and asked to identify which version was presented in the previous task. In the alerting/orienting task, participants made a speeded response to the location of a visual target; on a subset of trials, either nonspatial alerting or spatial orienting cues were presented 300ms prior to the target.

Response times were slower and judgment accuracy greater in older adults (ps<0.05). However, the groups showed comparable levels of immediate and delayed repetition priming along with chance levels of recognition memory accuracy. Cortical arousal was reduced (p<0.001) and costs associated with spatial attention were larger (p<0.01) in the older adults. Despite comparable priming, cortical arousal and spatial attention were differentially related to priming across groups. In the young group, lower cortical arousal was associated with greater delayed priming (r=-.47, p=0.017) and slower decay rate (r=.44, p=0.03). In the older group, higher cost of spatial orienting was associated with greater immediate priming (r=.40, p=0.003) and faster decay rate (r=.29, p=0.03). Better category fluency performance was also associated with greater immediate priming (r=.32, p=0.035) and faster decay rate (r=.34, p=0.025) in older adults.

These findings suggest that different attentional systems support repetition priming across age groups. Priming is modulated by the efficiency of cortical arousal in young adults, but by the costs of spatial attention in older adults with reduced cortical arousal, consistent with a shift from bottom-up to top-down attentional processes and broader attentional scope with age.

Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change.

This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories.

The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed.

FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions.