Implementation of the Modified Brain Injury Guidelines Might Be Feasible and Cost-Effective Even in a Nontrauma Hospital.

INTRODUCTION: The modified Brain Injury Guidelines (mBIG) provide a framework to stratify traumatic brain injury (TBI) patients based on clinical and radiographic factors in level 1 and 2 trauma centers. Approximately 75% of all U.S. hospitals do not carry any trauma designation yet could also benefit from these guidelines. To the best of our knowledge, this is the first report of applying the mBIG protocol in a community hospital without any trauma designation. METHODS: All adult patients with a TBI in a single center from 2020 to 2022 were retrospectively classified into mBIG categories. The primary outcomes included neurological deterioration, progression on computed tomography of the head, and surgical intervention. Additional outcomes included the hospital costs incurred by the mBIG 1 and mBIG 2 groups. RESULTS: Of the 116 included patients, 35 (30%) would have stratified into mBIG 1, 23 (20%) into mBIG 2, and 58 (50%) into mBIG 3. No patient in mBIG 1 had a decline in neurological examination findings or progression on computed tomography of the head or required neurosurgical intervention. Three patients in mBIG 2 had radiographic progression and one required surgical decompression. Two patients in mBIG 3 demonstrated a neurological decline and six had radiographic progression. Of the 21 patients who received surgical intervention, 20 were stratified into mBIG 3. Implementation of the mBIG protocol could have reduced costs by >$250,000 during the 2-year period. CONCLUSIONS: The mBIG protocol can safely stratify patients in a nontrauma hospital. Because nontrauma centers tend to see more patients with minor TBIs, implementation could result in significant cost savings, reduce unnecessary hospital and intensive care unit resources, and reduce transfers to a tertiary institution.

A comparison of presentations and outcomes of histoplasmosis across patients with varying immune status.

Few large cohorts have examined histoplasmosis in both immunocompromised and immunocompetent patients. We describe the differences in presentations and outcomes of histoplasmosis by immune and dissemination status. We assembled a retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Patients were grouped by immune status: people living with HIV (PLWH), patients who were HIV negative but had other-immunocompromise (OIC), and immunocompetent patients. Patients were further classified into asymptomatic lung nodule (ALN), localized and disseminated disease groups, and outcomes were compared across patients by these immune status categories We identified 261 patients with histoplasmosis: 54 (21%) PLWH, 98 (38%) OIC, and 109 (42%) immunocompetent. Disseminated disease was more common among PLWH than among other groups (P < .001). In localized disease, median time from symptom onset to diagnosis was longer in immunocompetent patients than in other groups (P = .012), and was not significant in disseminated disease. The 90-day mortality was higher in PLWH (25%) and OIC (26%) with localized disease compared to the immunocompetent group (4%) (P = .009), but this difference was not seen in disseminated disease. Patients with localized disease had lower 90-day mortality (14%) compared to those with disseminated disease (21%) (P = .034). We conclude that immunocompetent individuals present with fewer typical symptoms, laboratory findings, and radiographic features of Histoplasma infection, leading to potential delays in diagnosis in this group. Despite this, immunocompetent patients have lower 90-day mortality in localized disease, and do not experience increased 90-day mortality in disseminated disease. LAY SUMMARY: This article examines how the signs and symptoms of histoplasmosis vary by immune status and dissemination status. Immunocompetent patients with localized disease present with fewer typical signs and symptoms, are diagnosed later, but despite this have lower 90-day mortality.

Voriconazole Versus Itraconazole for the Initial and Step-down Treatment of Histoplasmosis: A Retrospective Cohort.

BACKGROUND: Itraconazole is the preferred azole for histoplasmosis in the current Infectious Diseases Society of America guidelines. Voriconazole is increasingly used as treatment for histoplasmosis; it has in vitro activity against Histoplasma capsulatum and has shown success in case reports and small case series, but may have a lower barrier to resistance. No comparative studies have been published. METHODS: We constructed a single-center, retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Individual charts were reviewed to gather clinical information, including demographics, clinical features, immune status, treatments, and mortality. Patients were categorized based on the choice of azole and use as an initial treatment or as a step-down therapy from amphotericin B. Initial therapies with other azoles were excluded. Mortality was compared using a multivariable Cox proportional hazards with Heaviside function at 42 days. RESULTS: We identified 261 cases of histoplasmosis from 2002 to 2017. After excluding patients not treated with itraconazole or voriconazole, 194 patients remained. Of these, 175 (90%) patients received itraconazole and 19 (10%) received voriconazole. There were no significant demographic differences between patient populations receiving either azole as their initial azole treatment. Death at 180 days occurred in 41 patients (23.4%) in the itraconazole group and 6 patients (31.6%) in the voriconazole group. Patients on voriconazole had a statistically significant increase in mortality during the first 42 days after initiation of treatment when compared to patients receiving itraconazole (hazard ratio, 4.30; 95% confidence interval, 1.3-13.9; P = .015), when controlled for other risk factors. CONCLUSIONS: Voriconazole in histoplasmosis was associated with increased mortality in the first 42 days when compared to itraconazole.

Rifampicin-resistant tuberculosis among known HIV-infected patients in Oyo State, Nigeria.

A major opportunistic infection among HIV-infected people is tuberculosis (TB). It accelerates the deadly progression of HIV which results in further decline in the patient's immune status and early death. More than 9 million people suffer from this debilitating coinfection worldwide. More worrisome is the fact that some patients now develop resistance to rifampicin, a first-line drug against TB. This study therefore aimed at determining the rifampicin-resistant TB prevalence rate among known HIV-positive patients in Oyo State. This cross-sectional study was performed by collecting suitable sputum samples from 397 known HIV patients who attended ART Clinic between January and December 2017. The samples were analyzed using the GeneXpert machine, a real-time polymerase chain reaction-based equipment. Of the total 397 tested, 172 (43.3%) were male while 225 (56.7%) were females. Fifty (12.6%) of the 397 known HIV patients tested positive to TB and 6 (12%) of the 50 were resistant to rifampicin. Four (2.3%) of the 172 males had rifampicin-resistant TB and 2 (0.9%) of the 225 females were resistant to rifampicin. Age group 31-40 years was the most affected with pulmonary TB while age group 10-20 years was the most affected with rifampicin-resistant TB. Six (1.5%) of the total 397 were rifampicin resistant. In conclusion, strict compliance with the infection control measures is strongly advocated for to prevent further transmission of Mycobacterium tuberculosis to people living with HIV most of whom have their immune system already weakened.

Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis.

BACKGROUND: Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear which intervention, if any, should be offered first. We aimed to estimate the comparative effectiveness of all available psychosocial interventions (alone or in combination) for the short- and long-term treatment of people with cocaine and/or amphetamine addiction. METHODS AND FINDINGS: We searched published and unpublished randomised controlled trials (RCTs) comparing any structured psychosocial intervention against an active control or treatment as usual (TAU) for the treatment of cocaine and/or amphetamine addiction in adults. Primary outcome measures were efficacy (proportion of patients in abstinence, assessed by urinalysis) and acceptability (proportion of patients who dropped out due to any cause) at the end of treatment, but we also measured the acute (12 weeks) and long-term (longest duration of study follow-up) effects of the interventions and the longest duration of abstinence. Odds ratios (ORs) and standardised mean differences were estimated using pairwise and network meta-analysis with random effects. The risk of bias of the included studies was assessed with the Cochrane tool, and the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We followed the PRISMA for Network Meta-Analyses (PRISMA-NMA) guidelines, and the protocol was registered in PROSPERO (CRD 42017042900). We included 50 RCTs evaluating 12 psychosocial interventions or TAU in 6,942 participants. The strength of evidence ranged from high to very low. Compared to TAU, contingency management (CM) plus community reinforcement approach was the only intervention that increased the number of abstinent patients at the end of treatment (OR 2.84, 95% CI 1.24-6.51, P = 0.013), and also at 12 weeks (OR 7.60, 95% CI 2.03-28.37, P = 0.002) and at longest follow-up (OR 3.08, 95% CI 1.33-7.17, P = 0.008). At the end of treatment, CM plus community reinforcement approach had the highest number of statistically significant results in head-to-head comparisons, being more efficacious than cognitive behavioural therapy (CBT) (OR 2.44, 95% CI 1.02-5.88, P = 0.045), non-contingent rewards (OR 3.31, 95% CI 1.32-8.28, P = 0.010), and 12-step programme plus non-contingent rewards (OR 4.07, 95% CI 1.13-14.69, P = 0.031). CM plus community reinforcement approach was also associated with fewer dropouts than TAU, both at 12 weeks and the end of treatment (OR 3.92, P < 0.001, and 3.63, P < 0.001, respectively). At the longest follow-up, community reinforcement approach was more effective than non-contingent rewards, supportive-expressive psychodynamic therapy, TAU, and 12-step programme (OR ranging between 2.71, P = 0.026, and 4.58, P = 0.001), but the combination of community reinforcement approach with CM was superior also to CBT alone, CM alone, CM plus CBT, and 12-step programme plus non-contingent rewards (ORs between 2.50, P = 0.039, and 5.22, P < 0.001). The main limitations of our study were the quality of included studies and the lack of blinding, which may have increased the risk of performance bias. However, our analyses were based on objective outcomes, which are less likely to be biased. CONCLUSIONS: To our knowledge, this network meta-analysis is the most comprehensive synthesis of data for psychosocial interventions in individuals with cocaine and/or amphetamine addiction. Our findings provide the best evidence base currently available to guide decision-making about psychosocial interventions for individuals with cocaine and/or amphetamine addiction and should inform patients, clinicians, and policy-makers.

Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder.

OBJECTIVE: Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. METHODS: We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. RESULTS: The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32-1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=-0.19-1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. CONCLUSION: Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.

Neural signature of hierarchically structured expectations predicts clustering and transfer of rule sets in reinforcement learning.

Often the world is structured such that distinct sensory contexts signify the same abstract rule set. Learning from feedback thus informs us not only about the value of stimulus-action associations but also about which rule set applies. Hierarchical clustering models suggest that learners discover structure in the environment, clustering distinct sensory events into a single latent rule set. Such structure enables a learner to transfer any newly acquired information to other contexts linked to the same rule set, and facilitates re-use of learned knowledge in novel contexts. Here, we show that humans exhibit this transfer, generalization and clustering during learning. Trial-by-trial model-based analysis of EEG signals revealed that subjects' reward expectations incorporated this hierarchical structure; these structured neural signals were predictive of behavioral transfer and clustering. These results further our understanding of how humans learn and generalize flexibly by building abstract, behaviorally relevant representations of the complex, high-dimensional sensory environment.

Motor Demands Constrain Cognitive Rule Structures.

Study of human executive function focuses on our ability to represent cognitive rules independently of stimulus or response modality. However, recent findings suggest that executive functions cannot be modularized separately from perceptual and motor systems, and that they instead scaffold on top of motor action selection. Here we investigate whether patterns of motor demands influence how participants choose to implement abstract rule structures. In a learning task that requires integrating two stimulus dimensions for determining appropriate responses, subjects typically structure the problem hierarchically, using one dimension to cue the task-set and the other to cue the response given the task-set. However, the choice of which dimension to use at each level can be arbitrary. We hypothesized that the specific structure subjects adopt would be constrained by the motor patterns afforded within each rule. Across four independent data-sets, we show that subjects create rule structures that afford motor clustering, preferring structures in which adjacent motor actions are valid within each task-set. In a fifth data-set using instructed rules, this bias was strong enough to counteract the well-known task switch-cost when instructions were incongruent with motor clustering. Computational simulations confirm that observed biases can be explained by leveraging overlap in cortical motor representations to improve outcome prediction and hence infer the structure to be learned. These results highlight the importance of sensorimotor constraints in abstract rule formation and shed light on why humans have strong biases to invent structure even when it does not exist.

Deadly pediatric poisons: nine common agents that kill at low doses.

More than 97% of pediatric exposures reported to the AAPCC in 2001 had either no effect or mild clinical effects. Despite the large number of exposures, only 26 of the 1074 reported fatalities occurred in children younger than age 6. These findings reflect the fact that, in contrast to adolescent or adult ingestions, pediatric ingestions are unintentional events secondary to development of exploration behaviors and the tendency to place objects in the mouth. Ingested substances typically are nontoxic or ingested in such small quantities that toxicity would not be expected. As a result, it commonly is believed that ingestion of one or two tablets by a toddler is a benign act and not expected to produce any consequential toxicity. Select agents have the potential to produce profound toxicity and death, however, despite the ingestion of only one or two tablets or sips. Although proven antidotes are a valuable resource, their value is diminished if risk after ingestion is not adequately appreciated and assessed. Future research into low-dose, high-risk exposures should be directed toward further clarification of risk, improvements in overall management strategies,and, perhaps most importantly, prevention of toxic exposure through parental education and appropriate safety legislation.