Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial.

BACKGROUND: Global guidelines recommend untargeted iron supplementation for women in regions of anemia prevalence ≥40%, such as Cambodia. However, the potential harms of untargeted iron on the gut have not been rigorously studied in women and likely vary depending on iron dose and form. OBJECTIVES: We investigated if a lower dose of a highly bioavailable iron amino acid chelate was as effective as the standard dose of iron salts in increasing ferritin concentrations and whether any differences were observed in gut inflammation or enteropathogen detection. METHODS: A double-blind, randomized placebo-controlled noninferiority trial was conducted in Cambodia. Nonpregnant women (n = 480, 18-45 y) were randomly assigned to 60-mg ferrous sulfate, 18-mg ferrous bisglycinate, or placebo for 12 wk. Nonfasting blood and stool specimens were collected at baseline and 12 wk. Ferritin and fecal calprotectin were measured with an ELISA. A molecular assay was used to detect 11 enteropathogens in a random subset of n = 100 women. Generalized linear mixed-effects models were used to estimate the adjusted mean difference in ferritin concentrations at 12 wk (primary outcome), as compared with our 'a priori' noninferiority margin of 20 µg/L. RESULTS: Baseline anemia and iron deficiency prevalence was low (17% and 6%, respectively). The adjusted mean difference in ferritin concentrations between the iron groups was 14.6 (95% confidence interval [CI]: 7.6, 21.6) µg/L. Mean ferritin concentration at 12 wk was higher in the ferrous sulfate (99 [95% CI: 95, 103] µg/L, P < 0.001) than in ferrous bisglycinate (84 [95% CI: 80, 88] µg/L) and placebo groups (78 [95% CI: 74, 82] µg/L). No differences in fecal calprotectin concentrations or enteropathogen detection were observed across groups at 12 wk. CONCLUSIONS: Ferrous bisglycinate (18-mg) was not as effective as ferrous sulfate (60-mg) in increasing ferritin concentrations and did not differentially influence biomarkers of gut health in this predominantly iron-replete population of Cambodian women. This trial was registered at clinicaltrials.gov registry as NCT04017598.

Neuroimaging markers of early neurological deterioration in acute isolated pontine infarction.

BACKGROUND: Imaging indicators of early neurological deterioration (END) in patients with acute isolated pontine infarctions (AIPI) remained ambiguous. We aimed to find more specific neuroimaging markers for the development of END in patients with AIPI. METHODS: Patients with AIPI within 72 h of stroke onset were screened from a stroke database from January 2018 to July 2021 in the First Affiliated Hospital of Zhengzhou University. Clinical characteristics, laboratory tests, and imaging parameters were collected. The layers having the largest infarct area on diffusion-weighted imaging (DWI) and T2 sequences were chosen. On the transverse plane of DWI and sagittal plane of T2-Flair images, the maximum length (a, m) and maximum width (b, n) vertical to the length of the infarcted lesions were measured respectively. On the sagittal plane of T2-Flair image, the maximum ventrodorsal length (f) and rostrocaudal thickness (h) were measured. On the sagittal plane, lesions were evenly split into upper, middle, and lower types based on the lesion's location in the pons. The ventral and dorsal types of location were separated based on whether the ventral borders of the pons were involved on transvers plane. END was defined as a ≥2 point increase in the National Institutes of Health Stroke Scale (NIHSS) total score or a ≥1 point increase in the motor items within 72 h after admission. Multivariate logistic regression analyses were used to explore risk factors associated with END. The receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) was performed to estimate the discriminative power and determine the optimal cut-off points of imaging parameters on the prediction of END. RESULTS: A total of 218 patients with AIPI were included in the final analysis. END occurred in 61 cases (28.0%). Multivariate logistic regression analysis showed that the ventral type of lesion location was associated with END in all models adjusted. In addition, in Model 1, b (odds ratio (OR) 1.145, 95% confidence interval (95% CI), 1.007-1.301) and n (OR 1.163, 95% CI 1.012-1.336); in Model 2, b*n (OR 1.010, 95% CI 1.002-1.018); in Model 3, n (OR 1.179, 95% CI, 1.028-1.353); and in Model 4, b (OR 1.143, 95% CI 1.006-1.298) and n (OR 1.167, 95% CI 1.016-1.341) were found to be associated with END respectively after different adjustments. ROC curve analysis with END showed that the AUC, the optimal cut-off value, and its sensitivity and specificity were 0.743 (0.671-0.815), 9.850 mm, and 68.9% and 79.0% for b; 0.724 (0.648-0.801), 10.800 mm, and 57.4% and 80.9% for n; and 0.772 (0.701-0.842), 108.274 mm2, and 62.3% and 85.4% for b*n, respectively (b*n vs b: P =0.213; b*n vs n: P =0.037; b vs n: P =0.645). CONCLUSIONS: Our study revealed that besides the ventral type of lesion location, the maximum width of lesion on the transverse plane of DWI and sagittal plane of T2 image (b, n) may be imaging markers for the development of END in AIPI patients, and the product of the two (b*n) showed a better prediction value on the risks of END.

Demographic and clinical profile of an inception cohort of road trauma survivors.

BACKGROUND: Road trauma is a major public health concern, often resulting in reduced health-related quality of life and prolonged absenteeism from work even after so-called 'minor' injuries that do not result in hospitalization. This manuscript compares pre-injury health, sociodemographic characteristics and injury details between age, sex, and road user categories in a cohort of 1,480 road trauma survivors. METHODS: This was a prospective observational inception cohort study of road trauma survivors recruited between July 2018 and March 2020 from three trauma centres in British Columbia, Canada. Participants were aged ≥ 16 years and arrived in a participating emergency department within 24 h of involvement in a motor vehicle collision. Data were collected from structured interviews and review of medical records. RESULTS: The cohort of 1,480 road trauma survivors included 280 pedestrians, 174 cyclists, 118 motorcyclists, 683 motor vehicle drivers, and 225 passengers. Median age was 40 (IQR = [27, 57]) years; 680 (46%) were female. Males and younger patients were significantly more likely to report better pre-injury physical health. Motorcyclists and cyclists tended to report better physical health and less severe somatic symptoms, whereas pedestrians and motor vehicle drivers reported better mental health. Injury severity and hospital admission rates were higher in pedestrians and motorcyclists and lower in motorists. Upper and lower extremity injuries were most common in pedestrians, cyclists and motorcyclists, whereas neck injuries were most common in motor vehicle drivers and passengers. CONCLUSIONS: In a large cohort of road trauma survivors, overall injury severity was low. Motorcyclists and pedestrians, but not cyclists, had more severe injuries than motorists. Extremity injuries were more common in vulnerable road users. Future research will investigate one-year recovery outcomes and identify risk factors for poor recovery.

Probiotic potential of Lactobacillus isolated from horses and its therapeutic effect on DSS-induced colitis in mice.

Inflammatory bowel disease (IBD) is a refractory disease that endangers both humans and animals. In recent times, Lactobacillus have been used to treat animal diseases. It may be a good choice to try to isolate Lactobacillus with probiotic potential to treat IBD. Equine, as a kind of hindgut fermentation animal has rich intestinal microflora, but data regarding this is scarce. The isolation of Lactobacillus with probiotic potential from equine may become a new method for the treatment of IBD. Four isolates of Lactobacillus were isolated from fresh feces of healthy male adult horses and analyzed their biological characteristics. According to the phylogenetic analysis, A2.5 and A7.1 were identified as Pediococcus pentosaceus, A3 as Lactobacillus plantarum, and B8.2 as Weissella cibaria. All four isolates showed tolerance to the environment of acid, bile salt concentration and simulated artificial gastrointestinal fluid. The hydrophobic rate and self-aggregation rate of A3 were close to 100%, and the adhesion rate was 28.85 ± 0.74%. Four isolates were negative in hemolysis test and sensitive to common antibiotics and different isolates had different sensitivity to antibiotics. The four isolates had antibacterial and antioxidant activities which can reflect their probiotic potential. Furthermore, they could regulate the LPS (Lipopolysaccharides) stimulated Caco-2 cells. We chose A3 as the treatment strain to intervene Dextran sulfate sodium salt (DSS)-induced mice. The results showed that compared with DSS group, DSS + A3 group exhibited reduced Disease activity index (DAI), increased colon length, reduced pathological score and regulated cytokine secretion at the level of gene expression. In this study, four isolates of Lactobacillus with probiotic potential were isolated, and Lactobacillus plantarum A3 with reduced ulcerative colitis in mice was screened. It might provide a potential treatment for IBD.

Interpretable CNN for ischemic stroke subtype classification with active model adaptation.

BACKGROUND: TOAST subtype classification is important for diagnosis and research of ischemic stroke. Limited by experience of neurologist and time-consuming manual adjudication, it is a big challenge to finish TOAST classification effectively. We propose a novel active deep learning architecture to classify TOAST. METHODS: To simulate the diagnosis process of neurologists, we drop the valueless features by XGB algorithm and rank the remaining ones. Utilizing active learning framework, we propose a novel causal CNN, in which it combines with a mixed active selection criterion to optimize the uncertainty of samples adaptively. Meanwhile, KL-focal loss derived from the enhancement of Focal loss by KL regularization is introduced to accelerate the iterative fine-tuning of the model. RESULTS: To evaluate the proposed method, we construct a dataset which consists of totally 2310 patients. In a series of sequential experiments, we verify the effectiveness of each contribution by different evaluation metrics. Experimental results show that the proposed method achieves competitive results on each evaluation metric. In this task, the improvement of AUC is the most obvious, reaching 77.4. CONCLUSIONS: We construct a backbone causal CNN to simulate the neurologist process of that could enhance the internal interpretability. The research on clinical data also indicates the potential application value of this model in stroke medicine. Future work we would consider various data types and more comprehensive patient types to achieve fully automated subtype classification.

Baseline Hemoglobin, Hepcidin, Ferritin, and Total Body Iron Stores are Equally Strong Diagnostic Predictors of a Hemoglobin Response to 12 Weeks of Daily Iron Supplementation in Cambodian Women.

BACKGROUND: The WHO recommends daily iron supplementation for all women in areas where the population-level anemia prevalence is ≥40%, despite the fact that hemoglobin (Hb) concentration is generally considered to be a poor prognostic indicator of iron status. OBJECTIVES: In this secondary analysis, we investigated the predictive power of ten baseline hematological biomarkers towards a 12-week Hb response to iron supplementation. METHODS: Data were obtained from a randomized controlled trial of daily iron supplementation in 407 nonpregnant Cambodian women (18-45 years) who received 60 mg elemental iron as ferrous sulfate for 12 weeks. Ten baseline biomarkers were included: Hb, measured with both a hematology analyzer and a HemoCue; inflammation-adjusted ferritin; soluble transferrin receptor; reticulocyte Hb; hepcidin; mean corpuscular volume; inflammation-adjusted total body iron stores (TBIS); total iron binding capacity; and transferrin saturation. Receiver operating characteristic (ROC) curves from fitted logistic regression models were used to make discrimination comparisons and variable selection methods were used to construct a multibiomarker prognostic model. RESULTS: Only 25% (n = 95/383) of women who completed the trial experienced a 12-week Hb response ≥10 g/L. The strongest univariate predictors of a Hb response were Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS (AUCROC = 0.81, 0.83, 0.82, and 0.82, respectively), and the optimal cutoffs to identify women who were likely to experience a Hb response were 117 g/L, 17.3 µg/L, 1.98 nmol/L, and 1.95 mg/kg, respectively. Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, and hepcidin had the best combined predictive ability (AUCROC=0.86). Hb measured with the HemoCue had poor discrimination ability (AUCROC = 0.65). CONCLUSIONS: Baseline Hb as measured with a hematology analyzer was as strong a predictor of Hb response to iron supplementation as inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS. This is positive given that the WHO currently uses the population-level anemia prevalence to guide recommendations for untargeted iron supplementation.

Influence of dietary supplementation with Bacillus velezensis on intestinal microbial diversity of mice.

Yaks are an aboriginal breed of the Qinghai-Tibet plateau (3000 m), which are highly adaptable to cold and hypoxic environments. It is noticed that hypoxia and hypothermia can induce changes in intestinal microbial structure in animals. Increasing evidences suggested that probiotics supplementation can improve the balance of gut microbiota of animals. However, so far, very few studies have emphasized on the probiotics isolated from yaks in the Qinghai-Tibet Plateau. Therefore, a potential probiotic strain Bacillus velezensis was isolated from yaks. In the present study, a total of 18 Kunming mice (15-18 g) were equally distributed into two groups; control and probiotic treated groups (1 × 109 CFU/day). During the experimental period, all the mice from both groups were given standard normal diet ad libitum. At the end of the experiment, mice were euthanized and the intestines (duodenum, jejunum, ileum, and cecum) were removed for high-throughput sequencing. The results demonstrated that Bacillus velezensis supplementation showed beneficial effects on the gut microbiota of mice. Specifically, Bacillus velezensis supplementation increased the population of Lactobacillus and Ruminococcus in the duodenum, and Candidatus Arthromitus in the jejunum. Additionally, Acinetobacter in the duodenum and Helicobacter in the cecum were decreased after feeding Bacillus velezensis. Altogether, these findings suggested that Bacillus velezensis isolated from Tibetan yaks can improve gut microbiota of mice.

Dehydration Status Predicts Short-Term and Long-Term Outcomes in Patients with Cerebral Venous Thrombosis.

BACKGROUND: Dehydration is associated with a higher risk of poor outcome and venous thromboembolism in acute ischemic stroke patients. However, the relationship between dehydration and prognosis in patients with cerebral venous thrombosis (CVT) has not yet been investigated. METHODS: Consecutive CVT patients at the First Affiliated Hospital of Zhengzhou University were retrospectively identified from November 2011 through January 2017. Dehydration was evaluated by blood urea/creatinine (U/Cr) ratio > 80. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3-6. Factors such as age, sex, coma, intracerebral hemorrhage, and straight sinus and/or deep CVT involved were adjusted to assess the relationship between dehydration, and prognosis at discharge and long-term follow-up in CVT patients. RESULTS: A total of 220 CVT patients were included, and 85 patients (38.64%) were dehydrated. Multivariate logistic regression analysis indicated that patients with dehydration had a higher risk of mRS of 3-6 at discharge (adjusted odds ratio [OR] 3.629, 95% confidence intervals [CI] 1.526-8.633, P = 0.004) and long-term outcome (adjusted OR 3.831, 95% CI 1.597-9.190, P = 0.003). Subgroup analysis stratified by potential factors that might be associated with dehydration, such as infection, vomiting, pregnancy, and/or postpartum, showed similar results. Multivariate Cox regression analysis further demonstrated that dehydration was associated with higher mortality (adjusted hazard ratio [HR] = 2.301, 95% CI 1.025-5.166, P = 0.043). CONCLUSIONS: The present findings indicate that dehydration is an independent predictor for short-term and long-term unfavorable functional outcome in patients with CVT.

Long-Term Outcomes in Patients with Anemia And Cerebral Venous Thrombosis.

BACKGROUND: Anemia is associated with unfavorable functional outcome in ischemic and hemorrhagic stroke. However, the relationship between anemia and prognosis in patients with cerebral venous thrombosis (CVT) has not been studied. METHODS: Consecutive CVT patients were retrospectively identified from November 2011, through January 2017. Anemia was defined according to the World Health Organization criteria (non-pregnant female hemoglobin level < 120 g/L, pregnant female < 110 g/L and male < 130 g/L), which was further classified as mild, moderate, and severe anemia according to hemoglobin concentration, and as microcytic, normocytic, and macrocytic anemia according to mean corpuscular volume. Unfavorable outcome was defined as modified Rankin Scale (mRS) of 3-6. Factors such as age, sex, coma, malignancy, intracerebral hemorrhage, and straight sinus and/or deep CVT involved, premorbid mRS were adjusted to evaluate the relationship between anemia and prognosis in CVT patients. RESULTS: A total of 238 CVT patients were included, among whom 73 patients (30.67%) were diagnosed with anemia. Multivariate logistic regression analysis showed that patients with anemia had a higher risk of mRS of 3-6 (OR = 3.62; 95% CI, 1.45-9.01; P = 0.006) and mortality (OR = 5.46; 95% CI, 1.90-15.70; P = 0.002). Subgroup analysis showed that severe anemia was independently associated with mRS of 3-6 (OR = 8.80; 95% CI, 1.90-40.81; P = 0.005) and mortality (OR = 9.82; 95% CI, 1.81-53.25; P = 0.010). Similarly, microcytic anemia increased the risk of mRS of 3-6 (OR = 4.64; 95% CI, 1.48-14.52; P = 0.008) and mortality (OR = 9.68; 95% CI, 2.61-35.91; P = 0.001). In addition, our study also revealed that lower hemoglobin level, evaluated as a continuous variable, was inversely associated with mRS of 3-6 (OR = 0.98; 95% CI, 0.96-0.99; P = 0.007) and mortality (OR = 0.97; 95% CI, 0.95-0.99; P = 0.005). CONCLUSIONS: Anemia was a significant and independent predictor of unfavorable functional outcome in patients with CVT.

Severity of White Matter Lesions Correlates with Subcortical Diffusion-Weighted Imaging Abnormalities and Predicts Stroke Risk.

BACKGROUND AND PURPOSE: The severity of white matter lesions (WMLs) has been strongly linked to small-vessel diseases or lacunar infarction. The present study aimed to investigate the correlation between severity of WMLs and distribution of diffusion-weighted imaging (DWI) hyperintensities, and to explore whether the severity of WMLs is an independent neuroimaging predictor of stroke risk after transient symptoms with infarction (TSI). METHODS: We evaluated the presence and severity of WMLs on fluid-attenuated inversion recovery sequences using the age-related white matter changes scale and the location and size of hyperintensities on DWI sequences, respectively, in a prospective cohort study of TSI patients. The primary end point was recurrent stroke within 90 days. RESULTS: A total of 191 consecutive TSI patients were eligible for inclusion in the present analysis. The average age of the patients was 57.3 ± 12.8 years. DWI abnormalities occurred more often in the deep white matter with increasing severity of WMLs (P < .001). During 90-day follow-up, Kaplan-Meier analysis showed that recurrent stroke was correlated to the severity of WMLs (P = .01). The Cox proportional hazards model revealed that WMLs were predictive of recurrent stroke (hazard ratio, 1.748; 95% confidence interval, 1.16-2.634; P = .008). CONCLUSIONS: Severe WMLs were correlated with DWI hyperintensities in the deep white matter in TSI patients and contributed to an increased risk of recurrent stroke.

Screening for harmful substance use in emergency departments: a systematic review.

BACKGROUND: Substance use-related emergency department (ED) visits have increased substantially in North America. Screening for substance use in EDs is recommended; best approaches are unclear. This systematic review synthesizes evidence on diagnostic accuracy of ED screening tools to detect harmful substance use. METHODS: We included derivation or validation studies, with or without comparator, that included adult (≥ 18 years) ED patients and evaluated screening tools to identify general or specific substance use disorders or harmful use. Our search strategy combined concepts Emergency Department AND Screening AND Substance Use. Trained reviewers assessed title/abstracts and full-text articles for inclusion, extracted data, and assessed risk of bias (QUADAS-2) independently and in duplicate. Reviewers resolved disagreements by discussion. Primary investigators adjudicated if necessary. Heterogeneity precluded meta-analysis. We descriptively summarized results. RESULTS: Our search strategy yielded 2696 studies; we included 33. Twenty-one (64%) evaluated a North American population. Fourteen (42%) applied screening among general ED patients. Screening tools were administered by research staff (n = 21), self-administered by patients (n = 10), or non-research healthcare providers (n = 1). Most studies evaluated alcohol use screens (n = 26), most commonly the Alcohol Use Disorders Identification Test (AUDIT; n = 14), Cut down/Annoyed/Guilty/Eye-opener (CAGE; n = 13), and Rapid Alcohol Problems Screen (RAPS/RAPS4/RAPS4-QF; n = 12). Four studies assessing six tools and screening thresholds for alcohol abuse/dependence in North American patients (AUDIT ≥ 8; CAGE ≥ 2; Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-2] ≥ 1; RAPS ≥ 1; National Institute on Alcohol Abuse and Alcoholism [NIAAA]; Tolerance/Worry/Eye-opener/Amnesia/K-Cut down [TWEAK] ≥ 3) reported both sensitivities and specificities ≥ 83%. Two studies evaluating a single alcohol screening question (SASQ) (When was the last time you had more than X drinks in 1 day?, X = 4 for women; X = 5 for men) reported sensitivities 82-85% and specificities 70-77%. Five evaluated screening tools for general substance abuse/dependence (Relax/Alone/Friends/Family/Trouble [RAFFT] ≥ 3, Drug Abuse Screening Test [DAST] ≥ 4, single drug screening question, Alcohol, Smoking and Substance Involvement Screening Test [ASSIST] ≥ 42/18), reporting sensitivities 64%-90% and specificities 61%-100%. Studies' risk of bias were mostly high or uncertain. CONCLUSIONS: Six screening tools demonstrated both sensitivities and specificities ≥ 83% for detecting alcohol abuse/dependence in EDs. Tools with the highest sensitivities (AUDIT ≥ 8; RAPS ≥ 1) and that prioritize simplicity and efficiency (SASQ) should be prioritized.

Health-related quality of life in the year following road trauma: Longitudinal analysis using piecewise latent curve modeling.

BACKGROUND: Road trauma (RT) survivors have reduced health-related quality of life (HRQoL). We identified phases and predictors of HRQoL change following RT injury. METHODS: In a prospective cohort study of 1480 Canadian RT survivors aged 16 to 103 years (July 2018 - March 2020), physical component (PCS) and mental component (MCS) summary scores from the SF-12v2 were measured pre-injury and 2, 4, 6, and 12 months post-injury and their trajectories were analyzed with piecewise latent growth curve modeling. Potential predictors of HRQoL changes included sociodemographic, psychological, medical, and trauma-related factors. RESULTS: PCS and MCS scores worsened from pre-injury to 2-months (phase 1) and then improved (phase 2), but never regained baseline values. Older age, somatic symptoms and pain catastrophizing were associated with lower preinjury PCS and MCS scores. Psychological distress was associated with lower preinjury MCS scores and higher preinjury PCS scores. Phase 1 PCS scores decreased most in females, participants with fewer pre-injury somatic symptoms and those without expectations for fast recovery. Phase 1 MCS decreases were associated with younger age, female sex, living alone, lower psychological distress, lack of expectation for fast recovery and higher injury pain. In phase 2, MCS improved most in participants not using recreational drugs; PCS improved most in participants with higher education and longer recovery expectations. LIMITATIONS: There may be recall bias with reporting pre-injury HRQoL. Selection bias is possible. CONCLUSIONS: Many factors influence HRQoL following RT. These findings may inform measures to minimize HRQoL reduction following RT and speed up subsequent recovery.

Twelve-month recovery following road trauma: Results from an inception cohort in Vancouver, Canada.

BACKGROUND: Injury-related disability following road trauma is a major public health concern. Unfortunately, outcome following road trauma and risk factors for poor recovery are inadequately studied, especially for road trauma survivors with minor injuries that do not require hospitalization. OBJECTIVES: This manuscript reports 12-month recovery outcomes for a large cohort of road trauma survivors. METHODS: This was a prospective, observational inception cohort study of 1,480 road trauma survivors recruited between July 2018 and March 2020 from 3 trauma centres in British Columbia, Canada. Participants were aged ≥16 years and arrived in a participating emergency department within 24 h of a motor vehicle collision. Data on baseline health and injury severity were collected from structured interviews and medical records. Outcome measures, including the SF-12, were collected during follow-up interviews at 2, 4, 6 and 12 months. Predictors of recovery outcomes were identified using Cox proportional hazards models and summarized using hazard ratios. RESULTS: Only 42 % of participants self-reported full recovery and only 66 % reported a return to usual daily activities. Females, older individuals, pedestrians, and those who required hospital admission had a poorer recovery than other groups. Similar patterns were observed for the SF-12 physical component. For the SF-12 mental component, no significant differences were observed between participants admitted to hospital and those discharged home from the ED. Return to work was reported by 77 % of participants who had a paying job at baseline, with no significant differences between sex and age groups. CONCLUSIONS: In a large cohort of road trauma survivors, under half self-reported full recovery one year after the injury. Poor mental health recovery was observed in both participants admitted to hospital and those discharged home from the ED. This finding may indicate a need for early intervention and continued mental health monitoring for all injured individuals, including for those with less serious injuries.

Schizophrenia, antipsychotic treatment adherence and driver responsibility for motor vehicle crash: a population-based retrospective study in British Columbia, Canada.

OBJECTIVE: To examine the relationship between schizophrenia, antipsychotic medication adherence and driver responsibility for motor vehicle crash. DESIGN: Retrospective observational cohort study using 20 years of population-based administrative health and driving data. SETTING: British Columbia, Canada. PARTICIPANTS: Licensed drivers who were involved in a police-attended motor vehicle crash in British Columbia over a 17-year study interval (2000-16). EXPOSURES: Incident schizophrenia was identified using hospitalisation and physician services data. Antipsychotic adherence was estimated using prescription fill data to calculate the 'medication possession ratio' (MPR) in the 30 days prior to crash. PRIMARY OUTCOME MEASURES: We deemed drivers 'responsible' or 'non-responsible' for their crash by applying a validated scoring tool to police-reported crash data. We used logistic regression to evaluate the association between crash responsibility and exposures of interest. RESULTS: Our cohort included 808 432 drivers involved in a police-attended crash and for whom crash responsibility could be established. In total, 1689 of the 2551 drivers with schizophrenia and 432 430 of the 805 881 drivers without schizophrenia were deemed responsible for their crash, corresponding to a significant association between schizophrenia and crash responsibility (66.2% vs 53.7%; adjusted OR (aOR), 1.67; 95% CI, 1.53 to 1.82; p<0.001). The magnitude of this association was modest relative to established crash risk factors (eg, learner license, age ≥65 years, impairment at time of crash). Among the 1833 drivers with schizophrenia, near-optimal antipsychotic adherence (MPR ≥0.8) in the 30 days prior to crash was not associated with lower crash responsibility (aOR, 1.04; 95% CI, 0.83 to 1.30; p=0.55). CONCLUSIONS: Crash-involved drivers with schizophrenia are more likely to be responsible for their crash, but the magnitude of risk is similar to socially acceptable risk factors such as older age or possession of a learner license. Contemporary driving restrictions for individuals with schizophrenia appear to adequately mitigate road risks, suggesting more stringent driving restrictions are not warranted.

Trajectories of health-related quality of life following road trauma: Latent growth mixture modeling across a 12-month cohort study.

INTRODUCTION: Health-related quality of life (HRQoL) should be considered when evaluating the burden of road trauma (RT) injuries. This study aimed to identify distinct HRQoL trajectories following minor to severe RT injury and determine characteristics of trajectory membership. METHODS: This prospective inception cohort study recruited 1480 RT survivors from three emergency departments in British Columbia, Canada (July 2018 - March 2020). HRQoL outcome was measured with the Short Form 12 survey (SF-12) and the 5-level version of the EuroQol instrument (EQ-5D-5L) at baseline (pre-injury) and at 2, 4, 6, and 12 months post-injury. Potential predictors of outcome trajectory included sociodemographic, psychological, medical, crash, and injury factors collected at baseline. We used a latent growth mixture model to identify distinct recovery trajectories and multinomial logistic regression to determine predictors of trajectory membership. RESULTS: Three distinct HRQoL trajectories were identified for SF-12 subscales and EQ-5D-5L measures: Low/Moderate-Stable, High-Large decline, and High-Slight decline. Participants in the Low/Moderate-Stable trajectory had persistent low to moderate HRQoL before and after the injury. Those in the High-Large decline trajectory had good pre-injury HRQoL followed by persistently decreased HRQoL afterwards. The High-Slight decline trajectory was characterized by good pre-injury HRQoL and only a slight decline afterwards. Participants in the Low/Moderate-Stable and High-Large decline trajectories were considered at risk of permanently poor HRQoL following RT injury given their low HRQoL over a long period of time. Characteristics that placed participants in the Low/Moderate-Stable trajectory were older age, female gender, poor pre-injury health (medical comorbidity, prescribed medication use, complaints in the injured body area(s)), pre-injury somatic symptoms, pain catastrophizing or psychological distress, injury severity (ISS) and injury pain. Patients with head injury were less likely to be in the Low/Moderate-Stable trajectory. Risk factors for membership in the High-Large decline trajectory included older age (for physical HRQoL), younger age (for mental HRQoL), female gender, living alone, pre-injury psychological distress, ISS, injury pain, no expectations for a fast recovery, as well as head injuries, spine/back injuries or lower extremity injuries. CONCLUSIONS: This study highlighted the heterogeneity of HRQoL trajectories following RT injury and the importance of considering differences between characteristics of survivors. In addition to injury type and severity, outcome is related to demographic factors, pre-injury health and pre-injury psychological factors.

Atrial Cardiomyopathy Predicts the Functional Outcome and Mortality in Stroke Patients.

AIM: Atrial cardiomyopathy (ACM) is characterized by atrial dysfunction. This study aims to assess the prognostic significance of ACM in patients with noncardioembolic stroke (NCS). METHODS: Patients with NCS within seven days of onset were prospectively enrolled between January 2019 and December 2020. ACM was defined as either an N-terminal pro-brain natriuretic peptide (NT-pro BNP) ＞250 pg/ml or a P-terminal force in precordial lead V1 (PTFV1) ≥ 5000µV·ms. A poor functional outcome was determined as a score of 3-6 on the modified Rankin Scale (mRS) within a 2-year follow-up period. Logistic regression and Cox regression analyses were employed to examine the relationship between ACM and the long-term prognosis of patients with NCS. RESULTS: A total of 1,346 patients were enrolled, of whom 299 (22.2%) patients were diagnosed with ACM. A total of 207(15.4%) patients experienced a poor functional outcome, and 58 (4.3%) patients died. A multivariate logistic regression analysis indicated that ACM was significantly associated with a poor functional outcome in NCS patients [adjusted odds ratio (aOR): 2.01; 95% confidence interval (CI): 1.42-2.87; p＜0.001]. Additionally, a multivariate Cox regression analysis showed that an NT-pro BNP ＞250 pg/ml was significantly associated with an increased risk of all-cause mortality [adjusted hazard ratio (aHR), 2.51; 95% CI: 1.42-4.43; p=0.001]. CONCLUSIONS: ACM may serve as a novel predictor of a poor long-term functional outcome in patients with NCS. Elevated NT-pro BNP levels (＞250 pg/ml) were found to be associated with a higher risk of all-cause mortality. These findings warrant further validation in multicenter studies.

Reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to oral iron supplementation.

AIM: We investigated the potential of reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to iron supplementation. METHODS: Data were obtained from a randomised controlled trial of daily iron supplementation in 356 Cambodian women (18-45 y) who received 60 mg elemental iron for 12 weeks. A fasted venous blood specimen was collected at baseline, 1-week and 12-week timepoints. Whole blood haemoglobin (g/L) and RET-He (pg) were measured using a Sysmex haematology analyser. RET-He measures were evaluated for their predictive ability on haemoglobin response to iron supplementation (defined as ≥10 g/L at 12 weeks). Receiver operating characteristic (ROC) curves were used to assess discrimination performance, and the area under the ROC curve (AUCROC) served as a measure of the ability of each predictor to discriminate between women likely or unlikely to elicit a haemoglobin response. RESULTS: Predictive ability (AUCROC (95% CI)) of baseline, 1-week, and change from baseline to 1-week RET-He on haemoglobin response was 0.70 (0.63 to 0.76), 0.48 (0.41 to 0.56) and 0.81 (0.75 to 0.87), respectively. Based on the Youden index, an absolute increase in RET-He of ~1.1 pg or a percentage increase of ~4.4% over 1 week were optimal thresholds to predict responsiveness to iron supplementation. CONCLUSION: Single timepoint RET-He measures have poor predictive ability; however, change in RET-He after 1 week was a strong predictor of haemoglobin response among Cambodian women receiving 60 mg elemental iron and can be measured easily and quickly after only 1 week of iron therapy.

Circumstances and outcome of active transportation injuries: protocol of a British Columbian inception cohort study.

INTRODUCTION: Active transport (AT) is promoted by urban planners and health officials for its environmental, economic and societal benefits and its uptake is increasing. Unfortunately, AT users can be injured or killed due to falls or collisions. Active transport injury (ATI) prevention efforts are hindered by limited research on the circumstances, associated infrastructure, injury pattern, severity and outcome of ATI events. This study seeks to address these knowledge gaps by identifying built environment features associated with injury and risk factors for a poor outcome following ATI. METHODS AND ANALYSIS: This prospective observational study will recruit an inception cohort of 2000 ATI survivors, including pedestrians, cyclists and micromobility users aged 16 years and older who arrive at a participating emergency department within 48 hours of sustaining an ATI. Baseline interviews capture demographic and socioeconomic information, pre-injury health and functional status, as well as circumstances of the injury event and recovery expectations. Follow-up interviews at 2, 4, 6 and 12 months postinjury (key stages of recovery) use standardised health-related quality of life tools to determine physical and mental health outcomes, functional recovery and healthcare resource use and lost productivity costs. ETHICS AND DISSEMINATION: The Active Transportation Injury Circumstances and Outcome Study is approved by our institutional research ethics board and the research ethics boards of all participating sites. This study aims to provide healthcare providers with knowledge of risk factors for poor outcome following ATI with the goal of improving patient management. Additionally, this study will provide insight into the circumstances of ATI events including built environment features and how those circumstances relate to recovery outcomes. This information can be used to inform city engineers and planners, policymakers and public health officials to plan roadway design and injury prevention policy.

Effects of Lactic Acid Bacteria Isolated from Equine on Salmonella-Infected Gut Mouse Model.

The aim of this study was to evaluate the antibacterial potential of lactic acid bacteria (Weissella confuse, Pediococcus acidilactici, and Ligilactobacillus equi) isolated from healthy equine in Wuhan against Salmonella Typhimurium CVCC542-induced mice model on intestinal microflora. In previous studies, these isolated strains showed good probiotic potentials in vitro. In this study, fifty healthy mice were randomly divided into five groups, the blank control group, the control group, the Pediococcus acidilactici group (1 × 108 CFU/day), the Ligilactobacillus equi group (1 × 108 CFU/day), and the Weissella confuse group (1 × 108 CFU/day). The body weight in control group and Weissella confuse group showed significant decreased (P < 0.05, P < 0.01), while Pediococcus acidilactici group and Ligilactobacillus equi group showed good recovering after treatments. The lowest diarrhea rate was shown in Ligilactobacillus equi group after treatment. In histopathology, Ligilactobacillus equi group showed the least structural damage in duodenum, and all probiotic treatment groups showed less damage in cecum. The sequence data and optical transform unit showed that Pediococcus acidilactici group and Ligilactobacillus equi group had higher number than control group, while the diversity data showed that the control group and Weissella confuse group had lower diversity in cecum. Microbial community analysis showed increased abundance of Firmicutes, Bacteroidetes, uncultured_bacterium_f_Muribaculaceae, and Lactobacillus in treatment groups, while potential microbes that can induce intestinal diseases such as Verrucomicrobia, Akkermansia, and Lachnospiraceae_NK4A136_group decreased in the treatment groups. In conclusion, lactic acid bacteria isolated from the healthy horses could alleviate the infection of Salmonella and regulate intestinal flora.

Gasdermin D inhibition ameliorates neutrophil mediated brain damage in acute ischemic stroke.

Acute ischemic stroke (AIS) induces high level of neutrophils, which correlates inversely with patient survival. Pyroptosis induced by gasdermin D (GSDMD) has been shown to have an important role in the pathophysiology of several inflammatory disorders. The role of GSDMD in the high level of neutrophils after AIS is unknown. Using a middle cerebral artery occlusion (MCAO) mouse model, we identified activation of pyroptosis signal, including expression of caspase-1/11, GSDMD, and interleukin-1ß/18 (IL-1ß/18), in the brain and spleen at early ischemic injury. Knockout of GSDMD in mice reduced infarct size, improved neurological function, and increased survival after MCAO. GSDMD deficiency decreased the overall degree of inflammation and the proportion of neutrophils in the brain after MCAO. Quantitative studies of neutrophils at several time intervals and organs demonstrated that early inflammatory leucocyte production and supplement (1 day after MCAO) was GSDMD-dependent. A series of bone marrow transplantation experiments, neutrophil depletion experiments, and RNA sequencing results demonstrated that neutrophil specific GSDMD is essential for the production and supply of neutrophil in bone marrow to blood. Moreover, pharmacological suppression of GSDMD decreased pathological abnormalities, infarct volume, and ameliorated neurological function. These results provided a new viewpoint on the immunological modulation of neutrophils after MCAO and suggest that suppression of GSDMD may relieve the neuroinflammatory load, thereby providing a potential treatment strategy for stroke. The absence of GSDMD reduces the high level of neutrophils in the brain, the production of neutrophils in bone marrow, and the supply of blood and spleen, while simultaneously the neutrophil-specific GSDMD signal deficiency restrains leukocytosis to improve the pathological outcome of AIS.