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The objective of this study is to evaluate the predictive ability of the TyG index for the presence of adenoma and multiple adenomas in an asymptomatic population. A secondary analysis was conducted on a prospective cohort of asymptomatic subjects aged between 50 and 75 who underwent CRC screening. Fasting blood glucose (FBG) and lipid profiles were measured within three months prior colonoscopy. TyG index was estimated as ln [fasting triglycerides (mg/dL) × FBG (mg/dL)/2]. Multivariate logistic regression was performed to assess the association between the TyG index and the risk of adenoma. Its association with multiple adenomas (≥5) and the continuous number of adenomas were assessed by multinomial regression and log-normal linear regression, respectively. A total of 1,538 subjects were recruited among which 876 subjects (57%) had at least one adenoma detected. Elevated TyG index was positively associated with the incidence of adenoma (adjusted odds ratio [aOR]: 1.26, 95% confidence interval [CI]: 1.04-1.54). Compared with the lowest TyG index (≤ 8) group, the risk of adenoma was the highest among subjects in the highest TyG index (> 10) group (aOR: 3.36, 95% CI: 1.44-7.73). As compared to the non-adenoma group, the TyG index was also positively associated with multiple adenomas (aOR: 1.74, 95% CI: 1.17-2.57), and the estimate was also the highest in the highest TyG group (aOR: 14.49, 95% CI: 3.12-67.20). As for the number of adenomas, the positive association was maintained (Estimates: 1.06, 95% CI: 1.01-1.12) while the number of adenomas increase the most in the highest TyG index group (Estimates: 1.35, 95% CI: 1.10-1.65). Elevated TyG index is associated with an increased risk of colorectal adenoma and an increased number of adenomas for asymptomatic subjects aged ≥50. This study was registered on clinicaltrials.gov (NCT03597204 and NCT04034953).

After upregulation of AHR in astrocytes by type I interferons, commensal-microbe-derived metabolites of dietary tryptophan act on astrocytes to suppress CNS inflammation. Astrocytes have important roles in the central nervous system (CNS) during health and disease. Through genome-wide analyses we detected a transcriptional response to type I interferons (IFN-Is) in astrocytes during experimental CNS autoimmunity and also in CNS lesions from patients with multiple sclerosis (MS). IFN-I signaling in astrocytes reduces inflammation and experimental autoimmune encephalomyelitis (EAE) disease scores via the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) and the suppressor of cytokine signaling 2 (SOCS2). The anti-inflammatory effects of nasally administered interferon (IFN)-β are partly mediated by AHR. Dietary tryptophan is metabolized by the gut microbiota into AHR agonists that have an effect on astrocytes to limit CNS inflammation. EAE scores were increased following ampicillin treatment during the recovery phase, and CNS inflammation was reduced in antibiotic-treated mice by supplementation with the tryptophan metabolites indole, indoxyl-3-sulfate, indole-3-propionic acid and indole-3-aldehyde, or the bacterial enzyme tryptophanase. In individuals with MS, the circulating levels of AHR agonists were decreased. These findings suggest that IFN-Is produced in the CNS function in combination with metabolites derived from dietary tryptophan by the gut flora to activate AHR signaling in astrocytes and suppress CNS inflammation.

The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n =60) and healthy controls ( n =43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas , and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella , and decreased Sarcina , compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis. The gut microbiome has been implicated in several autoimmune disorders. Here, the authors study the gut microbiome of patients with multiple sclerosis, and find correlations between altered abundance of certain gut microorganisms and changes in expression of immune defence genes.

The question of whether gender-related disparities still exist in the treatment and outcomes of patients presenting with acute coronary syndromes (ACS) remains controversial. Using data from 4 registries spanning a decade, we sought to determine whether sex-related differences have persisted over time and to examine the treating physician's rationale for adopting a conservative management strategy in women compared with men. From 1999 to 2008, 14,196 Canadian patients with non–ST-segment elevation ACS were recruited into the Acute Coronary Syndrome I (ACSI), ACSII, Global Registry of Acute Coronary Events (GRACE/GRACE2), and Canadian Registry of Acute Coronary Events (CANRACE) prospective multicenter registries. Women in the study population were found to be significantly older than men and were more likely to have a history of heart failure, diabetes, or hypertension. Fewer women were treated with thienopyridines, heparin, and glycoprotein IIb/IIIa inhibitors compared with men in GRACE and CANRACE. Female gender was independently associated with a lower in-hospital use of coronary angiography (adjusted odds ratio 0.76, 95% CI 0.69-0.84, P < .001) and higher in-hospital mortality (adjusted odds ratio 1.26, 95% CI 1.02-1.56, P = .036), irrespective of age (P for interaction =.76). Underestimation of patient risk was the most common reason for not pursuing an invasive strategy in both men and women. Despite temporal increases in the use of invasive cardiac procedures, women with ACS are still more likely to be treated conservatively, which may be due to underestimation of patient risk. Furthermore, they have worse in-hospital outcomes. Greater awareness of this paradox may assist in bridging the gap between current guidelines and management practices.

Despite the availability of several acute coronary syndrome (ACS) prognostic risk scores, there is no appropriate score for early-risk stratification at the time of the first medical contact with patients with ACS. The primary objective of this study is to develop a simple risk score that can be used for early-risk stratification of patients with ACS. We derived the risk score from the Acute Myocardial Infarction in Quebec and Canada ACS-1 registries and validated the risk score in 4 other large data sets of patients with ACS (Canada ACS-2 registry, Canada-GRACE, EFFECT-1, and the FAST-MI registries). The final risk score is named the Canada Acute Coronary Syndrome Risk Score (C-ACS) and ranged from 0 to 4, with 1 point assigned for the presence of each of these variables: age ≥75 years, Killip >1, systolic blood pressure <100 mm Hg, and heart rate >100 beats/min. The primary end points were short-term (inhospital or 30-day) and long-term (1- or 5-year) all-cause mortality. The C-ACS has good predictive values for short- and long-term mortality of patients with ST-segment elevation myocardial infarction and non–ST-segment elevation ACS. The negative predictive value of a C-ACS score ≥1 is excellent at ≥98% (95% CI 0.97-0.99) for short-term mortality and ≥93% (95% CI 0.91-0.96) for long-term mortality. In other words, a C-ACS score of 0 can potentially identify correctly ≥97% short-term survivors and ≥91% long-term survivors. The C-ACS risk score permits rapid stratification of patients with ACS. Because this risk score is simple and easy to memorize and calculate, it can be rapidly applied by health care professionals without advanced medical training.

The Global Registry of Acute Coronary Event (GRACE) risk score was developed in a large multinational registry to predict in-hospital mortality across the broad spectrum of acute coronary syndromes (ACS). Because of the substantial regional variation and temporal changes in patient characteristics and management patterns, we sought to validate this risk score in a contemporary Canadian population with ACS. The main GRACE and GRACE 2 registries are prospective, multicenter, observational studies of patients with ACS (June 1999 to December 2007). For each patient, we calculated the GRACE risk score and evaluated its discrimination and calibration by the c statistic and the Hosmer-Lemeshow goodness-of-fit test, respectively. To assess the impact of temporal changes in management on the GRACE risk score performance, we evaluated its discrimination and calibration after stratifying the study population into prespecified subgroups according to enrollment period, type of ACS, and whether the patient underwent coronary angiography or revascularization during index hospitalization. A total of 12,242 Canadian patients with ACS were included; the median GRACE risk score was 127 (25th and 75th percentiles were 103 and 157, respectively). Overall, the GRACE risk score demonstrated excellent discrimination ( c statistic 0.84, 95% CI 0.82-0.86, P < .001) for in-hospital mortality. Similar results were seen in all the subgroups (all c statistics ≥0.8). However, calibration was suboptimal overall (Hosmer-Lemeshow P = .06) and in various subgroups. GRACE risk score is a valid and powerful predictor of adverse outcomes across the wide range of Canadian patients with ACS. Its excellent discrimination is maintained despite advances in management over time and is evident in all patient subgroups. However, the predicted probability of in-hospital mortality may require recalibration in the specific health care setting and with advancements in treatment.

There are limited data on the recent trend in the use of optimal evidence-based medical therapies after acute coronary syndromes (ACSs). We sought to evaluate (1) the temporal changes in medical management of patients discharged after an ACS; (2) patient and practice characteristics associated with optimal medical therapy at discharge; and (3) the association between discharge medication use and 1-year outcome. The Canadian ACS I (September 1999-June 2001) and ACS II (October 2002-December 2003) Registries were prospective, multicenter, observational studies of 6853 patients admitted for ACS. We examined the discharge use of medications among 5833 hospital survivors who did not have any contraindications to antiplatelet/anticoagulant, β-blocker, angiotensin-converting enzyme inhibitor, or lipid-modifying therapies. Optimal medical therapy was defined as the use of all indicated medications. Follow-up data at 1 year were collected by telephone interview. We performed hierarchical logistic regression to identify patient characteristics and care patterns associated with optimal medical treatment and to examine its relationship with 1-year mortality. There were significant increases in the discharge use of all 4 classes of medications over time; 28.9% and 51.8% of patients in ACS I and ACS II Registries, respectively, were prescribed optimal medical therapy (P < .001). Advanced age, female sex, prior heart failure, renal dysfunction, and coronary bypass surgery during hospitalization were negative independent predictors of optimal medical therapy. Conversely, enrollment in ACS II Registry, history of dyslipidemia, presence of ST elevation and abnormal cardiac biomarker, previous myocardial infarction, and previous coronary revascularization were independently associated with the use of combination therapy. After adjusting for other validated prognosticators, patients receiving optimal medical therapy had significantly lower 1-year mortality (adjusted odds ratio 0.54, 95% confidence interval 0.36-0.81, P = .003) compared with those given 0 or 1 drug at discharge. Over the 1-year follow-up period, substantial numbers of patients discontinued therapies, whereas others were initiated on treatment. Despite the temporal increases in the combined use of evidence-based pharmacologic therapies, which is associated with improved outcome, medical management of ACS remains suboptimal. Quality improvement strategies are needed to enhance the appropriate use of effective therapies, targeting specifically the high-risk but undertreated patients who may derive the greatest therapeutic benefit.

BackgroundColorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality worldwide. Despite the organised CRC screening programme, the uptake rate of the population-based CRC screening was still low. Thus, we will conduct a randomised controlled trial in a community setting to evaluate the effectiveness of a theory-based chatbot in promoting CRC screening uptake.Methods and analysisA total of 500 eligible participants will be randomly assigned to a WhatsApp Messenger-initiated chatbot outreach group or a standard text reminder group at a ratio of 1:1. The intervention group will deliver Chinese culturally tailored education texts and videos developed based on the Health Belief Model and the Trans-Theoretical Model. The control group will deliver a standard text reminder of information about the Hong Kong organised CRC screening programme. In addition to the baseline assessment and postintervention assessment, all subjects will be followed up for 3 months and 6 months, respectively. The primary outcome will be the CRC screening uptake rate at the 3 month and 6 month follow-up. The secondary outcomes will be the intention to undergo CRC screening uptake, time interval to participate in and complete screening after recruitment, and reasons for not participating in screening at the 3 month and 6 month follow-up. Quantitative data will be analysed using Student’s t-test, Pearson’s χ2 test or Fisher’s exact test. Qualitative data will be analysed by thematic analysis.Ethics and disseminationEthical approval of this trial was granted by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (2022.614). Written informed consent will be obtained from study participants before enrolment. The findings will be disseminated through peer-reviewed journals.Trial registration numberThe study was registered on clinicaltrials.gov (NCT06192862).

We examined the relations between right bundle branch block (RBBB) and clinical characteristics, management, and outcomes among a broad spectrum of patients with acute coronary syndrome (ACS). Admission electrocardiograms of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) electrocardiogram substudy and the Canadian ACS Registry I were analyzed independently at a blinded core laboratory. We performed multivariable logistic regression analysis to assess the independent prognostic significance of admission RBBB on in-hospital and 6-month mortality. Of 11,830 eligible patients with ACS (mean age 65; 66% non–ST-elevation ACS), 5% had RBBB. RBBB on admission was associated with older age, male sex, more cardiovascular risk factors, worse Killip class, and higher GRACE risk score (all p <0.01). Patients with RBBB less frequently received in-hospital cardiac catheterization, coronary revascularization, or reperfusion therapy (all p <0.05). The RBBB group had higher unadjusted in-hospital (8.8% vs 3.8%, p <0.001) and 6-month mortality rates (15.1% vs 7.6%, p <0.001). After adjusting for established prognostic factors in the GRACE risk score, RBBB was a significant independent predictor of in-hospital death (odds ratio 1.45, 95% CI 1.02 to 2.07, p = 0.039), but not cumulative 6-month mortality (odds ratio 1.29, 95% CI 0.95 to 1.74, p = 0.098). There was no significant interaction between RBBB and the type of ACS for either in-hospital or 6-month mortality (both p >0.50). In conclusion, across a spectrum of ACS, RBBB was associated with preexisting cardiovascular disease, high-risk clinical features, fewer cardiac interventions, and worse unadjusted outcomes. After adjusting for components of the GRACE risk score, RBBB was a significant independent predictor of early mortality.

Background: Intravenous (IV) ketamine is a rapid acting antidepressant used primarily for treatment-resistant depression (TRD). It has been suggested that IV ketamine’s rapid antidepressant effects may be partially mediated via improved sleep and changes to the circadian rhythm. Objectives: This study explores IV ketamine’s association with changes in patient-reported sleep quality and circadian rhythm in an adult population with TRD. Methods: Adult patients (18–64 years) with TRD scheduled for IV ketamine treatment were recruited to complete patient rated outcomes measures on sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and circadian rhythm using the Morningness–Eveningness Questionnaire (MEQ). Over a 4-week course of eight ketamine infusions, reports were obtained at baseline (T0), prior to second treatment (T1), prior to fifth treatment (T2), and 1 week after eighth treatment (T3). Results: Forty participants with TRD (mean age = 42.8, 45% male) were enrolled. Twenty-nine (72.5%) had complete follow-up data. Paired t tests revealed statistically significant improvements at the end of treatment in sleep quality (PSQI) (p = 0.003) and depressive symptoms (Clinically Useful Depression Outcome Scale-Depression, p < 0.001) while circadian rhythm (MEQ) shifted earlier (p = 0.007). The PSQI subscale components of sleep duration (p = 0.008) and daytime dysfunction (p = 0.001) also improved. In an exploratory post hoc analysis, ketamine’s impact on sleep quality was more prominent in patients with mixed features, while its chronobiotic effect was prominent in those without mixed features. Conclusion: IV ketamine may improve sleep quality and advance circadian rhythm in individuals with TRD. Effects may differ in individuals with mixed features of depression as compared to those without. Since this was a small uncontrolled study, future research is warranted. Plain language summary Patient-reported changes in sleep during treatment with intravenous ketamine for depression Intravenous ketamine is a fast acting treatment for depression that does not respond to more conventional antidepressant medications. Almost all people with depression have problems with sleep as a symptom of their illness. This can include things like difficulties falling asleep, problems staying asleep, sleeping more or less than usual, and shifting the sleep schedule to stay up later than usual. It has been previously suggested that improving sleep in people with depression may be part of how ketamine exerts its antidepressant effect. This study surveyed patients with depression who received eight intravenous infusions of ketamine (two per week for 4 weeks) to ask them about their sleep quality and patterns before treatment, part way through their course of treatment and after the treatments were completed. Symptoms of depression were also measured. Data were collected on 29 people. People reported overall that sleep quality did improve with ketamine treatments, and that timing of sleep shifted earlier. Sleep duration increased and people had less problems with daytime functioning. There is a subtype of depression called depression with “mixed features,” meaning that these people, in addition to being depressed, may have some activating symptoms like irritability, restlessness, and agitation. It is thought that this type of depression may be biologically different from depression without these symptoms. In this study, around half (15/29) had mixed features. Sleep quality improved only in the group without mixed features. On the other hand, the group with mixed features had their sleep schedule shift earlier, but the group without mixed features did not. This supports the idea that these two types of depression may be biologically different, and ketamine treatment may exert different effects on the sleep of each group. This was a small study, but suggests a need for future research.