A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response.

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. RESULTS: Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. CONCLUSIONS: Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566.

Which messages about healthy and sustainable eating resonate best with consumers with low socio-economic status?

Consumers with low socioeconomic status (SES) eat less healthy and sustainable diets than consumers with higher status. This is attributed, at least in part, to inequalities in health communication. An online survey with 134 socioeconomically disadvantaged consumers in Italy was conducted to test the effectiveness of tailor-made communication material (infographics) about healthy and sustainable eating (HSE). Participants were recruited at two social supermarkets by a social service organisation as well as via a crowdsourcing platform. Participants found information about HSE delivered through infographics moderately effective in increasing motivation, capability, and opportunity for HSE, and moderately useful and likely to impact their behaviour. Certain messages were more effective than others for native consumers, while migrants showed more indifferent responses to the various messages and manifested lower motivation to shift towards HSE, limited access to and seeking of nutrition-related information, and lower trust in information sources. Selecting which messages to deliver strategically, while also considering differences between segments of the target audience and their preferred sources and channels for communication, is promising; yet, structural changes related to food's affordability and availability are also needed to facilitate an effective communication.

External Validation of the Recalibrated HEART Score for Evaluation of Possible Acute Coronary Syndrome.

A single high-sensitivity troponin-T (hs-TnT) measurement may be sufficient to risk-stratify emergency department (ED) patients with possible acute coronary syndrome (ACS) using the recalibrated History, Electrocardiogram, Age, Risk Factors, Troponin (rHEART) score. We sought to validate this approach in a multi-ethnic population of US patients and investigate sex-specific differences in performance. We conducted a secondary analysis of a prospective cohort study of adult ED patients with possible ACS at a single, urban, academic hospital. We investigated the diagnostic performance of rHEART for the incidence of type-1 acute myocardial infarction (AMI) and other major adverse cardiac events (MACE) at 30 days, using both single (19 ng/L) and sex-specific (14 ng/L for females, 22 ng/L for males) 99th percentile hs-TnT thresholds. The 821 patients included were 54% female, 57% Hispanic, and 26% Black. 4.6% patients had MACE, including 2.4% with AMI. Single threshold rHEART ≤ 3 had sensitivity of 94.4% (95% confidence interval, 81-99%) and negative predictive values (NPV) of 99.3% (98-100%) for MACE; sex-specific thresholds performed nearly identically. Sensitivity and NPV for AMI were 90.0% (67-98%) and 99.3% (97-100%). Excluding patients presenting < 3 hours from symptom onset improved sensitivity for MACE and AMI to 97.0% (84-100%) and 94.1% (71-100%). Logistic regression demonstrated odds of MACE increased with higher rHEART scores at a similar rate for males and females. In conclusion, a single initial hs-TnT and rHEART score can be used to risk-stratify male and female ED patients with possible ACS, especially when drawn > 3 hours after symptom onset.

Randomized Controlled Trial of Acupressure for Perception of Stress and Health-Related Quality of Life Among Health Care Providers During the COVID-19 Pandemic: The Self-Acupressure for Stress (SAS) Trial.

Background: The efficacy of providing self-acupressure educational materials in reducing stress and improving health-related quality of life (HRQOL) is uncertain. Evidence-based data to recommend for or against self-acupressure as an intervention for reducing stress and improving HRQOL is needed. Objective: The Self-Acupressure for Stress (SAS) trial evaluates whether providing self-acupressure educational materials would reduce stress and improve HRQOL among health care providers (HCPs). Design: Randomized behavioral clinical trial. Setting: The entire study took place remotely. Participants: One hundred fifty-nine adult HCPs with no prior experience or training in acupressure. Intervention: The intervention group received self-acupressure educational materials. Measurements: Primary outcomes were perception of stress measured by the Perceived Stress Scale (PSS), as well as scores on the physical and mental components of the 12-item Short Form Health Survey version 2 (SF-12v2). Results: From the baseline to midpoint evaluations, the intervention group significantly reduced their PSS score (P ≤ .001) and increased their SF-12v2 Mental score (P = .002) but not their SF-12v2 Physical score (P = .55). These findings persisted at the final follow-up (both PSS and SF-12v2 Mental changes from baseline P < .001). However the control group also significantly improved their SF-12v2 Mental from baseline to midpoint (P = .01) which was maintained at final follow-up (P = .02), whereas PSS and SF-12v2 Physical did not significantly change from baseline at either mid or final. Finally, the intervention group improved by significantly more than the control group from baseline to final follow-up for both PSS (P = .007) and SF-12v2 Mental (P = .02) HRQOL measures. Limitation: The trial was not blinded. Conclusion: Among HCPs during the coronavirus disease 2019 (COVID-19) pandemic, the provision of self-acupressure educational materials safely improved self-reported assessments of perception of stress and mental health. Self-acupressure represents a promising intervention for other populations. The study findings support the use of self-acupressure to reduce stress and improve HRQOL. Trial Registration: ClinicalTrials.gov: NCT04472559.