Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers.

Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.

Efficacy of a Spatial Repellent for Control of Malaria in Indonesia: A Cluster-Randomized Controlled Trial.

A cluster-randomized, double-blinded, placebo-controlled trial was conducted to estimate the protective efficacy (PE) of a spatial repellent (SR) against malaria infection in Sumba, Indonesia. Following radical cure in 1,341 children aged ≥ 6 months to ≤ 5 years in 24 clusters, households were given transfluthrin or placebo passive emanators (devices designed to release vaporized chemical). Monthly blood screening and biweekly human-landing mosquito catches were performed during a 10-month baseline (June 2015-March 2016) and a 24-month intervention period (April 2016-April 2018). Screening detected 164 first-time infections and an accumulative total of 459 infections in 667 subjects in placebo-control households, and 134 first-time and 253 accumulative total infections among 665 subjects in active intervention households. The 24-cluster protective effect of 27.7% and 31.3%, for time to first-event and overall (total new) infections, respectively, was not statistically significant. Purportedly, this was due in part to zero to low incidence in some clusters, undermining the ability to detect a protective effect. Subgroup analysis of 19 clusters where at least one infection occurred during baseline showed 33.3% (P-value = 0.083) and 40.9% (P-value = 0.0236, statistically significant at the one-sided 5% significance level) protective effect to first infection and overall infections, respectively. Among 12 moderate- to high-risk clusters, a statistically significant decrease in infection by intervention was detected (60% PE). Primary entomological analysis of impact was inconclusive. Although this study suggests SRs prevent malaria, additional evidence is required to demonstrate the product class provides an operationally feasible and effective means of reducing malaria transmission.

Single-rescuer cardiopulmonary resuscitation: 'two quick breaths'--an oxymoron.

The Guidelines 2000 for CPR and ECC recommend for single lay-rescuers performing basic life support, "two quick breaths followed by 15 chest compressions", repeated until professional help arrives. It is uncertain that this can actually be accomplished by the majority of lay rescuers. We evaluated 53 first-year medical students after completing BLS CPR training to determine if they could deliver the goal of 80 compressions per minute when following this AHA BLS recommendation. Alternatively, a simplified technique of uninterrupted chest compression (UCC) BLS CPR was also taught and compared with standard BLS CPR (STD). The mean number of chest compressions/minute delivered with AHA BLS CPR was only 43 +/- 1 immediately after initial training and 49 +/- 2 when tested 6 months later. Uninterrupted chest compression BLS resulted in 113 +/- 2 compressions/min delivered immediately after training and 91 +/- 4 six months later (STD versus UCC; P < 0.0001). The mean length of time needed to provide the two breaths during STD-CPR was 14 +/- 1 and 12 +/- 1s (immediately after first training and six months after training). For STD-CPR, the mean minute ventilation was poor immediately after initial training (3.3 +/- 0.3 l/min) and further declined (1.9 +/- 0.4 l/min) at 6 months (P = 0.003). For single rescuer basic cardiopulmonary resuscitation, motivated BLS CPR-trained medical students take nearly as long as previously reported for middle-aged lay individuals to deliver these "two quick breaths". The "Guidelines 2000" recommendation for "two quick breaths" is an oxymoron, as it averages more than 13s. New recommendations for single-rescuer CPR should be considered that emphasize uninterrupted chest compressions.