A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti-Wolbachia Candidate Macrofilaricide.

AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase 1, first-in-human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double-blind, placebo-controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700-mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.

Pilot study of autologous fecal microbiota transplants in nursing home residents: Feasibility and safety.

Introduction: Antibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population. Methods: Pilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE). Results: We screened 468 nursing home residents aged ≥18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2 ± 8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention. Conclusions: In this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe. Trial registration: ClinicalTrials.gov Identifier: NCT03061097.

Participatory action research: practical strategies for actively engaging and maintaining participation in immigrant and refugee communities.

In this research we examined the processes involved in implementing and maintaining a participatory action research (PAR) project by uncovering how theoretical PAR tenets hold up in the reality of a community-based project addressing immigrants' and refugees' mental health needs. Qualitative data from focus groups with these newcomers were analyzed for thematic content. Findings reveal that active participation is seen as the gateway into a PAR project, whereas knowledge attainment and empowerment are the stimuli for continued participation. The data also suggest that newcomers' motivations to participate in a PAR-oriented project might vary across ethno-cultural groups. Practitioners working in community-based initiatives would do well to appeal to the diversity of motivational factors, while endorsing individual and group strengths.

Assessment of auditory brainstem function in lead-exposed children using stapedius muscle reflexes.

The purpose of this study was to investigate the neurological integrity and physiological status of the auditory brainstem tracts and nuclei in children with chronic lead (Pb) exposure using non-invasive acoustic stapedius reflex (ASR) measurements of afferent and efferent-neuromuscular auditory function. Following audiological examinations, uncrossed (ipsilateral) and crossed (contralateral) brainstem ASR responses were evoked by pure tone (500, 1000, and 2000 Hz), and broadband noise (bandwidth: 125-4000 Hz) stimulus activators. The ASR threshold (ASRT), amplitude growth, and decay/fatigue were measured by conventional clinical middle ear immittance methods in a group of Andean children (age range: 2-18 years) with a history of chronic environmental Pb exposure from occupational Pb glazing. Blood lead (PbB) levels of the study group (n=117) ranged from 4.0 to 83.7 µg/dL with a mean PbB level of 33.5 µg/dL (SD: 23.6; median: 33.0: CDC III Classification). The PbB distribution data indicated that 77.8% (n=91) of the children had PbB levels greater than the CDC action line of 10 µg/dL. Repeatable, normal ASRTs were elicited for ipsilateral (mean: ≤90 dB HL) and contralateral (mean: ≤97 dB HL) stimulation for each acoustic activator. Spearman Rho correlation analysis indicated no significant association between PbB level and ipsilateral or contralateral ASRT for any of the stimulus activators. The ASR amplitude growth results showed typical growth functions with no Pb-associated aberrations. No statistical association was found between ASR decay/adaptation (ASRD) and PbB level for any of the stimulus activators. The results of stapedius muscle reflex testing using several stimulus activators showed no significant relationship between PbB level and the physiological integrity of the auditory brainstem mediated ASR responses in children with chronic Pb exposure and elevated PbB levels.