d-Mannose for Recurrent Urinary Tract Infection Prevention in Postmenopausal Women Using Vaginal Estrogen: A Randomized Controlled Trial.

IMPORTANCE: Further research is needed to determine whether d-mannose plus vaginal estrogen therapy (VET) is beneficial over VET alone for recurrent urinary tract infection (rUTI) prevention. OBJECTIVE: The aim of this study was to evaluate d-mannose efficacy for rUTI prevention in postmenopausal women using VET. STUDY DESIGN: We conducted a randomized controlled trial comparing d-mannose (2 g/d) with control. Participants were required to have a history of uncomplicated rUTIs and to remain on VET throughout the trial. They were followed up 90 days for incident UTIs. Cumulative UTI incidences were calculated by the Kaplan-Meier method and compared by Cox proportional hazards regression. For the planned interim analysis, P < 0.001 was considered statistically significant. Futility analysis was performed by generating post hoc conditional power for multiple scenarios. RESULTS: We evaluated 545 patients for frequent/recurrent UTIs from March 1, 2018, to January 18, 2020. Of these women, 213 had culture-proven rUTIs, 71 were eligible, 57 enrolled, 44 began their planned 90-day study period, and 32 completed the study. At interim analysis, the overall cumulative UTI incidence was 46.6%; 41.1% in the treatment arm (median time to first UTI, 24 days) and 50.4% in the control arm (median, 21 days); hazard ratio, 0.76; 99.9% confidence interval, 0.15-3.97. d-Mannose was well tolerated with high participant adherence. Futility analysis suggested the study lacked power to detect the planned (25%) or observed (9%) difference as statistically significant; the study was halted before conclusion. CONCLUSIONS: d-Mannose is a well-tolerated nutraceutical, but further research is needed to determine whether d-mannose in combination with VET has a significant, beneficial effect beyond VET alone in postmenopausal women with rUTIs.

Culturally sensitive prevention programs for substance use among adolescents of color: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aims to synthesize the efficacy of culturally sensitive prevention programs for substance use outcomes among U.S. adolescents of color (aged 11 to 18 years old) and explore whether the intervention effects vary by participant and intervention characteristics. Eight electronic databases and grey literature were searched for eligible randomized controlled trials through September 2022. Robust variance estimation in meta-regression was used to synthesize treatment effect size estimates and to conduct moderator analysis. After screening, 30 unique studies were included. The average treatment effect size across all substance use outcomes (including 221 effect sizes) was Hedges's g = -0.20, 95% CI = [-0.24, -0.16]. The synthesized effect sizes were statistically significant across types of substances (alcohol, cigarette, marijuana, illicit and other drugs, and unspecified substance use), racial/ethnic groups (Hispanic, Black, and Native American), and different follow-ups (0-12 months, >12 months). Very few studies reported substance use consequences as outcomes and the synthesized effect size was non-significant. Meta-regression findings suggest that the intervention effects may vary based on the type of substance. This meta-analysis found supportive evidence of culturally sensitive prevention programs' efficacy in preventing or reducing substance use among Black, Hispanic, and Native American adolescents. More substance use prevention efforts and evidence is needed for Asian American, Pacific Islander, and multiracial adolescents.

Prompt control of a Serratia marcescens outbreak in a neonatal intensive care unit informed by whole-genome sequencing and comprehensive infection control intervention package.

Objective: This report describes a cluster of patients infected by Serratia marcescens in a metropolitan neonatal intensive care unit (NICU) and a package of infection control interventions that enabled rapid, effective termination of the outbreak. Design: Cross-sectional analytical study using whole-genome sequencing (WGS) for phylogenetic cluster analysis and identification of virulence and resistance genes. Setting: NICU in a metropolitan tertiary-care hospital in Sydney, Australia. Patients: All neonates admitted to the level 2 and level 3 neonatal unit. Interventions: Active inpatient and environmental screening for Serratia marcescens isolates with WGS analysis for identification of resistance genes as well as cluster relatedness between isolates. Planning and implementation of a targeted, multifaceted infection control intervention. Results: The cluster of 10 neonates colonized or infected with Serratia marcescens was identified in a metropolitan NICU. Two initial cases involved devastating intracranial infections with brain abscesses, highlighting the virulence of this organism. A targeted and comprehensive infection control intervention guided by WGS findings enabled termination of this outbreak within 15 days of onset. WGS examination demonstrated phylogenetic linkage across the cluster, and genomic unrelatedness of later strains identified in the neonatal unit and elsewhere. Conclusions: A comprehensive, multipronged, infection control package incorporating close stakeholder engagement, frequent microbiological patient screening, environmental screening, enhanced cleaning, optimization of hand hygiene and healthcare worker education was paramount to the prompt control of Serratia marcescens transmission in this neonatal outbreak. WGS was instrumental in establishing relatedness between isolates and identification of possible transmission pathways in an outbreak setting.

Feasibility and Research Insights From a Randomized Controlled Trial for Recurrent Urinary Tract Infection Prevention in Postmenopausal Women Using Vaginal Estrogen Therapy.

OBJECTIVE: The aim of the study was to inform feasibility parameters (eligibility, enrollment, and retention) for a recurrent urinary tract infection (rUTI) prevention randomized controlled trial (RCT). METHODS: We assessed feasibility parameters of an RCT of postmenopausal women with uncomplicated rUTIs using vaginal estrogen. Participants were randomized to either d-mannose or a control arm. All participants were required to be using vaginal estrogen and to have a negative urine culture before 90-day trial participation. An RCT exit survey and separate survey for UTI patients (N = 196) were added to inform feasibility parameters and patient preferences for rUTI prevention and study participation after slower enrollment than anticipated. RESULTS: At the time of interim and subsequent futility analyses, 545 patients had been evaluated for frequent/recurrent UTIs from March 1, 2018, to January 18, 2020. Of these, 213 (39.1%) had culture-proven rUTIs and 71 (33.3% of those with culture-proven rUTIs) were eligible for the RCT. Reasons for ineligibility included complicated UTIs, premenopausal/perimenopausal status, or existing UTI prevention regimen. Of the 71 eligible participants, 57 (80.3%) enrolled, and 44 began their planned 90-day study period (77.2%; 80.0% after excluding 2 participants awaiting negative urine cultures at the time of analysis). The study was halted before conclusion. Study retention (76.0%-83.7%) was slightly lower than expected. Urinary tract infection survey patients demonstrated significant interest in rUTI research participation. CONCLUSIONS: We learned several important lessons that can benefit future research. Many patients with frequent/recurrent UTIs are interested in research, but rigorous eligibility criteria and referral urine culture documentation made recruitment challenging.

Human pegivirus in brain tissue of a patient with encephalitis.

We describe a case of meningoencephalitis in which meta-transcriptomic (RNA) sequencing detected human pegivirus (HPgV) in brain tissue, cerebrospinal fluid, and serum in the absence of other pathogens. This is the first detection of HPgV in antemortem brain tissue, although it is uncertain whether HPgV is responsible for the observed encephalitis.

Anncaliia algerae Microsporidial Myositis, New South Wales, Australia.

We describe the successful management of Anncaliia algerae microsporidial myositis in a man with graft versus host disease after hemopoietic stem cell transplantation. We also summarize clinical presentation and management approaches and discuss the importance of research into the acquisition of this infection and strategies for prevention.

Verruconis gallopava cardiac and endovascular infection with dissemination after renal transplantation: Case report and lessons learned.

Verruconis gallopava is an uncommon cause of phaeohyphomycosis. We describe an unusual case of disseminated V. gallopava infection in a renal transplant recipient involving the endocardium but without endocarditis, associated with fungaemia and infection in the skin, oral cavity, brain and lung. The isolate was first detected from blood cultures which is rare. Surgical resection of cardiac fungal mass was not possible. The patient died despite resolution of fungaemia and combination antifungal therapy.

The contraceptive potential of ZP3 and ZP3 peptides in a primate model.

It has been known for some time that antibodies raised against ZP3, the major component of the glycoprotein shell that surrounds all mammalian oocytes, can successfully inhibit sperm-egg interaction in vitro. In our own studies using the non-human primate Callithrix jacchus, active immunisation was successfully achieved when homologous or heterologous ZP3 was used as an immunogen. However this long-term suppression of fertility was at the expense of ovarian function. An ovarian pathology was observed which was characterised by a disruption of folliculogenesis and depletion of the primordial follicle pool. Adverse auto-immune reactions have also been observed in mice following induction of immunity to mouse ZP3. Following careful selection of B-cell epitopes on mouse ZP3, peptide vaccines were formulated which could circumvent these adverse side effects and induce reversible infertility in actively immunised mice. To identify similar epitopes on primate ZP3, epitope mapping studies were performed and several candidate regions of the molecule were identified. These were incorporated into chimeric peptide vaccines and administered as single or triple peptide vaccines. Active immunisation successfully induced antibodies that bound exclusively to the zona pellucida of marmoset and human ovarian sections. These antibodies were able to suppress human sperm-egg binding by up to 60% in vitro. Encouragingly, no adverse side effects on ovarian function were observed following long-term immunisation however, no loss of fertility was consistently observed in vivo. Thus considerable research is still required to identify a combination of ZP epitopes that will induce reversible infertility in the absence of any ovarian dysfunction.