Safety and immunogenicity of Px563L,a recombinant anthrax vaccine candidate,in a two-dose regimen for post-exposure prophylaxis in healthy adults

Px563L is a next-generation anthrax vaccine candidate consisting of a protein subunit, mutant recombinant protective antigen SNKE167-ΔFF-315-E308D (mrPA), and liposome-embedded monophosphoryl lipid A (MPLA) adjuvant. Px563L has the potential to deliver an improved safety and immunogenicity profile relative to the currently licensed vaccine, which is produced from filtered B. anthracis culture supernatants.We conducted a Phase 1, double–blind, placebo–controlled, dose–escalation study in 54 healthy subjects to evaluate Px563L at 3 dose levels of mrPA (10, 50, and 80 mcg). For each dose level, 18 subjects were randomized in an 8:8:2 ratio to Px563L (mrPA with adjuvant), RPA563 (mrPA only) or placebo (saline). Each subject received an intramuscular (IM) injection on Day 0 and Day 28. Primary safety and immunogenicity analysis was conducted after all subjects completed the Day 70 visit, a duration deemed clinically relevant for post-exposure prophylaxis. Long-term safety was assessed through Day 393.Vaccinations with Px563L at all dose levels were well-tolerated. There were no serious adverse events or adverse events (AE) leading to early withdrawal. In all treatment groups, most AEs were due to injection site reactions, and all AEs at the 10 and 50 mcg dose levels were mild. For the primary immunogenicity endpoint (protective toxin neutralizing antibody 50% neutralization factor [TNA NF₅₀]), titers started to increase significantly after the second administration of Px563L, from Day 35 through Day 70, with the geometric mean and lower bound of the 95% confidence interval exceeding 0.56, a threshold correlating with significant survival in animal models of anthrax exposure.In conclusion, Px563L, administered as two IM doses 28 days apart, was well-tolerated and elicited a protective antibody response starting at seven days after the second vaccination. These findings support the continued development of Px563L in a two-dose regimen for anthrax post-exposure prophylaxis. ClinicalTrials.gov identifier NCT02655549.     

Assessing Antibiotic Adherence and Improving Antibiotic Stewardship in Common Interventional Radiology Procedures

PurposeIn 2018, The Journal of Vascular and Interventional Radiology (JVIR) updated its guidelines regarding periprocedural antibiotics. However, some institutions are slower to adopt these new guidelines. Additionally, antibiotic-resistant bacteria and sepsis are serious concerns due in part to incorrect usage of antibiotics. The purpose of this study is to assess institutional adherence to 2018 JVIR guidelines for the purpose of improving antibiotic stewardship.Materials and methodsA total of 800 cases over a 10-month time period were retrospectively identified and charted following the release of guidelines. Inclusion criteria for the study were adults aged 21 years or older undergoing mediport placement, tunneled central line (TCL) placement, nephrostomy tube exchange, percutaneous biliary drain, or cholecystostomy tube exchange. Exclusion criteria included immunocompromised and pregnant individuals as 2018 guidelines may not fit these patient populations. Guideline adherence for each procedure was recorded as a percentage; the timing of the antibiotic usage was also recorded and compared to the guidelines (within 60 minutes before incision).ResultsIn total, 49 mediport placements, 118 tunneled central line placements – 44 hemodialysis (HD) catheters and 74 nonhemodialysis (non-HD) catheters, 100 nephrostomy exchanges, and 82 biliary tube exchanges were included. Antibiotics were used in 83.6% (41/49) of mediport patients, 11.3% (5/44) of non-HD TCL patients, 20.5% (15/74) of HD TCL patients, 55% (55/100) nephrostomy tube changes, and 65.4% (55/84) of biliary or cholecystostomy tube exchanges. Out of those given prophylaxis, guideline-recommended antibiotics were used in 100% (41/41) of mediport, 100% (20/20) of TCL (both HD and non-HD catheters), 9% (5/55) of nephrostomy tube exchanges, and 1.8% (1/55) of biliary tube exchanges. Guideline-recommended timing was followed in 75.3% across all cases (ranging from 72.2% in mediports to 79.3% in biliary exchanges).ConclusionThis study of antibiotic practices at a single university-based academic institution revealed that antibiotic usage is not fully up to date with 2018 guidelines. For mediports, non-HD TCL placements, and nephrostomy tube exchanges, institutional changes should be made to reduce periprocedural antibiotic use, as antibiotics are no longer recommended for these procedures. For HD TCL and biliary exchanges, proper adherence to recommended prophylactic antibiotics should be followed. In addition, education about the correct antibiotic timing should be emphasized to increase compliance with guidelines.     

Noise characterization of “effective quiet” areas on a U.S. Navy aircraft carrier

The purpose of this investigation was to characterize noise levels in spaces designated as “effective quiet” areas on a U.S. Navy aircraft carrier. Noise dosimetry samples were collected in 15 designated spaces, representing 15 noise measurements, while at-sea during airwing carrier qualifications. Equivalent sound level (L_eq) measurements were collected during flight operations (L_{eq (flt ops)}), non-flight operations (L_{eq (non-flt ops)}), and over 24-hr periods (L_{eq (24-hr)}). These data were compared to the 70 dBA American Conference of Governmental Industrial Hygienists (ACGIH^®) Threshold Limit Value (TLV^®) for “effective quiet” areas intended for temporary threshold shift recovery when personnel live and work in a potentially noise hazardous environment for periods greater than 24?hr. The monitored areas were selected based on personnel occupancy/use during off-duty time periods. Areas were classified by either (1) leisure areas that included mess (eating areas), gyms, lounges, an internet cafe, and the fantail social area or (2) berthing (sleeping) areas. The L_eq measurements in decibels “A” weighted (dBA) were compared to determine significant differences between L_{eq (flt ops)}, L_{eq (non-flt ops)}, and L_{eq (24-hr)} and were compared between leisure area and berthing area. Measured noise levels according to time period ranged as follows: (1) L_{eq (24-hr)}: 70.8–105.4 dBA; (2) L_{eq (flt ops)}: 70–101.2 dBA; and (3) L_{eq (non-flt ops)}: 39.4–104.6 dBA. All area measurements over the 24-hr period and during flight operations and 46.7% of the areas during the non-flight operation time period exceeded the “effective quiet” 70 dBA ACGIH TLV. Mean L_eqs were 15 dBA higher during flight operations compared to non-flight operations in “effective quiet” areas (p?=?0.001). The L_eqs in leisure areas were significantly higher than berthing areas by approximately 21 dBA during non-flight operation periods (p?=?0.001). Results suggest noise levels in “effective quiet” areas frequented by aircraft carrier personnel during off-duty hours when at-sea may inhibit auditory recovery from occupational noise exposures that occur on-duty.     

Management of recurrent urinary tract infections in adults

Many women will experience one or more urinary tract infection (UTI) during their life. The most unfortunate will have many. Men presenting with infections, and women with recurrent episodes, require further investigation. A diagnosis of a UTI is often based on a typical spectrum of symptoms, with confirmatory urine cultures lagging a few days behind. Unfortunately, symptoms of a UTI may not be typical, and other conditions can manifest similarly. Treatment of UTI with antibiotics is usually required, but there is increasing awareness of the need for antimicrobial stewardship to avoid the misuse and overuse of antibiotics, even as patients are increasingly reluctant to take them. Recurrent UTI can cause significant morbidity and disruption to daily activities yet investigations rarely demonstrate a reversible cause. There are a host of different antibiotic and non-antibiotic interventions that aim to lower the risk of further infections. However, these are not reliably effective, bring side effects of their own and are often proposed to this desperate population of patients on the back of weak evidence of efficacy.     

An overview of existing mesothelioma registries worldwide,and the need for a US Registry

The association between asbestos exposure, mainly in occupational settings, and malignant mesothelioma has been well established; this has prompted several countries to establish mesothelioma epidemiologic surveillance programs often at the request of national agencies. This review compares currently existing mesothelioma registries worldwide to develop a concept model for a US real-time case capture mesothelioma registry. Five countries were identified with a mesothelioma specific registry, including Italy, France, UK, Australia, and South Korea. All, except the UK, used interviews to collect exposure data. Linkage with the national death index was available or was in future plans for all registries. The registries have limited information on treatment, quality of life, and other patient-centered outcomes such as symptoms and pain management. To thoroughly collect exposure data, “real-time” enrollment is preferable; to maximize the capture of mesothelioma cases, optimal coverage, and a simplified consent process are needed.