A comprehensive literature scoping review of infection prevention and control methods for viral-mediated gene therapies.

Objective: This comprehensive literature scoping review outlines available infection prevention and control (IPC) methods for viral-mediated gene therapies and provides one IPC strategy for the healthcare setting based on a single-center recommendation. Methods: A team of experts in pharmacy, healthcare epidemiology, and biosafety with experience in viral-mediated gene therapy was assembled within a pediatric hospital to conduct a comprehensive literature scoping review. The comprehensive review included abstracts and full-text articles published since 2009 and utilized prespecified search terms of the five viral vectors of interest: adenovirus (AV), retrovirus (RV), adeno-associated virus (AAV), lentivirus (LV), and herpes simplex virus (HSV). Case reports, randomized controlled trials, and bench research studies were all included, while systematic reviews were excluded. Results: A total of 4473 case reports, randomized control trials, and benchtop research studies were identified using the defined search criteria. Chlorine compounds were found to inactivate AAV and AV, while alcohol-based disinfectants were ineffective. There was a relative paucity of studies investigating surface-based disinfection for HSV, however, alcohol-based disinfectants were effective in one study. Ultraviolent irradiation was also found to inactivate HSV in numerous studies. No studies investigated disinfection for LV and RV vectors. Conclusions: The need to define IPC methods is high due to the rapid emergence of viral-mediated gene therapies to treat rare diseases, but published clinical guidance remains scarce. In the absence of these data, our center recommends a 1:10 sodium hypochlorite solution in clinical and academic environments to ensure complete germicidal activity of viral-mediated gene therapies.

Safety and Efficacy of Prophylactic Levofloxacin in Pediatric and Adult Hematopoietic Stem Cell Transplantation Patients.

Levofloxacin has been widely used for bacteremia prophylaxis in the pre-engraftment setting for patients undergoing hematopoietic stem cell transplantation (HSCT), but data supporting this practice are inconsistent. In addition to concern for lack of benefit, there are also concerns that this practice could increase the rates of Clostridioides difficile (C diff) infections, the incidence of multidrug-resistant organisms (MDRO) or lead to increased incidence of acute graft-versus-host disease (aGVHD) by disrupting the gut microbiome. This study aimed to assess the safety and efficacy of levofloxacin as bacterial prophylaxis in pediatric and young adult patients undergoing allogeneic or autologous HSCT at a single pediatric center. We conducted a retrospective chart review evaluating patients age ≥6 months who underwent HSCT at our center between January 1, 2016, and July 31, 2020. Patients who underwent transplantation before March 2018 did not receive levofloxacin prophylaxis, whereas those who underwent transplantation after April 2018 did receive levofloxacin prophylaxis. Each transplantation was included as a separate episode if the patient underwent more than 1 transplantation during the inclusion time. The primary outcome of this study was the proportion of patients who experienced at least 1 bacterial bloodstream infection (BSI) in the first 100 days post-transplantation. Secondary outcomes included the number of non-levofloxacin antibiotic days post-transplantation, the incidence of aGVHD, the occurrence of C diff infections, and development of MDRO. A total of 370 HSCT recipients with a median age of 6.7 years (range, 0.5 to 39 years) were included in this study. Seventy-two patients had undergone more than 1 transplantation, and thus we had 443 transplantations to observe. Of these, 216 did not include levofloxacin prophylaxis and 227 included levofloxacin prophylaxis. There were no differences in baseline characteristics between the 2 groups except for age; patients in the non-levofloxacin prophylaxis group were younger (8.1 years vs 9.6 years; P = .05). There were no between-group differences in rates of death at 100 days, antibiotic use, fungal infections, or MDRO infections. Patients in the non-prophylaxis group developed more bacterial BSI in the first 100 days post-HSCT (27% versus 17%; P = .004) and more C diff infections (20% versus 9%; P = .003) than patients who received levofloxacin prophylaxis. In addition, more aGVHD was seen in the patients without levofloxacin prophylaxis (P = .014). Levofloxacin prophylaxis given from day -2 of HSCT through engraftment was significantly associated with decreased bacterial BSI in the first 100 days post-transplantation and was not associated with increased risks of C diff, aGVHD, or MDRO. Our study supports the use of levofloxacin prophylaxis in the peritransplantation period. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Protocol and Preliminary Results of the Nutritarian Women's Health Study: A Longitudinal Effectiveness-Implementation Hybrid Study Assessing Dietary Intake and Health Outcomes.

Whole-food plant-rich dietary patterns have been shown to be associated with significant health benefits and disease-risk reduction. One such program, which has been gaining popularity, is the micronutrient-dense plant-rich (mNDPR) "Nutritarian" diet. The goal of this study is to determine the feasibility of implementing an online mNDPR "Nutritarian" intervention program and to determine the effectiveness of this program in reducing risk of chronic disease in women. The Nutritarian Women's Health Study is a long-term online longitudinal hybrid effectiveness-implementation study. Participants are recruited through social media, medical professionals/offices, and nutrition-related events and conferences. Participants receive online nutrition education and complete regular self-reported questionnaires regarding lifestyle, nutrition practices, and health. The online intervention program appears to be feasible and effective. Some decline in dietary adherence, particularly for certain food types, was observed during the study. For groups at risk, based on body mass index or waist-to-height ratio, there were initial decreases in body mass index and waist-to-height that leveled off over time, in some cases returning to baseline measures. The study suggests the implementation of the Nutritarian dietary pattern, through an online intervention component, may be effective in reducing the risk of chronic disease, with implications for clinical and public health practice.

Impact of a 6-Month Micronutrient-Dense Plant-Rich Nutrition Intervention on Health and Well-Being at the Worksite.

This nonrandomized pilot study utilized the health belief model and the theory of planned behavior to assess the effectiveness of perceived behavioral control to determine the impact of a micronutrient-dense plant-rich (mNDPR) dietary intervention on employee health and wellness at the worksite. Seventy-one employees and/or spouses (≥18 years) who met the inclusion criteria were recruited from a regional medical center and a local university. Participants were provided more than 14 hours of in-person lecture combined with take-home materials, and electronic resources to support participants in their transition and adherence to the dietary plan. The study consisted of a 6-hour introductory session followed by weekly 1-hour meetings for 7 consecutive weeks and then monthly 1-hour meetings, for 4 consecutive months over the span of 6 months. Retention of participants was approximately 55 percent. Participants were assessed for measures of weight, waist circumference, and blood pressure; physiological measures of blood cholesterol, triglycerides, blood glucose, and hemoglobin A1c; and well-being measures of gastroesophageal reflux disease, depression, sleep, pain, and worksite productivity, pre-, mid-, and post-intervention. A significant reduction was seen in weight (F(2, 78) = 19.81, p < 0.001) with a mean reduction of 6.65 lb., waist circumference (F(2, 72) = 40.914, p < 0.001) with a mean reduction of 2.8 inches, total cholesterol (F(2, 70) = 19.09, p < 0.001) with a mean reduction of 17.81 mg/dL, HDL (F(2, 70) = 4.005, p=0.023) with a mean reduction of 3.61 mg/dL, LDL (F(2, 56) = 10.087, p < 0.001) with a mean reduction of 13.1 mg/dL, blood glucose (F(2, 70) = 6.995, p=0.002) with a mean reduction of 3.7 mg/dL, hemoglobin A1c (paired samples t (39) = 2.689, p=0.01) with a mean reduction of 0.118%, GERD (F(2, 72) = 7.940, p=0.001, MSE = 4.225) with a mean reduction of 1.4, depressive symptoms as measured by the PHQ 9 (F(2, 72) = 10.062, p < 0.001, MSE = 5.174) with a mean reduction of 2.0, and an improvement in sleep quality was seen as measured by the PSQI (F(2, 74) = 11.047, p < 0.001, MSE = 2.269) with a mean improvement of 1.3. In most cases, improvement occurred across the first two time periods and then leveled off. Blood pressure, triglycerides, pain measurements, and WPAI did not change over time. Effect sizes for significant pairwise comparisons indicated medium to large effects of practical significance. This intervention was therefore effective at improving employee health and well-being. Widespread worksite implementation should be considered to improve the overall wellness of employees.