"The Shifting Face of Aesthetic Care: A Systematic Survey of Independent Medspa Directorship and Practitioner Trends in Florida".

BACKGROUND: The rapid proliferation of medical spas in the US has raised concerns over the continued shift of non-surgical aesthetic treatments away from traditional core specialty integration and supervision, potentially affecting the surgical treatment guidance and education of cosmetic surgery patients. This study aimed to assess the current trends in the growth of independent medspa facilities as well as practitioner supervision, licensing, and specialization in the state of Florida. METHODS: A comprehensive, statewide survey of all independent medspas in Florida, by municipality, employing Google and Yellow Pages search engines. Information gathered included the number of locations, business stakeholders, and director/practitioner licensing and certification obtained from the Florida Division of Corporations/Department of Health databases and respective medical boards. RESULTS: A total of 1,038 medspas were identified, revealing a 100% increase in number relative to 2021 estimates. Non-physician practitioners represented 84% of medspa providers, with core specialty medical director supervision present in only 22% of facilities and a large proportion of directors lacking specialty training (77%) or board certification (42%). Additionally, 25% of medspas appeared to disregard state guidelines pertaining to medical directorship, autonomous non-physician practice, and numerical/geographic restrictions on directorship, with 96% of facilities lacking licensing/registration with Florida's Agency for Health Care Administration. CONCLUSIONS: Medspa growth in Florida has been explosive, with continued departure from core supervision, increasingly limited specialty training/integration, and non-adherence to state guidelines. Enhanced regulation and integrated non-physician practitioner training are likely necessary to ensure patient safety and the cohesive practice of aesthetic medicine and surgery.

Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University.

Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked the centennial of Felix d'Hérelle's first publication on the clinical applications of phages. At the Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established to offer safe and potent phages for single-patient investigational new drug applications while recognizing the time constraints imposed by infection(s). This study provides a practical walkthrough of the pipeline with an Autographiviridae phage targeting Pseudomonas aeruginosa (phage vB_PaeA_SB, abbreviated to ΦSB). Notably, a thorough phage characterization and the evolutionary selection pressure exerted on bacteria by phages, analogous to antibiotics, are incorporated into the pipeline.

Landscape of Phase II Trials in Alzheimer's Disease.

BACKGROUND: Drug development in Alzheimer's disease (AD) over the past two decades has had high rates of failure. Novel trial designs, such as adaptive designs, have the potential to improve the efficiency of drug development in AD. OBJECTIVE: To evaluate the design characteristics, temporal trends, and differences in design between sponsor types in phase II trials of investigational agents in AD. METHODS: Phase I/II, II, and II/III trials for AD with drug or other biological interventions registered from December 1996 to December 2021 in ClinicalTrials.gov were included. Descriptive statistics were used to summarize trial characteristics. Linear, logistic, and multinomial regression models assessed temporal trends and differences between sponsor types in design characteristics. RESULTS: Of N = 474 trials identified, randomized parallel group design was the most common design (72%). Only 12 trials (2.5%) used an adaptive design; adaptive features included early stopping rules, model-based dose-finding, adaptive treatment arm selection, and response adaptive randomization. The use of non-randomized parallel-group and open-label single arm designs increased over time. No temporal trend in the use of adaptive design was identified. Trials sponsored by industry only were more likely to use a randomized parallel-group design and have a larger estimated sample size than trials with other sponsor types. CONCLUSION: Our systematic review showed that very few phase II trials in AD used an adaptive trial design. Innovation and implementation of novel trial designs in AD trials can accelerate the drug development process.

Comparing analytical strategies for balancing site-level characteristics in stepped-wedge cluster randomized trials: a simulation study.

BACKGROUND: Stepped-wedge cluster randomized trials (SWCRTs) are a type of cluster-randomized trial in which clusters are randomized to cross-over to the active intervention sequentially at regular intervals during the study period. For SWCRTs, sequential imbalances of cluster-level characteristics across the random sequence of clusters may lead to biased estimation. Our study aims to examine the effects of balancing cluster-level characteristics in SWCRTs. METHODS: To quantify the level of cluster-level imbalance, a novel imbalance index was developed based on the Spearman correlation and rank regression of the cluster-level characteristic with the cross-over timepoints. A simulation study was conducted to assess the impact of sequential cluster-level imbalances across different scenarios varying the: number of sites (clusters), sample size, number of cross-over timepoints, site-level intra-cluster correlation coefficient (ICC), and effect sizes. SWCRTs assumed either an immediate "constant" treatment effect, or a gradual "learning" treatment effect which increases over time after crossing over to the active intervention. Key performance metrics included the relative root mean square error (RRMSE) and relative mean bias. RESULTS: Fully-balanced designs almost always had the highest efficiency, as measured by the RRMSE, regardless of the number of sites, ICC, effect size, or sample sizes at each time for SWCRTs with learning effect. A consistent decreasing trend of efficiency was observed by increasing RRMSE as imbalance increased. For example, for a 12-site study with 20 participants per site/timepoint and ICC of 0.10, between the most balanced and least balanced designs, the RRMSE efficiency loss ranged from 52.5% to 191.9%. In addition, the RRMSE was decreased for larger sample sizes, larger number of sites, smaller ICC, and larger effect sizes. The impact of pre-balancing diminished when there was no learning effect. CONCLUSION: The impact of pre-balancing on preventing efficiency loss was easily observed when there was a learning effect. This suggests benefit of pre-balancing with respect to impacting factors of treatment effects.

Feasibility of Using Bacteriophage Therapy to Reduce Morbidity and Mortality Associated with Spinal Epidural Abscesses.

BACKGROUND: The aim of this study was to determine the feasibility of using bacteriophage therapeutics in spinal epidural abscess (SEA) by reviewing the causes and outcomes of SEA at a single institution and testing a bacteriophage for activity against preserved SEA clinical isolates. MATERIALS AND METHODS: Medical records were reviewed of patients that received incision and drainage for SEA at a single medical center. Causative organisms, incidence of coinciding bacteremia and outcomes were recorded. A subset of SEA patients (N = 11), that had preserved clinical isolates, were assessed to evaluate if a bacteriophage therapeutic had ample activity to those isolates as seen with spot tests and growth inhibition assays. RESULTS: Staphylococcus aureus was the predominate bacterial cause (71%) and bacteremia was associated with 96% of S. aureus SEA. Over 50% of the patients either died within three months, had recurrence of their infection, required repeat debridement, or had long term sequalae. A single bacteriophage had positive spot tests for all the S. aureus clinical isolates and inhibited bacterial growth for more than 24 hours for 9 of the 11 (82%) clinical isolates. CONCLUSION: SEA is associated with significant mortality and morbidity making this a potential indication for adjuvant bacteriophage therapeutics. Since S. aureus is the predominate cause of SEA and most cases are associated bacteremia this creates a potential screening and treatment platform for Staphylococcal bacteriophages therapeutics, allowing for potential pilot studies to be devised.

A Meta-Research of Randomized Controlled Trials in the Field of Mental Health: Comparing Pharmacological to Non-Pharmacological Interventions from 1955 to 2020.

OBJECTIVE: This study aimed to provide a general overview of mental health randomized controlled trials (RCTs) and summarize the temporal trends in terms of the number of studies, median sample sizes, and median effect sizes using data collected from the Cochrane Database of Systematic Reviews (CDSR). METHODS: Using data collected from the CDSR, the temporal trends are compared in terms of the number of studies, median sample sizes, and median effect sizes between two broad categories of interventions: pharmacological RCT (ph-RCT) and non-pharmacological RCT (nph-RCT), and in conjunction with major mental disorder categories. RESULTS: Chronologically, the number of mental health RCTs reported in publications has increased exponentially from 1955 to 2020. While ph-RCT comprised a majority of mental health RCTs in the earlier years, the proportion of nph-RCTs increased more quickly over time and markedly exceeded ph-RCT after 2010. The median sample size for all 6,652 mental health RCTs was 61, with 61 for ph-RCT and 60 for nph-RCT. Over time, the median fluctuated but an increasing trend was observed over the past 60+ years. The median of the effect size, measured by Pearson's r, for overall RCTs was 0.18, and nph-RCT (0.19) had a larger median effect size compared to ph-RCT (0.16). Over the years, the nph-RCT had a larger median effect size than the ph-RCT. Differences in the median effect sizes among the categories of mental disorders were also noted. Schizophrenia had the most RCTs, with a median Pearson's r value of 0.17. Mood disorder had the second largest number of RCTs and a median Pearson's r value of 0.15. Neurotic/stress-related mental disorder had the third largest number of RCTs with the highest median Pearson's r being 0.23. CONCLUSIONS: This study provides meaningful information and filled the knowledge gap in mental health RCTs.

Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter.

The rise of antimicrobial resistant (AMR) bacteria is a global public health threat. AMR Achromobacter bacteria pose a challenging clinical problem, particularly for those with cystic fibrosis (CF) who are predisposed to chronic bacterial lung infections. Lytic bacteriophages (phages) offer a potential alternative to treat AMR infections, with the possible benefit that phage selection for resistance in target bacteria might coincide with reduced pathogenicity. The result is a genetic "trade-off," such as increased sensitivity to chemical antibiotics, and/or decreased virulence of surviving bacteria that are phage resistant. Here, we show that two newly discovered lytic phages against Achromobacter were associated with stabilization of respiratory status when deployed to treat a chronic pulmonary infection in a CF patient using inhaled (nebulized) phage therapy. The two phages demonstrate traits that could be generally useful in their development as therapeutics, especially the possibility that the phages can select for clinically useful trade-offs if bacteria evolve phage resistance following therapy. We discuss the limitations of the current study and suggest further work that should explore whether the phages could be generally useful in targeting pulmonary or other Achromobacter infections in CF patients.

Salphage: Salvage Bacteriophage Therapy for Recalcitrant MRSA Prosthetic Joint Infection.

Prosthetic joint infections are a devastating complication of joint replacement surgery. Consequently, novel therapeutics are needed to thwart the significant morbidity and enormous financial ramifications that are associated with conventional treatments. One such promising adjuvant therapeutic is bacteriophage therapy given its antibiofilm activity and its ability to self-replicate. Herein we discuss the case of a 70-year-old female who had a recalcitrant MRSA prosthetic knee and femoral lateral plate infection who was successfully treated with adjuvant bacteriophage therapy. Moreover, this case discusses the importance of propagating bacteriophage therapeutics on bacteria that are devoid of toxins and the need to ensure bacteriophage activity to all bacterial morphologies. Overall, this case reinforces the potential benefit of using personalized bacteriophage therapy for recalcitrant prosthetic joint infections, but more translational research is needed to thereby devise effective, reproducible clinical trials.

Multiyear Time-Shift Study of Bacteria and Phage Dynamics in the Phyllosphere.

AbstractCoevolution shapes diversity within and among populations but is difficult to study directly. Time-shift experiments, where individuals from one point in time are experimentally challenged against individuals from past, contemporary, and/or future time points, are a powerful tool to measure coevolution. This approach has proven useful both in directly measuring coevolutionary change and in distinguishing among coevolutionary models. However, these data are only as informative as the time window over which they were collected, and inference from shorter coevolutionary windows might conflict with those from longer time periods. Previous time-shift experiments from natural microbial communities of horse chestnut tree leaves uncovered an apparent asymmetry, whereby bacterial hosts were more resistant to bacteriophages from all earlier points in the growing season, while phages were most infective to hosts from only the recent past. Here, we extend the time window over which these infectivity and resistance ranges are observed across years and confirm that the previously observed asymmetry holds over longer timescales. These data suggest that existing coevolutionary theory should be revised to include the possibility of differing models for hosts and their parasites and examined for how such asymmetries might reshape the predicted outcomes of coevolution.