Effectiveness of team-focused CPR on in-hospital CPR quality and outcomes.

Objective: We sought to identify changes in neurological outcome over time following initial training and subsequent implementation of team-focused CPR in an inpatient setting where responders practice specific roles with emphasis on minimally interrupted chest compressions and early defibrillation. Methods: This retrospective pre- vs post-intervention study was conducted at an urban 900-bed teaching hospital and Level I Cardiac Resuscitation Center. We included adult patients suffering in-hospital cardiac arrest occurring in non-emergency department and non-intensive care unit areas who received CPR and/or defibrillation. We compared survival with good neurological outcome at time of hospital discharge in the one-year periods before and after implementation of team-focused CPR. To investigate skill degradation, we compared cumulative survival with good neurological outcome in 3-month intervals against the before team-focused CPR baseline. Trained research associates abstracted explicitly defined variables from electronic health records using a standardized form and data dictionary to achieve consistency between collaborators. Results: Of 296 IHCAs, 207 patients met inclusion criteria and were analyzed. In 104 patients before team-focused CPR initiation, survival with good neurological outcome was 21%. In the 12-month period following team-focused CPR initiation, survival with good neurological outcome was 31% in 101 patients, risk difference 9.9% (95% CI -2 to 22%; p = 0.14). By quarterly time intervals, following team-focused CPR implementation, the cumulative survival with good neurological outcome at 3 months was 42%; at 6 months 37%; at 9 months 31%; and at 12 months 31%. Conclusion: In our single-institution implementation of team-focused CPR for in-hospital cardiac arrest, outcomes significantly improved at 6 months before declining towards baseline.

Food waste tectonics: Points of friction between policy push and practice pull in council-led household-food-waste interventions in Australia.

Household food waste is increasingly recognised as a global wicked problem for its greenhouse gas emissions, economic damage, and resource loss. Although targeted in the UN's Sustainable Development Goals, countries can only respond according to their capacity. For Australia, national policy has put the pressure on states and territories to divert food waste away from landfill into a nascent circular economy. For councils, this increasingly means implementing a FOGO (Food Organics/Garden Organics) kerbside collection. Despite funding and infrastructure development, many are resisting. Framed by the tenets of policy diffusion, this paper presents the results of a nationwide exploratory survey aimed at identifying how and why council-based waste services staff resist, emulate or lead FOGO implementation. By assessing participants current kerbside systems and their attitudes towards household food waste management, the survey found costs, contamination, and capacity and were key concerns. However, responses to these varied considerably despite similarities of situation, often relating more to collaborative attitudes across waste services, council, and councillors. This paper recognises that a conducive environment for change is urgently needed for Australia to achieve organics diversion targets and shift household food towards a circular economy. It provides a starting point for further research into the complex and nuanced dynamics between council waste services and FOGO implementations, from external drivers and council paradigms to individual attitudes and perceptions.

Evaluating the Disease-Related Experiences of TikTok Users With Lupus Erythematosus: Qualitative and Content Analysis.

BACKGROUND: Lupus erythematosus (LE) is an autoimmune condition that is associated with significant detriments to quality of life and daily functioning. TikTok, a popular social networking platform for sharing short videos, provides a unique opportunity to understand experiences with LE within a nonclinical sample, a population that is understudied in LE research. This is the first qualitative study that explores LE experiences using the TikTok platform. OBJECTIVE: This study aims to evaluate the disease-related experiences of TikTok users with LE using qualitative and content analysis. METHODS: TikTok videos were included if the hashtags included #lupus, were downloadable, were in English, and involved the personal experience of an individual with LE. A codebook was developed using a standardized inductive approach of iterative coding until saturation was reached. NVivo (Lumivero), a qualitative analysis software platform, was used to code videos and perform content analysis. Inductive thematic analysis was used to derive themes from the data. RESULTS: A total of 153 TikTok videos met the inclusion criteria. The most common codes were experiences with symptoms (106/153, 69.3%), mucocutaneous symptoms (61/153, 39.9%), and experiences with treatment (59/153, 38.6%). Experiences with symptoms and mucocutaneous symptoms had the greatest cumulative views (25,381,074 and 14,879,109 views, respectively). Five thematic conclusions were derived from the data: (1) mucocutaneous symptoms had profound effects on the mental health and body image of TikTok users with LE; (2) TikTok users' negative experiences with health care workers were often derived from diagnostic delays and perceptions of "medical gaslighting"; (3) TikTok users tended to portray pharmacologic and nonpharmacologic interventions, such as diet and naturopathic remedies, positively, whereas pharmacologic treatments were portrayed negatively or referred to as "chemotherapy"; (4) LE symptoms, particularly musculoskeletal symptoms and fatigue, interfered with users' daily functioning; and (5) although TikTok users frequently had strong support systems, feelings of isolation were often attributed to battling an "invisible illness." CONCLUSIONS: This study demonstrates that social media can provide important, clinically relevant information for health practitioners caring for patients with chronic conditions such as LE. As mucocutaneous symptoms were the predominant drivers of distress in our sample, the treatment of hair loss and rash is vital in this population. However, pharmacologic therapies were often depicted negatively, reinforcing the significance of discussions on the safety and effectiveness of these treatments. In addition, while TikTok users demonstrated robust support systems, feelings of having an "invisible illness" and "medical gaslighting" dominated negative interactions with others. This underscores the importance of providing validation in clinical interactions.

Solution Structure and Dynamics of Hf-Al and Hf-Zn Heterobimetallic Adducts Mimicking Relevant Intermediates in Chain Transfer Reactions.

Cationic cyclometalated hafnocenes [CpPrCpCH2CH2CH2Hf][B(C6F5)4] (4Pr) and [CpiBuCpCH2CH(Me)CH2Hf][B(C6F5)4] (4aiBu and 4biBu) were synthesized from the corresponding [(CpPr)2HfMe][B(C6F5)4] (1Pr) and [(CpiBu)2HfMe][B(C6F5)4] (1iBu) complexes via C-H activation. 4aiBu, 4biBu, and 4Pr, mimicking a propagating M-polymeryl species (M = transition metal) with or without a ß-methyl branch on the metalated chains, serve to investigate whether and how the nature of the last inserted olefin molecules changes the structure, stability, and reactivity of the corresponding heterobimetallic complexes, formed in the presence of aluminum- or zinc-alkyl chain transfer agents (CTAs), which are considered relevant intermediates in coordinative chain transfer polymerization (CCTP) and chain shuttling polymerization (CSP) technologies. NMR and DFT data indicate no major structural difference between the resulting heterobridged complexes, all characterized by the presence of multiple α-agostic interactions. On the contrary, thermodynamic and kinetic investigations, concerning the reversible formation and breaking of heterobimetallic adducts, demonstrate that isomer 4aiBu, in which the ß-Me is oriented away from the reactive coordination site on Hf, but not 4biBu, having the ß-Me pointing in the opposite direction, is capable of reacting with CTAs. Quantification of kinetic rate constants highlights that the formation process is rate limiting and that the nature of the last inserted α-olefin unit modulates transalkylation kinetics. The reaction of 4aiBu, 4biBu, and 4Pr with diisobutylaluminum hydride (DiBAlH) allows the interception and characterization of new heterobinuclear and heterotrinuclear species, featuring both hydride and alkyl bridging moieties, which represent structural models of elusive intermediates in CCTP and CSP processes, capturing the instant when an alkyl chain has just transferred from a transition metal to a main group metal, while the two metals remain engaged in a single heterobimetallic intermediate.

Multicenter analysis to assess risk of major adverse cardiac events in patients undergoing high-sensitivity troponin testing in the emergency department.

Study hypothesis: Our objective was to evaluate 30-day major adverse cardiac events (MACE) in emergency department (ED) patients with normal high-sensitivity troponins (hs-trop). We hypothesized that MACE rates would be <1% in patients with (1) two normal troponins regardless of change in troponin (delta) and (2) index hs-trop below the limit of quantitation (LOQ) regardless of the institution modified HEART score. Methods: This was a multicenter, retrospective, cohort study of adult patients who presented to 1 of 18 EDs between July 2020 and April 2021 with acute coronary syndrome as defined by an institutional-modified HEART score completed by their treating physician or midlevel, no evidence of ST-elevation myocardial infarction, and an index or serial gender-adjusted hs-trop within normal limits. The primary outcome was MACE within 30 days of index ED encounter. A detailed case review was then performed for those patients experiencing a MACE. Results: Of the 9084 patients who had single or serial normal troponins, 31 (0.34%; confidence interval [CI] 0.23%-0.48%) experienced MACE. Of the 6140 patients with 2 normal hs-trop and a delta (change in troponin) <4, 27 patients (0.44%; CI 0.29%-0.64%) experienced MACE. Only 1 of the 69 patients with 2 normal hs-trop results but delta (change in troponin) ≥ 4 (1.45%; CI 0.04%-7.81%) suffered MACE. This patient was classified as non-low risk by our institutional HEART score. Of 7498 patients with an index hs-trop 

Autoimmune bullous disorder flares following severe acute respiratory syndrome coronavirus 2 vaccination: a case series.

BACKGROUND: Autoimmune bullous disorders develop due to autoantibodies targeting intercellular adhesion proteins of hemidesmosomes and desmosomes and may be triggered by viral infections and vaccines. Recent reports suggest that the coronavirus disease 2019 vaccination may trigger flares or exacerbations of preexisting autoimmune diseases, including new onset autoimmune bullous disorders. There are less data on whether vaccination against severe acute respiratory syndrome coronavirus 2 may also exacerbate preexisting autoimmune bullous disorders. CASE PRESENTATION: Here we present three cases, two white males (ages 69 years and 88 years) with bullous pemphigoid and one white 50-year-old female with pemphigus foliaceus, wherein all individuals developed minor, tractable flares of their preexisting autoimmune bullous disorders after receiving the coronavirus disease 2019 vaccination, which were readily treatable with topical or low-dose systemic corticosteroids. CONCLUSIONS: Dermatologists managing patients with autoimmune bullous disorders should be cognizant of the uncommon potential for flares of the disorder following vaccination for severe acute respiratory syndrome coronavirus 2. Flares of bullous pemphigoid and pemphigus foliaceus following vaccination for severe acute respiratory syndrome coronavirus 2 in these cases were mild and tractable.

Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles.

Biodegradable and biocompatible polymeric nanoparticles (NPs) stand out as a key tool for improving drug bioavailability, reducing the inherent toxicity, and targeting the intended site. Most importantly, the ease of polymer synthesis and its derivatization to add functional properties makes them potentially ideal to fulfill the requirements for intended therapeutic applications. Among many polymers, US FDA-approved poly(l-lactic-co-glycolic) acid (PLGA) is a widely used biocompatible and biodegradable co-polymer in drug delivery and in implantable biomaterials. While many studies have been conducted using PLGA NPs as a drug delivery system, less attention has been given to understanding the effect of NP weight on cellular behaviors such as uptake. Here we discuss the synthesis of PLGA NPs with varying NP weights and their colloidal and biological properties. Following nanoprecipitation, we have synthesized PLGA NP sizes ranging from 60 to 100 nm by varying the initial PLGA feed in the system. These NPs were found to be stable for a prolonged period in colloidal conditions. We further studied cellular uptake and found that these NPs are cytocompatible; however, they are differentially uptaken by cancer and immune cells, which are greatly influenced by NPs' weight. The drug delivery potential of these nanoparticles (NPs) was assessed using doxorubicin (DOX) as a model drug, loaded into the NP core at a concentration of 7.0 ± 0.5 wt % to study its therapeutic effects. The results showed that both concentration and treatment time are crucial factors for exhibiting therapeutic effects, as observed with DOX-NPs exhibiting a higher potency at lower concentrations. The observations revealed that DOX-NPs exhibited a higher cellular uptake of DOX compared to the free-DOX treatment group. This will allow us to reduce the recommended dose to achieve the desired effect, which otherwise required a large dose when treated with free DOX. Considering the significance of PLGA-based nanoparticle drug delivery systems, we anticipate that this study will contribute to the establishment of design considerations and guidelines for the therapeutic applications of nanoparticles.

Absorption, Distribution, Metabolism, and Excretion of [14C]iptacopan in Healthy Male Volunteers and in In Vivo and In Vitro Studies.

Iptacopan (LNP023) is an oral, small-molecule, first-in-class, highly potent proximal complement inhibitor that specifically binds factor B and inhibits the alternative complement pathway. Iptacopan is currently in development as a targeted treatment of paroxysmal nocturnal hemoglobinuria and multiple other complement-mediated diseases. In this study, the absorption, distribution, metabolism, and excretion (ADME) of iptacopan was characterized in six healthy volunteers after a single 100 mg oral dose of [14C]iptacopan. This was supplemented with an in vivo rat ADME study and metabolite exposure comparisons between human, rat, and dog, in addition to in vitro assays, to better understand the clearance pathways and enzymes involved in the metabolism of iptacopan. The fraction of [14C]iptacopan absorbed was estimated to be about 71%, with a time to maximum concentration of 1.5 hours and elimination half-life from plasma of 12.3 hours. Following a single dose of [14C]iptacopan, 71.5% of the radioactivity was recovered in feces and 24.8% in urine. [14C]iptacopan was primarily eliminated by hepatic metabolism. The main biotransformation pathways were oxidative metabolism via CYP2C8, with M2 being the major oxidative metabolite, and acyl glucuronidation via UGT1A1. The two acyl glucuronide metabolites in human plasma, M8 and M9, each accounted for ≤ 10% of the total circulating drug-related material; systemic exposure was also observed in toxicology studies in rat and dog, suggesting a low risk associated with these metabolites. Binding of iptacopan to its target, factor B, in the bloodstream led to a concentration-dependent blood:plasma distribution and plasma protein binding of [14C]iptacopan. SIGNIFICANCE STATEMENT: We characterized the pharmacokinetics, excretion, metabolism and elimination of [14C]iptacopan (an oral, selective small-molecule inhibitor of factor B) in healthy human subjects. [14C]iptacopan was primarily eliminated by metabolism. The primary biotransformation pathways were oxidative metabolism via CYP2C8 and acyl glucuronidation via UGT1A1. Direct secretion of iptacopan into urine and potentially bile represented additional elimination mechanisms. Binding of iptacopan to its target, factor B, in the bloodstream led to a concentration-dependent blood:plasma distribution and plasma protein binding of [14C]iptacopan.

Why people are bad at leftover food management? A systematic literature review and a framework to analyze household leftover food waste generation behavior.

Food waste is a significant global problem. In the Global North, households are a major driver of food waste generation and also a key enabler of solutions to address the issue. Leftover food management is identified as one of the key areas that can be targeted to reduce food waste at home. Although a large body of literature exists on household food waste and its drivers, managing food leftovers has received less attention. This state-of-the-art review focuses on leftover food management practices with the view of supporting practitioners in designing and prioritizing behavioral interventions to reduce leftover food waste in households. It uses the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to select articles for the review. Based on 42 primary studies, this systematic review identifies a range of psycho-social, socio-demographic and lifestyle factors influencing leftover food waste generation behavior at home. Moreover, household food handling skills and knowledge, and availability and accessibility to infrastructure facilities affect leftover food waste generation behavior. Based on the synthesized literature, Leftover Food Waste Generation Behavior (LFWGB) Framework has been developed. The framework conceptualizes psycho-social, personal and lifestyle factors driving leftover food management behaviors at home. Reducing food leftovers must be given top priority along with consumer meal planning and food preparation skills in household food waste reduction interventions and campaigns.

Outcomes of a Large Series of Laparoscopic Ventral Hernia Repairs after Liver Transplantation.

BACKGROUND: The hernia defects that develop in liver transplant recipients tend to be complex. Unfortunately, there is a paucity of data to guide post-transplant hernia management. Our goal was to evaluate the outcomes following laparoscopic ventral hernia repair (LVHR) in liver transplant recipients. METHODS: A retrospective review of a prospectively kept database of liver transplant patients at a single tertiary healthcare facility was completed. All patients between 2007 and 2020 who underwent LVHR for a hernia at their transplant incision site were included. The primary outcome studied was hernia recurrence. Secondary outcomes included time-to-hernia repair, complications, and length of stay (LOS). RESULTS: There were 89 patients who met inclusion criteria. 82% were male, mean age was 60 years, and mean body mass index was 30.2 kg/m2. 94.4% were on tacrolimus and 36% on mycophenolate mofetil. Median time-to-hernia repair was 16 months with a mean mesh size of 743 cm2 and length of stay of 3.7 days. None required conversion to an open operation. Postoperative complications included ileus (20.2%), acute kidney injury (11.2%), pneumonia (6.7%), and bleeding requiring re-operation (1.1%). Hernia-related complications included chronic suture site pain (1.1%), seroma requiring intervention (3.3%), surgical site infection (3.3%), nonoperative mesh infection (1.1%), and mesh infection requiring explantation (1.1%). Median follow-up was 23 months. Hernia recurrence occurred in 4.5% and no predictive variables for recurrence were identified. CONCLUSIONS: Although the hernia defects that develop in liver transplant recipients are complex and their comorbidities significant, LVHR can safely and effectively repair these defects with low rates of recurrence and complications.

A 20-Year Analysis of Medicare Reimbursement for Abdominal Wall Reconstruction (2000 to 2020).

BACKGROUND: The purpose of this study was to evaluate monetary trends in Medicare reimbursement rates for 30 abdominal wall reconstruction surgical procedures over a 20-year period (2000 to 2020). METHODS: The Physician Fee Schedule Look-Up Tool from the Centers for Medicare and Medicaid Services was used for each of the 30 included current CPT codes, and reimbursement data were extracted. Monetary data were adjusted for inflation to 2020 U.S. dollars using changes to the United States consumer price index. The R 2 values for the average annual percentage change and the average total percentage change in reimbursement were calculated based on these adjusted trends for all included procedures. RESULTS: After adjusting for inflation, the average reimbursement for all procedures decreased by 17.1% from 2000 to 2020. The greatest mean decrease was observed for CPT code 49568 (the implantation of mesh or other prosthesis for open incisional or ventral hernia repair or mesh for closure of débridement for necrotizing soft-tissue infection, -34.4%). The only procedure with an increased adjusted reimbursement rate throughout the study period was CPT code 20680 (+3.9%). From 2000 to 2020, the adjusted reimbursement rate for all included procedures decreased by an average of 0.85% each year, with an average R 2 value of 0.78, indicating a stable decline throughout the study period. CONCLUSIONS: Reimbursement rates are declining when adjusted for inflation. Increased awareness of these trends is helpful to maintain access to optimal abdominal reconstruction care in the United States.

Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results.

Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n = 4), 8 (n = 4), or -1 (n = 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).

Has the COVID-19 pandemic changed household food management and food waste behavior? A natural experiment using propensity score matching.

Household food management behavior changed considerably during the COVID-19 pandemic. A growing body of work has quantified the impact of lockdowns on household food waste. Yet, previous studies used a retrospective study design which undermines the accuracy of the causal effect on household food waste. This paper investigates the causal impact of the COVID-19 pandemic on household food management and food waste using a natural experiment approach. Using two large national-scale longitudinal data sets (n = 8157), this study quantifies the impact of COVID-19 on food waste and food behavior of Australian households. Propensity score matching (PSM) was carried out to address potential endogeneity issues and to select control and treatment groups for analysis. Findings reveal that Australian households reduced food waste by 9% on average in 2020 (during COVID-19) compared to the pre-pandemic (2019) level. The use of a grocery list, discount purchases, and 'just-in-case' purchases, and food refrigeration have recorded a marked increase during the pandemic compared to pre-pandemic times. The changes to food management and food discard behavior during the pandemic offer important insights for behavior change campaigns to reduce household food waste. Interventions to sustain good food planning and storage practices and involving food retailers are promising entry points in addressing household food waste. The study also highlights the considerable challenge in achieving SDG 12.3 target by 2030.

Multidisciplinary perceptions on robotic surgical training: the robot is a stimulus for surgical education change.

BACKGROUND: It is unclear how to best establish successful robotic training programs or if subspecialty robotic program principles can be adapted for general surgery practice. The objective of this study is to understand the perspectives of high-volume robotic surgical educators on best practices in robotic surgery training and to provide recommendations transferable across surgical disciplines. METHODS: This multi-institutional qualitative analysis involved semi-structured interviews with high-volume robotic educators from academic general surgery (AGS), community general surgery (CGS), urology (URO), and gynecology (GYN). Purposeful sampling and snowballing ensured high-volume status and geographically balanced representation across four strata. Interviews were transcribed, deidentified, and independently, inductively coded. A codebook was developed and refined using constant comparative method until interrater reliability kappa reached 0.95. A qualitative thematic, framework analysis was completed. RESULTS: Thirty-four interviews were completed: AGS (n = 9), CGS (n = 8), URO (n = 9), and GYN (n = 8) resulting in 40 codes and four themes. Theme 1: intangibles of culture, resident engagement, and faculty and administrative buy-in are as important as tangibles of robot and simulator access, online modules, and case volumes. Theme 2: robotic OR integration stresses the trainee-autonomy versus patient-safety balance. Theme 3: trainees acquire robotic skills along individual learning curves; benchmark assessments track progress. Theme 4: AGS can learn from URO and GYN through multidisciplinary collaboration but must balance pre-existing training program use with context-specific curricular needs. CONCLUSIONS: Robotic surgical experts emphasize the importance of universal training paradigms, such as a strong educational culture that balances autonomy and patient safety, collaboration between disciplines, and routine assessments for continuous growth. Often, introduction and acceptance of the robot serves as a stimulus to discuss broader surgical education change.

Human Pharmacokinetics of LYS006, an Oral Leukotriene A4 Hydrolase Inhibitor Displaying Target-Mediated Drug Disposition.

LYS006 is a potent leukotriene A4 hydrolase inhibitor currently in clinical development for long-term treatment of various neutrophil-driven inflammatory conditions. Here, we present pharmacokinetics from the first-in-human study with complementary metabolism and transporter profiling data. The randomized first-in-human study included nine cohorts receiving 5-2*100 mg of LYS006 or placebo, a crossover food-effect part, and a multiple-dose part consisting of two fasted (5 mg and 15 mg once daily) and three fed cohorts (20-80 mg twice a day) of LYS006 or placebo. LYS006 and metabolites were assessed in plasma and urine, and transporters involved in LYS006 disposition were analyzed in vitro. Systemic plasma exposure increased with dose; steady-state exposure was dose proportional up to 40 mg twice a day. Steady state was achieved after ∼3 days, with mean accumulation of 2.1-fold for 5 mg once daily and ≤1.4-fold for all higher doses. Despite limited accumulation, a long terminal half-life (T1/2) was observed. The long T1/2 and saturable binding to blood cells, which causes a highly nonlinear blood-to-plasma distribution, reflect a strong impact of target binding on drug distribution at lower concentrations. Skin biopsy and blister fluid concentration data indicated saturable binding in the former but not the latter, suggesting saturable binding in tissues beyond blood. Major excretion of LYS006 (∼90% of dose) through urine at steady state triggered renal transporter investigations that identified LYS006 as a substrate of organic anion transporter (OAT)3, OAT4, breast cancer resistance protein, and multidrug resistance-associated protein 4. Seven metabolites were identified in human plasma and urine, comprising only 4% of the dose recovered in urine at steady state. SIGNIFICANCE STATEMENT: Pharmacokinetic data from a first-in-human study combined with in vitro work support dose and regimen selection for patient studies with LYS006 and provide guidance on drug interaction investigations and other clinical pharmacology work needed for further development. Mass balance information at steady state without the use of a radiolabel, skin concentrations, and identification of the major clearance pathway, as well as the transporters driving elimination, make this a particularly conclusive early study despite nonlinear pharmacokinetics impacted by target binding.

The impact of genital lichen sclerosus and lichen planus on quality of life: A review.

Background: Lichen sclerosus (LS) and lichen planus (LP) are inflammatory diseases that demonstrate genital and extra-genital manifestations. Genital involvement may result in pruritus, sexual dysfunction, pain, and irritation. It is intuitive that the severity of symptoms may result in functional impairment and emotional distress, leading to a reduction in quality of life (QoL). Objective: Investigate the current literature on the impact of genital LS and LP on QoL. Methods: A literature review was performed using PubMed and results were summarized. Articles published between 1994 and 2020 were screened and reviewed by both the authors. Results: These diseases have been assessed with dermatological assessments, such as the Skindex-29 and the Dermatology Life Quality Index, general health surveys such as the Short Form-12 questionnaire, and mental health instruments including the Beck Depression Inventory, and others; these instruments consistently demonstrate impaired QoL. It follows that treatment may reduce these symptoms. Interventions, such as photodynamic therapy, have demonstrated improvement in the depressive symptoms that impact QoL. Although both females and males experience a reduction in QoL related to these diseases, they experience the symptomatology differently. Through interviewing, male patients were more likely to report no symptoms compared with female patients, while female patients were also more likely to report worse QoL in the work-school domain of the Dermatology Life Quality Index as compared with male patients. Limitations: Few studies have addressed the effect of disease severity or treatment on QoL. Conclusions: Understanding how genital LS and LP contribute to reduced QoL for patients is critical for health care providers to better prioritize treatment strategies. Future prospective studies should investigate how QoL correlates with disease severity and response to treatment.