Plastic Surgery Outreach Clinics Expand Access to Cleft and Craniofacial Care in Mississippi.

ABSTRACT: Accessing treatment at ACPA (American Cleft Palate-Craniofacial Association)-approved centers is challenging for individuals in rural communities. This study aims to assess how pediatric plastic surgery outreach clinics impact access for patients with orofacial cleft and craniosynostosis in Mississippi. An isochrone map was used to determine mean travel times from Mississippi counties to the sole pediatric hospital and the only ACPA-approved team in the state. This analysis was done before and after the establishment of two outreach clinics to assess differences in travel times and cost of travel to specialized plastic surgery care. Two sample t-tests were used for analysis.The addition of outreach clinics in North and South Mississippi led to a significant reduction in mean travel times for patients with cleft and craniofacial diagnoses across the state's counties (1.81 hours vs 1.46 hours, P < 0.001). Noteworthy travel cost savings were observed after the introduction of outreach clinics when considering both the pandemic gas prices ($15.27 vs $9.80, P < 0.001) and post-pandemic prices ($36.52 vs $23.43, P < 0.001).The addition of outreach clinics in Mississippi has expanded access to specialized healthcare for patients with cleft and craniofacial differences resulting in reduced travel time and cost savings for these patients. Establishing specialty outreach clinics in other rural states across the United States may contribute significantly to reducing burden of care for patients with clefts and craniofacial differences. Future studies can further investigate whether the inclusion of outreach clinics improves follow-up rates and surgical outcomes for these patients.

Implementation of an Enhanced Recovery After Surgery Protocol for Cleft Palate Repair.

OBJECTIVE: This study examines an Enhanced Recovery After Surgery (ERAS) protocol for patients with cleft palate and hypothesizes that patients who followed the protocol would have decreased hospital length of stay and decreased narcotic usage than those who did not. DESIGN: Retrospective cohort study. SETTING: The study takes place at a single tertiary children's hospital. PATIENTS: All patients who underwent cleft palate repair during a 10-year period (n = 242). INTERVENTIONS: All patients underwent cleft palate repair with the most recent cohort following a new ERAS protocol. MAIN OUTCOME MEASURES: Primary outcomes included hospital length of stay and narcotic usage in the first 24 hours after surgery. RESULTS: Use of local bupivacaine during surgery was associated with decreased initial 24-hour morphine equivalent usage: 2.25 vs 3.38 mg morphine equivalent (MME) (P < 0.01), and a decreased hospital length of stay: 1.71 days vs 2.27 days (P < 0.01). The highest 24-hour morphine equivalent a patient consumed prior to the ERAS protocol implementation was 24.53 MME, compared with 6.3 MME after implementation. Utilization of the ERAS protocol was found to be associated with a decreased hospital length of stay: 1.67 vs 2.18 days (P < 0.01). CONCLUSIONS: Use of the proposed ERAS protocol may lead to lower narcotic usage and decreased length of stay.

Longitudinal Speech and Fistula Outcomes Following Primary Cleft Palate Repair at a Single Institution.

INTRODUCTION: Fistula formation and velopharyngeal insufficiency (VPI) are complications of cleft palate repair that often require surgical correction. The goal of the present study was to examine a single institution's experience with cleft palate repair with respect to fistula formation and need for surgery to correct velopharyngeal dysfunction. METHODS: Institutional review board approval was obtained. Patient demographics and operative details over a 10-year period were collected. Primary outcomes measured were development of fistula and need for surgery to correct VPI. Chi-square tests and independent t tests were utilized to determine significance (0.05). RESULTS: Following exclusion of patients without enough information for analysis, 242 patients were included in the study. Fistulas were reported in 21.5% of patients, and surgery to correct velopharyngeal dysfunction was needed in 10.7% of patients. Two-stage palate repair was associated with need for surgery to correct VPI (P = 0.014). Furlow palatoplasty was associated with decreased rate of fistula formation (P = 0.002) and decreased need for surgery to correct VPI (P = 0.014). CONCLUSION: This study reiterates much of the literature regarding differing cleft palate repair techniques. A 2-stage palate repair is often touted as having less growth restriction, but the present study suggests this may yield an increased need for surgery to correct VPI. Prior studies of Furlow palatoplasty have demonstrated an association with higher rates of fistula formation. The present study demonstrated a decreased rate of fistula formation with the Furlow technique, which may be due to the use of the Children's Hospital of Philadelphia modification. This study suggests clinically superior outcomes of the Furlow palatoplasty over other techniques.

Mandibular Distraction in Patients With Pierre Robin Sequence: A Multisurgeon Experience.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) is rapidly becoming a standard of care for management of patients with severe Pierre Robin sequence. The tongue is brought forward to alleviate airway obstruction. This study will look at an institutional, multisurgeon experience with MDO over 10 years. DESIGN: A retrospective chart review was conducted. SETTING: All patients who underwent MDO at the authors' institution from 2012 to 2022 were included. Three craniofacial surgeons performed all interventions. PATIENTS: Demographics, preoperative and postoperative respiratory and feeding status, and distraction data were collected for 27 patients meeting inclusion criteria. MAIN OUTCOME MEASURES: Primary outcomes were avoidance of a gastrostomy tube, avoidance of a tracheostomy, discharge from hospital on room air, and complications. A significance value of 0.05 was utilized. RESULTS: The average age at MDO was 135 days, mean activation phase was 13.6 days, mean distraction length was 14.9 mm, and mean consolidation phase was 64.2 days. A longer activation phase was associated with discharge with a gastrostomy tube and a shorter activation phase was associated with discharge on full oral feeds. The ability to discharge on room air was associated with a shorter latency phase, shorter activation phase, and decreased distance of distraction. CONCLUSIONS: The goal of MDO is to achieve full oral feeds with no respiratory support. Several different latency periods were used in this study, and a short latency period was demonstrated to be safe.

Patients Requiring Multiple Surgeries for Velopharyngeal Insufficiency: Findings From a 10-Year Retrospective Review.

This study analyzed patients undergoing multiple surgeries for velopharyngeal insufficiency (VPI) and reviewed their preoperative evaluations and techniques selected for subsequent surgeries. A retrospective chart review was performed including patients having undergone multiple surgeries for VPI at the authors' institution between 2012 and 2022. All patients were evaluated and managed at the author's institution under the direction of 4 senior surgeons. The objective of this study was to provide insight into preoperative evaluation, surgical technique selection, and other factors that may contribute to patients who require multiple VPI surgeries. Of 71 patients having undergone surgery for VPI, 8 required at least 1 additional operation for persistent VPI following the initial intervention. Six patients who initially underwent a superiorly based posterior pharyngeal flap (PPF) required additional surgery, and for those patients' subsequent operations, 5 different techniques were used throughout their treatment. Of the remaining 2 patients who had multiple VPI surgeries, 1 initially received autologous fat transfer and 1 initially underwent a furlow palatoplasty. Finally, 0 patients that initially underwent buccal flaps or collagen injection required further unplanned surgical intervention. This study demonstrates the importance of selecting an appropriate surgical approach when operating on patients following a failed VPI surgery. The algorithm developed from these findings emphasizes the importance of properly identifying the anatomical deficiency resulting from the failed intervention. A review of the advantages of nasopharyngoscopy as a preoperative evaluative technique of velopharyngeal form and function when compared to lateral barium video fluoroscopy was also included.

Assessing risks from fuel contamination in Antarctica: Dynamics of diesel ageing in soil and toxicity to an endemic nematode.

Fuel spills are a major source of contamination in terrestrial environments in Antarctica. Little is known of the effects of hydrocarbon contaminants in fuels on Antarctic terrestrial biota, and how these change as fuel ages within soil. In this study we investigate the sensitivity of juveniles of the endemic Antarctic nematode Plectus murrayi to diesel-spiked soil. Toxicity tests were conducted on soil elutriates, and changes in concentrations of hydrocarbons, polar compounds and PAHs were assessed as the spiked soil was artificially aged at 3 °C over a 45-week period, representing multiple summer seasons of fuel degradation. Nematodes were most sensitive to elutriates made from freshly spiked soils (LC50 419 µg/L TPH and 156 µg/L TPH-SG), with a subsequent decline in toxicity observed in the first 6 weeks of laboratory ageing (LC50 2945 µg/L TPH and 694 µg/L TPH-SG). Effects were still evident up to 45 weeks (lowest observed effect concentration 2123 µg/L TPH) despite hydrocarbons being depleted from soils with ageing (84 % loss) and elutriates becoming dominated by polar metabolites (95 % polar). Nematode sensitivity throughout the ageing period showed evidence of a relationship between LC50 and the proportions of the lighter carbon range fraction of TPH in elutriates, the F2 fraction (C10-14). This study is the first to estimate the sensitivity of Antarctic terrestrial fauna to diesel and provides novel data on the dynamics of fuel chemistry under Antarctic conditions and how this influences toxicity. Findings contribute to predicting ecological risk at existing diesel fuel spill sites in Antarctica, to the derivation of site-specific remediation targets, and to environmental guidelines to assess ecosystem health.

A Digital Diabetes Storytelling Intervention for the Hmong Community: A Pilot Study.

Hmong-Americans experience higher rates of diabetes and poorer diabetes-related health outcomes than their White peers. Traditional methods of diabetes education do not reach Hmong patients effectively due to known socioeconomic and literacy barriers. The purpose of this study is to examine the acceptability of a culturally informed diabetes self-management education video tool, using digital storytelling that was created using a community-engaged approach, administered in a single academic clinic that sees a large percentage of Hmong patients. The video tool was successful in the areas of acceptability, story transformation, and story identification; 96% of participants stated that the video felt like something from their community, 88% stated that they could identify with the story, 79% stated that they wanted to know what happened next, and 70% of participants reported that they were motivated to do something different after watching. New methods to improve diabetes education and improve health outcomes in Hmong communities are needed. Culturally informed digital storytelling is one tool, which may be used to improve diabetes health outcomes in this population.

A theoretical model of contraceptive decision-making and behaviour in diabetes: A qualitative application of the Health Belief Model.

AIM: People with diabetes have contraceptive needs that have been inadequately addressed. The aim of this qualitative study was to develop a theoretical model that reflects contraceptive decision-making and behaviour in the setting of diabetes mellitus. METHODS: We conducted semi-structured, qualitative interviews of 17 women with type 1 or type 2 diabetes from Michigan, USA. Participants were recruited from a diabetes registry and local clinics. We adapted domains from the Health Belief Model (HBM) and applied reproductive justice principles to inform the qualitative data collection and analysis. Using an iterative coding template, we advanced from descriptive to theoretical codes, compared codes across characteristics of interest (e.g. diabetes type), and synthesized the theoretical codes and their relationships in an explanatory model. RESULTS: The final model included the following constructs and themes: perceived barriers and benefits to contraceptive use (effects on blood sugar, risk of diabetes-related complications, improved quality of life); perceived seriousness of pregnancy (harm to self, harm to foetus or baby); perceived susceptibility to pregnancy risks (diabetes is a 'high risk' state); external cues to action (one-size-fits-all/anxiety-provoking counselling vs. personalized/trust-based counselling); internal cues to action (self-perceived 'sickness'); self-efficacy (reproductive self-efficacy, contraceptive self-efficacy); and modifying factors (perceptions of biased counselling based upon one's age, race or severity of disease). CONCLUSIONS: This novel adaptation of the HBM highlights the need for condition-specific and person-centred contraceptive counselling for those with diabetes.

From Hospital to the Community: Redesigning the Human Immunodeficiency Virus (HIV) Clinical Service Model to Respond to an Outbreak of HIV Among People Who Inject Drugs.

An outbreak of human immunodeficiency virus (HIV) among people who inject drugs in Glasgow, Scotland started in 2014. We describe 156 cases over 5 years and evaluate the impact of clinical interventions using virological and phylogenetic analysis. We established (1) HIV services within homeless health facilities, including outreach nurses, and (2) antiretroviral therapy (ART) via community pharmacies. Implementation of the new model reduced time to ART initiation from 264 to 23 days and increased community viral load suppression rates to 86%. Phylogenetic analysis demonstrated that 2019 diagnoses were concentrated within a single network. Traditional HIV care models require adaptation for this highly complex population.

Assessing the Risk of Metals and Their Mixtures in the Antarctic Nearshore Marine Environment with Diffusive Gradients in Thin-Films.

Robust environmental assessments and contaminant monitoring in Antarctic near-shore marine environments need new techniques to overcome challenges presented by a highly dynamic environment. This study outlines an approach for contaminant monitoring and risk assessment in Antarctic marine conditions using diffusive gradients in thin-films (DGT) coupled to regionally specific ecotoxicology data and environmental quality standards. This is demonstrated in a field study where DGT samplers were deployed in the near-shore marine environment of East Antarctica around the operational Casey station and the abandoned Wilkes station to measure the time-averaged biologically available fraction of metal contaminants. The incorporation of DGT-labile concentrations to reference toxicity mixture models for three Antarctic organisms predicted low toxic effects (<5% effect to the growth or development of each organism). The comparison of metal concentrations to the Australian and New Zealand default water quality guideline values (WQGVs) showed no marine site exceeding the WQGVs for 95% species protection. However, all sites exceeded the 99% WQGVs due to copper concentrations that are likely of geogenic origin (i.e., not from anthropogenic sources). This study provides evidence supporting the use of the DGT technique to monitor contaminants and assess their environmental risk in the near-shore marine environment of Antarctica.

Chronic Rejection of Cardiac Allografts Is Associated With Increased Lymphatic Flow and Cellular Trafficking.

BACKGROUND: Cardiac transplantation is an excellent treatment for end-stage heart disease. However, rejection of the donor graft, in particular, by chronic rejection leading to cardiac allograft vasculopathy, remains a major cause of graft loss. The lymphatic system plays a crucial role in the alloimmune response, facilitating trafficking of antigen-presenting cells to draining lymph nodes. The encounter of antigen-presenting cells with T lymphocytes in secondary lymphoid organs is essential for the initiation of alloimmunity. Donor lymphatic vessels are not anastomosed to that of the recipient during transplantation. The pathophysiology of lymphatic disruption is unknown, and whether this disruption enhances or hinders the alloimmune responses is unclear. Although histological analysis of lymphatic vessels in donor grafts can yield information on the structure of the lymphatics, the function following cardiac transplantation is poorly understood. METHODS: Using single-photon emission computed tomography/computed tomography lymphoscintigraphy, we quantified the lymphatic flow index following heterotrophic cardiac transplantation in a murine model of chronic rejection. RESULTS: Ten weeks following transplantation of a minor antigen (HY) sex-mismatched heart graft, the lymphatic flow index was significantly increased in comparison with sex-matched controls. Furthermore, the enhanced lymphatic flow index correlated with an increase in donor cells in the mediastinal draining lymph nodes; increased lymphatic vessel area; and graft infiltration of CD4+, CD8+ T cells, and CD68+ macrophages. CONCLUSIONS: Chronic rejection results in increased lymphatic flow from the donor graft to draining lymph nodes, which may be a factor in promoting cellular trafficking, alloimmunity, and cardiac allograft vasculopathy.

AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.

BACKGROUND: The EGFR T790M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation (EGFR-mutated lung cancer). In preclinical models, the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. METHODS: We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors. The study included dose-escalation cohorts and dose-expansion cohorts. In the expansion cohorts, prestudy tumor biopsies were required for central determination of EGFR T790M status. Patients were assessed for safety, pharmacokinetics, and efficacy. RESULTS: A total of 253 patients were treated. Among 31 patients enrolled in the dose-escalation cohorts, no dose-limiting toxic effects occurred at the doses evaluated. An additional 222 patients were treated in five expansion cohorts. The most common all-cause adverse events were diarrhea, rash, nausea, and decreased appetite. The overall objective tumor response rate was 51% (95% confidence interval [CI], 45 to 58). Among 127 patients with centrally confirmed EGFR T790M who could be evaluated for response, the response rate was 61% (95% CI, 52 to 70). In contrast, among 61 patients without centrally detectable EGFR T790M who could be evaluated for response, the response rate was 21% (95% CI, 12 to 34). The median progression-free survival was 9.6 months (95% CI, 8.3 to not reached) in EGFR T790M-positive patients and 2.8 months (95% CI, 2.1 to 4.3) in EGFR T790M-negative patients. CONCLUSIONS: AZD9291 was highly active in patients with lung cancer with the EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01802632.).

Turning risk assessment and adaptation policy priorities into meaningful interventions and governance processes.

The UK is one of the first countries in the world to have set up a statutory system of national climate risk assessments followed by a national adaptation programme. Having this legal framework has been essential for enabling adaptation at the government level in a challenging political environment. However, using this framework to create an improvement in resilience to climate change across the country requires more than publishing a set of documents; it requires careful thought about what interventions work, how they can be enabled and what level of risk acceptability individuals, organizations and the country should be aiming for.This article is part of the theme issue 'Advances in risk assessment for climate change adaptation policy'.

Population pharmacokinetics and exposure-response of osimertinib in patients with non-small cell lung cancer.

AIMS: To develop a population (pop) pharmacokinetic (PK) model for osimertinib (AZD9291) and its metabolite (AZ5104) and investigate the exposure-response relationships for selected efficacy and safety parameters. METHODS: PK, safety and efficacy data were collected from two non-small cell lung cancer (NSCLC) patient studies (n = 748) and one healthy volunteer study (n = 32), after single or multiple once-daily dosing of 20-240 mg osimertinib. Nonlinear mixed effects modelling was used to characterise the popPK. Individual exposure values were used to investigate the relationship with response evaluation criteria in solid tumours (RECIST 1.1) efficacy parameters and key safety parameters (rash, diarrhoea, QTcF). RESULTS: A popPK model that adequately described osimertinib and its metabolite AZ5104 in a joint manner was developed. Body weight, serum albumin and ethnicity were identified as significant covariates on PK in the analysis, but were not found to have a clinically relevant impact on osimertinib exposure. No relationship was identified between exposure and efficacy over the dose range studied. A linear relationship was observed between exposure and the occurrence of rash or diarrhoea, and between concentration and QTcF, with a predicted mean (upper 90% confidence interval) increase of 14.2 (15.8) ms at the maximum concentration for an 80 mg once-daily dose at steady state. CONCLUSIONS: PopPK and exposure-response models were developed for osimertinib and AZ5104. There was no relationship between exposure and efficacy but a linear relationship between exposure and safety endpoints (rash, diarrhoea and QTcF) was observed.

Laser Initiation of Fe(II) Complexes of 4-Nitro-pyrazolyl Substituted Tetrazine Ligands.

The synthesis and characterization of new 1,2,4-triazolyl and 4-nitro-pyrazolyl substituted tetrazine ligands has been achieved. The strongly electron deficient 1,2,4-triazolyl substituted ligands did not coordinate Fe(II) metal centers, while the mildly electron deficient 4-nitro-pyrazolyl substituted ligands did coordinate Fe(II) metal centers in a 2:1 ratio of ligand to metal. The thermal stability and mechanical sensitivity characteristics of the complexes are similar to the conventional explosive pentaerythritol tetranitrate. The complexes had strong absorption in the visible region of the spectrum that extended into the near-infrared. In spite of having improved oxygen balances, increased mechanical sensitivity, and similar absorption of NIR light to recently reported Fe(II) tetrazine complexes, these newly synthesized explosives were more difficult to initiate with Nd:YAG pulsed laser light. Specifically, the complexes required lower densities (0.9 g/cm3) to initiate at the same threshold utilized to initiate previous materials at higher densities (1.05 g/cm3).

Energetic Chromophores: Low-Energy Laser Initiation in Explosive Fe(II) Tetrazine Complexes.

The synthesis and characterization of air stable Fe(II) coordination complexes with tetrazine and triazolo-tetrazine ligands and perchlorate counteranions have been achieved. Time-dependent density functional theory (TD-DFT) was used to model the structural, electrochemical, and optical properties of these materials. These compounds are secondary explosives that can be initiated with Nd:YAG laser light at lower energy thresholds than those of PETN. Furthermore, these Fe(II) tetrazine complexes have significantly lower sensitivity than PETN toward mechanical stimuli such as impact and friction. The lower threshold for laser initiation was achieved by altering the electronic properties of the ligand scaffold to tune the metal ligand charge transfer (MLCT) bands of these materials from the visible into the near-infrared region of the electromagnetic spectrum. Unprecedented decrease in both the laser initiation threshold and the mechanical sensitivity makes these materials the first explosives that are both safer to handle and easier to initiate than PETN with NIR lasers.

Advances in explosives analysis--part I: animal, chemical, ion, and mechanical methods.

The number and capability of explosives detection and analysis methods have increased substantially since the publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis (Moore and Goodpaster, Anal Bioanal Chem 395(2):245-246, 2009). Here we review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. The review consists of two parts. This part, Part I, reviews methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers, electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. Part II will review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons.

Advances in explosives analysis--part II: photon and neutron methods.

The number and capability of explosives detection and analysis methods have increased dramatically since publication of the Analytical and Bioanalytical Chemistry special issue devoted to Explosives Analysis [Moore DS, Goodpaster JV, Anal Bioanal Chem 395:245-246, 2009]. Here we review and critically evaluate the latest (the past five years) important advances in explosives detection, with details of the improvements over previous methods, and suggest possible avenues towards further advances in, e.g., stand-off distance, detection limit, selectivity, and penetration through camouflage or packaging. The review consists of two parts. Part I discussed methods based on animals, chemicals (including colorimetry, molecularly imprinted polymers, electrochemistry, and immunochemistry), ions (both ion-mobility spectrometry and mass spectrometry), and mechanical devices. This part, Part II, will review methods based on photons, from very energetic photons including X-rays and gamma rays down to the terahertz range, and neutrons.

Ultrafast chemical reactions in shocked nitromethane probed with dynamic ellipsometry and transient absorption spectroscopy.

Initiation of the shock driven chemical reactions and detonation of nitromethane (NM) can be sensitized by the addition of a weak base; however, the chemical mechanism by which sensitization occurs remains unclear. We investigated the shock driven chemical reaction in NM and in NM sensitized with diethylenetriamine (DETA), using a sustained 300 ps shock driven by a chirped Ti:sapphire laser. We measured the solutions' visible transient absorption spectra and measured interface particle and shock velocities of the nitromethane solutions using ultrafast dynamic ellipsometry. We found there to be a volume-increasing reaction that takes place around interface particle velocity up = 2.4 km/s and up = 2.2 km/s for neat NM and NM with 5% DETA, respectively. The rate at which transient absorption increases is similar in all mixtures, but with decreasing induction times for solutions with increasing DETA concentrations. This result supports the hypothesis that the chemical reaction mechanisms for shocked NM and NM with DETA are the same. Data from shocked NM are compared to literature experimental and theoretical data.

Gastric metastasis from an alveolar soft part sarcoma in a child: case report and review of the literature.

The authors report a child with alveolar soft part sarcoma who developed significant anemia due to gastrointestinal blood loss. Evaluation revealed the source of bleeding as a gastric metastasis, which was successfully removed. A brief review of gastrointestinal involvement by alveolar soft part sarcoma is discussed.