Planned Dental Extractions After Radiation Therapy.

Importance: Nonrestorable teeth are recommended to be extracted prior to radiation therapy (RT). Occasionally, preradiation extractions introduce unacceptable delays in treatment initiation. Planned dental extractions immediately postradiation presents an alternative strategy, though outcomes are uncertain. Objective: To evaluate the feasibility and safety of dental extractions immediately postradiation. Design, Setting, and Participants: A prospective cohort study including patients planned for curative-intent RT but unable or unwilling to proceed with 1 or more extractions recommended pretreatment was carried out. From January 2020 to September 2022, 58 patients were screened and 50 enrolled. The dental care was performed at a single academic department and the cancer care at regional centers. Analysis took place between September 22, 2023, and June 10, 2024. Exposure: On completion of RT, patients were recommended to complete extractions as soon as feasible, and ideally within 4 months. Main Outcomes and Measures: The primary end point was the actuarial cumulative incidence of exposed alveolar bone noted by any practitioner at any time after extraction, calculated using Gray method with death as a competing risk. As a pilot study, no formal power calculation was performed; resources allowed for 50 evaluable patients. Results: Among the 50 participants enrolled, RT was nonoperative for 32 patients (64%) and postoperative for 18 patients (36%). Intensity-modulated RT (IMRT) was delivered in all patients. Of the 50 patients, 20 (40%) declined dental extractions immediately postradiation and the remaining 30 (60%) underwent a median (range) of 8.5 (1-28) extractions at a median (range) of 64.5 (13-152) days after RT. The median (IQR) follow-up for survivors without exposed bone was 26 (17-35) months from the end of RT. The 2-year cumulative incidence of any exposed bone was 27% (95% CI, 14%-40%). The 2-year incidence of exposed bone for those who underwent dental extractions immediately postradiation was 40% (95% CI, 22%-58%) and 7% (95% CI, 0%-22%) for those who did not. Of the 13 who developed exposed bone: 4 resolved, 1 was lost to follow-up, and 8 were confirmed as osteoradionecrosis. Conclusions and Relevance: This cohort study found that postradiation dental extractions incur considerable risk, even if performed within a 4-month window.

Autologous versus synthetic midurethral transobturator sling: A systematic review and meta-analysis of outcomes.

INTRODUCTION: There have been concerns around the use of synthetic mesh for stress urinary incontinence (SUI) surgery with a renewed interest in the use of autologous tissues. Recently, an autologous transobturator sling (aTOT) has been described, but the comparative data with synthetic transobturator sling (sTOT) is limited. The objective of this systematic review and meta-analysis was to assess the outcome of aTOT and compare it with sTOT. METHODS: A systematic search of PubMed, Scopus, and Web of Science databases was performed and all articles available up to December 31, 2023 were screened. Studies reporting on the outcomes of aTOT and those comparing aTOT with sTOT were included. This review was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Eleven studies evaluating 323 patients that met the criteria were included in the final analysis, of which 6 were single arm (155 patients) and 5 were comparative. In single-arm studies, the pooled success rate, defined as negative cough stress test at 12 months follow-up was 96.8%, 3.8% had postoperative urinary retention, 6.1% had graft site-related complications and 7.6% required additional intervention for persistent SUI. The overall complication rate was 20.6% and there were no Clavien III-V complications. aTOT had similar success and complication rates when compared with sTOT but had a significantly longer operative time (weighted mean difference: 22.35 min, p < 0.00001) and superior sexual function outcomes. CONCLUSIONS: aTOT, at short-term follow-up (12 months), has similar efficacy and complication rates when compared to sTOT. However, given that the data is limited and not of very good quality, and the fact that long-term follow-up is not available, further studies are required to better define the role of aTOT in the management of female patients with SUI.

Costs of UK community care for individuals with recessive dystrophic epidermolysis bullosa: Findings of the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study.

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin fragility disorder requiring multidisciplinary management. Information regarding costs of current standard treatment is scant. Objectives: As part of a longitudinal natural history study, we explored the community care costs of UK patients with different forms of RDEB. Methods: Fifty-nine individuals with RDEB provided detailed information on multiple facets of RDEB including disease severity scores (iscorEB, BEBS) and patient reported outcomes (quality of life evaluation in epidermolysis bullosa, iscorEB patient questionnaire). Costs data included time spent doing dressings, frequency of dressing changes, details of materials used, and paid and unpaid care. Results: Overall costs of dressing materials and associated care were high in RDEB. Median annual costs across all subtypes for those using dressings (n = 51) were over £26 000. For severe RDEB (RDEB-S), median costs were almost £90 000 per annum, with a median of 18 h per week spent on dressing changes. Half of working-age adults with RDEB were unemployed and 39% of carers were unable to take on full-time or part-time paid employment, adding to indirect costs and the financial burden from RDEB on families and society. Conclusions: The findings demonstrate the high costs of care of RDEB, particularly for RDEB-S. The current expense supports the drive to develop new therapies which accelerate wound healing and diminish total wound burden, thereby reducing costs of dressings and care. While costly to bring to market, these might ultimately reduce the overall cost of treatment and also the impact on individuals living with this rare disease. The data also highlight the need for adequate reimbursement for EB care which can place significant financial strain on families.

Advancing public health informatics during the COVID-19 pandemic: Lessons learned from a public-private partnership with pharmacies.

To support efforts to vaccinate millions of Americans across the United States (US) against COVID-19, the US federal government (USG) launched the Pharmacy Partnership for Long-Term Care Program (PPP) in December 2020 and the Federal Retail Pharmacy Program (FRPP) in February 2021. These programs consisted of a collaborative partnership with the USG and 21 pharmacy organizations, including large retail chains, coordinating pharmacy services administrative organizations (PSAOs) representing independent retail and long-term care pharmacies, and pharmacy network administrators. These pharmacy organizations represented over 46,000 providers and created a robust channel for far-reaching COVID-19 vaccination across 56 state and local jurisdictions. PPP reported more than 8 million COVID-19 doses administered to residents and staff in long-term care facilities (LTCFs) as of June 2021. In addition, FRPP was responsible for administering more than 304 million doses, accounting for approximately 49% of all COVID-19 doses administered as of June 2023. This unprecedented public-private partnership allowed USG to rapidly adapt, expand, and aim to provide equitable access to vaccines for adults and eligible-aged children during the COVID-19 pandemic. As the largest federal COVID-19 vaccination program, the FRPP exemplifies how public-private partnerships can expand access to immunizations during a public health emergency. End-to-end informatics support helped pharmacies meet critical national public health goals and served as convenient access points for sustained health services. This manuscript describes lessons learned regarding informatics coordination with participating pharmacy partners to support the rapid and safe administration of COVID-19 vaccines across the US. The processes of onboarding to CDC's complex data network, establishing connections to state and local immunization information systems (IIS), and monitoring the quality of data pharmacy partners submitted to the CDC Data Clearinghouse (DCH) in alignment with the COVID-19 Vaccine Reporting Specifications (CVRS) are highlighted.

Program-Based Lung Cancer Care: A Prospective Observational Tumor Registry Linkage Study.

Introduction: Low-dose computed tomography screening (LDCT) and lung nodule programs (LNP) promote early lung cancer detection, improve survival; Multidisciplinary Care Programs (MDC) promote guideline-concordant care. The impact of such program-based care on "real-world" lung cancer survival is unquantified. We evaluated outcomes of lung cancer care delivered through structured programs in a community health care system. Methods: We conducted a cohort study linking institutional prospective observational LDCT, LNP and MDC databases with Tumor Registry of Baptist Cancer Center facilities. We categorized all patients diagnosed with lung cancer between 2011 and 2021 into program-based care versus non-program-based care cohorts. We compared patient characteristics, stage distribution, treatment modalities, survival and mortality in each pathway of care. Results: Of 12,148 patients, 237, 1,165, 1,140 and 9,606 were diagnosed through the LDCT, LNP, MDC or no program, respectively; non-program-based care sequentially diminished from 96.3% to 66.5%, diagnosis through LDCT increased from 0.5% to 7.1%, LNP from 3.5% to 20.8%; and MDC alone decreased from a high of 12.8% in 2014 to 5.6% in 2021. Program-based care was associated with earlier stage (p < 0.001), higher surgical resection rates (p < 0.001), greater use of adjuvant therapy (p < 0.001), better aggregate and stage-stratified survival (p < 0.001), and lower all-cause and lung cancer-specific mortality (p < 0.001). Recipients of non-program-based care were considerably less likely to receive lung cancer treatment; results remained consistent when patients receiving no treatment were excluded. Conclusions: Program-based care was associated with substantially better survival. Increasing access to program-based care should be explored as a matter of urgent public policy.

Getting up With Lateral Thinking.

Introduction: Falls in the community can have major impacts on patient lives. There can be long lasting physical and psychological consequences of a fall and subsequent long lie. The annual burden to ambulance services responding to falls at home is high. Affordable devices to help people get up from the floor, or reduce the risk of a long lie, would be useful and widely applicable. Case report: We present the case of 2 families who successfully used an air mattress and a bath lift to get the fallen person up off the floor following a fall, when they had previously called an ambulance. This has reduced their dependence on the ambulance service and has improved their confidence following falls. Discussion/conclusion: Affordable devices such as air mattresses can help people off the floor following a fall and prevent long lies as well as reduce the number of ambulance call outs.

Establishing initial resting abdominal pressure in children undergoing urodynamics.

INTRODUCTION: The International Continence Society recommends zeroing of transducers to the atmospheric pressure for invasive urodynamics. The range of abdominal pressure relative to atmospheric pressure is well-known in adults but has not been described in children. This prospective observational study was carried out to establish baseline abdominal in children. MATERIALS AND METHODS: Prospective, multicenter, observational study of 100 children aged 0-18 years undergoing invasive urodynamics using water-filled systems. Initial resting abdominal pressure, intravesical pressure and detrusor pressure were recorded in supine, sitting, and standing position (as age- and diagnosis-appropriate). This data was analyzed using SPSS 20.0.0 with regard to age, gender, height, weight, body mass index, and underlying diagnosis (classified as neurogenic or non-neurogenic). Nonparametric tests were used (2-sided p < 0.05, significant). RESULTS: Initial resting abdominal pressure (inter-quartile range) in children was between 5 and 15 cmH2 O in the supine, 13-20 cmH2 O in the sitting, and 15-21 cmH2 O in the standing position. These pressures were not consistently influenced by age, gender, height, weight or underlying diagnosis. The initial resting detrusor pressure was noted to be 0-4 cmH2 O without any difference based on posture. Limitations include use of two-tube technique, relatively small number of subjects across each age group, wide range of underlying diagnoses and need for manual smoothing of some traces. CONCLUSION: This study defines initial resting abdominal pressure at urodynamics in children and notes that, as with adults, it is possible to define widely applicable ranges regardless of individual characteristics. These pressures appear lower than those noted historically in adults.

External evaluation of the Dynamic Criticality Index: A machine learning model to predict future need for ICU care in hospitalized pediatric patients.

OBJECTIVE: To assess the single site performance of the Dynamic Criticality Index (CI-D) models developed from a multi-institutional database to predict future care. Secondarily, to assess future care-location predictions in a single institution when CI-D models are re-developed using single-site data with identical variables and modeling methods. Four CI-D models were assessed for predicting care locations >6-12 hours, >12-18 hours, >18-24 hours, and >24-30 hours in the future. DESIGN: Prognostic study comparing multi-institutional CI-D models' performance in a single-site electronic health record dataset to an institution-specific CI-D model developed using identical variables and modelling methods. The institution did not participate in the multi-institutional dataset. PARTICIPANTS: All pediatric inpatients admitted from January 1st 2018 -February 29th 2020 through the emergency department. MAIN OUTCOME(S) AND MEASURE(S): The main outcome was inpatient care in routine or ICU care locations. RESULTS: A total of 29,037 pediatric hospital admissions were included, with 5,563 (19.2%) admitted directly to the ICU, 869 (3.0%) transferred from routine to ICU care, and 5,023 (17.3%) transferred from ICU to routine care. Patients had a median [IQR] age 68 months (15-157), 47.5% were female and 43.4% were black. The area under the receiver operating characteristic curve (AUROC) for the multi-institutional CI-D models applied to a single-site test dataset was 0.493-0.545 and area under the precision-recall curve (AUPRC) was 0.262-0.299. The single-site CI-D models applied to an independent single-site test dataset had an AUROC 0.906-0.944 and AUPRC range from 0.754-0.824. Accuracy at 0.95 sensitivity for those transferred from routine to ICU care was 72.6%-81.0%. Accuracy at 0.95 specificity was 58.2%-76.4% for patients who transferred from ICU to routine care. CONCLUSION AND RELEVANCE: Models developed from multi-institutional datasets and intended for application to individual institutions should be assessed locally and may benefit from re-development with site-specific data prior to deployment.

Enhancing the dissolution rate of poorly soluble drug Febuxostat using spray dried amorphous solid dispersion technique / Mejora de la tasa de disolución del fármaco poco soluble Febuxostat utilizando la técnica de dispersión de sólido amorfo secado por aspersión

Introducción: El febuxostat pertenece a los fármacos clase II del Sistema de Clasificación Biofarmacéutica, los cuales presentan baja solubilidad y alta permeabilidad. La dispersión sólida amorfa es una de las técnicas que pueden ser útiles para mejorar la solubilidad y las características del polvo. Objetivo: optimizar la concentración de polímeros hidrofílicos e hidrofóbicos para mejorar la velocidad de disolución y la solubilidad de las tabletas de febuxostat. Métodos: La dispersión sólida amorfa de febuxostat se preparó mediante el método de secado por aspersión utilizando Kolliphor P237 (1:2). Esta dispersión sólida amorfa se utilizó además para comprimir el comprimido. Para mejorar la solubilidad y la tasa de disolución, se aplicó un diseño factorial completo para optimizar la concentración crítica de KollidonSR e hidroxi propil metil celulosa (HPMC K4M). Los comprimidos preparados se caracterizaron por parámetros de precompresión y poscompresión. Resultados: La velocidad de liberación del fármaco se mantuvo mediante la formulación de una técnica de dispersión sólida amorfa. Se encontró que el lote optimizado (FSRT-OB) era apto para la liberación promedio del 93,30 % del fármaco en forma de liberación sostenida hasta 12 horas. Los datos de la cinética de liberación sugieren que la liberación del fármaco estuvo controlada por una combinación de mecanismo de relajación de cadena y difusión. Se encontró que la concentración optimizada para Kollidon SR y HPMC K4M era 38,50 % y 7,72 % respectivamente. Conclusión: La técnica de dispersión sólida amorfa es útil para mejorar la solubilidad, la velocidad de disolución y la biodisponibilidad de la tableta de Febuxostat. (AU)

Introduction: Febuxostat belongs to Biopharmaceutical classification system (BCS) class II drugs, which have low solubility and high permeability. Amorphous solid dispersion is one of the techniques which can be useful to improve solubility and powder characteristics. Objective: To optimize the concentration of hydrophilic and hydrophobic polymers to improve the dissolution rate and solubility of febuxostat tablets. Methods: The amorphous solid dispersion of febuxostat was prepared by spray drying method using Kolliphor P237 (1:2). This amorphous solid dispersion was further used to compress the tablet. To improve solubility and dissolu-tion rate, a full factorial design was applied to optimize the critical concentration of Kollidon SR and hydroxypropyl methyl cellulose (HPMC K4M). The prepared tablets were characterized by pre-compression and post-compression parameters. Result: The rate of drug release was sustained by formulating an amorphous solid dispersion technique. The optimized batch (FSRT-OB) was found to be fit for release average 93.30 % of the drug in sustain release manner up to 12hrs. The release kinetic data suggests that the drug release was controlled by combination of diffusion and chain relaxation mechanism. The optimized concentration for Kollidon SR and HPMC K4Mwas found to be 38.50 % and 7.72 % respectively. Conclusion: Amorphous solid dispersion technique is useful to enhance solubility, dissolution rate, and bioavail-ability of the Febuxostat tablet. (AU)