Ultrafast dynamics of fluorene initiated by highly intense laser fields.

We present an investigation of the ultrafast dynamics of the polycyclic aromatic hydrocarbon fluorene initiated by an intense femtosecond near-infrared laser pulse (810 nm) and probed by a weak visible pulse (405 nm). Using a multichannel detection scheme (mass spectra, electron and ion velocity-map imaging), we provide a full disentanglement of the complex dynamics of the vibronically excited parent molecule, its excited ionic states, and fragments. We observed various channels resulting from the strong-field ionization regime. In particular, we observed the formation of the unstable tetracation of fluorene, above-threshold ionization features in the photoelectron spectra, and evidence of ubiquitous secondary fragmentation. We produced a global fit of all observed time-dependent photoelectron and photoion channels. This global fit includes four parent ions extracted from the mass spectra, 15 kinetic-energy-resolved ionic fragments extracted from ion velocity map imaging, and five photoelectron channels obtained from electron velocity map imaging. The fit allowed for the extraction of 60 lifetimes of various metastable photoinduced intermediates.

Exploring the ultrafast and isomer-dependent photodissociation of iodothiophenes via site-selective ionization.

C-I bond extension and fission following ultraviolet (UV, 262 nm) photoexcitation of 2- and 3-iodothiophene is studied using ultrafast time-resolved extreme ultraviolet (XUV) ionization in conjunction with velocity map ion imaging. The photoexcited molecules and eventual I atom products are probed by site-selective ionization at the I 4d edge using intense XUV pulses, which induce multiple charges initially localized to the iodine atom. At C-I separations below the critical distance for charge transfer (CT), charge can redistribute around the molecule leading to Coulomb explosion and charged fragments with high kinetic energy. At greater C-I separations, beyond the critical distance, CT is no longer possible and the measured kinetic energies of the charged iodine atoms report on the neutral dissociation process. The time and momentum resolved measurements allow determination of the timescales and the respective product momentum and kinetic energy distributions for both isomers, which are interpreted in terms of rival 'direct' and 'indirect' dissociation pathways. The measurements are compared with a classical over the barrier model, which reveals that the onset of the indirect dissociation process is delayed by ∼1 ps relative to the direct process. The kinetics of the two processes show no discernible difference between the two parent isomers, but the branching between the direct and indirect dissociation channels and the respective product momentum distributions show isomer dependencies. The greater relative yield of indirect dissociation products from 262 nm photolysis of 3-iodothiophene (cf. 2-iodothiophene) is attributed to the different partial cross-sections for (ring-centred) π∗ ← π and (C-I bond localized) σ∗ ← (n/π) excitation in the respective parent isomers.

Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline.

PURPOSE: With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS: The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy. CONCLUSIONS: These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.

Dosimetric and Clinical Factors Associated With Breast Reconstruction Complications in Patients Receiving Postmastectomy Radiation.

PURPOSE: Approximately 30% of women who receive postmastectomy radiation therapy in the setting of breast reconstruction suffer from reconstruction complications. This study aims to assess clinical and dosimetric factors associated with the risk of reconstruction complications after postmastectomy radiation therapy, with the ultimate goal of identifying a dosimetric constraint that can be used clinically to limit this risk. METHODS AND MATERIALS: We retrospectively identified 41 patients who underwent a modified radical or total mastectomy, followed by immediate or delayed reconstruction (autologous or implant-based) and radiation at a single institution between 2014 and 2020. Reconstruction complications were defined as a flap or implant failure, necrosis, capsular contracture, cellulitis/infection, implant rupture, implant malposition, leakage/rupture, unplanned operation, and hematoma/seroma. Clinical and dosimetric variables associated with complications were assessed with univariate analyses. RESULTS: Twelve patients (29%) suffered reconstruction complications, which led to a flap or implant failure in 5 patients. The median time to complication after reconstruction was 8 months. Thirty-two percent of patients with immediate and 20% with delayed reconstruction suffered a complication, respectively. There were no local failures. Smoking (P = .02), use of bolus (P = .03), and the percentage of the chest wall/reconstructed breast target volume that received ≥107% of the prescribed radiation dose (V107) > 11% (P = .03) were associated with increased complication rates. The complication rates were 42% when V107 > 11% versus 12% when V107 < 11%; 58% in smokers versus 17% in nonsmokers; and 42% with versus 7% without bolus. CONCLUSIONS: Plan heterogeneity appears to be associated with the risk of reconstruction complications. Pending further validation, V107 < 11% may serve as a reasonable guide to limit this risk. Further consideration should be given to the selective use of bolus in this setting and optimization of clinical factors, such as smoking cessation.

Demographic and clinical factors associated with variations in opioid administration using conscious sedation during HDR brachytherapy for cervical cancer.

PURPOSE/OBJECTIVES To examine patient characteristics that predispose to higher opioid administration during tandem and ovoid (T&O) high-dose rate (HDR) brachytherapy. METHODS A single-institution retrospective review was performed on patients who underwent brachytherapy for cervical cancer. Patients were included if they received at least one fraction of HDR T&O brachytherapy with analgesia administration recorded in the Medication Administration Record. Fentanyl dose was dichotomized as "low" (mean <125 µg per fraction), or "high" (mean ≥ 125 µg per fraction). Descriptive statistics and multiple logistic regression analysis were performed comparing mean opioid dose per fraction with demographic and clinical information. RESULTS From July 2014 through May 2020, 113 patients underwent 531 T&O HDR brachytherapy fractions with oral benzodiazepine and intravenous opioid fentanyl for conscious sedation. The median opioid dose per fraction was 100 µg fentanyl (range 0-250 µg). Using multiple logistic regression analysis, younger age (OR 1.071, p = 0.002) and higher BMI (OR 1.091, p = 0.019) were associated with increased opioid administration during brachytherapy. Black women received less opioid during brachytherapy when compared to White women (OR 0.296, p = 0.047). FIGO stage, ECOG score, smoking status, prior narcotic use, prior illicit drug use, parity, prior cervical procedure, Smit sleeve placement, and distance to treatment center were not associated with high opioid dose. CONCLUSION Cervical cancer patients who are younger or have higher BMI receive more narcotic analgesia during HDR brachytherapy whereas Black women received less narcotic analgesia, irrespective of age and BMI. This underscores the immediate need to address how pain is assessed and managed during brachytherapy.

The effect of a dementia awareness class on changing dementia attitudes in adolescents.

BACKGROUND: Current evidence suggests that negative and stigmatising attitudes towards dementia may develop at a young age. There are a number of dementia education and awareness initiatives aimed at reducing stigma, though they have not been robustly evaluated to establish the impact on dementia attitudes or suitability in adolescent populations. This study explored the efficacy and satisfaction of one such initiative (Dementia Friends) in a British adolescent sample. METHODS: 301 adolescents (M = 12.6 years old, SD = 0.73) were assigned to either receive Dementia Friends (a 60-min interactive class that teaches about dementia and its effects on people's lives) or education as usual. All participants completed a series of validated questionnaires pre- and post-intervention, related to dementia attitudes (Brief A-ADS and KIDS). RESULTS: Adolescents in the dementia awareness group showed little to no improvements between time-points. The change scores in the dementia awareness group did not significantly differ to the control group based on both KIDS (d = - 0.003, p = 0.98) and Brief A-ADS (d = 0.14, p = 0.13) measures. There was no Group x Time effect after controlling for confounding variables. CONCLUSIONS: Dementia Friends is successful in terms of reach and impact, though this study suggests that it may fall short of achieving its goal of improving attitudes towards dementia. Importantly, Dementia Friends did not have a negative effect on attitudes, and the majority of adolescents enjoyed the sessions. It is important that these findings are replicated in a larger randomised-controlled study.

Productivity of Advanced Clinical Practitioners in Emergency Medicine: A 1-year dual-centre retrospective analysis.

BACKGROUND: The ACP role is relatively new in Emergency Medicine (EM) nationally (RCEM, 2017). This work sought to establish the productivity of EM ACPs within our service, to enable evidence-based workforce planning and national benchmarking of this aspect of the role. METHODOLOGY: Data from 1st January 2018-31st December 2018 was retrospectively collected from two hospitals in the United Kingdom (UK) via electronic patient records. In addition to the number of patients seen by ACPs (attending), the number of patients who were seen by an ACP as a senior review (SR) was collected. The productivity was mapped to ACP experience, with patient acuity and disposal reported. RESULTS: In the study period 239,951 patients were seen in the Emergency Departments (EDs) of the two study hospitals. Overall 20,442 (8.5%) patients received care from an ACP. Mean productivity was 1.03 patients per hour (attending) and 1.53 patients per hour (attending and senior review). DISCUSSION: EM ACPs form part of the RCEM future workforce strategy to overcome some of the contemporary challenges in EM (Hassan, 2018). To our knowledge, this is the first study which has examined and reported the productivity of ACPs in UK EM. CONCLUSION: This paper sets a national benchmark for other EDs by reporting ACP productivity and contributes to the evidence by reporting productivity in other clinician groups. The data presented may be helpful in future national workforce planning for UK EDs.

Exploring the Use of Complementary and Alternative Medicine in Cancer Patients.

In Australia, it is estimated that around 17% to 87% of cancer patients have used one form of complementary therapy during their cancer treatment. There are numerous reasons and contributing factors for cancer patients to consider using complementary and alternative medicine (CAM). CAM information and products are readily available. However, the level of evidence to support the benefits of use in the cancer setting is limited, and the associated adverse effects and interactions with conventional medicine may not be fully studied. Besides, not all health professionals favor the concept of integrative health approaches, or have the confidence in dealing with CAM due to a lack of knowledge and standardization of practices. A thematic review of the literature was performed on the main contributing factors to cancer patients' use of CAM, as well as the current issues that may be encountered by the patients and health professionals.

Exploring the Use of Complementary and Alternative Medicine in Cancer Patients.

In Australia, it is estimated that around 17% to 87% of cancer patients have used one form of complementary therapy during their cancer treatment. There are numerous reasons and contributing factors for cancer patients to consider using complementary and alternative medicine (CAM). CAM information and products are readily available. However, the level of evidence to support the benefits of use in the cancer setting is limited, and the associated adverse effects and interactions with conventional medicine may not be fully studied. Besides, not all health professionals favor the concept of integrative health approaches, or have the confidence in dealing with CAM due to a lack of knowledge and standardization of practices. A thematic review of the literature was performed on the main contributing factors to cancer patients' use of CAM, as well as the current issues that may be encountered by the patients and health professionals.

Effect of internal mammary vessels radiation dose on outcomes of free flap breast reconstruction.

To assess the impact of internal mammary (IM) vessels radiation dose on autologous free-flap based breast reconstruction outcomes. We retrospectively evaluated the medical records of breast cancer patients who underwent mastectomy and free-flap breast reconstruction after postoperative radiation therapy (RT) to the breast/chest wall with (n = 9) or without (n = 11) electively including the IM lymph nodes. Twenty patients were included. Median age at diagnosis was 50 years (range, 33-63). The median time interval between the start of RT and reconstructive surgery was 16 months (range, 6-45). The maximal IM vessels dose was not associated with the risk of all complications (P = 0.44) or fat necrosis (P = 0.31). The mean IM vessels dose was not significant for the risk of all complications (P = 0.13) but was significant for fat necrosis (P = 0.04). A high mean IM vessels dose was related to the occurrence of fat necrosis.

Quantitative accuracy of positron emission tomography/magnetic resonance and positron emission tomography/computed tomography for cervical cancer.

With the spread of positron emission tomography/magnetic resonance (PET/MR), the question of comparability of studies becomes important. We aim to determine whether PET/MR and PET/computed tomography (PET/CT) are comparable for the case of cervical cancer. Fifteen cervical cancer patients identified by either a radiation oncologist or an oncologic surgeon had both PET/MR and PET/CT performed for initial staging within 3 weeks. We then compared the results both quantitatively (measuring standardized uptake values [SUVs] on visible lesions) as well as qualitatively (having radiologists and nuclear medicine physicians interprets the results). While interpretations between PET/MR and PET/CT varied in many cases, SUVs of primary lesions were similar to within 25% in all but one case, and correlation coefficient was 0.92. Maximum SUV ranged between 4.9 and 25.2 for PET-MR and between 5.8 and 30.4 for PET-CT for primary tumors and between 1.5 and 18.8 for PET-MR and between 1.8 and 20.8 for PET-CT for nodes. However, clinical reads often varied significantly between PET/MR and PET/CT. This suggests that SUV is similar on PET/MR and PET/CT although the differing anatomic modalities available for correlation may make the difference in terms of qualitative interpretation.

Qualitative study of patient experiences of responsibility in warfarin therapy.

PURPOSE: Results of a study to characterize the experiences of warfarin-treated patients, including their experiences in taking medication, communicating with clinical pharmacists, and International Normalized Ratio (INR) monitoring, are reported. METHODS: A qualitative analysis of data obtained during interviews with 40 patients at a Veterans Affairs medical center warfarin clinic was conducted. In semistructured interviews, the patients were asked to describe the process whereby their INR values were monitored by pharmacists and their understanding of self-management responsibilities, including medication adherence and implementation of lifestyle modifications that might influence the effectiveness of anticoagulation therapy. RESULTS: Analysis of interview results indicated that patients' experience in the event of variation in INR levels is characterized by misperceptions of the instructions regarding appropriate dietary and lifestyle behaviors, misattribution of responsibility for abnormal readings, and provider uncertainty in ascertaining causation for out-of-range INR values. Patients frequently reported that they interpret pharmacist questions to imply that they are responsible for variable INR values. This perception may indirectly lead to adverse consequences such as withholding of information from anticoagulation care providers and skipping clinic appointments, which could in turn result in suboptimal clinical outcomes. CONCLUSION: Analysis of results of qualitative interviews of patients receiving warfarin indicated that patients may interpret routine questioning about INR variation as implying that they are to blame for poor anticoagulation control.

Pentoxifylline and vitamin E for treatment or prevention of radiation-induced fibrosis in patients with breast cancer.

Radiation therapy (RT) plays an important role in the management of breast cancer. Radiation-induced fibrosis is a side effect of radiation therapy and may occur in up to 13% of the cases in patients (Radiother Oncol, 2009;90:80), fortunately usually is modest/localized and not associated with marked symptoms. However, occasionally, fibrosis can be moderate-to-severe, and cause clinically-meaningful symptoms. The current review summarizes the use of pentoxifylline and vitamin E of treatment or prevention of radiation-induced fibrosis in breast cancer patients. Even though data are limited, this regimen may reduce RT-associated toxicity.

Clinical analysis of speculum-based vaginal packing for high-dose-rate intracavitary tandem and ovoid brachytherapy in cervical cancer.

PURPOSE: Intra-vaginal packing is used to fix the applicator and displace organs at risk (OAR) during high-dose-rate intracavitary tandem and ovoid brachytherapy (HDR-ICB). We retain the speculum from applicator placement as a dual-function bladder and rectum retractor during treatment. Our objective is to review salient techniques for OAR displacement, share our packing technique, and determine the reduction in dose to OAR and inter-fraction variability of dose to OAR, associated with speculum-based vaginal packing (SBVP) in comparison to conventional gauze packing during HDR-ICB. MATERIAL AND METHODS: We reviewed HDR-ICB treatment plans for 45 patients, including 10 who underwent both conventional gauze packing and SBVP. Due to institutional inter-provider practice differences, patients non-selectively received either packing procedure. Packing was performed under conscious sedation, followed by cone beam computed tomography used for dosimetric planning. Maximum absolute and percent-of-prescription dose to the International Commission of Radiation Units bladder and rectal points in addition to D0.1cc, D1.0cc, and D2.0cc volumes of the bladder and rectum were analyzed and compared for each packing method using an independent sample t-test. RESULTS: Of the 179 fractions included, 73% and 27% used SBVP and gauze packing, respectively. For patients prescribed 6 Gy to point A, SBVP was associated with reduced mean D0.1cc bladder dose, inter-fraction variability in D0.1cc bladder dose by 9.3% (p = 0.026) and 9.0%, respectively, and statistically equivalent rectal D0.1cc, D1.0cc, and D2.0cc. Patients prescribed 5.5 Gy or 5 Gy to point A after dose optimization, were less likely to benefit from SBVP. In the intra-patient comparison, 80% of patients had reduction in at least one rectum or bladder parameter. CONCLUSIONS: In patients with conducive anatomy, SBVP is a cost-efficient packing method that is associated with improved bladder sparing and comparable rectal sparing relative to gauze packing during HDR-ICB without general anesthesia.

Management of Triple-Negative Breast Cancer in Older Patients: How Is It Different?

Triple-negative breast cancer, which affects about 10% of older women with breast cancer, represents a major treatment challenge in this population. Treatment decisions for these patients can best be made based on geriatric assessment, estimated life expectancy, whether the treatment goal is prolonged survival or palliation, the potential benefits and toxicities of a specific treatment, and the patient's personal goals for treatment. Treatment outcomes for healthy older and younger women are similar, but great challenges exist in managing the vulnerable and frail patient. The cornerstone of therapy for early-stage triple-negative breast cancer is local therapy (surgery and radiation) and, for most patients, adjuvant chemotherapy. In the management of metastatic triple-negative breast cancer, all therapy is palliative and chemotherapy is the treatment of choice. Since all treatment modalities in older patients-especially chemotherapy-can affect physical and mental function, a geriatric assessment is key in selecting the most appropriate treatment strategy. Many older patients (older than 70 years) are poor candidates for state-of-the-art therapy, and some who have substantial comorbidities not related to breast cancer may opt for palliative and hospice care. In this review, we will discuss the role of geriatric assessment, alternative treatment modalities for older women with triple-negative breast cancer, and other special considerations for this patient population.

Do Smokers Recall Source or Quitline on Cigarette Constituent Messages?

OBJECTIVES: The Food and Drug Administration (FDA) is required under the Family Smoking Prevention and Tobacco Control Act to communicate the risks of tobacco use to the public. Little research exists about methods to communicate the constituents of tobacco in a media campaign. This research examines specific strategies to increase effectiveness of a media campaign for cigarette smoking adults about tobacco constituents by including engagement text about smoking cessation and FDA as the source of the campaign. METHODS: In an eye tracking study of 211 current cigarette smokers, participants randomly viewed 4 cigarette constituent messages that varied engagement text for quitting (benefits of quitting and quitline number, presence, absence) and by FDA source (presence, absence). After the eye tracking session, participants were asked about recall of the national quitline number and the source of message. RESULTS: Participants in conditions with engagement text were significantly more likely than those in the no engagement conditions to recall the national quitline number. Few participants saw or recalled the FDA source. CONCLUSIONS: Engagement text for smoking cessation on constituent communication campaign messages significantly increases recall of the quitline, an important resource for smokers.

Clinical characteristics associated with racial disparities in endometrial cancer outcomes: A surveillance, epidemiology and end results analysis.

OBJECTIVES: Racial disparities exist for endometrial cancer. We examined patterns of care and factors associated with poor outcomes for Black women with endometrial cancer. METHODS: We studied 110,826 endometrial cancer patients diagnosed between 1980 and 2008 with minimum 5years follow-up in the Surveillance, Epidemiology, and End Results database. Trends over time in sociodemographics, disease characteristics and treatment factors were analyzed over four eras: 1980-1989, 1990-1999, 2000-2004, 2005-2008. Using sequential Cox proportional hazards and Fine-Gray competing risk models we determined the association between potential explanatory variables and racial disparities in all-cause mortality (ACM) and cancer-specific mortality (CSM), respectively. RESULTS: Clinical characteristics of Black and White women were relatively constant over time. The unadjusted hazard ratio (HR) among Black women for ACM and CSM were 1.91 (95% CI 1.86-1.97) and 2.35 (95% CI 2.26-2.43), respectively. Adjustment for sociodemographics, disease presentation and surgery decreased the ACM HR to 1.29 (95% CI 1.24-1.34) and CSM HR to 1.18 (95% CI 1.11-1.26) without further decrease from controlling for radiotherapy. Black women were less likely to undergo operative management even when prescribed. Total and radical hysterectomy, and vaginal brachytherapy (VBT) were associated with improved ACM and CSM. Combination VBT and external beam radiotherapy was associated with improved ACM. CONCLUSION: Racial disparities in endometrial cancer survival are predominantly attributable to increased advanced stage, high-grade and aggressive histologic subtype tumors and differential use of surgery in Black women. Intensified surgical and radiation treatment is associated with improved survival, raising questions about treatment adaptations that may potentially reduce survival disparities.