Early Impact of the COVID-19 Pandemic on Psycho-Oncological Support: A Latent Class Analysis.

INTRODUCTION: Research suggests a global shortfall of psycho-oncological assessment and care during the COVID-19 pandemic in addition to delayed diagnosis of cancer. The present study is the first to explore the effect of the pandemic on the provision of psycho-oncological care, stage of cancer at first diagnosis, and duration of hospitalizations. METHOD: Retrospective latent class analysis of 4,639 electronic patient files with all types, treatment types, and stages of cancer, 370 of which were treated during the pandemic prior to availability of vaccinations. DISCUSSION: Latent class analysis identified four subgroups based on differences in screening for distress, provision of psycho-oncological support (consultation with a psychiatrist or clinical psychologist), administration of psychotropic medication, use of 1:1 observation, stage of cancer at first diagnosis, and duration of hospitalizations. Yet, the pandemic had no effect on subgrouping. Thus, the COVID-19 pandemic had no effect on the provision of psycho-oncological support. CONCLUSION: Results are contrary to prior research. The efficiency and quality of procedures implemented to provide psycho-oncological support during and prior to the pandemic are critically reflected.

Towards identifying cancer patients at risk to miss out on psycho-oncological treatment via machine learning.

OBJECTIVE: In routine oncological treatment settings, psychological distress, including mental disorders, is overlooked in 30% to 50% of patients. High workload and a constant need to optimise time and costs require a quick and easy method to identify patients likely to miss out on psychological support. METHODS: Using machine learning, factors associated with no consultation with a clinical psychologist or psychiatrist were identified between 2011 and 2019 in 7,318 oncological patients in a large cancer treatment centre. Parameters were hierarchically ordered based on statistical relevance. Nested resampling and cross validation were performed to avoid overfitting. RESULTS: Patients were least likely to receive psycho-oncological (i.e., psychiatric/psychotherapeutic) treatment when they were not formally screened for distress, had inpatient treatment for less than 28 days, had no psychiatric diagnosis, were aged 65 or older, had skin cancer or were not being discussed in a tumour board. The final validated model was optimised to maximise sensitivity at 85.9% and achieved an area under the curve (AUC) of 0.75, a balanced accuracy of 68.5% and specificity of 51.2%. CONCLUSION: Beyond conventional screening tools, results might contribute to identify patients at risk to be neglected in terms of referral to psycho-oncology within routine oncological care.

Mental disorders, length of hospitalization, and psychopharmacy-New approaches to identify barriers to psychological support for patients with cancer.

BACKGROUND: Despite abundant evidence that emotional distress is frequent in cancer patients and associated with adverse health outcomes, distress screening rates and adequate referrals to psychological support programs among those in need are insufficient in many cancer centers. We therefore aimed to analyze patient- and treatment-related barriers to distress screening and referrals to psychological support as a mandatory component of best-practice cancer care. METHOD: In the present explorative study, latent class analysis was used to identify homogeneous subgroups among 4837 patients diagnosed with cancer between 2011 and 2019. RESULTS: Four subgroups were identified. Patients with a mental disorder and psychopharmacology were least probable to be screened for distress. Together with patients aged 65 or older and male patients, they were also less likely to receive psychological support. Patients hospitalized for 28 days or longer were most likely to be both screened and to receive psychological support. CONCLUSIONS: Clinicians and researchers are recommended not neglect patients with mental disorders and psychopharmacological treatment as well as male and elderly patients when screening for distress and providing access to psychological support.

Disease-Management-Programs in the Field of Diabetes Mellitus with Identification of the Best Practice in Europe: A Scoping Review.

The objective of this scoping review was to create an up-to-date descriptive overview of published Disease-Management-Program evaluations conducted within Europe. We also assessed the methodological quality of the evaluation and the comparability of the included studies. The Databases Pub Med via Medline and Embase via Ovid were searched for thematically fitting publications. Out of 649 initial titles and abstracts, 45 full-texts were screened for inclusions. Finally, 21 publications met all inclusion criteria. DMPs from Germany, Austria, Italy, the Netherlands and Great Britain were included. The results are tabulated in the results section and discussed descriptively. Due to the heterogeneity of the included studies and the application of sometimes potentially biased study design comparisons were difficult. A uniform European-wide evaluation strategy and common quality features would be desirable.

Spray-Dried Nanoparticle-in-Microparticle Delivery Systems (NiMDS) for Gene Delivery, Comprising Polyethylenimine (PEI)-Based Nanoparticles in a Poly(Vinyl Alcohol) Matrix.

Nucleic acid-based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid-based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready-to-use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine-based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray-dried nanoparticle-in-microparticle delivery system is presented for the encapsulation of polyethylenimine-based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy-to-handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine-based nanoparticles from the nanoparticle-in-microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle-in-microparticle delivery system is demonstrated as ready-to-use dry powder to be an efficient device for the inhalative delivery of polyethylenimine-based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration.

Path-Controlled Time Reordering of Paired Photons in a Dressed Three-Level Cascade.

The two-photon dressing of a "three-level ladder" system, here the ground state, the exciton, and the biexciton of a semiconductor quantum dot, leads to new eigenstates and allows one to manipulate the time ordering of the paired photons without unitary postprocessing. We show that, after spectral postselection of the single dressed states, the time ordering of the cascaded photons can be removed or conserved. Our joint experimental and theoretical study demonstrates the high potential of a "ladder" system to be a versatile source of orthogonally polarized, bunched or antibunched pairs of photons.

Multi-layer multi-configuration time-dependent Hartree (ML-MCTDH) approach to the correlated exciton-vibrational dynamics in the FMO complex.

The coupled quantum dynamics of excitonic and vibrational degrees of freedom is investigated for high-dimensional models of the Fenna-Matthews-Olson complex. This includes a seven- and an eight-site model with 518 and 592 harmonic vibrational modes, respectively. The coupling between local electronic transitions and vibrations is described within the Huang-Rhys model using parameters that are obtained by discretization of an experimental spectral density. Different pathways of excitation energy flow are analyzed in terms of the reduced one-exciton density matrix, focussing on the role of vibrational and vibronic excitations. Distinct features due to both competing time scales of vibrational and exciton motion and vibronically assisted transfer are observed. The question of the effect of initial state preparation is addressed by comparing the case of an instantaneous Franck-Condon excitation at a single site with that of a laser field excitation.

In vitro and in ovo photodynamic efficacy of nebulized curcumin-loaded tetraether lipid liposomes prepared by DC as stable drug delivery system.

Lung cancer is one of the most common causes of high mortality worldwide. Current treatment strategies, e.g., surgery, radiotherapy, chemotherapy, and immunotherapy, insufficiently affect the overall outcome. In this study, we used curcumin as a natural photosensitizer in photodynamic therapy and encapsulated it in liposomes consisting of stabilizing tetraether lipids aiming for a pulmonary drug delivery system against lung cancer. The liposomes with either hydrolyzed glycerol-dialkyl-glycerol tetraether (hGDGT) in different ratios or hydrolyzed glycerol-dialkyl-nonitol tetraether (hGDNT) were prepared by dual centrifugation (DC), an innovative method for liposome preparation. The liposomes' physicochemical characteristics before and after nebulization and other nebulization characteristics confirmed their suitability. Morphological characterization using atomic force and transmission electron microscopy showed proper vesicular structures indicative of liposomes. Qualitative and quantitative uptake of the curcumin-loaded liposomes in lung adenocarcinoma (A549) cells was visualized and proven. Phototoxic effects of the liposomes were detected on A549 cells, showing decreased cell viability. The generation of reactive oxygen species required for PDT and disruption of mitochondrial membrane potential were confirmed. Moreover, the chorioallantoic membrane (CAM) model was used to further evaluate biocompatibility and photodynamic efficacy in a 3D cell culture context. Photodynamic efficacy was assessed by PET/CT after nebulization of the liposomes onto the xenografted tumors on the CAM with subsequent irradiation. The physicochemical properties and the efficacy of tetraether lipid liposomes encapsulating curcumin, especially liposomes containing hGDNT, in 2D and 3D cell cultures seem promising for future PDT usage against lung cancer.

Evaluating the photodynamic efficacy of nebulized curcumin-loaded liposomes prepared by thin-film hydration and dual centrifugation: In vitro and in ovo studies.

Lung cancer, one of the most common causes of high mortality worldwide, still lacks appropriate and convenient treatment options. Photodynamic therapy (PDT) has shown promising results against cancer, especially in recent years. However, pulmonary drug delivery of the predominantly hydrophobic photosensitizers still represents a significant obstacle. Nebulizing DPPC/Cholesterol liposomes loaded with the photosensitizer curcumin via a vibrating mesh nebulizer might overcome current restrictions. In this study, the liposomes were prepared by conventional thin-film hydration and two other methods based on dual centrifugation. The liposomes' physicochemical properties were determined before and after nebulization, showing that liposomes do not undergo any changes. However, morphological characterization of the differently prepared liposomes revealed structural differences between the methods in terms of lamellarity. Internalization of curcumin in lung adenocarcinoma (A549) cells was visualized and quantified. The generation of reactive oxygen species because of the photoreaction was also proven. The photodynamic efficacy of the liposomal formulations was tested against A549 cells. They revealed different phototoxic responses at different radiant exposures. Furthermore, the photodynamic efficacy was investigated after nebulizing curcumin-loaded liposomes onto xenografted tumors on the CAM, followed by irradiation, and evaluated using positron emission tomography/computed tomography and histological analysis. A decrease in tumor metabolism could be observed. Based on the efficacy of curcumin-loaded liposomes in 2D and 3D models, liposomes, especially with prior film formation, can be considered a promising approach for PDT against lung cancer.

Inferior Frontal Sulcal Hyperintensities on Brain MRI Are Associated with Amyloid Positivity beyond Age-Results from the Multicentre Observational DELCODE Study.

Inferior frontal sulcal hyperintensities (IFSHs) on fluid-attenuated inversion recovery (FLAIR) sequences have been proposed to be indicative of glymphatic dysfunction. Replication studies in large and diverse samples are nonetheless needed to confirm them as an imaging biomarker. We investigated whether IFSHs were tied to Alzheimer's disease (AD) pathology and cognitive performance. We used data from 361 participants along the AD continuum, who were enrolled in the multicentre DELCODE study. The IFSHs were rated visually based on FLAIR magnetic resonance imaging. We performed ordinal regression to examine the relationship between the IFSHs and cerebrospinal fluid-derived amyloid positivity and tau positivity (Aß42/40 ratio ≤ 0.08; pTau181 ≥ 73.65 pg/mL) and linear regression to examine the relationship between cognitive performance (i.e., Mini-Mental State Examination and global cognitive and domain-specific performance) and the IFSHs. We controlled the models for age, sex, years of education, and history of hypertension. The IFSH scores were higher in those participants with amyloid positivity (OR: 1.95, 95% CI: 1.05-3.59) but not tau positivity (OR: 1.12, 95% CI: 0.57-2.18). The IFSH scores were higher in older participants (OR: 1.05, 95% CI: 1.00-1.10) and lower in males compared to females (OR: 0.44, 95% CI: 0.26-0.76). We did not find sufficient evidence linking the IFSH scores with cognitive performance after correcting for demographics and AD biomarker positivity. IFSHs may reflect the aberrant accumulation of amyloid ß beyond age.

Steriod-associated psychiatric burden in cancer patients.

This study explores the role of steroid administration in identifying distressed or even mentally disordered cancer patients (so-called case finding). Charts of 12 298 cancer patients (4499 treated with prednisone equivalents) were analysed descriptively. A subset of 10 945 was further explored via latent class analysis (LCA). LCA avoids confounding by indication because it subgroups patients without prior preconceptions based on homogeneous expression of traits (i.e. the variables examined). LCA identified four subgroups: two subgroups with high dosages of prednisone equivalent (≥80 mg/day on average over all treatment days) and two with low dosages. The two subgroups with high average dosages had an increased likelihood of psychotropic drug administration, but only one was more likely to require 1:1 observation. In one subgroup, low dosages of prednisone equivlents correlated with a slightly increased probability for a psychiatric assessment and psychotropic drug administration. The subgroup least likely to receive steroid treatment was also the least likely to receive a psychiatric assessment and psychotropic drug administration. Descriptive statistics on age, sex, cumulative inpatient treatment, type of cancer, stage of cancer at first diagnosis, mental disorders, severe mental disorders and psychotropic drug administration (antidepressants, antipsychotics, benzodiazepines, anticonvulsants/mood stabilizers, opioids) are provided for patients receiving no, less and more than 80 mg of prednisone equivalent.

A short screening tool identifying systemic barriers to distress screening in cancer care.

INTRODUCTION: International guidelines on cancer treatment recommend screening for early detection and treatment of distress. However, screening rates are insufficient. In the present study, a survey was developed to assess perceived systemic barriers to distress screening. METHODS: A three-step approach was used for the study. Based on qualitative content analysis of interviews and an expert panel, an initial survey with 53 questions on barriers to screening was designed. It was completed by 98 nurses in a large comprehensive cancer center in Switzerland. From this, a short version of the survey with 24 questions was derived using exploratory principal component analysis. This survey was completed by 150 nurses in four cancer centers in Switzerland. A confirmatory factor analysis was then performed on the shortened version, yielding a final set of 14 questions. RESULTS: The initial set of 53 questions was reduced to a set of 14 validated questions retaining 53% of the original variance. These 14 questions allow for an assessment within 2-3 min that identifies relevant barriers to distress screening from the perspective of those responsible for implementation of distress screening. Across several hospitals in Switzerland, the timing of the first distress screening, lack of capacity, patient and staff overload, and refusal of distressed patients to be referred to support services emerged as major problems. CONCLUSION: The validated 14 questions on barriers to screening cancer patients for distress enable clinicians and hospital administrators to quickly identify relevant issues and take action to improve screening programs.

Clinically Significant Distress and Physical Problems Detected on a Distress Thermometer are Associated With Survival Among Lung Cancer Patients.

BACKGROUND: The distress thermometer is a well-established screening tool to detect clinically significant distress in cancer patients. It is often administered in combination with the problem list, differentiating further between various (e.g., physical and emotional) sources of distress. OBJECTIVE: The present study aimed to extend previous research on the association between distress and overall survival. A further exploratory analysis aimed to evaluate the predictive value of the problem list for overall survival. METHODS: Patients (n = 323) with newly diagnosed lung cancer were recruited from a large cancer center. Patients were split into 2 groups, those with (distress thermometer score ≥5) and those without significant distress. The overall survival time was illustrated by a Kaplan-Meier curve and compared with a log-rank test. Univariable Cox proportional hazard models were built to control the association of distress with overall survival for age, gender, disease stage, comorbidity, and their interaction terms. Multiple linear regression was used to investigate the association of the items from the problem list with survival time. RESULTS: Patients with significant distress had a shorter survival time than patients without significant distress (25 vs. 43 months). Regression analysis revealed more problems with both "bathing and dressing" and "eating," as well as absence of "diarrhea" and increased "nervousness," to negatively associated with the overall survival time. CONCLUSIONS: Our results show that estimation of the survival function using cancer-related distress is possible. However, when using Cox regression, distress shows no significant value for survival as a predictor. Moreover, our study did not reveal an interaction effect among disease stage, comorbidity, and distress. Overall, results suggest that physical and emotional problems that arise from lung cancer may be useful to identify patients at risk of poor prognosis (on the basis of Kaplan-Meier estimator).

How to Xenograft Cancer Cells on the Chorioallantoic Membrane of a Fertilized Hen's Egg and Its Visualization by PET/CT and MRI.

The chorioallantoic membrane (CAM) of fertilized hen's eggs represents a unique and alternative model for cancer research. The CAM model provides an optimal platform for xenografting cancer cell lines and studying essential key factors. Tumor size and growth as well as angiogenesis can be investigated to evaluate the response of therapies and strategies against cancer. Preclinical imaging represented by magnetic resonance imaging and positron emission tomography/computed tomography can generate detailed anatomical and functional information and reveal excellent metabolic sensitivity. In the following, a guideline is introduced in order to find a simplified entrance to the CAM model in combination with modern preclinical imaging techniques. Finally, the presented procedures are additionally completed by histological studies in the form of hematoxylin and eosin as well as immunohistochemical staining.

Predictive Factors Associated with Declining Psycho-Oncological Support in Patients with Cancer.

(1) Background: International cancer treatment guidelines recommend low-threshold psycho-oncological support based on nurses' routine distress screening (e.g., via the distress thermometer and problem list). This study aims to explore factors which are associated with declining psycho-oncological support in order to increase nurses' efficiency in screening patients for psycho-oncological support needs. (2) Methods: Using machine learning, routinely recorded clinical data from 4064 patients was analyzed for predictors of patients declining psycho-oncological support. Cross validation and nested resampling were used to guard against model overfitting. (3) Results: The developed model detects patients who decline psycho-oncological support with a sensitivity of 89% (area under the cure of 79%, accuracy of 68.5%). Overall, older patients, patients with a lower score on the distress thermometer, fewer comorbidities, few physical problems, and those who do not feel sad, afraid, or worried refused psycho-oncological support. (4) Conclusions: Thus, current screening procedures seem worthy to be part of daily nursing routines in oncology, but nurses may need more time and training to rule out misconceptions of patients on psycho-oncological support.

Photoactive Parietin-loaded nanocarriers as an efficient therapeutic platform against triple-negative breast cancer.

The application of photodynamic therapy has become more and more important in combating cancer. However, the high lipophilic nature of most photosensitizers limits their parenteral administration and leads to aggregation in the biological environment. To resolve this problem and deliver a photoactive form, the natural photosensitizer parietin (PTN) was encapsulated in poly(lactic-co-glycolic acid) nanoparticles (PTN NPs) by emulsification diffusion method. PTN NPs displayed a size of 193.70 nm and 157.31 nm, characterized by dynamic light scattering and atomic force microscopy, respectively. As the photoactivity of parietin is essential for therapy, the quantum yield of PTN NPs and the in vitro release were assessed. The antiproliferative activity, the intracellular generation of reactive oxygen species, mitochondrial potential depolarization, and lysosomal membrane permeabilization were evaluated in triple-negative breast cancer cells (MDA-MB-231 cells). At the same time, confocal laser scanning microscopy (CLSM) and flow cytometry were used to investigate the cellular uptake profile. In addition, the chorioallantoic membrane (CAM) was employed to evaluate the antiangiogenic effect microscopically. The spherical monomodal PTN NPs show a quantum yield of 0.4. The biological assessment on MDA-MB-231 cells revealed that free PTN and PTN NPs inhibited cell proliferation with IC50 of 0.95 µM and 1.9 µM at 6 J/cm2, respectively, and this can be attributed to the intracellular uptake profile as proved by flow cytometry. Eventually, the CAM study illustrated that PTN NPs could reduce the number of angiogenic blood vessels and disrupt the vitality of xenografted tumors. In conclusion, PTN NPs are a promising anticancer strategy in vitro and might be a tool for fighting cancer in vivo.

Modern Photodynamic Glioblastoma Therapy Using Curcumin- or Parietin-Loaded Lipid Nanoparticles in a CAM Model Study.

Natural photosensitizers, such as curcumin or parietin, play a vital role in photodynamic therapy (PDT), causing a light-mediated reaction that kills cancer cells. PDT is a promising treatment option for glioblastoma, especially when combined with nanoscale drug delivery systems. The curcumin- or parietin-loaded lipid nanoparticles were prepared via dual asymmetric centrifugation and subsequently characterized through physicochemical analyses including dynamic light scattering, laser Doppler velocimetry, and atomic force microscopy. The combination of PDT and lipid nanoparticles has been evaluated in vitro regarding uptake, safety, and efficacy. The extensive and well-vascularized chorioallantois membrane (CAM) of fertilized hen's eggs offers an optimal platform for three-dimensional cell culture, which has been used in this study to evaluate the photodynamic efficacy of lipid nanoparticles against glioblastoma cells. In contrast to other animal models, the CAM model lacks a mature immune system in an early stage, facilitating the growth of xenografts without rejection. Treatment of xenografted U87 glioblastoma cells on CAM was performed to assess the effects on tumor viability, growth, and angiogenesis. The xenografts and the surrounding blood vessels were targeted through topical application, and the effects of photodynamic therapy have been confirmed microscopically and via positron emission tomography and X-ray computed tomography. Finally, the excised xenografts embedded in the CAM were analyzed histologically by hematoxylin and eosin and KI67 staining.

Electro-optical resonance modulation of vertical-cavity surface-emitting lasers.

Optical and electrical investigations of vertical-cavity surface-emitting lasers (VCSEL) with a monolithically integrated electro-optical modulator (EOM) allow for a detailed physical understanding of this complex compound cavity laser system. The EOM VCSEL light output is investigated to identify optimal working points. An electro-optic resonance feature triggered by the quantum confined Stark effect is used to modulate individual VCSEL modes by more than 20 dB with an extremely small EOM voltage change of less than 100 mV. Spectral mode analysis reveals modulation of higher order modes and very low wavelength chirp of < 0.5 nm. Dynamic experiments and simulation predict an intrinsic bandwidth of the EOM VCSEL exceeding 50 GHz.

Sustained cognitive impairments after clinical recovery of severe depression.

Neuropsychological impairment is prominent in patients with depression, but it is unclear whether deficits persist after clinical response. This study aimed to investigate neuropsychological functions in the course of the illness. Depressive patients were investigated in the acute state and after clinical response using an extensive neuropsychological test battery. After clinical response, there was only a partial improvement in learning and memory and there were no changes regarding working memory, executive functions, and attention. Transient impairments in visual learning and memory suggest a depression-related state effect. The continuing deficits in attention, working memory, and executive function might be considered a trait marker.

Severe mental illness in cancer is associated with disparities in psycho-oncological support.

Patients with both cancer and a severe mental illness (SMI) have a higher risk of advanced stage cancer at diagnosis and poorer survival in comparison to individuals with cancer alone. The present study explores if similar disparities exist in terms of psycho-oncological support. Latent class analysis (LCA) was used to group 10,945 patients with any type of cancer, of which 72 (0.7%) had been diagnosed with a SMI (ICD10-codes F20-F22, F24, F25, F28-F31, F32.3, F33.3), and 1056 (9.6%) with another mental disorder. Subgrouping was based on presence of SMI, other mental illnesses, stage of cancer at its first detection, screening for distress and receipt of information on psycho-oncology, consultation with a psychotherapist and/or psychiatrist, prescription of different psychotropic medication, and use of a patient care attendant. Five subgroups were identified. Patients with SMI were most likely to suffer from further mental comorbidities, to be prescribed antipsychotics, antidepressants, or mood stabilizers, and be in need of a patient care attendant. In comparison to patients without SMI, the larger one of 2 subgroups of patients with SMI had a low probability to be screened for distress and informed about psycho-oncological support services. A smaller subgroup of patients with SMI was probable to be diagnosed with an advanced stage of cancer. In subgroups without patients with mental disorders, screening for distress and offering psycho-oncological support seemed to be economized unless benzodiazepines or opioids were prescribed. Contrary to published evidence, distress screening and offering psycho-oncological support is neglected in patients with SMI unless an advanced stage of cancer is being diagnosed.