Organization of head and neck cancer rehabilitation care: a national survey among healthcare professionals in Dutch head and neck cancer centers.

PURPOSE: Head and neck cancer (HNC) treatment often leads to physical and psychosocial impairments. Rehabilitation can overcome these limitations and improve quality of life. The aim of this study is to obtain an overview of rehabilitation care for HNC, and to investigate factors influencing rehabilitation provision, in Dutch HNC centers, and to some extent compare it to other countries. METHODS: An online survey, covering five themes: organizational structure; rehabilitation interventions; financing; barriers and facilitators; satisfaction and future improvements, among HNC healthcare- and financial professionals of Dutch HNC centers. RESULTS: Most centers (86%) applied some type of rehabilitation care, with variations in organizational structure. A speech language therapist, physiotherapist and dietitian were available in all centers, but other rehabilitation healthcare professionals in less than 60%. Facilitators for providing rehabilitation services included availability of a contact person, and positive attitude, motivation, and expertise of healthcare professionals. Barriers were lack of reimbursement, and patient related barriers including comorbidity, travel (time), low health literacy, limited financial capacity, and poor motivation. CONCLUSION: Although all HNC centers included offer rehabilitation services, there is substantial practice variation, both nationally and internationally. Factors influencing rehabilitation are related to the motivation and expertise of the treatment team, but also to reimbursement aspects and patient related factors. More research is needed to investigate the extent to which practice variation impacts individual patient outcomes and how to integrate HNC rehabilitation into routine clinical pathways.

Do categorical representations modulate early perceptual or later cognitive visual processing? An ERP study.

Encoding of perceptual categorical information has been observed in later cognitive processing like memory encoding and maintenance, starting around 300 ms after stimulus onset (P300). However, it remains open whether categorical information is also encoded in early perceptual processing steps (reflected in the mismatch negativity component; vMMN). The main goal of this study was to assess the influence of categorical information on both early perceptual (i.e., vMMN component) and later cognitive (i.e., P300 component) processing within one paradigm. Hence, we combined an oddball paradigm with a delayed memory task. We used five-dot patterns belonging to different categories even though categorical information is not mirrored in their physical characteristics. Distinct vMMNs were observed for patterns belonging to the same as compared to different categories, suggesting that abstract categorical information was encoded during early perceptual processing. However, inconsistent with prior studies, we observed no effect of categories on the P300, indicating no additional encoding of categorical information in later cognitive stages of processing. Our findings emphasize that the encoding of categorical information depends on specific task demands and hence is more flexible and dynamic than previously suggested.

Study protocol of a prospective multicenter study comparing (cost-)effectiveness of a tailored interdisciplinary head and neck rehabilitation program to usual supportive care for patients treated with concomitant chemo- or bioradiotherapy.

BACKGROUND: Since 2011, a tailored, interdisciplinary head and neck rehabilitation (IHNR) program, covered by the basic healthcare insurance, is offered to advanced head and neck cancer (HNC) patients in the Netherlands Cancer Institute (NKI). This program is developed to preserve or restore patients' functioning, and to optimize health-related quality of life (HRQoL). It applies an integrated approach to define patients' individual goals and provide rehabilitation care throughout the cancer care continuum. The aim of the current study is to assess the (cost-) effectiveness of the IHNR approach compared to usual supportive care (USC) consisting of monodisciplinary and multidisciplinary care in advanced HNC patients. METHODS: This multicenter prospective observational study is designed to compare (cost-)effectiveness of the IHNR to USC for advanced HNC patients treated with chemoradiotherapy (CRT) or bioradiotherapy (BRT). The primary outcome is HRQoL represented in the EORTC QLQ-C30 summary score. Functional HRQoL, societal participation, utility values, return to work (RTW), unmet needs (UN), patient satisfaction and clinical outcomes are secondary outcomes, assessed using the EORTC QLQ-H&N35, USER-P, EQ-5D-5 L, and study-specific questionnaires, respectively. Both patient groups (required sample size: 64 per arm) are requested to complete the questionnaires at: diagnosis (baseline; T0), 3 months (T1), 6 months (T2), 9 months (T3) and 12 months (T4) after start of medical treatment. Differences in outcomes between the intervention and control group will be analyzed using mixed effects models, Chi-square test and descriptive statistics. In addition, a cost-effectiveness analysis (CEA) will be performed by means of a Markov decision model. The CEA will be performed using a societal perspective of the Netherlands. DISCUSSION: This prospective multicenter study will provide evidence on the effectiveness and cost-effectiveness of IHNR compared to USC. RTW and societal participation, included as secondary outcomes, have not been studied sufficiently yet in cancer rehabilitation. Interdisciplinary rehabilitation has not yet been implemented as usual care in all centers, which offers the opportunity to perform a controlled clinical study. If demonstrated to be (cost-)effective, national provision of the program can probably be advised. TRIAL REGISTRATION: The study has been retrospectively registered in the Netherlands Trial Registry on April 24th 2018 ( NTR7140 ).

Oncodermatology of the Head and Neck.

The European Academy of Facial Plastic Surgery celebrates its 40th anniversary. We aimed to describe innovations in the diagnostics and treatment in head and neck skin cancer over the past 40 years as well as future perspectives. Landmark events, developments, and highlights over the past decades for basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma are discussed.

Salivary duct carcinoma: evaluation of treatment and outcome in a tertiary referral institute.

PURPOSE: The aggressive behavior of salivary duct carcinoma (SDC) necessitates an aggressive treatment strategy, including surgery and radiotherapy (RT). We evaluated practice patterns and treatment outcomes in patients with SDC treated in our Institute. METHODS: Patients with SDC of the parotid or submandibular gland treated with curative intention in our Institute from 1998 until 2016 were reviewed. Our diagnostic workup and treatment strategy were evaluated together with treatment outcomes. RESULTS: Fifteen patients with SDC were included. Staging included MRI and ultrasound-guided fine needle aspiration cytology. Only in a minority (20%) of patients, the preoperative diagnosis of SDC was raised due to positive immunohistochemical staining for the androgen receptor (AR) on cytology. All patients were treated with (sub)total resection of the salivary gland and 53% underwent a therapeutic neck dissection. All patients except one received postoperative RT. Immunohistochemical staining was found positive for AR (100%) and human epidermal growth factor receptor 2 (HER2/neu) (13%). No local recurrences occurred. Regional and distant failure rates were 20% and 40%, respectively. CONCLUSIONS: Excellent local control rates can be achieved with extensive (local) surgical treatment and postoperative RT. In case of lymph node metastases, a neck dissection with adjuvant postoperative RT is warranted. In patients with node-negative disease, a less aggressive approach for the neck seems feasible to reduce treatment-related morbidity.

Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo.

Mutations in codon 132 of isocitrate dehydrogenase (IDH) 1 are frequent in diffuse glioma, acute myeloid leukemia, chondrosarcoma and intrahepatic cholangiocarcinoma. These mutations result in a neomorphic enzyme specificity which leads to a dramatic increase of intracellular D-2-hydroxyglutarate (2-HG) in tumor cells. Therefore, mutant IDH1 protein is a highly attractive target for inhibitory drugs. Here, we describe the development and properties of BAY 1436032, a pan-inhibitor of IDH1 protein with different codon 132 mutations. BAY 1436032 strongly reduces 2-HG levels in cells carrying IDH1-R132H, -R132C, -R132G, -R132S and -R132L mutations. Cells not carrying IDH mutations were unaffected. BAY 1436032 did not exhibit toxicity in vitro or in vivo. The pharmacokinetic properties of BAY 1436032 allow for oral administration. In two independent experiments, BAY 1436032 has been shown to significantly prolong survival of mice intracerebrally transplanted with human astrocytoma carrying the IDH1R132H mutation. In conclusion, we developed a pan-inhibitor targeting tumors with different IDH1R132 mutations.

The developmental trajectory of functional excitation-inhibition balance relates to language abilities in autistic and allistic children.

Autism is a neurodevelopmental condition that has been related to an overall imbalance between the brain's excitatory (E) and inhibitory (I) systems. Such an EI imbalance can lead to structural and functional cortical deviances and thus alter information processing in the brain, ultimately giving rise to autism traits. However, the developmental trajectory of EI imbalances across childhood and adolescence has not been investigated yet. Therefore, its relationship to autism traits is not well understood. In the present study, we determined a functional measure of the EI balance (f-EIB) from resting-state electrophysiological recordings for a final sample of 92 autistic children from 6 to 17 years of age and 100 allistic (i.e., non-autistic) children matched by age, sex, and nonverbal-IQ. We related the developmental trajectory of f-EIB to behavioral assessments of autism traits as well as language ability. Our results revealed differential EI trajectories for autistic compared to allistic children. Importantly, the developmental trajectory of f-EIB values related to individual language ability. In particular, elevated excitability in late childhood and early adolescence was linked to decreased listening comprehension. Our findings provide evidence against a general EI imbalance in autistic children when correcting for non-verbal IQ. Instead, we show that the developmental trajectory of EI balance shares variance with autism trait development at a specific age range. This is consistent with the proposal that the late development of inhibitory brain activity is a key substrate of autism traits.

Enzymatic assay for quantitative analysis of (D)-2-hydroxyglutarate.

Levels of (D)-2-hydroxyglutarate [D2HG, (R)-2-hydroxyglutarate] are increased in some metabolic diseases and in neoplasms with mutations in the isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) genes. Determination of D2HG is of relevance to diagnosis and monitoring of disease. Standard detection methods of D2HG levels are liquid-chromatography-mass spectrometry or gas-chromatography-mass spectrometry. Here we present a rapid, inexpensive and sensitive enzymatic assay for the detection of D2HG levels. The assay is based on the conversion of D2HG to α-ketoglutarate (αKG) in the presence of the enzyme (D)-2-hydroxyglutarate dehydrogenase (HGDH) and nicotinamide adenine dinucleotide (NAD(+)). Determination of D2HG concentration is based on the detection of stoichiometrically generated NADH. The quantification limit of the enzymatic assay for D2HG in tumor tissue is 0.44 µM and in serum 2.77 µM. These limits enable detection of basal D2HG levels in human tumor tissues and serum without IDH mutations. Levels of D2HG in frozen and paraffin-embedded tumor tissues containing IDH mutations or in serum from acute myeloid leukemia patients with IDH mutations are significantly higher and can be easily identified with this assay. In conclusion, the assay presented is useful for differentiating basal from elevated D2HG levels in tumor tissue, serum, urine, cultured cells and culture supernatants.

Is the dolphin a fish? ERP evidence for the impact of typicality during early visual processing in ultra-rapid semantic categorization in autism spectrum disorder.

BACKGROUND: Neurotypical individuals categorize items even during ultra-rapid presentations (20 ms; see Thorpe et al. Nature 381: 520, 1996). In cognitively able autistic adults, these semantic categorization processes may be impaired and/or may require additional time, specifically for the categorization of atypical compared to typical items. Here, we investigated how typicality structures influence ultra-rapid categorization in cognitively able autistic and neurotypical male adults. METHODS: Images representing typical or atypical exemplars of two different categories (food/animals) were presented for 23.5 vs. 82.3 ms (short/long). We analyzed detection rates, reaction times, and the event-related potential components dN150, N1, P2, N2, and P3 for each group. RESULTS: Behavioral results suggest slower and less correct responses to atypical compared to typical images. This typicality effect was larger for the category with less distinct boundaries (food) and observed in both groups. However, electrophysiological data indicate a different time course of typicality effects, suggesting that neurotypical adults categorize atypical images based on simple features (P2), whereas cognitively able autistic adults categorize later, based on arbitrary features of atypical images (P3). CONCLUSIONS: We found evidence that all three factors under investigation - category, typicality, and presentation time - modulated specific aspects of semantic categorization. Additionally, we observed a qualitatively different pattern in the autistic adults, which suggests that they relied on different cognitive processes to complete the task.

Caregivers' Experiences of Infant Feeding Problems: The Role of Self-Compassion and Stress Management.

Introduction Infant feeding problems are strongly associated with caregiver stress, which in turn is linked to poorer outcomes for children. Self-compassion is a modifiable trait strongly associated with improved mental health and greater resilience. The purpose of this study was to investigate the relationships among self-compassion, stress management practices, and caregiver stress in a sample of parents who identified feeding problems in their infants. Method Parents who identified feeding problems in their infants completed an online survey. They described the feeding problems, completed the Self-Compassion Scale and the Perceived Stress Scale, and detailed their stress management practices. Results Higher self-compassion was strongly associated with lower overall stress and more modestly associated with lower feeding-related distress. More severe feeding problems were significantly more stressful for caregivers. Participants reported a wide variety of stress management approaches. Discussion These findings indicate that higher self-compassion is associated with lower caregiver stress for parents whose infants experience feeding problems. Implications for service providers are reviewed. Supplemental Material https://doi.org/10.23641/asha.14831028.

Do categorical representations modulate early automatic visual processing? A visual mismatch-negativity study.

Perceptual categorization is an important cognitive function. In the auditory domain, categorization already occurs within the first 200 ms of information processing, as indexed by the mismatch negativity. Here, we assessed the characteristics of the visual mismatch negativity (vMMN) elicited during the categorization of previously unknown visual stimuli. To examine this, we used five-dot patterns with characteristics that allow for the formation of categories through rotation and reflection but not through other physical properties. To assess whether or not between-category and within-category vMMN differ in amplitude, the data was analyzed with the Bayesian approach. We observed that both between-category and within-category deviants elicited a vMMN, but that both vMMNs were comparable in magnitude. This finding suggests that abstract categorical representations are not always automatically processed at early visual stages and demonstrates limitations of generalization from the auditory domain to visual domain.

Cost-Effectiveness of Surgery Versus Organ Preservation in Advanced Laryngeal Cancer.

OBJECTIVE: Treatment decision-making for patients with laryngeal cancer consists of a complex trade-off between survival and quality of life. For decision makers on coverage and guidelines, costs come in addition to this equation. Our aim was to perform a cost-effectiveness analysis of surgery (laryngectomy with or without radiotherapy) versus organ preservation (OP: radiotherapy, chemo- and/or bioradiation) in advanced laryngeal cancer patients from a healthcare perspective. METHODS: A cost-effectiveness analysis was conducted using a Markov model. For each modality, data on survival and quality-adjusted life years (QALYs) were sourced from relevant articles in agreement with experts, and national benchmark cost prices were included regarding treatment, follow-up, adverse events, and rehabilitation. RESULTS: Total QALYs of the surgical approach (6.59) were substantially higher compared to the OP approach (5.44). Total lifetime costs were higher for the surgical approach compared to the OP approach, namely €95,881 versus €47,233. The surgical approach was therefore more effective and more costly compared to OP, resulting in an incremental cost-effectiveness ratio of €42,383/QALY. CONCLUSION: Based on current literature, surgical treatment was cost-effective compared to OP in advanced laryngeal cancer within most willingness-to-pay thresholds. The study provides information on the survival adjusted for quality of life in combination with costs of two different approaches for advanced laryngeal cancer, relevant for patients, physicians, and policy makers. As financial toxicity is a relevant aspect in this population, collection of real-world data on country-specific costs and utilities is strongly recommended to enable further generalization. LEVEL OF EVIDENCE: N/A. Laryngoscope, 131:E509-E517, 2021.

Factoring in the spatial effects of symbolic number representation.

Spatial constituents of adult symbolic number representation produce effects of size-value congruity, Spatial Numerical Association of Response Codes (SNARC), and numerical distance. According to behavioral experiments, these effects belong to distinct processing stages. Yet, these effects evoke overlapping responses in both early and late Event Related Potentials (ERPs). To probe whether these overlaps indicate sharing of resources, all relevant stimulus and response conditions were factorially combined in a numerical value comparison task. To secure ERP validity, same numbers were compared against variable reference values. This design resulted in previously unobserved interactions in behavior but inhibited late ERP effects. All effects arose early in the P1 component (around 100 ms) and most showed hemispheric specificity. Independency of congruity and SNARC effects was observed, whereas SNARC and numerical distance were closely intertwined. Differences in hemispheric specificity, rather than stage-wise separation, were key to independence.

Cost-effectiveness analysis of using the heat and moisture exchangers compared with alternative stoma covers in laryngectomy rehabilitation: US perspective.

BACKGROUND: This study aims to evaluate the cost-effectiveness of using heat and moisture exchangers (HMEs) vs alternative stoma covers (ASCs) following laryngectomy in the United States. METHODS: A cost-effectiveness and budget impact analysis were conducted including uncertainty analyses using real-world survey data with pulmonary events and productivity loss. RESULTS: HME use was more effective and less costly compared with ASCs. Quality-adjusted life years were slightly higher for HME-users. Total costs per patient (lifetime) were $59 362 (HME) and $102 416 (ASC). Pulmonary events and productivity loss occurred more frequently in the ASC-users. Annual budget savings were up to $40 183 593. Costs per pulmonary event averted were $3770. CONCLUSIONS: HME utilization in laryngectomy patients was cost-effective. Reimbursement of HME devices is thus recommended. Utilities may be underestimated due to the generic utility instrument used and sample size. Therefore, we recommend development of a disease-specific utility tool to incorporate in future analyses.

An investigation of aided language stimulation: does it increase AAC use with adults with developmental disabilities and complex communication needs?

A single subject ABAB design was used to determine the efficacy of aided language stimulation to teach the use of AAC techniques to adults with developmental disabilities. Sixteen participants were divided into two equal groups. In each group, half of the participants were able to communicate functionally using spoken language and half had complex communication needs and did not have functional, symbolic communication systems. Each group met twice weekly for 30 min per session. Researchers modeled the use of AAC and followed scripts during music-based interventions. Sessions focused on social greetings, choosing songs to play, learning words and movements for the songs, and discussing the songs. Participants were encouraged to interact with each other and to facilitate each other's communications. Results suggest that responsiveness and use of AAC increased for all participants with complex communication needs.

Mapping the EORTC QLQ-C30 and QLQ-H&N35 to the EQ-5D for head and neck cancer: Can disease-specific utilities be obtained?

INTRODUCTION: Innovations in head and neck cancer (HNC) treatment are often subject to economic evaluation prior to their reimbursement and subsequent access for patients. Mapping functions facilitate economic evaluation of new treatments when the required utility data is absent, but quality of life data is available. The objective of this study is to develop a mapping function translating the EORTC QLQ-C30 to EQ-5D-derived utilities for HNC through regression modeling, and to explore the added value of disease-specific EORTC QLQ-H&N35 scales to the model. METHODS: Data was obtained on patients with primary HNC treated with curative intent derived from two hospitals. Model development was conducted in two phases: 1. Predictor selection based on theory- and data-driven methods, resulting in three sets of potential predictors from the quality of life questionnaires; 2. Selection of the best out of four methods: ordinary-least squares, mixed-effects linear, Cox and beta regression, using the first set of predictors from EORTC QLQ-C30 scales with most correspondence to EQ-5D dimensions. Using a stepwise approach, we assessed added values of predictors in the other two sets. Model fit was assessed using Akaike and Bayesian Information Criterion (AIC and BIC) and model performance was evaluated by MAE, RMSE and limits of agreement (LOA). RESULTS: The beta regression model showed best model fit, with global health status, physical-, role- and emotional functioning and pain scales as predictors. Adding HNC-specific scales did not improve the model. Model performance was reasonable; R2 = 0.39, MAE = 0.0949, RMSE = 0.1209, 95% LOA of -0.243 to 0.231 (bias -0.01), with an error correlation of 0.32. The estimated shrinkage factor was 0.90. CONCLUSIONS: Selected scales from the EORTC QLQ-C30 can be used to estimate utilities for HNC using beta regression. Including EORTC QLQ-H&N35 scales does not improve the mapping function. The mapping model may serve as a tool to enable cost-effectiveness analyses of innovative HNC treatments, for example for reimbursement issues. Further research should assess the robustness and generalizability of the function by validating the model in an external cohort of HNC patients.

Effectiveness of a Method for Teaching Self-Compassion to Communication Sciences and Disorders Graduate Students.

Purpose: The purpose of this study is to explore the effects of a daily mindfulness practice and 2 types of journaling on participants' development of self-compassion. Method: This was a between-groups design. All participants in a graduate counseling course engaged in a short daily mindfulness practice at the beginning of every class. Participants were randomly assigned to a counseling journal or a gratitude journal group. Participants were to write in their journals 2 to 5 times a week for the duration of the class. Participants completed the Self-Compassion Scale (Neff, 2003) and a questionnaire created by the 1st author before any mindfulness sessions were held and again at the completion of the course. Results: Participants' level of self-compassion increased from pretest to posttest. The self-compassion scores of participants who kept counseling journals increased more than did those of participants who kept gratitude journals. Qualitative data indicated that participants believed that mindfulness was an important quality for clinicians to possess and that they were accepting of the daily mindfulness practice. Conclusions: Engaging in a 12-min daily mindfulness practice utilizing simple yoga postures, breath work, reflective writing, and journaling done at a separate time appears to be an effective technique for increasing students' levels of self-compassion. Maintaining a counseling journal as opposed to a gratitude journal appears to enhance the effect of the daily mindfulness practice on self-compassion.

A Mindfulness Practice for Communication Sciences and Disorders Undergraduate and Speech-Language Pathology Graduate Students: Effects on Stress, Self-Compassion, and Perfectionism.

PURPOSE: The purpose of the present study was to explore the effects of a mindfulness practice on participants' levels of self-compassion, perfectionism, attention, and perceived and biological stress. METHOD: This was a between-groups design. Experimental participants engaged in a short mindfulness practice weekly for one academic semester; control participants did not. All participants completed three self-report scales measuring perceived stress, self-compassion, and perfectionism before and after mindfulness sessions. In addition, electrophysiological measures were taken before and after to determine changes in biological markers of stress and attention. Experimental participants also kept reflective journals that were analyzed qualitatively. RESULTS: Compared with control participants, by the end of the semester, experimental participants' perceived stress levels and potentially negative aspects of perfectionism decreased and biological markers of stress and self-compassion improved. Experimental participants' reflective writings indicated they perceived the sessions to be beneficial. Although the results are promising, no significant effect was found for attention. CONCLUSIONS: Engaging in a 20-min mindfulness practice using simple yoga posture and breath work across an academic semester appears to be effective in reducing students' perceived and biological stress levels and maladaptive aspects of perfectionism and in increasing their self-compassion. These are all factors that can improve students' overall well-being.

Is awesome really awesome? How the inclusion of informal terms on an AAC device influences children's attitudes toward peers who use AAC.

Two videotapes were created of a child communicating with a voice output augmentative and alternative communication (AAC) device. In one the child communicated using formal English only and in the other the child communicated using formal English and age appropriate informal terms. Children in grades 4 and 5 viewed either the formal English only or the formal and informal English videotape. After viewing the videotape, children completed a measure of self-reported attitudes toward children who use AAC. Results indicated effects for gender and for the gender by grade interaction. These results are discussed along with clinical implications.

Concordance of folate receptor-α expression between biopsy, primary tumor and metastasis in breast cancer and lung cancer patients.

Folate receptor alpha (FRα) is known to be upregulated in a variety of cancers, including non-small cell lung cancer (NSCLC) and breast cancer. To ensure reliable implementation of diagnostic- and therapeutic agents, concordance of FRα expression between biopsy, primary tumor and metastases is important. Using immunohistochemistry (Mab 26B3.F2) these concordances were investigated in 60 NSCLC and 40 breast cancer patients. False positivity of FRα expression on breast and lung cancer biopsies was limited to less than 5%. In NSCLC, FRα expression was shown in 21/34 adenocarcinomas and 4/26 squamous cell carcinomas (SCC). Concordance of FRα expression between biopsy and primary tumor was achieved in respectively 83% and 91% of adenocarcinomas and SCCs. Approximately 80% of all local and distant metastases of NSCLC patients showed concordant FRα expression as their corresponding primary tumor. In breast cancer, FRα positivity was shown in 12/40 biopsies, 20/40 lumpectomies and 6/20 LN metastases, with concordance of 68% between biopsy and primary tumor and 60% between primary tumor and LN metastases. In conclusion, this study shows high concordance rates of FRα expression between biopsies and metastases compared to primary NSCLC and breast cancers, underscoring the applicability of FRα-targeted agents in these patients.