Disfluencies in spontaneous speech in persons with low-grade glioma before and after surgery.

Impaired lexical retrieval is common in persons with low-grade glioma (LGG). Several studies have reported a discrepancy between subjective word-finding difficulties and results on formal tests. Analysis of spontaneous speech might be more sensitive to signs of word-finding difficulties, hence we aimed to explore disfluencies in a spontaneous-speech task performed by participants with presumed LGG before and after surgery. Further, we wanted to explore how the presence of disfluencies in spontaneous speech differed in the participants with and without objectively established lexical-retrieval impairment and with and without self-reported subjective experience of impaired language, speech and communication. Speech samples of 26 persons with presumed low-grade glioma were analysed with regard to disfluency features. The post-operative speech samples had a higher occurrence of fillers, implying more disfluent language production. The participants performed worse on two of the word fluency tests, and after surgery the number of participants who were assessed as having an impaired lexical retrieval had increased from 6 to 12. The number of participants who experienced a change in their language, speech or communication had increased from 9 to 12. Additional comparisons showed that those with impaired lexical retrieval had a higher proportion of false starts after surgery than those with normal lexical retrieval, and differences in articulation rate and speech rate, favouring those not having experienced any change in language, speech or communication. Taken together, the findings from this study strengthen the existing claim that temporal aspects of language and speech are important when assessing persons with gliomas.

Experiences and Translatability of In Vitro and In Vivo Models to Evaluate Caprate as a Permeation Enhancer.

Transient permeation enhancers (PEs) have been widely used to improve the oral absorption of macromolecules. During pharmaceutical development, the correct selection of the macromolecule, PE, and the combination needs to be made to maximize oral bioavailability and ensure successful clinical development. Various in vitro and in vivo methods have been investigated to optimize this selection. In vitro methods are generally preferred by the pharmaceutical industry to reduce the use of animals according to the "replacement, reduction, and refinement" principle commonly termed "3Rs," and in vitro methods typically have a higher throughput. This paper compares two in vitro methods that are commonly used within the pharmaceutical industry, being Caco-2 and an Ussing chamber, to two in vivo models, being in situ intestinal instillation to rats and in vivo administration via an endoscope to pigs. All studies use solution formulation of sodium caprate, which has been widely used as a PE, and two macromolecules, being FITC-dextran 4000 Da and MEDI7219, a GLP-1 receptor agonist peptide. The paper shares our experiences of using these models and the challenges with the in vitro models in mimicking the processes occurring in vivo. The paper highlights the need to consider these differences when translating data generated using these in vitro models for evaluating macromolecules, PE, and combinations thereof for enabling oral delivery.

Detection of Subclinical Motor Speech Deficits after Presumed Low-Grade Glioma Surgery.

Motor speech performance was compared before and after surgical resection of presumed low-grade gliomas. This pre- and post-surgery study was conducted on 15 patients (mean age = 41) with low-grade glioma classified based on anatomic features. Repetitions of /pa/, /ta/, /ka/, and /pataka/ recorded before and 3 months after surgery were analyzed regarding rate and regularity. A significant reduction (6 to 5.6 syllables/s) pre- vs. post-surgery was found in the rate for /ka/, which is comparable to the approximate average decline over 10-15 years of natural aging reported previously. For all other syllable types, rates were within normal age-adjusted ranges in both preoperative and postoperative sessions. The decline in /ka/ rate might reflect a subtle reduction in motor speech production, but the effects were not severe. All but one patient continued to perform within normal ranges post-surgery; one performed two standard deviations below age-appropriate norms pre- and post-surgery in all syllable tasks. The patient experienced motor speech difficulties, which may be related to the tumor's location in an area important for speech. Low-grade glioma may reduce maximum speech-motor performance in individual patients, but larger samples are needed to elucidate how often the effect occurs.

Effect of expiratory muscle strength training on voice and speech: An exploratory study in persons with Parkinson's disease or multiple sclerosis.

PURPOSE: This study explored how respiration, voice, and speech were affected following expiratory muscle strength training (EMST) and maintenance training in persons with Parkinson's disease (PD) or multiple sclerosis (MS). METHOD: Nine participants with PD and six with MS participated in a randomised study, where the effects of EMST, sham, and maintenance treatment were investigated. Outcome measures included maximum expiratory pressure (MEP); maximum phonation time (MPT); intelligibility; verbal diadochokinesis (DDK); speech rate; a self-report form on voice, speech, and communication; and open questions about how the participants experienced the intervention. Group comparisons were performed within and between groups. RESULT: The PD and the MS groups both improved significantly in MEP, and this improvement remained after 3 months of maintenance EMST. An improvement was also seen in DDK. Post-EMST, 33% of the PD group and 80% of the MS group reported a positive effect on communication. CONCLUSION: The results of this study support previous evidence that EMST has positive effects on expiratory pressure in persons with PD or MS, but its effect on voice and speech remains unclear. Since subjective reports of the intervention and effects on communication were predominantly positive, further research is needed on larger groups to explore appropriate outcome measures.

Experiences of language and communication after brain-tumour treatment: A long-term follow-up after glioma surgery.

The purpose of this study was to explore how persons having received various treatments for glioma, a type of brain tumour, experience their language, speech, and communication in everyday life. Twelve persons with low-grade glioma and one with high-grade glioma who had undergone tumour resection in 2014-2016 in different tumour locations were interviewed using a semi-structured protocol. The video-recorded interviews were transcribed and analysed using qualitative content analysis, which revealed three manifest categories, nine sub-categories and one latent theme. Participants experienced changed communication that affected word finding, motor speech and comprehension. They also expressed how communication required a greater effort; time and context were important factors and participants felt frustrated with their communication. Further, they were dealing with changes and used multiple strategies to manage communication. For most participants it did not affect their everyday life, but it was not like before. In addition, participants adapted their way of living to manage illness-related problems. Uncertainty was a latent theme which emanated from the participants' illness experience, reflecting how living with a slow-growing brain tumour affects life-decisions and views of perceived symptoms. Discussion of how results can be interpreted in relation to previous research and health care are included.

Evaluation in pig of an intestinal administration device for oral peptide delivery.

The bioavailability of peptides co-delivered with permeation enhancers following oral administration remains low and highly variable. Two factors that may contribute to this are the dilution of the permeation enhancer in the intestinal fluid, as well as spreading of the released permeation enhancer and peptide in the lumen by intestinal motility. In this work we evaluated an Intestinal Administration Device (IAD) designed to reduce the luminal dilution of drug and permeation enhancer, and to minimize movement of the dosage form in the intestinal lumen. To achieve this, the IAD utilizes an expanding design that holds immediate release mini tablets and places these in contact with the intestinal epithelium, where unidirectional drug release can occur. The expanding conformation limits movement of the IAD in the intestinal tract, thereby enabling drug release at a single focal point in the intestine. A pig model was selected to study the ability of the IAD to promote intestinal absorption of the peptide MEDI7219 formulated together with the permeation enhancer sodium caprate. We compared the IAD to intestinally administered enteric coated capsules and an intestinally administered solution. The IAD restricted movement of the immediate release tablets in the small intestine and histological evaluation of the mucosa indicated that high concentrations of sodium caprate were achieved. Despite significant effect of the permeation enhancer on the integrity of the intestinal epithelium, the bioavailability of MEDI7219 was of the same order of magnitude as that achieved with the solution and enteric coated capsule formulations (2.5-3.8%). The variability in plasma concentrations of MEDI7219 were however lower when delivered using the IAD as compared to the solution and enteric coated capsule formulations. This suggests that dosage forms that can limit intestinal dilution and control the position of drug release can be a way to reduce the absorptive variability of peptides delivered with permeation enhancers but do not offer significant benefits in terms of increasing bioavailability.

Using a digital spelling aid to improve writing in persons with post-stroke aphasia: An intervention study.

BACKGROUND: Intervention studies aimed to improve the written production of single words by persons with aphasia have yielded promising results and there is growing interest in interventions targeting text writing. The development of technical writing aids offers opportunities for persons with aphasia, and studies have shown that using them can have a positive impact on written output. AIMS: The aim was to investigate what impact training to use a computerised spell checker had on text writing in persons with aphasia. METHODS & PROCEDURES: The study had a multiple-baseline single-case experimental design replicated across six male Swedish participants with mild-to-moderate post-stroke aphasia. The participants received training twice a week during 8 weeks, learning how to use the spell checker. At baseline and before every session, the participants wrote two texts which were logged in a keystroke-logging tool. Dependent variables were continuously measured in the texts, and the participants performed tests of language function and answered questionnaires on reading and writing habits and health-related quality of life before and after the intervention. The participants were also interviewed about how they had experienced the training. The results were evaluated on individual and group level. RESULTS: The study showed that systematic individual training involving a spell checker was experienced as positive by the participants and that they all described their writing ability in more positive terms after the intervention. Evaluation showed statistically significant improvements on group level for the dependent variables of spelling accuracy, rated syntax, writing speed and proportion of unedited text during text writing when using the spell checker. The intervention also had a generalising effect on writing speed and editing during text writing without the spell checker and on spelling accuracy in a dictation test. The participants who had the greatest spelling problems were the ones who showed the most progress, but participants with only minor writing difficulties at baseline also improved. CONCLUSIONS & IMPLICATIONS: The study shows that a digital spelling aid constitutes effective support for people with aphasia and may also affect levels other than spelling. The training had a generalising positive effect on text writing and spelling in a test. Although writing difficulties is a persisting symptom in aphasia, it can be supported and improved through use of digital spelling aids. Hence, treatment of writing ability should always be included in the rehabilitation of people with aphasia. WHAT THIS PAPER ADDS: What is already known on this subject Use of a technical writing aid can have a positive impact on the written output of persons with aphasia. Using a digital spell checker may improve spelling as well as other levels of writing, but it has not been investigated using a keystroke-logging tool in combination with language-test scores and results from questionnaires. What this paper adds to existing knowledge Through analyses on both individual and group level, this study shows that a digital spelling aid constitutes effective support for people with aphasia and also affects levels other than spelling. The training had a generalising positive effect on text writing and spelling in a test. What are the potential or actual clinical implications of this work? Digital spelling support, which is a relatively simple and inexpensive technology, can support and improve text writing in persons with post-stroke aphasia.

In Vitro and In Vivo Evaluation of 3D Printed Capsules with Pressure Triggered Release Mechanism for Oral Peptide Delivery.

In this study a 3D printed capsule designed to break from the physiological pressures in the antropyloric region was evaluated for its ability to deliver the synthetic octapeptide octreotide in beagle dogs when co-formulated with the permeation enhancer sodium caprate. The pressure sensitive capsules were compared to traditional enteric coated hard gelatin capsules and enteric coated tablets. Paracetamol, which is completely absorbed in dogs, was included in the formulations and used as an absorption marker to give information about the in vivo performance of the dosage forms. The pressure sensitive capsules released drug in 50% of the dogs. In the cases where drug was released, there was no difference in octreotide bioavailability or Cmax compared to the enteric coated dosage forms. When comparing all dosage forms, a correlation was seen between paracetamol Cmax and octreotide bioavailability, suggesting that a high drug release rate may be beneficial for peptide absorption when delivered together with sodium caprate.

Airway Epithelial Lining Fluid and Plasma Pharmacokinetics of Inhaled Fluticasone Propionate and Salmeterol Xinafoate in Mechanically Ventilated Pigs.

Background: The lower respiratory tract of the landrace pig has close anatomical and physiological similarities with that of the human, and hence, for inhalation studies this species is well suited for biopharmaceutical research. Methods: The objective of this study was to evaluate pharmacokinetics in pigs following one dose of Diskus™ Seretide™ forte device, labeled 500/50 fluticasone propionate (FP) and salmeterol xinafoate (SX), respectively. The PreciseInhale™ (PI) instrument was used to actuate the inhaler for in vitro testing and aerosol dosing to pigs. In vitro, the aerosol was characterized with a cascade impactor with respect to mass median aerodynamic diameter, geometric standard deviation, and fine particle dose. In vivo, dry powder inhalation exposure was delivered as a short bolus dose, to anesthetized and mechanically ventilated landrace pigs. In addition to plasma PK, PK assessment of airway epithelial lining fluid (ELF) was used in this study. ELF of the depth of three to fourth airway generation of the right lung was accessed using standard bronchoscopy and a synthetic absorptive matrix. Results and Conclusions: Dry powder inhalation exposures with good consistency and well characterized aerosols to the pig lung were achieved by the use of the PreciseInhale™ instrument. Drug concentrations of ELF for both FP and SX were demonstrated to be four to five orders of magnitude higher than its corresponding systemic plasma drug concentrations. Clinical PK following inhalation of the same dose was used as benchmark, and the clinical study did demonstrate similar plasma PK profiles and drug exposures of both FP and SX as the current pig study. Two factors explain the close similarity of PK (1) similiar physiology between species and (2) the consistency of dosing to animals. To conclude, our study demonstrated the utility and translational potential of conducting PK studies in pigs in the development of inhaled pharmaceuticals.

Using a Discourse Task to Explore Semantic Ability in Persons With Cognitive Impairment.

This paper uses a discourse task to explore aspects of semantic production in persons with various degree of cognitive impairment and healthy controls. The purpose of the study was to test if an in-depth semantic analysis of a cognitive-linguistic challenging discourse task could differentiate persons with a cognitive decline from those with a stable cognitive impairment. Both quantitative measures of semantic ability, using tests of oral lexical retrieval, and qualitative analysis of a narrative were used to detect semantic difficulties. Besides group comparisons a classification experiment was performed to investigate if the discourse features could be used to improve classification of the participants who had a stable cognitive impairment from those who had cognitively declined. In sum, both types of assessment methods captured difficulties between the groups, but tests of oral lexical retrieval most successfully differentiated between the cognitively stable and the cognitively declined group. Discourse features improved classification accuracy and the best combination of features discriminated between participants with a stable cognitive impairment and those who had cognitively declined with an area under the curve (AUC) of 0.93.

Writing fluency in patients with low-grade glioma before and after surgery.

BACKGROUND: Low-grade glioma (LGG) is a type of brain tumour often situated in or near areas involved in language, sensory or motor functions. Depending on localization and tumour characteristics, language or cognitive impairments due to tumour growth and/or surgical resection are obvious risks. One task that may be at risk is writing, both because it requires intact language and memory function and because it is a very complex and cognitively demanding task. The most commonly reported language deficit in LGG patients is oral lexical-retrieval difficulties, and poor lexical retrieval would be expected to affect writing fluency. AIMS: To explore whether writing fluency is affected in LGG patients before and after surgery and whether it is related to performance on tasks of oral lexical retrieval. METHODS & PROCEDURES: Twenty consecutive patients with presumed LGG wrote a narrative and performed a copy task before undergoing surgery and at 3-month follow-up using keystroke-logging software. The same tasks were performed by a reference group (N = 31). The patients were also tested using the Boston Naming Test (BNT) and word-fluency tests before and after surgery. Writing fluency was compared between the patients and the reference group, and between the patients before and after surgery. Relationships between performance on tests of oral lexical retrieval and writing fluency were investigated both before and after surgery. OUTCOME & RESULTS: Different aspects of writing fluency were affected in the LGG patients both before and after surgery. However, when controlling for the effect of typing speed, the LGG group differed significantly from the reference group only in the proportion of pauses within words. After surgery, a significant decline was seen in production rate and typing speed in the narrative task, and a significant increase was seen in pauses before words. Strong positive relationships were found between oral lexical retrieval and writing fluency both before and after surgery. CONCLUSIONS & IMPLICATIONS: Although aspects of writing fluency were affected both before and after surgery, the results indicate that typing speed is an important factor behind the pre-surgery differences. However, the decline in overall productivity and the increase in pauses before words after surgery could be related to a lexical deficit. This is supported by the finding that oral lexical-retrieval scores were strongly correlated with writing fluency. However, further exploration is needed to identify the language and cognitive abilities affecting writing processes in LGG patients.

Pre-operative language ability in patients with presumed low-grade glioma.

In patients with low-grade glioma (LGG), language deficits are usually only found and investigated after surgery. Deficits may be present before surgery but to date, studies have yielded varying results regarding the extent of this problem and in what language domains deficits may occur. This study therefore aims to explore the language ability of patients who have recently received a presumptive diagnosis of low-grade glioma, and also to see whether they reported any changes in their language ability before receiving treatment. Twenty-three patients were tested using a comprehensive test battery that consisted of standard aphasia tests and tests of lexical retrieval and high-level language functions. The patients were also asked whether they had noticed any change in their use of language or ability to communicate. The test scores were compared to a matched reference group and to clinical norms. The presumed LGG group performed significantly worse than the reference group on two tests of lexical retrieval. Since five patients after surgery were discovered to have a high-grade glioma, a separate analysis excluding them were performed. These analyses revealed comparable results; however one test of word fluency was no longer significant. Individually, the majority exhibited normal or nearly normal language ability and only a few reported subjective changes in language or ability to communicate. This study shows that patients who have been diagnosed with LGG generally show mild or no language deficits on either objective or subjective assessment.

High-level language ability in healthy individuals and its relationship with verbal working memory.

The aims of the study were to investigate healthy subjects' performance on a clinical test of high-level language (HLL) and how it is related to demographic characteristics and verbal working memory (VWM). One hundred healthy subjects (20-79 years old) were assessed with the Swedish BeSS test (Laakso, Brunnegård, Hartelius, & Ahlsén, 2000) and two digit span tasks. Relationships between the demographic variables, VWM and BeSS were investigated both with bivariate correlations and multiple regression analysis. The results present the norms for BeSS. The correlations and multiple regression analysis show that demographic variables had limited influence on test performance. Measures of VWM were moderately related to total BeSS score and weakly to moderately correlated with five of the seven subtests. To conclude, education has an influence on the test as a whole but measures of VWM stood out as the most robust predictor of HLL.

Training conversation partners of persons with communication disorders related to Parkinson's disease--a protocol and a pilot study.

This paper reports on the adaptation of a training programme for conversation partners of persons with Parkinson's disease, and a protocol for assessment of possible changes in conversational interaction as a result of intervention. We present data from an explorative multiple case study with three individuals with Parkinson's disease and their spouses. Repeated analysis of natural conversational interaction and measures of the participants' perception of communication as well as measures of different cognitive abilities were obtained. The results show that the communication in all three dyads was affected by both speech and language problems and that the conversation training model and the assessment protocol may work well after minor adjustments. Influence of different aspects of cognition on communication is discussed.