Physical activity with person-centered guidance supported by a digital platform or with telephone follow-up for persons with chronic widespread pain: Health economic considerations along a randomized controlled trial.

OBJECTIVES: The aim was to investigate the resource use and costs associated with the co-creation of a physical activity plan for persons with chronic widespread pain (CWP) followed by support through a digital platform, compared to telephone follow-up. METHODS: In this 12-month cost comparison study following up results after a randomized controlled trial, individuals with CWP, aged 20-65 years, were recruited at primary healthcare units in Western Sweden. All participants developed a person-centered health-enhancing physical activity plan together with a physiotherapist. Participants were then randomized to either an intervention group (n = 69) who had a follow-up visit after 2 weeks and was thereafter supported through a digital platform, or an active control group (n = 70) that was followed up through one phone call after a month. Costs to the health system were salary costs for the time recorded by physiotherapists when delivering the interventions. RESULTS: The reported time per person (2.8 h during the 12 months) corresponded to costs of SEK 958 (range: 746-1,517) for the initial visits and follow-up (both study groups), and an additional 2.5 h (corresponding to a mean SEK 833; range: 636-1,257) for the time spent in the digital platform to support the intervention group. CONCLUSION: After co-creation of a physical activity plan, it was more costly to support persons through a digital platform, compared to telephone follow-up.

Nanostructures of etherified arabinoxylans and the effect of arabinose content on material properties.

To further our understanding of a thermoplastic arabinoxylan (AX) material obtained through an oxidation-reduction-etherification pathway, the role of the initial arabinose:xylose ratio on the material properties was investigated. Compression molded films with one molar substitution of butyl glycidyl ether (BGE) showed markedly different tensile behaviors. Films made from low arabinose AX were less ductile, while those made from high arabinose AX exhibited elastomer-like behaviors. X-ray scattering confirmed the presence of nanostructure formation resulting in nano-domains rich in either AX or BGE, from side chain grafting. The scattering data showed variations in the presence of ordered structures, nano-domain sizes and their temperature response between AX with different arabinose contents. In dynamic mechanical testing, three transitions were observed at approximately -90 °C, -50 °C and 80 °C, with a correlation between samples with more structured nano-domains and those with higher onset transition temperatures and lower storage modulus decrease. The mechanical properties of the final thermoplastic AX material can therefore be tuned by controlling the composition of the starting material.

Towards personalized drug delivery via semi-solid extrusion: Exploring poly(vinyl alcohol-co-vinyl acetate) copolymers for hydrochlorothiazide-loaded films.

The increasing need for personalized drug delivery requires developing systems with tailorable properties. The copolymer poly(vinyl alcohol-co-vinyl acetate) (PVA/PVAc) allows for adjusting the monomer ratio. This study explored the effect of vinyl alcohol (VA) and vinyl acetate (VAc) monomer ratio on the properties of hydrochlorothiazide (HCT) films. Five copolymers with different VA/VAc ratios were selected and characterized. Semi-solid extrusion was employed as a method for the preparation of HCT-PVA/PVAc films to address the challenges of HCT´s low water solubility, high melting point, and low permeability. All copolymers were suitable for semi-solid extrusion, however, the mechanical properties of films with higher VA proportions were more suitable. The drug was found to be homogeneously distributed on a micrometer level throughout the prepared films. It was found that using different monomer ratios in the copolymer allows for drug release tuning - higher VA proportions showed an increased rate of drug release. Experiments through HT29-MTX cell monolayers revealed differences in HCT permeability between the different formulations. In addition, no cytotoxicity was observed for the tested formulations. The results highlight the effect of monomer ratio on film properties, providing valuable guidance for formulators in selecting PVA/PVAc copolymers for achieving desired high-quality films. In addition, varying the monomer ratio allows tuning of the film properties, and can be applied for personalization, with flexible-dose adjustment and design of appealing shapes of the pharmaceutics, not least attractive for pediatric drug delivery.

Anion-Specific Adsorption of Carboxymethyl Cellulose on Cellulose.

Integration of fiber modification step with a modern pulp mill is a resource efficient way to produce functional fibers. Motivated by the need to integrate polymer adsorption with the current pulping system, anion-specific effects in carboxymethylcellulose (CMC) adsorption have been studied. The QCM-D adsorption experiments revealed that CMC adsorption to the cellulose model surface is prone to anion-specific effects. A correlation was observed between the adsorbed CMC and the degree of hydration of the co-ions present in the magnesium salts. The presence of a chaotropic co-ion such as nitrate increased the adsorption of CMC on cellulose compared to the presence of the kosmotropic sulfate co-ion. However, anion-specificity was not significant in the case of salts containing zinc cations. The hydration of anions determines the distribution of the ions at the interface. Chaotropic ions, such as nitrates, are likely to be distributed near the chaotropic cellulose surface, causing changes in the ordering of water molecules and resulting in greater entropy gain once released from the surface, thus increasing CMC adsorption.

Multiscale X-ray imaging and characterisation of pharmaceutical dosage forms.

A correlative, multiscale imaging methodology for visualising and quantifying the morphology of solid dosage forms by combining ptychographic X-ray computed nanotomography (PXCT) and scanning small- and wide-angle X-ray scattering (S/WAXS) is presented. The methodology presents a workflow for multiscale analysis, where structures are characterised from the nanometre to millimetre regime. Here, the method is demonstrated by characterising a hot-melt extruded, partly crystalline, solid dispersion of carbamazepine in ethyl cellulose. Characterisation of the morphology and solid-state phase of the drug in solid dosage forms is central as this affects the performance of the final formulation. The 3D morphology was visualised at a resolution of 80 nm over an extended volume through PXCT, revealing an oriented structure of crystalline drug domains aligned in the direction of extrusion. Scanning S/WAXS showed that the nanostructure is similar over the cross section of the extruded filament, with minor radial changes in domain sizes and degree of orientation. The polymorphic forms of carbamazepine were qualified with WAXS, showing a heterogeneous distribution of the metastable forms I and II. This demonstrates the methodology for multiscale structural characterization and imaging to enable a better understanding of the relationships between morphology, performance, and processing conditions of solid dosage forms.

Molecular Dynamics Simulations of Cellulose and Dialcohol Cellulose under Dry and Moist Conditions.

The development of wood-based thermoplastic polymers that can replace synthetic plastics is of high environmental importance, and previous studies have indicated that cellulose-rich fiber containing dialcohol cellulose (ring-opened cellulose) is a very promising candidate material. In this study, molecular dynamics simulations, complemented with experiments, were used to investigate how and why the degree of ring opening influences the properties of dialcohol cellulose, and how temperature and presence of water affect the material properties. Mechanical tensile properties, diffusion/mobility-related properties, densities, glass-transition temperatures, potential energies, hydrogen bonds, and free volumes were simulated for amorphous cellulosic materials with 0-100% ring opening, at ambient and high (150 °C) temperatures, with and without water. The simulations showed that the impact of ring openings, with respect to providing molecular mobility, was higher at high temperatures. This was also observed experimentally. Hence, the ring opening had the strongest beneficial effect on "processability" (reduced stiffness and strength) above the glass-transition temperature and in wet conditions. It also had the effect of lowering the glass-transition temperature. The results here showed that molecular dynamics is a valuable tool in the development of wood-based materials with optimal thermoplastic properties.

Digital physiotherapy assessment vs conventional face-to-face physiotherapy assessment of patients with musculoskeletal disorders: A systematic review.

BACKGROUND: This systematic review aimed to assess the certainty of evidence for digital versus conventional, face-to-face physiotherapy assessment of musculoskeletal disorders, concerning validity, reliability, feasibility, patient satisfaction, physiotherapist satisfaction, adverse events, clinical management, and cost-effectiveness. METHODS: Eligibility criteria: Original studies comparing digital physiotherapy assessment with face-to-face physiotherapy assessment of musculoskeletal disorders. Systematic database searches were performed in May 2021, and updated in May 2022, in Medline, Cochrane Library, Cinahl, AMED, and PEDro. Risk of bias and applicability of the included studies were appraised using the Quality Assessment of Diagnostic Accuracy Studies-2 tool and the Quality Appraisal of Reliability Studies tool. Included studies were synthesised narratively. Certainty of evidence was evaluated for each assessment component using GRADE. RESULTS: Ten repeated-measures studies were included, involving 193 participants aged 23-62 years. Reported validity of digital physiotherapy assessment ranged from moderate/acceptable to almost perfect/excellent for clinical tests, range of motion, patient-reported outcome measures (PROMs), pain, neck posture, and management decisions. Reported validity for assessing spinal posture varied and was for clinical observations unacceptably low. Reported validity and reliability for digital diagnosis ranged from moderate to almost perfect for exact+similar agreement, but was considerably lower when constrained to exact agreement. Reported reliability was excellent for digital assessment of clinical tests, range of motion, pain, neck posture, and PROMs. Certainty of evidence varied from very low to high, with PROMs and pain assessment obtaining the highest certainty. Patients were satisfied with their digital assessment, but did not perceive it as good as face-to-face assessment. DISCUSSION: Evidence ranging from very low to high certainty suggests that validity and reliability of digital physiotherapy assessments are acceptable to excellent for several assessment components. Digital physiotherapy assessment may be a viable alternative to face-to-face assessment for patients who are likely to benefit from the accessibility and convenience of remote access. TRIAL REGISTRATION: The review was registered in the PROSPERO database, CRD42021277624.

Experimental and simulated distribution and interaction of water in cellulose esters with alkyl chain substitutions.

This study investigated the effect of the average length of substituted side chains in different cellulose esters on water sorption and the water association mechanism. For this purpose, a set of esters with a similar total degree of substitution was selected: cellulose acetate, cellulose acetate propionate, and cellulose acetate butyrate. Dynamic vapor sorption was used to determine the effect of the side chain length on sorption, desorption, and the occurrence of water clustering. Since water association in the structure was of interest, molecular dynamics simulations were performed on cellulose acetate and cellulose acetate propionate. This study showed that cellulose acetate appears to be water-sensitive and experiences hysteresis upon water sorption, which was attributed to structural changes. The simulations also showed that water is screened out by the side chains and forms intermolecular hydrogen bonds, primarily to the carbonyl oxygen rather than the residual hydroxyl groups.

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.

Person-centred health plans for physical activity in persons with chronic widespread pain (CWP) - a retrospective descriptive review.

PURPOSE: Physical activity is recommended as first-choice treatment in chronic pain conditions. The aim was to describe the content and perceptions of person-centred health plans, and to evaluate patients' implementation of the health plan in their everyday life. MATERIALS AND METHODS: A descriptive retrospective review was conducted of person-centred health plans to support physical activity in 133 participants. Quantitative content analysis was used to analyse the content of the health plans. Questionnaires on physical activity and on implementation and perception of the health plans, and a test of physical capacity were administered. RESULTS: Participants' goals were found to be related to physical function (n = 118), general health (n = 90), activity and participation (n = 80) and symptoms (n = 35). Participants identified personal (n = 174), social (n = 69) and material resources (n = 36). They identified fears and obstacles related to health issues (n = 95), difficulties getting it done (n = 41), competing priorities (n = 19) and contextual factors (n = 12). Participants identified need for external support (n = 110). Participants' level of physical activity and physical capacity increased significantly during the first 6 months of the study. CONCLUSION: The person-centred approach seems helpful in enhancing motivation to achieve set goals and strengthen self-efficacy in physical activity also supported by increased physical activity and physical capacity. Implications for rehabilitationA person-centred approach can be helpful to enhance motivation to achieve set goals and self-efficacy to manage symptoms when engaging in physical activity.Shared documentation of a personal health plan helps to visualize resources to promote regular physical activity as well as alternative ways to reach set goals.The co-created health-plan captures the participant's goals, resources, fears and need of support, helps the participant to overcome challenges, and supports the participant to be physically active.

Mass Transport of Lignin in Confined Pores.

A crucial step in the chemical delignification of wood is the transport of lignin fragments into free liquor; this step is believed to be the rate-limiting step. This study has investigated the diffusion of kraft lignin molecules through model cellulose membranes of various pore sizes (1-200 nm) by diffusion cells, where the lignin molecules diffuse from donor to acceptor cells through a membrane, where diffusion rate increases by pore size. UV-vis spectra of the donor solutions showed greater absorbance at higher wavelengths (~450 nm), which was probably induced by scattering due to presence of large molecules/clusters, while acceptor samples passed through small pore membranes did not. The UV-vis spectra of acceptor solutions show a characteristic peak at around 350 nm, which corresponds to ionized conjugated molecules: indicating that a chemical fractionation has occurred. Size exclusion chromatography (SEC) showed a difference in the molecular weight (Mw) distribution between lignin from the donor and acceptor chambers. The results show that small pore sizes enable the diffusion of small individual molecules and hinder the transport of large lignin molecules or possible lignin clusters. This study provides more detail in understanding the mass transfer events of pulping processes.

Experience of co-creation of a health plan and support for sustainable physical activity among people with chronic widespread pain: a qualitative interview study in Sweden.

OBJECTIVES: The aim of this study was to gain deeper knowledge about how people with chronic widespread pain (CWP) experience the co-creation of a health plan for sustainable physical activity, working in partnership with a physiotherapist, supported by a digital platform. DESIGN: Qualitative semistructured in-depth individual interviews were analysed with qualitative content analysis. SETTING: Five primary healthcare centres in western Sweden. PARTICIPANTS: The interviewees comprised 19 individuals with CWP who had previously participated in a person-centred intervention involving co-creation of a health plan and support via a digital platform. The interviews were carried out from late 2019 to spring 2020, 1-6 months after the respondents' final follow-up. RESULTS: The analysis resulted in an overarching theme; hope for physical activity that actually works, illustrating the experience of taking part in co-creating a reasonable health plan, based on the respondents' own goals and interests with the potential to actually work. This theme was based on two categories: a plan tailored for me and a frame for participation and accessibility to help fulfil the plan. The digital platform provided a way to participate and an assurance that there was someone there for them if necessary. CONCLUSIONS: The co-creation of a health plan nurtured hope of having developed a manageable plan for physical activity that could lead to improved future health and well-being. Digital support may serve as a valuable complement in order to sustain and adjust the planned physical activity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03434899.

Screening of hydrogen bonds in modified cellulose acetates with alkyl chain substitutions.

This study aimed to elucidate how the glass transition temperature and water interactions in cellulose esters are affected by the structures of their side chains. Cellulose acetate, cellulose acetate propionate and cellulose acetate butyrate with three fractions of butyrates, all having the same total degree of substitution, were selected, and hot-melt pressed. The degree of substitution, structural properties, and water interactions were determined. The Hansen solubility parameters were calculated and showed that the dispersive energy dominates the total cohesive energy, followed by hydrogen bonding and polar energy. The glass transition temperature (Tg) decreased, counter-intuitively, with an increased total cohesive energy, which can be explained by the short-range hydrogen bonds being screened by the increased length of the substituents. The solubility and penetration of water in the cellulose esters decreased with increased side chain length, although the hydrogen bonding energies for all the esters were approximately constant.

Side chains affect the melt processing and stretchability of arabinoxylan biomass-based thermoplastic films.

Hydrophobization of hemicellulose causes melt processing and makes them stretchable thermoplastics. Understanding how native and/or appended side chains in various hemicelluloses after chemical modification affect melt processing and material properties can help in the development of products for film packaging and substrates for stretchable electronics applications. Herein, we describe a one-step and two-step strategy for the fabrication of flexible and stretchable thermoplastics prepared by compression molding of two structurally different arabinoxylans (AX). For one-step synthesis, the n-butyl glycidyl ether epoxide ring was opened to the hydroxyl group, resulting in the introduction of alkoxide side chains. The first step in the two-step synthesis was periodate oxidation. Because the melt processability for AXs having low arabinose to xylose ratio (araf/xylp<0.5) have been limited, two structurally distinct AXs extracted from wheat bran (AXWB, araf/xylp = 3/4) and barley husk (AXBH, araf/xylp = 1/4) were used to investigate the effect of araf/xylp and hydrophobization on the melt processability and properties of the final material. Melt compression processability was achieved in AXBH derived samples. DSC and DMA confirmed that the thermoplastics derived from AXWB and AXBH had dual and single glass transition (Tg) characteristics, respectively, but the thermoplastics derived from AXBH had lower stretchability (maximum 160%) compared to the AXWB samples (maximum 300%). Higher araf/xylp values, and thus longer alkoxide side chains in AXWB-derived thermoplastics, explain the stretchability differences.

Calcium Ion-Induced Structural Changes in Carboxymethylcellulose Solutions and Their Effects on Adsorption on Cellulose Surfaces.

The adsorption of carboxymethylcellulose (CMC) on cellulose surfaces is one of the most studied examples of the adsorption of an anionic polyelectrolyte on a like-charged surface. It has been suggested that divalent ions can act as a bridge between CMC chains and the surface of cellulose and enhance the CMC adsorption: they can, however, also alter the structure of CMCs in the solution. In previous investigations, the influence of cations on solution properties has been largely overlooked. This study investigates the effect of Ca2+ ions on the properties of CMC solutions as well as the influence on cellulose nanofibers (CNFs), which was studied by dynamic light scattering and correlated with the adsorption of CMC on a cellulose surface probed using QCM-D. The presence of Ca2+ facilitated the multichain association of CMC chains and increased the hydrodynamic diameter. This suggests that the adsorption of CMCs at high concentrations of CaCl2 is governed mainly by changes in solution properties rather than by changes in the cellulose surface. Furthermore, an entropy-driven mechanism has been suggested for the adsorption of CMC on cellulose. By comparing the adsorption of CMC from H2O and D2O, it was found that the release of water from the cellulose surface is driving the adsorption of CMC.

Fundamental aspects of the non-covalent modification of cellulose via polymer adsorption.

The increasing need for new material applications based on cellulose demands increased functional diversity and thus new functionalisation/modification approaches. The non-covalent modification of cellulose fibres via the adsorption of functional polymers has emerged as a promising route for tailoring the properties of material. This review focuses on fundamental aspects of polymer adsorption on cellulose surfaces, where the adsorption of polyelectrolytes and non-polyelectrolytes are treated separately. Adsorption studies on model surfaces as well as cellulose macro-fibres are reviewed. A correlation of the adsorption findings with the Scheutjens-Fleer polymer adsorption theory is provided, allowing the fundamentals behind the polymer adsorption phenomenon and its context in utilization of cellulose fibres to be understood.

Scattering studies of the size and structure of cellulose dissolved in aqueous hydroxide base solvents.

Combining NaOH with other hydroxide bases with superior dissolution properties can be a means of improving dissolution of cellulose. However, this raises questions about how the size and structure of cellulose vary when dissolved in different hydroxide bases. Here, cellulose in aqueous solutions of NaOH, Tetramethylammonium hydroxide (TMAH), Benzyltrimethylammonium hydroxide (Triton B) and previously studied equimolar solutions of NaOH/TMAH and NaOH/Triton B were investigated using small angle X-ray scattering, static and dynamic light scattering. The results show that cellulose in NaOH(aq) is largely aggregated and that the more hydrophobic TMAH and Triton are capable of molecularly dissolving cellulose into worm-like conformations, stiffer than in NaOH. The dissolution properties of mixtures are highly dependent on the compatibility of the individual bases; in line with previous observations of the properties of the solutions which now could be correlated to the structure of the cellulose on a nano- and microscale.

Polymers in pharmaceutical additive manufacturing: A balancing act between printability and product performance.

Materials and manufacturing processes share a common purpose of enabling the pharmaceutical product to perform as intended. This review on the role of polymeric materials in additive manufacturing of oral dosage forms, focuses on the interface between the polymer and key stages of the additive manufacturing process, which determine printability. By systematically clarifying and comparing polymer functional roles and properties for a variety of AM technologies, together with current and emerging techniques to characterize these properties, suggestions are provided to stimulate the use of readily available and sometimes underutilized pharmaceutical polymers in additive manufacturing. We point to emerging characterization techniques and digital tools, which can be harnessed to manage existing trade-offs between the role of polymers in printer compatibility versus product performance. In a rapidly evolving technological space, this serves to trigger the continued development of 3D printers to suit a broader variety of polymers for widespread applications of pharmaceutical additive manufacturing.

Influence of Drug Load on the Printability and Solid-State Properties of 3D-Printed Naproxen-Based Amorphous Solid Dispersion.

Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon® VA 64 at 10-30% w/w drug load. The extrudates (filaments) were characterised using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). It was confirmed that an amorphous solid dispersion was formed. A temperature profile was developed based on the results from TGA, DSC, and DMA and temperatures used for 3D printing were selected from the profile. The 3D-printed tablets were characterised using DSC, X-ray computer microtomography (XµCT), and X-ray powder diffraction (XRPD). From the DSC and XRPD analysis, it was found that the drug in the 3D-printed tablets (20 and 30% NAP) was amorphous and remained amorphous after 23 weeks of storage (room temperature (RT), 37% relative humidity (RH)). This shows that adjusting the drug ratio can modulate the brittleness and improve printability without compromising the physical stability of the amorphous solid dispersion.

Hydrophobization of arabinoxylan with n-butyl glycidyl ether yields stretchable thermoplastic materials.

Hemicelluloses are regarded as one of the first candidates for the development of value-added materials due to their renewability, abundance, and functionality. However, because most hemicelluloses are brittle, they can only be processed as a solution and cannot be processed using industrial melt-based polymer processing techniques. In this study, arabinoxylan (AX) was hydrophobized by incorporating butyl glycidyl ether (BuGE) into the hydroxyl groups through the opening of the BuGE epoxide ring, yielding alkoxy alcohols with terminal ethers. The formed BuGE derivatives were melt processable and can be manufactured into stretchable thermoplastic films through compression molding, which has never been done before with hemicellulose modified in a single step. The structural and thermomechanical properties of the one-step synthesis approach were compared to those of a two-step synthesis with a pre-activation step to demonstrate its robustness. The strain at break for the one-step synthesized AX thermoplastic with 3 mol of BuGE is ≈200%. These findings suggest that thermoplastic polymers can be composited with hemicelluloses or that thermoplastic polymers made entirely of hemicelluloses can be designed as packaging and stretchable electronics supports.