Clinical and preclinical pulmonary disease in newly diagnosed rheumatoid arthritis: a two-year follow-up study.

OBJECTIVE: Pulmonary disease is a major cause of excess mortality among patients with rheumatoid arthritis (RA). Interstitial lung disease (ILD) is a feared complication, but the benefit of screening is unknown. The aim of this study was to assess the frequency of pulmonary disease, including ILD, in early RA. METHOD: Patients with newly diagnosed RA were recruited prospectively at a single centre and underwent systematic pulmonary function tests (PFTs) and computed tomography (CT) scans at inclusion and after two years. RESULTS: The study included 150 patients (mean age 57 years, 63% female; 59% current or former smokers). Of these, 136 underwent baseline PFTs and 137 CT. Mean forced expiratory volume in one second was 99% predicted and forced vital capacity 106%. Mean diffusing capacity of the lungs for carbon monoxide (DLCO) was 84% predicted. Frequently detected CT abnormalities were pulmonary nodules (42%), bronchiectasis (29%), and emphysema (20%). Two patients had clinically significant ILD and six had mild reticulation suggestive of preclinical ILD. No ILD progression was identified at two-year follow-up. Smoking was associated with DLCO<80% (p=0.004), combined hyperinflation and diffusion impairment (residual volume>120% and DLCO<80%) (p=0.004), and visual emphysema on CT (p<0.001). CONCLUSION: Emphysema and bronchiectasis were common, but most patients had mild disease with preserved lung function. Preclinical or clinical ILD was seen in a minority in this early phase of RA. These findings suggest symptom-based screening and primary intervention focusing on smoking cessation rather than screening for ILD at the time of RA diagnosis.

Does receptor balance matter? - Comparing the efficacies of the dual amylin and calcitonin receptor agonists cagrilintide and KBP-336 on metabolic parameters in preclinical models.

Cagrilintide is a novel long-acting amylin receptor agonist, which has shown a potent induction of weight loss. Interestingly, cagrilintide is a Dual Amylin and Calcitonin Receptor Agonist (DACRA) derived from an amylin backbone. Another class of long-acting DACRAs exists, namely the KBPs. These are salmon calcitonin-based and have shown preclinical potential; however, how and if they differentiate from amylin-derived molecules remain to be studied. Here, we compare cagrilintide to the DACRA KBP-336 with respect to receptor activation balance in vitro and using metabolic in vivo models. Peptide potencies were assessed using receptor-specific assays in vitro and in vivo. In vivo efficacies on body weight and glucose homeostasis were investigated head-to-head in high-fat diet (HFD) fed obese and T2D (ZDF) rat models. Both peptides activate the amylin and the calcitonin receptor in vitro and in vivo, with KBP-336 being more potent, and showing a CTR bias. KBP-336 and cagrilintide induced a potent and dose-dependent weight loss in HFD rats, with the highest dose of KBP-336 being superior to cagrilintide. In diabetic ZDF rats, DACRA treatment improved fasting blood glucose, HbA1c levels, and insulin action, with KBP-336 being superior to cagrilintide in improving glucose control. In summary, both KBP-336 and cagrilintide are DACRAs, however with KBP-336 being biased towards the CTR resulting in a different receptor activation balance. Interestingly, KBP-336 showed superior long-term efficacy on both weight loss and glucose control, supporting relevance of the receptor balance, and highlighting KBP-336 as a promising agent for the treatment of obesity and T2D.

Sintering temperature accuracy and its effect on translucent yttria-stabilized zirconia: Flexural strength, crystal structure, tetragonality and light transmission.

OBJECTIVES: A crucial step in the preparation of yttria-stabilized zirconia materials (YSZ) is the final sintering step. Sintering parameters affect phase composition, grain growth and porosity of the material which, in turn, influence both mechanical and optical properties. Discrepancies of + /- 5% are common between actual and displayed firing temperatures depending on sintering furnace brand and condition. The aim of this study was therefore to investigate how such sintering temperature deviations in dental furnaces compared to the recommended firing protocols affected certain material properties of different yttria-stabilized zirconia materials. METHODS: Disc-shaped specimens were made from four different translucent and high translucent YSZ-powders and analysed regarding crystal structure; unit cell volume for the c, t, and t' -phases along with the tetragonality for the t and t' phases. Biaxial flexure strength and the spectral transmittance through the ceramic specimens were also measured. RESULTS: Deviations of 5% from the sintering temperature recommended for YSZ materials with different yttria content influenced material properties such as light transmittance, flexural strength, crystal phase fractions, tetragonality, and grain growth. Too low temperature resulted in decreased strength for some of the translucent zirconia materials, while others where less affected. Light transmittance varied depending on several factors such as grain size, crystal phase fractions and binder content in the start material prior to pre-sintering. SIGNIFICANCE: The use of high quality, wellcalibrated furnaces is crucial when sintering YSZ materials to avoid unwanted material changes. CONCLUSIONS: Deviations of 5% from the sintering temperature recommended for YSZ materials with different yttria content influence material properties such as light transmittance, flexural strength, crystal phase fractions, tetragonality, and grain growth. Too low temperature results in decreased strength for some translucent zirconia materials, while others are less affected. Light transmittance varies depending on several factors such as grain size, crystal phase fractions and binder content in the start material prior to pre-sintering. Consequently, the use of high quality, well-calibrated furnaces is crucial when sintering YSZ materials to avoid unwanted material changes.

Combined dual energy and iterative metal artefact reduction for PET/CT in head and neck cancer.

Metal artefacts in PET/CT images hamper diagnostic accuracy in head and neck cancer (HNC). The aim of this study is to characterise the clinical effects of metal artefacts on PET/CT in HNC and to inform decision-making concerning implementation of MAR techniques. We study a combined dual energy CT and inpainting-based metal artefact reduction (DECT-I-MAR) technique for PET/CT in three settings: (A) A dental phantom with a removable amalgam-filled tooth to evaluate the PET error in comparison to a known reference. (B) PET-positive patients with metallic implants to demonstrate the relationship between CT metal artefacts and PET error. (C) Metabolic tumour volumes delineated in PET-positive patients with metal implants to evaluate the clinical impact. In (A) DECT-I-MAR reduced the PET error significantly. In (B) we demonstrate an increasing PET error with increasing CT artefact severity in patients. In (C) it is shown that the presence of artefacts in the same axial slices as the tumour significantly decreases biomarker stability and increase delineation variability. This work shows the practical feasibility of DECT-I-MAR-based PET/CT imaging, and indicates a positive clinical impact of using the technique routinely for HNC patients. The impact of CT artefacts on PET is considerable, especially in workflows where quantitative PET biomarkers and tumour volumes are used. In such cases, and for patients with tumours in proximity of metals, we recommend that a MAR technique for PET/CT is employed.

A changed life: the life experiences of patients with psoriasis receiving biological treatment.

BACKGROUND: Psoriasis has a large negative impact on quality of life and is associated with both depression and anxiety. The introduction of biologics has improved treatment outcomes, but the ways in which patients perceive these improvements are not well characterized. OBJECTIVES: To investigate the everyday life experiences of patients with psoriasis receiving biological treatment in order to gain an understanding of their needs and to improve the quality of care. METHODS: A qualitative narrative methodology was utilized. In total 48 h of participant observations during consultations, and 15 semistructured interviews, were conducted with patients receiving biological treatment. Data were analysed according to Ricoeur's theory of interpretation. RESULTS: Receiving biological treatment was experienced as a turning point, with a significant impact on physical, psychological and emotional levels. However, psychological consequences, such as isolation and social withdrawal, seemed to be a part of the patient's identity; the negative perceptions of psoriasis left marks behind that affected the patient's self-image. Perceived fear of discontinuation of the biological treatment resulted in insecurity, and patients were reluctant to initiate discussion about these concerns with healthcare professionals. CONCLUSIONS: Providing assistance when patients enter the transition of receiving biological treatment may be important. Patients' fear of biological treatment being discontinued is an ongoing issue that healthcare professionals could address.

Use of topical antipsoriatic drugs in Denmark: a nationwide drug utilization study.

BACKGROUND: The reported real-life use of prescribed topical antipsoriatic drugs is conflicting and based on heterogeneous data sources. OBJECTIVES: To describe the utilization of topical antipsoriatic drugs among patients with psoriasis in Denmark. METHODS: A drug utilization study was performed based on nationwide Danish health registry data. We identified patients who received a first-time hospital diagnosis of psoriasis and redeemed at least one topical drug prescription in the period 2005-2015 (n = 7743). Patients were followed for 3 years from the time of diagnosis. Use of topical and systemic antipsoriatic drugs was described, specified by the type of treatment. RESULTS: The total use of topical drugs was divided between corticosteroids with calcipotriol (31%), calcipotriol (6·5%), very potent corticosteroids (24%), potent corticosteroids (30%), moderate corticosteroids (7·2%) and corticosteroids with antimicrobials (1·6%). There was a 19% reduction in the overall use of topical drugs during the study period. Use increased around the time of diagnosis and the majority of patients redeemed more than two packages of topical drugs during the first year after being diagnosed. Regional differences in patients' use of topical drugs varied considerably. The distribution of use of topical drugs was uneven, with a minority of all patients (25%) using 70% of the total amount of topical treatment. There was a 70% increase in the use of methotrexate over the study period. Biologics were used by up to 6%. CONCLUSIONS: The study provides further evidence that the use of topical antipsoriatic drugs shows considerable heterogeneity over time and regional practices, and differences between patients.

Safety Assessment of PEG-150 Pentaerythrityl Tetrastearate as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of polyethylene glycol (PEG)-150 pentaerythrityl tetrastearate, which functions as a viscosity-increasing agent-aqueous in cosmetic products and is being used at concentrations up to 5%. Given the chemical structure (large molecule), skin penetration is not likely. The available toxicity data and the low ingredient use concentrations suggest that systemic toxicity would not be likely even if percutaneous absorption were to occur. Additionally, the negative human repeated insult patch test data on the undiluted ingredient were deemed sufficient for evaluating skin irritation and sensitization potential. The Panel concluded that PEG-150 pentaerythrityl tetrastearate is safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Safety Assessment of Tocopherols and Tocotrienols as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 14 tocopherols and tocotrienols and concluded these ingredients are safe as used in cosmetics. The tocopherols are reported to function in cosmetics as antioxidants or skin-conditioning agents; in contrast, tocotrienols are not reported to function as an antioxidants in cosmetics but as a light stabilizer, oral care agent, or skin-conditioning agent. The Panel reviewed the new and existing animal and clinical data to determine the safety of these ingredients and found it appropriate to extrapolate the existing information to conclude on the safety of all the tocopherols and tocotrienols.

Safety Assessment of Magnesium Sulfate as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of magnesium sulfate, which functions as a bulking agent in cosmetic products and is reportedly used at concentrations up to 11% and 25% in leave-on and rinse-off products, respectively. The Panel noted that the history of safe medical use of magnesium sulfate provides further confidence that there are no significant toxicity concerns relating to systemic exposure to this ingredient after cosmetic product application. Furthermore, the extensive clinical experience of the Panel, including the results of numerous patch tests, indicates that magnesium salts do not have the potential to induce sensitization. The Panel also noted that results were negative for 50% magnesium sulfate in a mouse skin irritation study and in an in vitro sensitization assay. The Panel concluded that magnesium sulfate is safe in cosmetics in the present practices of use and concentration described in the safety assessment.

Safety Assessment of Hydrolyzed Wheat Protein and Hydrolyzed Wheat Gluten as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the product use, formulation, and safety data on hydrolyzed wheat protein and hydrolyzed wheat gluten, which function as skin- and hair-conditioning agents. The Panel determined that data from clinical and laboratory studies were sufficient to demonstrate that these ingredients will not elicit type 1 immediate hypersensitivity reactions in sensitized individuals and will not induce sensitization when the polypeptide lengths of the hydrolysates do not exceed 30 amino acids. The Panel concluded that hydrolyzed wheat gluten and hydrolyzed wheat protein are safe for use in cosmetics when formulated to restrict peptides to an average molecular weight of 3,500 Da or less.

Safety Assessment of Alkyl Betaines as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 11 alkyl betaines as used in cosmetics. These ingredients are reported to function as hair and skin conditioning agents, antistatic agents, surfactants-cleansing agents, and viscosity-increasing agents in cosmetic products. Although there are data gaps, the shared chemical core structure, similar functions and concentrations of use in cosmetics, and the expected similarities in physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group. The Panel concluded alkyl betaines were safe as cosmetic ingredients in the present practices of use and concentration, when formulated to be nonirritating.

Safety Assessment of Polyether Lanolins as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 39 polyether lanolin ingredients as used in cosmetics. These ingredients function mostly as hair conditioning agents, skin conditioning agent-emollients, and surfactant-emulsifying agents. The Panel reviewed available animal and clinical data, from previous CIR safety assessments of related ingredients and components. The similar structure, properties, functions, and uses of these ingredients enabled grouping them and using the available toxicological data to assess the safety of the entire group. The Panel concluded that these polyether lanolin ingredients are safe in the practices of use and concentration as given in this safety assessment.

A smartphone application supporting patients with psoriasis improves adherence to topical treatment: a randomized controlled trial.

BACKGROUND: Adherence to topical psoriasis treatments is low, which leads to unsatisfactory treatment results. Smartphone applications (apps) for patient support exist but their potential to improve adherence has not been systematically evaluated. OBJECTIVES: To evaluate whether a study-specific app improves adherence and reduces psoriasis symptoms compared with standard treatment. METHODS: We conducted a randomized controlled trial (RCT, clinicaltrials.gov registration: NCT02858713). Patients received once-daily medication [calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam] and were randomized to no app (n = 66) or app intervention (n = 68) groups. In total, 122 patients (91%) completed the 22-week follow-up. The primary outcome was adherence, which was defined as medication applied ≥ 80% of days during the treatment period and assessed by a chip integrated into the medication dispenser. Secondary outcomes were psoriasis severity measured by the Lattice System Physician's Global Assessment (LS-PGA) and quality of life, measured using the Dermatology Life Quality Index (DLQI) at all visits. RESULTS: Intention-to-treat analyses using regression was performed. More patients in the intervention group were adherent to Cal/BD cutaneous foam than those in the nonintervention group at week 4 (65% vs. 38%, P = 0·004). The intervention group showed a greater LS-PGA reduction than the nonintervention group at week 4 (mean 1·86 vs. 1·46, P = 0·047). A similar effect was seen at weeks 8 and 26, although it did not reach statistical significance. CONCLUSIONS: This RCT demonstrates that the app improved short-term adherence to Cal/BD cutaneous foam treatment and psoriasis severity.

Safety Assessment of Plant-Derived Fatty Acid Oils.

The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 244 plant-derived fatty acid oils as used in cosmetics. Oils are used in a wide variety of cosmetic products for their skin conditioning, occlusive, emollient, and moisturizing properties. Since many of these oils are edible, and their systemic toxicity potential is low, the review focused on potential dermal effects. The Panel concluded that the 244 plant-derived fatty acid oils are safe as used in cosmetics.

Safety Assessment of Benzyl Alcohol, Benzoic Acid and its Salts, and Benzyl Benzoate.

Benzyl alcohol, benzoic acid and its salts, and benzyl benzoate function mostly as fragrance ingredients/preservatives in cosmetic products. The Cosmetic Ingredient Review Expert Panel previously established concentration limits for benzyl alcohol, benzoic acid, and sodium benzoate in cosmetics and determined that the available data were insufficient to support the safety of these ingredients during inhalation exposure. After reviewing newly available data, it was concluded that benzyl alcohol, benzoic acid and its salts, and benzyl benzoate are safe in the present practices of use and concentration described in this safety assessment.

Safety Assessment of Dimethiconol and Its Esters and Reaction Products as Used in Cosmetics.

Dimethiconol and its esters and reaction products are used in cosmetics as either skin-conditioning agents or hair-conditioning agents. The Cosmetic Ingredient Review (CIR) Expert Panel reviewed relevant data and concluded that these ingredients are safe in the present practices of use and concentration described in this safety assessment. While there is an absence of data on reproductive and developmental toxicity and limited tumorigenicity and toxicokinetics data, the Panel reasoned that these ingredients would not be absorbed through the skin, obviating concern over potential reproductive and developmental toxicity or carcinogenicity.

Safety Assessment of Cross-Linked Alkyl Acrylates as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of cross-linked alkyl acrylates as used in cosmetics. The 23 cross-linked alkyl acrylates included in this safety assessment are reported to function as absorbents, film formers, emulsion stabilizers, viscosity increasing agents, suspending agents, binders, and/or skin-conditioning agents. The Panel reviewed available animal and clinical data, as well as information from previous CIR reports on monomer components. Because data were not available for the individual ingredients, and because residual monomer may be present, the Panel extrapolated from previous reports to support safety. The Panel concluded that cross-linked alkyl acrylates are safe in the present practices of use and concentration, provided that they are not polymerized in benzene. For those ingredients polymerized in benzene, the data available were insufficient to make a determination of safety. A risk assessment for the amount of benzene present would be needed.

Safety Assessment of Diethanolamine and Its Salts as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of diethanolamine and its salts as used in cosmetics. Diethanolamine functions as a pH adjuster; the 16 salts included in this rereview reportedly function as surfactants, emulsifying agents, viscosity increasing agents, hair or skin conditioning agents, foam boosters, or antistatic agents. The Panel reviewed available animal and clinical data, as well as information from previous CIR reports. Since data were not available for each individual ingredient, and since the salts dissociate freely in water, the Panel extrapolated from previous reports to support safety. The Panel concluded that diethanolamine and its salts are safe for use when formulated to be nonirritating. These ingredients should not be used in cosmetic products in which N-nitroso compounds can be formed.