Relationship between Patient Preferences, Attitudes to Treatment, Adherence, and Quality of Life in New Users of Teriflunomide.

Background: A poor patient adherence often limits the real-world effectiveness of an oral disease-modifying therapy (DMT) for multiple sclerosis (MS). In the present study, we aimed to map patient preferences, attitudes toward treatment, and quality of life to identify the predictors of non-adherence to teriflunomide. Methods: This was a single-arm, non-interventional, multicenter study (Czech Act 378/2007 Coll.) consisting of three visits: the first at treatment initiation (teriflunomide 14 mg), and then after 3 and 9 months of therapy. We enrolled both DMT-naïve and patients who had undergone a DMT diagnosed with a clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS). The functional status and MS activity were estimated using the Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR); the quality of life via the Multiple Sclerosis Impact Scale (MSIS-29); the medication adherence with the Morisky Medication Adherence Scale (MMAS-8); the confidence in the ability to take medications by the Self-Efficacy for Appropriate Medication Score (SEAMS); and the attitude to the therapy via the Beliefs about Medicines Questionnaire (BMQ). After nine months of therapy, we predicted the adherence to teriflunomide (MMAS-8) by fitting a multivariate ordinal logistic model with EDSS changes, gender, previous DMT, MSIS-29, BMQ, and SEAMS as the explanatory variables. Results: Between 2018 and 2019, 114 patients were enrolled at 10 sites in the Czech Republic. The mean age was 41.2 years, 64.8% were diagnosed with a CIS, 52.4% were DMT-naïve, and 98.1% of patients preferred an oral administration at the baseline. The mean EDSS baseline was 1.97 and remained constant during the 9 months of therapy. The ARR baseline was 0.72 and dropped to 0.19 and 0.15 after 3 and 9 months, respectively. Despite a more than 4-fold higher ARR baseline, the treatment-naïve patients achieved an ARR at 9 months comparable with those previously treated. There were ten non-serious adverse reactions. After nine months of teriflunomide therapy, 63.3%, 21.2%, and 15.4% of patients had a high, medium, and low adherence, respectively, as per the MMAS-8; 100% of patients preferred an oral administration. The SEAMS score (odds ratio (OR) = 0.91; p = 0.013) and previous DMT (OR = 4.28; p = 0.005) were the only significant predictors of non-adherence. The disability, the quality of life, and beliefs about medicines had no measurable effect on adherence. Conclusion: After nine months of teriflunomide therapy, both the disability and quality of life remained stable; the relapse rate significantly decreased, 63.3% of patients had a high adherence, and 100% of patients preferred an oral administration. A low adherence was associated with previous DMT experiences and a low self-efficacy for the appropriate medication (i.e., the confidence in one's ability to take medication correctly).

Health and economic impact of subcutaneous allergen immunotherapy in patients with pollen-induced allergic rhinoconjunctivitis: real-word evidence from the Czech Republic.

Background: The prevalence of allergic rhinoconjunctivitis (AR) has been increasing over the years, and allergen immunotherapy (AIT) remains the only disease-modifying treatment. However, cost-effectiveness data remain scarce. Methods: In this single-arm, noninterventional, prospective, multicenter study, we describe the effectiveness, safety and costs of subcutaneous AIT for pollen-induced allergic rhinoconjunctivitis. Results: Of 471 new AIT users, 317 completed three courses of treatment, and symptoms improved in 96%; no serious adverse reactions were reported. The cost of symptomatic medication decreased by 49% and the cost of unscheduled specialist visits decreased by 73%. Except for AIT administration, total healthcare costs decreased by 54% compared with the baseline pollen season without AIT. Conclusion: In clinical practice, subcutaneous AIT is an effective treatment generating savings on symptomatic medication and unscheduled consultations.

Hay fever has become more frequent over the years, and allergen immunotherapy (AIT) remains the only treatment able to reduce both symptoms and the root cause of this condition. However, it is not clear whether the benefits outweigh the price of the therapy. In this study, we observed patients in the common practice and described the effectiveness, safety and costs of injected AIT for pollen-induced hay fever. Of 471 new AIT users, 317 completed three courses of treatment in 3 consecutive years. Symptoms improved in 96% of them; no serious adverse reactions were reported. The cost of symptom-relieving medication decreased by 49% and the cost of unscheduled physician visits decreased by 73%. Except for costs related to AIT administration, total healthcare costs decreased by 54% compared with the years before AIT. In clinical practice, injected AIT is an effective treatment which generates savings on other medication and unscheduled physician consultations.

Direct costs in patients with nonvalvular atrial fibrillation newly indicated to apixaban: a retrospective prospective single arm cohort study.

BACKGROUND: Atrial fibrillation (AF) affects 46.3 million people; its prevalence has tripled over the last 50 years. AF leads to formation of blood clots increasing four-fold the risk of a stroke. Preventive anticoagulant therapy with warfarin has been well established for over 50 years but has efficacy and safety limitations. New anticoagulants do not require laboratory monitoring of prothrombin time, have low risk of adverse events, yet are more costly. METHODS: This non-interventional (Act 378/2007 Coll.) retrospective-prospective single-arm cohort study consisted of 3 visits. The primary objective was to compare the total direct cost of treatment with warfarin and apixaban. Patients with non-valvular AF were enrolled at the time of discontinuation of warfarin and switching to apixaban. Costs were derived from the care provided and the list of medical procedures (Decrees 268/ 2019 Coll.). Satisfaction was assessed using SAFUCA® questionnaire. RESULTS: Between February 2017 and June 2019, 499 patients were enrolled in 29 Czech internal medicine clinics. The mean age of the patients was 73.6 ± 10.2 years, 36.5% were at high risk of bleeding (HAS-BLED score). Previous warfarin treatment lasted 5.9 ± 2.7 months, 63% were unable to achieve target prothrombin time, 18% switched due to adverse reactions. New apixaban treatment was followed for the first 6 months. Treatment with warfarin was associated with higher rates of major bleeding and adverse events (22 vs. 2), stroke (17 vs. 0), ischemic heart attack (11 vs. 0), and minor bleeding (173 vs. 2). The average daily cost following the switch to apixaban decreased from CZK 65.2 to CZK 4.8 (p.

[Quality of Life After High-dose Brachytherapy in Patients with Early Oral Carcinoma]. / Kvalita zivota pacientu s castými nádory dutiny ústní lécených pooperacní brachyterapií s vysokým dávkovým príkonem pro tesné nebo pozitivní okraje.

BACKGROUND: The prevalence of head and neck tumors has continually increased over the past decades, which is a serious medical and social problem. This study retrospectively assessed the quality of life of patients with early-stage oral cavity tumors after high-dose rate (HDR) brachytherapy. MATERIAL AND METHODS: Quality of life was evaluated in 14 patients with early-onset oral cavity tumors who underwent HDR brachytherapy at the Department of Oncology and Radiotherapy, University Hospital Hradec Kralove. The standardized EORTC QLQ-C30 and EORTC QLQ-H&N 35 questionnaires were used. Patients completed these questionnaires at 12 months after treatment. RESULTS: The general health status was scored 70 points using the EORTC QLQ-C30 questionnaire. Fatigue, insomnia, loss of appetite, dyspnea, and financial problems were the most severe problems reported. The main problems identified by the EORTC QLQ-H&N 35 questionnaire were weight gain, coughing, pain, sticky saliva, and difficulties eating in public. On the contrary, patients did not significantly suffer weight loss, speech impairments, difficulties in mouth opening or swallowing, or sensory problems. CONCLUSION: HDR brachytherapy is an effective treatment for early oral cancer that leaves patients with an acceptable quality of life. A prospective, multicentric study focused on the quality of life of patients with head and neck tumors is required.Key worlds: oral cancer - brachytherapy - quality of life This article was supported by grant PROGRES Q 40/13. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 17. 1. 2018Accepted: 4. 2. 2018.

The Osteogenic Potential of Human Nondifferentiated and Pre-differentiated Mesenchymal Stem Cells Combined with an Osteoconductive Scaffold - Early Stage Healing.

Despite the huge research into stem cells and their regenerative properties for bone healing, there are still unanswered questions including the recipient's respond to the presence of the stem cells, the fate of stem cells inside the bone defect and the possible advantage in utilizing pre-differentiated cells. To address these problems, we used human multipotent mesenchymal stromal/stem cells (MSCs), GMP Grade, in a rat model of bone formation. In a "bioreactor concept" approach seven Wistar rats were implanted with 0.2 g of synthetic bone scaffold seeded with 2 × 106 MSCs, seven Wistar rats were implanted with 0.2 g of synthetic bone scaffold seeded with 1 × 106 predifferentiated osteoblasts and 1 × 106 pre-differentiated endothelial cells and 14 Wistar rats were implanted with 0.2 g of synthetic bone scaffold without seeded cells into an intramuscular pocket on the left side of their back. The right side of each rat was used as a control, and 0.2 g of synthetic bone scaffold was implanted into the intramuscular pocket alone. To see the early stage healing the samples were harvested 14 days after the implantation, MSCs were detected by positive DAPI and MTCO2 staining in 43% of all the samples implanted with MSCs, and no inflammation signs were present in any implanted animal. New vessels could be found in both groups implanted with MSCs, but not in the control group of animals. However, hematoxylin-eosin staining could not detect newly created bone within the implant in any of the groups. These results were in line with COLL1 staining, where we could detect positive staining only in three cases, all of which were implanted with un-differentiated MSCs. According to our findings, there were no benefits of using the pre-differentiated of MSC.

Deep Neck infections of Odontogenic Origin and Their Clinical Significance. A Retrospective Study from Hradec Králové, Czech Republic.

INTRODUCTION: Cellulitis remains a very serious disease even today. Mortality, which varied between 10-40%, has been reduced owing to the standard securing of airway patency and use of an appropriate surgical treatment approach. MATERIALS AND METHODS: A total of 195 patients were hospitalised for cellulitis at the University Hospital in Hradec Králové during 2007-2011. The following parameters were evaluated: age, gender, dependence of incidence of the disease on the season of the year, frequency of attacks of the particular areas and their clinical characteristics, aetiology of the inflammation, types of patient complaints, prevalence of current systemic diseases, results of microbiological and selected laboratory analyses, socio-economic status of the patients, and duration of patient stay at the hospital. Statistical analysis was performed by using Pearson's correlation coefficient, the statistical significance level was p < 0.05. RESULTS: The mean age of the patients was 39.8 years. The group of 195 patients included 108 (55%) males and 87 (45%) females. The mean time between the first symptoms of the disease and admission to the Department was 5 days. From among the 195 patients, 116 (59.5%) were working persons, 79 (40.5%) were non-working (children, students, unemployed persons, women on maternity leave, retired people). The odontogenic origin of the disease was verified in 173 (88.7%) patients. In total, 65 (33.3%) patients had no coinciding complicating systemic disease, 22 (11.3%) patients had diabetes mellitus. The most frequent symptom of cellulitis was painful swelling, found in 194 (99.5%) patients, followed by jaw contracture, found in 153 (78.5%) patients. CONCLUSION: The results are largely very similar to those of previous studies performed in other countries, except that we found no correlation between the prevalence of cellulitis and the socio-economic status, nor have we confirmed Klebsiella pneumoniae sp. as the cause of cellulitis in patients with diabetes mellitus.

High-dose-rate brachytherapy in early oral cancer with close or positive margins.

PURPOSE: Retrospective evaluation of high-dose-rate brachytherapy (HDR BT) in early oral cancer and factors influencing tumor control. METHODS AND MATERIALS: A total of 30 patients with T1-T3N0 tongue and floor of mouth cancer were treated with tumor excision±elective neck dissection and HDR BT 18×3 Gy b.i.d. The Kaplan-Meier model was used for survival analyses, and the log-rank test and Cox regression analyses were used to evaluate the influence of T-stage, histologic grade, resection margin, depth of invasion, and vascular endothelial growth factor (VEGF) intensity on local control (LC), nodal control (NC), disease-free survival (DFS), and overall survival (OS). Median followup was 40 months (6-145). RESULTS: Actuarial 3-year LC, NC, DFS, DFS after salvage treatment, and OS were 85.4%, 69.2%, 65.4%, 75.6%, and 73.0%, respectively. The log-rank test and univariate Cox regression analysis revealed the following correlations, namely tumor grade correlated with LC, DFS, and OS; T-stage with NC and DFS; depth of invasion and VEGF intensity with NC, DFS, and OS. Associations detected on the multivariate analysis were as follows: tumor grade with LC, depth of invasion with NC, depth of invasion and tumor grade with DFS, and VEGF intensity with DFS after salvage treatment. Only one case of osteoradionecrosis and two cases of soft tissue necrosis occurred. CONSLUSION: The HDR BT 18×3 Gy b.i.d. is a safe treatment of early oral cancer with a good LC. The T-stage, tumor grade, depth of invasion, and intensity of VEGF were significant predictors of locoregional control.

Plasma cell granuloma of the oral cavity: a mucosal manifestation of immunoglobulin G4-related disease or a mimic?

The aim of the study was to test the hypothesis that oral plasma cell granuloma may represent a mucosal manifestation of immunoglobulin (Ig)G4-related disease (IgG4-RD) in the oral cavity. The study sample comprised two males and four females, aged 54-79 years (median 62 years). The lesions were localized on gingival/alveolar mucosa (four cases), hard palate, and floor of the mouth, measuring 17-40 mm (median 31 mm). The duration of the lesions ranged from 3 months to several years. Information on IgG4 serum levels was available for two patients, and these were increased to 1.85 and 1.65 g/L, respectively. The follow-up period ranged 11-30 months (median 13 months). None of the lesions recurred, and none of the patients developed any manifestation of IgG4-RD. Microscopically, all cases presented as nodular lesions composed of numerous polyclonal plasma cells admixed with lymphocytes, histiocytes, mast cells, and eosinophils, set within collagenized stroma in variable proportions. Obliterative phlebitis was observed in two cases. The number of IgG4-positive plasma cells ranged between 51 and 142 per HPF (median 114), while the IgG4/IgG ratio values ranged between 0.16 and 0.72 (median 0.44) and were above 0.40 in three cases. Based on international criteria, two cases were diagnosed as definite and one as probable IgG4-RD. Oral plasma cell granuloma is a heterogeneous group of lesions, and a subset may represent a mucosal manifestation of IgG4-RD in the oral cavity.

Predicting factors for locoregional failure of high-dose-rate brachytherapy for early-stage oral cancer.

AIM: Brachytherapy is an alternative to surgery in the treatment of the early stages of oral tongue cancer. The aim of this retrospective study was to analyze the clinical risk factors and possible candidate biomarkers of local and regional tumor control. PATIENTS & METHODS: Twenty-four patients were treated between the years 2001 and 2010. Median follow-up was 37.4 months. Correlation between disease-free survival and clinical stage, tumor grade, resection margin, depth of invasion, and p16, EGF receptor, NF-κB, HIF-1α, HER2, Ku-80, COX-2 and VEGF expression was evaluated. RESULTS: The estimated 5-year local control was 81% and locoregional control was 62%. Depth of tumor invasion (p = 0.018) and higher VEGF expression (p = 0.016) were significantly predictive for worse disease-free survival in Cox multivariate analysis. CONCLUSION: Intensity of VEGF expression and depth of tumor invasion may be significantly negative predictors of disease-free survival in tongue cancer patients treated by brachytherapy alone. Predictive value of VEGF deserves evaluation in larger studies.

Chronic sclerosing sialadenitis as one of the immunoglobulin G4-related diseases: a clinicopathological study of six cases from Central Europe.

AIMS: Chronic sclerosing sialadenitis (CSS) has been proposed recently to be a member of the group of IgG4-related diseases in Japanese and American series. The aim of our study was to validate these results in a cohort of European patients. METHODS AND RESULTS: Our CSS series included four females and two males, aged 32-76 years, all presenting with unilateral swelling of submandibular gland. Microscopically, all CSS-cases showed similar morphology with preservation of lobular architecture accentuated by cellular fibrous bands, dense lymphoplasmacytic inflammation and varied acinar atrophy. Ductal lymphocytes were detected in three cases. In five cases, the presence of intraductal secretory material accompanied by parenchymal neutrophils was observed. Obliterative phlebitis was seen in three cases. The inflammatory infiltrate was composed of T and B lymphocytes and polyclonal plasma cells. The median number of IgG-positive plasma cells per high-power field (HPF) was 157; median number of IgG4-positive plasma cells per HPF was 133. Median value of the IgG4:IgG ratio was 0.84. CONCLUSIONS: This is the first European series to demonstrate that CSS belongs to the family of IgG4-related disease. Unlike previous studies, in CSS we found rarely described ductal lymphocytes and parenchymal neutrophils. CSS displays consistent morphology with increased numbers of IgG4-positive plasma cells, and should be regarded as a member of the IgG4-related disease group.

The role of high-risk human papillomavirus infection in oral and oropharyngeal squamous cell carcinoma in non-smoking and non-drinking patients: a clinicopathological and molecular study of 46 cases.

The aim of the study was to investigate the role of high-risk human papillomavirus (HR-HPV) infection in the etiopathogenesis of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma in non-smoking and non-drinking patients (NSNDP). Twenty-four OSCCs and 22 OPSCCs were analyzed by immunohistochemistry for p16(INK4a) protein (p16) expression and by chromogene in situ hybridization (CISH) and polymerase chain reaction (PCR) for HR-HPV DNA presence. The series included 23 males and 23 females aged 35-93 years. p16 expression was seen in 7 out of 24 (29%) OSCCs and in 22 out of 22 (100%) OPSCCs. Using CISH, HR-HPV DNA was observed in 6 out of 24 (25%) OSCCs and in 21 out of 22 (95%) OPSCCs. HPV DNA was found in 3 out of 24 (13%) OSCCs and in 18 out of 22 (82%) OPSCCs using PCR. HPV 16 and 33 were detected in 16 and in two cases, respectively. Compared with OSCCs, OPSCCs more frequently showed basaloid morphology (p < 0.0001), lymph node involvement (p = 0.0063), diffuse p16 expression (p < 0.0001), HR-HPV DNA presence using both CISH and PCR (p < 0.0001; p < 0.0001), and better outcome. The sensitivity and specificity of p16 expression for HR-HPV DNA presence detected by CISH were 0.89 and 0.95, respectively, and 0.95 and 0.85 for PCR detected HPV DNA. The sensitivity and specificity of CISH for PCR detected presence of HPV DNA were 1.00 and 0.73, respectively. Our study is the first larger study analyzing OSCC and OPSCC in NSNDP. Our results indicate that unlike OSCC, a vast majority of OPSCCs may be associated with HR-HPV infection.

Hyperfractionated high-dose rate brachytherapy in the treatment of oral tongue cancer.

BACKGROUND: Low-dose rate brachytherapy is a well established treatment modality of oral cancer. Data about high-dose rate (HDR) brachytherapy are still sparse with various fractionation schedules and heterogeneous results. AIM: The aim of our retrospective study was to evaluate the results of HDR brachytherapy with doses of 3 Gy twice daily. PATIENTS AND METHODS: Twenty patients with squamous cell tongue cancer were treated in the years 2001-2009 by exclusive HDR BT 18 × 3 Gy twice daily. The plastic tube technique was used. Median follow up was 47 months (7.8-118) since brachytherapy. RESULTS: The local and locoregional control was 85% and 68%, respectively. Bone necrosis developed in one case treated without mandibular shielding and soft tissue necrosis in 2 cases. CONCLUSION: It can be concluded that HDR brachytherapy with 18 × 3 Gy twice daily is safe with promising local control. The risk of nodal recurrences is substantial.

Low-grade cribriform cystadenocarcinoma of the parotid gland: a neoplasm with favorable prognosis, distinct from salivary duct carcinoma.

Low-grade cribriform cystadenocarcinoma of salivary glands is a recently described rare tumor with favorable prognosis. This study reports the case of 50-year-old woman with swelling lasting for 9 months in the right parotideomasseteric area. Grossly, the tumor was well circumscribed and dominated by cystic space. Microscopically, the neoplasm consisted of well-demarcated islets, some of them cystically dilated. The architecture of islets varied from solid to cribriform and micropapillary without comedo-type necroses. The tumor cells featured no significant cytologic atypia. Immunohistochemically, luminal cells showed expression of cytokeratins (CK), CK7, CK18, and S100 protein. In addition, immunostains for CK5/6, CK14, p63 protein, and smooth muscle actin displayed a continuous rim of myoepithelial cells around all tumor nests. In contrast, detection of CK20, hormonal receptors (androgen, estrogen, and progesterone), epidermal growth factor receptor and Her-2/neu oncoprotein was negative. The patient is free of disease for 2 years. The relationship between low-grade cribriform cystadenocarcinoma and salivary duct carcinoma is discussed.